WO2020175631A1 - Method for reducing unsaturated hydrocarbon compound - Google Patents
Method for reducing unsaturated hydrocarbon compound Download PDFInfo
- Publication number
- WO2020175631A1 WO2020175631A1 PCT/JP2020/008069 JP2020008069W WO2020175631A1 WO 2020175631 A1 WO2020175631 A1 WO 2020175631A1 JP 2020008069 W JP2020008069 W JP 2020008069W WO 2020175631 A1 WO2020175631 A1 WO 2020175631A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- group
- compound
- general formula
- unsaturated hydrocarbon
- reaction
- Prior art date
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- 150000002430 hydrocarbons Chemical class 0.000 title claims abstract description 154
- 229930195735 unsaturated hydrocarbon Natural products 0.000 title claims abstract description 152
- 238000000034 method Methods 0.000 title claims abstract description 94
- -1 alkyne compound Chemical class 0.000 claims abstract description 267
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 59
- 150000001340 alkali metals Chemical class 0.000 claims abstract description 58
- 239000002904 solvent Substances 0.000 claims abstract description 54
- 239000006185 dispersion Substances 0.000 claims abstract description 48
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 25
- 239000004327 boric acid Substances 0.000 claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims description 110
- 239000000126 substance Substances 0.000 claims description 88
- 125000001424 substituent group Chemical group 0.000 claims description 87
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 55
- 125000001931 aliphatic group Chemical group 0.000 claims description 35
- 125000006848 alicyclic heterocyclic group Chemical group 0.000 claims description 31
- 125000002723 alicyclic group Chemical group 0.000 claims description 30
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 29
- 229910052708 sodium Inorganic materials 0.000 claims description 18
- 239000011734 sodium Substances 0.000 claims description 18
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 241000307523 Xenostegia media Species 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 95
- 238000006722 reduction reaction Methods 0.000 description 130
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 102
- 239000000203 mixture Substances 0.000 description 77
- 239000000047 product Substances 0.000 description 60
- 239000000758 substrate Substances 0.000 description 53
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical group CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 37
- 239000007787 solid Substances 0.000 description 33
- YWYQOEKJHFVGGK-UHFFFAOYSA-N 2-(2-phenylethynyl)naphthalene Chemical compound C1=CC=CC=C1C#CC1=CC=C(C=CC=C2)C2=C1 YWYQOEKJHFVGGK-UHFFFAOYSA-N 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
- 125000004432 carbon atom Chemical group C* 0.000 description 24
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 238000003786 synthesis reaction Methods 0.000 description 22
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- 238000000605 extraction Methods 0.000 description 20
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 20
- JRXXLCKWQFKACW-UHFFFAOYSA-N biphenylacetylene Chemical group C1=CC=CC=C1C#CC1=CC=CC=C1 JRXXLCKWQFKACW-UHFFFAOYSA-N 0.000 description 19
- 239000012044 organic layer Substances 0.000 description 19
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 125000004122 cyclic group Chemical group 0.000 description 18
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 15
- 229910001873 dinitrogen Inorganic materials 0.000 description 15
- 239000011521 glass Substances 0.000 description 15
- 125000005842 heteroatom Chemical group 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- 125000004429 atom Chemical group 0.000 description 14
- 238000010586 diagram Methods 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- 125000004659 aryl alkyl thio group Chemical group 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 10
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 10
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 10
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 9
- 125000005110 aryl thio group Chemical group 0.000 description 9
- 125000004104 aryloxy group Chemical group 0.000 description 9
- 239000008204 material by function Substances 0.000 description 9
- 229910052751 metal Inorganic materials 0.000 description 9
- 239000002184 metal Substances 0.000 description 9
- 235000021286 stilbenes Nutrition 0.000 description 9
- 125000004149 thio group Chemical group *S* 0.000 description 9
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 8
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 125000003277 amino group Chemical group 0.000 description 8
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 8
- 125000005366 cycloalkylthio group Chemical group 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 8
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 125000004430 oxygen atom Chemical group O* 0.000 description 8
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical compound C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 8
- 229910052717 sulfur Inorganic materials 0.000 description 8
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 7
- 125000003282 alkyl amino group Chemical group 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 125000000000 cycloalkoxy group Chemical group 0.000 description 7
- 125000005843 halogen group Chemical group 0.000 description 7
- 125000002950 monocyclic group Chemical group 0.000 description 7
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- UZIXCCMXZQWTPB-UHFFFAOYSA-N trimethyl(2-phenylethynyl)silane Chemical group C[Si](C)(C)C#CC1=CC=CC=C1 UZIXCCMXZQWTPB-UHFFFAOYSA-N 0.000 description 7
- GHWZBGLVFJZCGC-UHFFFAOYSA-N 1-methoxy-2-[2-(2-methoxyphenyl)ethynyl]benzene Chemical group COC1=CC=CC=C1C#CC1=CC=CC=C1OC GHWZBGLVFJZCGC-UHFFFAOYSA-N 0.000 description 6
- YKUOFMNGWLZXHA-UHFFFAOYSA-N 1-methoxy-4-[2-(4-methoxyphenyl)ethynyl]benzene Chemical group C1=CC(OC)=CC=C1C#CC1=CC=C(OC)C=C1 YKUOFMNGWLZXHA-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- 238000006027 Birch reduction reaction Methods 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 125000001691 aryl alkyl amino group Chemical group 0.000 description 6
- 125000001769 aryl amino group Chemical group 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 6
- 229910052796 boron Inorganic materials 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 6
- 239000011593 sulfur Substances 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 125000000707 boryl group Chemical group B* 0.000 description 5
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 239000012776 electronic material Substances 0.000 description 5
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- 239000010410 layer Substances 0.000 description 5
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- 229930014626 natural product Natural products 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 229910052697 platinum Inorganic materials 0.000 description 5
- 238000006257 total synthesis reaction Methods 0.000 description 5
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 4
- WGLLSSPDPJPLOR-UHFFFAOYSA-N 2,3-dimethylbut-2-ene Chemical group CC(C)=C(C)C WGLLSSPDPJPLOR-UHFFFAOYSA-N 0.000 description 4
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 4
- IZLRZCVZUWQQMW-UHFFFAOYSA-N 2-phenylethynyl-tri(propan-2-yl)silane Chemical group CC(C)[Si](C(C)C)(C(C)C)C#CC1=CC=CC=C1 IZLRZCVZUWQQMW-UHFFFAOYSA-N 0.000 description 4
- ASZZHBXPMOVHCU-UHFFFAOYSA-N 3,9-diazaspiro[5.5]undecane-2,4-dione Chemical compound C1C(=O)NC(=O)CC11CCNCC1 ASZZHBXPMOVHCU-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 150000001345 alkine derivatives Chemical class 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 4
- 150000001639 boron compounds Chemical class 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- PJANXHGTPQOBST-QXMHVHEDSA-N cis-stilbene Chemical compound C=1C=CC=CC=1/C=C\C1=CC=CC=C1 PJANXHGTPQOBST-QXMHVHEDSA-N 0.000 description 4
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
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- 239000010419 fine particle Substances 0.000 description 4
- 150000002739 metals Chemical class 0.000 description 4
- XWYXLYCDZKRCAD-BQYQJAHWSA-N p-Methoxystilbene Chemical compound C1=CC(OC)=CC=C1\C=C\C1=CC=CC=C1 XWYXLYCDZKRCAD-BQYQJAHWSA-N 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
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- 150000001336 alkenes Chemical class 0.000 description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 3
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- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 3
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- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 150000002391 heterocyclic compounds Chemical class 0.000 description 3
- VBRLZTLFLNZEPZ-UHFFFAOYSA-N hex-1-ynylbenzene Chemical compound CCCCC#CC1=CC=CC=C1 VBRLZTLFLNZEPZ-UHFFFAOYSA-N 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
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- FLQOKJWUYDGZIT-VAWYXSNFSA-N 1-methoxy-2-[(e)-2-phenylethenyl]benzene Chemical compound COC1=CC=CC=C1\C=C\C1=CC=CC=C1 FLQOKJWUYDGZIT-VAWYXSNFSA-N 0.000 description 2
- QABCSPDGWHIRHC-UHFFFAOYSA-N 1-methoxy-4-(2-methylprop-1-enyl)benzene Chemical group COC1=CC=C(C=C(C)C)C=C1 QABCSPDGWHIRHC-UHFFFAOYSA-N 0.000 description 2
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- SVIUEMOZHFTFEZ-UHFFFAOYSA-N 1-methyl-2-[2-(2-methylphenyl)ethynyl]benzene Chemical group CC1=CC=CC=C1C#CC1=CC=CC=C1C SVIUEMOZHFTFEZ-UHFFFAOYSA-N 0.000 description 2
- LKQPWCKHMPJWGN-UHFFFAOYSA-N 1-methylsulfanyl-3-(2-phenylethynyl)benzene Chemical group CSC=1C=C(C=CC=1)C#CC1=CC=CC=C1 LKQPWCKHMPJWGN-UHFFFAOYSA-N 0.000 description 2
- 125000004825 2,2-dimethylpropylene group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[*:1])C([H])([H])[*:2] 0.000 description 2
- FEKPXSPSTYPWLB-UHFFFAOYSA-N 2-(cyclohexen-1-yl)ethynylbenzene Chemical group C1CCCC(C#CC=2C=CC=CC=2)=C1 FEKPXSPSTYPWLB-UHFFFAOYSA-N 0.000 description 2
- XNMQEEKYCVKGBD-UHFFFAOYSA-N 2-butyne Chemical compound CC#CC XNMQEEKYCVKGBD-UHFFFAOYSA-N 0.000 description 2
- 125000003229 2-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
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- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
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- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 125000003914 fluoranthenyl group Chemical group C1(=CC=C2C=CC=C3C4=CC=CC=C4C1=C23)* 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000020169 heat generation Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- PNLSTDKQAPNMDU-UHFFFAOYSA-N hept-1-enylbenzene Chemical compound CCCCCC=CC1=CC=CC=C1 PNLSTDKQAPNMDU-UHFFFAOYSA-N 0.000 description 1
- 125000003824 heptacenyl group Chemical group C1(=CC=CC2=CC3=CC4=CC5=CC6=CC7=CC=CC=C7C=C6C=C5C=C4C=C3C=C12)* 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- SQJAIKOMNGMZEX-UHFFFAOYSA-N hexan-1-ol;propan-1-ol Chemical compound CCCO.CCCCCCO SQJAIKOMNGMZEX-UHFFFAOYSA-N 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000003427 indacenyl group Chemical group 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- MXAYKZJJDUDWDS-LBPRGKRZSA-N ixazomib Chemical compound CC(C)C[C@@H](B(O)O)NC(=O)CNC(=O)C1=CC(Cl)=CC=C1Cl MXAYKZJJDUDWDS-LBPRGKRZSA-N 0.000 description 1
- 229960003648 ixazomib Drugs 0.000 description 1
- 229940046892 lead acetate Drugs 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- WBLCYYFORJVCJV-UHFFFAOYSA-N n,n-dimethyl-4-(2-phenylethynyl)aniline Chemical group C1=CC(N(C)C)=CC=C1C#CC1=CC=CC=C1 WBLCYYFORJVCJV-UHFFFAOYSA-N 0.000 description 1
- SFMJNHNUOVADRW-UHFFFAOYSA-N n-[5-[9-[4-(methanesulfonamido)phenyl]-2-oxobenzo[h][1,6]naphthyridin-1-yl]-2-methylphenyl]prop-2-enamide Chemical compound C1=C(NC(=O)C=C)C(C)=CC=C1N1C(=O)C=CC2=C1C1=CC(C=3C=CC(NS(C)(=O)=O)=CC=3)=CC=C1N=C2 SFMJNHNUOVADRW-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 description 1
- 125000005029 naphthylthio group Chemical group C1(=CC=CC2=CC=CC=C12)S* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 125000005244 neohexyl group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 description 1
- JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 description 1
- RCALDWJXTVCBAZ-UHFFFAOYSA-N oct-1-enylbenzene Chemical compound CCCCCCC=CC1=CC=CC=C1 RCALDWJXTVCBAZ-UHFFFAOYSA-N 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000005069 octynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- KHMYONNPZWOTKW-UHFFFAOYSA-N pent-1-enylbenzene Chemical compound CCCC=CC1=CC=CC=C1 KHMYONNPZWOTKW-UHFFFAOYSA-N 0.000 description 1
- DEGIOKWPYFOHGH-UHFFFAOYSA-N pent-1-ynylbenzene Chemical compound CCCC#CC1=CC=CC=C1 DEGIOKWPYFOHGH-UHFFFAOYSA-N 0.000 description 1
- 125000003933 pentacenyl group Chemical group C1(=CC=CC2=CC3=CC4=CC5=CC=CC=C5C=C4C=C3C=C12)* 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 125000005327 perimidinyl group Chemical group N1C(=NC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- 125000002080 perylenyl group Chemical group C1(=CC=C2C=CC=C3C4=CC=CC5=CC=CC(C1=C23)=C45)* 0.000 description 1
- 125000001828 phenalenyl group Chemical group C1(C=CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000004932 phenoxathinyl group Chemical group 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- QDLYEPXRLHYMJV-UHFFFAOYSA-N propan-2-yloxyboronic acid Chemical compound CC(C)OB(O)O QDLYEPXRLHYMJV-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000001725 pyrenyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- LFQDNHWZDQTITF-UHFFFAOYSA-N tavaborole Chemical compound FC1=CC=C2B(O)OCC2=C1 LFQDNHWZDQTITF-UHFFFAOYSA-N 0.000 description 1
- 229960002636 tavaborole Drugs 0.000 description 1
- 125000001935 tetracenyl group Chemical group C1(=CC=CC2=CC3=CC4=CC=CC=C4C=C3C=C12)* 0.000 description 1
- AFNWSIIBAYUTTL-UHFFFAOYSA-N tetradec-7-yne Chemical compound CCCCCCC#CCCCCCC AFNWSIIBAYUTTL-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 description 1
- 150000005691 triesters Chemical class 0.000 description 1
- KDQYHGMMZKMQAA-UHFFFAOYSA-N trihexyl borate Chemical compound CCCCCCOB(OCCCCCC)OCCCCCC KDQYHGMMZKMQAA-UHFFFAOYSA-N 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- GZKLCETYSGSMRA-UHFFFAOYSA-N trioctadecyl borate Chemical compound CCCCCCCCCCCCCCCCCCOB(OCCCCCCCCCCCCCCCCCC)OCCCCCCCCCCCCCCCCCC GZKLCETYSGSMRA-UHFFFAOYSA-N 0.000 description 1
- DTBRTYHFHGNZFX-UHFFFAOYSA-N trioctyl borate Chemical compound CCCCCCCCOB(OCCCCCCCC)OCCCCCCCC DTBRTYHFHGNZFX-UHFFFAOYSA-N 0.000 description 1
- MDCWDBMBZLORER-UHFFFAOYSA-N triphenyl borate Chemical compound C=1C=CC=CC=1OB(OC=1C=CC=CC=1)OC1=CC=CC=C1 MDCWDBMBZLORER-UHFFFAOYSA-N 0.000 description 1
- 125000003960 triphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C3=CC=CC=C3C12)* 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- LTEHWCSSIHAVOQ-UHFFFAOYSA-N tripropyl borate Chemical compound CCCOB(OCCC)OCCC LTEHWCSSIHAVOQ-UHFFFAOYSA-N 0.000 description 1
- YZYKZHPNRDIPFA-UHFFFAOYSA-N tris(trimethylsilyl) borate Chemical compound C[Si](C)(C)OB(O[Si](C)(C)C)O[Si](C)(C)C YZYKZHPNRDIPFA-UHFFFAOYSA-N 0.000 description 1
- WAXLMVCEFHKADZ-UHFFFAOYSA-N tris-decyl borate Chemical compound CCCCCCCCCCOB(OCCCCCCCCCC)OCCCCCCCCCC WAXLMVCEFHKADZ-UHFFFAOYSA-N 0.000 description 1
- WTBVYJWHTHPPKB-UHFFFAOYSA-N tritetradecyl borate Chemical compound CCCCCCCCCCCCCCOB(OCCCCCCCCCCCCCC)OCCCCCCCCCCCCCC WTBVYJWHTHPPKB-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
Definitions
- the present invention relates to a method for reducing unsaturated hydrocarbon compounds.
- Birch (8 _) reduction and catalytic hydrogenation reduction are known as methods for reducing unsaturated hydrocarbon compounds.
- the Birch reduction is a method of reducing an unsaturated hydrocarbon compound by reacting the unsaturated hydrocarbon compound with an alkali metal simple substance such as metallic sodium or metallic lithium in liquid ammonia. When a single alkali metal is put into liquid ammonia, the alkali metal dissolves and turns into ions. The outermost shell electrons of the dissolved alkali metal move to the solvent, and the electrons are surrounded by the solvent to be in the form of solvated electrons.
- the Birch reduction utilizes the strong reducing power of this solvated electron. When the Birch reduction is applied to the internal alkyne compound as an unsaturated hydrocarbon compound, it can be reduced to a 3 ⁇ -alkene compound.
- Catalytic hydrogenation reduction includes a method in which an unsaturated hydrocarbon compound reacts with hydrogen in the presence of a palladium or platinum catalyst to reduce the unsaturated hydrocarbon compound.
- catalytic hydrogenation reduction with a palladium or platinum catalyst reduces the corresponding alkane compound, but the reduction is stopped at the alkene compound stage by adjusting the activity of the catalyst. be able to.
- the reduction reaction of the alkyne compound can be stopped in the first step, and the corresponding alkene compound is produced.
- the Lindlar catalyst can be prepared by treating palladium supported on calcium carbonate with quinoline and lead acetate. When the Lindlar catalyst is applied to an internal alkyne compound as an unsaturated hydrocarbon compound, it can be reduced to the corresponding __-alkene compound, which is different from the Birch reduction in stereoselectivity. ⁇ 2020/175631 2
- Patent Document 1 discloses that under argon, bis(pinacolato)diboron Anhydrous containing Then, tetradeca-7-yne, which is an alkyne compound, was added to the mixture, and the mixture was reacted at 80° for 1 hour to cause a diboration reaction, which was reduced to the corresponding alkene compound (())- It has been reported that 2,2'-(tetradec-7-ene-7,8-diyl)bis(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolen) was obtained. .. Similarly, it has been reported that the diboration reaction proceeds also for alkyne compounds of 2-butyne and 3-hexyne. As described above, according to the method described in Patent Document 1, the internal alkyne compound can be reduced to the corresponding O_13-alkene compound.
- a borated alkene compound for example, an alkyl borate prepared by a reaction of styrene and 9-borabicyclo[3.3.1]nonane dimer ((9 ⁇ ) 2 ) is tributyl
- a method of reacting with an alkyne compound such as ethyl 3-phenylpropionate in the presence of a phosphine (hereinafter sometimes abbreviated as "84") catalyst has been reported (see Non-Patent Document 2). thing) . It is reported that the resulting borated alkene compound has a substituent introduced at the 3-position.
- a diboronated alkene compound or a diboronated alkane compound is included.
- Organic boron compounds are used in the total synthesis of natural products, medical and agricultural chemicals, electronic materials such as liquid crystals and organic EL, and organic synthetic reactions of a wide variety of functional materials such as intermediates thereof.
- the diboronated alkene compound produced in Patent Document 1 is also used as a synthetic intermediate for semiconductor materials.
- the organoboron compound bortezmib ixazomib has been developed as a therapeutic agent for multiple myeloma
- tavaborole is an antifungal agent
- crisaborole has been developed as a therapeutic agent for atopic dermatitis. Attention has been paid to various physiological activities of organic boron compounds.
- Patent Document 1 International Publication No. 2015/097078
- Non-Patent Document 1 Yuki Nagashima et al., "Trans-Diborylation of Alkynes: Pseudo-Intramo lecu lar Strategy Utilizing a Propargy 11 c Alcohol Unit", J. Am. Chem. Soc., 2014, 136 (24 ), pp 8532-8535
- Non-Patent Document 2 Kazunor i Nagao et al., "Phosphine-Catalyzed Ant i-Carbobora ion of Alkynoates with Alkyl-, Alkenyl-, and Ary Iboranes", J. Am. Chem. Soc., 2014, 136 (30). , pp 10605-10608
- the Birch reduction uses liquid ammonia (boiling point: 33°C) that is cooled to below the boiling point and liquefied, and is usually performed at a low temperature of -35°C or lower. Equipment for cooling is required. Moreover, ammonia used as a solvent is highly toxic. When a metal mass such as a simple substance of alkali metal is used, it may be difficult to form a uniform reaction system due to local heat generation. Therefore, the cost burden such as equipment for perch reduction, safety management, and energy cost will increase. ⁇ 2020/175631 4 ⁇ (: 171? 2020 /008069
- catalytic hydrogenation reduction and the method described in Patent Document 1 using a platinum catalyst all use very expensive catalysts such as palladium and platinum, and therefore the cost is increased. To do.
- industrial use requires complicated steps for catalyst recovery and regeneration, which increases the number of steps and complicates the steps.
- palladium is a rare metal among precious metals, so there is a problem in terms of sustainability.
- catalytic hydrogenation is not an alternative to Birch reduction because of its stereoselectivity when adapted to internal alkynes, and vice versa.
- Non-Patent Document 1 there is also a problem that a device and equipment suitable for handling are required so that it can be suitably used as a base (for example, in Japan, the It is designated as a Class 3 pyrophoric substance and a water-prohibiting substance.).
- Grignard reagent and NaH also have a problem that they require careful handling from the viewpoint of stability and danger of the reagent. It is also used as a catalyst in the method described in Non-Patent Document 2. Also has the problem that it is spontaneously ignitable, and similarly, it requires equipment and facilities suitable for handling (for example, in Japan, it is designated as a Class 4 flammable liquid by the Fire Service Law). ..
- an unsaturated hydrocarbon compound can be reduced easily in a small number of steps without using a device that requires complicated temperature control or safety control, or a reagent that requires careful handling or an expensive reagent. It is desired to build a technology that can.
- the unsaturated hydrocarbon compound can be easily and inexpensively and efficiently reduced with a small number of steps by using reagents that are easy to handle and handle.
- the degree of reduction can be controlled by reacting with a diboronic acid ester compound or a boric acid ester compound.
- organic boron compounds such as diboron alkene compounds and diboron alkene compounds obtained as a result of reduction of unsaturated hydrocarbon compounds by such a reduction method are used in organic synthesis reactions of a wide variety of functional materials. It is something. The present inventors have completed the present invention based on these findings.
- the present invention relates to a method for reducing an unsaturated hydrocarbon compound, which comprises: a reaction solvent containing an alkali metal dispersed in a dispersion solvent;
- [ ⁇ , [ ⁇ , are each independently an aliphatic hydrocarbon group which may have a substituent that does not react with an alkali metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or an aromatic group.
- a heterocyclic group ⁇ 2020/175631 6 ⁇ (:171? 2020 /008069
- the unsaturated hydrocarbon compound can be reduced under mild conditions by using the dispersion in which the alkali metal is dispersed in the dispersion solvent. Therefore, it does not require complicated temperature control or safety control, and does not require expensive reagents or reagents that require careful handling. Therefore, unsaturated hydrocarbon compounds can be reduced inexpensively and efficiently in a short time with a small number of steps using reagents that are easy to obtain and handle, which is very economically and industrially advantageous. is there.
- Alkali metals, especially sodium, are metals that are extremely widely distributed on the globe, so the reduction method of this configuration is also a method with excellent sustainability. Furthermore, organoboron compounds such as diboron alkane compounds obtained as a result of reduction of unsaturated hydrocarbon compounds by the reduction method of the present construction are used in organic synthesis reactions of a wide variety of functional materials. .. Therefore, the reduction method of this configuration can be applied to a wide variety of natural products such as total synthesis, medical and agricultural chemicals, electronic materials such as liquid crystals and organic compounds, and intermediates thereof. ⁇ 2020/175631 7 ⁇ (:171? 2020 /008069
- Another characteristic configuration is that in the presence of a dispersion prepared by dispersing an alkali metal in a dispersion solvent in a reaction solvent,
- (3 ⁇ 4 (3 ⁇ 4 ⁇ Oyobi are each independently of the alkali metals and does not react with an aliphatic substituted hydrocarbon group, an alicyclic hydrocarbon group An alicyclic heterocyclic group, an aromatic hydrocarbon group, or an aromatic heterocyclic group, and may be bonded to each other to form a ring].
- the unsaturated hydrocarbon compound can be reduced under mild conditions by using the dispersion in which the alkali metal is dispersed in the dispersion solvent. Therefore, complicated temperature control and safety control are not required, and expensive reagents and reagents that require careful handling are not required. Therefore, by using reagents that are easy to obtain and handle, the unsaturated hydrocarbon compound can be reduced inexpensively and efficiently in a small number of steps in a short time, which is very economical and industrially advantageous. Is.
- Alkali metals, especially sodium, are metals that are extremely widely distributed on the earth, so the reduction method of this configuration is also excellent in sustainability.
- the organic boron compounds such as diboron alkene compounds obtained as a result of the reduction of unsaturated hydrocarbon compounds by the reduction method of the present constitution are used in the organic synthesis reaction of a wide variety of functional materials. .. Therefore, the reduction method of this configuration is used for the total synthesis of natural products, organic and pharmaceutical compounds, electronic materials such as liquid crystals and organic compounds, and organic synthesis reactions of various functional materials such as intermediates thereof. Can be used for.
- Another characteristic configuration is that in the presence of a dispersion prepared by dispersing an alkali metal in a dispersion solvent in a reaction solvent,
- the unsaturated hydrocarbon compound can be reduced under mild conditions by using the dispersion in which the alkali metal is dispersed in the dispersion solvent. Therefore, complicated temperature control and safety control are not required, and expensive reagents and reagents that require careful handling are not required. Therefore, by using reagents that are easy to obtain and handle, the unsaturated hydrocarbon compound can be reduced inexpensively and efficiently in a small number of steps in a short time, which is very economical and industrially advantageous. Is.
- Alkali metals, especially sodium, are metals that are extremely widely distributed on the earth, so the reduction method of this configuration is also excellent in sustainability. Furthermore, organoboron compounds such as diboron alkane compounds obtained as a result of the reduction of unsaturated hydrocarbon compounds by the reduction method of this configuration are used in organic synthesis reactions of a wide variety of functional materials. .. Therefore, the reduction method of this configuration is used for the total synthesis of natural products, organic and pharmaceutical compounds, electronic materials such as liquid crystals and organic compounds, and organic synthesis reactions of various functional materials such as intermediates thereof. Can be used for.
- Another characteristic configuration is that the molar ratio of the dispersion obtained by dispersing the alkali metal in a dispersion solvent to the unsaturated hydrocarbon compound is 2 or more and 4 or less. ⁇ 2020/175631 1 1 ⁇ (: 171? 2020 /008069
- the unsaturated hydrocarbon compound can be reduced more efficiently by optimizing the amount of the dispersion in which the alkali metal is dispersed in the dispersion solvent.
- FIG. 1 is a diagram summarizing synthesis conditions and results of Example 1 — 1 (reduction reaction of diphenylacetylene (1)).
- FIG. 2 is a diagram summarizing synthesis conditions of Example 1-2 (reduction reaction of bis(4-methoxyphenyl)acetylene (1)).
- FIG. 3 is a diagram summarizing synthesis conditions of Example 1 — 1 3 (reduction reaction of diphenylacetylene (2)).
- FIG. 4 is a diagram summarizing synthesis conditions of Example 1 — 14 (reduction reaction of diphenylacetylene (3)).
- FIG. 5 is a diagram summarizing synthesis conditions and results of Example 2 — 1 (reduction reaction of diphenylacetylene (4)).
- FIG. 6 is a diagram summarizing the synthesis conditions of Example 2-2 (reduction reaction of diphenylacetylene (5)).
- FIG. 7 is a diagram summarizing synthesis conditions of Example 2-9 (reduction reaction of diphenylacetylene (6)).
- FIG. 8 is a diagram outlining the synthesis conditions for Example 2 — 16 (reduction reaction of 1-phenyl-...!-hexyne).
- FIG. 9 is a diagram summarizing synthesis conditions and results of Example 3 — 1 (reduction reaction of _ — stilbene).
- FIG. 10 is a diagram summarizing the synthesis conditions of Example 3-2 (reduction reaction of 3 ⁇ 4 -methoxystilbene).
- FIG. 11 is a diagram summarizing the synthesis conditions for Example 3 — 18 (stilbene (isomer mixture) reduction reaction (2) ).
- FIG. 12 is a diagram summarizing synthesis conditions and results of Example 4 (styrene reduction reaction). ⁇ 2020/175631 12 ⁇ (:171? 2020 /008069
- FIG. 13 is a diagram summarizing synthesis conditions and results of Example 5 (reduction reaction of phenanthrene).
- FIG. 14 is a diagram summarizing the synthesis conditions of Example 6 (reduction reaction of 4-methoxyphenylarene).
- the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is an alkyne compound having one or more carbon-carbon triple bonds in the molecule, converting the carbon-carbon triple bond into a single bond, and reducing it to the corresponding alkane compound. Including the method.
- an alkyne compound which is an unsaturated hydrocarbon compound represented by the general formula and a diboronic acid ester represented by the general formula 114 It includes a step of reducing the unsaturated hydrocarbon compound by reacting with a compound.
- examples of the unsaturated hydrocarbon compound to be reduced include an alkyne compound containing one or more carbon-carbon triple bonds in the molecule. it can.
- An alkyne compound is a terminal alkyne compound in which at least one of two carbon atoms forming a carbon-carbon triple bond is bonded to a hydrogen atom, but both carbon atoms form a carbon atom forming a carbon-carbon triple bond. In addition to the bond with, it may be an internal alkyne compound bonded to a group other than a hydrogen atom.
- the alkyne compound represented by the general formula I 3 are each independently a hydrogen atom or an aliphatic group which may have a substituent that does not react with an alkyl metal.
- Hydrocarbon group alicyclic hydrocarbon group, alicyclic heterocyclic group, aromatic hydrocarbon group, aromatic heterocyclic group, halogen atom, alkoxy group, cycloalkoxy group, aryloxy group, aralkyloxy group, fat Cyclic heterocyclic oxy group, aromatic heterocyclic oxy group, alkylthio group, cycloalkylthio group, arylthio group, aralkylthio group, alicyclic heterocyclic thio group, aromatic heterocyclic thio group, alkylamino group, cyclo An alkylamino group, an arylamino group, an aralkylamino group, a moon heterocyclic heterocyclic amino group, an aromatic heterocyclic amino group, or a silyl group, which has a substituent reactive with an alkali metal, This is not preferable because a dispersion in which a substituent and sodium are dispersed in a dispersion solvent reacts with each other to induce a
- the aliphatic hydrocarbon group may be linear or branched, or saturated or unsaturated.
- the chain length is also not particularly limited.
- the substituent is not particularly limited as long as it does not react with an alkali metal.
- Examples of the aliphatic hydrocarbon group include, but are not limited to, preferably an alkyl group having 1 to 20 carbon atoms, particularly preferably an alkyl group having 3 to 20 carbon atoms, an alkenyl group, and an alkynyl group. To be done. Therefore, an unsaturated hydrocarbon compound containing two or more carbon-carbon triple bonds in the molecule can also be a target of reduction in the method for reducing an unsaturated hydrocarbon compound according to this embodiment.
- the aliphatic hydrocarbon group includes, specifically, as an alkyl group, a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, an isoptyl group, and a -butyl group.
- alkenyl group examples include, but are not limited to, an ethenyl group, a probenyl group, a butenyl group, a pentenyl group, a hexenyl group, a heptenyl group and an octenyl group.
- alkynyl group examples include, but are not limited to, an ethynyl group, a propynyl group, afugyl group, a pentynyl group, a heptynyl group and an octynyl group.
- the aliphatic hydrocarbon group may further have a substituent.
- the substituent may have one or a plurality of substituents, and when having a plurality of substituents, they may be the same or different from each other.
- an aliphatic which may have a substituent ⁇ 2020/175631 15 ⁇ (:171? 2020 /008069
- Hydrocarbon group alicyclic hydrocarbon group, alicyclic heterocyclic group, aromatic hydrocarbon group, aromatic heterocyclic group, halogen atom, alkoxy group, cycloalkoxy group, aryloxy group, aralkyloxy group, alicyclic group Formula heterocyclic oxy group, aromatic heterocyclic oxy group, alkylthio group, cycloalkylthio group, arylthio group, aralkylthio group, alicyclic heterocyclic thio group, aromatic heterocyclic thio group, alkylamino group, cycloalkyl Examples thereof include, but are not limited to, an amino group, an arylamino group, an aralkylamino group, an alicyclic heterocyclic amino group, an aromatic heterocyclic amino group, and a silyl group.
- the aliphatic hydrocarbon group is the same as the above-mentioned ones, such as an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, an aromatic heterocyclic group, a halogen atom, an alkoxy group.
- the number of ring members is not particularly limited, regardless of whether the bond between ring-constituting atoms is saturated or unsaturated. Moreover, not only a single ring but also a ring having a ring assembly such as a condensed ring or a spit ring is included.
- the alicyclic hydrocarbon group is not limited to these, but preferably has 3 to 10 carbon atoms, particularly preferably 3 to 7 cycloalkyl groups, preferably 4 to 10 carbon atoms, Particularly preferred are 4 to 7 cycloalkenyl groups, cycloalkynyl groups and the like.
- cycloalkyl group examples include, but are not limited to, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group.
- cycloalkenyl group examples include, but are not limited to, a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group, a cycloheptenyl group, a cyclooctenyl group and the like.
- a cycloalkynyl group ⁇ 2020/175631 16 ⁇ (:171? 2020/008069
- Examples thereof include, but are not limited to, cyclooctynyl group and the like.
- the alicyclic hydrocarbon group may have a substituent.
- the substituents may have one or a plurality of substituents, and when they have a plurality of substituents, they may be the same or different from each other.
- the position of the substituent is also not particularly limited. Examples of the substituent are the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
- the alicyclic heterocyclic group is a non-aromatic heterocyclic group having one or more heteroatoms as ring-constituting atoms. Not only a single ring but also those having a ring assembly such as a condensed ring or a spiro ring are included.
- the bond between ring members may be saturated or unsaturated, and the number of ring members is not particularly limited.
- the heteroatom is not particularly limited as long as it does not react with sodium as a ring-constituting atom.
- the number of heteroatoms is not particularly limited, and the position of heteroatoms is also not limited.
- Preferred examples of the hetero atom include an oxygen atom, a nitrogen atom, a sulfur atom and the like.
- an alicyclic heterocyclic group having preferably 2 to 7 carbon atoms, particularly preferably 2 to 5 carbon atoms, and preferably 1 to 5 and particularly preferably 1 to 3 heteroatoms. Is mentioned.
- it when it has a plurality of heteroatoms, it may be the same kind of atoms or different kinds of atoms.
- the alicyclic heterocyclic group includes a nitrogen-containing alicyclic heterocyclic group such as a monocyclic four-membered ring azetidinyl group, a five-membered ring pyrrolidinyl group, a six-membered ring piperidyl group, and a piperazinyl group.
- a nitrogen-containing alicyclic heterocyclic group such as a monocyclic four-membered ring azetidinyl group, a five-membered ring pyrrolidinyl group, a six-membered ring piperidyl group, and a piperazinyl group.
- An oxygen-containing alicyclic compound cyclic group such as a monocyclic three-membered cyclic oxiranyl group, a four-membered cyclic oxetanyl group, a five-membered cyclic tetrahydrofuryl group, a six-membered tetrahydropyranyl group, Sulfur-containing alicyclic heterocyclic groups such as monocyclic five-membered tetrahydrothiophenyl groups, nitrogen-containing oxygen alicyclic heterocyclic groups such as monocyclic six-membered morpholinyl groups, monocyclic Examples thereof include nitrogen-containing sulfur alicyclic heterocyclic groups such as 6-membered thiomorpholinyl groups, but are not limited thereto.
- the alicyclic heterocycle may further have a substituent.
- the substituents may have one or a plurality of substituents, and when they have a plurality of substituents, they may be the same or different. ⁇ 2020/175631 17 ⁇ (: 171? 2020/008069
- the position of the substituent is also not particularly limited. Examples of the substituent are the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
- the aromatic hydrocarbon group is not particularly limited as long as it has an aromatic ring. Not only a single ring but also those having a ring assembly such as a condensed ring or a spiro ring are included. There is no particular limitation on the number of members. For example, an aromatic hydrocarbon group having preferably 6 to 22, and particularly preferably 6 to 14 carbon atoms can be mentioned.
- Aromatic hydrocarbon groups include monocyclic six-membered ring phenyl groups, etc., bicyclic naphthyl groups, pentalenyl groups, indenyl groups, azulenyl groups, etc., tricyclic biphenylenyl groups, indacenyl groups, acenaphthylenyl groups, fluorenyl groups.
- phenalenyl group, phenanthryl group, anthryl group, etc. tetracyclic fluoranthenyl, aceanthrylenyl group, triphenylenyl group, pyrenyl group, naphthacenyl group, etc., pentacyclic perylenyl group, tetraphenylenyl group, etc.
- examples include, but are not limited to, a hexacyclic pentacenyl group and the like, a heptcyclic rubicenyl group, a coronenyl group, a heptacenyl group, and the like. Particularly preferred is a phenyl group.
- the aromatic hydrocarbon group may further have a substituent.
- the substituent may have one or a plurality of substituents, and when having a plurality of substituents, they may be the same or different from each other.
- the position of the substituent is also not particularly limited. Examples of the substituent are the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
- the aromatic heterocyclic group is an aromatic heterocyclic group having one or more heteroatoms as ring-constituting atoms. Not only a single ring, but also those having a ring assembly such as a condensed ring or a spiro ring are included.
- the number of ring members is also not particularly limited.
- the heteroatom is not particularly limited as long as it does not react with sodium as a ring-constituting atom.
- the number of heteroatoms is not particularly limited, and the position of heteroatoms is also not limited.
- Preferred examples of the hetero atom include oxygen atom, nitrogen atom, sulfur atom and the like.
- an aromatic compound having 1 to 5 carbon atoms, particularly preferably 3 to 5 carbon atoms, and preferably 1 to 4 heteroatoms, particularly preferably 1 to 3 heteroatoms.
- Heterocyclic groups may be mentioned.
- the atoms may be the same or different.
- examples of the monocyclic aromatic heterocyclic group include a 5-membered pyrrolyl group, a pyrazolyl group, a pyridyl group, an imidazolyl group, a 6-membered pyrazinyl group, a pyrimidinyl group, a pyridazinyl group.
- nitrogen-containing aromatic heterocyclic groups five-membered furyl groups and other oxygen-containing aromatic heterocyclic groups, five-membered cyclic cenyl groups and other oxygen-containing aromatic heterocyclic groups, and five-membered oxazolyl groups Group, an isoxazolyl group, a nitrogen-containing oxygen aromatic heterocyclic group such as a flazanyl group, a five-membered thiazolyl group, a nitrogen-containing sulfur aromatic heterocyclic group such as an isothiazolyl group, and the like, but are not limited to these. Absent.
- Examples of the polycyclic aromatic heterocyclic group include a bicyclic indolizinyl group, an isoindolyl group, an indolyl group, an indazolyl group, a purinyl group, an isoquinolyl group, a quinolyl group, a phthalazinyl group, a naphthyridinyl group, a quinoxalinyl group, Nitrogen-containing aromatic heterocyclic groups such as quinazolinyl groups, cinnolinyl groups, tricyclic carbazolyl groups, carborinyl groups, phenatridinyl groups, acridinyl groups, perimidinyl groups, phenanthrolinyl groups, phenazinyl groups, and bicyclic benzofuranyl groups.
- Oxygen-containing aromatic heterocyclic groups such as isobenzofuranyl group, benzopyranyl group, sulfur-containing aromatic heterocyclic groups such as bicyclic benzocenyl group, tricyclic thianthrenyl group, and bicyclic benzoxazolyl Group, benzoisoxazolyl group and other nitrogen-containing oxygen aromatic heterocyclic groups, bicyclic benzothiazolyl group, benzoisothiazolyl group, tricyclic phenothiazinyl group and other nitrogen-containing sulfur aromatic heterocyclic groups, three Examples thereof include, but are not limited to, oxygen-containing sulfur aromatic heterocyclic groups such as cyclic phenoxathinyl groups.
- the aromatic heterocyclic group may further have a substituent.
- the substituent may have one or a plurality of substituents, and when having a plurality of substituents, they may be the same or different from each other.
- the position of the substituent is also not particularly limited. Examples of the substituent include the same groups as those exemplified as the substituent of the aliphatic hydrocarbon group. ⁇ 2020/175631 19 ⁇ (:171? 2020 /008069
- halogen atom examples include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
- the alkoxy group is preferably an alkoxy group having 1 to 10 carbon atoms, and specific examples thereof include a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a pentyloxy group and a hexyloxy group.
- the cycloalkoxy group is preferably a cyclobropoxy group having 3 to 10 carbon atoms, and examples thereof include a cyclobutoxy group, a cyclopentyloxy group and a cyclohexyloxy group.
- the aryloxy group is preferably an aryloxy group having 6 to 20 carbon atoms, and specific examples thereof include a phenyloxy group and a naphthyloxy group, but the aryloxy group is not limited thereto.
- the aralkyloxy group is preferably an aralkyloxy group having 7 to 11 carbon atoms, and specific examples thereof include a benzyloxy group and a phenethyloxy group.
- Examples of the alicyclic heterocyclic oxy group and the aromatic heterocyclic oxy group include the alicyclic heterocyclic group and aromatic heterocyclic group shown above as the heterocyclic moiety. In addition, these may further have a substituent.
- the substituents may have one or a plurality of substituents, and when they have a plurality of substituents, they may be the same or different from each other.
- the position of the substituent is also not particularly limited. Examples of the substituent are the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
- the alkylthio group is preferably an alkylthio group having 1 to 20 carbon atoms, and examples thereof include a methylthio group, an ethylthio group, a propylthio group, a pentylthio group, a pentylthio group, and a hexylthio group. Not something to do.
- Examples of the cycloalkylthio group include cycloalkylthio groups having 3 to 10 carbon atoms, and specific examples thereof include a cyclopropylthio group, a cyclobutylthio group, a cyclopentylthio group, and a cyclohexylthio group. It is not limited to.
- the arylthio group is preferably an arylthio group having 6 to 20 carbon atoms, and specific examples thereof include a phenylthio group and a naphthylthio group, but the arylthio group is not limited thereto.
- the aralkylthio group is ⁇ 2020/175631 20 ⁇ (:171? 2020 /008069
- Preferable examples are aralkylthio groups having 7 to 11 carbon atoms, and specific examples thereof include a benzylthio group and a phenethylthio group, but the aralkylthio group is not limited thereto.
- Examples of the alicyclic heterocyclic thio group and the aromatic heterocyclic thio group include the alicyclic heterocyclic group and aromatic heterocyclic group represented by the above as the heterocyclic moiety. Moreover, these may further have a substituent.
- the substituents may have one or a plurality of substituents, and when they have a plurality of substituents, they may be the same or different from each other.
- the position of the substituent is also not particularly limited. Examples of the substituent include the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
- the silyl group is a substitution of, on the silicon, three or more aliphatic hydrocarbon groups, alicyclic hydrocarbon groups, alicyclic heterocyclic groups, aromatic hydrocarbon groups, aromatic heterocyclic groups, and the like. It is a monovalent group having a group. Substituents such as an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group and an aromatic heterocyclic group may be the same as those mentioned above.
- a dimethylsilyl group a diphenylsilyl group, a trimethylsilyl group, a triethylsilyl group, a triisopropylsilyl group, a dimethyl-1-butylsilyl group, and a diphenyl-1-butylsilyl group. ..
- [0046] may be the same group or different groups.
- the carbon-carbon triple bond is not particularly limited, and the ring formed by the bond that can form part of the ring is exemplified by cycloalkyne ring such as cyclooctyne ring. be able to.
- the unsaturated hydrocarbon compound to be reduced in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment specifically includes diphenylacetylene, phenylacetylene, and 1-phenyl-1-propyne. , 1-phenyl-1-butyne, 1-phenyl-1-pentyne, 1-phenyl-!!-hexyne, 1-phenyl-2-(trimethylsilyl)acetylene, 1-phenyl-2-acetyl(acetyl), Bis (trimethylsilyl) acetylene, 2-phenyl-1-ethynylboronic acid pinacola ⁇ 2020/175631 21
- the unsaturated hydrocarbon compound to be reduced in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment a commercially available one may be used, or a method known in the art may be used. You may use what was manufactured.
- the diboronic acid ester compound used in the method for reducing an unsaturated hydrocarbon compound according to this embodiment is represented by the following general formula 1.
- [ ⁇ , [ ⁇ , are each independently an aliphatic hydrocarbon group which may have a substituent that does not react with an alkali metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or an aromatic group. It is a heterocyclic group.
- aliphatic hydrocarbon group alicyclic hydrocarbon group, alicyclic heterocyclic group, aromatic hydrocarbon group, and aromatic heterocyclic group, those mentioned above can be exemplified.
- Examples include, but are not limited to, a heptane-2,3-diyl group, where a ring structure composed of a boron atom, two oxygen atoms bonded to it, and an atom bonded to each oxygen atom is used. , Preferably having 4 to 8 ring members.
- the atom forming the cyclic structure may have a substituent, and the substituents introduced into the cyclic structure are bonded to each other to form a further cyclic structure. You may.
- diboronic acid ester compound used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment specifically, bis(pinacolato)diboron (4, 4, 4', 4', 5, 5 , 5', 5'-Octamethyl-2,2'-bi-1,3,2-dioxapororane), bis(neopentylglycolate)diborone (5,5,5,5,5-tetramethyl-2,2 ,-Bi-1,3,2-dioxaborinane), bis(hexylene glycolate)diborone (4,4,4',4',6,6'-hexamethyl-2,2'-bi-1,3,3 2-dioxaborinane), bis(catecholate) diborone (2,2'-bi -1,3,2-benzodioxaporol), 2-(4,4,5,5-tetramethyl-1 ,3,2 -Dioxaborolan-2-yl)-2,3
- the diboronic acid ester compound used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment may be a commercially available one, or may be one produced by a method known in the art. May be used.
- the dispersion obtained by dispersing an alkali metal in a dispersion solvent used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is a dispersion of an alkali metal as fine particles in an insoluble solvent, or an alkali metal. Is dispersed in an insoluble solvent in a liquid state.
- the alkali metal include sodium, potassium, lithium and alloys containing these metals.
- the average particle size of the fine particles is preferably less than 10 111, and particularly preferably less than 5 111.
- the average particle diameter was represented by the diameter of a sphere having a projected area equivalent to the projected area obtained by image analysis of a micrograph. ⁇ 2020/175631 23 ⁇ (: 171? 2020 /008069
- a dispersion prepared by dispersing an alkali metal in a dispersion solvent may be abbreviated as “30”. It is an abbreviation for Sod i um, and is labeled with a symbol because a dispersion using sodium as an alkali metal is used in the examples described below. However, the sign of does not exclude alkali metals other than sodium.
- the concentration of the alkali metal contained in [0057] is not particularly limited, but for example, 5 The following can be illustrated.
- any solvent known in the art can be used as long as the alkali metal can be dispersed as fine particles or the alkali metal can be dispersed in a liquid state in an insoluble solvent.
- mineral oils such as normal paraffinic solvents such as normal decane, normal hexane, normal heptane, and normal pentane, aromatic solvents such as xylene and toluene, heterocyclic compound solvents such as tetrahydrothiophene, and mixed solvents thereof.
- mineral oils such as normal paraffinic solvents such as normal decane, normal hexane, normal heptane, and normal pentane
- aromatic solvents such as xylene and toluene
- heterocyclic compound solvents such as tetrahydrothiophene, and mixed solvents thereof.
- a solvent used as a reaction solvent a solvent known in the technical field may be used as long as it does not inhibit the reaction in the reduction method. it can.
- an aprotic polar solvent is preferable.
- an ether solvent a paraffin solvent such as normal paraffin solvent or cycloparaffin solvent, an aromatic solvent, an amine solvent, or a heterocyclic compound solvent can be used.
- ether solvents cyclic ethers ⁇ 2020/175631 24 ⁇ (:171? 2020 /008069
- a solvent is preferable, and tetrahydrofuran (hereinafter sometimes abbreviated as “Cho #”) or the like can be preferably used.
- the paraffinic solvent cyclohexane, normal hexane, normal decane and the like are particularly preferable.
- the aromatic solvent xylene, toluene, benzene and the like are preferable.
- Ethylenediamine and the like can be preferably used as the amine solvent.
- Tetrahydrothiophene or the like can be used as the solvent for the heterocyclic compound. Further, these may be used alone or in combination of two or more and used as a mixed solvent.
- the dispersion solvent and the reaction solvent may be of the same kind or different kinds.
- the reaction temperature in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is not particularly limited, and an unsaturated hydrocarbon compound to be reduced, a diboronic acid ester compound, It can be appropriately set depending on the kind and amount of the reaction solvent, the reaction pressure and the like.
- the reaction temperature is preferably set to a temperature that does not exceed the boiling point of the reaction solvent.
- the reaction temperature can be set at a high temperature because it becomes higher than the boiling point under atmospheric pressure under pressure.
- the reaction can be carried out at room temperature, preferably 0 to 100 ° , particularly preferably 0 to 80 ° , and further preferably 0 to 50 ° . It is not necessary to provide a temperature control means for special heating or cooling, but a temperature control means may be provided if necessary.
- the reaction time in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is not particularly limited, and is an unsaturated hydrocarbon compound to be reduced, a diboronic acid ester compound, It may be appropriately set according to the kind and amount of the reaction solvent, the reaction pressure, the reaction temperature, and the like. Usually, it is carried out for 15 minutes to 24 hours, preferably 20 minutes to 6 hours.
- the unsaturated hydrocarbon compound reduction method according to the present embodiment is preferably carried out in an inert gas atmosphere filled with argon gas, nitrogen gas, or the like.
- the unsaturated hydrocarbon compound is reacted in a molar ratio of 1: 2 or more. More preferably, the reaction is carried out at 1:2 or more and 1:4 or less. By reacting in this amount, the unsaturated hydrocarbon compound can be efficiently reduced. on the other hand, If the amount is too large, post-treatment that remains after the reaction may be required, which may complicate the operation.
- unsaturated hydrocarbon The molar ratio of the diboronic acid ester compound is 1: 2 to 2.2: 1 to 1.
- the substance amount of It means the amount of the substance contained in alkaline metal equivalent.
- the unsaturated hydrocarbon compound reduction method further includes 2-propanol, methanol, ethanol, butanol, phenol, 2,2,2-trifluoroethanol, 1, 1, 1,
- the reduction reaction may be carried out by adding a lower alcohol such as 3,3,3-hexafluoro-2-propanol or a phenol or the like.
- a lower alcohol such as 3,3,3-hexafluoro-2-propanol or a phenol or the like.
- the triple bond of the unsaturated hydrocarbon compound can be reduced to a single bond.
- the boron ester can be bonded to the site of reduction of the unsaturated hydrocarbon compound.
- unsaturated hydrocarbon compounds It may be added 15 to 30 minutes after reacting the diboronic acid ester compound.
- an alkyne compound which is an unsaturated hydrocarbon compound to be reduced is reduced to a corresponding diborated alkane compound represented by the following general formula III 3.
- the boron-boron single bond) of the diboronic acid ester is cleaved, and the alkyne that is the unsaturated hydrocarbon compound to be reduced is
- the carbon-carbon triple bond of the compound one boryl group derived from diboronic acid ester and one hydrogen atom are added to each carbon atom constituting the triple bond. This reduces the alkyne compound to the corresponding diboronated alkane compound.
- the alkane compound obtained by the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is obtained as a stereoisomer, but when a reaction is carried out by adding a lower alcohol such as 2-propanol, a (13, 23) form, When the (, 2(3 ⁇ 4) form is reacted with phenol, the (, 23) form and the (13, 21 ⁇ ) form are preferentially obtained.
- the reduced alkane compound may be purified by a purification means known in the art.
- the reduced alkane compound is subjected to an extraction treatment using an organic solvent such as ethyl acetate as an extraction solvent, and the concentrated solution obtained is concentrated and applied to a purified carrier such as silica gel chromatography. Can be purified with.
- the unsaturated hydrocarbon compound reduction method according to the present embodiment is an alkyne compound having one or more carbon-carbon triple bonds in the molecule, wherein the carbon-carbon triple bond is converted into a double bond and reduced to the corresponding alkene compound. Including how to do.
- a dispersion prepared by dispersing an alkali metal in a dispersion solvent in a reaction solvent an alkyne compound which is an unsaturated hydrocarbon compound represented by the general formula and a borate ester represented by the general formula 114 It includes a step of reducing the unsaturated hydrocarbon compound by reacting with a compound.
- the unsaturated hydrocarbon compound to be reduced as in the above [1], one or more carbon-carbon triple bonds in the molecule are included.
- the alkyne compound include: Alkyne ⁇ 2020/175631 27 ⁇ (:171? 2020 /008069
- the compound is a terminal alkyne compound in which at least one of two carbon atoms forming a carbon-carbon triple bond is bonded to a hydrogen atom, both carbon atoms are bonded to a carbon atom forming a carbon-carbon triple bond.
- it may be an internal alkyne compound bonded to a group other than a hydrogen atom.
- a hydrogen atom an aliphatic hydrocarbon group which may have a substituent which does not react with an alkyl metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or , Aromatic heterocyclic group, halogen atom, alkoxy group, cycloalkoxy group, aryloxy group, aralkyloxy group, alicyclic heterocyclic oxy group, aromatic compound ring oxy group, alkylthio group, cycloalkylthio group, arylthio group , Aralkylthio group, alicyclic heterocyclic thio group, aromatic heterocyclic thio group, alkylamino group, cycloalkylamino group, arylamino group, aralkylamino group, alicyclic heterocyclic amino group, aromatic heterocycle An amino group and a silyl
- the alkyne compound is represented by the general formula [1] above, terms in can as the alkyne compound represented by the general formula and the same description, and thus, the Oyobi is in the general formula, and the formula I 3 Can be equivalent to
- ester borate compound used in the method for reducing an unsaturated hydrocarbon compound according to this embodiment is represented by the following general formula 114. ⁇ 0 2020/1756 31 28 ⁇ (: 17 2020 /008069
- 1 ⁇ , (3 ⁇ 4 ⁇ Oyobi are each independently of the alkali metals and does not react with an aliphatic substituted hydrocarbon group, an alicyclic hydrocarbon group
- aromatic heterocyclic group those described in the above item [1] can be exemplified.
- ⁇ and 1 b are both may be combined to form a ring, presence bonded as groups independently without binding to one another and two oxygen atoms bonded to the boron atom and a boron atom bonded to each other There is no particular restriction on the position.
- 1,1,2,2-tetramethylethylene group which is a group forming a pinacol ring, 1,1,2-trimethylpropylene group, 2,2-dimethylpropylene group, propylene Group, ⁇ -phenylene group, 1-(4-methoxyphenyl)-2,2-dimethylethylene group, (112( ⁇ 33,5-2,6,6-trimethylbicyclo[3.1.1]]heptane
- Examples include, but are not limited to, a boron atom, two oxygen atoms bonded to it, and a cyclic structure composed of atoms bonded to each oxygen atom is a ring.
- the number of members is preferably 4 to 8.
- the atom forming the cyclic structure may have a substituent, and even if the substituents introduced into the cyclic structure are bonded to each other to form a further cyclic structure. Good.
- ester borate compound used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment include trimethyl borate (trimethoxyborane). ⁇ 2020/175631 29 ⁇ (:171? 2020 /008069
- Triethyl borate (triethoxyborane), tripropyl borate, triisopropyl borate, tributyl borate, trihexyl borate, trioctyl borate, tridecyl borate, tritetradecyl borate, trioctadecyl borate, etc.
- Boric acid trialkyl esters, triphenyl borate, tri-borate triaryl esters such as boric acid triethanolamine, boric acid triisopropanolamine, tris(trimethylsilyl)borate having silyloxy group Acid triesters are mentioned.
- pinacol ethoxyboronate (2-ethoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane)
- pinacol isopropoxyboronate (2-isopropoxy-4,4,5,5) -Tetramethyl-1 ,3,2-dioxaborolane
- pinacol methoxyboronate (2-methoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane)
- trimethoxyborane examples thereof include catechol borate, neopentyl glycol borate, and biscyclohexyl diol borate. Particularly preferably, trimethoxyborane can be used
- reaction solvent used in the method for reducing an unsaturated hydrocarbon compound according to this embodiment the reaction solvent described in the above item [1] can be exemplified.
- reaction conditions such as reaction temperature, reaction time, reaction atmosphere, etc. in the method for reducing unsaturated hydrocarbon compounds according to the present embodiment, and the conditions described in the above item [1] are exemplified. can do
- the unsaturated hydrocarbon compound to be reduced the boric acid ester compound, and the type of reaction solvent, etc. It can be set appropriately according to the amount and the like.
- the unsaturated hydrocarbon compound is reacted in a molar ratio of 1:2 or more. More preferably, the reaction is carried out at 1:2 or more and 1:4 or less. By reacting with this amount, unsaturated hydrocarbon compounds can be efficiently returned. ⁇ 2020/175631 30 boxes (:171? 2020 /008069
- the substance amount of It means the mass of the substance contained in terms of alkali metal.
- the unsaturated hydrocarbon compound reduction method according to the present embodiment may be further post-treated with a dihydric alcohol such as pinacol or neopentyl glycol, or potassium hydrogen fluoride.
- a dihydric alcohol such as pinacol or neopentyl glycol, or potassium hydrogen fluoride.
- the -0( ⁇ group of the borate ester compound is protected by divalent alcohol or potassium hydrogen fluoride, and boric acid or boroxine generated by the reaction of the borate ester compound with the water in the reaction system.
- borate triesters such as trimethyl borate are used as borate ester
- pinacol is added to obtain a borated alkene compound with a pinacol boryl group.
- such a dihydric alcohol or the like it is preferably performed after adding the borate ester compound.
- the alkyne compound that is the unsaturated hydrocarbon compound to be reduced is reduced to the corresponding diboronated alkene compound represented by the following general formula 11. ..
- the boron-oxygen single bond of 1 in the borate ester -O) bond is cleaved to reduce ⁇ 2020/175631 31 ⁇ (: 171? 2020 /008069
- the alkyne compound which is the target unsaturated hydrocarbon compound
- one boryl group derived from borate ester is added to each carbon constituting the triple bond.
- the alkyne compound is reduced to the corresponding alkene compound.
- the alkyne compound is an internal alkyne compound
- the alkene compound formed is one in which a boryl group is introduced into the __13 type.
- the reduced alkene compound may be purified by a purification means known in the art.
- the reduced alkane compound is subjected to an extraction treatment using an organic solvent such as ethyl acetate as an extraction solvent, and the concentrated solution obtained is concentrated and applied to a purified carrier such as silica gel chromatography. Can be purified with.
- the unsaturated hydrocarbon compound reduction method according to the present embodiment is an alkene compound containing one or more carbon-carbon double bonds in the molecule, the carbon-carbon double bond is converted into a single bond, and the corresponding alkane compound is converted to the corresponding alkane compound. Including a method of reducing.
- examples of unsaturated hydrocarbon compounds to be reduced include alkene compounds containing one or more carbon-carbon double bonds in the molecule. It is possible to reduce a substance containing two or more carbon-carbon double bonds.
- the alkene compound at least one of the two carbon atoms forming the carbon-carbon double bond is bonded only to the hydrogen atom except the bond to the carbon atom forming the carbon-carbon double bond, and is bonded to another group. Even if the terminal alkene compound is not present, both carbon atoms form a carbon-carbon double bond. ⁇ 0 2020/175631 32 ⁇ (: 17 2020 /008069
- an internal alkene compound bonded with a group other than a hydrogen atom may be used.
- the arrangement of these groups is not limited to the general arrangement (including type 0). Even the £ placement Including the mold).
- I is the general formula.
- the carbon-carbon double bond can form a part of the ring by forming a ring by bonding with the or.
- they may exist as independent groups without being bonded to each other.
- the ring formed by the bond of and or is not particularly limited, and examples thereof include a cycloalkene ring such as a cyclohexene ring and an aromatic ring such as a benzene ring.
- a cycloalkene ring such as a cyclohexene ring
- an aromatic ring such as a benzene ring.
- the atom forming the cyclic structure may have a substituent, and the substituents introduced into the cyclic structure may be bonded to each other to form a further cyclic structure.
- ( ⁇ and ( ⁇ may be bonded to each other to form a ring, or may be present as independent groups without being bonded to each other.
- the ring formed by the bond is not particularly limited, and examples thereof include a cycloalkane ring such as a cyclohexane ring and a cycloalkene ring such as a cyclohexene ring. Also, similarly, they may be bonded to each other to form a ring, or they may exist as groups independent of each other. Further, the atom forming the cyclic structure may have a substituent, and the substituents introduced into the cyclic structure may be bonded to each other to form a further cyclic structure.
- the unsaturated hydrocarbon compound to be reduced in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment a commercially available one may be used, or the unsaturated hydrocarbon compound may be prepared by a method known in the art. You may use what was manufactured.
- the unsaturated hydrocarbon compound according to the present embodiment is used as a target of reduction in the reduction method. ⁇ 2020/175631 34 ⁇ (:171? 2020 /008069
- saturated hydrocarbon compound examples include styrene, ⁇ _-stilbene, 3-stilbene, /3-methylstyrene, /3-ethylstyrene, /3-propylstyrene, /3-butylstyrene and /3-pentyl.
- Styrene /3-hexylstyrene, ⁇ -methylstyrene, ⁇ -ethylstyrene, Propyl styrene, Petit Styrene, Pentyl styrene, Hexylstyrene, 1-methyl-1,2-diphenylethylene, 1,2,3-triphenylethylene, indene, 1,2-dihydronaphthalene, butadiene, isoprene, 1,3-cyclohexagen, norbornene, norbornadiene, etc. Can be mentioned.
- the ester borate compound used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment has the following general formula II. As shown in.
- 1 ⁇ , (3 ⁇ 4 ⁇ Oyobi are each independently of the alkali metals and does not react with an aliphatic substituted hydrocarbon group, an alicyclic hydrocarbon group, an alicyclic heterocyclic A group, an aromatic hydrocarbon group, or an aromatic heterocyclic group.
- the boric acid ester compound shown in can be equivalent to the boric acid ester compound represented by the general formula described in the section [2] above, and therefore can be represented by the general formula II.
- trimethoxyborane can be used.
- reaction solvent used in the method for reducing an unsaturated hydrocarbon compound according to this embodiment the reaction solvent described in the above item [1] can be exemplified.
- reaction conditions such as reaction temperature, reaction time, reaction atmosphere, etc. in the method for reducing unsaturated hydrocarbon compounds according to the present embodiment. ⁇ 2020/175631 35 ⁇ (: 171? 2020 /008069
- the unsaturated hydrocarbon compound to be reduced In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment and the amount of the boric acid ester compound used, the unsaturated hydrocarbon compound to be reduced, the boric acid ester compound, and the type of reaction solvent and the like, It can be set appropriately according to the amount and the like.
- the unsaturated hydrocarbon compound is reacted in a molar ratio of 1:2 or more. More preferably, the reaction is carried out at 1:2 or more and 1:4 or less. By reacting in this amount, the unsaturated hydrocarbon compound can be efficiently recovered.
- the amount is too large, post-treatment that remains after the reaction becomes necessary, and the operation may be complicated.
- the substance amount of It means the mass of the substance contained in terms of alkali metal.
- lithium iodide may be added. This has the effect of improving the yield and stereoselectivity of the product. When adding such lithium iodide, It is preferable to add before adding.
- the method for reducing an unsaturated hydrocarbon compound according to the present embodiment further includes 1 ⁇ 1, 1 ⁇ 1, 1 ⁇ 1', 1 ⁇ 1'-tetramethylethylenediamine (chome 1 ⁇ 8), triethylamine, etc.
- the amines may be added. This improves the product yield and diastereoselectivity.
- Is preferably added before the addition of.
- a post-treatment with a dihydric alcohol such as pinacol or neopentyl glycol or potassium hydrogen fluoride may be further performed.
- a dihydric alcohol such as pinacol or neopentyl glycol or potassium hydrogen fluoride
- the 0 ( ⁇ group of the borate ester compound is protected by a divalent alcohol or potassium hydrogen fluoride, and boric acid, boroxine, etc., which are generated by reacting the borate ester compound with water in the reaction system.
- a boric acid triester such as trimethyl borate
- An alkene compound borated by a ruboryl group can be obtained. Further, when such a dihydric alcohol is added, it is preferable to add it after adding the borate ester compound.
- the alkyne compound that is the unsaturated hydrocarbon compound to be reduced is represented by the following general formula III. Is reduced to the corresponding diboronated alkene compound shown in.
- the ⁇ bond of 1 of boric acid ester is cleaved, and the alkene compound which is the unsaturated hydrocarbon compound to be reduced is
- the alkene compound which is the unsaturated hydrocarbon compound to be reduced is
- one boryl group derived from borate ester is added to each carbon atom constituting the double bond.
- the alkene compound is reduced to the corresponding alkane compound.
- the internal alkene is used as the raw material, a mixture of the (1, 2) form and the (, 2(3 ⁇ 4) form is obtained diastereoselectively from both __13 type and “3 type” alkenes.
- the reduced alkane compound may be purified by a purification means known in the art.
- the reduced alkane compound is subjected to extraction treatment using an organic solvent such as ethyl acetate as an extraction solvent, and the concentrated extract obtained is concentrated and applied to a purified carrier such as silica gel chromatography. Can be purified with.
- Example [0105] Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited to these Examples.
- SD in the following examples a dispersion in which metallic sodium is dispersed as fine particles in normal paraffin oil is used, and the substance amount of SD is a numerical value in terms of metallic sodium contained in SD.
- Lithium iodide (0.27 g. 2.0 mmol), bis(4-methoxyphenyl)acetylene (0.24 g, 1.0 mmol) and bis(pinacolato)diborone (0.25 g, 1.0 mmol) were placed in a glass test tube containing a stir bar. And add nitrogen gas to the test tube. ⁇ 2020/175631 38 ⁇ (: 171? 2020 /008069
- the collected organic layer was dehydrated with sodium sulfate, and then all volatile compounds were removed with a mouth rotary evaporator.
- the ratio of the compound 82 and the compound 82 in the product was 75:25.
- Substrate General formula (1) General formula (2) (Examples 1 to 4) Reduction reaction of bis(2-methoxyphenyl)acetylene Example 1 except that the substrate was changed to bis(2-methoxyphenyl)acetylene (the following formula) (0.24 9 , 1.0 1111110 0) -When the reaction was performed under the same conditions as in -2, the product was obtained as a white solid, 0.31 9 (0.62 111 111 ⁇ 62%). 1 ⁇ (determined by 3 ⁇ 4, the general formula (1) in the product) And the mass ratio of the compounds represented by the general formula (2) was 74:26.
- Example 1-5 Reduction reaction of bis (2-methylphenyl) acetylene (1)
- the reaction was performed under the same conditions as in 1-2, the product was obtained as a white solid, 0.37 9 (0.79 111 111 ⁇ then 79%).
- the amount ratio of the compounds represented by the general formula (1) and the compound represented by the general formula (2) in the product was 70:30, respectively.
- Example 1_2 The reaction was carried out under the same conditions as in Example 1_2 except that the substrate was changed to 2-(phenylethynyl)naphthalene (the following formula) (0.239, 1.011111100) and the reaction temperature in the first step was changed to 0 ° .
- the product was obtained as a white solid, 0.32 9 (0.65 111111 ⁇ then 65%).
- 1 H-stain (determined by 3 ⁇ 4, respectively, according to the general formula (1) and the general formula (2) in the product)
- the mass ratio of the represented compounds was 89:11. [Chemical 22]
- Example 1_2 The reaction was carried out under the same conditions as in Example 1_2 except that the substrate was changed to 1-(4-methylsulfanylphenyl)-2-phenylenylacetylene (the following formula) (0.22 g, 1.0 mmol).
- the product was obtained as a white solid in an amount of 0.23 g (0.49 mm ⁇ U 49%).
- the mass ratio of the compounds represented by the general formula (1) and the general formula (2) in the product was 95:5.
- Substrate 1 - phenyl - 2 - (trimethylsilyl) acetylene (the following formulas) (0.17 9, 1.0, the reaction temperature in the first stage was changed to 0 °, also 2 - using hexanol - propanol in cash forte 1 Other than that, when the reaction was performed under the same conditions as in Examples 1 and 2, the product was 0.31 9 (0.73 111 111 ⁇ and 73%) as a white solid.
- the general formula in the product The mass ratio of the compounds represented by 1) and general formula (2) was 46:54, respectively.
- Example 1_ except that the substrate was changed to 1-phenyl-2-(triisopropylsilyl)acetylene (the following formula) (0 ⁇ 25 g, 0.95 mmol) and the reaction temperature in the first step was changed to 0°C.
- Lithium iodide (0.27 g, 2.0 mmol), diphenylacetylene (0.18 g, 1.0 mmol) and bis(pinacolato)diboron (0.25 g, 1.0 mmol) were added to a glass test tube containing a stir bar and tested. The inside of the tube was replaced with nitrogen gas. After cooling the test tube to 0 °C in an ice bath, THF (3.6 mL) and N, N, N', N'-tetramethylethylenediamine (0.4 mL) were added, and SD (9.9 M) was added to the mixture. , 0.20 mL, 2.0 mmol) was added dropwise.
- Diphenylacetylene (0.18 9 , 1.0 11111101) and bis(pinacolato)diboron (0.25 9 , 1.0 11111100) were added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas. After cooling to 0 ° , use the # (3.
- Tetramethylethylenediamine (0.4 ⁇ !) was added, and (9.9 11/1, 0.20 111 and 2.0 11111100) was added dropwise to this mixture. After completion of the addition, the mixture was stirred at 0° for 30 minutes and then 1,3- Dichloropropane (0.19 111 and 2.0 11111101) was added, and the reaction solution was heated to 60 ° and stirred for 5 hours.
- Lithium iodide (0.27 g, 2.0 mmol), diphenylacetylene (0.18 g, 1.0 mmol) and bis(pinacolato)diboron (0.25 g, 1.0 mmol) were added to a glass test tube containing a stir bar and tested. The inside of the tube was replaced with nitrogen gas. After cooling the test tube to 0 °C in an ice bath, THF (3.6 mL) and N, N, N', N'-tetramethylethylenediamine (0.4 mL) were added, and SD (9.9 M) was added to the mixture. , 0.20 mL, 2.0 mmol) was added dropwise.
- Example 2-4 Reduction reaction of bis(2-methoxyphenyl)acetylene (2) Using bis(2-methoxyphenyl)acetylene (the following formula) (0.24 9 , 1.0 1111110 [) as a substrate, one step When the reaction was performed under the same conditions as in Example 2_2 except that the eye reaction temperature was changed to room temperature, the compound represented by the general formula (3) was obtained as a white solid in an amount of 0.30 9 (0.60 11111101, 60%). Was given.
- Example 2-5 Reduction reaction of 1-phenyl-2464-butylacetylene (2) Substrate 1-phenyl-2-diamine 6"1;-butylacetylene (the following formula) (0.15 9, 0 ⁇ 94 11111101), the reaction was conducted under the same conditions as in Example 2_2 except that the reaction temperature in the first step was changed to room temperature. As a result, the compound represented by the general formula (3) was found to be 0.32 9 (0.
- Example 2-2 The reaction was carried out under the same conditions as in Example 2-2 except that the substrate was changed to 1-phenyl-2-(trimethylsilyl)acetylene (the following formula) (0.17 9 and 1.0), and was expressed by the general formula (3).
- the compound was obtained as a white solid in 0.37 9 (0.861 ⁇ 0 and 86%).
- Example 2 _ 2 The reaction was carried out under the same conditions as in Example 2 _ 2 except that the substrate was changed to 1-phenyl-2-(triisopropylsilyl)acetylene (the following formula) (0 25 g, 0.95 mmol), and the general formula (3 0.39 g (0.76 mm ⁇ U 76%) was obtained as a white solid.
- the substance ratio was 75:25.
- the compound represented by () was obtained in a yield of 83%.
- Example 2-15 Reduction reaction of 2-(phenylethynyl)naphthalene (3)
- the substrate was changed to 2-(phenylethynyl)naphthalene (the following formula) (0.23 9, 1.0 11111100)
- the reaction was performed under the same conditions as in Example 2_9, the compound represented by the general formula (4) was obtained (the yield was 55%).
- Example 2_1 was used except for some conditions.
- Anhydrous lithium iodide (0.33 g, 2.5 mmol) was added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas.
- the test tube was cooled to 0 ° C in an ice bath, and then THF (3.6 mL), N, N, N', N'-tetramethylethylenediamine (0.4 mL), cis-stilbene (ci s- 1,2-diphenylethene) (0.18 mL, 1.0 mmol) and trimethoxyborane (0.67 mU 6.0 mmol) were added. SD (9.2 M, 0.27 mU 2.5 mmol) was added dropwise to this mixture.
- Anhydrous lithium iodide (0.34 g, 2.5 mmol) was added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas.
- the test tube was cooled to 0 ° C in an ice bath, followed by THF (3.6 mL), N, N, N', N'-tetramethylethylenediamine (0.
- Example 3-3 to 3_15 examples in which the reaction was performed under the same conditions as in Example 3_2 except for some conditions will be described.
- the product in each of the following examples is represented by the general formula (5) and the general formula (6) (below) corresponding to the substrate in each example.
- the substrate can be a cis form, a trans form, or a mixture of isomers. ⁇ 2020/1756 31 53 2020 /008069
- Substrate Toxistilbene (the following formula) (0.10 9 ,0.49
- the product was 0.15 9 (0.31 1111110, 64%) as a white solid.
- the ratio of the compounds represented by the general formula (5) and the compound represented by the general formula (6) in the product was 94:6.
- the amount ratio of the compounds represented by the general formula (5) and the compound represented by the general formula (6) in the product was 93:7.
- the product was obtained as a white solid, 0.34 9 (0.74111111 ⁇ 74%) 1 ⁇ (determined by 3 ⁇ 4, represented by the general formula (5) and general formula (6) in the product, respectively)
- the mass ratio of the compounds was 92:8.
- heterogeneous mixture E/Z 67/33, 0.20 g, 0.99 mmol
- the product was obtained as a colorless liquid, 0.26 9 (0.51 1 ⁇ 0, 53%).
- the 1 H ratio (determined by 3 ⁇ 4, the ratio of the amount of the compound represented by the general formula (5) and the amount of the compound represented by the general formula (6) in the product was 50:50, respectively.
- the substrate is 1,2-dihydronaphthalene (the following formula) (0.13 9, 1.0
- Compound 11/1 was obtained as a colorless liquid in an amount of 0.17 9 (0.441111110, 44%).
- Substrate )-2-Pinacolatoboryl styrene (the following formula) (0.18 9 ,1.03
- the reaction was performed under the same conditions as in Example 3_2 except that 10 11111101 was used as the trimethoxyborane, and the compound 1 ⁇ 1 was obtained as a white solid in an amount of 0.31 9 (0.641111110, 62%). ..
- Anhydrous lithium iodide (0.34 g, 2.5 mmol) was added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas.
- THF 4.0 mL
- trimetoxyborane (0.11 mL, 1.0 mmol) were added.
- the test tube was cooled to -78 °C with dry ice/acetone, and SD (10.0 M, 0.25 mL, 2.5 mmol) was added dropwise to this mixture.
- Examples 3 _ 19 and 3-20 below examples in which the reaction was performed under the same conditions as in Example 3-18 except for some conditions will be described.
- the product in each of the following examples is represented by the general formula (7) and the general formula (8) (below) corresponding to the substrate in each example.
- the substrate is either a 3 ⁇ body or a mixture of isomers.
- Example 3 _ 18 The reaction was performed under the same conditions as in Example 3 _ 18 except that the substrate was changed to 3-stilbene (0.18 9, 1.01 1111110 ⁇ ) and methyl iodide was changed to butyl iodide (0.55, 3.0 11111100). 0.14 9 (0.39 1 ⁇ then 39%) was obtained as a white solid.
- 1 H (determined by 3 ⁇ 4, represented by the general formula (7) and general formula (8) in the product, respectively) The mass ratio of these compounds was 10:90.
- Example 3 (Example 3 _ 20) Reduction reaction of stilbene (mixture of isomers) (3)
- the present invention relates to all technical fields in which reduction of unsaturated hydrocarbon compounds is required, in particular, total synthesis of natural products, medical and agricultural chemicals, and electronic materials such as liquid crystal and organic! , It is a useful technology in organic synthesis technology of various functional materials such as intermediates.
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Abstract
In this method, an unsaturated hydrocarbon compound is reduced by reacting an alkyne compound, which is an unsaturated hydrocarbon compound, with a diboronic acid ester compound or a boric acid ester compound, or by reacting an alkene compound, which is an unsaturated hydrocarbon compound, with a boric acid ester compound, such reactions carried out in a reaction solvent and in the presence of a dispersion of an alkali metal dispersed in a dispersion solvent.
Description
\¥0 2020/175631 1 卩(:17 2020 /008069 明 細 書 \¥0 2020/175631 1 卩 (: 17 2020 /008069 Clarification
発明の名称 : 不飽和炭化水素化合物の還元方法 Title of invention: Method for reducing unsaturated hydrocarbon compound
技術分野 Technical field
[0001 ] 本発明は、 不飽和炭化水素化合物の還元方法に関する。 The present invention relates to a method for reducing unsaturated hydrocarbon compounds.
背景技術 Background technology
[0002] 不飽和炭化水素化合物を還元する方法としては、 バーチ (8 _ ) 還元や接 触水素化還元が知られている。 バーチ還元は、 液体アンモニア中で、 不飽和 炭化水素化合物と金属ナトリウムや金属リチウム等のアルカリ金属単体を反 応させることにより、 不飽和炭化水素化合物を還元する方法である。 液体ア ンモニアの中にアルカリ金属単体を投入すると、 アルカリ金属は溶解してイ オン化する。 溶解したアルカリ金属の最外殻電子は溶媒に移動し、 この電子 は溶媒に囲まれて溶媒和電子の形態となる。 バーチ還元は、 この溶媒和電子 の強い還元力を利用するものである。 また、 バーチ還元を、 不飽和炭化水素 化合物として内部アルキン化合物に適用した場合には、 3^-アルケン化合 物に還元できる。 [0002] Birch (8 _) reduction and catalytic hydrogenation reduction are known as methods for reducing unsaturated hydrocarbon compounds. The Birch reduction is a method of reducing an unsaturated hydrocarbon compound by reacting the unsaturated hydrocarbon compound with an alkali metal simple substance such as metallic sodium or metallic lithium in liquid ammonia. When a single alkali metal is put into liquid ammonia, the alkali metal dissolves and turns into ions. The outermost shell electrons of the dissolved alkali metal move to the solvent, and the electrons are surrounded by the solvent to be in the form of solvated electrons. The Birch reduction utilizes the strong reducing power of this solvated electron. When the Birch reduction is applied to the internal alkyne compound as an unsaturated hydrocarbon compound, it can be reduced to a 3^-alkene compound.
[0003] 接触水素化還元は、 パラジウムや白金触媒の存在下で、 不飽和炭化水素化 合物が水素と反応し、 不飽和炭化水素化合物を還元する方法がある。 パラジ ウムや白金触媒での接触水素化還元を、 アルキン化合物に適用した場合には 対応のアルカン化合物まで還元するものであるが、 触媒の活性度を調節する ことでアルケン化合物の段階で還元を止めることができる。 例えば、 パラジ ウムの触媒活性を低減したリンドラー 〇_ _1 1〇 触媒を用いることで、 アル キン化合物の還元反応を第 1段階で止めることができ対応のアルケン化合物 が生成する。 リンドラー触媒は、 炭酸カルシウムに担持したパラジウムを、 キノリンと酢酸鉛等で処理することにより調製することができる。 なお、 リ ンドラー触媒を、 不飽和炭化水素化合物として内部アルキン化合物に適用し た場合には、 対応の〇_ -アルケン化合物に還元することができ、 立体選択性 の点でバーチ還元とは異なる。
〇 2020/175631 2 卩(:171? 2020 /008069 [0003] Catalytic hydrogenation reduction includes a method in which an unsaturated hydrocarbon compound reacts with hydrogen in the presence of a palladium or platinum catalyst to reduce the unsaturated hydrocarbon compound. When applied to an alkyne compound, catalytic hydrogenation reduction with a palladium or platinum catalyst reduces the corresponding alkane compound, but the reduction is stopped at the alkene compound stage by adjusting the activity of the catalyst. be able to. For example, by using a Lindlar _ _ 1 110 catalyst with reduced palladium catalytic activity, the reduction reaction of the alkyne compound can be stopped in the first step, and the corresponding alkene compound is produced. The Lindlar catalyst can be prepared by treating palladium supported on calcium carbonate with quinoline and lead acetate. When the Lindlar catalyst is applied to an internal alkyne compound as an unsaturated hydrocarbon compound, it can be reduced to the corresponding __-alkene compound, which is different from the Birch reduction in stereoselectivity. 〇 2020/175631 2
[0004] また、 白金触媒の存在下で、 アルキン化合物にジボロン酸エステル化合物 を反応させることで対応のジホウ素化アルケン化合物が得られることが報告 されている (例えば、 特許文献 1 を参照のこと) 。 特許文献 1 には、 アルゴ ン下で、 ビス(ピナコラト)ジボロンと
を含む無水
に、 アルキン化 合物であるテトラデカ- 7 -インを添加し、 混合物を 80°〇にて 1時間反応させる ことで、 ジホウ素化反応が起こり、 対応のアルケン化合物に還元されて(å)-2 , 2’ -(テトラデカ- 7 -エン -7, 8 -ジイル)ビス(4, 4, 5, 5 -テトラメチル- 1 , 3, 2 -ジ オキサボロレン)が得られたことが報告されている。 また、 同様にして、 2 -ブ チン、 及び、 3 -ヘキシンのアルキン化合物についても、 ジホウ素化反応が進 行することが報告されている。 このように、 特許文献 1 に記載の方法によれ ば、 内部アルキン化合物を対応の〇_13 -アルケン化合物に還元できる。 [0004] Further, it has been reported that a corresponding diboronated alkene compound can be obtained by reacting an alkyne compound with a diboronic acid ester compound in the presence of a platinum catalyst (see, for example, Patent Document 1). ). Patent Document 1 discloses that under argon, bis(pinacolato)diboron Anhydrous containing Then, tetradeca-7-yne, which is an alkyne compound, was added to the mixture, and the mixture was reacted at 80° for 1 hour to cause a diboration reaction, which was reduced to the corresponding alkene compound (())- It has been reported that 2,2'-(tetradec-7-ene-7,8-diyl)bis(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolen) was obtained. .. Similarly, it has been reported that the diboration reaction proceeds also for alkyne compounds of 2-butyne and 3-hexyne. As described above, according to the method described in Patent Document 1, the internal alkyne compound can be reduced to the corresponding O_13-alkene compound.
[0005] 更に、 塩基の存在下で、 三重結合を含むアルコール化合物及び末端アルキ ン化合物等のアルキン化合物に、 ビス(ピナコラト)ジボロン等のジボロン酸 エステル化合物を反応させることで対応のジホウ素化アルケン化合物が得ら れることが報告されている (非特許文献 1 を参照のこと) 。 塩基として、 门- プチルリチウム (以下、 「 1£丨」 と称する場合がある) 、 メチルマグネシウ ムブロミ ド (以下、
と称する場合がある) 等のグリニヤール試薬 及び水素化ナトリウム (以下、 「 と称する場合がある) 等を用いること ができることが報告され、 得られるジホウ素アルケン化合物が 1「3 -アルケ ン化合物であることが報告されている。 [0005] Furthermore, in the presence of a base, an alcohol compound containing a triple bond and an alkyne compound such as a terminal alkyne compound are reacted with a diboronic acid ester compound such as bis(pinacolato)diborone to give a corresponding diboronated alkene. It has been reported that a compound can be obtained (see Non-Patent Document 1). As the base, there is stil-putyllithium (hereinafter sometimes referred to as "1£"), methylmagnesium bromide (hereinafter, It is reported that it is possible to use a Grignard reagent such as (hereinafter sometimes referred to as ") and sodium hydride (hereinafter sometimes referred to as "), and the resulting diboron alkene compound is a 1"3-alkene compound. It has been reported.
[0006] また、 ホウ素化アルケン化合物を得る方法として、 例えば、 スチレンと 9- ボラビシクロ[3. 3. 1]ノナンダイマー ((9^^)2) との反応により調製した アルキルホウ酸塩を、 トリブチルホスフィン (以下、 「 84」 と略する場合が ある) 触媒の存在下で、 エチル 3 -フエニルプロビオネート等のアルキン化 合物と反応させる方法が報告されている (非特許文献 2を参照のこと) 。 得 られるホウ素化アルケン化合物は、 「 3 位に置換基が導入されていることが 報告されている。 [0006] In addition, as a method of obtaining a borated alkene compound, for example, an alkyl borate prepared by a reaction of styrene and 9-borabicyclo[3.3.1]nonane dimer ((9^^) 2 ) is tributyl A method of reacting with an alkyne compound such as ethyl 3-phenylpropionate in the presence of a phosphine (hereinafter sometimes abbreviated as "84") catalyst has been reported (see Non-Patent Document 2). thing) . It is reported that the resulting borated alkene compound has a substituent introduced at the 3-position.
[0007] ここで、 ジホウ素化アルケン化合物やジホウ素化アルカン化合物を含む有
機ホウ素化合物は、 天然物全合成や、 医農薬、 及び、 液晶や有機 EL等の電子 材料、 並びに、 それらの中間体等の多種多様な機能性材料の有機合成反応等 に使用されている。 上記した特許文献 1で生成したジホウ素化アルケン化合 物も、 半導体材料の合成中間体としてされたものである。 近年、 有機ホウ素 化合物であるボルテゾミブ (bortezmib) イキサゾミブ (ixazomib) が多発性 骨髄腫の治療薬、 タバボロール (tavaborole) が抗真菌剤、 クリサポロール (crisaborole) がアトピー性皮膚炎の治療薬として開発される等、 有機ホウ 素化合物が有する様々な生理活性が注目されている。 [0007] Here, a diboronated alkene compound or a diboronated alkane compound is included. Organic boron compounds are used in the total synthesis of natural products, medical and agricultural chemicals, electronic materials such as liquid crystals and organic EL, and organic synthetic reactions of a wide variety of functional materials such as intermediates thereof. The diboronated alkene compound produced in Patent Document 1 is also used as a synthetic intermediate for semiconductor materials. In recent years, the organoboron compound bortezmib ixazomib has been developed as a therapeutic agent for multiple myeloma, tavaborole is an antifungal agent, and crisaborole has been developed as a therapeutic agent for atopic dermatitis. Attention has been paid to various physiological activities of organic boron compounds.
先行技術文献 Prior art documents
特許文献 Patent literature
[0008] 特許文献 1 :国際公開第 2015/097078号 [0008] Patent Document 1: International Publication No. 2015/097078
非特許文献 Non-patent literature
[0009] 非特許文献 1 : Yuki Nagashima他著、 “Trans-Diborylation of Alkynes: Pse udo-Intramo lecu lar Strategy Utilizing a Propargy 11 c Alcohol Unit” , J . Am. Chem. Soc. , 2014, 136 (24), pp 8532-8535 [0009] Non-Patent Document 1: Yuki Nagashima et al., "Trans-Diborylation of Alkynes: Pseudo-Intramo lecu lar Strategy Utilizing a Propargy 11 c Alcohol Unit", J. Am. Chem. Soc., 2014, 136 (24 ), pp 8532-8535
非特許文献 2 : Kazunor i Nagao他著、 “Phosphine-Catalyzed Ant i-Carbobora t ion of Alkynoates with Alkyl-, Alkenyl-, and Ary Iboranes" , J. Am. Chem. Soc., 2014, 136 (30), pp 10605-10608 Non-Patent Document 2: Kazunor i Nagao et al., "Phosphine-Catalyzed Ant i-Carbobora ion of Alkynoates with Alkyl-, Alkenyl-, and Ary Iboranes", J. Am. Chem. Soc., 2014, 136 (30). , pp 10605-10608
発明の概要 Summary of the invention
発明が解決しようとする課題 Problems to be Solved by the Invention
[0010] しかしながら、 バーチ還元は、 沸点以下まで冷却して液化させた液体アン モニア (沸点一 33°C) を使用し、 通常、 -35°C以下の低温下で行われるもので あるため、 冷却のための装置が必要となる。 しかも、 溶媒として用いるアン モニアは毒性が強い。 アルカリ金属単体のような金属塊を用いた場合には、 局所的な発熱が生じる等、 均一な反応系を形成することが困難となるおそれ がある。 そのため、 パーチ還元を行うための装置や安全管理、 エネルギーコ スト等、 コスト負担が増大する。
〇 2020/175631 4 卩(:171? 2020 /008069 [0010] However, the Birch reduction uses liquid ammonia (boiling point: 33°C) that is cooled to below the boiling point and liquefied, and is usually performed at a low temperature of -35°C or lower. Equipment for cooling is required. Moreover, ammonia used as a solvent is highly toxic. When a metal mass such as a simple substance of alkali metal is used, it may be difficult to form a uniform reaction system due to local heat generation. Therefore, the cost burden such as equipment for perch reduction, safety management, and energy cost will increase. 〇 2020/175631 4 卩 (: 171? 2020 /008069
[001 1 ] また、 接触水素化還元、 及び、 白金触媒を用いる特許文献 1 に記載の方法 は、 何れもパラジウムや白金等の非常に高価な触媒を利用するものであるた め、 コストが増加する。 しかも、 工業的に利用するためには触媒の回収及び 再生等のための煩雑な工程が必要となり、 工程数が増加すると共に工程が複 雑化する。 特に、 パラジウムは貴金属の中でも希少性が高いことから、 サス テナピリティの点でも問題がある。 また、 接触水素化還元は、 内部アルキン に適応した際の立体選択性の面から、 バーチ還元の代替法とはならず、 その 逆も同様である。 [001 1] Further, catalytic hydrogenation reduction and the method described in Patent Document 1 using a platinum catalyst all use very expensive catalysts such as palladium and platinum, and therefore the cost is increased. To do. In addition, industrial use requires complicated steps for catalyst recovery and regeneration, which increases the number of steps and complicates the steps. In particular, palladium is a rare metal among precious metals, so there is a problem in terms of sustainability. Also, catalytic hydrogenation is not an alternative to Birch reduction because of its stereoselectivity when adapted to internal alkynes, and vice versa.
[0012] 更に、 非特許文献 1 に記載の方法において、 塩基として好適に利用できる には、 取り扱いに適した装置や設備等が必要となるとの問題もある (たと えば日本では、 消防法で第 3類自然発火性物質及び禁水性物質に指定されて いる。 ) 。 グリニャール試薬及び NaHについても、 試薬の安定性及び危険性の 観点から、 取り扱いに注意を要するとの問題がある。 また、 非特許文献 2に 記載の方法において、 触媒として用いられる
についても、 自然発火性があ り、 同様に、 取り扱いに適した装置や設備等が必要となるとの問題がある ( たとえば日本では、 消防法で第 4類引火性液体に指定されている。 ) 。 [0012] Further, in the method described in Non-Patent Document 1, there is also a problem that a device and equipment suitable for handling are required so that it can be suitably used as a base (for example, in Japan, the It is designated as a Class 3 pyrophoric substance and a water-prohibiting substance.). Grignard reagent and NaH also have a problem that they require careful handling from the viewpoint of stability and danger of the reagent. It is also used as a catalyst in the method described in Non-Patent Document 2. Also has the problem that it is spontaneously ignitable, and similarly, it requires equipment and facilities suitable for handling (for example, in Japan, it is designated as a Class 4 flammable liquid by the Fire Service Law). ..
[0013] そこで、 煩雑な温度管理や安全管理等を要する装置や、 取り扱いに注意を 要する試薬類や高価な試薬類を使用せずに、 少ない工程数で簡便に、 不飽和 炭化水素化合物を還元できる技術の構築が望まれている。 [0013] Therefore, an unsaturated hydrocarbon compound can be reduced easily in a small number of steps without using a device that requires complicated temperature control or safety control, or a reagent that requires careful handling or an expensive reagent. It is desired to build a technology that can.
課題を解決するための手段 Means for solving the problem
[0014] 本発明者らは、 上記課題を解決すべく研究を重ねた結果、 反応溶媒中、 ナ トリウム等のアルカリ金属を分散溶媒に分散させた分散体の存在下で、 不飽 和炭化水素化合物とジボロン酸エステル化合物又はホウ酸エステル化合物と を反応させることにより、 不飽和炭化水素化合物を効率よく還元できること を見出した。 また、 かかる還元方法は、 取扱いが容易なアルカリ金属を分散 溶媒に分散させた分散体を使用することから、 温和な条件下で不飽和炭化水 素化合物を還元できる。 また、 煩雑な温度管理等や安全管理等を必要とせず 、 また、 高価な試薬類や取り扱いに注意を要する試薬類をも必要とせず、 入
〇 2020/175631 5 卩(:171? 2020 /008069 [0014] As a result of repeated studies to solve the above problems, the present inventors have found that in the presence of a dispersion in which an alkali metal such as sodium is dispersed in a reaction solvent in a reaction solvent, an unsaturated hydrocarbon is present. It was found that the unsaturated hydrocarbon compound can be efficiently reduced by reacting the compound with a diboronic acid ester compound or a boric acid ester compound. Moreover, since such a reduction method uses a dispersion in which an alkali metal which is easy to handle is dispersed in a dispersion solvent, the unsaturated hydrocarbon compound can be reduced under mild conditions. In addition, it does not require complicated temperature control or safety control, and does not require expensive reagents or reagents that require careful handling. 〇 2020/175631 5
手及び取り扱い容易な試薬類を使用して少ない工程数で簡便に不飽和炭化水 素化合物を安価かつ効率よく還元できる。 特に、 不飽和炭化水素化合物とし てアルキン化合物に適用した場合には、 ジボロン酸エステル化合物又はホウ 酸エステル化合物と反応させることで、 還元の程度を制御することができる 。 また、 かかる還元方法により不飽和炭化水素化合物の還元の結果として得 られるジホウ素アルケン化合物やジホウ素アルケン化合物等の有機ホウ素化 合物は、 多種多様な機能性材料の有機合成反応等に使用されるものである。 本発明者らは、 これらの知見に基づいて本発明を完成するに至った。 The unsaturated hydrocarbon compound can be easily and inexpensively and efficiently reduced with a small number of steps by using reagents that are easy to handle and handle. In particular, when applied to an alkyne compound as an unsaturated hydrocarbon compound, the degree of reduction can be controlled by reacting with a diboronic acid ester compound or a boric acid ester compound. In addition, organic boron compounds such as diboron alkene compounds and diboron alkene compounds obtained as a result of reduction of unsaturated hydrocarbon compounds by such a reduction method are used in organic synthesis reactions of a wide variety of functional materials. It is something. The present inventors have completed the present invention based on these findings.
[0015] すなわち、 本発明は、 不飽和炭化水素化合物の還元方法であって、 反応溶 媒中、 アルカリ金属を分散溶媒に分散させた分散体の存在下で、 [0015] That is, the present invention relates to a method for reducing an unsaturated hydrocarbon compound, which comprises: a reaction solvent containing an alkali metal dispersed in a dispersion solvent;
_般式 I3 _ General formula I 3
〔ここで、 一般式 中、 及び は、 それぞれ独立的に、 水素原子、 アルカリ 金属と反応しない置換基を有していてもよい脂肪族炭化水素基、 脂環式炭化 水素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環基であり 、 と とは互いに結合して環を形成していてもよい〕 に示す不飽和炭化水 素化合物であるアルキン化合物と、 [Wherein, and are each independently a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent that does not react with an alkali metal, an alicyclic hydrocarbon group, and an alicyclic heterocyclic group. A ring group, an aromatic hydrocarbon group, or an aromatic heterocyclic group, and may be bonded to each other to form a ring], and an alkyne compound that is an unsaturated hydrocarbon compound,
—般式 II3 — General formula II 3
[化 2] [Chemical 2]
〔ここで、 一般式 II3中、 [^、 [^、
は、 それぞれ独立的に、 アルカリ 金属と反応しない置換基を有していてもよい脂肪族炭化水素基、 脂環式炭化 水素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環基であり
〇 2020/175631 6 卩(:171? 2020 /008069 [Wherein, in the general formula II 3 , [^, [^, Are each independently an aliphatic hydrocarbon group which may have a substituent that does not react with an alkali metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or an aromatic group. Is a heterocyclic group 〇 2020/175631 6 卩 (:171? 2020 /008069
、 と とは互いに結合して環を形成していてもよく、 と とは互いに結 合して環を形成していてもよい〕 に示すジボロン酸エステル化合物とを、 反 応させることにより、 , And may be bonded to each other to form a ring, and and may be bonded to each other to form a ring] by reacting a diboronic acid ester compound shown in
—般式 III3 — General formula III 3
[化 3] [Chemical 3]
〔ここで、 一般式 III3中、 及び は、 一般式 の 及び と同様であり、[Wherein, in the general formula III 3 , and are the same as and in the general formula,
3、 1^、
一般式 1 の(^、 [^、
に示すジ ホウ素化アルカン化合物を生成して不飽和炭化水素化合物を還元する、 点に ある。 3 , 1^, (^, [^, in general formula 1 The point is to reduce the unsaturated hydrocarbon compound by generating the diboronated alkane compound shown in.
[0016] 本構成によれば、 不飽和炭化水素化合物であるアルキン化合物を、 アルカ ン化合物までの効率的に還元する不飽和炭化水素化合物の還元方法を提供す ることができる。 本構成によれば、 アルカリ金属を分散溶媒に分散させた分 散体を使用することにより、 温和な条件下で、 不飽和炭化水素化合物を還元 できる。 そのため、 煩雑な温度管理や安全管理等を必要とせず、 また、 高価 な試薬類や取り扱いに注意を要する試薬類を必要としない。 したがって、 入 手及び取り扱い容易な試薬類を使用して、 少ない工程数で簡便かつ短時間に 不飽和炭化水素化合物を安価かつ効率的に還元できることから、 経済的かつ 工業的にも非常に有利である。 アルカリ金属、 特には、 ナトリウム等は、 地 球上に極めて広く分布している金属であることから、 本構成の還元方法はサ ステナビリティにも優れた方法である。 更に、 本構成の還元方法により不飽 和炭化水素化合物の還元の結果として得られるジホウ素アルカン化合物等の 有機ホウ素化合物は、 多種多様な機能性材料の有機合成反応等に使用される ものである。 したがって、 本構成の還元方法は、 天然物全合成や、 医農薬、 及び、 液晶や有機 £!_等の電子材料、 並びに、 それらの中間体等の多種多様な
〇 2020/175631 7 卩(:171? 2020 /008069 [0016] According to this configuration, it is possible to provide a method for reducing an unsaturated hydrocarbon compound that efficiently reduces an alkyne compound that is an unsaturated hydrocarbon compound to an alkane compound. According to this configuration, the unsaturated hydrocarbon compound can be reduced under mild conditions by using the dispersion in which the alkali metal is dispersed in the dispersion solvent. Therefore, it does not require complicated temperature control or safety control, and does not require expensive reagents or reagents that require careful handling. Therefore, unsaturated hydrocarbon compounds can be reduced inexpensively and efficiently in a short time with a small number of steps using reagents that are easy to obtain and handle, which is very economically and industrially advantageous. is there. Alkali metals, especially sodium, are metals that are extremely widely distributed on the globe, so the reduction method of this configuration is also a method with excellent sustainability. Furthermore, organoboron compounds such as diboron alkane compounds obtained as a result of reduction of unsaturated hydrocarbon compounds by the reduction method of the present construction are used in organic synthesis reactions of a wide variety of functional materials. .. Therefore, the reduction method of this configuration can be applied to a wide variety of natural products such as total synthesis, medical and agricultural chemicals, electronic materials such as liquid crystals and organic compounds, and intermediates thereof. 〇 2020/175631 7 卩 (:171? 2020 /008069
機能性材料の有機合成反応等に利用することができる。 It can be used for organic synthesis reaction of functional materials.
[0017] 他の特徴構成は、 反応溶媒中、 アルカリ金属を分散溶媒に分散させた分散 体の存在下で、 [0017] Another characteristic configuration is that in the presence of a dispersion prepared by dispersing an alkali metal in a dispersion solvent in a reaction solvent,
_般式 _ General formula
〔ここで、 一般式 中、
それぞれ独立的に、 水素原子、 ナトリウ ムと反応しない置換基を有していてもよい脂肪族炭化水素基、 脂環式炭化水 素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環基であり、 bと とは互いに結合して環を形成していてもよい〕 に示す不飽和炭化水素化 合物であるアルキン化合物と、 [Where, in the general formula, Each independently, a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent that does not react with sodium, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or An aromatic heterocyclic group, and b and may combine with each other to form a ring], an alkyne compound that is an unsaturated hydrocarbon compound,
一般式 1 General formula 1
[化 5] [Chemical 5]
〔ここで、 一般式 1 中、 (¾ (¾■及び は、 それぞれ独立的に、 アルカリ金 属と反応しない置換基を有していてもよい脂肪族炭化水素基、 脂環式炭化水 素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環基であり、 とは互いに結合して環を形成していてもよい〕 に示すホウ酸エステル化 合物とを、 反応させることにより、 [Here, in the general formula 1, (¾ (¾ ■ Oyobi are each independently of the alkali metals and does not react with an aliphatic substituted hydrocarbon group, an alicyclic hydrocarbon group An alicyclic heterocyclic group, an aromatic hydrocarbon group, or an aromatic heterocyclic group, and may be bonded to each other to form a ring]. By reacting,
一般式 11
\¥0 2020/175631 8 卩(:171? 2020 /008069 General formula 11 \¥0 2020/175631 8 卩 (: 171? 2020 /008069
[化 6] [Chemical 6]
は、 一般式 11の ■及び と同様である〕 に示すジホウ素化アルケ ン化合物を生成して不飽和炭化水素化合物を還元する、 点にある。 Is of the general formula 11 ■ Oyobi and generates a diboric fluorinated alkenyl emissions compounds shown in the a] similar reducing unsaturated hydrocarbon compound, in a point.
[0018] 本構成によれば、 不飽和炭化水素化合物であるアルキン化合物を、 アルケ ン化合物に効率的に還元する不飽和炭化水素化合物の還元方法を提供するこ とができる。 本構成によれば、 アルカリ金属を分散溶媒に分散させた分散体 を使用することにより、 温和な条件下で、 不飽和炭化水素化合物を還元でき る。 そのため、 煩雑な温度管理や安全管理等を必要とせず、 また、 高価な試 薬類や取り扱いに注意を要する試薬類を必要としない。 したがって、 入手及 び取り扱い容易な試薬類を使用して、 少ない工程数で簡便かつ短時間に不飽 和炭化水素化合物を安価かつ効率的に還元できることから、 経済的かつ工業 的にも非常に有利である。 アルカリ金属、 特には、 ナトリウム等は、 地球上 に極めて広く分布している金属であることから、 本構成の還元方法はサステ ナビリティにも優れた方法である。 更に、 本構成の還元方法により不飽和炭 化水素化合物の還元の結果として得られるジホウ素アルケン化合物等の有機 ホウ素化合物は、 多種多様な機能性材料の有機合成反応等に使用されるもの である。 したがって、 本構成の還元方法は、 天然物全合成や、 医農薬、 及び 、 液晶や有機 £!_等の電子材料、 並びに、 それらの中間体等の多種多様な機能 性材料の有機合成反応等に利用することができる。 [0018] According to this configuration, it is possible to provide a method for reducing an unsaturated hydrocarbon compound that efficiently reduces an alkyne compound that is an unsaturated hydrocarbon compound to an alkene compound. According to this configuration, the unsaturated hydrocarbon compound can be reduced under mild conditions by using the dispersion in which the alkali metal is dispersed in the dispersion solvent. Therefore, complicated temperature control and safety control are not required, and expensive reagents and reagents that require careful handling are not required. Therefore, by using reagents that are easy to obtain and handle, the unsaturated hydrocarbon compound can be reduced inexpensively and efficiently in a small number of steps in a short time, which is very economical and industrially advantageous. Is. Alkali metals, especially sodium, are metals that are extremely widely distributed on the earth, so the reduction method of this configuration is also excellent in sustainability. Furthermore, the organic boron compounds such as diboron alkene compounds obtained as a result of the reduction of unsaturated hydrocarbon compounds by the reduction method of the present constitution are used in the organic synthesis reaction of a wide variety of functional materials. .. Therefore, the reduction method of this configuration is used for the total synthesis of natural products, organic and pharmaceutical compounds, electronic materials such as liquid crystals and organic compounds, and organic synthesis reactions of various functional materials such as intermediates thereof. Can be used for.
[0019] 他の特徴構成は、 反応溶媒中、 アルカリ金属を分散溶媒に分散させた分散 体の存在下で、 [0019] Another characteristic configuration is that in the presence of a dispersion prepared by dispersing an alkali metal in a dispersion solvent in a reaction solvent,
_般式 I。
\¥0 2020/175631 9 卩(:171? 2020 /008069 _ General formula I. \¥0 2020/175631 9 卩 (: 171? 2020 /008069
[化 7] [Chemical 7]
〔ここで、 一般式 I。中、 (^、 、
は、 それぞれ独立的に、 水素原子 アルカリ金属と反応しない置換基を有していてもよい脂肪族炭化水素基、 月旨 環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環 基であり、
して環を形成していてもよく、 (^と 3。又は とは互いに結合して環を形成していてもよく、
とは互いに結合 して環を形成していてもよく、
と とは互いに結合して環を形成していて もよい〕 に示す不飽和炭化水素化合物であるアルケン化合物と、 [Where General Formula I. Medium, (^,, Are each independently a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent that does not react with an alkali metal, a cyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, Or an aromatic heterocyclic group, To form a ring, and (^ and 3. or may be bonded to each other to form a ring, And may combine with each other to form a ring, And may be bonded to each other to form a ring], and an alkene compound which is an unsaturated hydrocarbon compound,
—般式 II。 — General formula II.
#-〇一巳 #-〇ichi
〔ここで、 一般式 II。中、 、 (¾ 及び は、 それぞれ独立的に、 アルカリ金 属と反応しない置換基を有していてもよい脂肪族炭化水素基、 脂環式炭化水 素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環基であり、 0。と[^。とは互いに結合して環を形成していてもよい〕 に示すホウ酸エステル化 合物とを、 反応させることにより、 [Where General Formula II. Wherein, (and each independently, an aliphatic hydrocarbon group which may have a substituent that does not react with an alkali metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic group A group of a hydrocarbon group or an aromatic heterocyclic group, wherein 0. and [^. may combine with each other to form a ring] with a boric acid ester compound Due to
—般式 III。
\¥02020/175631 10 卩(:17 2020/008069 — General formula III. \¥02020/175631 10 boxes (: 17 2020/008069
[化 9] [Chemical 9]
〔ここで、 一般式 III。中、 1^、 、
一般式 1。の(^、 、
。と同様であり、 及び は、 一般式 11。の[^及び と同様である〕 に示す ジホウ素化アルカン化合物を生成して不飽和炭化水素化合物を還元する、 点 にある。 [Where General Formula III. Medium, 1^,, General formula 1. Of (^,, .. Is the same as, and and is the general formula 11. Of [similar to ^ and] to generate a diboronated alkane compound and reduce an unsaturated hydrocarbon compound.
[0020] 本構成によれば、 不飽和炭化水素化合物であるアルケン化合物を、 アルカ ン化合物に効率的に還元する不飽和炭化水素化合物の還元方法を提供するこ とができる。 本構成によれば、 アルカリ金属を分散溶媒に分散させた分散体 を使用することにより、 温和な条件下で、 不飽和炭化水素化合物を還元でき る。 そのため、 煩雑な温度管理や安全管理等を必要とせず、 また、 高価な試 薬類や取り扱いに注意を要する試薬類を必要としない。 したがって、 入手及 び取り扱い容易な試薬類を使用して、 少ない工程数で簡便かつ短時間に不飽 和炭化水素化合物を安価かつ効率的に還元できることから、 経済的かつ工業 的にも非常に有利である。 アルカリ金属、 特には、 ナトリウム等は、 地球上 に極めて広く分布している金属であることから、 本構成の還元方法はサステ ナビリティにも優れた方法である。 更に、 本構成の還元方法により不飽和炭 化水素化合物の還元の結果として得られるジホウ素アルカン化合物等の有機 ホウ素化合物は、 多種多様な機能性材料の有機合成反応等に使用されるもの である。 したがって、 本構成の還元方法は、 天然物全合成や、 医農薬、 及び 、 液晶や有機 £!_等の電子材料、 並びに、 それらの中間体等の多種多様な機能 性材料の有機合成反応等に利用することができる。 [0020] According to this configuration, it is possible to provide a method for reducing an unsaturated hydrocarbon compound that efficiently reduces an alkene compound that is an unsaturated hydrocarbon compound to an alkane compound. According to this configuration, the unsaturated hydrocarbon compound can be reduced under mild conditions by using the dispersion in which the alkali metal is dispersed in the dispersion solvent. Therefore, complicated temperature control and safety control are not required, and expensive reagents and reagents that require careful handling are not required. Therefore, by using reagents that are easy to obtain and handle, the unsaturated hydrocarbon compound can be reduced inexpensively and efficiently in a small number of steps in a short time, which is very economical and industrially advantageous. Is. Alkali metals, especially sodium, are metals that are extremely widely distributed on the earth, so the reduction method of this configuration is also excellent in sustainability. Furthermore, organoboron compounds such as diboron alkane compounds obtained as a result of the reduction of unsaturated hydrocarbon compounds by the reduction method of this configuration are used in organic synthesis reactions of a wide variety of functional materials. .. Therefore, the reduction method of this configuration is used for the total synthesis of natural products, organic and pharmaceutical compounds, electronic materials such as liquid crystals and organic compounds, and organic synthesis reactions of various functional materials such as intermediates thereof. Can be used for.
[0021 ] 他の特徴構成は、 前記アルカリ金属を分散溶媒に分散させた分散体の前記 不飽和炭化水素化合物に対するモル比は、 2以上 4以下である、 点にある。
〇 2020/175631 1 1 卩(:171? 2020 /008069 [0021] Another characteristic configuration is that the molar ratio of the dispersion obtained by dispersing the alkali metal in a dispersion solvent to the unsaturated hydrocarbon compound is 2 or more and 4 or less. 〇 2020/175631 1 1 卩 (: 171? 2020 /008069
[0022] 本構成によれば、 前記アルカリ金属を分散溶媒に分散させた分散体の使用 量の最適化を図ることにより、 不飽和炭化水素化合物を更に効率良く還元で きる。 [0022] According to this configuration, the unsaturated hydrocarbon compound can be reduced more efficiently by optimizing the amount of the dispersion in which the alkali metal is dispersed in the dispersion solvent.
図面の簡単な説明 Brief description of the drawings
[0023] [図 1]実施例 1 _ 1 (ジフエニルアセチレンの還元反応 (1) ) の合成条件及 び結果を要約する図である。 FIG. 1 is a diagram summarizing synthesis conditions and results of Example 1 — 1 (reduction reaction of diphenylacetylene (1)).
[図 2]実施例 1 - 2 (ビス (4 -メ トキシフエニル) アセチレンの還元反応 ( 1 ) ) の合成条件を要約する図である。 FIG. 2 is a diagram summarizing synthesis conditions of Example 1-2 (reduction reaction of bis(4-methoxyphenyl)acetylene (1)).
[図 3]実施例 1 _ 1 3 (ジフエニルアセチレンの還元反応 (2) ) の合成条件 を要約する図である。 FIG. 3 is a diagram summarizing synthesis conditions of Example 1 — 1 3 (reduction reaction of diphenylacetylene (2)).
[図 4]実施例 1 _ 1 4 (ジフエニルアセチレンの還元反応 (3) ) の合成条件 を要約する図である。 FIG. 4 is a diagram summarizing synthesis conditions of Example 1 — 14 (reduction reaction of diphenylacetylene (3)).
[図 5]実施例 2 _ 1 (ジフエニルアセチレンの還元反応 (4) ) の合成条件及 び結果を要約する図である。 FIG. 5 is a diagram summarizing synthesis conditions and results of Example 2 — 1 (reduction reaction of diphenylacetylene (4)).
[図 6]実施例 2— 2 (ジフエニルアセチレンの還元反応 (5) ) の合成条件を 要約する図である。 FIG. 6 is a diagram summarizing the synthesis conditions of Example 2-2 (reduction reaction of diphenylacetylene (5)).
[図 7]実施例 2— 9 (ジフエニルアセチレンの還元反応 (6) ) の合成条件を 要約する図である。 FIG. 7 is a diagram summarizing synthesis conditions of Example 2-9 (reduction reaction of diphenylacetylene (6)).
[図 8]実施例 2 _ 1 6 (1 -フエニル-·! -ヘキシンの還元反応) の合成条件を要 約する図である。 FIG. 8 is a diagram outlining the synthesis conditions for Example 2 — 16 (reduction reaction of 1-phenyl-...!-hexyne).
[図 9]実施例 3 _ 1 (〇_ -スチルベンの還元反応) の合成条件及び結果を要約 する図である。 FIG. 9 is a diagram summarizing synthesis conditions and results of Example 3 — 1 (reduction reaction of _ — stilbene).
[図 1 0]実施例 3— 2 ( 3 -4 -メ トキシスチルベンの還元反応) の合成条件 を要約する図である。 FIG. 10 is a diagram summarizing the synthesis conditions of Example 3-2 (reduction reaction of 3 −4 -methoxystilbene).
[図 1 1]実施例 3 _ 1 8 (スチルベン (異性体混合物) の還元反応 (2) ) の 合成条件を要約する図である。 FIG. 11 is a diagram summarizing the synthesis conditions for Example 3 — 18 (stilbene (isomer mixture) reduction reaction (2) ).
[図 12]実施例 4 (スチレンの還元反応) の合成条件及び結果を要約する図で ある。
〇 2020/175631 12 卩(:171? 2020 /008069 FIG. 12 is a diagram summarizing synthesis conditions and results of Example 4 (styrene reduction reaction). 〇 2020/175631 12 卩 (:171? 2020 /008069
[図 13]実施例 5 (フエナントレンの還元反応) の合成条件及び結果を要約す る図である。 FIG. 13 is a diagram summarizing synthesis conditions and results of Example 5 (reduction reaction of phenanthrene).
[図 14]実施例 6 (4 -メ トキシフエニルアレンの還元反応) の合成条件を要約 する図である。 FIG. 14 is a diagram summarizing the synthesis conditions of Example 6 (reduction reaction of 4-methoxyphenylarene).
発明を実施するための形態 MODE FOR CARRYING OUT THE INVENTION
[0024] 以下、 本発明の実施形態に係る不飽和炭化水素化合物の還元方法について 詳細に説明する。 ただし、 本発明は、 後述する実施形態に限定されるもので はない。 [0024] Hereinafter, the method for reducing an unsaturated hydrocarbon compound according to the embodiment of the present invention will be described in detail. However, the present invention is not limited to the embodiments described below.
[0025] 〔1〕 不飽和炭化水素化合物の還元方法ーアルキン化合物のアルカン化合物 への還元 [0025] [1] Reduction method of unsaturated hydrocarbon compound-reduction of alkyne compound to alkane compound
本実施形態に係る不飽和炭化水素化合物の還元方法は、 分子中に 1以上の炭 素間三重結合を含むアルキン化合物において、 炭素間三重結合を一重結合に 変換し、 対応のアルカン化合物へ還元する方法を含む。 The method for reducing an unsaturated hydrocarbon compound according to the present embodiment is an alkyne compound having one or more carbon-carbon triple bonds in the molecule, converting the carbon-carbon triple bond into a single bond, and reducing it to the corresponding alkane compound. Including the method.
[0026] 詳細には、 反応溶媒中、 アルカリ金属を分散溶媒に分散させた分散体の存 在下で、 一般式 に示す不飽和炭化水素化合物であるアルキン化合物と、 一般 式 114こ示すジボロン酸エステル化合物とを、 反応させることにより、 前記不 飽和炭化水素化合物を還元する工程を含むものである。 [0026] Specifically, in the presence of a dispersion prepared by dispersing an alkali metal in a dispersion solvent in a reaction solvent, an alkyne compound which is an unsaturated hydrocarbon compound represented by the general formula and a diboronic acid ester represented by the general formula 114 It includes a step of reducing the unsaturated hydrocarbon compound by reacting with a compound.
[0027] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 還元の対象 となる不飽和炭化水素化合物としては、 分子中に 1以上の炭素間三重結合を含 むアルキン化合物を挙げることができる。 アルキン化合物は、 炭素間三重結 合を構成する 2つの炭素原子の少なくとも一方が水素原子と結合している末端 アルキン化合物であっても、 双方の炭素原子が炭素間三重結合を形成する炭 素原子との結合に加えて、 水素原子以外の基と結合している内部アルキン化 合物であってもよい。 [0027] In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, examples of the unsaturated hydrocarbon compound to be reduced include an alkyne compound containing one or more carbon-carbon triple bonds in the molecule. it can. An alkyne compound is a terminal alkyne compound in which at least one of two carbon atoms forming a carbon-carbon triple bond is bonded to a hydrogen atom, but both carbon atoms form a carbon atom forming a carbon-carbon triple bond. In addition to the bond with, it may be an internal alkyne compound bonded to a group other than a hydrogen atom.
[0028] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 還元の対象 となるアルキン化合物を示す一般式 は下記に示すとおりである。
\¥0 2020/175631 13 卩(:17 2020 /008069 [0028] In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, a general formula showing an alkyne compound to be reduced is as shown below. \¥0 2020/175631 13 卩 (: 17 2020 /008069
[化 10] _(: º〇— ここで、 一般式 I3に示すアルキン化物において、 及び は、 それぞれ独立 的に、 水素原子、 アルキル金属と反応しない置換基を有していてもよい脂肪 族炭化水素基、 脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 芳 香族複素環基、 ハロゲン原子、 アルコキシ基、 シクロアルコキシ基、 アリー ルオキシ基、 アラルキルオキシ基、 脂環式複素環オキシ基、 芳香族複素環才 キシ基、 アルキルチオ基、 シクロアルキルチオ基、 アリールチオ基、 アラル キルチオ基は、 脂環式複素環チオ基、 芳香族複素環チオ基、 アルキルアミノ 基、 シクロアルキルアミノ基、 アリールアミノ基、 アラルキルアミノ基、 月旨 環式複素環アミノ基、 芳香族複素環アミノ基、 又は、 シリル基である。 アル カリ金属と反応性を有する置換基を有すると、 当該置換基とナトリウムを分 散溶媒に分散させた分散体が反応し、 副反応を誘発するため好ましくない。 したがって、 アルカリ金属と反応性を有する置換基を有するアルキン化合物 を還元の対象とする場合には、 当該置換基を適切な保護基等で保護すること が必要となる。 [Chemical Formula 10] _(: º 〇 — Here, in the alkyne compound represented by the general formula I 3 , and are each independently a hydrogen atom or an aliphatic group which may have a substituent that does not react with an alkyl metal. Hydrocarbon group, alicyclic hydrocarbon group, alicyclic heterocyclic group, aromatic hydrocarbon group, aromatic heterocyclic group, halogen atom, alkoxy group, cycloalkoxy group, aryloxy group, aralkyloxy group, fat Cyclic heterocyclic oxy group, aromatic heterocyclic oxy group, alkylthio group, cycloalkylthio group, arylthio group, aralkylthio group, alicyclic heterocyclic thio group, aromatic heterocyclic thio group, alkylamino group, cyclo An alkylamino group, an arylamino group, an aralkylamino group, a moon heterocyclic heterocyclic amino group, an aromatic heterocyclic amino group, or a silyl group, which has a substituent reactive with an alkali metal, This is not preferable because a dispersion in which a substituent and sodium are dispersed in a dispersion solvent reacts with each other to induce a side reaction, and therefore, when an alkyne compound having a substituent reactive with an alkali metal is used as a reduction target. Requires that the substituent be protected with an appropriate protecting group or the like.
[0029] 脂肪族炭化水素基は、 直鎖及び分枝の別を問わず、 飽和及び不飽和の別も 問わない。 また、 その鎖長についても特に制限はない。 置換基を有する場合 、 当該置換基は、 アルカリ金属と反応しないものである限り特に制限はない 。 また、 置換基の数及び導入位置についても特に制限はない。 脂肪族炭化水 素基としては、 これらに限定するものではないが、 好ましくは炭素原子数 1〜 20個、 特に好ましくは炭素原子数 3〜 20個のアルキル基、 アルケニル基、 アル キニル基が例示される。 したがって、 分子内に二以上の炭素間三重結合を含 む不飽和炭化水素化合物も、 本実施形態に係る不飽和炭化水素化合物の還元 方法の還元の対象とすることができる。 [0029] The aliphatic hydrocarbon group may be linear or branched, or saturated or unsaturated. The chain length is also not particularly limited. When it has a substituent, the substituent is not particularly limited as long as it does not react with an alkali metal. Further, there is no particular limitation on the number of substituents and the introduction position. Examples of the aliphatic hydrocarbon group include, but are not limited to, preferably an alkyl group having 1 to 20 carbon atoms, particularly preferably an alkyl group having 3 to 20 carbon atoms, an alkenyl group, and an alkynyl group. To be done. Therefore, an unsaturated hydrocarbon compound containing two or more carbon-carbon triple bonds in the molecule can also be a target of reduction in the method for reducing an unsaturated hydrocarbon compound according to this embodiment.
[0030] 脂肪族炭化水素基は、 具体的には、 アルキル基としては、 メチル基、 エチ ル基、 プロピル基、 イソプロピル基、 n -ブチル基、 イソプチル基、 -ブチ
〇 2020/175631 14 卩(:171? 2020 /008069 [0030] The aliphatic hydrocarbon group includes, specifically, as an alkyl group, a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, an isoptyl group, and a -butyl group. 〇 2020/175631 14 卩(:171? 2020/008069
ル基、 1 -ブチル基、 ペンチル基、 イソペンチル基、 ネオペンチル基、 -ぺ ンチル基、
ペンチル基、 2 -メチルブチル基、 1 -エチルプロピル基、 2 -エチ ルプロピル基、 ヘキシル基、 イソヘキシル基、 ネオヘキシル基、 トヘキシ ル基、 2, 2 -ジメチルプチル基、 2 -メチルペンチル基、 3 -メチルペンチル基、 1 -エチルブチル基、 2 -エチルブチル基、 トプロピルプロピル基、 ヘプチル基 、 イソへプチル基、
ヘプチル基、 トヘプチル基、 2, 2 -ジメチルペンチル基 、 3, 3 -ジメチルペンチル基、 1 -メチルヘキシル基、 2 -メチルヘキシル基、 3- メチルヘキシル基、 4 -メチルヘキシル基、 1 -エチルペンチル基、 2 -エチルべ ンチル基、 3 -エチルペンチル基、 1 -プロピルプチル基、 2 -プロピルプチル基 、 n -オクチル基、 イソオクチル基、 1;-オクチル基、 ネオオクチル基、 2, 2 -ジ メチルヘキシル基、 3, 3 -ジメチルヘキシル基、 4, 4 -ジメチルヘキシル基、 1 - メチルへプチル基、 2 -メチルへプチル基、 3 -メチルへプチル基、 4 -メチルへ プチル基、 5 -メチルへプチル基、 1 -エチルヘキシル基、 2 -エチルヘキシル基 、 3 -エチルヘキシル基、 4 -エチルヘキシル基、 1 -プロピルペンチル基、 2 -プ ロピルペンチル基、 3 -プロピルペンチル基、 n -ノニル基、 イソノニル基、 卜 ノニル基、 1 -メチルオクチル基、 2 -メチルオクチル基、 3 -メチルオクチル基 、 4 -メチルオクチル基、 5 -メチルオクチル基、 6 -メチルオクチル基、 デシ ル基、 イソデシル基、 トデシル基、 1 -メチルノニル基、 2 -メチルノニル基、 3 -メチルノニル基、 4 -メチルノニル基、 5 -メチルノニル基、 6 -メチルノニル基 、 7 -メチルノニル基等が挙げられるが、 これらに限定するものではない。 ア ルケニル基としては、 エテニル基、 プロべニル基、 ブテニル基、 ペンテニル 基、 ヘキセニル基、 ヘプテニル基、 オクテニル基等が挙げられるが、 これら に限定するものではない。 アルキニル基としては、 エチニル基、 プロピニル 基、 プチニル基、 ペンチニル基、 ヘプチニル基、 オクチニル基等が挙げられ るが、 これらに限定するものではない。 Group, 1-butyl group, pentyl group, isopentyl group, neopentyl group, -pentyl group, Pentyl group, 2-methylbutyl group, 1-ethylpropyl group, 2-ethylpropyl group, hexyl group, isohexyl group, neohexyl group, tohexyl group, 2,2-dimethylputyl group, 2-methylpentyl group, 3-methyl group Pentyl group, 1-ethylbutyl group, 2-ethylbutyl group, toppropylpropyl group, heptyl group, isoheptyl group, Heptyl group, toheptyl group, 2,2-dimethylpentyl group, 3,3-dimethylpentyl group, 1-methylhexyl group, 2-methylhexyl group, 3-methylhexyl group, 4-methylhexyl group, 1-ethylpentyl group Group, 2-ethylpentyl group, 3-ethylpentyl group, 1-propylputyl group, 2-propylputyl group, n-octyl group, isooctyl group, 1;-octyl group, neooctyl group, 2,2-dimethyl group Hexyl group, 3,3-dimethylhexyl group, 4,4-dimethylhexyl group, 1-methylheptyl group, 2-methylheptyl group, 3-methylheptyl group, 4-methylheptyl group, 5-methyl group Heptyl group, 1-ethylhexyl group, 2-ethylhexyl group, 3-ethylhexyl group, 4-ethylhexyl group, 1-propylpentyl group, 2-propylpentyl group, 3-propylpentyl group, n-nonyl group, isononyl group, Nonyl group, 1-methyloctyl group, 2-methyloctyl group, 3-methyloctyl group, 4-methyloctyl group, 5-methyloctyl group, 6-methyloctyl group, decyl group, isodecyl group, todecyl group, Examples thereof include 1-methylnonyl group, 2-methylnonyl group, 3-methylnonyl group, 4-methylnonyl group, 5-methylnonyl group, 6-methylnonyl group and 7-methylnonyl group, but are not limited thereto. Examples of the alkenyl group include, but are not limited to, an ethenyl group, a probenyl group, a butenyl group, a pentenyl group, a hexenyl group, a heptenyl group and an octenyl group. Examples of the alkynyl group include, but are not limited to, an ethynyl group, a propynyl group, a putinyl group, a pentynyl group, a heptynyl group and an octynyl group.
[0031 ] 脂肪族炭化水素基は、 更に、 置換基を有していてもよい。 置換基は、 1個 又は複数個を有していてよく、 複数個の置換基を有する場合には、 互いに同 —又は異なっていてもよい。 置換基としては、 置換基を有してもよい脂肪族
〇 2020/175631 15 卩(:171? 2020 /008069 [0031] The aliphatic hydrocarbon group may further have a substituent. The substituent may have one or a plurality of substituents, and when having a plurality of substituents, they may be the same or different from each other. As the substituent, an aliphatic which may have a substituent 〇 2020/175631 15 卩 (:171? 2020 /008069
炭化水素基、 脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 芳香 族複素環基、 ハロゲン原子、 アルコキシ基、 シクロアルコキシ基、 アリール オキシ基、 アラルキルオキシ基、 脂環式複素環オキシ基、 芳香族複素環オキ シ基、 アルキルチオ基、 シクロアルキルチオ基、 アリールチオ基、 アラルキ ルチオ基は、 脂環式複素環チオ基、 芳香族複素環チオ基、 アルキルアミノ基 、 シクロアルキルアミノ基、 アリールアミノ基、 アラルキルアミノ基、 脂環 式複素環アミノ基、 芳香族複素環アミノ基、 シリル基等が例示されるが、 こ れらに限定するものではない。 なお、 脂肪族炭化水素基は上記で示されるも のと同様なものを、 脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基 、 芳香族複素環基、 ハロゲン原子、 アルコキシ基、 シクロアルコキシ基、 ア リールオキシ基、 アラルキルオキシ基、 脂環式複素環オキシ基、 芳香族複素 環オキシ基、 アルキルチオ基、 シクロアルキルチオ基、 アリールチオ基、 ア ラルキルチオ基は、 脂環式複素環チオ基、 芳香族複素環チオ基、 アルキルア ミノ基、 シクロアルキルアミノ基、 アリールアミノ基、 アラルキルアミノ基 、 脂環式複素環アミノ基、 芳香族複素環アミノ基、 シリル基としては、 下記 で示されるものと同様なものが挙げられる。 Hydrocarbon group, alicyclic hydrocarbon group, alicyclic heterocyclic group, aromatic hydrocarbon group, aromatic heterocyclic group, halogen atom, alkoxy group, cycloalkoxy group, aryloxy group, aralkyloxy group, alicyclic group Formula heterocyclic oxy group, aromatic heterocyclic oxy group, alkylthio group, cycloalkylthio group, arylthio group, aralkylthio group, alicyclic heterocyclic thio group, aromatic heterocyclic thio group, alkylamino group, cycloalkyl Examples thereof include, but are not limited to, an amino group, an arylamino group, an aralkylamino group, an alicyclic heterocyclic amino group, an aromatic heterocyclic amino group, and a silyl group. The aliphatic hydrocarbon group is the same as the above-mentioned ones, such as an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, an aromatic heterocyclic group, a halogen atom, an alkoxy group. Group, cycloalkoxy group, aryloxy group, aralkyloxy group, alicyclic heterocyclic oxy group, aromatic heterocyclic oxy group, alkylthio group, cycloalkylthio group, arylthio group, aralkylthio group, alicyclic heterocyclic group Thio group, aromatic heterocyclic thio group, alkylamino group, cycloalkylamino group, arylamino group, aralkylamino group, alicyclic heterocyclic amino group, aromatic heterocyclic amino group, and silyl group are shown below. The same thing as what is mentioned is mentioned.
[0032] 脂環式炭化水素基は、 環構成原子間の結合は飽和及び不飽和の別は問わず 、 環員数についても特に制限はない。 また、 単環だけでなく、 縮合環やスピ 口環等の環集合を持つものも含まれる。 脂環式炭化水素基としては、 これら に制限するものではないが、 好ましくは炭素原子数 3〜 10個、 特に好ましくは 3〜 7個のシクロアルキル基、 好ましくは炭素原子数 4〜 10個、 特に好ましくは 4〜 7個のシクロアルケニル基、 若しくは、 シクロアルキニル基等が例示され る。 具体的には、 シクロアルキル基として、 シクロプロピル基、 シクロブチ ル基、 シクロペンチル基、 シクロヘキシル基、 シクロへプチル基、 シクロオ クチル基等が挙げられるが、 これらに限定するものではない。 シクロアルケ ニル基としては、 シクロプロべニル基、 シクロブテニル基、 シクロペンテニ ル基、 シクロヘキセニル基、 シクロヘプテニル基、 シクロオクテニル基等が 挙げられるが、 これらに限定するものではない。 また、 シクロアルキニル基
〇 2020/175631 16 卩(:171? 2020 /008069 [0032] In the alicyclic hydrocarbon group, the number of ring members is not particularly limited, regardless of whether the bond between ring-constituting atoms is saturated or unsaturated. Moreover, not only a single ring but also a ring having a ring assembly such as a condensed ring or a spit ring is included. The alicyclic hydrocarbon group is not limited to these, but preferably has 3 to 10 carbon atoms, particularly preferably 3 to 7 cycloalkyl groups, preferably 4 to 10 carbon atoms, Particularly preferred are 4 to 7 cycloalkenyl groups, cycloalkynyl groups and the like. Specific examples of the cycloalkyl group include, but are not limited to, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group. Examples of the cycloalkenyl group include, but are not limited to, a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group, a cycloheptenyl group, a cyclooctenyl group and the like. In addition, a cycloalkynyl group 〇2020/175631 16 卩(:171? 2020/008069
としては、 シクロオクチニル基等が挙げられるが、 これらに限定するもので はない。 Examples thereof include, but are not limited to, cyclooctynyl group and the like.
[0033] 脂環式炭化水素基は、 置換基を有していてもよい。 置換基は、 1個又は複数 個を有していてよく、 複数個の置換基を有する場合には、 互いに同一又は異 なっていてもよい。 また、 置換基の位置についても特に制限はない。 置換基 は、 脂肪族炭化水素基の置換基として例示したものと、 同様のものが挙げら れる。 [0033] The alicyclic hydrocarbon group may have a substituent. The substituents may have one or a plurality of substituents, and when they have a plurality of substituents, they may be the same or different from each other. The position of the substituent is also not particularly limited. Examples of the substituent are the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
[0034] 脂環式複素環基は、 環構成原子として 1個又は複数個のヘテロ原子を有する 非芳香族複素環基である。 単環だけでなく、 縮合環やスピロ環等の環集合を 持つものも含まれる。 環構成原子間の結合は飽和及び不飽和の別は問わず、 環員数についても特に制限はない。 ヘテロ原子は、 環構成原子としてナトリ ウムと反応しないものである限り特に制限はない。 [0034] The alicyclic heterocyclic group is a non-aromatic heterocyclic group having one or more heteroatoms as ring-constituting atoms. Not only a single ring but also those having a ring assembly such as a condensed ring or a spiro ring are included. The bond between ring members may be saturated or unsaturated, and the number of ring members is not particularly limited. The heteroatom is not particularly limited as long as it does not react with sodium as a ring-constituting atom.
ヘテロ原子の数は特に制限はなく、 ヘテロ原子の位置についても制限はない 。 ヘテロ原子としては、 好ましくは、 酸素原子、 窒素原子、 硫黄原子等が例 示される。 例えば、 炭素原子数が、 好ましくは 2〜 7個、 特に好ましくは、 2〜 5個、 ヘテロ原子数が、 好ましくは 1〜 5個、 特に好ましくは 1〜 3個である脂環 式複素環基が挙げられる。 なお、 複数個のヘテロ原子を有する場合には、 同 —種類の原子であっても異なる種類の原子であってもよい。 脂環式複素環基 としては、 単環の四員環式のアゼチジニル基、 五員環式のピロリジニル基、 六員環式のピペリジル基、 ピぺラジニル基等の含窒素脂環式複素環基、 単環 の三員環式のオキシラニル基、 四員環式のオキセタニル基、 五員環式のテト ラヒドロフリル基、 六員環式のテトラヒドロピラニル基等の含酸素脂環式複 素環基、 単環の五員環式のテトラヒドロチオフエニル基等の含硫黄脂環式複 素環基、 単環の六員環式のモルホリニル基等の含窒素酸素脂環式複素環基、 単環の六員環式のチオモルホリニル基等の含窒素硫黄脂環式複素環基等が挙 げられるが、 これらに限定するものではない。 The number of heteroatoms is not particularly limited, and the position of heteroatoms is also not limited. Preferred examples of the hetero atom include an oxygen atom, a nitrogen atom, a sulfur atom and the like. For example, an alicyclic heterocyclic group having preferably 2 to 7 carbon atoms, particularly preferably 2 to 5 carbon atoms, and preferably 1 to 5 and particularly preferably 1 to 3 heteroatoms. Is mentioned. In addition, when it has a plurality of heteroatoms, it may be the same kind of atoms or different kinds of atoms. The alicyclic heterocyclic group includes a nitrogen-containing alicyclic heterocyclic group such as a monocyclic four-membered ring azetidinyl group, a five-membered ring pyrrolidinyl group, a six-membered ring piperidyl group, and a piperazinyl group. An oxygen-containing alicyclic compound cyclic group such as a monocyclic three-membered cyclic oxiranyl group, a four-membered cyclic oxetanyl group, a five-membered cyclic tetrahydrofuryl group, a six-membered tetrahydropyranyl group, Sulfur-containing alicyclic heterocyclic groups such as monocyclic five-membered tetrahydrothiophenyl groups, nitrogen-containing oxygen alicyclic heterocyclic groups such as monocyclic six-membered morpholinyl groups, monocyclic Examples thereof include nitrogen-containing sulfur alicyclic heterocyclic groups such as 6-membered thiomorpholinyl groups, but are not limited thereto.
[0035] 脂環式複素環は、 更に、 置換基を有していてもよい。 置換基は、 1個又は複 数個を有していてよく、 複数個の置換基を有する場合には、 互いに同一又は
〇 2020/175631 17 卩(:171? 2020 /008069 [0035] The alicyclic heterocycle may further have a substituent. The substituents may have one or a plurality of substituents, and when they have a plurality of substituents, they may be the same or different. 〇 2020/175631 17 卩(: 171? 2020/008069
異なっていてもよい。 また、 置換基の位置についても特に制限はない。 置換 基は、 脂肪族炭化水素基の置換基として例示したものと、 同様のものが挙げ られる。 It may be different. The position of the substituent is also not particularly limited. Examples of the substituent are the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
[0036] 芳香族炭化水素基は、 芳香環を有する限り特に制限はない。 単環だけでな く、 縮合環やスピロ環等の環集合を持つものも含まれる。 環員数についても 特に制限はない。 例えば、 炭素原子数が、 好ましくは 6〜 22個、 特に好ましく は、 6〜 14個である芳香族炭化水素基が挙げられる。 芳香族炭化水素基として は、 単環式の六員環フエニル基等、 二環式のナフチル基、 ペンタレニル基、 インデニル基、 アズレニル基等、 三環式のビフエニレニル基、 インダセニル 基、 アセナフチレニル基、 フルオレニル基、 フエナレニル基、 フエナントリ ル基、 アントリル基等、 四環式のフルオランテニル、 アセアントリレニル基 、 トリフエニレニル基、 ピレニル基、 ナフタセニル基等、 五環式のペリ レニ ル基、 テトラフエニレニル等、 六環式のペンタセニル基等、 七環式のルビセ ニル基、 コロネニル基、 ヘプタセニル基等が挙げられるが、 これらに限定す るものではない。 特に好ましくは、 フエニル基である。 [0036] The aromatic hydrocarbon group is not particularly limited as long as it has an aromatic ring. Not only a single ring but also those having a ring assembly such as a condensed ring or a spiro ring are included. There is no particular limitation on the number of members. For example, an aromatic hydrocarbon group having preferably 6 to 22, and particularly preferably 6 to 14 carbon atoms can be mentioned. Aromatic hydrocarbon groups include monocyclic six-membered ring phenyl groups, etc., bicyclic naphthyl groups, pentalenyl groups, indenyl groups, azulenyl groups, etc., tricyclic biphenylenyl groups, indacenyl groups, acenaphthylenyl groups, fluorenyl groups. Group, phenalenyl group, phenanthryl group, anthryl group, etc., tetracyclic fluoranthenyl, aceanthrylenyl group, triphenylenyl group, pyrenyl group, naphthacenyl group, etc., pentacyclic perylenyl group, tetraphenylenyl group, etc. Examples include, but are not limited to, a hexacyclic pentacenyl group and the like, a heptcyclic rubicenyl group, a coronenyl group, a heptacenyl group, and the like. Particularly preferred is a phenyl group.
[0037] 芳香族炭化水素基は、 更に、 置換基を有していてもよい。 置換基は、 1個又 は複数個を有していてよく、 複数個の置換基を有する場合には、 互いに同一 又は異なっていてもよい。 また、 置換基の位置についても特に制限はない。 置換基は、 脂肪族炭化水素基の置換基として例示したものと、 同様のものが 挙げられる。 [0037] The aromatic hydrocarbon group may further have a substituent. The substituent may have one or a plurality of substituents, and when having a plurality of substituents, they may be the same or different from each other. The position of the substituent is also not particularly limited. Examples of the substituent are the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
[0038] 芳香族複素環基は、 環構成原子として 1個又は複数個のヘテロ原子を有する 芳香族複素環基である。 単環だけでなく、 縮合環やスピロ環等の環集合を持 つものも含まれる。 環員数についても特に制限はない。 ヘテロ原子は、 環構 成原子としてナトリウムと反応しないものである限り特に制限はない。 へテ 口原子の数は特に制限はなく、 ヘテロ原子の位置についても制限はない。 へ テロ原子としては、 好ましくは、 酸素原子、 窒素原子、 硫黄原子等が例示さ れる。 例えば、 炭素原子数が、 好ましくは 1〜 5個、 特に好ましくは、 3〜 5個 、 ヘテロ原子数が、 好ましくは 1〜 4個、 特に好ましくは 1〜 3個である芳香族
〇 2020/175631 18 卩(:171? 2020 /008069 [0038] The aromatic heterocyclic group is an aromatic heterocyclic group having one or more heteroatoms as ring-constituting atoms. Not only a single ring, but also those having a ring assembly such as a condensed ring or a spiro ring are included. The number of ring members is also not particularly limited. The heteroatom is not particularly limited as long as it does not react with sodium as a ring-constituting atom. The number of heteroatoms is not particularly limited, and the position of heteroatoms is also not limited. Preferred examples of the hetero atom include oxygen atom, nitrogen atom, sulfur atom and the like. For example, an aromatic compound having 1 to 5 carbon atoms, particularly preferably 3 to 5 carbon atoms, and preferably 1 to 4 heteroatoms, particularly preferably 1 to 3 heteroatoms. 〇 2020/175631 18 卩 (:171? 2020 /008069
複素環基が挙げられる。 なお、 複数個のヘテロ原子を有する場合には、 同一 種類の原子であっても異なる種類の原子であってもよい。 Heterocyclic groups may be mentioned. In addition, when it has a plurality of heteroatoms, the atoms may be the same or different.
[0039] 例えば、 単環式の芳香族複素環基としては、 五員環式のピロリル基、 ピラ ゾリル基、 ピリジル基、 イミダゾリル基等、 六員環式のピラジニル基、 ピリ ミジニル基、 ピリダジニル基等の含窒素芳香族複素環基、 五員環式のフリル 基等の含酸素芳香族複素環基、 五員環式のチェニル基等の含酸素芳香族複素 環基、 五員環式のオキサゾリル基、 イソオキサゾリル基、 フラザニル基等の 含窒素酸素芳香族複素環基、 五員環式のチアゾリル基、 イソチアゾリル基等 の含窒素硫黄芳香族複素環基等が挙げられるが、 これらに限定するものでは ない。 [0039] For example, examples of the monocyclic aromatic heterocyclic group include a 5-membered pyrrolyl group, a pyrazolyl group, a pyridyl group, an imidazolyl group, a 6-membered pyrazinyl group, a pyrimidinyl group, a pyridazinyl group. And other nitrogen-containing aromatic heterocyclic groups, five-membered furyl groups and other oxygen-containing aromatic heterocyclic groups, five-membered cyclic cenyl groups and other oxygen-containing aromatic heterocyclic groups, and five-membered oxazolyl groups Group, an isoxazolyl group, a nitrogen-containing oxygen aromatic heterocyclic group such as a flazanyl group, a five-membered thiazolyl group, a nitrogen-containing sulfur aromatic heterocyclic group such as an isothiazolyl group, and the like, but are not limited to these. Absent.
[0040] 多環式の芳香族複素環基としては、 二環式のインドリジニル基、 イソイン ドリル基、 インドリル基、 インダゾリル基、 プリニル基、 イソキノリル基、 キノリル基、 フタラジニル基、 ナフチリジニル基、 キノキサリニル基、 キナ ゾリニル基、 シンノリニル基等、 三環式のカルバゾリル基、 カルボリニル基 、 フェナトリジニル基、 アクリジニル基、 ペリミジニル基、 フェナントロリ ニル基、 フェナジニル基等の含窒素芳香族複素環基、 二環式のベンゾフラニ ル基、 イソベンゾフラニル基、 ベンゾピラニル基等の含酸素芳香族複素環基 、 二環式のベンゾチェニル基等、 三環式のチアントレニル基等の含硫黄芳香 族複素環基、 二環式のベンゾオキサゾリル基、 ベンゾイソオキサゾリル基等 の含窒素酸素芳香族複素環基、 二環式のベンゾチアゾリル基、 ベンゾイソチ アゾリル基、 三環式のフェノチアジニル基等の含窒素硫黄芳香族複素環基、 三環式のフェノキサチイニル基等の含酸素硫黄芳香族複素環基等が挙げられ るが、 これらに限定するものではない。 [0040] Examples of the polycyclic aromatic heterocyclic group include a bicyclic indolizinyl group, an isoindolyl group, an indolyl group, an indazolyl group, a purinyl group, an isoquinolyl group, a quinolyl group, a phthalazinyl group, a naphthyridinyl group, a quinoxalinyl group, Nitrogen-containing aromatic heterocyclic groups such as quinazolinyl groups, cinnolinyl groups, tricyclic carbazolyl groups, carborinyl groups, phenatridinyl groups, acridinyl groups, perimidinyl groups, phenanthrolinyl groups, phenazinyl groups, and bicyclic benzofuranyl groups. , Oxygen-containing aromatic heterocyclic groups such as isobenzofuranyl group, benzopyranyl group, sulfur-containing aromatic heterocyclic groups such as bicyclic benzocenyl group, tricyclic thianthrenyl group, and bicyclic benzoxazolyl Group, benzoisoxazolyl group and other nitrogen-containing oxygen aromatic heterocyclic groups, bicyclic benzothiazolyl group, benzoisothiazolyl group, tricyclic phenothiazinyl group and other nitrogen-containing sulfur aromatic heterocyclic groups, three Examples thereof include, but are not limited to, oxygen-containing sulfur aromatic heterocyclic groups such as cyclic phenoxathinyl groups.
[0041 ] 芳香族複素環基は、 更に、 置換基を有していてもよい。 置換基は、 1個又は 複数個を有していてよく、 複数個の置換基を有する場合には、 互いに同一又 は異なっていてもよい。 また、 置換基の位置についても特に制限はない。 置 換基は、 脂肪族炭化水素基の置換基として例示したものと、 同様のものが挙 げられる。
〇 2020/175631 19 卩(:171? 2020 /008069 [0041] The aromatic heterocyclic group may further have a substituent. The substituent may have one or a plurality of substituents, and when having a plurality of substituents, they may be the same or different from each other. The position of the substituent is also not particularly limited. Examples of the substituent include the same groups as those exemplified as the substituent of the aliphatic hydrocarbon group. 〇 2020/175631 19 卩 (:171? 2020 /008069
[0042] ハロゲン原子は、 フッ素原子、 塩素原子、 臭素原子、 ヨウ素原子等が例示 される。 [0042] Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
[0043] アルコキシ基は、 好ましくは炭素原子数 1〜 10個のアルコキシ基が例示され 、 具体的には、 メ トキシ基、 エトキシ基、 プロポキシ基、 ブトキシ基、 ペン チルオキシ基、 ヘキシルオキシ基等が挙げられるが、 これらに限定するもの ではない。 シクロアルコキシ基は、 好ましくは炭素原子数 3〜 10個のシクロブ ロポキシ基が例示され、 シクロブトキシ基、 シクロペンチルオキシ基、 シク ロヘキシルオキシ基が挙げられる。 アリールオキシ基は、 好ましくは炭素原 子数 6〜 20個のアリールオキシ基が例示され、 具体的には、 フエニルオキシ基 、 ナフチルオキシ基等が挙げられるが、 これらに限定するものではない。 ア ラルキルオキシ基は、 好ましくは炭素原子数 7〜 1 1個のアラルキルオキシ基が 例示され、 具体的には、 ベンジルオキシ基、 及び、 フエネチルオキシ基が挙 げられる。 脂環式複素環オキシ基、 及び、 芳香族複素環オキシ基は、 複素環 部として上記で示される脂環式複素環基及び芳香族複素環基が挙げられる。 また、 これらは、 更に、 置換基を有していてもよい。 置換基は、 1個又は複数 個を有していてよく、 複数個の置換基を有する場合には、 互いに同一又は異 なっていてもよい。 また、 置換基の位置についても特に制限はない。 置換基 は、 脂肪族炭化水素基の置換基として例示したものと、 同様のものが挙げら れる。 The alkoxy group is preferably an alkoxy group having 1 to 10 carbon atoms, and specific examples thereof include a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a pentyloxy group and a hexyloxy group. However, the present invention is not limited to these. The cycloalkoxy group is preferably a cyclobropoxy group having 3 to 10 carbon atoms, and examples thereof include a cyclobutoxy group, a cyclopentyloxy group and a cyclohexyloxy group. The aryloxy group is preferably an aryloxy group having 6 to 20 carbon atoms, and specific examples thereof include a phenyloxy group and a naphthyloxy group, but the aryloxy group is not limited thereto. The aralkyloxy group is preferably an aralkyloxy group having 7 to 11 carbon atoms, and specific examples thereof include a benzyloxy group and a phenethyloxy group. Examples of the alicyclic heterocyclic oxy group and the aromatic heterocyclic oxy group include the alicyclic heterocyclic group and aromatic heterocyclic group shown above as the heterocyclic moiety. In addition, these may further have a substituent. The substituents may have one or a plurality of substituents, and when they have a plurality of substituents, they may be the same or different from each other. The position of the substituent is also not particularly limited. Examples of the substituent are the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
[0044] アルキルチオ基は、 好ましくは炭素原子数 1〜 20個のアルキルチオ基が例示 され、 メチルチオ基、 エチルチオ基、 プロピルチオ基、 プチルチオ基、 ペン チルチオ基、 ヘキシルチオ基等が挙げられるが、 これらに限定するものでは ない。 シクロアルキルチオ基は、 炭素原子数 3〜 10個のシクロアルキルチオ 基が例示され、 具体的には、 シクロプロピルチオ基、 シクロブチルチオ基、 シクロペンチルチオ基、 シクロへキシルチオ基等が挙げられるが、 これらに 限定するものではない。 アリールチオ基は、 好ましくは炭素原子数 6〜 20個の アリールチオ基が例示され、 具体的には、 フエニルチオ基、 ナフチルチオ基 等が挙げられるが、 これらに限定するものではない。 アラルキルチオ基は、
〇 2020/175631 20 卩(:171? 2020 /008069 [0044] The alkylthio group is preferably an alkylthio group having 1 to 20 carbon atoms, and examples thereof include a methylthio group, an ethylthio group, a propylthio group, a pentylthio group, a pentylthio group, and a hexylthio group. Not something to do. Examples of the cycloalkylthio group include cycloalkylthio groups having 3 to 10 carbon atoms, and specific examples thereof include a cyclopropylthio group, a cyclobutylthio group, a cyclopentylthio group, and a cyclohexylthio group. It is not limited to. The arylthio group is preferably an arylthio group having 6 to 20 carbon atoms, and specific examples thereof include a phenylthio group and a naphthylthio group, but the arylthio group is not limited thereto. The aralkylthio group is 〇 2020/175631 20 卩 (:171? 2020 /008069
好ましくは炭素原子数 7〜 1 1個のアラルキルチオ基が例示され、 具体的には、 ベンジルチオ基、 フエネチルチオ基等が挙げられるが、 これらに限定するも のではない。 脂環式複素環チオ基、 及び、 芳香族複素環チオ基は、 複素環部 として上記で示される脂環式複素環基及び芳香族複素環基が挙げられる。 ま た、 これらは、 更に、 置換基を有していてもよい。 置換基は、 1個又は複数個 を有していてよく、 複数個の置換基を有する場合には、 互いに同一又は異な っていてもよい。 また、 置換基の位置についても特に制限はない。 置換基は 、 脂肪族炭化水素基の置換基として例示したものと、 同様のものが挙げられ る。 Preferable examples are aralkylthio groups having 7 to 11 carbon atoms, and specific examples thereof include a benzylthio group and a phenethylthio group, but the aralkylthio group is not limited thereto. Examples of the alicyclic heterocyclic thio group and the aromatic heterocyclic thio group include the alicyclic heterocyclic group and aromatic heterocyclic group represented by the above as the heterocyclic moiety. Moreover, these may further have a substituent. The substituents may have one or a plurality of substituents, and when they have a plurality of substituents, they may be the same or different from each other. The position of the substituent is also not particularly limited. Examples of the substituent include the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
[0045] シリル基は、 ケイ素上に·!〜 3個の脂肪族炭化水素基、 脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 芳香族複素環基等の置換基を有する一 価の基である。 脂肪族炭化水素基、 脂環式炭化水素基、 脂環式複素環基、 芳 香族炭化水素基、 芳香族複素環基等の置換基としては、 上記したものと同様 のものが挙げられる。 具体的には、 ジメチルシリル基、 ジフエニルシリル基 、 トリメチルシリル基、 トリエチルシリル基、 トリイソプロピルシリル基、 ジメチル- 1 -ブチルシリル基、 ジフエニル- 1 -ブチルシリル基等が挙げられる が、 これらに限定するものではない。 [0045] The silyl group is a substitution of, on the silicon, three or more aliphatic hydrocarbon groups, alicyclic hydrocarbon groups, alicyclic heterocyclic groups, aromatic hydrocarbon groups, aromatic heterocyclic groups, and the like. It is a monovalent group having a group. Substituents such as an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group and an aromatic heterocyclic group may be the same as those mentioned above. Specific examples thereof include, but are not limited to, a dimethylsilyl group, a diphenylsilyl group, a trimethylsilyl group, a triethylsilyl group, a triisopropylsilyl group, a dimethyl-1-butylsilyl group, and a diphenyl-1-butylsilyl group. ..
[0046] と とは、 同一の基であっても、 異なる基であってもよい。 [0046] may be the same group or different groups.
[0047] と とは、 互いに結合して環を形成していてもよい。 したがって、 炭素 間三重結合は、 環の一部を構成するものとできる と との結合で形成され る環は、 特に限定されるものではないが、 シクロオクチン環等のシクロアル キン環等を例示することができる。 [0047] and may be bonded to each other to form a ring. Therefore, the carbon-carbon triple bond is not particularly limited, and the ring formed by the bond that can form part of the ring is exemplified by cycloalkyne ring such as cyclooctyne ring. be able to.
[0048] 本実施形態に係る不飽和炭化水素化合物の還元方法の還元の対象となる不 飽和炭化水素化合物としては、 具体的には、 ジフエニルアセチレン、 フエニ ルアセチレン、 1 -フエニル- 1 -プロピン、 1 -フエニル- 1 -ブチン、 1 -フエニル- 1 -ペンチン、 1 -フエニル-·! -ヘキシン、 1 -フエニル- 2 - (トリメチルシリル) アセチレン、 1 -フエニル- 2 - (トリイソプロピルシリル) アセチレン、 ビス ( トリメチルシリル) アセチレン、 2 -フエニル- 1 -エチニルボロン酸ピナコラー
〇 2020/175631 21 卩(:171? 2020 /008069 [0048] The unsaturated hydrocarbon compound to be reduced in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment specifically includes diphenylacetylene, phenylacetylene, and 1-phenyl-1-propyne. , 1-phenyl-1-butyne, 1-phenyl-1-pentyne, 1-phenyl-!!-hexyne, 1-phenyl-2-(trimethylsilyl)acetylene, 1-phenyl-2-acetyl(acetyl), Bis (trimethylsilyl) acetylene, 2-phenyl-1-ethynylboronic acid pinacola ○ 2020/175631 21
トエステル等を挙げることができる。 Toester and the like can be mentioned.
[0049] 本実施形態に係る不飽和炭化水素化合物の還元方法の還元の対象となる不 飽和炭化水素化合物は、 市販されているものを使用してもよいし、 当該技術 分野で公知の方法により製造されたものを使用してよい。 [0049] As the unsaturated hydrocarbon compound to be reduced in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, a commercially available one may be used, or a method known in the art may be used. You may use what was manufactured.
[0050] 本実施形態に係る不飽和炭化水素化合物の還元方法で用いるジボロン酸エ ステル化合物は、 下記一般式 1 に示すとおりである。 [0050] The diboronic acid ester compound used in the method for reducing an unsaturated hydrocarbon compound according to this embodiment is represented by the following general formula 1.
[化 1 1 ] [Chemical 1 1]
ここで、 一般式 II3中、 [^、 [^、
は、 それぞれ独立的に、 アルカリ 金属と反応しない置換基を有していてもよい脂肪族炭化水素基、 脂環式炭化 水素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環基である 。 脂肪族炭化水素基、 脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素 基、 及び、 芳香族複素環基については、 上記したものを例示することができ る。 Here, in general formula II 3 , [^, [^, Are each independently an aliphatic hydrocarbon group which may have a substituent that does not react with an alkali metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or an aromatic group. It is a heterocyclic group. As the aliphatic hydrocarbon group, alicyclic hydrocarbon group, alicyclic heterocyclic group, aromatic hydrocarbon group, and aromatic heterocyclic group, those mentioned above can be exemplified.
[0051 ] 、 、 及び は、 全てが同一の基であっても、 一部が同一の基であっ てもよく、 また、 何れもが異なる基であってもよい。 [0051],, and may all be the same group, or part of them may be the same group, and all of them may be different groups.
[0052] と とは互いに結合して環を形成していてもよく、 と とは互いに結 合して環を形成していてもよい。 したがって、 と は、 互いに結合してホ ウ素原子及びホウ素原子に結合する 2個の酸素原子と共に環を形成していて もよいし、 互いに結合せずに独立した基として存在してもよい。
も同 様である。 また、 環を形成している場合、 1^と(^、
若 しくは、 双方が環を形成していてもよく、 特に制限はない。 また結合位置に ついても特に制限はない。 このような と 、
して形成され る基としては、 例えば、 ピナコール環を形成する基である 1 , 1 , 2, 2 -テトラメ チルエチレン基、 1 , 1 , 2 -トリメチルプロピレン基、 2, 2 -ジメチルプロピレン
〇 2020/175631 22 卩(:171? 2020 /008069 [0052] and may combine with each other to form a ring, and and may combine with each other to form a ring. Therefore, and may form a ring together with two oxygen atoms bonded to each other to a hydrogen atom and a boron atom, or may exist as independent groups without bonding to each other. Is the same. Also, when forming a ring, 1^ and (^, Both of them may form a ring, and there is no particular limitation. There are no particular restrictions on the binding position. Like this, Examples of the group thus formed include 1,1 ,2,2-tetramethylethylene group, which is a group forming a pinacol ring, 1, 1, 2-trimethylpropylene group, 2, 2-dimethylpropylene group. 〇 2020/175631 22 卩(:171? 2020/008069
基、 プロピレン基、 〇-フエニレン基、 1 -(4 -メ トキシフエニル)- 2, 2 -ジメチル エチレン基、 (11 2(^ 33, 5 -2, 6, 6 -トリメチルビシクロ [3. 1 1 ]ヘプタン- 2, 3 -ジイル基等が挙げられるが、 特に制限はない。 ここで、 ホウ素原子及びそれ に結合する 2個の酸素原子、 各酸素原子に結合する原子により構成される環 状構造が、 環員数 4〜 8であることが好ましい。 また、 環状構造を形成する原 子は置換基を有していてもよく、 環状構造に導入された置換基同士が結合し 更なる環状構造を形成してもよい。 Group, propylene group, 〇-phenylene group, 1-(4-methoxyphenyl)-2,2-dimethylethylene group, (11 2 (^ 33, 5 -2, 6, 6-trimethylbicyclo [3. 1 1] Examples include, but are not limited to, a heptane-2,3-diyl group, where a ring structure composed of a boron atom, two oxygen atoms bonded to it, and an atom bonded to each oxygen atom is used. , Preferably having 4 to 8 ring members. Further, the atom forming the cyclic structure may have a substituent, and the substituents introduced into the cyclic structure are bonded to each other to form a further cyclic structure. You may.
[0053] 本実施形態に係る不飽和炭化水素化合物の還元方法で用いるジボロン酸エ ステル化合物としては、 具体的には、 ビス(ピナコラート)ジボロン (4, 4, 4’, 4’, 5, 5, 5’, 5’-オクタメチル- 2, 2’-ビ -1 , 3, 2 -ジオキサポロラン) 、 ビス(ネオ ペンチルグリコラート)ジボロン (5, 5, 5,, 5, -テトラメチル- 2, 2,-ビ -1 , 3, 2- ジオキサボリナン) 、 ビス(ヘキシレングリコラート)ジボロン (4, 4, 4’, 4’, 6 , 6’-ヘキサメチル- 2, 2’-ビ -1 , 3, 2 -ジオキサボリナン) 、 ビス(カテコラート) ジボロン (2, 2’-ビ -1 , 3, 2 -ベンゾジオキサポロール) 、 2 - (4, 4, 5, 5 -テトラ メチル- 1 , 3, 2 -ジオキサボロラン- 2 -イル)- 2, 3 -ジヒドロ- 1 ナフト [1 , 8 -(^] [ 1 , 3, 2]ジアザボリニン等を挙げることができる。 特に好ましくは、 ビス(ピナ コラート)ジボロンを用いることができる。 [0053] As the diboronic acid ester compound used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, specifically, bis(pinacolato)diboron (4, 4, 4', 4', 5, 5 , 5', 5'-Octamethyl-2,2'-bi-1,3,2-dioxapororane), bis(neopentylglycolate)diborone (5,5,5,5,5-tetramethyl-2,2 ,-Bi-1,3,2-dioxaborinane), bis(hexylene glycolate)diborone (4,4,4',4',6,6'-hexamethyl-2,2'-bi-1,3,3 2-dioxaborinane), bis(catecholate) diborone (2,2'-bi -1,3,2-benzodioxaporol), 2-(4,4,5,5-tetramethyl-1 ,3,2 -Dioxaborolan-2-yl)-2,3-dihydro-1 naphtho[1,8-(^][1,3,2]diazaborinine, etc. can be mentioned. Particularly preferably, bis(pinacolato)diborone is used. Can be used.
[0054] 本実施形態に係る不飽和炭化水素化合物の還元方法で用いるジボロン酸エ ステル化合物は、 市販されているものを使用してもよいし、 当該技術分野で 公知の方法により製造されたものを使用してよい。 [0054] The diboronic acid ester compound used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment may be a commercially available one, or may be one produced by a method known in the art. May be used.
[0055] 本実施形態に係る不飽和炭化水素化合物の還元方法において用いるアルカ リ金属を分散溶媒に分散させた分散体は、 アルカリ金属を微粒子として不溶 性溶媒に分散させたもの、 又は、 アルカリ金属を液体の状態で不溶性溶媒に 分散させたものである。 アルカリ金属としては、 ナトリウム、 カリウム、 リ チウムやこれらの金属を含む合金等が挙げられる。 微粒子の平均粒子径とし て、 好ましくは、 10 111未満であり、 特に好ましくは、 5 111未満のものを用い ることができる。 平均粒子径は、 顕微鏡写真の画像解析によって得られた投 影面積と同等の投影面積を有する球の径で表した。
〇 2020/175631 23 卩(:171? 2020 /008069 The dispersion obtained by dispersing an alkali metal in a dispersion solvent used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is a dispersion of an alkali metal as fine particles in an insoluble solvent, or an alkali metal. Is dispersed in an insoluble solvent in a liquid state. Examples of the alkali metal include sodium, potassium, lithium and alloys containing these metals. The average particle size of the fine particles is preferably less than 10 111, and particularly preferably less than 5 111. The average particle diameter was represented by the diameter of a sphere having a projected area equivalent to the projected area obtained by image analysis of a micrograph. 〇 2020/175631 23 卩 (: 171? 2020 /008069
[0056] 以下、 アルカリ金属を分散溶媒に分散させた分散体につき、 「30」 と略す る場合がある。
Sod i um の略号であり、 下記で説明する実施 例ではアルカリ金属としてナトリウムを用いた分散体を用いることから の 符号を付している。 しかしながら、 の符号がナトリウム以外のアルカリ金 属を除外するものではない。 Hereinafter, a dispersion prepared by dispersing an alkali metal in a dispersion solvent may be abbreviated as “30”. It is an abbreviation for Sod i um, and is labeled with a symbol because a dispersion using sodium as an alkali metal is used in the examples described below. However, the sign of does not exclude alkali metals other than sodium.
[0057] に含まれるアルカリ金属の濃度についても特に制限はないが、 例えば、 5
以下であるものを例示することができる。 The concentration of the alkali metal contained in [0057] is not particularly limited, but for example, 5 The following can be illustrated.
[0058] 分散溶媒としては、 アルカリ金属を微粒子として分散、 又はアルカリ金属 を液体の状態で不溶性溶媒に分散できる限り、 当該技術分野で公知の溶媒を 用いることができる。 例えば、 ノルマルデカン、 ノルマルヘキサン、 ノルマ ルヘプタン、 ノルマルペンタン等のノルマルパラフィン系溶媒等の鉱物油、 キシレン、 トルエン等の芳香族系溶媒や、 テトラヒドロチオフエン等の複素 環化合物溶媒、 又はそれらの混合溶媒等が挙げられる。 As the dispersion solvent, any solvent known in the art can be used as long as the alkali metal can be dispersed as fine particles or the alkali metal can be dispersed in a liquid state in an insoluble solvent. For example, mineral oils such as normal paraffinic solvents such as normal decane, normal hexane, normal heptane, and normal pentane, aromatic solvents such as xylene and toluene, heterocyclic compound solvents such as tetrahydrothiophene, and mixed solvents thereof. Etc.
[0059] クロロベンゼンに対して 2. 1モル当量以上で反応溶媒中で反応させた 場合に、 添加したクロロベンゼンに対するフエニルナトリウムの収率が 99. 0 %以上となる活性を有するものを使用することが好ましい。 このような高活 性な を使用することにより、 更に効率的に不飽和炭化水素化合物の還元を 行うことができる。
の活性を高く維持するためには、 好ましくは、 ガラス バイアル等のガスバリア性の高い容器に保管することが好ましい。 しかしな がら、 ガスバリア性の低い容器に保管することを排除するものではなく、 そ の場合には、
の製造後、 速やかに、 例えば数週間内、 好ましくは 3週間内に 使用する。 [0059] Use a compound having an activity such that the yield of sodium phenyl on the added chlorobenzene is 99.0% or more when the reaction is carried out in a reaction solvent at 2.1 molar equivalents or more with respect to chlorobenzene. Is preferred. By using such a highly active compound, the unsaturated hydrocarbon compound can be reduced more efficiently. In order to maintain high activity of the above, it is preferable to store in a container having a high gas barrier property such as a glass vial. However, this does not preclude storage in containers with low gas barrier properties, in which case: Use immediately after manufacture, eg within a few weeks, preferably within 3 weeks.
[0060] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 反応溶媒と して用いる溶媒としては、 当該還元方法の反応を阻害しない限り、 当該技術 分野で公知の溶媒を使用することができる。 特には、 非プロトン性の極性溶 媒が好ましい。 例えば、 エーテル系溶媒、 ノルマルパラフィン系やシクロパ ラフィン系等のパラフィン系溶媒、 芳香族系溶媒、 アミン系溶媒、 複素環化 合物溶媒を使用することができる。 エーテル系溶媒としては、 環状エーテル
〇 2020/175631 24 卩(:171? 2020 /008069 [0060] In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, as a solvent used as a reaction solvent, a solvent known in the technical field may be used as long as it does not inhibit the reaction in the reduction method. it can. In particular, an aprotic polar solvent is preferable. For example, an ether solvent, a paraffin solvent such as normal paraffin solvent or cycloparaffin solvent, an aromatic solvent, an amine solvent, or a heterocyclic compound solvent can be used. As ether solvents, cyclic ethers 〇 2020/175631 24 卩 (:171? 2020 /008069
溶媒が好ましく、 テトラヒドロフラン (以下、 「丁#」 と略する場合がある) 等を好ましく使用することができる。 パラフィン系溶媒としては、 シクロへ キサン、 ノルマルヘキサン、 及び、 ノルマルデカン等が特に好ましい。 芳香 族系溶媒としては、 キシレン、 トルエン及びベンゼン等が好ましい。 アミン 系溶媒としては、 エチレンジアミン等を好ましく使用することができる。 複 素環化合物溶媒としては、 テトラヒドロチオフエン等を利用することができ る。 また、 これらは 1種類のみを使用してもよいし、 2種以上を併用し混合溶 媒として使用することもできる。 ここで、 前述の分散溶媒と反応溶媒とは同 —の種類のものを使用してもよいし、 異なる種類のものを使用してもよい。 A solvent is preferable, and tetrahydrofuran (hereinafter sometimes abbreviated as “Cho #”) or the like can be preferably used. As the paraffinic solvent, cyclohexane, normal hexane, normal decane and the like are particularly preferable. As the aromatic solvent, xylene, toluene, benzene and the like are preferable. Ethylenediamine and the like can be preferably used as the amine solvent. Tetrahydrothiophene or the like can be used as the solvent for the heterocyclic compound. Further, these may be used alone or in combination of two or more and used as a mixed solvent. Here, the dispersion solvent and the reaction solvent may be of the same kind or different kinds.
[0061 ] 本実施形態に係る不飽和炭化水素化合物の還元方法における反応温度は、 特に限定されず、 還元の対象である不飽和炭化水素化合物、 ジボロン酸エス テル化合物、
及び反応溶媒の種類や量、 並びに反応圧力等により適宜設定 することができる。 具体的には、 反応温度は、 反応溶媒の沸点を越えない温 度に設定することが好ましい。 加圧下では大気圧下での沸点よりも高くなる ため反応温度を高い温度で設定することができる。 反応は、 室温で行うこと もでき、 好ましくは 0〜 100°〇であり、 特に好ましくは 0〜 80°〇、 更に好ましく は 0〜 50°〇である。 特段の加熱や冷却等のための温度制御手段を設ける必要は ないが、 必要に応じて、 温度制御手段を設けても良い。 [0061] The reaction temperature in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is not particularly limited, and an unsaturated hydrocarbon compound to be reduced, a diboronic acid ester compound, It can be appropriately set depending on the kind and amount of the reaction solvent, the reaction pressure and the like. Specifically, the reaction temperature is preferably set to a temperature that does not exceed the boiling point of the reaction solvent. The reaction temperature can be set at a high temperature because it becomes higher than the boiling point under atmospheric pressure under pressure. The reaction can be carried out at room temperature, preferably 0 to 100 ° , particularly preferably 0 to 80 ° , and further preferably 0 to 50 ° . It is not necessary to provide a temperature control means for special heating or cooling, but a temperature control means may be provided if necessary.
[0062] 本実施形態に係る不飽和炭化水素化合物の還元方法における反応時間につ いても、 特に限定されず、 還元の対象である不飽和炭化水素化合物、 ジボロ ン酸エステル化合物、
及び反応溶媒の種類や量、 並びに反応圧力や反応温 度等に応じて適宜設定すればよい。 通常は、 15分間〜 24時間、 好ましくは 20 分間〜 6時間で行われる。 [0062] The reaction time in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is not particularly limited, and is an unsaturated hydrocarbon compound to be reduced, a diboronic acid ester compound, It may be appropriately set according to the kind and amount of the reaction solvent, the reaction pressure, the reaction temperature, and the like. Usually, it is carried out for 15 minutes to 24 hours, preferably 20 minutes to 6 hours.
[0063] 本実施形態に係る不飽和炭化水素化合物の還元方法は、 原則として、 アル ゴンガスや窒素ガス等を充填した不活性ガス雰囲気下行うことが好ましい。 [0063] In principle, the unsaturated hydrocarbon compound reduction method according to the present embodiment is preferably carried out in an inert gas atmosphere filled with argon gas, nitrogen gas, or the like.
[0064] 本実施形態に係る不飽和炭化水素化合物の還元方法において 及びジボロ ン酸エステル化合物の使用量は、 還元対象の不飽和炭化水素化合物、 ジボロ ン酸エステル化合物、 及び、 反応溶媒等の種類や量等に応じて適宜設定する
〇 2020/175631 25 2020 /008069 [0064] In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment and the amount of the diboronic acid ester compound used, the unsaturated hydrocarbon compound to be reduced, the diboronic acid ester compound, and the type of the reaction solvent, etc. Set appropriately according to the amount and quantity 〇 2020/1756 31 25 2020 /008069
ことができる。 好ましくは、 不飽和炭化水素化合物: のモル比は、 1 : 2以 上となる量で反応させる。 より好ましくは 1 : 2以上 1 : 4以下で反応させるこ とが好ましい。 この量で反応させることにより、 不飽和炭化水素化合物を効 率よく還元できる。 一方、
量が多くなりすぎると反応後に残存した の後 処理が必要となり操作が煩雑となるおそれがある。 また、 不飽和炭化水素化
ジボロン酸エステル化合物のモル比を 1 : 2~2. 2 : 1 ~ 1.be able to. Preferably, the unsaturated hydrocarbon compound: is reacted in a molar ratio of 1: 2 or more. More preferably, the reaction is carried out at 1:2 or more and 1:4 or less. By reacting in this amount, the unsaturated hydrocarbon compound can be efficiently reduced. on the other hand, If the amount is too large, post-treatment that remains after the reaction may be required, which may complicate the operation. In addition, unsaturated hydrocarbon The molar ratio of the diboronic acid ester compound is 1: 2 to 2.2: 1 to 1.
1で反応させることが好ましい。 ここで、
の物質量は、
中に含まれるア ルカリ金属換算での物質量を意味する。 It is preferable to react at 1. here, The substance amount of It means the amount of the substance contained in alkaline metal equivalent.
[0065] 本実施形態に係る不飽和炭化水素化合物の還元方法は、 更に、 2 -プロパノ —ル、 メタノール、 エタノール、 ブタノール、 フエノール、 2, 2, 2 -トリフル オロエタノール、 1, 1, 1,3, 3, 3 -ヘキサフルオロ- 2 -プロパノール等の低級アル コールやフエノール等を加えて還元反応を行ってもよい。 これにより、 不飽 和炭化水素化合物の三重結合を単結合まで還元することができる。 かかる低 級アルコール等を添加する場合、
の添加により不飽和炭化水素化合物の三 重結合が二重結合まで還元された後に添加すると良い。 低級アルコールの添 加により、 不飽和炭化水素化合物の還元される部位にホウ素エステルを結合 させることができる。 具体的には、 不飽和炭化水素化合物、
ジボロン酸 エステル化合物を反応させて 15〜 30分後に添加すると良い。 [0065] The unsaturated hydrocarbon compound reduction method according to the present embodiment further includes 2-propanol, methanol, ethanol, butanol, phenol, 2,2,2-trifluoroethanol, 1, 1, 1, The reduction reaction may be carried out by adding a lower alcohol such as 3,3,3-hexafluoro-2-propanol or a phenol or the like. As a result, the triple bond of the unsaturated hydrocarbon compound can be reduced to a single bond. When adding such low-grade alcohol, Is preferably added after the triple bond of the unsaturated hydrocarbon compound has been reduced to a double bond. By adding a lower alcohol, the boron ester can be bonded to the site of reduction of the unsaturated hydrocarbon compound. Specifically, unsaturated hydrocarbon compounds, It may be added 15 to 30 minutes after reacting the diboronic acid ester compound.
[0066] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 還元対象の 不飽和炭化水素化合物であるアルキン化合物は、 下記一般式 III3に示す対応す るジホウ素化アルカン化合物に還元される。 [0066] In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, an alkyne compound which is an unsaturated hydrocarbon compound to be reduced is reduced to a corresponding diborated alkane compound represented by the following general formula III 3. It
[化 12] [Chemical 12]
ここで、 一般式 III3中、 及び は、 一般式 I3の 及び と同様であり、 Here, in the general formula III 3 , and are the same as and in the general formula I 3 ,
3、 、
一般式 113の(^、 、
〇 2020/175631 26 卩(:171? 2020 /008069 3 , In general formula 11 3 (^,, 〇2020/175631 26 卩(: 171-1?2020/008069
[0067] このように本実施形態に係る不飽和炭化水素化合物の還元方法によれば、 ジボロン酸エステルのホウ素ーホウ素間単結合 結合) が開裂され、 還元 対象の不飽和炭化水素化合物であるアルキン化合物の炭素間三重結合に対し て、 当該三重結合を構成する各炭素原子にジボロン酸エステル由来のボリル 基及び水素原子が 1つずつ付加される。 これにより、 アルキン化合物が対応の ジホウ素化されたアルカン化合物に還元される。 本実施形態に係る不飽和炭 化水素化合物の還元方法で得られるアルカン化合物は、 立体異性体として得 られるが、 2 -プロパノール等の低級アルコールを加えて反応を行うと(13, 23) 体、 及び、 ( , 2(¾)体が、 フエノールを加えて反応を行うと( , 23)体、 及び 、 (13, 21^)体が優先して得られる。 As described above, according to the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, the boron-boron single bond) of the diboronic acid ester is cleaved, and the alkyne that is the unsaturated hydrocarbon compound to be reduced is For the carbon-carbon triple bond of the compound, one boryl group derived from diboronic acid ester and one hydrogen atom are added to each carbon atom constituting the triple bond. This reduces the alkyne compound to the corresponding diboronated alkane compound. The alkane compound obtained by the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is obtained as a stereoisomer, but when a reaction is carried out by adding a lower alcohol such as 2-propanol, a (13, 23) form, When the (, 2(¾) form is reacted with phenol, the (, 23) form and the (13, 21^) form are preferentially obtained.
[0068] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 還元された アルカン化合物は、 当該技術分野で公知の精製手段により精製してもよい。 例えば、 還元されたアルカン化合物に対して、 抽出溶媒として、 酢酸エチル 等の有機溶媒を用いて抽出処理し、 得られた抽出液を濃縮した濃縮液をシリ カゲルクロマトグラフィー等の精製担体に供することで精製することができ る。 [0068] In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, the reduced alkane compound may be purified by a purification means known in the art. For example, the reduced alkane compound is subjected to an extraction treatment using an organic solvent such as ethyl acetate as an extraction solvent, and the concentrated solution obtained is concentrated and applied to a purified carrier such as silica gel chromatography. Can be purified with.
[0069] 〔2〕 不飽和炭化水素化合物の還元方法ーアルキン化合物のアルケン化合物 への還元 [0069] [2] Reduction method of unsaturated hydrocarbon compound-reduction of alkyne compound to alkene compound
本実施形態に係る不飽和炭化水素化合物の還元方法は、 分子中に 1以上の炭 素間三重結合を含むアルキン化合物において、 炭素間三重結合を二重結合に 変換し、 対応のアルケン化合物へ還元する方法を含む。 The unsaturated hydrocarbon compound reduction method according to the present embodiment is an alkyne compound having one or more carbon-carbon triple bonds in the molecule, wherein the carbon-carbon triple bond is converted into a double bond and reduced to the corresponding alkene compound. Including how to do.
[0070] 詳細には、 反応溶媒中、 アルカリ金属を分散溶媒に分散させた分散体の存 在下で、 一般式 に示す不飽和炭化水素化合物であるアルキン化合物と、 一般 式 114こ示すホウ酸エステル化合物とを、 反応させることにより、 前記不飽和 炭化水素化合物を還元する工程を含むものである。 [0070] Specifically, in the presence of a dispersion prepared by dispersing an alkali metal in a dispersion solvent in a reaction solvent, an alkyne compound which is an unsaturated hydrocarbon compound represented by the general formula and a borate ester represented by the general formula 114 It includes a step of reducing the unsaturated hydrocarbon compound by reacting with a compound.
[0071 ] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 還元の対象 となる不飽和炭化水素化合物としては、 上記 〔1〕 と同様に、 分子中に一以 上の炭素間三重結合を含むアルキン化合物を挙げることができる。 アルキン
〇 2020/175631 27 卩(:171? 2020 /008069 [0071] In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, as the unsaturated hydrocarbon compound to be reduced, as in the above [1], one or more carbon-carbon triple bonds in the molecule are included. Examples of the alkyne compound include: Alkyne 〇 2020/175631 27 卩 (:171? 2020 /008069
化合物は、 炭素間三重結合を構成する 2つの炭素原子の少なくとも一方が水素 原子と結合している末端アルキン化合物であっても、 双方の炭素原子が炭素 間三重結合を形成する炭素原子との結合に加えて、 水素原子以外の基と結合 している内部アルキン化合物であってもよい。 Even if the compound is a terminal alkyne compound in which at least one of two carbon atoms forming a carbon-carbon triple bond is bonded to a hydrogen atom, both carbon atoms are bonded to a carbon atom forming a carbon-carbon triple bond. In addition, it may be an internal alkyne compound bonded to a group other than a hydrogen atom.
[0072] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 還元の対象 となるアルキン化合物を示す一般式 は下記に示すとおりである。 [0072] In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, a general formula showing an alkyne compound to be reduced is as shown below.
[化 13]
ここで、 一般式 に示すアルキン化物において、
それぞれ独立 的に、 水素原子、 アルキル金属と反応しない置換基を有していてもよい脂肪 族炭化水素基、 脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 又 は、 芳香族複素環基、 ハロゲン原子、 アルコキシ基、 シクロアルコキシ基、 アリールオキシ基、 アラルキルオキシ基、 脂環式複素環オキシ基、 芳香族複 素環オキシ基、 アルキルチオ基、 シクロアルキルチオ基、 アリールチオ基、 アラルキルチオ基は、 脂環式複素環チオ基、 芳香族複素環チオ基、 アルキル アミノ基、 シクロアルキルアミノ基、 アリールアミノ基、 アラルキルアミノ 基、 脂環式複素環アミノ基、 芳香族複素環アミノ基、 シリル基である。 アル カリ金属と反応性を有する置換基を有すると、 当該置換基とナトリウムを分 散溶媒に分散させた分散体が反応し、 副反応を誘発するため好ましくない。 したがって、 アルカリ金属と反応性を有する置換基を有するアルキン化合物 を還元の対象とする場合には、 当該置換基を適切な保護基等で保護すること が必要となる。 [Chemical 13] Here, in the alkyne compound represented by the general formula, Independently of each other, a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent which does not react with an alkyl metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or , Aromatic heterocyclic group, halogen atom, alkoxy group, cycloalkoxy group, aryloxy group, aralkyloxy group, alicyclic heterocyclic oxy group, aromatic compound ring oxy group, alkylthio group, cycloalkylthio group, arylthio group , Aralkylthio group, alicyclic heterocyclic thio group, aromatic heterocyclic thio group, alkylamino group, cycloalkylamino group, arylamino group, aralkylamino group, alicyclic heterocyclic amino group, aromatic heterocycle An amino group and a silyl group. When a substituent having reactivity with an alkali metal is included, the substituent and sodium are dispersed in a dispersion solvent to react with each other, which induces a side reaction, which is not preferable. Therefore, when an alkyne compound having a substituent having reactivity with an alkali metal is targeted for reduction, it is necessary to protect the substituent with an appropriate protecting group or the like.
[0073] なお、 一般式 に示すアルキン化物は、 上記 〔1〕 の項で説明した一般式 に示すアルキン化合物と同等のものとでき、 したがって、 一般式 中の 及び は、 一般式 I3の 及び と同等のものとできる。 [0073] Incidentally, the alkyne compound is represented by the general formula [1] above, terms in can as the alkyne compound represented by the general formula and the same description, and thus, the Oyobi is in the general formula, and the formula I 3 Can be equivalent to
[0074] 本実施形態に係る不飽和炭化水素化合物の還元方法で用いるホウ酸エステ ル化合物は下記一般式 114こ示すとおりである。
\¥0 2020/175631 28 卩(:17 2020 /008069 [0074] The ester borate compound used in the method for reducing an unsaturated hydrocarbon compound according to this embodiment is represented by the following general formula 114. \¥0 2020/1756 31 28 卩 (: 17 2020 /008069
[化 14] [Chemical 14]
ここで、 一般式 11中、 1^、 (¾■及び は、 それぞれ独立的に、 アルカリ金 属と反応しない置換基を有していてもよい脂肪族炭化水素基、 脂環式炭化水 素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環基である。 脂肪族炭化水素基、 脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基 、 及び、 芳香族複素環基については、 上記 〔1〕 の項で説明したものを例示 することができる。 Here, in the formula 11, 1 ^, (¾ ■ Oyobi are each independently of the alkali metals and does not react with an aliphatic substituted hydrocarbon group, an alicyclic hydrocarbon group An alicyclic heterocyclic group, an aromatic hydrocarbon group, or an aromatic heterocyclic group an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, As the aromatic heterocyclic group, those described in the above item [1] can be exemplified.
[0075] (^、 (¾■及び は、 全てが同一の基であっても、 一部が同一の基であっても よく、 また、 何れもが異なる基であってもよい。 [0075] (^, (¾ ■ Oyobi also all be the same group, part may be the same group, also both may be different groups.
[0076] とは互いに結合して環を形成していてもよい。 したがって、 ■と 1 bは、 互いに結合してホウ素原子及びホウ素原子に結合する 2個の酸素原子と 共に環を形成していてもよいし、 互いに結合せずに独立した基として存在し の結合位置についても特に制限はない。 このような
成される基としては、 例えば、 ピナコール環を形成す る基である 1 , 1 , 2, 2 -テトラメチルエチレン基、 1 , 1 , 2 -トリメチルプロピレン 基、 2, 2 -ジメチルプロピレン基、 プロピレン基、 〇-フエニレン基、 1 -(4 -メ ト キシフエニル)- 2, 2 -ジメチルエチレン基、 (11 2(^ 33, 5 -2, 6, 6 -トリメチル ビシクロ [3. 1 . 1 ]ヘプタン- 2, 3 -ジイル基等が挙げられるが、 特に制限はない 。 ここで、 ホウ素原子及びそれに結合する 2個の酸素原子、 各酸素原子に結 合する原子により構成される環状構造が、 環員数 4〜 8であることが好ましい 。 また、 環状構造を形成する原子は置換基を有していてもよく、 環状構造に 導入された置換基同士が結合し更なる環状構造を形成してもよい。 [0076] and may combine with each other to form a ring. Therefore, ■ and 1 b are both may be combined to form a ring, presence bonded as groups independently without binding to one another and two oxygen atoms bonded to the boron atom and a boron atom bonded to each other There is no particular restriction on the position. like this Examples of the group formed are 1,1,2,2-tetramethylethylene group which is a group forming a pinacol ring, 1,1,2-trimethylpropylene group, 2,2-dimethylpropylene group, propylene Group, 〇-phenylene group, 1-(4-methoxyphenyl)-2,2-dimethylethylene group, (112(^33,5-2,6,6-trimethylbicyclo[3.1.1]]heptane Examples include, but are not limited to, a boron atom, two oxygen atoms bonded to it, and a cyclic structure composed of atoms bonded to each oxygen atom is a ring. The number of members is preferably 4 to 8. Further, the atom forming the cyclic structure may have a substituent, and even if the substituents introduced into the cyclic structure are bonded to each other to form a further cyclic structure. Good.
[0077] 本実施形態に係る不飽和炭化水素化合物の還元方法で用いるホウ酸エステ ル化合物としては、 具体的には、 ホウ酸トリメチル (トリメ トキシボラン)
〇 2020/175631 29 卩(:171? 2020 /008069 [0077] Specific examples of the ester borate compound used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment include trimethyl borate (trimethoxyborane). 〇 2020/175631 29 卩 (:171? 2020 /008069
、 ホウ酸トリエチル (トリエトキシボラン) 、 ホウ酸トリプロピル、 ホウ酸 トリイソプロピル、 ホウ酸トリブチル、 ホウ酸トリヘキシル、 ホウ酸トリオ クチル、 ホウ酸トリデシル、 ホウ酸トリテトラデシル、 ホウ酸トリオクタデ シル等のホウ酸トリアルキルエステル、 ホウ酸トリフエニル、 ホウ酸トリ-〇- トリル等のホウ酸トリアリールエステル、 ホウ酸トリエタノールアミンやホ ウ酸トリイソプロパノールアミン、 シリルオキシ基を有するトリス(トリメチ ルシリル)ボラート等のホウ酸トリエステルが挙げられる。 更に、 エトキシボ ロン酸ピナコール (2 -エトキシ -4, 4, 5, 5 -テトラメチル- 1 , 3, 2 -ジオキサボロ ラン) 、 イソプロポキシボロン酸ピナコール (2 -イソプロポキシ -4, 4, 5, 5 -テ トラメチル- 1 , 3, 2 -ジオキサボロラン) 、 メ トキシボロン酸ピナコール (2 -メ トキシ -4, 4, 5, 5 -テトラメチル- 1 , 3, 2 -ジオキサボロラン) 等のホウ酸ピナコ —ルエステル、 2 -イソプロポキシ -4, 4, 6 -トリメチル- 1 , 3, 2 -ジオキサボリナ ン、 トリメ トキシシクロトリボロキサン (2, 4, 6 -トリメ トキシボロキシン), Triethyl borate (triethoxyborane), tripropyl borate, triisopropyl borate, tributyl borate, trihexyl borate, trioctyl borate, tridecyl borate, tritetradecyl borate, trioctadecyl borate, etc. Boric acid trialkyl esters, triphenyl borate, tri-borate triaryl esters such as boric acid triethanolamine, boric acid triisopropanolamine, tris(trimethylsilyl)borate having silyloxy group Acid triesters are mentioned. Furthermore, pinacol ethoxyboronate (2-ethoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane), pinacol isopropoxyboronate (2-isopropoxy-4,4,5,5) -Tetramethyl-1 ,3,2-dioxaborolane), pinacol methoxyboronate (2-methoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane), etc. 2-isopropoxy-4,4,6-trimethyl-1,1 ,3,2-dioxaborinane, trimethoxycyclotriboroxane (2,4,6-trimethoxyboroxine)
、 ホウ酸カテコールエステル、 ホウ酸ネオペンチルグリコールエステル、 ホ ウ酸ビスシクロヘキシルジオールエステル等を例示することができる。 特に 好ましくは、 トリメ トキシボランを用いることができる Examples thereof include catechol borate, neopentyl glycol borate, and biscyclohexyl diol borate. Particularly preferably, trimethoxyborane can be used
[0078] 本実施形態に係る不飽和炭化水素化合物の還元方法において用いる や反 応溶媒に関しては、 上記 〔1〕 の項で説明したものを例示することができる [0078] Regarding the reaction solvent used in the method for reducing an unsaturated hydrocarbon compound according to this embodiment, the reaction solvent described in the above item [1] can be exemplified.
[0079] 本実施形態に係る不飽和炭化水素化合物の還元方法における反応温度、 反 応時間、 反応雰囲気等の反応条件についは、 特に制限はなく、 上記 〔1〕 の 項で説明した条件を例示することができる [0079] There are no particular restrictions on the reaction conditions such as reaction temperature, reaction time, reaction atmosphere, etc. in the method for reducing unsaturated hydrocarbon compounds according to the present embodiment, and the conditions described in the above item [1] are exemplified. can do
[0080] 本実施形態に係る不飽和炭化水素化合物の還元方法において 及びホウ酸 エステル化合物の使用量は、 還元対象の不飽和炭化水素化合物、 ホウ酸エス テル化合物、 及び、 反応溶媒等の種類や量等に応じて適宜設定することがで きる。 好ましくは、 不飽和炭化水素化合物: のモル比は、 1 : 2以上となる 量で反応させる。 より好ましくは 1 : 2以上 1 : 4以下で反応させることが好ま しい。 この量で反応させることにより、 不飽和炭化水素化合物を効率よく還
〇 2020/175631 30 卩(:171? 2020 /008069 In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment and the amount of the boric acid ester compound used, the unsaturated hydrocarbon compound to be reduced, the boric acid ester compound, and the type of reaction solvent, etc. It can be set appropriately according to the amount and the like. Preferably, the unsaturated hydrocarbon compound is reacted in a molar ratio of 1:2 or more. More preferably, the reaction is carried out at 1:2 or more and 1:4 or less. By reacting with this amount, unsaturated hydrocarbon compounds can be efficiently returned. 〇 2020/175631 30 boxes (:171? 2020 /008069
元できる。 一方、
量が多くなりすぎると反応後に残存した の後処理が必 要となり操作が煩雑となるおそれがある。 また、 不飽和炭化水素化合物: :ホウ酸エステル化合物のモル比を 1 : 2〜 4 : 2〜 6で反応させることが 好ましい。 ここで、
の物質量は、
中に含まれるアルカリ金属換算での物 質量を意味する。 I can do it. on the other hand, If the amount is too large, post-treatment that remains after the reaction becomes necessary, and the operation may be complicated. Further, it is preferable to react the unsaturated hydrocarbon compound::borate ester compound at a molar ratio of 1:2 to 4:2 to 6. here, The substance amount of It means the mass of the substance contained in terms of alkali metal.
[0081 ] 本実施形態に係る不飽和炭化水素化合物の還元方法は、 更に、 ピナコール やネオペンチルグリコール等の二価アルコール、 フッ化水素カリウムによる 後処理を行ってもよい。 これにより、 ホウ酸エステル化合物の -0(^基が二価ア ルコール、 又は、 フッ化水素カリウムで保護され、 ホウ酸エステル化合物が 反応系内の水分と反応することにより生じるホウ酸やボロキシン等の副生成 物の生成を防ぐことができる。 ホウ酸エステルとして、 ホウ酸トリメチル等 のホウ酸トリエステルを使用した場合にピナコールを添加することで、 ピナ コールボリル基によりホウ素化されたアルケン化合物を得ることができるま た、 かかる二価アルコール等を添加する場合、 ホウ酸エステル化合物を添加 した後に行うことが好ましい。 The unsaturated hydrocarbon compound reduction method according to the present embodiment may be further post-treated with a dihydric alcohol such as pinacol or neopentyl glycol, or potassium hydrogen fluoride. As a result, the -0(^ group of the borate ester compound is protected by divalent alcohol or potassium hydrogen fluoride, and boric acid or boroxine generated by the reaction of the borate ester compound with the water in the reaction system. When borate triesters such as trimethyl borate are used as borate ester, pinacol is added to obtain a borated alkene compound with a pinacol boryl group. In addition, when such a dihydric alcohol or the like is added, it is preferably performed after adding the borate ester compound.
[0082] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 還元対象の 不飽和炭化水素化合物であるアルキン化合物は、 下記一般式 11 に示す対応す るジホウ素化アルケン化合物に還元される。 In the unsaturated hydrocarbon compound reduction method according to the present embodiment, the alkyne compound that is the unsaturated hydrocarbon compound to be reduced is reduced to the corresponding diboronated alkene compound represented by the following general formula 11. ..
[化 1 5] [Chemical 1 5]
及び は、 一般式 11の ■及び と同様である。 And are ■ Oyobi same as the general formula 11.
[0083] このように、 本実施形態に係る不飽和炭化水素化合物の還元方法によれば 、 ホウ酸エステルの 1のホウ素一酸素間単結合 -〇) 結合が開裂され、 還元
〇 2020/175631 31 卩(:171? 2020 /008069 [0083] As described above, according to the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, the boron-oxygen single bond of 1 in the borate ester -O) bond is cleaved to reduce 〇 2020/175631 31 卩 (: 171? 2020 /008069
対象の不飽和炭化水素化合物であるアルキン化合物の炭素間三重結合に対し て、 当該三重結合を構成する各炭素に対してホウ酸エステル由来のボリル基 が 1つずつ付加される。 これにより、 アルキン化合物が対応のアルケン化合物 に還元される。 このとき、 アルキン化合物が内部アルキン化合物であった場 合には、 生成されるアルケン化合物は〇_13型にボリル基が導入されたものとな る。 For the carbon-carbon triple bond of the alkyne compound, which is the target unsaturated hydrocarbon compound, one boryl group derived from borate ester is added to each carbon constituting the triple bond. As a result, the alkyne compound is reduced to the corresponding alkene compound. At this time, if the alkyne compound is an internal alkyne compound, the alkene compound formed is one in which a boryl group is introduced into the __13 type.
[0084] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 還元された アルケン化合物は、 当該技術分野で公知の精製手段により精製してもよい。 例えば、 還元されたアルカン化合物に対して、 抽出溶媒として、 酢酸エチル 等の有機溶媒を用いて抽出処理し、 得られた抽出液を濃縮した濃縮液をシリ カゲルクロマトグラフィー等の精製担体に供することで精製することができ る。 [0084] In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, the reduced alkene compound may be purified by a purification means known in the art. For example, the reduced alkane compound is subjected to an extraction treatment using an organic solvent such as ethyl acetate as an extraction solvent, and the concentrated solution obtained is concentrated and applied to a purified carrier such as silica gel chromatography. Can be purified with.
[0085] 〔3〕 不飽和炭化水素化合物の還元方法ーアルケン化合物のアルカン化合物 への還元 [3] Reduction Method of Unsaturated Hydrocarbon Compound-Reduction of Alkene Compound to Alkane Compound
本実施形態に係る不飽和炭化水素化合物の還元方法は、 分子中に 1以上の炭 素間二重結合を含むアルケン化合物において、 炭素間二重結合を一重結合に 変換し、 対応のアルカン化合物へ還元する方法を含む。 The unsaturated hydrocarbon compound reduction method according to the present embodiment is an alkene compound containing one or more carbon-carbon double bonds in the molecule, the carbon-carbon double bond is converted into a single bond, and the corresponding alkane compound is converted to the corresponding alkane compound. Including a method of reducing.
[0086] 詳細には、 反応溶媒中、 アルカリ金属を分散溶媒に分散させた分散体の存 在下で、 一般式 I。に示す不飽和炭化水素化合物であるアルケン化合物と、 一般 式 II。に示すホウ酸エステル化合物とを、 反応させることにより、 前記不飽和 炭化水素化合物を還元する工程を含むものである。 [0086] Specifically, in the presence of a dispersion prepared by dispersing an alkali metal in a dispersion solvent in a reaction solvent, the compound represented by the general formula I: And an alkene compound which is an unsaturated hydrocarbon compound shown in Formula II. And a boric acid ester compound shown in (4) are reacted with each other to reduce the unsaturated hydrocarbon compound.
[0087] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 還元の対象 となる不飽和炭化水素化合物としては、 分子中に一以上の炭素間二重結合を 含むアルケン化合物を挙げることができ、 二以上の炭素間二重結合を含むも のについても還元の対象とすることができる。 アルケン化合物は、 炭素間二 重結合を構成する 2つの炭素原子の少なくとも一方が、 炭素間二重結合を形成 する炭素原子との結合を除いては水素原子とのみ結合し他の基と結合してい ない末端アルケン化合物であっても、 双方の炭素原子が炭素間二重結合を形
\¥0 2020/175631 32 卩(:17 2020 /008069 In the method for reducing unsaturated hydrocarbon compounds according to the present embodiment, examples of unsaturated hydrocarbon compounds to be reduced include alkene compounds containing one or more carbon-carbon double bonds in the molecule. It is possible to reduce a substance containing two or more carbon-carbon double bonds. In the alkene compound, at least one of the two carbon atoms forming the carbon-carbon double bond is bonded only to the hydrogen atom except the bond to the carbon atom forming the carbon-carbon double bond, and is bonded to another group. Even if the terminal alkene compound is not present, both carbon atoms form a carbon-carbon double bond. \¥0 2020/175631 32 卩 (: 17 2020 /008069
成する炭素原子との結合に加えて、 水素原子以外の基と結合している内部ア ルケン化合物であってもよい。 また、 アルケン化合物が炭素間二重結合を形 成する炭素原子の双方に 1以上が水素原子以外の基と結合している場合、 これ らの基の配置が、 å配置 (〇 型を含む) であっても、 £配置
型を含む ) であつてもよい。 In addition to the bond with the carbon atom formed, an internal alkene compound bonded with a group other than a hydrogen atom may be used. Further, when at least one of the carbon atoms forming the carbon-carbon double bond of the alkene compound is bonded to a group other than a hydrogen atom, the arrangement of these groups is not limited to the general arrangement (including type 0). Even the £ placement Including the mold).
[0088] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 還元の対象 となるアルケン化合物を示す一般式 I。は下記に示すとおりである。 [0088] In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, a general formula I showing an alkene compound to be reduced. Is as shown below.
[化 16] 1。 # [Chemical 16] 1. #
\ / \/
0, = 0 0, = 0
#ノ \ # ここで、 一般式 I。中、 (^、 、 及び は、 それぞれ独立的に、 水素原子 アルカリ金属と反応しない置換基を有していてもよい脂肪族炭化水素基、 脂 環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環 基、 ハロゲン原子、 アルコキシ基、 シクロアルコキシ基、 アリールオキシ基 、 アラルキルオキシ基、 脂環式複素環オキシ基、 芳香族複素環オキシ基、 ア ルキルチオ基、 シクロアルキルチオ基、 アリールチオ基、 アラルキルチオ基 は、 脂環式複素環チオ基、 芳香族複素環チオ基、 アルキルアミノ基、 シクロ アルキルアミノ基、 アリールアミノ基、 アラルキルアミノ基、 脂環式複素環 アミノ基、 芳香族複素環アミノ基、 シリル基である。 脂肪族炭化水素基、 脂 環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環 基、 ハロゲン原子、 アルコキシ基、 シクロアルコキシ基、 アリールオキシ基 、 アラルキルオキシ基、 脂環式複素環オキシ基、 芳香族複素環オキシ基、 ア ルキルチオ基、 シクロアルキルチオ基、 アリールチオ基、 アラルキルチオ基 は、 脂環式複素環チオ基、 芳香族複素環チオ基、 アルキルアミノ基、 シクロ アルキルアミノ基、 アリールアミノ基、 アラルキルアミノ基、 脂環式複素環 アミノ基、 芳香族複素環アミノ基、 シリル基については、 上記 〔1〕 で説明
〇 2020/175631 33 卩(:171? 2020 /008069 #No \# where I is the general formula. Wherein (^,, and are each independently a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent that does not react with an alkali metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, Aromatic hydrocarbon group, or aromatic heterocyclic group, halogen atom, alkoxy group, cycloalkoxy group, aryloxy group, aralkyloxy group, alicyclic heterocyclic oxy group, aromatic heterocyclic oxy group, aralkylthio group , Cycloalkylthio group, arylthio group, aralkylthio group, alicyclic heterocyclic thio group, aromatic heterocyclic thio group, alkylamino group, cycloalkylamino group, arylamino group, aralkylamino group, alicyclic heterocyclic group Amino group, aromatic heterocyclic amino group, silyl group Aliphatic hydrocarbon group, alicyclic hydrocarbon group, alicyclic heterocyclic group, aromatic hydrocarbon group, or aromatic heterocyclic group, halogen Atom, alkoxy group, cycloalkoxy group, aryloxy group, aralkyloxy group, alicyclic heterocyclic oxy group, aromatic heterocyclic oxy group, aralkylthio group, cycloalkylthio group, arylthio group, aralkylthio group, alicyclic group Formula heterocyclic thio group, aromatic heterocyclic thio group, alkylamino group, cycloalkylamino group, arylamino group, aralkylamino group, alicyclic heterocyclic amino group, aromatic heterocyclic amino group, silyl group, Described in [1] above 〇2020/175631 33 卩(:171? 2020/008069
したものを例示することができる。 アルカリ金属と反応性を有する置換基を 有すると、 当該置換基とナトリウムを分散溶媒に分散させた分散体が反応し 、 副反応を誘発するため好ましくない。 したがって、 アルカリ金属と反応性 を有する置換基を有するアルケン化合物を還元の対象とする場合には、 当該 置換基を適切な保護基等で保護することが必要となる。 The above can be exemplified. Having a substituent reactive with an alkali metal reacts with the dispersion in which the substituent and sodium are dispersed in a dispersion solvent and induces a side reaction, which is not preferable. Therefore, when an alkene compound having a substituent having reactivity with an alkali metal is targeted for reduction, it is necessary to protect the substituent with an appropriate protecting group or the like.
[0089] 1^。、 、 1^。及び 。は、 全てが同一の基であっても、 一部が同一の基であっ てもよく、 また、 何れもが異なる基であってもよい。 [0089] 1^. ,, 1^. as well as . May all be the same group, or some may be the same group, and all may be different groups.
[0090] 又は と互いに結合して環を形成していてもよい。 したがって、 は、 又は と互いに結合して環を形成することで、 炭素間二重結合が環の —部を構成するものとできる。 また、 互いに結合せずに独立した基として存 在してもよい。
と、 又は との結合で形成される環は特に限定するもの ではないが、 シクロヘキセン環等のシクロアルケン環、 ベンゼン環等の芳香 環等を例示することができる。 また、
同様に、 又は と互いに結合 して環を形成していてもよいし、 互いに独立した基として存在してもよい。 また、 環状構造を形成する原子は置換基を有していてもよく、 環状構造に導 入された置換基同士が結合し更なる環状構造を形成してもよい。 [0090] Or may be bonded to each other to form a ring. Therefore, the carbon-carbon double bond can form a part of the ring by forming a ring by bonding with the or. In addition, they may exist as independent groups without being bonded to each other. The ring formed by the bond of and or is not particularly limited, and examples thereof include a cycloalkene ring such as a cyclohexene ring and an aromatic ring such as a benzene ring. Also, Similarly, or may be combined with each other to form a ring, or may exist as groups independent of each other. Further, the atom forming the cyclic structure may have a substituent, and the substituents introduced into the cyclic structure may be bonded to each other to form a further cyclic structure.
[0091 ] また、 (^と(^とは互いに結合して環を形成していてもよく、 また、 互いに結 合せずに独立した基として存在してもよい。 (^と(^2との結合で形成される環は 特に限定するものではないが、 シクロヘキサン環等のシクロアルカン環、 シ クロヘキセン環等のシクロアルケン環等を例示することができる。 また、
と も、 同様に、 互いに結合して環を形成していてもよいし、 互いに独立し た基として存在してもよい。 また、 環状構造を形成する原子は置換基を有し ていてもよく、 環状構造に導入された置換基同士が結合し更なる環状構造を 形成してもよい。 [0091] Also, (^ and (^ may be bonded to each other to form a ring, or may be present as independent groups without being bonded to each other. (^ and (^ 2 The ring formed by the bond is not particularly limited, and examples thereof include a cycloalkane ring such as a cyclohexane ring and a cycloalkene ring such as a cyclohexene ring. Also, similarly, they may be bonded to each other to form a ring, or they may exist as groups independent of each other. Further, the atom forming the cyclic structure may have a substituent, and the substituents introduced into the cyclic structure may be bonded to each other to form a further cyclic structure.
[0092] 本実施形態に係る不飽和炭化水素化合物の還元方法の還元の対象となる不 飽和炭化水素化合物は、 市販されているものを使用してもよいし、 当該技術 分野で公知の方法により製造されたものを使用してよい。 [0092] As the unsaturated hydrocarbon compound to be reduced in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, a commercially available one may be used, or the unsaturated hydrocarbon compound may be prepared by a method known in the art. You may use what was manufactured.
[0093] 本実施形態に係る不飽和炭化水素化合物の還元方法の還元の対象となる不
〇 2020/175631 34 卩(:171? 2020 /008069 [0093] The unsaturated hydrocarbon compound according to the present embodiment is used as a target of reduction in the reduction method. 〇 2020/175631 34 卩 (:171? 2020 /008069
飽和炭化水素化合物としては、 具体的には、 スチレン、 〇_ -スチルベン、 3 -スチルベン、 /3 -メチルスチレン、 /3 -ェチルスチレン、 /3 -プロピルスチ レン、 /3 -ブチルスチレン、 /3 -ペンチルスチレン、 /3 -ヘキシルスチレン、 《 -メチルスチレン、 《 -ェチルスチレン、
プロピルスチレン、
プチルス チレン、
ペンチルスチレン、
ヘキシルスチレン、 1 -メチル- 1 , 2 -ジフェ ニルェチレン、 1 , 2, 3 -トリフェニルェチレン、 インデン、 1 , 2 -ジヒドロナフ タレン、 ブタジェン、 イソプレン、 1 , 3 -シクロへキサジェン、 ノルボルネン 、 ノルボルナジェン等を挙げることができる。 Specific examples of the saturated hydrocarbon compound include styrene, 〇_-stilbene, 3-stilbene, /3-methylstyrene, /3-ethylstyrene, /3-propylstyrene, /3-butylstyrene and /3-pentyl. Styrene, /3-hexylstyrene, <<-methylstyrene, <<-ethylstyrene, Propyl styrene, Petit Styrene, Pentyl styrene, Hexylstyrene, 1-methyl-1,2-diphenylethylene, 1,2,3-triphenylethylene, indene, 1,2-dihydronaphthalene, butadiene, isoprene, 1,3-cyclohexagen, norbornene, norbornadiene, etc. Can be mentioned.
[0094] 本実施形態に係る不飽和炭化水素化合物の還元方法で用いるホウ酸ェステ ル化合物は、 下記一般式 II。に示すとおりである。 [0094] The ester borate compound used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment has the following general formula II. As shown in.
[化 17] [Chemical 17]
ここで、 一般式 II。中、 1^、 (¾■及び は、 それぞれ独立的に、 アルカリ金 属と反応しない置換基を有していてもよい脂肪族炭化水素基、 脂環式炭化水 素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環基である。 Where general formula II. Among, 1 ^, (¾ ■ Oyobi are each independently of the alkali metals and does not react with an aliphatic substituted hydrocarbon group, an alicyclic hydrocarbon group, an alicyclic heterocyclic A group, an aromatic hydrocarbon group, or an aromatic heterocyclic group.
[0095] なお、 一般式 II。に示すホウ酸エステル化合物は、 上記 〔2〕 の項で説明し た一般式 に示すホウ酸エステル化合物と同等のものとでき、 したがって、 —般式 II。中の[^、 (¾ 及び は、 上記 〔2〕 の項で説明した一般式 1 の(^、 ■及び と同等のものとできる。 特に好ましくは、 トリメ トキシボランを用 いることができる [0095] Note that the general formula II. The boric acid ester compound shown in can be equivalent to the boric acid ester compound represented by the general formula described in the section [2] above, and therefore can be represented by the general formula II. [^, (¾ and can be the same as (^, 2) and (^) in the general formula 1 described in the section [2] above. Particularly preferably, trimethoxyborane can be used.
[0096] 本実施形態に係る不飽和炭化水素化合物の還元方法において用いる や反 応溶媒に関しては、 上記 〔1〕 の項で説明したものを例示することができる [0096] Regarding the reaction solvent used in the method for reducing an unsaturated hydrocarbon compound according to this embodiment, the reaction solvent described in the above item [1] can be exemplified.
[0097] 本実施形態に係る不飽和炭化水素化合物の還元方法における反応温度、 反 応時間、 反応雰囲気等の反応条件についは、 特に制限はなく、 上記 〔1〕 の
〇 2020/175631 35 卩(:171? 2020 /008069 [0097] There are no particular restrictions on the reaction conditions such as reaction temperature, reaction time, reaction atmosphere, etc. in the method for reducing unsaturated hydrocarbon compounds according to the present embodiment. 〇 2020/175631 35 卩 (: 171? 2020 /008069
項で説明した条件を例示することができる。 The conditions described in the section can be exemplified.
[0098] 本実施形態に係る不飽和炭化水素化合物の還元方法において 及びホウ酸 エステル化合物の使用量は、 還元対象の不飽和炭化水素化合物、 ホウ酸エス テル化合物、 及び、 反応溶媒等の種類や量等に応じて適宜設定することがで きる。 好ましくは、 不飽和炭化水素化合物: のモル比は、 1 : 2以上となる 量で反応させる。 より好ましくは 1 : 2以上 1 : 4以下で反応させることが好ま しい。 この量で反応させることにより、 不飽和炭化水素化合物を効率よく還 元できる。 一方、
量が多くなりすぎると反応後に残存した の後処理が必 要となり操作が煩雑となるおそれがある。 また、 不飽和炭化水素化合物: :ホウ酸エステル化合物のモル比を 1 : 2〜 3 : 2〜 6で反応させることが 好ましい。 ここで、
の物質量は、
中に含まれるアルカリ金属換算での物 質量を意味する。 In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment and the amount of the boric acid ester compound used, the unsaturated hydrocarbon compound to be reduced, the boric acid ester compound, and the type of reaction solvent and the like, It can be set appropriately according to the amount and the like. Preferably, the unsaturated hydrocarbon compound is reacted in a molar ratio of 1:2 or more. More preferably, the reaction is carried out at 1:2 or more and 1:4 or less. By reacting in this amount, the unsaturated hydrocarbon compound can be efficiently recovered. on the other hand, If the amount is too large, post-treatment that remains after the reaction becomes necessary, and the operation may be complicated. Further, it is preferable to react the unsaturated hydrocarbon compound::borate compound at a molar ratio of 1:2 to 3:2 to 6. here, The substance amount of It means the mass of the substance contained in terms of alkali metal.
[0099] 本実施形態に係る不飽和炭化水素化合物の還元方法は、 更に、 ヨウ化リチ ウムを添加してもよい。 これにより、 収率及び生成物の立体選択性が向上す る効果が得られる。 また、 かかるヨウ化リチウムを添加する場合、
を添加 する前に添加するのが好ましい。 [0099] In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, lithium iodide may be added. This has the effect of improving the yield and stereoselectivity of the product. When adding such lithium iodide, It is preferable to add before adding.
[0100] 本実施形態に係る不飽和炭化水素化合物の還元方法は、 更に、 1\1, 1\1, 1\1’, 1\1’ - テトラメチルエチレンジアミン (丁1^ 八) 、 トリエチルアミン等のアミン類を 添加してもよい。 これにより、 生成物の収率、 及び、 ジアステレオ選択性が 向上する。 また、 かかるアミン類を添加する場合、
を添加する前に添加す るのが好ましい。 [0100] The method for reducing an unsaturated hydrocarbon compound according to the present embodiment further includes 1\1, 1\1, 1\1', 1\1'-tetramethylethylenediamine (chome 1^8), triethylamine, etc. The amines may be added. This improves the product yield and diastereoselectivity. When adding such amines, Is preferably added before the addition of.
[0101 ] 本実施形態に係る不飽和炭化水素化合物の還元方法は、 更に、 ピナコール やネオペンチルグリコール等の二価アルコール、 フッ化水素カリウムによる 後処理を行ってもよい。 これにより、 ホウ酸エステル化合物の 0(^基が二価ア ルコール、 又は、 フッ化水素カリウムで保護され、 ホウ酸エステル化合物と 反応系内の水分と反応することにより生じるホウ酸やボロキシン等の副生成 物の生成を防ぐことができる。 ホウ酸エステルとして、 ホウ酸トリメチル等 のホウ酸トリエステルを使用した場合ピナコールを添加することで、 ピナコ
\¥0 2020/175631 36 卩(:17 2020 /008069 [0101] In the method for reducing an unsaturated hydrocarbon compound according to this embodiment, a post-treatment with a dihydric alcohol such as pinacol or neopentyl glycol or potassium hydrogen fluoride may be further performed. As a result, the 0 (^ group of the borate ester compound is protected by a divalent alcohol or potassium hydrogen fluoride, and boric acid, boroxine, etc., which are generated by reacting the borate ester compound with water in the reaction system, When a boric acid triester such as trimethyl borate is used as the boric acid ester, the addition of pinacol can help to prevent the formation of by-products. \¥0 2020/1756 31 36
—ルボリル基によりホウ素化されたアルケン化合物を得ることができる。 ま た、 かかる二価アルコールを添加する場合、 ホウ酸エステル化合物を添加し た後に行うことが好ましい。 — An alkene compound borated by a ruboryl group can be obtained. Further, when such a dihydric alcohol is added, it is preferable to add it after adding the borate ester compound.
[0102] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 還元対象の 不飽和炭化水素化合物であるアルキン化合物は、 下記一般式 III。に示す対応す るジホウ素化アルケン化合物に還元される。 [0102] In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, the alkyne compound that is the unsaturated hydrocarbon compound to be reduced is represented by the following general formula III. Is reduced to the corresponding diboronated alkene compound shown in.
[化 18] [Chemical 18]
ここで、 一般式 111。中、 1^、 、
一般式 の!^。、 、 及び 4 。と同様であり、 及び は、 一般式 11。の(^及び と同様である Where the general formula 111. Medium, 1^,, General formula!^. ,, and 4 . Is the same as, and and is the general formula 11. Of (similar to ^ and
[0103] このように、 本実施形態に係る不飽和炭化水素化合物の還元方法によれば 、 ホウ酸エステルの 1の 〇結合が開裂され、 還元対象の不飽和炭化水素化合 物であるアルケン化合物の炭素間二重結合に対して、 当該二重結合を構成す る各炭素原子に対してホウ酸エステル由来のボリル基が 1つずつ付加される。 これにより、 アルケン化合物が対応のアルカン化合物に還元される。 内部ア ルケンを原料とした場合には、 〇 _13型及び 「3 型どちらのアルケンからも(1 , 2 )体、 及び、 ( , 2(¾)体の混合物がジアステレオ選択的に得られる。 [0103] As described above, according to the method for reducing an unsaturated hydrocarbon compound according to the present embodiment, the ∘ bond of 1 of boric acid ester is cleaved, and the alkene compound which is the unsaturated hydrocarbon compound to be reduced is For the carbon-carbon double bond, one boryl group derived from borate ester is added to each carbon atom constituting the double bond. Thereby, the alkene compound is reduced to the corresponding alkane compound. When the internal alkene is used as the raw material, a mixture of the (1, 2) form and the (, 2(¾) form is obtained diastereoselectively from both __13 type and “3 type” alkenes.
[0104] 本実施形態に係る不飽和炭化水素化合物の還元方法において、 還元された アルカン化合物は、 当該技術分野で公知の精製手段により精製してもよい。 例えば、 還元されたアルカン化合物に対して、 抽出溶媒として、 酢酸エチル 等の有機溶媒を用いて抽出処理し、 得られた抽出液を濃縮した濃縮液をシリ カゲルクロマトグラフィー等の精製担体に供することで精製することができ る。 [0104] In the unsaturated hydrocarbon compound reduction method according to the present embodiment, the reduced alkane compound may be purified by a purification means known in the art. For example, the reduced alkane compound is subjected to extraction treatment using an organic solvent such as ethyl acetate as an extraction solvent, and the concentrated extract obtained is concentrated and applied to a purified carrier such as silica gel chromatography. Can be purified with.
実施例
[0105] 以下、 実施例により本発明を具体的に説明するが、 本発明は、 これらの実 施例に限定されるものではない。 なお、 以下の実施例における SDとしては、 金属ナトリウムを微粒子としてノルマルパラフィン油に分散させた分散体を 使用し、 SDの物質量は、 SDに含まれる金属ナトリウム換算での数値である。 Example [0105] Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited to these Examples. In addition, as SD in the following examples, a dispersion in which metallic sodium is dispersed as fine particles in normal paraffin oil is used, and the substance amount of SD is a numerical value in terms of metallic sodium contained in SD.
[0106] (実施例 1) 不飽和炭化水素化合物の還元反応 (アルキン化合物のアルカン 化合物への還元反応) の検討 Example 1 Investigation of Reduction Reaction of Unsaturated Hydrocarbon Compound (Reduction Reaction of Alkyne Compound to Alkane Compound)
本実施例では、 SDの存在下で、 ジボロン酸エステル化合物を用いて、 アル キン化合物のアルカン化合物への還元を検討した。 In this example, reduction of an alkyne compound to an alkane compound was examined using a diboronic acid ester compound in the presence of SD.
[0107] (実施例 1 - 1) ジフエニルアセチレンの還元反応 (1) (図 1) [0107] (Example 1-1) Reduction reaction of diphenylacetylene (1) (Fig. 1)
撹拌子を入れたガラス試験管にジフエニルアセチレン (0.18 g、 1.0 mmo I ) 及びビス (ピナコラート) ジボロン (0.25 g、 1.0 mmol) を添加し、 試験 管内を窒素ガスで置換した。 続いて、 THF (4 mL) を添加した。 この混合物に 対して SD (9.2 M、 0.26 mU 2.4 mmol) を滴下した。 滴下終了後、 常温で 30 分間撹拌した後、 2 -プロパノール (0.23 mU 3.0 mmol) を添加し、 続いて、 蒸留水 (10 mL) 、 飽和塩化アンモニウム水溶液 (0.5 mL) 、 酢酸エチル (10 mL) を添加して撹拌した。 有機層を抽出し、 残った水層に酢酸エチルを添加 して、 撹拌した。 酢酸エチルによる抽出操作を合計 5回繰り返した。 回収した 有機層を硫酸ナトリウムにより脱水した後、 口ータリーエバポレーターによ り揮発性化合物を全て除去した。 得られた残渣をシリカゲルクロマトグラフ ィー (溶離液:ヘキサン/酢酸エチル =40/1) により精製することで、 化合物 A 1及び化合物 B1の混合物が白色固体として 0.29 g (0.68 mm〇U 68%) 得られ た。 iH NMRにより決定したところ、 生成物中の化合物 A1及び化合物 B1の物質量 比は 1.4 : 1であった。 Diphenylacetylene (0.18 g, 1.0 mmo I) and bis(pinacolato)diboron (0.25 g, 1.0 mmol) were added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas. Subsequently, THF (4 mL) was added. SD (9.2 M, 0.26 mU 2.4 mmol) was added dropwise to this mixture. After completion of dropping, the mixture was stirred at room temperature for 30 minutes, 2-propanol (0.23 mU 3.0 mmol) was added, and then distilled water (10 mL), saturated ammonium chloride aqueous solution (0.5 mL), ethyl acetate (10 mL). Was added and stirred. The organic layer was extracted, ethyl acetate was added to the remaining aqueous layer, and the mixture was stirred. The extraction operation with ethyl acetate was repeated 5 times in total. After the collected organic layer was dehydrated with sodium sulfate, all volatile compounds were removed with a mouth rotary evaporator. By purifying the obtained residue by silica gel chromatography (eluent: hexane/ethyl acetate = 40/1), the mixture of compound A 1 and compound B1 was 0.29 g (0.68 mm 〇 U 68%) as a white solid. ) Got it. As determined by i H NMR, the mass ratio of compound A1 and compound B1 in the product was 1.4:1.
[0108] (実施例 1 -2) ビス (4 -メ トキシフエニル) アセチレンの還元反応 ( 1) (Example 1-2) Reduction Reaction of Bis(4-methoxyphenyl)acetylene (1)
(図 2) (Figure 2)
撹拌子を入れたガラス試験管にヨウ化リチウム (0.27 g。 2.0 mmol) 、 ビ ス (4 -メ トキシフエニル) アセチレン (0.24 g、 1.0 mmol) 及びビス (ピナ コラート) ジボロン (0.25 g、 1.0 mmol) を添加し、 試験管内を窒素ガスで
〇 2020/175631 38 卩(:171? 2020 /008069 Lithium iodide (0.27 g. 2.0 mmol), bis(4-methoxyphenyl)acetylene (0.24 g, 1.0 mmol) and bis(pinacolato)diborone (0.25 g, 1.0 mmol) were placed in a glass test tube containing a stir bar. And add nitrogen gas to the test tube. 〇 2020/175631 38 卩 (: 171? 2020 /008069
置換した。 丁# (3.6 1111) および1\1,1\1,1\1’,1\1’-テトラメチルエチレンジアミン ( 0.4 を添加し、 この混合物に対して (9.9 11/1、 0.20 111し 2.0 111111〇〇 を 滴下した。 滴下終了後、 30分間撹拌した後、 試験管を- 78° に冷却した。 2- プロパノール (0.20 111し 2.6 11111100 を添加し、 続いて、 蒸留水 (10 し) 、 飽和塩化アンモニウム水溶液 (0.5
、 酢酸エチル (10
を添加して撹 拌した。 有機層を抽出し、 残った水層に酢酸エチルを添加して、 撹拌した。 酢酸エチルによる抽出操作を合計 5回繰り返した。 回収した有機層を硫酸ナト リウムにより脱水した後、 口ータリーエバポレーターにより揮発性化合物を 全て除去した。 得られた残渣をシリカゲルクロマトグラフィー (溶離液:へ キサン/酢酸エチル =40/1) により精製することで、 化合物八2及び化合物 82の 混合物が白色固体として 0.37 9 (0.74 111111〇し 74%) 得られた。 1 關(¾により 決定したところ、 生成物中の化合物八2及び化合物 82の物質量比は 75:25であっ た。 Replaced. Ding # (3.6 1111) and 1\1,1\1,1\1',1\1'-tetramethylethylenediamine (0.4 was added and for this mixture (9.9 11/1, 0.20 111 then 2.0 111111 After dropping, stir for 30 minutes and then cool the test tube to -78° 2-Propanol (0.20 111 and 2.6 11111100) was added, followed by distilled water (10) and saturation. Ammonium chloride aqueous solution (0.5 , Ethyl acetate (10 Was added and stirred. The organic layer was extracted, ethyl acetate was added to the remaining aqueous layer, and the mixture was stirred. The extraction operation with ethyl acetate was repeated 5 times in total. The collected organic layer was dehydrated with sodium sulfate, and then all volatile compounds were removed with a mouth rotary evaporator. The obtained residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate = 40/1) to give a mixture of compound 82 and compound 82 as a white solid 0.37 9 (0.74 111111 ○ 74%) Was obtained. The ratio of the compound 82 and the compound 82 in the product was 75:25.
[0109] (実施例 1 -3) ビス (4 -メ トキシフエニル) アセチレンの還元反応 (2) (Example 1-3) Reduction Reaction of Bis(4-methoxyphenyl)acetylene (2)
2 -プロパノールを 2464 -ブチル- 4 -メ トキシフエノールに変更した他は実 施例 1 _ 2と同じ条件で反応を行ったところ、 化合物八2及び化合物 82の混合 物が白色固体として 0.28 9 (0.56 111111〇し 56%) 得られた。 1 關[¾により決定 したところ、 生成物中の化合物八2及び化合物 82の物質量比は 26:74であった。 When the reaction was performed under the same conditions as in Example 1_2 except that 2-propanol was changed to 2464-butyl-4-methoxyphenol, the mixture of Compound 82 and Compound 82 was 0.28 9 ( 0.56 111111 ○ and 56%) was obtained. The ratio of the amounts of compound 82 and compound 82 in the product was 26:74 as determined by the method described in Section 1.
[0110] 以下の実施例 1 _4〜 1 _ 1 1 では、 一部の条件を除いて実施例 1 _ 2と 同じ条件で反応を行った例について説明する。 以下の各実施例における生成 物は、 各実施例における基質に対応する一般式(1)および一般式(2) (下記) で表される。 [0110] In Examples 1_4 to 1_11 below, examples in which the reaction was performed under the same conditions as in Example 1-2 except for some conditions will be described. The product in each of the following examples is represented by the general formula (1) and the general formula (2) (below) corresponding to the substrate in each example.
[化 19] [Chemical 19]
基質 一般式(1) —般式(2)
[0111] (実施例 1 —4) ビス (2 -メ トキシフエニル) アセチレンの還元反応 基質をビス (2 -メ トキシフエニル) アセチレン (下式) (0.249、 1.0 1111110 0 に変更した他は実施例 1 — 2と同じ条件で反応を行ったところ、 生成物が 白色固体として 0.31 9 (0.62 111111〇し 62%) 得られた。 1 關(¾により決定した ところ、 生成物中の一般式(1)および一般式(2)でそれぞれ表される化合物の 物質量比は 74: 26であった。 Substrate General formula (1) — General formula (2) (Examples 1 to 4) Reduction reaction of bis(2-methoxyphenyl)acetylene Example 1 except that the substrate was changed to bis(2-methoxyphenyl)acetylene (the following formula) (0.24 9 , 1.0 1111110 0) -When the reaction was performed under the same conditions as in -2, the product was obtained as a white solid, 0.31 9 (0.62 111 111 ○ 62%). 1關 (determined by ¾, the general formula (1) in the product) And the mass ratio of the compounds represented by the general formula (2) was 74:26.
〇 Me Me〇 〇 Me Me 〇
[0112] (実施例 1 —5) ビス (2 -メチルフエニル) アセチレンの還元反応 (1) 基質をビス (2 -メチルフエニル) アセチレン (下式) (0.21 9、 1.0 11111101 ) に変更した他は実施例 1 — 2と同じ条件で反応を行ったところ、 生成物が 白色固体として 0.37 9 (0.79 111111〇し 79%) 得られた。 1 關(¾により決定した ところ、 生成物中の一般式(1)および一般式(2)でそれぞれ表される化合物の 物質量比は 70 : 30であった。 [0112] (Example 1-5) Reduction reaction of bis (2-methylphenyl) acetylene (1) Example except that the substrate was changed to bis (2-methylphenyl) acetylene (the following formula) (0.21 9 , 1.0 11111101) When the reaction was performed under the same conditions as in 1-2, the product was obtained as a white solid, 0.37 9 (0.79 111 111 ○ then 79%). The amount ratio of the compounds represented by the general formula (1) and the compound represented by the general formula (2) in the product was 70:30, respectively.
[0113] (実施例 1 —6) 2 - (フエニルエチニル) ナフタレンの還元反応 (1) (Example 1-6) Reduction reaction of 2-(phenylethynyl)naphthalene (1)
基質を 2 - (フエニルエチニル) ナフタレン (下式) (0.23 9、 1.0 11111100 に、 1段階目の反応温度を 0° に変更した他は実施例 1 _2と同じ条件で反応 を行ったところ、 生成物が白色固体として 0.32 9 (0.65 111111〇し 65%) 得られ た。 1 H 關(¾により決定したところ、 生成物中の一般式(1)および一般式(2)でそ れぞれ表される化合物の物質量比は 89 : 11であった。
[化 22]
The reaction was carried out under the same conditions as in Example 1_2 except that the substrate was changed to 2-(phenylethynyl)naphthalene (the following formula) (0.239, 1.011111100) and the reaction temperature in the first step was changed to 0 ° . The product was obtained as a white solid, 0.32 9 (0.65 111111 ○ then 65%). 1 H-stain (determined by ¾, respectively, according to the general formula (1) and the general formula (2) in the product) The mass ratio of the represented compounds was 89:11. [Chemical 22]
(実施例 1 —7) 1- (4 -メチルスルファニルフエニル) -2 -フエニルアセチレ ンの還元反応 (Example 1-7) Reduction reaction of 1-(4-methylsulfanylphenyl)-2-phenylacetylene
基質を 1- (4 -メチルスルファニルフエニル) -2 -フエニルアセチレン (下式 ) (0.22 g、 1.0 mmol) に変更した他は実施例 1 _ 2と同じ条件で反応を行 ったところ、 生成物が白色固体として 0.23 g (0.49 mm〇U 49%) 得られた。 1 H NMRにより決定したところ、 生成物中の一般式(1)および一般式(2)でそれぞ れ表される化合物の物質量比は 95: 5であった。 The reaction was carried out under the same conditions as in Example 1_2 except that the substrate was changed to 1-(4-methylsulfanylphenyl)-2-phenylenylacetylene (the following formula) (0.22 g, 1.0 mmol). The product was obtained as a white solid in an amount of 0.23 g (0.49 mm ○ U 49%). As determined by 1 H NMR, the mass ratio of the compounds represented by the general formula (1) and the general formula (2) in the product was 95:5.
[0114] (実施例 1 -8) 1- (4 -ジメチルアミノフエニル) -2 -フエニルアセチレンの 還元反応 (Example 1-8) Reduction Reaction of 1-(4-Dimethylaminophenyl)-2-phenylacetylene
基質を 1- (4 -ジメチルアミノフエニル) -2 -フエニルアセチレン (下式) ( 0.22 g、 1.0 mmol) に変更した他は実施例 1 _ 2と同じ条件で反応を行った ところ、 生成物が白色固体として 0.14 g (0.28 mm〇U 28%) 得られた。 1 H NM Rにより決定したところ、 生成物中の一般式( 1)および一般式(2)でそれぞれ表 される化合物の物質量比は 63: 37であった。 When the reaction was performed under the same conditions as in Example 1-2, except that the substrate was changed to 1-(4-dimethylaminophenyl)-2-phenylenylacetylene (the following formula) (0.22 g, 1.0 mmol), the product was formed. As a white solid, 0.14 g (0.28 mm 〇 U 28%) was obtained. As determined by 1 H N MR, the substance ratio of the compounds represented by the general formula (1) and the general formula (2) in the product was 63:37, respectively.
[0115] (実施例 1 —9) 1-フエニル- 2-tert-プチルアセチレンの還元反応 (1) [0115] (Example 1-9) Reduction Reaction of 1-Phenyl-2-tert-putylacetylene (1)
基質を 1-フエニル- 2-tert-ブチルアセチレン (下式) (0.16 g、 0.99 mmol ) に変更した他は実施例 1 _ 2と同じ条件で反応を行ったところ、 生成物が
白色固体として 0.27 9 (0.65 111111〇し 65%) 得られた。 1 關(¾により決定した ところ、 生成物中の一般式(1)および一般式(2)でそれぞれ表される化合物の 物質量比は 86: 14であった。 When the reaction was carried out under the same conditions as in Example 1_2 except that the substrate was changed to 1-phenyl-2-tert-butylacetylene (the following formula) (0.16 g, 0.99 mmol), the product was found to be 0.27 9 (0.65 111111 ○ 65%) was obtained as a white solid. The ratio of the compounds represented by the general formula (1) and the compound represented by the general formula (2) in the product was 86:14.
[0116] (実施例 1 — 1 0) 1 -フエニル- 2 - (トリメチルシリル) アセチレンの還元反 応 ( 1) (Example 1 — 10) Reduction Reaction of 1-Phenyl-2-(trimethylsilyl)acetylene (1)
基質を 1 -フエニル- 2 - (トリメチルシリル) アセチレン (下式) (0.17 9、 1.0 に、 1段階目の反応温度を 0° に変更し、 また 2 -プロパノールに代 えて 1 -へキサノールを使用した他は実施例 1 — 2と同じ条件で反応を行った ところ、 生成物が白色固体として 0.31 9 (0.73 111111〇し 73%) 得られた。 1 により決定したところ、 生成物中の一般式( 1)および一般式(2)でそれぞれ表 される化合物の物質量比は 46: 54であった。 Substrate 1 - phenyl - 2 - (trimethylsilyl) acetylene (the following formulas) (0.17 9, 1.0, the reaction temperature in the first stage was changed to 0 °, also 2 - using hexanol - propanol in cash forte 1 Other than that, when the reaction was performed under the same conditions as in Examples 1 and 2, the product was 0.31 9 (0.73 111 111 ○ and 73%) as a white solid. When determined by 1 , the general formula in the product ( The mass ratio of the compounds represented by 1) and general formula (2) was 46:54, respectively.
[0117] (実施例 1 - 1 1) 1-フエニル- 2 - (トリイソプロピルシリル) アセチレンの 還元反応 ( 1) [0117] (Example 1-11-1) Reduction Reaction of 1-phenyl-2-(triisopropylsilyl)acetylene (1)
基質を 1-フエニル- 2 - (トリイソプロピルシリル) アセチレン (下式) (0■ 25 g、 0.95 mmol) に、 1段階目の反応温度を 0° Cに変更した他は実施例 1 _Example 1_, except that the substrate was changed to 1-phenyl-2-(triisopropylsilyl)acetylene (the following formula) (0 ■ 25 g, 0.95 mmol) and the reaction temperature in the first step was changed to 0°C.
2と同じ条件で反応を行ったところ、 生成物が白色固体として 0.41 g (0.80 mm〇U 84%) 得られた。 1 H NMRにより決定したところ、 生成物中の一般式(1) および一般式(2)でそれぞれ表される化合物の物質量比は 24: 76であった。 When the reaction was performed under the same conditions as in 2, 0.41 g (0.80 mm 〇 U 84%) of the product was obtained as a white solid. As determined by 1 H NMR, the substance ratio of the compounds represented by the general formula (1) and the general formula (2) in the product was 24:76, respectively.
[化 27]
[0118] (実施例 1 — 1 2) 1 -フエニル- 2 - (ピナコラートボリル) アセチレンの還元 反応 [Chemical 27] (Example 1 — 1 2) 1-Phenyl-2-(pinacolatoboryl) Reduction Reaction of Acetylene
基質を 1 -フエニル- 2 - (ピナコラートボリル) アセチレン (下式) (0.23 9 、 0.95 1^〇〇 に、 1段階目の反応温度を 0° に変更し、 実施例と同じ条件で 反応を行ったところ、 下記の化合物 が白色固体として 0.31 9 (0.63 (^〇し 6 3%) 得られた。 Substrate 1 - phenyl - 2 - (pinacolato boryl) acetylene (the following formulas) (0.23 9, 0.95 1 ^ hundred, the reaction temperature of the first stage was changed to 0 °, the reaction under the same conditions as in Example As a result, the following compound was obtained as a white solid in an amount of 0.319 (0.63 (^○, 63%).
[化 29] [Chemical 29]
Bpin Bpin
化合物 c Compound c
[0119] (実施例 1 - 1 3) ジフエニルアセチレンの還元反応 (2) (図 3) [0119] (Examples 1 to 13) Reduction reaction of diphenylacetylene (2) (Fig. 3)
撹拌子を入れたガラス試験管にヨウ化リチウム (0.27 g。 2.0 mmol) 、 ジ フエニルアセチレン (0.18 g、 1.0 mmol) 及びビス (ピナコラート) ジボロ ン (0.25 g、 1.0 mmol) を添加し、 試験管内を窒素ガスで置換した。 試験管 を氷浴で 0° Cまで冷却したのち、 THF (3.6 mL) および N, N, N’, N’ -テトラメチ ルエチレンジアミン (0.4 mL) を添加し、 この混合物に対して SD (9.9 M、 0. 20 mL、 2.0 mmol) を滴下した。 滴下終了後、 0° Cで 30分間撹拌した後、 ジメ チル硫酸 (0.47 mU 5.0 mmol) を添加した。 反応溶液を室温まで昇温し、 3. 5時間攪拌した。 続いて、 蒸留水 (2.5 mL) 、 飽和塩化アンモニウム水溶液 ( 0.4 mL) 、 酢酸エチル (10 mL) を添加して携拌した。 有機層を抽出し、 残つ た水層に酢酸エチルを添加して、 撹拌した。 酢酸エチルによる抽出操作を合 計 5回繰り返した。 回収した有機層を硫酸ナトリウムにより脱水した後、 口一
〇 2020/175631 43 卩(:171? 2020 /008069 Lithium iodide (0.27 g, 2.0 mmol), diphenylacetylene (0.18 g, 1.0 mmol) and bis(pinacolato)diboron (0.25 g, 1.0 mmol) were added to a glass test tube containing a stir bar and tested. The inside of the tube was replaced with nitrogen gas. After cooling the test tube to 0 °C in an ice bath, THF (3.6 mL) and N, N, N', N'-tetramethylethylenediamine (0.4 mL) were added, and SD (9.9 M) was added to the mixture. , 0.20 mL, 2.0 mmol) was added dropwise. After completion of the dropwise addition, the mixture was stirred at 0°C for 30 minutes, and dimethylsulfate (0.47 mU 5.0 mmol) was added. The reaction solution was heated to room temperature and stirred for 3.5 hours. Subsequently, distilled water (2.5 mL), saturated aqueous ammonium chloride solution (0.4 mL) and ethyl acetate (10 mL) were added and the mixture was stirred. The organic layer was extracted, ethyl acetate was added to the remaining aqueous layer, and the mixture was stirred. The extraction operation with ethyl acetate was repeated 5 times in total. After dehydrating the collected organic layer with sodium sulfate, 〇 2020/175631 43 卩 (:171? 2020 /008069
タリーエバポレーターにより揮発性化合物を全て除去した。 得られた残渣を シリカゲルクロマトグラフィー (溶離液:ヘキサン/酢酸エチル =49/1) によ り精製することで、 化合物 が白色固体として 0.36 9 (0.78 111.1101, 78%) 得 られた。 All the volatile compounds were removed by a tally evaporator. The obtained residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate = 49/1) to give the compound as a white solid, 0.36 9 (0.78 111.1101, 78%).
[0120] (実施例 1 - 1 4) ジフエニルアセチレンの還元反応 (3) (図 4) [0120] (Examples 1 to 14) Reduction reaction of diphenylacetylene (3) (Fig. 4)
撹拌子を入れたガラス試験管にジフエニルアセチレン (0.18 9、 1.0 11111101 ) 及びビス (ピナコラート) ジボロン (0.25 9、 1.0 11111100 を添加し、 試験 管内を窒素ガスで置換した。 試験管を氷浴で 0° まで冷却したのち、 丁# (3.Diphenylacetylene (0.18 9 , 1.0 11111101) and bis(pinacolato)diboron (0.25 9 , 1.0 11111100) were added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas. After cooling to 0 ° , use the # (3.
6
テトラメチルエチレンジアミン (0.4〇!) を添加し 、 この混合物に対して (9.9 11/1、 0.20 111し 2.0 11111100 を滴下した。 滴下終 了後、 0° で 30分間撹拌した後、 1,3 -ジクロロプロパン (0.19 111し 2.0 11111101 ) を添加した。 反応溶液を 60° まで昇温し、 5時間攪拌した。 続いて、 蒸留 水
6 Tetramethylethylenediamine (0.4 〇!) was added, and (9.9 11/1, 0.20 111 and 2.0 11111100) was added dropwise to this mixture. After completion of the addition, the mixture was stirred at 0° for 30 minutes and then 1,3- Dichloropropane (0.19 111 and 2.0 11111101) was added, and the reaction solution was heated to 60 ° and stirred for 5 hours.
) を添加して撹拌した。 有機層を抽出し、 残った水層に酢酸エチルを添加し て、 撹拌した。 酢酸エチルによる抽出操作を合計 5回繰り返した。 回収した有 機層を硫酸ナトリウムにより脱水した後、 口ータリーエバポレーターにより 揮発性化合物を全て除去した。 得られた残渣をシリカゲルクロマトグラフィ - (溶離液:ヘキサン/酢酸エチル =49/1) により精製することで、 化合物巳及 び化合物ドの混合物が白色固体として 0.349 (0.72 (^〇し 72%) 得られた。 1 H 關 により決定したところ、 生成物中の化合物 £及び化合物ドの物質量比は 28: 72であった。 ) Was added and stirred. The organic layer was extracted, ethyl acetate was added to the remaining aqueous layer, and the mixture was stirred. The extraction operation with ethyl acetate was repeated 5 times in total. The recovered organic layer was dehydrated with sodium sulfate, and then all volatile compounds were removed with a mouth rotary evaporator. By purifying the obtained residue by silica gel chromatography (eluent: hexane/ethyl acetate = 49/1), the mixture of compound and compound was 0.34 9 (0.72 (^ 〇 and 72%) as a white solid. As a result of determination by 1 H-screen, the compound amount ratio of the compound £ and the compound de in the product was 28:72.
[0121] (実施例 2) 不飽和炭化水素化合物の還元反応 (アルキン化合物のアルケン 化合物への還元反応) の検討 (Example 2) Investigation of reduction reaction of unsaturated hydrocarbon compound (reduction reaction of alkyne compound to alkene compound)
本実施例では、
の存在下で、 ホウ酸エステル化合物を用いて、 アルキン 化合物のアルケン化合物への還元を検討した。 In this example, In the presence of, the reduction of alkyne compounds to alkene compounds was investigated using boric acid ester compounds.
[0122] (実施例 2- 1) ジフエニルアセチレンの還元反応 (4) (図 5) [0122] (Example 2-1) Reduction reaction of diphenylacetylene (4) (Fig. 5)
撹拌子を入れたガラス試験管内を窒素ガスで置換した。 試験管を氷浴で 0°〇 に冷却した後、 ジフエニルアセチレン (0.18 9、 1.0 1111110〇 、 丁# (4111し) 、
及び、 トリメ トキシボラン (0.67 mU 6.0 mmol) を添加した。 この混合物に 対して SD (10.3 M、 0.19 mU 2.0 mmol) を滴下した。 滴下終了後、 0°Cで 1時 間携拌した後、 ピナコール (0.71 g、 6.0 mmol) を添加して、 室温で更に 30 分間撹拌した。 続いて、 塩酸 (1.0 M、 7.0 mL) を添加し、 酢酸エチル (10 m D による抽出操作を合計 5回繰り返した。 回収した有機層を硫酸ナトリウム により脱水した後、 口ータリーエバポレーターにより揮発性化合物を全て除 去した。 1 H NMR (溶媒: クロロホルム- d) により収率を算出したところ、 化合 物 Gが収率 58%で得られた。 また、 未反応のジフエニルアセチレンの回収率は 32%であった。 The inside of the glass test tube containing the stirring bar was replaced with nitrogen gas. After cooling the test tube to 0 ° 〇 with an ice bath, diphenylacetylene (0.18 9, 1.0 1111110 〇, Ding # (4111), And, trimethoxyborane (0.67 mU 6.0 mmol) was added. SD (10.3 M, 0.19 mU 2.0 mmol) was added dropwise to this mixture. After completion of the dropping, the mixture was stirred at 0°C for 1 hour, pinacol (0.71 g, 6.0 mmol) was added, and the mixture was further stirred at room temperature for 30 minutes. Then, hydrochloric acid (1.0 M, 7.0 mL) was added, and the extraction operation with ethyl acetate (10 m D was repeated 5 times in total. The collected organic layer was dehydrated with sodium sulfate, and then volatilized with a mouth evaporator. All the compounds were removed, and the yield was calculated by 1 H NMR (solvent: chloroform-d) to obtain a compound G in a yield of 58%. It was 32%.
[0123] (実施例 2 -2) ジフエニルアセチレンの還元反応 (5) (図 6) [0123] (Example 2-2) Reduction Reaction of Diphenylacetylene (5) (Fig. 6)
撹拌子を入れたガラス試験管にヨウ化リチウム (0.27 g。 2.0 mmol) 、 ジ フエニルアセチレン (0.18 g、 1.0 mmol) 及びビス (ピナコラート) ジボロ ン (0.25 g、 1.0 mmol) を添加し、 試験管内を窒素ガスで置換した。 試験管 を氷浴で 0° Cまで冷却したのち、 THF (3.6 mL) および N, N, N’, N’ -テトラメチ ルエチレンジアミン (0.4 mL) を添加し、 この混合物に対して SD (9.9 M、 0. 20 mL、 2.0 mmol) を滴下した。 滴下終了後、 0° Cで 30分間撹拌した後、 反応 溶液を室温まで昇温した。 続いて 2, 3 -ジブロモブタン (0.24 mU 2.0 mmol) を加え、 15分間攪拌した。 続いて、 蒸留水 (2.5 mL) 、 飽和塩化アンモニウ ム水溶液 (0.4 mL) 、 酢酸エチル (10 mL) を添加して撹拌した。 有機層を抽 出し、 残った水層に酢酸エチルを添加して、 撹拌した。 酢酸エチルによる抽 出操作を合計 5回繰り返した。 回収した有機層を硫酸ナトリウムにより脱水し た後、 口ータリーエバポレーターにより揮発性化合物を全て除去した。 得ら れた残渣をシリカゲルクロマトグラフィー (溶離液:ヘキサン/酢酸エチル =3 9/1) により精製することで、 化合物 Hが白色固体として 0.25 g (0.58 mmol、 58%) 得られた。 Lithium iodide (0.27 g, 2.0 mmol), diphenylacetylene (0.18 g, 1.0 mmol) and bis(pinacolato)diboron (0.25 g, 1.0 mmol) were added to a glass test tube containing a stir bar and tested. The inside of the tube was replaced with nitrogen gas. After cooling the test tube to 0 °C in an ice bath, THF (3.6 mL) and N, N, N', N'-tetramethylethylenediamine (0.4 mL) were added, and SD (9.9 M) was added to the mixture. , 0.20 mL, 2.0 mmol) was added dropwise. After the completion of dropping, the mixture was stirred at 0°C for 30 minutes, and then the reaction solution was warmed to room temperature. Subsequently, 2,3-dibromobutane (0.24 mU 2.0 mmol) was added, and the mixture was stirred for 15 minutes. Subsequently, distilled water (2.5 mL), saturated ammonium chloride aqueous solution (0.4 mL) and ethyl acetate (10 mL) were added and stirred. The organic layer was extracted, ethyl acetate was added to the remaining aqueous layer, and the mixture was stirred. The extraction operation with ethyl acetate was repeated 5 times in total. After the collected organic layer was dehydrated with sodium sulfate, all volatile compounds were removed with a mouth rotary evaporator. The obtained residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=39/1) to obtain 0.25 g (0.58 mmol, 58%) of compound H as a white solid.
[0124] 以下の実施例 2— 3〜 2— 7では、 一部の条件を除いて実施例 2— 2と同 じ条件で反応を行った例について説明する。 以下の各実施例における生成物 は、 各実施例における基質に対応する一般式(3) (下記) で表される。
〇 2020/175631 45 2020 /008069 [0124] In Examples 2-3 to 2-7 below, examples in which the reaction is performed under the same conditions as in Example 2-2 except for some conditions will be described. The product in each of the following Examples is represented by the general formula (3) (below) corresponding to the substrate in each Example. 〇 2020/1756 31 45 2020 /008069
[化 30] [Chemical 30]
[0125] (実施例 2 -3) 2 - (フエニルエチニル) ナフタレンの還元反応 (2) (Example 2-3) Reduction reaction of 2-(phenylethynyl)naphthalene (2)
基質を 2 - (フエニルエチニル) ナフタレン (下式) (0.23 9、 1.0 11111100 に変更し、 実施例 2と同じ条件で反応を行ったところ、 一般式(3)で表される 化合物が白色固体として 0.26 9 (0.54111111〇し 54%) 得られた。 When the substrate was changed to 2-(phenylethynyl)naphthalene (the following formula) (0.23 9, 1.0 11111100) and the reaction was performed under the same conditions as in Example 2, the compound represented by the general formula (3) was a white solid. As a result, 0.26 9 (0.54111111 ○ and 54%) was obtained.
[0126] (実施例 2-4) ビス (2 -メ トキシフエニル) アセチレンの還元反応 (2) 基質をビス (2 -メ トキシフエニル) アセチレン (下式) (0.249、 1.0 1111110 【) に、 1段階目の反応温度を室温に変更した他は実施例 2 _ 2と同じ条件で 反応を行ったところ、 一般式(3)で表される化合物が白色固体として 0.30 9 ( 0.60 11111101、 60%) 得られた。 [0126] (Example 2-4) Reduction reaction of bis(2-methoxyphenyl)acetylene (2) Using bis(2-methoxyphenyl)acetylene (the following formula) (0.24 9 , 1.0 1111110 [) as a substrate, one step When the reaction was performed under the same conditions as in Example 2_2 except that the eye reaction temperature was changed to room temperature, the compound represented by the general formula (3) was obtained as a white solid in an amount of 0.30 9 (0.60 11111101, 60%). Was given.
[化 32] [Chemical 32]
[0127] (実施例 2— 5) 1 -フエニル- 2464 -ブチルアセチレンの還元反応 (2) 基質を 1 -フエニル- 2 -士6「1;-ブチルアセチレン (下式) (0.15 9、 0■ 94 11111101 ) に、 1段階目の反応温度を室温に変更した他は実施例 2 _ 2と同じ条件で反 応を行ったところ、 一般式(3)で表される化合物が白色固体として 0.32 9 (0. [0127] (Example 2-5) Reduction reaction of 1-phenyl-2464-butylacetylene (2) Substrate 1-phenyl-2-diamine 6"1;-butylacetylene (the following formula) (0.15 9, 0 ■ 94 11111101), the reaction was conducted under the same conditions as in Example 2_2 except that the reaction temperature in the first step was changed to room temperature. As a result, the compound represented by the general formula (3) was found to be 0.32 9 (0.
[0128] (実施例 2— 6) 1 -フエニル- 2 - (トリメチルシリル) アセチレンの還元反応(Example 2-6) Reduction Reaction of 1-phenyl-2-(trimethylsilyl)acetylene
(2) (2)
基質を 1 -フエニル- 2 - (トリメチルシリル) アセチレン (下式) (0.17 9、 1.0 に変更した他は実施例 2— 2と同じ条件で反応を行ったところ、 一般式(3)で表される化合物が白色固体として 0.37 9 (0.861^〇し 86%) 得 られた。 The reaction was carried out under the same conditions as in Example 2-2 except that the substrate was changed to 1-phenyl-2-(trimethylsilyl)acetylene (the following formula) (0.17 9 and 1.0), and was expressed by the general formula (3). The compound was obtained as a white solid in 0.37 9 (0.861^0 and 86%).
[0129] (実施例 2 -7) 1-フエニル- 2 - (トリイソプロピルシリル) アセチレンの還 元反応 (2) (Example 2-7) Reduction Reaction of 1-phenyl-2-(triisopropylsilyl)acetylene (2)
基質を 1-フエニル- 2 - (トリイソプロピルシリル) アセチレン (下式) (0 25 g、 0.95 mmol) に変更した他は実施例 2 _ 2と同じ条件で反応を行ったと ころ、 一般式(3)で表される化合物が白色固体として 0.39 g (0.76 mm〇U 76 %) 得られた。 The reaction was carried out under the same conditions as in Example 2 _ 2 except that the substrate was changed to 1-phenyl-2-(triisopropylsilyl)acetylene (the following formula) (0 25 g, 0.95 mmol), and the general formula (3 0.39 g (0.76 mm ○ U 76%) was obtained as a white solid.
[0130] (実施例 2— 8) 1 -フヱニル-·!-ヘキシンの還元反応 [0130] (Example 2-8) Reduction reaction of 1-phenyl-...!-hexyne
基質を 1 -フエニル- 1 -ヘキシン (下式) (0.16 9、
に、 1段階目 の反応温度を室温に変更した他は実施例 2— 2と同じ条件で反応を行ったと ころ、 化合物 I及び化合物」の混合物が白色固体として 0.21 9 (0.52 (^〇し 52 %) 得られた。 1 關(¾により決定したところ、 生成物中の化合物 I及び化合物」
\¥02020/175631 47 2020/008069 Substitute the substrate with 1-phenyl-1-hexyne (the formula below) (0.16 9, In addition, when the reaction was performed under the same conditions as in Example 2-2 except that the reaction temperature in the first step was changed to room temperature, the mixture of Compound I and Compound ``was 0.21 9 (0.52 (^ ◯. %) was obtained. 1 % (determined by ¾, compound I and compound in product) \\02020/1756 31 47 2020/008069
の物質量比は 75: 25であった。 The substance ratio was 75:25.
化合物 I 化合物」 Compound I Compound"
[0131] (実施例 2-9) ジフエニルアセチレンの還元反応 (6) (図 7) [0131] (Example 2-9) Reduction reaction of diphenylacetylene (6) (Fig. 7)
撹拌子を入れたガラス試験管内を窒素ガスで置換し、 ジフエニルアセチレ ン (0.18 9, 1.0 111111〇〇 、 丁# (4111し) 、 及び、 トリメ トキシボラン (0.34111 し 3.0 11111100 を添加した。 この混合物に対して室温条件下で (10.0 11/1、 0. 22 111し 2.2 11111100 を滴下した。 滴下終了後、 室温で 0.5時間撹拌した後、 ピ ナコール (0.35 9、 3.0 11111101) を添加して、 室温で更に 30分間携拌した。 続 いて、 塩酸 (2.0 11/1、 3.0
を添加し、 酢酸エチル (2
による抽出操作 を合計 4回繰り返した。 回収した有機層を硫酸ナトリウムにより脱水した後、 口—タリ—エバポレーターにより揮発性化合物を全て除去した。 關(¾ (溶媒 : クロロホルム-〇1) により収率を算出したところ、 化合物 が収率 93%で得ら れた。 The inside of a glass test tube containing a stir bar was replaced with nitrogen gas, and diphenylacetylene (0.18 9, 1.0 111111 〇 〇, Ding # (4111)) and trimetoxyborane (0.34111 3.0 3.0 11111100) were added. (10.0 11/1, 0.22 111 and 2.2 11111100) was added dropwise to the mixture at room temperature. After the addition was completed, the mixture was stirred at room temperature for 0.5 hours, and then Pinacol (0.35 9, 3.0 11111101) was added. The mixture was stirred at room temperature for another 30 minutes, followed by hydrochloric acid (2.0 11/1, 3.0 Add ethyl acetate (2 The extraction operation with was repeated 4 times in total. The collected organic layer was dehydrated with sodium sulfate, and then all volatile compounds were removed by a mouth-tally evaporator. When the yield was calculated using a paper (¾ (solvent: chloroform-O1)), the compound was obtained with a yield of 93%.
[0132] 以下の実施例 2— 1 〇〜 2— 1 6では、 一部の条件を除いて実施例 2 _ 9 と同じ条件で反応を行った例について説明する。 以下の各実施例における生 成物は、 各実施例における基質に対応する一般式(4) (下記) で表される。 [0132] In Examples 2-100 to 2-16 below, examples in which the reaction was performed under the same conditions as in Example 2_9 except for some conditions will be described. The product in each of the following Examples is represented by the general formula (4) (below) corresponding to the substrate in each Example.
[化 37] [Chemical 37]
基質 一般式(4) Substrate general formula (4)
[0133] (実施例 2- 1 0) ビス (2 -メ トキシフエニル) アセチレンの還元反応 (3 基質をビス (2 -メ トキシフエニル) アセチレン (下式) (0.249、 1.0 1111110
〇 2020/175631 48 卩(:171? 2020 /008069 (Example 2-10) Reduction reaction of bis(2-methoxyphenyl)acetylene (3 substrates were bis(2-methoxyphenyl)acetylene (the following formula) (0.249, 1.0 1111110) 〇 2020/175631 48 卩 (: 171? 2020 /008069
0 に変更した他は実施例 2— 9と同じ条件で反応を行ったところ、 一般式(4 )で表される化合物が (¾収率 78%で得られた。 When the reaction was performed under the same conditions as in Example 2-9 except that the value was changed to 0, the compound represented by the general formula (4) was obtained (with an yield of 78%).
[化 38] [Chemical 38]
[0134] (実施例 2- 1 1) ビス (4 -メ トキシフエニル) アセチレンの還元反応 (3 基質をビス (4 -メ トキシフエニル) アセチレン (下式) (0.249、 1 0 1111110 0 に変更した他は実施例 2 _ 9と同じ条件で反応を行ったところ、 一般式(4(Example 2-1 1) Reduction reaction of bis(4-methoxyphenyl)acetylene (3 substrates were changed to bis(4-methoxyphenyl)acetylene (the following formula) (0.24 9 , 1 0 1111110 0) Was subjected to the reaction under the same conditions as in Example 2_9, the general formula (4
)で表される化合物が (¾収率 83%で得られた。 The compound represented by () was obtained in a yield of 83%.
[0135] (実施例 2— 1 2) 1- (3 -フルオロフエニル) -2 -フエニルアセチレンの還元 反応 (Example 2-12) Reduction Reaction of 1-(3-Fluorophenyl)-2-phenylacetylene
基質を 1 - (3 -フルオロフエニル) -2 -フエニルアセチレン (下式) (0.20 9 、 1.0 (11(1100 に変更した他は実施例 2— 9と同じ条件で反応を行ったところ 、 一般式(4)で表される化合物が (¾収率 78%で得られた。 When the reaction was carried out under the same conditions as in Example 2-9 except that the substrate was changed to 1-(3-fluorophenyl) -2-phenylacetylene (the following formula) (0.20 9, 1.0 (11 (1100), The compound represented by the general formula (4) was obtained (the yield was 78%).
[化 40] [Chemical 40]
[0136] (実施例 2— 1 3) 1- (3 -メチルスルファニルフエニル) -2 -フエニルアセチ レンの還元反応 (Example 2-13) Reduction Reaction of 1-(3-Methylsulfanylphenyl)-2-phenylacetylene
基質を 1 - (3 -メチルスルファニルフエニル) -2 -フエニルアセチレン (下式 ) (0.22 9、 1.0 1^00 に変更した他は実施例 2— 9と同じ条件で反応を行
〇 2020/175631 49 卩(:171? 2020 /008069 The reaction was performed under the same conditions as in Example 2-9 except that the substrate was changed to 1-(3-methylsulfanylphenyl) -2 -phenylacetylene (the following formula) (0.22 9 , 1.0 1^00). 〇 2020/1756 31 49 卩 (: 171-1? 2020 /008069
ったところ、 一般式(4)で表される化合物が (¾収率 76%で得られた。 As a result, the compound represented by the general formula (4) was obtained (with a yield of 76%).
[化 41] [Chemical 41]
[0137] (実施例 2— 1 4) 士61^ -ブチル メチル[4 - (フエニルエチニル) フエニル] カルバマートの還元反応 (Example 2-14) Reduction Reaction of 61^-Butylmethyl[4-(phenylethynyl)phenyl]carbamate
基質を士6 -ブチル メチル[4 - (フエニルエチニル) フエニル]カルバマー 卜 (下式) (0.31 9、 1.0 11111100 に変更し、 4.0 11111101の ^01^)3およびピナコ —ルを使用した他は実施例 2— 9と同じ条件で反応を行ったところ、 一般式( 4)で表される化合物が (¾収率 81 %で得られた。 Substrate was changed to 6-butylmethyl[4-(phenylethynyl)phenyl]carbamer (formula) (0.319, 1.0 11111100, 4.011111101^01^)3 and pinacol. When the reaction was carried out under the same conditions as in Examples 2-9, the compound represented by the general formula (4) was obtained (with a yield of 81%.
[化 42] [Chemical 42]
[0138] (実施例 2— 1 5) 2 - (フエニルエチニル) ナフタレンの還元反応 (3) 基質を 2 - (フエニルエチニル) ナフタレン (下式) (0.23 9、 1.0 11111100 に変更した他は実施例 2 _ 9と同じ条件で反応を行ったところ、 一般式(4)で 表される化合物が (¾収率 55%で得られた。 (Example 2-15) Reduction reaction of 2-(phenylethynyl)naphthalene (3) The substrate was changed to 2-(phenylethynyl)naphthalene (the following formula) (0.23 9, 1.0 11111100) When the reaction was performed under the same conditions as in Example 2_9, the compound represented by the general formula (4) was obtained (the yield was 55%).
[0139] (実施例 2— 1 6) 1 -シクロヘキセニル- 2 -フエニルアセチレンの還元反応 ( (Example 2-16) Reduction Reaction of 1-Cyclohexenyl-2-phenylacetylene (
3) 3)
基質を 1 -シクロヘキセニル- 2 -フエニルアセチレン (下式) (0.18 9、 1.0
1^00 に変更した他は実施例 2— 9と同じ条件で反応を行ったところ、 一般 式(4)で表される化合物が (¾収率 63%で得られた。 Substitute the substrate with 1-cyclohexenyl-2-phenylacetylene (the following formula) (0.18 9, 1.0 When the reaction was carried out under the same conditions as in Example 2-9 except that the value was changed to 1^00, the compound represented by the general formula (4) was obtained (yield 63%).
[0140] (実施例 2— 1 7) 1-フエニル- 1-ヘキシンの還元反応 (図 8) [0140] (Example 2-17) Reduction reaction of 1-phenyl-1-hexyne (Fig. 8)
撹拌子を入れたガラス試験管内を窒素ガスで置換し、 1-フエニル- 1-ヘキシ ン (0.16 g、 1.0 mmol) % THF (4 mL) % 及び、 トリメ トキシボラン (0.67 m し 6.0 mmol) を添加した。 この混合物に対して室温条件下で SD (10.0 M、 0. 30 mL、 3.0 mmol) を滴下した。 滴下終了後、 室温で 0.5時間撹拌した後、 ピ ナコール (0.71 g、 6.0 mmol) を添加して、 室温で更に 30分間携拌した。 続 いて、 塩酸 (2.0 M、 3.0 mL) を添加し、 酢酸エチル (2 mL) による抽出操作 を合計 4回繰り返した。 回収した有機層を硫酸ナトリウムにより脱水した後、 口ータリーエバポレーターにより揮発性化合物を全て除去した。 iH NMR (溶媒 : クロロホルム- d) により収率を算出したところ、 化合物 Lが収率 80%で得ら れた。 The inside of a glass test tube containing a stir bar was replaced with nitrogen gas, and 1-phenyl-1-hexyne (0.16 g, 1.0 mmol) % THF (4 mL) % and trimethoxyborane (0.67 m and 6.0 mmol) were added. did. SD (10.0 M, 0.30 mL, 3.0 mmol) was added dropwise to this mixture at room temperature. After the dropping was completed, the mixture was stirred at room temperature for 0.5 hour, pinacol (0.71 g, 6.0 mmol) was added, and the mixture was further stirred at room temperature for 30 minutes. Subsequently, hydrochloric acid (2.0 M, 3.0 mL) was added, and the extraction operation with ethyl acetate (2 mL) was repeated 4 times in total. The collected organic layer was dehydrated with sodium sulfate, and then all volatile compounds were removed with a mouth rotary evaporator. When the yield was calculated by i H NMR (solvent: chloroform-d), Compound L was obtained in a yield of 80%.
[0141] 以下の実施例 2_ 1 8〜 2— 20では、 一部の条件を除いて実施例 2 _ 1 [0141] In Examples 2_1 to 8-20 below, Example 2_1 was used except for some conditions.
7と同じ条件で反応を行った例について説明する。 以下の各実施例における 生成物は、 各実施例における基質に対応する一般式(4) (前述) で表される。 An example of performing the reaction under the same conditions as in 7 will be described. The product in each of the following examples is represented by the general formula (4) (described above) corresponding to the substrate in each example.
[0142] (実施例 2— 1 8) 1-フエニル- 1-プロピンの還元反応 [0142] (Example 2-18) Reduction reaction of 1-phenyl-1-propyne
基質を 1-フエニル- 1-プロピン (下式) (0.12 g、 1.0 mmol) に変更した他 は実施例 2— 1 7と同じ条件で反応を行ったところ、 一般式(4)で表される化 合物が NMR収率 80%で得られた。 The reaction was carried out under the same conditions as in Example 2-17 except that the substrate was changed to 1-phenyl-1-propyne (the following formula) (0.12 g, 1.0 mmol), which was represented by the general formula (4). The compound was obtained with an NMR yield of 80%.
[0143] (実施例 2- 1 9) 1 -シクロペンチル- 2-(4 -メ トキシフエニル)アセチレンの
還元反応 [0143] (Example 2-1 9) 1-Cyclopentyl-2-(4-methoxyphenyl)acetylene Reduction reaction
基質を 1 -シクロペンチル- 2-(4 -メ トキシフエニル)アセチレン (下式) (0. 20 9、 1.0
に変更した他は実施例 2_ 1 7と同じ条件で反応を行った ところ、 一般式(4)で表される化合物が (¾収率 28%で得られた。 Substrate 1 - cyclopentyl - 2- (4 - Main Tokishifueniru) acetylene (the following formulas) (0.20 9, 1.0 When the reaction was carried out under the same conditions as in Example 2 — 17 except that the above was changed to, the compound represented by the general formula (4) was obtained (the yield was 28%).
[0144] (実施例 2 -20) 1 -フエニル- 2 - (トリメチルシリル) アセチレンの還元反 応 (3) (Example 2-20) Reduction reaction of 1-phenyl-2-(trimethylsilyl)acetylene (3)
基質を 1 -フエニル- 2 - (トリメチルシリル) アセチレン (0.17 9、 1.0 11111101 ) に変更した他は実施例 2_ 1 7と同じ条件で反応を行ったところ、 一般式( 4)で表される化合物が (¾収率 82%で得られた。 When the reaction was performed under the same conditions as in Example 2_1 17 except that the substrate was changed to 1-phenyl-2-(trimethylsilyl)acetylene (0.17 9, 1.0 11111101 ), the compound represented by the general formula (4) was obtained. (The yield was 82%.
[0145] (実施例 3) 不飽和炭化水素化合物の還元反応 (アルケン化合物のアルカン 化合物への還元反応) の検討 (Example 3) Investigation of reduction reaction of unsaturated hydrocarbon compound (reduction reaction of alkene compound to alkane compound)
本実施例では、 SDの存在下で、 ホウ酸エステル化合物を用いて、 アルケン 化合物のアルカン化合物への還元を検討した。 In this Example, reduction of an alkene compound to an alkane compound was examined using a borate ester compound in the presence of SD.
[0146] (実施例 3_ 1) cis-スチルベンの還元反応 (図 9) [0146] (Example 3_1) Reduction reaction of cis-stilbene (Fig. 9)
撹拌子を入れたガラス試験管に無水ヨウ化リチウム (0.33 g、 2.5 mmol) を添加して、 試験管内を窒素ガスで置換した。 試験管を氷浴で 0°Cに冷却した 後、 続いて、 THF (3.6 mL) 、 N, N, N’, N’ -テトラメチルエチレンジアミン (0. 4 mL) 、 cis-スチルベン (c i s-1 , 2 -ジフエニルエテン) (0.18 mL, 1.0 mmol ) 、 及び、 トリメ トキシボラン (0.67 mU 6.0 mmol) を添加した。 この混合 物に対して SD (9.2 M、 0.27 mU 2.5 mmol) を滴下した。 滴下終了後、 0°Cで 30分間撹拌した後、 ピナコール (0.71 g、 6.0 mmol) を添加して、 室温で更
に 10分間撹拌した。 続いて、 塩酸 (1.0 M、 7.0 mL) を添加し、 酢酸エチル ( 10 mL) による抽出操作を合計 5回繰り返した。 回収した有機層を硫酸ナトリ ウムにより脱水した後、 口ータリーエバポレーターにより揮発性化合物を全 て除去した。 得られた残渣に対しクロロホルム (10 mL) を添加して、 40°Cで 2時間撹拌した。 口ータリーエバポレーターによりクロロホルムを留去した後 、 〗H NMR (溶媒: クロロホルム- d) により収率を算出したところ、 化合物 A1の 収率は 9%、 化合物 B1の収率は 74%であった。 Anhydrous lithium iodide (0.33 g, 2.5 mmol) was added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas. The test tube was cooled to 0 ° C in an ice bath, and then THF (3.6 mL), N, N, N', N'-tetramethylethylenediamine (0.4 mL), cis-stilbene (ci s- 1,2-diphenylethene) (0.18 mL, 1.0 mmol) and trimethoxyborane (0.67 mU 6.0 mmol) were added. SD (9.2 M, 0.27 mU 2.5 mmol) was added dropwise to this mixture. After the dropping was completed, the mixture was stirred at 0°C for 30 minutes, pinacol (0.71 g, 6.0 mmol) was added, and the mixture was further stirred at room temperature. And stirred for 10 minutes. Subsequently, hydrochloric acid (1.0 M, 7.0 mL) was added, and the extraction operation with ethyl acetate (10 mL) was repeated 5 times in total. After the collected organic layer was dehydrated with sodium sulfate, all volatile compounds were removed with a mouth rotary evaporator. Chloroform (10 mL) was added to the obtained residue, and the mixture was stirred at 40°C for 2 hr. After distilling off chloroform with a mouth evaporator, the yield was calculated by 〗H NMR (solvent: chloroform-d). The yield of compound A1 was 9%, and the yield of compound B1 was 74%. ..
[0147] (実施例 3 -2) trans-4 -メ トキシスチルベンの還元反応 (図 1 0) (Example 3 -2) Reduction reaction of trans-4-methoxystilbene (Fig. 10)
撹拌子を入れたガラス試験管に無水ヨウ化リチウム (0.34 g、 2.5 mmol) を添加して、 試験管内を窒素ガスで置換した。 試験管を氷浴で 0°Cに冷却した 後、 続いて、 THF (3.6 mL) 、 N, N, N’, N’ -テトラメチルエチレンジアミン (0.Anhydrous lithium iodide (0.34 g, 2.5 mmol) was added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas. The test tube was cooled to 0 ° C in an ice bath, followed by THF (3.6 mL), N, N, N', N'-tetramethylethylenediamine (0.
4 mL) 、 trans-4 -メ トキシスチルベン (0.21 g, 0.99 mmol) % 及び、 トリメ トキシボラン (0.67 mU 6.0 mmol) を添加した。 この混合物に対して SD (10 .0 M、 0.25 mU 2.5 mmol) を滴下した。 滴下終了後、 0°Cで 30分間撹拌した 後、 ピナコール (0.71 g、 6.0 mmol) を添加して、 0°Cで更に 10分間撹拌した 。 続いて、 塩酸 (1.0 M、 7.0 mL) を添加し、 酢酸エチル (10 mL) による抽 出操作を合計 5回繰り返した。 回収した有機層を硫酸ナトリウムにより脱水し た後、 口ータリーエバポレーターにより揮発性化合物を全て除去した。 得ら れた残渣に対しクロロホルム (10 mL) を添加して、 40°Cで 2時間撹拌した。 口ータリーエバポレーターによりクロロホルムを留去した後、 得られた残渣 をシリカゲルクロマトグラフィー (溶離液:ヘキサン/酢酸エチル =30/1) に より精製することで、 化合物 A3及び化合物 B3の混合物が白色固体として 0.31 g (0.66 mm〇U 67%) 得られた。 1 H NMRにより決定したところ、 生成物中の化 合物 A3及び化合物 B3の物質量比は 93: 7であった。 4 mL), trans-4-methoxystilbene (0.21 g, 0.99 mmol) %, and trimethoxyborane (0.67 mU 6.0 mmol) were added. SD (10.0 M, 0.25 mU 2.5 mmol) was added dropwise to this mixture. After completion of the dropwise addition, the mixture was stirred at 0°C for 30 minutes, pinacol (0.71 g, 6.0 mmol) was added, and the mixture was further stirred at 0°C for 10 minutes. Subsequently, hydrochloric acid (1.0 M, 7.0 mL) was added, and extraction operation with ethyl acetate (10 mL) was repeated 5 times in total. After the collected organic layer was dehydrated with sodium sulfate, all volatile compounds were removed with a mouth rotary evaporator. Chloroform (10 mL) was added to the obtained residue, and the mixture was stirred at 40 ° C for 2 hours. After distilling off chloroform with a mouth evaporator, the resulting residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate = 30/1) to give a white solid mixture of compound A3 and compound B3. As a result, 0.31 g (0.66 mm ○ U 67%) was obtained. As determined by 1 H NMR, the mass ratio of compound A3 and compound B3 in the product was 93:7.
[0148] 以下の実施例 3— 3〜 3_ 1 5では、 一部の条件を除いて実施例 3 _ 2と 同じ条件で反応を行った例について説明する。 以下の各実施例における生成 物は、 各実施例における基質に対応する一般式(5)および一般式(6) (下記) で表される。 ただし基質は、 cis体、 trans体、 および異性体混合物のいずれ
〇 2020/175631 53 2020 /008069 [0148] In Examples 3-3 to 3_15 below, examples in which the reaction was performed under the same conditions as in Example 3_2 except for some conditions will be described. The product in each of the following examples is represented by the general formula (5) and the general formula (6) (below) corresponding to the substrate in each example. However, the substrate can be a cis form, a trans form, or a mixture of isomers. 〇 2020/1756 31 53 2020 /008069
かである。 It is.
[化 48] [Chemical 48]
基質 一般式(5) —般式(6) Substrate General formula (5) — General formula (6)
[0149] (実施例 3 -3) 〇_13-4 -メ トキシスチルベンの還元反応 (Example 3 -3) 〇_13-4-Reduction reaction of methoxystilbene
基質を
トキシスチルベン (下式) (0.10 9, 0.49
に変更し た他は実施例 3— 2と同じ条件で反応を行ったところ、 生成物が白色固体と して 0.15 9 (0.31 1111110し 64%) 得られた。 1 關(¾により決定したところ、 生 成物中の一般式(5)および一般式(6)でそれぞれ表される化合物の物質量比は 9 4: 6であった。 Substrate Toxistilbene (the following formula) (0.10 9 ,0.49 When the reaction was performed under the same conditions as in Example 3-2 except that the above was changed to, the product was 0.15 9 (0.31 1111110, 64%) as a white solid. The ratio of the compounds represented by the general formula (5) and the compound represented by the general formula (6) in the product was 94:6.
[0150] (実施例 3 _4) 4 -メ トキシスチルベン (異性体混合物) の還元反応 [0150] (Example 3 _4) Reduction reaction of 4-methoxystilbene (isomer mixture)
基質を 4 -メ トキシスチルベン (下式) (異性体混合物 £/å = 51/49, 1.1 9 , 5.0
に変更した他は実施例 3— 2と同じ条件で反応を行ったところ 、 生成物が白色固体として 1.7 9 (3.7 111111〇し 73%) 得られた。 1 關(¾により 決定したところ、 生成物中の一般式(5)および一般式(6)でそれぞれ表される 化合物の物質量比は 93: 7であった。 Substrate 4-methoxystilbene (formula) (isomer mixture £/å = 51/49, 1.1 9 ,5.0 Where the exception that the reaction was performed under the same conditions as in Example 3-2, the product is 1.7 9 (3.7 111111_Rei to 73%) as a white solid were obtained. The amount ratio of the compounds represented by the general formula (5) and the compound represented by the general formula (6) in the product was 93:7.
[0151] (実施例 3 _ 5) 8 -スチルベンの還元反応 [0151] (Example 3_5) Reduction reaction of 8-stilbene
基質を 3 -スチルベン (下式) (0.18 9, 1.0 11111100 に変更した他は実 施例 3— 2と同じ条件で反応を行ったところ、 生成物が白色固体として 0.30 9 (0.68 111111〇し 68%) 得られた。 1 關[¾により決定したところ、 生成物中の一 般式(5)および一般式(6)でそれぞれ表される化合物の物質量比は 94: 6であっ た。 When the reaction was performed under the same conditions as in Example 3-2 except that the substrate was changed to 3-stilbene (the following formula) (0.18 9, 1.0 11111100), the product was 0.30 9 (0.68 111111 ○ 68) as a white solid. %) obtained 1 Jour [was determined by ¾, substance amount ratio one general formula (5) and a compound represented respectively by the general formula (6) in the product 94:. 6 met.
基質を〇 -スチルベン (0.18 9, 0.98 11111100 に変更した他は実施例 3 _ 2 と同じ条件で反応を行ったところ、 生成物が白色固体として 0.31 9 (0.72 rn.ii 〇し 74%) 得られた。 1 H 關(¾により決定したところ、 生成物中の一般式(5)お よび一般式(6)でそれぞれ表される化合物の物質量比は 93: 7であった。 When the reaction was performed under the same conditions as in Example 3_2 except that the substrate was changed to ◯-stilbene (0.18 9, 0.98 11111100), 0.31 9 (0.72 rn.ii 〇 and 74%) of the product was obtained as a white solid. The 1 H ratio (determined by ¾ was found to be 93:7 in terms of the mass ratio of the compounds represented by the general formula (5) and the general formula (6), respectively, in the product.
[0153] (実施例 3 _ 7) スチルベン (異性体混合物) の還元反応 (1) [0153] (Example 3_7) Reduction reaction of stilbene (mixture of isomers) (1)
基質をスチルベン (異性体混合物 £/å = 51/49, 0.18 9, 0.97 1^〇1) に変 更した他は実施例 3 _ 2と同じ条件で反応を行ったところ、 生成物が白色固 体として 0.29 9 (0.66 1111110し 68%) 得られた。 1 關(¾により決定したところ 、 生成物中の一般式(5)および一般式(6)でそれぞれ表される化合物の物質量 比は 93: 7であった。 When the reaction was performed under the same conditions as in Example 3_2 except that the substrate was changed to stilbene (isomer mixture £/å = 51/49, 0.18 9, 0.97 1^〇1), the product was found to be a white solid. As a body, 0.29 9 (0.66 1111110 and 68%) was obtained. The amount ratio of the compounds represented by the general formula (5) and the compound represented by the general formula (6) in the product was 93:7.
[0154] (実施例 3 _ 8) 4 - (メチルスルファニル) スチルベン (異性体混合物) の 還元反応 [0154] (Example 3_8) 4-(methylsulfanyl)stilbene (mixture of isomers) reduction reaction
基質を 4 - (メチルスルファニル) スチルベン (下式) (異性体混合物
= 50/50, 0.21 9, 0.93 11111100 に変更した他は実施例 3 _ 2と同じ条件で反 応を行ったところ、 生成物が白色固体として 0.20 9 (0.42 111111〇し 45%) 得ら れた。 1 H 關(¾により決定したところ、 生成物中の一般式(5)および一般式(6)で それぞれ表される化合物の物質量比は 94: 6であった。
〇 2020/175631 55 卩(:171? 2020 /008069 Substrate 4-(methylsulfanyl) stilbene (the following formula) (mixture of isomers = 50/50, 0.21 9 , 0.93 11111100 except that the reaction was carried out under the same conditions as in Example 3_2, the product was 0.20 9 (0.42 111 111 ○ then 45%) as a white solid. It was The 1 H ratio (determined by ¾, the substance ratio of the compounds represented by the general formulas (5) and (6) in the product was 94:6, respectively. 〇 2020/175631 55 卩 (: 171? 2020 /008069
[0155] (実施例 3 _ 9) 2 -メチルスチルベン (異性体混合物) の還元反応 (Example 3_9) Reduction reaction of 2-methylstilbene (mixture of isomers)
基質を 2 -メチルスチルベン (下式) (異性体混合物 £/å = 41/59, 0.20 9, 1.1 1^01) に変更した他は実施例 3— 2と同じ条件で反応を行ったところ、 生成物が白色固体として 0.36 9 (0.81 111111〇し 77%) 得られた。 1 關(¾により 決定したところ、 生成物中の一般式(5)および一般式(6)でそれぞれ表される 化合物の物質量比は 91 : 9であった。 When the reaction was carried out under the same conditions as in Example 3-2 except that the substrate was changed to 2-methylstilbene (the following formula) (isomer mixture £/å = 41/59, 0.20 9 , 1.1 1^01), The product was obtained as a white solid, 0.36 9 (0.81 111111 ○ 77%). 1 (determined by ¾, the substance ratio of the compounds represented by the general formula (5) and the general formula (6) in the product was 91:9.
[0156] (実施例 3 _ 1 0) 2 -メ トキシスチルベン (異性体混合物) の還元反応 (Example 3 _ 10) Reduction reaction of 2-methoxystilbene (isomer mixture)
基質を 2 -メ トキシスチルベン (下式) (異性体混合物 £/å = 43/57, 0.21 9, 1.0 1^00 に変更した他は実施例 3— 2と同じ条件で反応を行ったところ 、 生成物が白色固体として 0.349 (0.74111111〇し 74%) 得られた。 1 關(¾によ り決定したところ、 生成物中の一般式(5)および一般式(6)でそれぞれ表され る化合物の物質量比は 92:8であった。 The reaction was performed under the same conditions as in Example 3-2, except that the substrate was changed to 2-methoxystilbene (the following formula) (isomer mixture £/å = 43/57, 0.21 9, 1.0 1^00). The product was obtained as a white solid, 0.34 9 (0.74111111 〇 74%) 1關 (determined by ¾, represented by the general formula (5) and general formula (6) in the product, respectively) The mass ratio of the compounds was 92:8.
[化 54] [Chemical 54]
[0157] (実施例 3 _ 1 1 ) )-1 -フエニル-·!-プロペンの還元反応 (Example 3 _ 1 1 ))-1-Reduction reaction of -phenyl-...!-Propene
基質を )-1 -フエニル-·!-プロペン (下式) (0.11 9, 0.92 11111100 に変更 した他は実施例 3 _ 2と同じ条件で反応を行ったところ、 生成物が無色液体
として 0.17 g (0.45 mm〇U 49%) 得られた。 1 H NMRにより決定したところ、 生成物中の一般式(5)および一般式(6)でそれぞれ表される化合物の物質量比 は 76: 24であった。 When the reaction was performed under the same conditions as in Example 3_2 except that the substrate was changed to )-1-phenyl-...!-Propene (the following formula) (0.11 9, 0.92 11111100), the product was a colorless liquid. As 0.17 g (0.45 mm 〇 U 49%) was obtained. As determined by 1 H NMR, the substance ratio of the compounds represented by the general formula (5) and the general formula (6) in the product was 76:24.
[0158] (実施例 3_ 1 2) (Z)-1-フエニル- 1-プロペンの還元反応 (Example 3_12) Reduction Reaction of (Z)-1-phenyl-1-propene
基質を(Z)-1-フエニル- 1-プロペン (0.12 g, 1.0 mmol) に変更した他は実 施例 3 _ 2と同じ条件で反応を行ったところ、 生成物が無色液体として 0.20 g (0.54 mm〇U 54%) 得られた。 1 H NMRにより決定したところ、 生成物中の一 般式(5)および一般式(6)でそれぞれ表される化合物の物質量比は 76: 24であっ た。 When the reaction was performed under the same conditions as in Example 3_2 except that the substrate was changed to (Z)-1-phenyl-1-propene (0.12 g, 1.0 mmol), the product was 0.20 g ( 0.54 mm ○ U 54%) was obtained. As determined by 1 H NMR, the mass ratio of the compounds represented by general formula (5) and general formula (6) in the product was 76:24.
[0159] (実施例 3— 1 3) 1-シクロヘキシル- 2 -フエニルエテンの還元反応 (Example 3—13) Reduction Reaction of 1-Cyclohexyl-2-phenylethene
基質を 1-シクロヘキシル- 2 -フエニルエテン (下式) (異性体混合物 E/Z = 78/22, 0.09 g, 0.48 mmol) に変更した他は実施例 3 _ 2と同じ条件で反応 を行ったところ、 生成物が白色固体として 0.08 g (0.17 mm〇U 36%) 得られ た。 1 H NMRにより決定したところ、 生成物中の一般式(5)および一般式(6)でそ れぞれ表される化合物の物質量比は 61 : 39であった。 Reaction was carried out under the same conditions as in Example 3_2 except that the substrate was changed to 1-cyclohexyl-2-phenylethene (the following formula) (isomer mixture E/Z = 78/22, 0.09 g, 0.48 mmol). , 0.08 g (0.17 mm 〇 U 36%) of the product was obtained as a white solid. As determined by 1 H NMR, the mass ratio of the compounds represented by the general formula (5) and the general formula (6) in the product was 61:39.
[0160] (実施例 3— 1 4) 1-(4-tert-プチルフエニル)- 2 -シクロプロピルエテン ( 異性体混合物) の還元反応 (Example 3-14) Reduction Reaction of 1-(4-tert-Putylphenyl)-2-cyclopropylethene (mixture of isomers)
基質を 1-(4-tert-プチルフエニル)- 2 -シクロプロピルエテン (下式) (異 性体混合物 E/Z = 67/33, 0.20 g, 0.99 mmol) に変更した他は実施例 3 _ 2 と同じ条件で反応を行ったところ、 生成物が白色固体として 0.24 g (0.52 mm 〇U 53%) 得られた。 1 H NMRにより決定したところ、 生成物中の一般式(5)お
〇 2020/175631 57 卩(:171? 2020 /008069 Example 3 _ 2 except that the substrate was changed to 1-(4-tert-Putylphenyl)-2-cyclopropylethene (formula below) (heterogeneous mixture E/Z = 67/33, 0.20 g, 0.99 mmol) When the reaction was performed under the same conditions as in (1), 0.24 g (0.52 mm 〇 U 53%) of the product was obtained as a white solid. As determined by 1 H NMR, the general formula (5) and 〇 2020/175631 57 卩 (: 171-1? 2020 /008069
よび一般式⑹でそれぞれ表される化合物の物質量比は 69: 31であった。 And the mass ratio of the compounds represented by the general formula (6) was 69:31.
[化 57] [C57]
[0161] (実施例 3_ 1 5) 1 -フエニル- 1,11 -ドデカジエン (異性体混合物) の還元 反応 [0161] (Example 3_15) Reduction Reaction of 1-phenyl-1,11-dodecadienes (mixture of isomers)
基質を 1 -フエニル- 1,11 -ドデカジエン (下式) (異性体混合物 £/å = 50/5 0, 0.249, 0.97
に変更した他は実施例 3— 2と同じ条件で反応を行 つたところ、 生成物が無色液体として 0.26 9 (0.51 1^〇し 53%) 得られた。 1 H關(¾により決定したところ、 生成物中の一般式(5)および一般式(6)でそれぞ れ表される化合物の物質量比は 50: 50であった。 Substrate 1-phenyl-1,11-dodecadiene (formula) (isomer mixture £/å = 50/5 0, 0.24 9 , 0.97 When the reaction was performed under the same conditions as in Example 3-2 except that the above was changed to, the product was obtained as a colorless liquid, 0.26 9 (0.51 1 ^ 0, 53%). The 1 H ratio (determined by ¾, the ratio of the amount of the compound represented by the general formula (5) and the amount of the compound represented by the general formula (6) in the product was 50:50, respectively.
[0162] (実施例 3— 1 6) 1,2 -ジヒドロナフタレンの還元反応 [0162] (Example 3-16) Reduction Reaction of 1,2-Dihydronaphthalene
基質を 1,2 -ジヒドロナフタレン (下式) (0.13 9, 1.0
に変更した 他は実施例 3— 2と同じ条件で反応を行ったところ、 化合物 11/1が無色液体とし て 0.17 9 (0.441111110し 44%) 得られた。
The substrate is 1,2-dihydronaphthalene (the following formula) (0.13 9, 1.0 When the reaction was performed under the same conditions as in Example 3-2 except that the above was changed to, Compound 11/1 was obtained as a colorless liquid in an amount of 0.17 9 (0.441111110, 44%).
Bpin Bpin
pin pin
化合物 IV! Compound IV!
[0163] (実施例 3— 1 7) )-2 -ピナコラトボリルスチレンの還元反応 [0163] (Example 3-17) )-Reduction reaction of 2-pinacolatoborylstyrene
基質を )-2 -ピナコラトボリルスチレン (下式) (0.18 9, 1.03
に 変更し、 10 11111101のトリメ トキシボランを用いた他は実施例 3 _ 2と同様の条 件で反応を行ったところ、 化合物 1\1が白色固体として 0.31 9 (0.641111110し 62 %) 得られた。 Substrate )-2-Pinacolatoboryl styrene (the following formula) (0.18 9 ,1.03 The reaction was performed under the same conditions as in Example 3_2 except that 10 11111101 was used as the trimethoxyborane, and the compound 1\1 was obtained as a white solid in an amount of 0.31 9 (0.641111110, 62%). ..
[化 62] [Chemical 62]
[0164] (実施例 3_ 1 8) スチルベン (異性体混合物) の還元反応 (2) (図 1 1[0164] (Example 3_18) Reduction reaction of stilbene (mixture of isomers) (2) (Fig. 1 1
) )
撹拌子を入れたガラス試験管に無水ヨウ化リチウム (0.34 g、 2.5 mmol) を添加して、 試験管内を窒素ガスで置換した。 THF (4.0 mL) 、 スチルベン ( 異性体混合物 E/Z = 49/51、 0.18 g, 1.0 mmol) , 及び、 トリメ トキシボラ ン (0.11 mL、 1.0 mmol) を添加した。 試験管をドライアイス/アセトンによ り- 78 °Cに冷却し、 この混合物に対して SD (10.0 M、 0.25 mL、 2.5 mmol) を 滴下した。 滴下終了後、 -78 °Cで 30分間撹拌した後、 ヨウ化メチル (0.19 mL 、 3.0 mmol) を加え、 反応溶液を室温まで昇温し、 さらに 30分間撹拌した。
\¥02020/175631 59 卩(:17 2020 /008069 Anhydrous lithium iodide (0.34 g, 2.5 mmol) was added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas. THF (4.0 mL), stilbene (isomer mixture E/Z = 49/51, 0.18 g, 1.0 mmol), and trimetoxyborane (0.11 mL, 1.0 mmol) were added. The test tube was cooled to -78 °C with dry ice/acetone, and SD (10.0 M, 0.25 mL, 2.5 mmol) was added dropwise to this mixture. After completion of dropping, the mixture was stirred at -78 ° C for 30 minutes, methyl iodide (0.19 mL, 3.0 mmol) was added, the reaction solution was warmed to room temperature, and further stirred for 30 minutes. \¥02020/175631 59 卩 (: 17 2020 /008069
ピナコール (0.249、 2.0 11111100 を添加して、 更に 10分間撹拌し、 続いて塩 酸 (1.0 11/1、
を添加し、 酢酸エチル
による抽出操作を合計 5 回繰り返した。 回収した有機層を硫酸ナトリウムにより脱水した後、 ロータ リーエバポレーターにより揮発性化合物を全て除去した。 得られた残渣に対 しクロロホルム
を添加して、 40°〇で 2時間撹拌した。 口ータリーエ バポレーターによりクロロホルムを留去した後、 得られた残渣をシリカゲル クロマトグラフィー (溶離液:ヘキサン/酢酸エチル =30/1) により精製する ことで、 化合物 及び化合物 0の混合物が白色固体として 0.22 9 (0.69 111(1101、 69%) 得られた。 1 關(¾により決定したところ、 生成物中の化合物 及び化合 物 0の物質量比は 5: 95であった。 Add pinacol (0.249, 2.0 11111100) and stir for another 10 minutes, then add hydrochloric acid (1.0 11/1, Add ethyl acetate The extraction operation with was repeated 5 times in total. The collected organic layer was dehydrated with sodium sulfate, and then all volatile compounds were removed with a rotary evaporator. Chloroform was added to the obtained residue. Was added and the mixture was stirred at 40° for 2 hours. After distilling off the chloroform by mouth Tarie Baporeta, The resulting residue was purified by silica gel chromatography is purified by (eluent hexane / ethyl acetate = 30/1), 0.22 mixture of compound and compound 0 as a white solid 9 (0.69 111 (1101, 69%) was obtained. The amount ratio of the compound and the compound 0 in the product was 5: 95, as determined by 1 ).
[0165] 以下の実施例 3 _ 1 9および 3— 20では、 一部の条件を除いて実施例 3 - 1 8と同じ条件で反応を行った例について説明する。 以下の各実施例にお ける生成物は、 各実施例における基質に対応する一般式(7)および一般式(8) (下記) で表される。 ただし基質は、 3^体および異性体混合物のいずれか である。 [0165] In Examples 3 _ 19 and 3-20 below, examples in which the reaction was performed under the same conditions as in Example 3-18 except for some conditions will be described. The product in each of the following examples is represented by the general formula (7) and the general formula (8) (below) corresponding to the substrate in each example. However, the substrate is either a 3^ body or a mixture of isomers.
[化 63] [Chemical 63]
[0166] (実施例 3_ 1 9) 1;「3 -スチルベンの還元反応 (Example 3_1 9) 1; “Reduction reaction of 3-stilbene
基質を 3 -スチルベン (0.18 9, 1.01 1111110〇 に、 ヨウ化メチルをヨウ化 プチル (0.55、 3.0 11111100 に変更した他は実施例 3 _ 1 8と同じ条件で反応 を行ったところ、 生成物が白色固体として 0.149 (0.39 1^〇し 39%) 得られ た。 1 H 關(¾により決定したところ、 生成物中の一般式(7)および一般式(8)でそ れぞれ表される化合物の物質量比は 10:90であった。 The reaction was performed under the same conditions as in Example 3 _ 18 except that the substrate was changed to 3-stilbene (0.18 9, 1.01 1111110 〇) and methyl iodide was changed to butyl iodide (0.55, 3.0 11111100). 0.14 9 (0.39 1^〇 then 39%) was obtained as a white solid. 1 H (determined by ¾, represented by the general formula (7) and general formula (8) in the product, respectively) The mass ratio of these compounds was 10:90.
[0167] (実施例 3 _ 20) スチルベン (異性体混合物) の還元反応 (3)
基質をスチルベン (異性体混合物 E/Z = 50/50、 0.18 g, 0.98 mmol) に、 ヨウ化メチルを塩化アリル (0.23 g、 3.0 mmol) に変更した他は実施例 3—(Example 3 _ 20) Reduction reaction of stilbene (mixture of isomers) (3) Example 3—except that the substrate was changed to stilbene (isomer mixture E/Z = 50/50, 0.18 g, 0.98 mmol) and methyl iodide was changed to allyl chloride (0.23 g, 3.0 mmol)
2と同じ条件で反応を行ったところ、 生成物が白色固体として 0.21 g (0.60 mm〇U 61%) 得られた。 1 H NMRにより決定したところ、 生成物中の一般式(7) および一般式(8)でそれぞれ表される化合物の物質量比は 3: 97であった。 When the reaction was performed under the same conditions as in 2, 0.21 g (0.60 mm U 61%) of the product was obtained as a white solid. As determined by 1 H NMR, the substance ratio of the compounds represented by the general formula (7) and the general formula (8) in the product was 3:97.
[0168] (実施例 4) 不飽和炭化水素化合物の還元反応 (アルケン化合物のアルカン 化合物への還元反応) の検討 (Example 4) Investigation of reduction reaction of unsaturated hydrocarbon compound (reduction reaction of alkene compound to alkane compound)
本実施例では、 SDの存在下で、 ホウ酸エステル化合物を用いて、 アルケン 化合物のアルカン化合物への還元を検討した。 具体的には、 スチレンの還元 反応 (図 1 2) を検討した。 In this example, reduction of an alkene compound to an alkane compound was examined using a borate ester compound in the presence of SD. Specifically, we examined the reduction reaction of styrene (Fig. 12).
[0169] 撹拌子を入れたガラス試験管に無水ヨウ化リチウム (0.33 g、 2.5 mmol) を添加して、 試験管内を窒素ガスで置換した。 試験管を氷浴で 0°Cに冷却した 後、 続いて、 THF (3.6 mL) 、 N, N, N’, N’ -テトラメチルエチレンジアミン (0.[0169] Anhydrous lithium iodide (0.33 g, 2.5 mmol) was added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas. The test tube was cooled to 0 ° C in an ice bath, followed by THF (3.6 mL), N, N, N', N'-tetramethylethylenediamine (0.
4 mL) 、 スチレン (0.11 mL, 1.0 mmol) , 及び、 トリメ トキシボラン (0.67 mL、 6.0 mmol) を添加した。 この混合物に対して SD (9.2 M、 0.27 mL、 2.5 mmol) を滴下した。 滴下終了後、 0°Cで 30分間撹拌した後、 ピナコール (0.71 g、 6.0 mmol) を添加して、 室温で更に 10分間撹拌した。 続いて、 塩酸 (1.0 M、 7.0 mL) を添加し、 酢酸エチル (10 mL) による抽出操作を合計 5回繰り 返した。 回収した有機層を硫酸ナトリウムにより脱水した後、 口ータリーエ バポレーターにより揮発性化合物を全て除去した。 得られた残渣に対しクロ ロホルム (10 mL) を添加して、 40°Cで 2時間撹拌した。 口ータリーエバポレ —夕一によりクロロホルムを留去した後、 得られた残渣をシリカゲルクロマ トグラフィー (溶離液:ヘキサン/酢酸エチル =40/1) により精製することで 、 化合物 R (ラセミ体) が白色固体として 0.12 g (0.33 mm〇U 33%) 得られ た。 iH NMRにより決定したところ、 生成物が目的化合物であることが確認され た。 4 mL), styrene (0.11 mL, 1.0 mmol), and trimetoxyborane (0.67 mL, 6.0 mmol) were added. SD (9.2 M, 0.27 mL, 2.5 mmol) was added dropwise to this mixture. After completion of the dropwise addition, the mixture was stirred at 0°C for 30 minutes, pinacol (0.71 g, 6.0 mmol) was added, and the mixture was further stirred at room temperature for 10 minutes. Subsequently, hydrochloric acid (1.0 M, 7.0 mL) was added, and the extraction operation with ethyl acetate (10 mL) was repeated 5 times in total. The collected organic layer was dehydrated with sodium sulfate, and then all volatile compounds were removed with a mouth rotary evaporator. Chloroform (10 mL) was added to the obtained residue, and the mixture was stirred at 40°C for 2 hr. After the chloroform was removed by evaporation, the residue obtained was purified by silica gel chromatography (eluent: hexane/ethyl acetate = 40/1) to give compound R (racemic compound) as a white solid. As a result, 0.12 g (0.33 mm 〇 U 33%) was obtained. As determined by i H NMR, the product was confirmed to be the target compound.
[0170] (実施例 5) 芳香族炭化水素化合物のジボリル化反応の検討 (Example 5) Investigation of diborylation reaction of aromatic hydrocarbon compounds
本実施例では、 SDの存在下で、 ホウ酸エステル化合物を用いて、 芳香族炭
化水素化合物のジボリル化反応を検討した。 具体的には、 フエナントレンの 還元反応 (図 1 3) を検討した。 In this example, in the presence of SD, a boric acid ester compound was used to The diborylation reaction of hydrogenated compounds was investigated. Specifically, we examined the reduction reaction of phenanthrene (Fig. 13).
[0171] 攪拌子を入れたガラス試験管に無水ヨウ化リチウム (0.33 g、 2.5 mmol) を添加して、 試験管内を窒素ガスで置換した。 試験管を氷浴で 0°Cに冷却した 後、 続いて、 THF (3.6 mL) 、 N, N, N’, N’ -テトラメチルエチレンジアミン (0.[0171] Anhydrous lithium iodide (0.33 g, 2.5 mmol) was added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas. The test tube was cooled to 0 ° C in an ice bath, followed by THF (3.6 mL), N, N, N', N'-tetramethylethylenediamine (0.
4 mL) 、 フエナントレン (0 18 g, 1 0 mmo I) 、 及び、 トリメ トキシボラン (0.67 mU 6.0 mmol) を添加した。 この混合物に対して SD (9.2 M、 0.27 mL 、 2.5 mmol) を滴下した。 滴下終了後、 0°Cで 30分間撹拌した後、 ピナコール (0.71 g、 6.0 mmol) を添加して、 室温で更に 10分間撹拌した。 続いて、 塩 酸 (1.0 M、 7.0 mL) を添加し、 酢酸エチル (10 mL) による抽出操作を合計 5 回繰り返した。 回収した有機層を硫酸ナトリウムにより脱水した後、 ロータ リーエバポレーターにより揮発性化合物を全て除去した。 得られた残渣に対 しクロロホルム (10 mL) を添加して、 40°Cで 2時間撹拌した。 口ータリーエ バポレーターによりクロロホルムを留去した後、 1 H NMR (溶媒: クロロホルム -d) により収率を算出したところ、 化合物 Sの収率は 37%であった。 4 mL), phenanthrene (0 18 g, 10 mmo I), and trimethoxyborane (0.67 mU 6.0 mmol) were added. SD (9.2 M, 0.27 mL, 2.5 mmol) was added dropwise to this mixture. After completion of the dropwise addition, the mixture was stirred at 0°C for 30 minutes, pinacol (0.71 g, 6.0 mmol) was added, and the mixture was further stirred at room temperature for 10 minutes. Subsequently, hydrochloric acid (1.0 M, 7.0 mL) was added, and the extraction operation with ethyl acetate (10 mL) was repeated 5 times in total. The collected organic layer was dehydrated with sodium sulfate, and then all volatile compounds were removed with a rotary evaporator. Chloroform (10 mL) was added to the obtained residue, and the mixture was stirred at 40°C for 2 hr. After distilling off chloroform with a mouth evaporator, the yield was calculated by 1 H NMR (solvent: chloroform -d), and the yield of compound S was 37%.
[0172] (実施例 6) アレン化合物のジボリル化反応の検討 [0172] (Example 6) Examination of diborylation reaction of allene compound
本実施例では、 SDの存在下で、 ホウ酸エステル化合物を用いて、 アレン化 合物のジボリル化反応を検討した。 具体的には、 4 -メ トキシフエニルアレン の還元反応 (図 1 4) を検討した。 In this example, a diborylation reaction of an allene compound was examined using a borate ester compound in the presence of SD. Specifically, we examined the reduction reaction of 4-methoxyphenylarene (Fig. 14).
[0173] 撹拌子を入れたガラス試験管を窒素ガスで置換した。 THF (4 mL) 、 4 -メ ト キシフエニルアレン (0.15 g, 1.0 mmol) % 及び、 トリメ トキシボラン (0.3 4 mL、 3.0 mmol) を添加した。 この混合物に対して SD (9.9 M、 0.20 mL、 2.0 mmol) を滴下した。 滴下終了後、 室温で 30分間撹拌した後、 ピナコール (0. 36 g、 3.0 mmol) を添加して、 室温で更に 10分間撹拌した。 続いて、 塩酸 (1 .0 M, 7.0 mL) を添加し、 酢酸エチル (10 mL) による抽出操作を合計 5回繰 り返した。 回収した有機層を硫酸ナトリウムにより脱水した後、 口ータリー エバポレーターにより揮発性化合物を全て除去した。 1 H NMR (溶媒: クロロホ ルム -d) により収率を算出したところ、 化合物 Tの収率は 55%であった。
〇 2020/175631 62 卩(:171? 2020 /008069 [0173] The glass test tube containing the stir bar was replaced with nitrogen gas. THF (4 mL), 4-methoxyphenylarene (0.15 g, 1.0 mmol) % and trimethoxyborane (0.34 mL, 3.0 mmol) were added. SD (9.9 M, 0.20 mL, 2.0 mmol) was added dropwise to this mixture. After completion of dropping, the mixture was stirred at room temperature for 30 minutes, pinacol (0.36 g, 3.0 mmol) was added, and the mixture was further stirred at room temperature for 10 minutes. Subsequently, hydrochloric acid (1.0 M, 7.0 mL) was added, and the extraction operation with ethyl acetate (10 mL) was repeated 5 times in total. After the collected organic layer was dehydrated with sodium sulfate, all volatile compounds were removed with a mouth rotary evaporator. When the yield was calculated by 1 H NMR (solvent: chloroform-d), the yield of compound T was 55%. 〇2020/175631 62 卩(: 171-1?2020/008069
産業上の利用可能性 Industrial availability
[0174] 本発明は、 不飽和炭化水素化合物の還元が必要とされる全ての技術分野、 特には、 天然物全合成や、 医農薬、 及び、 液晶や有機 !_等の電子材料、 並び に、 それらの中間体等の多種多様な機能性材料の有機合成技術等において有 用な技術である。
INDUSTRIAL APPLICABILITY [0174] The present invention relates to all technical fields in which reduction of unsaturated hydrocarbon compounds is required, in particular, total synthesis of natural products, medical and agricultural chemicals, and electronic materials such as liquid crystal and organic! , It is a useful technology in organic synthesis technology of various functional materials such as intermediates.
Claims
〔ここで、 一般式 中、
それぞれ独立的に、 水素原子、 アルカリ金属と反応しない置換基を有していてもよい脂肪族炭化水素 基、 脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環基であり、
と とは互いに結合して環を形成してい てもよい〕 に示す不飽和炭化水素化合物であるアルキン化合物と、 —般式 II3 [Where, in the general formula, Each independently, a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent that does not react with an alkali metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or An aromatic heterocyclic group, And may form a ring by bonding to each other], and an alkyne compound represented by the general formula II 3
〔ここで、 一般式 II3中、 、 、 及び は、 それぞれ独立的に、 アルカリ金属と反応しない置換基を有していてもよい脂肪族炭化水素 基、 脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環基であり、
と とは互いに結合して環を形成してい てもよく、 と とは互いに結合して環を形成していてもよい〕 に 示すジボロン酸エステル化合物とを、 反応させることにより、[Wherein, in general formula II 3 ,,, and, each independently, an aliphatic hydrocarbon group which may have a substituent which does not react with an alkali metal, an alicyclic hydrocarbon group, an alicyclic group A heterocyclic group, an aromatic hydrocarbon group, or an aromatic heterocyclic group, And may combine with each other to form a ring, and and may combine with each other to form a ring], and a diboronic acid ester compound represented by
—般式 III3
〇 2020/175631 64 卩(:171? 2020 /008069 — General formula III 3 〇 2020/175631 64 卩 (: 171? 2020 /008069
[化 3] [Chemical 3]
〔ここで、 一般式 III3中、 及び は、 一般式 I3の 及び と同様で あり、 、 、
一般式 113の(^、 、
ある〕 に示すジホウ素化アルカン化合物を生成して不飽和炭化水素化 合物を還元する、 不飽和炭化水素化合物の還元方法。 [Wherein and in the general formula III 3 , and are the same as and in the general formula I 3 , In general formula 11 3 (^,, [1] A method for reducing an unsaturated hydrocarbon compound, which comprises forming a diboronated alkane compound to reduce an unsaturated hydrocarbon compound.
[請求項 2] 不飽和炭化水素化合物の還元方法であって、 [Claim 2] A method for reducing an unsaturated hydrocarbon compound, comprising:
反応溶媒中、 アルカリ金属を分散溶媒に分散させた分散体の存在下 で、 In a reaction solvent, in the presence of a dispersion prepared by dispersing an alkali metal in a dispersion solvent,
_般式 _ General formula
〔ここで、 一般式 中、
それぞれ独立的に、 水素原子、 ナトリウムと反応しない置換基を有していてもよい脂肪族炭化水素基 、 脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳 香族複素環基であり、
と とは互いに結合して環を形成していて もよい〕 に示す不飽和炭化水素化合物であるアルキン化合物と、 一般式 1 [Where, in the general formula, Independently of each other, a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent that does not react with sodium, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or an aromatic hydrocarbon group. An aromatic heterocyclic group, And may be bonded to each other to form a ring] and an alkyne compound that is an unsaturated hydrocarbon compound,
[化 5] [Chemical 5]
〔ここで、 一般式 11中、 1^、 (¾■及び は、 それぞれ独立的に、 アル カリ金属と反応しない置換基を有していてもよい脂肪族炭化水素基、
〇 2020/175631 65 卩(:171? 2020 /008069 [Here, in the formula 11, 1 ^, (¾ ■ Oyobi are each independently, alkali metal and does not react with an optionally substituted aliphatic hydrocarbon group, 〇 2020/175631 65 卩 (: 171-1? 2020 /008069
脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香 族複素環基であり、 ■と とは互いに結合して環を形成していても よい〕 に示すホウ酸エステル化合物とを、 反応させることにより、 一般式 11 Alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group or an aromatic heterocyclic group, boric shown in bonded to each other and ■ may form a ring] By reacting with an acid ester compound, the compound of the general formula 11
[化 6] [Chemical 6]
あり、 (¾■及び は、 一般式 1 の ■及び と同様である〕 に示すジ ホウ素化アルケン化合物を生成して不飽和炭化水素化合物を還元する 、 不飽和炭化水素化合物の還元方法。 Yes, (¾ ■ Oyobi are of the general formula 1 ■ Oyobi and generates a di-boronated alkene compounds shown in the a] similar reducing unsaturated hydrocarbon compounds, the reduction method of the unsaturated hydrocarbon compound.
[請求項 3] 不飽和炭化水素化合物の還元方法であって、 [Claim 3] A method for reducing an unsaturated hydrocarbon compound, comprising:
反応溶媒中、 アルカリ金属を分散溶媒に分散させた分散体の存在下 で、 In a reaction solvent, in the presence of a dispersion prepared by dispersing an alkali metal in a dispersion solvent,
_般式 I。 _ General formula I.
[化 7] [Chemical 7]
〔ここで、 一般式 I。中、 1^、 、
それぞれ独立的に、 水 素原子アルカリ金属と反応しない置換基を有していてもよい脂肪族炭 化水素基、 脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香族複素環基であり、 と 又は とは互いに結合して環 を形成していてもよく、 又は とは互いに結合して環を形成 していてもよく、 と とは互いに結合して環を形成していてもよ
〇 2020/175631 66 卩(:171? 2020 /008069 [Where General Formula I. Medium, 1^,, Each independently, an aliphatic hydrocarbon group which may have a substituent that does not react with a hydrogen atom alkali metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or , Is an aromatic heterocyclic group, and or may be bonded to each other to form a ring, or may be bonded to each other to form a ring, and is bonded to each other to form a ring. Can be formed 〇 2020/175631 66 卩(: 171-1?2020/008069
く、 と とは互いに結合して環を形成していてもよい〕 に示す不 飽和炭化水素化合物であるアルケン化合物と、 And may be bonded to each other to form a ring], and an alkene compound which is an unsaturated hydrocarbon compound,
—般式 II。 — General formula II.
[化 8] [Chemical 8]
〔ここで、 一般式 II。中、 (^、 [¾10。及び は、 それぞれ独立的に、 アル カリ金属と反応しない置換基を有していてもよい脂肪族炭化水素基、 脂環式炭化水素基、 脂環式複素環基、 芳香族炭化水素基、 又は、 芳香 族複素環基であり、
とは互いに結合して環を形成していても よい〕 に示すホウ酸エステル化合物とを、 反応させることにより、 —般式 III。 [Where General Formula II. In the formula, (^, [¾ 10, and are each independently an aliphatic hydrocarbon group which may have a substituent which does not react with an alkali metal, an alicyclic hydrocarbon group, and an alicyclic heterocycle. A group, an aromatic hydrocarbon group, or an aromatic heterocyclic group, May be bonded to each other to form a ring], and are reacted with a boric acid ester compound represented by the general formula III.
[化 9] [Chemical 9]
-〇/ ヽ〇- -〇/ヽ〇-
〔ここで、 一般式 111。中、 1^、 、
一般式
、
。と同様であり、 1^。及び 1^。は、 一般式 II。の 1^0。及び 1^。と同様 である〕 に示すジホウ素化アルカン化合物を生成して不飽和炭化水素 化合物を還元する、 不飽和炭化水素化合物の還元方法。 [Where General Formula 111. Medium, 1^,, General formula , .. Is the same as, 1^. And 1^. Is the general formula II. Of 1^ 0 . And 1^. The same as the above]], the unsaturated hydrocarbon compound is reduced by forming a diboronated alkane compound to reduce the unsaturated hydrocarbon compound.
[請求項 4] 前記アルカリ金属を分散溶媒に分散させた分散体の前記不飽和炭化 水素化合物に対するモル比は、 2以上 4以下である、 請求項 1〜 3の何 れか一項に記載の不飽和炭化水素化合物の還元方法。
[Claim 4] The molar ratio of the dispersion in which the alkali metal is dispersed in a dispersion solvent to the unsaturated hydrocarbon compound is 2 or more and 4 or less, The method according to any one of claims 1 to 3. A method for reducing unsaturated hydrocarbon compounds.
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