JP5032161B2 - 光学活性なビス(アルキニルホスフィノ)エタンーボラン誘導体及びその製造方法 - Google Patents
光学活性なビス(アルキニルホスフィノ)エタンーボラン誘導体及びその製造方法 Download PDFInfo
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- JP5032161B2 JP5032161B2 JP2007060784A JP2007060784A JP5032161B2 JP 5032161 B2 JP5032161 B2 JP 5032161B2 JP 2007060784 A JP2007060784 A JP 2007060784A JP 2007060784 A JP2007060784 A JP 2007060784A JP 5032161 B2 JP5032161 B2 JP 5032161B2
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- ethane
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- RCLPHCJMHYUGSX-UHFFFAOYSA-N B.CC Chemical class B.CC RCLPHCJMHYUGSX-UHFFFAOYSA-N 0.000 title claims description 11
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 49
- -1 Alkynyl lithium Chemical compound 0.000 claims description 35
- 230000005595 deprotonation Effects 0.000 claims description 8
- 238000010537 deprotonation reaction Methods 0.000 claims description 8
- 229910052744 lithium Inorganic materials 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 230000031709 bromination Effects 0.000 claims description 6
- 238000005893 bromination reaction Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 238000005691 oxidative coupling reaction Methods 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- ADWWHWHUDRLYFK-UHFFFAOYSA-N B.CP(Br)C(C)(C)C Chemical compound B.CP(Br)C(C)(C)C ADWWHWHUDRLYFK-UHFFFAOYSA-N 0.000 claims description 4
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 3
- LJPFWCBUSPMLGW-UHFFFAOYSA-N B.CPC(C)(C)C Chemical compound B.CPC(C)(C)C LJPFWCBUSPMLGW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 43
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical class CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 34
- 229910052717 sulfur Inorganic materials 0.000 description 26
- 239000011541 reaction mixture Substances 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- 125000000217 alkyl group Chemical group 0.000 description 11
- 239000011982 enantioselective catalyst Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 239000003446 ligand Substances 0.000 description 9
- 239000010948 rhodium Substances 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 229910052703 rhodium Inorganic materials 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 238000011914 asymmetric synthesis Methods 0.000 description 6
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 238000004679 31P NMR spectroscopy Methods 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 229910000085 borane Inorganic materials 0.000 description 4
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 4
- GNSLYOGEBCFYDE-UHFFFAOYSA-N lithium;ethynylbenzene Chemical compound [Li+].[C-]#CC1=CC=CC=C1 GNSLYOGEBCFYDE-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000005103 alkyl silyl group Chemical group 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 238000006138 lithiation reaction Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- MQLASKWWRMSSBU-UHFFFAOYSA-N CCP(C#CC(C)(C)C)C(C)(C)C Chemical compound CCP(C#CC(C)(C)C)C(C)(C)C MQLASKWWRMSSBU-UHFFFAOYSA-N 0.000 description 2
- PCIPEERXEVWFIF-UHFFFAOYSA-N CCP(C#CC)C(C)(C)C Chemical compound CCP(C#CC)C(C)(C)C PCIPEERXEVWFIF-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 229940125907 SJ995973 Drugs 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
- 125000002723 alicyclic group Chemical group 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 2
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- ZKPRFGFRFQXTIU-UHFFFAOYSA-N ctk1a3528 Chemical class C1=CC=CC2=C(O3)C=CC3=C21 ZKPRFGFRFQXTIU-UHFFFAOYSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 150000001993 dienes Chemical class 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- XZMHJYWMCRQSSI-UHFFFAOYSA-N n-[5-[2-(3-acetylanilino)-1,3-thiazol-4-yl]-4-methyl-1,3-thiazol-2-yl]benzamide Chemical compound CC(=O)C1=CC=CC(NC=2SC=C(N=2)C2=C(N=C(NC(=O)C=3C=CC=CC=3)S2)C)=C1 XZMHJYWMCRQSSI-UHFFFAOYSA-N 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- 238000012746 preparative thin layer chromatography Methods 0.000 description 2
- RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 2
- 150000003283 rhodium Chemical class 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- ASQOQJYHIYYTEJ-GBESFXJTSA-N (1r,7s,9as)-7-decyl-2,3,4,6,7,8,9,9a-octahydro-1h-quinolizin-1-ol Chemical compound O[C@@H]1CCCN2C[C@@H](CCCCCCCCCC)CC[C@H]21 ASQOQJYHIYYTEJ-GBESFXJTSA-N 0.000 description 1
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
- VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 description 1
- JNPGUXGVLNJQSQ-BGGMYYEUSA-M (e,3r,5s)-7-[4-(4-fluorophenyl)-1,2-di(propan-2-yl)pyrrol-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)N1C(C(C)C)=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C1 JNPGUXGVLNJQSQ-BGGMYYEUSA-M 0.000 description 1
- APQIUTYORBAGEZ-UHFFFAOYSA-N 1,1-dibromoethane Chemical compound CC(Br)Br APQIUTYORBAGEZ-UHFFFAOYSA-N 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 1
- TXBOKWJUQMJRAO-UHFFFAOYSA-N 3,3-dimethylbut-1-yne Chemical compound CC(C)(C)C#[C-] TXBOKWJUQMJRAO-UHFFFAOYSA-N 0.000 description 1
- MWDVCHRYCKXEBY-LBPRGKRZSA-N 3-chloro-n-[2-oxo-2-[[(1s)-1-phenylethyl]amino]ethyl]benzamide Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(Cl)=C1 MWDVCHRYCKXEBY-LBPRGKRZSA-N 0.000 description 1
- HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- JCNOYYWDWSRPFE-UHFFFAOYSA-N C[Zn]C.CCCCCC Chemical compound C[Zn]C.CCCCCC JCNOYYWDWSRPFE-UHFFFAOYSA-N 0.000 description 1
- 229910020366 ClO 4 Inorganic materials 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001336 alkenes Chemical group 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- VWWMOACCGFHMEV-UHFFFAOYSA-N dicarbide(2-) Chemical compound [C-]#[C-] VWWMOACCGFHMEV-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000006459 hydrosilylation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- WDDOQHLJFOUQMW-UHFFFAOYSA-N lithium;ethynyl(trimethyl)silane Chemical compound [Li+].C[Si](C)(C)C#[C-] WDDOQHLJFOUQMW-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- PHVXTQIROLEEDB-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-n-pyrrolidin-3-ylbenzamide Chemical compound CC1=CC=CC=C1C1CN(CC=2C=CC(=CC=2)C(=O)N(CCC=2C(=CC=CC=2)Cl)C2CNCC2)CCC1 PHVXTQIROLEEDB-UHFFFAOYSA-N 0.000 description 1
- RCSBCWXPGSPJNF-UHFFFAOYSA-N n-[4-[5-[3-chloro-4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-yl]butyl]-4-(1,8-naphthyridin-2-yl)butanamide Chemical compound C1=C(Cl)C(OC(F)(F)F)=CC=C1C(O1)=NN=C1CCCCNC(=O)CCCC1=CC=C(C=CC=N2)C2=N1 RCSBCWXPGSPJNF-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- HBEDNENASUYMPO-LJQANCHMSA-N n-hydroxy-4-[[(2r)-3-oxo-2-(thiophen-2-ylmethyl)-2,4-dihydroquinoxalin-1-yl]methyl]benzamide Chemical compound C1=CC(C(=O)NO)=CC=C1CN1C2=CC=CC=C2NC(=O)[C@H]1CC1=CC=CS1 HBEDNENASUYMPO-LJQANCHMSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 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
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- YWWARDMVSMPOLR-UHFFFAOYSA-M oxolane;tetrabutylazanium;fluoride Chemical compound [F-].C1CCOC1.CCCC[N+](CCCC)(CCCC)CCCC YWWARDMVSMPOLR-UHFFFAOYSA-M 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- QGLVEAGMVUQOJP-UHFFFAOYSA-N prop-2-enylboronic acid Chemical compound OB(O)CC=C QGLVEAGMVUQOJP-UHFFFAOYSA-N 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000000547 structure data Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 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
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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/5027—Polyphosphines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/5013—Acyclic unsaturated phosphines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Description
下記一般式(2)で表されるt−ブチルメチルホスフィン−ボランをブロモ化して下記一般式(3)で表されるt−ブチルメチルブロモホスフィン−ボランを得;
これにアルキニルリチウムを作用させて、立体配置が反転した下記一般式(4)で表される化合物を得;
一般式(4)で表される化合物を脱プロトン化した後に酸化的カップリングを行う;工程を有する光学活性なビス(アルキニルホスフィノ)エタン−ボラン誘導体の製造方法を提供するものである。
13C NMR (125 MHz, CDCl3) δ 8.37 (d, J = 40 Hz), 24.96 (d, J = 4 Hz), 29.03 (d, J = 37 Hz), 79.42 (d, J = 90 Hz), 106.00 (d, J = 12 Hz), 120.77, 128.42, 130.01, 132.20.
31P NMR(162 MHz, CDCl3) δ 17.95 (q, J = 62Hz).
[α]22D 0.97 (c 1.00, CHCl3).
HPLC: Daicel Chiralcel OD-H, Hexane/i-PrOH=199/1, Flow rate=0.5 ml/min, UV=254 nm, tR=11.9 min (R), tR=13.1 min (S).
31P NMR (162 MHz, CDCl3) δ 29.62 (d, J = 15 Hz).
[α]22D 111.1 (c 1.00, CHCl3).
1H NMR (400 MHz, CDCl3) δ 0.23-0.89 (m, 3H), 1.21 (d, J = 15.1 Hz, 9H), 1.27 (s, 9H), 1.38 (d, J = 10.0 Hz, 3H).
13C NMR (100 MHz, CDCl3) δ 0, 8.54 (d, J = 40 Hz), 24.77 (d, J = 3 Hz), 28.62 (d, J = 35 Hz), 30.20 (d, J = 2 Hz), 68.70 (d, J = 95), 116.79 (d, J = 10 Hz).
31P NMR (162 MHz, CDCl3) δ 15.71 (q, J = 65 Hz).
HPLC: Daicel Chiralpak IA, Hexane/i-PrOH=1000/1, Flow rate=0.5 ml/min, UV=230 nm, tR=13.7 min (R), tR=15.3 min (S).
1H NMR (500 MHz, CDCl3) δ 0.22-0.87 (m, 6H), 1.21-1.25 (d, J = 15.1 Hz, 18H), 1.27 (s, 18H), 1.98 (m, 4H).
1H NMR (400 MHz, CDCl3) δ 0.27-0.73 (m, 3H), 1.09-1.10 (m, 21H), 1.24 (d, J = 15.4 Hz, 9H), 1.43 (d, J = 10.2 Hz, 3H).
13C NMR (100 MHz, CDCl3) δ 8.45 (d, J = 40 Hz), 10.90, 18.43, 24.82 (d, J = 3 Hz), 28.62 (d, J = 38 Hz), 98.26 (d, J = 77 Hz), 113.26 (d, J = 3 Hz).
31P NMR (162 MHz, CDCl3) δ 17.48 (q, J = 63 Hz).
HPLC: Daicel Chiralpak IA, Hexane/i-PrOH=1000/1, Flow rate=0.5 ml/min, UV=230 nm, tR=11.0 min (R), tR=13.6 min (S).
1H NMR (500 MHz, CDCl3) δ 0.50-0.70 (m, 6H), 1.06-1.14 (m, 42H), 1.27 (d, J = 15.3 Hz, 18H), 1.99-2.11(m, 4H).
1H NMR (400 MHz, CDCl3) δ 0.24-0.90 (m, 6H), 1.29 (d, J = 15.7 Hz, 18H), 2.00-2.12 (m, 4H), 3.06 (d, J = 7.4 Hz, 2H).
1H NMR (400 MHz, CDCl3) δ 0.22 (s, 3H), 1.23 (d, J = 15.4 Hz, 9H), 1.42 (d, J = 10.2 Hz, 3H).
13C NMR (125 MHz, CDCl3) δ 0, 8.92 (d, J = 40 Hz), 25.45 (d, J = 4 Hz), 29.28 (d, J = 38 Hz), 96.79 (d, J = 77 Hz), 116.66 (d, J = 3 Hz).
31P NMR (162 MHz, CDCl3) δ 17.12 (q, J = 60 Hz).
[α]22D -1.59 (c 1.00, CHCl3).
HPLC: Daicel Chiralcel OJ-H, Hexane/i-PrOH=99/1, Flow rate=0.5 ml/min, UV=230 nm, tR=8.8 min (R), tR=9.7 min (S).
1H NMR (400 MHz, CDCl3) δ 0.25-0.89 (m, 3H), 1.22 (d, J = 15.4 Hz, 9H), 1.40 (d, J = 9.9 Hz, 3H), 2.02 (d, J = 3.7 Hz, 3H).
1H NMR (400 MHz, CDCl3) δ 0.25-0.88 (m, 3H), 1.23 (d, J = 15.4 Hz, 18H), 1.42 (d, J = 9.8 Hz, 6H), 2.63 (s, 6H).
[Rh(nbd)2]BF4(1.9mg、5.0μmol)及び(S,S)−1,2−ビス((t−ブチル)フェニルエチニルホスフィノ)エタン7a(7.5μmol)をジオキサン(1mL)に溶かした溶液を、窒素雰囲気下、40℃で15分撹拌した。反応混合物に1.5MのKOH水溶液(0.1mL、0.15mmol)を添加し、反応液を15分撹拌した。アリルボロン酸(1.0mmol)及びα,β−不飽和カルボニル化合物(0.50mmol)を反応液に添加し、40℃で2時間撹拌熟成した。反応混合物を飽和重曹水溶液でクエンチした。反応混合物をジエチルエーテルで5回抽出し、有機層合わせ、飽和食塩水で分液洗浄し、無水硫酸ナトリウムで乾燥させた。ろ過後、ろ液を減圧濃縮し、濃縮残留物をシリカゲル分取TLC(ヘキサン/酢酸エチル=3/1)にて精製した。また、配位子として7aに代えて、7b、7c及び7eを用いて同様の反応を行った。これらの結果を表1に示す。
50mLの水素化用容器[オートクレーブ]に0.5mmolの基質を装填した。容器はステンレス管を経由して水素ボンベにつないだ。容器内は真空とした後に、1atmの水素ガスで満たした(日本酸素、99.9999%)。[Rh(nbd)2]BF4(1.9mg、5.0μmol)及び(S,S)−1,2−ビス((t−ブチル)フェニルエチニルホスフィノ)エタン7a(7.5μmol)を脱気したMeOH(1mL)に溶かした溶液を、シリンジを経由して容器に添加し、次いで水素圧を3atmまで上昇させた。反応混合物を濃縮し、残留物をシリカゲルフラッシュクロマトグラフィーにて溶離液として酢酸エチルを用いて精製した。また、配位子として7aに代えて、7b、7c、7d及び7eを用いて同様の反応を行った。これらの結果を表2に示す。
PdCl2(cod)(1.1mg、4.0μmol)及び(S,S)−1,2−ビス((t−ブチル)エチニルホスフィノ)エタン7d(6μmol)をCH2Cl2(1mL)に溶かした溶液を、窒素雰囲気下、40℃で15分撹拌した。この溶液に、オキサベンゾノルボルナジエン(58mg、0.4 mmol)をCH2Cl2(3mL)に溶かした溶液を添加した。続いてジメチル亜鉛1.0Mヘキサン溶液(0.6ml、0.6mmol)を添加した。反応が完結するまで室温で溶液を撹拌熟成した。反応後、数滴の水の添加によりクエンチし、反応混合物をセライトの短いカラムに通した後に濃縮した。残留物を分取TLC(ヘキサン/酢酸エチル)にて精製した。また、配位子として7dに代えて、7a、7b、7c及び7eを用いて同様の反応を行った。これらの結果を表3に示す。
Claims (4)
- 一般式(1)においてR1とR2とが同一であり、それらがメチル基、t−ブチル基、フェニル基、トリイソプロピルシリル基又は水素原子である請求項1記載の誘導体。
- 一般式(1)においてR3がt−ブチル基である請求項1又は2記載の誘導体。
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JP2007060784A JP5032161B2 (ja) | 2007-03-09 | 2007-03-09 | 光学活性なビス(アルキニルホスフィノ)エタンーボラン誘導体及びその製造方法 |
US12/073,415 US7534920B2 (en) | 2007-03-09 | 2008-03-05 | Optically-active bis(alkynylphosphino) ethane-borane derivative and process for producing the same |
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CN108101737B (zh) * | 2017-12-29 | 2021-08-27 | 玉林师范学院 | 一种氢化萘结构单元的手性化合物的合成方法 |
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JP2972887B1 (ja) | 1998-10-29 | 1999-11-08 | 千葉大学長 | 光学活性ビスホスフィノメタン並びにそれらのロジウム又は銅錯体を用いる不斉合成 |
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