CN113292422A - Allylation coupling reaction method and application thereof - Google Patents
Allylation coupling reaction method and application thereof Download PDFInfo
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- CN113292422A CN113292422A CN202110387338.7A CN202110387338A CN113292422A CN 113292422 A CN113292422 A CN 113292422A CN 202110387338 A CN202110387338 A CN 202110387338A CN 113292422 A CN113292422 A CN 113292422A
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- Prior art keywords
- alkyl
- aryl
- radical
- cycloalkyl
- ring
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 23
- 238000005859 coupling reaction Methods 0.000 title claims abstract description 21
- 238000005937 allylation reaction Methods 0.000 title claims abstract description 17
- -1 alkenyl thianthrene salt Chemical class 0.000 claims abstract description 74
- 239000000758 substrate Substances 0.000 claims abstract description 18
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 239000003513 alkali Substances 0.000 claims abstract description 4
- 230000008878 coupling Effects 0.000 claims abstract description 3
- 238000010168 coupling process Methods 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 123
- 150000001875 compounds Chemical class 0.000 claims description 93
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 88
- 125000003118 aryl group Chemical group 0.000 claims description 51
- 125000001424 substituent group Chemical group 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 150000003254 radicals Chemical class 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 25
- 125000003342 alkenyl group Chemical group 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000004043 oxo group Chemical group O=* 0.000 claims description 15
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 12
- 229920002554 vinyl polymer Chemical group 0.000 claims description 12
- 125000002950 monocyclic group Chemical group 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 10
- 125000000746 allylic group Chemical group 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000003435 aroyl group Chemical group 0.000 claims description 8
- 150000005347 biaryls Chemical group 0.000 claims description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000002585 base Substances 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- LKUDPHPHKOZXCD-UHFFFAOYSA-N 1,3,5-trimethoxybenzene Chemical compound COC1=CC(OC)=CC(OC)=C1 LKUDPHPHKOZXCD-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims description 4
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 4
- 125000005592 polycycloalkyl group Polymers 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 2
- 229910017048 AsF6 Inorganic materials 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 2
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- 239000001099 ammonium carbonate Substances 0.000 claims description 2
- 235000012501 ammonium carbonate Nutrition 0.000 claims description 2
- 229910001914 chlorine tetroxide Inorganic materials 0.000 claims description 2
- 229960001701 chloroform Drugs 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 229910021645 metal ion Inorganic materials 0.000 claims description 2
- 125000003518 norbornenyl group Chemical group C12(C=CC(CC1)C2)* 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000007789 gas Substances 0.000 claims 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims 1
- 150000001412 amines Chemical class 0.000 abstract description 5
- 150000004945 aromatic hydrocarbons Chemical class 0.000 abstract description 4
- 229910052723 transition metal Inorganic materials 0.000 abstract description 4
- 150000003624 transition metals Chemical class 0.000 abstract description 4
- 239000004215 Carbon black (E152) Substances 0.000 abstract description 3
- 229930195733 hydrocarbon Natural products 0.000 abstract description 3
- 238000003889 chemical engineering Methods 0.000 abstract description 2
- 239000012847 fine chemical Substances 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 166
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 41
- 238000005160 1H NMR spectroscopy Methods 0.000 description 41
- 239000012299 nitrogen atmosphere Substances 0.000 description 41
- 238000002390 rotary evaporation Methods 0.000 description 41
- 239000002904 solvent Substances 0.000 description 41
- 238000004440 column chromatography Methods 0.000 description 35
- 238000004587 chromatography analysis Methods 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 125000000623 heterocyclic group Chemical group 0.000 description 12
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 11
- 125000004122 cyclic group Chemical group 0.000 description 9
- 229910052717 sulfur Inorganic materials 0.000 description 9
- 229910052698 phosphorus Inorganic materials 0.000 description 8
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 7
- 239000000126 substance Chemical group 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 6
- 125000006413 ring segment Chemical group 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 125000002837 carbocyclic group Chemical group 0.000 description 5
- 125000004430 oxygen atom Chemical group O* 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 238000006555 catalytic reaction Methods 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 150000001336 alkenes Chemical group 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000002785 azepinyl group Chemical group 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
- UZHVXJZEHGSWQV-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrole Chemical compound C1NCC2CCCC21 UZHVXJZEHGSWQV-UHFFFAOYSA-N 0.000 description 1
- KOFLVDBWRHFSAB-UHFFFAOYSA-N 1,2,4,5-tetrahydro-1-(phenylmethyl)-5,9b(1',2')-benzeno-9bh-benz(g)indol-3(3ah)-one Chemical compound C1C(C=2C3=CC=CC=2)C2=CC=CC=C2C23C1C(=O)CN2CC1=CC=CC=C1 KOFLVDBWRHFSAB-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- OHZAHWOAMVVGEL-UHFFFAOYSA-N 2,2'-bithiophene Chemical group C1=CSC(C=2SC=CC=2)=C1 OHZAHWOAMVVGEL-UHFFFAOYSA-N 0.000 description 1
- IHKOXYNAMXNNDK-UHFFFAOYSA-N 2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan Chemical compound C1COC2OCCC21 IHKOXYNAMXNNDK-UHFFFAOYSA-N 0.000 description 1
- PHXGAJLBHUUAKB-UHFFFAOYSA-N 2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound O1CCC2OCCC21 PHXGAJLBHUUAKB-UHFFFAOYSA-N 0.000 description 1
- HTFNVAVTYILUCF-UHFFFAOYSA-N 2-[2-ethoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5-methyl-11-methylsulfonylpyrimido[4,5-b][1,4]benzodiazepin-6-one Chemical compound CCOc1cc(ccc1Nc1ncc2N(C)C(=O)c3ccccc3N(c2n1)S(C)(=O)=O)C(=O)N1CCC(CC1)N1CCN(C)CC1 HTFNVAVTYILUCF-UHFFFAOYSA-N 0.000 description 1
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- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
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- LZCDAPDGXCYOEH-UHFFFAOYSA-N adapalene Chemical compound C1=C(C(O)=O)C=CC2=CC(C3=CC=C(C(=C3)C34CC5CC(CC(C5)C3)C4)OC)=CC=C21 LZCDAPDGXCYOEH-UHFFFAOYSA-N 0.000 description 1
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- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
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- DERZBLKQOCDDDZ-JLHYYAGUSA-N cinnarizine Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C\C=C\C1=CC=CC=C1 DERZBLKQOCDDDZ-JLHYYAGUSA-N 0.000 description 1
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- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
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- 238000003912 environmental pollution Methods 0.000 description 1
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- 125000000524 functional group Chemical group 0.000 description 1
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- 230000002452 interceptive effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
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- 229920000554 ionomer Polymers 0.000 description 1
- 125000002462 isocyano group Chemical group *[N+]#[C-] 0.000 description 1
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- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- SMEROWZSTRWXGI-HVATVPOCSA-N lithocholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 SMEROWZSTRWXGI-HVATVPOCSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- OZGNYLLQHRPOBR-DHZHZOJOSA-N naftifine Chemical compound C=1C=CC2=CC=CC=C2C=1CN(C)C\C=C\C1=CC=CC=C1 OZGNYLLQHRPOBR-DHZHZOJOSA-N 0.000 description 1
- 229960004313 naftifine Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- HLIAVLHNDJUHFG-HOTGVXAUSA-N neotame Chemical compound CC(C)(C)CCN[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 HLIAVLHNDJUHFG-HOTGVXAUSA-N 0.000 description 1
- 235000019412 neotame Nutrition 0.000 description 1
- 108010070257 neotame Proteins 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 238000006772 olefination reaction Methods 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003585 oxepinyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 229960003081 probenecid Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl 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
- ADRDEXBBJTUCND-UHFFFAOYSA-N pyrrolizidine Chemical compound C1CCN2CCCC21 ADRDEXBBJTUCND-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- NYVGTLXTOJKHJN-UHFFFAOYSA-N thianthrene 5-oxide Chemical compound C1=CC=C2S(=O)C3=CC=CC=C3SC2=C1 NYVGTLXTOJKHJN-UHFFFAOYSA-N 0.000 description 1
- 125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000005503 thioxanyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
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- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
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- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
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- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
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- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
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- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D499/44—Compounds with an amino radical acylated by carboxylic acids, attached in position 6
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Abstract
The invention discloses a novel allylation coupling reaction method, which comprises the following steps: taking alkenyl thianthrene salt as an allylation reagent, respectively taking a carboxylic acid compound and organic amine as substrates, and reacting in an organic solvent at room temperature in the presence of alkali or directly taking the carboxylic acid compound and aromatic hydrocarbon/heterocyclic hydrocarbon as substrates to obtain an allylation coupling product; the preparation method has mild conditions, does not involve transition metal, can efficiently realize the preparation of various allyl esters, allyl substituted amine and allyl substituted aromatic hydrocarbon/heterocyclic hydrocarbon compounds, and has ideal application prospects in the fields of fine chemical engineering, material science and pharmacy.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis methods, and particularly relates to a metal-catalysis-free allylation coupling reaction method and application thereof.
Background
Allylamines, esters are ubiquitous compounds in biologically active molecules and organic materials and can be used as universal starting materials for a variety of chemical transformations. To date, Pd-catalyzed allyl CH activation is the predominant method for the synthesis of allylamines, with only a mono-substituted terminal olefin being a suitable substrate (chem. Sci. DOI: 10.1039/d0sc05952 h). The allylation reaction of acid and amine is an important reaction in organic synthesis, and the catalytic reaction participated by transition metal is the main path for constructing allyl functional group at present. The Ritter group reported that allylation of terminal olefins was achieved under Ir metal catalysis and light irradiation using primary amines as starting materials and thianthrene imine as substrate, but this reaction was limited to primary amine substrates and failed to achieve allylation of secondary amines with other types of substrates (j.am.chem.soc.doi.org/10.1021/jacs.0c08248). Alkenyl thianthrene salt is an organic chemical reagent that can be prepared by a simple reaction of olefin and thianthrene oxide, and can be used as an alkenyl reagent to realize an olefination reaction of a nucleophilic reagent under the catalysis of a metal Pd/Ru complex (Angew. chem. int. Ed.2020, 59, 5616).
Disclosure of Invention
Definition of
To facilitate an understanding of the invention, some terms, abbreviations or other abbreviations used herein are defined as follows, unless otherwise indicated.
The term "alkyl" or "alkyl group" as used herein, denotes a saturated straight or branched chain monovalent hydrocarbon radical containing from 1 to 20 carbon atoms. Unless otherwise specified, an alkyl group contains 1 to 20 carbon atoms, some embodiments being where the alkyl group contains 1 to 10 carbon atoms, other embodiments being where the alkyl group contains 1 to 8 carbon atoms, other embodiments being where the alkyl group contains 1 to 6 carbon atoms, other embodiments being where the alkyl group contains 1 to 4 carbon atoms, other embodiments being where the alkyl group contains 1 to 3 carbon atoms, and other embodiments being where the alkyl group contains 1 to 2 carbon atoms.
Examples of alkyl groups include, but are not limited to, methyl (Me, -CH)3) Ethyl (Et, -CH)2CH3) N-propyl (n-Pr, -CH)2CH2CH3) Isopropyl (i-Pr, i-propyl, -CH (CH)3)2) N-butyl (n-Bu, n-butyl, -CH)2CH2CH2CH3) Isobutyl (i-Bu, i-butyl, -CH)2CH(CH3)2) Sec-butyl (s-Bu, s-butyl, -CH (CH)3)CH2CH3) T-butyl (t-Bu, t-butyl, -C (CH)3)3) N-pentyl (n-pentyl, -CH)2CH2CH2CH2CH3) 2-pentyl (-CH (CH)3)CH2CH2CH3) 3-pentyl (-CH (CH)2CH3)2) 2-methyl-2-butyl (-C (CH)3)2CH2CH3) 3-methyl-2-butyl (-CH (CH)3)CH(CH3)2) 3-methyl-1-butyl (-CH)2CH2CH(CH3)2) 2-methyl-1-butyl (-CH)2CH(CH3)CH2CH3) N-hexyl (-CH)2CH2CH2CH2CH2CH3) 2-hexyl (-CH (CH)3)CH2CH2CH2CH3) 3-hexyl (-CH (CH)2CH3)(CH2CH2CH3) 2-methyl-2-pentyl (-C (CH))3)2CH2CH2CH3) 3-methyl-2-pentyl (-CH (CH)3)CH(CH3)CH2CH3) 4-methyl-2-pentyl (-CH (CH)3)CH2CH(CH3)2) 3-methyl-3-pentyl (-C (CH)3)(CH2CH3)2) 2-methyl-3-pentyl (-CH (CH)2CH3)CH(CH3)2) 2, 3-dimethyl-2-butyl (-C (CH)3)2CH(CH3)2) 3, 3-dimethyl-2-butyl (-CH (CH)3)C(CH3)3) N-heptyl, n-octyl, and the like. Wherein the alkyl groups may be independently unsubstituted or substituted with one or more substituents described herein.
The term "alkyl" and its prefix "alk", as used herein, are intended to encompass both straight and branched saturated carbon chains.
The term "alkoxy" denotes an alkyl group attached to the rest of the molecule through an oxygen atom, wherein "C" is1-6Alkyl "has the meaning as described in the present invention. Examples of alkoxy groups include, but are not limited to: methoxy, ethoxy, 1-propoxy, 2-propoxy, 1-butoxy, 2-methyl-1-propoxy, 2-butoxy, 2-methyl-2-propoxy, 1-pentoxy, 2-pentoxy, 3-pentoxy, 2-methyl-2-butoxy, 3-methyl-1-butoxy, 2-methyl-1-butoxy, and the like.
The terms "carbocycle", "carbocyclyl" or "carbocyclic" refer to a mono-or polyvalent, non-aromatic, saturated or partially unsaturated, monocyclic, bicyclic, tricyclic or tetracyclic ring system containing from 3 to 16 carbon atoms. Carbocycles include fused rings, bridged rings, spiro rings, or combinations thereof. Suitable carbocyclic groups include, but are not limited to, cycloalkyl, cycloalkenyl, cycloalkynyl, steroidal ring, adamantyl, norbornyl. Examples of carbocyclic groups further include, but are in no way limited to, cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopentyl-1-alkenyl, 1-cyclopentyl-2-alkenyl, 1-cyclopentyl-3-alkenyl, cyclohexyl, 1-cyclohexyl-1-alkenyl, 1-cyclohexyl-2-alkenyl, 1-cyclohexyl-3-alkenyl, cyclohexadienyl, and the like. Wherein the carbocyclic group may independently be unsubstituted or substituted with one or more substituents described herein.
The terms "heterocycle", "heterocyclyl" or "heterocyclic" are used interchangeably herein and all refer to a monocyclic, bicyclic or tricyclic ring system in which one or more atoms in the ring are independently optionally substituted with a heteroatom, and the ring may be fully saturated or contain one or more degrees of unsaturation, but is by no means aromatic, having only one point of attachment to another molecule. Heterocyclic groups include monocyclic, fused, bridged, spiro, or combinations thereof. One or more of the ring hydrogen atoms are independently optionally substituted with one or more substituents described herein. Some of the examples are "heterocycle", "heterocyclyl" or "heterocyclic" groups which are monocyclic (2 to 7 carbon atoms and 1 to 3 heteroatoms selected from N, O, P, S, where S or P is optionally substituted with one or more oxygen atoms to give the formula S ═ O, SO2，PO，PO2When the ring is a three-membered ring, there is only one heteroatom). In other embodiments, a monocyclic ring of 3 to 6 atoms (2 to 5 carbon atoms and 1 to 3 heteroatoms selected from N, O, P, S, where S or P is optionally substituted with one or more oxygen atoms to give a ring structure like S ═ O, SO2，PO，PO2When said ring is a three-membered ring, in which there is only one heteroatom), or a bicyclic ring of 7 to 10 atoms (4 to 9 carbon atoms and 1 to 3 heteroatoms selected from N, O, P, S, where S or P is optionally substituted by one or more oxygen atoms to give a ring such as S ═ O, SO, or2，PO，PO2The group of (1).
The heterocyclic group may be a carbon-based or heteroatom group. Examples of heterocycles include, but are not limited to, pyrrolidinyl, tetrahydrofuryl, dihydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thioxanyl, piperazinyl, homopiperazinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, epoxypropyl, azepinyl, oxepinyl, azepinyl, diazepinyl, thiazepinyl, 2-pyrrolinyl, 3-pyrrolinyl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxacyclohexyl, 1, 3-dioxolanyl, pyrazolinyl, dithianyl, dithienyl, dithienoalkyl, dihydrothienyl, pyrazolidinylimidazolinyl, imidazolidinyl, hexahydrofuro [3, 2-b ] furan, hexahydrofuro [2, 3-b ] furan, octahydrocyclopenta [ c ] pyrrole, hexahydro-1H-pyrrolizine. Examples of heterocyclic groups also include pyrimidinedionyl and 1, 1-dioxothiomorpholinyl groups in which two carbon atoms in the ring are replaced by oxygen (═ O). Examples of heterocyclic groups also include hexahydrofuro [2, 3-b ] furyl, and the like.
The term "heteroatom" means one or more of O, S, N, P or Si, including any oxidation state form of N, S and P; primary, secondary, tertiary amines and quaternary ammonium salt forms; or a form in which a hydrogen on a nitrogen atom in the heterocycle is substituted, for example, N (like N in 3, 4-dihydro-2H-pyrrolyl), NH (like NH in pyrrolidinyl) or NR (like NR in N-substituted pyrrolidinyl).
The terms "aryl" and "aromatic ring" are used interchangeably herein to refer to monocyclic, bicyclic, and tricyclic carbon ring systems containing a total of 6 to 14 ring atoms, or 6 to 12 ring atoms, or 6 to 10 ring atoms, wherein at least one ring system is aromatic, and wherein each ring system contains 3 to 7 atoms making up the ring. The aryl group can be independently unsubstituted or substituted with one or more substituents described herein.
The terms "heteroaryl", "aromatic heterocycle" and "heteroaromatic" are used interchangeably herein and refer to monocyclic, bicyclic, and tricyclic ring systems containing a total of 5 to 14 ring atoms, or 5 to 12 ring atoms, or 5 to 10 ring atoms, wherein at least one ring system is aromatic and at least one ring system contains one or more heteroatoms, wherein each ring system contains a ring of 5 to 7 atoms. In some embodiments, a heteroaryl group of 5-10 atoms contains 1, 2, 3, or 4 heteroatoms independently selected from O, S, and N.
The term "optional" or "optionally" means that the subsequently described event or circumstance may, but need not, occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. For example, "optional bond" means that the bond may or may not be present, and the description includes single, double, or triple bonds.
As used herein to describe a compound or chemical moiety as being "substituted" means that at least one hydrogen atom of the compound or chemical moiety is replaced with a second chemical moiety. Non-limiting examples of substituents are those present in the exemplary compounds and embodiments disclosed herein, as well as fluorine, chlorine, bromine, iodine; oxo; imino and nitro; cyano, isocyano, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkenyl, cycloalkenyl, alkynyl; lower alkoxy, aryloxy; acyl, thiocarbonyl, sulfonyl; amides, sulfonamides; a ketone; an aldehyde; esters, sulfonates; haloalkyl (e.g., difluoromethyl, trifluoromethyl); a carbocyclic alkyl group which may be monocyclic or fused or non-fused polycyclic (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl); or a heterocycloalkyl group which may be a single ring or fused or non-fused polycyclic (e.g., pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or thiazinyl); or may be a monocyclic or fused aryl group (e.g., phenyl, naphthyl, thiazolyl, oxazolyl, imidazolyl, isoxazolyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, thienyl, furyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolyl, quinolyl, isoquinolyl, quinoxalyl, quinazolinonyl, benzimidazolyl, benzofuryl, benzothienyl, benzothiazolyl, benzoxazolyl, benzisoxazolyl); or can also be: aryl-lower alkyl; -CHO; -CO (alkyl); -CO (aryl); -CO2(alkyl); -CO2(aryl); -CONH2；-SO2NH2；-OCH2CONH2；-OCHF2；-OCF3；-CF3(ii) a -N (alkyl) (aryl); -N (aryl)2(ii) a Further, when the substituent is oxygen, it means that two hydrogen atoms on the same or different carbons are substituted with the same oxygen atom to form a carbonyl group or a cyclic ether, such as a ketocarbonyl group, an aldehyde carbonyl group, an ester carbonyl group, an amide carbonyl group, ethylene oxide, etc.; in addition, these moieties may also optionally be substituted with fused ring structures or bridges (e.g., -OCH2O-) is substituted. In the present invention, it is preferred that one, two, three substituents independently selected from halogen, nitro, cyano, alkyl, alkoxy or perhalo are substituted, such as trifluoromethyl, pentafluoroethyl, and, when the substituents contain hydrogen, these substituents may optionally be further substituted with a substituent selected from such groups.
As used herein, describing a compound or chemical moiety as being "independently" should be understood as meaning that the plurality of compounds or chemical moieties defined before the term should each enjoy the selection ranges provided thereafter equally, without interfering with each other, and should not be understood as defining any spatial connection relationship between the various groups; spatially connected relationships are referred to herein by the terms "independently of one another," "connected," and the like; should be distinguished; in the present invention, "independently" and "independently each other" and "independently selected from" have substantially the same meaning.
The term "room temperature" means 0 ℃ to 40 ℃, with some embodiments being 10 ℃ to 30 ℃, and other embodiments being 20 ℃ to 30 ℃, and the term "room temperature" of the present invention may also be abbreviated as "RT".
As used herein, the description of two "adjacent" chemical moieties being linked to form a cyclic structure should be understood to include both the situation where two chemical moieties are positionally adjacent, illustratively including the situation where two groups on the same aromatic ring are in the ortho position, and the situation where two groups are sterically adjacent, illustratively including the situation where two groups are on different linked or fused aromatic rings, but can be in close spatial proximity to each other.
The "combination group" described in the description of substitution by "any plural number of combination groups formed of the same or different groups" in the listed groups as used herein: including the case where the groups are combined by at least one of substitution, linkage, thickening or bridging.
As used herein, the description of a "parent ring" should be understood to be a concept as opposed to the "substituents" described in context in connection therewith, i.e., the ring structure substituted by the "substituent" in question.
Detailed Description
Aiming at the defects of the prior art, the invention provides a novel allylation reaction method which is mild in condition, free of transition metal catalysis, wide in substrate application range, green and environment-friendly, and capable of effectively improving reaction efficiency and reducing environmental pollution risks.
In a first aspect, the present invention provides an allylation coupling reaction method, comprising: an alkenylthianthrene salt of formula A
Reacting with a substrate Mx in an organic solvent, wherein the reaction is one of the following:
generating a corresponding allylated coupling product Px, said substrate Mx being selected from a compound of formula Ma, Mb or Mc;
wherein,
R1is C1-12Alkyl radical, C3-8Cycloalkyl, aryl, wherein, said C1-12Alkyl radical, C3-8Cycloalkyl, aryl optionally substituted with one or more groups independently selected from aryl, alkenyl, hydroxy, halogen, trifluoromethyl, acyloxy, dialkylamino, sulfonyl, alkyl, cycloalkyl or a combination of any plurality thereof, the same or different; r2Is H or C1-6An alkyl group; r1Optionally with the adjacent allylic carbon or with R2Connected to form a 5-8 membered ring; x is a common organic salt anion including, but not limited to, halogen, BF4、PF6、AsF6、SbF6、ClO4Or the organic salt anion is a carboxylate or sulfonate-containing ionomer, e.g. CF3COO, OTf, OTs, etc.
R3Is H, C1-12Alkyl radical, C3-8Cycloalkyl radical, C2-7Heterocycloalkyl, aryl, heteroaryl, alkenyl, alkynyl, acyl, or a combination of any two or more thereof, wherein C is1-12Alkyl radical, C3-8Cycloalkyl radical, C2-7Heterocycloalkyl, aryl, heteroaryl are optionally substituted with one or more substituents independently selected from: halogen, hydroxy, oxo, trifluoromethyl, aryl, alkyl, cycloalkyl, alkoxy, alkylamino, amido, aminoacyl, ester, acyloxy, sulfonyl, or a combination formed by any plurality of the same or different groups; r4Is H or a metal ion capable of forming a salt with a carboxylic acid;
R5and R6Each independently is H, C1-8Alkyl radical, C3-8Cycloalkyl, aryl, or any combination thereof, said C1-6Alkyl radical, C3-8Cycloalkyl, aryl are optionally substituted with one or more substituents independently selected from: halogen, hydroxyl, oxo, trifluoromethyl, alkyl, aryl, alkoxy and alkylamino; optionally, R5And R6Directly connected or connected through heteroatom to form a ring;
y is CH or N; z is NRaO, S or
Wherein R isaIs H or C1-6An alkyl group; rn 7Is one or more selected from hydroxyl and C1-4Alkyl radical, C1-4Alkoxy, amino, C1-4A substituent of an alkylamino group, said substituent replacing a hydrogen on CH or NH on the parent ring, optionally, each Rn 7Can be connected to form a ring, wherein n is each R7Numbering of substituents, and n is smallThe sum of CH and NH on the parent ring substituted with said substituent;
wherein, when the R substrate is a compound shown as a formula Ma or Mc, and R in Ma is4When the hydrogen is H, the reaction is also carried out under the condition of alkali.
In some embodiments, R1Is C1-8Alkyl or aryl, wherein, said C1-8Alkyl, aryl optionally substituted with one or more groups independently selected from aryl, alkenyl, hydroxy, halogen, trifluoromethyl, aryl-C (O), cycloalkyl-C (O), O-, alkyl-C (O), O-, dialkylaminosulfonyl, fused ring alkyl, or a combination of any 2 to 3 of these groups, which may be the same or different; r2Is H or C1-4An alkyl group; r1Optionally with the adjacent allylic carbon or with R2Connected to form a 5-or 6-membered ring.
In some embodiments, R1Is C1-8A linear alkyl, phenyl, naphthyl or a 6-membered ring linked to the adjacent allylic or terminal alkenyl carbon, wherein said C is1-8The linear alkyl end is optionally substituted by phenyl, naphthyl, vinyl, hydroxy, halogen, trifluoromethyl, phenyl-C (O) O-, cyclohexyl-C (O) O-, C1-8alkyl-C (O) O-, di-C1-4Alkylaminosulfonyl, fused ring alkyl-C2-8alkyl-C (O) O-, or is substituted by a combination of any 2 different groups therein; r2Is H, C1-4Alkyl or with R1Are connected.
Preferably, in some embodiments, R1Is C1-8Alkyl, aryl-C1-8Alkyl, aryl-C (O) O-C1-8Alkyl radical, C5-6cycloalkyl-C (O) O-C1-8Alkyl, condensed ring radicals-C2-5alkyl-C (O) O-C1-8Alkyl radical, C1-5alkyl-C (O) O-C1-8Alkyl or a 6-membered ring formed by linking to an adjacent allylic or terminal alkenyl carbon1-8Alkyl, aryl-C1-8Alkyl, aryl-C (O) O-C1-8Alkyl radical, C5-6cycloalkyl-C (O) O-C1-8Alkyl, condensed ring radicals-C2-5alkyl-C (O) O-C1-8Alkyl radical, C1-5alkyl-C (O) O-C1-8Alkyl radicalOptionally substituted with one or more substituents independently selected from the group consisting of: vinyl, hydroxy, halogen, trifluoromethyl, C1-4Alkyl, oxo, di-C1-4An alkylaminosulfonyl group; r2Is H or with R1Are connected.
Preferably, in some embodiments, the alkenylthianthrene salt of formula A is selected from one of the following structures,
in some embodiments, R3Is H, C1-8Alkyl radical, C5-6Cycloalkyl radical, C2-5Heterocycloalkyl, aryl, biaryl, heteroaryl, vinyl, conjugated alkenyl, aralkynyl, alkanyl, aroyl, alkanoyl or a combination of 2 to 3 of these optionally in combination, wherein C is1-4Alkyl radical, C5-6Cycloalkyl radical, C2-5Heterocycloalkyl, aryl, heteroaryl, vinyl, conjugated alkenyl, aralkynyl, alkanyl, aroyl, alkanoyl optionally substituted with one or more substituents independently selected from: halogen, hydroxy, oxo, trifluoromethyl, aryl, C1-4Alkyl, monocyclic or fused or bridged cycloalkyl, mono-or fused or bridged heterocycloalkyl, C1-4Alkoxy, monoalkyl or dialkylamino, dialkylaminosulfonyl, alkylamido, alkylaminoacyl, ester, acyloxy or a combination of any 2 to 3 of these groups, which may be the same or different.
In some embodiments, R3Is H, C1-4Alkyl radical, C5-6Cycloalkyl radical, C2-5Heterocycloalkyl, aryl, heteroaryl, vinyl, conjugated alkenyl, aroyl, aryl-C1-4Alkyl, aryl-ethynyl, C2-8Conjugated alkenyl, condensed ring/bridged ring radical-C1-4Alkyl, biaryl, fused heterocycloalkyl, heterocyclyl-C1-4Alkyl, aryl-C1-4alkyl-N (H) C (O) -C1-4Alkyl or aryl-C1-4alkyl-C (O) N (H) -heterocyclyl; said C is1-4Alkyl radical, C5-6CycloalkanesBase, C2-5Heterocycloalkyl, aryl, heteroaryl, vinyl, conjugated alkenyl, aroyl, aryl-C1-4Alkyl, aryl-ethynyl, C2-8Conjugated alkenyl, condensed ring/bridged ring radical-C1-4Alkyl, biaryl, fused heterocycloalkyl, heterocyclyl-C1-4Alkyl, aryl-C1-4alkyl-N (H) C (O) -C1-4Alkyl or aryl-C1-4alkyl-C (O) N (H) -heterocyclyl is optionally substituted with one or more substituents independently selected from: halogen, hydroxy, oxo, trifluoromethyl, phenyl, C1-4Alkyl radical, C1-4Alkoxy, di-C1-4Alkylamino radical, C5-6Cycloalkyl, adamantyl, norbornenyl, steryl; r4H, Na or K.
Preferably, in some embodiments, R3Is H, phenyl, methyl, tert-butyl, cyclohexyl, benzyl, isopropyl, phenylethynyl, pentadienyl, benzoyl, quinolinyl, thienyl, indolyl, furyl or pyrrolyl; said phenyl, methyl, t-butyl, cyclohexyl, benzyl, isopropyl, phenylethynyl, pentadienyl, benzoyl, quinolinyl, thienyl, indolyl, furyl, or pyrrolyl group being optionally substituted with one or more substituents independently selected from the group consisting of: halogen, methyl, hydroxy, methoxy, phenyl;
preferably, in some embodiments, R3Is one of the following groups:
in some embodiments, R5And R6Each independently is H, C1-5Alkyl, aryl, biaryl, aryl-C1-5Alkyl radical, C3-6Cycloalkyl, polycycloalkyl; said C is1-5Alkyl, aryl-C1-5Alkyl radical, C3-6Cycloalkyl, polycycloalkyl are optionally substituted with one or more substituents independently selected from the group consisting of: hydroxy, oxo, halogen, trifluoromethyl, C1-4Alkyl radical, C1-4Haloalkyl, benzhydryl; optionally, R5And R6Directly connected or connected by heteroatoms to form a 5-8 membered ring containing N atoms;
in some embodiments, R5And R6Each independently is H, C1-5Alkyl, phenyl, naphthyl, biphenyl, aryl-C1-5Alkyl or adamantyl, said C1-5Alkyl, phenyl, naphthyl, biphenyl, aryl-C1-5Alkyl, adamantyl, optionally substituted with one or more substituents independently selected from the group consisting of: hydroxy, halogen, oxo, C1-6Alkyl, haloalkyl, benzhydryl; optionally, R5And R6Directly connected or connected through a heteroatom to form a 5-8 membered ring containing the N atom.
Preferably, in some embodiments, R5And R6Each independently is H, phenyl, benzyl, methyl, tert-butyl, pentyl,
Preferably, in some embodiments, the compound of formula Mb is selected from one of the following structures,
in some embodiments, Y is CH and Z is
Each Rn 7Is 2-4 substituents independently selected from hydroxy, methyl, ethyl, methoxy, amino, methylamino, dimethylamino, optionally, each Rn 7Can be connected into a ring.
Illustratively, in some embodiments, Mc contains 3 Rsn 7Substituent, each Rn 7The substituents are respectively represented as: r1 7、R2 7And R3 7。
Preferably, the compound of formula Mc is 1, 3, 5-trimethoxybenzene.
In some embodiments, the organic solvent is dichloromethane, trichloromethane, carbon tetrachloride, acetonitrile, acetone, tetrahydrofuran, or a combination thereof.
In some embodiments, the base is an inorganic base.
In some embodiments, the mass ratio of the alkenylthianthrene salt of formula (A) to the substrate Ma is 1.0: 1.2 to 1.0: 3.0;
in some embodiments, the mass ratio of the alkenylthianthrene salt of formula (A) to the substrate Mb is 1.0: 2.0 to 1.0: 3.0.
In some embodiments, the base is potassium carbonate, sodium carbonate, ammonium carbonate, sodium bicarbonate, or a combination thereof;
in some embodiments, the mass ratio of the alkenyl thianthrene salt of formula (A) to the base is 1.0: 0.5 to 1.0: 2.0.
In another aspect, the present invention also provides the use of an alkenylthianthrene salt of formula a as allylation reagent in an allylation coupling reaction process or in the preparation of an allylic compound.
In some embodiments, the allylic coupling reaction or allylic compound is as previously described.
Has the advantages that:
the allylation coupling reaction method provided by the invention adopts a room temperature approach, takes alkenyl thianthrene salt as an allyl reagent, takes stable and easily obtained carboxylic acid or salt compounds thereof, amine, aromatic hydrocarbon/heterocyclic hydrocarbon as a substrate, can efficiently realize the preparation of various allyl substituted ester, amine and aromatic hydrocarbon compounds in the absence of transition metal, and has wide and ideal application prospects in the fields of fine chemical engineering, material science and pharmacy.
Detailed Description
The above route of the present invention is described in detail by the following examples, which should be noted that the present invention is only for further illustration and not limited to the present invention. Those skilled in the art may make insubstantial modifications and adaptations to the present invention.
Example 1
Compound M01(29.3mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, and dry-chromatography (300-400 mesh silica gel chromatography) (petroleum ether-ethyl acetate 19: 1) gave 41.9mg of product P01 in 91% yield.
1H NMR(400MHz，CDCl3)δ(ppm)：8.09-8.01(m，2H)，7.59-7.50(m，1H)，7.43(dd，J＝8.4，7.0Hz，2H)，5.42(tt，J＝7.2，1.3Hz，1H)，4.84(d，J＝7.2Hz，2H)，2.32-2.24(m，2H)，2.20-2.12(m，2H)，1.58(p，J＝2.3Hz，6H)；
13C NMR(101MHz，CDCl3)δ(ppm)：166.81，147.21，132.88，130.73，129.72，128.41，115.36，61.28，37.14，29.27，28.50，27.93，26.75；
HRMS-ESI(m/z)：231.1378[M+H]+。
Example 2
Firstly, weighing K2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) and Compound M02(14.4mg, 0.24mmol) were added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, and dry-chromatography (300-400 mesh silica gel chromatography) (petroleum ether-ethyl acetate 19: 1) was carried out to give 21.6mg of the product P02 in 64% yield.
1H NMR(400MHz，CDCl3)δ(ppm)：5.28(tt，J＝7.3，1.2Hz，1H)，4.58(d，J＝7.3Hz，2H)，2.22-2.17(m，2H)，2.11(d，J＝5.6Hz，2H)，2.05(s，3H)，1.56(tt，J＝6.9，4.5Hz，6H)；
13C NMR(100MHz，CDCl3)δ(ppm)：171.29，147.07，115.26，60.81，37.14，29.14，28.46，27.86，26.74，21.25；
HRMS-ESI(m/z)：169.1225[M+H]+。
Example 3
Firstly, weighing K2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) and Compound M03(11.0mg, 0.24mmol) were added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, and dry-chromatography (300-400 mesh silica gel chromatography) (petroleum ether-ethyl acetate 19: 1) was carried out to give 22.8mg of product P03 in 74% yield.
1H NMR(400MHz，CDCl3)δ(ppm)：8.06(s，1H)，5.31(tt，J＝7.4，1.3Hz，1H)，4.68(d，J＝7.4Hz，2H)，2.21(t，J＝5.5Hz，2H)，2.16-2.09(m，2H)，1.56(h，J＝4.2Hz，7H)；
13C NMR(100MHz，CDCl3)δ(ppm)：161.26，147.99，114.64，60.17，37.12，29.15，28.44，27.84，26.69；
HRMS-ESI(m/z)：155.1066[M+H]+。
Example 4
Firstly, weighing K2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) and Compound M04(24.5mg, 0.24mmol) were added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction, the solvent was removed by rotary evaporation, and the product P04 was obtained in 27.4mg and 65% yield by dry loading and column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：5.27(tt，J＝7.1，1.2Hz，1H)，4.55(d，J＝7.1Hz，2H)，2.23-2.15(m，2H)，2.10(d，J＝5.2Hz，2H)，1.55(q，J＝3.0，2.6Hz，6H)，1.18(s，9H)；
13C NMR(101MHz，CDCl3)δ178.72，146.62，115.61，60.69，38.84，37.07，29.23，28.55，27.93，27.35，26.76；
HRMS-ESI(m/z)：211.1689[M+H]+。
Example 5
Compound M05(30.8mg, 0.24mmol) and K were weighed out first2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product P05 was obtained in 41.7mg and 88% yield by dry column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：5.26(tt，J＝7.1，1.3Hz，1H)，4.55(d，J＝7.2Hz，2H)，2.27(tt，J＝11.3，3.6Hz，1H)，2.18(t，J＝5.5Hz，2H)，2.11(d，J＝5.5Hz，2H)，1.92-1.83(m，2H)，1.73(dq，J＝9.9，3.7Hz，3H)，1.54(h，J＝4.5，4.0Hz，6H)，1.47-1.37(m，2H)，1.31-1.21(m，3H)；
13C NMR(101MHz，CDCl3)δ(ppm)：176.28，146.78，115.51，60.43，43.39，37.09，29.17，29.15，28.47，27.87，26.73，25.90，25.59；
HRMS-ESI(m/z)：237.1847[M+H]+。
Example 6
Compound M06(39.4mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product P06 was obtained in 48.5mg and 89% yield by dry loading and column chromatography (300-400 mesh silica gel) (petroleum ether-ethyl acetate: 19: 1).
1H NMR(400MHz，CDCl3)δ(ppm)：7.36-7.28(m，4H)，7.23(ddt，J＝8.4，6.0，2.0Hz，1H)，5.22(tt，J＝7.1，1.3Hz，1H)，4.57(d，J＝7.1Hz，2H)，2.16-2.10(m，2H)，2.08(d，J＝5.4Hz，2H)，1.58(s，6H)，1.53(p，J＝3.3，2.9Hz，4H)，1.50-1.44(m，2H)；
13C NMR(101MHz，CDCl3)δ(ppm)：176.81，147.06，145.02，128.41，126.66，125.82，125.79，115.27，61.11，46.69，37.02，29.18，28.51，27.85，26.71；
HRMS-ESI(m/z)：273.1844[M+H]+。
Example 7
Compound M07(35.1mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated three times through a vacuum line, DCM (2.0mL) was added under nitrogen atmosphere, and the chamber was evacuatedAnd reacting at the temperature for 24 hours. After the reaction was completed, the solvent was removed by rotary evaporation, and the product P07 was obtained in 43.7mg with 86% yield by dry loading and column chromatography (300-.
1H NMR(600MHz，CDCl3)δ(ppm)：7.61-7.55(m，2H)，7.44(td，J＝7.3，1.4Hz，1H)，7.36(dd，J＝8.4，7.1Hz，2H)，5.36(t，J＝7.5Hz，1H)，4.75(d，J＝7.4Hz，2H)，2.24(d，J＝5.6Hz，2H)，2.15(t，J＝5.5Hz，2H)，1.57(dq，J＝7.1，3.9，3.2Hz，6H)；
13C NMR(150MHz，CDCl3)δ(ppm)：154.29，148.35，133.12，130.69，128.68，119.86，114.40，86.22，80.87，62.30，37.17，29.21，28.40，27.83，26.70；
HRMS-ESI(m/z)：255.1375[M+H]+。
Example 8
Compound M08(26.9mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product P08 was obtained in 39.8mg and 90% yield by dry loading and column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：7.24(dd，J＝15.3，9.8Hz，1H)，6.26-6.05(m，2H)，5.77(d，J＝15.4Hz，1H)，5.31(tt，J＝7.3，1.3Hz，1H)，4.64(d，J＝7.2Hz，2H)，2.21(d，J＝6.0Hz，2H)，2.11(d，J＝5.5Hz，2H)，1.84(d，J＝5.9Hz，3H)，1.55(tt，J＝6.8，4.7，4.0Hz，6H)；
13C NMR(101MHz，CDCl3)δ(ppm)：167.48，146.82，145.05，139.30，129.95，119.18，115.48，60.57，37.12，29.16，28.44，27.84，26.73，18.75；
HRMS-ESI(m/z)：243.1354[M+H]+。
Example 9
Compound M09(36.0mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction, the solvent was removed by rotary evaporation, and the product P09 was obtained in 40.0mg (77% yield) by dry column chromatography (300-400 mesh silica gel) (19: 1 petroleum ether-ethyl acetate).
1H NMR(600MHz，CDCl3)δ(ppm)：8.04-7.98(m，2H)，7.65(td，J＝7.4，1.4Hz，1H)，7.51(td，J＝7.7，1.3Hz，2H)，5.42(tt，J＝7.5，1.3Hz，1H)，4.90(d，J＝7.5Hz，2H)，2.27(d，J＝5.6Hz，2H)，2.16(t，J＝5.4Hz，2H)，1.57(h，J＝4.2，3.2Hz，6H)；
13C NMR(150MHz，CDCl3)δ(ppm)：186.63，164.05，149.17，134.97，132.71，130.18，128.99，114.07，62.40，37.16，29.28，28.45，27.87，26.66；
HRMS-ESI(m/z)：281.1147[M+H]+。
Example 10
Compound M10(41.6mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction is finished, removing the solvent by rotary evaporation, loading the sample by a dry method,column chromatography (300-400 mesh silica gel) (9: 1 petroleum ether-ethyl acetate) gave 44.3mg of product P10 in 79% yield.
1H NMR(400MHz，CDCl3)δ(ppm)：8.30(ddd，J＝15.7，8.5，3.0Hz，2H)，8.17(dd，J＝8.5，2.6Hz，1H)，7.86(dd，J＝8.4，2.9Hz，1H)，7.82-7.74(m，1H)，7.63(td，J＝8.2，7.7，2.7Hz，1H)，5.50(t，J＝7.4Hz，1H)，5.01(d，J＝7.2Hz，2H)，2.29(d，J＝5.6Hz，2H)，2.14(d，J＝5.5Hz，2H)，1.62-1.52(m，6H)；
13C NMR(101MHz，CDCl3)δ(ppm)：165.44，148.41，147.63，147.41，137.40，137.38，130.84，130.31，129.39，128.63，127.60，121.18，115.14，62.55，37.17，29.30，28.40，27.84，26.72；
HRMS-ESI(m/z)：282.1485[M+H]+。
Example 11
Compound M11(49.7mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction, the solvent was removed by rotary evaporation, and the product P11 was obtained in 50.5mg and 80% yield by dry loading and column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：7.36(d，J＝5.8Hz，1H)，7.20(d，J＝5.8Hz，1H)，5.39(tt，J＝7.2，1.3Hz，1H)，4.79(d，J＝7.2Hz，2H)，2.29-2.21(m，2H)，2.13(d，J＝5.4Hz，2H)，1.57(q，J＝2.4Hz，6H)；
13C NMR(101MHz，CDCl3)δ(ppm)：162.11，147.45，131.44，129.56，125.82，119.79，115.10，61.19，37.12，29.26，28.47，27.88，26.73；
HRMS-ESI(m/z)：315.0042[M+H]+。
Example 12
Compound M12(42.0mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction, the solvent was removed by rotary evaporation, and the product P12 was obtained in 44.0mg and 78% yield by dry loading and column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：7.68(dq，J＝7.9，1.1Hz，1H)，7.41-7.31(m，3H)，7.15(ddt，J＝7.9，6.6，1.4Hz，1H)，5.44(ddq，J＝8.4，7.0，1.3Hz，1H)，4.84(dd，J＝7.2，1.5Hz，2H)，4.09(s，2H)，2.33-2.27(m，2H)，2.17(d，J＝5.4Hz，2H)，1.60(dt，J＝4.3，2.3Hz，6H)；
13C NMR(101MHz，CDCl3)δ(ppm)：162.43，147.30，139.76，128.23，126.04，124.99，122.66，120.59，115.34，110.34，110.30，60.81，37.16，31.75，29.30，28.51，27.94，26.76；
HRMS-ESI(m/z)：284.1646[M+H]+。
Example 13
Compound M13(26.9mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction is finished, the solvent is removed by rotary evaporation and driedColumn chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：8.00(d，J＝1.5Hz，1H)，7.43-7.39(m，1H)，6.74(d，J＝1.8Hz，1H)，5.35(t，J＝7.2Hz，1H)，4.76(d，J＝7.2Hz，2H)，2.24(d，J＝5.8Hz，2H)，2.13(d，J＝5.4Hz，2H)，1.61-1.52(m，6H)；
13C NMR(101MHz，CDCl3)δ(ppm)：163.33，147.76，147.14，143.72，119.75，115.28，110.01，60.80，37.13，29.24，28.48，27.90，26.74；
HRMS-ESI(m/z)：221.1169[M+H]+。
Example 14
Compound M14(30.0mg, 0.24mmol) and K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product P14 was obtained in 38.6mg (83% yield) by dry column chromatography (300-400 mesh silica gel) (petroleum ether-ethyl acetate 9: 1).
1H NMR(400MHz，CDCl3)δ(ppm)：6.95(dd，J＝4.0，1.8Hz，1H)，6.76(t，J＝2.2Hz，1H)，6.10(dd，J＝3.9，2.5Hz，1H)，5.38(ddq，J＝7.1，5.9，1.2Hz，1H)，4.73(d，J＝7.1Hz，2H)，3.92(s，3H)，2.28-2.22(m，2H)，2.13(d，J＝5.6Hz，3H)，1.56(tt，J＝4.9，2.9Hz，7H)；
13C NMR(101MHz，CDCl3)δ(ppm)：161.52，146.65，129.42，122.87，117.87，115.74，107.86，60.09，37.11，36.95，29.24，28.49，27.90，26.77；
HRMS-ESI(m/z)：234.1485[M+H]+。
Example 15
The compound M15 (lithocholic acid, 56.5mg, 0.15mmol) and K were weighed first2CO3(13.8mg, 0.10mmol) and Compound A01(41.2mg, 0.10mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 hours. After the reaction was completed, the solvent was removed by rotary evaporation, and the product P15 was obtained in 34.4mg with a yield of 71% by dry loading and column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：5.28(t，J＝7.3Hz，1H)，4.57(d，J＝7.3Hz，2H)，3.61(tq，J＝9.7，4.7Hz，1H)，2.34(ddd，J＝15.2，9.9，5.2Hz，1H)，2.26-2.14(m，3H)，2.11(d，J＝5.2Hz，2H)，1.95(dt，J＝12.4，3.0Hz，1H)，1.90-1.71(m，4H)，1.72-1.60(m，4H)，1.55(tt，J＝8.4，6.0，5.0Hz，7H)，1.37(dtd，J＝17.4，10.6，8.6，3.7Hz，6H)，1.25(dddd，J＝14.2，10.1，8.3，3.9Hz，4H)，1.17-0.94(m，6H)，0.93-0.88(m，6H)，0.63(s，3H)；
13C NMR(101MHz，CDCl3)δ(ppm)：174.51，146.92，115.43，72.01，60.59，56.64，56.13，42.88，42.25，40.58，40.31，37.13，36.60，35.99，35.49，34.72，31.52，31.17，31.06，30.69，29.16，28.47，28.33，27.87，27.34，26.75，26.56，24.35，23.52，20.97，18.42；
HRMS-ESI(m/z)：485.4001[M+H]+。
Example 16
Compound M16 (adapalene, 61.9mg, 0) was weighed out first.15mmol)、K2CO3(13.8mg, 0.10mmol) and Compound A01(41.2mg, 0.10mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 hours. After the reaction was completed, the solvent was removed by rotary evaporation, and dry-chromatography (300-400 mesh silica gel chromatography) (petroleum ether-ethyl acetate 9: 1) was carried out to give 34.8mg of the product P16 in 67% yield.
1H NMR(400MHz，CDCl3)δ(ppm)：8.62(d，J＝1.6Hz，1H)，8.09(dd，J＝8.6，1.7Hz，1H)，8.05-7.96(m，2H)，7.91(d，J＝8.7Hz，1H)，7.79(dd，J＝8.5，1.8Hz，1H)，7.61(d，J＝2.4Hz，1H)，7.55(dd，J＝8.4，2.4Hz，1H)，7.00(d，J＝8.5Hz，1H)，5.53-5.45(m，1H)，4.92(d，J＝7.2Hz，2H)，3.91(s，3H)，2.31(d，J＝5.7Hz，2H)，2.20(d，J＝2.9Hz，8H)，2.15-2.09(m，3H)，1.82(d，J＝3.0Hz，6H)，1.65-1.58(m，6H)；
13C NMR(101MHz，CDCl3)δ(ppm)：167.02，159.02，147.15，141.39，139.10，136.03，132.72，131.38，130.88，129.81，128.25，127.46，126.52，126.09，125.84，125.80，124.84，115.48，112.23，61.42，55.29，40.75，37.34，37.27，37.19，29.32，29.25，28.51，27.95，26.78；
HRMS-ESI(m/z)：521.3054[M+H]+。
Example 17
Firstly weighing compound M17 (oxaliplatin, 44mg, 0.15mmol) and K2CO3(13.8mg, 0.10mmol) and Compound A01(41.2mg, 0.10mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 hours. After the reaction, the solvent was removed by rotary evaporation, and the product P17 was obtained in 28.5mg (71% yield) by dry column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：7.66-7.62(m，2H)，7.59-7.54(m，2H)，7.40-7.29(m，6H)，5.29(tt，J＝7.2，1.2Hz，1H)，4.65(d，J＝7.3Hz，2H)，3.20(dd，J＝8.2，6.8Hz，2H)，2.91(dd，J＝8.2，6.8Hz，2H)，2.19(t，J＝5.4Hz，2H)，2.09(d，J＝5.3Hz，2H)，1.58-1.49(m，J＝3.7Hz，6H)；
13C NMR(101MHz，CDCl3)δ(ppm)：172.12，162.01，147.30，145.53，135.11，132.45，129.06，128.76，128.67，128.59，128.20，128.03，126.63，126.60，115.10，61.12，37.08，31.36，29.16，28.44，27.85，26.70，23.71；
HRMS-ESI(m/z)：402.2061[M+H]+。
Example 18
Firstly, weighing the compound M18 (probenecid, 42.8mg, 0.15mmol) and K2CO3(13.8mg, 0.10mmol) and Compound A01(41.2mg, 0.10mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 hours. After the reaction, the solvent was removed by rotary evaporation, and the product P18 was obtained in 37.6mg (95% yield) by dry column chromatography (300-.
1H NMR(600MHz，CDCl3)δ(ppm)：8.17-8.13(m，2H)，7.85(dd，J＝8.5，1.7Hz，2H)，5.40(t，J＝7.3Hz，1H)，4.85(d，J＝7.3Hz，2H)，3.08(dd，J＝8.8，6.7Hz，4H)，2.26(d，J＝4.9Hz，2H)，2.19-2.10(m，2H)，1.63-1.49(m，10H)，0.86(t，J＝7.4Hz，6H)；
13C NMR(151MHz，CDCl3)δ(ppm)：165.43，147.89，144.19，134.02，130.33，127.06，114.83，61.87，50.03，37.14，29.27，28.46，27.92，26.69，22.04，11.27；
HRMS-ESI(m/z)：394.2057[M+H]+。
Example 19
Compound M19 (naproxen, 34.5mg, 0.15mmol) and K were weighed first2CO3(13.8mg, 0.10mmol) and Compound A01(41.2mg, 0.10mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 hours. After the reaction was completed, the solvent was removed by rotary evaporation, and the product P19 was obtained in 28.5mg and 84% yield by dry column chromatography (300-.
1H NMR(600MHz，CDCl3)δ(ppm)：7.72-7.68(m，2H)，7.66(d，J＝1.8Hz，1H)，7.41(dd，J＝8.7，1.8Hz，1H)，7.13(dd，J＝8.8，2.6Hz，1H)，7.11(d，J＝2.5Hz，1H)，5.30-5.19(m，1H)，4.62(dd，J＝12.3，7.2Hz，1H)，4.55(dd，J＝12.3，7.2Hz，1H)，3.91(t，J＝1.4Hz，3H)，3.85(q，J＝7.2Hz，1H)，2.13(t，J＝6.1Hz，2H)，2.06(d，J＝5.5Hz，2H)，1.57(d，J＝7.1Hz，3H)，1.51(qd，J＝6.0，3.9，2.8Hz，4H)，1.47-1.42(m，2H)；
13C NMR(151MHz，CDCl3)δ(ppm)：174.82，157.70，147.14，136.01，133.78，129.39，129.07，127.19，126.44，126.05，119.01，115.22，105.71，61.12，55.44，45.64，37.05，29.16，28.45，27.81，26.70，18.82；
HRMS-ESI(m/z)：339.1955[M+H]+。
Example 20
First weighing compound M20 (biotin, 36.6mg, 0.15mmol) and K2CO3(13.8mg, 0.10mmol) and neutralizedCompound A01(41.2mg, 0.10mmol) was added to the reaction tube, the tube was purged three times through a vacuum line, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction, the solvent was removed by rotary evaporation, and the product P20 was obtained in 26.9mg (76% yield) by dry column chromatography (300-.
1H NMR(600MHz，CDCl3)δ(ppm)：5.26(t，J＝7.4Hz，1H)，4.56(d，J＝7.3Hz，2H)，4.50(dd，J＝7.7，5.1Hz，1H)，4.30(dd，J＝7.9，4.6Hz，1H)，3.14(dt，J＝11.4，5.7Hz，1H)，2.89(dd，J＝12.9，4.9Hz，1H)，2.74(d，J＝12.8Hz，1H)，2.32(t，J＝7.5Hz，2H)，2.18(t，J＝5.6Hz，2H)，2.10(d，J＝5.3Hz，2H)，1.68(dhept，J＝27.8，6.7Hz，4H)，1.54(h，J＝6.3，5.1Hz，6H)，1.43(dp，J＝20.9，6.8Hz，2H)；
13C NMR(151MHz，CDCl3)δ(ppm)：173.86，163.85，147.06，115.26，62.13，60.70，60.34，55.58，40.64，37.10，34.11，29.14，28.47，28.44，28.34，27.84，26.70，24.93；
HRMS-ESI(m/z)：353.1902[M+H]+。
Example 21
First, compound M21 (neotame, 113.5mg, 0.30mmol) and K were weighed2CO3(27.6mg, 0.20mmol) and Compound A01(82.4mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction was complete, the solvent was removed by rotary evaporation, dry loading was carried out, and column chromatography (300-400 mesh chromatography on silica gel) (dichloromethane-methanol 10: 1) gave 82.0mg of product P21 in 84% yield.
1H NMR(400MHz，CDCl3)δ(ppm)：7.84(d，J＝8.5Hz，1H)，7.35-7.21(m，3H)，7.18-7.11(m，2H)，5.27(tt，J＝7.2，1.3Hz，1H)，4.85(dt，J＝8.6，6.1Hz，1H)，4.65-4.50(m，2H)，3.71(s，3H)，3.43(dd，J＝8.7，3.8Hz，1H)，3.20-3.04(m，2H)，2.74(dd，J＝16.5，3.8Hz，1H)，2.53(dddd，J＝17.0，15.5，12.5，7.7Hz，3H)，2.23-2.15(m，3H)，2.13(d，J＝5.5Hz，2H)，1.55(hept，J＝4.5，4.0Hz，7H)，1.37-1.29(m，2H)，0.86(s，8H)；
13C NMR(101MHz，CDCl3)δ(ppm)：172.60，171.84，171.70，147.45，136.08，129.37，128.65，127.19，114.91，61.13，59.40，52.83，52.33，44.61，44.13，38.11，37.08，36.59，29.87，29.64，29.14，28.42，27.84，26.67；
HRMS-ESI(m/z)：487.3179[M+H]+。
Example 22
Compound M22 (penicillin potassium, 117.4mg, 0.30mmol) and compound a01(82.4mg, 0.20mmol) were weighed into a reaction tube, evacuated through a vacuum line three times, added DCM (2.0mL) under nitrogen atmosphere and reacted at room temperature for 24 h. After the reaction was complete, the solvent was removed by rotary evaporation, dry loading was carried out, and column chromatography (300-400 mesh chromatography on silica gel) (dichloromethane-methanol 10: 1) gave 81.2mg of product P22 in 92% yield.
1H NMR(400MHz，CDCl3)δ(ppm)：7.34-7.25(m，3H)，7.22-7.19(m，3H)，6.03(dt，J＝6.8，3.4Hz，1H)，5.57(dd，J＝9.0，4.2Hz，1H)，5.43(d，J＝4.2Hz，1H)，5.25-5.17(m，1H)，4.58(dd，J＝7.5，2.3Hz，2H)，4.28(s，1H)，3.57(s，2H)，2.13(t，J＝5.5Hz，3H)，2.05(d，J＝5.7Hz，3H)，1.48(q，J＝4.0Hz，9H)，1.36(d，J＝3.3Hz，6H)；
13C NMR(101MHz，CDCl3)δ(ppm)：173.53，170.48，167.64，148.73，133.95，129.71，129.59，129.27，129.12，128.87，127.78，114.19，70.45，68.20，64.71，61.77，58.90，43.55，37.10，32.16，29.18，28.45，28.43，27.84，26.91，26.64；
HRMS-ESI(m/z)：443.2011[M+H]+。
Example 23
Compound A01(82.4mg, 0.20mmol) was weighed into a reaction tube, evacuated through a vacuum line three times, and added with compound M23(42.9mg, 0.40mmol) and DCM (2.0mL) under nitrogen atmosphere and reacted at room temperature for 48 h. After the reaction was complete, the solvent was removed by rotary evaporation, dry loading was carried out, and column chromatography (300-400 mesh chromatography on silica gel) (dichloromethane-methanol 19: 1) gave 27.5mg of product P23 in 64% yield.
1H NMR(600MHz，CDCl3)δ(ppm)：7.24(td，J＝8.3，7.2，2.1Hz，2H)，6.79(d，J＝8.1Hz，2H)，6.73(t，J＝7.3Hz，1H)，5.17(t，J＝6.7Hz，1H)，3.92(d，J＝6.7Hz，2H)，2.90(s，3H)，2.24(t，J＝5.5Hz，2H)，2.10(t，J＝5.9Hz，2H)，1.56(dq，J＝16.7，4.7，4.0Hz，6H)；
13C NMR(151MHz，CDCl3)δ(ppm)：149.79，143.09，129.21，117.10，116.77，113.31，49.81，37.99，37.20，29.02，28.69，27.93，26.92；
HRMS-ESI(m/z)：216.1752[M+H]+。
Example 24
Compound A01(82.4mg, 0.20mmol) was weighed into a reaction tube, evacuated three times through a vacuum line, and added with compound M24(78.9mg, 0.40mmol) and DCM (2.0mL) under nitrogen atmosphere and reacted at room temperature for 48 h. After the reaction was complete, the solvent was removed by rotary evaporation, dry loading was carried out, and column chromatography (300-400 mesh chromatography on silica gel) (dichloromethane-methanol 10: 1) gave 46.5mg of product P24 in 76% yield.
1H NMR(400MHz，CDCl3)δ(ppm)：7.44(d，J＝7.4Hz，4H)，7.36(t，J＝7.5Hz，4H)，7.32-7.27(m，2H)，5.34-5.29(m，1H)，3.62(s，4H)，3.08(d，J＝6.9Hz，2H)，2.15(p，J＝5.8，5.4Hz，4H)，1.57(tp，J＝11.5，5.4Hz，6H)；
13C NMR(101MHz，CDCl3)δ(ppm)：143.28，140.13，128.95，128.23，126.83，118.59，57.97，50.23，37.45，29.11，28.81，27.87，26.97；
HRMS-ESI(m/z)：306.2222[M+H]+。
Example 25
Compound M25(60.5mg, 0.40mmol) and compound A01(82.4mg, 0.20mmol) were weighed into a reaction tube, evacuated through a vacuum line three times, added DCM (2.0mL) under nitrogen atmosphere and reacted at room temperature for 48 h. After the reaction was complete, the solvent was removed by rotary evaporation, dry loading was carried out, and column chromatography (300-400 mesh chromatography on silica gel) (dichloromethane-methanol 10: 1) gave 36.8mg of product P25 in 71% yield.
1H NMR(600MHz，CDCl3)δ(ppm)：6.72-6.50(br，1H)，5.33-5.25(m，1H)，3.61(q，J＝6.7Hz，2H)，2.22-2.16(m，5H)，2.11(q，J＝4.4，3.2Hz，2H)，1.96(d，J＝3.0Hz，6H)，1.76-1.66(m，6H)，1.55(q，J＝6.3，4.0Hz，6H)；
13C NMR(151MHz，CDCl3)δ(ppm)：150.12，110.70，58.76，38.56，38.02，37.14，35.52，29.23，29.05，28.02，27.32，26.55；
HRMS-ESI(m/z)：260.2370[M+H]+。
Example 26
Compound A01(82.4mg, 0.20mmol) was weighed into a reaction tube, evacuated through a vacuum line three times, and added with compound M26(29.3mg, 0.40mmol) and DCM (2.0mL) under nitrogen atmosphere and reacted at room temperature for 48 h. After the reaction was complete, the solvent was removed by rotary evaporation, dry loading was carried out, and column chromatography (300-400 mesh chromatography on silica gel) (dichloromethane-methanol 10: 1) gave 22.4mg of product P26 in 62% yield.
1H NMR(600MHz，CDCl3)δ(ppm)：6.71(br，1H)，5.28(t，J＝7.7Hz，1H)，3.59(td，J＝7.4，4.0Hz，2H)，2.18(t，J＝5.6Hz，2H)，2.12(d，J＝5.5Hz，2H)，1.55(q，J＝6.8，3.9Hz，6H)，1.43(s，9H)；
13C NMR(151MHz，CDCl3)δ(ppm)：150.51，110.34，58.32，39.86，37.13，29.02，28.02，27.35，26.50，25.93；
HRMS-ESI(m/z)：182.1902[M+H]+。
Example 27
Compound A01(82.4mg, 0.20mmol) was weighed into a reaction tube, evacuated through a vacuum line three times, and added with compound M27(34.9mg, 0.40mmol) and DCM (2.0mL) under nitrogen atmosphere and reacted at room temperature for 48 h. After the reaction was complete, the solvent was removed by rotary evaporation, dry loading was carried out, and column chromatography (300-400 mesh chromatography on silica gel) (dichloromethane-methanol 10: 1) gave 19.4mg of product P27 in 50% yield.
1H NMR(600MHz，CDCl3)δ(ppm)：7.31(br，1H)，5.26(t，J＝7.7Hz，1H)，3.69(dt，J＝7.6，4.8Hz，2H)，2.94(dtd，J＝11.6，7.8，5.2Hz，2H)，2.21-2.14(m，4H)，1.74(q，J＝7.8，7.4Hz，2H)，1.57(d，J＝5.9Hz，6H)，1.35(dh，J＝11.2，3.7，3.3Hz，6H)，0.90(t，J＝6.6Hz，3H)；
13C NMR(151MHz，CDCl3)δ(ppm)：151.77，109.80，46.52，44.53，37.28，29.21，28.61，28.36，27.74，26.52，25.61，22.19，13.89；
HRMS-ESI(m/z)：196.2064[M+H]+。
Example 28
Compound A01(82.4mg, 0.20mmol) and K were weighed out first2CO3(27.6mg, 0.20mmol) and Compound M28(100.9mg, 0.60mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 72 h. After the reaction, the solvent was removed by rotary evaporation, and the product P28 was obtained in 34.4mg (62% yield) by dry loading and column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：6.13(s，2H)，5.10(tt，J＝7.2，1.2Hz，1H)，3.80(d，J＝1.3Hz，9H)，3.27(d，J＝7.3Hz，2H)，2.33(t，J＝5.2Hz，2H)，2.02(t，J＝5.8Hz，2H)，1.54(dq，J＝6.2，3.5Hz，4H)，1.51-1.44(m，2H)；
13C NMR(101MHz，CDCl3)δ(ppm)：159.29，158.74，138.69，120.05，111.20，90.85，55.86，55.46，37.32，28.85，28.71，28.00，27.23，21.04；
HRMS-ESI(m/z)：277.1796[M+H]+。
Example 29
Compound M01(29.3mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A02(76.8mg, 0.20mmol) were added to a reaction tube, the tube was evacuated three times through a vacuum line, DCM (2.0mL) was added under a nitrogen atmosphere, and the reaction was carried out at room temperatureAnd the time is 24 hours. After the reaction, the solvent was removed by rotary evaporation, and the product P29 was obtained in 28.1mg (69% yield) by dry column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：8.08-8.02(m，2H)，7.58-7.51(m，1H)，7.43(dd，J＝8.4，7.0Hz，2H)，6.01(dtd，J＝10.0，3.7，1.2Hz，1H)，5.84(ddt，J＝10.1，4.1，2.2Hz，1H)，5.51(tdq，J＝5.3，3.4，1.6Hz，1H)，2.19-2.04(m，1H)，1.98(dddd，J＝13.3，9.8，5.1，3.4Hz，1H)，1.94-1.79(m，2H)，1.71(dddd，J＝13.8，11.5，5.9，3.4Hz，1H)；
13C NMR(101MHz，CDCl3)δ(ppm)：166.36，132.98，132.87，130.93，129.72，128.39，125.87，68.73，28.56，25.10，19.09；
HRMS-ESI(m/z)：203.1064[M+H]+。
Example 30
Compound M01(29.3mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A03(86.9mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product P30 was obtained in 46.7mg and 92% yield by dry column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：7.98(ddd，J＝7.3，3.4，1.4Hz，2H)，7.47(tq，J＝7.4，1.7Hz，1H)，7.40-7.30(m，2H)，7.26-7.17(m，2H)，7.13(q，J＝7.1，6.6Hz，3H)，6.02-5.61(m，2H)，4.97-4.68(m，2H)，3.50-3.31(m，2H)；
13C NMR(101MHz，CDCl3)δ(ppm)：166.63，139.94，133.81，133.06，130.36，129.75，128.68，128.52，128.47，126.32，124.41，60.80，34.00；
HRMS-ESI(m/z)：253.1229[M+H]+。
Example 31
Compound M01(29.3mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A04(82.5mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction, the solvent was removed by rotary evaporation, and the product P31 was obtained in 33.7mg and 73% yield by dry loading and column chromatography (300-.
1H NMR(600MHz，CDCl3)δ(ppm)：8.05(dt，J＝8.4，1.9Hz，2H)，7.57-7.53(m，1H)，7.44(t，J＝7.7Hz，2H)，5.89-5.65(m，3H)，5.02(ddq，J＝17.1，3.8，1.8Hz，1H)，4.96(dp，J＝10.3，1.7Hz，1H)，4.90-4.75(m，2H)，2.23-2.04(m，4H)，1.55-1.47(m，2H)；
13C NMR(151MHz，CDCl3)δ(ppm)：166.69，138.55，135.29，133.01，132.99，129.74，128.46，123.85，114.95，61.01，33.33，28.74，27.16；
HRMS-ESI(m/z)：231.1382[M+H]+。
Example 32
Compound M01(29.3mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A05(91.7mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction is finished, removing the solvent by rotary evaporation, loading the sample by a dry method, and carrying out columnChromatography (300-400 mesh silica gel) (9: 1. RTM. petroleum ether-ethyl acetate) gave 39.2mg of product P32 in 71% yield.
1H NMR(400MHz，CDCl3)δ(ppm)：8.05(dd，J＝8.2，1.5Hz，2H)，7.57-7.52(m，1H)，7.43(t，J＝7.6Hz，2H)，5.92-5.60(m，2H)，4.89-4.73(m，2H)，3.63(td，J＝6.6，2.5Hz，2H)，2.22-2.02(m，2H)，1.55(qd，J＝8.1，6.6，2.3Hz，2H)，1.45-1.28(m，8H)；
13C NMR(101MHz，CDCl3)δ(ppm)：166.72，135.74，133.02，130.44，129.73，128.45，123.49，63.12，61.00，32.84，29.44，29.33，29.23，27.70，25.78；
HRMS-ESI(m/z)：277.1803[M+H]+。
Example 33
Compound M01(29.3mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A06(82.9mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction, the solvent was removed by rotary evaporation, and the product P33 was obtained in 41.0mg and 88% yield by dry loading and column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：8.06(dt，J＝8.5，1.6Hz，2H)，7.59-7.52(m，1H)，7.43(dd，J＝8.4，7.1Hz，2H)，5.94-5.60(m，2H)，4.94-4.73(m，2H)，2.23-2.03(m，2H)，1.46-1.37(m，2H)，1.30(td，J＝6.4，5.7，3.0Hz，4H)，0.89(td，J＝6.9，1.6Hz，3H)；
13C NMR(101MHz，CDCl3)δ(ppm)：166.70，135.88，132.99，130.49，129.73，128.44，123.41，61.01，31.54，29.26，27.74，22.66，14.17；
HRMS-ESI(m/z)：233.1541[M+H]+。
Example 34
Compound M01(29.3mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A07(98.5mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction, the solvent was removed by rotary evaporation, and the product P34 was obtained in 50.9mg (82% yield) by dry column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：8.03(dq，J＝8.7，1.8Hz，4H)，7.54(tddd，J＝8.9，5.6，2.6，1.3Hz，2H)，7.46-7.34(m，4H)，6.02-5.72(m，2H)，5.00-4.75(m，2H)，4.40(td，J＝6.6，0.9Hz，2H)，2.76-2.52(m，2H)；
13C NMR(101MHz，CDCl3)δ(ppm)：166.64，166.55，133.06，133.04，131.28，130.44，130.28，129.73，129.67，128.46，126.49，63.96，60.73，27.47；
HRMS-ESI(m/z)：333.1094[M+H]+。
Example 35
Compound M01(29.3mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A08(95.8mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction, the solvent was removed by rotary evaporation, and the product P35 was obtained in 56.4mg and 95% yield by dry loading and column chromatography (300-.
1H NMR(600MHz，CDCl3)δ(ppm)：8.05(ddd，J＝8.4，3.5，1.4Hz，2H)，7.57-7.52(m，1H)，7.47-7.41(m，2H)，5.89-5.63(m，2H)，4.91-4.75(m，2H)，3.41(td，J＝6.7，1.8Hz，2H)，2.17(dq，J＝58.0，6.8Hz，2H)，1.89(ddd，J＝14.8，7.8，5.9Hz，2H)，1.62-1.51(m，2H)；
13C NMR(151MHz，CDCl3)δ(ppm)：166.55，134.73，133.00，130.32，129.67，128.42，124.20，60.74，33.63，32.26，27.97，26.81；
HRMS-ESI(m/z)：297.0482[M+H]+。
Example 36
Compound M01(14.6mg, 0.12mmol) and K were weighed out first2CO3(13.8mg, 0.10mmol) and Compound A09(64.2mg, 0.10mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 hours. After the reaction, the solvent was removed by rotary evaporation, and the product P36 was obtained in 31.5mg (69% yield) by dry column chromatography (300-.
1H NMR(600MHz，CDCl3)δ(ppm)：8.16(ddd，J＝12.7，8.5，1.3Hz，2H)，8.08-8.01(m，2H)，7.90-7.84(m，2H)，7.56(tdp，J＝7.6，4.2，1.4Hz，1H)，7.44(dddd，J＝10.7，4.6，3.1，1.4Hz，3H)，6.11-5.91(m，2H)，5.07-4.84(m，4H)，3.09(dd，J＝8.8，6.6Hz，4H)，1.54(hd，J＝7.4，1.3Hz，4H)，0.86(dd，J＝8.1，6.6Hz，5H)；
13C NMR(151MHz，CDCl3)δ(ppm)：166.29，164.99，144.51，133.25，130.42，129.76，129.01，128.54，128.24，127.86，127.59，127.14，65.08，64.31，50.02，22.03，11.27；
HRMS-ESI(m/z)：460.1785[M+H]+。
Example 37
Compound M01(14.6mg, 0.12mmol) and K were weighed out first2CO3(13.8mg, 0.10mmol) and Compound A10(77.5mg, 0.10mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction, the solvent was removed by rotary evaporation, and the product P37 was obtained in 48.5mg (82% yield) by dry column chromatography (300-.
1H NMR(600MHz，CDCl3)δ(ppm)：8.05(ddd，J＝9.5，8.0，1.5Hz，2H)，7.57(tdd，J＝7.3，3.2，1.5Hz，1H)，7.50-7.39(m，2H)，6.02-5.91(m，1H)，5.93-5.77(m，1H)，4.94(d，J＝6.6Hz，1H)，4.84(d，J＝4.6Hz，1H)，4.77-4.68(m，2H)，4.63-4.59(m，1H)，2.37(dtd，J＝15.3，10.0，5.1Hz，1H)，2.24(dtd，J＝16.3，10.4，6.6Hz，1H)，2.03(s，3H)，1.95(d，J＝12.4Hz，1H)，1.90-1.76(m，5H)，1.72-1.65(m，1H)，1.59-1.51(m，2H)，1.48-1.30(m，8H)，1.25(ddt，J＝22.7，12.9，9.1Hz，3H)，1.17-0.99(m，6H)，0.95-0.87(m，6H)，0.63(d，J＝3.6Hz，3H)；
13C NMR(151MHz，CDCl3)δ(ppm)：174.02，170.79，166.33，133.21，130.16，129.79，128.53，128.38，128.17，74.54，64.50，60.65，56.63，42.88，42.03，40.55，40.28，35.93，35.49，35.18，34.73，32.40，31.36，31.33，31.11，28.34，27.16，26.78，26.46，24.32，23.48，21.63，20.97，18.42.12.18；
HRMS-ESI(m/z)：615.3654[M+H]+。
Example 38
Compound M01(29.3mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A11(97.7mg, 0.20mmol) were added to the reaction tube, the tube was evacuated through a vacuum line three times, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, and dry-chromatography (300-400 mesh silica gel chromatography) (petroleum ether-ethyl acetate 19: 1) was carried out to give 43.5mg of the product P38 in 71% yield.
1H NMR(400MHz，CDCl3)δ(ppm)：8.15-8.04(m，2H)，7.68-7.55(m，3H)，7.53-7.39(m，4H)，6.81-6.73(m，1H)，6.50(dt，J＝16.0，6.1Hz，1H)，5.10-4.98(m，2H)；
13C NMR(101MHz，CDCl3)δ(ppm)：166.42，139.83，133.27，132.51，129.95(q，J＝36.0Hz)，129.81，128.57，126.92，126.24，125.71(q，J＝3.8Hz)，124.19(q，J＝272.7Hz)，65.15；
19F NMR(376MHz，CDCl3)δ(ppm)：-62.54(s，3F)；
HRMS-ESI(m/z)：329.0770[M+H]+。
Example 39
Compound M01(29.3mg, 0.24mmol), K were weighed first2CO3(27.6mg, 0.20mmol) and Compound A12(96.9mg, 0.20mmol) were added to the reaction tube, the tube was evacuated three times through a vacuum line, DCM (2.0mL) was added under nitrogen atmosphere, and the reaction was carried out at room temperature for 24 h. After the reaction, the solvent was removed by rotary evaporation, and the product P39 was obtained in 44.9mg and 74% yield by dry loading and column chromatography (300-.
1H NMR(400MHz，CDCl3)δ(ppm)：8.05(tt，J＝6.5，1.4Hz，2H)，7.61-7.52(m，1H)，7.43(td，J＝7.8，3.0Hz，2H)，5.93-5.76(m，2H)，4.88(dd，J＝40.4，5.3Hz，2H)，4.78-4.55(m，2H)，2.31(tdt，J＝11.5，7.6，3.7Hz，1H)，1.97-1.85(m，2H)，1.80-1.69(m，3H)，1.44(qd，J＝11.5，3.8Hz，2H)，1.34-1.19(m，3H)；
13C NMR(101MHz，CDCl3)δ(ppm)：175.89，166.40，133.16，130.13，129.75，128.67，128.49，128.14，64.51，60.67，43.24，29.10，25.85，25.55，25.54；
HRMS-ESI(m/z)：325.1416[M+H]+。
Example 40
Compound A13(84.1mg, 0.20mmol) was weighed into a reaction tube, evacuated through a vacuum line three times, and added with compound M29(68.5mg, 0.40mmol) and DCM (2.0mL) under nitrogen atmosphere and reacted at room temperature for 48 h. After the reaction, the solvent was removed by rotary evaporation, and the product P40 (naftifine) was obtained in 41.1mg with 71% yield by dry loading and column chromatography (300-.
1H NMR(600MHz，CDCl3)δ(ppm)：8.33(d，J＝8.5Hz，1H)，7.87(t，J＝6.5Hz，1H)，7.80(dd，J＝8.4，4.4Hz，1H)，7.54(t，J＝6.9Hz，1H)，7.52-7.46(m，1H)，7.42(q，J＝7.2，6.6Hz，3H)，7.33(q，J＝6.9Hz，2H)，7.30-7.20(m，2H)，6.60(dd，J＝16.1，4.7Hz，1H)，6.40(dq，J＝15.2，6.5，5.8Hz，1H)，3.98(d，J＝3.5Hz，2H)，3.35-3.28(m，2H)，2.31(s，3H)；
13C NMR(151MHz，CDCl3)δ(ppm)：137.26，134.95，134.03，132.88，132.64，128.69，128.59，128.11，127.80，127.64，127.54，126.47，126.05，125.73，125.27，124.75，60.53，60.20，42.58。
EXAMPLE 41
Compound A13(84.1mg, 0.20mmol) was weighed into a reaction tube, evacuated through a vacuum line three times, and added with compound M30(68.5mg, 0.40mmol) and DCM (2.0mL) under nitrogen atmosphere and reacted at room temperature for 48 h. After the reaction is finished, the solvent is removed by rotary evaporation, the sample is loaded by a dry method, and column chromatography (300-400 mesh chromatography silica gel) (petroleum ether-ethyl acetate is 4: 1) is carried out to obtain the product P41 (cinnarizine) of 49.0mg with 66 percent of yield.
1H NMR(600MHz，CDCl3)δ(ppm)：7.35-7.31(m，4H)，7.28(d，J＝7.8Hz，2H)，7.21(t，J＝7.7Hz，2H)，7.20-7.12(m，5H)，7.09(t，J＝7.4Hz，2H)，6.43(d，J＝15.8Hz，1H)，6.20(dt，J＝14.9，6.8Hz，1H)，4.17(s，1H)，3.10(d，J＝6.8Hz，2H)，2.67-2.13(m，8H)；
13C NMR(151MHz，CDCl3)δ(ppm)：142.84，137.04，133.28，128.67，128.58，128.06，127.60，127.03，126.58，126.45，76.29，61.13，53.55，51.92。
It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should also be understood that various alterations, modifications and/or variations can be made to the present invention by those skilled in the art after reading the technical content of the present invention, and all such equivalents fall within the protective scope defined by the claims of the present application.
It will be appreciated by those skilled in the art that the invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The embodiments disclosed above are therefore to be considered in all respects as illustrative and not restrictive. All changes which come within the scope of or equivalence to the invention are intended to be embraced therein.
Claims (10)
1. The allylation coupling reaction method is characterized in that: an alkenylthianthrene salt of formula A
Reacting with a substrate Mx in an organic solvent, wherein the reaction is one of the following:
generating a corresponding allylated coupling product Px, said substrate Mx being selected from a compound of formula Ma, Mb or Mc;
wherein,
R1is C1-12Alkyl radical, C3-8Cycloalkyl, aryl, wherein, said C1-12Alkyl radical, C3-8Cycloalkyl, aryl optionally substituted with one or more groups independently selected from aryl, alkenyl, hydroxy, halogen, trifluoromethyl, acyloxy, dialkylamino, sulfonyl, alkyl, cycloalkyl or a combination of any plurality thereof, the same or different; r2Is H or C1-6An alkyl group; r1Optionally with the adjacent allylic carbon or with R2Connected to form a 5-8 membered ring; x is selected from halogen and BF4、PF6、AsF6、SbF6、ClO4、CF3COO、OTf、OTs；
R3Is H, C1-12Alkyl radical, C3-8Cycloalkyl radical, C2-7Heterocycloalkyl, aryl, heteroaryl, alkenyl, alkynyl, acyl, or a combination of any two or more thereof, wherein C is1-12Alkyl radical, C3-8Cycloalkyl radical, C2-7Heterocycloalkyl, aryl, heteroaryl are optionally substituted with one or more substituents independently selected from: halogen, hydroxy, oxo, trifluoromethyl, aryl, alkyl, cycloalkyl, alkoxy, alkylamino, amido, aminoacyl, ester, acyloxy, sulfonyl, or a combination formed by any plurality of the same or different groups; r4Is H or a metal ion capable of forming a salt with a carboxylic acid;
R5and R6Each of which isIndependently H, C1-8Alkyl radical, C3-8Cycloalkyl, aryl, or any combination thereof, said C1-6Alkyl radical, C3-8Cycloalkyl, aryl are optionally substituted with one or more substituents independently selected from: halogen, hydroxyl, oxo, trifluoromethyl, alkyl, aryl, alkoxy and alkylamino; optionally, R5And R6Directly connected or connected through heteroatom to form a ring;
y is CH or N; z is NRaO, S or
Wherein R isaIs H or C1-6An alkyl group; rn 7Is one or more selected from hydroxyl and C1-4Alkyl radical, C1-4Alkoxy, amino, C1-4A substituent of an alkylamino group, said substituent replacing a hydrogen on CH or NH on the parent ring, optionally, each Rn 7Can be connected to form a ring, wherein n is each R7The number of substituents, and n is less than the sum of CH and NH on the parent ring substituted with the substituent;
wherein, when the R substrate is a compound shown as a formula Ma or Mc, and R in Ma is4When the hydrogen is H, the reaction is also carried out under the condition of alkali.
2. The allylated coupling reaction process of claim 1,
R1is C1-8Alkyl or aryl, wherein, said C1-8Alkyl, aryl optionally substituted with one or more groups independently selected from aryl, alkenyl, hydroxy, halogen, trifluoromethyl, aryl-C (O), cycloalkyl-C (O), O-, alkyl-C (O), O-, dialkylaminosulfonyl, fused ring alkyl, or a combination of any 2 to 3 of these groups, which may be the same or different; r2Is H or C1-4An alkyl group; r1Optionally with the adjacent allylic carbon or with R2Connected to form a 5-or 6-membered ring.
3. The allylated coupling reaction process of claim 1, wherein:
R1is C1-8A linear alkyl, phenyl, naphthyl or a 6-membered ring linked to the adjacent allylic or terminal alkenyl carbon, wherein said C is1-8The linear alkyl end is optionally substituted by phenyl, naphthyl, vinyl, hydroxy, halogen, trifluoromethyl, phenyl-C (O) O-, cyclohexyl-C (O) O-, C1-8alkyl-C (O) O-, di-C1-4Alkylaminosulfonyl, fused ring alkyl-C2-8alkyl-C (O) O-, or is substituted by a combination of any 2 different groups therein; r2Is H, C1-4Alkyl or with R1Are connected.
4. The allylated coupling reaction process of claim 1, wherein:
R3is H, C1-8Alkyl radical, C5-6Cycloalkyl radical, C2-5Heterocycloalkyl, aryl, biaryl, heteroaryl, vinyl, conjugated alkenyl, aralkynyl, alkanyl, aroyl, alkanoyl or a combination of 2 to 3 of these optionally in combination, wherein C is1-4Alkyl radical, C5-6Cycloalkyl radical, C2-5Heterocycloalkyl, aryl, heteroaryl, vinyl, conjugated alkenyl, aralkynyl, alkanyl, aroyl, alkanoyl optionally substituted with one or more substituents independently selected from: halogen, hydroxy, oxo, trifluoromethyl, aryl, C1-4Alkyl, monocyclic or fused or bridged cycloalkyl, mono-or fused or bridged heterocycloalkyl, C1-4Alkoxy, monoalkyl or dialkylamino, dialkylaminosulfonyl, alkylamido, alkylaminoacyl, ester, acyloxy or a combination of any 2 to 3 of these groups, which may be the same or different;
R5and R6Each independently is H, C1-5Alkyl, aryl, biaryl, aryl-C1-5Alkyl radical, C3-6Cycloalkyl, polycycloalkyl; said C is1-5Alkyl, aryl-C1-5Alkyl radical, C3-6The cycloalkyl, polycycloalkyl groups are optionally substituted with one or more substituents independently selected from: hydroxy, oxo, halogen, trifluoromethyl, C1-4Alkyl radical, C1-4Haloalkyl, benzhydryl; optionally, R5And R6Directly connected or connected by heteroatoms to form a 5-8 membered ring containing N atoms;
y is CH and Z is
Each Rn 7Is 2-4 substituents independently selected from hydroxy, methyl, ethyl, methoxy, amino, methylamino, dimethylamino, optionally, each Rn 7Can be connected into a ring.
5. The allylated coupling reaction process of claim 1, wherein:
R3is H, C1-4Alkyl radical, C5-6Cycloalkyl radical, C2-5Heterocycloalkyl, aryl, heteroaryl, vinyl, conjugated alkenyl, aroyl, aryl-C1-4Alkyl, aryl-ethynyl, C2-8Conjugated alkenyl, condensed ring/bridged ring radical-C1-4Alkyl, biaryl, fused heterocycloalkyl, heterocyclyl-C1-4Alkyl, aryl-C1-4alkyl-N (H) C (O) -C1-4Alkyl or aryl-C1-4alkyl-C (O) N (H) -heterocyclyl; said C is1-4Alkyl radical, C5-6Cycloalkyl radical, C2-5Heterocycloalkyl, aryl, heteroaryl, vinyl, conjugated alkenyl, aroyl, aryl-C1-4Alkyl, aryl-ethynyl, C2-8Conjugated alkenyl, condensed ring/bridged ring radical-C1-4Alkyl, biaryl, fused heterocycloalkyl, heterocyclyl-C1-4Alkyl, aryl-C1-4alkyl-N (H) C (O) -C1-4Alkyl or aryl-C1-4alkyl-C (O) N (H) -heterocyclyl is optionally substituted with one or more substituents independently selected from: halogen, hydroxy, oxo, trifluoromethyl, phenyl, C1-4Alkyl radical, C1-4Alkoxy, di-C1-4Alkylamino radical, C5-6Cycloalkyl, adamantyl, norbornenyl, steryl; r4H, Na or K;
R5and R6Each independently is H, C1-5Alkyl, phenyl, naphthyl, biphenyl, aryl-C1-5Alkyl or adamantyl, said C1-5Alkyl, phenyl, naphthyl, biphenyl, aryl-C1-5Alkyl, adamantyl, optionally substituted with one or more substituents independently selected from the group consisting of: hydroxy, halogen, oxo, C1-6Alkyl, haloalkyl, benzhydryl; optionally, R5And R6Directly connected or connected through a heteroatom to form a 5-8 membered ring containing the N atom.
6. The allylated coupling reaction process of claim 1, wherein:
R1is C1-8Alkyl, aryl-C1-8Alkyl, aryl-C (O) O-C1-8Alkyl radical, C5-6cycloalkyl-C (O) O-C1-8Alkyl, condensed ring radicals-C2-5alkyl-C (O) O-C1-8Alkyl radical, C1-5alkyl-C (O) O-C1-8Alkyl or a 6-membered ring formed by linking to an adjacent allylic or terminal alkenyl carbon1-8Alkyl, aryl-C1-8Alkyl, aryl-C (O) O-C1-8Alkyl radical, C5-6cycloalkyl-C (O) O-C1-8Alkyl, condensed ring radicals-C2-5alkyl-C (O) O-C1-8Alkyl radical, C1-5alkyl-C (O) O-C1-8Alkyl is optionally substituted with one or more substituents independently selected from the group consisting of: vinyl, hydroxy, halogen, trifluoromethyl, C1-4Alkyl, oxo, di-C1-4An alkylaminosulfonyl group; r2Is H or with R1Connecting; or an alkenylthianthrene salt of formula (A) is selected from one of the following structures,
R3is H, phenyl, methyl, tert-butyl, cyclohexyl, benzyl, isopropyl, phenylethynyl, pentadienyl, benzoyl, quinolyl, thienyl, indolyl, furylOr a pyrrolyl group; said phenyl, methyl, t-butyl, cyclohexyl, benzyl, isopropyl, phenylethynyl, pentadienyl, benzoyl, quinolinyl, thienyl, indolyl, furyl, or pyrrolyl group being optionally substituted with one or more substituents independently selected from the group consisting of: halogen, methyl, hydroxy, methoxy, phenyl; or R3Is composed of
R5And R6Each independently is H, phenyl, benzyl, methyl, tert-butyl, pentyl,
Alternatively, the compound of formula Mb is selected from one of the following structures,
the compound of formula Mc is 1, 3, 5-trimethoxybenzene.
7. The allylated coupling reaction process of claim 1, wherein:
the organic solvent is dichloromethane, trichloromethane, carbon tetrachloride, acetonitrile, acetone, tetrahydrofuran or the combination thereof;
and/or the like and/or,
the base is an inorganic base.
8. The allylated coupling reaction process of claim 1, wherein:
the mass ratio of the alkenyl thianthrene salt shown in the formula (A) to the substrate Ma is 1.0: 1.2-1.0: 3.0;
the mass ratio of the alkenyl thianthrene salt shown in the formula (A) to the substrate Mb is 1.0: 2.0-1.0: 3.0.
9. The allylated coupling reaction process of claim 1, wherein:
the base is potassium carbonate, sodium carbonate, ammonium carbonate, sodium bicarbonate, or a combination thereof;
and/or the presence of a gas in the atmosphere,
the mass ratio of the alkenyl thianthrene salt shown in the formula (A) to the alkali is 1.0: 0.5-1.0: 2.0.
10. Use of an alkenyl thianthrene salt of formula a according to any of claims 1 to 9 as allylation reagent in a process for allylation coupling reactions or in the preparation of allyl compounds.
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| WO2024105421A1 (en) | 2022-11-17 | 2024-05-23 | Természettudományi Kutatóközpont | SYNTHESIS OF α,β-UNSATURATED CARBONYLS FROM ALKENES VIA SULFONIUM INTERMEDIATES AND THEIR APPLICATION IN THE SYNTHESIS OF CONJUGATED DIENE PHEROMONES, KAIROMONES, AND RELATED COMPOUNDS |
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| CN114853653A (en) * | 2022-05-11 | 2022-08-05 | 南方科技大学 | Preparation method of three-membered ring without metal catalysis |
| WO2024105421A1 (en) | 2022-11-17 | 2024-05-23 | Természettudományi Kutatóközpont | SYNTHESIS OF α,β-UNSATURATED CARBONYLS FROM ALKENES VIA SULFONIUM INTERMEDIATES AND THEIR APPLICATION IN THE SYNTHESIS OF CONJUGATED DIENE PHEROMONES, KAIROMONES, AND RELATED COMPOUNDS |
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