CN110590690B - 一种通过铜催化的sp2杂化碳氢键的烯基化反应方法 - Google Patents
一种通过铜催化的sp2杂化碳氢键的烯基化反应方法 Download PDFInfo
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- CN110590690B CN110590690B CN201910866561.2A CN201910866561A CN110590690B CN 110590690 B CN110590690 B CN 110590690B CN 201910866561 A CN201910866561 A CN 201910866561A CN 110590690 B CN110590690 B CN 110590690B
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- copper
- alkenyl
- potassium
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- 238000006243 chemical reaction Methods 0.000 title claims abstract description 67
- 125000003342 alkenyl group Chemical group 0.000 title claims abstract description 28
- 229910052739 hydrogen Inorganic materials 0.000 title claims abstract description 22
- 239000001257 hydrogen Substances 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims abstract description 20
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 title claims description 11
- 229910052802 copper Inorganic materials 0.000 title claims description 11
- 239000010949 copper Substances 0.000 title claims description 11
- 239000000758 substrate Substances 0.000 claims abstract description 50
- -1 carboxamide compound Chemical class 0.000 claims abstract description 36
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 8
- 239000004327 boric acid Substances 0.000 claims abstract description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 69
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 claims description 50
- WFMNHCSATCWAAQ-UHFFFAOYSA-M potassium;2,2-dimethylpropanoate Chemical compound [K+].CC(C)(C)C([O-])=O WFMNHCSATCWAAQ-UHFFFAOYSA-M 0.000 claims description 26
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 25
- 229910001923 silver oxide Inorganic materials 0.000 claims description 25
- 239000002904 solvent Substances 0.000 claims description 25
- ITFUHOHJQIDNQW-UHFFFAOYSA-L copper;2,2-dimethylpropanoate Chemical compound [Cu+2].CC(C)(C)C([O-])=O.CC(C)(C)C([O-])=O ITFUHOHJQIDNQW-UHFFFAOYSA-L 0.000 claims description 22
- ZMCUDHNSHCRDBT-UHFFFAOYSA-M caesium bicarbonate Chemical compound [Cs+].OC([O-])=O ZMCUDHNSHCRDBT-UHFFFAOYSA-M 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 6
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 6
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 6
- 239000011736 potassium bicarbonate Substances 0.000 claims description 6
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
- 238000005859 coupling reaction Methods 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-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
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000011630 iodine Substances 0.000 claims description 4
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 4
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 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
- 239000004280 Sodium formate Substances 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 2
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 claims description 2
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 claims description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- 235000003270 potassium fluoride Nutrition 0.000 claims description 2
- 239000011698 potassium fluoride Substances 0.000 claims description 2
- WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 claims description 2
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- 235000013024 sodium fluoride Nutrition 0.000 claims description 2
- 239000011775 sodium fluoride Substances 0.000 claims description 2
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 claims description 2
- 235000019254 sodium formate Nutrition 0.000 claims description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 claims 1
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims 1
- JIDMEYQIXXJQCC-UHFFFAOYSA-L copper;2,2,2-trifluoroacetate Chemical compound [Cu+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F JIDMEYQIXXJQCC-UHFFFAOYSA-L 0.000 claims 1
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims 1
- UWJJYHHHVWZFEP-UHFFFAOYSA-N pentane-1,1-diol Chemical compound CCCCC(O)O UWJJYHHHVWZFEP-UHFFFAOYSA-N 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 20
- 125000005842 heteroatom Chemical group 0.000 abstract description 5
- 150000001879 copper Chemical class 0.000 abstract description 3
- 238000007306 functionalization reaction Methods 0.000 abstract description 2
- 150000002611 lead compounds Chemical class 0.000 abstract 1
- 238000010189 synthetic method Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 144
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 66
- 239000012044 organic layer Substances 0.000 description 54
- 229910052757 nitrogen Inorganic materials 0.000 description 34
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- 235000011114 ammonium hydroxide Nutrition 0.000 description 24
- 239000007795 chemical reaction product Substances 0.000 description 24
- 239000012043 crude product Substances 0.000 description 24
- 239000000203 mixture Substances 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- 238000009472 formulation Methods 0.000 description 20
- RTHRTBILAWPYGT-UHFFFAOYSA-N C(=CCCC)OB(O)O Chemical compound C(=CCCC)OB(O)O RTHRTBILAWPYGT-UHFFFAOYSA-N 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 238000001816 cooling Methods 0.000 description 15
- 238000001035 drying Methods 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- 238000010791 quenching Methods 0.000 description 15
- 230000000171 quenching effect Effects 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 238000000967 suction filtration Methods 0.000 description 15
- 238000005406 washing Methods 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 150000001336 alkenes Chemical class 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 239000011737 fluorine Substances 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000007341 Heck reaction Methods 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 125000006575 electron-withdrawing group Chemical group 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 3
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- JJLJMEJHUUYSSY-UHFFFAOYSA-L Copper hydroxide Chemical compound [OH-].[OH-].[Cu+2] JJLJMEJHUUYSSY-UHFFFAOYSA-L 0.000 description 2
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Chemical group 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- UJZQBMQZMKFSRV-RGKBJLTCSA-N (2s,3s)-4-[(e)-3-[(1r)-1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy]-3-oxoprop-1-enyl]-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydro-1-benzofuran-3-carboxylic acid Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C=2[C@H](C(O)=O)[C@H](OC=2C(O)=CC=1)C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 UJZQBMQZMKFSRV-RGKBJLTCSA-N 0.000 description 1
- GGQQNYXPYWCUHG-RMTFUQJTSA-N (3e,6e)-deca-3,6-diene Chemical compound CCC\C=C\C\C=C\CC GGQQNYXPYWCUHG-RMTFUQJTSA-N 0.000 description 1
- YAXGBZDYGZBRBQ-UHFFFAOYSA-N 4,5-dihydro-1,3-oxazol-2-amine Chemical compound NC1=NCCO1 YAXGBZDYGZBRBQ-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- UJZQBMQZMKFSRV-PHQFMFTGSA-N Lithospermic acid Natural products O([C@@H](C(=O)O)Cc1cc(O)c(O)cc1)C(=O)/C=C/c1c2[C@@H](C(=O)O)[C@H](c3cc(O)c(O)cc3)Oc2c(O)cc1 UJZQBMQZMKFSRV-PHQFMFTGSA-N 0.000 description 1
- NFOCYHUCMXEHDG-UHFFFAOYSA-N Monomethyl lithospermate Natural products COC(=O)C1C(C=2C=C(O)C(O)=CC=2)OC(C(=CC=2)O)=C1C=2C=CC(=O)OC(C(O)=O)CC1=CC=C(O)C(O)=C1 NFOCYHUCMXEHDG-UHFFFAOYSA-N 0.000 description 1
- IIBOGKHTXBPGEI-UHFFFAOYSA-N N-benzylformamide Chemical compound O=CNCC1=CC=CC=C1 IIBOGKHTXBPGEI-UHFFFAOYSA-N 0.000 description 1
- 208000001140 Night Blindness Diseases 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000005396 acrylic acid ester group Chemical group 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- LGVUAXNPXVXCCW-UHFFFAOYSA-M cesium;2,2-dimethylpropanoate Chemical compound [Cs+].CC(C)(C)C([O-])=O LGVUAXNPXVXCCW-UHFFFAOYSA-M 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
- C07B37/04—Substitution
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明公开了一种通过铜盐催化(杂)芳基或烯基碳氢键的烯基化反应合成方法以及其应用。该新方法以甲酰胺化合物为底物,以烯基硼酸酯为烯基化试剂,在铜催化剂催化下快速高效构建C(sp2)‑H的各种烯基化产物,可用于潜在先导化合物中烯基的官能团化或引入。该反应方法条件温和、底物耐受性广泛。
Description
技术领域
本发明涉及化学技术领域,具体涉及一类新型的铜盐催化芳基或烯基碳氢键烯基化反应合成方法以及其应用。该方法利用铜可实现各类sp2杂化化合物(芳基、杂环、烯烃等)碳氢键的多种烯基官能团化,条件温和、底物耐受性广泛。
背景技术
烯基结构广泛存在于天然产物和活性药物分子当中 [1],并且作为重要的合成中间体可进行多种转化[2]。例如:多烯一元醇-Vitamin A,可促进眼内感光色素的形成,防止夜盲症和视力减退;FR901512 是HMG-CoA 还原酶抑制剂(IC50 = 0.95 nM),其可用于降血脂;(-)-Dictyostain是潜在的抗肿瘤活性药物分子等(图1),这些活性分子均含有一个或多个烯基结构。因而,发展简单且高效的方法来构建烯基化合物意义重大。同时碳碳双键是有机合成中最常见的官能团,可以实现氧化,还原及直接官能团化,在有机合成中具有重要的意义。
目前最常用的烯烃引入方法主要包括双键的直接合成(Wittig反应等)、炔烃的氢化、金属催化的Heck反应、及金属参与的烯基试剂的偶联反应。其中,利用芳基或烯基卤化物(或伪卤代物)与活化端烯烃的Heck反应和与烯基试剂发生偶联反应由于其底物来源简单,反应高效目前被广泛研究,这类反应的一般通式如图2所示。尽管如此,使用碳氢键的直接出发构建碳碳双键仍然是最具吸引力和应用前景的方法,其可以避免提前引入预活化定位基团(如Br、I、OTf等);原子经济性和利用率更高。
近年来,过渡金属参与的C–H键的烯基化反应研究主要集中在氧化Heck反应。图3中列举我们组近期的一个代表性例子:利用醋酸钯为催化剂,经过一步C–H烯基化直接快速构建天然活性分子紫草酸的母环,再经过一步脱甲基直接得到目标产物[3]。尽管这种C–H的直接烯基化反应极具吸引力,但目前仍然具有明显的局限性:1)目前催化剂主要集中在贵金属(如:钯、铑、钌等),廉价金属鲜有报道;2)烯基底物主要为芳基乙烯或丙烯酸酯等活化的烯烃化合物等。2014年和2018年,Maiti组[4]和我们组[5]相继实现了配体促进的钯催化苄基甲酰胺类底物的C–H烯基化,该类烯烃试剂可以延伸到非活化烯烃,但也只局限于部分端位非活化烯烃,而多取代烯烃、含杂原子烯烃、内烯烃、环状烯烃、顺式烯烃等通过此氧化Heck途径无法实现。因而,本发明涉及一种通过铜催化,实现各类sp2杂化底物(芳基、杂环、烯烃等)碳氢键的多种烯基官能团化的新方法,此方法条件温和、底物耐受性广泛。
参考文献:
[1] a) Sauer, S. et al. Org Lett, 2015, 17, 194; b) Panek, J. S. etal. Org. Lett. 2004, 6, 55; c) Hattori, H. et al. Acc. Chem. Res. 2008, 41,1474; d) Humpf, H. U. et al. J. Agric. Food Chem. 2007, 55, 8353; e) Nakada,M. et al. J. Am. Chem. Soc. 2007, 129, 4164; f) Hazra, D. et al. Org. Lett. 2007, 9, 157.
[2] a) Reek, J. N. H. et al. Angew. Chem. Int. Ed. 2013, 52, 3878; b) Marder, T. B. et al. Chem Commun. 2012, 48, 9986.
[3] Yu, J. Q. et al. J. Am. Chem. Soc. 2011, 33, 5767.
[4] Maiti, D. et al. J. Am. Chem. Soc. 2014, 136, 13602
[5] Yu, J. Q. et al. Chem. Sci. 2018, 9, 1311。
发明内容
本发明的目的是提供一种新型的铜盐催化芳基或烯基碳氢键多种烯基化反应的新方法。本发明通过设计引入双齿导向基团快速构建系列(杂)芳香类(以及α,β-不饱和类)甲酰胺底物。在铜催化下与不同的烯基硼酸试剂进行C–H直接烯基化反应,得到多种芳基-烯基产物、烯基-烯基产物,该方法底物范围广,产率良好到优秀,同时得到烯基化产物可以作为中间合成子,转化为多种产物,实用性强,有助于加快药物分子创制的进程。
本发明提供的合成方法通式如图4所示,其中芳香类甲酰胺化合物的芳香环中的R1,R2,R3和R4可以为氢,甲基,乙基,异丙基,叔丁基等C1-10烷基基团中一种或几种;可以为甲氧基,氨基,取代苯基,取代萘基等给电子基团中一种或几种;可以为氟,氯,溴,碘等卤素基团中一种或几种;可以为三氟甲基,乙酰基,甲酸甲酯,乙烯基,对-2-吡啶基,氰基,硝基等吸电子基团中一种或几种。
甲酰胺化合物的甲酰胺基邻位的一个或两个配基为氢,烯基硼酸酯试剂特异性的与甲酰胺化合物的甲酰胺基邻位的氢发生偶联反应。
芳香杂环类甲酰胺化合物可以为吡啶,吡啶衍生物,咪唑,咪唑衍生物,吡唑,吡唑衍生物,呋喃,呋喃衍生物,噻吩,噻吩衍生物类杂环中任一种。
烯基硼酸酯中的R5,R6和R7可以为可以为氢,甲基,乙基,异丙基,叔丁基,苄基等C1-10烷基基团中一种或几种;可以为甲氧基,已氧基、氨基,取代苯基,取代萘基等给电子基团中一种或几种;可以为氟,氯,溴,碘等卤素基团中一种或几种;可以为三氟甲基,乙酰基,甲酸甲酯,乙烯基,对-2-吡啶基,氰基,硝基等吸电子基团中一种或几种;R5、R7与烯基硼酸酯可以组合为各个位置(含或不含)氮、氧、硫、氟等杂原子的单环状烯基基团(丙、丁、戊、己、庚、辛、壬、癸等)、多环状烯基基团中任一种; R8可以为氢,甲基,乙基,异丙基,叔丁基,苄基等C1-10烷基基团中任一种;可以与硼酸组合为各种环状(取代)乙二醇、频哪醇、(取代)丙二醇、(取代)丁二醇、(取代)戊二醇等硼酸酯中任一种。
α,β-不饱和烯基甲酰胺化合物中R9和R10可以为氢,甲基,乙基,异丙基,叔丁基,苄基等C1-10烷基基团中一种或几种;可以为甲氧基,已氧基、氨基,取代苯基,取代萘基等给电子基团中一种或几种;可以为氟,氯,溴,碘等卤素基团中一种或几种;可以为三氟甲基,乙酰基,甲酸甲酯,乙烯基,对-2-吡啶基,氰基,硝基等吸电子基团中一种或几种;R9和R10与烯基可组合为各个位置(含或不含)氮、氧、硫、氟等杂原子的单环状烯基基团(丙、丁、戊、己、庚、辛、壬、癸等)、多环状烯基基团(降冰片烯等)。
导向基团为氨基噁唑啉及其衍生物,其中R11可以是氢,甲基,乙基,异丙基,叔丁基和苯基;R12可以是氢和甲基。
铜催化剂可以为醋酸亚铜,溴化亚铜,氯化亚铜,碘化亚铜,六氟磷酸四乙氰铜(I),噻吩-2-甲酸亚铜,醋酸铜,醋酸铜水合物,溴化铜,氯化铜,氢氧化铜,氧化铜,特戊酸铜,三氟甲磺酸铜或三氟乙酸铜中任一种。
催化体系中的碱可以为醋酸钾,醋酸钠,醋酸铯,醋酸锂,碳酸钾,碳酸钠,碳酸铯,碳酸锂,碳酸氢钾,碳酸氢钠,碳酸氢铯,特戊酸钾,特戊酸钠,特戊酸铯,甲醇钠,甲醇钾,乙醇钠,乙醇钾,甲酸钾,甲酸钠,磷酸钾,磷酸二氢钾,磷酸氢二钾,氟化钠,氟化铯或氟化钾中任一种。
反应溶剂可以为DMF, DMA, DMSO, NMP, DMPU, THF, MeOH, EtOH, t-Amyl-OH,Acetone或 CH3CN中任一种。
该反应体系的浓度范围为0.01M-5.0M。催化剂与底物的摩尔比为1:1 - 1:20;底物与偶联试剂的摩尔比1:1 - 1:3;底物与碱的摩尔比为1:1 - 1:3。反应温度为25℃-120℃;反应时间为1-48小时。
附图说明:
图1:常见含有烯基的天然产物和药物分子;
图2:传统过渡金属参与构建烯基的一般通式;
图3:C-H烯基化反应直接构建紫草酸;
图4:本发明提供的合成方法通式;
图5:实施例1反应式及反应产物3a和3a’结构式;
图6:实施例2反应式及反应产物3b和3b’结构式;
图7:实施例3反应式及反应产物3c和3c’结构式;
图8:实施例4反应式及反应产物3d和3d’结构式;
图9:实施例5反应式及反应产物3e和3e’结构式;
图10:实施例6反应式及反应产物3f和3f’结构式;
图11:实施例7反应式及反应产物3g结构式;
图12:实施例8反应式及反应产物3h结构式;
图13:实施例9反应式及反应产物3i结构式;
图14:实施例10反应式及反应产物3j结构式;
图15:实施例11反应式及反应产物3k结构式;
图16:实施例12反应式及反应产物3l结构式;
图17:实施例13反应式及反应产物3m结构式;
图18:实施例14反应式及反应产物3n结构式;
图19:实施例15反应式及反应产物3o结构式;
图20:实施例16反应式及反应产物4b结构式;
图21:实施例17反应式及反应产物4c结构式;
图22:实施例18反应式及反应产物4d结构式;
图23:实施例19反应式及反应产物4e结构式;
图24:实施例20反应式及反应产物4f结构式;
图25:实施例21反应式及反应产物4g结构式;
图26:实施例22反应式及反应产物4h结构式;
图27:实施例23反应式及反应产物4i结构式;
图28:实施例24反应式及反应产物4j结构式。
具体实施方法:
通过下述实施例有助于进一步理解本发明,但并不局限于实施例的内容。
实施例1:如图5所示,向25 mL的Schlenk管中依次加入芳香类底物1a (0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢钾(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化(PE: EA = 20:1)得到白色固体3a(17.1 mg)和3a’(9.9 mg)收率77%。
其中3a:1H NMR (400 MHz, CDCl3) δ 12.57 (s, 1H), 8.94 (d, J = 8.6 Hz,1H), 7.89 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 7.9 Hz, 2H), 7.52 (t, J = 7.8 Hz,1H), 7.40 (t, J = 7.6 Hz, 1H), 7.31-7.27 (m, 1H), 7.12 (t, J = 7.7 Hz, 1H),6.91 (d, J = 15.5 Hz, 1H), 6.27 – 6.17 (m, 1H), 4.34 (t, J = 9.5 Hz, 2H),4.02 (t, J = 9.5 Hz, 2H), 2.18 (q, J = 7.4 Hz, 2H), 1.46 (dd, J = 14.7, 7.4Hz, 2H), 0.92 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 167.46, 163.44,139.04, 135.98, 134.41, 132.35, 131.52, 129.13, 128.16, 126.71, 126.55,125.60, 125.43, 121.45, 118.81, 112.49, 65.14, 53.64, 34.24, 21.49, 12.72.HRMS (ESI-TOF) m/z Calcd for C21H23N2O2 [M+H]+: 335.1754, found: 335.1759。
3a’:1H NMR (400 MHz, CDCl3) δ 12.29 (s, 1H), 8.95 (d, J = 8.3 Hz, 1H),7.87 (d, J = 8.0 Hz, 1H), 7.54 (t, J = 7.6 Hz, 1H), 7.41 (d, J = 7.7 Hz, 2H),7.31-7.27 (m, 1H), 7.14 (t, J = 7.7 Hz, 1H), 6.51 (d, J = 15.8 Hz, 2H), 6.25– 6.13 (m, 2H), 4.29 (t, J = 9.5 Hz, 2H), 3.90 (t, J = 9.4 Hz, 2H), 2.10 (q,J = 7.2 Hz, 4H), 1.39 (dd, J = 14.6, 7.4 Hz, 4H), 0.86 (t, J = 7.4 Hz, 6H).13C NMR (100 MHz, CDCl3) δ 168.83, 164.04, 139.61, 135.24, 135.03, 133.43,132.46, 129.14, 128.84, 127.06, 123.92, 122.69, 120.27, 113.73, 66.12, 54.70,35.22, 22.45, 13.60. HRMS (ESI-TOF) m/z Calcd for C26H31N2O2 [M+H]+: 403.2380,found: 403.2391。
实施例2:如图6所示,向25 mL的Schlenk管中依次加入芳香类底物1b (0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体3b(15.7 mg)和3b’(10.5 mg)收率72%。
其中,3b:1H NMR (400 MHz, CDCl3) δ 12.52 (s, 1H), 8.93 (d, J = 8.4 Hz,1H), 7.88 (d, J = 7.5 Hz, 1H), 7.96-7.48 (m, 2H)), 7.40 (s, 1H), 7.15-7.05(m, 2H) 6.92 (d, J = 15.9 Hz, 1H), 6.25 – 6.16 (m, 1H), 4.34 (t, J = 9.5 Hz,2H), 4.02 (t, J = 9.5 Hz, 2H), 2.39 (s, 3H), 2.18 (q, J = 7.3 Hz, 2H), 1.47(dd, J = 14.8, 7.3 Hz, 2H), 0.92 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3)δ 168.47, 164.43, 140.18, 140.15, 137.11, 132.98, 132.63, 132.49, 129.13,127.87, 127.74, 127.39, 127.11, 122.29, 119.76, 113.41, 66.12, 54.67, 35.25,22.53, 21.45, 13.75. HRMS (ESI-TOF) m/z Calcd for C22H25N2O2 [M+H]+: 349.1911,found: 349.1920。
3b’:1H NMR (400 MHz, CDCl3) δ 12.24 (s, 1H), 8.95 (d, J = 8.4 Hz, 1H),7.87 (d, J = 8.1 Hz, 1H), 7.53 (t, J = 7.7 Hz, 1H), 7.22 (s, 2H), 7.14 (d, J= 7.5 Hz, 1H), 6.50 (d, J = 15.7 Hz, 2H), 6.23 – 6.13 (m, 2H), 4.29 (t, J =9.5 Hz, 2H), 3.91 (t, J = 9.5 Hz, 2H), 2.36 (s, 3H), 2.09 (q, J = 7.0 Hz,4H), 1.39 (dd, J = 14.6, 7.3 Hz, 4H), 0.86 (t, J = 7.4 Hz, 6H). 13C NMR (100MHz, CDCl3) δ 169.05, 164.01, 139.68, 138.36, 135.19, 133.07, 132.67, 132.44,129.13, 127.19, 124.67, 122.59, 129.24, 113.68, 66.10, 54.73, 35.22, 22.48,21.51, 13.61. HRMS (ESI-TOF) m/z Calcd for C27H33N2O2 [M+H]+: 417.2537, found:417.2549。
实施例3:如图7所示,向25 mL的Schlenk管中依次加入芳香类底物1c (0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),乙腈(2.0 mL),旋紧瓶盖,置于45℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化(PE: EA = 20:1)得到白色固体3c(13.4 mg)和3c’(11.4 mg)收率66%。
其中,3c:1H NMR (400 MHz, CDCl3) δ 12.52 (s, 1H), 8.91 (d, J = 8.4 Hz,1H), 7.88 (d, J = 7.8 Hz, 1H), 7.62 (d, J = 8.6 Hz, 1H), 7.51 (t, J = 7.9 Hz,1H), 7.10 (m, 2H). 6.98 (d, J = 15.6 Hz, 1H), 6.82 (dd, J = 8.5, 2.5 Hz, 1H),6.25 – 6.15 (m, 1H), 4.35 (t, J = 9.5 Hz, 2H), 4.04 (t, J = 9.5 Hz, 2H), 3.87(s, 3H), 2.19 (q, J = 7.6 Hz, 2H), 1.53 – 1.42 (m, 2H), 0.93 (t, J = 7.4 Hz,3H). 13C NMR (100 MHz, CDCl3) δ168.05, 164.50, 160.92, 140.24, 139.48, 133.39,132.51, 129.73, 129.15, 128.10, 127.89, 122.21, 119.71, 113.36, 112.12,111.60, 66.13, 55.31, 54.67, 35.19, 22.49, 13.77. HRMS (ESI-TOF) m/z Calcdfor C22H25N2O3 [M+H]+: 365.1860, found: 365.1867。
3c’:1H NMR (400 MHz, CDCl3) δ 12.25 (s, 1H), 8.95 (d, J = 8.4 Hz, 1H),7.87 (d, J = 6.8 Hz, 1H), 7.53 (t, J = 7.9 Hz, 1H), 7.13 (t, J = 7.5 Hz, 1H),6.93 (s, 2H), 6.51 (d, J = 15.6 Hz, 2H), 6.23 – 6.14 (m, 2H), 4.29 (t, J =9.5 Hz, 2H), 3.91 (t, J = 9.5 Hz, 2H), 3.87 (s, 3H), 2.10 (q, J = 6.9 Hz,4H), 1.45 – 1.33 (m, 4H), 0.86 (t, J = 7.4 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ168.75, 163.96, 159.61, 139.65, 136.98, 133.47, 132.41, 129.08, 128.72,127.12, 122.54, 120.08, 113.57, 109.26, 66.05, 55.26, 54.68, 35.12, 22.39,13.59. HRMS (ESI-TOF) m/z Calcd for C27H33N2O3 [M+H]+: 433.2486, found:433.2503。
实施例4:如图8所示,向25 mL的Schlenk管中依次加入芳香类底物1d (0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),乙腈(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体3d(19.4 mg)和3d’(11.7 mg)收率73%。
其中,3d:1H NMR (400 MHz, CDCl3) δ 12.67 (s, 1H), 8.96 (d, J = 8.4 Hz,1H), 8.73 (d, J = 4.6 Hz, 1H), 8.22 (d, J = 1.6 Hz, 1H), 7.89 (dt, J = 7.9,1.7 Hz, 2H), 7.80 – 7.77 (m, 2H), 7.73 (d, J = 8.0 Hz, 1H), 7.53 (t, J = 8.0Hz, 1H), 7.29 – 7.25 (m, 1H), 7.13 (t, J = 8.0 Hz, 1H), 6.98 (d, J = 15.8 Hz,1H), 6.37 (dt, J = 15.7, 7.0 Hz, 1H), 4.34 (t, J = 9.5 Hz, 2H), 4.01 (t, J =9.5 Hz, 2H), 2.21 (q, J = 8.0 Hz, 2H), 1.54 – 1.44 (m, 2H), 0.93 (t, J = 7.4Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 168.18, 164.45, 156.75, 149.74, 140.93,140.02, 137.53, 136.84, 135.63, 133.87, 132.53, 129.18, 128.34, 127.46,125.15, 125.03, 122.54, 122.50, 120.92, 119.80, 113.50, 66.17, 54.69, 35.33,22.49, 13.80. HRMS (ESI-TOF) m/z Calcd for C26H26N3O2 [M+H]+: 412.2020, found:412.2029。
3d’:1H NMR (400 MHz, CDCl3) δ 12.38 (s, 1H), 8.98 (d, J = 7.9 Hz, 1H),8.73 (d, J = 4.8 Hz, 1H), 8.01 (s, 2H), 7.88 (dd, J = 7.9, 1.5 Hz, 1H), 7.81- 7.77 (m, 2H), 7.55 (t, J = 8.0 Hz, 1H), 7.30 – 7.25 (m, 1H), 7.15 (t, J =7.6 Hz, 1H), 6.58 (d, J = 15.7 Hz, 2H), 6.40 – 6.29 (m, 2H), 4.29 (t, J = 9.5Hz, 2H), 3.90 (t, J = 9.5 Hz, 2H), 2.13 (q, J = 6.9 Hz, 4H), 1.41 (dd, J =14.7, 7.4 Hz, 4H), 0.87 (t, J = 7.4 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ168.65, 164.00, 157.31, 149.67, 139.81, 139.58, 136.78, 135.83, 135.33,133.95, 132.44, 129.12, 126.90, 122.69, 122.61, 122.36, 120.97, 120.17,113.68, 66.11, 54.72, 35.27, 22.42, 12.63. HRMS (ESI-TOF) m/z Calcd forC31H34N3O2 [M+H]+: 480.2646, found: 480.2663。
实施例5:如图9所示,向25 mL的Schlenk管中依次加入芳香类底物1e (0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢钾(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体3e(13.8 mg)和3e’(10.0 mg)收率60%。
其中,3e:1H NMR (400 MHz, CDCl3) δ 12.56 (s, 1H), 8.91 (d, J = 8.2 Hz,1H), 7.88 (d, J = 8.0 Hz, 1H), 7.60 – 7.48 (m, 2H), 7.42 (s, 1H), 7.16 – 7.08(m, 2H), 6.92 (d, J = 15.7 Hz, 1H), 6.26 – 6.15 (m, 1H), 4.35 (t, J = 9.5 Hz,2H), 4.03 (t, J = 9.5 Hz, 2H), 2.54 (s, 3H), 2.18 (q, J = 7.3 Hz, 2H), 1.47(dq, J = 14.4, 7.2 Hz, 2H), 0.92 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3)δ 167.97, 164.55, 141.39, 140.13, 137.85, 133.85, 132.58, 131.98, 129.21,128.40, 127.50, 123.89, 123.85, 122.44, 119.82, 113.48, 66.19, 54.71, 35.26,22.48, 15.31, 13.78. HRMS (ESI-TOF) m/z Calcd for C22H25N2O2S [M+H]+: 381.1631,found: 381.1639。
3e’:1H NMR (400 MHz, CDCl3) δ 12.29 (s, 1H), 8.94 (d, J = 8.4 Hz, 1H),7.87 (d, J = 7.9 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.27 - 7.26 (m, 1H), 7.14(t, J = 7.7 Hz, 1H), 6.49 (d, J = 15.7 Hz, 2H), 6.26 – 6.13 (m, 2H), 4.29 (t,J = 9.5 Hz, 2H), 3.92 (t, J = 9.6 Hz, 2H), 2.54 (s, 3H), 2.10 (q, J = 7.2 Hz,4H), 1.44 – 1.33 (m, 4H), 0.86 (t, J = 7.4 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ168.41, 164.01, 139.55, 139.09, 135.88, 133.94, 132.44, 132.28, 129.12,126.74, 122.67, 121.72, 120.14, 113.63, 66.10, 54.71, 35.18, 22.38, 15.66,13.60. HRMS (ESI-TOF) m/z Calcd for C27H33N2O2S [M+H]+: 449.2257, found:449.2273。
实施例6:如图10所示,向25 mL的Schlenk管中依次加入芳香类底物1f (0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 5:1)得到白色固体3f(14.1 mg)和3f’(9.5 mg)收率54%。
其中,3f:1H NMR (400 MHz, CDCl3) δ 12.50 (s, 1H), 8.91 (d, J = 8.4 Hz,1H), 7.87 (d, J = 7.9 Hz, 1H), 7.62 (d, J = 8.6 Hz, 1H), 7.50 (t, J = 8.0 Hz,1H), 7.09 (t, J = 7.6 Hz, 1H), 7.05 – 6.97 (m, 2H), 6.81 (dd, J = 8.6, 2.4Hz, 1H), 6.19 – 6.11 (m, 1H), 4.35 (t, J = 9.5 Hz, 2H), 4.05 (t, J = 9.5 Hz,2H), 3.91 – 3.84 (m, 4H), 3.31 – 3.25 (m, 4H), 2.19 (q, J = 7.4 Hz, 2H), 1.47(dt, J = 14.7, 7.4 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H).13C NMR (100 MHz, CDCl3)δ 168.06, 164.51, 152.39, 140.37, 139.20, 132.85, 132.49, 129.52, 129.14,128.68, 126.41, 122.07, 119.71, 113.31, 113.15, 112.69, 66.77, 66.10, 54.71,48.43, 35.21, 22.52, 13.82. HRMS (ESI-TOF) m/z Calcd for C25H29N3NaO3 [M+Na]+:442.2101, found: 442.2111。
3f’:1H NMR (400 MHz, CDCl3) δ 12.22 (s, 1H), 8.95 (d, J = 8.3 Hz, 1H),7.86 (d, J = 7.8 Hz, 1H), 7.53 (t, J = 7.6 Hz, 1H), 7.12 (t, J = 7.7 Hz, 1H),6.93 (s, 2H), 6.52 (d, J = 15.6 Hz, 2H), 6.20 – 6.10 (m, 2H), 4.29 (t, J =9.5 Hz, 2H), 3.97 – 3.83 (m, 6H), 3.29 – 3.20 (m, 4H), 2.09 (q, J = 7.1 Hz,4H), 1.44 – 1.33 (m, 4H), 0.85 (t, J = 7.4 Hz, 7H). 13C NMR (100 MHz, CDCl3) δ168.86, 163.95, 151.26, 139.71, 136.48, 133.12, 132.40, 129.07, 128.01,127.63, 122.46, 120.07, 113.53, 111.30, 66.90, 66.04, 54.72, 49.24, 35.16,22.42, 13.62. HRMS (ESI-TOF) m/z Calcd for C30H37N3NaO3 [M+Na]+: 510.2727,found: 510.2747。
实施例7:如图11所示,向25 mL的Schlenk管中依次加入芳香类底物1g (0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),DMSO(1.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体3g (16.3 mg)收率47%。
其中,3g:1H NMR (400 MHz, CDCl3) δ 12.29 (s, 1H), 8.95 (d, J = 8.4 Hz,1H), 7.92 – 7.86 (m, 1H), 7.54 (t, J = 7.9 Hz, 1H), 7.39 (d, J = 7.8 Hz, 1H),7.23 (d, J = 7.8 Hz, 1H), 7.14 (t, J = 7.6 Hz, 1H), 7.09 (d, J = 7.6 Hz, 1H),6.51 (d, J = 15.7 Hz, 1H), 6.25 – 6.14 (m, 1H), 4.30 (t, J = 9.5 Hz, 2H),3.93 (t, J = 9.5 Hz, 2H), 2.38 (s, 3H), 2.10 (q, J = 7.2 Hz, 2H), 1.39 (dd, J= 14.7, 7.3 Hz, 2H), 0.86 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ169.05, 164.15, 139.56, 136.62, 134.97, 134.45, 133.25, 132.48, 129.16,128.72, 128.56, 127.10, 122.90, 122.66, 120.15, 113.59, 66.09, 54.69, 35.20,22.44, 19.46, 13.59. HRMS (ESI-TOF) m/z Calcd for C22H25N2O2 [M+H]+: 349.1911,found: 349.1913。
实施例8:如图12所示,向25 mL的Schlenk管中依次加入芳香类底物1h (0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢钾(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化(PE: EA = 20:1)得到白色固体3h (15.1 mg)收率40%。
其中,3h:1H NMR (400 MHz, CDCl3) δ 12.27 (s, 1H), 8.94 (d, J = 8.4 Hz,1H), 7.88 (d, J = 7.8 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.37 (d, J = 8.6 Hz,1H), 7.14 (t, J = 7.6 Hz, 1H), 6.85 (d, J = 8.6 Hz, 1H), 6.44 (d, J = 15.6Hz, 1H), 6.13 – 6.01 (m, 1H), 4.30 (t, J = 9.5 Hz, 2H), 3.95 (d, J = 9.5 Hz,2H), 3.85 (s, 3H), 2.23 (s, 3H), 2.08 (q, J = 7.1 Hz, 2H), 1.44 – 1.32 (m,2H), 0.85 (t, J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ168.81, 164.12,156.54, 139.53, 137.93, 132.45, 131.11, 129.15, 127.47, 126.79, 123.85,122.91, 122.67, 120.21, 113.66, 110.87, 66.09, 55.66, 54.73, 35.19, 22.58,13.60, 12.86. HRMS (ESI-TOF) m/z Calcd for C23H27N2O3 [M+H]+: 379.2016, found:379.2015。
实施例9:如图13所示,向25 mL的Schlenk管中依次加入芳香类底物1i (0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化(PE: EA = 20:1)得到白色固体3i (23.4 mg)收率57%。
其中,3i:1H NMR (400 MHz, CDCl3) δ 12.70 (s, 1H), 8.97 (d, J = 8.3 Hz,1H), 7.94 – 7.87 (m, 2H), 7.69 – 7.62 (m, 4H), 7.53 (t, J = 7.9 Hz, 1H), 7.44(t, J = 7.6 Hz, 2H), 7.34 (t, J = 7.3 Hz, 1H), 7.12 (t, J = 7.4 Hz, 1H), 6.99(d, J = 15.7 Hz, 1H), 6.33 – 6.22 (m, 1H), 4.34 (t, J = 9.5 Hz, 2H), 4.02 (t,J = 9.5 Hz, 2H), 2.21 (q, J = 7.3 Hz, 2H), 1.49 (dd, J = 14.8, 7.4 Hz, 2H),0.94 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ168.24, 164.60, 140.13,140.09, 139.30, 136.16, 135.57, 133.46, 132.60, 129.25, 128.81, 128.69,127.49, 127.26, 126.99, 126.84, 126.48, 122.53, 119.82, 113.51, 66.18, 54.71,35.37, 22.57, 13.79. HRMS (ESI-TOF) m/z Calcd for C27H27N2O2 [M+H]+: 411.2067,found: 411.2077。
实施例10:如图14所示,向25 mL的Schlenk管中依次加入芳香类底物1j(0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),乙腈(2.0 mL),旋紧瓶盖,置于50 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体3j (27.3 mg)收率75%。
其中,3j:1H NMR (400 MHz, CDCl3) δ 12.70 (s, 1H), 8.94 (d, J = 8.4 Hz,1H), 7.89 (dd, J = 7.9, 1.3 Hz, 1H), 7.57 – 7.49 (m, 2H), 7.19 – 7.07 (m,2H), 6.96 (dd, J = 8.7, 2.6 Hz, 1H), 6.83 (d, J = 15.7 Hz, 1H), 6.10 (dt, J =15.6, 7.0 Hz, 1H), 4.34 (t, J = 9.4 Hz, 2H), 4.02 (t, J = 9.5 Hz, 2H), 3.84(s, 3H), 2.20 – 2.10 (m, 2H), 1.43 (dt, J = 14.6, 7.3 Hz, 2H), 0.91 (t, J =7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ168.16, 164.48, 158.20, 139.98, 136.19,132.57, 131.45, 129.67, 129.20, 127.80, 126.98, 122.52, 119.80, 116.95,113.48, 112.08, 66.16, 55.43, 54.69, 35.26, 22.64, 13.76. HRMS (ESI-TOF) m/zCalcd for C22H25N2O3 [M+H]+: 365.1860, found: 365.1870。
实施例11:如图15所示,向25 mL的Schlenk管中依次加入芳香类底物1k(0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化(PE: EA = 20:1)得到白色固体3k (22.1 mg)收率60%。
其中,3k:1H NMR (400 MHz, CDCl3) δ 12.67 (s, 1H), 8.88 (d, J = 8.4 Hz,1H), 7.89 (d, J = 7.8 Hz, 1H), 7.62 (d, J = 2.1 Hz, 1H), 7.56 – 7.50 (m, 2H),7.36 (dd, J = 8.5, 1.7 Hz, 1H), 7.14 (t, J = 7.6 Hz, 1H), 6.85 (d, J = 15.7Hz, 1H), 6.27 – 6.16 (m, 1H), 4.37 (t, J = 9.5 Hz, 2H), 4.06 (t, J = 9.6 Hz,2H), 2.17 (dd, J = 14.5, 7.2 Hz, 2H), 1.46 (dd, J = 14.8, 7.4 Hz, 2H), 0.92(t, J = 7.4 Hz, 4H). 13C NMR (100 MHz, CDCl3) δ166.90, 164.52, 139.75, 136.54,135.53, 134.05, 132.57, 132.20, 130.17, 129.20, 127.84, 126.55, 122.76,119.84, 113.59, 66.27, 54.56, 35.24, 22.42, 13.73. HRMS (ESI-TOF) m/z Calcdfor C21H22ClN2O2 [M+H]+: 369.1364, found: 369.1371。
实施例12:如图16所示,向25 mL的Schlenk管中依次加入芳香类底物1l(0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化(PE: EA = 20:1)得到白色固体3l (24.1 mg)收率71%。
其中,3l:1H NMR (400 MHz, CDCl3) δ 12.77 (s, 1H), 8.81 (d, J = 8.5 Hz,1H), 7.87 (dd, J = 7.9, 1.5 Hz, 1H), 7.52 – 7.45 (m, 1H), 7.35 – 7.29 (m,3H), 7.13 – 7.06 (m, 1H), 6.26 (dt, J = 15.9, 7.0 Hz, 1H), 4.39 (t, J = 9.4Hz, 2H), 4.14 (t, J = 9.6 Hz, 2H), 2.22 (td, J = 8.2, 1.4 Hz, 2H), 1.55 –1.44 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ164.59,161.90, 143.85, 140.04, 134.80, 132.43, 130.50, 129.11, 127.30, 126.87,123.88, 122.37, 120.08, 113.51, 66.29, 54.56, 35.29, 22.51, 13.80. HRMS (ESI-TOF) m/z Calcd for C19H21N2O2S [M+H]+: 341.1318, found: 341.1323。
实施例13:如图17所示,向25 mL的Schlenk管中依次加入α,β-不饱和甲酰类底物1m(0.1 mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2 mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),DMSO(1.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体3m(26.6 mg)收率71%。
其中,3m:1H NMR (400 MHz, CDCl3) δ 12.45 (s, 1H), 8.90 (d, J = 8.6 Hz,1H), 7.88 (d, J = 7.9 Hz, 1H), 7.51 (t, J = 7.9 Hz, 1H), 7.40 (t, J = 7.3 Hz,2H), 7.32 (t, J = 7.4 Hz, 1H), 7.17 (d, J = 7.0 Hz, 2H), 7.11 (t, J = 7.6 Hz,1H), 6.80 (d, J = 15.4 Hz, 1H), 5.24 – 5.15 (m, 1H), 4.37 (t, J = 9.4 Hz,2H), 4.08 (t, J = 9.6 Hz, 2H), 1.98 (q, J = 7.1 Hz, 2H), 1.84 (s, 3H), 1.33 –1.19 (m, 4H), 0.78 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ170.27,164.50, 141.86, 139.96, 139.28, 136.81, 132.56, 130.23, 130.18, 129.34,129.20, 128.17, 126.94, 122.37, 119.95, 113.44, 66.21, 54.62, 35.09, 22.38,18.22, 13.64. HRMS (ESI-TOF) m/z Calcd for C24H27N2O2 [M+H]+: 375.2067, found:375.2076。
实施例14:如图18所示,向25 mL的Schlenk管中依次加入α,β-不饱和甲酰类底物1n(0.1 mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2 mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体3n(23.0mg)收率68%。
其中,3n:1H NMR (400 MHz, CDCl3) δ 12.16 (s, 1H), 8.86 (d, J = 8.4 Hz,1H), 7.86 (d, J = 7.9 Hz, 1H), 7.48 (t, J = 7.9 Hz, 1H), 7.08 (t, J = 7.6 Hz,1H), 6.58 (d, J = 15.5 Hz, 1H), 5.83 – 5.73 (m, 1H), 4.35 (t, J = 9.5 Hz,2H), 4.07 (t, J = 9.5 Hz, 2H), 2.47 (s, 2H), 2.30 (s, 2H), 2.09 – 2.00 (m,2H), 1.71 (s, 4H), 1.36 (dd, J = 14.8, 7.4 Hz, 2H), 0.86 (t, J = 7.4 Hz, 3H).13C NMR (100 MHz, CDCl3) δ170.48, 164.34, 139.96, 135.30, 132.44, 132.32,130.73, 129.17, 129.12, 122.17, 119.92, 113.33, 66.12, 54.69, 35.21, 27.82,25.44, 22.71, 22.37, 22.18, 13.71. HRMS (ESI-TOF) m/z Calcd for C21H27N2O2 [M+H]+: 339.2067, found: 339.2075。
实施例15:如图19所示,向25 mL的Schlenk管中依次加入α,β-不饱和甲酰类底物1o(0.1 mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢钾(0.2 mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入1-戊烯基硼酸酯2a(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体3o(23.0mg)收率68%。
其中,3o:1H NMR (400 MHz, CDCl3) δ 12.10 (s, 1H), 8.83 (d, J = 8.4 Hz,1H), 7.88 – 7.81 (m, 1H), 7.46 (t, J = 7.3 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H),6.92 (d, J = 15.4 Hz, 1H), 6.37 – 6.24 (m, 1H), 4.37 (t, J = 9.5 Hz, 2H),4.14 – 4.06 (m, 4H), 2.56 (t, J = 6.5 Hz, 2H), 2.12 (q, J = 7.2 Hz, 2H), 2.01– 1.91 (m, 2H), 1.42 (dt, J = 14.6, 7.3 Hz, 2H), 0.90 (t, J = 7.4 Hz, 3H). 13CNMR (100 MHz, CDCl3) δ 167.38, 163.54, 155.39, 139.40, 133.87, 131.40,128.11, 122.77, 120.79, 118.92, 112.20, 106.14, 65.08, 64.87, 53.69, 33.86,21.76, 21.34, 21.02, 12.79. HRMS (ESI-TOF) m/z Calcd for C20H24N2NaO3 [M+Na]+:363.1679, found: 363.1687。
实施例16:如图20所示,向25 mL的Schlenk管中依次加入苯甲酰类底物1j(0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入烯基硼酸酯类底物 2b(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于50 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化(PE: EA = 20:1)得到白色固体4b(23.0 mg)收率68%。
其中,4b:1H NMR (400 MHz, CDCl3) δ 12.58 (s, 1H), 8.94 (d, J = 8.5 Hz,1H), 7.89 (d, J = 6.8 Hz, 1H), 7.56 – 7.49 (m, 2H), 7.18 – 7.08 (m, 2H), 6.96(dd, J = 8.7, 2.7 Hz, 1H), 6.82 (d, J = 15.6 Hz, 1H), 6.09 (dt, J = 15.5, 7.0Hz, 1H), 4.34 (t, J = 9.4 Hz, 2H), 4.02 (t, J = 9.5 Hz, 2H), 3.83 (s, 3H),2.16 (q, J = 7.3 Hz, 2H), 1.47 – 1.36 (m, 2H), 1.35 – 1.20 (m, 6H), 0.86 (t,J = 6.7 Hz, 3H).13C NMR (100 MHz, CDCl3) δ 167.13, 163.45, 157.17, 138.97,135.17, 131.53, 130.73, 128.67, 128.18, 126.80, 125.77, 121.47, 118.76,115.91, 112.45, 111.06, 76.34, 76.02, 75.70, 65.12, 54.40, 53.66, 32.18,30.72, 28.41, 27.91, 21.57, 13.08. HRMS (ESI-TOF) m/z Calcd for C25H31N2O3 [M+H]+: 407.2329, found: 407.2341。
实施例17:如图21所示,向25 mL的Schlenk管中依次加入苯甲酰类底物1j(0.1mmol),醋酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢钠(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入烯基硼酸酯类底物2c(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体4c(28.6mg)收率85%。
其中,4c:1H NMR (400 MHz, CDCl3) δ 12.59 (s, 1H), 8.95 (d, J = 8.5 Hz,1H), 7.89 (d, J = 7.9 Hz, 1H), 7.56 - 7.47 (m, 2H), 7.19 – 7.10 (m, 2H), 6.96(dd, J = 8.7, 2.6 Hz, 1H), 6.85 (d, J = 14.9 Hz, 1H), 4.35 (t, J = 9.6 Hz,2H), 4.03 (t, J = 9.5 Hz, 2H), 3.84 (s, 3H), 1.85 (dd, J = 6.6, 1.5 Hz, 3H).13C NMR (100 MHz, CDCl3) δ168.15, 164.54, 158.24, 140.03, 136.06, 132.61,129.82, 129.23, 128.22, 127.85, 126.19, 122.56, 119.87, 117.00, 113.55,112.15, 55.46, 54.72, 18.70. HRMS (ESI-TOF) m/z Calcd for C20H21N2O3 [M+H]+:337.1547, found: 337.1551。
实施例18:如图22所示,向25 mL的Schlenk管中依次加入苯甲酰类底物1j(0.1mmol),特戊酸铜(0.03 mmol), 氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入烯基硼酸酯类底物2d(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化(PE : EA = 20:1)得到白色固体4d(25.2 mg)收率75%。
其中,4d:1H NMR (400 MHz, CDCl3) δ 12.54 (s, 1H), 8.92 (d, J = 8.4 Hz,1H), 7.88 (d, J = 7.9 Hz, 1H), 7.50 (t, J = 7.9 Hz, 1H), 7.30 - 7.26 (m, 2H),7.11 (t, J = 7.6 Hz, 1H), 6.99 (dd, J = 8.5, 2.7 Hz, 1H), 6.69 (d, J = 11.6Hz, 1H), 5.77 (dd, J = 11.5, 7.0 Hz, 1H), 4.35 (t, J = 9.5 Hz, 2H), 4.04 (t,J = 9.5 Hz, 2H), 3.86 (s, 3H), 1.79 (dd, J = 7.1, 1.4 Hz, 3H). 13C NMR (100MHz, CDCl3) δ 167.94, 164.46, 158.10, 139.93, 137.45, 132.53, 131.62, 129.18,128.55, 127.95, 126.56, 122.47, 119.85, 116.20, 113.49, 112.60, 66.10, 55.40,54.72, 14.46. HRMS (ESI-TOF) m/z Calcd for C20H21N2O3 [M+H]+: 337.1547, found:337.1552。
实施例19:如图23所示,向25 mL的Schlenk管中依次加入苯甲酰类底物1j(0.1mmol),特戊酸铜(0.03 mmol), 氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢钠(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入烯基硼酸酯类底物2e(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体4e(26.7 mg)收率73%。
其中,4e:1H NMR (400 MHz, CDCl3) δ 12.57 (s, 1H), 8.94 (d, J = 8.4 Hz,1H), 7.89 (d, J = 7.9 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 7.33 (d, J = 8.7 Hz,1H), 7.19 (d, J = 2.6 Hz, 1H), 7.12 (t, J = 7.2 Hz, 1H), 6.94 (dd, J = 8.5,2.5 Hz, 1H), 6.86 (d, J = 12.9 Hz, 1H), 6.33 (d, J = 12.8 Hz, 1H), 4.36 (t, J= 9.5 Hz, 2H), 4.04 (t, J = 9.5 Hz, 2H), 3.87 – 3.80 (m, 5H), 1.28 (t, J =7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 167.18, 163.41, 156.57, 146.93,138.96, 134.55, 131.52, 128.17, 126.95, 126.09, 121.46, 118.80, 116.16,112.46, 111.57, 102.26, 65.15, 63.94, 54.41, 53.64, 13.66. HRMS (ESI-TOF) m/zCalcd for C20H21N2O3 [M+H]+: 367.1652, found: 367.1660。
实施例20:如图24所示,向25 mL的Schlenk管中依次加入苯甲酰类底物1j(0.1mmol),特戊酸铜(0.03 mmol), 氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入烯基硼酸酯类底物2f(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体4f(26.4 mg)收率67%。
其中,4f:1H NMR (400 MHz, CDCl3) δ 12.59 (s, 1H), 8.94 (d, J = 8.4 Hz,1H), 7.89 (d, J = 7.8 Hz, 1H), 7.62 (d, J = 8.7 Hz, 1H), 7.53 (t, J = 7.9 Hz,1H), 7.26 (d, J = 1.8 Hz, 1H), 7.16 (d, J = 2.6 Hz, 1H), 7.13 (t, J = 7.6 Hz,1H), 6.99 (dd, J = 8.8, 2.6 Hz, 1H), 6.33 (d, J = 19.0 Hz, 1H), 4.34 (t, J =9.6 Hz, 2H), 4.00 (t, J = 9.5 Hz, 2H), 3.86 (d, J = 7.3 Hz, 3H), 0.07 (s,9H). 13C NMR (100 MHz, CDCl3) δ 166.90, 163.44, 157.97, 139.70, 138.90,136.06, 131.59, 129.14, 128.84, 128.17, 126.78, 121.51, 118.75, 115.91,112.37, 111.10, 65.13, 54.44, 53.61, -2.26. HRMS (ESI-TOF) m/z Calcd forC22H27N2O3Si [M+H]+: 395.1785, found: 395.1794。
实施例21:如图25所示,向25 mL的Schlenk管中依次加入苯甲酰类底物1j(0.1mmol),特戊酸铜(0.03 mmol), 氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入烯基硼酸酯类底物2g(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体4g(31.5 mg)收率90%。
其中:4g:1H NMR (400 MHz, CDCl3) δ 12.44 (s, 1H), 8.91 (d, J = 8.4 Hz,1H), 7.87 (d, J = 7.9 Hz, 1H), 7.50 (t, J = 7.9 Hz, 1H), 7.25 (d, J = 2.7 Hz,1H), 7.20 (d, J = 8.5 Hz, 1H), 7.10 (t, J = 7.6 Hz, 1H), 6.97 (dd, J = 8.5,2.7 Hz, 1H), 6.46 (s, 1H), 4.33 (t, J = 9.5 Hz, 2H), 4.02 (t, J = 9.5 Hz,2H), 3.84 (s, 3H), 1.82 (s, 3H), 1.75 (s, 3H). 13C NMR (100 MHz, CDCl3) δ168.16, 164.38, 157.77, 139.98, 137.33, 135.32, 132.49, 131.92, 129.67,129.20, 123.03, 122.98, 122.41, 119.91, 116.31, 113.54, 112.58, 66.09, 55.37,54.81, 26.35, 19.48. HRMS (ESI-TOF) m/z Calcd for C21H23N2O3 [M+H]+: 351.1703,found: 351.1711。
实施例22:如图26所示,向25 mL的Schlenk管中依次加入苯甲酰类底物1j(0.1mmol),醋酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢钠(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入烯基硼酸酯类底物2h(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体4h(31.5 mg)收率90%。
其中,4h:1H NMR (400 MHz, CDCl3) δ 12.18 (s, 1H), 8.79 (d, J = 8.4 Hz,1H), 7.91 – 7.84 (m, 1H), 7.49 (t, J = 7.8 Hz, 1H), 7.20 (d, J = 2.7 Hz, 1H),7.09 (dd, J = 15.8, 8.0 Hz, 2H), 6.97 (dd, J = 8.4, 2.7 Hz, 1H), 4.33 (t, J =9.4 Hz, 2H), 4.02 (t, J = 9.6 Hz, 2H), 3.84 (s, 3H), 1.95 (s, 3H), 1.70 (s,3H), 1.53 (s, 3H). 13C NMR (100 MHz, CDCl3) δ167.44, 163.22, 156.67, 138.96,136.36, 135.25, 131.40, 130.13, 128.13, 127.31, 126.99, 121.33, 119.09,115.44, 112.58, 111.27, 65.02, 54.35, 53.82, 21.23, 20.09, 19.33. HRMS (ESI-TOF) m/z Calcd for C22H25N2O3 [M+H]+: 365.1860, found: 365.1869。
实施例23:如图27所示,向25 mL的Schlenk管中依次加入苯甲酰类底物1j(0.1mmol),特戊酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入烯基硼酸酯类底物2i(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体4i(28.7 mg)收率76%。
其中,4i:1H NMR (400 MHz, CDCl3) δ 12.45 (s, 1H), 8.88 (d, J = 8.3 Hz,1H), 7.89 (d, J = 7.9 Hz, 1H), 7.50 (t, J = 7.7 Hz, 1H), 7.23 – 7.18 (m, 2H),7.11 (t, J = 7.4 Hz, 1H), 6.98 (dd, J = 8.5, 2.7 Hz, 1H), 5.75 (s, 1H), 4.35(t, J = 9.5 Hz, 2H), 4.17 (d, J = 2.4 Hz, 2H), 4.00 (t, J = 9.5 Hz, 2H), 3.84(s, 3H), 3.76 (t, J = 5.3 Hz, 2H), 2.40 (s, 2H). 13C NMR (100 MHz, CDCl3) δ168.48, 164.43, 158.58, 139.86, 136.90, 134.99, 133.51, 132.61, 130.03,129.29, 124.64, 122.54, 119.59, 116.51, 113.34, 112.98, 66.08, 65.67, 64.37,55.44, 54.67, 29.69. HRMS (ESI-TOF) m/z Calcd for C22H23N2O4 [M+H]+: 379.1652,found: 379.1662。
实施例24:如图28所示,向25 mL的Schlenk管中依次加入苯甲酰类底物1j(0.1mmol),醋酸铜(0.03 mmol),氧化银(0.2 mmol),特戊酸钾(0.2 mmol),碳酸氢铯(0.2mmol),抽换氮气5分钟,共3次,在氮气氛下依次加入烯基硼酸酯类底物2j(0.3 mmol),DMSO(2.0 mL),旋紧瓶盖,置于45 ℃油浴中搅拌12小时。反应结束后冷却至室温,依次加入少量乙酸乙酯和氨水淬灭反应,乙酸乙酯反复萃取,合并有机层,然后用饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压蒸出溶剂,粗产物经制备板分离纯化( PE: EA = 20:1)得到白色固体4j(28.0 mg)收率72%。
其中,4j:1H NMR (400 MHz, CDCl3) δ 12.40 (s, 1H), 8.92 (d, J = 8.4 Hz,1H), 7.86 (d, J = 7.8 Hz, 1H), 7.51 (t, J = 7.9 Hz, 1H), 7.22 (d, J = 8.6 Hz,1H), 7.14 – 7.07 (m, 2H), 6.93 (dd, J = 8.6, 2.7 Hz, 1H), 6.03 (d, J = 2.8Hz, 1H), 4.36 – 4.29 (m, 2H), 3.98 (t, J = 9.7 Hz, 2H), 3.83 (s, 3H), 3.10(s, 1H), 2.84 (s, 1H), 1.71 – 1.59 (m, 2H), 1.42 (d, J = 8.0 Hz, 1H), 1.15 –1.00 (m, 3H). 13C NMR (100 MHz, CDCl3) δ 169.17, 164.18, 158.42, 146.13,140.04, 137.52, 132.59, 131.27, 129.73, 129.20, 127.44, 122.44, 119.77,116.18, 113.43, 112.91, 66.15, 55.47, 54.69, 47.97, 46.34, 43.24, 26.21,24.78. HRMS (ESI-TOF) m/z Calcd for C24H25N2O3 [M+H]+: 389.1860, found:389.1868。
Claims (4)
1.一种通过铜催化的sp2杂化碳氢键的烯基化反应方法,其特征在于,该方法以甲酰胺化合物为底物,在铜催化剂、氧化银、特戊酸钾、碱、溶剂在氮气氛围下与烯基硼酸酯试剂进行偶联反应,得到各种烯基化合物;
所述的反应用以下反应方程式来表示:
其中,R1、R2、R3和R4选自氢、甲基、甲氧基、氟、氯、溴、碘中任一种;
R5为氢或甲基;R6、R7选自氢或C1-10烷基中任一种;
R8为与硼酸组合为环状乙二醇、频哪醇、丙二醇、丁二醇、戊二醇的硼酸酯中任一种;
R11为氢;R12为氢;
所述铜催化剂选自醋酸铜、醋酸铜水合物、特戊酸铜、三氟甲磺酸铜或三氟乙酸铜中任一种;
所述碱选自醋酸钾,醋酸钠,醋酸铯,醋酸锂,碳酸钾,碳酸钠,碳酸铯,碳酸锂,碳酸氢钾,碳酸氢钠,碳酸氢铯,甲醇钠,甲醇钾,乙醇钠,乙醇钾,甲酸钾,甲酸钠,磷酸钾,磷酸氢二钾,氟化钠,氟化铯或氟化钾中任一种。
2.根据权利要求1所述的一种通过铜催化的sp2杂化碳氢键的烯基化反应方法,其特征在于,催化剂与底物的摩尔比为1:1-1:20;底物与烯基硼酸酯试剂的摩尔比1:1-1:3;底物与碱的摩尔比为1:1-1:3。
3.根据权利要求1所述的一种通过铜催化的sp2杂化碳氢键的烯基化反应方法,其特征在于,反应溶剂为DMF、DMA、DMSO、NMP、DMPU、THF、MeOH、EtOH、t-Amyl-OH、Acetone或CH3CN中任一种。
4.根据权利要求1所述的一种通过铜催化的sp2杂化碳氢键的烯基化反应方法,其特征在于,反应温度为25℃-120℃;反应时间为1-48小时。
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