CN114573472A - α-高烯丙基酰胺衍生物及其合成方法 - Google Patents
α-高烯丙基酰胺衍生物及其合成方法 Download PDFInfo
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- CN114573472A CN114573472A CN202210111333.6A CN202210111333A CN114573472A CN 114573472 A CN114573472 A CN 114573472A CN 202210111333 A CN202210111333 A CN 202210111333A CN 114573472 A CN114573472 A CN 114573472A
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- Prior art keywords
- phenyl
- atom
- product
- benzyl
- cdcl
- Prior art date
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- 238000010189 synthetic method Methods 0.000 title claims description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 75
- 239000002994 raw material Substances 0.000 claims abstract description 53
- 150000001408 amides Chemical class 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 16
- -1 1, 3-diene compound Chemical class 0.000 claims abstract description 11
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 11
- 150000003953 γ-lactams Chemical class 0.000 claims abstract description 10
- 150000003950 cyclic amides Chemical class 0.000 claims abstract description 9
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 92
- 238000004440 column chromatography Methods 0.000 claims description 59
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 50
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 claims description 37
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 16
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 16
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 16
- 229910052796 boron Inorganic materials 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 229910052710 silicon Inorganic materials 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 238000006467 substitution reaction Methods 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- XUWHAWMETYGRKB-UHFFFAOYSA-N delta-valerolactam Natural products O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 9
- 150000003954 δ-lactams Chemical class 0.000 claims description 9
- LLVWLCAZSOLOTF-UHFFFAOYSA-N 1-methyl-4-[1,4,4-tris(4-methylphenyl)buta-1,3-dienyl]benzene Chemical compound C1=CC(C)=CC=C1C(C=1C=CC(C)=CC=1)=CC=C(C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 LLVWLCAZSOLOTF-UHFFFAOYSA-N 0.000 claims description 8
- 239000000654 additive Substances 0.000 claims description 8
- 230000000996 additive effect Effects 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 238000001308 synthesis method Methods 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 3
- 239000006259 organic additive Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 215
- 239000000047 product Substances 0.000 description 161
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 54
- 238000005160 1H NMR spectroscopy Methods 0.000 description 54
- 239000012043 crude product Substances 0.000 description 53
- 239000007788 liquid Substances 0.000 description 53
- 239000002904 solvent Substances 0.000 description 53
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 51
- 238000001816 cooling Methods 0.000 description 51
- 239000000741 silica gel Substances 0.000 description 51
- 229910002027 silica gel Inorganic materials 0.000 description 51
- 238000002390 rotary evaporation Methods 0.000 description 50
- 238000003756 stirring Methods 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 229910002651 NO3 Inorganic materials 0.000 description 6
- 150000001728 carbonyl compounds Chemical class 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229910001868 water Inorganic materials 0.000 description 3
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000006579 Tsuji-Trost allylation reaction Methods 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 238000005937 allylation reaction Methods 0.000 description 2
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 238000011925 1,2-addition Methods 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- JSSIAXXILAGJKE-FOWTUZBSSA-N Mahanimbinol Chemical compound N1C2=CC=CC=C2C2=C1C(C/C=C(C)/CCC=C(C)C)=C(O)C(C)=C2 JSSIAXXILAGJKE-FOWTUZBSSA-N 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000005825 carbonyl allylation reaction Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000006772 olefination reaction Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000011911 α-alkylation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—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
- C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
- C07D207/06—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 no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- 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
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/08—Oxygen atoms
- C07D223/10—Oxygen atoms attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—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
- C07D295/16—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 acylated on ring nitrogen atoms
- C07D295/18—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 acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
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Abstract
本发明公开了一种α‑高烯丙基取代酰胺衍生物的制备方法，以γ‑内酰胺等环状酰胺或直链酰胺和共轭1,3‑二烯化合物为原料，在有机溶剂和添加剂存在的条件下，以高收率、高区域选择性得到目标产物。本发明具有高原子经济性、高区域选择性等优势，可实现酰胺化合物的α‑高烯丙基化反应。本发明合成的α‑高烯丙基酰胺衍生物是一种潜在的合成中间体，在医药化工等领域具有潜在应用前景。
Description
技术领域
本发明属于化学合成领域，具体涉及一种α-高烯丙基酰胺衍生物及其合成方法。
背景技术
构建C-C键是有机合成最主要的目标之一，羰基化合物α-烷基化反应是构建C-C键最直接有效的方法。近些年，有机合成化学家尝试开发更加绿色高效和原子经济性更好的转化方法，而过渡金属催化的羰基化合物与不饱和碳氢化合物的α-烯丙基化反应成为研究的重点领域(Chem.Rev.2017,117,9333-9403)。这其中，共轭1,3-丁二烯在与各种羰基化合物发生α-烯丙基烷基化反应显示出了良好的底物适用性。
在传统的过渡金属催化羰基化合物与共轭1,3-二烯发生α-烯丙基烷基化反应过程中，首先会生成一类金属氢物种，它可以活化共轭1,3-二烯从而生成一类金属-π-烯丙基物种，然后羰基化合物做为亲核试剂选择性进攻金属-π-烯丙基物种发生1,2-加成生成相应的支链选择性产物(J.Am.Chem.Soc.,2018,140,11627-11630)。另一方面，羰基化合物与取代的1,3-二烯选择性2,1-加成生成相应的直链选择性α-高烯丙基烷基化产物还没有报导。因此，从容易获得的简单酰胺和共轭1,3-二烯开发原子经济性和无副产物的α-高烯基化反应生成直链选择性产物具有高度重要性。
发明内容
本发明的目的是克服现有技术存在的上述缺陷，公开一种经济、绿色、高效、选择性好、底物范围广的酰胺与共轭1,3-二烯的α-高烯丙基烷基化反应，通过使用碱作为添加剂，以92％的产率获得所需的α-高烯丙基化目标产物3a即所述α-高烯丙基酰胺衍生物，并具有优异的区域选择性和原子经济性。
本发明提出一种α-高烯丙基酰胺衍生物的合成方法，在有机溶剂、添加剂存在的条件下，以式(1a)所示的酰胺、式(2a)所示的共轭1,3-二烯为反应原料，进行反应，得到式(3a)所示的α-高烯丙基酰胺衍生物；所述反应如下反应式(A)所示：
其中：
R1为以下所列基团中的一种，包括链状烷烃，苯基，苄基，烷基取代的苯基，烷氧基取代的苯基，烷氧基取代的苄基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代基的苯基；
R2为以下所列基团中的一种，包括链状烷烃，苯基，苄基，烷基取代的苯基；
R3为氢；或当R3不是氢时，式(1a)为包括γ-内酰胺、δ-内酰胺在内，碳个数在4-6的各种环状酰胺；
R4为以下所列基团中的一种，包括链状烷烃，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的链状烷烃，环烷基，苯基，苄基，烷基取代的苯基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的苯基，芳环或芳杂环取代的苯基，芳杂环；
R5为以下所列基团中的一种，包括氢，烷基，苯基；
R6为以下所列基团中的一种，包括苯基，烷基取代的苯基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的苯基，芳环或芳杂环取代的苯基，芳杂环。
优选地，
R1为甲基，苯基，苄基，对甲氧基苯基，对甲氧基苄基，烯丙基；
R2为甲基，苄基，烷基取代的苯基；
R3为氢；或当R3不是氢时，式(1a)为包括γ-内酰胺、δ-内酰胺在内，碳个数在4-6的各种环状酰胺；
R4为C1-C6烷基，含有氧原子取代的链状烷烃，苯基，苄基，C1-C6烷基取代的苯基，卤素原子取代的苯基；
R5为以下所列基团中的一种，包括氢，甲基，苯基；
R6为苯基，C1-C6烷基取代的苯基，卤素原子取代的苯基，N，N-二甲基取代的苯基，萘基，呋喃基。
进一步优选地，
R1苯基，苄基；
R2为甲基，苄基；
R3为氢；
R4为甲基，乙基，异丙基，正丁基，苯基，苄基；
R5为氢，甲基，苯基；
R6为苯基，对甲基苯基，对氯苯基，对甲氧基苯基，萘基，呋喃基。
本发明中，所述酰胺包括γ-内酰胺，δ-内酰胺，直链烷基酰胺等。
本发明中，所述有机溶剂为1，2-二氯乙烷，甲苯，乙腈，四氢呋喃，1，4-二氧六环，甲基叔丁基醚，CPME，乙二醇二甲醚，二甲亚砜中的一种或多种；优选地，为CPME。
本发明中，所述添加剂为叔丁醇钾，叔丁醇钠，叔丁醇锂，氢氧化钾，六甲基二硅基胺基钾中一种或多种；优选地，为叔丁醇钾。
本发明中，当所述酰胺:共轭1,3-二烯:添加剂的摩尔比为：1:(1-3):(0.1-1.2)；优选地，为1:1.2:0.2。
本发明中，以酰胺的用量为基准，所述有机溶剂的加入量为1mL/mmol酰胺；
本发明中，所述反应温度为25–100℃；优选地，为50℃。
本发明中，所述反应的时间为12-48h；优选地，为24h。
本发明合成方法，还包括后处理步骤：将反应得到的粗反应液用体积比为乙醚:石油醚＝1:10～1:5的溶液进行柱层析，高收率、高区域选择性得到α-高烯丙基酰胺衍生物。
本发明方法中粗产物分离纯化的方法为将粗反应液用体积比为乙醚:石油醚＝1:10～1:5的流动相进行柱层析。
在一个具体的实施方案中，本发明α-高烯丙基酰胺衍生物的合成过程包括:向装有搅拌子的4mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。
本发明还提出一种α-高烯丙基酰胺衍生物，其结构如式(3a)所示：
其中：R1为以下所列基团中的一种，包括链状烷烃，苯基，苄基，烷基取代的苯基，烷氧基取代的苯基，烷氧基取代的苄基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代基的苯基；
R2为以下所列基团中的一种，包括链状烷烃，苯基，苄基，烷基取代的苯基；
R3为氢；或当R3不是氢时，式(1a)为包括γ-内酰胺、δ-内酰胺在内，碳个数在4-6的各种环状酰胺；
R4为以下所列基团中的一种，包括链状烷烃，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的链状烷烃，环烷基，苯基，苄基，烷基取代的苯基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的苯基，芳环或芳杂环取代的苯基，芳杂环；
R5为以下所列基团中的一种，包括氢，烷基，苯基；
R6为以下所列基团中的一种，包括苯基，烷基取代的苯基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的苯基，芳环或芳杂环取代的苯基，芳杂环。
优选地，
R1为甲基，苯基，苄基，对甲氧基苯基，对甲氧基苄基，烯丙基；
R2为甲基，苄基，烷基取代的苯基；
R3为氢；或当R3不是氢时，式(1a)为包括γ-内酰胺、δ-内酰胺在内，碳个数在4-6的各种环状酰胺；
R4为C1-C6烷基，含有氧原子取代的链状烷烃，苯基，苄基，C1-C6烷基取代的苯基，卤素原子取代的苯基；
R5为以下所列基团中的一种，包括氢，甲基，苯基；
R6为苯基，C1-C6烷基取代的苯基，卤素原子取代的苯基，N，N-二甲基取代的苯基，萘基，呋喃基。
本发明还提出按如上方法合成制备得到的如式(3a)所示的α-高烯丙基酰胺衍生物。
本发明还提供了所述α-高烯丙基酰胺衍生物在合成药物中间体等中的应用。
本发明所述的合成方法可以用于很多生物活性物质的结构优化及合成。
本发明具有高原子经济性、高区域选择性等优势，可实现廉价基础的有机化学品到高附加值α-高烯丙基酰胺衍生物的高效转化。本发明合成的α-高烯丙基酰胺衍生物是一种潜在的合成中间体，在精细化学品合成和药物中间体合成中具有潜在应用前景。
本发明有益效果还包括：采用共轭1,3-二烯作为烯丙基烷基化试剂，可替代传统方法中通常所需要的带离去基团的烯丙基化试剂，反应步骤得到简化，原子经济性高，不产生副产物；同时，采用催化量的叔丁醇钾做为添加剂，有效克服了传统方法中需要用到当量的金属强碱，如LDA、LiHMDS、KHMDS等，反应条件温和、收率高、选择性好、底物适用性广、操作安全简单。同时，本发明所得到的α-高烯丙基酰胺衍生物可以发生进一步转化，得到其他方法较难合成化合物或者药物分子，在精细化学品的合成中具有潜在的应用前景。
具体实施方式
结合以下具体实施例，对本发明作进一步的详细说明，本发明的保护内容不局限于以下实施例。在不背离发明构思的精神和范围下，本领域技术人员能够想到的变化和优点都被包括在本发明中，并且以所附的权利要求书为保护范围。实施本发明的过程、条件、试剂、实验方法等，除以下专门提及的内容之外，均为本领域的普遍知识和公知常识，本发明没有特别限制内容。
实施例1：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为92％。1HNMR(400MHz,CDCl3)δ7.47(d,J＝7.6Hz,2H),7.25-7.18(m,4H),7.12-7.09(m,1H),6.82(d,J＝8.0Hz,2H),6.33(d,J＝15.6Hz,1H),6.18-6.10(m,1H),3.72(s,3H),3.69-3.64(m,2H),2.31-2.25(m,1H),2.18-2.04(m,2H),1.90-1.84(m,1H),1.72-1.67(m,2H),1.19(s,3H).13C NMR(101MHz,CDCl3)δ177.76,156.47,136.16,132.92,132.43,130.99,128.92,128.60,127.15,121.48,114.00,55.50,45.56,44.99,37.39,30.82,28.14,23.24.IR(v/cm-1):3732,3448,2945,2830,2171,2016,1121,1028cm-1.HRMS(ESI):calcd.C22H26NO2[M+H]+:336.1964.Found:336.1959.
实施例2：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的甲苯，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为91％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.21(d,J＝8.0Hz,2H),7.09(d,J＝8.0Hz,2H),6.89(d,J＝9.2Hz,2H),6.37(d,J＝16.0Hz,1H),6.19-6.12(m,1H),3.80(s,3H),3.75-3.71(m,2H),2.32(s,3H),2.24-2.12(m,2H),1.96-1.90(m,1H),1.79-1.74(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ178.01,156.54,136.75,134.99,133.08,130.02,129.30,125.95,121.63,114.11,55.61,45.72,45.16,37.65,30.98,28.25,23.29,21.27.IR(V/cm-1):3732,3448,2945,2830,2171,2016,1121,1023cm-1.HRMS(ESI):calcd.C23H28NO2[M+H]+:350.2120.Found:350.2133.
实施例3：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钠(1.0eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为82％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.24(d,J＝8.0Hz,2H),6.89(d,J＝9.2Hz,2H),6.82(d,J＝8.4Hz,2H),6.35(d,J＝16.0Hz,1H),6.10-6.03(m,1H),3.80(s,6H),3.74(t,J＝7.2Hz,2H),2.36-2.28(m,1H),2.23-2.12(m,2H),1.97-1.90(m,1H),1.81-1.72(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ178.00,158.84,156.55,133.11,130.65,129.56,128.18,127.14,121.62,114.12,114.04,55.60,55.40,45.70,45.14,37.76,30.97,28.23,23.32.IR(V/cm-1):3749,3724,3569,3376,2843,2832,2339,1973,1126,1022cm-1.HRMS(ESI):calcd.C23H28NO3[M+H]+:366.2069.Found:336.2045.
实施例4：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为90％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.37(dd,J＝7.6,1.6Hz,1H),7.19-7.15(m,1H),6.91-6.87(m,3H),6.83(d,J＝8.0Hz,1H),6.73(d,J＝16.0Hz,1H),6.24-6.16(m,1H),3.81(s,3H),3.79(s,3H),3.73(t,J＝7.2Hz,2H),2.43-2.31(m,1H),2.30-2.20(m,1H),2.21-2.11(m,1H),1.97-1.88(m,1H),1.83-1.74(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ178.04,156.52,156.38,133.11,131.03,128.03,126.84,126.55,124.82,121.63,120.74,114.09,110.85,55.59,55.52,45.71,45.15,37.66,30.92,28.70,23.33.IR(V/cm-1):3749,3647,3563,3376,2843,2839,2027,1512,1126,1022cm-1.HRMS(ESI):calcd.C23H28NO3[M+H]+:366.2069.Found:366.2045.
实施例5：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的四氢呋喃，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为82％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.21(d,J＝8.4Hz,2H),6.89(d,J＝9.2Hz,2H),6.66(d,J＝8.8Hz,2H),6.32(d,J＝16.0Hz,1H),6.03-5.96(m,1H),3.80(s,3H),3.73(t,J＝7.2Hz,2H),2.93(s,6H),2.37-2.25(m,1H),2.24-2.12(m,2H),1.98-1.88(m,1H),1.78-1.73(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ178.10,156.51,149.84,133.14,129.93,126.90,126.14,121.62,114.10,112.73,55.60,45.72,45.18,40.75,37.91,30.99,28.28,23.30.IR(V/cm-1):3820,3750,3446,2996,2829,2108,1997,1120,1022cm-1.HRMS(ESI):calcd.C24H31N2O2[M+H]+:379.2386.Found:379.2359.
实施例6：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的1,4-二氧六环，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为89％。1HNMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.30-7.22(m,2H),6.96(t,J＝8.4Hz,2H),6.89(d,J＝9.2Hz,2H),6.36(d,J＝16.0Hz,1H),6.15-6.08(m,1H),3.79(s,3H),3.75-3.71(m,2H),2.40-2.28(m,1H),2.27-2.10(m,2H),1.96-1.90(m,1H),1.84-1.74(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ177.91,163.24,160.80,156.56,133.93,133.90,133.03,130.09,130.07,129.01,127.49,127.41,121.60,115.52,115.31,114.10,55.59,45.68,45.10,37.58,30.92,28.19,23.33.IR(V/cm-1):3709,3610,2941,2830,2271,2046,1515,1124,1023cm-1.HRMS(ESI):calcd.C22H25FNO2[M+H]+:354.1869.Found:354.1898.
实施例7：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的二甲亚砜，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为89％。1H NMR(400MHz,CDCl3)δ7.53(d,J＝9.2Hz,2H),7.27-7.21(m,4H),6.89(d,J＝9.2Hz,2H),6.35(d,J＝15.6Hz,1H),6.23-6.15(m,1H),3.80(s,3H),3.76-3.72(m,2H),2.42-2.29(m,1H),2.29-2.09(m,2H),2.00-1.88(m,1H),1.84-1.70(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ177.87,156.58,136.28,133.04,132.55,131.11,129.04,128.72,127.26,121.60,114.12,55.61,45.68,45.10,37.51,30.94,28.26,23.36.IR(V/cm-1):3751,3660,3486,2941,2830,2271,2046,1516,1124,1022cm-1.HRMS(ESI):calcd.C22H25ClNO2[M+H]+:370.1574.Found:370.1572.
实施例8：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的1,2-二氯乙烷，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为87％。1HNMR(400MHz,CDCl3)δ7.53(d,J＝9.2Hz,2H),7.38(d,J＝8.4Hz,2H),7.16(d,J＝8.4Hz,2H),6.89(d,J＝9.2Hz,2H),6.34(d,J＝16.0Hz,1H),6.24-6.16(m,1H),3.80(s,3H),3.76-3.71(m,2H),2.40-2.28(m,1H),2.27-2.10(m,2H),1.97-1.90(m,1H),1.80-1.74(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ177.88,156.61,136.73,133.04,131.66,131.27,129.10,127.62,121.63,120.66,114.14,55.63,45.70,45.10,37.48,30.95,28.28,23.37.IR(V/cm-1):3868,3651,3552,2946,2889,2169,1513,1125,1022cm-1.HRMS(ESI):calcd.C22H25BrNO2[M+H]+:414.1069.Found:414.1088.
实施例9：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇锂(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为91％。1HNMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.22-7.08(m,3H),7.00(d,J＝7.2Hz,1H),6.89(d,J＝9.2Hz,2H),6.38(d,J＝15.6Hz,1H),6.23-6.19(m,1H),3.80(s,3H),3.73(d,J＝7.2Hz,2H),2.32(s,4H),2.28-2.10(m,2H),1.99-1.89(m,1H),1.84-1.71(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ177.94,156.54,138.10,137.72,133.10,130.26,130.15,128.50,127.82,126.80,123.21,121.65,121.60,114.11,55.60,45.69,45.13,37.63,30.98,28.28,23.31,21.52.IR(V/cm-1):3732,3448,2945,2830,2171,2016,1121,1023cm-1.HRMS(ESI):calcd.C23H28NO2[M+H]+:350.2120.Found:350.2133.
实施例10：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和氢氧化钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为56％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.28(s,1H),7.21-7.12(m,3H),6.89(d,J＝9.2Hz,2H),6.34(d,J＝16.0Hz,1H),6.26-6.18(m,1H),3.79(s,3H),3.76-3.72(m,2H),2.41-2.30(m,1H),2.29-2.09(m,2H),1.96-1.90(m,1H),1.80-1.74(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ177.82,156.57,139.67,134.51,133.04,132.01,129.80,128.97,126.95,126.00,124.28,121.59,114.12,55.60,45.66,45.09,37.45,30.96,28.24,23.34.IR(V/cm-1):3709,3660,3486,2841,2630,2170,2046,1516,1124,1022cm-1.HRMS(ESI):calcd.C22H25ClNO2[M+H]+:370.1574.Found:370.1572.
实施例11：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和六甲基二硅基胺基钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为63％。1H NMR(400MHz,CDCl3)δ7.82-7.72(m,3H),7.64(s,1H),7.55(d,J＝9.2Hz,3H),7.48-7.37(m,2H),6.88(d,J＝9.2Hz,2H),6.57(d,J＝16.0Hz,1H),6.38-6.31(m,1H),3.79(s,3H),3.75(t,J＝7.2Hz,2H),2.47-2.36(m,1H),2.34-2.14(m,2H),2.01-1.92(m,1H),1.85-1.79(m,2H),1.29(s,3H).13C NMR(101MHz,CDCl3)δ177.95,156.56,135.26,133.80,133.10,132.82,130.87,130.35,128.20,127.97,127.74,126.25,125.62,125.55,123.65,121.62,114.12,55.61,45.71,45.17,37.65,31.00,28.43,23.39.IR(V/cm-1):3732,3448,2945,2830,2171,2016,1121,1022cm-1.HRMS(ESI):calcd.C26H27NO2Na[M+Na]+:408.1939.Found:408.1938.
实施例12：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热12小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为92％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.30(d,J＝2.0Hz,1H),6.90(d,J＝9.2Hz,2H),6.33(dd,J＝3.6,2.0Hz,1H),6.27-6.09(m,3H),3.80(s,3H),3.75-3.71(m,2H),2.37-2.26(m,1H),2.25-2.09(m,2H),1.95-1.91(m,1H),1.80-1.72(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ177.87,156.57,153.21,141.44,133.06,129.32,121.64,118.93,114.12,111.18,106.31,55.60,45.68,45.08,37.45,31.02,27.97,23.20.IR(V/cm-1):3863,3647,3252,2947,2831,2215,2013,1514,1120,1022cm-1.HRMS(ESI):calcd.C20H24NO3[M+H]+:326.1756.Found:326.1746.
实施例13：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热48小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为38％。1.4:1dr.1H NMR(400MHz,Chloroform-d)δ7.49(d,J＝3.6Hz,2H),7.32-6.97(m,10H),6.89(d,J＝8.4Hz,2H),6.29(d,J＝15.6Hz,1H),5.98-5.91(m,1H),3.80(s,3H),3.61(q,J＝8.4Hz,1H),3.49-3.30(m,1H),3.22-3.08(m,1H),2.80-2.72(m,1H),2.69-2.43(m,2H),2.24-1.98(m,1H),1.83-1.75(m,1H),1.41(s,1H),1.13(s,2H).13C NMR(101MHz,CDCl3)δ177.39,176.35,156.66,142.50,141.85,140.99,138.83,137.80,132.98,132.90,131.25,129.75,129.25,128.96,128.80,128.41,128.36,128.25,128.07,127.96,126.97,126.90,126.86,126.09,125.82,121.87,114.10,114.09,55.62,55.60,52.46,51.54,49.48,45.80,45.67,35.96,35.18,32.04,31.27,28.33,24.06,23.52.IR(V/cm-1):3691,3667,2947,2832,2146,1515,1119,1022cm-1.HRMS(ESI):calcd.C28H30NO2[M+H]+:412.2277.Found:412.2245.
实施例14：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热48小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为52％。1.4:1dr.1HNMR(400MHz,CDCl3)δ7.54(d,J＝8.8Hz,2H),7.35-7.27(m,4H),7.20(t,J＝7.2Hz,1H),6.89(dd,J＝8.8,5.6Hz,2H),6.39(t,J＝16.0Hz,1H),6.23-6.16(m,1H),3.80(s,3H),3.77-3.66(m,2H),2.66-2.57(m,1H),2.64-2.59(m,0.6H),2.38-2.33(m,0.4H),2.23-2.15(m,1H),2.09-1.88(m,2H),1.81-1.74(m,1H),1.28(s,3H),0.97(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ178.15,178.06,156.63,137.82,133.05,131.46,131.40,129.76,129.53,128.65,128.60,127.08,127.01,126.12,126.09,121.80,121.78,114.16,114.14,55.64,49.18,48.82,45.94,45.85,39.10,38.91,36.69,34.95,27.23,26.80,22.91,22.26,15.20,13.86.IR(V/cm-1):3773,3667,2947,2832,2146,1515,1119,1022cm-1.HRMS(ESI):calcd.C23H28NO2[M+H]+:350.2120.Found:350.2133.
实施例15：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的甲基叔丁基醚，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为78％。1HNMR(400MHz,CDCl3)δ7.66(d,J＝8.0Hz,2H),7.41-7.25(m,6H),7.22-7.10(m,2H),6.41(d,J＝16.0Hz,1H),6.25-6.17(m,1H),3.80-3.76(m,2H),2.41-2.30(m,1H),2.28-2.11(m,2H),1.98-1.92(m,1H),1.81-1.76(m,2H),1.28(s,3H).13C NMR(101MHz,CDCl3)δ178.33,139.81,137.76,130.29,130.25,128.92,128.60,127.04,126.06,124.48,119.84,45.37,45.30,37.55,30.92,28.23,23.23.IR(V/cm-1):3648,3463,2944,2829,2167,1980,1472,1118,1022cm- 1.HRMS(ESI):calcd.C21H24NO[M+H]+:306.1858.Found:306.1877.
实施例16：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的乙二醇二甲醚，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为69％。1HNMR(400MHz,CDCl3)δ7.35-7.26(m,7H),7.25-7.16(m,3H),6.39(d,J＝16.0,1H),6.24-6.17(m,1H),4.45(d,J＝3.2Hz,2H),3.15(t,J＝7.2Hz,2H),2.33-2.25(m,1H),2.22-2.12(m,1H),2.05-1.95(m,1H),1.83-1.68(m,3H),1.20(s,3H).13C NMR(101MHz,CDCl3)δ178.85,137.80,136.83,130.47,130.10,128.78,128.76,128.60,128.20,127.63,127.02,126.04,46.89,44.03,43.44,37.49,31.16,28.26,23.32.IR(V/cm-1):3684,3347,2943,2830,2336,2043,1472,1120,1022cm-1.HRMS(ESI):calcd.C22H26NO2[M+OH]+:336.1964.Found:336.1959.
实施例17：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的乙腈，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为92％。1H NMR(400MHz,CDCl3)δ7.34-7.26(m,4H),7.21-7.14(m,3H),6.85(d,J＝9.2Hz,2H),6.38(d,J＝16.0Hz,1H),6.24-6.16(m,1H),4.38(d,J＝5.6Hz,2H),3.79(s,3H),3.13(t,J＝6.4Hz,2H),2.34-2.22(m,1H),2.21-2.10(m,1H),2.03-1.93(m,1H),1.79-1.68(m,3H),1.18(s,3H).13C NMR(101MHz,CDCl3)δ178.73,159.14,137.83,130.52,130.09,129.57,128.94,128.62,127.03,126.06,114.15,55.39,46.29,44.11,43.33,37.49,31.15,28.28,23.32.IR(V/cm-1):3690,3456,2946,2830,2193,2002,1516,1126,1023cm-1.HRMS(ESI):calcd.C23H28NO2[M+H]+:350.2120.Found:350.2133.
实施例18：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为87％。1H NMR(400MHz,CDCl3)δ7.35-7.24(m,5H),7.22-7.14(m,1H),6.88(dd,J＝19.6,2.4Hz,1H),6.39(d,J＝16.0Hz,1H),6.22-6.12(m,1H),5.02-4.90(m,1H),3.41(t,J＝9.6Hz,2H),2.36-2.05(m,3H),1.95-1.81(m,1H),1.78-1.66(m,5H),1.20(s,3H).13C NMR(101MHz,CDCl3)δ176.68,137.74,130.21,130.18,128.58,127.02,126.04,124.86,106.88,44.67,42.34,37.67,30.96,28.25,23.55,15.33.IR(V/cm-1):3750,3464,3051,2828,2196,1506,1125,1023cm-1.HRMS(ESI):calcd.C18H24NO[M+H]+:270.1858.Found:270.1855.
实施例19：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的甲苯，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为93％。1HNMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.35-7.24(m,4H),7.22-7.14(m,1H),6.89(d,J＝9.2Hz,2H),6.39(d,J＝16.0Hz,1H),6.24-6.16(m,1H),3.79(s,3H),3.72(t,J＝7.2Hz,2H),2.37-2.15(m,2H),2.12-2.04(m,2H),1.83-1.71(m,2H),1.65-1.56(m,2H),1.49-1.38(m,1H),1.35-1.24(m,1H),0.93(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ177.34,156.57,137.77,132.97,130.39,130.16,128.57,126.99,126.03,121.74,114.10,55.59,48.75,46.13,39.79,36.89,28.13,17.68,14.73.IR(V/cm-1):3711,3567,2946,2828,2365,1996,1669,1183,1023cm-1.HRMS(ESI):calcd.C24H30NO2[M+H]+:364.2277.Found:364.2291.
实施例20：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为89％。1HNMR(400MHz,CDCl3)δ7.55(d,J＝9.2Hz,2H),7.33-7.24(m,4H),7.21-7.14(m,1H),6.89(d,J＝9.2Hz,2H),6.39(d,J＝16.0Hz,1H),6.24-6.16(m,1H),3.79(s,3H),3.72(t,J＝7.2Hz,2H),2.38-2.27(m,1H),2.27-2.16(m,1H),2.11-2.04(m,2H),1.86-1.71(m,2H),1.65-1.60(m,2H),1.42-1.26(m,4H),0.90(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ177.28,156.49,137.69,132.91,130.31,130.07,128.48,126.91,125.95,121.66,114.02,55.51,48.58,46.03,37.12,36.78,28.05,26.45,23.29,14.07.IR(V/cm-1):3751,3690,2943,2830,2339,2148,1514,1120,1023cm-1.HRMS(ESI):calcd.C25H32NO2[M+H]+:378.2433.Found:378.2408.
实施例21：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热48小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为91％。柱层析法分离粗产物(硅胶，PE/Et2O＝100:1～60:1)，得到纯产品。产物为无色液体，产率为72％。1H NMR(400MHz,CDCl3)δ7.55(d,J＝9.2Hz,2H),7.33-7.25(m,4H),7.21-7.16(m,1H),6.90(d,J＝9.2Hz,2H),6.38(d,J＝16.0Hz,1H),6.23-6.17(m,1H),3.80(s,3H),3.78-3.64(m,2H),2.35-2.20(m,2H),2.19-2.09(m,2H),1.92-1.69(m,3H),0.93(t,J＝6.8Hz,6H).13C NMR(101MHz,CDCl3)δ177.18,156.68,137.77,132.84,130.43,130.21,128.58,127.00,126.04,121.97,114.15,114.12,55.61,52.49,46.56,36.90,33.55,28.31,23.52,18.42,16.96.IR(V/cm-1):3751,3690,3417,2943,2830,2389,1514,1120,1024cm-1.HRMS(ESI):calcd.C24H30NO2[M+H]+:364.2277.Found:364.2291.
实施例22：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为89％。1H NMR(400MHz,CDCl3)δ7.34-7.27(m,5H),7.26-7.15(m,7H),6.84(d,J＝9.2Hz,2H),6.42(d,J＝16.0Hz,1H),6.26-6.19(m,1H),3.77(s,3H),3.40-3.34(m,1H),3.14(d,J＝12.8Hz,1H),2.82-2.78(m,1H),2.71(d,J＝13.6Hz,1H),2.43-2.24(m,2H),2.14-1.92(m,3H),1.79-1.75(m,1H).13C NMR(101MHz,CDCl3)δ176.53,156.72,137.73,137.61,132.61,130.31,130.19,130.15,128.58,128.30,127.03,126.79,126.05,122.19,114.02,55.53,50.33,46.02,43.71,37.98,28.22,26.73.IR(V/cm-1):3709,3647,3436,2944,2832,2371,1983,1558,1119,1023cm-1.HRMS(ESI):calcd.C28H30NO2[M+H]+:412.2277.Found:412.2245.
实施例23：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的1,4-二氧六环，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为86％。1HNMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.33-7.26(m,4H),7.22-7.15(m,1H),6.90(d,J＝9.2Hz,2H),6.40(d,J＝16.0Hz,1H),6.24-6.16(m,1H),3.80(s,3H),3.76-3.72(m,2H),3.54-3.49(m,2H),3.31(s,3H),2.41-2.29(m,1H),2.27-2.16(m,2H),2.14-2.07(m,1H),2.02-1.87(m,2H),1.86-1.74(m,2H).13CNMR(101MHz,CDCl3)δ176.86,156.68,137.73,132.94,130.32,130.18,128.61,127.06,126.07,121.86,114.15,69.45,58.85,55.63,47.58,46.13,36.96,36.37,28.52,28.06.IR(V/cm-1):3735,3647,2944,2832,2371,1983,1119,1023cm-1.HRMS(ESI):calcd.C24H30NO3[M+H]+:380.2226.Found:380.2251.
实施例24：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为87％。1H NMR(400MHz,CDCl3)δ7.53(d,J＝9.2Hz,2H),7.33-7.24(m,4H),7.21-7.15(m,1H),6.89(d,J＝9.2Hz,2H),6.39(d,J＝16.0Hz,1H),6.23-6.15(m,1H),5.86-5.75(m,1H),5.20-5.08(m,2H),3.79(s,3H),3.74-3.65(m,2H),2.49-2.43(m,1H),2.38-2.18(m,3H),2.15-2.01(m,2H),1.88-1.80(m,1H),1.78-1.72(m,1H).13CNMR(101MHz,CDCl3)δ176.69,156.65,137.71,133.90,132.85,130.28,130.17,128.57,127.02,126.04,121.82,118.78,114.11,55.58,48.70,46.11,41.94,36.89,28.10,27.34.IR(V/cm-1):3608,3509,3297,2944,2830,2338,1115,1022cm-1.HRMS(ESI):calcd.C24H28NO2[M+H]+:362.2120.Found:362.2100.
实施例25：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为68％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.4Hz,4H),7.36(t,J＝7.6Hz,2H),7.31-7.26(m,5H),7.19-7.17(m,1H),6.89(d,J＝8.8Hz,2H),6.35(d,J＝16.0Hz,1H),6.20-6.13(m,1H),3.79(s,3H),3.75-3.69(m,2H),2.70-2.65(m,1H),2.43-2.34(m,1H),2.33-2.02(m,4H).13C NMR(101MHz,CDCl3)δ175.46,156.67,140.89,137.79,132.95,130.26,130.16,128.75,128.60,127.15,127.02,126.71,126.05,121.74,114.13,55.63,53.28,45.89,38.93,31.13,28.48.IR(V/cm-1):3614,3466,3335,3048,2950,2137,1646,1224,952cm-1.HRMS(ESI):calcd.C27H28NO2[M+H]+:398.2120.Found:398.2148.
实施例26：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为83％。1H NMR(400MHz,CDCl3)δ7.35-7.26(m,4H),7.21-7.17(m,1H),7.09(d,J＝8.8Hz,2H),6.87(d,J＝8.8Hz,2H),6.42(d,J＝16.0Hz,1H),6.26-6.19(m,1H),3.79(s,3H),3.67-3.59(m,1H),3.59-3.54(m,1H),2.39-2.17(m,2H),2.07-1.93(m,4H),1.73-1.66(m,2H),1.33(s,3H).13C NMR(101MHz,CDCl3)δ175.67,158.02,137.91,136.89,130.94,129.98,128.59,127.53,126.95,126.07,114.42,55.58,52.60,42.11,39.85,33.18,28.35,26.70,20.30.IR(V/cm-1):3712,3460,2944,2826,2380,1540,1199,1029cm-1.HRMS(ESI):calcd.C23H27NO2Na[M+Na]+:372.1939.Found:372.1912.
实施例27：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为77％。1H NMR(400MHz,CDCl3)δ7.37-7.27(m,4H),7.22-7.18(m,1H),7.03(d,J＝8.8Hz,2H),6.87(d,J＝8.8Hz,2H),6.43(d,J＝16.0Hz,1H),6.30-6.23(m,1H),3.92-3.83(m,1H),3.79(s,3H),3.64-3.56(m,1H),2.42-2.18(m,2H),2.01-1.93(m,1H),1.91-1.69(m,7H),1.33(s,3H).13C NMR(101MHz,CDCl3)δ177.73,157.83,140.01,137.78,130.86,129.90,128.50,127.63,126.88,125.96,114.43,55.49,51.12,46.31,35.80,28.36,28.24,26.64,23.30.IR(V/cm-1):3566,3249,2943,2899,2228,1558,1123,1021cm-1.HRMS(ESI):calcd.C24H30NO2[M+H]+:364.2277.Found:364.2291.
实施例28：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为58％。1H NMR(400MHz,CDCl3)δ7.33-7.27(m,4H),7.25-7.12(m,8H),7.09-7.03(m,1H),6.71(d,J＝7.6Hz,1H),6.15(d,J＝16.0Hz,1H),6.17-6.00(m,1H),4.91(d,J＝15.6Hz,1H),4.78(d,J＝15.6Hz,1H),2.24-2.15(m,1H),2.03-1.93(m,2H),1.90-1.80(m,1H),1.44(s,3H).13C NMR(101MHz,CDCl3)δ180.75,142.65,137.68,136.30,133.85,130.36,129.65,128.89,128.57,127.84,127.68,127.42,127.07,126.08,122.80,122.67,109.23,48.37,43.82,37.91,28.67,24.67.IR(V/cm-1):3522,3419,2945,2860,2143,1521,1122,1020cm-1.HRMS(ESI):calcd.C26H26NO[M+H]+:368.2014.Found:368.1994.
实施例29：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的1,4-二氧六环，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热12小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为68％。1HNMR(400MHz,CDCl3)δ7.38-7.25(m,9H),7.24-7.09(m,6H),6.29(d,J＝16.0Hz,1H),6.11(m,1H),4.64(d,J＝4.8Hz,2H),4.45(s,2H),2.76(m,1H),2.28-2.13(m,2H),1.99(m,1H),1.60(m,1H),1.18(d,J＝6.4Hz,3H).13C NMR(101MHz,CDCl3)δ177.16,137.74,137.60,136.90,130.50,130.10,128.92,128.65,128.47,128.30,127.57,127.41,126.94,126.34,125.94,49.76,48.40,35.13,34.01,30.78,18.11.IR(V/cm-1):3405,2973,2900,1378,1153,1087,1046,880cm- 1.HRMS(ESI):calcd.C27H30NO[M+H]+:384.2327.Found:384.2310.
实施例30：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的1,4-二氧六环，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热12小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为82％。1HNMR(400MHz,CDCl3)δ7.30(m,12H),7.16(m,3H),6.29(d,J＝15.6Hz,1H),6.10(m,1H),4.66(q,J＝14.4Hz,2H),4.47(s,2H),2.62(m,1H),2.30-2.07(m,2H),1.91(m,1H),1.69(m,3H),0.88(t,J＝7.2Hz,3H).13CNMR(101MHz,CDCl3)δ176.44,137.83,137.61,136.98,130.43,130.18,128.88,128.63,128.48,128.46,127.57,127.41,126.94,126.48,125.95,49.75,48.48,42.21,32.08,30.81,25.75,12.03.IR(V/cm-1):3393,2972,2897,2062,1379,1081,1048,880cm- 1.HRMS(ESI):calcd.C28H32NO[M+H]+:398.2484.Found:398.2515.
实施例31：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为80％。1H NMR(400MHz,CDCl3)δ7.38-7.22(m,12H),7.16(m,3H),6.28(d,J＝16.0Hz,1H),6.09(m,1H),4.67(s,2H),4.46(s,2H),2.75-2.57(m,1H),2.16(m,2H),1.97-1.83(m,1H),1.66(m,2H),1.54-1.45(m,1H),1.24(m,4H),0.90-0.78(t,J＝6.8Hz,3H).13C NMR(101MHz,CDCl3)δ176.66,137.85,137.63,137.04,130.47,130.19,128.89,128.63,128.49,127.58,127.44,126.95,126.48,125.96,49.83,48.62,40.69,32.52,32.38,30.85,29.74,22.88,14.01.IR(V/cm-1):3407,2970,2885,2017,1941,1450,1086,1047,880cm-1.HRMS(ESI):calcd.C30H36NO[M+H]+:426.2797.Found:426.2789.
实施例32：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为91％。1H NMR(400MHz,CDCl3)δ7.40-7.26(m,10H),7.17(m,5H),6.28(d,J＝16.0Hz,1H),6.13(m,1H),4.88(d,J＝14.4Hz,1H),4.55(d,J＝17.2Hz,1H),4.42(m,2H),2.52(m,1H),2.25(m,1H),2.04-1.93(m,3H),0.94(m,6H).13C NMR(101MHz,CDCl3)δ175.83,137.88,137.71,136.97,130.51,130.19,128.89,128.79,128.63,128.58,128.53,128.47,127.62,127.41,126.89,126.71,125.94,49.87,48.21,47.01,31.01,30.64,28.63,21.52,19.09.IR(V/cm-1):3370,2971,2872,2164,1992,1456,1087,1047,880cm-1.HRMS(ESI):calcd.C29H34NO[M+H]+:412.2640.Found:412.2619.
实施例33：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为74％。1H NMR(400MHz,CDCl3)δ7.38-7.24(m,12H),7.17(d,J＝7.7Hz,3H),6.26(d,J＝15.9Hz,1H),6.18-6.05(m,1H),4.73(d,J＝14.5Hz,1H),4.64-4.44(m,3H),2.62(d,J＝8.6Hz,1H),2.32-1.90(m,5H),1.86-1.73(m,2H),1.53(p,J＝11.6Hz,5H),1.12(dt,J＝30.6,10.0Hz,2H).13C NMR(101MHz,CDCl3)δ176.35,137.85,137.68,136.96,130.45,130.20,128.89,128.74,128.58,128.50,127.63,127.44,126.92,126.76,126.43,125.94,49.92,48.28,45.61,43.38,32.73,31.65,31.21,30.75,30.25,25.04,24.98,24.91.IR(V/cm-1):3305,2973,2935,1382,1086,1047,880cm-1.HRMS(ESI):calcd.C31H36NO[M+H]+:438.2797.Found:438.2787.
实施例34：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为92％。1H NMR(400MHz,CDCl3)δ7.37-7.25(m,12H),7.18(t,J＝6.8Hz,1H),7.12(d,J＝7.6Hz,2H),6.28(d,J＝16.0Hz,1H),6.17-6.04(m,1H),4.78(d,J＝14.8Hz,1H),4.56(d,J＝14.8Hz,1H),4.42(s,2H),2.24(m,2H),2.07(m,2H),1.89-1.77(m,1H),1.21-1.10(m,1H),0.61-0.41(m,2H),0.15-0.01(m,2H).13CNMR(101MHz,CDCl3)δ176.23,137.74,137.62,136.94,130.49,130.23,128.90,128.65,128.50,128.44,127.64,127.46,126.97,126.45,125.95,49.83,48.42,44.81,33.24,30.67,14.14,4.19,3.15.IR(V/cm-1):3563,3377,2055,1975,1558,1055,1047,880cm- 1.HRMS(ESI):calcd.C29H32NO[M+H]+:410.2484.Found:410.2477.
实施例35：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为79％。1H NMR(400MHz,CDCl3)δ7.29-7.16(m,14H),7.13(m,2H),7.06(m,2H),6.91-6.83(m,2H),6.26(d,J＝15.6Hz,1H),6.03(m,1H),4.58(s,2H),4.31-4.10(m,2H),2.98(m,2H),2.79(dd,J＝12.0,4.8Hz,1H),2.30-2.06(m,2H),1.92(m,1H),1.76-1.68(m,1H).13C NMR(101MHz,CDCl3)δ175.85,139.82,137.54,137.44,136.81,130.59,129.83,129.28,128.87,128.54,128.49,128.46,127.46,127.38,127.00,126.39,126.30,125.98,49.69,48.80,43.41,39.09,32.70,30.67.IR(V/cm-1):3503,3075,2105,1992,1456,1087,1047,880cm-1.HRMS(ESI):calcd.C33H34NO[M+H]+:460.2640.Found:460.2650.
实施例36：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的甲苯，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为68％。1H NMR(400MHz,CDCl3)δ7.32-7.21(m,17H),7.11(d,J＝7.2Hz,2H),7.00(d,J＝6.8Hz,2H),6.31(d,J＝15.6Hz,1H),6.11(m,1H),5.02(d,J＝14.8Hz,1H),4.53(d,J＝17.2Hz,1H),4.20(t,J＝13.6Hz,2H),3.78(t,J＝7.2Hz,1H),2.37(m,1H),2.18(m,2H),1.91(m,1H).13C NMR(101MHz,CDCl3)δ173.49,139.99,137.68,137.47,136.70,130.59,130.02,128.90,128.87,128.52,128.45,128.11,127.97,127.54,127.28,127.12,126.90,126.38,125.98,49.65,48.53,48.31,34.97,30.99.IR(V/cm-1):3517,2982,2104,1997,1446,1089,1047,880cm-1.HRMS(ESI):calcd.C33H32NO[M+H]+:446.2484.Found:446.2468.
实施例37：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的甲苯，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为84％。1H NMR(400MHz,CDCl3)δ7.36-7.15(m,13H),7.11(d,J＝7.2Hz,2H),7.02(d,J＝6.8Hz,2H),6.84(d,J＝8.0Hz,2H),6.30(d,J＝16.0Hz,1H),6.10(m,1H),5.01(d,J＝14.8Hz,1H),4.54(d,J＝17.2Hz,1H),4.20(t,J＝14.6Hz,2H),3.79(s,3H),3.72(t,J＝7.2Hz,1H),2.31(m,1H),2.16(m,2H),1.88(m,1H).13C NMR(101MHz,CDCl3)δ173.84,158.68,137.70,137.52,136.79,132.01,130.52,130.09,129.00,128.90,128.53,128.49,128.45,128.11,127.52,127.28,126.89,126.36,125.98,114.23,55.31,49.67,48.55,47.36,34.97,30.93,26.94.IR(V/cm-1):3404,2978,2148,2020,1456,1087,1047,879cm-1.HRMS(ESI):calcd.C33H34NO[M+H]+:476.2590.Found:476.2563.
实施例38：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为72％。1HNMR(400MHz,CDCl3)δ7.58(d,J＝7.6Hz,1H),7.30-7.09(m,16H),7.04-6.95(m,2H),6.35(d,J＝16.0Hz,1H),6.16(m,1H),5.02(d,J＝14.8Hz,1H),4.51-4.31(m,2H),4.19(dd,J＝20.8,14.8Hz,2H),2.34(m,2H),2.15(m,1H),1.84(m,1H).13C NMR(101MHz,CDCl3)δ172.94,137.88,137.76,137.36,136.44,133.09,130.55,129.95,129.63,128.79,128.75,128.53,128.44,128.40,128.12,127.51,127.46,127.33,126.85,126.50,126.00,49.45,48.31,44.07,34.25,31.11.IR(V/cm-1):3392,2973,2897,2180,1975,1380,1086,1045,879cm-1.HRMS(ESI):calcd.C32H31ClNO[M+H]+:480.2094.Found:480.2062.
实施例39：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为58％。1H NMR(400MHz,CDCl3)δ7.27(m,15H),7.13(m,2H),7.07-6.97(m,4H),6.94(m,1H),6.30(d,J＝16.0Hz,1H),6.10(m,1H),4.96(d,J＝14.8Hz,1H),4.50(d,J＝17.2Hz,1H),4.26(dd,J＝27.2,14.8Hz,2H),3.78(t,J＝7.2Hz,1H),2.34(m,1H),2.17(m,2H),1.91(m,1H).13C NMR(101MHz,CDCl3)δ173.03,142.42,137.54,137.33,136.53,130.81,130.28,130.19,129.66,128.95,128.60,128.47,128.15,127.64,127.42,126.99,126.26,125.99,123.73,115.00,114.20,113.99,49.74,48.79,47.86,34.89,30.89.IR(V/cm-1):3342,2980,2887,2150,1540,1392,1080,1047,878cm-1.HRMS(ESI):calcd.C32H31FNO[M+H]+:464.2390.Found:464.2431.
实施例40：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的四氢呋喃，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为69％。1H NMR(400MHz,CDCl3)δ7.36-7.18(m,10H),6.36(d,J＝15.6Hz,1H),6.19(m,1H),3.77(t,J＝7.2Hz,1H),2.93(s,3H),2.90(s,3H),2.37-2.09(m,3H),1.88(m,1H).13C NMR(101MHz,CDCl3)δ172.91,140.02,137.74,130.50,130.27,128.77,128.51,128.00,126.93,126.91,125.96,47.96,37.16,35.95,34.44,31.10.IR(V/cm-1):3503,3327,2014,1507,1050,1047,880cm-1.HRMS(ESI):calcd.C20H24NO[M+H]+:294.1858.Found:294.1871.
实施例41：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为87％。1H NMR(400MHz,CDCl3)δ7.38-7.16(m,10H),6.37(d,J＝15.6Hz,1H),6.20(m,1H),3.77(t,J＝7.8Hz,1H),3.68(m,1H),3.42(m,1H),3.32(t,J＝5.6Hz,2H),2.24(m,3H),1.88(m,1H),1.55-1.27(m,6H),0.96(m,1H).13C NMR(101MHz,CDCl3)δ170.93,140.55,137.78,130.47,130.35,128.76,128.70,128.50,127.89,126.90,126.78,125.96,47.82,46.61,43.21,34.36,31.10,26.03,25.57,24.54.IR(V/cm-1):3514,3304,2068,1976,1553,1097,1047,880cm-1.HRMS(ESI):calcd.C23H27NO[M+H]+:334.2171.Found:334.2159.
实施例42：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为95％。1H NMR(400MHz,CDCl3)δ7.26(m,13H),7.17-7.03(m,6H),7.00(m,2H),6.28(d,J＝15.6Hz,1H),6.05(m,1H),5.00(d,J＝14.4Hz,1H),4.52(d,J＝16.8Hz,1H),4.21(t,J＝15.2Hz,2H),3.78(t,J＝7.2Hz,1H),2.43-2.29(m,4H),2.16(m,2H),1.91(m,1H).13C NMR(101MHz,CDCl3)δ173.53,140.04,137.50,136.72,136.61,134.93,130.45,129.16,128.97,128.91,128.87,128.53,128.13,127.99,127.55,127.29,127.11,126.42,125.89,49.67,48.52,48.30,35.06,31.00,21.17.IR(V/cm-1):3350,2973,2887,2338,1381,1087,1047,880cm-1.HRMS(ESI):calcd.C33H34NO[M+H]+:460.2640.Found:460.2650.
实施例43：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为82％。1H NMR(400MHz,CDCl3)δ7.35-7.20(m,12H),7.17(d,J＝7.6Hz,2H),7.11(d,J＝6.8Hz,2H),7.00(d,J＝6.4Hz,2H),6.81(d,J＝7.6Hz,2H),6.25(d,J＝15.6Hz,1H),6.04-5.88(m,1H),5.00(d,J＝14.8Hz,1H),4.52(d,J＝16.8Hz,1H),4.21(t,J＝15.2Hz,2H),3.79(s,4H),2.35(m,1H),2.16(m,2H),1.89(m,1H).13C NMR(101MHz,CDCl3)δ173.54,158.73,140.06,137.50,136.73,130.57,129.96,128.90,128.86,128.53,128.13,127.99,127.84,127.55,127.29,127.10,127.07,126.42,113.90,55.31,49.66,48.52,48.29,35.14,30.98.IR(V/cm-1):3361,2970,2879,2150,1989,1457,1087,1048,878cm-1.HRMS(ESI):calcd.C33H34NO2[M+H]+:476.2590.Found:476.2563.
实施例44：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为71％。1H NMR(400MHz,CDCl3)δ7.40-7.18(m,13H),7.17-7.07(m,4H),6.99(d,J＝6.8Hz,2H),6.74-6.59(m,2H),6.23(d,J＝16.0Hz,1H),5.91(m,1H),4.95(d,J＝14.8Hz,1H),4.51(d,J＝16.8Hz,1H),4.23(dd,J＝23.2,14.8Hz,2H),3.80(t,J＝7.6Hz,1H),2.93(s,6H),2.36(m,1H),2.15(m,2H),1.89(m,1H).13CNMR(101MHz,CDCl3)δ173.62,149.77,140.16,137.54,136.73,130.41,128.89,128.82,128.52,128.15,128.03,127.53,127.27,127.04,126.86,126.50,125.79,112.62,49.68,48.45,48.24,40.68,35.32,31.06.IR(V/cm-1):3393,2971,2899,2173,1455,1087,1045,879cm-1.HRMS(ESI):calcd.C34H37N2O[M+H]+:489.2906.Found:489.2933.
实施例45：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为64％。1H NMR(400MHz,CDCl3)δ7.38-7.18(m,13H),7.18-7.07(m,4H),7.01(d,J＝6.8Hz,2H),6.25(d,J＝15.6Hz,1H),6.07(m,1H),5.05(d,J＝14.8Hz,1H),4.53(d,J＝17.2Hz,1H),4.18(m,2H),3.75(t,J＝7.2Hz,1H),2.35(m,1H),2.16(m,2H),1.90(m,1H).13C NMR(101MHz,CDCl3)δ173.43,139.92,137.45,136.73,136.19,132.44,130.81,129.37,128.92,128.58,128.54,128.12,127.98,127.94,127.58,127.32,127.18,126.33,49.65,48.61,48.37,34.88,30.97.IR(V/cm-1):3393,2971,2899,2029,1453,1089,1048,881cm-1.HRMS(ESI):calcd.C32H31ClNO[M+H]+:480.2094.Found:480.2062.
实施例46：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为69％。1HNMR(400MHz,CDCl3)δ7.37(d,J＝8.8Hz,2H),7.34-7.20(m,13H),7.09(m,4H),7.01(d,J＝6.8Hz,2H),6.23(d,J＝16.0Hz,1H),6.09(m,1H),5.05(d,J＝14.4Hz,1H),4.53(d,J＝17.2Hz,1H),4.18(m,2H),3.74(t,J＝7.2Hz,1H),2.36(m,1H),2.16(m,2H),1.89(m,1H).13C NMR(101MHz,CDCl3)δ173.43,139.91,137.44,136.73,136.63,131.52,130.96,129.41,128.92,128.54,128.11,127.98,127.93,127.58,127.53,127.32,127.19,126.32,120.54,49.65,48.62,48.37,34.84,30.98.IR(V/cm-1):3325,2980,2900,2015,1558,1075,1048,879cm-1.HRMS(ESI):calcd.C32H31BrNO[M+H]+:524.1589.Found:524.1581.
实施例47：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为60％。1H NMR(400MHz,CDCl3)δ7.36-7.06(m,17H),7.01(d,J＝6.8Hz,2H),6.23(d,J＝16.0Hz,1H),6.09(m,1H),5.06(d,J＝14.8Hz,1H),4.53(d,J＝17.2Hz,1H),4.19(dd,J＝16.0,8.8Hz,2H),3.74(t,J＝7.2Hz,1H),2.35(m,1H),2.17(m,2H),1.90(m,1H).13C NMR(101MHz,CDCl3)δ173.42,139.87,139.54,137.44,136.72,134.38,131.63,129.65,129.33,128.93,128.91,128.53,128.10,127.94,127.61,127.31,127.18,126.83,126.28,125.88,124.21,49.66,48.67,48.27,34.77,30.89.IR(V/cm-1):3361,2981,2885,2331,1970,1558,1080,1041,878cm-1.HRMS(ESI):calcd.C32H31ClNO[M+H]+:480.2094.Found:480.2062.
实施例48：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的甲苯，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为72％。1H NMR(400MHz,CDCl3)δ7.84-7.69(m,3H),7.56(s,1H),7.43(m,3H),7.35-7.29(s,4H),7.24(m,7H),7.12(d,J＝6.8Hz,2H),7.01(d,J＝7.2Hz,2H),6.47(d,J＝16.0Hz,1H),6.24(m,1H),5.03(d,J＝14.4Hz,1H),4.53(d,J＝17.2Hz,1H),4.21(t,J＝15.2Hz,2H),3.80(t,J＝7.2Hz,1H),2.41(m,1H),2.24(m,2H),1.95(m,1H).13C NMR(101MHz,CDCl3)δ173.51,140.00,137.49,136.72,135.14,133.68,132.72,130.73,130.51,128.90,128.54,128.14,128.03,127.99,127.84,127.64,127.55,127.30,127.15,126.37,126.14,125.51,125.44,123.59,49.67,48.58,48.31,35.00,31.13.IR(V/cm-1):3343,2973,2889,2331,2150,2032,1448,1085,1046,879cm- 1.HRMS(ESI):calcd.C36H34NO[M+H]+:496.2640.Found:496.2670.
实施例49：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为82％。1H NMR(400MHz,CDCl3)δ7.38-7.18(m,14H),7.10(d,J＝7.2Hz,2H),7.00(d,J＝6.8Hz,2H),6.32(s,1H),6.21-6.01(m,3H),4.99(d,J＝14.8Hz,1H),4.52(d,J＝16.8Hz,1H),4.21(t,J＝17.2Hz,2H),3.77(t,J＝8.0Hz,1H),2.34(m,1H),2.15(m,2H),1.89(m,1H).13C NMR(101MHz,CDCl3)δ173.42,153.13,141.28,139.96,137.48,136.69,128.97,128.88,128.83,128.52,128.12,127.97,127.54,127.28,127.12,126.44,126.41,119.30,111.08,106.19,49.68,48.51,48.26,34.85,30.72.IR(V/cm-1):3377,2971,2879,2143,1635,1558,1379,1082,1047,879cm- 1.HRMS(ESI):calcd.C30H29NO2[M+H]+:436.2277.Found:436.2249.
基于以上本发明各实施例中的γ-烯基酮，本发明进一步针对其主要结构，对部分产品进行应用性的衍生化，以证明本发明实施例制备的α-高烯丙基酰胺衍生物的实用性，具体结构和合成步骤如下：
衍生实施例1:
化合物3a(200mg,0.59mmol)溶于4mL乙腈中，降温至0℃，硝酸铈铵(654mg,1.19mmol)溶于4mL去离子水中，滴加至上述反应液中，反应在0℃下搅拌1小时。乙酸乙酯和水萃取洗涤，无水硫酸钠干燥。过滤，减压旋蒸除去溶剂，柱层析法分离纯化，最终得到产物7。
无色液体，产率70％。1HNMR(400MHz,CDCl3)δ7.33-7.28(m,4H),7.18(t,J＝7.2Hz,1H),6.41(d,J＝15.2Hz,2H),6.24-6.17(m,1H),3.31(t,J＝7.2Hz,2H),2.35-2.27(m,1H),2.25-2.10(m,2H),1.94-1.87(m,1H),1.69(t,J＝8.4Hz,2H),1.20(s,3H).13C NMR(101MHz,CDCl3)δ182.85,137.83,130.42,130.14,128.61,127.03,126.05,42.93,38.96,37.17,33.74,28.24,23.01.IR(V/cm-1):3711,3577,3046,2829,2123,1735,1513,1368,1237,965,734cm-1.HRMS(ESI):calcd.C15H20NO[M+H]+:230.1545.Found:230.1528.
衍生实施例2:
化合物3a(200mg，0.59mmol)溶于2mL四氢呋喃中，降温至0℃，分批加入四氢铝锂(68mg，1.79mmol)，反应在70℃下搅拌3h。降温至0℃，加饱和硫酸钠溶液淬灭，二氯甲烷萃取，饱和食盐水洗，无水硫酸钠干燥。过滤，减压旋蒸除去溶剂，柱层析法分离纯化，最终得到产物8。
无色液体，产率84％。1HNMR(400MHz,CDCl3)δ7.37-7.26(m,4H),7.19(t,J＝7.2Hz,1H),6.84(d,J＝8.4Hz,2H),6.48(d,J＝8.4Hz,2H),6.41(d,J＝16.0Hz,1H),6.26-6.19(m,1H),3.75(s,3H),3.36-3.31(m,2H),3.10(d,J＝8.8Hz,1H),3.01(d,J＝8.8Hz,1H),2.31-2.24(m,2H),1.88-1.76(m,2H),1.63(t,J＝8.4Hz,2H),1.13(s,3H).13C NMR(101MHz,CDCl3)δ150.73,143.23,137.88,131.07,129.90,128.63,127.01,126.03,115.22,112.15,60.37,56.19,47.38,41.58,40.21,38.15,29.01,24.31.IR(V/cm-1):3675,3463,2942,2199,1732,1514,1264,733cm-1.HRMS(ESI):calcd.C22H28NO[M+H]+:322.2171.Found:322.2139.
衍生实施例3:
化合物3a(100mg，0.30mmol)溶于5mL甲醇中，加入10mg Pd/C催化剂，反应在H2球氛围下室温搅拌过夜。过滤出去Pd/C,减压蒸馏，柱层析分离得到产物9。
无色液体，产率92％。1H NMR(400MHz,CDCl3)δ7.53(d,J＝7.6Hz,2H),7.27-7.23(m,2H),7.16(m,3H),6.89(d,J＝7.2Hz,2H),3.79(s,3H),3.69(m,2H),2.62(t,J＝8.0Hz,2H),2.06(m,1H),1.87(m,1H),1.68-1.55(m,4H),1.46(m,1H),1.37-1.28(m,1H),1.21(s,3H).13C NMR(101MHz,CDCl3)δ178.22,156.43,142.58,133.06,128.40,128.29,125.67,121.51,114.02,55.51,45.64,45.15,37.84,35.83,31.97,30.76,24.13,23.18.IR(V/cm-1):3392,3259,2971,2162,1964,1676,1514,1249,1089,1046,879cm-1.HRMS(ESI):calcd.C22H27NO2Na[M+Na]+:360.1939.Found:360.1965.
衍生实施例4:
化合物3a(200mg，0.59mmol)溶于5mL二氯甲烷中，加入间氯过氧苯甲酸(152mg，0.88mmol)，反应在室温下搅拌过夜。加饱和硫代硫酸钠溶液淬灭，乙酸乙酯萃取，无水硫酸钠干燥。过滤，减压旋蒸除去溶剂，柱层析法分离纯化，最终得到产物10。
无色液体，产率92％。dr＝1.4:1.1HNMR(400MHz,CDCl3)δ7.53(d,J＝7.6Hz,2H),7.31(m,3H),7.26-7.19(m,2H),6.89(d,J＝6.8Hz,2H),3.79(s,3H),3.77-3.68(m,2H),3.64(s,1H),2.98(s,1H),2.10(m,1H),1.99-1.89(m,1H),1.89-1.64(m,4H),1.25(s,3H).13C NMR(101MHz,CDCl3)δ177.50,156.54,137.58,137.56,132.85,128.46,128.08,125.57,121.58,121.56,114.05,62.90,62.86,58.63,58.51,55.50,45.57,45.55,44.80,44.66,33.92,33.61,31.04,30.75,27.61,27.47,23.27,22.66.IR(V/cm-1):3355,2975,2888,1675,1514,1456,1251,1088,1047,879cm-1.HRMS(ESI):calcd.C22H26NO3[M+H]+:352.1913.Found:352.1918.
衍生实施例5:
化合物3a(200mg，0.59mmol)溶于5mL乙醇中，依次加入苯硅烷(128mg，1.2mmol)和三氯化铁(2.8mg，3mol％)。反应敞口搅拌过夜，粗产品直接浓缩，柱层析分离纯化得到产物11。
无色液体，产率83％。1H NMR(400MHz,CDCl3)δ7.95(d,J＝7.6Hz,2H),7.62-7.50(m,3H),7.46(t,J＝7.6Hz,2H),6.89(d,J＝8.4Hz,2H),3.80(s,3H),3.78-3.69(m,2H),3.01(t,J＝6.5Hz,2H),2.21(m,1H),1.92(m,2H),1.78-1.64(m,3H),1.25(s,3H).13C NMR(101MHz,CDCl3)δ200.01,178.01,156.47,137.00,133.03,132.98,128.61,128.01,121.56,114.02,55.50,45.68,45.23,38.65,37.45,30.47,23.06,19.08.IR(V/cm-1):3687,2993,2209,1738,1514,1372,1236,1095,1045,879cm-1.HRMS(ESI):calcd.C22H26NO3[M+H]+:352.1913.Found:352.1918.
本发明保护内容不局限于以上实施例。在不背离发明构思的精神和范围下，本领域技术人员能够想到的变化和优点都被包括在本发明中，并且以所附的权利要求书为保护范围。
Claims (11)
1.一种α-高烯丙基酰胺衍生物的合成方法，其特征在于，在有机溶剂、添加剂存在的条件下，以式(1a)所示的酰胺、式(2a)所示的共轭1,3-二烯为反应原料，进行反应，得到式(3a)所示的α-高烯丙基酰胺衍生物；所述反应如下反应式(A)所示：
其中：
R1为以下所列基团中的一种，包括链状烷烃，苯基，苄基，烷基取代的苯基，烷氧基取代的苯基，烷氧基取代的苄基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代基的苯基；
R2为以下所列基团中的一种，包括链状烷烃，苯基，苄基，烷基取代的苯基；
R3为氢；或当R3不是氢时，式(1a)为包括γ-内酰胺、δ-内酰胺在内，碳个数在4-6的各种环状酰胺；
R4为以下所列基团中的一种，包括链状烷烃，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的链状烷烃，环烷基，苯基，苄基，烷基取代的苯基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的苯基，芳环或芳杂环取代的苯基，芳杂环；
R5为以下所列基团中的一种，包括氢，烷基，苯基；
R6为以下所列基团中的一种，包括苯基，烷基取代的苯基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的苯基，芳环或芳杂环取代的苯基，芳杂环。
2.根据权利要求1所述的合成方法，其特征在于，
R1为甲基，苯基，苄基，对甲氧基苯基，对甲氧基苄基，烯丙基；
R2为甲基，苄基，烷基取代的苯基；
R3为氢；或当R3不是氢时，式(1a)为包括γ-内酰胺、δ-内酰胺在内，碳个数在4-6的各种环状酰胺；
R4为C1-C6烷基，含有氧原子取代的链状烷烃，苯基，苄基，C1-C6烷基取代的苯基，卤素原子取代的苯基；
R5为以下所列基团中的一种，包括氢，甲基，苯基；
R6为苯基，C1-C6烷基取代的苯基，卤素原子取代的苯基，N，N-二甲基取代的苯基，萘基，呋喃基。
3.根据权利要求1所述的合成方法，其特征在于，所述添加剂为叔丁醇钾，叔丁醇钠，叔丁醇锂，氢氧化钾，六甲基二硅基胺基钾中的一种或多种。
4.根据权利要求1所述的合成方法，其特征在于，所述有机溶剂为1，2-二氯乙烷，甲苯，乙腈，四氢呋喃，1，4-二氧六环，甲基叔丁基醚，CPME，乙二醇二甲醚，二甲亚砜中的一种或多种。
5.根据权利要求1所述的合成方法，其特征在于，所述酰胺:共轭1,3-二烯:添加剂的摩尔比为：1:(1-3):(0.1-1.2)；和/或，以所述酰胺的用量为基准，所述有机溶剂的加入量为1mL/mmol酰胺。
6.根据权利要求1所述的合成方法，其特征在于，所述反应温度为25–100℃；所述反应的时间为12-48小时。
7.根据权利要求1所述的合成方法，其特征在于，进一步包括后处理步骤，将反应得到的粗反应液用体积比为乙酸乙酯:石油醚＝1:10～1:5的溶液进行柱层析，高收率、高区域选择性得到α-高烯丙基酰胺衍生物。
8.一种α-高烯丙基酰胺衍生物，其特征在于，其结构如式(3a)所示：
其中：
R1为链状烷烃，苯基，苄基，烷基取代的苯基，烷氧基取代的苯基，烷氧基取代的苄基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代基的苯基；
R2为链状烷烃，苯基，苄基，烷基取代的苯基；
R3为氢；或当R3不是氢时，式(1a)为包括γ-内酰胺、δ-内酰胺在内，碳个数在4-6的各种环状酰胺；
R4为链状烷烃，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的链状烷烃，环烷基，苯基，苄基，烷基取代的苯基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的苯基，芳环或芳杂环取代的苯基，芳杂环；
R5为氢，烷基，苯基；
R6为苯基，烷基取代的苯基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的苯基，芳环或芳杂环取代的苯基，芳杂环。
9.根据权利要求8所述的α-高烯丙基酰胺衍生物，其特征在于，
R1为甲基，苯基，苄基，对甲氧基苯基，对甲氧基苄基，烯丙基；
R2为甲基，苄基，烷基取代的苯基；
R3为氢；或当R3不是氢时，式(1a)为包括γ-内酰胺、δ-内酰胺在内，碳个数在4-6的各种环状酰胺；
R4为C1-C6烷基，含有氧原子取代的链状烷烃，苯基，苄基，C1-C6烷基取代的苯基，卤素原子取代的苯基；
R5为以下所列基团中的一种，包括氢，甲基，苯基；
R6为苯基，C1-C6烷基取代的苯基，卤素原子取代的苯基，N，N-二甲基取代的苯基，萘基，呋喃基。
10.根据权利要求8或9所述的α-高烯丙基酰胺衍生物，其特征在于，其按如权利要求1-7之任一项方法制备得到。
11.根据权利要求8或9所述的α-高烯丙基酰胺衍生物在进行相关结构改造方面的应用。
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