CN112939750B - 一种配体接力策略促进的镍氢催化烯烃迁移不对称官能团化的方法 - Google Patents
一种配体接力策略促进的镍氢催化烯烃迁移不对称官能团化的方法 Download PDFInfo
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- CN112939750B CN112939750B CN202110153643.XA CN202110153643A CN112939750B CN 112939750 B CN112939750 B CN 112939750B CN 202110153643 A CN202110153643 A CN 202110153643A CN 112939750 B CN112939750 B CN 112939750B
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- nickel
- ligand
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- olefin
- bromide
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- 239000003446 ligand Substances 0.000 title claims abstract description 83
- 150000001336 alkenes Chemical class 0.000 title claims abstract description 58
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 238000007306 functionalization reaction Methods 0.000 title claims abstract description 27
- 229910052739 hydrogen Inorganic materials 0.000 title claims abstract description 25
- 239000001257 hydrogen Substances 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims abstract description 24
- 238000006555 catalytic reaction Methods 0.000 title description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 72
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 14
- 230000009471 action Effects 0.000 claims abstract description 9
- 125000000524 functional group Chemical group 0.000 claims abstract description 8
- 239000000654 additive Substances 0.000 claims abstract description 7
- 230000000996 additive effect Effects 0.000 claims abstract description 7
- 229910052751 metal Inorganic materials 0.000 claims abstract description 7
- 239000002184 metal Substances 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 239000003513 alkali Substances 0.000 claims abstract description 5
- 230000005012 migration Effects 0.000 claims abstract description 3
- 238000013508 migration Methods 0.000 claims abstract description 3
- 150000002815 nickel Chemical class 0.000 claims abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 45
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 40
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 claims description 34
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- AOPCKOPZYFFEDA-UHFFFAOYSA-N nickel(2+);dinitrate;hexahydrate Chemical compound O.O.O.O.O.O.[Ni+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O AOPCKOPZYFFEDA-UHFFFAOYSA-N 0.000 claims description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 17
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 15
- 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- -1 boric acid ester Chemical class 0.000 claims description 9
- OCMNCWNTDDVHFK-UHFFFAOYSA-L dichloronickel;1,2-dimethoxyethane Chemical compound Cl[Ni]Cl.COCCOC OCMNCWNTDDVHFK-UHFFFAOYSA-L 0.000 claims description 7
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 6
- 150000001347 alkyl bromides Chemical class 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 235000009518 sodium iodide Nutrition 0.000 claims description 5
- VHSVJTYBTJCDFL-UHFFFAOYSA-L 1,2-dimethoxyethane;nickel(2+);dibromide Chemical compound Br[Ni]Br.COCCOC VHSVJTYBTJCDFL-UHFFFAOYSA-L 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 claims description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 claims description 4
- LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 claims description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 150000001502 aryl halides Chemical class 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 230000001699 photocatalysis Effects 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 229910052710 silicon Inorganic materials 0.000 claims description 3
- 239000010703 silicon Substances 0.000 claims description 3
- JRTIUDXYIUKIIE-KZUMESAESA-N (1z,5z)-cycloocta-1,5-diene;nickel Chemical compound [Ni].C\1C\C=C/CC\C=C/1.C\1C\C=C/CC\C=C/1 JRTIUDXYIUKIIE-KZUMESAESA-N 0.000 claims description 2
- RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 150000001350 alkyl halides Chemical class 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 229910000085 borane Inorganic materials 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 150000001768 cations Chemical class 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- UCDHYFZYUGDETN-UHFFFAOYSA-N cyanophosphonic acid Chemical compound OP(O)(=O)C#N UCDHYFZYUGDETN-UHFFFAOYSA-N 0.000 claims description 2
- RRSIMIHTHWYRRA-UHFFFAOYSA-L dibromonickel;1-methoxy-2-(2-methoxyethoxy)ethane Chemical compound Br[Ni]Br.COCCOCCOC RRSIMIHTHWYRRA-UHFFFAOYSA-L 0.000 claims description 2
- 229940019778 diethylene glycol diethyl ether Drugs 0.000 claims description 2
- IBSOYFJDSVROOT-UHFFFAOYSA-L diiodonickel;hexahydrate Chemical compound O.O.O.O.O.O.I[Ni]I IBSOYFJDSVROOT-UHFFFAOYSA-L 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- BLQJIBCZHWBKSL-UHFFFAOYSA-L magnesium iodide Chemical compound [Mg+2].[I-].[I-] BLQJIBCZHWBKSL-UHFFFAOYSA-L 0.000 claims description 2
- 229910001641 magnesium iodide Inorganic materials 0.000 claims description 2
- VWQUXHVMSWBXML-UHFFFAOYSA-L magnesium;dibromide;hydrate Chemical compound O.Br[Mg]Br VWQUXHVMSWBXML-UHFFFAOYSA-L 0.000 claims description 2
- LAIZPRYFQUWUBN-UHFFFAOYSA-L nickel chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ni+2] LAIZPRYFQUWUBN-UHFFFAOYSA-L 0.000 claims description 2
- UQPSGBZICXWIAG-UHFFFAOYSA-L nickel(2+);dibromide;trihydrate Chemical compound O.O.O.Br[Ni]Br UQPSGBZICXWIAG-UHFFFAOYSA-L 0.000 claims description 2
- WHGYCGOFTBFDLW-UHFFFAOYSA-L nickel(2+);diperchlorate;hexahydrate Chemical compound O.O.O.O.O.O.[Ni+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O WHGYCGOFTBFDLW-UHFFFAOYSA-L 0.000 claims description 2
- BFSQJYRFLQUZKX-UHFFFAOYSA-L nickel(ii) iodide Chemical compound I[Ni]I BFSQJYRFLQUZKX-UHFFFAOYSA-L 0.000 claims description 2
- 229920001843 polymethylhydrosiloxane Polymers 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 229940124530 sulfonamide Drugs 0.000 claims description 2
- 150000003456 sulfonamides Chemical class 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 2
- 150000003568 thioethers Chemical class 0.000 claims description 2
- BZLZKLMROPIZSR-UHFFFAOYSA-N triphenylsilicon Chemical compound C1=CC=CC=C1[Si](C=1C=CC=CC=1)C1=CC=CC=C1 BZLZKLMROPIZSR-UHFFFAOYSA-N 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000012039 electrophile Substances 0.000 claims 2
- 239000004327 boric acid Substances 0.000 claims 1
- 229910052759 nickel Inorganic materials 0.000 claims 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims 1
- 230000001737 promoting effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 122
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 48
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 44
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 38
- 238000007254 oxidation reaction Methods 0.000 description 32
- 229910052757 nitrogen Inorganic materials 0.000 description 22
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 21
- 238000005160 1H NMR spectroscopy Methods 0.000 description 21
- 239000007810 chemical reaction solvent Substances 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 21
- 238000004128 high performance liquid chromatography Methods 0.000 description 21
- 239000012230 colorless oil Substances 0.000 description 19
- 239000011698 potassium fluoride Substances 0.000 description 19
- 235000003270 potassium fluoride Nutrition 0.000 description 19
- 238000000926 separation method Methods 0.000 description 19
- 238000000746 purification Methods 0.000 description 18
- 230000006837 decompression Effects 0.000 description 17
- 230000003647 oxidation Effects 0.000 description 17
- 235000019445 benzyl alcohol Nutrition 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 238000004607 11B NMR spectroscopy Methods 0.000 description 14
- 239000011734 sodium Substances 0.000 description 13
- RWZVFCIPMBYBCY-UHFFFAOYSA-N methyl 2,2-dihydroxyoctadecanoate Chemical compound CCCCCCCCCCCCCCCCC(O)(O)C(=O)OC RWZVFCIPMBYBCY-UHFFFAOYSA-N 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- CZNGTXVOZOWWKM-UHFFFAOYSA-N methyl 4-bromobenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1 CZNGTXVOZOWWKM-UHFFFAOYSA-N 0.000 description 6
- 238000004293 19F NMR spectroscopy Methods 0.000 description 5
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 5
- 238000011065 in-situ storage Methods 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- SYSZENVIJHPFNL-UHFFFAOYSA-N (alpha-D-mannosyl)7-beta-D-mannosyl-diacetylchitobiosyl-L-asparagine, isoform B (protein) Chemical compound COC1=CC=C(I)C=C1 SYSZENVIJHPFNL-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- RMNIZOOYFMNEJJ-UHFFFAOYSA-K tripotassium;phosphate;hydrate Chemical compound O.[K+].[K+].[K+].[O-]P([O-])([O-])=O RMNIZOOYFMNEJJ-UHFFFAOYSA-K 0.000 description 3
- MYUQKYGWKHTRPG-UHFFFAOYSA-N 5-bromo-2-fluoropyridine Chemical compound FC1=CC=C(Br)C=N1 MYUQKYGWKHTRPG-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229910000144 sodium(I) superoxide Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 229910052727 yttrium Inorganic materials 0.000 description 2
- UNYUEWLAYXLXHK-UHFFFAOYSA-N (4-bromophenyl) trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=C(Br)C=C1 UNYUEWLAYXLXHK-UHFFFAOYSA-N 0.000 description 1
- LZJHACNNMBYMSO-UHFFFAOYSA-N 1,1-dimethyl-3-propylurea Chemical compound CCCNC(=O)N(C)C LZJHACNNMBYMSO-UHFFFAOYSA-N 0.000 description 1
- WBOMXUMQOVQNKT-UHFFFAOYSA-N 1-bromo-3-methylsulfonylbenzene Chemical compound CS(=O)(=O)C1=CC=CC(Br)=C1 WBOMXUMQOVQNKT-UHFFFAOYSA-N 0.000 description 1
- HUSPSWKWFREKSS-UHFFFAOYSA-N 1-bromo-4-(difluoromethyl)benzene Chemical compound FC(F)C1=CC=C(Br)C=C1 HUSPSWKWFREKSS-UHFFFAOYSA-N 0.000 description 1
- SEAOBYFQWJFORM-UHFFFAOYSA-N 1-bromo-4-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=C(Br)C=C1 SEAOBYFQWJFORM-UHFFFAOYSA-N 0.000 description 1
- FRNLBIWVMVNNAZ-UHFFFAOYSA-N 2-iodonaphthalene Chemical compound C1=CC=CC2=CC(I)=CC=C21 FRNLBIWVMVNNAZ-UHFFFAOYSA-N 0.000 description 1
- HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 238000005906 dihydroxylation reaction Methods 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
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- 230000037361 pathway Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229930015698 phenylpropene Natural products 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 238000007146 photocatalysis Methods 0.000 description 1
- 239000011941 photocatalyst Substances 0.000 description 1
- HJWLCRVIBGQPNF-UHFFFAOYSA-N prop-2-enylbenzene Chemical compound C=CCC1=CC=CC=C1 HJWLCRVIBGQPNF-UHFFFAOYSA-N 0.000 description 1
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 229910052990 silicon hydride Inorganic materials 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- IJJNTMLAAKKCML-UHFFFAOYSA-N tribenzyl borate Chemical compound C=1C=CC=CC=1COB(OCC=1C=CC=CC=1)OCC1=CC=CC=C1 IJJNTMLAAKKCML-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
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Abstract
本发明公开了一种配体接力策略促进的镍氢催化烯烃迁移不对称官能团化的方法。在金属镍盐、非手性配体、手性配体、碱、氢源、添加剂等作用下，使烯烃分别和多种亲电试剂溶于有机溶剂中进行反应，得到区域选择性和对映选择性优秀的手性化合物。本发明方法可高效合成含多种官能团的手性化合物且产物具有高对映选择性，该方法原料简单易得，操作简便。
Description
技术领域
本发明方法属于有机化学和药物化学领域，涉及烯烃和各种偶联试剂发生迁移不对称官能团化制备具有光学活性的含有1,1-二芳基、苄胺、苄醚、苄基硼酸酯、烯丙基苯、烯丙基胺、炔丙基苯、炔丙基胺、二烷基羧酸及其衍生物、二烷基醇或醚、二烷基磷酸酯等结构化合物的方法。
背景技术
选择性地在某个惰性sp3 C–H键位置引入官能团能极大地简化合成路线，使得反合成分析可以使用更简单易得的原料。但是目前发展的策略还存在一定的局限性，为了区分多个非常相似的sp3 C–H键，提高选择性，大多数策略都需要引入极性导向基来和金属配位提高反应的选择性，官能团化也局限在导向基附近的位置。另一方面，导向基的引入和脱除降低了反应的效率，也极大的限制了其在合成化学领域中的应用[(a)Gutekunst,W.R.；Baran,P.S.Chem.Soc.Rev.2011,40,1976-1991.(b)McMurray,L.；O’Hara,F.；Gaunt,M.J.Chem.Soc.Rev.2011,40,1885-1898.(c)Yamaguchi,J.；Yamaguchi,A.D.；Itami,K.Angew.Chem.,Int.Ed.2012,51,8960-9009.(d)He,J.；Wasa,M.；Chan,K.S.L.；Shao,Q.；Yu,J.-Q.Chem.Rev.2017,117,8754-8786.]。
烯烃来源广泛、制备容易，是理想的合成原料。从含烯烃的原料出发，人们发展了多种多样的转化，包括烯烃的氢化、双官能团化(例如著名的双羟化、环氧化)和氢单官能团化等。为了提高反应的选择性(区域选择性、对映选择性)，人们发展了各种催化的途径如金属催化、光催化、电催化以及有机催化等，以金属催化为例，人们发展了系列的手性配体高效地实现了对映选择性。但是以上这些转化主要集中在烯烃C＝C双键的原位发生，从烯烃出发，如何实现更具挑战性的远程惰性sp3 C–H键选择性活化在合成上具有十分重要的意义[(a)Cui,X.；Burgess,K.Chem.Rev.2005,105,3272.(b)Xie,J.-H.；Zhu,S.-F.；Zhou,Q.-L.Chem.Rev.2011,111,1713.(c)Chen,Q.-A.；Ye,Z.-S.；Duan,Y.；Zhou,Y.-G.Chem.Soc.Rev.2013,42,497.(d)Verendel,J.J.；Pamies,O.；Dieguez,M.；Andersson,P.G.Chem.Rev.2014,114,2130.(e)Zhang,Z.；Butt,N.A.；Zhang,W.Chem.Rev.2016,116,14769.(f)Jensen,K.H.；Sigman,M.S.Org.Biomol.Chem.2008,6,4083.(g)McDonald,R.I.；Liu,G.；Stahl,S.S.Chem.Rev.2011,111,2981.(h)Schultz,D.M.；Wolfe,J.P.Synthesis2012,44,351.(i)Egami,H.；Sodeoka,M.Angew.Chem.,Int.Ed.2014,53,8294.(j)Merino,E.；Nevado,C.Chem.Soc.Rev.2014,43,6598.(k)Kohlhepp,S.V.；Gulder,T.Chem.Soc.Rev.2016,45,6270.(l)Wu,K.；Liang,Y.；Jiao,N.Molecules 2016,21,352.(m)Yin,G.；Mu,X.；Liu,G.Acc.Chem.Res.2016,49,2413.(n)Lan,X.W.；Wang,N.X.；Xing,Y.L.Eur.J.Org.Chem.2017,2017,5821.(o)Wang,F.；Chen,P.；Liu,G.Acc.Chem.Res.2018,51,2036.(p)Lin,J.；Song,R.J.；Hu,M.；Li,J.H.Chem.Rec.2019,19,440.(q)Liu,Z.；Gao,Y.；Zeng,T.；
(r)Zeng,X.Chem.Rev.2013,113,6864.]。
近年来快速发展的远程氢官能团化策略同时结合金属氢催化的烯烃异构化和金属催化的偶联反应，反应净结果是烯烃双键被无痕还原而远程特定的sp3C–H键选择性发生偶联反应引入所需的官能团化。该策略有三大优势：1、反应条件温和，一般不需要高的反应温度；2、不需要额外引入极性导向基，也就不涉及到导向基的引入和脱除；3、反应的位点选择性和对映选择性可以通过配体来调控。该策略为远程惰性sp3 C–H键选择性官能团化提供了新颖高效的新途径。但目前，烯烃不对称氢官能团化仅限于烯烃原位的氢官能团化(如下反应式)，而对于烯烃远程的不对称氢官能团化未有报道。[(a)Larionov,E.；Li,H.；Mazet,C.Chem.Commun.2014,50,9816–9826.(b)Vasseur,A.；Bruffaerts,J.；Marek,I.Nat.Chem.2016,8,209–219.(c)Sommer,H.；Juliá-Hernández,F.；Martin,R.；Marek,I.ACS Cent.Sci.2018,4,153–165.(d)Janssen-Müller,D.；Sahoo,B.；Sun,S.-Z.；Martin,R.Isr.J.Chem.2020,60,195–206.(e)Lee,W.-C.；Wang,C.-H.；Lin,Y.-H.；Shih,W.-C.；Ong,T.-G.Org.Lett.2013,15,5358–5361.(f)Bair,J.S.；Schramm,Y.；Sergeev,A.G.；Clot,E.；Eisenstein,O.；Hartwig,J.F.J.Am.Chem.Soc.2014,136,13098–13101.(g)Busolv,I.；Becouse,J.；Mazza,S.；Montandon-Clerc,M.；Hu,X.Angew.Chem.,Int.Ed.2015,54,14523–14526.(h)Buslov,I.；Song,F.；Hu,X.Angew.Chem.,Int.Ed.2016,55,12295–12299.(i)He,Y.；Cai,Y.Zhu,S.J.Am.Chem.Soc.2017,139,1061–1064.(j)Juliá-Hernández,F.；Moragas,T.；Cornella,J.；Martin,R.Nature 2017,545,84–88.(k)Gaydou,M.；Moragas,T.；Juliá-Hernández,F.；Martin,R.J.Am.Chem.Soc.2017,139,12161–12164.(l)Chen,F.；Chen,K.；Zhang,Y.；He,Y.；Wang,Y.-M.；Zhu,S.J.Am.Chem.Soc.2017,139,13929–13935.(m)Zhou,F.；Zhu,J.；Zhang,Y.；Zhu,S.Angew.Chem.,Int.Ed.2018,57,4058–4062.(n)Xiao,J.；He,Y.；Ye,F.；Zhu,S.Chem2018,4,1645–1657.(o)Sun,S.-Z.；
M.；Martin-Montero,R.；Martin,R.J.Am.Chem.Soc.2018,140,12765–12769.(p)Wang,Z.；Yin,H.；Fu,G.C..Nature 2018,563,379–383.(q)Zhou,F.；Zhang,Y.；Xu,X.；Zhu,S.Angew.Chem.,Int.Ed.2018,58,1754–1758.(r)He,J.；Song,P.；Xu,X.；Zhu,S.；Wang,Y.ACS.Catal.2019,9,3253–3259；(s)Zhang,Y.；Xu,X.；Zhu,S.Nat.Commun.2019,10,1752；(t)Liu,B.；Hu,P.；Xu,F.；Cheng,L.；Tan,M.；Han,W.Commun.Chem.2019,2,5；(u)Zhou,L.；Zhu,C.；Bi,P.；Feng,C.Chem.Sci.2019,10,1144–1149；(v)Zhang,Y.；Han,B.；Zhu,S.Angew.Chem.,Int.Ed.2019,58,13860–13864；(w)Sun,S.-Z.；Romano,C.；Martin,R.J.Am.Chem.Soc.2019,141,16197–16201；(x)Qian,D.；Hu,X.Angew.Chem.,Int.Ed.2019,58,18519–18523.(y)Jiao,K.-J.；Liu,D.；Ma,H.-X.；Qiu,H.；Fang,P.；Mei,T.-S.Angew.Chem.Int.Ed.2020,59,6520.(z)He,Y.；Liu C.；Yu,L.；Zhu,S.Angew.Chem.Int.Ed.2020,59,9186.]。
本发明可将烯烃不对称氢官能团化反应从原位推广到远程不对称氢官能团化反应。因此，通过来源广泛、制备容易的非活化烯烃原料和官能团化的亲电试剂，在镍氢催化下一步高效制备手性化合物的方法具有重要的研究价值。
发明内容
本发明的目的是提供一种含多种官能团的手性类化合物的合成方法，该方法原料便宜易得，操作简便，底物范围广且官能团兼容性好，具有良好的区域选择性和对映选择性。
本发明实现上述目的之一采用以下技术方案：
一种镍催化非活化烯烃的远程不对称官能团化的方法，包括以下步骤：在惰性气体中，将金属镍类催化剂、非手性配体L、手性配体L*、碱、氢源、添加剂溶于干燥的有机溶剂中，然后加入烯烃
和芳基卤化物ArX、烷基卤化物(Alkyl-X)、烯基卤化物(Alkenyl-X)、炔基卤化物(Alkynyl-X)、羟胺活化酯(R1R2NOBz)和硝基芳烃(ArNO2)等亲电试剂中的一种，得到反应混合物，随后将上述反应混合物密封并从惰性气体中取出，反应完全后，减压浓缩除去有机溶剂，再经柱层析分离纯化得到目标的手性化合物
或者
所述手性化合物，是具有如下结构式：
或者
其中，1)FG＝芳基、硼酸酯、胺基、酰胺基、醚、酯基、硅基等定位官能团；2)FG2＝芳基、酰胺、氰基、磷酸酯、醚、磺酰胺等；中的一种；3)R为原烯烃的取代基，为氢原子(-H)、烷基(-Alkyl)、酯基(-CO2R或者-OCOR)、酰胺基(-NHCOR或者-CONR1R2)、磺酰基、烷氧基(-OR)、硅醚(-OSiR1R2R3)、芳基(-Ar，如苯基、噻吩、呋喃、吡啶)、卤素(-X)中的任一种；4)E来自亲电试剂，为芳基(-Ar)、烷基(-Alkyl)、烯基(-Alkenyl)、炔基(-Alkynyl)、胺基(包括烷基胺-R1R2N或者芳基胺-NHAr)、酰胺基(-NHCOR或者-CONR1R2)、酯基(-CO2R或者-OCOR)、烷氧基(-OR)、硫醚基(-SR)中的任一种；5)n指大于或等于0的整数。
优选的，所述方法合成路线如下：
反应式(1)中，为烯烃在非手性配体作用下异构到定位官能团FG的邻位，再在手性配体作用下与亲电试剂进行不对称官能团化；反应式(2)中，为烯烃在非手性配体作用下异构到端位，再在手性配体作用下与二级或三级亲电试剂进行不对称官能团化，所述亲电试剂卤代物中X为原子氯、溴或碘中的一种。
优选地，金属镍类催化剂：非手性配体：手性配体：碱：硅氢：添加剂：含硼烯烃：芳基卤代物ArX：有机溶剂的用量比为摩尔：摩尔：摩尔：摩尔：摩尔：摩尔：体积mL＝0.01-0.10：0.005-0.05：0.02-0.20：1.5-3.5：1.5-3.5：0.1-3.0：1.0-3.0：1.0-3.0：0.2-4.0。
优选地，所述的金属镍盐是碘化镍、碘化镍水合物、氯化镍、氯化镍六水合物、氯化镍乙二醇二甲醚复合物、溴化镍、溴化镍三水合物、溴化镍二乙二醇二甲醚复合物、溴化镍乙二醇二甲醚复合物、双-(1,5-环辛二烯)镍复合物、硝酸镍六水合物、高氯酸镍六水合物、四氟硼酸镍六水合物中的任一种；
优选地，所述的非手性配体L为以下的任一种：
优选地，所述的手性配体L*为以下的任一种：
优选地，所述的碱，其阳离子为Li+、Na+、K+、Mg2+和Cs+中的任一种，阴离子为[CO3]2-、[HCO3]-、[PO4]3-、[HPO4]2-、[H2PO4]-、F-、[OH]-、[CH3COO]-、[OMe]-和[OtBu]-中的任一种。
优选地，所述的氢源为聚甲基氢硅氧烷、三甲氧基氢硅烷、三乙氧基氢硅烷、二乙氧基甲基氢硅烷、二甲氧基甲基氢硅烷、苯基氢硅烷、二苯基氢硅烷、三苯基氢硅烷、硼烷及其复合物、频那醇硼烷(HBpin)、烷基溴和锰粉的组合(Alkylbromide/Mn)、烷基溴和锌粉的组合(Alkylbromide/Zn)、电化学还原、光催化还原剂(如二异丙基胺和光催化剂的组合)中的任一种。
优选地，所述的添加剂为氯化锂、氯化钠、溴化锂、溴化钾、溴化镁、溴化镁水合物、碘化锂、碘化钠、碘化钾、碘化锌、碘化镁、四丁基氯化铵、四丁基溴化铵、四丁基碘化铵、乙酸钠、乙酸钾、甲醇、异丙醇、苄醇、乙腈中的一种或多种。
优选地，所述的溶剂为四氢呋喃、甲苯、1,2-二氯乙烷、氯仿、乙腈、N,N-二甲基乙酰胺、N,N-二甲基甲酰胺、N,N-二甲基丙烯基脲、N-甲基吡咯烷酮、甲醇、乙醇、水、甲苯、乙二醇二甲醚、二乙二醇二乙醚和二甲基亚砜中的一种或多种。
优选地，所述的反应温度为0～40℃。
本发明的目的是提供一种全新的合成该类手性化合物的方法。
本发明的有益效果是：
目前，烯烃不对称氢官能团化仅限于烯烃原位的氢官能团化(如下反应式)，而对于烯烃远程的不对称氢官能团化未有报道。为实现烯烃远程的不对称氢官能团化，传统的策略使用单一手性配体，对使用的手性配体要求较高，要求该单一配体能同时促进烯烃的异构化和不对称偶联，因而导致配体的设计和合成难度增加。本发明通过使用两种或者多配体接力的策略，将催化循环中的不同步骤交由不同的配体来促进，一方面可将烯烃不对称氢官能团化反应从烯烃原位推广到烯烃远程不对称氢官能团化反应，另一方面也降低了配体设计的难度，可以通过已知配体的组合和进一步改造优化轻松实现单一配体难以达到的效果。本发明通过配体组合来接力促进多步反应的策略，在催化反应中相应的增加非手性配体，可以轻松实现挑战性的非活化内烯的区域专一性不对称官能团化反应；且利用本发明可以实现远程非活化sp3 C–H键的不对称官能团化。
另外，利用本发明，可以对工业上难以分离的混合烯烃实现区域专一性的不对称转化，无需对混合烯烃原料进行分离纯化，归一化地得到高附加价值的光学活性产物。
本发明同时具备以下优势：1、反应条件温和，一般不需要高的反应温度；2、不需要额外引入极性导向基，也就不涉及到导向基的引入和脱除；3、反应的位点选择性和对映选择性可以通过配体来调控。
附图说明
下面结合附图对本发明的作进一步说明。
图1是实施例1产物的H谱；
图2是实施例1产物的C谱；
图3是实施例2产物的H谱；
图4是实施例2产物的C谱；
图5是实施例5产物的H谱；
图6是实施例5产物的C谱；
图7是实施例8产物的H谱；
图8是实施例8产物的C谱。
具体实施方式
通过以下详细说明可以进一步理解本发明的特点和优点。所提供的实施例仅是对本发明方法的说明，而不以任何方式限制本发明揭示的其余内容。
下述实施例中，rt指室温(23-29℃)，Bdmpd指
Bpin指
NiCl2·glyme指氯化镍乙二醇二甲醚复合物，Ni(NO3)2·6H2O指硝酸镍六水合物，DMMS指二甲氧基甲基氢硅烷，DEMS指二乙氧基甲基氢硅烷，DMPU指N,N-二甲基丙烯基脲，Tol指甲苯，DMA指N,N-二甲基乙酰胺，DCE指1,2-二氯乙烷。
实施例1
在充满氮气的手套箱中，将氯化镍乙二醇二甲醚复合物(2.2mg,5.0mol％)，手性配体L26*(7.2mg,6.0mol％)，氟化钾(23.2mg,2.0equiv)，非手性配体L21[0.21mg,0.1mL(2.1mg/mL甲苯溶液)]溶于甲苯(0.60mL)和DMPU(0.20mL)中，搅拌10分钟后加入上述烯烃(30μL,0.20mmol)，4-碘苯甲醚(94.0mg,0.40mmol)和DMMS(49.3μL,0.40mmol)，将反应管密封并从手套箱中取出，在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率75％)，1H NMR(500MHz,CDCl3)δ7.34–7.29(m,2H),7.29–7.25(m,2H),7.20(d,J＝8.8Hz,3H),6.87(d,J＝8.7Hz,2H),3.91(t,J＝7.8Hz,1H),3.81(s,3H),2.04(q,J＝7.8Hz,2H),1.37–1.28(m,2H),0.97(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ157.8,145.8,137.5,128.8,128.4,127.8,125.9,113.8,55.4,55.2,50.2,38.1,21.2,14.1；HRMS(APCI)calcd.for C17H20NaO[M+Na]+m/z 263.1406,found 263.1411；IR(neat,cm-1)2953,1509,1246,696；[α]D 20＝–4.7(c＝2.0,CHCl3)；94％ee；HPLC analysisCHIRALCEL OJ-H column,1％EtOH in hexane,0.8mL/min,220nm UV detector,tR(minor)＝11.4min,tR(major)＝12.6min.
实施例2
在充满氮气的手套箱中，将氯化镍乙二醇二甲醚复合物(2.2mg,5.0mol％),手性配体L26*(7.2mg,6.0mol％)，氟化钾(23.2mg,2.0equiv)，非手性配体L21[0.42mg,0.2mL(2.1mg/mL甲苯溶液)]溶于甲苯(0.60mL)和DMPU(0.20mL)中，搅拌10分钟后加入上述烯烃(26μL,0.20mmol)，4-碘苯甲醚(94.0mg,0.40mmol)和DMMS(49.3μL,0.40mmol)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率73％)，1H NMR(500MHz,CDCl3)δ7.18–7.12(m,2H),7.08–7.02(m,3H),6.90–6.84(m,3H),4.10(t,J＝6.7Hz,1H),3.82(s,3H),2.98–2.84(m,2H),2.21–2.13(m,1H),1.95–1.84(m,2H),1.82–1.74(m,1H)；13C NMR(126MHz,CDCl3)δ157.8,139.8,139.7,137.6,130.2,129.7,129.0,125.8,125.6,113.6,55.2,44.8,33.4,29.8,21.0；HRMS(APCI)calcd.for C17H18NaO[M+Na]+m/z 261.1250,found 261.1255；IR(neat,cm-1)2923,1507,1241,1031,737；m.p.71–73℃；[α]D 20＝+14.2(c＝1.0,CHCl3)；88％ee；HPLC analysis CHIRALCEL OJ-H column,1％EtOH in hexane,0.8mL/min,220nm UVdetector,tR(major)＝15.0min,tR(minor)＝16.9min.
实施例3
在充满氮气的手套箱中，将氯化镍乙二醇二甲醚复合物(2.2mg,5.0mol％),手性配体L26*(7.2mg,6.0mol％)，氟化钾(23.2mg,2.0equiv)，非手性L21[0.42mg,0.2mL(2.1mg/mL甲苯溶液)]溶于甲苯(0.60mL)和DMPU(0.20mL)中，搅拌10分钟后加入上述烯烃(32.2mg,0.20mmol)，4-碘苯甲醚(94.0mg,0.40mmol)和DMMS(49.3μL,0.40mmol)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(白色固体，产率81％)，1H NMR(500MHz,CDCl3)δ7.78(d,J＝6.9Hz,2H),7.49(t,J＝7.4Hz,1H),7.42(t,J＝7.5Hz,2H),7.30(d,J＝8.6Hz,2H),6.90(d,J＝8.6Hz,2H),6.44(d,J＝8.2Hz,1H),5.06(q,J＝7.6Hz,1H),3.81(s,3H),2.03–1.85(m,2H),0.96(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ166.8,158.9,134.8,134.2,131.4,128.5,127.9,126.9,114.1,55.3,54.9,29.1,10.9；HRMS(ESI)calcd.for C17H20NO2[M+H]+m/z 270.1489,found 270.1488；IR(neat,cm-1)3331,1629,1511,1244,691；m.p.135.3–136.7℃；[α]D 23＝–40.8(c＝2.0,CHCl3)；99％ee；HPLC analysis CHIRALCEL OD-Hcolumn,10％EtOH in hexane,1.0mL/min,220nm UV detector,tR(minor)＝6.5min,tR(major)＝7.5min.
实施例4
在充满氮气的手套箱中，将氯化镍乙二醇二甲醚复合物(2.2mg,5.0mol％),手性配体L26*(7.2mg,6.0mol％)，氟化钾(23.2mg,2.0equiv)，非手性L21[0.42mg,0.2mL(2.1mg/mL甲苯溶液)]溶于甲苯(0.60mL)和DMPU(0.20mL)中，搅拌10分钟后加入上述烯烃(32.2mg,0.20mmol)，2-氟-5-溴吡啶(66.9mg,0.30mmol,1.5equiv)和DMMS(49.3μL,0.40mmol)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(白色固体，产率81％)，1H NMR(500MHz,CDCl3)δ7.78(d,J＝6.9Hz,2H),7.49(t,J＝7.4Hz,1H),7.42(t,J＝7.5Hz,2H),7.30(d,J＝8.6Hz,2H),6.90(d,J＝8.6Hz,2H),6.44(d,J＝8.2Hz,1H),5.06(q,J＝7.6Hz,1H),3.81(s,3H),2.03–1.85(m,2H),0.96(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ166.8,158.9,134.8,134.2,131.4,128.5,127.9,126.9,114.1,55.3,54.9,29.1,10.9；HRMS(ESI)calcd.for C17H20NO2[M+H]+m/z 270.1489,found 270.1488；IR(neat,cm-1)3331,1629,1511,1244,691；m.p.135.3–136.7℃；[α]D 23＝–40.8(c＝2.0,CHCl3)；99％ee；HPLCanalysis CHIRALCEL OD-H column,10％EtOH in hexane,1.0mL/min,220nm UVdetector,tR(minor)＝6.5min,tR(major)＝7.5min.
实施例5
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),非手性配体L9(1.6mg,3.0mol％)，手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，对溴苯甲酸甲酯(86.0mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(39.2mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率70％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(93％)。1H NMR(500MHz,CDCl3)δ7.89(d,J＝8.3Hz,2H),7.28(d,J＝8.3Hz,2H),3.88(s,3H),2.21(t,J＝7.9Hz,1H),1.85–1.76(m,1H),1.73(s,2H),1.63–1.53(m,1H),1.30–1.20(m,14H),0.88(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ167.7,151.6,129.4,128.3,126.6,70.7,52.0,48.9,34.6,31.7,31.7,22.6,14.3；11B NMR(160MHz,CDCl3)δ29.3；HRMS(ESI)calcd.for C19H29BNaO4[M+Na]+m/z 355.2051,found 355.2050；IR(neat,cm-1)2954,2928,1720,1370,1272,769；[α]D 23＝–8.6(c＝0.96,CHCl3)；HPLCanalysis:the ee(93％)was determined after oxidation using a
OD-Hcolumn,10％iPrOH in hexane,1.0mL/min,254nm UV detector,tR(major)＝8.3min,tR(minor)＝9.7min.
实施例6
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),非手性配体L9(1.6mg,3.0mol％)，手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，对溴苯甲酸甲酯(86.0mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(36.4mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率66％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(93％)。1H NMR(500MHz,CDCl3)δ7.90(d,J＝8.3Hz,2H),7.28(d,J＝8.3Hz,2H),3.88(s,3H),2.11(t,J＝7.8Hz,1H),1.92–1.82(m,1H),1.74(s,2H),1.67–1.57(m,1H),1.27(s,6H),1.25(s,6H),0.87(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ167.7,151.4,129.4,128.3,126.7,70.7,52.0,48.9,31.8,31.7,25.5,14.1；11B NMR(160MHz,CDCl3)δ29.4；HRMS(ESI)calcd.for C18H27BNaO4[M+Na]+m/z 341.1895,found 341.1893；IR(neat,cm-1)2955,2929,1720,1370,1274,1107,770；[α]D 23＝–9.0(c＝0.85,CHCl3)；HPLCanalysis:the ee(93％)was determined after oxidation using a
IG-3column,8％EtOH in hexane,1.0mL/min,254nm UV detector,tR(major)＝15.2min,tR(minor)＝16.2min.
实施例7
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),非手性配体L9(1.6mg,3.0mol％)，手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，对溴苯甲酸甲酯(86.0mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(70.9mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率60％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(86％)。1H NMR(500MHz,CDCl3)δ7.92(d,J＝8.1Hz,2H),7.26(d,J＝8.1Hz,2H),3.88(s,3H),3.56(t,J＝6.6Hz,2H),2.37(t,J＝7.9Hz,1H),1.91–1.81(m,1H),1.70–1.61(m,1H),1.50–1.43(m,2H),1.31–1.22(m,6H),1.19(s,6H),1.17(s,6H),0.88(s,9H),0.03(s,6H)；13C NMR(126MHz,CDCl3)δ167.5,149.5,129.8,128.4,127.2,83.6,63.4,52.0,32.9,32.2,29.5,29.4,26.1,25.8,24.7,24.7,18.5,-5.1；11B NMR(160MHz,CDCl3)δ33.9；HRMS(ESI)calcd.for C27H47BNaO5Si[M+Na]+m/z 513.3178,found 513.3180；IR(neat,cm-1)2929,2856,1723,1276,1103,834,774；[α]D 23＝–9.1(c＝0.70,CHCl3)；HPLC analysis:theee(86％)was determined after oxidation using a
OJ-H column,5％iPrOH in hexane,1.0mL/min,254nm UV detector,tR(minor)＝6.4min,tR(major)＝6.9min.
实施例8
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),非手性配体L9(1.6mg,3.0mol％)，手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，对溴苯甲酸甲酯(86.0mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(36.4mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率71％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(90％)。1H NMR(500MHz,CDCl3)δ7.92(d,J＝8.3Hz,2H),7.27(d,J＝8.3Hz,2H),3.88(s,3H),2.39(t,J＝7.9Hz,1H),1.89–1.78(m,1H),1.69–1.61(m,1H),1.30–1.24(m,2H),1.19(s,6H),1.17(s,6H),0.88(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ167.5,149.5,129.7,128.4,127.2,83.6,52.0,34.4,24.7,24.7,22.5,14.2；11B NMR(160MHz,CDCl3)δ33.4；HRMS(ESI)calcd.for C18H28BO4[M+H]+m/z 319.2075,found 319.2072；IR(neat,cm-1)2955,2928,1721,1274,1141,1108；[α]D 23＝–13.9(c＝0.98,CHCl3)；HPLCanalysis:the ee(90％)was determined after oxidation using a
OD-Hcolumn,10％iPrOH in hexane,1.0mL/min,254nm UV detector,tR(major)＝8.5min,tR(minor)＝9.9min.
40℃下反应时，目标产物的收率、区域选择性与室温时相差不大，ee值略有下降；使用硝酸镍六水合物(10mol％)，非手性配体L9(5mol％)，手性配体L*47(20mol％)时，反应效果相差不大。
实施例9
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),非手性配体L9(1.6mg,3.0mol％)，手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，2-碘萘(101.6mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(39.2mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率57％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(90％)。1H NMR(500MHz,CDCl3)δ.80–7.61(m,4H),7.47–7.34(m,3H),2.31(t,J＝7.9Hz,1H),1.92–1.85(m,1H),1.74(s,2H),1.72–1.64(m,1H),1.33–1.24(m,14H),0.91(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ143.2,133.9,131.7,127.9,127.6,127.5,127.2,126.0,125.5,124.5,70.6,48.9,35.0,31.8,31.8,22.7,14.4；11B NMR(160MHz,CDCl3)δ29.7；HRMS(ESI)calcd.for C21H30BO2[M+H]+m/z 325.2333,found 325.2331.IR(neat,cm-1)2973,2928,1368,1200,741；[α]D 23＝–12.0(c＝0.70,CHCl3)；HPLC analysis:the ee(90％)was determined after oxidation using a
OD-H column,10％iPrOH in hexane,1.0mL/min,220nm UV detector,tR(minor)＝9.2min,tR(major)＝10.4min.
实施例10
在充满氮气的手套箱中，将硝酸镍六水合物(58.2mg,4.0mol％),非手性配体L9(40.2mg,3.0mol％)，手性配体L*47(80.3mg,8.0mol％)，氟化钾(581.0mg,2.0equiv),碘化锂(669.2mg,1.0equiv)，对溴三氟甲苯(2.25g,10mmol,2.0equiv)溶于干燥的DMA(25mL,0.20M)中，搅拌10分钟后加入上述烯烃(1.12g,5mmol)和DEMS(1.68g,12.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率68％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(90％)。1H NMR(500MHz,CDCl3)δ7.49(d,J＝8.1Hz,2H),7.30(d,J＝8.1Hz,2H),2.37(t,J＝7.9Hz,1H),1.89–1.80(m,1H),1.69–1.59(m,1H),1.29–1.22(m,6H),1.20(s,6H),1.19(s,6H),0.85(t,J＝6.7Hz,3H)；13C NMR(126MHz,CDCl3)δ148.0,128.7,127.5(q,J＝32.1Hz),125.3(q,J＝3.8Hz),124.7(q,J＝271.6Hz),83.6,32.4,31.9,29.0,24.8,24.7,22.7,14.2；19F NMR(471MHz,CDCl3)δ-62.2；11B NMR(160MHz,CDCl3)δ33.7；HRMS(ESI)calcd.for C19H28BF3NaO2[M+Na]+m/z 379.2027,found 379.2025；IR(neat,cm-1)2928,2858,1617,1321,1118,1068；[α]D 23＝–11.0(c＝1.02,CHCl3)；HPLCanalysis:the ee(90％)was determined after oxidation using a
OJ-Hcolumn,0.8％iPrOH in hexane,0.8mL/min,220nm UV detector,tR(minor)＝9.6min,tR(major)＝10.3min.
实施例11
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),非手性配体L9(1.6mg,3.0mol％)，手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，对溴二氟甲基苯(82.8mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(39.2mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率63％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(92％)。1H NMR(500MHz,CDCl3)δ7.35(d,J＝8.1Hz,2H),7.30(d,J＝8.1Hz,2H),6.60(t,J＝56.8Hz,1H),2.18(t,J＝7.9Hz,1H),1.84–1.75(m,1H),1.74(s,2H),1.61–1.52(m,1H),1.31–1.20(m,14H),0.88(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ148.7,130.7(t,J＝22.2Hz),128.6,125.3(t,J＝5.9Hz),115.4(t,J＝237.5Hz),70.7,48.9,35.0,31.8,31.8,22.6,14.4；19F NMR(471MHz,CDCl3)δ-109.2；11B NMR(160MHz,CDCl3)δ29.5；HRMS(ESI)calcd.for C18H27BF2NaO2[M+Na]+m/z 347.1964,found 347.1963；IR(neat,cm-1)2974,2928,1369,1204,1021,770；[α]D 23＝–2.4(c＝0.50,EtOAc)；HPLCanalysis:the ee(92％)was determined after oxidation using a
AD-Hcolumn,1％iPrOH in hexane,1.0mL/min,220nm UV detector,tR(major)＝18.2min,tR(minor)＝19.2min.
实施例12
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),非手性配体L9(1.6mg,3.0mol％)，手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，对溴三氟甲氧基苯(96.4mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(39.2mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率63％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(92％)。1H NMR(500MHz,CDCl3)δ7.22(d,J＝8.6Hz,2H),7.05(d,J＝8.1Hz,2H),2.13(t,J＝7.9Hz,1H),1.82–1.71(m,3H),1.56–1.49(m,1H),1.29–1.23(m,14H),0.88(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ146.7,144.2,129.4,120.7(q,J＝256.4Hz),120.5,70.7,48.9,35.2,31.8,31.7,22.6,14.4；19F NMR(471MHz,CDCl3)δ-57.9；11B NMR(160MHz,CDCl3)δ29.6；HRMS(ESI)calcd.for C18H26BF3NaO3[M+Na]+m/z 381.1819,found 381.1819；IR(neat,cm-1)2975,2929,1369,1256,1204,1159,770；[α]D 23＝–3.5(c＝0.57,EtOAc)；HPLC analysis:the ee(93％)was determined after oxidation using a
IC column,0.8％iPrOH in hexane,0.8mL/min,220nm UV detector,tR(major)＝7.0min,tR(minor)＝7.4min.
实施例13
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),非手性配体L9(1.6mg,3.0mol％)，手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，对溴苯氰(72.8mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(39.2mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率51％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(83％)。1H NMR(500MHz,CDCl3)δ7.50(d,J＝8.3Hz,2H),7.30(d,J＝8.2Hz,2H),2.21(t,J＝7.9Hz,1H),1.84–1.75(m,1H),1.74(s,2H),1.60–1.52(m,1H),1.30–1.19(m,14H),0.88(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ151.7,131.9,129.0,119.8,108.2,70.9,48.8,34.4,31.7,31.7,22.5,14.3；11B NMR(160MHz,CDCl3)δ29.4；HRMS(ESI)calcd.for C18H26BNNaO2[M+Na]+m/z 322.1949,found 322.1947；IR(neat,cm-1)2928,2226,1605,1370,1203,770；[α]D 23＝–7.1(c＝0.48,CHCl3)；HPLC analysis:the ee(83％)wasdetermined after oxidation using a
OJ-H column,10％iPrOH inhexane,1.0mL/min,220nm UV detector,tR(minor)＝9.8min,tR(major)＝11.6min.
实施例14
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),非手性配体L9(1.6mg,3.0mol％)，手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，间溴苯基甲基砜(94.0mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(39.2mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率56％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(93％)。1H NMR(500MHz,CDCl3)δ7.82(t,J＝1.7Hz,1H),7.67(dt,J＝7.7,1.4Hz,1H),7.49(d,J＝7.8Hz,1H),7.40(t,J＝7.7Hz,1H),3.03(s,3H),2.24(t,J＝7.9Hz,1H),1.86–1.77(m,1H),1.75(s,2H),1.62–1.53(m,1H),1.31–1.19(m,14H),0.88(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ147.6,140.0,133.9,128.8,127.0,123.6,70.9,48.8,44.7,34.9,31.8,31.7,22.6,14.3；11B NMR(160MHz,CDCl3)δ29.7；HRMS(ESI)calcd.forC18H29BNaO4S[M+Na]+m/z 375.1772,found 375.1768；IR(neat,cm-1)2973,2928,1299,1143,532；[α]D 23＝–1.4(c＝0.72,CHCl3)；HPLC analysis:the ee(93％)was determined afteroxidation(General procedure B)using a
OD-H column,10％iPrOH inhexane,1.0mL/min,220nm UV detector,tR(minor)＝20.7min,tR(major)＝22.6min.
实施例15
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),非手性配体L9(1.6mg,3.0mol％)，手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，对溴苯酚三氟甲磺酸酯(122.0mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(39.2mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率53％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(93％)。1H NMR(500MHz,CDCl3)δ7.27(d,J＝8.7Hz,2H),7.11(d,J＝8.7Hz,2H),2.16(t,J＝7.9Hz,1H),1.82–1.72(m,3H),1.58–1.50(m,1H),1.31–1.20(m,14H),0.88(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ147.2,146.2,129.8,120.6,118.9(q,J＝320.7Hz),70.8,48.8,35.0,31.7,31.7,22.6,14.3；19F NMR(471MHz,CDCl3)δ-73.0；11B NMR(160MHz,CDCl3)δ29.4；HRMS(ESI)calcd.for C18H27BF3O5S[M+H]+m/z423.1619,found 423.1618；IR(neat,cm-1)2975,2930,1371,1203,1137,884；[α]D 23＝–4.9(c＝0.73,CHCl3)；HPLC analysis:the ee(93％)was determined after oxidationusing a
OJ-H column,0.8％iPrOH in hexane,0.8mL/min,220nm UVdetector,tR(minor)＝21.1min,tR(major)＝22.9min.
实施例16
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),非手性配体L9(1.6mg,3.0mol％)，手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，碘苯(81.6mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(39.2mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率53％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(90％)。1H NMR(500MHz,CDCl3)δ7.25–7.18(m,4H),7.12–7.06(m,1H),2.12(t,J＝7.9Hz,1H),1.83–1.75(m,1H),1.74(s,2H),1.60–1.51(m,1H),1.31–1.21(m,14H),0.88(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ145.5,128.5,128.0,124.6,70.5,48.9,35.3,31.8,31.8,22.7,14.4；11B NMR(160MHz,CDCl3)δ29.6；HRMS(ESI)calcd.for C17H27BNaO2[M+Na]+m/z 297.1996,found 297.1997；IR(neat,cm-1)2974,2928,1368,1204,762,699；[α]D 23＝–3.5(c＝0.17,EtOAc)；HPLC analysis:the ee(90％)was determined afteroxidation using a
IG-3column,1％EtOH in hexane,0.5mL/min,220nm UVdetector,tR(minor)＝31.0min,tR(major)＝32.3min.
实施例17
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),非手性配体L9(1.6mg,3.0mol％)，手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，2-氟-5-溴吡啶(70.4mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(39.2mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率48％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(92％)。1H NMR(500MHz,CDCl3)δ8.00(d,J＝2.1Hz,1H),7.71–7.58(m,1H),6.78(dd,J＝8.4,2.9Hz,1H),2.12(t,J＝7.9Hz,1H),1.81–1.71(m,3H),1.55–1.48(m,1H),1.31–1.19(m,14H),0.87(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ161.8(d,J＝234.9Hz),146.8(d,J＝13.8Hz),140.9(d,J＝7.3Hz),138.2(d,J＝4.4Hz),108.6(d,J＝37.2Hz),70.9,48.8,35.0,31.8,31.7,22.4,14.2；19F NMR(471MHz,CDCl3)δ-74.5；11B NMR(160MHz,CDCl3)δ29.5；HRMS(ESI)calcd.for C16H25BFNNaO2[M+Na]+m/z 316.1855,found316.1851；IR(neat,cm-1)2926,1592,1481,1371,1242,1202,770；[α]D 23＝–8.8(c＝0.16,CHCl3)；HPLC analysis:the ee(92％)was determined after oxidation using a
IG-3column,10％EtOH in hexane,1.0mL/min,220nm UV detector,tR(minor)＝9.8min,tR(major)＝15.0min.
实施例18
在充满氮气的手套箱中，将溴化镍乙二醇二甲醚复合物(6.2mg,10mol％),非手性配体L36(1.0mg,3.0mol％)，手性配体L*83(15.3mg,12.0mol％)，磷酸钾一水合物(138.2mg,3.0equiv),碘化钠(60.0mg,2.0equiv)，α-溴代酰胺(48.4mg,0.20mmol)溶于干燥的DMA/甲苯混合溶剂(1mL,0.20M)中，搅拌10分钟后加入烯烃(33.7mg,0.40mmol)和DMMS(77μL,0.6mmol,3.0equiv)，将反应管密封并从手套箱中取出，在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率70％)。1H NMR(400MHz,CDCl3)δ7.64–7.53(m,2H),7.43–7.33(m,2H),7.31(s,1H),7.17–7.08(m,1H),2.20–2.07(m,1H),1.79–1.68(m,2H),1.64–1.45(m,2H),1.40–1.24(m,8H),0.98(t,J＝7.4Hz,3H),0.89(t,J＝6.0Hz,3H)；13C NMR(126MHz,CDCl3)δ174.5,137.9,128.9,124.2,119.9,50.9,32.9,31.7,29.4,27.7,26.3,22.6,14.1,12.2；HRMS(ESI)calcd.for C16H26NO[M+H]+m/z 248.2014,found 248.2011；IR(neat,cm-1)3292,2957,1657,1500,1442,1310,1200,754；[α]D 24＝–10.4(c＝1.0,CHCl3)；HPLC analysis:the ee(90％)was determinedafter oxidation using a
OD-H column,10％iPrOH in hexane,1.0mL/min,254nm UV detector,tR(major)＝6.9min,tR(minor)＝8.0min.
实施例19
在充满氮气的手套箱中，将溴化镍乙二醇二甲醚复合物(6.2mg,10mol％),非手性配体L36(1.0mg,3.0mol％)，手性配体L*89(17.2mg,12.0mol％)，磷酸钾一水合物(138.2mg,3.0equiv),碘化钠(60.0mg,2.0equiv)，α-溴代磷酸酯(67.0mg,0.20mmol)溶于干燥的DMA/DCE混合溶剂(1mL,0.20M)中，搅拌10分钟后加入烯烃(33.7mg,0.40mmol)和DMMS(77μL,0.6mmol,3.0equiv)，将反应管密封并从手套箱中取出，在20℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率66％)。1H NMR(400MHz,CDCl3)δ7.31–7.27(m,2H),7.21–7.16(m,3H),4.15–4.04(m,4H),2.81–2.67(m,2H),2.09–1.93(m,1H),1.86–1.75(m,2H),1.75–1.66(m,1H),1.58–1.47(m,1H),1.47–1.35(m,2H),1.31(td,J＝7.1,3.9Hz,6H),1.28–1.20(m,10H),0.88(t,J＝6.8Hz,3H)；13CNMR(126MHz,CDCl3)δ142.4,128.9,128.8,126.4,61.9(d,J＝5.9Hz),61.8(d,J＝5.6Hz),35.8(d,J＝138.3Hz),34.2(d,J＝8.7Hz),32.3,30.5(d,J＝3.3Hz),30.1,29.9,29.7,28.6(d,J＝3.6Hz),27.9(d,J＝9.4Hz),23.1,17.0(d,J＝5.9Hz),14.6；HRMS(ESI)calcd.forC21H38O3P[M+H]+m/z 369.2553,found 369.2555；IR(neat,cm-1)3285,2962,1650,1468,1312,765；[α]D 24＝+4.0(c＝1.0,CHCl3)；HPLC analysis:the ee(90％)was determinedafter oxidation using a
AD-H column,10％iPrOH in hexane,0.7mL/min,254nm UV detector,tR(minor)＝6.2min,tR(major)＝6.9min.
实施例20
在充满氮气的手套箱中，将溴化镍乙二醇二甲醚复合物(6.2mg,10mol％),非手性配体L36(1.0mg,3.0mol％)，手性配体L*83(15.3mg,12.0mol％)，磷酸钾一水合物(138.2mg,3.0equiv),碘化钠(60.0mg,2.0equiv)，O-α-溴代羧酸酯(44.6mg,0.20mmol)溶于干燥的DMA/甲苯混合溶剂(1mL,0.20M)中，搅拌10分钟后加入烯烃(70.5mg,0.40mmol)和DMMS(77μL,0.6mmol,3.0equiv)，将反应管密封并从手套箱中取出，在20℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率62％)。1H NMR(400MHz,CDCl3)δ7.32–7.23(m,2H),6.96–6.86(m,3H),4.94–4.82(m,1H),3.95(t,J＝6.5Hz,2H),2.04(s,3H),1.83–1.71(m,2H),1.59–1.41(m,6H),1.40–1.18(m,10H),0.95–0.81(m,3H)；13C NMR(126MHz,CDCl3)δ171.1,159.2,129.5,120.6,114.6,74.5,67.9,34.21,34.18,31.9,29.4,29.3,26.1,25.4,25.1,22.7,21.4,14.2；HRMS(ESI)calcd.forC20H32NaO3[M+H]+m/z 343.2244,found343.2245；IR(neat,cm-1)2928,1732,1601,1496,1373,1243,754；[α]D 24＝+2.0(c＝1.0,CHCl3)；HPLC analysis:the ee(91％)wasdetermined after oxidation using a
OD-H column,2％iPrOH in hexane,1.0mL/min,220nm UV detector,tR(minor)＝11.0min,tR(major)＝14.0min.
实施例21
在充满氮气的手套箱中，将硝酸镍六水合物(4.6mg,4.0mol％),非手性配体L9(3.2mg,3.0mol％)，手性配体L*47(7.4mg,8.0mol％)，氟化钾(46.4mg,2.0equiv),碘化锂(53.6mg,1.0equiv)，对溴苯甲酸甲酯(172.0mg,0.80mmol)溶于干燥的DMA(2mL,0.20M)中，搅拌10分钟后加入上述四种烯烃(各分别加入18.2mg,0.10mmol)和DEMS(160μL,1.0mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色油，产率72％)，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(93％)。1H NMR(500MHz,CDCl3)δ7.89(d,J＝8.4Hz,2H),7.28(d,J＝8.3Hz,2H),3.88(s,3H),2.19(t,J＝7.9Hz,1H),1.87–1.78(m,1H),1.73(s,2H),1.62–1.54(m,1H),1.30–1.22(m,18H),0.85(t,J＝6.8Hz,3H)；13C NMR(126MHz,CDCl3)δ167.7,151.6,129.4,128.3,126.6,70.7,52.0,48.9,32.3,32.1,31.7,31.7,29.2,22.7,14.2；11B NMR(160MHz,CDCl3)δ26.9；HRMS(ESI)calcd.for C21H33BNaO4[M+Na]+m/z383.2364,found 383.2359.IR(neat,cm-1)2926,2856,1720,1607,1370,1273,1110,769；[α]D 23＝–8.7(c＝1.20,CHCl3)；HPLC analysis:the ee(93％)was determined afteroxidation using a
IG-3column,5％EtOH in hexane,1.0mL/min,254nm UVdetector,tR(major)＝18.8min,tR(minor)＝20.4min.
对比例1(与实施例5对比)
在充满氮气的手套箱中，将硝酸镍六水合物(2.3mg,4.0mol％),手性配体L*47(3.7mg,8.0mol％)，氟化钾(23.2mg,2.0equiv),碘化锂(26.8mg,1.0equiv)，对溴苯甲酸甲酯(86.0mg,0.40mmol)溶于干燥的DMA(1mL,0.20M)中，搅拌10分钟后加入上述烯烃(39.2mg,0.20mmol)和DEMS(80μL,0.5mmol,2.5equiv)，将反应管密封并从手套箱中取出，在室温下反应24小时。反应结束后，通过气相色谱法(内标法)测得该反应的目标产物收率为21％，区域选择性(rr，即目标产物收率：目标产物的其他异构体的收率)为58：42，将目标产物用NaBO3·4H2O氧化成相应的手性苄醇测ee值(94％)。不加非手性配体的情况下，得到目标产物的异构体混合物，反应的区域选择性差，所需目标产物的收率较差且难以分离。
Claims (10)
1.一种配体接力策略促进的镍氢催化烯烃迁移不对称官能团化的方法，其特征在于，包括以下步骤：将金属镍类催化剂、非手性配体L、手性配体L*、碱、氢源、添加剂溶于有机溶剂中，然后加入烯烃
和亲电试剂，反应后，再经分离纯化得到目标的手性化合物
或
其中，1)FG＝芳基、硼酸酯、胺基、酰胺基、醚、酯基、硅基定位官能团中的一种；2)FG2＝芳基、酰胺、氰基、磷酸酯、醚、磺酰胺中的一种；3)R为原烯烃的取代基，为氢原子、烷基、酯基、酰胺基、磺酰基、烷氧基、硅醚、芳基、卤素中的任一种；R2为非氢取代基；4)E来自亲电试剂，为芳基、烷基、烯基、炔基、胺基、酰胺基、酯基、烷氧基、硫醚基中的任一种；5)n指大于或等于0的整数。
2.根据权利要求1所述的镍氢催化非活化烯烃的远程不对称官能团化的方法，其特征在于：具体制备方法反应路线如下，为反应式(1)或(2)中的一种：
反应式(1)中，为烯烃在非手性配体作用下异构到定位官能团FG的邻位，再在手性配体作用下与亲电试剂进行不对称官能团化；反应式(2)中，为烯烃在非手性配体作用下异构到端位，再在手性配体作用下与二级或三级亲电试剂进行不对称官能团化；所述亲电试剂为：芳基卤化物、烷基卤化物、烯基卤化物、炔基卤化物、羟胺活化酯和硝基芳烃亲电试剂中的一种；所述亲电试剂卤代物中X为原子氯、溴或碘中的一种。
3.根据权利要求1所述的镍氢催化非活化烯烃的远程不对称官能团化的方法，其特征在于，金属镍类催化剂：非手性配体：手性配体：碱：氢源：添加剂：烯烃：亲电试剂：有机溶剂的用量比为摩尔：摩尔：摩尔：摩尔：摩尔：摩尔：体积mL＝0.01-0.10：0.005-0.05：0.02-0.20：1.5-3.5：1.5-3.5：0.1-3.0：1.0-3.0：1.0-3.0：0.2-4.0。
4.根据权利要求1所述的镍氢催化非活化烯烃的远程不对称官能团化的方法，其特征在于，所述的金属镍盐是碘化镍、碘化镍水合物、氯化镍、氯化镍六水合物、氯化镍乙二醇二甲醚复合物、溴化镍、溴化镍三水合物、溴化镍二乙二醇二甲醚复合物、溴化镍乙二醇二甲醚复合物、双-(1,5-环辛二烯)镍复合物、硝酸镍六水合物、高氯酸镍六水合物、四氟硼酸镍六水合物中的任一种。
5.根据权利要求1所述的镍氢催化非活化烯烃的远程不对称官能团化的方法，其特征在于，所述的非手性配体L为以下的任一种：
6.根据权利要求1所述的镍氢催化非活化烯烃的远程不对称官能团化的方法，其特征在于，所述的手性配体L*为以下的任一种：
7.根据权利要求1所述的镍氢催化非活化烯烃的远程不对称官能团化的方法，其特征在于，所述的碱，其阳离子为Li+、Na+、K+、Mg2+和Cs+中的任一种，阴离子为[CO3]2-、[HCO3]-、[PO4]3-、[HPO4]2-、[H2PO4]-、F-、[OH]-、[CH3COO]-、[OMe]-和[OtBu]-中的任一种。
8.根据权利要求1所述的镍氢催化非活化烯烃的远程不对称官能团化的方法，其特征在于，所述的氢源为聚甲基氢硅氧烷、三甲氧基氢硅烷、三乙氧基氢硅烷、二乙氧基甲基氢硅烷、二甲氧基甲基氢硅烷、苯基氢硅烷、二苯基氢硅烷、三苯基氢硅烷、硼烷及其复合物、频那醇硼烷、烷基溴和锰粉的组合、烷基溴和锌粉的组合、电化学还原、光催化还原剂中的任一种。
9.根据权利要求1所述的镍氢催化非活化烯烃的远程不对称官能团化的方法，其特征在于，所述的添加剂为氯化锂、氯化钠、溴化锂、溴化钾、溴化镁、溴化镁水合物、碘化锂、碘化钠、碘化钾、碘化锌、碘化镁、四丁基氯化铵、四丁基溴化铵、四丁基碘化铵、乙酸钠、乙酸钾、甲醇、异丙醇、苄醇、乙腈中的一种或多种。
10.根据权利要求1所述的镍氢催化非活化烯烃的远程不对称官能团化的方法，其特征在于，所述的溶剂为四氢呋喃、甲苯、1,2-二氯乙烷、氯仿、乙腈、N,N-二甲基乙酰胺、N,N-二甲基甲酰胺、N,N-二甲基丙烯基脲、N-甲基吡咯烷酮、甲醇、乙醇、水、甲苯、乙二醇二甲醚、二乙二醇二乙醚和二甲基亚砜中的一种或多种；所述的方法反应温度为0～40℃。
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