CN116854744A - 手性螺[色满-4,1'-二氢茚]双齿配体铱络合物的合成与应用 - Google Patents
手性螺[色满-4,1'-二氢茚]双齿配体铱络合物的合成与应用 Download PDFInfo
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- CN116854744A CN116854744A CN202310694976.2A CN202310694976A CN116854744A CN 116854744 A CN116854744 A CN 116854744A CN 202310694976 A CN202310694976 A CN 202310694976A CN 116854744 A CN116854744 A CN 116854744A
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- chromane
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- 239000003446 ligand Substances 0.000 title claims abstract description 45
- 229910052741 iridium Inorganic materials 0.000 title claims abstract description 29
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 25
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 11
- XMIHHJXMRZAABF-UHFFFAOYSA-N spiro[1,2-dihydroindene-3,4'-2,3-dihydrochromene] Chemical compound C12(CCC3=CC=CC=C13)CCOC1=CC=CC=C12 XMIHHJXMRZAABF-UHFFFAOYSA-N 0.000 title claims description 24
- -1 beta, beta-disubstituted acrylic acid salt compounds Chemical class 0.000 claims abstract description 53
- 238000000034 method Methods 0.000 claims abstract description 52
- 239000003054 catalyst Substances 0.000 claims abstract description 29
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 19
- 239000003513 alkali Substances 0.000 claims abstract description 12
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 8
- 229910052751 metal Inorganic materials 0.000 claims abstract description 7
- 239000002184 metal Substances 0.000 claims abstract description 7
- 239000002243 precursor Substances 0.000 claims abstract description 7
- 125000003003 spiro group Chemical group 0.000 claims abstract description 7
- 239000007858 starting material Substances 0.000 claims abstract description 6
- 238000001308 synthesis method Methods 0.000 claims abstract description 6
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910000077 silane Inorganic materials 0.000 claims abstract description 5
- 238000005859 coupling reaction Methods 0.000 claims abstract description 4
- 150000002503 iridium Chemical class 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 78
- 238000006243 chemical reaction Methods 0.000 claims description 57
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 44
- 229910052708 sodium Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- 239000003960 organic solvent Substances 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 229910052786 argon Inorganic materials 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 239000000758 substrate Substances 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical group FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 238000006555 catalytic reaction Methods 0.000 claims description 6
- NJQFCQXFOHVYQJ-PMACEKPBSA-N BF 4 Chemical compound C1([C@@H]2CC(=O)C=3C(O)=C(C)C4=C(C=3O2)[C@H](C(C)C)C2=C(O4)C(C)=C(C(C2=O)(C)C)OC)=CC=CC=C1 NJQFCQXFOHVYQJ-PMACEKPBSA-N 0.000 claims description 5
- 229910018286 SbF 6 Inorganic materials 0.000 claims description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 230000032050 esterification Effects 0.000 claims description 4
- 238000005886 esterification reaction Methods 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- RRKODOZNUZCUBN-CCAGOZQPSA-N (1z,3z)-cycloocta-1,3-diene Chemical compound C1CC\C=C/C=C\C1 RRKODOZNUZCUBN-CCAGOZQPSA-N 0.000 claims description 3
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims description 3
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- 229910001392 phosphorus oxide Inorganic materials 0.000 claims description 3
- 125000004436 sodium atom Chemical group 0.000 claims description 3
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 claims description 3
- 239000005052 trichlorosilane Substances 0.000 claims description 3
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 claims description 2
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical group C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 claims description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 150000002641 lithium Chemical group 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 238000010189 synthetic method Methods 0.000 claims 2
- 150000001253 acrylic acids Chemical class 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 239000000562 conjugate Substances 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 125000004185 ester group Chemical group 0.000 claims 1
- 150000003949 imides Chemical class 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001624 naphthyl group Chemical group 0.000 claims 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 abstract description 42
- 150000001875 compounds Chemical class 0.000 abstract description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract description 3
- 238000011914 asymmetric synthesis Methods 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 229930014626 natural product Natural products 0.000 abstract description 3
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 230000008878 coupling Effects 0.000 abstract description 2
- 238000010168 coupling process Methods 0.000 abstract description 2
- 229910052763 palladium Inorganic materials 0.000 abstract 1
- 239000002304 perfume Substances 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 129
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 73
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 68
- 239000011734 sodium Substances 0.000 description 67
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- 239000007787 solid Substances 0.000 description 58
- 238000002844 melting Methods 0.000 description 44
- 230000008018 melting Effects 0.000 description 44
- 238000004128 high performance liquid chromatography Methods 0.000 description 39
- 238000001514 detection method Methods 0.000 description 34
- 230000003287 optical effect Effects 0.000 description 34
- 238000000926 separation method Methods 0.000 description 32
- 239000000047 product Substances 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 13
- 239000000243 solution Substances 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000001212 derivatisation Methods 0.000 description 4
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 4
- 125000004494 ethyl ester group Chemical group 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000012046 mixed solvent Substances 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 150000007942 carboxylates Chemical class 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000010948 rhodium Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 description 2
- PEXWJYDPDXUVSV-UHFFFAOYSA-N 3-phenylbut-2-enoic acid Chemical compound OC(=O)C=C(C)C1=CC=CC=C1 PEXWJYDPDXUVSV-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- PEXWJYDPDXUVSV-FPLPWBNLSA-N (z)-3-phenylbut-2-enoic acid Chemical compound OC(=O)/C=C(/C)C1=CC=CC=C1 PEXWJYDPDXUVSV-FPLPWBNLSA-N 0.000 description 1
- KRWLHLVFJSURTL-UHFFFAOYSA-N 3,4-diphenylbut-2-enoic acid Chemical compound C=1C=CC=CC=1C(=CC(=O)O)CC1=CC=CC=C1 KRWLHLVFJSURTL-UHFFFAOYSA-N 0.000 description 1
- AXCCQHVRLZOUFS-UHFFFAOYSA-N 3-(3-chlorophenyl)but-2-enoic acid Chemical compound OC(=O)C=C(C)C1=CC=CC(Cl)=C1 AXCCQHVRLZOUFS-UHFFFAOYSA-N 0.000 description 1
- QVWAEZJXDYOKEH-UHFFFAOYSA-N 3-(3-hydroxyphenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC(O)=C1 QVWAEZJXDYOKEH-UHFFFAOYSA-N 0.000 description 1
- GTVHLYBUAHVRRK-UHFFFAOYSA-N 3-(3-methoxyphenyl)but-2-enoic acid Chemical compound COC1=CC=CC(C(C)=CC(O)=O)=C1 GTVHLYBUAHVRRK-UHFFFAOYSA-N 0.000 description 1
- SINDTVUVNPIJMY-UHFFFAOYSA-N 3-(4-chlorophenyl)but-2-enoic acid Chemical compound OC(=O)C=C(C)C1=CC=C(Cl)C=C1 SINDTVUVNPIJMY-UHFFFAOYSA-N 0.000 description 1
- DCEOLKDAOUIFHW-UHFFFAOYSA-N 3-(4-fluorophenyl)but-2-enoic acid Chemical compound OC(=O)C=C(C)C1=CC=C(F)C=C1 DCEOLKDAOUIFHW-UHFFFAOYSA-N 0.000 description 1
- FUINODAYLGQWJL-UHFFFAOYSA-N 3-(4-methoxyphenyl)but-2-enoic acid Chemical compound COC1=CC=C(C(C)=CC(O)=O)C=C1 FUINODAYLGQWJL-UHFFFAOYSA-N 0.000 description 1
- YAOUORFQUQWGHU-UHFFFAOYSA-N 3-(4-methylphenyl)but-2-enoic acid Chemical compound OC(=O)C=C(C)C1=CC=C(C)C=C1 YAOUORFQUQWGHU-UHFFFAOYSA-N 0.000 description 1
- SZRLLDRXZMDGKV-UHFFFAOYSA-N 3-naphthalen-2-ylbut-2-enoic acid Chemical compound C1=CC=CC2=CC(C(=CC(O)=O)C)=CC=C21 SZRLLDRXZMDGKV-UHFFFAOYSA-N 0.000 description 1
- ONLKHDUCXDPCLH-UHFFFAOYSA-N 3-phenylhept-2-enoic acid Chemical compound CCCCC(=CC(O)=O)c1ccccc1 ONLKHDUCXDPCLH-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- CRJPCFXDUJZWOJ-UHFFFAOYSA-M C(CC(=O)[O-])(=O)OCC.[Mg+] Chemical compound C(CC(=O)[O-])(=O)OCC.[Mg+] CRJPCFXDUJZWOJ-UHFFFAOYSA-M 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
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- 239000007864 aqueous solution Substances 0.000 description 1
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- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- WVRIPRILKKOIQL-UHFFFAOYSA-N cicrotoic acid Chemical compound OC(=O)C=C(C)C1CCCCC1 WVRIPRILKKOIQL-UHFFFAOYSA-N 0.000 description 1
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- 238000010668 complexation reaction Methods 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical class [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- QPMJENKZJUFOON-PLNGDYQASA-N ethyl (z)-3-chloro-2-cyano-4,4,4-trifluorobut-2-enoate Chemical compound CCOC(=O)C(\C#N)=C(/Cl)C(F)(F)F QPMJENKZJUFOON-PLNGDYQASA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 238000005930 hydroaminomethylation reaction Methods 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 238000005669 hydrocyanation reaction Methods 0.000 description 1
- 238000007037 hydroformylation reaction Methods 0.000 description 1
- 238000006459 hydrosilylation reaction Methods 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- ZOGYOOUMDVKYLM-UHFFFAOYSA-N phosphane phosphorous acid Chemical compound P.OP(O)O ZOGYOOUMDVKYLM-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical class O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003303 ruthenium Chemical class 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
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000009901 transfer hydrogenation reaction Methods 0.000 description 1
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Abstract
本发明涉及一种手性螺[色满‑4,1'‑二氢茚]双齿配体铱络合物的合成与应用。其合成方法是以(R/S)‑2‑氧代螺[色满‑4,1'‑二氢茚]‑7'‑酚为起始原料，经三氟甲磺酸酯化、钯催化偶联和硅烷还原即可方便地合成相应的手性螺[色满‑4,1'‑二氢茚]双齿配体，该配体可以与铱金属前体络合得到催化剂；得到的手性螺[色满‑4,1'‑二氢茚]双齿配体铱催化剂可以应用于β,β–双取代丙烯酸盐类化合物（或β,β–双取代丙烯酸和碱）的不对称催化氢化反应从而高效高选择性地得到手性羧酸，催化剂用量可降低至0.02 mol%，并达到99%的收率和97% ee，这是该类化合物迄今为止所能取得的最好的不对称催化氢化的结果，该催化剂和氢化的方法在手性药物、天然产物和香精香料的不对称合成中具有重要的应用价值与潜力。
Description
技术领域
本发明涉及一种新型手性螺[色满-4,1'-二氢茚]双齿配体铱络合物的合成与应用。该手性螺[色满-4,1'-二氢茚]双齿配体铱络合物可以作为手性催化剂应用于不对称催化反应中，在不对称催化领域具有很高的应用价值，属于不对称催化领域。
背景技术
目前工业生产中，对β–手性丙酸类化合物具有很高的需求。制备该类化合物最为高效的方法便是对β,β–双取代丙烯酸盐类化合物进行不对称催化氢化。针对该反应目前仅有双膦配体钌络合物（Ohta, T.; Takaya, H.; Kitamura, M.; Nagai, K.; Noyori, R.J. Org. Chem.1987, 52, 3174–3176.）、双膦配体铑络合物（Yan, Q.; Kong, D.; Zhao,W.; Zi, G.; Hou, G. J. Org. Chem.2016, 81, 2070–2077.）以及次磷酸酯铑络合物（Li, Y.; Dong, K.; Wang, Z.; Ding, K. Angew. Chem. Int. Ed.2013, 52, 6748–6752.）三个催化体系。目前的这三个催化剂的用量很高（0.2–1 mol%），无法满足实际生产的要求。为解决这一问题，需要一类全新的基于手性螺[色满-4,1'-二氢茚]双齿配体铱络合物被设计合成。
中国专利CN 109970697 B 公开了一种手性螺[色满-4,1'-二氢茚]分子的合成方法，对研究和发现手性螺[色满-4,1'-二氢茚]分子的实际用途和应用价值具有重要的意义。这一全新的配体和催化剂合成简洁、性质稳定、底物应用范围广、对映选择性高。基于手性螺[色满-4,1'-二氢茚]双齿配体铱络合物的合成，针对β,β–双取代丙烯酸盐类化合物可以取得大于5000的转化数、99%的收率和97%的对映选择性，具有极高的研究和应用价值。
发明内容
本发明的目的是提供一种手性螺[色满-4,1'-二氢茚]双齿配体铱络合物的合成与应用。该手性螺[色满-4,1'-二氢茚]双齿配体铱络合物作为催化剂可应用于β,β–双取代丙烯酸盐类化合物（或β,β–双取代丙烯酸和碱）的不对称催化氢化反应，从而高效高选择性地得到手性羧酸，催化剂用量可降低至0.02 mol%，并达到99%的收率和97% ee，这是迄今为止所能取得的最好的不对称催化氢化的结果。该手性螺[色满-4,1'-二氢茚]双齿配体铱络合物催化剂和氢化的方法在手性药物、天然产物和香精香料的不对称合成中具有重要的应用价值与潜力。
本发明提供的手性螺[色满-4,1'-二氢茚]双齿配体铱络合物具有以下通式（I）结构：
通式（I）中：
R1为芳基，R2为卤原子、羧基、BF4 -、PF6 -、[Rh(cod)2]SbF6 -、OTf-。
上述术语烷基优选为甲基、乙基、丙基、丁基等；
芳基优选为被烷基或者烷氧基取代或者未取代的苯基等，烷基如上定义，烷氧基优选为甲氧基、乙氧基、丙氧基、丁氧基等。
所述的双齿配体铱络合物记作为（±）手性螺[色满-4,1'-二氢茚]双齿配体铱络合物，（－）手性螺[色满-4,1'-二氢茚]双齿配体铱络合物，（＋）手性螺[色满-4,1'-二氢茚]双齿配体铱络合物。
本发明提供的手性螺[色满-4,1'-二氢茚]双齿配体铱络合物的合成方法包括的步骤：
具体步骤为：
步骤一：起始原料(R/S)-7′-羟基-2′,3′-二氢螺[色满-4,1′-茚]-2-酮(R/S)-1在有机溶剂中在碱的促进下与三氟甲磺酸酯化试剂在0~60 ℃温度范围内反应得到(R/S)-7'-三氟甲基磺酰基氧基-2',3'-二氢螺[色满-4,1'-茚]-2-酮(R/S)-2。
所述有机溶剂为二氯甲烷、甲苯、四氢呋喃、甲醇中的一种或几种；所述的碱为三乙胺、二异丙基乙基胺、碳酸钾、碳酸铯、1,4-二氮杂二环[2.2.2]辛烷、1,8-二氮杂二环[5.4.0]十一碳-7-烯、二甲胺基吡啶；所述三氟甲磺酸酯化试剂为三氟甲磺酸酐、N-苯基双(三氟甲烷磺酰)亚胺。
步骤二：(R/S)-7'-三氟甲基磺酰基氧基-2',3'-二氢螺[色满-4,1'-茚]-2-酮(R/ S)-2在有机溶剂、碱和0~160 ℃温度范围条件下，在膦配体和醋酸钯的催化下与二芳基磷氧发生偶联反应，随后在硅烷和碱的条件下还原得到目标配体(R/S)-7'-二芳基膦基-2',3'-二氢螺[色满-4,1'-茚]-2-酮(R/S)-II。
所述二芳基磷氧中芳基为被烷基或者烷氧基取代或者未取代的苯基，烷基为甲基、乙基、丙基、丁基、芳基取代甲基，烷氧基为甲氧基、乙氧基、丙氧基、丁氧基。所述有机溶剂为二氯甲烷、甲苯、四氢呋喃、甲醇中的一种或几种；所述的碱为三乙胺、二异丙基乙基胺、碳酸钾、碳酸铯、1,4-二氮杂二环[2.2.2]辛烷、1,8-二氮杂二环[5.4.0]十一碳-7-烯、二甲胺基吡啶；所述膦配体为常见双膦配体如1,3-双(二苯基膦)丙烷、1,4-双(二苯基膦)丁烷、1,1'-双(二苯基膦)二茂铁、1,1'-联萘-2,2'-双二苯膦；硅烷为二苯基硅烷、三氯硅烷。
步骤三：配体(R/S)-7'-二芳基膦基-2',3'-二氢螺[色满-4,1'-茚]-2-酮(R/S)-II在有机溶剂中和铱金属前体在0~60 ℃温度范围内反应得到催化剂（I）。
所述有机溶剂为二氯甲烷、甲苯、四氢呋喃、甲醇中的一种或几种，铱金属前体为[Ir(cod)Cl]2（cod = 环辛二烯）、[Ir(cod)2]BF4、[Ir(cod)2]PF6、[Ir(cod)2]SbF6、[Ir(cod)2]OTf）。
本发明提供了前述手性螺[色满-4,1'-二氢茚]双齿配体铱络合物（I）作为催化剂、式（II）配体在不对称催化反应中的应用。所述不对称反应包括氢化反应，氢甲酰化反应，硅氢化反应，硼氢化反应，氢羟基化反应，氢氨化反应，氢氰基化反应，异构化甲酰基化反应，氢氨甲基化反应，转移氢化反应，烯丙基化反应，烯烃复分解反应，环异构化反应，Diels-Alder反应，不对称偶联反应，Aldol反应，Michael加成反应，不对称环氧化反应，动力学拆分和[m+n]环化反应。
根据前述的应用，该催化剂在有机溶剂中对β,β–双取代丙烯酸以及β,β–双取代丙烯酸盐类化合物的氢化具有很高的活性和对映选择性，得到光学活性手性羧酸盐，其催化氢化反应过程是：
在氩气或氮气保护下，于有机溶剂中，并在0~100℃下搅拌反应3~200小时得到光学活性手性羧酸。
具体步骤是：在氩气或氮气保护下，于氢化釜中加入羧酸盐（或羧酸和碱）、催化剂（I）（或配体II和金属前体），随后加入有机溶剂搅拌溶解，充入氢气并在0~100 ℃温度范围内反应和2~100 atm氢气压力下搅拌反应3~200小时得到光学活性手性羧酸盐；其中铱金属前体为[Ir(cod)Cl]2（cod = 环辛二烯）、[Ir(cod)2]BF4、[Ir(cod)2]PF6、[Ir(cod)2]SbF6、[Ir(cod)2]Otf。
所述有机溶剂为二氯甲烷、甲苯、四氢呋喃、甲醇、乙醇、异丙醇、叔丁醇中的一种或几种。在通式（III）中：R3、R4、R5为氢原子或卤原子、C1~C8烷基、C1~C8卤代烷基、C2~C8链烯基、C5~C14芳基烷基、C6~C12芳基烯基、-C1~C8烷氧基，芳氧基；R6为氢原子、钠原子、钾原子、锂原子、钙原子；当R6为氢原子时，需要加入碱如三乙胺、二异丙基乙基胺、碳酸钠、碳酸铯、碳酸钾；所得手性羧酸的构型既可以是(R)-构型也可以是(S)-构型；在低催化剂用量（底物/催化剂>500）时需要在反应体系中加入1-5% mol%的酸作为添加剂，如乙酸、甲酸、盐酸、硫酸或与底物相对应的共轭酸。
本发明提供了一种手性螺[色满-4,1'-二氢茚]双齿配体铱络合物的合成与应用。其特点是:1）该手性螺[色满-4,1'-二氢茚]双齿配体铱络合物具有中心手性，因此有左旋手性螺[色满-4,1'-二氢茚]双齿配体铱络合物和右旋手性螺[色满-4,1'-二氢茚]双齿配体铱络合物，消旋的螺[色满-4,1'-二氢茚]双齿配体铱络合物可以通过消旋的螺[色满-4,1'-二氢茚]单酚为原料合成得到。2）本发明可以作为手性催化剂应用于不对称氢化当中，该化合物在有机溶剂中对β,β–双取代丙烯酸盐类化合物的不对称催化氢化具有很高的活性和对映选择性，取得了目前文献报道的最高的催化剂效率和转化数。
该手性螺[色满-4,1'-二氢茚]双齿配体铱络合物作为催化剂可应用于β,β–双取代丙烯酸盐类化合物（或β,β–双取代丙烯酸和碱）的不对称催化氢化反应，从而高效高选择性地得到手性羧酸，催化剂用量可降低至0.02 mol%，并达到99%的收率和97% ee，这是迄今为止所能取得的最好的不对称催化氢化的结果。并且该手性螺[色满-4,1'-二氢茚]双齿配体铱络合物催化剂和氢化的方法在手性药物、天然产物和香精香料的不对称合成中具有重要的应用价值与潜力。
实施方式
本发明通过下列实施例进一步举例说明，但以下实施例仅有助于进一步理解本发明，但不能限制本发明的内容。实施例中未注明具体条件的实验方法，通常按照常规条件以及手册中所述的条件，或按照制造厂商所建议的条件；所用的通用设备、材料、试剂等，如无特殊说明，均可从商业途径得到。
实施例1：(R)-7'-三氟甲基磺酰基氧基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成:
取(R)-螺[色满-4,1'-二氢茚]单酚a（1.28 g, 4.8 mmol）于100 ml 干燥的Schlenck瓶中，置换瓶中为氩气氛围，随后加入二氯甲烷（20 mL）和吡啶（0.69 mL, 8.5mmol）搅拌溶解并冰浴冷却至0 ℃。随后滴加三氟甲磺酸酐（0.97 mL，5.8 mmol）。自然升至室温搅拌反应，TLC （PE/EA = 10: 1）监测反应情况，待原料消失后，加入饱和硫酸铜溶液（5 mL）淬灭反应，二氯甲烷（20 mL×2）萃取水相，并使用饱和食盐水洗涤有机相，随后使用无水硫酸钠干燥，真空脱溶，柱层析（PE/EA = 10:1 to 5:1）分离纯化得到目标产物(R)-7'-三氟甲基磺酰基氧基-2',3'-二氢螺[色满-4,1'-茚]-2-酮，1.89 g，收率99%，白色固体，熔点：81–82℃，旋光：[a]26D = –130 (c 0.1, CHCl3)， 1H NMR (400 MHz, CDCl3) δ7.46 (t, J = 7.8 Hz, 1H), 7.40 (d, J = 7.5 Hz, 1H), 7.36–7.22 (m, 2H), 7.15(d, J = 8.1 Hz, 1H), 7.06 (t, J = 7.5 Hz, 1H), 6.68 (dd, J = 7.7, 1.6 Hz,1H), 3.43 (d, J = 15.5 Hz, 1H), 3.09 (td, J = 7.3, 3.8 Hz, 2H), 2.94 (d, J =15.5 Hz, 1H), 2.48–2.36 (m, 1H), 2.32–2.20 (m, 1H). 13C NMR (101 MHz, CDCl3) δ166.8, 150.3, 148.8, 146.1, 134.9, 130.8, 129.0, 127.8, 125.6, 125.0, 124.8,119.5, 118.0 (q, J = 319.9 Hz), 117.33, 50.24, 40.69, 39.27, 30.44. HRMS(ESI) Calcd for C18H13F3NaO5S+ ([M+Na]+): 421.0333; Found: 421.0331.
其中(R)-螺[色满-4,1'-二氢茚]单酚a参照中国专利CN 109970697 B进行制备(也参考本申请人同日申请，发明名称为：手性螺[色满-4,1'-二氢茚]亚磷酸酯单磷配体的合成与应用)，具体合成路线如下：
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步骤一：向干燥的2000 mL反应瓶中称入3-(3-羟基苯基)丙酸（37.3 g, 224mmol），加入二氯甲烷（300 mL）和乙腈（150 mL），室温下搅拌溶解。使用冰水浴使体系降温至5℃以下，随后使用恒压滴液漏斗，滴加液溴的二氯甲烷溶液（11.5 mL Br2加150 mL二氯甲烷），1小时滴加完毕。然后继续在冰水浴的条件下，搅拌反应1.5小时。核磁氢谱监测反应结束后，加饱和硫代硫酸钠溶液淬灭体系，减压脱溶，加乙酸乙酯（500 mL）溶解稀释，分液，水相用乙酸乙酯（150 mL×2）萃取，合并有机相，无水硫酸镁干燥，抽滤，脱溶，得到3-(2-溴-5-羟基苯基)-丙酸：浅黄色固体，54.3 g，收率 99%，熔点：152-155℃（可不经纯化直接用于下一步反应）。1H NMR (400 MHz, CD3OD) δ: 7.30 (d, J = 8.6 Hz, 1H), 6.77 (s,1H), 6.57 (d, J = 8.7 Hz, 1H), 5.02 (brs, 2H), 2.94 (t, J = 7.8 Hz, 2H), 2.59(t, J = 7.8 Hz, 2H). 13C NMR (101 MHz, CD3OD) δ 175.0, 156.8, 140.6, 133.0,116.9, 115.0, 112.5, 33.5, 31.1.
步骤二：向3000 mL干燥的反应瓶中，加入3-(2-溴-5-羟基苯基)-丙酸（40 g, 163mmol）和羰基二咪唑CDI（28.6 g, 176 mmol），加入四氢呋喃（700 mL）溶解。置换为氩气氛围，室温下搅拌反应8小时。将丙二酸单乙酯镁盐(39 g, 253 mmol)的四氢呋喃(300 mL)溶液加入到反应体系中，继续室温搅拌反应12小时，TLC监测反应完全。向体系中加入1N HCl酸化，乙醚（2 × 150 mL）萃取，合并有机相，然后用饱和氯化钠水溶液洗涤，无水硫酸钠干燥。加硅藻土抽滤，减压脱溶，柱层析（石油醚/乙酸乙酯 = 5:1），得到5-(2-溴-5-羟基苯基)-3-羰基戊酸乙酯b：浅黄色泡沫状固体，39 g，收率76%。1H NMR (400 MHz, CDCl3) δ 7.25 (d, J = 8.7 Hz, 1H), 6.66 (d, J = 3.0 Hz, 1H), 6.50 (dd, J = 8.7, 3.1Hz, 1H), 4.04 (q, J = 7.2 Hz, 2H), 3.63 (s, 3H), 3.31 (s, 2H), 2.84 (ddd, J =9.3, 7.4, 2.1 Hz, 2H), 2.78–2.72 (m, 2H), 1.13 (t, J = 7.1 Hz, 3H). 13C NMR(101 MHz, CDCl3) δ 202.4, 167.5, 155.5, 140.7, 133.6, 117.6, 115.5, 114.2,61.7, 49.3, 42.7, 30.0, 14.1.
步骤三：向1000 mL干燥的反应瓶中，加入5-(2-溴-5-羟基苯基)-3-羰基戊酸乙酯b（17.8 g, 56.5 mmol），加入二氯甲烷（300 mL）溶解。置换体系内为氩气氛，使用冰水浴控制体系内温度至5℃以下。然后缓慢滴加三氟甲磺酸（15.0 mL, 169 mmol）。滴加完毕之后，撤去冰浴，使体系在室温下搅拌反应0.5小时，TLC监测原料全部转换完全，并且体系中伴随有大量黄色固体析出。将间苯二酚（6.2 g, 56.5 mmol）加入反应体系，继续在室温下搅拌反应1小时，TLC监测中间体全部转换完全。加冰水淬灭反应，用乙酸乙酯（2 × 150 mL）萃取，合并有机相，用饱和氯化钠水溶液洗涤，无水硫酸镁干燥有机相，加硅藻土抽滤，减压脱溶，柱层析（石油醚/乙酸乙酯 = 5:1）。得到4’-溴-5-羟基-7’-羟基-螺[色满-4,1’-二氢茚]-2-酮c：黄色泡沫状固体，16.9 g，收率83%。1H NMR (400 MHz, CDCl3) δ 7.38 (d, J =8.9 Hz, 1H), 6.79 (d, J = 9.0 Hz, 1H), 6.65 (d, J = 8.5 Hz, 1H), 6.55 (d, J =2.3 Hz, 1H), 6.39–6.33 (dd, 1H), 3.42 (d, J = 15.8 Hz, 1H), 3.30–3.13 (m,1H), 2.94–2.83 (m, 2H), 2.78 (d, J = 15.9 Hz, 1H), 2.56–2.49 (m, 1H), 2.28(m, 1H). 13C NMR (101 MHz, CDCl3) δ 170.5, 158.8, 155.2, 152.4, 146.9, 133.3,132.8, 127.5, 121.5, 117.1, 112.7, 108.8, 104.7, 54.8, 51.4, 40.9, 40.8,33.1.
步骤四：向250 mL干燥的反应瓶中，加入4’-溴-5-羟基-7’-羟基-螺[色满-4,1’-二氢茚]-2-酮c（6.8 g, 18.8 mmol），加入二氯甲烷（120 mL）溶解，然后加入吡啶（3.0 mL,37.6 mmol）。将体系置于冰水浴中使体系内温度至5 ℃以下，然后缓慢滴加三氟甲磺酸酐（3.2 mL, 18.8 mmol）。滴加完毕之后，撤去冰浴，使体系在室温下搅拌反应12小时，TLC监测原料全部转换完全。加冰水淬灭反应，用乙酸乙酯（2 × 50 mL）萃取，合并有机相，用饱和氯化钠水溶液洗涤，无水硫酸镁干燥有机相，加硅藻土抽滤，减压脱溶，柱层析（石油醚/乙酸乙酯 = 10:1）。得到4’-溴-5-三氟甲磺酰氧基-7’-羟基-螺[色满-4,1’-二氢茚]-2-酮d：黄色泡沫状固体，7.0 g，收率76%。1H NMR (400 MHz, CDCl3) δ 7.35 (d, J = 8.4 Hz,1H), 7.06 (d, J = 2.4 Hz, 1H), 6.95 (dd, J = 8.6, 2.5 Hz, 1H), 6.87 (d, J =8.6 Hz, 1H), 6.58 (dd, J = 8.5, 0.8 Hz, 1H), 5.55 (s, 1H), 3.58 (d, J = 16.0Hz, 1H), 3.11–2.96 (m, 2H), 2.87 (d, J = 16.0 Hz, 1H), 2.36 (m, J = 13.3,8.6, 6.9 Hz, 1H), 2.25–2.16 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 167.3, 151.9,150.9, 148.6, 146.2, 133.0, 130.2, 129.6, 127.3, 120.2, 117.4, 116.4, 110.8,110.7, 50.4, 39.3, 39.0, 32.3.
步骤五：向500 mL干燥的反应瓶中，加入4’-溴-5-三氟甲磺酰氧基-7’-羟基-螺[色满-4,1’-二氢茚]-2-酮d（19.6 g, 39.7 mmol），加入无水乙醇（230 mL）溶解，然后加入三乙胺（14 mL, 100 mmol）和10% Pd/C（2.0 g, 1.9 mmol），置换H2氛。在1 atm H2条件下，室温反应48小时，核磁氢谱监测反应完全。减压脱溶，加乙酸乙酯（200 mL）溶解稀释，加1NHCl酸化至不溶物消失。分液，乙酸乙酯（3 × 50 mL）萃取水相，合并有机相，用饱和氯化钠水溶液洗涤，无水硫酸镁干燥有机相，加硅藻土抽滤，脱溶，乙醚（3 × 20 mL）洗涤固体，得到(rac)-2-氧代螺[色满-4,1'-二氢茚]-7'-酚(rac)-a，9.6 g，收率91%。1H NMR (400MHz, CDCl3) δ 7.27 (m, 1H), 7.21 (t, J = 7.7 Hz, 1H), 7.12 (dd, J = 8.2, 1.2Hz, 1H), 7.03 (td, J = 7.5, 1.3 Hz, 1H), 6.92 (dd, J = 7.5, 1.0 Hz, 1H), 6.82(dd, J = 7.7, 1.6 Hz, 1H), 6.67–6.62 (m, 1H), 4.90 (s, 1H), 3.54 (d, J = 15.9Hz, 1H), 3.00 (t, J = 7.3 Hz, 2H), 2.84 (d, J = 15.9 Hz, 1H), 2.33 (dt, J =12.8, 7.4 Hz, 1H), 2.24–2.13 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 168.4, 152.4,150.7, 146.7, 130.0, 128.7, 125.6, 124.8, 117.7, 117.3, 114.4, 49.3, 40.4,39.2, 30.6.
步骤六：将(rac)-2-氧代螺[色满-4,1'-二氢茚]-7'-酚(rac)-a（7.0 g, 26.3mmol）和N-苄基氯代的辛可宁定e（3.2 g, 7.5 mmol）依次称入250 mL干燥的反应瓶中，放入搅拌子，加入干燥的叔丁基甲基醚（130 mL）。将反应体系放置入提前升至60℃的油浴中回流，设置搅拌器磁力搅拌速度为1000 r/min，持续搅拌24小时。体系中有大量白色不溶物生成，待体系冷却至室温，抽滤，分离滤液和不溶物。母液回收：用乙酸乙酯（3 ´ 20 mL）洗涤不溶物，合并滤液和洗涤液，减压脱溶，即得未与拆分试剂发生包结的(S)-a。收率：62%，62% ee。包结物解离：将不溶物置于250 mL烧杯中，加入乙酸乙酯（80 mL）稀释，向其中持续添加1N HCl直至无不溶物存在。使用分液漏斗分液，乙酸乙酯（2 ´ 50 mL）萃取水相，合并有机相，无水硫酸镁干燥，加硅藻土抽滤，减压脱溶，即得与拆分试剂发生包结的(R)-a。收率：40%，95% ee。
使用正己烷-甲基叔丁基醚作为溶剂对两者进行重结晶，分别得到(S)-a，收率：36%，ee值：>99%；(R)-a，收率：34%，>99% ee。HPLC条件：Chiralcel IC-3 column (25 cm ×0.46 cm ID); n-hexane/2-propanol = 85:15; temp, rt; flow rate = 1.0 mL/min;88 bars; 220 nm UV detector。
实施例2：(R)-7'-二苯基磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成:
取(R)-7'-三氟甲基磺酰基氧基-2',3'-二氢螺[色满-4,1'-茚]-2-酮（80 mg,0.2 mmol），1,3-双（二苯基膦）丙烷（4.2 mg, 0.01 mmol）, 醋酸钯（1.7 mg 0.01 mmol）于50 ml 干燥的Schlenk瓶中，置换瓶中为氩气氛围，随后加入二甲基亚砜（10 mL）和二异丙基乙基胺（155 mg, 1.2 mmol）搅拌溶解并脱气。随后95 ℃下加热反应。TLC （PE/EA = 10:1）监测反应情况，待原料消失后，冷却至室温加入饱和氯化铵（2 mL）淬灭反应，并使用1NHCl（10 mL）洗涤有机相，乙酸乙酯（20 mL×2）萃取水相，饱和NaHCO3、饱和食盐水洗涤有机相，随后使用无水硫酸钠干燥，真空脱溶后，取固体于100 ml 干燥的封管中，置换瓶中为氩气氛围，随后加入甲苯（40 mL）和二异丙基乙基胺（1.3 g, 10 mmol），冰浴冷却至0 ℃后滴加三氯硅烷（271 mg，2 mmol）。回流反应3天后，冷却至0 ℃后加入饱和碳酸氢钠溶液（2mL）淬灭反应，并加入硅藻土、乙酸乙酯（20 mL）搅拌，待体系内没有气泡生成后，抽滤除去固体，并使用乙酸乙酯（10 mL ×2）洗涤固体，真空脱溶，柱层析（PE/EA = 50:1–20:1）分离纯化得到目标配体。白色固体，81 mg，收率 93%，1H NMR (400 MHz, CDCl3) δ 7.34 (d, J= 7.4 Hz, 1H), 7.30–7.19 (m, 7H), 7.17–7.02 (m, 7H), 6.57 (td, J = 7.3, 1.7Hz, 1H), 6.48 (dd, J = 7.6, 1.7 Hz, 1H), 4.28–4.15 (m, 1H), 3.10–2.91 (m,2H), 2.86 (d, J = 15.4 Hz, 1H), 2.43–2.30 (m, 1H), 2.23–2.11 (m, 1H). 13C NMR(101 MHz, CDCl3) δ 167.7, 150.2, 149.4, 149.2, 145.2, 145.1, 137.5, 137.4,136.0, 135.9, 135.7, 135.7, 133.7, 133.6, 133.5, 133.4, 133.0, 132.9, 130.7,128.7, 128.6, 128.5, 128.4, 128.3, 128.3, 128.1, 127.1, 127.1, 126.1, 124.1,116.9, 51.6, 41.8, 41.6, 40.8, 30.0. 31P NMR (162 MHz, CDCl3) δ -22.29. 旋光：[a]27D = –128 (c 0.1, CHCl3)，熔点：205–206 ℃，HRMS (ESI) Calcd for C29H24O2P+([M+H]+): 435.1508; Found: 435.1512.
实施例3：(R)-7'-二(3,5-二甲基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成：
操作与实施例2相同，白色固体，87 mg，收率 88%. 1H NMR (400 MHz, CDCl3) δ:1H NMR (400 MHz, CDCl3) δ 7.36–7.23 (m, 2H), 7.20–7.03 (m, 3H), 6.90 (d, J =6.6 Hz, 2H), 6.68 (t, J = 8.2 Hz, 4H), 6.58 (td, J = 7.4, 1.5 Hz, 1H), 6.42(dd, J = 7.7, 1.5 Hz, 1H), 4.33 (dd, J = 15.5, 10.7 Hz, 1H), 3.09–2.91 (m,3H), 2.85 (d, J = 15.4 Hz, 1H), 2.42–2.31 (m, 1H), 2.20 (s, 12H). 13C NMR (101MHz, CDCl3) δ 167.9, 150.2, 149.1, 148.8, 145.0, 145.0, 137.8, 137.7, 137.5,137.4, 137.1, 137.1, 135.6, 135.5, 131.7, 131.5, 130.7, 130.7, 130.5, 130.4,130.1, 128.5, 127.9, 127.2, 127.2, 125.8, 123.9, 116.8, 51.6, 51.6, 41.9,41.7, 40.9, 30.0, 26.9, 21.3, 21.3. 31P NMR (162 MHz, CDCl3) δ -22.38. 旋光：[a]27D =–129 (c 0.25, CHCl3)，熔点：84–85 ℃ HRMS (ESI) Calcd for C33H32O2P+ ([M+H]+): 491.2134; Found: 491.2133.
实施例4：(R)-7'-二(3,5-二叔丁基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成：
操作与实施例2相同，白色固体，111 mg，收率 84%. 1H NMR (400 MHz, CDCl3) δ:1H NMR (400 MHz, CDCl3) δ 7.36–7.24 (m, 4H), 7.15–7.02 (m, 3H), 7.01–6.84 (m,4H), 6.55–6.46 (m, 1H), 6.46–6.37 (m, 1H), 4.42 (dd, J = 15.5, 10.8 Hz, 1H),3.16–2.93 (m, 2H), 2.87 (d, J = 15.5 Hz, 1H), 2.49–2.30 (m, 1H), 2.24–2.10(m, 1H), 1.19 (d, J = 8.5 Hz, 36H). 13C NMR (101 MHz, CDCl3) δ 168.0, 150.4,150.3, 150.3, 150.2, 149.0, 148.7, 144.9, 144.8, 136.3, 136.2, 135.5, 135.5,135.1, 135.0, 134.9, 134.7, 130.6, 128.2, 128.0, 127.8, 127.6, 127.4, 127.3,127.2, 125.7, 123.8, 122.2, 122.0, 116.8, 51.6, 51.5, 41.8, 41.6, 40.9, 34.8,34.8, 31.4, 31.3, 30.0. 31P NMR (162 MHz, CDCl3) δ -20.13. 旋光：[a]27D =–96 (c0.25, CHCl3)，熔点：85–87 ℃ HRMS (ESI) Calcd for C45H56O2P+ ([M+H]+): 659.4012;Found: 659.4007.
实施例5：(R)-7'-二(3,5-二叔丁基-4-甲氧基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成：
操作与实施例2相同，白色固体，114 mg，收率 79%. 1H NMR (400 MHz, CDCl3) δ:1H NMR (400 MHz, CDCl3) δ 7.38–7.24 (m, 2H), 7.13–6.99 (m, 3H), 6.86 (d, J =8.2 Hz, 4H), 6.60–6.47 (m, 1H), 6.40 (d, J = 6.8 Hz, 1H), 4.43 (dd, J = 15.6,10.9 Hz, 1H), 3.65 (d, J = 2.4 Hz, 6H), 3.12–2.93 (m, 2H), 2.87 (d, J = 15.5Hz, 1H), 2.47–2.30 (m, 1H), 2.26–2.10 (m, 1H), 1.28 (d, J = 7.9 Hz, 36H). 13CNMR (101 MHz, CDCl3) δ 168.0, 160.0, 159.7, 150.2, 148.8, 148.6, 144.9,144.8, 143.4, 143.3, 143.2, 143.1, 135.2, 135.2, 135.0, 134.8, 132.0, 131.8,131.6, 131.4, 130.5, 130.5, 130.4, 129.5, 129.4, 128.1, 127.9, 127.3, 127.3,125.7, 123.6, 116.7, 64.2, 64.2, 51.5, 51.5, 41.6, 41.4, 40.9, 35.7, 35.7,31.9, 31.9, 30.0. 31P NMR (162 MHz, CDCl3) δ -22.50.旋光：[a]27D = –64 (c 0.1,CHCl3)，熔点：168–169℃ HRMS (ESI) Calcd for C47H60O4P+ ([M+H]+): 719.4224; Found:719.4218.
实施例6：(R)-7'-二(3,5-二金刚烷基-4-甲氧基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成：
操作与实施例2相同，白色固体，76 mg，收率 37%. 1H NMR (400 MHz, CDCl3) δ:1H NMR (400 MHz, CDCl3) δ 7.38–7.27 (m, 2H), 7.12–6.97 (m, 3H), 6.83 (dd, J =8.0, 2.8 Hz, 4H), 6.47 (ddd, J = 8.2, 6.0, 2.6 Hz, 1H), 6.37 (d, J = 7.6 Hz,1H), 4.50 (dd, J = 15.6, 11.1 Hz, 1H), 3.63 (d, J = 1.6 Hz, 6H), 3.03 (h, J =8.8 Hz, 2H), 2.89 (d, J = 15.6 Hz, 1H), 2.39 (ddd, J = 12.9, 8.2, 6.3 Hz,1H), 2.17 (ddd, J = 12.9, 8.3, 6.4 Hz, 1H), 2.09–1.85 (m, 36H), 1.70 (dd, J =11.8, 3.1 Hz, 24H). 13C NMR (101 MHz, CDCl3) δ 168.2, 160.9, 160.6, 150.1,148.8, 148.5, 144.9, 144.8, 143.4, 143.3, 143.2, 143.1, 135.3, 135.2, 135.0,131.7, 131.5, 131.4, 131.2, 130.4, 130.3, 129.4, 129.4, 128.0, 127.9, 127.4,127.4, 125.6, 123.7, 116.7, 65.8, 65.7, 51.5, 51.5, 42.7, 42.6, 41.5, 41.3,40.9, 38.5, 36.9, 36.8, 30.1, 29.2, 29.2. 31P NMR (162 MHz, CDCl3) δ -22.38,旋光：[a]27D =–52 (c 0.1, CHCl3)，熔点：225–226 ℃ HRMS (ESI) Calcd for C71H84O4P+([M+H]+): 1031.6102; Found: 1031.6097
实施例7：(R)-7'-二(3,5-二三甲基硅基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成：
操作与实施例2相同，白色固体，89 mg，收率55% 1H NMR (400 MHz, CDCl3) δ: 1HNMR (400 MHz, CDCl3) δ 7.53 (s, 2H), 7.35 (d, J = 7.4 Hz, 1H), 7.28 (t, J =7.7 Hz, 2H), 7.24–7.11 (m, 4H), 7.12–7.04 (m, 2H), 6.56–6.44 (m, 1H), 6.45–6.34 (m, 1H), 4.37 (dd, J = 15.5, 10.6 Hz, 1H), 3.13–2.93 (m, 2H), 2.87 (dd,J = 15.5, 0.9 Hz, 1H), 2.48–2.32 (m, 1H), 2.27–2.12 (m, 1H), 0.15 (d, J =10.4 Hz, 36H). 13C NMR (101 MHz, CDCl3) δ 167.9, 150.3, 145.1, 139.5, 139.4,139.2, 139.2, 139.1, 138.9, 138.6, 138.4, 138.1, 137.9, 135.7, 135.7, 135.5,135.4, 134.5, 134.4, 134.2, 134.0, 130.7, 128.4, 128.1, 127.3, 127.3, 126.0,123.9, 117.0, 51.7, 41.9, 41.7, 41.0, 30.2, 29.8, –1.0, –1.0. 31P NMR (162MHz, CDCl3) δ -22.43., 旋光：[a]27D = –74 (c 0.1, CHCl3)，熔点：126–127 ℃, HRMS(ESI) Calcd for C41H56O2PSi4 + ([M+H]+): 723.3090; Found: 723.3086.
实施例8：(R)-7'-二[3,5-二(二环己基甲基)苯基]磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成：
操作与实施例2相同，白色固体，154 mg，收率 23%，1H NMR (400 MHz, CDCl3) δ:1H NMR (400 MHz, CDCl3) δ 7.72 (dd, J = 5.7, 3.4 Hz, 1H), 7.53 (dd, J = 5.7,3.3 Hz, 1H), 7.29 (d, J = 7.4 Hz, 1H), 7.19 (td, J = 7.5, 2.8 Hz, 2H), 7.13(d, J = 8.1 Hz, 1H), 7.04–6.92 (m, 5H), 6.80 (t, J = 7.4 Hz, 1H), 6.68 (d, J= 7.8 Hz, 1H), 3.90 (dd, J = 15.3, 8.5 Hz, 1H), 3.26 (d, J = 6.2 Hz, 12H),2.97 (t, J = 7.4 Hz, 2H), 2.58 (d, J = 15.3 Hz, 1H), 2.36–2.23 (m, 1H), 2.20–2.09 (m, 1H), 2.07–0.57 (m, 88H). 13C NMR (101 MHz, CDCl3) δ 166.6, 166.1,149.6, 147.4, 147.1, 143.7, 139.2, 135.1, 134.2, 134.0, 132.8, 132.7, 131.3,130.7, 130.5, 130.3, 129.8, 129.6, 129.4, 127.8, 127.0, 126.8, 125.6, 124.5,123.0, 116.2, 84.6, 64.5, 52.7, 50.5, 42.4, 42.3, 42.2, 42.1, 41.1, 40.9,39.4, 30.9, 29.5, 28.9, 28.6, 28.6, 28.3, 27.7, 27.0, 27.0, 26.9, 26.5, 26.4,26.2, 26.1, 26.0, 25.9, 25.9, 25.8, 21.6, 18.1, 13.1, 12.7. 31P NMR (162 MHz,CDCl3) δ –20.51.HRMS (ESI) Calcd for C85H120O7P+ ([M+H]+): 1283.8766; Found:1283.8763.
实施例9：(R)-7'-二(3,5-二苯基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成：
操作与实施例2相同，白色固体，136 mg，收率 76%. 1H NMR (400 MHz, CDCl3) δ :1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 19.6 Hz, 2H), 7.63 (t, J = 8.3 Hz, 8H),7.57–7.37 (m, 19H), 7.20 (d, J = 8.0 Hz, 1H), 7.15–7.07 (m, 1H), 6.58 (d, J =4.4 Hz, 2H), 4.61 (dd, J = 15.5, 10.6 Hz, 1H), 3.24–3.01 (m, 3H), 2.58–2.42(m, 1H), 2.37–2.23 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 168.3, 150.9, 150.8,150.7, 147.3, 147.2, 142.2, 142.1, 142.0, 140.0, 136.5, 135.5, 134.1, 134.0,133.0, 129.8, 129.6, 129.4, 129.3, 129.3, 129.1, 129.0, 128.9, 128.8, 128.6,128.1, 128.1, 127.8, 127.7, 127.6, 127.6, 127.4, 127.3, 126.6, 123.1, 116.6,52.4, 42.4, 40.3, 30.4. 31P NMR (162 MHz, CDCl3) δ –20.92. 旋光：[a]27D =–95 (c0.25, CHCl3)，熔点：239–240 ℃ HRMS (ESI) Calcd for C53H40O2P+ ([M+H]+): 739.2760;Found: 739.2759.
实施例10：(R)-7'-二(3,5-二(2,4,6-三异丙基苯基)苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成：
操作与实施例2相同，白色固体，224 mg，收率 27%. 1H NMR (400 MHz, CDCl3) δ:1H NMR (400 MHz, CDCl3) δ 7.33 (d, J = 7.1 Hz, 1H), 7.27–7.10 (m, 7H), 7.00(d, J = 15.8 Hz, 10H), 6.91 (s, 1H), 6.66 (d, J = 7.6 Hz, 1H), 6.55 (t, J =7.4 Hz, 1H), 3.94 (dd, J = 15.2, 8.4 Hz, 1H), 3.02 (dt, J = 14.1, 8.0 Hz,2H), 2.92 (dq, J = 13.5, 6.8 Hz, 4H), 2.79 (d, J = 15.2 Hz, 1H), 2.65 (ddq, J= 41.7, 13.6, 6.7 Hz, 8H), 2.35 (dt, J = 13.8, 7.1 Hz, 1H), 2.18 (dt, J =12.8, 7.4 Hz, 1H), 1.31 (dd, J = 10.1, 6.9 Hz, 24H), 1.09–1.00 (m, 24H),0.95–0.84 (m, 24H). 13C NMR (101 MHz, CDCl3) δ 166.0, 149.4, 148.7, 148.4,146.8, 146.7, 145.2, 145.1, 145.1, 144.1, 144.0, 139.6, 139.6, 139.5, 139.4,135.6, 135.5, 135.4, 135.3, 134.4, 134.3, 130.8, 130.7, 130.6, 130.5, 130.4,130.3, 129.9, 127.8, 127.2, 125.7, 125.3, 122.8, 119.3, 119.2, 116.1, 50.6,50.5, 40.9, 40.7, 39.4, 33.2, 33.2, 29.4, 29.3, 29.2, 28.8, 25.8, 23.2, 23.1,23.0, 23.0, 22.9, 22.9, 22.8, 31P NMR (162 MHz, CDCl3) δ –18.07.旋光：[a]27D =–14 (c 0.1, CHCl3)，熔点：174–176 ℃, HRMS (ESI) Calcd for C89H112O2P+ ([M+H]+):1243.8394; Found: 1243.8398.
实施例11：(R)-7'-二[3,5-二-(二苯基甲基)苯基]磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成：
操作与实施例2相同，白色固体，164.7 mg，收率 75%. 1H NMR (400 MHz, CDCl3)δ: 1H NMR (400 MHz, CDCl3) δ 7.26–7.13 (m, 26H), 7.05 (t, J = 7.6 Hz, 1H),6.98–6.87 (m, 17H), 6.83 (dd, J = 17.6, 1.7 Hz, 2H), 6.71 (ddd, J = 9.4, 7.6,3.1 Hz, 3H), 6.55 (dd, J = 7.3, 1.6 Hz, 2H), 6.22 (td, J = 7.2, 6.7, 1.9 Hz,1H), 6.15 (d, J = 6.9 Hz, 1H), 5.31 (d, J = 6.6 Hz, 4H), 3.65 (dd, J = 15.4,8.9 Hz, 1H), 3.00–2.85 (m, 2H), 2.45 (d, J = 15.4 Hz, 1H), 2.29–2.18 (m, 1H),2.10–1.99 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 167.4, 150.1, 149.2, 148.9,144.5, 144.4, 143.6, 143.6, 143.6, 143.5, 137.6, 137.4, 136.2, 136.1, 135.4,133.5, 133.3, 132.2, 132.0, 131.8, 131.6, 131.0, 130.9, 130.6, 129.1, 128.4,128.1, 127.8, 126.8, 126.8, 126.2, 126.1, 126.1, 125.7, 124.0, 56.5, 56.4,51.2, 51.2, 40.4, 29.9. 31P NMR (162 MHz, CDCl3) δ –21.63.旋光：[a]27D =–70 (c0.1, CHCl3)，熔点：105–106 ℃ HRMS (ESI) Calcd for C81H64O2P+ ([M+H]+): 1099.4635;Found: 1099.4638.
实施例12：(R)-7'-二{3,5-二-[二-(3,5-二甲基苯基)甲基]苯基}磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成：
操作与实施例2相同，白色固体，130 mg，收率 36%.1H NMR (400 MHz, CDCl3) δ:1H NMR (400 MHz, CDCl3) δ 7.20 (d, J = 7.4 Hz, 1H), 7.03–6.88 (m, 4H), 6.77(dd, J = 192.4, 7.1 Hz, 10H), 6.71 (d, J = 7.8 Hz, 2H), 6.55 (d, J = 7.4 Hz,3H), 6.53–6.44 (m, 15H), 6.16 (d, J = 4.1 Hz, 2H), 5.12 (s, 4H), 3.68 (dd, J= 15.4, 9.0 Hz, 1H), 2.91 (t, J = 8.1 Hz, 2H), 2.43 (d, J = 15.4 Hz, 1H),2.32–2.23 (m, 1H), 2.13 (d, J = 4.1 Hz, 48H), 2.09–1.94 (m, 1H).31P NMR (162MHz, CDCl3) δ –21.62. 13C NMR (101 MHz, CDCl3) δ 167.5, 150.5, 149.4, 149.2,144.7, 144.6, 143.9, 143.9, 143.8, 140.0, 139.9, 137.5, 137.5, 135.3, 135.1,133.0, 133.0, 131.6, 130.2, 130.2, 130.0, 128.5, 128.2, 127.9, 127.8, 127.3,126.8, 126.8, 125.7, 124.1, 117.2, 77.3, 56.5, 51.5, 51.4, 41.9, 41.7, 40.7,30.1, 28.7, 28.5, 27.6, 27.4, 24.3, 24.2, 21.4, 13.7. 31P NMR (162 MHz, CDCl3)δ –21.62.旋光：[a]27D =–72 (c 0.1, CHCl3)，熔点：132–133 ℃ HRMS (ESI) Calcd forC97H96O2P+ ([M+H]+): 1323.7142; Found: 1323.7137.
实施例13：(R)-7'-二{3,5-二-[二-(3,5-二异丙基苯基)甲基]苯基}磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮的合成：
操作与实施例2相同，白色固体，301 mg，收率 60%. 1H NMR (400 MHz, CDCl3) δ：1HNMR (400 MHz, CDCl3) δ 7.14 (dd, J = 5.8, 2.6 Hz, 1H), 6.98 (dd, J = 5.7, 2.2Hz, 2H), 6.94 (d, J = 1.7 Hz, 1H), 6.91–6.84 (m, 4H), 6.84–6.78 (m, 8H), 6.69(dd, J = 7.4, 1.8 Hz, 3H), 6.64 (dd, J = 7.1, 1.6 Hz, 8H), 6.59 (dd, J = 7.0,1.7 Hz, 8H), 6.06 (d, J = 8.1 Hz, 1H), 5.74 (t, J = 7.5 Hz, 1H), 5.16 (d, J =4.8 Hz, 4H), 3.77 (dd, J = 15.3, 9.4 Hz, 1H), 2.94–2.77 (m, 2H), 2.67 (ddt, J= 9.7, 6.7, 4.8 Hz, 16H), 2.47 (d, J = 15.3 Hz, 1H), 2.27–2.09 (m, 1H), 2.05–1.92 (m, 1H), 1.12–1.00 (m, 96H). 13C NMR (101 MHz, CDCl3) δ 167.3, 150.0,149.3, 149.0, 148.3, 148.2, 148.2, 148.1, 144.4, 144.4, 144.3, 144.3, 144.2,144.0, 143.8, 143.7, 143.6, 137.1, 137.0, 136.1, 136.0, 135.6, 134.0, 133.8,132.8, 132.6, 131.9, 131.7, 131.0, 130.7, 130.2, 128.4, 127.7, 127.2, 125.6,125.2, 125.1, 125.0, 124.1, 122.0, 121.9, 121.9, 116.5, 57.4, 57.2, 40.3,34.1, 34.0, 34.0, 34.0, 30.0, 24.1, 24.1, 24.0, 24.0. 31P NMR (162 MHz, CDCl3)δ –22.64. 旋光：[a]27D =–66 (c 0.1, CHCl3)，熔点：88–89 ℃ HRMS (ESI) Calcd forC129H160O2P+ ([M+H]+): 1772.2150; Found:.1772.2154.
实施例14：(R)-7'-二(3,5-二叔丁基-4-甲氧基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮（环辛二烯）氯化铱络合物的合成：
在手套箱中，取配体(R)-7'-二(3,5-二叔丁基-4-甲氧基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮，[Ir(COD)Cl]2（336 mg，0.5 mmol）于干燥洁净装有磁力搅拌子的50 mL Schlenk管中并封口取出。在氩气下加入无水二氯甲烷（20 mL），室温下搅拌反应30min，溶液由橙红色变为无色，TLC点板监测络合情况，（石油醚/乙酸乙酯 = 5:1）。反应结束后真空脱除溶剂，柱层析分离（石油醚/乙酸乙酯 = 5:1-1:1），得到催化剂(R)-7'-二(3,5-二叔丁基-4-甲氧基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮（环辛二烯）氯化铱络合物，白色固体，1.0 g，收率95%。熔点：269- 270 ℃。旋光：[a]26D = –50.8 (c 0.5,CHCl3)，HRMS (ESI) Calcd for C55H71ClIrNaO4P+ ([M + Na]+): 1077.4300; Found:1077.4260.1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 7.4 Hz, 1H), 7.43 (t, J = 7.6Hz, 1H), 7.36 (t, J = 8.6 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 6.80 (t, J = 7.6Hz, 1H), 5.90 (t, J = 7.4 Hz, 1H), 5.77 (d, J = 11.0 Hz, 1H), 5.30 (d, J =7.6 Hz, 1H), 5.17 (q, J = 6.6 Hz, 1H), 5.03–4.89 (m, 1H), 3.93 (d, J = 4.9Hz, 2H), 3.72 (s, 3H), 3.64 (s, 3H), 3.41–3.23 (m, 1H), 3.09 (td, J = 9.4,9.0, 4.9 Hz, 2H), 2.89 (dd, J = 16.0, 8.5 Hz, 1H), 2.78–2.50 (m, 4H), 2.40(dtd, J = 20.0, 12.4, 11.7, 8.8 Hz, 2H), 2.29–2.16 (m, 2H), 1.55–1.13 (m,36H), -16.79 (d, J = 9.4 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 175.5, 161.3,161.1, 161.1, 150.4, 149.2, 149.0, 147.3, 147.2, 143.3, 131.7, 130.2, 128.4,127.6, 127.3, 127.1, 126.9, 126.8, 124.3, 123.8, 123.7, 123.2, 122.9, 122.3,121.2, 115.1, 98.6, 98.4, 98.2, 98.1, 89.5, 78.8, 64.2, 51.9, 51.8, 46.1,38.0, 37.9, 35.9, 35.4, 34.8, 34.7, 31.9, 30.4, 29.6, 29.4, 28.2, 26.9, 26.8,26.8, 26.4, 26.3. 31P NMR (162 MHz, CDCl3) δ 3.22.
实施例15：不对称催化氢化(E)-3-苯基-2-丁烯酸钠：
在手套箱中称取底物(E)-3-苯基-2-丁烯酸钠（0.3 mmol），催化剂(R)-7'-二(3,5-二叔丁基-4-甲氧基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮（环辛二烯）氯化铱络合物（0.0015 mmol）加入到装有磁力搅拌子的氢化内管中封口取出，并置于氢化釜中。用氩气快速置换反应釜中的气体三次，随后用注射器将甲苯与甲醇的混合溶剂4 mL（甲苯/甲醇 = 98：2，v/v）加入氢化反应釜中，搅拌溶解。用氢气快速置换反应釜中的气体三次，调节氢气压力到20 atm，置于65 ℃油浴中加热反应24 h后，缓慢释放出反应釜中的氢气。反应液用旋转蒸发仪脱除溶剂，然后用乙酸乙酯（0.5 mL）洗涤产物得到产物，1H NMR测定转化率。产物用亚硫酰氯和乙醇衍生化为相应的乙酯后使用手性高效液相色谱测定ee值。白色固体，收率99%，95% ee，旋光：[a]26D = -18.8 (c 0.5, MeOH)，熔点：205–206 ℃1H NMR(400 MHz, CD3OD) δ 7.20–7.09 (m, 4H), 7.01 (tt, J = 5.7, 2.7 Hz, 1H), 3.13(dp, J = 9.2, 6.8 Hz, 1H), 2.36 (dd, J = 13.8, 6.2 Hz, 1H), 2.25 (dd, J =13.8, 9.1 Hz, 1H), 1.17 (d, J = 6.9 Hz, 3H). 13C NMR (101 MHz, CD3OD) δ 179.9,147.4, 127.8, 127.8, 126.4, 125.4, 37.3, 20.9.HRMS (ESI) Calcd for C10H11O2 –([M–Na]–): 163.0765; Found: 163.0755. 高效液相色谱分离条件：Chiralcel OD-Hcolumn (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 98:2；温度：20 ℃；流速：0.5 mL/min；检测波长：210 nm；t R (major) = 9.63 min；t S (minor) = 15.48 min。
实施例16：不对称催化氢化(E)-3-对甲基苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%，95% ee，旋光：[a]26D =-20.4 (c 0.5, MeOH)，熔点：198–200 ℃，1H NMR (400 MHz, CD3OD) δ 7.15 (d, J = 8.1Hz, 2H), 7.07 (d, J = 7.9 Hz, 2H), 3.21 (dp, J = 9.2, 6.8 Hz, 1H), 2.51–2.31(m, 2H), 2.29 (s, 3H), 1.26 (d, J = 6.9 Hz, 3H).13C NMR (101 MHz, CD3OD) δ180.1, 144.3, 134.7, 128.4, 126.3, 36.8, 20.9, 19.6. HRMS (ESI) Calcd forC11H13O2 –([M–Na]–): 177.0921; Found: 177.0913. 高效液相色谱分离条件：ChiralcelOJ-3 column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 99:1；温度：20 ℃；流速：0.5 mL/min；检测波长：210 nm；t 1 (minor) = 9.63 min；t 2 (major) = 15.48 min。
实施例17：不对称催化氢化(E)-3-对甲氧基苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%，97% ee，旋光：[a]26D=-24.8 (c 0.5, MeOH)，熔点：201–203 ℃ 1H NMR (400 MHz, CD3OD) δ 7.17 (d, J = 8.6Hz, 2H), 6.81 (d, J = 8.7 Hz, 2H), 3.73 (s, 3H), 3.20 (dp, J = 8.9, 6.8 Hz,1H), 2.51–2.29 (m, 2H), 1.25 (d, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CD3OD) δ180.2, 157.8, 139.4, 127.2, 113.2, 54.2, 36.4, 21.2.HRMS (ESI) Calcd forC10H13O3 –([M–Na]–): 193.0870; Found:193.0863. 高效液相色谱分离条件：ChiralcelOJ-3 column (25 cm ´ 0.46 cm ID)+OJ-H column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 99.5:0.5；温度：20 ℃；流速：0.5 mL/min；检测波长：210 nm；t 1 (major) = 37.45min；t 2 (minor) = 41.22 min。
实施例18：不对称催化氢化(E)-3-对氯苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%，93% ee，旋光：[a]26D =-25.6 (c 0.5, MeOH)，熔点：227–229 ℃ 1H NMR (400 MHz, CD3OD) δ 7.26 (s, 3H),3.25 (dp, J = 8.5, 6.8 Hz, 1H), 2.52–2.26 (m, 2H), 1.27 (d, J = 7.0 Hz, 3H).13C NMR (101 MHz, CD3OD) δ 179.6, 146.1, 131.0, 128.1, 127.9, 46.6, 36.7,20.9.HRMS (ESI) Calcd for C10H10ClO2 – ([M–Na]–): 197.0375; Found:197.0370. 高效液相色谱分离条件：AD-3Chiralcel column (25 cm ´ 0.46 cm ID) + AD-H Chiralcelcolumn (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 99.5:0.5 ；温度：20 ℃；流速：0.5 mL/min；检测波长：210 nm；t 1 (minor) = 20.75 min；t 2 (major) = 21.60 min。
实施例19：不对称催化氢化(E)-3-对氟苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%， 96% ee，旋光：[a]26D =-22.4 (c 0.5, MeOH)，熔点：206–208 ℃ 1H NMR (400 MHz, CD3OD) δ 7.32–7.20 (m,2H), 7.02–6.90 (m, 2H), 3.24 (dp, J = 8.8, 6.9 Hz, 1H), 2.49–2.29 (m, 2H),1.25 (d, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CD3OD) δ 180.3, 144.4, 128.2,127.3, 125.2, 48.7, 43.2, 41.4, 30.9, 30.3, 26.3, 26.3, 26.2. HRMS (ESI)Calcd for C10H10FO2 – ([M–Na]–):181.0661; Found: 181.0670. 高效液相色谱分离条件：OJ-3 Chiralcel column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 90:10；温度：20 ℃；流速：1.0 mL/min；检测波长：210 nm；t 1 (major) = 13.51 min；t 2 (minor) = 15.68 min。
实施例20：不对称催化氢化(E)-3-对溴苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%，92 % ee，旋光：[a]26D =-24.4 (c 0.5, MeOH)，熔点：245–246 ℃ 1H NMR (400 MHz, CD3OD) δ 7.37 (d, J = 8.0Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 3.30–3.15 (m, 1H), 2.50–2.28 (m, 2H), 1.26(d, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CD3OD) δ 179.6, 146.6, 130.9, 128.5,118.9, 46.5, 36.8, 20.9.HRMS (ESI) Calcd for C10H10BrO2 – ([M–Na]–): 240.9870,242.9849; Found: 240.9875, 242.9853. 高效液相色谱分离条件：AD-H Chiralcelcolumn (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 90:10；温度：20 ℃；流速： 1.0 mL/min；检测波长：210 nm；t 1 (major) = 11.30 min；t 2 (minor) = 12.79 min。
实施例21：不对称催化氢化(E)-3-间甲基苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%，94% ee，旋光：[a]26D =-24.4 (c 0.5, MeOH)，熔点：204–206 ℃ 1H NMR (400 MHz, CD3OD) δ 7.12 (t, J = 7.5Hz, 1H), 7.09–7.00 (m, 2H), 6.94 (d, J = 7.4 Hz, 1H), 3.21 (dp, J = 9.1, 6.8Hz, 1H), 2.46 (dd, J = 13.8, 6.2 Hz, 1H), 2.35 (dd, J = 13.8, 9.0 Hz, 1H),2.29 (s, 3H), 1.26 (d, J = 6.9 Hz, 3H). 13C NMR (101 MHz, CD3OD) δ 180.1,147.3, 137.3, 127.7, 127.1, 126.1, 123.4, 46.8, 37.2, 21.0, 20.2. HRMS (ESI)Calcd for C11H13O2 – ([M–Na]–): 177.0921; Found:. 177.0913高效液相色谱分离条件：OD-H Chiralcel column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 98:2；温度：20 ℃；流速：0.5 mL/min；检测波长：210 nm；t 1 (major) = 8.59 min；t 2 (minor) = 11.76 min。
实施例22：不对称催化氢化(E)-3-间甲氧基苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%，91% ee，旋光：[a]26D =-21.6(c 0.5, MeOH)，熔点：195–197 ℃, 1H NMR (400 MHz, CD3OD) δ 7.17 (t, J = 7.9Hz, 1H), 6.89–6.80 (m, 2H), 6.71 (ddd, J = 8.2, 2.5, 0.9 Hz, 1H), 3.78 (s,3H), 3.23 (dp, J = 9.0, 6.8 Hz, 1H), 2.48 (dd, J = 13.9, 6.2 Hz, 1H), 2.37(dd, J = 13.9, 9.0 Hz, 1H), 1.28 (d, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CD3OD)δ 180.1, 159.6, 149.0, 128.8, 118.8, 112.2, 110.8, 54.2, 46.7, 37.3,20.9.HRMS (ESI) Calcd for C11H13O3 – ([M–Na]–): 193.0870; Found:193.0863. 高效液相色谱分离条件：OJ-3Chiralcel column (25 cm ´ 0.46 cm ID)+ OJ-H Chiralcelcolumn (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 99.5:0.5；温度：20 ℃；流速： 0.5mL/min；检测波长：210 nm；t 1 (major) = 12.45 min；t 2 (minor) = 19.00 min。
实施例23：不对称催化氢化(E)-3-间氯苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%， 86% ee，旋光：[a]26D= -12.4(c 0.5, MeOH)，熔点：197–199 ℃ 1H NMR (400 MHz, CD3OD) δ 7.35 (ddd, J =12.1, 7.9, 1.5 Hz, 2H), 7.25 (td, J = 7.6, 1.4 Hz, 1H), 7.13 (td, J = 7.6,1.7 Hz, 1H), 3.88–3.68 (m, 1H), 2.56 (dd, J = 14.2, 5.6 Hz, 1H), 2.39 (dd, J= 14.2, 9.5 Hz, 1H), 1.27 (d, J = 6.9 Hz, 3H). 13C NMR (101 MHz, CD3OD) δ179.6, 144.3, 129.0, 127.0, 126.8, 126.8, 44.6, 33.2, 19.8.HRMS (ESI) Calcdfor C10H10ClO2 – ([M–Na]–): 197.0375; Found:197.0369. 高效液相色谱分离条件：IC-3Chiralcel column (25 cm ´ 0.46 cm ID)×2；正己烷/异丙醇 = 99.5:0.5；温度：20 ℃；流速：0.5 mL/min；检测波长：210 nm；t 1 (major) = 23.63 min；t 2 (minor) = 15.04 min。
实施例24：不对称催化氢化(E)-3-邻甲基苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%， 94% ee，旋光：[a]26D =-13.2(c 0.5, MeOH)，熔点：206–208 ℃ 1H NMR (400 MHz, CD3OD) δ 7.21 (d, J = 7.7Hz, 1H), 7.14–7.05 (m, 2H), 7.00 (td, J = 7.4, 1.4 Hz, 1H), 3.53 (dp, J =9.3, 6.7 Hz, 1H), 2.47 (dd, J = 14.0, 5.9 Hz, 1H), 2.42–2.32 (m, 4H), 1.23(d, J = 6.9 Hz, 3H). 13C NMR (101 MHz, CD3OD) δ 180.2, 145.3, 134.8, 129.7,125.7, 125.1, 124.8, 45.7, 32.2, 20.5, 18.3. HRMS (ESI) Calcd for C11H13O2 –([M–Na]–): 177.0921; Found:177.0912.高效液相色谱分离条件：OJ-3 Chiralcelcolumn (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 =90:10；温度：20 ℃；流速： 1 mL/min；检测波长：210 nm；t 1 (major) = 13.96 min；t 2 (minor) = 16.00 min。
实施例25：不对称催化氢化(E)-3-邻甲氧基苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%，90% ee，旋光：[a]26D =-7.6(c 0.5, MeOH)，熔点：153–155 ℃, 1H NMR (400 MHz, CD3OD) δ 7.20 (dd, J =7.5, 1.7 Hz, 1H), 7.13 (ddd, J = 8.2, 7.4, 1.7 Hz, 1H), 6.94–6.82 (m, 2H),3.82 (s, 3H), 3.74–3.60 (m, 1H), 2.54 (dd, J = 13.9, 5.5 Hz, 1H), 2.36 (dd, J= 14.0, 9.8 Hz, 1H), 1.24 (d, J = 6.9 Hz, 3H). 13C NMR (101 MHz, CD3OD) δ180.4, 156.9, 135.3, 126.3, 126.2, 120.1, 110.1, 54.3, 44.8, 30.4, 19.6. HRMS(ESI) Calcd for C11H13O3 – ([M–Na]–): 193.0870; Found:193.0862.高效液相色谱分离条件：OJ-3 Chiralcel column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 =98:2；温度：20℃；流速：0.5 mL/min；检测波长： 210 nm；t 1 (major) = 13.87 min；t 2 (minor) = 15.33min。
实施例26：不对称催化氢化(E)-3-邻氯苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%，88 % ee，旋光：[a]26D =-36 (c 0.5, MeOH)，熔点：146–149 ℃, 1H NMR (400 MHz, CD3OD) δ 7.29–7.15 (m,3H), 7.13 (dt, J = 7.6, 1.9 Hz, 1H), 3.23 (dt, J = 8.6, 6.8 Hz, 1H), 2.44(dd, J = 13.9, 6.7 Hz, 1H), 2.35 (dd, J = 13.9, 8.6 Hz, 1H), 1.26 (d, J = 6.9Hz, 3H). 13C NMR (101 MHz, CD3OD) δ 179.6, 149.7, 133.6, 129.4, 126.6, 125.5,125.0, 46.4, 37.1, 20.9. HRMS (ESI) Calcd for C10H10ClO2 – ([M–Na]–): 197.0375;Found:197.0368. 高效液相色谱分离条件：AD-H Chiralcel column (25 cm ´ 0.46 cmID)；正己烷/异丙醇 = 98:2；温度：20 ℃；流速：0.5 mL/min；检测波长：210 nm； t 1 (minor)= 8.16 min；t 2 (major) = 9.43 min。
实施例27：不对称催化氢化(E)-3-邻三氟甲基苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%，96% ee，旋光：[a]26D = -20 (c 0.5, MeOH)，熔点：273–276 ℃, 1H NMR (400 MHz, CD3OD) δ 7.69–7.51 (m, 3H),7.37–7.25 (m, 1H), 3.80–3.67 (m, 1H), 2.58–2.40 (m, 2H), 1.32 (d, J = 6.7 Hz,3H). 13C NMR (101 MHz, CD3OD) δ 179.2, 146.7, 131.9, 127.8, 127.2 (d, J = 28.7Hz), 125.6, 125.0 (q, J = 5.9 Hz), δ 124.7 (q, J = 273.4 Hz), 45.9, 32.4,21.4. HRMS (ESI) Calcd for C11H10F3O2 – ([M–Na]–): 231.0638; Found: 231.0636. 高效液相色谱分离条件：OJ-3 Chiralcel column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 =90:10；温度：20 ℃；流速：1.0 mL/min；检测波长：220 nm；t 1 (major) = 9.35 min；t 2(minor) = 10.06 min。
实施例28：不对称催化氢化(E)-3,4-二苯基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%， 92% ee，旋光：[a]26D =55.6 (c 0.5, MeOH)，熔点：149 ℃, 1H NMR (400 MHz, CD3OD) δ 7.10 (dt, J = 26.4,8.0 Hz, 8H), 7.00 (d, J = 7.5 Hz, 2H), 3.48–3.36 (m, 1H), 3.01 (dd, J = 13.4,5.7 Hz, 1H), 2.81 (dd, J = 13.4, 9.1 Hz, 1H), 2.59–2.43 (m, 2H). 13C NMR (101MHz, CD3OD) δ 179.7, 144.7, 140.5, 128.9, 127.5, 127.5, 127.4, 125.4, 125.2,45.1, 44.5, 42.5. HRMS (ESI) Calcd for C16H15O2 – ([M–Na]–): 239.1078; Found:239.1075.高效液相色谱分离条件：OD-3 Chiralcel column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 99.5:0.5；温度：20 ℃；流速：210 mL/min；检测波长：210 nm；t 1 (major) =17.88 min；t 2 (minor) = 25.23 min。
实施例29：不对称催化氢化(E)-3-环丙基-3-苯基丙烯酸钠：
操作与实施例15相同，白色固体，收率99%，94% ee，旋光：[a]26D =28.8 (c 0.5, MeOH)，熔点：245–247 ℃, 1H NMR (400 MHz, CD3OD) δ 7.31–7.18 (m,4H), 7.12 (t, J = 7.1 Hz, 1H), 2.62 (dd, J = 13.6, 7.4 Hz, 1H), 2.54 (dd, J =13.6, 7.7 Hz, 1H), 2.45–2.34 (m, 1H), 1.08–0.94 (m, 1H), 0.54 (dp, J = 10.1,3.6 Hz, 1H), 0.34 (tt, J = 8.8, 4.2 Hz, 2H), 0.08 (dh, J = 9.1, 4.2 Hz, 1H).13C NMR (101 MHz, CD3OD) δ 178.4, 144.0, 126.0, 125.6, 123.8, 43.4, 15.6, 2.8,1.4. HRMS (ESI) Calcd for C12H13O2 – ([M–Na]–):189.0921 ; Found: 189.0914.高效液相色谱分离条件：OD-H Chiralcel column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 99:1；温度：20 ℃；流速：1.0 mL/min；检测波长：210 nm；t 1 (major) = 8.92 min；t 2 (minor) =14.45 min。
实施例30：不对称催化氢化(E)-3-环己基-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%，90% ee，旋光：[a]26D =-27.2 (c 0.5, MeOH)，熔点：317–320 ℃, 1H NMR (400 MHz, CD3OD) δ 7.27–7.16 (m,4H), 7.16–7.09 (m, 1H), 2.96 (dt, J = 9.0, 6.7 Hz, 1H), 2.70 (dd, J = 14.2,6.4 Hz, 1H), 2.43 (dd, J = 14.2, 9.0 Hz, 1H), 1.88 (dt, J = 12.7, 3.2 Hz,1H), 1.75 (ddt, J = 12.5, 4.8, 2.4 Hz, 1H), 1.69–1.57 (m, 2H), 1.56–1.45 (m,2H), 1.33–0.93 (m, 4H), 0.89–0.76 (m, 1H). 13C NMR (101 MHz, CD3OD) δ 180.5,144.4, 128.2, 127.3, 125.3, 48.7, 43.2, 41.4, 31.0, 30.3, 26.4, 26.3, 26.3.HRMS (ESI) Calcd for C15H19O2 – ([M–Na]–): 231.1391; Found:231.1388.高效液相色谱分离条件：OD-H Chiralcel column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 99:1；温度：20 ℃；流速：0.5 mL/min；检测波长：210 nm；t 1 (minor) = 11.28 min；t 2 (major) =12.58 min。
实施例31：不对称催化氢化(E)-3-(2-萘基)-2-丁烯酸钠：
操作与实施例15相同，白色固体，收率99%，91% ee，旋光：[a]26D= 4.8 (c 0.5, MeOH)，熔点：195–198 ℃, 1H NMR (400 MHz, CD3OD) δ 8.33 (d, J =8.5 Hz, 1H), 7.81 (dd, J = 8.2, 1.3 Hz, 1H), 7.66 (d, J = 7.9 Hz, 1H), 7.51(ddd, J = 8.5, 6.7, 1.5 Hz, 1H), 7.47–7.36 (m, 3H), 4.19 (ddd, J = 9.8, 7.0,5.1 Hz, 1H), 2.74 (dd, J = 14.2, 5.0 Hz, 1H), 2.49 (dd, J = 14.2, 9.8 Hz,1H), 1.45 (d, J = 6.8 Hz, 3H). 13C NMR (101 MHz, CD3OD) δ 180.2, 143.3, 134.1,131.3, 128.4, 125.9, 125.3, 125.2, 124.8, 123.1, 121.9, 46.1, 31.5, 20.5.HRMS(ESI) Calcd for C14H13O2 – ([M–Na]–): 213.0921 ; Found: 213.0924. 高效液相色谱分离条件： OD-H Chiralcel column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 98:2；温度：20 ℃；流速：1.0 mL/min；检测波长：210 nm；t 1 (major) = 5.55 min；t 2 (minor) = 18.50min。
实施例32：(Z)-5-甲氧基-5-氧代-3-苯基-2-戊烯酸钠：
操作与实施例15相同，白色固体，收率99%，86% ee，旋光：[a]26D =3.2 (c 0.5, MeOH)，熔点：148–150 ℃, 1H NMR (400 MHz, CD3OD) δ 7.33–7.17 (m,4H), 7.18–7.07 (m, 1H), 3.67–3.55 (m, 1H), 3.50 (s, 3H), 2.80 (dd, J = 15.2,5.6 Hz, 1H), 2.61 (dd, J = 15.2, 9.7 Hz, 1H), 2.47 (d, J = 8.2 Hz, 2H). 13CNMR (101 MHz, CD3OD) δ 178.9, 173.1, 144.1, 127.9, 127.0, 125.9, 50.4, 44.6,40.2, 39.6. HRMS (ESI) Calcd for C12H13O4 – ([M–Na]–): 221.0819 ; Found:221.0816.高效液相色谱分离条件： OJ-3 Chiralcel column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 90:10；温度：20 ℃；流速：1.0 mL/min；检测波长：210 nm；t 1 (minor) =32.89 min；t 2 (major) = 38.73 min。
实施例33：(E)-2-甲基-3-苯基丙烯酸钠：
操作与实施例15相同，白色固体，收率99%，81% ee，1H NMR (400MHz, CD3OD) δ 7.28–7.23 (m, 4H), 7.18–7.09 (m, 1H), 3.11–2.96 (m, 1H), 2.63–2.49 (m, 2H), 1.08 (d, J = 6.4 Hz, 3H). HRMS (ESI) Calcd for C10H17O2 – ([M–Na]–): 169.1234 ; Found: 169.1225. 高效液相色谱分离条件：OB-H Chiralcel column(25 cm ´ 0.46 cm ID)；正己烷/异丙醇= 99.5:0.5；温度：20 ℃；流速：0.5 mL/min；检测波长：220 nm；t 1 (major) = 11.72 min；t 2 (minor) = 14.07 min。
实施例34：(E)-3-苯基-2-庚烯酸钠：
操作与实施例15相同，白色固体，收率99%，91% ee，旋光：[a]26D =-3.2 (c 0.5, MeOH)，熔点：300–302 ℃, 1H NMR (400 MHz, CD3OD) δ 7.22 (d, J = 7.1Hz, 4H), 7.16–7.06 (m, 1H), 3.14–2.99 (m, 1H), 2.53–2.34 (m, 2H), 1.79–1.66(m, 1H), 1.66–1.48 (m, 1H), 1.38–0.99 (m, 4H), 0.82 (t, J = 7.2 Hz, 3H). 13CNMR (101 MHz, CD3OD) δ 180.1, 145.7, 127.7, 127.2, 125.4, 45.8, 43.1, 35.6,29.5, 22.3, 13.0. HRMS (ESI) Calcd for C13H17O2 – ([M–Na]–): 205.1234; Found:205.1227高效液相色谱分离条件：AD-H Chiralcel column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 90:10；温度：20 ℃；流速：1.0 mL/min；检测波长：210 nm；t 1 (minor) = 8.43min；t 2 (major) = 9.96 min。
实施例35：不对称催化氢化(E)-3-环丙基-3-(3-甲氧基苯基)丙烯酸钠：
在手套箱中称取底物(E)-3-环丙基-3-(3-甲氧基苯基)丙烯酸钠（1.2 g，5 mmol），催化剂(R)-7'-二(3,5-二叔丁基-4-甲氧基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮（环辛二烯）氯化铱络合物（10 mg，0.01 mmol）以及乙酸（0.2 mmol）加入到装有磁力搅拌子的氢化内管中封口取出，并置于氢化釜中。用氩气快速置换反应釜中的气体三次，随后用注射器将甲苯与甲醇的混合溶剂（甲苯/甲醇 = 98:2，v/v）125 mL加入氢化反应釜中，搅拌溶解。用氢气快速置换反应釜中的气体三次，调节氢气压力到20atm，置于65℃油浴中加热反应48 h后，缓慢释放出反应釜中的氢气。反应液用旋转蒸发仪脱除溶剂，然后用乙酸乙酯（0.5 mL）洗涤产物，1H NMR测定转化率。产物用亚硫酰氯和乙醇衍生化为相应的乙酯后使用手性高效液相色谱测定ee值。产物白色固体，1.2 g，收率99%，95% ee，旋光：[a]26D = 26.0 (c 0.5, MeOH)，熔点：196-198 ℃，1H NMR (400 MHz, CD3OD) δ 7.20–7.09 (m, 4H), 7.01 (tt, J = 5.7, 2.7 Hz, 1H), 3.13 (dp, J = 9.2, 6.8 Hz, 1H),2.36 (dd, J = 13.8, 6.2 Hz, 1H), 2.25 (dd, J = 13.8, 9.1 Hz, 1H), 1.17 (d, J= 6.9 Hz, 3H). 13C NMR (101 MHz, CD3OD) δ 179.9, 147.4, 127.8, 127.8, 126.4,125.4, 37.3, 20.9. HRMS (ESI) Calcd for C13H15O3 –([M–Na]–): 219.1027; Found:219.1029. 高效液相色谱分离条件：OD-H Chiralcel column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 99:1；温度：20 ℃；流速：1.0 mL/min；检测波长：210 nm；t 1 (major) =6.93min；t 2 (minor)= 12.02 min。
实施例36：低催化剂用量下(E)-3-苯基-2-丁烯酸钠的不对称催化氢化：
在手套箱中称取底物(E)-3-苯基-2-丁烯酸钠（7.5 mmol），催化剂(R)-7'-二(3,5-二叔丁基-4-甲氧基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮（环辛二烯）氯化铱络合物（0.0015 mmol），(E)-3-苯基-2-丁烯酸（0.3 mmol%）加入到装有磁力搅拌子的氢化内管中封口取出，并置于氢化釜中。用氩气快速置换反应釜中的气体三次，随后用注射器将甲苯与甲醇的混合溶剂1000 mL（甲苯/甲醇 = 98：2，v/v）加入氢化反应釜中，搅拌溶解。用氢气快速置换反应釜中的气体三次，调节氢气压力到20 atm，置于65 ℃油浴中加热反应3天后，缓慢释放出反应釜中的氢气。反应液用旋转蒸发仪脱除溶剂，然后用乙酸乙酯（2 mL）洗涤产物得到产物，1H NMR测定转化率。产物用亚硫酰氯和乙醇衍生化为相应的乙酯后使用手性高效液相色谱测定ee值。白色固体，收率99%，93% ee。
实施例37：(E)-3-苯基-3-对甲基苯基丙烯酸钠的不对称催化氢化：
在手套箱中称取底物(E)-3-苯基-3-对甲基苯基丙烯酸钠（0.3 mmol），催化剂(R)-7'-二(3,5-二叔丁基-4-甲氧基苯基)磷基-2',3'-二氢螺[色满-4,1'-茚]-2-酮（环辛二烯）氯化铱络合物（0.0015 mmol）加入到装有磁力搅拌子的氢化内管中封口取出，并置于氢化釜中。用氩气快速置换反应釜中的气体三次，随后用注射器将甲苯与甲醇的混合溶剂（甲苯/甲醇 = 95：5，v/v）4 mL加入氢化反应釜中，搅拌溶解。用氢气快速置换反应釜中的气体三次，调节氢气压力到20 atm，室温（25-30 ℃）搅拌反应。反应结束后缓慢释放出反应釜中的氢气。反应液用旋转蒸发仪脱除溶剂，然后用乙酸乙酯（0.5 mL）洗涤产物，1H NMR测定转化率。产物用亚硫酰氯和乙醇衍生化为相应的乙酯后使用手性高效液相色谱测定ee值。
实施例38：(E)-3-苯基-3-对甲氧基苯基丙烯酸钠的不对称催化氢化：
操作与实施例37相同，白色固体，收率99%，92% ee，旋光：[a]29D = 0.4 (c 0.5, MeOH)，熔点：310-312 ℃1H NMR (400 MHz, CD3OD) δ 7.22 (dt, J =23.6, 8.1 Hz, 6H), 7.09 (t, J = 7.2 Hz, 1H), 6.78 (d, J = 8.4 Hz, 2H), 4.51(t, J = 7.9 Hz, 1H), 3.70 (s, 3H), 2.85 (d, J = 7.9 Hz, 2H). 13C NMR (101 MHz,CD3OD) δ 179.2, 157.9, 145.6, 137.3, 128.5, 127.8, 127.5, 125.4, 113.2, 54.2,47.3, 44.5.HRMS (ESI) Calcd for C16H15O3 –([M–Na]–): 255.1027; Found: 255.1026.高效液相色谱分离条件：Chiralcel OD-H column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇=95：5；温度：20 ℃；流速：1 mL/min；检测波长：210 nm；t 1 (minor) = 6.90 min；t 2 (major) = 8.6 min。
实施例39：(E)-3-苯基-3-对氯苯基丙烯酸钠的不对称催化氢化：
操作与实施例37相同，白色固体，收率99%，87% ee，旋光：[a]29D = 0.4 (c 0.5, MeOH)，熔点：242-244℃1H NMR (400 MHz, CD3OD) δ 7.29–7.17 (m,8H), 7.17–7.08 (m, 1H), 4.54 (t, J = 7.9 Hz, 1H), 2.86 (d, J = 8.0 Hz, 2H).13C NMR (101 MHz, CD3OD) δ 178.7, 144.7, 144.0, 131.2, 129.2, 128.0, 127.8,127.5, 125.7, 47.5, 44.2. HRMS (ESI) Calcd for C15H12ClO2 –([M–Na]–): 259.0531;Found: 259.0532.高效液相色谱分离条件：Chiralcel OD-H column (25 cm ´ 0.46 cmID)；正己烷/异丙醇 = 95：5；温度：20 ℃；流速：1 mL/min；检测波长：210 nm；t 1 (minor) =5.55 min；t 2 (major) = 7.17 min。
实施例39：(E)-3-苯基-3-对氟苯基丙烯酸钠的不对称催化氢化：
操作与实施例37相同，白色固体，收率99%，89% ee，旋光：[a]29D= -2.4 (c 0.5, MeOH)，熔点：242-245℃1H NMR (400 MHz, CD3OD) δ 7.32–7.18 (m,6H), 7.16–7.07 (m, 1H), 6.95 (t, J = 8.8 Hz, 2H), 4.55 (t, J = 7.9 Hz, 1H),2.86 (d, J = 8.0 Hz, 2H). 13C NMR (101 MHz, CD3OD) δ 178.8, 162.4, 160.0,145.0, 141.1 (d, J = 3.1 Hz), 129.2, 129.1, 127.9, 127.5, 125.6, 114.4,114.2, 44.4.HRMS (ESI) Calcd for C15H12FO2 –([M–Na]–): 243.0827; Found:243.0825.高效液相色谱分离条件：Chiralcel OD-H column (25 cm ´ 0.46 cm ID)+Chiralcel IA-3 column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 98:2；温度：20 ℃；流速：0.5 mL/min；检测波长：210 nm；t 1 (minor) = 26.7 min；t 2 (major) = 31.8 min。
实施例40：(E)-3-苯基-3-对氟苯基丙烯酸钠的不对称催化氢化：
操作与实施例37相同，白色固体，收率99%，88% ee，旋光：[a]29D = -0.4 (c 0.5, MeOH)，熔点：245-247℃1H NMR (400 MHz, CD3OD) δ 7.41–7.32 (m,2H), 7.30–7.16 (m, 6H), 7.16–7.08 (m, 1H), 4.54 (t, J = 7.9 Hz, 1H), 2.87 (d,J = 8.0 Hz, 2H). 13C NMR (101 MHz, CD3OD) δ 178.7, 144.6, 144.4, 130.8, 129.6,128.0, 127.5, 125.8, 119.2, 47.6, 44.1. HRMS (ESI) Calcd for C15H12BrO2 –([M–Na]–): 303.0026, 305.0006; Found: 303.0027，306.0036. 高效液相色谱分离条件：Chiralcel OD-H column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 95：5；温度：20 ℃；流速：1 mL/min；检测波长：210 nm；t 1 (minor) = 5.77 min；t 2 (major) = 7.50 min。
实施例41：(E)-3-苯基-3-间甲基苯基丙烯酸钠的不对称催化氢化：
操作与实施例37相同，白色固体，收率99%，88% ee，旋光：[a]29D= -4.8 (c 0.5, MeOH)，熔点：252-254℃1H NMR (400 MHz, CD3OD) δ 7.27 (d, J = 7.3Hz, 2H), 7.21 (t, J = 7.6 Hz, 2H), 7.13–7.03 (m, 4H), 6.92 (d, J = 7.0 Hz,1H), 4.52 (t, J = 7.9 Hz, 1H), 2.87 (d, J = 7.9 Hz, 2H), 2.25 (s, 3H). 13C NMR(101 MHz, CD3OD) δ 179.0, 145.3, 145.1, 137.3, 128.3, 127.7, 127.7, 127.5,126.1, 125.4, 124.6, 48.0, 44.3, 20.1. HRMS (ESI) Calcd for C16H15O2 –([M–Na]–):239.1078; Found: 239.1076.高效液相色谱分离条件：Chiralcel OD-H column (25 cm ´0.46 cm ID)；正己烷/异丙醇 = 95：5；温度：20 ℃；流速：1 mL/min；检测波长：210 nm；t 1 (minor) = 5.68 min；t 2 (major) = 6.27 min。
实施例42：(E)-3-苯基-3-间甲氧基苯基丙烯酸钠的不对称催化氢化：
操作与实施例37相同，白色固体，收率99%，88% ee，旋光：[a]29D= -2.4 (c 0.5, MeOH)，熔点：241-245 ℃. 1H NMR (400 MHz, CD3OD) δ 7.31–7.19 (m,4H), 7.16–7.06 (m, 2H), 6.89–6.80 (m, 2H), 6.68 (ddd, J = 8.2, 2.6, 0.9 Hz,1H), 4.53 (t, J = 7.9 Hz, 1H), 3.71 (s, 3H), 2.87 (d, J = 7.9 Hz, 2H). 13C NMR(101 MHz, CD3OD) δ 179.0, 159.6, 146.8, 145.1, 128.7, 127.8, 127.5, 125.5,119.9, 113.4, 110.9, 54.1, 48.1, 44.2. HRMS (ESI) Calcd for C16H15O3 –([M–Na]–):255.1027; Found: 255.1027. 高效液相色谱分离条件：Chiralcel OD-H column (25 cm´ 0.46 cm ID)；正己烷/异丙醇 =95：5；温度：20 ℃；流速：1 mL/min；检测波长：210 nm；t 1 (minor) = 6.90 min；t 2 (major) = 8.55 min。
实施例43：(E)-3-苯基-3-氯苯基丙烯酸钠的不对称催化氢化：
操作与实施例37相同，白色固体，收率99%，84% ee，旋光：[a]29D= -4.4 (c 0.5, MeOH)，熔点：253-255 ℃. 1H NMR (400 MHz, MeOD) δ 7.31–7.17 (m,7H), 7.17–7.07 (m, 2H), 4.55 (t, J = 7.94 Hz, 1H), 2.87 (d, J = 7.96 Hz, 2H).13C NMR (101 MHz, MeOD) δ 178.5, 147.6, 144.4, 133.7, 129.4, 128.1, 127.7,127.5, 126.1, 125.9, 125.7, 48.5, 44.0. HRMS (ESI) Calcd for C15H12ClO2 –([M–Na]–): 259.0531; Found: 259.0532. 高效液相色谱分离条件：Chiralcel OD-H column(25 cm ´ 0.46 cm ID)+ Chiralcel IA-3 column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 98：2；温度：20 ℃；流速：0.5 mL/min；检测波长：210 nm；t 1 (minor) = 27.73 min；t 2 (major) = 35.88 min。
实施例44：(E)-3-苯基-3-邻甲基苯基丙烯酸钠的不对称催化氢化：
操作与实施例37相同，白色固体，收率99%，97% ee，旋光：[a]29D= 76 (c 0.5, MeOH)，熔点：276-278 ℃. 1H NMR (400 MHz, CD3OD) δ 7.23–7.16 (m,4H), 7.17–7.08 (m, 2H), 7.08–7.02 (m, 2H), 4.78 (t, J = 7.9 Hz, 1H), 2.85(qd, J = 14.7, 7.9 Hz, 2H), 2.24 (s, 3H). 13C NMR (101 MHz, CD3OD) δ 179.2,145.0, 142.5, 136.2, 129.9, 127.7, 126.4, 125.6, 125.4, 125.4, 44.8, 44.2,18.7.HRMS (ESI) Calcd for C16H15O2 –([M–Na]–): 239.1078; Found: 239.1076.高效液相色谱分离条件：Chiralcel OD-H column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 95：5；温度：20 ℃；流速：1 mL/min；检测波长：210 nm；t 1 (major) = 5.98 min；t 2 (minor) =7.43 min。
实施例45：(E)-3-苯基-3-邻甲氧基苯基丙烯酸钠的不对称催化氢化：
作与实施例37相同，白色固体，收率99%，90% ee，旋光：[a]29D =-11.2 (c 0.5, MeOH)，熔点：260-262℃ 1H NMR (400 MHz, CD3OD) δ 7.28 (d, J = 7.6Hz, 3H), 7.20 (t, J = 7.5 Hz, 2H), 7.14 (t, J = 7.8 Hz, 1H), 7.11–7.05 (m,1H), 6.93–6.82 (m, 2H), 4.99 (t, J = 8.2 Hz, 1H), 3.72 (s, 3H), 2.97–2.79 (m,2H). 13C NMR (101 MHz, CD3OD) δ 179.4, 157.0, 145.2, 133.3, 127.7, 127.5,127.4, 126.8, 125.1, 119.9, 110.4, 54.4, 43.3, 41.1.HRMS (ESI) Calcd forC16H15O3 –([M–Na]–): 255.1027; Found: 255.1027. 高效液相色谱分离条件：ChiralcelOD-H column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 = 95：5；温度：20 ℃；流速：1 mL/min；检测波长：210 nm；t 1 (major) = 6.39 min；t 2 (minor) = 15.15 min。
实施例46：(E)-3-苯基-3-邻氯苯基丙烯酸钠的不对称催化氢化：
操作与实施例37相同，白色固体，收率99%，89% ee，旋光：[a]29D= 26 (c 0.2, MeOH)，熔点：280-284℃1H NMR (400 MHz, CD3OD) δ 7.46 (dd, J = 7.8,1.7 Hz, 1H), 7.36–7.28 (m, 2H), 7.28–7.19 (m, 4H), 7.13 (dtd, J = 7.2, 5.1,2.3 Hz, 2H), 5.10 (t, J = 8.0 Hz, 1H), 2.99–2.83 (m, 2H). 13C NMR (101 MHz,CD3OD) δ 178.6, 143.8, 142.1, 133.9, 129.2, 128.5, 127.8, 127.1, 126.5,125.6, 44.5, 43.8.HRMS (ESI) Calcd for C15H12ClO2 –([M–Na]–): 259.0531; Found:259.0533. 高效液相色谱分离条件：Chiralcel OD-H column (25 cm ´ 0.46 cm ID)+Chiralcel IA-3 column (25 cm ´ 0.46 cm ID)；正己烷/异丙醇 =98：2；温度：20 ℃；流速：0.5 mL/min；检测波长：210 nm；t 1 (minor) = 6.40 min；t 2 (major) = 8.62 min。
实施例47：(Z)-3-苯基-3-对甲基苯基丙烯酸钠的不对称催化氢化：
操作与实施例37相同，白色固体，收率99%，92% ee，旋光：[a]29D = -6.6 (c 1, MeOH) 高效液相色谱分离条件：Chiralcel OD-H column (25 cm ´0.46 cm ID)；正己烷/异丙醇 = 95：5；温度：20 ℃；流速：1 mL/min；检测波长：210 nm；t 1 (minor) = 4.85 min；t 2 (major) = 6.40 min。
实施例48：(Z)-3-苯基-3-对甲氧基苯基丙烯酸钠的不对称催化氢化：
操作与实施例37相同，白色固体，收率99%，91% ee，旋光：[a]29D = -7.6 (c 1, MeOH)高效液相色谱分离条件：Chiralcel OD-H column (25 cm ´0.46 cm ID)；正己烷/异丙醇 =95：5；温度：20 ℃；流速：1 mL/min；检测波长：210 nm；t 1 (major) = 6.89 min；t 2 (minor) = 8.55 min。
实施例49：(Z)-3-苯基-3-对氯苯基丙烯酸钠的不对称催化氢化：
操作与实施例37相同，白色固体，收率99%，84% ee，旋光：[a]29D = -2.0 (c 1, MeOH)高效液相色谱分离条件：Chiralcel OD-H column (25 cm ´0.46 cm ID)；正己烷/异丙醇 = 95：5；温度：20 ℃；流速：1 mL/min；检测波长：210 nm；t 1 (major) = 5.54 min；t 2 (minor) = 7.14 min。/>
Claims (10)
1.一种手性螺[色满-4,1'-二氢茚]双齿配体铱络合物，其特征在于具有以下通式（I）结构：
通式（I）中：
R1为芳基，R2为卤原子、羧基、BF4 -、PF6 -、[Rh(cod)2]SbF6 -、OTf-。
2.按照权利要求1所述的手性螺[色满-4,1'-二氢茚]双齿配体铱络合物，其特征在于R1为芳基为被烷基或者烷氧基取代或者未取代的苯基，烷基=甲基、乙基、丙基、丁基；烷氧基为甲氧基、乙氧基、丙氧基、丁氧基。
3.权利要求1所述的手性螺[色满-4,1'-二氢茚]双齿配体铱络合物的合成方法，其特征在于通过下面的路线合成得到：
具体步骤为：
步骤一：起始原料(R/S)-7′-羟基-2′,3′-二氢螺[色满-4,1′-茚]-2-酮(R/S)-1在有机溶剂中在碱的促进下与三氟甲磺酸酯化试剂在0~60 ℃温度范围内反应得到(R/S)-7'-三氟甲基磺酰基氧基-2',3'-二氢螺[色满-4,1'-茚]-2-酮(R/S)-2；
步骤二：(R/S)-7'-三氟甲基磺酰基氧基-2',3'-二氢螺[色满-4,1'-茚]-2-酮(R/S)-2在有机溶剂、碱和0~60 ℃温度范围条件下，在膦配体和醋酸钯的催化下与二芳基磷氧发生偶联反应，随后在硅烷和碱的条件下还原得到目标配体(R/S)-7'-二芳基膦基-2',3'-二氢螺[色满-4,1'-茚]-2-酮(R/S)-II；
步骤三：配体(R/S)-7'-二芳基膦基-2',3'-二氢螺[色满-4,1'-茚]-2-酮(R/S)-II在有机溶剂中和铱金属前体在在0 ~60 ℃温度范围内反应得到催化剂（I）。
4.按照权利要求3所述的合成方法，其特征在于步骤一、步骤二所述的有机溶剂为二氯甲烷、甲苯、四氢呋喃、甲醇中的一种或几种。
5.按照权利要求3所述的合成方法，其特征在于步骤一、步骤二所述的碱为三乙胺、二异丙基乙基胺、碳酸钾、碳酸铯、1,4-二氮杂二环[2.2.2]辛烷、1,8-二氮杂二环[5.4.0]十一碳-7-烯、二甲胺基吡啶。
6.按照权利要求3所述的合成方法，其特征在于步骤一所述三氟甲磺酸酯化试剂为三氟甲磺酸酐、N-苯基双(三氟甲烷磺酰)亚胺；步骤二所述膦配体为1,3-双(二苯基膦)丙烷、1,4-双(二苯基膦)丁烷、1,1'-双(二苯基膦)二茂铁、1,1'-联萘-2,2'-双二苯膦；硅烷为二苯基硅烷、三氯硅烷。
7.按照权利要求3所述的合成方法，其特征在于步骤三所用二芳基磷氧中芳基为被烷基或者烷氧基取代或者未取代的苯基，烷基=甲基、乙基、丙基、丁基、芳基取代甲基，烷氧基为甲氧基、乙氧基、丙氧基、丁氧基。
8.按照权利要求3所述的合成方法，其特征在于步骤三所述有机溶剂为二氯甲烷、甲苯、四氢呋喃、甲醇中的一种或几种；铱金属前体为[Ir(cod)Cl]2（cod = 环辛二烯）、[Ir(cod)2]BF4、[Ir(cod)2]PF6、[Ir(cod)2]SbF6、[Ir(cod)2]OTf）。
9.权利要求1所述的手性螺[色满-4,1'-二氢茚]双齿配体铱络合物催化β,β–双取代丙烯酸以及盐的不对称氢化的方法，其特征在于经过如下步骤：
具体反应为：在氩气或氮气保护下，于氢化釜中加入β,β–双取代丙烯酸以及盐，随后加入有机溶剂搅拌溶解，充入氢气并在0~100 ℃温度范围内反应和2~100 atm氢气压力下搅拌反应3~200小时得到光学活性手性羧酸以及盐；所述有机溶剂为二氯甲烷、甲苯、四氢呋喃、甲醇、乙醇、异丙醇、叔丁醇中的一种或几种；在通式（III）中：R3、R4、R5为氢原子或卤原子、C1~C8烷基、C1~C8卤代烷基、C2~C8链烯基、C5~C14芳基烷基、C6~C12芳基烯基、-C1~C8烷氧基，芳氧基；R6为氢原子、钠原子、钾原子、锂原子、钙原子；当R6为氢原子时，需要加入碱如三乙胺、二异丙基乙基胺、碳酸钠、碳酸铯、碳酸钾；所得手性羧酸的构型既可以是(R)-构型也可以是(S)-构型；在低催化剂用量，即底物/催化剂>500时需要在反应体系中加入1-5% mol%的酸作为添加剂，包括乙酸、甲酸、盐酸或与底物相对应的共轭酸。
10.按照权利要求9所述的不对称氢化的方法，其特征在于R3为氢原子、甲基；R4为苯基或甲基、甲氧基、卤原子、三氟甲基取代芳基、萘基；R5为苯基或甲基、甲氧基、卤原子取代芳基、环己基、环丙基、苄基、正丁基、酯基；R6为钠原子。
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