CN116178232A - 一种手性羟基硒醚及其不对称合成方法 - Google Patents
一种手性羟基硒醚及其不对称合成方法 Download PDFInfo
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- CN116178232A CN116178232A CN202211584758.5A CN202211584758A CN116178232A CN 116178232 A CN116178232 A CN 116178232A CN 202211584758 A CN202211584758 A CN 202211584758A CN 116178232 A CN116178232 A CN 116178232A
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- Prior art keywords
- chiral
- asymmetric synthesis
- hydroxyseleno
- ether
- synthesis method
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- 238000011914 asymmetric synthesis Methods 0.000 title claims abstract description 49
- 238000000034 method Methods 0.000 title claims abstract description 27
- -1 hydroxy seleno Chemical group 0.000 title claims description 82
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 title abstract description 71
- 239000003054 catalyst Substances 0.000 claims abstract description 47
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- 238000009901 transfer hydrogenation reaction Methods 0.000 claims abstract description 6
- 150000004985 diamines Chemical class 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 150000004696 coordination complex Chemical class 0.000 claims abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 196
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 108
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 100
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 68
- 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 34
- 235000019253 formic acid Nutrition 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052741 iridium Inorganic materials 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical compound CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003446 ligand Substances 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 claims description 4
- 229910052707 ruthenium Inorganic materials 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 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
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-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
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 2
- 229910018286 SbF 6 Inorganic materials 0.000 claims description 2
- 239000004280 Sodium formate Substances 0.000 claims description 2
- 239000007864 aqueous solution Substances 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
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- YUWFEBAXEOLKSG-UHFFFAOYSA-N hexamethylbenzene Chemical compound CC1=C(C)C(C)=C(C)C(C)=C1C YUWFEBAXEOLKSG-UHFFFAOYSA-N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- BEZDDPMMPIDMGJ-UHFFFAOYSA-N pentamethylbenzene Chemical compound CC1=CC(C)=C(C)C(C)=C1C BEZDDPMMPIDMGJ-UHFFFAOYSA-N 0.000 claims description 2
- WQIQNKQYEUMPBM-UHFFFAOYSA-N pentamethylcyclopentadiene Chemical compound CC1C(C)=C(C)C(C)=C1C WQIQNKQYEUMPBM-UHFFFAOYSA-N 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229910052703 rhodium Inorganic materials 0.000 claims description 2
- 239000010948 rhodium Substances 0.000 claims description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 2
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 claims description 2
- 235000019254 sodium formate Nutrition 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- 150000003624 transition metals Chemical class 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 abstract description 3
- 229910052711 selenium Inorganic materials 0.000 abstract description 3
- 239000011669 selenium Substances 0.000 abstract description 3
- BTJGGGIJCQVKEV-UHFFFAOYSA-N O[Se]O Chemical compound O[Se]O BTJGGGIJCQVKEV-UHFFFAOYSA-N 0.000 abstract 1
- 150000001298 alcohols Chemical class 0.000 abstract 1
- 239000000758 substrate Substances 0.000 abstract 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 64
- 238000004128 high performance liquid chromatography Methods 0.000 description 64
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 64
- 239000012071 phase Substances 0.000 description 33
- 239000008346 aqueous phase Substances 0.000 description 32
- 239000012074 organic phase Substances 0.000 description 32
- 239000003208 petroleum Substances 0.000 description 32
- 238000000926 separation method Methods 0.000 description 32
- 238000002360 preparation method Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- UOPFIWYXBIHPIP-SFTDATJTSA-N n-[(1s,2s)-2-amino-1,2-diphenylethyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 UOPFIWYXBIHPIP-SFTDATJTSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 1
- RKLQIYWNDDRJHD-AWEZNQCLSA-N (1R)-1-phenyl-2-phenylselanylethanol Chemical compound C1(=CC=CC=C1)[C@H](C[Se]C1=CC=CC=C1)O RKLQIYWNDDRJHD-AWEZNQCLSA-N 0.000 description 1
- QZYCRLZJNSHFKJ-MRVPVSSYSA-N (2r)-1-phenylselanylpropan-2-ol Chemical compound C[C@@H](O)C[Se]C1=CC=CC=C1 QZYCRLZJNSHFKJ-MRVPVSSYSA-N 0.000 description 1
- 150000000179 1,2-aminoalcohols Chemical class 0.000 description 1
- ITUFDGWZZMDRLE-UHFFFAOYSA-N 1-(4-bromophenyl)-2-phenylselanylethanone Chemical compound C1=CC(Br)=CC=C1C(=O)C[Se]C1=CC=CC=C1 ITUFDGWZZMDRLE-UHFFFAOYSA-N 0.000 description 1
- JYZQJYHHWAITJQ-UHFFFAOYSA-N 1-methyl-4-propan-2-ylbenzene;ruthenium(2+) Chemical compound [Ru+2].CC(C)C1=CC=C(C)C=C1 JYZQJYHHWAITJQ-UHFFFAOYSA-N 0.000 description 1
- XARLJWRXSHZQKB-UHFFFAOYSA-N 1-naphthalen-2-yl-2-phenylselanylethanone Chemical compound O=C(C[Se]c1ccccc1)c1ccc2ccccc2c1 XARLJWRXSHZQKB-UHFFFAOYSA-N 0.000 description 1
- DNZZBCWKTYSELN-UHFFFAOYSA-N 1-phenyl-2-phenylselanylethanone Chemical compound C=1C=CC=CC=1C(=O)C[Se]C1=CC=CC=C1 DNZZBCWKTYSELN-UHFFFAOYSA-N 0.000 description 1
- JSSLATKTLCWQNP-UHFFFAOYSA-N 1-phenylselanylpropan-2-one Chemical compound CC(=O)C[Se]C1=CC=CC=C1 JSSLATKTLCWQNP-UHFFFAOYSA-N 0.000 description 1
- ATJIWFFNCMNQLC-UHFFFAOYSA-N 2-phenylselenophene Chemical compound C1=C[se]C(C=2C=CC=CC=2)=C1 ATJIWFFNCMNQLC-UHFFFAOYSA-N 0.000 description 1
- DQTKLICLJUKNCG-UHFFFAOYSA-N A-72363 A-1 Natural products CC(=O)NC1NCC(C(O)=O)C(O)C1O DQTKLICLJUKNCG-UHFFFAOYSA-N 0.000 description 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- QVLTVILSYOWFRM-UHFFFAOYSA-L CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C Chemical class CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C QVLTVILSYOWFRM-UHFFFAOYSA-L 0.000 description 1
- QICBZCXKJSWKQI-UHFFFAOYSA-N ClC=1C(=C(C=CC=1)[Ru+])Cl Chemical class ClC=1C(=C(C=CC=1)[Ru+])Cl QICBZCXKJSWKQI-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 1
- OHKMFOAYJDGMHW-UHFFFAOYSA-N [Si].[Se] Chemical compound [Si].[Se] OHKMFOAYJDGMHW-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical class [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- YWWZCHLUQSHMCL-UHFFFAOYSA-N diphenyl diselenide Chemical compound C=1C=CC=CC=1[Se][Se]C1=CC=CC=C1 YWWZCHLUQSHMCL-UHFFFAOYSA-N 0.000 description 1
- 238000007337 electrophilic addition reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- MMAGMBCAIFVRGJ-UHFFFAOYSA-J iridium(3+);1,2,3,4,5-pentamethylcyclopenta-1,3-diene;tetrachloride Chemical compound Cl[Ir+]Cl.Cl[Ir+]Cl.CC=1C(C)=C(C)[C-](C)C=1C.CC=1C(C)=C(C)[C-](C)C=1C MMAGMBCAIFVRGJ-UHFFFAOYSA-J 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- AJAZMOFONMJGNP-WMZOPIPTSA-N n-[(2s)-4-methyl-1-oxo-1-[[(2s)-3-oxo-4-(pyridin-2-ylsulfonylamino)butan-2-yl]amino]pentan-2-yl]-1-benzofuran-2-carboxamide Chemical class O=C([C@H](C)NC(=O)[C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)CNS(=O)(=O)C1=CC=CC=N1 AJAZMOFONMJGNP-WMZOPIPTSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Chemical class 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- DQTKLICLJUKNCG-ZTYPAOSTSA-N siastatin b Chemical compound CC(=O)N[C@H]1NC[C@H](C(O)=O)[C@H](O)[C@@H]1O DQTKLICLJUKNCG-ZTYPAOSTSA-N 0.000 description 1
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- PTMFUWGXPRYYMC-UHFFFAOYSA-N triethylazanium;formate Chemical compound OC=O.CCN(CC)CC PTMFUWGXPRYYMC-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C391/00—Compounds containing selenium
- C07C391/02—Compounds containing selenium having selenium atoms bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/02—Formation or introduction of functional groups containing oxygen of hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明涉及一种手性羟基硒醚及其不对称合成方法。该方法以α‑硒酮为原料,手性二胺与金属配合物为催化剂,通过不对称转移氢化的方式合成手性羟基硒醚。该方法操作简便、反应条件温和、原料易合成、底物适应性范围广、对映选择性高,在含硒的手性醇合成方面具有广阔应用前景。
Description
技术领域
本发明属于不对称催化技术领域,具体涉及一种手性羟基硒醚及其不对称合成方法。
背景技术
羟基硒醚是有机合成中的重要中间体,其可以转化为α,β-不饱和酮、1,3-噁唑烷酮、取代1,2-氨基醇,含氧杂环,取代四氢呋喃等多种类型化合物,此外还可用于天然产物的合成,如抗凝血的鞘氨醇,抗有丝分裂剂Siastatin B。
目前手性羟基硒醚的合成主要依靠金属有机硒试剂、二苯二硒、有机硅硒试剂及苯硒酚对环氧化合物的开环或者芳基硒卤对特定构型的烯烃亲电加成,这些方法涉及到敏感的硒试剂或复杂的制备方法,因此还需发展新的合成方法。目前不对称转移氢化方法尚未应用到手性羟基硒醚的合成中,该方法具有操作简单,条件温和,对映选择性高的特点。
发明内容
本发明涉及一种手性羟基硒醚及其不对称合成方法,所述的合成方法以α-硒酮为原料,单磺酰手性二胺配体与金属的配合物为催化剂,甲酸盐的水溶液或甲酸-三乙胺共沸物为氢源,经不对称转移氢化的方式得到手性羟基硒醚,反应式如下:
R1为C1-C10的烷基或芳基;
R2为C1-C10的烷基、C1-C10的烷氧基、卤代烷基、卤素、羟基、氨基、硝基、氰基、羧基、苯基中的任意一种;
上面给出的手性羟基硒醚化合物的定义中,所用术语不论单独使用还是用在复合词中,代表如下取代基:
烷基:指直链或支链烷基;
卤素:指氟、氯、溴、碘中的任意一种;
烷氧基:指直链或支链烷氧基;
卤代烷基:指直链或支链烷基,在这些烷基上的氢原子部分或全部被卤原子取代。
本发明提供的不对称合成方法中所涉及的手性催化剂为(R,R)-或(S,S)-N-单磺酰-二芳基手性乙二胺与过渡金属钌﹑铑或铱的配合物,其结构通式如式Ⅲ、式Ⅳ所示,
通式Ⅲ或Ⅳ中,M为Ru、Rh或Ir;
Ar为苯基或对甲氧基、甲基取代苯基、萘基;
R为-CH3、-CF3、-C6H5、4-CH3C6H4、4-CF3C6H4、4-(t-Bu)-C6H4-、3,4-(CH3)2-C6H3-、2,4,6-(CH3)3-C6H2-、2,6-Cl2-C6H3-、2,4,6-(i-Pr)3-C6H2-、-C6F5或萘基;
R’为H、CH3或i-Pr;
L为苯、1,4-二甲基苯、1-甲基-4-异丙基苯、1,3,5-三甲基苯、1,2,3,4,5-五甲基苯、1,2,3,4,5,6-六甲基苯或五甲基环戊二烯;
X为Cl-、[OTf]-、[PF6]-、[BF4]-、[SbF6]-或手性磷酸阴离子,Y为C或O。
进一步优化本发明不对称合成方法的催化剂结构如下所示:
本发明提供的不对称合成方法中所用氢源为甲酸/三乙胺任意比例混合物或甲酸钠,优选甲酸/三乙胺=1.1:1。
本发明提供的不对称合成方法中所涉及的溶剂为水、甲醇、乙醇、乙酸乙酯、二氯甲烷、N,N-二甲基甲酰胺、氯仿、甲苯中的任意一种或多种上述溶剂的任意比例混合物,优选二氯甲烷。
本发明提供的不对称合成方法中所涉及的反应温度为0-50℃,反应时间为2-24小时。
本发明首次将不对称转移氢化应用到手性羟基硒醚的不对称合成。本发明与现有技术相比具有以下优点:所用手性二胺配体稳定、合成简单、价格相对便宜;实验操作方便、安全、反应条件温和等。利用本发明提供的方法所得到的手性产物,是重要的有机合成中间体,因而本方法具有重要的工业应用价值。
具体实施方式
下面结合具体实施例,对本发明作进一步说明,但本发明并不限于以下实施例。
本发明所用催化剂来源如下:
催化剂C的合成:0.004mmol N-((1S,2S)-2-氨基-1,2-二苯基乙基)-3-(三氟甲基)苯磺酰胺和0.002mmol二氯双(4-甲基异丙基苯基)钌(II)溶解在0.5mL二氯甲烷中,加入0.004mmol三乙胺,室温下反应30分钟,水洗,水相用1mL二氯甲烷萃取3次,合并后浓缩至干,直接用于催化反应,结构式如下。
催化剂E的合成:方法、步骤同催化剂C的制备,仅N-((1S,2S)-2-氨基-1,2-二苯基乙基)-3-(三氟甲基)苯磺酰胺更换为N-((1S,2S)-2-氨基-1,2-二苯基乙基)-4-甲基苯磺酰胺,二氯双(4-甲基异丙基苯基)钌(II)更换为二氯(五甲基环戊二烯基)合铑(III)二聚体,结构式如下。
催化剂F的合成:方法、步骤同催化剂C的制备,仅N-((1S,2S)-2-氨基-1,2-二苯基乙基)-3-(三氟甲基)苯磺酰胺更换为N-((1S,2S)-2-氨基-1,2-二苯基乙基)-4-甲基苯磺酰胺,二氯双(4-甲基异丙基苯基)钌(II)更换为二氯(五甲基环戊二烯基)合铱(III)二聚体,结构式如下。
催化剂G的合成:方法、步骤同催化剂C的制备,仅N-((1S,2S)-2-氨基-1,2-二苯基乙基)-3-(三氟甲基)苯磺酰胺更换为N-((1S,2S)-2-氨基-1,2-二苯基乙基)-4-甲基苯磺酰胺,二氯双(4-甲基异丙基苯基)钌(II)更换为二氯苯基钌(II)二聚体,结构式如下。
催化剂A、B、D、H为商业购买,结构式如下。
实施例1
(R)-1-苯基-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-苯基-2-(苯基硒基)乙烷-1-酮,2mL溶剂,0.004mmol催化剂,1mmol氢源,密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产物(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=11.95min,t2=12.90min。1H NMR(400MHz,CDCl3):δ=7.55-7.53(m,2H),7.34-7.27(m,8H),4.74(dd,J=9.6,2.0Hz,1H),3.30(dd,J=12.8,4.0Hz,1H),3.13(dd,J=12.8,9.2Hz,1H),2.83(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=142.5,133.1,129.3,129.1,128.6,128.0,127.4,125.8,72.2,38.5ppm.
实施例2
(R)-2-(苯基硒基)-1-(对甲苯基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的2-(苯基硒基)-1-(对甲苯基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:81%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为98%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=9.42min,t2=10.38min。1H NMR(400MHz,CDCl3):δ=7.54-7.52(m,2H),7.28-7.21(m,5H),7.13(d,J=8.0Hz,2H),4.71(dd,J=9.2,4.0Hz,1H),3.27(dd,J=12.8,3.6Hz,1H),3.13(dd,J=12.8,9.6Hz,1H),2.81(s,1H),2.33(s,3H)ppm;13C NMR(100MHz,CDCl3):δ=139.6,137.7,133.11,133.06,129.3,129.2,127.4,125.8,72.1,38.4,21.2ppm.
实施例3
(R)-1-(4-乙基苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-(4-乙基苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:70%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为99%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=11.48min,t2=12.34min。1H NMR(400MHz,CDCl3):δ=7.54-7.52(m,2H),7.27-7.24(m,5H),7.16(d,J=8.0Hz,2H),4.73(d,J=8.0Hz,1H),3.29(dd,J=12.8,4.0Hz,1H),3.14(dd,J=12.8,9.6Hz,1H),2.77(d,J=2.0Hz,1H),2.63(q,J=7.6Hz,2H),1.22(t,J=7.6Hz,3H)ppm;13CNMR(100MHz,CDCl3):δ=144.1,139.8,133.1,129.30,129.26,128.1,127.3,125.8,72.2,38.4,28.6,15.6ppm.
实施例4
(R)-1-(4-异丙基苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-(4-异丙基苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:72%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为99%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=10.65min,t2=11.35min。1H NMR(400MHz,CDCl3):δ=7.54-7.51(m,2H),7.27-7.25(m,5H),7.19(d,J=8.0Hz,2H),4.73(dd,J=9.6,2.4Hz,1H),3.29(dd,J=12.8,4.0Hz,1H),3.15(dd,J=12.8,9.2Hz,1H),2.92-2.85(m,1H),2.76(d,J=2.0Hz,1H),1.23(d,J=6.8Hz,6H)ppm;13CNMR(100MHz,CDCl3):δ=148.7,139.9,130.0,129.3,129.2,127.3,126.6,125.9,72.2,38.3,33.9,24.0ppm.
实施例5
(R)-1-(4-(叔丁基)苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-(4-(叔丁基)苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:72%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为98%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=12.06min,t2=13.44min。1H NMR(400MHz,CDCl3):δ=7.54-7.51(m,2H),7.36-7.34(m,2H),7.28-7.24(m,5H),4.73(dd,J=8.8,1.6Hz,1H),3.30(dd,J=12.4,4.0Hz,1H),3.15(dd,J=12.8,9.6Hz,1H),2.78(d,J=2.4Hz 1H),1.30(s,9H)ppm;13C NMR(100MHz,CDCl3):δ=150.9,139.5,133.0,129.3,129.2,127.3,125.6,125.5,72.1,38.3,34.6,31.4ppm.
实施例6
(R)-1-([1,1'-联苯]-4-基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-([1,1'-联苯]-4-基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:67%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为95%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=31.43min,t2=34.57min。1H NMR(400MHz,CDCl3):δ=7.58-7.53(m,6H),7.44-7.38(m,4H),7.36-7.32(m,1H),7.28-7.26(m,3H),4.78(dd,J=9.2,3.6Hz,1H),3.33(dd,J=12.8,3.6Hz,1H),3.16(dd,J=12.8,9.2Hz,1H),2.90(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=141.5,140.9,140.8,133.2,129.3,129.1,128.8,127.5,127.4,127.3,127.1,126.3,72.0,38.5ppm.
实施例7
(R)-1-(4-氟苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-(4-氟苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:88%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为96%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=14.41min,t2=15.61min。1H NMR(400MHz,CDCl3):δ=7.54-7.51(m,2H),7.31-7.27(m,5H),7.03-6.98(m,2H),4.71(dd,J=9.2,3.6Hz,1H),3.26(dd,J=12.8,4.0Hz,1H),3.09(dd,J=12.8,9.6Hz,1H),2.90(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=162.4(d,JC-F=244.3Hz),138.2(d,JC-F=3.0Hz),133.2,129.3,128.9,127.6(d,JC-F=1.9Hz),127.5,115.4(d,JC-F=21.2Hz),71.6,38.5ppm.
实施例8
(R)-1-(4-氯苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-(4-氯苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:90%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为94%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=9.95min,t2=10.85min。1H NMR(400MHz,CDCl3):δ=7.53-7.51(m,2H),7.29-7.23(m,7H),4.69(dd,J=9.2,4.0Hz,1H),3.24(dd,J=12.8,3.6Hz,1H),3.06(dd,J=12.8,9.2Hz,1H),2.98(brs,1H)ppm;13C NMR(100MHz,CDCl3):δ=140.9,133.6,133.3,129.4,128.8,128.7,127.6,127.2,71.5,38.4ppm.
实施例9
(R)-1-(4-溴苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-(4-溴苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:91%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为95%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=10.49min,t2=11.52min。1H NMR(400MHz,CDCl3):δ=7.53-7.51(m,2H),7.43(d,J=8.4Hz,2H),7.28-7.27(m,3H),7.19(d,J=8.0Hz,2H),4.67(dd,J=9.6,3.6Hz,1H),3.24(dd,J=12.8,3.6Hz,1H),3.06(dd,J=12.8,9.2Hz,1H),2.94(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=141.4,133.3,131.6,129.4,128.8,127.6,121.7,71.5,38.4ppm.
实施例10
(R)-1-(3-甲氧基苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-(3-甲氧基苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:95%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为98%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=17.11min,t2=18.84min。1H NMR(400MHz,CDCl3):δ=7.54-7.52(m,2H),7.27-7.24(m,4H),6.90-6.88(m,2H),6.82-6.79(m,2H),4.72(dd,J=9.4,3.6Hz,1H),3.78(s,3H),3.29(dd,J=12.8,3.6Hz,1H),3.13(dd,J=12.8,9.6Hz,1H),2.85(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=159.8,144.2,133.1,129.6,129.3,127.4,118.1,113.4,111.3,72.2,55.3,38.4ppm.
实施例11
(R)-1-(3-氯苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-(3-氯苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:83%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为96%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=8.55min,t2=9.37min。1H NMR(400MHz,CDCl3):δ=7.55-7.53(m,2H),7.34-7.33(m,1H),7.30-7.28(m,3H),7.25-7.23(m,2H),7.20-7.18(m,1H),4.70(dd,J=9.2,3.6Hz,1H),3.27(dd,J=12.8,4.0Hz,1H),3.07(dd,J=12.8,9.2Hz,1H),2.93(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=144.5,134.4,133.3,129.8,129.3,128.7,128.0,127.6,126.0,124.0,71.5,38.4ppm.
实施例12
(R)-1-(3-溴苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-(3-溴苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:88%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为98%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=8.48min,t2=9.37min。1H NMR(400MHz,CDCl3):δ=7.57-7.51(m,3H),7.41(d,J=8.0Hz,1H),7.31-7.18(m,5H),4.69(d,J=7.6Hz,1H),3.28(dd,J=12.8,3.6Hz,1H),3.08(m,1H),2.98(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=144.7,133.3,131.0,130.1,129.4,129.0,128.7,127.7,124.5,122.7,71.4,38.4ppm.
实施例13
(R)-1-(2-乙基苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-(2-乙基苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:70%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为98%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=10.84min,t2=11.43min。1H NMR(400MHz,CDCl3):δ=7.55-7.52(m,2H),7.29-7.23(m,4H),7.17-7.11(m,3H),4.72(dd,J=8.8,2.8Hz,1H),3.30(dd,J=12.8,3.6Hz,1H),3.14(dd,J=12.8,3.6Hz,1H),2.83(s,1H),2.63(q,J=7.6Hz,2H),1.22(t,J=7.6Hz,3H)ppm;13C NMR(100MHz,CDCl3):δ=144.6,142.5,133.1,129.3,128.5,128.1,127.4,125.9,125.3,123.2,72.3,38.5,28.9,15.6ppm.
实施例14
(R)-1-(2-甲氧基苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-(2-甲氧基苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:57%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为96%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=98:2(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=34.56min,t2=36.14min。1H NMR(400MHz,CDCl3):δ=7.57-7.55(m,2H),7.45(dd,J=7.2,1.6Hz,1H),7.30-7.26(m,4H),7.00(td,J=7.2,0.8Hz,1H),6.86(d,J=8.0Hz,1H),5.09-5.05(m,1H),3.82(s,3H),3.48(dd,J=12.8,4.0Hz,1H),3.16(dd,J=12.8,9.2Hz,1H),3.07(d,J=4.8Hz,1H)ppm;13C NMR(100MHz,CDCl3):δ=156.1,132.4,130.4,129.9,129.0,128.7,126.8,126.7,120.8,110.3,69.0,55.2,36.1ppm.
实施例15
(R)-2-(1-羟基-2-(苯基硒基)乙基)苯酚的不对称合成
向试管中依次加入0.2mmol的1-(2-羟基苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:61%(石油醚:乙酸乙酯=10:1),HPLC测定产物ee值为98%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=24.61min,t2=25.89min。1H NMR(400MHz,CDCl3):δ=7.95(s,1H),7.57-7.55(m,2H),7.32-7.30(m,3H),7.19-7.15(m,1H),6.89-6.79(m,3H),4.77(dd,J=10.4,3.2Hz,1H),3.68(s,1H),3.33(dd,J=13.2,3.6Hz,1H),3.24(dd,J=13.2,10.4Hz,1H)ppm;13C NMR(100MHz,CDCl3):δ=155.4,133.3,129.5,129.4,128.1,127.8,127.3,125.0,120.0,117.5,73.3,36.9ppm.
实施例16
(R)-1-(萘-2-基)-2-(苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-(萘-2-基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:84%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为95%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=11.89min,t2=13.03min。1H NMR(400MHz,CDCl3):δ=7.82-7.80(m,4H),7.58-7.56(m,2H),7.48-7.43(m,3H),7.29-7.27(m,3H),4.91(dd,J=9.2,3.6Hz,1H),3.39(dd,J=12.8,4.0Hz,1H),3.21(dd,J=12.8,9.2Hz,1H),2.95(brs,1H)ppm;13C NMR(100MHz,CDCl3):δ=139.8,133.3,133.2,133.1,129.3,129.0,128.4,128.0,127.7,127.5,126.2,126.0,124.7,123.8,72.3,38.5ppm.
实施例17
(R)-2-(苯基硒基)-1-(吡啶-4-基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的2-(苯基硒基)-1-(吡啶-4-基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:60%(石油醚:乙酸乙酯=1:1),HPLC测定产物ee值为99%。HPLC分离条件:手性AD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=42.64min,t2=47.09min。1H NMR(400MHz,CDCl3):δ=8.50-8.48(m,2H),755-7.53(m,2H),7.30-7.27(m,5H),4.76(dd,J=9.2,4.0Hz,1H),3.29(dd,J=12.8,4.0Hz,1H),3.10(dd,J=12.8,8.8Hz,1H)ppm;13C NMR(100MHz,CDCl3):δ=151.9,149.6,133.31,133.26,129.4,128.8,127.7,121.0,70.8,37.8ppm.
实施例18
(R)-2-(苯基硒基)-1-(噻吩-3-基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的2-(苯基硒基)-1-(噻吩-3-基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:46%(石油醚:乙酸乙酯=7:1),HPLC测定产物ee值为97%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=98:2(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=37.75min,t2=39.83min。1H NMR(400MHz,CDCl3):δ=7.54-7.52(m,2H),7.29-7.22(m,5H),7.05-7.04(m,1H),4.86(dd,J=8.8,3.6Hz,1H),3.33(dd,J=12.4,4.0Hz,1H),3.19(dd,J=12.8,8.8Hz,1H),2.84(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=143.8,133.2,129.3,129.2,127.4,126.3,125.5,121.3,68.7,37.8ppm.
实施例19
(R)-1-(苯基硒基)丙-2-醇的不对称合成
向试管中依次加入0.2mmol的1-(苯基硒基)丙-2-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:37%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为28%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=7.60min,t2=10.69min。1HNMR(400MHz,CDCl3):δ=7.57-7.54(m,2H),7.30-7.28(m,3H),3.91-3.85(m,1H),3.13(dd,J=12.8,4.0Hz,1H),2.90(dd,J=12.8,8.4Hz,1H),2.49(brs,1H),1.30(d,J=6.4Hz,3H)ppm;13C NMR(100MHz,CDCl3):δ=133.1,129.2,127.3,66.0,38.6ppm.
实施例20
(R)-2-((4-甲基苯基)硒基)-1-苯基乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-苯基-2-(对甲苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:89%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为97%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=11.70min,t2=13.60min。1H NMR(400MHz,CDCl3):δ=7.45(d,J=8.0Hz,2H),7.33-7.26(m,5H),7.10(d,J=7.8Hz,2H),4.71(dd,J=9.6,3.6Hz,1H),3.25(dd,J=12.8,3.6Hz,1H),3.08(dd,J=12.8,9.6Hz,1H),2.87(s,1H),2.33(s,3H)ppm;13C NMR(100MHz,CDCl3):δ=142.5,137.6,133.6,130.1,128.5,127.9,125.8,125.1,72.1,38.9,21.1ppm.
实施例21
(R)-2-((4-甲氧基苯基)硒基)-1-苯基乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的2-((4-甲氧基苯基)硒基)-1-苯基乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:93%(石油醚:乙酸乙酯=10:1),HPLC测定产物ee值为98%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=11.14min,t2=12.23min。1H NMR(400MHz,CDCl3):δ=7.51-7.48(m,2H),7.34-7.25(m,5H),6.84-6.81(m,2H),4.67(dd,J=9.6,3.6Hz,1H),3.79(s,3H),3.19(dd,J=12.8,3.6Hz,1H),3.03(dd,J=12.8,9.6Hz,1H),2.91(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=159.6,142.5,136.0,128.5,127.9,125.9,118.8,115.0,72.0,55.3,39.6ppm.
实施例22
(R)-2-((4-氟苯基)硒基)-1-苯基乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的2-((4-氟苯基)硒基)-1-苯基乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:95%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为96%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=18.12min,t2=20.66min。1H NMR(400MHz,CDCl3):δ=7.53-7.50(m,2H),7.34-7.28(m,5H),7.00-6.96(m,2H),4.72(dd,J=9.2,3.6Hz,1H),3.24(dd,J=12.8,3.6Hz,1H),3.11(dd,J=12.8,9.2Hz,1H),2.78(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=162.6(d,JC-F=246.1Hz),142.3,135.8(d,JC-F=7.9Hz),128.6,128.0,125.8,123.5,116.5(d,JC-F=21.5Hz),72.2,39.2ppm.
实施例23
(R)-2-((4-氯苯基)硒基)-1-苯基乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的2-((4-氯苯基)硒基)-1-苯基乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:92%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为94%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=15.65min,t2=17.56min。1H NMR(400MHz,CDCl3):δ=7.45-7.43(m,2H),7.34-7.28(m,5H),7.24-7.22(m,2H),4.75(dd,J=9.2,3.6Hz,1H),3.26(dd,J=12.8,4.0Hz,1H),3.14(dd,J=12.8,9.2Hz,1H),2.77(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=142.3,134.5,133.6,129.4,128.6,128.1,127.4,125.8,72.4,38.6ppm.
实施例24
(R)-1-苯基-2-(间甲苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-苯基-2-(间甲苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:95%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为95%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=13.98min,t2=15.46min。1H NMR(400MHz,CDCl3):δ=7.54-7.52(m,1H),7.39-7.30(m,5H),7.24-7.13(m,3H),4.79(dd,J=9.6,4.0Hz,1H),3.30(dd,J=12.8,4.0Hz,1H),3.16(dd,J=12.4,9.2Hz,1H),2.91(s,1H),2.45(s,3H)ppm;13C NMR(100MHz,CDCl3):δ=142.6,139.8,132.3,130.25,130.19,128.6,128.0,127.3,126.7,125.8,72.3,37.2,22.6ppm.
实施例25
(R)-2-((3-氯苯基)硒基)-1-苯基乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的2-((3-氯苯基)硒基)-1-苯基乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:46%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为96%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=17.40min,t2=18.30min。1H NMR(400MHz,CDCl3):δ=7.48(t,J=1.6Hz,1H),7.38(dt,J=7.2,1.6Hz,1H),7.35-7.26(m,5H),7.24-7.16(m,2H),4.79(dd,J=8.8,4.0Hz,1H),3.30(dd,J=12.8,4.0Hz,1H),3.19(dd,J=12.8,8.8Hz,1H),2.74(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=142.3,134.8,132.4,131.2,130.7,130.2,128.6,128.1,127.4,125.8,72.5,38.2ppm.
实施例26
(R)-1-苯基-2-((3-(三氟甲基)苯基)硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-苯基-2-((3-(三氟甲基)苯基)硒基)乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:93%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为92%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=13.14min,t2=14.40min。1H NMR(400MHz,CDCl3):δ=7.76(s,1H),7.70(d,J=8.0Hz,1H),7.52(d,J=7.6Hz,1H),7.41-7.30(m,6H),4.85(dd,J=8.8,4.0Hz,1H),3.36(dd,J=12.8,4.0Hz,1H),3.26(dd,J=12.8,8.8Hz,1H),2.76(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=142.3,135.8,131.4(q,JC-F=32.1Hz),130.8,129.4,129.1(q,JC-F=3.8Hz),128.7,128.2,125.8,123.9(q,JC-F=271.1Hz),123.6(q,JC-F=3.7Hz)ppm.
实施例27
(R)-1-苯基-2-(邻甲苯基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-苯基-2-(邻甲苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:90%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为96%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=13.98min,t1=15.55min。1H NMR(400MHz,CDCl3):δ=7.35-7.27(m,7H),7.17(t,J=8.0Hz,1H),7.08(d,J=6.8Hz,1H),4.74(dd,J=9.6,3.6Hz,1H),3.30(dd,J=12.8,3.6Hz,1H),3.12(dd,J=12.8,9.6Hz,1H),2.87(s,1H),2.33(s,3H)ppm;13C NMR(100MHz,CDCl3):δ=142.5,139.1,133.8,130.1,129.1,128.8,128.5,128.3,127.9,125.8,72.2,38.5,21.3ppm.
实施例28
(R)-2-((3,5-二甲基苯基)硒基)-1-苯基乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的2-((3,5-二甲基苯基)硒基)-1-苯基乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:82%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为98%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=10.10min,t2=11.84min。1H NMR(400MHz,CDCl3):δ=7.35-7.34(m,4H),7.31-7.27(m,1H),7.15(s,2H),6.90(s,1H),4.74(dd,J=9.6,4.0Hz,1H),3.29(dd,J=12.8,4.0 1H),3.11(dd,J=12.8,9.6Hz,1H),2.89(s,1H),2.29(s,6H)ppm;13C NMR(100MHz,CDCl3):δ=142.5,138.9,130.8,129.3,128.5,127.9,125.8,72.2,38.4,21.2ppm.
实施例29
(R)-2-(萘-2-基硒基)-1-苯基乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的2-(萘-2-基硒基)-1-苯基乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:95%(石油醚:乙酸乙酯=20:1),HPLC测定产物ee值为97%。HPLC分离条件:手性AD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=10.75min,t2=12.14min。1H NMR(400MHz,CDCl3):δ=8.40(d,J=8.4Hz,1H),7.85-7.80(m,3H),7.58-7.49(m,2H),7.39-7.35(m,1H),7.29-7.22(m,5H),4.70(dd,J=9.2,3.6Hz,1H),3.30(dd,J=12.8,4.0Hz,1H),3.18(dd,J=12.8,9.6Hz,1H),2.83(s,1H).ppm;13C NMR(100MHz,CDCl3):δ=142.5,134.3,134.1,133.2,128.9,128.8,128.5,128.3,127.9,127.6,126.9,126.4,125.84,125.81,72.4,38.4ppm.
实施例30
(R)-1-苯基-2-(吡啶-2-基硒基)乙烷-1-醇的不对称合成
向试管中依次加入0.2mmol的1-苯基-2-(吡啶-2-基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:96%(石油醚:乙酸乙酯=5:1),HPLC测定产物ee值为96%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=20.93min,t2=23.41min。1H NMR(400MHz,CDCl3):δ=8.45-8.43(m,1H),7.50-7.42(m,4H),7.37-7.33(m,2H),7.29-7.25(m,1H),7.12-7.08(m,1H),6.54(s,1H),5.17(dd,J=8.0,3.2Hz,1H),3.50(dd,J=13.6,2.8Hz,1H),3.40(dd,J=14.0,7.6Hz,1H)ppm;13C NMR(100MHz,CDCl3):δ=155.4,149.6,144.6,136.5,128.3,127.4,126.0,125.9,120.9,74.3,36.4ppm.
实施例31
4-((R)-1-羟基-2-(苯基硒基)乙基)苯基(S)-2-((叔丁氧基羰基)氨基)-3,3-二甲基丁酸酯
向试管中依次加入0.2mmol的4-(2-(苯基硒基)乙酰基)苯基(S)-2-((叔丁氧基羰基)氨基)-3,3-二甲基丁酸酯,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:70%(石油醚:乙酸乙酯=5:1),HPLC测定产物ee值为94%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=9.60min,t2=10.61min。1H NMR(400MHz,CDCl3):δ=7.54-7.52(m,2H),7.35(d,J=8.4Hz,2H),7.28-7.26(m,3H),7.07(d,J=8.4Hz,2H),5.17(d,J=9.2Hz,1H),4.74(dd,J=9.2,3.2Hz,1H),4.31(d,J=9.2Hz,1H),3.27(dd,J=12.8,3.8Hz,1H),3.10(dd,J=12.8,9.2Hz,1H),2.91(s,1H),1.46(s,9H),1.09(s,9H).ppm;13C NMR(100MHz,CDCl3):δ=170.6,155.6,149.9,140.4,133.2,129.3,129.0,127.5,127.0,121.5,80.1,71.7,61.8,38.4,35.0,29.7,28.3,26.7ppm.
实施例32
(1R,2S,5R)-2-异丙基-5-甲基环己基4-((R)-1-羟基-2-(苯基硒基)乙基)苯甲酸酯
向试管中依次加入0.2mmol的(1R,2S,5R)-2-异丙基-5-甲基环己基4-(2-(苯基硒基)乙酰基)苯甲酸酯,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:92%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为90%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=12.29min,t2=16.73min。1H NMR(400MHz,CDCl3):δ=7.99(d,J=8.4Hz,2H),7.54-7.52(m,2H),7.39(d,J=8.4Hz,2H),7.29-7.26(m,2H),4.92(td,J=10.8,4.4Hz,1H),4.79(dd,J=9.2,3.6Hz,1H),3.29(dd,J=12.8,4.0Hz,1H),3.10(dd,J=12.8,9.2Hz,1H),3.00(s,1H),2.12-2.09(m,1H),1.98-1.91(m,1H),1.75-1.68(m,2H),1.75-1.68(m,2H),1.57-1.51(m,2H),0.93-0.90(m,7H),0.79(d,J=7.2 Hz,3H)ppm;13CNMR(100 MHz,CDCl3):δ=165.8,147.3,133.3,130.4,129.8,129.3,128.8,127.6,125.7,74.9,71.8,47.3,41.0,38.4,34.3,31.5,26.5,23.7,22.1,20.8,16.6 ppm.
Claims (9)
4.权利要求2所述的手性羟基硒醚的不对称合成方法,其特征在于,所述的金属的配合物的催化剂为(R,R)-或(S,S)-N-单磺酰-二芳基手性乙二胺与过渡金属钌或铑或铱的配合物,其结构通式如式Ⅲ、式Ⅳ所示,
通式Ⅲ或Ⅳ中,M为Ru、Rh或Ir;
Ar为苯基或对甲氧基、甲基取代苯基、萘基;
R为-CH3、-CF3、-C6H5、4-CH3C6H4、4-CF3C6H4、4-(t-Bu)-C6H4-、3,4-(CH3)2-C6H3-、2,4,6-(CH3)3-C6H2-、2,6-Cl2-C6H3-、2,4,6-(i-Pr)3-C6H2-、-C6F5或萘基;
R’为H、CH3或i-Pr;
L为苯、1,4-二甲基苯、1-甲基-4-异丙基苯、1,3,5-三甲基苯、1,2,3,4,5-五甲基苯、1,2,3,4,5,6-六甲基苯或五甲基环戊二烯;
X为Cl-、[OTf]-、[PF6]-、[BF4]-、[SbF6]-或手性磷酸阴离子;
Y为C或O。
6.根据权利要求2所述的手性羟基硒醚的不对称合成方法,其特征在于,所述的氢源为甲酸/三乙胺任意比例混合物或甲酸钠的水溶液。
7.根据权利要求2所述的手性羟基硒醚的不对称合成方法,其特征在于,所述的氢源甲酸与三乙胺以1.1:1形成的混合物。
8.根据权利要求2所述的手性羟基硒醚的不对称合成方法,其特征在于,所用溶剂为水、甲醇、乙醇、乙酸乙酯、二氯甲烷、N,N-二甲基甲酰胺、氯仿、甲苯中的任意一种或多种上述溶剂的任意比例混合物。
9.根据权利要求2所述的手性羟基硒醚的不对称合成方法,其特征在于,不对称转移氢化反应的反应温度为0-50℃,反应时间为2-24小时。
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