CN108101740B - 一种芳香炔烃一锅法直接转化成手性醇的方法 - Google Patents
一种芳香炔烃一锅法直接转化成手性醇的方法 Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000005580 one pot reaction Methods 0.000 title claims abstract description 12
- -1 aromatic alkyne Chemical class 0.000 title claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 30
- 239000003054 catalyst Substances 0.000 claims abstract description 28
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 claims abstract description 20
- 235000019254 sodium formate Nutrition 0.000 claims abstract description 20
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims abstract description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 90
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 19
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 17
- 239000012074 organic phase Substances 0.000 claims description 16
- 239000003208 petroleum Substances 0.000 claims description 15
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- WAPNOHKVXSQRPX-ZETCQYMHSA-N (S)-1-phenylethanol Chemical compound C[C@H](O)C1=CC=CC=C1 WAPNOHKVXSQRPX-ZETCQYMHSA-N 0.000 claims description 11
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- 238000000605 extraction Methods 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 abstract description 17
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 abstract description 9
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- 239000004280 Sodium formate Substances 0.000 abstract description 5
- 229910052731 fluorine Inorganic materials 0.000 abstract description 5
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- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 abstract description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 4
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- 238000006555 catalytic reaction Methods 0.000 abstract description 4
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- 238000011914 asymmetric synthesis Methods 0.000 description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
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- DDUBOVLGCYUYFX-LURJTMIESA-N (1s)-1-(2-chlorophenyl)ethanol Chemical compound C[C@H](O)C1=CC=CC=C1Cl DDUBOVLGCYUYFX-LURJTMIESA-N 0.000 description 2
- MVOSNPUNXINWAD-LURJTMIESA-N (1s)-1-(4-chlorophenyl)ethanol Chemical compound C[C@H](O)C1=CC=C(Cl)C=C1 MVOSNPUNXINWAD-LURJTMIESA-N 0.000 description 2
- IUUULXXWNYKJSL-ZETCQYMHSA-N (1s)-1-(4-methoxyphenyl)ethanol Chemical compound COC1=CC=C([C@H](C)O)C=C1 IUUULXXWNYKJSL-ZETCQYMHSA-N 0.000 description 2
- CRJFHXYELTYDSG-LURJTMIESA-N (1s)-1-(4-nitrophenyl)ethanol Chemical compound C[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 CRJFHXYELTYDSG-LURJTMIESA-N 0.000 description 2
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 2
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 239000007848 Bronsted acid Substances 0.000 description 2
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- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
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- 150000001298 alcohols Chemical class 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- HBRQLSFKMQAUJB-UHFFFAOYSA-N 1,4-dichloro-2-ethynylbenzene Chemical group ClC1=CC=C(Cl)C(C#C)=C1 HBRQLSFKMQAUJB-UHFFFAOYSA-N 0.000 description 1
- DGLHLIWXYSGYBI-UHFFFAOYSA-N 1-chloro-2-ethynylbenzene Chemical group ClC1=CC=CC=C1C#C DGLHLIWXYSGYBI-UHFFFAOYSA-N 0.000 description 1
- LFZJRTMTKGYJRS-UHFFFAOYSA-N 1-chloro-4-ethynylbenzene Chemical group ClC1=CC=C(C#C)C=C1 LFZJRTMTKGYJRS-UHFFFAOYSA-N 0.000 description 1
- KBIAVTUACPKPFJ-UHFFFAOYSA-N 1-ethynyl-4-methoxybenzene Chemical group COC1=CC=C(C#C)C=C1 KBIAVTUACPKPFJ-UHFFFAOYSA-N 0.000 description 1
- GAZZTEJDUGESGQ-UHFFFAOYSA-N 1-ethynyl-4-nitrobenzene Chemical group [O-][N+](=O)C1=CC=C(C#C)C=C1 GAZZTEJDUGESGQ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 229930007927 cymene Natural products 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- VBRLZTLFLNZEPZ-UHFFFAOYSA-N hex-1-ynylbenzene Chemical compound CCCCC#CC1=CC=CC=C1 VBRLZTLFLNZEPZ-UHFFFAOYSA-N 0.000 description 1
- YUWFEBAXEOLKSG-UHFFFAOYSA-N hexamethylbenzene Chemical compound CC1=C(C)C(C)=C(C)C(C)=C1C YUWFEBAXEOLKSG-UHFFFAOYSA-N 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- BEZDDPMMPIDMGJ-UHFFFAOYSA-N pentamethylbenzene Chemical compound CC1=CC(C)=C(C)C(C)=C1C BEZDDPMMPIDMGJ-UHFFFAOYSA-N 0.000 description 1
- WQIQNKQYEUMPBM-UHFFFAOYSA-N pentamethylcyclopentadiene Chemical compound CC1C(C)=C(C)C(C)=C1C WQIQNKQYEUMPBM-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
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- 125000001424 substituent group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2282—Unsaturated compounds used as ligands
- B01J31/2295—Cyclic compounds, e.g. cyclopentadienyls
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
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- C07—ORGANIC CHEMISTRY
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- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/26—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydration of carbon-to-carbon triple bonds
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0225—Complexes comprising pentahapto-cyclopentadienyl analogues
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
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- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/821—Ruthenium
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- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
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Abstract
本发明涉及一种芳香炔烃一锅法直接转化成手性醇的方法，该方法以廉价易得的炔烃I为原料，采用“两步一锅法”策略直接合成手性醇II，具体包括步骤1)：以含氟的醇和水为溶剂，在三氟甲烷磺酸催化下发生水合反应生成中间体酮；步骤2)：直接在反应体系中加入单磺酰手性二胺与金属钌或铑或铱的络合物为催化剂，以甲酸钠水溶液或者甲酸‑三乙胺的混合物为氢源，通过不对称转移氢化反应得到产物II。该方法操作简便，反应条件温和、底物适用范围广、对映选择性高。具体反应通式如下：
Description
技术领域
本发明属于不对称催化技术领域，具体涉及一种芳香炔烃一锅法直接转化成手性醇的方法。
背景技术
手性醇通常由酮的不对称还原或者酮与有机金属试剂不对称加成反应来制备，但是有些酮和有机金属试剂合成复杂，不易得到。炔烃是一类廉价易得的原料，从炔烃出发，采用“水合反应-不对称还原两步一锅法”策略直接合成手性醇的方法具有原子经济性和步骤经济性，符合绿色化学原则，具有重要应用前景。采用该策略实现炔烃直接转化成手性醇的方法已有报道，但是需要采用双金属催化体系，比如：(IPr)AuBF4]/Ru-TsDPEN(Chem.Commun.2017,53, 1638–1641),Co-Porphyrin/Rh-TsDPEN(J.Am.Chem.Soc.2015,137,12984–12989)。因此开发反应条件温和、操作简单、单金属催化体系具有更重要的应用价值。本发明报道一种以炔烃为原料，三氟乙醇为溶剂，20mol％三氟甲烷磺酸为催化剂，40℃反应4小时生成中间体酮，然后在反应体系中加入手性二胺金属络合物催化剂，不同比例的甲酸和三乙胺的混合物或甲酸钠水溶液为氢源,在40℃下发生不对称转移氢化合成手性醇。该方法具有反应条件简单、温和，底物适应范围广，对映选择性高等优点。
发明内容
本发明涉及一种芳香炔烃一锅法直接转化成手性醇的方法。该方法以炔烃为原料，采取“两步一锅法”策略，步骤1)：以含氟的醇和水为溶剂，在布朗斯特酸催化下，多乙炔基取代的苯进行水合反应生成中间体酮；
步骤2)：将中间体酮的反应体系中直接加入单磺酰手性二胺与金属钌或铑或铱的络合物为催化剂，以甲酸钠水溶液或者甲酸-三乙胺的混合物为氢源，通过不对称转移氢化反应得到产物 II；具体反应通式如下：
所述化合物I或II，Ar选自
或
R是氢、C1-C3烷基、C1-C3烷基氧基、三氟甲基、氟、氯、溴、羟基、氨基、硝基、氰基中的任意一种；
上面给出的化合物I或II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：
卤素：指氟、氯、溴、碘；
烷基：指直链或支链烷基；
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。
所述步骤1)：水合反应的溶剂为含氟醇和水的混合物，进一步优选为：1毫升三氟乙醇和2当量水或者1毫升六氟异丙醇和2当量水；
所述步骤1)：水合反应的催化剂为布朗斯特酸，进一步优选为：20mol％三氟甲磺酸；
所述步骤1)：水合反应的温度为25-70℃；反应时间为4-48小时；
所述步骤2)：不对称转移氢化所用催化剂为(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者铱的配合物，其结构通式如式III、式IV所示，
所述结构通式III和IV中，M为Ru、Rh或Ir；
Ar为苯基或对甲氧基、甲基取代的苯基、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。
所述步骤2)：不对称转移氢化所用催化剂，进一步优选，代表性催化剂结构如下：
所述步骤2)：不对称转移氢化，氢源为不同比例的甲酸和三乙胺的混合物或甲酸钠水溶液；进一步优选为：10当量的甲酸钠和1毫升水。
所述步骤2)：不对称转移氢化，反应温度为25-80℃，进一步优选为：50℃。
所述步骤2)：不对称转移氢化，反应时间为4-72小时。
本发明所涉及的一种芳香炔烃一锅法直接转化成手性醇的方法，该方法以廉价易得的炔烃I为原料，采用“两步一锅法”策略直接合成手性醇II。该方法操作简便，反应条件温和、底物适用范围广、对映选择性高。
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。
本发明中所用手性催化剂通用制备方法,以催化剂A合成为例：0.005mmol(S,S)-N-五氟苯磺酰二苯基手性乙二胺和0.0025mmol[Ru(cymene)]2Cl2溶解在0.5毫升二氯甲烷中，加入 0.005mmol三乙胺，室温下反应30分钟，水洗，水相用1毫升二氯甲烷萃取3次，合并后浓缩至干得到催化剂A，直接用于催化反应。
实施例1：(S)-1-苯乙醇的不对称合成
将0.5mmol的苯乙炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2equiv.,20 uL),CF3CH2OH(1mL),40℃反应4h后，加入0.005mmol催化剂A,HCOONa(0.5mmol,34mg, 2.5mmol,170mg)，H2O(1mL)，50℃反应5小时。反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：93％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-苯乙醇的ee 值为97％的。HPLC分离条件：手性柱大赛璐OD-H-H柱，流动相：正己烷/异丙醇＝97:3(体积比)，流速：1.0毫升/分钟，波长：254纳米，柱温：30摄氏度，t1＝11.58分钟，t2＝13.82分钟；1H NMR(400MHz,CDCl3):δ＝7.43-7.37(m,4H),7.34-7.30(m,1H),4.93(dd,J1＝12.8Hz, J2＝12.8Hz,1H),2.03(s,3H),1.54(d,J＝6.4Hz,3H)ppm；13C NMR(100MHz,CDCl3):δ＝ 145.83,128.53,127.50,125.41,70.44,25.19ppm.
实施例2：(S)-1-苯乙醇的不对称合成
将0.5mmol的苯乙炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2equiv.,20 uL),CF3CH2OH(1mL),40℃反应4h后，加入0.005mmol催化剂B,HCOONa(0.5mmol,34 mg)，H2O(1mL)，50℃反应5小时。反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：41％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-苯乙醇的ee值为93％的。
实施例3：(S)-1-苯乙醇的不对称合成
将0.5mmol的苯乙炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2equiv.,20 uL),CF3CH2OH(1mL),40℃反应4h后，加入0.005mmol催化剂D,HCOONa(0.5mmol,34 mg)，H2O(1mL)，50℃反应5小时。反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：68％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-苯乙醇的ee值为95％的。
实施例4：(S)-1-苯乙醇的不对称合成
将0.5mmol的苯乙炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2equiv.,20 uL),CF3CH2OH(1mL),40℃反应4h后，加入0.005mmol催化剂E,HCOONa(0.5mmol,34 mg)，H2O(1mL)，50℃反应5小时。反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：48％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-苯乙醇的ee值为79％的。
实施例5：(S)-1-苯乙醇的不对称合成
将0.5mmol的苯乙炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2equiv.,20 uL),CF3CH2OH(1mL),40℃反应4h后，加入0.005mmol催化剂A,HCOOH/TEA(摩尔比1.1:1, 1mL)，50℃反应5小时。反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：69％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-苯乙醇的ee值为95％的。
实施例6：(S)-1-(4-甲基苯基)乙醇的不对称合成
将0.5mmol的4-甲基苯乙炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2equiv.,20uL),CF3CH2OH(1mL),50℃反应6h后，加入0.005mmol催化剂A,HCOONa(0.5 mmol,34mg)，H2O(1mL)，50℃反应5小时。反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：83％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-(4-甲基苯基)乙醇的ee值为98％的。HPLC分离条件：手性柱大赛璐OJ-H柱，流动相：正己烷/异丙醇＝95:5(体积比)，流速：1.0毫升/分钟，波长：220纳米，柱温：30摄氏度，t1＝10.14分钟，t2＝11.59分钟；1HNMR(400MHz,CDCl3):δ＝7.31(dd,J1＝6.0Hz,J2＝6.0Hz,2H),7.21(t,J＝8.0Hz, 2H),4.90(dd,J1＝13.2Hz,J2＝13.2Hz,1H),2.39(s,3H),1.97(s,1H),1.52(d,J＝6.4Hz,3H) ppm；13C NMR(100MHz,CDCl3):δ＝142.90,137.16,129.18,125.38,70.26,25.10,21.12ppm.
实施例7：(S)-1-苯己醇的不对称合成
将0.5mmol的1-苯己炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2equiv., 20uL),CF3CH2OH(1mL),50℃反应48h后，加入0.005mmol催化剂A,HCOONa(0.5mmol, 34mg)，H2O(1mL)，50℃反应5小时。反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：60％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-苯己醇的ee值为81％的。HPLC分离条件：手性柱大赛璐OD-H柱，流动相：正己烷/异丙醇＝99:1(体积比)，流速： 1.0毫升/分钟，波长：220纳米，柱温：30摄氏度，t1＝19.25分钟，t2＝20.70分钟；1H NMR(400 MHz,CDCl3):δ＝7.38(dd,J1＝5.2Hz,J2＝8.4Hz,2H),7.33-7.31(m,J＝6.0Hz,2H),4.68(dd, J1＝7.2Hz,J2＝7.6Hz,1H),2.14(s,1H),1.77-1.73(m,1H),1.48-1.44(m,1H),1.37-1.31(m,5H), 0.92(dd,J1＝6.4Hz,J2＝6.4Hz,3H)ppm；13C NMR(100MHz,CDCl3):δ＝145.00,128.42, 127.46,125.94,74.70,39.10,31.77,25.54,22.61,14.07ppm.
实施例8：(S)-1-(4-甲氧基苯基)乙醇的不对称合成
将0.5mmol的4-甲氧基苯乙炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2 equiv.,20uL),CF3CH2OH(1mL),40℃反应4h，加入0.005mmol催化剂A,HCOONa(0.5mmol,34mg)，H2O(1mL)，50℃反应5小时。反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：77％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-(4-甲氧基苯基)乙醇的ee值为92％的。HPLC分离条件：手性柱大赛璐OD-H柱，流动相：正己烷/异丙醇＝97:3(体积比)，流速：1.0毫升/分钟，波长：254纳米，柱温：30摄氏度，t1＝15.98分钟，t2＝17.12分钟；1H NMR(400MHz,CDCl3):δ＝7.32(dd,J1＝6.4Hz,J2＝6.4Hz,2H),6.91(dd,J1＝6.8Hz, J2＝6.4Hz,2H),4.86(dd,J1＝12.8Hz,J2＝12.8Hz,1H),3.83(s,3H),2.22(s,1H),1.50(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ＝158.92,138.07,126.70,113.83,69.93,55.31,25.05.
实施例9：(S)-1-(2-氯苯基)乙醇的不对称合成
将0.5mmol的2-氯苯乙炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2equiv.,20uL),CF3CH2OH(1mL),50℃反应12h后，加入0.005mmol催化剂A,HCOONa(0.5 mmol,34mg)，H2O(1mL)，50℃反应5小时。反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：88％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-(2-氯苯基)乙醇的ee值为87％的。HPLC分离条件：手性柱大赛璐OD-H柱，流动相：正己烷/异丙醇＝99:1(体积比)，流速：1.0毫升/分钟，波长：220纳米，柱温：30摄氏度，t1＝20.65分钟，t2＝22.23分钟；1H NMR(400MHz,CDCl3):δ＝7.38-7.32(m,2H),7.26-7.22(m,1H),5.33(dd,J1＝6.8Hz,J2＝6.8Hz,1H),2.04(s,1H),1.53(d,J＝6.4Hz,3H)ppm；13C NMR(100MHz,CDCl3):δ＝143.05,131.665,129.43,128.44127.24,126.42,67.01,23.54.
实施例10：(S)-1-(4-氯苯基)乙醇的不对称合成
将0.5mmol的4-氯苯乙炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2equiv.,20uL),CF3CH2OH(1mL),40℃反应24h，加入0.005mmol催化剂A,HCOONa(0.5 mmol,34mg)，H2O(1mL)，50℃反应5小时。反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：75％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-(4-氯苯基)乙醇的ee值为92％的。HPLC分离条件：手性柱大赛璐OD-H柱，流动相：正己烷/异丙醇＝97:3(体积比)，流速：1.0毫升/分钟，波长：220纳米，柱温：30摄氏度，t1＝10.73分钟，t2＝11.91分钟；1H NMR(400MHz,CDCl3):δ＝7.37-7.32(m,4H),4.90(dd,J1＝12.8Hz,J2＝12.8Hz,1H), 2.05(s,1H),1.50(d,J＝6.4Hz,3H)ppm；13C NMR(100MHz,CDCl3):δ＝144.25,133.07, 128.61,126.81,69.75,25.29ppm.
实施例11：(S)-1-(4-硝基苯基)乙醇的不对称合成
将0.5mmol的4-硝基苯乙炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2equiv.,20uL),(CF3)2CHOH(1mL),50℃反应24h后，加入0.005mmol催化剂A,HCOONa(0.5mmol,34mg)，H2O(1mL)，50℃反应5小时。反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：66％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-(4-硝基苯基)乙醇的ee值为86％的。HPLC分离条件：手性柱大赛璐OJ-H柱，流动相：正己烷/异丙醇＝95:5(体积比)，流速：1.0毫升/分钟，波长：254纳米，柱温：30摄氏度，t1＝30.88分钟，t2＝34.17分钟；1H NMR(400MHz,CDCl3):δ＝8.21(dd,J1＝6.8Hz,J2＝6.8Hz,2H),7.57-7.55(m,2H), 5.03(dd,J1＝14.2Hz,J2＝14.2Hz,1H),2.37(s,1H),1.54(d,J＝6.4Hz,3H)ppm；13C NMR(100MHz,CDCl3):δ＝153.17,147.13,126.15,123.76,69.50,25.51ppm.
实施例12：(S)-1-(2,5-二氯苯基)乙醇的不对称合成
将0.5mmol的2,5-二氯苯乙炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2 equiv.,20uL),CF3CH2OH(1mL),50℃反应24h后，加入0.005mmol催化剂A,HCOONa(0.5mmol,34mg)，H2O(1mL)，50℃反应5小时。反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：79％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-(2,5-二氯苯基) 乙醇的ee值为86％，HPLC分离条件：手性柱大赛璐OD-H柱，流动相：正己烷/异丙醇＝99:1(体积比)，流速：1.0毫升/分钟，波长：220纳米，柱温：30摄氏度，t1＝19.90分钟，t2＝21.43 分钟；1H NMR(400MHz,CDCl3):δ＝7.51(d,J＝8.4Hz,1H),7.34(d,J＝6.0Hz,1H),7.27(dd, J1＝8.4Hz,J2＝8.4Hz,1H),5.22(dd,J1＝12.8Hz,J2＝12.8Hz,1H),2.78(s,1H),1.45(d,J＝6.4Hz,3H)ppm；13C NMR(100MHz,CDCl3):δ＝141.72,133.34,132.09,129.06,127.48,127.41,66.50,23.58ppm.
实施例13：(S)-1-萘乙醇的不对称合成
将0.5mmol的2-萘乙炔加入到试管中，依次加入CF3SO3H(20mol％,9uL),H2O(2equiv., 20uL),CF3CH2OH(1mL),50℃反应24h后，加入0.005mmol催化剂A,HCOONa(0.5mmol, 34mg)，H2O(1mL)，50℃反应5小时，反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，分离产率：89％(石油醚：乙酸乙酯＝5:1)，HPLC测定产物(S)-1-萘乙醇的ee值为88％， HPLC分离条件：手性柱大赛璐OJ-H柱，流动相：正己烷/异丙醇＝95:5(体积比)，流速：1.0 毫升/分钟，波长：230纳米，柱温：30摄氏度，t1＝23.63分钟，t2＝31.74分钟；1H NMR(400 MHz,CDCl3):δ＝7.89-7.85(m,4H),7.56-7.49(m,3H),5.13-5.08(m,1H),2.08(d,J＝3.2Hz, 1H),1.62(d,J＝6.4Hz,3H)ppm；13C NMR(100MHz,CDCl3):δ＝143.21,133.39,132.94, 128.34,127.96,127.70,126.18,125.83,123.85,123.83,70.56,25.17ppm。
Claims (3)
1.一种芳香炔烃一锅法直接转化成手性醇的方法，其特征在于，包括如下步骤：
将0.5mmol的苯乙炔加入到试管中，依次加入9μL 20mol％的CF3SO3H，20μL 2equiv的H2O，1mL的CF3CH2OH，40℃反应4h后，加入0.005mmol催化剂A
34mg0.5mmol的HCOONa，1mL的H2O，50℃反应5小时，反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，在石油醚：乙酸乙酯＝5:1下分离，分离产率：93％，HPLC测定产物(S)-1-苯乙醇的ee值为97％。
2.一种芳香炔烃一锅法直接转化成手性醇的方法，其特征在于，包括如下步骤：
将0.5mmol的4-甲基苯乙炔加入到试管中，依次加入9μL 20mol％的CF3SO3H，20μL2equiv的H2O，1mL的CF3CH2OH，50℃反应6h后，加入0.005mmol催化剂A
34mg 0.5mmol的HCOONa，1mL的H2O，50℃反应5小时，反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，在石油醚：乙酸乙酯＝5:1下分离，分离产率：83％，HPLC测定产物(S)-1-(4-甲基苯基)乙醇的ee值为98％。
3.一种芳香炔烃一锅法直接转化成手性醇的方法，其特征在于，包括如下步骤：
将0.5mmol的2-萘乙炔加入到试管中，依次加入9μL 20mol％的CF3SO3H，20μL 2equiv的H2O，1mL的CF3CH2OH，50℃反应24h后，加入0.005mmol催化剂A
34mg0.5mmol的HCOONa，1mL的H2O，50℃反应5小时，反应结束后用乙酸乙酯萃取3次，合并有机相浓缩至干，在石油醚：乙酸乙酯＝5:1下分离，分离产率：89％，HPLC测定产物(S)-1-萘乙醇的ee值为88％。
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