CN108117569A - 一种有机催化傅克反应合成手性胺基膦酸酯的方法 - Google Patents
一种有机催化傅克反应合成手性胺基膦酸酯的方法 Download PDFInfo
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- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 title claims abstract description 18
- 238000005727 Friedel-Crafts reaction Methods 0.000 title claims abstract description 12
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims abstract description 11
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 11
- 125000003277 amino group Chemical group 0.000 title claims abstract description 7
- 238000006555 catalytic reaction Methods 0.000 title claims abstract description 6
- -1 amino phosphonate ester Chemical class 0.000 claims abstract description 35
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 32
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- 150000002475 indoles Chemical class 0.000 claims abstract description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- 239000000758 substrate Substances 0.000 claims description 13
- 239000003960 organic solvent Substances 0.000 claims description 9
- 238000000926 separation method Methods 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 4
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- 239000011574 phosphorus Substances 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 claims 2
- 239000012046 mixed solvent Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 abstract description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 54
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- 230000014759 maintenance of location Effects 0.000 description 16
- 238000004679 31P NMR spectroscopy Methods 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000006722 reduction reaction Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 0 C*(C)C(C(C(C)=CC=C(C)C*)=C)=NC Chemical compound C*(C)C(C(C(C)=CC=C(C)C*)=C)=NC 0.000 description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000004293 19F NMR spectroscopy Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BCXBKOQDEOJNRH-UHFFFAOYSA-N NOP(O)=O Chemical class NOP(O)=O BCXBKOQDEOJNRH-UHFFFAOYSA-N 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 241000208340 Araliaceae Species 0.000 description 1
- IVHVNMLJNASKHW-UHFFFAOYSA-M Chlorphonium chloride Chemical compound [Cl-].CCCC[P+](CCCC)(CCCC)CC1=CC=C(Cl)C=C1Cl IVHVNMLJNASKHW-UHFFFAOYSA-M 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- QLDHWVVRQCGZLE-UHFFFAOYSA-N acetyl cyanide Chemical compound CC(=O)C#N QLDHWVVRQCGZLE-UHFFFAOYSA-N 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000008301 phosphite esters Chemical class 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical class NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- DHNUAKOQUGJUGA-UHFFFAOYSA-N silicon;sulfane Chemical compound [Si].S DHNUAKOQUGJUGA-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- 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
- C07B2200/09—Geometrical isomers
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
一种有机催化傅克反应合成手性胺基膦酸酯的方法，其用到的有机催化剂是手性磷酸。催化一系列亚胺膦酸酯与吲哚发生不对称傅克反应能得到相应的季碳中心手性胺基膦酸酯，其对映体过量可达到98％。本发明操作简便实用易行，催化剂商业可得，反应条件温和。此外，通过不对称傅克反应合成手性胺基膦酸酯，对映选择性高，产率好，且反应具有原子经济性，环境友好等优点。
Description
技术领域
本发明涉及一种应用手性磷酸的均相体系高度对映选择性催化亚胺膦酸酯与吲哚发生不对称傅克反应合成手性胺基膦酸酯的方法。
背景技术
光学活性的胺基膦酸与氨基酸在结构上具有相似性，同样具备广泛的生理活性，可作为酶抑制剂，抗真菌剂，抗菌剂和抗癌剂等(参考文献一：(a)Senten,K.；L.；Van der Veken,P.；De Meester,I.；Lambeir,A.-M.；Scharpé,S.；Haemers,A.；Augustyns,K.J.Comb.Chem.2003,5,336.(b)Maier,L.；Diel,P.J.Phosphorous,Sulfur SiliconRelat.Elem.1994,90,259.(c)Grembecka,J.；Mucha,A.；Cierpicki,T.Kafarski,P.J.Med.Chem.2003,46,2641.(d)Yao,G.；Ye,M.；Huang,R.；Li,Y.；Pan,Y.；Xu,Q.；Liao,Z.；Wang,H.Bioorg.Med.Chem.Lett.2014,24,501.)。基于此，胺基膦酸及其衍生物的不对称合成受到了科研工作者的广泛关注，根据成键方式的不同，手性胺基膦酸及其衍生物的合成策略主要包括立体选择性的C-P键形成，C-C键形成，C-N键形成，C-H键形成(参考文献二：(a)M.；Rojas-Cabrera,H.；Cativiela,C.Tetrahedron 2009,65,17.(b)M.；Viveros-Ceballos,J.L.；Cativiela,C.；Sayago,F.J.Tetrahedron 2015,71,1745.)。
手性季碳中心的构建始终是一个充满挑战的课题。目前，已经发展了一些有效策略构建四级碳手性氨基膦酸酯化合物，如含碳或氮亲电试剂对膦酸酯底物的亲电进攻(参考文献三：(a)Studer,A.；Seebach,D.Heterocycles1995,40,357.(b)Kuwano,R.；Nishio,R.；Ito,Y.Org.Lett.1999,1,837.(c)Sawamura,M.；Hamashima,H.；Ito,Y.Bull.Chem.Soc.Jpn.2000,73,2559.(d)Kim,S.M.；Kim,H.R.；Kim,D.Y.Org.Lett.2005,7,2309.(e)Bernardi,L.；Zhuang,W.；K.A.J.Am.Chem.Soc.2005,127,5772.(f)Wilt,J.C.；Pink,M.；Johnston,J.N.；Chem.Commun.2008,4177.(g)Bera,K.；Namboothiri,I.N.N.Org.Lett.2012,14,980)，亚磷酸酯与酮亚胺底物的不对称加成反应(参考文献四：(a)Mikolajczyk,M.；P.；Drabowicz,J.Tetrahedron:Asymmetry 1997,8,3991.(b)Davis,F.A.；Lee,S.；Yan,H.；Titus,D.D.Org.Lett.2001,3,1757.(c)Chen,Q.；Li,J.；Yuan,C.Synthesis2008,2986.(d)Nakamura,S.；Hayashi,M.；Hiramatsu,Y.；Shibata,N.；Funahashi,Y.；Toru,T.J.Am.Chem.Soc.2009,131,18240.)，以及含碳亲核试剂对酮亚胺底物的不对称加成反应(参考文献五：(a)Rassukana,Y.V.；Yelenich,I.P.；Vlasenko,Y.G.；Onys’ko,P.P.Tetrahedron:Asymmetry 2014,25,1234.(b)Vicario,J.；Ezpeleta,J.M.；Palacios,F.Adv.Synth.Catal.2012,354,2641.(c)Vicario,J.；Ortiz,P.；Ezpeleta,J.M.；Palacios,F.J.Org.Chem.2015,80,156.(d)Yan,Z.；Wu,B.；Gao,X.；Zhou,Y.-G.Chem.Commun.2016,52,10882.)。值得一提的是，亲核加成策略中，亲核试剂仅局限于丙酮、乙酰氰、硝基甲烷和芳基硼酸等，为满足多样的季碳中心手性氨基膦酸酯的合成需求，亲核试剂仍有待进一步的丰富。手性磷酸催化吲哚对一系列亚胺底物的不对称加成反应已有一些报道(参考文献六：(a)Jia,Y.-X.；Zhong,J.；Zhu,S.-F.,Zhang,C.-M.；Zhou,Q.-L.Angew.Chem.2007,119,5661.(b)Rueping,M.；Raja,S.；A.Adv.Synth.Catal.2011,353,563.(c)Yin,Q.；You,S.-L.Chem.Sci.2011,2,1344.(d)Husmann,R.；Sugiono,E.；Mersmann,S.；Raabe,G.；Rueping,M.；Bolm,C.Org.Lett.2011,13,1044.(e)Qian,Y.；Jing,C.-C.；Zhai,C.-W.；Hu,W.-H.Adv.Synth.Catal.2012,354,301.(f)Feng,J.-C.；Yan,W.-J.；Wang,D.；Li,P.；Sun,Q.-T.；Wang,R.Chem.Commun.2012,48,8003.)，基于以上背景，我们设想能否采用相同的策略，利用手性磷酸催化吲哚与亚胺膦酸酯底物进行不对称加成反应来合成季碳中心手性氨基膦酸酯化合物。
发明内容
本发明的目的是提供一种有机催化傅克反应合成手性胺基膦酸酯的方法。本发明操作简便实用，对映选择性高，产率好，且反应具有原子经济性，环境友好等优点。
为实现上述目的，本发明的技术方案如下：
本发明以手性磷酸作催化剂，亚胺膦酸酯与吲哚发生不对称加成反应得到相应的手性胺基膦酸酯，反应式和条件如下：
式中：
温度：0-50℃；
溶剂：有机溶剂；
时间：24-48小时；
催化剂：手性磷酸
所述R为C1-C10的烷基，苯环上的取代基为F、Cl、Me、MeO、Et、CN中的一种或二种以上取代基，取代基个数为1-3；
反应步骤为：
反应步骤为：在反应瓶中投入亚胺膦酸酯底物，吲哚(式1中底物用量的2equiv–4equiv)和手性磷酸(式1中底物用量的5mol％-10mol％)，加入有机溶剂，0-50℃下反应24-48小时；除去溶剂后直接柱层析分离得到纯的产物。
所述催化剂为手性磷酸，均为市售且无需任何处理。
所述有机溶剂为二氯甲烷、乙醚、甲苯、均三甲苯中的一种或两种以上的混合。
本发明具有以下优点
1.反应活性和对映选择性高，反应完全，生成产物专一，核磁氢谱没有检测到副反应，使得能分离方便，能获得高的对映体过量纯品。
2.能得到季碳中心手性胺基膦酸酯。
3.催化剂制备方便，反应操作简便实用。
4.反应条件温和。
具体实施方式
下面通过实施例详述本发明，但本发明并不限于下述的实施例。
实施例1：条件的优化
空气中，依次向反应瓶中加入五元环亚胺膦酸酯2a(33mg,0.1mmol)，手性磷酸(式1中底物用量的10mol％)和有机溶剂(2mL)，室温下搅拌十分钟，随后加入吲哚3(35mg,0.3mmol)，30℃下反应，TLC监测反应进程。反应结束后，直接柱层析分离得到纯的产物，反应式和手性磷酸结构如下：
其产率为分离收率，产物的对映体过量用手性液相色谱测定，详见表1。
表1.亚胺膦酸酯2a与吲哚的不对称加成反应a
实施例2：手性磷酸催化傅克反应合成各种手性胺基膦酸酯4
空气中，依次向反应瓶中加入五元环亚胺膦酸酯2(0.1mmol)，手性磷酸(式1中底物用量的5mol％)和有机溶剂(2mL)，室温下搅拌十分钟，随后加入吲哚3(35mg,0.3mmol)，30℃下反应，TLC监测反应进程。反应结束后，直接柱层析分离得到纯的产物，反应式和手性磷酸结构如下：
产率为分离收率，产物的对映体过量用手性液相色谱测定，见表2。
表2.手性磷酸催化傅克反应合成各种手性胺基膦酸酯4a
(R)-diisopropyl
(3-(1H-indol-3-yl)-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-3-yl)phosphonate(4a):44mg,98％yield,96％ee,[α]20 D＝+49.09(c 0.66,6.77(t,J＝7.3Hz,1H),4.85-4.60(m,1H),4.50-4.25(m,1H),1.40-1.05(m,9H),0.81(d,J＝5.8Hz,3H)；13C NMR(100MHz,DMSO)δ138.4(d,JPC＝4.5Hz),137.6,136.8(d,JPC＝5.2Hz),134.0,131.4,127.8,127.4(d,JPC＝2.6Hz),126.1(d,JPC＝11.5Hz),122.6,122.0,121.2,120.1,112.9,111.6(d,JPC＝3.8Hz),73.6(d,JPC＝8.2Hz),73.4(d,JPC＝6.7Hz),64.7(d,JPC＝166.3Hz),25.3,25.1(d,JPC＝2.7Hz),24.8(d,JPC＝5.4Hz),23.9(d,JPC＝5.5Hz)；31P NMR(162MHz,DMSO)δ16.4.HPLC:Chiralcel AD-H column,230nm,30℃,n-hexane/i-propanol＝70/30,flow＝0.7mL/min,retention time 14.9min and 18.3min(maj).HRMSCalculated for C21H26N2O5PS[M+H]+449.1295,found 449.1301.
(R)-diisopropyl
(3-(2-methyl-1H-indol-3-yl)-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-3-yl)phos-phonate(4b):42mg,91％yield,59％ee,[α]20 D＝+18.29
(m,1H),4.49-4.35(m,1H),2.19(s,3H),1.29(d,J＝6.2Hz,3H),1.26(d,J＝6.2Hz,3H),1.08(d,J＝6.2Hz,3H),0.79(d,J＝6.2Hz,3H)；13C NMR(100MHz,CDCl3)δ139.0(d,JPC＝5.2Hz),135.7(d,JPC＝5.1Hz),135.2(d,JPC＝8.1Hz),134.9,132.8(d,JPC＝2.1Hz),130.1(d,JPC＝2.1Hz),128.1(d,JPC＝2.5Hz),127.1(d,JPC＝6.4Hz),121.7,121.5,121.0,120.2,110.4,106.9(d,JPC＝3.2Hz),74.2(d,JPC＝8.1Hz),73.6(d,JPC＝7.7Hz),65.8(d,JPC＝165.9Hz),24.5(d,JPC＝2.7Hz),24.4(d,JPC＝3.3Hz),23.7(d,JPC＝5.7Hz),23.0(d,JPC＝5.9Hz),15.6；31P NMR(162MHz,CDCl3)δ15.6.HPLC:Chiralcel AD-H column,230nm,30℃,n-hexane/i-propanol＝70/30,flow＝0.7mL/min,retention time 10.8min(maj)and16.8min.HRMS Calculated for C22H28N2O5PS[M+H]+463.1451,found 463.1460.
(R)-diisopropyl
(3-(4-methyl-1H-indol-3-yl)-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-3-yl)phos-phonate(4c):42mg,91％yield,87％ee,[α]20 D＝+9.64
7.02(t,J＝7.6Hz,1H),6.70(d,J＝7.1Hz,1H),5.40(d,J＝7.3Hz,1H),4.98-4.85(m,1H),4.40-4.28(m,1H),1.72(s,3H),1.35(d,J＝6.1Hz,6H),1.28(d,J＝6.1Hz,3H),0.74(d,J＝6.2Hz,3H)；13C NMR(100MHz,CDCl3)δ140.4(d,JPC＝4.8Hz),137.7,137.0(d,JPC＝4.9Hz),133.1(d,JPC＝2.9Hz),131.1,130.2(d,JPC＝2.9Hz),129.7(d,JPC＝5.3Hz),127.3(d,JPC＝3.1Hz),124.2(d,JPC＝12.6Hz),123.3,122.7,122.0(d,JPC＝2.3Hz),109.7,74.3(d,JPC＝1.7Hz),74.2(d,JPC＝3.0Hz),65.9(d,JPC＝159.1Hz),24.5(d,JPC＝2.8Hz),24.3(d,JPC＝4.2Hz),24.1(d,JPC＝4.4Hz),22.8(d,JPC＝5.9Hz),22.4；31P NMR(162MHz,CDCl3)δ16.3.HPLC:Chiralcel AD-H column,230nm,30℃,n-hexane/i-propanol＝80/20,flow＝0.7mL/min,retention time 33.9min and 37.1min(maj).HRMS Calculated forC22H28N2O5PS[M+H]+463.1451,found 463.1460.
(dichloromethane/methanol 80/1).1H NMR(400MHz,CDCl3)δ8.85(s,1H),7.90(d,J＝7.7Hz,1H),7.74(s,1H),7.65-7.51(m,3H),7.23(d,J＝8.3Hz,1H),7.02(s,1H),6.96(d,J＝8.2Hz,1H),5.33(d,J＝4.8Hz,1H),4.95-4.80(m,1H),4.52-4.34(m,1H),2.27(s,3H),1.39-1.17(m,9H),0.77(d,J＝6.1Hz,3H)；13C NMR(100MHz,CDCl3)δ137.8(d,JPC＝3.8Hz),135.5(d,JPC＝5.2Hz),135.0,133.3(d,JPC＝2.3Hz),130.1(d,JPC＝2.5Hz),129.8,127.3(d,JPC＝2.6Hz),126.1(d,JPC＝4.3Hz),125.0(d,JPC＝10.5Hz),124.4,121.5(d,JPC＝1.7Hz),119.9,111.4,110.5,74.0(d,JPC＝8.4Hz),73.7(d,JPC＝7.7Hz),64.8(d,JPC＝165.4Hz),24.5,24.3(d,JPC＝3.7Hz),24.0(d,JPC＝5.1Hz),22.9(d,JPC＝5.9Hz),21.8；31PNMR(162MHz,CDCl3)δ15.4(d,J＝5.9Hz).HPLC:Chiralcel AD-H column,230nm,30℃,n-hexane/i-propanol＝80/20,flow＝0.7mL/min,retention time 20.3min(maj)and23.0min.HRMS Calculated for C22H28N2O5PS[M+H]+463.1451,found463.1458.
(R)-diisopropyl
(3-(6-methyl-1H-indol-3-yl)-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-3-yl)phos-phonate(4e):43mg,93％yield,94％ee,[α]20 D＝
4.95-4.81(m,1H),4.52-4.36(m,1H),2.35(s,3H),1.33(d,J＝6.1Hz,3H),1.31-1.21(m,6H),0.79(d,J＝6.1Hz,3H)；13C NMR(100MHz,CDCl3)δ137.8(d,JPC＝4.0Hz),137.2,135.5(d,JPC＝5.0Hz),133.3(d,JPC＝2.5Hz),132.6,130.2(d,JPC＝2.5Hz),127.2(d,JPC＝2.7Hz),125.6(d,JPC＝4.0Hz),122.6(d,JPC＝11.0Hz),122.3,121.5(d,JPC＝1.9Hz),119.8,111.7,110.8(d,JPC＝3.6Hz),74.0(d,JPC＝8.3Hz),73.7(d,JPC＝7.7Hz),64.7(d,JPC＝166.0Hz),24.5(d,JPC＝2.7Hz),24.3(d,JPC＝3.6Hz),24.0(d,JPC＝5.2Hz),23.0(d,JPC＝5.8Hz),21.7；31P NMR(162MHz,CDCl3)δ15.3(d,J＝5.4Hz).HPLC:Chiralcel AD-H column,230nm,30℃,n-hexane/i-propanol＝70/30,flow＝0.7mL/min,retention time 20.5min(maj)and 24.5min.HRMS Calculated for C22H28N2O5PS[M+H]+463.1451,found 463.1461.
(R)-diisopropyl
(3-(7-methyl-1H-indol-3-yl)-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-3-yl)phos-phonate(4f):44mg,96％yield,95％ee,[α]20 D＝+60.11(c 0.88,THF),
4.49-4.35(m,1H),2.46(s,3H),1.35(d,J＝6.1Hz,3H),1.32-1.25(m,6H),0.79(d,J＝6.2Hz,3H)；13C NMR(100MHz,CDCl3)δ137.8(d,JPC＝3.8Hz),136.3,135.6(d,JPC＝5.0Hz),133.3(d,JPC＝2.5Hz),130.2(d,JPC＝2.5Hz),127.2(d,JPC＝2.7Hz),126.2(d,JPC＝3.9Hz),124.3(d,JPC＝11.5Hz),123.3,121.5(d,JPC＝2.0Hz),121.0,120.8,117.7,111.2(d,JPC＝4.1Hz),74.1(d,JPC＝8.4Hz),73.8(d,JPC＝7.8Hz),64.8(d,JPC＝165.4Hz),24.5(d,JPC＝2.8Hz),24.3(d,JPC＝3.8Hz),24.1(d,JPC＝5.0Hz),22.9(d,JPC＝5.8Hz),16.7；31PNMR(162MHz,CDCl3)δ15.2.HPLC:Chiralcel AD-H column,230nm,30℃,n-hexane/i-propanol＝70/30,flow＝0.7mL/min,retention time 18.5min and 21.4min(maj).HRMSCalculated for
1H NMR(400MHz,CDCl3)δ9.35(s,1H),7.98(s,1H),7.90(d,J＝7.5Hz,1H),7.66-7.42(m,3H),7.05-6.83(m,3H),5.26(d,J＝4.6Hz,1H),5.01-4.83(m,1H),4.53-4.29(m,1H),3.00-2.70(m,2H),1.45-1.15(m,12H),0.78(d,J＝5.8Hz,3H)；13C NMR(100MHz,CDCl3)δ137.8(d,JPC＝3.9Hz),135.6,135.6(d,JPC＝5.3Hz),133.3(d,JPC＝2.2Hz),130.2(d,JPC＝2.5Hz),127.3(d,JPC＝2.6Hz),127.2,126.1(d,JPC＝3.6Hz),124.5(d,JPC＝11.5Hz),121.5(d,JPC＝2.0Hz),121.3,120.9,117.7,111.2(d,JPC＝4.2Hz),74.1(d,JPC＝8.4Hz),73.9(d,JPC＝7.6Hz),64.8(d,JPC＝165.4Hz),24.5(d,JPC＝2.6Hz),24.3(d,JPC＝3.8Hz),24.2(d,JPC＝5.0Hz),24.0,22.9(d,JPC＝5.9Hz),14.0；31P NMR(162MHz,CDCl3)δ15.2(d,J＝5.8Hz).HPLC:Chiralcel AD-H column,230nm,30℃,n-hexane/i-propanol＝70/30,flow＝0.7mL/min,retention time 16.1min and 20.4min(maj).HRMS Calculated forC23H30N2O5PS[M+H]+477.1608,found 477.1613.
(R)-diisopropyl
(3-(5-methoxy-1H-indol-3-yl)-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-3-yl)phos-phonate(4h):47mg,98％yield,94％ee,[α]20 D＝(d,J＝1.7Hz,1H),4.78-4.64(m,1H),4.41-4.25(m,1H),3.46(s,3H),1.25(d,J＝6.1Hz,3H),1.21-1.12(m,6H),0.78(d,J＝6.2Hz,3H)；13C NMR(100MHz,DMSO)δ154.1,138.4(d,JPC＝4.8Hz),136.9(d,JPC＝4.9Hz),134.0(d,JPC＝1.6Hz),132.6,131.3(d,JPC＝2.0Hz),127.8(d,JPC＝2.4Hz),127.7(d,JPC＝3.5Hz),126.5(d,JPC＝11.4Hz),121.9,113.4,112.7,111.3(d,JPC＝5.3Hz),103.2,73.6(d,JPC＝8.0Hz),73.3(d,JPC＝7.5Hz),64.8(d,JPC＝165.8Hz),56.2,25.3(d,JPC＝2.7Hz),25.1(d,JPC＝3.3Hz),24.8(d,JPC＝5.5Hz),23.9(d,JPC＝5.6Hz)；31P NMR(162MHz,DMSO)δ16.5.HPLC:Chiralcel OD-H column,230nm,30℃,n-hexane/i-propanol＝80/20,flow＝0.7mL/min,retention time 10.0min and 12.5min(maj).HRMS Calculated for C22H28N2O6PS[M+H]+479.1400,found 479.1408.
(R)-diisopropyl
(3-(5-fluoro-1H-indol-3-yl)-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-3-yl)phos-phonate(4i):44mg,94％yield,94％ee,[α]20 D＝+25.79
(c 0.88,THF),unknown compound,white solid,m.p.＝233-234℃,Rf＝0.20(dichloromethane/methanol 80/1).1H NMR(400MHz,DMSO)δ11.36(d,J＝2.0Hz,1H),8.83(s,1H),7.98-7.90(m,1H),7.76(d,J＝2.5Hz,1H),7.73-7.65(m,2H),7.57-7.50(m,1H),7.37(dd,J＝8.8,4.8Hz,1H),6.94-6.79(m,2H),4.77-4.63(m,1H),4.40-4.26(m,1H),1.25(d,J＝6.2Hz,3H),1.19(d,J＝6.1Hz,3H),1.13(d,J＝6.2Hz,3H),0.78(d,J＝6.2Hz,3H)；13C NMR(100MHz,DMSO)δ157.8(d,JFC＝231.1Hz),138.0(d,JPC＝4.7Hz),136.7(d,JPC＝5.0Hz),134.3,134.1(d,JPC＝2.4Hz),131.5(d,JPC＝1.5Hz),129.1(d,JPC＝4.3Hz),127.7(d,JPC＝2.4Hz),126.2(d,JPC＝10.4Hz),122.1,113.9(d,JFC＝10.2Hz),112.1,110.9(d,JFC＝26.0Hz),106.2(d,JFC＝24.6Hz),73.7(d,JPC＝8.0Hz),73.5(d,JPC＝7.4Hz),64.5(d,JPC＝166.1Hz),25.3(d,JPC＝2.8Hz),25.1(d,JPC＝3.3Hz),24.7(d,JPC＝5.6Hz),23.9(d,JPC＝5.7Hz)；19F NMR(376MHz,DMSO)δ-124.2；31P NMR(162MHz,DMSO)δ16.3(t,J＝6.5Hz).HPLC:Chiralcel AS-H column,230nm,30℃,n-hexane/i-propanol＝80/20,flow＝0.7mL/min,retention time 12.0min(maj)and 23.4min.HRMS Calculated for C21H25FN2O5PS[M+H]+467.1200,found 467.1205.
(dichloromethane/methanol 40/1).1H NMR(400MHz,CDCl3)δ8.82(s,1H),7.90(d,J＝7.8Hz,1H),7.75(d,J＝1.8Hz,1H),7.67-7.53(m,3H),7.22(dd,J＝8.9,5.2Hz,1H),7.00(dd,J＝9.2,2.0Hz,1H),6.78-6.67(m,1H),5.33(d,J＝5.5Hz,1H),4.92-4.79(m,1H),4.50-4.34(m,1H),1.34(d,J＝6.2Hz,3H),1.28(d,J＝6.1Hz,3H),1.23(d,J＝6.2Hz,3H),0.78(d,J＝6.2Hz,3H)；13C NMR(100MHz,CDCl3)δ160.2(d,JFC＝239.6Hz),137.5(d,JPC＝4.2Hz),136.8(d,JFC＝12.3Hz),135.4(d,JPC＝5.0Hz),133.4(d,JPC＝2.5Hz),130.4(d,JPC＝2.4Hz),127.1(d,JPC＝2.7Hz),126.3,121.6(d,JPC＝1.8Hz),121.5(d,JFC＝9.9Hz),110.2,109.5(d,JFC＝24.2Hz),97.9(d,JFC＝25.8Hz),74.1(d,JPC＝8.2Hz),73.9(d,JPC＝7.6Hz),64.4(d,JPC＝164.2Hz),24.5(d,JPC＝2.7Hz),24.3(d,JPC＝3.6Hz),24.0(d,JPC＝5.2Hz),23.0(d,JPC＝5.9Hz)；19F NMR(376MHz,CDCl3)δ-120.1；31P NMR(162MHz,CDCl3)δ15.3.HPLC:Chiralcel AD-H column,230nm,30℃,n-hexane/i-propanol＝80/20,flow＝0.7mL/min,retention time 22.5min(maj)and 28.6min.HRMS Calculated forC21H25FN2O5PS[M+H]+467.1200,found 467.1207.
(R)-diisopropyl
(3-(5-chloro-1H-indol-3-yl)-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-3-yl)phos-phonate(4k):47mg,98％yield,95％ee,[α]20 D＝-5.11
1H),7.71-7.51(m,4H),7.30(s,1H),7.17(d,J＝8.7Hz,1H),7.03(d,J＝8.7Hz,1H),5.56(d,J＝5.4Hz,1H),4.90-4.75(m,1H),4.49-4.32(m,1H),1.33(d,J＝6.1Hz,3H),1.27(d,J＝6.1Hz,3H),1.19(d,J＝6.1Hz,3H),0.75(d,J＝6.1Hz,3H)；13C NMR(100MHz,CDCl3)δ137.2(d,JPC＝4.3Hz),135.5(d,JPC＝5.2Hz),135.1,133.4(d,JPC＝2.3Hz),130.4(d,JPC＝2.2Hz),127.1(d,JPC＝4.9Hz),127.1(d,JPC＝2.9Hz),126.2,125.9(d,JPC＝9.1Hz),123.1,121.8(d,JPC＝1.5Hz),120.1,112.7,111.1(d,JPC＝3.5Hz),74.2(d,JPC＝8.2Hz),74.0(d,JPC＝7.7Hz),64.2(d,JPC＝165.2Hz),24.5(d,JPC＝2.7Hz),24.3(d,JPC＝3.6Hz),23.9(d,JPC＝5.3Hz),23.0(d,JPC＝5.9Hz)；31P NMR(162MHz,CDCl3)δ15.3(d,J＝5.9Hz).HPLC:Chiralcel AD-H column,230nm,30℃,n-hexane/i-propanol＝80/20,flow＝0.7mL/min,retention time 21.3min and 22.9min(maj).HRMS Calculated for C21H25ClN2O5PS[M+H]+483.0905,found 483.0910.
(R)-diisopropyl
(3-(5-bromo-1H-indol-3-yl)-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-3-yl)phos-phonate(4l):52mg,98％yield,96％ee,[α]20 D＝
4.47-4.33(m,1H),1.32(d,J＝6.1Hz,3H),1.26(d,J＝6.1Hz,3H),1.18(d,J＝6.2Hz,3H),0.74(d,J＝6.2Hz,3H)；13C NMR(100MHz,CDCl3)δ137.2(d,JPC＝4.3Hz),135.5(d,JPC＝5.3Hz),135.4,133.3(d,JPC＝2.2Hz),130.4(d,JPC＝2.1Hz),127.1(d,JPC＝2.6Hz),127.0(d,JPC＝4.8Hz),126.5(d,JPC＝8.9Hz),125.6,123.2,121.7(d,JPC＝1.6Hz),113.7,113.2,110.9,74.3(d,JPC＝8.3Hz),74.0(d,JPC＝7.8Hz),64.2(d,JPC＝165.7Hz),24.5(d,JPC＝2.7Hz),24.3(d,JPC＝3.6Hz),23.9(d,JPC＝5.3Hz),23.0(d,JPC＝5.9Hz)；31P NMR(162MHz,CDCl3)δ15.3(d,J＝5.8Hz).HPLC:Chiralcel AD-H column,230nm,30℃,n-hexane/i-propanol＝80/20,flow＝0.7mL/min,retention time 21.9min and 27.1min(maj).HRMSCalculated for C21H25BrN2O5PS[M+H]+527.0400,found 527.0409.
(dichloromethane/methanol 40/1).1H NMR(400MHz,CDCl3)δ9.64(s,1H),7.90(d,J＝7.0Hz,1H),7.77-7.51(m,5H),7.24-7.12(m,2H),6.05(d,J＝3.3Hz,1H),4.88-4.70(m,1H),4.54-4.34(m,1H),1.31(d,J＝6.1Hz,3H),1.26(d,J＝6.1Hz,3H),1.15(d,J＝6.1Hz,3H),0.79(d,J＝6.1Hz,3H)；13C NMR(100MHz,CDCl3)δ138.4,136.9(d,JPC＝5.2Hz),135.4(d,JPC＝5.2Hz),133.5(d,JPC＝1.6Hz),130.7,128.1(d,JPC＝4.9Hz),126.9(d,JPC＝2.4Hz),126.4,125.3,124.6(d,JPC＝8.7Hz),121.9,120.6,112.8,112.3,103.4,74.5(d,JPC＝8.0Hz),74.2(d,JPC＝7.7Hz),63.8(d,JPC＝165.5Hz),24.4(d,JPC＝2.7Hz),24.3(d,JPC＝3.4Hz),23.8(d,JPC＝5.5Hz),23.1(d,JPC＝5.8Hz)；31P NMR(162MHz,CDCl3)δ15.2(d,J＝5.7Hz).HPLC:Chiralcel AS-H column,230nm,30℃,n-hexane/i-propanol＝70/30,flow＝0.7mL/min,retention time9.2min(maj)and 13.9min.HRMS Calculated forC22H25N3O5PS[M+H]+474.1247,found 474.1255.
(R)-diisopropyl
(3-(1H-indol-3-yl)-5-methyl-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-3-yl)phos-phonate(4n):40mg,87％yield,96％ee,[α]20 D＝
1H),4.78-4.62(m,1H),4.43-4.27(m,1H),2.32(s,3H),1.26(d,J＝6.1Hz,3H),1.19(d,J＝6.1Hz,3H),1.15(d,J＝6.2Hz,3H),0.83(d,J＝6.2Hz,3H)；13C NMR(100MHz,DMSO)δ144.1(d,JPC＝2.4Hz),138.8(d,JPC＝4.3Hz),137.6,134.4(d,JPC＝5.0Hz),132.2(d,JPC＝2.4Hz),127.6(d,JPC＝2.6Hz),127.4(d,JPC＝3.4Hz),126.1(d,JPC＝11.8Hz),122.6,121.8(d,JPC＝1.7Hz),121.2,120.1,112.9,111.7(d,JPC＝5.0Hz),73.6(d,JPC＝8.1Hz),73.3(d,JPC＝7.4Hz),64.6(d,JPC＝165.2Hz),25.3(d,JPC＝2.9Hz),25.2(d,JPC＝3.2Hz),24.8(d,JPC＝5.5Hz),24.0(d,JPC＝5.4Hz),22.5；31P NMR(162MHz,DMSO)δ16.5.HPLC:ChiralcelAD-H column,230nm,30℃,n-hexane/i-propanol＝70/30,flow＝0.7mL/min,retentiontime 13.7min and 17.2min(maj).HRMS Calculated for C22H28N2O5PS[M+H]+463.1451,found 463.1456.
(R)-diisopropyl
(5-methyl-3-(5-methyl-1H-indol-3-yl)-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-3-yl)phosphonate(4o):42mg,88％yield,96％ee,
1H),7.23(d,J＝8.3Hz,1H),6.91(s,1H),6.84(d,J＝8.2Hz,1H),4.77-4.63(m,1H),4.39-4.26(m,1H),2.33(s,3H),2.15(s,3H),1.26(d,J＝6.1Hz,3H),1.18(d,J＝6.1Hz,3H),1.15(d,J＝6.2Hz,3H),0.80(d,J＝6.2Hz,3H)；13C NMR(100MHz,DMSO)δ144.0(d,JPC＝2.4Hz),138.8(d,JPC＝4.5Hz),135.9,134.4(d,JPC＝5.0Hz),132.1(d,JPC＝2.2Hz),128.3,127.7(d,JPC＝2.3Hz),127.2(d,JPC＝3.8Hz),126.4(d,JPC＝11.1Hz),124.1,121.8,121.2,112.5,111.2(d,JPC＝4.8Hz),73.6(d,JPC＝8.0Hz),73.3(d,JPC＝7.6Hz),64.7(d,JPC＝165.6Hz),25.3(d,JPC＝2.8Hz),25.2(d,JPC＝3.3Hz),24.8(d,JPC＝5.5Hz),23.9(d,JPC＝5.5Hz),22.7,22.5；31P NMR(162MHz,DMSO)δ16.6.HPLC:Chiralcel AS-H column,230nm,30℃,n-hexane/i-propanol＝80/20,flow＝0.7mL/min,retention time 8.9min(maj)and12.9min.HRMS Calculated for C23H30N2O5PS[M+H]+477.1608,found 477.1613.
(R)-diethyl
(3-(1H-indol-3-yl)-1,1-dioxido-2,3-dihydrobenzo[d]isothiazol-3-yl)phosphon
1H),7.12(t,J＝7.5Hz,1H),6.98(d,J＝8.0Hz,1H),6.90(t,J＝7.5Hz,1H),5.50(s,1H),4.42-4.22(m,2H),4.04-3.88(m,1H),3.87-3.67(m,1H),1.30(t,J＝7.0Hz,3H),1.12(t,J＝7.0Hz,3H)；13C NMR(100MHz,CDCl3)δ137.6(d,JPC＝3.9Hz),136.7,135.5(d,JPC＝4.7Hz),133.4(d,JPC＝2.4Hz),130.4(d,JPC＝2.5Hz),127.4(d,JPC＝2.7Hz),126.4(d,JPC＝3.9Hz),124.6(d,JPC＝11.7Hz),122.9,121.5(d,JPC＝2.1Hz),120.7,119.9,111.8,110.7(d,JPC＝4.3Hz),65.6(d,JPC＝7.6Hz),64.5(d,JPC＝165.8Hz),64.2(d,JPC＝7.5Hz),16.7(d,JPC＝5.3Hz),16.3(d,JPC＝5.6Hz)；31P NMR(162MHz,CDCl3)δ17.2.HPLC:Chiralcel AS-H column,230nm,30℃，n-hexane/i-propanol＝80/20,flow＝0.7mL/min,retention time23.3min(maj)and 30.9min.HRMS Calculated for C19H22N2O5PS[M+H]+421.0982,found421.0987.
本发明涉及一种应用手性磷酸的均相体系高度对映选择性催化亚胺膦酸酯与吲哚发生不对称傅克反应合成季碳中心手性胺基膦酸酯的方法，其产率可达98％，对映体过量可达到98％。本发明操作简便易行，原料及催化剂均简单易得，反应条件温和。
Claims (7)
1.一种有机催化傅克反应合成手性胺基膦酸酯的方法，其用到的有机催化剂是手性磷酸，反应式和条件如下：
式中：
温度：0-50℃；
溶剂：有机溶剂；
时间：24-48小时；
所述R为C1-C10的烷基，R1、R2分别为H或苯环上的取代基，苯环上的取代基为F、Cl、Me、MeO、Et、CN中的一种或二种以上取代基，取代基个数为1-3。
2.如权利要求1所述的方法，其特征在于：
反应步骤为：在反应瓶中投入亚胺膦酸酯底物，吲哚(式1中底物用量的2equiv–4equiv)和手性磷酸(式1中底物用量的5mol％-10mol％)，加入有机溶剂，0-50℃下反应24-48小时；除去溶剂后直接柱层析分离得到纯的产物。
3.如权利要求1所述的方法，其特征在于：所述催化剂为手性磷酸，均为市售且无需任何处理。
4.如权利要求1或2所述的方法，其特征在于：底物亚胺膦酸酯与催化剂的物质的量的比是20/1-10/1。
5.如权利要求1所述的合成方法，其特征在于：反应所用的有机溶剂为二氯甲烷、乙醚、甲苯、均三甲苯中的一种或两种以上的混合溶剂。
6.如权利要求1、2或5所述的合成方法，其特征在于：当亚胺膦酸酯底物用量为0.1mmol时，有机溶剂的用量为2.0mL。
7.如权利要求1或2所述的方法，其特征在于：所述反应式为亚胺膦酸酯与吲哚发生不对称傅克反应得到相应的手性胺基膦酸酯，催化剂为手性磷酸，溶剂为均三甲苯，温度为30℃时所述结果最佳。
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| CN111423332A (zh) * | 2020-05-25 | 2020-07-17 | 上海科技大学 | 一种拆分手性化合物的方法 |
| CN114057785A (zh) * | 2021-12-13 | 2022-02-18 | 河南师范大学 | 手性α-二氟甲基硅烷化合物的合成方法 |
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| CN104710377A (zh) * | 2013-12-13 | 2015-06-17 | 中国科学院大连化学物理研究所 | 一种仿生不对称氢化合成手性胺的方法 |
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| CN104710377A (zh) * | 2013-12-13 | 2015-06-17 | 中国科学院大连化学物理研究所 | 一种仿生不对称氢化合成手性胺的方法 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111423332A (zh) * | 2020-05-25 | 2020-07-17 | 上海科技大学 | 一种拆分手性化合物的方法 |
| CN111423332B (zh) * | 2020-05-25 | 2023-02-10 | 上海科技大学 | 一种拆分手性化合物的方法 |
| CN114057785A (zh) * | 2021-12-13 | 2022-02-18 | 河南师范大学 | 手性α-二氟甲基硅烷化合物的合成方法 |
| CN114057785B (zh) * | 2021-12-13 | 2023-03-28 | 河南师范大学 | 手性α-二氟甲基硅烷化合物的合成方法 |
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