Ir-Catalyzed Asymmetric Hydrogenation of Unprotected Indoles:Scope Investigations and Mechanistic Studies

查看全文 作　　者：Gongyi [1,2]Liu;Lini [3]Zheng;Kui [1]Tian;Haifeng [2]Wang;Lung Wa [3]Chung;Xumu [3]Zhang;Xiu-Qin [1,4]Dong 机构地区：[1]Engineering Research Center of Organosilicon Compounds and Materials,Ministry of Education,College of Chemistry and Molecular Sciences,Wuhan University,Wuhan,Hubei 430072;[2]Pharmaceutical Research Institute,Wuhan Institute of Technology,Wuhan,Hubei 430205;[3]Department of Chemistry,Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis,Southern University of Science and Technology,Shenzhen,Guangdong 518000;[4]Suzhou Institute of Wuhan University,Suzhou,Jiangsu 215123 出　　处：《CCS Chemistry》索引2023年第5卷第6期,共13页 基　　金：We are grateful for financial support from the National Natural Science Foundation of China(grant no.22071187);the Natural Science Foundation of Jiangsu Province(grant no.BK20190213);the Shenzhen Nobel Prize Scientists Laboratory Project(grant no.C17783101);the Guangdong Provincial Key Laboratory of Catalysis(grant no.2020B121201002);the Natural Science Foundation of Hubei Province(grant nos.2020CFA036 and 2021CFA069);the Scientific Research Project of Education Department of Hubei Province(grant no.B2020057).We are grateful to the High Performance Computing Center and the CHEM high performance supercomputer cluster(CHEM HPC)of the Southern University of Science and Technology. 摘　　要：Transition metal-catalyzed asymmetric hydrogenation(AH)of unprotected indoles has mainly been applied to alkyl substituted unprotected indoles.However,the challenging aryl substituted unprotected indoles with poor reactivity and enantioselectivity(≤42%ee)could not be hydrogenated well.In this work,a highly efficient Ir/bisphosphine-thiourea ligand ZhaoPhos catalytic system for the AH of challenging aryl substituted unprotected indoles has been successfully developed for the first time with high reactivity and excellent stereoselective control.Moreover,a series of 2-alkyl-substituted and 2,3-disubstituted unprotected indoles were also well tolerated in this catalytic system.A wide variety of chiral indoline derivatives were obtained in good to high yields with excellent stereoselectivities(75–99%yields,>20:1 dr,and 86–99%ee).The anion-binding activation strategy played an important role in accessing both high reactivity and excellent stereoselectivity,which was formed between the catalyst and unprotected indoles in situ-generating iminium ion with the assistance of Brønsted acid.A possible catalytic mechanism was proposed for this Ir-catalyzed AH according to density functional theory calculations and control experiment results.Readily available substrates,a broad range of substrate tolerance,an efficient chiral catalytic system,and a gram-scale protocol further demonstrated the potential practicality of this methodology. 关 键 词：asymmetric hydrogenation unprotected indoles anion-binding activation strategy chiral indoline derivatives ENANTIOSELECTIVITY