Regio- and Enantioselective Hydroalkylations of Unactivated Olefins Enabled by Nickel Catalysis: Reaction Development and Mechanistic Insights

Yang，Peng Fei1; Zhu，Lei2; Liang，Jian Xing1; Zhao，Han Tong1; Zhang，Jian Xin1; Zeng，Xian Wang1; Ouyang，Qin2; Shu，Wei1

2022-04-01

10.1021/acscatal.2c00665

ACS Catalysis   影响因子和分区

2155-5435

Direct construction of fully alkyl-substituted tertiary chiral centers remote to activating groups is highly challenging and desirable. Herein, a Ni-catalyzed enantioselective hydroalkylation of unactivated alkenes with unactivated alkyl halides at room temperature is reported, providing a general and practical access to fully alkyl-substituted tertiary stereogenic carbon centers not adjacent to activating groups. This reaction undergoes the regio-and stereoselective hydrometalation of unactivated alkenes with a nontrivial Markovnikov selectivity, followed by the cross-coupling with unactivated alkyl electrophiles to access trialkyl tertiary saturated stereogenic centers not adjacent to activating groups. The mild and robust conditions enable the use of terminal and internal unactivated alkenes and unactivated primary and secondary alkyl, benzyl, and propargyl halides to construct diverse trialkyl tertiary stereogenic carbon centers with broad functional group tolerance. Moreover, experimental investigations support the reaction undergoing irreversible and stereoselective hydrometalation of alkenes. Density functional theory calculations provide further insights into the reaction mechanism, suggesting a stereoselective migration insertion of alkenes with Ni(II)-H species. Finally, the origin of the regio- and enantioselectivities is also investigated.

enantioselective hydroalkylation unactivated olefins tertiary stereogenic center nickel catalysis mechanistic investigations

SCI ; EI

英语

第一 ; 通讯

NSFC["21971101","21801126","22171127"] ; Guangdong Basic and Applied Basic Research Foundation["2022A1515011806","2019A1515011976"] ; Department of Education of Guangdong Province[2021KTSCX106] ; Pearl River Talent Recruitment Program[2019QN01Y261] ; Stable Support Plan Program of Shenzhen Natural Science Fund[20200925152608001] ; Thousand Talents Program for Young Scholars, Guangdong Provincial Key Laboratory of Catalysis[2020B121201002]

Chemistry

Chemistry, Physical

WOS:000821150900001

AMER CHEMICAL SOC

20222012122050

Carbon ; Catalysis ; Chemical activation ; Density functional theory ; Enantioselectivity ; Nickel compounds ; Stereoselectivity

Chemistry:801 ; Physical Chemistry:801.4 ; Chemical Reactions:802.2 ; Chemical Products Generally:804 ; Organic Compounds:804.1 ; Probability Theory:922.1 ; Atomic and Molecular Physics:931.3 ; Quantum Theory; Quantum Mechanics:931.4

Web of Science

1.Shenzhen Grubbs Institute,Department of Chemistry,Guangdong Provincial Key Laboratory of Catalysis,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China
2.Department of Medicinal Chemistry,College of Pharmacy,Third Military Medical University,Chongqing,400038,China

Yang，Peng Fei,Zhu，Lei,Liang，Jian Xing,et al. Regio- and Enantioselective Hydroalkylations of Unactivated Olefins Enabled by Nickel Catalysis: Reaction Development and Mechanistic Insights[J]. ACS Catalysis,2022,12(10):5795-5805.

Yang，Peng Fei.,Zhu，Lei.,Liang，Jian Xing.,Zhao，Han Tong.,Zhang，Jian Xin.,...&Shu，Wei.(2022).Regio- and Enantioselective Hydroalkylations of Unactivated Olefins Enabled by Nickel Catalysis: Reaction Development and Mechanistic Insights.ACS Catalysis,12(10),5795-5805.

Yang，Peng Fei,et al."Regio- and Enantioselective Hydroalkylations of Unactivated Olefins Enabled by Nickel Catalysis: Reaction Development and Mechanistic Insights".ACS Catalysis 12.10(2022):5795-5805.