General and Modular Access to Enantioenriched α-Trifluoromethyl Ketones via Nickel-Catalyzed Reductive Trifluoroalkylation  

作　　者：Dengkai Lin Yongzhi Chen Zhan Dong Pan Pei Haiting Ji Lanzhu Tai Liang-An Chen 

机构地区：[1]Jiangsu Collaborative Innovation Center of Biomedical Functional Materials,Jiangsu Key Laboratory of New Power Batteries,School of Chemistry and Materials Science,Nanjing Normal University,Nanjing 210023

出　　处：《CCS Chemistry》2023年第6期1386-1397,共12页中国化学会会刊（英文）

基　　金：We gratefully acknowledge funding from the Jiangsu Specially Appointed Professor Plan,National Natural Science Foundation of China(grant no.22071111);Natural Science Foundation of Jiangsu Province of China(grant no.BK20201368).

摘　　要：The development of new catalytic enantioselective access to stereogenic CF_(3)-containingmolecules is of great interest for expediting the discovery of lead compounds that remain challenging.Specifically,enantioselective synthesis of valuable ketones featuring stereogenicα-CF_(3) has rarely been reported.We devise a general and modular approach to facilely access enantioenrichedα-CF_(3) ketones via nickel-catalyzed reductive cross-coupling of readily available acid chlorides and racemicα-CF_(3) alkyl bromides in an enantioconvergent fashion under mild conditions.This protocol features neighboring directing group-free,high chemoselectivity,excellent functional group tolerance,facile scale-up,and notable amenability to straightforward downstream elaboration toward pharmaceutically useful enantioenrichedβ-trifluoromethylated secondary and tertiary alcohols,thus constituting a reliable,direct,practical,and efficient synthetic alternative to furnish enantiopureα-CF_(3) carbonyls.Interestingly,an appropriate choice of the phosphine ligand as coligand plays an important role in high efficiency and asymmetric induction.Mechanistic studies suggest a radical chain pathway.

关 键 词：nickel catalysis ENANTIOSELECTIVE TRIFLUOROMETHYL KETONES RADICAL 

分 类 号：O62[理学—有机化学]