Copper-Catalyzed Asymmetric Defluoroborylation of 1-(Trifluoromethyl)Alkenes

Abstract

Summary gem-Difluoroalkenes have steric and electronic profiles similar to those of ketones, aldehydes, and esters, and consequently have been used widely as carbonyl isosteres in modern drug discovery. Although many attempts have been made to achieve gem-difluoroalkenes, the induction of enantioselectivity at the α position of a gem-difluorovinyl group still remains a challenge. Herein, an efficient method for the construction of gem-difluoroallylboronates with high enantiomeric excess via a copper-catalyzed defluoroborylation of 1-(trifluoromethyl)alkenes with B2pin2 is described. The reaction conditions were mild, and a variety of common functional groups, such as ether, fluoride, chloride, bromide, iodide, ester, cyano, sulfide, amino, and indoyl groups, were well tolerated. Furthermore, we not only applied this developed system as a powerful synthetic tool for the late-stage modification of complex compounds but also highlighted the utility of the formed compounds in synthesis.