The Bifunctional Silyl Reagent Me<sub>2</sub>(CH<sub>2</sub>Cl)SiCF<sub>3</sub> Enables Highly Enantioselective Ketone Trifluoromethylation and Related Tandem Processes
Bo‐Shuai Mu, Yang Gao, Yang Fu-ming, Wen‐Biao Wu, Ying Zhang, Xin Wang, Jin‐Sheng Yu, Jian Zhou
Abstract
Abstract We report the development of bifunctional trifluoromethylsilyl reagents for selective trifluoromethylation. The newly developed reagent, Me 2 (CH 2 Cl)SiCF 3 , allows highly enantioselective trifluoromethylations of ketones with broad scope. Notably, by taking advantage of the chloromethyl group, a tandem synthesis of chiral trifluoromethylated oxasilacyclopentanes is developed, paving way to α‐CF 3 tertiary alcohols with vicinal tertiary or quaternary stereocenters. Theoretical studies revealed the important role of nonclassical C−H⋅⋅⋅F−C interactions in stabilizing the transition state, and that the presence of the chlorine atom enhances such interactions for better enantiofacial control.