Nickel-Catalyzed Enantio- and Diastereoselective Synthesis of Fluorine-Containing Vicinal Stereogenic Centers
Uttam Dhawa, Lara Lavrencic, Xile Hu
Abstract
The construction of fluorinated architectures has been a topic of interest to medicinal chemists due to their unique ability to improve the pharmacokinetic properties of bioactive compounds. However, the stereoselective synthesis of fluoro-organic compounds with vicinal stereogenic centers is a challenge. Herein, we present a directing-groupfree nickel-hydride catalyzed hydroalkylation of fluoroalkenes to afford fluorinated motifs with two adjacent chiral centers in excellent yields and stereoselectivities. Our method provides expedient access to biologically relevant, highly enantioenriched organofluorine compounds. Furthermore, the strategy can be used for the diastereo- and enantioselective synthesis of vicinal difluorides, which have recently gained attention in the fields of organocatalysis and peptide mimics.