Enantioselective Construction of C-SCF3 Stereocenters via Nickel Catalyzed Asymmetric Negishi Coupling Reaction

Abstract

The construction of the SCF₃-containing 1,1-diaryl tertiary carbon stereocenters with high enantioselectivities is reported via a nickel-catalyzed asymmetric C-C coupling strategy. This method demonstrates simple operations, mild conditions and excellent functional group tolerance, with newly designed SCF₃-containing synthon, which can be easily obtained from commercially available benzyl bromide and trifluoromethylthio anion in a two-step manner. Further substrate exploration indicated that the reaction system could be extended to diverse perfluoroalkyl sulfide (SC₂F₅, SC₃F₇, SC₄F₉, SCF₂CO₂Et)-substituted 1,1-diaryl compounds with excellent enantioselectivities. The synthetic utility of this transformation was further demonstrated by convenient derivatization to optical SCF₃-containing analogues of bioactive compounds without an apparent decrease in enantioselectivity.

Keywords: 1,1-diarylalkane; C−C coupling; nickel catalysis; trifluoromethylthiolated benzylic bromide; trifluoromethylthiolated tertiary stereocenters.