Copper-Catalyzed Asymmetric Tertiary Radical Cyanation for the Synthesis of Chiral Tetrasubstituted Monofluoroacyl Nitriles

Abstract

The construction of chiral tetrasubstituted α-fluoro-α-cyano carbonyl compounds remains a key challenge in synthetic organic chemistry because of their popularity in multiple disciplines. In this paper, we report the copper-catalyzed asymmetric fluorinated tertiary radical cyanation reaction of cyclic α-iodo-α-fluoroindanones with TMSCN to achieve chiral nitriles with carbon–fluorine quaternary stereogenic centers. Thus, an array of optically active tetrasubstituted monofluoroacyl nitriles were synthesized with high reaction efficiency and excellent enantioselectivities (up to 91% yield, 99% ee). Moreover, mechanistic investigations, including experiments, were conducted to clarify the reaction pathway and stereochemical outcomes.