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.