Stereodivergent Construction of Adjacent Tetrasubstituted Stereocenters Enabled by CPA-Catalyzed Enantioselective Desymmetric Friedel-Crafts Reaction of α-Aryl-α-fluoro-1,3-indanediones.

Abstract

Here we report the asymmetric Friedel-Crafts reaction between compounds α-aryl-α-fluoro-1,3-indanediones and indoles, catalyzed by an efficient chiral phosphoric acid catalyst. Using this methodology, a series of cyclic β-fluoroalcohols bearing two adjacent chiral centers were synthesized in up to 95% yield, with excellent enantioselectivity (99% ee) and diastereomeric ratio (>20:1 dr). The resulting products can be readily transformed into other valuable compounds through straightforward synthetic transformations while preserving their absolute configuration. This catalytic system offers both theoretical insights and practical methodology for the efficient construction of asymmetric all-carbon quaternary stereocenters in β-fluoroalcohol frameworks.