Enantioselective [2π + 2σ] Photocycloaddition Enabled by Brønsted Acid Catalyzed Chromophore Activation

J Am Chem Soc. 2024 Nov 20;146(46):31400-31404. doi: 10.1021/jacs.4c13596. Epub 2024 Nov 7.

Abstract

Bicyclo[2.1.1]hexanes have emerged as valuable scaffolds for the design of new pharmaceutical and agrochemical active ingredients. These structures can be efficiently synthesized via [2π + 2σ] photocycloadditions; however, control over the absolute stereochemistry of these strain-releasing reactions has remained challenging. Herein, we demonstrate that Brønsted acid catalyzed chromophore activation of C-acyl imidazoles enables highly enantioselective [2π + 2σ] photocycloadditions. Because this approach is agnostic to the identity of the coupling partner, the same strategy can be used to synthesize several other medicinally relevant strained small-ring structures.