Carbene and Photocatalyst-Catalyzed Decarboxylative Radical Coupling of Carboxylic Acids and Acyl Imidazoles to Form Ketones

Abstract

The carbene and photocatalyst co-catalyzed radical coupling of acyl electrophile and a radical precursor is emerging as attractive method for ketone synthesis. However, previous reports mainly limited to prefunctionalized radical precursors and two-component coupling. Herein, an N-heterocyclic carbene and photocatalyst catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles is disclosed, in which the carboxylic acids were directly used as radical precursors. The acyl imidazoles could also be generated in situ by reaction of a carboxylic acid with CDI thus furnishing a formally decarboxylative coupling of two carboxylic acids. In addition, the reaction was successfully extended to three-component coupling by using alkene as a third coupling partner via a radical relay process. The mild conditions, operational simplicity, and use of carboxylic acids as the reacting partners make our method a powerful strategy for construction of complex ketones from readily available starting materials, and late-stage modification of natural products and medicines.

Radical acylation: concepts, synthetic applications and directions

“…Very recently, Chi's group disclosed the direct decarboxylative acylation of carboxylic acids with acyl imidazoles by merging NHC catalysis and photoredox catalysis, which features mild conditions, a broad substrate scope and wide functional group tolerance (Scheme 20). 40 Notably, the direct use of carboxylic acids avoids the tedious preparation of redox-active esters (RAE), and acyl imidazoles could be formed in situ via the reaction of carboxylic acid with CDI, thus providing a straightforward strategy for the construction of ketone moieties from two different carboxylic acids.…”