Carbene and photocatalyst-catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles to form ketones

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 are 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 is 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. The combination of carbene- and photocatalysis has enabled unorthodox routes to ketone syntheses, but usually requires engineered or activated substrates. Herein the authors present a carbene- and photocatalytic decarboxylative radical coupling of carboxylic acids and acyl imidazoles, in which the carboxylic acids are directly used as radical precursors.

Automated summary

This study reports a decarboxylative radical coupling of carboxylic acids and acyl imidazoles catalyzed by an N-heterocyclic carbene and photocatalyst. The carboxylic acids serve as direct radical precursors, and suitable acyl imidazoles can also be generated in situby a reaction with CDI. The method is extended to three-component coupling by using alkenes as a third coupling partner via a radical relay process. The mild reaction conditions, simplicity, and use of easily available starting materials make this method a powerful strategy for constructing complex ketones and modifying natural products and medicines.