A Platform For Decarboxylative Couplings Via Photoredox Catalysis: Direct Access To Carbocations From Carboxylic Acids For Carbon-Oxygen Bond Formation

Within the past decade, photoredox catalysis has enabled numerous decarboxylative transformations to couple carboxylic acids with a variety of partners primarily through carbon-centered radical intermediates. Herein, we describe a method for the construction of carbon-oxygen bonds using a dual photoredox/iodine(III) platform directly from simple carboxylic acids and alcohols. This activation platform enables the direct utilization of readily available acids and alcohols without the need for prefunctionalization and works broadly across primary, secondary, and tertiary carboxylic acid substrates. We propose that this transformation proceeds via a radical-polar crossover event to generate a discrete carbocation intermediate which is intercepted by a nucleophilic coupling partner, thereby overcoming the electronically mismatched nature inherent in previous radical-based decarboxylative couplings. The application of this mechanistic approach toward additional nucleophiles is also demonstrated using water, enabling a direct decarboxylative-hydroxylation reaction. Finally, we demonstrated that the decarboxylative etherification can be applied to a peptide substrate, selectively functionalizing serine over other nucleophilic residues, providing support for future potential bioconjugation applications.