Fragment Couplings via CO2 Extrusion-Recombination: Expansion of a Classic Bond-Forming Strategy via Metallaphotoredox

In this study we demonstrate that molecular fragments, which can be readily coupled via a simple, in situ RO-C=OR bond-forming reaction, can subsequently undergo metal insertion decarboxylation recombination to generate C-sp(2)-C-sp(3) bonds when subjected to metallaphotoredox catalysis. In this embodiment the conversion of a wide variety of mixed anhydrides (formed in situ from carboxylic acids and acyl chlorides) to fragment-coupled ketones is accomplished in good to high yield. A three-step synthesis of the medicinal agent edivoxetine is also described using this new decarboxylation recombination protocol.