Light-Mediated Synthesis of Aliphatic Anhydrides by Cu-Catalyzed Carbonylation of Alkyl Halides

Abstract

Acid anhydrides are valuable in the chemical industry for their role in synthesizing polymers, pharmaceuticals, and other commodities, but their syntheses often involve multiple steps with precious metal catalysts. The simplest anhydride, acetic anhydride, is currently produced by two Rh-catalyzed carbonylation reactions on a bulk scale for its use in synthesizing products ranging from aspirin to cellulose acetate. Here, we report a light-mediated, Cu-catalyzed process for producing aliphatic, symmetric acid anhydrides directly by carbonylation of alkyl (pseudo)halides in a single step without any precious metal additives. The transformation requires only simple Cu salts and abundant bases to generate a heterogeneous Cu 0 photocatalyst in situ, maintains high efficiency and selectivity upon scale-up, and operates by a radical mechanism with several beneficial features. This discovery will enable the engineering of bulk processes for producing commodity anhydrides efficiently and sustainably.