Hydroacylation

Hydroacylation is a class of organometallic reactions in which an aldehyde adds across a carbon–carbon multiple bond, typically yielding a ketone after workup. The process can be intramolecular or intermolecular and is mediated by transition metals that enable activation of the aldehyde C–H bond, formation of a metal–acyl (or formyl) intermediate, and coupling to an alkene or alkyne to forge a new C–C bond.

Mechanistically, many hydroacylations proceed via oxidative addition of the aldehyde C–H to a low-valent metal, transformation into a metal–acyl species, migratory insertion into the coordinated C=C or C≡C bond to generate a metal–alkyl or –vinyl intermediate, and subsequent reductive elimination to release the ketone while regenerating the catalyst. Dehydrogenative variants use a hydrogen acceptor or oxidant to avoid formed hydrides. Intramolecular hydroacylation often affords cyclic ketones with good regio- and stereocontrol.

Catalysts and scope: Rhodium and iridium complexes are among the most developed catalysts for intermolecular hydroacylation of aldehydes with alkenes, with additional examples using nickel, iron, cobalt, palladium, and photoredox systems. Substrates include a broad range of aldehydes (aromatic and aliphatic) and alkenes or alkynes (terminal or internal), with selectivity influenced by ligand, substrate electronics, and chelation effects.

Applications and challenges: Hydroacylation provides a direct route to ketones and cyclic ketones from simple starting materials, complementing other acylation strategies. Challenges include decarbonylation side reactions, controlling regio- and enantioselectivity in asymmetrical variants, and expanding substrate compatibility and reaction conditions to more practical settings.