Direct Acylation of Alkyl and Aryl Bromides via Nickel-Catalyzed Aldehyde C-H Functionalization.

Aldehyde C-H activation followed by coupling of the acyl fragment with a functionalized reagent represents an attractive approach for the synthesis of functionalized ketones. Although this strategy has been utilized for the formation of ketones with diverse substitution patterns, the majority of approaches are tailored for the synthesis of ketones that possess aryl functionality derived from either or both substrates involved in the catalytic union. In this work, the development of acylation reactions of alkyl and aryl bromides to directly access ketones from aliphatic and (hetero)aromatic aldehydes is described. A key feature of the reactions is the thermal generation of acyl radicals via hydrogen atom transfer (HAT) with a peroxide-based HAT agent. In line with previous photochemical methods utilizing alternative HAT agents, judicious choice of tridentate (terpyridine) or bidentate (phenanthroline) ligands enables C(sp3) and C(sp2) bromides to participate as coupling partners. Optimal conditions for C(sp2) or C(sp3) bromides involve different ligands based on mechanistic differences in the organobromide addition step, and a computational basis for ligand choice according to organobromide structural features is described.