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.