Transition Metal- and Catalyst-Free Acylation of Alkyl Halides Using α-Hydroxyketones as Acyl Anion Equivalents

The development of practical acyl anion equivalents for carbonyl umpolung reactivity remains a formidable challenge in organic synthesis, as classical strategies are frequently hindered by the requirement of toxic reagents, mandatory deprotection steps, or sophisticated catalysts. Herein, we report that readily available α-hydroxyketones function as versatile acyl anion equivalents under exceptionally simple, transition-metal-free, and catalyst-free conditions. This protocol enables the direct acylation of alkyl halides, affording a diverse range of ketones in moderate to good yields. Mechanistic studies elucidate a novel pathway, which involves initial C1-alkylation followed by a unique "CH₂O" transfer through tandem aldol/retro-aldol reactions, distinguishing it from classical umpolung processes. The reaction exhibits broad functional group tolerance and was successfully applied to the late-stage functionalization of complex bioactive molecules.