Evaluation of diphenylphosphine oxide in the reduction of aldehydes and ketones.

Alcohols represent a fundamental class of compounds with broad biological relevance and widespread utility in organic synthesis. Despite the central role of carbonyl reduction in alcohol synthesis, commonly used methods such as catalytic hydrogenation or hydride-based reductions may require specialized equipment or careful handling. Herein, we introduce a mild and operationally simple protocol for the synthesis of primary and secondary alcohols based on a Pudovik-phospha-Brook rearrangement. The transformation proceeds via reaction of aldehydes and ketones with diphenylphosphine oxide in the presence of sodium hydroxide in dry THF, where the optimized basic conditions promote the formation and subsequent cleavage of phosphinate intermediates to furnish the corresponding alcohols. Notably, the optimized conditions enable chemoselective reduction of aromatic ketones in the presence of aliphatic ketones, as well as selective reduction of aldehydes. The synthetic utility of this methodology is demonstrated by the preparation of pharmaceutically relevant alcohols.