[3,3]-Acyloxy Rearrangement-Triggered Regioselective Hydration of δ‑Acetoxy-α,β-Alkynoates/Halo Alkynes

Herein, we report a simple, efficient, highly regioselective, and broad-scope hydration method that is facilitated by an unusual interception of an electrophilic intermediate by water generated via acetate group participation during [3,3]-acyloxy rearrangement. Various carboxylate-directing groups including acetate, acrylates, pivalates, benzoate or its derivatives, and those derived from bioactive natural products were successfully implemented to direct the regioselective hydration for various functionalized δ-acyloxy-β-ketoester synthesis. The reaction pathway was further confirmed by ¹⁸O labeling experiments, and to the best of our knowledge, this is the first report of hydration through an electrophilic intermediate generated during [3,3]-acyloxy rearrangement. Synthetic application includes the synthesis of a modifiable C5-carbon chain, five-, six-, and seven-membered heterocycles, and natural product diversification.