One-Pot Mitsunobu Protocol to Access Ketene S,S-/N,S-Acetals at Room Temperature

With unique chemical reactivity, alpha-oxoketene S,S- and N,S-acetals have attracted enormous attention in the past decades, whereas limited reports exist for their synthesis via eco-compatible protocols. Herein, we developed a one-pot protocol for symmetrical and unsymmetrical alpha-oxoketene S,S-/N,S-acetals through chemoselective alkylation of alpha-enolic dithioesters using Mitsunobu chemistry at room temperature. The operationally simple and user-friendly mild protocol tolerates a wide range of alcohols and alpha-enolic dithioesters/beta-ketothioamides. Short reaction time, good yields, highly selective C-S functionalization, and E/Z-stereoselectivity are imperative characteristics of this strategy.

Automated summary

A one-pot protocol was developed for the synthesis of symmetrical and unsymmetrical alpha-oxoketene S,S-/N,S-acetals through chemoselective alkylation of alpha-enolic dithioesters using Mitsunobu chemistry at room temperature. This user-friendly method tolerates a wide range of alcohols and alpha-enolic dithioesters/beta-ketothioamides, providing good yields and highly selective C-S functionalization with E/Z-stereoselectivity.