α‑Lithiation–Electrophile Trapping of <i>N</i>‑Thiopivaloylazetidin-3-ol: Stereoselective Synthesis of 2‑Substituted 3‑Hydroxyazetidines

Abstract

α-Lithiation of <i>N</i>-thiopivaloylazetidin-3-ol and subsequent electrophile trapping provides access to a range of 2-substituted 3-hydroxyazetidines with generally good <i>trans</i>-diastereoselectivity, aside from deuteration, which gives the <i>cis</i>-diastereoisomer. Deuterium labeling studies indicate that the initial α-deprotonation occurs preferentially, but not exclusively, in a <i>trans</i>-selective manner. These studies also suggest that the stereochemical outcome of the electrophile trapping depends on the electrophile used but is independent of which α-proton (<i>cis</i> or <i>trans</i> to the hydroxyl group) is initially removed