Generation and Electrophile Trapping of <i>N</i>‑Boc-2-lithio-2-azetine: Synthesis of 2‑Substituted 2‑Azetines

<i>s</i>-BuLi-induced α-lithiation–elimination of LiOMe from <i>N</i>-Boc-3-methoxyazetidine and further in situ α-lithiation generates <i>N</i>-Boc-2-lithio-2-azetine which can be trapped with electrophiles, either directly (carbonyl or heteroatom electrophiles) or after transmetalation to copper (allowing allylations and propargylations), providing a concise access to 2-substituted 2-azetines

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

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

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

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