Enantiocontrolled Azetidine Library Synthesis via Strain-Release Functionalization of 1‑Azabicyclobutanes

A simple, modular, and programmable approach to access
complex
stereopure azetidines through strain-release functionalization is
disclosed. The synthetic methods developed enable the parallel synthesis
of stereodefined azetidines that would be otherwise laborious to produce.
Given the privileged nature of these structures, a set of stereoprobes
for use in activity-based protein profiling was prepared and evaluated,
revealing proteins in human cancer cells, which were liganded with
clear stereo- and chemo-selectivity.