In conclusion, a modular approach enabling rapid access to enantiopure 2,3-disubstituted azetidines with either cis-or trans-orientation has been disclosed. The protocols outlined herein allow for installation of a diverse array of functionalization patterns as well as the creation of products with fully substituted stereocenters. A wide array of azetidines was prepared in addition to a complete set of acrylamide stereoprobes for use in chemical proteomic studies that revealed distinct protein interactions for 3-aryl-vs 3amino stereoprobes in human cancer cells. Future studies can include expanding the complexity of accessible azetidines even further (higher order substition), mapping the liganded cysteines on 3-amino stereoprobe targets by cysteine-directed ABPP, and understanding the functional impact of these interactions.