Screening of deprotection conditions of TBDMS protecting group on β-lactams.

Monocyclic β-lactams are valuable scaffolds for the development of novel antibacterial agents, and synthetic flexibility at the C3 position of the β-lactam ring is of particular interest. In this study, we evaluated multiple procedures for the deprotection of the tert‑butyldimethylsilyl (TBDMS) group in model azetidinone derivatives to enable early-stage functionalization of the C3 hydroxyl group. Given the sensitivity of the strained β-lactam ring and the presence of additional labile functionalities, careful selection of reaction conditions was required. Two optimized deprotection protocols were identified that successfully afforded the corresponding free alcohols, even in the presence of an acid- and base-sensitive dithiocarbamate moiety. In contrast, several literature-reported procedures proved ineffective under the tested conditions. Although the isolated yields were modest, the results demonstrate the feasibility of selective TBDMS removal in structurally complex monocyclic β-lactam systems. These findings establish a foundation for further optimization and provide a basis for expanding C3 functionalization strategies in the synthesis of novel β-lactam derivatives.