Strategic advances in the synthesis of β-sultams: exploiting a privileged scaffold for sulfur-containing heterocycles

β-Sultams, recognized as the sulfur congeners of β-lactams, constitute a privileged scaffold among four-membered heterocycles. Defined by a strained cyclic sulfonamide motif, β-sultams possess a unique architecture that underpins distinct reactivity and biological significance, establishing them as compelling targets for synthetic and medicinal chemists. However, the strategic assembly of the β-sultam core, especially with precise chemo-, regio-, and stereocontrol, remains a persistent synthetic hurdle. This review provides a critical overview of the strategic evolution in β-sultam synthesis, spanning from classical thermal [2 + 2] cycloadditions to state-of-the-art catalytic and click-chemistry paradigms. Special emphasis is placed on the transformative impact of SuFEx (Sulfur(VI) Fluoride Exchange) chemistry in mediating efficient [3 + 1] cyclizations, alongside the revitalization of the Staudinger reaction via asymmetric catalysis. Additionally, we discuss innovative ring-expansion and functionalization tactics that underscore the scaffold's versatility. By dissecting the mechanistic subtleties and synthetic utility of these approaches, this work offers a strategic roadmap for engineering functionalized sulfur heterocycles, effectively bridging fundamental methodology with pharmaceutical applications.