Skeletal Editing: Access to Benzo[e][1,3]thiazin-4-ones

Abstract:

Benzo[e][1,3] thiazin-4-ones are an important class of benzene-fused six-membered S, Nheterocyclic scaffolds. Their core structures are widely found in natural products and pharmaceuticals. A large number of derivatives based on this skeleton exhibit valuable pharmacological activities, including antibacterial, anti-inflammatory, anticancer, and so on. However, previous methods for this skeleton primarily rely on intramolecular cyclization of ortho-functionalized aromatic precursors bearing both sulfur and nitrogen moieties. These existing approaches suffer from several inherent limitations: multistep reactions, pre-installation of functional groups, generation of halogencontaining waste residues, harsh reaction conditions, and residual transition metals. These drawbacks significantly restrict the substrate scope and functional group tolerance of existing approaches. Consequently, the development of green and efficient methods for accessing benzo[e][1,3] thiazin-4-ones remains a long-standing goal in organic synthesis. Skeletal editing strategy has recently emerged as a powerful and innovative methodology for the precise insertion, deletion, or exchange of atoms within heterocyclic or carbocyclic rings. It allows the efficient preparation of structurally diverse heterocycles from readily available simple cyclic precursors via relatively short reaction sequences. To date, substantial efforts have been dedicated to skeletal editing methodologies. However, no dedicated reviews currently focus on skeletal editing strategies for the synthesis of benzo[e][1,3] thiazine-4- ones. This minireview summarizes recent advances in the skeletal editing synthesis of benzo[e][1,3] thiazin-4-ones. These advances include ring expansion of benzo[c][1,2] dithiol-3-ones via sulfur atom exchange with C=N or C–N moieties, as well as the ring expansion of benzo[d]isothiazol- 3(2H)-ones via single-carbon insertion. Furthermore, this review is organized by the structural classification of benzo[e][1,3] thiazin-4-ones. Additionally, the plausible reaction mechanisms of these skeletal editing transformations and future perspectives for the field are also discussed.