Synthesis of 4,4-Disubstituted 1,2-Thiazinane-5-one 1,1-Dioxides via the CSIC^[≠] Reaction Strategy

A series of sp³-enriched 2,2-disubstituted 1,2-thiazinane-5-one 1,1-dioxides (including spirocyclic derivatives) has been synthesized through the CSIC [Carbanion mediated Sulfonate (Sulfonamido) Intramolecular Cyclization] reaction strategy. In particular, 2,2‑disubstituted alkyl 3‑aminopropanoates were subsequently sulfonylated with mesyl chloride followed by alkylation with methyl iodide to give the key precursor 2,2‑disubstituted methyl 3‑(methylsulfonamido)propanoates. The latter were treated with sodium hydride and underwent the intramolecular sulfa-Dieckmann cyclization yielding the target 4,4‑disubstituted 1,2‑thiazinane‑5‑one 1,1‑dioxides (so-called β-keto-δ-sultams). The structure of the target compounds was confirmed by an X-ray diffraction study.