Non-cephem drugs with 1,3-thiazine-derived rings are very rare, although a number of bioactive 1,3-thiazine derivatives are known. Similarly, 1,4-thiazepine-derived drugs are rare, but many 1,4-thiazepine derivatives show interesting biological activities. Therefore, our aim was the synthesis of such N,S-heterocycles using a versatile and short (1–3 steps) literature method. First, a three-component reaction of a cycloalkene, a thioamide, and an aldehyde provided 5,6-dihydro-4H-1,3-thiazines. Afterwards, Staudinger ketene–imine cycloaddition with chloroketene resulted in β-lactam-fused 1,3-thiazinanes. Finally, treatment with sodium methoxide induced ring expansion, yielding 4,5,6,7-tetrahydro-1,4-thiazepines. This synthetic pathway generates 3–5 new chiral centers with the help of pericyclic reactions, and almost every cycloaddition proceeded in a diastereoselective manner. Two-dimensional NOESY as well as single-crystal X-ray diffraction enabled unequivocal determination of the stereochemistry of all synthesized compounds
