One-Pot, Base- and Metal-Free Practical Synthesis of Novel Cycloalkene-Fused [1,4]Thiazepines through the Sequential Ugi/SNCsp2 Reactions

A one-pot and sequential Ugi/S(N)Csp(2) four-component reaction was introduced for the synthesis of cycloalkene-fused [1,4]thiazepine derivatives. A variety of cyclic.-bromovinyl aldehyde with different sizes, amines, and isocyanides were reacted with thioglycolic acid. This approach can provide a practical and rapid access to the fused bioactive cycloalkene structures containing thiazepine, and peptide unit, which proved the achievement of a significant structural diversity. Further use of this method has been successfully applied in synthesizing a variety of quinoline-fused [1,4]thiazepines with satisfactory results. The practical nature of this approach was demonstrated by a gram-scale synthesis of a selected product.