One-Pot, Base- and Metal-Free Practical Synthesis of Novel Cycloalkene-Fused [1,4]Thiazepines through the Sequential Ugi/S_NCsp² Reactions

Abstract

A one-pot and sequential Ugi/S_NCsp² four-component reaction was introduced for the synthesis of cycloalkene-fused [1,4]thiazepine derivatives. A variety of cyclic β-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.

Key words

thiazepines - sequential reactions - Ugi reaction - fused heterocycles - β-bromovinyl aldehyde

Publication History

Received: 06 April 2022

Accepted after revision: 14 September 2022

Accepted Manuscript online:
14 September 2022

Article published online:
06 October 2022

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