Domino Synthetic Strategy for Tetrahydrothiopyran Derivatives from Benzaldehydes, 2-Acetylfuran/2-Acetylthiophene, and Sodium Sulfide

J Org Chem. 2020 Jul 17;85(14):9088-9095. doi: 10.1021/acs.joc.0c01006. Epub 2020 Jun 26.

Abstract

A novel domino reaction from benzaldehydes and 2-acetylfuran/2-acetylthiophene with sodium sulfide was developed to synthesize a series of tetrahydrothiopyran (THTP) derivatives. The reaction proceeded well to construct a tetrahydrothiopyran ring and five new bonds in one step. A mechanism is proposed, involving a stepwise Aldol/double Michael addition/Aldol (AMMA) reaction cascade. In this transformation, sodium sulfide acts as a nucleophile and base. This method is characterized by transition-metal-free, commercially available starting materials and mild reaction conditions.