Pummerer Reactions of Thiopyran Derivatives as a Method for the Preparation of Trifluoro-Methyl-Substituted Thiolanes with Antiviral Activity

Abstract

2-(p-Tolylsulfanyl)-2-trifluoromethyl-3,6-dihydro-2Н-thiopyran 1-oxides undergo a vinylogous Pummerer reaction upon interaction with trifluoroacetic anhydride, forming 2-(p-tolylsulfanyl)-4-tri-fluoroacetoxy-2-trifluoromethyl-3,4-dihydro-2Н-thiopyrans. The hydrolysis, acetylation, and free radical desulfanylation of these compounds with a subsequent oxidation of the sulfur atom leads to 4-acetoxy-2-trifluoromethyl-3,4-dihydro-2Н-thiopyran 1-oxides. The Pummerer addition reaction of the latter with acetic anhydride and boron trifluoride etherate results in a ring contraction and formation of 3-acet-oxy-2-diacetoxymethyl-5-(trifluoromethyl)thiolanes, which could be converted with sodium boro-hydride to 3-hydroxy-2-hydroxymethyl-5-(trifluoromethyl)thiolanes having antiviral activity.