Regioselective Synthesis of Highly Substituted Aromatic Sulfides via Carbonyl−Alkyne Exchange Reaction

Abstract

Carbonyl−alkyne exchange reaction of 2,2-dimethyldihydropyran-4-thione-derived dienes with acetylenic ketones leads to highly substituted aromatic sulfides. The reaction proceeds with a high degree of regioselectivity and in good yields. Addition of Et2AlCl considerably increases the scope of usable acetylenic ketones. The starting materials, dihydropyran-4-one and α-alkynyl ketone derivatives, are readily available reactive building blocks. Additional diversity can be introduced through straightforward derivatization reactions at the sulfur atom. The use of solid-supported reagents and trapping agents allows the reaction to be carried out in a parallel format which might render such a concept attractive for the synthesis of compound libraries.