Intramolecular thia-anti-Michael addition of a sulfur anion to enones: a regiospecific approach to multisubstituted thiophene derivatives.

The intramolecular thia-anti-Michael addition starting from readily available alpha-alkenoyl-alpha'-carbamoyl ketene-(S,S)-acetals 1 containing a 1,3-dithiolane moiety was developed. In particular, in the presence of aliphatic primary amines, a series of tetrasubstituted thiophene derivatives, 2-(alkylamino)-5-alkyl-4-hydroxythiophene-3-carboxamides 2, were synthesized via tandem fragmentation, substitution, and intramolecular thia-anti-Michael addition reactions of 1, where amine played the dual roles of a base and a nucleophile. The intramolecular thia-anti-Michael addition, as the key step, proceeded in a regiospecific manner and showed a general scope to the beta-substituents of enones 1. A possible mechanism for the formation of the multisubstituted thiophenes was proposed. By this research, a new and efficient route to various tetrasubstituted thiophene derivatives was created.