Synthesis of Substituted 2,5-Dihydrothiophene-2-Carboxylic Acids by Lithium/Ammonia Reduction

Abstract

The lithium/ammonia reduction of thiophene-2-carboxylic acid (1) has been reported independently by different investigators^1,2 to afford 2,5-dihydrothiophene-2-carboxylic acid (2) as the major product. The isolation of this compound, however, is made difficult by its susceptibility to further reduction or reductive cleavage under the reaction conditions employed. Compounds with allylic carbon-sulfur bonds, for example, are readily cleaved in metal/ammonia solutions^3a,b to give the corresponding mercaptans. With 2, reductive cleavage affords cis-5-mercapto-3-pentenoic acid (3) which, in fact can be made the exclusive reaction product from 1 by appropriate modification of reaction conditions.