Regioselective Synthesis of 1,2,3-Trisubstituted Pyrroles via Addition–Cyclization of Crotonate-Derived Sulfonium Salts with a Carboxylic Acid and an Amine

A sequential addition-cyclization reaction between carboxylic acids, crotonate sulfonium salts, and amines has been developed for the construction of 1,2,3-trisubstituted pyrroles. The reaction involves regioselective addition of crotonate sulfonium salts directly to <i>in situ</i>-activated carboxylic acids to construct the first C-C bond, followed by cyclization with a primary amine to create the two C-N bonds in one pot. The new transformation appears to have a general substrate scope, uses readily accessible starting materials, and proceeds rapidly at room temperature. The reaction is versatile and scalable, making it suitable for applications in process and medicinal chemistry.