Optimization of organocatalyzed sulfa-Michael/aldol cascade reaction of benzylidene-pyrrolone derivative using 2-mercaptoacetaldehyde was carried out. Under optimized reaction conditions, a library of 10 spirocyclic compounds was synthesized from respective heteroarylidene-pyrroline-4-ones. Reactions proved to be highly stereoselective (up to >99% ee, dr 96:4), yielding decent amounts of isolated spirocyclic compounds (32–84%). The end products contain spirocyclic, pyrrolone and tetrahidrothiophene motifs that frequently exhibit biological activity.
Amino acid building blocks have been used to synthesize pyrroline-4-one related tetramic acid and its benzylidene derivative. Benzylidene-tetramic acid has been subsequently reacted with 1,4-dithiane-2,5-diol in the presence of an organocatalyst yielding a novel spirocyclic product. The application of two different organocatalysts led to the formation of two different diastereomers.