Theoretical Studies on the Bifunctionality of Thiourea-Based Organocatalysts

Significance

A computational mechanistic study of the enantioselective Michael addition of acetyl­acetone to nitroolefin promoted by a thiourea-based chiral bifunctional organocatalyst is presented. The optimal structural arrangement of the active sites of the catalyst has been attained via protonation of its basic center by the nucleophilic substrate through a reversible kinetic process. The generally accepted mechanism for the adduct formation involves electrophile activation through hydrogen bonds with the thiourea moiety and subsequent C-C bond formation between simultaneously activated components (pathway 1). An alternative reaction mechanism for the C-C coupling step is the electrophile activation by the protonated amine group of the catalyst (pathway 2), involving a ternary H-bonded complex and a transition state more stable than those formed along the former pathway. Both reaction pathways account for the observed enantioselectivity.