Transition state analysis of an enantioselective Michael addition by a bifunctional thiourea organocatalyst

The mechanism of the enantioselective Michael addition of diethyl malonate to trans-beta-nitrostyrene catalyzed by a tertiary amine thiourea organocatalyst is explored using experimental C-13 kinetic isotope effects and density functional theory calculations. Large primary C-13 KIEs on the bond-forming carbon atoms of both reactants suggest that carbon-carbon bond formation is the rate-determining step in the catalytic cycle. This work resolves conflicting mechanistic pictures that have emerged from prior experimental and computational studies.