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

ABSTRACT

The mechanism of the enantioselective Michael addition of diethyl malonate to trans-ß-nitrostyrene catalyzed by a tertiary amine thiourea organocatalyst is explored using experimental 13C kinetic isotope effects and density functional theory calculations. Large primary 13C 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.