Transition State Analysis of Enantioselective Brønsted Base Catalysis by Chiral Cyclopropenimines

Experimental 13C kinetic isotope effects have been used
to interrogate the rate-limiting step of the Michael addition of glycinate
imines to benzyl acrylate catalyzed by a chiral 2,3-bis­(dicyclohexylamino)
cyclopropenimine catalyst. The reaction is found to proceed via rate-limiting
carbon–carbon bond formation. The origins of enantioselectivity
and a key noncovalent CH···O interaction responsible
for transition state organization are identified on the basis of density
functional theory calculations and probed using experimental labeling
studies. The resulting high-resolution experimental picture of the
enantioselectivity-determining transition state is expected to guide
new catalyst design and reaction development.