An electrostatically enhanced bifunctional enantioselective thiourea catalyst

Abstract

A new bifunctional thiourea featuring a methylated pyridinium ion and a chiral amine is reported. This readily prepared organocatalyst is more active than its analogous 3,5-bis(trifluoromethyl)phenyl substituted thiourea (“Takemoto's catalyst”), significantly reducing reaction times in the Michael additions of diethyl malonate and other pronucleophiles to various aryl nitroolefins. Excellent enantioselectivities accompany this enhanced rate, ranging from 91–98% in most cases. Aggregation and kinetic data indicate that the resting state and active form of the catalyst is monomeric while NOE experiments and DFT calculations point to the importance of the thiourea Z,Z-conformer. These results suggest that the charged catalyst behaves in a mechanistically similar manner to its noncharged analog, and that electrostatic enhancement is a viable design strategy for the improvement of bifunctional organocatalysts.