Environmental Modulation of Chiral Prolinamide Catalysts for Stereodivergent Conjugate Addition.

Synthetic chiral catalysts generally rely on proximal functional groups or ligands for chiral induction. Enzymes often employ environmental chirality to achieve stereoselectivity. Environmentally controlled catalysis has benefits such as size and shape selectivity but is underexplored by chemists. We here report molecularly imprinted nanoparticles (MINPs) that utilized their environmental chirality to either augment or reverse the intrinsic selectivity of a chiral prolinamide cofactor. The latter ability allowed the catalyst to produce products otherwise disfavored in the conjugate addition of aldehyde to nitroalkene. The catalysis occurred in water at room temperature and afforded γ-nitroaldehydes with excellent yields (up to 94%) and ee (>90% in most cases). Up to 25:1 syn/anti and 1:6 syn/anti ratios were achieved through a combination of catalyst-derived and environmentally enabled selectivity. The high enantioselectivity of the MINP also made it possible for racemic catalysts to perform asymmetric catalysis, with up to 80% ee for the conjugate addition.