Enantioselective beta-functionalization of enals via N-heterocyclic carbene catalysis

A series of delta-nitroesters were synthesized through the N-heterocyclic carbene catalyzed coupling of enals and nitroalkenes. The asymmetric coupling of these substrates via the homoenolate pathway afford delta-nitroesters in good yield, diastereoselectivity, and enantioselectivity. This methodology allows for the rapid synthesis of delta-lactams. Using this approach, we synthesized the pharmaceutically relevant piperidines paroxetine and femoxetine.;A novel single-electron oxidation pathway for the N-heterocyclic carbene generated Breslow intermediate has been developed. Nitroarenes have been shown to transfer an oxygen from the nitro group to the beta-position of an enal in an asymmetric fashion to generate beta-hydroxy esters. This reaction affords desired beta-hydroxy ester products in good yield and enantioselectivity and tolerates a wide range of enal substrates.;A dimerization of aromatic enals to form 3,4-disubstituted cyclopentanones has been investigated. Using a single-electron oxidant, aromatic enals couple to form cyclopenanone products in good yield, good enantioselectivity, and excellent diastereoselectivity. A cross coupling has also been developed to afford non-symmetrical cyclopentanone products.