Highly Enantioselective Reduction with Novel, Bridged NADH Models

Biomimetic reduction of benzoylformate to mandelate with 97–99% ee was achieved with the diastereomeric, bridge NADH models (S,S)-1 and (R,S)-1. The oligomethylene bridge acts as an “enzyme wall” and hinders the approach of the substrate from one side of the dihydropyridine ring. Isomers 1 were synthesized from the corresponding bridged nicotinate precursor, which was prepared by the reaction of formyl-substituted (vinylimino)phosphorane with methyl propiolate.