Chiral biomimetic NADH models in the benzo[b]-1,6-naphthyridine series. A novel class of stable, reactive and highly enantioselective NADH mimics

The preparation of a new class of tricyclic models based on a Friedländer reaction between chiral piperidine-2,4-diones and azomethine is reported. Alkylation of the lactam allowed to install various pendant arms on the chiral cyclic inducer. The so-obtained mimics were involved in the reduction of methyl benzoylformate to furnish methyl mandelate in 4–87% ee (R). The presence of a coordinating pendant arm proved to be essential to reach optimum results in terms of enantioinduction. Asymmetric reduction of 2-benzoylpyridine with mimics produced α-phenyl-2-pyridinemethanol in 30–84% ee (R).