Rational design of novel axially chiral NADH models based on configurational control of atropisomeric lactams

The preparation of a new class of axially chiral NADH models based on configurational control of atropisomeric lactams is described. The configurational control of this chiral axis is achieved via the presence of a second chirality element installed on the lactam moiety of the reagent 2. Reduction of methyl benzoylformate led to methyl mandelate in 89% yield and 92% e.e. This result suggests that the chiral axis about C3CO bond is the main configurational element responsible for the high enantioselectivity observed with this biomimetic model.