NAD(P)+‐NADPH Models. 60. Induction of Double Asymmetry in the Reduction of α‐Keto Esters

Using a chiral 1,4‐dihydronicotinamide derivative, N‐α‐methylbenzyl‐1‐propyl‐2,4‐dimethyl‐1,4‐dihydronicotinamide (Me2PNPH), we have studied the reduction of various α‐keto esters that have a chiral center in the acid‐moiety. All of the four possible diastereomers of the corresponding α‐hydroxy esters were afforded. A detailed investigation into the diastereomeric composition of the product has revealed that the molecular arrangement and the conformations of the substrate at the transition state of the reduction are controlled by the polarity and/or the polarizability of the substituents. The 2R,3R‐isomer is the most predominant product when 4R,9R‐Me2PNPH is employed as the reductant.