Organocatalytic Asymmetric Conjugate Nucleophilic Glyoxylation

Organocatalytic nucleophilic glyoxylation reactions have been developed for the first time in asymmetric Michael additions of aminonitriles to α,β-unsaturated aldehydes employing iminium activation with a diphenylprolinol catalyst. After reduction and TBS protection or conversion into camphanoyl derivatives of the resulting alcohols, the final 3-substituted 2-ketoesters were ­obtained in acceptable yields over four steps (ee = 83-87%, de = 49-88%). Recrystallisation of the camphanoyl derivatives ­afforded the pure diastereomers (de ³ 98%)