A highly stereoselective synthesis of (E)-alkene dipeptide isosteres via organocyanocopper-Lewis acid mediated reaction

A stereoselective synthesis of protected (E)-alkene dipeptide isosteres by the reaction of the mesylates of homochiral δ-aminated γ-hydroxy (E)-α,β-enoates with either RCu(CN)Li-BF 3 or RCu(CN)MgX-BF 3 reagent is described. The degree of diastereoselectivity has been found to be uniformly high except for the serine- and threonine-derived acetonides 77 and 81. The synthesis permits the introduction of sterically hindered appendages such as isopropyl and tert-butyl groups at the α position to the ester group. This methodology provides a new route to a wide range of modified (E)-alkene peptide mimics that may have biological importance