Experimental and theoretical study of the 1,3-dipolar cycloaddition between D-glyceraldehyde nitrones and acrylates. Diastereoselective approach to 4-hydroxy pyroglutamic acid derivatives

The 1,3-dipolar cycloaddition reactions of five D-glyceraldehyde nitrones with alkyl acrylates and Oppolzer’s sultam acrylamide have been studied in detail, the study including double chiral induction experiments. A complete theoretical study of the reaction has also been carried out using density functional methods (B3LYP/6-31G*) in which both ortho and meta channels leading to 3,5- and 3,4-disubstituted isoxazolidines, respectively, were considered. The adducts obtained from the cycloaddition reactions have been further used for the stereoselective synthesis of protected 4-hydroxy pyroglutamic acids, particularly the (2S,4S)-isomer, which is prepared from the major adducts of the cycloaddition reactions.