The use of two optically active N-sulfinyl α-imino esters in the stereoselective aza-Diels–Alder reaction

Diastereoselective aza-Diels–Alder (aza-DA) reactions of ethyl (S)-N-(tert-butanesulfinyl)iminoacetate (2a) and ethyl (S)-N-(p-toluenesulfinyl)iminoacetate (2b) with different dienes including activated, non-activated, cyclic, and acyclic dienes in the presence of Lewis acids are described. Reactions with 2a were found to be more selective. Reactions of unactivated dienes (acyclic and cyclic) with stoichiometric amounts of TMSOTf as Lewis acid afforded the aza-DA adducts in modest yields and in diastereoselectivities up to 99%. A strong preference for Re-approach was observed for 2a. Cyclic dienes gave the exo adducts as major products. For the aza-DA reaction with activated Danishefsky type dienes poor diastereoselectivities were observed. In these cases, the best results were obtained using stoichiometric amounts of BF3·Et2O as Lewis acid (up to 69% de, 76% yield). The absolute configurations of six of the addition products were established by chemical correlation with known compounds. Acidic cleavage of the sulfinyl group occurred without racemization to optically active non-proteinogenic α-amino acid ethyl esters.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide