Stereoselective nucleophilic formylation and cyanation of alpha-alkoxy- and alpha-aminoaldehydes

The spontaneous 1,2-addition of formaldehyde N,N-dialkylhydrazones to carbohydrate-derived alpha-alkoxyaldehydes takes place under neutral conditions and in the absence of catalysts or promoters to afford the corresponding alpha-hydroxyhydrazones in good to excellent yields and with highly anti diastereoselectivities. Subsequent transformations of the hydrazono group into aldehydes and nitriles following known procedures provide a new entry into the homologation of carbohydrates and the synthesis of cyanohydrins, respectively. Additionally, reaction of methyleneaminopyrrolidine with N-Boc-protected alpha-aminoaldehydes from natural amino acids efficiently affords the corresponding adducts under the same conditions. From these adducts, a variety of biologically interesting alpha-hydroxy-beta-aminocarbonyl compounds can be accessed upon manipulation of the hydrazone moiety.