Stereoselective Nucleophilic Formylation and Cyanation of α-Alkoxy- and α-Aminoaldehydes

TLDR: The spontaneous 1,2-addition of formaldehyde N,N-dialkylhydrazones to carbohydrate-derived α-alkoxyaldehydes takes place under neutral conditions and in the absence of catalysts or promoters to afford the corresponding α-hydroxy hydrazones in good to excellent yields and with highly anti diastereoselectivities.

Abstract: The spontaneous 1,2-addition of formaldehyde N,N-dialkylhydrazones to carbohydrate-derived α-alkoxyaldehydes takes place under neutral conditions and in the absence of catalysts or promoters to afford the corresponding α-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 α-aminoaldehydes from natural amino acids efficiently affords the corresponding adducts under the same conditions. From these adducts, a variety of biologically interesting α-hydroxy-β-aminocarbonyl compounds can be accessed upon manipulation of the hydrazone moiety.