ABSTRACT
N-protected glycosylamines are important synthetic scaffolds in bioorganic and medicinal chemistry and precursors of a diversity of compounds of biological interest. In particular, such sugar derivatives behave as latent imine equivalents and are capable of reacting with a variety of C-nucleophiles to provide, after an activation-cyclization reaction sequence, imino sugar C glycosyl compounds. 1 Over the past three decades, N-benzyl, N-alkyl, and N-carbonylated glycosylamines have been efficiently used in that respect. For instance, glycosylamines carrying N-benzyl and N-alkyl groups have been shown to react mostly with large excess of Grignard reagents to provide the 1,2-syn aminoalditols in good yields and moderate-to-good degrees of stereoselectivity. 1c–4 However, the resulting diastereomers are often difficult to separate by conventional chromatography techniques, limiting their use for synthetic purposes. N-Benzyl-N-glycosyl compounds are somewhat unstable substrates; they slowly hydrolyze to the parent aldoses. 5 More recently, N-carbonylated glycosylamines have also been shown to behave under Lewis acid catalysis as imine equivalents for the stereoselective reaction with silylated nucleophiles, opening an approach to 1,2-syn-imino sugar-C-glycosyl compounds carrying a greater diversity of aglycones (allyl, allenyl, oxoalkyl, etc). 6,1c,3c,7 The addition process occurs at lower temperature, with good degrees of stereoselectivity. The limited stability of carbonylated glycosylamines can make them act as activated glycosyl donors, leading to C-glycosyl compounds.
