Synthesis and Characterization of Monosaccharide Derivatives and Application of Sugar-Based Prolinamides in Asymmetric Synthesis

For the first time, the beta-anomer of N-acetylglucosamine derivative methyl 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-beta-D-glucopyranoside (9b) was synthesized, isolated, and used in the synthesis of sugar-based primary amine 4b. Sugar-based primary amine 5a, an anomeric pair of monosaccharide derivatives 6a and 6b, and precursors to all these compounds were also synthesized, isolated, and well studied by standard spectroscopic methods, including 2D NMR spectroscopy experiments such as (HH)-H-1-H-1 COSY and HSQC. Then sugar-based primary amines 4a, 5a, 6a, and 6b were converted into the corresponding prolinamide organocatalysts (i.e., 1a, 2a, 3a, and 3b) in high yields. The catalytic activity of these sugar-based prolinamide organocatalysts was demonstrated in asymmetric aldol reactions in various solvents and at different temperatures. The oraganocatalyst 3a was shown to be an efficient and powerful organocatalyst for the enantioselective aldol reaction of various cyclic or acyclic ketones with aromatic aldehydes in a mild and facile reaction, which gave the corresponding aldol adducts with high levels of diastereoselectivity (up to 99:1) and enantioselectivity (up to > 99?%) in almost all cases.