The Sharpless asymmetric aminohydroxylation reaction: optimising ligand/substrate control of regioselectivity for the synthesis of 3- and 4-aminosugars

An investigation of the factors responsible for the sense and magnitude of regioselectivity in the Sharpless asymmetric aminohydroxylation (AA) has been conducted. Theoretical investigations of ligand-osmium binding geometry and experimental investigations of the Sharpless AA reaction on a series of functionalized pent-2-enoic acid ester substrates demonstrate that the opposite regioselectivity afforded using PHAL and AQN ligands results from a change in substrate orientation with respect to the catalyst. Two distinct ligand binding domains within the catalyst have been proposed that undergo attractive interactions with the substrates. Selective access to each of the four potential regio- and stereo-isomeric AA products could be achieved through the appropriate choice of ligand and substrate. These results have been applied toward the efficient stereoselective synthesis of naturally occurring and regioisomeric 3- and 4-aminosugar derivatives.