Asymmetric Induction of Sugar-Derived Dipole and Dipolarophile in 1,3-Dipolar Cycloadditions Leading to Pyrrolidines

Abstract

The 1,3-dipolar cycloaddition reaction of achiral dipolarophiles (maleates) with chiral, open-chain sugar-derived azomethine ylides yielded enantiomerically pure or diastereomeric mixtures of pyrrolidine cycloadducts. The outcome of the reaction, whether diastereoselective or not, depended on the substitution pattern and length of the sugar chain in the dipole. Diastereoselectivity was successfully achieved for 3-deoxy sugar imino esters (precursors of ylides) having a seven-membered sugar chain substituted with two isopropylidene rings. The use of pyranones, which are derived from common pentoses, as chiral dipolarophiles with chiral or achiral azomethine ylides led to pyrrolidines in a highly diastereoselective manner. The asymmetry was induced by the stereocenter of the dipolarophile, which prevailed over the stereocenters of the sugar chain of the dipole (dipolarophile-based stereocontrol). In many instances, the resulting pyrrolidines were entirely carbohydrate-based, as both the dipolarophile and dipole were derived from sugars.