Diastereoselective synthesis of atropisomeric pyrazolyl pyrrolo[3,4-: D] isoxazolidines via pyrazolyl nitrone cycloaddition to facially divergent maleimides: Intensive NMR and DFT studies

Abstract

A pyrazolyl nitrone (2) underwent 1,3-dipolar cycloadditions to afford some N-substituted maleimides (3a-o). An atropisomeric character was introduced into the formed cycloadducts by using maleimides that have a restricted rotation around the C-N bond. Also, facial selectivity of both endo and exo cycloaddition was observed where the major atropisomer was one that is formed by attacking the nitrone from the less hindered face of the dipolarophile. On the other hand, maleimides with free rotation around the C-N bond led to endo and exo cycloadducts without atropisomerism. The presence of atropisomerism in the formed cycloadducts was confirmed by extensive NMR studies and DFT calculations.