Unprecedented Synthesis of 4-Ylidene (3 S)-3-hydroxy-1-aryl (alkyl)-pyrrolidine-2,5-diones Based on 1,3-Dipolar Cycloaddition of a Sugar-derived Nitrone to N-Substituted Maleimides

Abstract

1,3-Dipolar cycloaddition of a sugar-based nitrone to differently N-substituted maleimides afforded mixtures of isoxazolidine-based cycloadducts. The obtained predominant cycloadducts displayed three new contiguous stereogenic centers placing the protons in syn and anti-relationship, respectively at the fused bond, and for H5 and H6. This was explained by an endo approach of the maleimide derivatives to the Si-face of the nitrone reacting in its Z-form. The mCPBA-mediated oxidative cleavage N−O bond of the isoxazolidine occurred almost quantitatively to afford unprecedented sugar nitrones. Their pyrolysis under thermal or microwave activation led to new 4-ylidene (3 S)-3-hydroxy-1-aryl (alkyl)-pyrrolidine-2,5-diones.