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.