Umpolung Amide Synthesis with Nitrosoalkane Electrophiles: Pursuit of the Elusive N -Acyl Nitrone for Dipolar Cycloadditions

Abstract

Abstract Nitrones are reactive dipoles for cycloadditions that have been used for powerful alkene difunctionalization reactions, often stereocontrolled. Despite the wealth of knowledge generated over a half-century of study, reports of N-acyl nitrones are exceedingly rare, with limited options for their access. We report a new diverted Umpolung Amide Synthesis (UmAS) reaction that leads to N-acyl nitrones through an intermolecular carbon–nitrogen bond formation. These nitrones are rare examples of doubly acylated species (C- and N-acyl) that are expected to engage electron-rich alkenes in Type III dipolar cycloadditions. Our findings suggest, unexpectedly, that these species are more fleeting than previously reported, succumbing to a rapid N→O acyl transfer reaction that leads to stable O-acyl oximes.