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

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.