Substituent-rebound skeletal editing for precise boron-to-carbon single-atom swapping

Abstract

Abstract Developing methods that enable single-atom exchange within an aromatic scaffold, while preserving its peripheral substitution, represents an important but highly ambitious goal in synthesis. In principle, such approaches would allow the impact of a single-atom change within a molecular framework to be distinguished from the effects of also altering the peripheral substituents. Yet despite this conceptual power, single-step methodologies for single-atom exchange in aromatic systems remain rare. Herein, we present a boron-to-carbon swapping reaction via a substituent-rebound process, converting 1,2-benzazaborines into the corresponding quinolines. The employment of glyoxylic acid as the carbon-atom source allows the original substituent on the boron atom to be recaptured and incorporated into the quinoline product, representing a rare example of true single-atom skeletal editing. The transformation exhibits high levels of functional group tolerance and is applicable to the late-stage modifications of natural product and pharmaceutical derivatives. Furthermore, comprehensive mechanistic investigations elucidate the intricacies of this process, establishing a foundation for future single-atom editing manifolds that can facilitate the interrogation of structure–function relationships with atom-level precision.