A pyridine-boryl radical mediated cascade reaction towards the synthesis of indolizines: a computational mechanistic analysis†

The pyridine-boryl radical chemistry has witnessed significant advancements in the last decade, enabling an array of novel synthetic applications. In this context, density functional theory calculations provide a computational mechanistic analysis of the pyridine/B₂pin₂-mediated cascade synthesis of indolizines. The radical–radical cross-coupling pathway is dissected to be energetically more feasible than the conventionally assumed Minisci-type radical addition route. Furthermore, the computations reveal that a 1,4-O[B] migration step leads to the formation of zwitterionic intermediates, whose cyclization then generates the indolizine scaffolds. H-shuttles, generated from water, alcohol, or amine molecules, are found to play pivotal roles in facilitating the elimination or aromatization processes.