Diastereoselective Hydrogen‐Transfer Reactions: An Experimental and DFT Study

Radical reductions of halogenated precursors bearing a heterocycle exo (α) to the carbon‐centered radical proceed with enhanced anti‐selectivity, a phenomenon that we termed “exocyclic effect”. New experimental data and DFT calculations at the BHandHLYP/TZVP level demonstrate that the origin of the exocyclic effect is linked to the strain energy required for a radical intermediate to reach its reactive conformation at the transition state (ΔE^≠_strain). Furthermore, radical reductions of constrained THP systems indicate that high 2,3‐anti inductions are reached only when the radical chain occupies an equatorial orientation. Hydride deliveries to different acyclic substrates and calculations also suggest that the higher anti‐selectivities obtained with borinate intermediates are not related to the formation of a complex mimicking an exocycle. From a broader standpoint, this study reveals important conformational factors for reactions taking place at a center vicinal to a heterocycle or an α‐alkoxy group.