Computational Analysis of Mechanistic Divergence in Amino– and Alkyl–Arylation of Unbiased Olefins with Bifunctional Sulfur Reagents

Radicals derived from a range of sulfur-based reagents have recently proven effective for overcoming challenges in amino– and alkyl–arylations of unbiased olefins through open-shell olefin-addition/desulfonylative Smiles-Truce cascades. Despite their similar structures, these reagents have complementary synthetic features. A central source of these intricacies is that the most easily accessed potential such amino–arylation reagents, N-acyl sulfonamides, are not viable reagents for intermolecular amino–arylation because N-acyl sulfonamidyl radicals undergo intramolecular decomposition before adding to olefins. Closely related N-acyl sulfinamides and N-triazinyl sulfonamides have thus been developed to circumvent this problem. Moreover, related alkyl–aryl sulfones serve as effective alkyl–arylating agents without corresponding complications, and when their analogs to N-acyl sulfonamides bearing C-acyl groups are used, additions to olefins become more efficient. This work seeks to better understand these reactivity differences through computational analyses. By considering the LUMO energies of the reagent-derived radicals, as well as the radical delocalization and stereoelectronically enabled polar effects predicted in the competing olefin-addition and decomposition transition states for each reagent class, the experimentally observed reactivities were rationalized. We anticipate that this work will guide ongoing development efforts to address the remaining challenges among these systems.