Radical Arene Addition vs Radical Reduction: Why Organometal Hydride Chain Reactions Stop and How To Make Them Go

Nonideal kinetic chain analysis was used to examine the kinetic limitations of free-radical synthesis. Homolytic aromatic substitution (HAS: ArH + R^• → ArR + H^•) occurs in a chain-terminating side reaction to the tributyltin hydride ( SnH) reduction chain (RX + SnH + ( i^•)_cat. → RH + SnX). Kinetic modeling of premixed and slow reagent addition reactions have clarified the mechanisms of SM HAS, with the azo initiator ( iNN i) acting not only as radical source but also (as an H^• acceptor) as the redox catalyst for aromatization, and/or as a postaddition oxidant. Refractory halides and other hitherto baffling anomalies may arise from the build up of ipso (rather than ortho)-cycloadduct radicals in the steady-state radical population. The implications of these findings for "tin-free" radical chains (and emerging photoredox methods) are considered via historical and recent examples of the effects of chain-degrading radical transfer (to substrate, product, solvent, initiator, and/or reagent ligands) on the reagent's chain.