An assay for aryl radicals using BHAS coupling

Abstract

Aryl radicals are intermediates in many reactions, but determining their presence unambiguously is often challenging. As we recently reported, reaction of 2-iodo-1,3-dimethylbenzene (7) in benzene with KOtBu and a suitable organic additive, leads to a base-induced homolytic aromatic substitution (BHAS) coupling reaction giving 2,6-dimethylbiphenyl (12) and biphenyl (3) as coupled products, together with xylene (13). In this case, biphenyl arises from a radical translocation and is the major coupling product. This paper now quantitatively investigates that reaction, which shows a very similar ratio for 3 : 12 [ca. 4 : 1] when using different sources of radical initiation. Deuterium isotope studies provide detailed mechanistic support for the proposed mechanism; when carried out in C₆D₆vs. C₆H₆, the reaction is characterised by a strong isotope effect for formation of 3-d₁₀vs. 3, but not for formation of 12-d₅vs. 12. These distinctive properties mean that the transformation can act as an assay for aryl radicals. An advantage of such a BHAS process is its sensitivity, since it involves a chain reaction that can amplify radical activity.