A green and selective method for the generation of biaryl compounds through C−H arylation of heterocyclic N-oxides, in which the addition of ascorbic acid as a promoter is not required for either the generation of an aryldiazonium species or the subsequent arylation, is presented. Reaction conditions were optimized through multivariate data analysis, including orthogonal projections to latent structures (OPLS) and design of experiments (DoE) methodologies, resulting in further sustainability improvements, and were then applied to a range of substrates to establish the scope and limitations of the process. The reaction was studied using in situ infrared spectroscopy and a mechanism is presented that accounts for the available data from this and previous studies. The reaction was also performed on a multigram scale, with calorimetry studies to support further scale-up of this promoter-free transformation.

A green and selective method for the generation of heterocyclic bi-aryl compounds through C-H arylation of heterocyclic N-oxides is presented in which ascorbic acid acts as the sole promoter for both the in-situ generation of an aryldiazonium species and the subsequent arylation. Reaction conditions were optimised through Multivariate Data Analysis and Design of Experiments methodologies resulting in further sustainability improvements, and were then applied to a range of substrates to establish the scope and limitations of the new methodology. This reaction was ultimately performed on a multigram scale and subjected to reaction calorimetry studies to support further scale-up and identify opportunities to elucidate the mechanistic course of this metal-free transformation.