Taming the reactivity of nitrosoarenes with an interdisciplinary approach

The unique nitrogen-oxygen combination located next to a specific carbonated backbone of C-nitroso derivatives is responsible for a complex reactivity that renders them not only widely effective in various processes, such as in nitroso Diels-Alder reactions, but also difficult to demystify [1]. Within this context, we have started a research program that relies on an interdisciplinary perspective for exploiting these species at the fullest for electrophilic aminations (Figure 1). While computational chemistry was used for determining the intrinsic properties of nitrosoarenes during polar additions [2], its integration in machine learning enabled to predict the best experimental conditions, hence saving time and resource-consuming synthetic work [3]. Moreover, the combination of in-line monitoring, automation and engineering through continuous flow technology ensured the reproducibility of the protocol through accurate control of paramount local parameters, such as the local stoichiometry and temperature [4,5]. The strategy has been validated via automated kinetic studies under microfluidic conditions that provided experimental activation parameters comparable to the computated ones.