C–N coupling reactions with arenes through C–H activation: the state-of-the-art versus the principles of green chemistry

Abstract

Arylamine and N-arylamide moieties are omnipresent in various classes of compounds, ranging from bulk materials (e.g., polymer precursors) to fine chemicals, such as pharmaceuticals or agrochemicals. Efficient, green synthetic methods to construct the C–N bond are thus highly desired; yet due to kinetic and thermodynamic barriers and a mismatch in polarity, the ideal coupling of simple arenes and amines (or amides) is far from straightforward. Current industrial practice therefore relies on multi-step syntheses employing pre-functionalised arenes (such as aryl halides or aryl triflates), which leads to stoichiometric amounts of (salt) waste. In addition, regioselectivity problems, if any, are simply shifted to earlier synthetic stages. As an intrinsically greener alternative, direct C–N coupling strategies employing C–H activation of the arene have recently emerged, rendering pre-functionalisation of the arene obsolete. These approaches can be roughly divided in two categories: cross-dehydrogenative couplings and electrophilic amination reactions. In this perspective article, we present a brief overview of the current state-of-the-art in C–N coupling reactions through C–H activation and discuss to what extent reported systems comply with the principles of green chemistry, with a focus on heterogeneously catalysed reactions.