Since the definition of the “12 Principles of Green Chemistry” more than 20 years ago, chemists have become increasingly mindful of the need to conserve natural resources and protect the environment through the judicious choice of synthetic routes and materials. The direct activation and functionalization of C–H bonds, bypassing intermediate functional group installation is, in abstracto , step and atom economic, but numerous factors still hinder the sustainability of large-scale applications. In this Outlook, we highlight the research areas seeking to overcome the sustainability challenges of C–H activation: the pursuit of abundant metal catalysts, the avoidance of static directing groups, the replacement of metal oxidants, and the introduction of bioderived solvents. We close by examining the progress made in the subfield of aryl C–H borylation from its origins, through highly efficient but precious Ir-based systems, to emerging 3d metal catalysts. The future growth of this field will depend on industrial uptake, and thus we urge researchers to strive toward sustainable C–H activation.

Arene hydrogenation provides direct access to saturated carbo‐ and heterocycles and thus its strategic application may be used to shorten synthetic routes. This powerful transformation is widely applied in industry and is expected to facilitate major breakthroughs in the applied sciences. The ability to overcome aromaticity while controlling diastereo‐, enantio‐, and chemoselectivity is central to the use of hydrogenation in the preparation of complex molecules. In general, the hydrogenation of multisubstituted arenes yields predominantly the cis isomer. Enantiocontrol is imparted by chiral auxiliaries, Brønsted acids, or transition‐metal catalysts. Recent studies have demonstrated that highly chemoselective transformations are possible. Such methods and the underlying strategies are reviewed herein, with an emphasis on synthetically useful examples that employ readily available catalysts.

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C-H activation reactions with high catalyst turnover numbers are still very rare in the literature and 10 mol % is a common catalyst loading in this field. We offer a representative overview of efficient C-H activation catalysis to highlight this neglected aspect of catalysis development and inspire future effort towards more efficient C-H activation. Examples ranging from palladium catalysis, Cp*Rh - and Cp*Co -catalysis, the C-H borylation and silylation to methane C-H activation are presented. In these reactions, up to tens of thousands of catalyst turnovers have been observed.

The catalytic dearomatization of pyridines, accessing medicinally relevant N-heterocycles, is of high interest. Currently direct, dearomative strategies rely generally on reduction or nucleophilic addition, thus limiting the architecture of the dearomatized products to a six-membered ring. We herein introduce a catalytic, dearomative cycloaddition reaction with pyridines using photoinduced energy transfer catalysis, thereby advancing dearomatization methodology and increasing the topology of pyridine dearomatization products. This unprecedented method features high yields, broad substrate scope (44 examples), excellent functional group tolerance, and facile scalability. Furthermore, a recyclable and sustainable polymer immobilized photocatalyst was employed. Computational and experimental investigations support a mechanism in which a cinnamyl moiety is promoted to its corresponding excited triplet state through visible-light-mediated energy transfer catalysis, followed by a regioselective and dearomative [4+2] cycloaddition to pyridines. This work demonstrates the contribution of visible light catalysis toward enabling thermally challenging organic transformations.