2.2 Chemoselective Hydrogenation of Arenes

Abstract Arene hydrogenation converts widely available arenes into scarce cycloalkanes, making it valuable for the production of bulk chemicals such as cyclohexane and cyclohexene, as well as simple pharmaceuticals such as tranexamic acid. Moreover, the recognition that increasing the proportion of C(sp3)-hybridized carbon atoms in drug candidates improves their clinical success rate has highlighted the enormous potential of arene hydrogenation for lead optimization in drug discovery. However, the development of chemoselective transformations that tolerate the diverse functional groups of complex drug candidates is challenging, as the aromatic stabilization energy increases the kinetic barrier of the reaction and limits the number of applicable catalyst systems. This review presents broadly applicable catalysts and chemoselective transformations with a focus on those that provide access to medicinally relevant cycloalkane motifs. This review also discusses remaining challenges, including the tolerance of strongly coordinating, reducible, or labile functional groups, and identifies promising developments.