Dual relay Rh-/Pd-catalysis enables β-C(sp3)-H arylation of α-substituted amines.

A dual relay catalytic protocol, built on reversible dehydrogenation of amines by Rh catalysis and C-H functionalisation of transient imines by Pd catalysis, is reported to enable regioselective arylation of amines at their unactivated β-C(sp3)-H bond. Notably, the new strategy is applicable to secondary anilines and N-PMP-protected primary aliphatic amines of intermediate steric demands, which is in contrast to the existing strategies that involve either free-amine-directed C-H activation for highly sterically hindered secondary aliphatic amines or steric-controlled migrative cross-coupling for unhindered N-Boc protected secondary aliphatic amines. Regioselectivity of the reaction is imposed by the electronic effects of transient imine intermediates rather than by the steric effects between specific starting materials and catalysts, thereby opening the uncharted scope of amines. In a broader sense, this study demonstrates new opportunities in dual relay catalysis involving hydrogen borrowing chemistry, previously explored in the functionalisation of alcohols, to execute otherwise challenging transformations for amines, commonly present in natural products, pharmaceuticals, biologically active molecules, and functional materials.