Controlling Regioselectivity in Palladium-Catalyzed C-H Activation/Aryl-Aryl Coupling of 4-Phenylamino[2.2]paracyclophane.

Selective activation/functionalization of C-H bonds has emerged as an atom- and step-economical process at the forefront of modern synthetic chemistry. This work reports palladium-catalyzed exclusively para-selective C-H activation/aryl-aryl bond formation with a preference over N-arylation under the Buchwald-Hartwig amination reaction of 4-phenylamino[2.2]paracyclophane. This innovative synthetic strategy allows a facile preparation of [2.2]paracyclophane derivatives featuring disparate para-substitutions at C-4 and C-7 positions in a highly selective manner, gives access to a series of potential candidates for [2.2]paracyclophane-derived new planar chiral ligands. The unprecedented behavior in reactivity and preferential selectivity of C-C coupling over C-N bond formation via C-H activation is unique to the [2.2]paracyclophane scaffold compared to the non-cyclophane analogue under the same reaction conditions. Selective C-H activation/aryl-aryl bond formation and sequential C-N coupling product formation is evidenced unambiguously by X-ray crystallography.