Palladium-Catalyzed C(sp3)-H Arylation of N-Boc Benzylalkylamines via a Deprotonative Cross-Coupling Process

Diarylmethylamines are key intermediates and products in the pharmaceutical industry. Herein we disclose a novel method toward the synthesis of these important compounds via C-H functionalization. Presented is a reversible deprotonation of N-Boc benzylalkylamines at the benzylic C-H with in situ arylation by a NiXantPhos-based palladium catalyst (50-93% yield, 29 examples). The method is also successful with N-Boc-tetrahydroisoquinolines. The advantages of this method are it avoids strong bases, low temperatures, and the need to transmetallate to main group metals for the coupling.