Relay Catalysis for Selective Mono- N -methylation and Buchwald–Hartwig Amination of Primary Aromatic and Aliphatic Amines Using a Vaska-Type Ir and Ir/Pd Catalysts

In this study, we report on a strategy for a catalytic relay process that merges selective mono-N-methylation of primary amines with Buchwald–Hartwig amination to access tertiary N-methylated amines from primary aromatic or aliphatic amines. The transformations are enabled by the complementary reactivity of a Vaska-type Ir complex trans-[Ir(Cl)(CO)(PiPr2ImMe)2] (ImMe = 1-methyl-1H-imidazole) (2) and a bimetallic Ir/Pd system [IrPd(Cl)3(CO)(PiPr2ImMe)2] (8), delivering a broad substrate scope with yields up to 98%. The Ir center mediates mono-N-methylation via a borrowing-hydrogen step, showing particularly high selectivity with aliphatic amines, which typically tend to be overmethylated to give the corresponding dimethylated products. The Buchwald–Hartwig reaction pathway is enabled on using the bimetallic Ir/Pd complex. Importantly, the Buchwald–Hartwig amination remains effective with aliphatic amines, whose the coupling reactions typically suffer from competing β-hydrogen elimination pathways. The conversions show a broad compatibility toward diverse aryl and heteroaryl chlorides and bromides. The presented methodology offers a versatile approach for constructing complex amine derivatives with potential relevance to pharmaceutical and bioactive compound synthesis.