Homogeneous Copper(I)-Catalyzed One-Pot Tandem Synthesis of Bio-Relevant Five- to Seven-Membered N-Heterocycles from...

A family of copper complexes supported by a π-acidic tridentate bis(azo-pyridyl) pincer ligand has been synthesized to elucidate the influence of the coordination environment and metal oxidation state on acceptorless dehydrogenative catalysis. The series comprises a coordinatively unsaturated pentacoordinate Cu(II) complex (1a), a coordinatively saturated Cu(II) complex (1b), and tetracoordinate Cu(I) complexes (1c-d). The strongly electron-withdrawing bis(azo) framework stabilizes reactive intermediates and facilitates efficient alcohol dehydrogenation under mild conditions. These air- and moisture-stable, earth-abundant, coordinatively unsaturated copper complexes catalyze the acceptorless coupling of aromatic diamines with both primary and secondary alcohols to furnish aza-heterocycles of diverse ring sizes. A broad substrate scope (47 examples) provides access to five- and six-membered heterocycles in good to excellent yields and even enables the formation of sterically demanding seven-membered annulated products from secondary alcohols. The catalytic transformation proceeds with high atom economy, generating merely water and hydrogen peroxide as byproducts. Tetracoordinate Cu(I) complexes exhibit markedly higher activity than their Cu(II) counterparts, whereas the coordinatively saturated Cu(II) complex remains largely inactive, highlighting the crucial role of coordinative unsaturation. Excellent catalyst robustness is demonstrated by turnover numbers (TON) approaching ∼104 at catalyst loadings as low as 0.005 mol %. Mechanistic investigations support a nonradical hydride-transfer (HT) pathway for Cu(I)-mediated alcohol dehydrogenation followed by oxidative N-annulation.