Propargyl amines by aldehyde-amine-acetylene coupling mediated by Ag(I) and Cu(I) complexes of super bulky N-heterocyclic carbenes: Unveiling the role of the super bulky ligands in the coupling reaction

Abstract

The copper (1–2)a and the silver (1–2)b complexes of the super bulky N-heterocyclic carbene (NHC) variants namely, [1,3-{2,4,6-(Ph2CH)3C6H2}2-imidazol-2-ylidene]MX [where, M = Cu; X = Cl (1a), Br (2a): M = Ag; X = Cl (1b), Br (2b)] effectively facilitated the A3 coupling reaction of diverse amine, aldehyde, and acetylene substrates yielding a wide array of propargylamines in moderate to good (ca. 24−89 %) yields. A metal bound acetylide species, [1,3-{2,4,6-(Ph2CH)3C6H2}2-imidazol-2-ylidene]M(CCPh) [where, M = Cu (A), Ag (B)] has been identified as a key catalytic species by mass spectrometric studies. The Density functional theory (DFT) studies further revealed the rate-limiting step as the formation of the C-C coupling transition state (TS2) from the silver-acetylide species (Int2). The super bulky ligand framework plays a pivotal role in this step by anchoring the protonated Schiff's base imine in the vicinity of the alkyne through several non-covalent-interactions, including a strong C–H•••O interaction, thereby reducing the corresponding kinetic barrier leading to an efficient catalytic transformation as reflected in the high propargylamine yields. Furthermore, the catalytic utility of the coupling reaction was further extended by synthesising pargyline, which is a monoamine oxidase B (MAO-B) inhibitor drug molecule, in a one-pot manner and that to in a gram-scale synthesis.