Directly accessing the alkyne-aldehyde-amine (A3) coupling catalytic cycle using molecular gold(I) acetylide complexes for synthesizing propargylamines and amino indolizines

Abstract

The gold(I) acetylide complexes of Acyclic Aminooxy Carbene (AAOC) ligands, [{(4-R1-2,6-t-Bu2-C6H2O)(NCy2)}methylidene]Au[CC(p-C6H4R2)] [where R1 = H; R2 = H (1), and R1 = t-Bu; R2 = H (4)] efficiently catalyzed the three-component Alkyne-Aldehyde-Amine (A3) coupling yielding propargylamine and amino indolizine compounds, thereby implicating its direct role in the catalytic cycle. The DFT studies performed on a simplified gold(I) precatalyst, [{(2,4,6-Me3-C6H2O)(NCy2)}methylidene]Au[CCPh] (4’), at B3LYP-D3/def2-TZVP of theory implicated the role of non-covalent Au•••H–C interactions in the A3 coupling reactions producing propargylamine and subsequently amino indolizine via intramolecular cyclization of propargylamine followed by an intramolecular 1,2-hydrogen transfer-step for the 2-formylpyridine substrate. The non-covalent Au•••H–C(alkyl) and Au•••H–C(aryl) interactions participate in tandem to influence the overall reaction kinetic barrier, and thereby illustrating the importance of such interactions in gold catalysis. The gold(I) acetylide complexes, [{(4-R1-2,6-t-Bu2-C6H2O)(NCy2)}methylidene]Au[CC(p-C6H4R2)] [where R1 = H; R2 = H (1), Me (2), OPh (3): R1 = t-Bu; R2 = H (4), Me (5), OPh (6)] were conveniently synthesized from the corresponding chloro analogues [{(4-R1-2,6-t-Bu2-C6H2O)(NCy2)}methylidene]AuCl (where R1 = H, t-Bu) by the treatment with terminal alkyne HCC(p-C6H4R2) (where R2 = H, Me, OPh) in the presence of K2CO3 as a base in ca. 88−95 % yield.