Convenient access to amidines by mesoionic singlet palladium carbene catalyzed hydrazone-isocyanide-amine (HIA) coupling: Scope and mechanistic insights

Abstract

Facile synthesis of amidines 5(a-j), 6(a-g) and 7(a-j) by the tandem three-component coupling of N-tosylhydrazones, isocyanides and amines catalysed by the molecular binuclear Pd mesoionic singlet carbene complexes namely, [(R)-1,1′-(C10H6)2–2,2′-(OCH2(1-CH2Ph-3-R-1,2,3-triazol-5-ylidene))2]Pd2I4(NC5H5)2 [R = Me (4a) and Et (4b)] was achieved in good to excellent yields of ca. 51–97% at a low catalyst loading of 0.5 mol% in 6 h of the reaction time. A large opportunity for the utility of this coupling reaction was evident from its broader substrate scope arising from the use of a wide range of N-tosyl hydrazones, amines, and aromatic as well as aliphatic isocyanides. Combined experimental and computational studies performed on the representative substrates namely, PhCHNNHTs, 2,6-Me2C6H3NC, and morpholine indicated that the catalysis proceeded via the formation of palladium (0) active species [(R)-1,1′-(C10H6)2–2,2′-(OCH2(1-CH2Ph-3-R-1,2,3-triazol-5-ylidene))2]Pd2(2,6-Me2C6H3NC)2 [R = Me (B1), Et (B2)] alongside the generation of a ketenimine intermediate 2,6-Me2C6H3NCCHPh in the tricomponent coupling reaction. The dinitrogen elimination from the metal-coordinated diazo intermediate represents the rate-determining step of the reaction. The mechanistic revelations brought forth in this study hold promising potential for enriching our understanding of multi-component reactions leading to amidines enabled by transition metal catalysts.