Ultra-fast Cu-based A3-coupling catalysts: faceted Cu2O microcrystals as efficient catalyst-delivery systems in batch and flow conditions

Cu(I) catalysts were studied for the synthesis of a propargylamine via A3-coupling of aldehyde, amine, and alkyne, under solvent-free and low loading conditions, using batch microwave or flow thermal heating. We explore ultra-low loading conditions with Cu(I) salts as ultra fast and active catalysts featuring TOFs above 105 h-1. Well-defined octahedral and cubic Cu2O microcrystals were also successfully applied and compared to this reaction. Both types of microcrystals exhibited excellent catalytic activities within minutes, via in-situ generation of low dose of Cu(I) ions within the reaction medium, to achieve TON beyond 2000 and recycling up to 10 times in a flow reactor. The study of the catalytic system demonstrated that the activity was surface-structure dependent and allowed for the design of low Cu contamination A3-coupling systems, affording a product at the decigram scale, with Cu contamination below FDA recommendations for drug synthesis, without the need for a purification procedure.

Ultrasmall Monodisperse NiO Nanocrystals as a Heterogeneous Catalyst for the A3-Coupling Reaction Toward Propargylamines

Ultrasmall monodisperse NiO nanoparticles (7–9 nm) were synthesized through thermal decomposition of Ni-oleylamine complexes. Various measurement techniques involving Fourier-transform infrared spectroscopy (FT-IR), diffuse reflectance UV-Vis spectroscopy (DRS), X-ray diffractometer (XRD), energy dispersive X-ray analysis (EDX), scanning electron microscopy (SEM), dynamic light scattering technique (DLS), and vibrating sample magnetometer (VSM) were employed to characterize the synthesized catalyst. Propargylamine derivatives were synthesized with aldehydes, terminal alkynes and primary amines through a one-pot A3-coupling reaction by using a 3 mol% amount of the NiO nanocrystals at 80 °C under solvent-free conditions with good to excellent yields. The structures of the products were confirmed by 1H and 13C NMR spectroscopy. The catalyst presents many advantages including being environmentally friendly, easy to recover, reusable, stable, and applicable to a wide variety of substrates, as well as having cost-effective preparation.

Unconventional Gold-Catalyzed One-Pot/Multicomponent Synthesis of Propargylamines Starting from Benzyl Alcohols

A formal homogeneous gold-catalyzed A3-coupling, starting from benzyl alcohols, is reported for the straightforward synthesis of propargylamines. This is the first process where these highly valuable compounds have been synthesized, starting from the corresponding alcohols in a one-pot oxidation procedure using MnO2, followed by a HAuCl4·3H2O catalyzed multicomponent reaction. The final products are obtained with very good yields in short reaction times, which is of fundamental interest for the synthesis of pharmaceuticals. The usefulness and efficiency of our methodology is successfully compared against the same reaction starting from aldehydes.

Defect engineering: an effective tool for enhancing the catalytic performance of copper-MOFs for the click reaction and the A3 coupling

A series of Cu(i)-enriched and Lewis basic site-containing defect-engineering MOFs was investigated for significantly enhanced catalytic performance in the click reaction and the A3 coupling.