Metal-Catalysed A3 Coupling Methodologies: Classification and Visualisation

Abstract

The multicomponent reaction of aldehydes, amines, and alkynes, known as A3 coupling, yields propargylamines, a valuable organic scaffold, and has received significant interest and attention in the last years. In order to fully realise the potential of the metal-based catalytic protocols that facilitate this transformation, we summarise substrates, in situ and well-characterised synthetic methods that provide this scaffold and attempt a monumental classification considering several variables (Metal, Coordinating atom(s), Ligand type and name, in-situ or well-characterised, co-catalyst, catalyst and ligand Loading (mol%), solvent, volume, atmosphere, temperature, microwave, time, yield, selectivity (e.e. d.r.), substrate name, functionality, loading (amines, aldehydes, alkynes), and use of molecular sieves). This pioneering work creates a valuable database that contains 2376 entries and allows us to produce graphs and better visualise their impact on the reaction.

Chemical Chartographisis: a contemporary perspective in molecular design and synthesis

“…35 This organic transformation involves an in situ imine formation with concomitant activation of the alkyne to yield the propargylamine, and it is well established to be promoted by Cu I species. 41 Our protocol required elevated temperatures, thus prohibiting monitoring with EPR, and the triflate component (entry 8) surpasses perchlorate (entry 1). Cyclic voltammetry of [Cu II ( L1 ) 2 (OTf) 2 ] identified a reversible one-electron redox process.…”

Mechanochemical Cu(ii) complexes and propargylamine synthetic adventures

“…8 Propargylamines (PAs) are valuable precursors for organic scaffolds used for neurodegenerative diseases or as antidepressants, anti-platelets and anticonvulsants. 14,15 They can be synthesized via traditional catalytic protocols, based on alkylation or reductive amination paths, that incorporate Pd-based or Zn alkynyl reagents or sodium borohydride in signicant amounts. 16 The A 3 coupling reaction is a popular organic pathway for synthesizing PAs in the presence of late (Cu, Pd, or Au) transition metals.…”

HAuCl4 Catalyzed and Dibenzyl amine Centered A3 coupling reaction: Synthesis, Spectroscopic Proofing and Anti‐microbial Efficacy

“…From a chemical perspective, the A 3 coupling processes have been examined extensively in the microwave, ultrasonic irradiation, smoothly in water, and even in solvent-free circumstances. [21] Chemists are now increasingly lean towards "green chemistry" due to rising environmental awareness. Consequently, heterogeneous catalysts that may be recovered can play a role in the prevention or minimization of chemical wastes, especially in the context of large-scale and industrial processes.…”

“…In particular, Gold has emerged as a leading contender for catalysing the reactions of alkynes, alkenes, and allenes, and, more intriguingly, has been found to provide divergent reaction pathways relative to other metal catalysts, [20] likely as a result of the maximum relativistic effects exhibited by the Gold. From a chemical perspective, the A 3 coupling processes have been examined extensively in the microwave, ultrasonic irradiation, smoothly in water, and even in solvent‐free circumstances [21] …”