Three-component coupling of aldehydes, amines and alkynes catalyzed by supported copper nanoparticles

MARÍA JOSE ALBALADEJO; FRANCISCO ALONSO; YANINA MOGLIE; MIGUEL YUS

Jaca

Congreso; V International School on Organometallic Chemistry Marcial Moreno Mañas; 2012

Consolider Ingenio 2010-Orfeo Team

Propargylamines are versatile intermediates in the synthesis of compounds with important biological activity. Conventional methods toward the formation of the propargylamine moiety include the direct amination of propargyl halides, triflates, phosphates and acetates, or the more widely practiced addition of alkynylmetal reagents to imines In recent years, the metal-catalyzed coupling of aldehydes, amines, and alkynes (A3 coupling) has emerged as a powerful tool that enables the direct addition of alkynes to in-situ generated imines in a multicomponent and more efficient manner. Based on the latter methodology, a screening was carried out in order to optimize the catalyst support, solvent, and conditions, with the coupling of benzaldehyde, piperidine, and phenylacetylene as a model reaction. We selected CuNPs/TiO2 (mainly as Cu2O) at 70 ºC under solvent-free conditions as the catalyst of choice, to the detriment of the potentially good performance of CuNPs/C in CH2Cl2 at 40 ºC. The catalyst was easy to prepare, reusable at a low copper loading, and exhibited higher catalytic activity than some commercially available copper sources. A variety of aromatic and aliphatic aldehydes, different secondary amines alkyl, cyclic, and aromatic, and various terminal alkynes, were combined to provide a wide range of propargylamines in moderate-to-excellent yields. Two examples of the ketone-amine-alkyne (KA2) coupling are also included. Some mechanistic aspects of the reaction have been undertaken which unveil the participation of copper(I) acetylides in a heterogeneous process.