Oxidative Alpha-Functionalization of 1,2,3,4-Tetrahydroisoquinolines Catalyzed by a Magnetically Recoverable Copper Nanocatalyst. Application in the Aza-Henry Reaction and the Synthesis of 3,4-dihydroisoquinolones

Abstract

The oxidative α-functionalization of 2-aryl-1,2,3,4-tetrahydroisoquinolines (THIQs) promoted by a versatile heterogeneous nanocatalyst consisting of copper nanoparticles immobilized on silica-coated maghemite (CuNPs/MagSilica) has been accomplished. The methodology was successfully applied in the cross-dehydrogenative coupling (CDC) reaction of N-aryl THIQs and other tertiary amines with nitromethane as a pro-nucleophile (aza-Henry reaction) and the α-oxidation of THIQs with O2 as a green oxidant. Phosphite, alkyne, or indole derivatives were also shown to be suitable candidates for their use as pro-nucleophiles in the CDC reaction with THIQs. The catalyst, with very low copper loading (0.4-1.0 mol % Cu), could be easily recovered by means of an external magnet and reused in four cycles without significant loss of activity.