Palladium Nanocatalysts for Cascade C-N Cross-Coupling/Heck Reaction

Highly stable nanocatalysts have been synthesized in aqueous medium at room temperature by the in situ formation of Pd nanoparticles (PdNPs) embedded in an enzyme net. Different parameters in the synthesis were evaluated such as T, ratio enzyme/Pd salt, using Candida antarctica B lipase (CALB) as enzyme. In all different CALB/PdNPs hybrids synthesized, crystalline Pd(0) as a unique metallic species was confirmed by XRD. Spherical nanoparticles were obtained with diameter size from 2 to 11 nm, depending on the synthetic conditions. These CALB/PdNPs hybrids were employed as catalyst in the C-N/Heck reaction cross-coupling cascade for the synthesis of substituted azaindoles using various amino-o-bromopyridines as starting material in moderate conditions. The best conversion with high selectivity of the formation of C2-substituted azaindoles was obtained at 90 degrees C using dioxane containing 5% water as the best reaction solvent from the different solvents tested, using potassium carbonate as milder base. The catalysis with these CALB/PdNPs hybrids at these conditions was also successful in the production of several isomers of azaindoles, especially relevant for the formation of the 7- azaindole, where 65% conversion was obtained, a very good improvement when compared to the reported protocol using a Pd-2(dba)(3)/XPhos/t-BuONa catalytic system.

Automated summary

Highly stable nanocatalysts were synthesized in aqueous medium at room temperature by in situ formation of Pd nanoparticles embedded in an enzyme net. The synthesized CALB/PdNPs hybrids showed crystalline Pd(0) as the unique metallic species, with spherical nanoparticles ranging in diameter size from 2 to 11 nm. These hybrids were employed as catalyst in C-N/Heck reaction cross-coupling cascade to synthesize substituted azaindoles with high selectivity.