Palladium(II)-Catalyzed Regioselective Hydrocarbofunctionalization of N-Alkenyl Amides: Synthesis of Tryptamine Derivatives

The hydrocarbofunctionalization of allyl amines connected to the picolinamide directing group is developed under Pd(II) catalysis. The strategy is grounded on a nucleopalladation concept, and a wide range of indoles effectively participated to produce valuable tryptamine derivatives in high yields. Synthetic utilities were showcased through the substrate diversification bearing bioactive core, Pictet-Spengler cyclization, and beta-carboline synthesis. A mechanistic study suggested an irreversible nucleopalladation step, while protodepalladation follows a reversible pathway.

Automated summary

This study introduces a Pd(II)-catalyzed hydrocarbofunctionalization method for allyl amines connected to the picolinamide directing group. The approach is based on the concept of nucleopalladation and a wide range of indoles effectively participate to produce valuable tryptamine derivatives with high yields. Synthetic utilities are showcased through substrate diversification bearing bioactive core, Pictet-Spengler cyclization, and beta-carboline synthesis. A mechanistic study suggests an irreversible nucleopalladation step, while protodepalladation follows a reversible pathway.