A Tandem Catalysis for Isoindolinone Synthesis over Single‐Atom Pd/TiO₂ Catalyst

Developing an efficient strategy to replace the conventional synthesis method for producing isoindolinone (IIO) scaffold, a crucial structural motif for constructing pharmaceutical molecules, remains to be a great challenge. Herein, a single-atom Pd/TiO₂ tandem catalysis has been developed for the IIO scaffold synthesis by using readily available phthalic anhydride (PA), ammonia, and H₂. The single-atom Pd/TiO₂ catalyst demonstrates superior catalytic performance, achieving a PA conversion of 99 %, an IIO selectivity of 91 %, and a turnover frequency (TOF) up to 4807 h^-1. This exceptional performance can be attributed to the tandem catalysis between TiO₂ support and single-atom Pd. The TiO₂ efficiently catalyzes the conversion of PA with ammonia to form phthalimide (PAM), subsequently transformed into IIO over TiO₂ through the reaction of PAM with NH₃ and the spillover hydrogen species derived from single-atom Pd. Notably, NH₃ functions not only as a reactant but also as a promoter to accelerate the reduction of amides combined with the Pd/TiO₂ catalyst. This tandem catalysis of a single-atom Pd/TiO₂ catalyst provides a promising strategy for the synthesis of the crucial IIO platform molecules.