A Tandem Catalysis for Isoindolinone Synthesis over Single‐Atom Pd/TiO ₂ Catalyst

Abstract 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/TiO 2 tandem catalysis has been developed for the IIO scaffold synthesis by using readily available phthalic anhydride (PA), ammonia, and H 2 . The single‐atom Pd/TiO 2 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 TiO 2 support and single‐atom Pd. The TiO 2 efficiently catalyzes the conversion of PA with ammonia to form phthalimide (PAM), subsequently transformed into IIO over TiO 2 through the reaction of PAM with NH 3 and the spillover hydrogen species derived from single‐atom Pd. Notably, NH 3 functions not only as a reactant but also as a promoter to accelerate the reduction of amides combined with the Pd/TiO 2 catalyst. This tandem catalysis of a single‐atom Pd/TiO 2 catalyst provides a promising strategy for the synthesis of the crucial IIO platform molecules.