Controlling Selectivity at the First Hydrogenation Level: Synthesis of 3‐Hydroxyisoindolines by Heterogeneously Silver‐Catalyzed Monohydrogenation of Phthalimides

3‐Hydroxylactams are obtained from phthalimides through a heterogeneous catalyzed chemoselective hydrogenation, able to stop the process at the first hydrogenation level. By using a rationally designed [Ag/Al2O3] recyclable solid nanocatalyst, a wide range of cyclic hemiamidals are accesed through a full atom‐economical reaction that preserves (hetero)aromatic rings for the first time. Abstract The development of robust nanocatalysts able to mediate important organic transformations with high levels of selectivity constitutes a hot topic in fine‐chemistry and catalysis fields. In this context, the rational design of heterogeneous catalysts featuring suitable active sites for obtaining 3‐hydroxyisoindolinones by the direct monohydrogenation of highly accessible phthalimides is an attractive approach. This work presents the design and successful catalytic application of a robust and recyclable [Ag/Al2O3] nanomaterial capable to promote the synthesis of a wide range of 3‐hydroxylactams through the catalytic monohydrogenation of phthalimides with total atom‐economy. It is important to remark that this transformation proceeds with full chemoselectivity, exhibiting complete tolerance to the presence of (hetero)aromatic rings and being able to stop the hydrogenation at the first intermediate level. A deep effort concerning material catalyst optimization and characterization study are performed, determining that the optimal [Ag/Al2O3] is composed of silver nanoparticles with an overall size of 2.3 nm homogeneously distributed across the alumina matrix. The characterization together with the performance of kinetic/mechanistic investigations allows to propose an intimate contact between accessible Ag0 sites and Lewis acidic centers is crucial for the catalyst system to perform the hydrogenative process with complete efficiency. 3-Hydroxylactams are obtained from phthalimides through a heterogeneous catalyzed chemoselective hydrogenation, able to stop the process at the first hydrogenation level. By using a rationally designed [Ag/Al 2 O 3 ] recyclable solid nanocatalyst, a wide range of cyclic hemiamidals are accesed through a full atom-economical reaction that preserves (hetero)aromatic rings for the first time. Abstract The development of robust nanocatalysts able to mediate important organic transformations with high levels of selectivity constitutes a hot topic in fine-chemistry and catalysis fields. In this context, the rational design of heterogeneous catalysts featuring suitable active sites for obtaining 3-hydroxyisoindolinones by the direct monohydrogenation of highly accessible phthalimides is an attractive approach. This work presents the design and successful catalytic application of a robust and recyclable [Ag/Al 2 O 3 ] nanomaterial capable to promote the synthesis of a wide range of 3-hydroxylactams through the catalytic monohydrogenation of phthalimides with total atom-economy. It is important to remark that this transformation proceeds with full chemoselectivity, exhibiting complete tolerance to the presence of (hetero)aromatic rings and being able to stop the hydrogenation at the first intermediate level. A deep effort concerning material catalyst optimization and characterization study are performed, determining that the optimal [Ag/Al 2 O 3 ] is composed of silver nanoparticles with an overall size of 2.3 nm homogeneously distributed across the alumina matrix. The characterization together with the performance of kinetic/mechanistic investigations allows to propose an intimate contact between accessible Ag 0 sites and Lewis acidic centers is crucial for the catalyst system to perform the hydrogenative process with complete efficiency. Advanced Science, Volume 13, Issue 2, 9 January 2026.