Induced-Fit in Rhodium-Catalysis: How t-butyls influence selectivity through ligand NCI networks

The 3,5-di-t-butyl benzene motif (DTB) has been incorporated across diverse ligand scaffolds families to enhance catalyst performance. In this mechanistic study, we reveal a surprising way that DTB enables selectivity in Rh-catalysis through the ligand’s network of non-covalent interactions (NCI). To gain these insights, we applied a modified version of the distor-tion/interaction strain model to study a Rh-catalyzed cycloi-somerization that gives rise to different constitutional isomers. Compared to the unsubstituted parent ligand, the DTB ligand generates a distinctive binding pocket. However, the substrate transition-state geometries remain unvaried. This rigid geome-try induces a conformational change in the DTB ligand to provide a more favorable fit. While commonly used to rational-ize enzyme catalysis, induced-fit is rarely invoked in transition-metal catalysis. This study spotlights how DTB can enhance selectivity using an induced-fit model driven by ligand NCI networks.