Impact of Induced Fitting and Secondary Noncovalent Interactions on Site-Selective and Enantioselective C-H Functionalization of Arylcyclohexanes.

Abstract

A major challenge in organic synthesis is the selective functionalization of C-H bonds. As most organic compounds contain multiple C-H bonds with similar properties, distinguishing between them requires precise control. In this study, we show how transition metal catalysts can adopt many of the characteristics associated with enzymes, leading to unprecedented site-selectivity in the C-H functionalization step. The catalysts are dirhodium complexes that adopt a bowl-shaped shape on formation. The flexible microenvironment within the bowl causes an induced fitting to occur as the reagent and substrate approach the catalyst. The key factors controlling the selectivity are noncovalent interactions between the approaching substrate and the catalyst wall, which cause a specific C-H bond in the substrate to be placed close to the metal-bound reagent.