Enzyme‐like Supramolecular Iridium Catalysis Enabling C−H Bond Borylation of Pyridines with meta‐Selectivity

Abstract

The use of secondary interactions between substrates and catalysts is a promising strategy to discover selective transition metal catalysts for atom‐economy C−H bond functionalization. The most powerful catalysts are found via trial‐and‐error screening due to the low association constants between the substrate and the catalyst in which small stereo‐electronic modifications within them can lead to very different reactivities. To circumvent these limitations and to increase the level of reactivity prediction in these important reactions, we report herein a supramolecular catalyst harnessing Zn⋅⋅⋅N interactions that binds to pyridine‐like substrates as tight as it can be found in some enzymes. The distance and spatial geometry between the active site and the substrate binding site is ideal to target unprecedented meta‐selective iridium‐catalyzed C−H bond borylations with enzymatic Michaelis–Menten kinetics, besides unique substrate selectivity and dormant reactivity patterns.

Mimicking Enzymes: Taking Advantage of the Substrate-Recognition Properties of Metalloporphyrins in Supramolecular Catalysis

“…In 2021, a similar approach was implemented for the challenging iridium-catalyzed C–H bond borylation of pyridines (Scheme 7 ). 88 The employed supramolecular catalyst featured a zinc(II)-porphyrin site, enabling the binding of pyridine derivatives via Zn … N interactions, and a peripheral iridium-based N,N-chelating site. Although the substrate-recognition site and the catalytically active site are far apart (nine chemical bonds), the ideal geometry and distance makes it possible to achieve exclusive C–H bond activation at the meta position of pyridines and at the β position of imidazoles.…”

Transition-Metal-Catalyzed Regioselective C–H Borylation of ­Pyridines

“…21 To increase the level of reactivity prediction, Gramage-Doria and co-workers recently employed an enzyme-like supramolecular iridium catalyst in C–H borylation, affording excellent meta -regioselectivity (Scheme 3 ). 22 The supramolecular catalyst, nonetheless, are only compatible with meta -functionalized pyridines because ­ortho - and para -functionalized substrates do not meet the required steric profile to enter in the catalyst recognition pocket in order to react. It is worth noting that, in contrast to previous works, the chloride version of the iridium pre-catalyst [Ir(COD)Cl] 2 works better than the methoxy derivative [Ir(COD)(OMe)] 2 in this system.…”

Hydration of Propargyl Esters Catalyzed by Gold(I) Complexes with Phosphoramidite Calix[4]pyrrole Cavitands as Ligands

“…8−15 A closely related methodology relies on the covalent placement of a catalytic metal center in close proximity to a binding site (Figure 1). 16,17 Highly relevant to this work are the reports of Iwasava and Schramm describing the use of gold(I) complexes of phosphoramidite ligands derived from resorcin [4]arene deep cavitands 1 (Figure 2, left). 18−23 More recently, Echavarren introduced chiral versions of structurally related phosphoramidite ligands and their gold(I) complexes.…”