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 ap romising strategy to discover selective transition metal catalysts for atom-economy CÀHb ond 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 whichs mall stereoelectronic modifications within them can lead to very different reactivities.T ocircumvent these limitations and to increase the level of reactivity prediction in these important reactions,w e report herein as upramolecular catalyst harnessing Zn•••N interactions that binds to pyridine-like substrates as tight as it can be found in some enzymes.T he distance and spatial geometry between the active site and the substrate binding site is ideal to target unprecedented meta-selective iridium-catalyzed CÀHb ond borylations with enzymatic Michaelis-Menten kinetics,b esides unique substrate selectivity and dormant reactivity patterns.

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

“…[18] Moreover,s ingle crystals suitable for X-ray diffraction studies were obtained from as olution containing L and pyridine in an equimolar ratio (Figure 2, left). [21] As anticipated, the nitrogen atom from pyridine binds to the zinc(II) center of L.Gratifyingly,the coordinating arm of L stands in the same face as the substrate with av olumetric space between both motifs enough to accommodate ac atalytically active iridium center. Analogously single crystals with apotential substrate, N-methylimidazole,were also obtained and analyzed by X-ray diffraction studies (Figure 2, right).…”

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

“…21 To increase the level of reactivity prediction, Gramage-Doria and coworkers recently employed an enzyme-like supramolecular iridium catalyst in C-H borylation, affording excellent metaregioselectivity (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 shields to enter in the catalyst recognition pocket in order to react. It is worth noting that, in contrast to previous works, chloride version of the iridium precatalyst [Ir(COD)Cl]2 works better than the methoxy one [Ir(COD)(OMe)]2 in this system.…”

Recent Progress in Iridium-Catalyzed Remote Regioselective C—H Borylation of (Hetero)Arenes

“…Very recently, the Gramage-Doria group [48] realized a highly meta-selective C-H borylation of pyridines enabled by enzyme-like supermolecular iridium catalysis (Scheme 14). With a rationally-designed Zn(II)-porphyrinbased N,N-chelating ligand L9, they found its iridium complex exhibiting a strong affinity for pyridine derivatives (K＞10 4 L•mol -1 ) by means of kinetically labile Zn-N coordination (Scheme 14, INT-9).…”