Hydrogen Bond Directed ortho‐Selective C−H Borylation of Secondary Aromatic Amides

Abstract

Reported is an iridium catalyst for ortho‐selective C−H borylation of challenging secondary aromatic amide substrates, and the regioselectivity is controlled by hydrogen‐bond interactions. The BAIPy‐Ir catalyst forms three hydrogen bonds with the substrate during the crucial activation step, and allows ortho‐C−H borylation with high selectivity. The catalyst displays unprecedented ortho selectivities for a wide variety of substrates that differ in electronic and steric properties, and the catalyst tolerates various functional groups. The regioselective C−H borylation catalyst is readily accessible and converts substrates on gram scale with high selectivity and conversion.

Predictable Selectivity in Remote C−H Oxidation of Steroids: Analysis of Substrate Binding Mode

“…Predictable remote (or intermolecular) functionalization demands a supramolecular, biomimetic strategy, where binding of a substrate to a receptor controls its orientation . This pioneering approach has already unlocked elusive transformations, such as remote or enantioselective C(sp 3 )−H oxidations, meta and ortho C−H borylations, or selective olefin hydroformylation . The selectivity in these systems can be rationalized and somehow predicted by computational methods, design of the catalyst and substrate structure, and analysis of product distribution.…”

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

“…[8] As such, different strategies have been developed to design transition metal catalysts incorporating remote functionalities to pre-organize substrates in as pecific geometry to access unprecedented C À Hb ond functionalizations. [9] In this context, the incorporation of hydrogen bonding, [10] ion-pairing [11] or Lewis adducts formation, [12] respectively,t ot ransitionmetal catalysts has emerged as promising approaches to control the regio-selectivity in iridium-catalyzed CÀHb ond borylation reactions (Figure 1A). [13] Borylated products are relevant as they can straightforwardly be engaged in state-ofthe-art carbon-carbon and carbon-heteroatom bond forming process.…”

“…[14] Unfortunately,the predictability of these catalytic systems is still poorly rationalized, basically due to the low association constants between the substrate and the catalyst, generally with K < 10 2 M À1 . [10][11][12] Consequently,s mall modifications in the commonly used bipyridine-derived ligand and/ or the substrate can lead to ac omplete lack of reactivity or absence of selectivity. [10][11][12] Precisely,w ea imed at circumventing the poor reactivity of pyridine derivatives at meta position.…”

“…[10][11][12] Consequently,s mall modifications in the commonly used bipyridine-derived ligand and/ or the substrate can lead to ac omplete lack of reactivity or absence of selectivity. [10][11][12] Precisely,w ea imed at circumventing the poor reactivity of pyridine derivatives at meta position. [15a] Iridium-catalyzed CÀHb ond borylations typically occur at the meta position of pyridine derivatives when bulky substituents are present in the ortho site in order to prevent the undesired coordination of the pyridine nitrogen lone pair to the iridium catalyst, which gives unproductive and unselective catalysis (Figure 1B).…”

Urea‐Substituted Tetramethylcyclopentadienyl Ligands for Supramolecularly Accelerated RhIII‐Catalyzed ortho‐C−H Olefination of Benzoic Acid Derivatives

“…[1,2] Inspired chemists have been able to benefit from this toolbox by designing artificial enzymesf eaturing biomimetic catalytic properties for several decades. [3,4] Recent publications have successfully demonstrated that similarc oncepts can also be appliedt ot ransition metal-catalyzed CÀHa ctivation: bipyridine ligands designed for iridium-catalyzed CÀHb orylation of aromatic substrates have been studied intensively and have provided access to regioselective meta-, [5,6] para-, [7] and ortho-functionalization [8] (Figure 1a). Our own group'se fforts to develop supramolecular catalyst systems have been focused on reactions catalyzedb yr hodium.…”