A meta-selective C–H borylation directed by a secondary interaction between ligand and substrate

Abstract

Regioselective C-H bond transformations are potentially the most efficient method for the synthesis of organic molecules. However, the presence of many C-H bonds in organic molecules and the high activation barrier for these reactions make these transformations difficult. Directing groups in the reaction substrate are often used to control regioselectivity, which has been especially successful for the ortho-selective functionalization of aromatic substrates. Here, we describe an iridium-catalysed meta-selective C-H borylation of aromatic compounds using a newly designed catalytic system. The bipyridine-derived ligand that binds iridium contains a pendant urea moiety. A secondary interaction between this urea and a hydrogen-bond acceptor in the substrate places the iridium in close proximity to the meta-C-H bond and thus controls the regioselectivity. (1)H NMR studies and control experiments support the participation of hydrogen bonds in inducing regioselectivity. Reversible direction of the catalyst through hydrogen bonds is a versatile concept for regioselective C-H transformations.

Exploiting directional long range secondary forces for regulating electrostatics-dominated noncovalent interactions

“…Furthermore, noncovalent interactions have recently been exploited in stereochemical induction, where the approach of prochiral substrates to the chiral catalysts was allowed only from a specific direction. 1–4,69 Our EF analysis approach would provide meaningful insights into the mechanistic understanding of such reactions, and that would help in tuning such systems for superior catalytic performance. This model could also be useful in understanding the behavior of ionic crystals.…”

Achieving High Ortho Selectivity in Aniline C–H Borylations by Modifying Boron Substituents

“…39 The electrostatic mechanism is a more subtle variant of the ion-pairing mechanisms proposed by Phipps and co-workers in recently designed meta-selective CHBs, 40 which complements other meta-selective CHBs where outer-sphere mechanisms are proposed to account for selectivity. 34,37,41 …”

Mild metal-catalyzed C–H activation: examples and concepts

“…Very recently, Kuninobu and Kanai very astutely illustrated that the extremely mild character of these borylation reactions and their compatibility with N,N-bidentate ligands can facilitate very challenging and original transformations (Scheme 18). 39 They hypothesized that embedding a pendant hydrogen-bond donor moiety on the bipyridine ligand should enable secondary interactions between this ligand and a C-H substrate bearing a hydrogen-bond acceptor DG. Such ligand-substrate coordination could result in otherwise inaccessible regioselectivity in the borylation process.…”