Use of Hemilabile N,N Ligands in Nitrogen‐Directed Iridium‐Catalyzed Borylations of Arenes

Abstract

The direct activation of unreactive C À H bonds has emerged as a very active field in organic synthesis.[1] One of the best established reactions in this area is the direct borylation of arenes with bis(pinacolato)diboron (B 2 pin 2 ) or pinacolborane (HBpin). After the seminal work by Smith, Hartwig, Miyaura, and their respective co-workers, this method has reached an impressive level of chemical efficiency, [2] mainly because of the introduction of the [Ir(m-X)(cod)] 2 /di-tert-butylbipyridine (dtbpy; X = Cl, OMe; cod = 1,5-cyclooctadiene) precatalyst system. The regioselectivity of this reaction is typically driven by steric factors, [3] thus making the method complementary to directed ortho-metalation (DoM) reactions.[4] Very recently, however, directed ortho borylations have been accomplished by using directing groups such as siloxide or silylamine [5] and carbonyl functionalities, [6] but the absence of any nitrogendirected borylation is noteworthy. Herein, we present our results on the regioselective ortho CÀH borylation of 2-arylpyridines (isoquinolines) and aromatic hydrazones.The regioselectivity of Ir III /dtbpy-catalyzed reactions can be arguably attributed to the lack of a coordination site in complex B, which results from coordination of the directing atom Y to the established catalytic species A[2c] (Scheme 1). In this scenario, the direct activation of arene CÀH bonds can only proceed through intermediate C and is therefore mainly controlled by steric factors. On the other hand, the ability of transition metals to selectively activate arene C À H bonds in 2-aryl pyridines [1d] made us speculate that such a reaction would only require the generation of an additional coordination site at an appropriate stage. Therefore, we decided to investigate the behavior of potentially hemilabile N,N ligands, [7] in which one of the nitrogen atoms is a weaker donor that is prone to dissociation and therefore able to generate the required coordination site. It was foreseen that an ideal ligand should still be a good donor in order to maintain a high level of reactivity as in the reference dtbpy-based system. Based on our own experience with related ligands, [8] pyridine hydrazones 2-4, which maintain one of the pyridine units in their structures, and bishydrazone 5 were considered as candidates (Scheme 2). Additionally, pyridine imine 6 [9] and pyridine amine 7 were included for comparison in the preliminary screenings. The relative activity of in situ formed [IrCl(cod)] 2 /N,N-ligand catalysts (ligand = 1-7) was investigated by using the borylation of 1-

C(sp2)–H Borylation of Fluorinated Arenes Using an Air-Stable Cobalt Precatalyst: Electronically Enhanced Site Selectivity Enables Synthetic Opportunities

“…Fluoroarenes containing a benzylic hydrosilane group and a benzylic dimethylamine, well-known ortho -directing groups in iridium-catalyzed C–H borylation, 22,23b were selectively borylated ortho to fluorine rather than ortho to these functional groups to yield fluoroarenes 6g and 6h (Scheme 2). In iridium catalysis, benzylic hydrosilanes are proposed to direct ortho -borylation from formation of a putative iridium bis(boryl) silyl intermediate arising from reaction of the silane Si–H bond with the iridium tris(boryl) followed by selective C–H activation (Scheme 3).…”

“…Iridium catalysts containing hemilabile N , N ligands 23a promote ortho -borylation using a benzylic dimethylamine as a directing group. 23b The ortho selectivity is proposed to arise from coordination of the [NMe 2 ] group to the metal followed by dissociation of an amine nitrogen from the supporting N , N chelate, opening a site for C–H activation (Scheme 4).…”

“…23b The ortho selectivity is proposed to arise from coordination of the [NMe 2 ] group to the metal followed by dissociation of an amine nitrogen from the supporting N , N chelate, opening a site for C–H activation (Scheme 4). 23b With cobalt, the benzylic dimethylamino group has proven ineffective for directing ortho selectivity, likely due to the tridentate pincer.…”

Strongly Emissive and Photostable Four‐Coordinate Organoboron N,C Chelates and Their Use in Fluorescence Microscopy

“…[32] The boryl moiety can be subsequently transformed into a bromide using Hartwig´s methodology. [33] This route provides a versatile access to arylbromides that can be converted into the target compounds by a bromide-lithium exchange at 78 C, followed by trapping of the lithiated species with (Mes)2BF (Scheme 2).…”

A Traceless Directing Group for CH Borylation

“…[1],[2] Similarly, it has been shown that directing groups can alter regioselectivities in Ir-catalyzed C–H borylations. [3] Examples fall into two classes: (i) those where the directing group is already present in the substrate, [4] and (ii) those where it must be installed. [5] An example of the latter class is Hartwig’s use of silylhydrides to facilitate the borylation ortho to OH and NH functionality and effect the functionalization at sp 2 positions in arylsilanes.…”