Iridium-Catalyzed sp³ C–H Borylation in Hydrocarbon Solvent Enabled by 2,2′-Dipyridylarylmethane Ligands

Abstract

Iridium-catalyzed alkane C−H borylation has long suffered from poor atom economy, resulting from both the inclusion of only 1 equiv of boron from the diboron reagent and a requirement for neat substrate. An appropriately substituted dipyridylarylmethane ligand was found to give highly active alkane borylation catalysts that facilitate C−H borylation with improved efficiency. This system provides for complete consumption of the diboron reagent, producing 2 molar equivalents of product at low catalyst loadings. The superior efficacy of this system also enables borylation of unactivated alkanes in hydrocarbon solvent with a reduced excess of substrate and improved functional group compatibility. The effectiveness of this ligand is displayed across a selection of functional groups, both under traditional borylation conditions in neat substrate and under atypical conditions in cyclohexane solvent. The utility of this catalytic system is exemplified by the borylation of substrates containing polar functionality, which are unreactive toward C−H borylation under neat conditions.

Ligand-Driven Advances in Iridium-Catalyzed sp3 C–H Borylation: 2,2′-Dipyridylarylmethane

“…[16][17] Additionally, cyclometalation of the aryl ring under the reaction conditions would allow for the use of the same pre-catalysts previously found to be effective in diimine systems. As we recently reported, 15 we found that while the dipyridylphenylmethane ligand L1, does give an active catalyst for n-octane borylation, it significantly underperforms the benchmark Me4Phen/Ir system ( Figure 4). As part of an effort to examine the fate of the ligand during catalysis, we prepared the fluorinated derivatives L2 and L3.…”

“…As we recently reported, 15 we found that, although the dipyridylphenylmethane ligand L1 did give an active catalyst for n-octane borylation, it significantly underperformed the benchmark Me 4 phen/Ir system (Scheme 3). As part of an effort to examine the fate of the ligand during catalysis, we prepared the fluorinated derivatives L2 and L3.…”

“…Catalysts have been developed for the sp 3 borylation of activated (including benzylic, cyclopropane, and alkylsilane substrates) [27][28][29][30] or directed substrates, 29,[31][32][33][34][35] however, the C-H borylation of unactivated alkyl substrates in solvent was largely unaddressed prior to recent work by Hartwig 18 and ourselves. 15 The success of the [(cod)IrOMe]2/L2 system in neat n-octane ( Figure 4) inspired us to survey potential conditions for borylation in solvent. We ultimately identified a procedure that allowed for the sp 3 C-H borylation of unactivated substrates in cyclohexane, with a key improvement resulting from a switch in the iridium precursor from [(cod)IrOMe]2 to [(Mes)Ir(Bpin)3].…”

“…In a recent publication 15 we detailed a new catalytic system based on a dipyridylarylmethane ligand that offers notable improvements over the Cp*Ir, Cp*Rh, and Me 4 phen/Ir systems. Our approach to the design of new ligands for iridium-catalyzed sp 3 C-H borylation was informed to a significant extent by mechanistic studies published by Hartwig, Sakaki, and their respective co-workers.…”

“…Catalysts based on iridium or rhodium have been broadly applied in thermal C-H borylation reactions across these subclasses, whereas other elements have found more-limited applications in the borylation of activated or directed Scheme 1 Review of C-H borylation catalysts and ligands for the sp 3 C-H borylation of unactivated substrates with Cp*, 7 Me 4 phen, [13][14] and L2. 15 Yields are reported relative to either 1 equivalent of B 2 pin 2 or relative to total boron equivalents. See discussion of both conventions below.…”