Aromatic C-H borylation

Under conditions similar to those used for aliphatic C-H borylation, rhodium complexes catalyze the borylation of arenes by pin2B2 [53], Cp Rh( n -QMeJ (19), which in situ generates a coordinatively unsaturated rhodium species (20) active for oxidative addition, was found to be the best catalyst, giving a 92% yield after 2.5 h with 5 mol% catalyst loading and an 82% yield (328 turnover number of the catalyst, TON) with 0.5 mol% loading at 150 °C. 

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Ishiyama, T., Takagi, J., Hartwig, J.F. and Miyaura, N., A stoichiometric aromatic C—H borylation catalysed by iridium(I)/2,2 -bipyridine complexes at room temperature, Angew. Chem., Int. Ed. Engl, 2002, 41, 3056-3058. 

Aromatic C-H borylation is catalyzed by an Ir complex with a small and electron-donating ligand, for example PMe3, l,2-bis(dimethylphosphino)ethane (dmpe), 2,2 -bipyridine (bpy), and 4,4,-di-tert-butyl-2,2 -bipyridine (dtbpy) (Table 1)... 

The mechanism proposed for aromatic C-H borylation of aromatic compounds 1 by B2pin2 3 catalyzed by the Ir-bpy complex is depicted in Scheme 3 [6-9]. A tris(boryl)Ir (III) species [5, 6, 11] 6 generated by reaction of an Ir(I) complex 5 with 3 is chemically and kinetically suitable to be an intermediate in the catalytic process. Oxidative addition of 1 to 6 yields an Ir(V) species 7 that reductively eliminates an aromatic boron compound 4 to give a bis(boryl)Ir(III) hydride complex 8. Oxidative addition of 3 to 8 can be followed by reductive elimination of HBpin 2 from 9 to regenerate 6. 2 also participates in the catalytic cycle via a sequence of oxidative addition to 8 and reductive elimination of H2 from an 18-electron Ir(V) intermediate 10. Borylation of 1 by 2 may occur after consumption of 3, because the catalytic reaction is a two-step process - fast borylation by 3 then slow borylation by 2 [6],... 

Table 3 Aromatic C-H borylation with B2pin2 and [lr(OMe)(COD)]2-2dtbpy at room temperature...

The reaction of HBpin in toluene in the presence of RhCl P(/-Pr)3 2(N2) (1 mol%) at 140 °C resulted in a mixture of (borylmethyl)benzene (69%) and bis(boryl)methyl benzene (7%), along with several products arising from aromatic C-H borylation (ca. 15%).345 Rhodium-bpy complexes catalyzed the borylation at the benzylic C-H bond.351 Pd/C was found to be a unique catalyst for selective benzylic C-H borylation of alkylbenzenes by B2pin2 or HBpin (Equation (70)).360 Toluene, xylenes, and mesitylene were all viable substrates however, the reaction can be strongly retarded by the presence of heteroatom functionalities such as MeO and F. Ethylbenzene resulted in a 3 1 mixture of pinacol 1-phenylethylboron and 2-phenylethylboron derivatives. 

Intensive studies also showed that many transition metal complexes are able to catalyze aromatic C-H borylation of various arenes (Scheme 7), e.g., Cp Ir(H)(Bpin)(PMe3) [64,65], Cp Rh(Ti4-C6Me6) [65,66], ( 75-Ind)Ir(COD) [67], (776-mesitylene)Ir(Bpin)3 [67], [IrX(COD)]2/bpy (X = Cl, OH, OMe, OPh) [68-70]. A very recent study by Marder and his coworkers showed that [Ir(OMe)(COD)]2 can also catalyze borylation of C-H bonds in N-containing heterocycles [71]. For the Ir-catalyzed borylation reactions, it is now believed that tris(boryl)iridium(III) complexes [67,69], 40c, [72] are likely the reactive intermediates and a mechanism involving an Ir(III)-Ir(V) catalytic cycle is operative [67,69]. A recent theoretical study [73] provided further support for this hypothesis. A mechanism, shown in Scheme 8, was proposed. Interestingly, there are no cr-borane complexes involved in the Ir-catalyzed reactions. The very electropositive boryl and hydride ligands may play important roles in stabilizing the iridium(V) intermediates. 

A class of iridium(I) complex (30) possessing 2,2 -bipyridine (bpy) or 4,4 -di-fe/t-butyl-2,2 -bipyridine (dtbpy) ligands exhibits excellent activity and selectivity for aromatic C-H borylation with Bzpinj [59] or HBpin [60], An Ir catalyst prepared from %[IrCl(COD)2l2 (COD = 1,5-cyclooctadiene) and dtbpy achieves a maximum turnover number (8000) with 0.02 mol% catalyst loading at 100 °C. The reaction was first demonstrated at 80-100 °C using an Ir-Cl complex, but was foimd to proceed smoothly even at room temperature when the catalyst is prepared from... 

Scheme 2.11 shows the orientation of aromatic C-H borylation. The proportion of coupling products at the ortho carbon is negligible because of the high sensitivity of the catalyst to steric hindrance, and the reaction rather results in a mixture of meta and para products in statistical ratios (ca. 2 1) for mono-substituted arenes (entries 1-3) [59-61]. The reaction behaves as a nucleophilic substitution of aromatic C-H bonds. Thus, trifluoromethylbenzene reacts 6-times faster than anisole, but such... 

The ready availability of arylboronates by an aromatic C-H borylation provides a synthetic link to the well-established palladium-catalyzed cross-coupling reactions, rhodium-catalyzed 1,4-addition to a,p-unsaturated carbonyl compounds, and other bond forming reactions using arylboronic esters (Scheme 2.12). Borylation of 1,3-dichlorobenzene with pinacolborane is followed directly by a cross-coupling reaction with methyl p-bromobenzoate for the synthesis of a biaryl product in 91% yield [60]. Pinacol esters of arylboronic acids react much slower than the free acids [62], but both derivatives achieve high isolated yields and comparable enantioselectivities (91% ee) in asymmetric 1,4-addition to N-benzyl crotonamides [63]. Borylation of arenes followed by oxidation of the C-B bond is synthetically equivalent to an aromatic C-H oxidation to phenols [64]. Oxidation of the resulting arylboronates with Oxone in a 1 1 acetone-water solution is completed within 10 min at room temperature. 

Scheme2.14 Proposed cataiytic cycle for aromatic C-H borylation.

Benzylic C-H borylation giving benzylboronates was first reported by Marder [58]. The reaction of HBpin in toluene in the presence of RhCl P(i-Pr)j 2(N2) (1 mol%) at 140 °C gives (borylmethyl)benzene and bis(boryl)methyl benzene in 69% and 7% yields respectively, along with several products arising from aromatic C-H borylation (ca. 15%). 

Aromatic C-H borylation catalyzed by Ir-bpy complexes was carried out as a joint project in collaboration with Professor Hartwig s group. We are greatly indebted to Professor John F. Hartwig and his co-workers for their contribution to the elucidation of the mechanism and for helpful discussions with him. 

Manufacturing costs for B2(pin)2 have diminished significantly such that it is now a reagent that may be used in process chemistry and it is available from a number of suppliers. Since the last update, the scope of aromatic C-H borylations has continued to expand. An increased focus on stereoselective transformations involving B2(pin)2 is apparent and these newer methods are emphasized in this update. 

Iwadate N, Suginome M. Synthesis of masked haloareneboronic acids via iridium-catalyzed aromatic C-H borylation with 1,8-naphthalenediaminatoborane (danBH). J Organomet Chem. 2009 694 1713-1717. 

Synthesis of Functionalized Aryl Boranes by Catalytic Aromatic C-H Borylation... 

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