Aromatic borylation arenes

Borylation. Arenes (including thiophene ) are borylated by pinacolatoborane using [(cod)IrOMe]2 as catalyst. Tbe remarkable feature of this reaction is m-substitution, through such unusually patterned aromatic compounds become available. " ... 

For each case we will also present catalytic analogues, namely (1) the activation of methane to form methanol with platinum, the reaction of certain aromatics with palladium to give alkene-substituted aromatics, and (2) the alkylation of aromatics with ruthenium catalysts, and the borylation of alkanes and arenes with a variety of metal complexes. 

The scope and value of the benzannulation reaction is further increased by the substitution pattern of the arene ring, which can be modified by the incorporation of allcynes bearing additional functional groups such as silyl, stannyl, or boryl substituents. These functional groups have been used in various palladium-catalyzed (cross)-coupling reactions [63, 64]. Further structural elaboration may be based on benzannulation followed by nucleophilic aromatic addition [63b]. 

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. 

The catalytic borylation offers unique selectivity when compared to traditional aromatic substitution reactions. Thus, mono- and 1,3-disubstituted (type 32) arenes react predominantly at meta-positions. This high meta-selectivity is a sterically controlled process. In the case of 1,3-difunctionized substrates borylation occurs exclusively at the 5-position even where functionalizations at the... 

The functionalization of benzylic or arene C-H bonds with boranes leads to synthetically useful boranates. Shimada and co-workers showed that [RhCl(P/Pr3)2(N2)] is an effective catalyst precursor for the borylation of aromatic and benzylic C-H bonds with the use of pinacolborane, resulting in high selectivity for benzylic C-H functionalization. ... 

A number of systems have been developed for the functionalization of C-H bonds by their conversion into carbon-boron or carbon-silicon bonds. The substrates can be alkenes (Scheme 3.35), arenes (Schemes 3.36-3.38), heteroarenes (Schemes 3.39-3.41)" ° and even alkanes (Scheme 3.42)." With arenes, the electronic properties of the aromatic ring do not always seem to control the regioselectivity, as mixtures of isomers are often formed. Methyl-substituted aromatics may be borylated on the side chain depending on the choice of catalyst." ... 

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. 

The Iridium-catalyzed borylation reaction was found to he suitable for arenes possessing various functional groups such as OMe, halides, COOMe, CN, CF3, and benzyhc C-H bonds. Because the borylation reaction is not electrophihc aromatic substitution, the electronic property of the substituents has httle influence on regioselectivity. The reactions of monosubstituted arenes result in a mixture of meta- and para-products in statistical ratios (ca. 2 1) in most cases. Regioisomerically pure products were obtained in... 

As an alternative to the electrophific functionalization of PS, the iridium-catalyzed borylation of aromatic C—H bonds to functionalize PSs with different tacticities (atactic, isotactic, and syndiotactic Fig. 24A) was reported. Because the borylation did not occur at the C—H bonds of sp carbons, it did not affect the tacticity of PSs. Similar to the case of molecular arenes, this C—H borylation of PS was achievable with bis(pinacolato) diboron (B2pin2) or pinacolborane (HBpin) and generated a mixture of meta- and para-substituted borylated PSs. However, the ratio of the two isomers was different than that of isopropylbenzene because a phenyl ring was attached to every other carbon in the PS backbone, the meta C—H bonds of PS were more sterically hindered than the para C—H bonds. Thus, while the ratio of meta- and para-substituted isomers in the C—H borylation of isopropylbenzene was 7 3, the C—H borylation of PS under identical... 

This result represents the first example of a synthetic cycle for arene borylation facihtated by an f-element. The authors investigated the reaction mechanism and proposed a concerted direct B—H attack on an aromatic C—H bond, which resulted in the formation of the B—C bond and the release of one molecule of H2. This type of reactivity resembles a-bond metathesis if boron is considered a metal center. Albeit uranium was not directly involved in the borylation of the arene C—H bond, the formation of the diuranium arene inverse-sandwich complex plays an important role. The arene, i.e., benzene or naphthalene, is partially reduced upon coordination to uranium,which makes it more susceptible to attack by an electrophile such as borane. Therefore, although uranium is not direcdy involved in the C—H bond activation step, this example illustrates that f-elements can render arenes reactive in nonmetal-mediated transformations by forming activated arene metal complexes. 

There has been a review of the electrophilic borylation of arenes. It has been shown that the direct reaction of arylboroxines with 0-benzoylhydroxylamines in the presence of base, but without transition metal catalysis, may yield aromatic amines. 

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