Arylboronic pinacolate

The total synthesis of the proteasome inhibitor cyclic peptide TMC-95A was accomplished by. S.J. Danishefsky and co-workers. The biaryl linkage in the natural product was constructed by a Suzuki cross-coupling between an aryl iodide and an arylboronic ester derived from L-tyrosine. The required arylboronic pinacolate substrate was prepared using the Miyaura boration. The aryl iodide was exposed to b/s(pinacolato)diboron in the presence of a palladium catalyst and potassium acetate in DMSO. The coupling proceeded in high yield and no symmetrical biaryl by-product was observed. 

Recently, a novel coupling reaction, based on the used of pinacolborane as an efficient reagent for the electrochemical functionalization of aryl halides in the presence of an Mg anode afforded arylboronic pinacol esters [2]. However, this reaction presents some limitations low faradic efficiencies with aryl chlorides,... 

Synthesis of pinacol arylboronates 190 200 via cross-coupling reaction of bis(pinacolato)diborane(4) with chloroarenes catalyzed by palladium(O)-tricyclohexyl-phosphine complexes has been demonstrated by Ishiyama et al. (Scheme 31).115... 

Iron-catalyzed Suzuki-Miyaura coupling reactions were also reported by Nakamura and colleagues (entry 27) [67]. Alkyl halides 1 and mixed pinacol aryl(butyl)borates, generated in situ from arylboronates and butyllithium, were used as the reagents and 10 mol% of the iron complexes 16a or 16b as the catalysts. The addition of 20 mol% of MgBr2 was essential for the success of the reaction. Products 3 were isolated in 65-99% yield. The methodology tolerates ester and nitrile functions. The reaction starts probably by initial boron-iron transmetalation to generate a diaryliron(II) complex. 

Stepwise double coupling of two different arylboronic acids with a dihaloarene afforded one-pot, two-step method for synthesizing unsymmetrical teraryls, quateraryls, and other higher order polyaryls.882 The first total synthesis of dragmacidin D involved a sequential double coupling of two different pinacol 3-indoleboronic esters (ArBpin Equation (207)).882... 

Boronic acids (5a) were among the first examples of low-molecular-weight, reversible inhibitors of serine proteinases [151, 152]. Significant inhibition was initially demonstrated against a-chymotrypsin. Unlike the carbonyl-derived reversible inhibitors, which require a polypeptide or peptide-like chain, activity was found with simple alkylboronic acids (e.g. the value for PhCH2CH2B(OH)2 with a-chymotrypsin was = 40 //M) [153], Weak inhibition of elastase (PPE) was first reported for a series of arylboronic acids, for example, (10-1) [123]. Some of the boron-based inhibitors Figure 2.5) were tested as either the difluoroboranes (5b) or as the pinacol boronate esters (5c). These modifications were employed because they were more readily synthesized and/or purified than the boronic acids. For both of these derivatives inhibition was shown to be due to in situ hydrolysis to the parent boronic acid (5a) [154, 155]. 

Ishiyama, T., Ishida, K., Miyaura, N. Synthesis of pinacol arylboronates via cross-coupling reaction of bis(pinacolato)diboron with chloroarenes catalyzed by palladium(0)-tricyclohexylphosphine complexes. Tetrahedron 2001, 57, 9813-9816. 

Wittig reagents. Magnesium generation from alkylphosphonium sj Arylboronic acids.Aryl hahe ultrasonication. Hydrolysis of the reac Pinacols." A simple method presence of NH Cl. 

Several new synthetic methods of arylboronates, such as pinacol ester, have been developed. A convenient preparative method of arylboronates 4 is Pd-catalyzed cross-coupling of aryl halides and triflates with bis(pinacolato)diboron (3), which can be handled easily in air. The best ligand for the coupling is DPPF [12]. In addition, one-pot biaryl synthesis can be carried out most conveniently without isolation of the boronate 4 to provide 5 [13], Ligandless Pd(OAc)2 is active for... 

The Pd-catalyzed cross-coupling reaction of the pinacol ester of diboronic acid with aryl halides and triflates gives a direct procedure for various functionalized arylboronic esters (Table 6), which are useful for highly efficient and selective carbon-carbon bond formation by Pd catalysts (Sect. III.2.2). The combination of PdCl2(dppf) with KOAc (and dppf) is effective in the carbon-boron bond formation. KOAc is essential not only to accelerate the reaction but also to prevent the formation of biaryl by-products. 

Thus formed, organometallics are trapped with tiialkyl borates to produce whether the desired arylboronic [149-151,153] or diarylboronic esters [152], depending on the reaction conditions discussed above. The diarylboronic acids have also been successfully used in the Pd(PPh3)4-catalysed SM reactions with aryl triflates, under the standard conditions [152]. Beside trialkyl borates, A,A-dimethylaminoboron bromide has been trapped with organolithiums to give an unstable bis-aminoboronate 349, which, upon esterification with pinacol, gave the 1,4-phenylene-bis-pinacolato boronate (266) in 21% overall yield [154], Scheme 50. 

Esterification of arylboronic acids Preparation of phenyl-1,4- diboronic acid bis-pinacol ester (266) 18/... 

Scheme 14.6 Diethanolamine and MIDA adducts, and pinacolates of DoM-derived boronic acids. Borodesilylation route to arylboronic acids [24-28].

Along with their work on the nickel-catalyzed Suzuki-Miyaura coupling of neopentylglycol boronic esters, Percec and coworkers examined the speed of transesterification of a cyclic arylboronic ester with a diol under anhydrous conditions. In both assays in Scheme 3.2, some transesterification had taken place after 10 h (equilibrium was not reached). This result shows that transesterification of cyclic boronic esters is always possible, even starting from pinacol esters. This should be kept in mind when considering reactions in the presence of alcohol solvents and water. 

Heterocyclic aromatic boronic acids, in particular pyridinyl, pyrrolyl, indolyl, thienyl, and furyl derivatives, are popular cross-coupling intermediates in natural product synthesis and medicinal chemistry. The synthesis of heterocyclic boronic acids has been reviewed recently [222], and will not be discussed in detail here. In general, these compounds can be synthesized using methods similar to those described in the above section for arylboronic acids. Of particular note, all three isomers of pyridineboronic acid have been described, including the pinacol ester of the unstable and hitherto elusive 2-substituted isomer, which is notorious for its tendency to pro-todeboronate [223]. Improvements and variants of the established methods for synthesizing heterocyclic boronic acids have been constantly reported [13, 182]. For example, a Hg-to-B transmetallation procedure was recently employed to synthesize a highly functionalized indolylboronic acid (entry 19, Table 1.3) [187]. 

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 Pd-catalyzed cross-coupling reaction of the pinacol ester of diboronic acid with aryl halides and triflates gives a direct procedure for various functionalized arylboronic esters (Table which are useful for highly efficient and selective carbon-carbon bond... 

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