Hydrolysis arylboronic acids

Arylboronic acids have traditionally been prepared via the addition of an organomagnesium or organolithium intermediate to a trialkyl borate. Subsequent acidic hydrolysis produces the free arylboronic acid. This limits the type of arylboronic acids one can access via this method, as many functional groups are not compatible with the conditions necessary to generate the required organometallic species, or these species may not be stable intermediates. 

Boro nophenyl) alanine (BPA) is a practical boron compound which is clinically used for the treatment of not only malignant melanoma but also of brain tumors, in neutron capture therapy (Scheme 1-40) [105, 152, 153]. Although (pinacolato)di-boron (82) is an excellent reagent to afford the corresponding boronate in 88% yield, it strongly resists the hydrolysis to arylboronic acids. Alternatively, the 1,3-diphenyl-propanediol ester (85) is more convenient to deprotect the diol moiety by catalytic hydrogenolysis [105]. 

The last electrophilic substitution reaction of a Grignard compound we want to consider is a transmetalation, namely one that leads to an arylboronic ester (Figure 5.45). Arylboronic esters or their hydrolysis products, the arylboronic acids, are valuable reagents in modem aro-... 

The hydrolysis of salicylaldehyde imines is catalyzed by boric acid, substituted arylboronic acids, and diphenylborinic acid. The effects of different substituted phenyl-boronic acids on the rate of hydrolysis at pH 6.0 has been studied by Rao and Philipp [168]. The second-order rate constants, are higher for phenylboronic... 

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]. 

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

Arylboronic acids.Aryl halides, alkyl borates, and magnesium in THF react under ultrasonication. Hydrolysis of the reaction mixtures provides arylboronic acids. 

Homogeneous, aqueous tv o-phase catalysis is also of industrial interest for the production of the important intermediate phenylacetic acid (PAA), -which is used in perfume and pesticides syntheses. The previous process (benzyl chloride to benzyl cyanide -with hydrolysis of the latter) suffered from the formation of large amounts of salt (1400 kg per kg of PAA). The new carbonylation method reduces the amount of salt by 60% and makes use of the great cost difference between —CN and —CO [79-81]. Finally, the Suzuki coupling of aryl halides and arylboronic acids, substituting Pd/TPPMS with Pd/TPPTS catalysts, should be also mentioned. 

Work on mechanistic details is in progress, but the present transformation may result from a catalytic cycle that involves the transmetalation between the hydroxo-rhodium(I) 4 and arylboronic acid to give the arylrhodium(I) species 5, and the insertion of enone to the Ar-Rh bond. The hydrolysis of the rhodium(I) enolate with water reproduces the hydroxorhodium species, as shown in Figure 1. The arylrhodium(I) complexes are unstable such as to preclude isolation in pure form, but they have been reasonably speculated to be the key intermediates carrying out various coupling reactions with organic halides and the addition to alkenes and alkynes. 

Zou, G., Wang, Z., Zhu, J. and Tang, J. (2003) Rhodium-catalyzed Heck-type reaction of arylboronic acids with a,/3-unsaturated esters tuning /3-hydrogen elimination versus hydrolysis of alkylrhodium species. Chem. Commun., 2438-9. 

The reaction of arylboronic acids with copper(II) acetate is speculated to form an arylcopper species which can add in a 1,2-fashion to an azodicarboxylate. Subsequent transmetallation with the arylboronic acid and hydrolysis would give the desired product selectively (Scheme 4.21). Indeed, it was found that several copper(I) and copper(II) salts would facilitate this reaction. While Cul (55%), CuCl (73%) and Cu(OTf)2 (86%) could be used-in contrast to the reaction depicted in Scheme 4.19-Cu(OAc)2 (88%) proved to be superior [58]. Additional azodicarboxylate derivatives function equally well under the optimized reaction conditions. Non-symmetrical azodicarboxylates are also useful substrates and can be arylated in a reproducibly regioselective manner in excellent to quantitative yields at ambient temperature. In this case, methanol was the preferred reaction solvent [59]. 

The transmetallation with organoboron reagent precedes the carbometallative addition of the arylrhodium intermediates 394 to the unsaturated substrate, and the intermediate alkenylrhodium species 395 then undergo hydrolysis to close the catalytic cycle with regeneration of the catalytically active species 393 and formation of the observed enamide products. An intermolecular carborhodation event was proposed to occur in a three-component coupling of arylboronic acids with disubstituted alkynes in the presence of methyl acrylate (Scheme 10.135) [113]. 

Alkyl and arylboronic acids form cyclic esters with diols. The aryl derivatives are usually crystalline, air-stable materials which resist hydrolysis under neutral or acid conditions. They have been used to characterize compounds which contain the cis diol function and to protect it during syntheses. 

The increasing importance of boronic acids as synthetic intermediates has justified the development of new, mild and efficient methods to provide access to a large pool. Of particular interest is the synthesis of arylboronic acids substituted with a wide range of other functional groups. As a consequence of their growing popularity and improvements in methods available for their preparation, many functionahzed boronic acids have become available from several commercial sources. Although several methods, like the oxidation or hydrolysis of trialkylboranes, have significant historical and fundamental relevance, this section is devoted mainly to modem methods of practical value to synthetic chemists. 

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