Borate esters, boronic acids from

A number of boron chemicals are prepared directly from boric acid. These include synthetic inorganic borate salts, boron phosphate, fluoborates, boron ttihaHdes, borate esters, boron carbide, and metal aHoys such as ferroboron [11108-67-1]. 

The procedure described4 is a modification of the method of Khotinsky and Melamed,8 who first reported the preparation of boronic acids from Grignard reagents and borate esters. Benzeneboronic acid and the corresponding anhydride also have been prepared by reaction of phenylmugnesium bromide with boron... 

In recent years, a variety of aryl boronic acids are commercially available, albeit in some cases they may be expensive for large scale purposes. During our work in the mid-1990 s boronic acid (II) was not commercially available and so two different protocols were used to prepare this acid. The first approach involved the transmetallation with n-butyl lithium of aryl bromide (I) and trapping the lithio species generated with trialkyl borate followed by an acid quench. Aryl bromide (I) is easily prepared by reaction of o-bromobenzenesulfonyl chloride with 2-propanol in the presence of pyridine as a base. The second approach was a directed metallation of isopropyl ester of benzene sulfonic acid (VII), to generate the same lithio species and reaction with trialkyl borate. The sulfonyl ester is prepared by reaction of 2-propanol with benzenesulfonyl chloride. From a long-term strategy the latter approach is... 

The addition of allylic boron reagents to carbonyl compounds first leads to homoallylic alcohol derivatives 36 or 37 that contain a covalent B-O bond (Eqs. 46 and 47). These adducts must be cleaved at the end of the reaction to isolate the free alcohol product from the reaction mixture. To cleave the covalent B-0 bond in these intermediates, a hydrolytic or oxidative work-up is required. For additions of allylic boranes, an oxidative work-up of the borinic ester intermediate 36 (R = alkyl) with basic hydrogen peroxide is preferred. For additions of allylic boronate derivatives, a simpler hydrolysis (acidic or basic) or triethanolamine exchange is generally performed as a means to cleave the borate intermediate 37 (Y = O-alkyl). The facility with which the borate ester is hydrolyzed depends primarily on the size of the substituents, but this operation is usually straightforward. For sensitive carbonyl substrates, the choice of allylic derivative, borane or boronate, may thus be dictated by the particular work-up conditions required. 

Hydrolysis of the ethyl ester proceeded smoothly using hydrochloric acid in acetic acid to give carboxylic acid 69 in 88% yield (Scheme 4.9). Previously, amines were allowed to react with the carboxylic acid core in hot DMSO to deliver the C7 products however, the difluoroborate 70, derived from the carboxylic acid 69, greatly increased the reactivity of the C7 position. Consequently, the displacement of the C7-F with amines was accomplished at lower temperature (Baker et al., 2004 Cecchetti et al., 1996 Domalaga et al., 1993 Ellsworth et al., 2005a,b Hu et al., 2003). In this event, the carboxylic acid was allowed to react with boron trifluoride to deliver difluroboronate 70 in excellent yield. The thus afforded borate ester reacted with A -methylpiperidine in DMSO in the presence of triethylamine at ambient temperature to furnish ( —)-ofloxacin (1, levofloxacin) in 56% yield. 

B NMR was used to quantify the concentrations of the various boron species in solution. Borate diesters exhibit signals distinct from those of borate esters, and both are distinct from unbound boron. Therefore, with knowledge of the solution pH — to partition the unbound boron signal into boric acid and the active borate anion — as well as total boron concentration, the actual species concentrations can be determined. 

Aryl halides of many different types, including simple unsubstituted halides, may be conveniently converted into phenols by an indirect route involving the preparation of an arylboronic acid and its subsequent oxidation with hydrogen peroxide. The arylboronic acid (3) is normally prepared by reaction of the corresponding arylmagnesium halide with a borate ester (typically tributyl borate) at between —60 and — 80 °C, to yield the dialkyl boronate ester (2) which is then hydrolysed to the arylboronic acid (3). The latter may be isolated, purified and then oxidised with hydrogen peroxide as described in the preparation of m-cresol (Expt 6.101). Alternatively the crude reaction mixture from the preparation of (3) may be treated directly with hydrogen peroxide.36... 

Recently, highly functionalized allyl boronates such as 150 were synthesized from allylic acetates 148 and pinacolatodiboron 149. These boronates were employed for the allylation of aldehydes, furnishing the borate esters 151 which undergo lactonization to furnish the a-methylene-7-butyrolactones in high yield and selectivity. The strength of Lewis acids as well as the substituents on the aromatic aldehydes have a profound influence on the stereochemical outcome of the reaction (Scheme 25) <20040L481>. 

Addition of a wide range of boronic acids [RB(OH)2] or esters [RB(OR )2] to the pinanediols gives the very stable pinanediol boronic esters. For example, propylboronic acid (available from the addition of propylmagnesium bromide to trimethyl borate followed by acid hydrolysis) and the (s) pinanediol combine to give a homochiral boronic ester as shown in Equation B6.3. 

Myers et al. reported that partially dehydrated APB is an effective intumescent flame retardant in thermoplastic polyurethane.77 APB at 5-10 phr loading in TPU can provide 7- to 10-fold improvement in burn-through test. It is believed that in the temperature range of 230°C-450°C, the dehydrated APB and its released boric oxide/boric acid may react with the diol and/or isocyanate, the decomposed fragments from TPU, to produce a highly cross-linked borate ester and possibly boron-nitrogen polymer that can reduce the rate of formation of flammable volatiles and result in intumescent char. 

Ebelman and Bouquet prepared the first examples of boric acid esters in 1846 from boron trichloride and alcohols. Literature reviews of this subject are available. B The general class of boric acid esters includes the more common orthoboric acid based trialkoxy- and triaryloxyboranes, B(0R)3 (1), and also the cyclic boroxins, (ROBO)3, which are based on metaboric acid (2). The boranes can be simple trialkoxyboranes, cyclic diol derivatives, or more complex trigonal and tetrahedral derivatives of polyhydric alcohols. Nomenclature is confusing in boric acid ester chemistry. Many trialkoxy- and triaryloxyboranes such as methyl, ethyl, and phenyl are commonly referred to simply as methyl, ethyl, and phenyl borates. The lUPAC boron nomenclature committee has recommended the use of trialkoxy- and triaryloxyboranes for these compounds, but they are referred to in the literature as boric acid esters, trialkoxy and triaryloxy borates, trialkyl and triaryl borates or orthoborates, and boron alkoxides and aryloxides. The lUPAC nomenclature will be used in this review except for relatively common compounds such as methyl borate. Boroxins are also referred to as metaborates and more commonly as boroxines. Boroxin is preferred by the lUPAC nomenclature committee and will be used in this review. 

However, the application of these classical procedures for 1-alkenylboronic acid or ester synthesis may suffer from the formation of small amounts of the opposite stereoisomers, or from bis-alkenylation leading to the boronic acid derivatives. Also, formation of trialkylboranes may occur. A recent useful variant utilizes organolithium reagents and triisopropyl borate, followed by acidification with HCl to give directly alkyl-, aryl-, 1-alkynyl-, and 1-alkenylboronic esters in high yields, often over 90% (Scheme 2-6) [27]. Triisopropyl borate was shown to be the best of the available alkyl borates to avoid multiple alkylation of the borates. 

The first two and last two steps for the catalytic cycle of Suzuki cross-coupling are much the same as those for the Stille reaction (Scheme 12.18) the transmeta-lation step, however, is unique. Transmetalation involves transfer of R to Pd from a borane, borate ester, or boronic acid. Both recent experimental investigations and analysis using DFT calculations indicate that transmetalation is not simply a concerted process as suggested by transition state structure 38. 

The metaboric acid is fed to the oxidation train continuously and the mole ratio of boron added to O2 utilized is kept in the 0.65 to 1 range. The primary role of the metaboric acid is to esterify the cyclohexanol, thereby preventing selectivity robbing overoxidation. The boric acid also serves to catalyze the de-peroxidation of the cyclohexylhydroperoxide to cyclohexanol in high yield (-95%) at the expense of other uncatalyzed decomposition products such as cyclohexanone. This effect arises from the ability of the boron compound to reduce the intermediate hydroperoxide to the corresponding cyclohexyl borate ester, dioxygen, and water (Scheme l)M... 

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