Boroxines boronic acids

Boronic acids readily dehydrate at moderate temperatures (or over P4O10 at room temperature) to give trimeric cyclic anhydrides known as trialkyl(aryl)boroxines ... 

Boronic acids (69 and 70) (Fig. 45) with more than one boronic acid functionality are known to form a polymer system on thermolysis through the elimination of water.93 Specifically, they form a boroxine (a boron ring system) glass that could lead to high char formation on burning. Tour and co-workers have reported the synthesis of several aromatic boronic acids and the preparation of their blends with acrylonitrile-butadiene-styrene (ABS) and polycarbonate (PC) resins. When the materials were tested for bum resistance using the UL-94 flame test, the bum times for the ABS samples were found to exceed 5 minutes, thereby showing unusual resistance to consumption by fire.94... 

Figure 45 Boronic acids (69 and 70) with multiple boronic acid functionalities that form boroxine ring systems on thermolysis through the elimination of water. (Adapted from ref. 93.)...

Cyclotriboroxanes (RBO)3 (also known as boroxines) are formally anhydrides of the corresponding boronic acids RB(OH)2 only mild heating is required to convert these dibasic acids into a wide range of cyclic trimeric anhydrides [eqn (9.18)]. This dehydration process can be adapted for the synthesis of B3O3 rings with different aryl groups on the boron atoms by using two or more arylboronic acids in the appropriate stoichiometric ratio. 

Boroxines result from the condensation of boronic acids. RBfOH). The cyclic Irimeric anhydride of methylboronic acid is (IVfeBO),. Give a balanced equation for the reaction of (MeBO)j with water (See Brown, H. C. Cole, T. E. Organometallics 1985.4. 816.)... 

Two different approaches can be followed to prepare and use the catalyst. The first is to prepare it in situ by mixing (R)- or (S)-diphenylprolinol (DPP) (4) and a borane complex (Scheme 16.2). This route is advantageous because there is no need to use boronic acids (or boroxines) and to remove water to form the catalyst. Another possible way is to use preformed catalysts, some of which are commercially available from suppliers such as Callery. 

The oxazaborolidine is finally made by heating diphenylprolinol (4) under reflux with a suitable alkyl(aryl)boronic acid or, better, with the corresponding boroxine in toluene in the presence of molecular sieves—the water can also be removed by azeotropic distillation. According to the literature, methyl-oxazaborolidine (Me-CBS) can be either distilled or recrystallized. The key point is that the catalyst must be free from any trace of water or alkyl(aryl)boronic acid because those impurities decrease enantioselection. 

A second peptide coupling employing 2-pyrazine carboxylic acid (24) and TBTU affords 25. Finally the boronic ester moiety is removed under acidic conditions using isobutyl boronic acid. This regenerates pinanediol boronic ester 16, which can be used in another batch run of the process. Crystallization from ethyl acetate gives bortezomib in its anhydride (boroxine) form 26. The overall yield for the route is 35% with a typical purity of > 99% w/w. 

Boronic acids readily undergo self-condensation to give cyclic anhydrides, and either these trisubstituted boroxins (11), or the acids themselves, react spontaneously, but not necessarily completely, in solution, with suitable diols, to give cyclic boronates 12 (see Scheme 1),... 

Heating boronic acids or treatment with P4Oi0 at room temperature results in loss of H20 to form boroxines, a much-studied class of cyclic organoboranes. 

Oxazaborolidines substituted at boron (1 R = alkyl, aryl) are prepared from a chiral p-amino alcohol and the corresponding boronic acid in a two-step process (eq S). Heat and an efficient method of water removal (i.e. azeotropic distillation, molecular sieves) are required to drive the second step. When R and R are connected, more forcing conditions are necessary, both to complete the second step and to prevent the intermediate from proceeding to an alternate disproportionation product. Alternative procedures using bis(diethylamino)-phenylborane (eq trisubstituted boroxines (eq 7), - and... 

The mechanism we have proposed to explain boronic acid-catalyzed amidation is depicted in Sch. 2. Arylboronic acid usually contains different amounts of cyclic tri-meric anhydrides (boroxines). The rate-determining step is the generation of ArB (OCOR)(OH). 

The amount of the boroxine significantly increases if the solid is left under reduced pressure for a longer period of time. The boroxine is always a contaminant of the boronic acid (see discussion). 

Organo derivatives of boroxine are much more stable than boroxine or its halo derivatives. They are formally anydrides of boronic acids, and most are prepared nearly quantitatively by dehydration of the corresponding acid ... 

Phenylboronic acid (17) and its derivatives are widely used. Boronic acids are sometimes difficult to purify because they undergo cyclotrimerizadon with loss of water to form boroxines. On the other hand, organotrifluoroborate salts 18 are easily prepared, purified, and handled [23]. Aryltrifluoroborate salts 18 are prepared by the reaction of arylboronic acid with HF and base [24]. Alkenyltrifluorobo-rates 19 are prepared by hydroboration of 1-alkynes, followed by treatment with KHF2 [25]. 

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