Methylboronic acid

Trimethyl boroxine [823-96-1] M 125.5, b 80"/742mm, 79.3"/755mm, d 0.902. Possible impurity is methylboronic acid. If present then add a few drops of cone H2SO4 and distil immediately, then... 

This observation has led to the preparation of more effective bicyclic oxaza-borolidines such as 1, prepared from (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine and BH3 (la) or methylboronic acid (lb). Both reagents catalyze borane reduction of alkyl aryl ketones to furnish (R)-alcohols in > 95% ee, by face-selective hydride transfer within a complex such as B. Catalyst lb is somewhat more effective than... 

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.)... 

For assaying the enantiomeric purity of dilevalol in the DBTA salt, the Schering Research Analytical Department worked out an efficient glc procedure, utilizing methylboronic acid. Although the method did not separate RR and SS enantiomers or RS and SR enantiomers, it served to quickly indicate the efficiency of the resolution process since no racemization of the R-amine moiety was ever found. A typical glc trace was as follows ... 

The methods reported for the preparation of the oxazaborolidine include the reaction of diphenylprolinol with methylboronic acid 1) in toluene at 23°C for 1.5 hr with 4 A molecular sieves present and 2) in toluene at reflux for 3 hr using a Dean-Stark trap, bolh followed by evaporation of solvent and molecular distillation (0.1 mm, 170°C).5( An alternate method involved heating a toluene solution of 2-naphthylprolinol and methylboronic acid at reflux for 10 hr using a Soxhlet extractor containing 4 A molecular sieves.5 These methods afforded erratic results. The submitters therefore developed an alternate synthesis. 

Although the reaction of alkylboronic acids is significantly slower than that of trialkylboranes, methylboroxine (MeBO)3 or methylboronic acid exceptionally alkylates bromo- and chloroarenes [125, 126]. Methylation of electron-poor bromoarenes was efficient, whereas prolonged reaction time was required for more electron-rich substrates. The reaction times can be shortened by use of the polar solvent DMF at 115 °C. B-Methyl-9-BBN and its oxy-derivative (48) [127] undergo methylation of aryl and vinyl halides under more mild conditions (Scheme 22). 

Problems with the preparation and stability of oxazaborolidine (6) led to the development of a series of B-substituted ox-azaborolidines derived from diphenylprolinol. The B-methyl substituted oxazaborolidine (9a) was first prepared (eq 5) by reaction of diphenylprolinol (1) with methylboronic acid under dehydrating conditions (toluene at 23 °C in the presence of 4 X molecular sieves or toluene at reflux using a Dean-Stark trap) followed by vacuum distillation (0.1 mmHg, 170°C). Based on NMR evidence, the product (mp 74-87 °C) was reported to be a mixture of monomer and dimer. The corresponding B-butyloxazaborolidine (9c), prepared in a similar manner from n-butylboronic acid, was also reported to be a mixture of monomer and dimer. Subsequent investigations demonstrated that the reported dimers were in fact the intermediate (8) and the more stable disproportionation product (10) (eq 6). Furthermore, the presence of (8) or (10) was demonstrated to be deleterious to the enantioselectivity of the catalyst. ... 

Both non-capped and tin-capped products were cross-linked with an excess of the boric and methylboronic acids to form the corresponding semiclathrochelate [TcD(HD)2(BR2)] cations [89, 90],... 

Preparation. This compound was prepared initially in 12% yield by dehydration of methylboronic acid synthesized from trimethyl borate and methylmagnesium halide. Then Rathke and Brown found a practical preparative method in the reaction of... 

Aryl and 6-methyl-2-(4-fluorophenyl)imidazo[l,2-Z ]pyridazines (87) were obtained from 6-chloro-2-(4-fluoroplienyl)imidazo[l,2-Z ]pyridazine (86) via Suzuki coupling with methylboronic acid and arylboronic acids, respectively [53]. Best yields were obtained with sodium hydroxide as the base in coupling reactions of 86 with arylboronic acids, whereas yields decreased as the strength of the base increased (Na2CO3 (27%), NaOH (19%), Ba(OH)2 (11%)) in the reaction with methylboronic acid. 

A more-efficient method for asymmetric reduction uses the chiral inducing agent as a catalyst. A suitable system involves the oxazaborolidine 111, which can be prepared from the corresponding amino-alcohol and methylboronic acid, or is available commercially in either enantiomeric form Addition of borane to this... 

To make the CBS heterocycle, (5)-proline has to be protected as its N-Cbz derivative (Chapter 23) and converted to its methyl ester. Esters react with Grignard twice to give tertiary alcohols (Chapter 10), so PhMgBr followed by deprotection gives the amino alcohol needed. Condensation with methylboronic acid (MeB(0H)2) gives the stable catalyst. 

Boron Reagents. The Suzuki coupling with methylboronic acid and 2-chloro-3-nitropyridine gives the 2-methyl product 249 (Scheme 91) in high yield. 3-Amino-2-chloropyridine reacts less readily and 2-chloropyridine failed to react. 

Further studies by Yu and coworkers [62] were devoted to the search for more efficient directing groups. Thus, simple benzoic acids could be ortho-methylated with methylboronic acid in 63-75% yield. Subsequently, a broader scope and milder conditions were found for the alkylation of the more challenging C(sp )-H bonds [63] by using 0-methyl hydroxamic adds, which are stronger directing groups than carboxyUc adds and easily functionalizable (Scheme 19.41) [64]. 

The use of oxidant such as molecular oxygen [60] or di-terf-bntylperoxide [61] with catalytic amount of copper led to eliminate the use of base in the boronic acid oxidative coupling (Scheme 20.28). Fu and coworkers used atmospheric oxygen as oxidant with Cu O for the selective synthesis of primary amines at room temperature using aqueous ammonia as an amine source [62]. Yamamoto and coworkers developed air- and water-stable cyclic triolborate complex to increase the nucleophilicity of the attached group in boronic acid derivative [63]. Copper-mediated selective coupling of methylboronic acids with primary amines has been subsequently developed [64]. 

Methylboronic acid, IOC I. 9CI. Methylboric acid. Methaneboric acid. Methyldihydroxyborane [13061-96-6]... 

A -Methylbis(trifluoroacetamide), in B-00461 Methylboric acid, see D-00649 Methylboronic acid, see D-00649... 

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