Dihydroxy(phenyl)borane1

PhB(OH)2

[98-80-6]  · C6H7BO2  · Dihydroxy(phenyl)borane  · (MW 121.93) (anhydride)

[3262-89-3]  · C18H15B3O3  · Dihydroxy(phenyl)borane Anhydride  · (MW 311.74)

(protective group for diols,1c template for C-C bond formation; phenylating agent;2 catalyst for hydroalumination;3 chromatography agent1c)

Alternate Name: phenylboric acid.

Physical Data: mp 216 °C (anhyd); dipole moment 1.72 D (dioxane); pKa 8.86 (25 °C, H2O).

Solubility: sol H2O 2.5%, benzene 1.75%, xylene 1.2%, ether 30.2%, methanol 178%.

Form Supplied in: white solid, widely available; contains varying amounts of the anhydride.

Preparative Method: from Phenylmagnesium Bromide and Trimethyl Borate.1d

Purification: crystallization from H2O.

Handling, Storage, and Precautions: readily forms trimeric anhydride upon standing or heating (eq 1); moderately toxic by ingestion; mildly toxic by skin contact.4

Reactions with Diols, Amino Alcohols, Diamines, Hydroxy Acids, and Catechols.1c

Most of the chemistry of dihydroxy(phenyl)borane (1) centers around its ready formation of cyclic boronate esters (eq 2). With diols the ease of formation follows the order n = 3 > 2 > 4. cis-Cycloalkene-1,2-diols readily form the cyclic boronates, whereas the trans-diols react with 2 equiv of (1) (eq 3) or form polymeric diesters. This latter feature has been used to separate cis/trans mixtures of polyols by distillation of the butylboronates or by crystallization of the phenylboronates. In the total synthesis of anthracyclines, the desired 7,9-cis-diol relationship was established by reaction of (1) with a cis/trans mixture of an early intermediate, which gave the cis-boronate exclusively (eq 4).5

Catalytic osmylation of alkenes in the presence of (1) immediately gives the cyclic boronates. In this way a bisboronate with host properties was prepared (eq 5).6

In alkaline aqueous solutions, (1) forms stable anionic adducts with diols (eq 6).7 A large variety of anionic ligands has been prepared through the condensation of (1) with 3 equiv of pyrazole under basic conditions.8

Azeotropic reflux is the most frequently used method of preparation of cyclic boronate esters; simple heating in polar solvents like acetone, pyridine, DMF, or even 2-methoxyethanol can be used with polar diols. Most cyclic boronates can be hydrolyzed easily by adding water to their solutions in organic solvents. In more reluctant cases, alkaline or acidic solutions or aqueous Hydrogen Peroxide have been used. In the latter case, (1) is concomitantly oxidized to phenol.9 If the use of water is precluded, exchange with Ethylene Glycol or more particularly 1,3-Propanediol followed by removal of the volatile adduct offers a useful alternative.

Protective Group.

Due to its easy attachment and removal, (1) is ideally suited as protective group for diols, particularly carbohydrates1c and nucleosides.10 The phenylboronate protective group is compatible with the following reaction types, mostly on hydroxy groups: acylation, sulfonation, methylation (Diazomethane-Boron Trifluoride), phosphorylation, tritylation, silylation, bromination (Bromoform-Triphenylphosphine), reaction with Phenyl Isocyanate, nucleophilic substitution, and Swern oxidation.1c

Chromatographic Separations.

Cyclic esters of polyols, amino alcohols, or catechols with either (1) or dihydroxy(butyl)borane have been used for gas chromatographic analysis, particularly for the measurement of drugs in biological fluids.1c,11 Addition of (1) to eluents for paper chromatography1c or TLC12 leads to a much increased separation of polyols that differ mainly in relative configuration but are very similar in polarity, such as carbohydrates and glycosides. An affinity gel or HPLC stationary phase suited for the separation of carbohydrates, glycosides, nucleosides, and enzymes can be prepared by covalent attachment of (1) to a solid support like agarose, polyacrylamide, polystyrene, or silica. Many of these are commercially available.13

Template for C-C Bond Formations.

Dihydroxy(phenyl)borane is ideally suited as a template, serving to facilitate and direct reactions between two oxygen-containing substrates. Hydroxyalkylation of phenols with aldehydes, in the presence of 1 equiv of (1), gave the ortho products exclusively via the cyclic boronate esters (eq 7).14 Pyrolysis of the same esters resulted in formation of ortho-quinone methides (2) which could be trapped in the usual way (eq 7).15 Condensation of (1) with benzoin gave the dioxaborole, which by virtue of its enforced cis configuration could be easily photocyclized (eq 8). The product gave 9,10-phenanthrenequinone upon hydrolysis with base in the presence of air.16 The dioxaboroles obtained from azeotropic reflux of acyloins and (1) undergo aldol condensation with aldehydes to give a,b-dihydroxy ketones after hydrolytic workup (eq 9).17 The parent compound polymerizes when treated with catalytic amounts of Zinc Chloride and a starter aldehyde (eq 10).18

Suzuki and Heck Reactions.

Cross-coupling reactions of (1) with Ar-X (X = Br, I, OTf) (eq 11),2 heteroaryl-X (X = Cl, Br, I, or OTf),19 and vinyl-X (X = Br,20 OTf21) are catalyzed by several Pd compounds in the presence of base. The reaction can be performed in two-phase or aqueous solvents.22 Because of the ready availability and stability of (1) this method has superseded earlier approaches using Grignard reagents and organostannanes. If the Suzuki reaction is performed in the presence of CO, diaryl ketones, biaryls, or arylcarboxylic acids may be obtained, depending on the conditions.23

Heck reactions of (1) with styrene (eq 12) and Acrylic Acid have been reported.24

Hydroalumination.

The hydroalumination of alkenes with Dichloroalane is catalyzed by (1) (eq 13).3

Asymmetric Synthesis.

Homologation of the boronate ester of (+)-pinanediol with Dichloromethyllithium, followed by alkylation with Methylmagnesium Bromide, proceeds with 97% diastereoselectivity (eq 14).25 The sequence was repeated and the product oxidized with NaBO3 to give (2S,3S)-3-phenyl-2-butanol in high optical purity. Treatment of several chiral boronate esters with Potassium Hydride gave chiral dialkoxymonoalkylborohydrides, which were used for the asymmetric reduction of ketones with moderate enantioselectivity.26


1. (a) Washburn, R. M.; Levens, E.; Albright, C. F.; Billig, F. A.; Cernak, C. S. Adv. Chem. Ser. 1959, 23, 102. (b) Washburn, R. M.; Billig, F. A.; Bloom, M.; Albright, C. F.; Levens, E. Adv. Chem. Ser. 1961, 32, 208. (c) Ferrier, R. J. Adv. Carbohydr. Chem. B 1978, 35, 31. (d) Washburn, R. M.; Levens, E.; Albright, C. F.; Billig, F. A. OSC 1963, 4, 68.
2. Miyaura, N.; Yanagi, T.; Suzuki, A. SC 1981, 11, 513.
3. Maruoka, K.; Sano, H.; Shinoda, K.; Nakai, S.; Yamamoto, H. JACS 1986, 108, 6036.
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6. Narasaka, K.; Sakurai, H.; Kato, T.; Iwasawa, N. CL 1990, 1271.
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13. For a compilation of references, see Pierce Handbook and Catalogue, available from the Pierce Chemical Co. (Rockford, IL, USA) or from Pierce Europe BV (Oud Beijerland, The Netherlands).
14. Nagata, W.; Okada, K.; Aoki, T. S 1979, 365.
15. Chambers, J. D.; Crawford, J.; Williams, H. W. R.; Dufresne, C.; Scheigetz, J.; Bernstein, M. A.; Lau, C. K. CJC 1992, 70, 1717.
16. de Vries, J. G.; Hubbard, S. A. CC 1988, 1172.
17. Mukaiyama, T.; Yamaguchi, M. CL 1982, 509.
18. Wulff, G.; Birnbrich, P.; Hansen, A. AG 1988, 100, 1197.
19. Kalinin, V. N. S 1992, 413.
20. Abe, S.; Miyaura, N.; Suzuki, A. BCJ 1992, 2863.
21. Yasuda, N.; Xavier, L.; Rieger, D. L.; Li, Y.; DeCamp, A. E.; Dolling, U.-H. TL 1993, 34, 3211.
22. Casalnuovo, A. L.; Calabrese, J. C. JACS 1990, 112, 4324.
23. Bumagin, N. A.; Nikitin, K. V.; Beletskaya, I. P. Dokl. Akad. Nauk SSSR 1991, 320, 619.
24. (a) Yatsimirskii, A. K. Kinet. Katal. 1982, 23, 366. (b) Nizova, G. V.; Lederer, P.; Shul'pin, G. B. Oxid. Commun. 1983, 4, 131.
25. Matteson, D. S.; Ray, R. JACS 1980, 102, 7590.
26. Brown, H. C.; Cho, B. T.; Park, W. S. JOC 1987, 52, 4020.

Johannes G. de Vries

DSM Research, Geleen, The Netherlands



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