Catecholborane1

[274-07-7]  · C6H5BO2  · Catecholborane  · (MW 119.92)

(reducing agent for several functional groups;2 used to prepare alkyl- and alkenylboronic acids and esters via hydroboration of alkenes and alkynes;3 can be used for synthesis of amides and macrocyclic lactams from carboxylic acids4)

Physical Data: mp 12 °C; bp 50 °C/50 mmHg; d 1.125 g cm-3.

Solubility: sol diethyl ether, THF, CH2Cl2, CHCl3, CCl4, toluene, and benzene; reacts readily with water and other protic solvents.

Form Supplied in: available as a colorless liquid; 1.0 M solution in THF.

Analysis of Reagent Purity: the technical bulletin Quantitative Analysis of Active Boron Hydrides, available upon request from the Aldrich Chemical Company, Milwaukee, WI, USA, describes methodology to determine reagent purity by hydrogen gas evolution.

Purification: the neat reagent may be purified by distillation at reduced pressure.

Handling, Storage, and Precautions: should be stored in a cold room or refrigerator, without exposure to atmospheric moisture; cold storage has been found to minimize loss of hydrogen activity as well as pressure build-up; the neat reagent may be stored as a solid at 0 °C; a sample stored over one year at 0-5 °C showed no detectable loss in hydride activity;1a syringe and double-tipped needle techniques are recommended for reagent transfer. Use in a fume hood.

Functional Group Reductions.

Catecholborane (CB) is one of the most versatile boron hydride reducing agents. This reagent possesses enhanced thermal stability and solubility characteristics as compared with other boron hydride reagents. Reductions can be carried out in several organic solvents including CCl4, CHCl3, benzene, toluene, diethyl ether, and THF, as well as in the absence of solvent.1a

Several functional groups do not react with catecholborane. Alkyl and aryl halides, nitro groups, sulfones, disulfides, thiols, primary amides, ethers, sulfides and alcohols are all inert toward the reagent. Nitriles, esters, and acid chlorides react slowly, while aldehydes, ketones, imines, and sulfoxides are readily reduced in a few hours at room temperature.1a

Catecholborane readily reduces tosylhydrazones2 to the corresponding methylene derivatives (eqs 1 and 2). This mild method may be used to advantage with substrates possessing sensitive functional groups which preclude the use of the more conventional Wolff-Kishner and Clemmensen reductions.5

Evans6a has demonstrated that catecholborane will undergo conjugate reduction of a,b-unsaturated ketones at room temperature (eqs 3 and 4).6,7 This reaction is limited to a,b-unsaturated ketones that can adopt an s-cis conformation, while a,b-unsaturated imides, esters, and amides are unreactive under these conditions. It was also determined that catalytic quantities of Chlorotris(triphenylphosphine)rhodium(I) greatly accelerate the 1,4-addition process such that reduction occurs readily at -20 °C.

Cyclic enones bearing an endocyclic alkene, e.g. (1) and (2), do not undergo 1,4-addition but are instead reduced exclusively at the carbonyl group. It is also possible to selectively reduce trans-1,2-disubstituted enones in the presence of 1,1-disubstituted systems. The trapping of the intermediate boron enolate by aldehyde electrophiles has also been demonstrated.6

Several diastereoselective and enantioselective reductions of ketones mediated by catecholborane have also been reported. Acyclic b-hydroxy ketones are stereoselectively reduced to syn 1,3-diols by catecholborane (eq 5).8 In several instances it was found that stereoselectivity could be enhanced by performing the reaction with RhI catalysis. The high levels of diastereoselectivity are believed to be due to the ability of catecholborane to preorganize the substrate prior to intermolecular delivery of hydride by a second molecule of catecholborane. The incorporation of a methyl group between the hydroxyl and carbonyl groups can affect the syn diastereoselectivity, the extent depending upon the stereochemical relationship between the two substituents (eqs 6 and 7).

Chiral oxazaborolidines, initially reported by Itsuno9 and later developed by Corey,10 have been used for the enantioselective reduction of ketones. Corey has demonstrated that oxazaborolidine (3), prepared from a,a-Diphenyl-2-pyrrolidinemethanol and butylboronic acid, is a highly effective catalyst for the asymmetric reduction of ketones using catecholborane as a stoichiometric reductant. This system was also shown to be superior for the asymmetric 1,2-reduction of enones.

Hydroboration of Alkenes.

Hydroborations of alkenes by catecholborane3 are generally much slower than those employing dialkylboranes.11 Elevated temperatures are usually required; however, the reaction rates may be enhanced by the use of Wilkinson's catalyst,12 N,N-dimethylaniline-borane,13 and Lithium Borohydride.14 The alkylboronic esters obtained are easily hydrolyzed to the corresponding alkylboronic acids or converted to aldehydes,15 ketones,16 carboxylic acids,17 and alcohols.3e,8 The esters may also be homologated, thus making possible the synthesis of substituted boronic esters, which have become increasingly useful as reagents for stereodirected synthesis.18

Catecholborane has been widely used for the transition metal catalyzed hydroborations of alkenes.12,19 Both RhI and IrI have been used as the metal catalyst. Catalysis not only has a beneficial effect on rate, but has also been found to alter the chemo-, regio- and stereochemical course of the hydroboration when compared to the uncatalyzed reaction.19

Evans has established that the rate of the transition metal catalyzed hydroboration is very sensitive to the alkene substitution pattern.20,21 Terminal alkenes undergo complete hydroboration within minutes at room temperature, while 1,1- and 1,2-disubstituted alkenes require several hours. Trisubstituted alkenes are unreactive. The sensitivity of the catalyzed reaction to steric effects affords the possibility for selective hydroboration of the less hindered of two alkenyl groups in a given substrate (eq 8).20

Good to excellent levels of 1,2-asymmetric induction are obtained in the catalyzed hydroboration of chiral 1,1-disubstituted alkenes with catecholborane (eq 9). The extent of asymmetric induction has been found to depend on the size of X and, to a lesser extent, the size of RŽ. The catalyzed and uncatalyzed reactions are stereocomplementary, with the former favoring the formation of products with syn stereochemistry while the latter favors products with anti stereochemistry.20,22 Allylic and homoallylic diphenyl phosphinite and amide functional groups have also been used to direct the regiochemistry of the catalyzed hydroboration reaction. Examples of this methodology with both cyclic and acyclic substrates have been reported.20,23

Several groups have reported catalyst systems for the asymmetric hydroboration of prochiral alkenes using the catalyzed hydroboration reaction with a chirally modified metal catalyst.24 Most of the reactions employ a RhI catalyst modified with chirally modified bidentate phosphine ligands. Enantiomeric excesses obtained with several alkene substrates are in the good to excellent range.24b,f

Hydroboration of Alkynes.

The hydroboration of alkynes with catecholborane is an efficient route to alkenylboronic esters and acids. The regioselectivity of the addition to unsymmetrical alkenes is very similar to that displayed by Disiamylborane.3c-e The rate of reaction can be enhanced through use of N,N-dimethylaniline-borane complex.13

The alkenylboronic esters and acids obtained have proven to be valuable synthetic intermediates. Perhaps the most widespread use of these intermediates has been in the Pd0 catalyzed cross-coupling reaction with alkenyl, alkynyl, and aryl halides to give the corresponding alkenes (eq 10).25

Protonolysis of alkenylboronic esters deriving from internal alkynes provides a route for the stereospecific synthesis of cis-disubstituted alkenes, while an oxidative workup will afford the corresponding ketone.3d,e Iodo- and bromoalkenes can also be prepared stereospecifically from alkenylboronic ester intermediates.26 These compounds are useful in alkene cross-coupling reactions as well as in the preparation of alkenylmagnesium and alkenyllithium compounds. Haloalkenes may also be prepared from alkenylboronic acids via organomercurial intermediates (eq 11).27

Reagent for Amide and Lactam Synthesis.

Carboxylic acids react rapidly with catecholborane to produce 2-acyloxy-1,3,2-benzodioxaborolanes, e.g. (4). This reaction has been used as the carboxyl activation step for the synthesis of amides and macrocyclic lactams (eq 12).4

Related Reagents.

Bis(benzoyloxy)borane; Disiamylborane.


1. (a) Lane, C. F.; Kabalka, G. W. T 1976, 32, 981. (b) Wietelmann, U. Janssen Chim. Acta 1992, 10, 16. (c) Pelter, A.; Smith, K.; Brown, H. C. Borane Reagents; Academic Press: New York, 1988. (d) Brown, H. C. Organic Synthesis via Boranes; Wiley: New York, 1975. (e) Brown, H. C.; Chandrasekharan, J. JOC 1983, 48, 5080. (f) Kabalka, G. W. OPP 1977, 9, 131.
2. Kabalka, G. W.; Baker, J. D., Jr. JOC 1975, 40, 1834.
3. (a) COS 1991, 8, Chapter 3.10, p 703. (b) Suzuki, A.; Dhillon, R. S. Top. Curr. Chem. 1986, 130, 23. (c) Brown, H. C.; Gupta, S. K. JACS 1971, 93, 1816. (d) Brown, H. C.; Gupta, S. K. JACS 1972, 94, 4370. (e) Brown, H. C.; Gupta, S. K. JACS 1975, 97, 5249.
4. Collum, D. B.; Shen, S.-C.; Ganem, B. JOC 1978, 43, 4393.
5. COS 1991, 8, Chapter 1.13-1.14, pp 307 and 327.
6. (a) Evans, D. A.; Fu, G. C. JOC 1990, 55, 5678. (b) Matsumoto, Y.; Hayashi, T. SL 1991, 349.
7. Other methods: (a) COS 1991, 8, Chapter 3.5, p 503 (b) Larock, R. C. Comprehensive Organic Transformations; VCH: New York, 1989, pp 8-17.
8. Evans, D. A.; Hoveyda, A. H. JOC 1990, 55, 5190.
9. (a) Hirao, A.; Itsuno, S.; Nakahama, S.; Yamazaki, N. CC 1981, 315. (b) Itsuno, S.; Hirao, A.; Nakahama, S.; Yamazaki, N. JCS(P1) 1983, 1673. (c) Itsuno, S.; Ito, K.; Hirao, A, Nakahama, S. CC 1983, 469. (d) Itsuno, S.; Ito, K.; Hirao, A, Nakahama, S. JOC 1984, 49, 555. (e) Itsuno, S.; Nakano, M.; Miyazaki, K.; Masuda, H.; Ito, K.; Hirao, A.; Nakahama, S. JCS(P1) 1985, 2039. (f) Itsuno, S.; Ito, K.; Maruyama, T.; Kanda, N.; Hirao, A.; Nakahama, S. BCJ 1986, 59, 3329.
10. (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. JACS 1987, 109, 5551. (b) Corey, E. J.; Bakshi, R. K.; Shibata, S.; Chen, C.-P.; Singh, V. K. JACS 1987, 109, 7925. (c) Corey, E. J.; Shibata, S.; Bakshi, R. K. JOC 1988, 53, 2861. (d) Corey, E. J.; Jardine, P. D. S.; Rohloff, J. C. JACS 1988, 110, 3672. (e) Corey, E. J.; Gavai, A. V. TL 1988, 29, 3201. (f) Corey, E. J.; Bakshi, R. K. TL 1990, 31, 611.
11. (a) Fish, R. H. JOC 1973, 38, 158. (b) See also ref. 1e.
12. Männig, D.; Nöth, H. AG(E) 1985, 24, 878.
13. Suseela, Y.; Prasad, A. S. B.; Periasamy, M. CC 1990, 446.
14. Arase, A.; Nunokawa, Y.; Masuda, Y.; Hoshi, M. CC 1991, 205.
15. Brown, H. C.; Imai, T. JACS 1983, 105, 6285.
16. Brown, H. C.; Srebnik, M.; Bakshi, R. K.; Cole, T. E. JACS 1987, 109, 5420.
17. Brown, H. C.; Imai, T.; Desai, M. C.; Singaram, B. JACS 1985, 107, 4980.
18. Matteson, D. S. T 1989, 45, 1859.
19. Burgess, K.; Ohlmeyer, M. J. CRV 1991, 91, 1179.
20. Evans, D. A.; Fu, G. C.; Hoveyda, A. H. JACS, 1992, 114, 6671.
21. Mechanistic studies: (a) Evans, D. A.; Fu, G. C.; Anderson, B. A. JACS 1992, 114, 6679. (b) Burgess, K.; van der Donk, W. A.; Westcott, S. A.; Marder, T. B.; Baker, R. T.; Calabrese, J. C. JACS 1992, 114, 9350.
22. (a) Burgess, K.; Ohlmeyer, M. J. TL 1989, 30, 395. (b) Burgess, K.; Ohlmeyer, M. J. JOC 1991, 56, 1027.
23. Evans, D. A.; Fu, G. C.; Hoveyda, A. H. JACS 1988, 110, 6917.
24. (a) Burgess, K.; Ohlmeyer, M. J. JOC 1988, 53, 5178. (b) Hayashi, T.; Matsumoto, Y.; Ito, Y. JACS 1989, 111, 3426. (c) Sato, M.; Miyaura, N.; Suzuki, A. TL 1990, 31, 231. (d) Burgess, K.; van der Donk, W.; Ohlmeyer, M. J. TA 1991, 2, 613. (e) Matsumoto, Y.; Hayashi, T. TL 1991, 32, 3387. (f) Hayashi, T.; Matsumoto, Y.; Ito, Y. TA 1991, 2, 601. (g) Burgess, K.; Ohlmeyer, M. J.; Whitmire, K. H. OM 1992, 11, 3588.
25. (a) Miyaura, N.; Yamada, K.; Suzuki, A. TL 1979, 20, 3437. (b) Miyaura, N.; Suginome, H.; Suzuki, A. TL 1981, 22, 127. (c) Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. JACS 1985, 107, 972. (d) Suzuki, A. PAC 1985, 57, 1749. (e) Suzuki, A. PAC 1991, 63, 419.
26. Brown, H. C.; Hamaoka, T.; Ravindran, N. JACS 1973, 95, 6456.
27. Brown, H. C.; Larock, R. C.; Gupta, S. K.; Rajagopalan, S.; Bhat, N. G. JOC 1989, 54, 6079.

Michael S. VanNieuwenhze

The Scripps Research Institute, La Jolla, CA, USA



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