Dicyclohexylborane1

[1568-65-6]  · C12H23B  · Dicyclohexylborane  · (MW 178.12)

(reagent for the reduction of ketones2 and a,b-unsaturated ketones;3 used for the hydroboration of alkynes, alkenes, and allenes4)

Physical Data: mp 103-105 °C.

Solubility: sol THF, diethyl ether, dichloromethane, pentane.

Analysis of Reagent Purity: a method to determine reagent purity by hydrogen gas evolution is available.26

Preparative Methods: is a stable white solid available via the hydroboration of cyclohexene with either Borane-Tetrahydrofuran or Borane-Dimethyl Sulfide.5 Recently, dicyclohexylborane has been prepared via the hydroboration of cyclohexene with borane-1,4-thioxane.6

Purification: may be purified by sublimation under vacuum.5a

Handling, Storage, and Precautions: must be used immediately upon generation or stored as a solid under dry nitrogen.7 Use in a fume hood.

Reduction of Ketones and a,b-Unsaturated Ketones.

Dicyclohexylborane has proven to be a useful reagent for the stereoselective reduction of cyclic, bicyclic, and polycyclic ketones.2 In reductions of substituted cyclic ketones this reagent often displays stereoselectivities that are opposite to those observed for the hydride reagents. For example, the reduction of 2-methylcyclohexanone with dicyclohexylborane in THF yields predominantly the cis diastereomer, while the reduction with Lithium Aluminum Hydride in THF leads to preferential formation of the trans diastereomer (eq 1).

Dicyclohexylborane has also been used to obtain (Z)-vinyloxyboranes via the conjugate reduction of (E)-a,b-unsaturated ketones (eq 2). Treatment of the hydroboration mixture with aldehydes has allowed the preparation of stereochemically pure syn aldols in good yields.3 Similar reactivity has also been demonstrated with catecholborane.8

Hydroboration of Alkenes and Allenes.

Dicyclohexylborane has found many applications in the hydroboration of alkenes. It may be used to advantage for the hydroboration of sterically hindered alkenes where other regioselective hydroborating agents (e.g. Disiamylborane and Diisopinocampheylborane) may suffer from significant amounts of retrohydroboration. In addition, dicyclohexylborane is less prone to isomerization than disiamylborane although the regioselectivity characteristics of the two reagents are comparable. The sterically encumbered nature of the reagent also allows for the possibility of selective hydroboration of different alkenes within the same molecule, although selective monohydroboration of conjugated dienes may be difficult.4a

The transformations of the trialkylborane products deriving from the hydroboration of alkenes have been extensively reviewed.1,4 The trialkylborane products may be converted to alkenes, alkyl halides, alcohols, amines, aldehydes, ketones, and carboxylic acids. Trialkylboranes readily undergo isomerization at elevated temperatures, thus making it possible to isomerize an internal alkene to a terminal one.1,4,9 Brown has extensively studied and optimized conditions for the hydroboration of vinyl and propenyl heterocycles with dicyclohexylborane as well as other representative hydroborating reagents.10 Although dicyclohexylborane has not seen the widespread use that other hydroborating reagents have, virtually all of the transformations described for trialkylboranes may be adapted to trialkylboranes derived from hydroboration of alkenes with this reagent; this is particularly useful if a highly discriminating hydroboration reagent is desired. Some of its recent applications for the hydroboration of alkenes and allenes are outlined below.

A synthesis of carboxylic acids via the hydroboration of terminal alkenes has recently been developed (eq 3).11 Several hydroborating reagents were evaluated for this transformation and it was determined that dicyclohexylborane and thexylborane are the reagents of choice.

Dicyclohexylborane has shown useful levels of diastereoselection in the hydroboration of steroidal alkenes (eq 4).2b Several hydroborating reagents were studied, including Thexylborane, 9-Borabicyclo[3.3.1]nonane, disiamylborane, and Borane-Dimethyl Sulfide. Only the sterically hindered bis(trans-2-methylcyclohexyl)borane proved to be superior to dicyclohexylborane in this application.

Allenes have also been used as substrates in reactions mediated by dicyclohexylborane.12 The types of hydroboration products obtained in these reactions have been found to depend upon the type of allene employed. For example, internal allenes yield preferentially vinylborane products with dicyclohexylborane, whereas 9-BBN will result in preferential formation of allylboranes.12a Terminal allenes give rise to allylborane products.12a

Hydroboration of Alkynes.

Dicyclohexylborane is an extremely useful reagent for the hydroboration of alkynes. The transformations of the resulting vinylboranes have been reviewed.1,4 Both terminal and internal alkynes react readily with dicyclohexylborane to provide the corresponding vinylborane. Dihydroboration, which is often a problem with reagents such as 9-BBN, is kept to a minimum even with excess reagent.13 Conjugated diynes may be monohydroborated with dicyclohexylborane.14 In addition, it is possible to selectively reduce an alkyne in the presence of an alkene,14,15 and hydroboration of alkynes in the presence of other functional groups is possible.16

Alkyl group transfer reactions of vinylborane intermediates have proven to be of enormous value in organic synthesis. Perhaps the most well known of these transformations is the Zweifel cis-alkene synthesis.17 Treatment of the dialkylborane adduct with Sodium Hydroxide and Iodine results in the transfer of an alkyl group and the formation of the cis-alkene (eq 5).

The capacity of alkyl groups to migrate from boron ate complexes have made possible the stereoselective synthesis of several additional alkene derivatives from vinylboranes.1,4 In addition, methods have been developed for the coupling of alkenyldialkylboranes via alkenylcopper intermediates which leads to the stereoselective production of (E,E)-18 and (Z,Z)-1,3-dienes19 as well as 1,4-dienes (eq 6).20

Several recent applications of dicyclohexylborane for the hydroboration of alkynes have been reported. The alkenyldialkylborane intermediates have been converted into 2-alkylbuta-1,3-dienes,21 (E)-1-alkenylboronic esters,22 a,b-unsaturated nitriles,23 and (Z)-1-halo-1-alkenes.24 Several additional hydroboration applications have been reported.25


1. (a) Pelter, A.; Smith, K.; Brown, H. C. Borane Reagents; Academic: New York, 1988. (b) Brown, H. C. Organic Synthesis via Boranes; Wiley; New York, 1975. (c) Brown, H. C.; Zaidlewicz, M.; Negishi, E. In Comprehensive Organometallic Chemistry; Wilkinson, G.; Stone, F. G. A.; Abel, E. W., Eds.; Pergamon: Oxford, 1982; Vol. 7, Chapters 45.1-45.7.
2. (a) Brown, H. C.; Varma, V. JOC 1974, 39, 1631. (b) Midland, M. M.; Kwon, Y. C. JACS 1983, 105, 3725.
3. (a) Boldrini, G. P.; Bortolotti, M.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. TL 1991, 32, 1229. (b) Boldrini, G. P.; Mancini, F.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. CC 1990, 1680.
4. (a) COS 1991, 8, 703. (b) Suzuki, A.; Dhillon, R. S. Top. Curr. Chem. 1986, 130, 23.
5. (a) Brown, H. C.; Desai, M. C.; Jadhav, P. K. JOC 1982, 47, 5065. (b) Pelter, A.; Hutchings, M. G.; Rowe, K.; Smith K. JCS(P1) 1975, 138. (c) Zweifel, G.; Ayyangar, N. R.; Brown, H. C. JACS 1963, 85, 2072.
6. Brown, H. C.; Mandal A. K. JOC 1992, 57, 4970.
7. Pelter, A.; Smith, K. In Comprehensive Organic Chemistry; Barton, D. H. R.; Ollis, W. D., Eds.; Pergamon: Oxford; 1979, Vol. 3, part 14, p 689.
8. (a) Evans, D. A.; Fu, G. C. JOC 1990, 55, 5678. (b) Matsumoto, Y.; Hayashi, T. SL 1991, 349.
9. Brown, H. C.; Racherla, U. S.; Taniguchi, H. JOC 1981, 46, 4314.
10. (a) Brown, H. C.; Vara Prasad, J. V. N.; Zee, S.-H. JOC 1985, 50, 1582. (b) Brown, H. C.; Vara Prasad, J. V. N.; Zee, S.-H. JOC 1986, 51, 439.
11. (a) Brown, H. C.; Kulkarni, S. V.; Khanna, V. V.; Patil, V. D.; Racherla, U. S. JOC 1992, 57, 6173. (b) Racherla, U. S.; Khanna, V. V.; Brown, H. C. TL 1992, 33, 1037.
12. (a) Brown, H. C.; Liotta, R.; Kramer, G. W. JACS 1979, 101, 2966. (b) Gu, Y. G.; Wang, K. K. TL 1991, 32, 3029.
13. (a) Brown, H. C.; Zweifel, G. W. JACS 1961, 83, 3834. (b) Zweifel, G.; Arzoumanian, H. JACS 1967, 89, 291. (c) Brown, H. C.; Chandrasekharan, J. JACS 1984, 106, 1863.
14. Zweifel, G.; Polston, N. L. JACS 1970, 92, 4068.
15. Clark, G. M.; Hancock, K. G.; Zweifel, G. JACS 1971, 93, 1308.
16. (a) Zweifel, G.; Arzoumanian, H. JACS 1967, 89, 5086. (b) Zweifel, G.; Horng, A.; Snow, J. T. JACS 1970, 92, 1427. (c) Zweifel, G.; Horng, A.; Plamondon, J. E. JACS 1974, 96, 316.
17. (a) Zweifel, G.; Arzoumanian, H.; Whitney, C. C. JACS 1967, 89, 3652. (b) Zweifel, G.; Clark, G. M.; Polston, N. L. JACS 1971, 93, 3395.
18. Yamamoto, Y.; Yatagai, H.; Maruyama, K.; Sonoda, A.; Murahashi, S.-I. JACS 1977, 99, 5652.
19. Campbell, Jr., J. B.; Brown, H. C. JOC 1980, 45, 549.
20. Brown, H. C.; Campbell Jr., J. B. JOC 1980, 45, 550.
21. Arase, A.; Hoshi, M. CC 1987, 531.
22. Hoffmann, R. W.; Dresely, S. S 1988, 103.
23. Masuda, Y.; Hoshi, M.; Arase, A. CC 1991, 748.
24. Brown, H. C.; Blue, C. D.; Nelson, D. J.; Bhat, N. G. JOC 1989, 54, 6064.
25. (a) Stracker, E. C.; Leong, W.; Miller, J. A.; Shoup, T. M.; Zweifel, G. TL 1989, 30, 6487. (b) Zweifel, G.; Najafi, M. R.; Rajagopalan, S. TL 1988, 29, 1895.
26. Quantitative Analysis of Active Boron Hydrides; Aldrich: Milwaukee, WI, USA.

Michael S. VanNieuwenhze

The Scripps Research Institute, La Jolla, CA, USA



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