[110-51-0]  · C5H8BN  · Borane-Pyridine  · (MW 92.93)

(mild reducing agent with greater hydrolytic stability than NaBH4 in protic solvents and higher solubility in aprotic organic solvents; in solution with a weak organic acid or complexed with Lewis acids it is useful for reductive aminations, reduction of carbonyls, heterocycles, tosylhydrazones, and oximes; in strong acid it converts aldehydes to symmetrical ethers; weak hydroborating agent)

Physical Data: mp 10-11 °C; bp (dec).

Solubility: very sol methanol, THF, toluene, dichloromethane; sol water, diethyl ether; insol hexane.1

Form Supplied in: viscous liquid.

Handling, Storage, and Precautions: hydrolytically stable in neutral aqueous solution. Excess reagent may be decomposed with dilute HCl.1 Use in a fume hood.

Reductive Amination.

Borane-pyridine in neutral or acidic solution is an inexpensive and less toxic alternative to Sodium Cyanoborohydride for the reductive amination of aldehydes and ketones.2 Side products in reductive aminations of aldehydes, related to the presence of cyanide in cyanoborohydride, may be avoided using borane-pyridine in ethanol.3 Borane-pyridine in acetic acid/toluene affords higher yields and product quality compared to Sodium Borohydride in the 3-aminofluoranthene tagging of aliphatic ketones and aldehydes.4 Due to its solubility in aqueous solvent, borane-pyridine is the reagent of choice for the reductive methylation of proteins with formaldehyde5 and is useful for the immobilization of proteins on oxidized agarose beads in neutral aqueous media.6

Carbonyl Reductions.

Borane-pyridine is less reactive than borane complexes of primary and secondary amines and in aprotic solvents generally affords lower stereo- and chemoselectivity.1,7a,7b However, reduction rates are accelerated by weak organic acids. For example, the chemoselective reduction of the 2-oxo moiety of 2,5-diketogluconic acid in aqueous solution at 0 °C affords a 92:8 mixture of 2-ketogulonic to 2-ketogluconic acids in 79% yield.7c Polymers of 2- and 4-vinylpyridine-borane complexed with Boron Trifluoride Etherate, or uncomplexed in acetic acid solution, exhibit enhanced reactivity and chemoselectivity in the reduction of aliphatic and aromatic ketones, enones, and aldehydes.8,9

Carbonyl Deoxygenation.

Borane-pyridine is effective for the reduction of tosylhydrazones of aryl carbonyl derivatives, affording the corresponding tosylhydrazines in 91-98% yields.10a This is a key feature in a procedure for the deoxygenation of aromatic ketone tosylhydrazones without the intermediate mercuration stage required for metal hydride reduction.10b

Other Functional Group Reductions.

Borane-pyridine in acetic acid reduces quinoline and indole at rt to 1,2,3,4-tetrahydroquinoline and indoline in 71 and 86% yields, respectively.1 The indole rings of protein tryptophan residues are reduced under these conditions.5 In ethanol/10% HCl solution, borane-pyridine converts aromatic and aliphatic oximes to hydroxylamines in the presence of ester, nitrile, nitro, amide and halide moieties.11a Its solubility in water facilitates the reduction of phosphorylacetaldehyde oximes to phosphorylhydroxylamines.11b Borane-pyridine in TFA reduces aliphatic and aromatic aldehydes to symmetric ethers in 55-87% yields. The reduction of aldehydes in alcohol produces unsymmetrical ethers. Aryl ketones are reduced directly to arenes, while dialkyl ketones are reduced to the corresponding alcohols.12a,12b Benzyl heptyl sulfide was obtained in 73% yield by the reduction of benzaldehyde with borane-pyridine/Aluminum Chloride in the presence of 1-heptanethiol in dichloromethane.12c

Borane-pyridine has also been used as a weak hydroborating agent, for the reductive hydrogenolysis of aryl halide and the reduction of ozonides.1

1. Hutchins, R. O.; Learn, K.; Nazer, B.; Pytlewski, D.; Pelter, A. OPP 1984, 16, 335.
2. Pelter, A.; Rosser, R. M.; Mills, S. JCS(P1) 1984, 717.
3. Moormann, A. E. SC 1993, 23, 789.
4. Mann, B.; Grayeski, M. L. J. Chromatogr. 1987, 386, 149.
5. Wong, W. S. D.; Osuga, D. T.; Feeney, R. E. Anal. Biochem. 1984, 139, 58.
6. Stults, N. L.; Asta, L. M.; Lee, Y.-C. Anal. Biochem. 1989, 180, 114.
7. (a) Andrews, G. C.; Crawford, T. C. TL 1980, 21, 693. (b) Andrews, G. C. TL 1980, 21, 697. (c) Andrews, G. C. U. S. Patent 4 212 988, 1980.
8. (a) Babler, J. H.; Sarussi, S. J. JOC 1983, 48, 4416. (b) Menger, F. M.; Shinozaki, H.; Lee, H.-C. JACS 1980, 45, 2724.
9. Domb, A.; Avny, Y. J. Macromol. Sci.-Chem. 1985, A22, 183.
10. Kikugawa, Y.; Kawase, M. SC 1979, 9, 49. (b) Rosini, G.; Medici, A. S 1976, 530.
11. (a) Kikugawa, Y.; Kawase, M. CL 1977, 1279. (b) Liorber, B. G.; Pavlov, V. A.; Hamatova, Z. M. ZOB 1989, 59, 2634.
12. (a) Kikugawa, Y. CL 1979, 415. (b) Kikugawa, Y.; Ogawa, Y. CPB 1979, 27, 2405. (c) Kikugawa, Y. Jpn. Patent 5 918 453, 1984.

Glenn C. Andrews

Pfizer Central Research, Groton, CT, USA

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