Borane-Ammonia1

NH3.BH3

[13774-81-7]  · BH6N  · Borane-Ammonia  · (MW 30.86)

(strong chemo- and stereoselective, hydride-like reducing agent with greater hydrolytic stability than NaBH4 in protic solvents (including water) and higher solubility in aprotic organic solvents; useful for the reduction of carbonyls and carbon-nitrogen double bonds)

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

Form Supplied in: waxy solid; commercially available as 90% technical grade.

Handling, Storage, and Precautions: explodes when heated; use in a fume hood. Borane-ammonia thermally decomposes to aminoborane with the evolution of hydrogen.1 Heating the solid reagent presents an explosion hazard. BH3.NH3 is hygroscopic and undergoes slow degradation in the presence of moisture to ammonia and hydrogen gas. Bottles of ammonia borane should be stored in the cold, flushed with nitrogen, sealed to avoid contamination by atmospheric moisture and opened carefully due to potential pressure build-up. Because of its greater purity, indistinguishable reactivity and thermal and hydrolytic stability, the commercially available reagent borane-t-butylamine1 should be substituted for borane-ammonia whenever possible.

Carbonyl Reductions.

Borane-ammonia is a non-ionic dative complex with reducing properties equivalent to Sodium Borohydride. It is a mild reducing agent which is useful in a wide range of solvents (including water) at temperatures as low as -50 °C. Aliphatic and aromatic ketones, aldehydes, and enones are reduced, affording the corresponding alcohols in 65-97% isolated yields.1 It is capable of transferring all three hydride equivalents and excess reagent can conveniently be hydrolyzed by quenching with dilute HCl. Because of its being intermediate in reactivity between the electrophilic reagent borane and the nucleophilic hydride reagents, BH3.HN3 exhibits unique stereo- and chemoselective reactivity.

Stereoselectivity.

In the reduction of 4-t-butylcyclohexanone, BH3.HN3 in methanol at -50 °C affords a high ratio (96:4) of axial hydride delivery.2a Stereoselective carbonyl reductions have been reported in the synthesis of lubimin,3 and in the stereospecific reduction of a protected octulopyranosylonic acid.4

The reduction of (S)-g-methytetronic acid in methanol/water (eq 1) gave a 25:75 ratio of the cis:trans hydroxy lactones (a ratio opposite to that observed with catalytic hydrogenation over rhodium).5a Six-member-ring analogs of tetronic acids were found to be reducible with BH3.NH3 but not with sodium borohydride or sodium cyanoborohydride.5b

Diastereoselectivity has been observed in the reduction of an acyclic sterically hindered a-keto ester (eq 2).6

Reductions of aromatic ketones with BH3.NH3 complex and chiral 18-Crown-6 derivatives afford 63-80% yields of the corresponding alcohols with enantiomeric excesses of 28-67%.7

Chemoselectivity.

The reduction of a 1:1 molar mixture of benzaldehyde and acetophenone with 1 hydride equivalent affords a 98:2 ratio of benzyl alcohol to phenylethanol.2b The relative reduction rates decrease in the order aliphatic aldehyde > aromatic aldehyde > hexanone > pentanone > arylketone > enone. Thus ketones may be reduced selectively in the presence of enones,8,2b and aliphatic aldehydes in the presence of ketone and/or lactone moieties.9a,9b

Reduction of Imines.

In the reduction of 4-substituted cyclohexyl imines, iminium salts, and enamines with BH3.NH3,10 in contrast to the case with carbonyl reduction, equatorial attack of hydride is favored affording the corresponding reduced amines in 60-89% yield.

Related Reagents.

Sodium Borohydride; Sodium Cyanoborohydride.


1. Hutchins, R. O.; Learn, K.; Nazer, B.; Pytlewski, D.; Pelter, A. OPP 1984, 16, 335.
2. (a) Andrews, G. C.; Crawford, T. C. TL 1980, 21, 693. (b) Andrews, G. C. TL 1980, 21, 697.
3. Murai, A.; Sato, S.; Masamune, T. BCJ 1984, 57, 2291.
4. Gass, J.; Strobl, M.; Loibner, A.; Kosma, P.; Zahringer, U. Carbohydr. Res. 1993, 244, 69.
5. (a) Brandange, S.; Jansbo, K.; Minassie, T. ACS 1987, B41, 736. (b) Hausler, J. LA 1983, 982.
6. Willson, T. M.; Kocienski, P.; Jarowicki, K.; Isaac, K.; Faller, A.; Campbell, S. F.; Bordner, J. T 1990, 46, 1757.
7. Allwood, B. L.; Shariari-Zavareh, H.; Stoddard, J. F.; Williams, D. J. CC 1984, 22, 1461.
8. Chang, F. C. SC 1981, 11, 875.
9. (a) Masamune, S.; Lu, L. D.-L.; Jackson, W. P.; Kaiho, T.; Toyoda, T. JACS 1982, 104, 5523. (b) Paquette, L. A.; Annis, G. D.; Shostarez, H. JACS 1982, 104, 6646.
10. Hutchins, R. O.; Su, W.-Y.; Sivakumar, R.; Cistone, F.; Stercho, Y. P. JOC 1983, 48, 3412.

Glenn C. Andrews

Pfizer Central Research, Groton, CT, USA



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