Lithium Trisiamylborohydride

[60217-34-7]  · C15H31BLi  · Lithium Trisiamylborohydride  · (MW 232.19)

(highly chemo- and stereoselective reducing agent)

Alternate Name: LS-Selectride®.

Physical Data: d420 = 0.903 for 1 M solution in THF.

Solubility: sol THF, diethyl ether.

Form Supplied in: 1 M solution in THF.

Preparative Methods: by the reaction of t-Butyllithium with trisiamylborane,1 of Lithium Aluminum Hydride with trisiamylborane in the presence of triethylenediamine,2 or of lithium trimethoxyaluminohydride with trisiamylborane.3

Analysis of Reagent Purity: 11B NMR (THF), d, ppm, two pairs of doublets, -12.5 (d, J = 78 Hz), -13.9 (d, J = 79 Hz) area 3:1;1 IR: 2150 cm-1. Active hydride is determined by hydrolysis and measuring the hydrogen evolved according to the standard procedure.4

Handling, Storage, and Precautions: air- and moisture-sensitive, flammable liquid. Reacts violently with water. Handle and store under nitrogen or argon. Use in a fume hood.

Lithium trisiamylborohydride (LiBSia3H) is a highly hindered trialkylborohydride containing three bulky b-methyl-substituted secondary alkyl groups. The reagent reduces, rapidly and quantitatively, unhindered cyclic and bicyclic ketones with exceptional steric control. Thus, 2-, 3-, and 4-methylcyclohexanones are all reduced at -78 °C in >99% stereoselectivity to give the less stable isomer of the corresponding methylcyclohexanol (Table 1). Attack from the less hindered side is also favored for the alkaloid and steroidal ketones.6-8

Conjugate reduction of the macrocyclic keto lactone occurs only as a minor side-reaction, accounting for 10% of the reaction product, whereas with L-Selectride (Lithium Tri-s-butylborohydride) (but not with K-Selectride (Potassium Tri-s-butylborohydride)), 53% of the product is the saturated ketone (eq 1).9 Both L- and K-Selectrides reduce a,b-enones and a,b-enoates in a conjugate fashion.10

High stereoselectivity is also observed in the reduction of acyclic ketones with LS-Selectride. Thus, the a,b-dialkoxy ketone is reduced with 97% syn diastereoselectivity (eq 2).11 The reagent is the most stereoselective among the borohydrides used for the reduction of (-)-menthyl phenylglyoxalate and (-)-menthyl pyruvate (eq 3).12 Only lithium trialkoxyaluminohydrides derived from very hindered tertiary alcohols show higher stereoselectivity in this reaction (86-90% de).12

Chemoselective reduction of a tertiary amide to an aldehyde in the presence of an ester group is possible with LS-Selectride, but L-Selectride gives better results.13 Unsymmetrical cyclic anhydrides are reduced to lactones at the less hindered carbonyl group. In contrast, other less bulky hydrides attack the anhydride preferentially at the more hindered carbonyl group (eq 4).14-16

1. (a) Krishnamurthy, S.; Brown, H. C. JACS 1976, 98, 3383. (b) Brown, H. C.; Kramer, G. W.; Hubbard, J. L.; Krishnamurthy, S. JOM 1980, 188, 1.
2. (a) Brown, H. C.; Hubbard, J. L.; Singaram, B. T 1981, 37, 2359. (b) Brown, H. C.; Hubbard, J. L.; Singaram, B. JOC 1979, 44, 5004.
3. Brown, H. C.; Krishnamurthy, S.; Hubbard, J. L. JOM 1979, 166, 271.
4. Brown, H. C. Organic Syntheses via Boranes; Wiley: New York, 1975; p. 239.
5. (a) Brown, C.; Krishnamurthy, S. CC 1972, 868. (b) Yoon, N. M.; Yang, H. S.; Hwang, Y. S. Bull. Korean Chem. Soc. 1987, 8, 285. (c) Brown, C. A.; Krishnamurthy, S. JOC 1986, 51, 238.
6. Brown, J. D.; Foley, M.; Comins, D. L. JACS 1988, 110, 7445.
7. Templeton, J. F.; Kumar, V. P. S.; Gupta, R. K.; Friesen, A. M. Steroids 1986, 48, 339.
8. Templeton, J. F.; Kumar, V. P. S.; Kim, R. S.; La Bella, F. S. JCS(P1) 1987, 1361.
9. Keller, T. H.; Weiler, L. TL 1990, 31, 6307.
10. (a) Fortunato, J. M.; Ganem, B. JOC 1976, 41, 2194. (b) Chamberlin, A. R.; Reich, S. H. JACS 1985, 107, 1440.
11. Yamazaki, N.; Kibayashi, C. TL 1988, 29, 5767.
12. Boireau, G.; Deberly, A. TA 1991, 2, 771.
13. Tsay, S-C.; Robl. J. A.; Hwu, J. R. JCS(P1) 1990, 757.
14. Krishnamurthy, S.; Vreeland, W. B. H 1982, 18, 265.
15. Kayser, M. M.; Morand, P. CJC 1978, 56, 1524.
16. Bailey, D. M.; Johnson, R. E. JOC 1970, 35, 3574.

Marek Zaidlewicz

Nicolaus Copernicus University, Torun, Poland

Herbert C. Brown

Purdue University, West Lafayette, IN, USA

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