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Lithium triethylborohydride
Chemical compound

Lithium triethylborohydride is the organoboron compound with the formula LiEt3BH. Commonly referred to as LiTEBH or Superhydride, it is a powerful reducing agent used in organometallic and organic chemistry. It is a colorless or white liquid but is typically marketed and used as a THF solution. The related reducing agent sodium triethylborohydride is commercially available as toluene solutions.

LiBHEt3 is a stronger reducing agent than lithium borohydride and lithium aluminium hydride.

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Preparation

LiBHEt3 is prepared by the reaction of lithium hydride (LiH) and triethylborane (Et3B) in tetrahydrofuran (THF):

LiH + Et3B → LiEt3BH

The resulting THF complex is stable indefinitely in the absence of moisture and air.

Reactions

Alkyl halides are reduced to the alkanes by LiBHEt3.234

LiBHEt3 reduces a wide range of functional groups, but so do many other hydride reagents. Instead, LiBHEt3 is reserved for difficult substrates, such as sterically hindered carbonyls, as illustrated by reduction of 2,2,4,4-tetramethyl-3-pentanone. Otherwise, it reduces acid anhydrides to alcohols and the carboxylic acid, not to the diol. Similarly lactones reduce to diols. α,β-Enones undergo 1,4-addition to give lithium enolates. Disulfides reduce to thiols (via thiolates). LiBHEt3 deprotonates carboxylic acids, but does not reduce the resulting lithium carboxylates. For similar reasons, epoxides undergo ring-opening upon treatment with LiBHEt3 to give the alcohol. With unsymmetrical epoxides, the reaction can proceed with high regio- and stereo- selectivity, favoring attack at the least hindered position:

Acetals and ketals are not reduced by LiBHEt3. It can be used in the reductive cleavage of mesylates and tosylates.5 LiBHEt3 can selectively deprotect tertiary N-acyl groups without affecting secondary amide functionality.6 It has also been shown to reduce aromatic esters to the corresponding alcohols as shown in eq 6 and 7.

LiBHEt3 also reduces pyridine and isoquinolines to piperidines and tetrahydroisoquinolines respectively.7 The reduction of β-hydroxysulfinyl imines with catecholborane and LiBHEt3 produces anti-1,3-amino alcohols shown in (8).8

Precautions

LiBHEt3 reacts exothermically, potentially violently, with water, alcohols, and acids, releasing hydrogen and the pyrophoric triethylborane.9

References

  1. Zaidlewicz, M.; Brown, H.C. (2001). "Lithium Triethylborohydride". Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. doi:10.1002/047084289X.rl148. ISBN 0471936235. Retrieved 2022-02-18. 0471936235

  2. Marek Zaidlewicz; Herbert C. Brown (2001). "Lithium Triethylborohydride". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rl148. ISBN 0471936235. 0471936235

  3. Brown, H. C.; Kim, S. C.; Krishnamurthy, S. (1980-02-01). "Selective reductions. 27. Reaction of alkyl halides with representative complex metal hydrides and metal hydrides. Comparison of various hydride reducing agents". J. Org. Chem. 45 (5): 849–856. doi:10.1021/jo01293a018. Retrieved 2022-02-18. https://pubs.acs.org/doi/10.1021/jo01293a018

  4. Zaidlewicz, M.; Brown, H.C. (2001). "Lithium Triethylborohydride". Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. doi:10.1002/047084289X.rl148. ISBN 0471936235. Retrieved 2022-02-18. 0471936235

  5. Baer, H.H.; Mekarska-Falicki, M. (November 1985). "Stereochemical dependence of the mechanism of deoxygenation, with lithium triethylborohydride, in 4,6-O-benzylidenehexopyranoside p-toluenesulfonates". Canadian Journal of Chemistry. 63 (11): 3043. doi:10.1139/v85-505. Retrieved 2022-02-18. https://doi.org/10.1139/v85-505

  6. Tanaka, H.; Ogasawara, K. (2002-06-17). "Utilization oh lithium triethylborohydride as a selective N-acyl deprotecting agent". Tetrahedron Lett. 43 (25): 4417. doi:10.1016/S0040-4039(02)00844-4. Retrieved 2022-02-18. https://doi.org/10.1016/S0040-4039(02)00844-4

  7. Blough, B.E.; Carroll, F.I. (1993-11-05). "Reduction of isoquinoline and pyridine-containing heterocycles with lithium triethylborohydride (Super-Hydride®)". Tetrahedron Lett. 34 (45): 7239. doi:10.1016/S0040-4039(00)79297-5. Retrieved 2022-02-18. https://www.sciencedirect.com/science/article/abs/pii/S0040403900792975

  8. Kochi, T.; Tang, T.P.; Ellman, J.A. (2002-05-14). "Asymmetric Synthesis of syn- and anti-1,3-Amino Alcohols". J. Am. Chem. Soc. 124 (23): 6518–6519. doi:10.1021/ja026292g. PMID 12047156. Retrieved 2022-02-18. https://doi.org/10.1021/ja026292g

  9. Zaidlewicz, M.; Brown, H.C. (2001). "Lithium Triethylborohydride". Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. doi:10.1002/047084289X.rl148. ISBN 0471936235. Retrieved 2022-02-18. 0471936235