Lithium triethylborohydride explained

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.[1] 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.

Preparation

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

LiH + Et3B → LiEt3BHThe resulting THF complex is stable indefinitely in the absence of moisture and air.

Reactions

Alkyl halides are reduced to the alkanes by LiBHEt3.[2] [3] [1]

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.[4] LiBHEt3 can selectively deprotect tertiary N-acyl groups without affecting secondary amide functionality.[5] 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.[6]
The reduction of β-hydroxysulfinyl imines with catecholborane and LiBHEt3 produces anti-1,3-amino alcohols shown in (8).[7]

Precautions

LiBHEt3 reacts exothermically, potentially violently, with water, alcohols, and acids, releasing hydrogen and the pyrophoric triethylborane.[1]

References

  1. Book: Zaidlewicz, M.. Brown, H.C.. Herbert C. Brown. Lithium Triethylborohydride. Encyclopedia of Reagents for Organic Synthesis. 2001. John Wiley & Sons. 10.1002/047084289X.rl148. 0471936235. 2022-02-18.
  2. Lithium Triethylborohydride. Marek Zaidlewicz. Herbert C. Brown. Encyclopedia of Reagents for Organic Synthesis. 2001. 10.1002/047084289X.rl148. 0471936235.
  3. Brown, H. C.. Kim, S. C.. Krishnamurthy, S.. Selective reductions. 27. Reaction of alkyl halides with representative complex metal hydrides and metal hydrides. Comparison of various hydride reducing agents. J. Org. Chem.. 1980-02-01. 45. 5. 849–856. 10.1021/jo01293a018. 2022-02-18.
  4. Baer, H.H.. Mekarska-Falicki, M.. Stereochemical dependence of the mechanism of deoxygenation, with lithium triethylborohydride, in 4,6-O-benzylidenehexopyranoside p-toluenesulfonates. Canadian Journal of Chemistry. November 1985. 63. 11. 3043. 10.1139/v85-505. 2022-02-18. free.
  5. Tanaka, H.. Ogasawara, K.. Utilization oh lithium triethylborohydride as a selective N-acyl deprotecting agent. Tetrahedron Lett.. 2002-06-17. 43. 25. 4417. 10.1016/S0040-4039(02)00844-4. 2022-02-18.
  6. Blough, B.E.. Carroll, F.I.. Reduction of isoquinoline and pyridine-containing heterocycles with lithium triethylborohydride (Super-Hydride®). Tetrahedron Lett.. 1993-11-05. 34. 45. 7239. 10.1016/S0040-4039(00)79297-5. 2022-02-18.
  7. Kochi, T.. Tang, T.P.. Ellman, J.A.. Asymmetric Synthesis of syn- and anti-1,3-Amino Alcohols. J. Am. Chem. Soc.. 2002-05-14. 124. 23. 6518–6519. 10.1021/ja026292g. 12047156. 2022-02-18.