Lithium triethylborohydride
Encyclopedia
Lithium triethylborohydride (Li
Et3
B
H
), commonly abbreviated to LiTEBH or Superhydride, is a powerful and selective reducing agent
used in inorganic and organic chemistry
. LiTEBH is far more powerful than lithium borohydride
and more powerful than lithium aluminium hydride
(LAH) in many cases. One of the main advantages of LiTEBH is that it is safer than LAH.
LiTEBH rapidly reduces:
(LiH) and triethylborane
(Et3B) in tetrahydrofuran
(THF)
which gives a very high yield of approximately 99%. The subsequent solution is collected by filtration
of any excess LiH to give a crystal clear solution. LiTEBH in THF has appeared to be stable indefinitely under an inert atmosphere.
LiTEBH can be used to form the alcohol even when these compounds possess sterically hindered substituents as shown with 2,2,4,4-tetramethyl-3-pentanone in (3).
Esters and lactones rapidly take up 2 equivalents of LiTEBH, undergoing reduction to the alcohol and diol groups respectively. The example shown below involves the reduction of γ-butyrolactone to 1,4-butanediol which formed in a 94% yield in (4).
The opening of the epoxide
ring with LiTEBH proceeds with exceptional regio- and stereo- selectivity, yielding only the Markovnikov alcohol.[2] The example shown below is of 1,2-epoxybutane being reduced to give 1-methylcyclohexanol in (5).
The acetal
and ketal will not be reduced by LiTEBH. LiTEBH can be used in the reductive cleavage of mesylates and tosylates. LiTEBH can selectively deprotect tertiary N-acyl groups without affecting secondary amide functionality.
LiTEBH has also shown high reactivity toward ester groups by the selective reduction of the ester group of aromatic carboxylic acids to alcohols as shown in (6) and (7).[2]
LiTEBH can also effectively reduce pyridine
and isoquinolines to piperidines and tetrahydroisoquinolines respectively.
The reduction of β-hydroxysulfinyl imines with catecholborane and LiTEBH produces anti-1,3-amino alcohols shown in (8).
vapor can ignite spontaneously. It can cause severe eye, skin, and respiratory tract burns.
Lithium
Lithium is a soft, silver-white metal that belongs to the alkali metal group of chemical elements. It is represented by the symbol Li, and it has the atomic number 3. Under standard conditions it is the lightest metal and the least dense solid element. Like all alkali metals, lithium is highly...
Et3
Ethyl group
In chemistry, an ethyl group is an alkyl substituent derived from ethane . It has the formula -C2H5 and is very often abbreviated -Et.Ethylation is the formation of a compound by introduction of the ethyl functional group, C2H5....
B
Boron
Boron is the chemical element with atomic number 5 and the chemical symbol B. Boron is a metalloid. Because boron is not produced by stellar nucleosynthesis, it is a low-abundance element in both the solar system and the Earth's crust. However, boron is concentrated on Earth by the...
H
Hydride
In chemistry, a hydride is the anion of hydrogen, H−, or, more commonly, a compound in which one or more hydrogen centres have nucleophilic, reducing, or basic properties. In compounds that are regarded as hydrides, hydrogen is bonded to a more electropositive element or group...
), commonly abbreviated to LiTEBH or Superhydride, is a powerful and selective reducing agent
Reducing agent
A reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...
used in inorganic and organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
. LiTEBH is far more powerful than lithium borohydride
Lithium borohydride
Lithium borohydride is a tetrahydroborate and known in organic synthesis as a reducing agent for esters. Although less common than the related sodium borohydride, the lithium salt offers some advantages of being highly soluble in ethers and being a stronger reducing agent but still safer to...
and more powerful than lithium aluminium hydride
Lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH or known as LithAl, is an inorganic compound with the chemical formula LiAlH4. It was discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic synthesis, especially for the reduction of esters,...
(LAH) in many cases. One of the main advantages of LiTEBH is that it is safer than LAH.
LiTEBH rapidly reduces:
- Aldehydes, ketones, acid chlorides and esters to alcohols
- Lactones to diols
- Acid anhydrides to alcohols
- α,β-enones by 1,4-addition to give lithium enolates
- Disulfides to thiols
- Tertiary amideAmideIn chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
s to an alcohol
History
Compounds of lithium hydride and sodium hydride with trialkylboranes such as LiTEBH were first discovered in the course of War Research in the period of 1942-45 at the University of Chicago by Professor H.C. Brown and Professor H.I. Schlesinger.Preparation
LiTEBH is most commonly produced by the reaction between lithium hydrideLithium hydride
Lithium hydride is the inorganic compound with the formula LiH. It is a colorless solid, although commercial samples are gray. Characteristic of a salt-like, or ionic, hydride, it has a high melting point and is not soluble in any solvent with which it does not react...
(LiH) and triethylborane
Triethylborane
Triethylborane , also called triethylborine and triethylboron, is an organoborane , a near-colorless to yellowish transparent liquid with pungent ether-like odor. Its chemical formula can be written as C6H15B, or 3B, or 3B, or Et3B.Triethylborane is strongly pyrophoric, igniting spontaneously in...
(Et3B) in tetrahydrofuran
Tetrahydrofuran
Tetrahydrofuran is a colorless, water-miscible organic liquid with low viscosity at standard temperature and pressure. This heterocyclic compound has the chemical formula 4O. As one of the most polar ethers with a wide liquid range, it is a useful solvent. Its main use, however, is as a precursor...
(THF)
- LiH + Et3B → LiEt3BH
which gives a very high yield of approximately 99%. The subsequent solution is collected by filtration
Filtration
Filtration is commonly the mechanical or physical operation which is used for the separation of solids from fluids by interposing a medium through which only the fluid can pass...
of any excess LiH to give a crystal clear solution. LiTEBH in THF has appeared to be stable indefinitely under an inert atmosphere.
Structure and chemical properties
The structure of LiTEBH causes the compound to be a very strong hydride source. Hydrogen is more electronegative than boron which causes the B-H bond to be strongly polarized with boron having a partial positive charge and hydrogen having a partial negative charge. The ethyl groups on the boron also aids to this abnormal polarizability by removing additional electron density from the boron making it even more electropositive. This polarization of the B-Et and B-H bonds causes the hydrogen to be in the (-I) oxidation state instead of its usual (+I) oxidation state which leads to its high reactivity with atoms that can accept electrons to allow the hydrogen to go to its (+I) oxidation state.Uses
Aldehydes and ketones rapidly utilizes 1 equivalent of LiTEBH to form the alcohol shown respectively in (1) and (2).LiTEBH can be used to form the alcohol even when these compounds possess sterically hindered substituents as shown with 2,2,4,4-tetramethyl-3-pentanone in (3).
Esters and lactones rapidly take up 2 equivalents of LiTEBH, undergoing reduction to the alcohol and diol groups respectively. The example shown below involves the reduction of γ-butyrolactone to 1,4-butanediol which formed in a 94% yield in (4).
The opening of the epoxide
Epoxide
An epoxide is a cyclic ether with three ring atoms. This ring approximately defines an equilateral triangle, which makes it highly strained. The strained ring makes epoxides more reactive than other ethers. Simple epoxides are named from the parent compound ethylene oxide or oxirane, such as in...
ring with LiTEBH proceeds with exceptional regio- and stereo- selectivity, yielding only the Markovnikov alcohol.[2] The example shown below is of 1,2-epoxybutane being reduced to give 1-methylcyclohexanol in (5).
The acetal
Acetal
An acetal is a molecule with two single-bonded oxygen atoms attached to the same carbon atom.Traditional usages distinguish ketals from acetals...
and ketal will not be reduced by LiTEBH. LiTEBH can be used in the reductive cleavage of mesylates and tosylates. LiTEBH can selectively deprotect tertiary N-acyl groups without affecting secondary amide functionality.
LiTEBH has also shown high reactivity toward ester groups by the selective reduction of the ester group of aromatic carboxylic acids to alcohols as shown in (6) and (7).[2]
LiTEBH can also effectively reduce pyridine
Pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...
and isoquinolines to piperidines and tetrahydroisoquinolines respectively.
The reduction of β-hydroxysulfinyl imines with catecholborane and LiTEBH produces anti-1,3-amino alcohols shown in (8).
Precautions
LiTEBH reacts violently and exothermically with water, alcohols, or acids releasing flammable hydrogen gas which can ignite explosively and the pyrophoric triethylboraneTriethylborane
Triethylborane , also called triethylborine and triethylboron, is an organoborane , a near-colorless to yellowish transparent liquid with pungent ether-like odor. Its chemical formula can be written as C6H15B, or 3B, or 3B, or Et3B.Triethylborane is strongly pyrophoric, igniting spontaneously in...
vapor can ignite spontaneously. It can cause severe eye, skin, and respiratory tract burns.