[22560-16-3] · C6H16BLi · Lithium Triethylborohydride · (MW 105.97)
(exceptionally powerful nucleophile in SN2 displacement reactions with super hydride activity; powerful and selective reducing agent)
Alternate Name: Super Hydride®.
Physical Data: mp 66-67 °C;2 d
Solubility: sol THF, benzene; reacts violently with water.
Form Supplied in: 1 M solution in THF.
Analysis of Reagent Purity: IR: 2060 cm-1 (BH). 11B NMR (THF) d, ppm, -12.2 (d, JB-H = 61 Hz).3a Active hydride is determined by hydrolysis of an aliquot and measuring the hydrogen evolved according to the standard procedure.4 Low concentrations may be determined by iodometric titration.5
Handling, Storage, and Precautions: corrosive flammable liquid. Handle and store under nitrogen or argon in a cool dry place. Avoid contact with skin and clothing. Use in a fume hood.
Lithium triethylborohydride shows super hydride activity. Its reactivity in comparison to other nucleophiles is given in Table 1.6 The reduction of representative functionalities by the reagent under standard conditions has been described.7
Lithium triethylborohydride is the reagent of choice for dehalogenation of alkyl halides (eq 1).6,8 Primary iodides are the most reactive. Fluorides are reduced at slower rates (eq 2).9 Secondary halides may give elimination products in some cases. Mechanistic aspects of the reaction have been studied.10
Tosylates,11 mesylates,12 and alkoxytris(dimethylamino)phosphonium salts13 of primary alcohols are cleanly reduced to hydrocarbons. Tosylates of secondary alcohols may undergo elimination reactions. Even in such cases the reduction may be synthetically useful (eq 3).11f Differences in the reactivity of tosylates and alkylsulfonates have been observed.11e
Allylic groups such as -OR, -SR, -SO2R, -SeR, and -OTBDMS undergo reductive cleavage by lithium triethylborohydride catalyzed by palladium compounds (eq 4).14a Squalene (E/Z = 97:3) has been prepared using this reaction as a key step.14b
The reduction of epoxides by the reagent is quite facile, yielding exclusively the Markovnikov product.5,7,15 Its advantage is evident in the reduction of labile epoxides prone to electrophilic rearrangements (eq 5).16 Oxetanes are opened in a similar fashion.17 Conjugated epoxides may undergo 1,4-reduction.18
Aldehydes and ketones are reduced by lithium triethylborohydride rapidly and quantitatively to the corresponding alcohols, even at -78 °C.7 Enthalpies of these reactions have been estimated.19 Selective reduction of a keto group in the presence of an electron-rich aldehyde group has been achieved.20a Although the stereoselectivity of the reagent is lower as compared to other trialkylborohydrides containing bulky sterically demanding groups, several a-, b-, or g-substituted ketones undergo reduction with high selectivity.20b-j a,b-Unsaturated ketones and esters undergo 1,4-additions.21 N-Alkylimines derived from cyclic ketones are reduced to the corresponding secondary amines which can be transformed into primary amines.22
The reduction of a-trityl ketones with lithium triethylborohydride proceeds with cleavage of the trityl group. Stereoselective aldol reaction, combined with the reduction, provides access to stereodefined acyclic 1,3-diols23 (eq 6).23b Trityl alkynic ketones are cleaved without affecting the triple bond.24 Acetals are stable to the reagent and can be used as protective groups (eq 2).7,9,11c,d However, acetals are cleaved in the presence of Titanium(IV) Chloride.25
The inertness of carboxylic acids to the reagent is noteworthy. Anhydrides are reduced to alcohols and acids. Cyclic anhydrides can be transformed into the corresponding lactones via intermediate hydroxy acids. The reactivity of lithium triethylborohydride toward ester groups is exceptionally high. Even esters of aromatic carboxylic acids are selectively reduced to alcohols in the presence of other functional groups (eq 7).26 Selective reduction of the less hindered MEM ester groups of a diester has been achieved.27a The reduction of esters with Lithium Borohydride is catalyzed by lithium triethylborohydride.27b
Unlike most other hydride reducing agents, lithium triethylborohydride reduces tertiary amides to the corresponding alcohols.7,28 Benzonitrile cleanly gives benzylamine with an excess of the reagent. With an equimolar ratio of the reactants, an 85-97% yield of benzaldehyde is obtained.7 Aliphatic nitriles give lower yields of the corresponding amines.
The formation of ethylbenzene in the reaction of lithium triethylborohydride with diphenyl sulfone illustrates a general reactivity pattern of trialkylborohydrides with aromatic sulfones (eq 8).29
a,b-Unsaturated nitro compounds are transformed into lithium nitroalkanes.30a In the presence of borane, N-ethylamine derivatives are formed (eq 9).30b 1,2-Iodo thiocyanates31a and vinylthiophthalimides31b yield thiiranes (eq 10). The reagent is useful for selective demethylation of quaternary ammonium salts containing at least two methyl groups.32 It also finds application in the synthesis of di- and trialkyldihydronaphthalenenes.33a Pyridine is reduced to tetrahydropyridine.7,33b
The reagent hydroborates aromatically conjugated alkenes in a Markovnikov fashion (eq 11).34 Substituents that decrease the electron density of the double bond increase the rate of reaction. Lithium triethylborohydride promotes hydroboration of alkenes by dialkoxyboranes; the addition is anti-Markovnikov.35
The reagent promotes the reaction of alcohol with borane to give borates in high yields36 (see also Borane-Dimethyl Sulfide). Ethyl boronates can be conveniently prepared by the reaction with 1,2-diols.37
Lithium triethylborohydride is recommended for the generation of chloro(cyclopentadienyl)hydrozirconium (Schwartz hydrozirconation reagent).39 The reagent is used for the reduction of other transition metal halide complexes.40 The major area of its application in transition metal chemistry involves metal-metal and metal-metalloid bond cleavage38,41 and formation of anionic and neutral formyl complexes.38,42 It finds various other applications.43-45
Nicolaus Copernicus University, Torun, Poland
Herbert C. Brown
Purdue University, West Lafayette, IN, USA