Triethylborane

Et3B

[97-94-9]  · C6H15B  · Triethylborane  · (MW 98.02)

(precursor of triethylborohydride reducing agents;1 enoxytriethylborates and -diethylboranes for aldol19,22 and alkylation17 reactions; regio- and stereoselective reactions of allyltriethylborates;26,27 alkylating reagents;1b stereocontrol of carbanion reactions;39,41 radical initiator44)

Physical Data: mp -93 °C; bp 95 °C; d 0.677 g cm-3.

Solubility: sol ethanol, acetone, THF, ether, hexane, benzene, CHCl3.

Form Supplied in: colorless liquid; widely available. Since it is highly flammable, triethylborane diluted with hexane or THF (1.0 M solution) is also available.

Handling, Storage, and Precautions: neat triethylborane ignites instantaneously upon contact with air. The reagent should be handled with a syringe under Ar or N2 atmosphere. It is stable toward moisture and water, and reputed to be toxic. Use in a fume hood.

Reducing Reagents.

Lithium Triethylborohydride, known as Super-Hydride, is prepared in THF by the reaction of lithium hydride with triethylborane (eq 1).1 Alkali metal trialkylborohydrides are exceptionally powerful nucleophilic reducing agents capable of cleaving cyclic ethers,2 reducing hindered halides,3 p-toluenesulfonate esters of hindered and cyclic alcohols,4 epoxides,5 and activated alkenes6 rapidly and quantitatively to the desired products. The advantage of LiEt3BH is especially evident in the reduction of labile bicyclic epoxides (eq 2). Thus benzonorbornadiene oxide, which invariably gives rearranged products with conventional reducing agents, undergoes facile reduction with LiEt3BH yielding 93% of exo-benzonorborneol in >99.9% isomeric purity. The reactivity of the trialkylborohydrides and the stereochemical course of their reactions are strongly influenced by the steric bulk of the alkyl group on boron.7 The lithium hydride route (eq 1) provides a convenient entry only to the relatively unhindered lithium trialkylborohydrides. However, Potassium Hydride reacts rapidly and quantitatively with the hindered trialkylboranes, such as tri-s-butylborane, yielding the corresponding sterically hindered trialkylborohydride Potassium Tri-s-butylborohydride.8 A general synthesis of lithium trialkylborohydrides has been developed using lithium trimethoxyaluminohydride (eq 3).9

The combination of Lithium Tri-t-butoxyaluminum Hydride and triethylborane induces a rapid, essentially quantitative, reductive ring opening of THF to produce 1-butanol upon hydrolysis (eq 4).10 Cyclohexene oxide and 1-methylcyclohexene oxide are instantaneously and quantitatively cleaved to their corresponding carbinols. Oxetane is readily cleaved to give 1-propanol in 98% yield. The reductive cleavage of both tetrahydropyran and oxepan is very sluggish and incomplete.

Triethyl- or triisopropylborane/Trifluoromethanesulfonic Acid (triflic acid) is a convenient reagent for the selective reduction of hydroxy substituted carboxylic acids, ketones, and aldehydes to yield the corresponding carbonyl compounds (eq 5).11 Not only tertiary hydroxy but also primary, secondary, and benzylic hydroxy groups are reduced in good to high yields. In general, the triisopropylborane/triflic acid system gives better results than triethylborane/triflic acid.

Preparation of R2BORŽ is generally carried out by treating alcohols RŽOH with trialkylboranes R3B in the presence of activating reagents like pivalic acid13 or air.14 However, Et2BOMe can be prepared simply by mixing Et3B with MeOH in THF at room temperature.12 Using the Et2BOMe thus generated as a chelating agent, syn-1,3-diols are prepared in >98% stereochemical purity by reducing b-hydroxy ketones with Sodium Borohydride.12

Enoxytriethylborates and Enoxydiethylboranes.

Potassium enolates of ketones react with an unhindered trialkylborane such as triethylborane to form a potassium enoxytriethylborate, which undergoes selective a-monoalkylation with alkyl halides in high yields (eq 6).15 In the absence of Et3B, the potassium enolate itself gives a mixture of 43% mono- and 31% diallylated cyclohexanone along with 28% of recovered cyclohexanone. Monomethylation, -benzylation, and -propargylation of acetophenone also proceed in high yield in the presence of Et3B. Lithium enolates, such as those obtained from acetophenone and cyclohexanone, do not form the corresponding enoxytriethylborates. Use of Potassium Hexamethyldisilazide as a base at -78 °C generates the less stable enolate (1) with high regioselectivity, while use of potassium hydride at 25 °C generates the most stable enolate (2) with &egt;90% regioselectivity (eq 7).16 The alkylations of these enolates proceed without complication in the presence of Et3B (eq 7). Comparable regioselectivities are observed in the alkylations of 2-heptanone.

Allylation of potassium enoxyborates can be catalyzed by Tetrakis(triphenylphosphine)palladium(0).17 Zinc enolates, readily obtained by treating lithium enolates with dry Zinc Chloride, also undergo the Pd-catalyzed allylation with high regio- and stereoselectivities. Overall retention is observed with respect to the allylic cation center (eq 8).17 In the presence of Pd(PPh3)4 catalyst and 2 equiv of BEt3, lithium enolates of cyclopentanone and cyclohexanone derivatives react with (E)- or (Z)-allylic acetate (3) to provide (E)- or (Z)-allylation products with high stereospecificity (eq 9).18 Both the Pd catalyst and BEt3 are essential for the stereospecific allylation.

The aldol reaction of preformed lithium enolates with aldehydes in the presence of trialkylboranes, such as BEt3 and B(n-Bu)3, leads to product mixtures rich in the more stable anti-aldol (eq 10).19 Use of 3 equiv of BEt3 gives high anti selectivity, while the stereoselectivity is low when 1 equiv of BEt3 is used (eq 10). When lithium enolates are generated from silyl enol ethers and n-Butyllithium in THF, use of 1 equiv of BEt3 is enough to produce high anti selectivity. The condensation of the lithio dianion of ethyl 3-hydroxybutyrate with N-anisyl cinnamylideneimine in the presence of Et3B produces excellent 1Ž,3-syn/3,4-cis stereoselectivity (eq 11), whereas 1Ž,3-syn/3,4-trans selectivity is obtained in the presence of t-BuMgCl.20 Aldol condensation of acetaldehyde and benzaldehyde with the lithium enolate of ethyl N,N-dimethylglycine in the presence of 1 equiv of Et3B results in the formation of the corresponding syn 3-hydroxy-2-amino acid esters with excellent stereocontrol (>95% de).21 The stereochemical outcome of these reactions is rationalized via the selective formation of the (Z)-enolate of ethyl N,N-dimethylglycine in the presence of triethylborane.

There are several methods for generation of enoxyboranes (boron enolates).22 Ketenes react with dialkylthioalkylboranes, R2BS(t-Bu), to yield alkenyloxyboranes formally derived from thioesters.22a A variety of ketones and carboxylic acid derivatives are converted to boron enolates upon treatment with dialkylboryl triflates in the presence of a tertiary amine, and the subsequent aldol condensation of these boron enolates has been studied22b,c Trialkylboranes readily react with diazoacetaldehyde to give alkenyloxyboranes.22d Trialkylboranes spontaneously transfer an alkyl group to the b-position of b-unsubstituted a,b-unsaturated aldehydes and ketones to give alkenyloxyboranes, which are produced regio- but not stereospecifically.22e In the presence of 1-10 mol % of diethylboryl pivalate, Et3B and ketones RCOCH2RŽ react at 85-110 °C to give diethyl(vinyloxy)boranes, Et2BOCR=CHRŽ, in 70-90% yield.22f Reaction of a-bromo ketones with Triphenylsilane in the presence of Et3B provides boron enolates which react with carbonyl compounds to give b-hydroxy ketones in good yields (eq 12).23 The Et3B-induced Reformatsky type reaction of a-iodo ketones with aldehydes or ketones proceeds without Ph3SnH.23,24 a-Bromocyclopentanone and -cyclohexanone provide anti-adducts with high diastereoselectivity (78-100%), whereas the reaction of 7-bromo-6-dodecanone with benzaldehyde gives a 65:35 mixture of the syn- and anti-adduct. It is proposed that vinyloxy(diethyl)boranes are involved as intermediates.

Allylborates.

2-Butenyllithium reacts with aldehydes to afford the anti- and syn-b-methylhomoallyl alcohols in nearly equal amounts. However, if trialkylboranes such as Et3B are present, the anti-product predominates (eq 13).25 The corresponding allylic borate complexes are presumably involved as intermediates. Lithium allylic boronates, prepared by the addition of trialkylboranes (Et3B, Tri-n-butylborane, or n-Bu-9-BBN) to an ether solution of allylic lithium compounds, regioselectively react with allylic halides to produce head-to-tail 1,5-dienes (eq 14).26 Regio- and stereocontrol via boron ate complexes is applicable to not only simple allylic but also heteroatom substituted allylic anions.27 The allyloxy carbanions (4) generally react with alkyl halides at the a-position, but react with carbonyl compounds at the g-position. The Et3B (or Triethylaluminum) ate complexes of (4) react with a ldehydes, ketones, and reactive halides at the a-position. The (alkylthio)allyl carbanion (5) reacts with alkyl halides at the g-position, but with carbonyl compounds at the a-position. The Et3B (or Et3Al) ate complexes of (5) react with aldehydes, ketones, and allylic halides at the a-position. In general, the aluminum ate complex gives higher regioselectivity than the boron ate complex. The regioselectivity of Me3Si- or pyrrolidine (N-atom)-substituted allylic anions is also controlled by the addition of Et3B (or Et3Al).27 Either branched or linear homoallyl alcohols may be prepared by the reaction of (phenylselenyl)allyl carbanion with aldehydes and triethylborane under appropriate reaction conditions (eq 15).28 The ethyl group of Et3B in the initially formed ate complex PhSeCH(-BEt3)CH=CH2 Li+ undergoes a facile migration from boron to the a-carbon to give (6), which reacts with benzaldehyde to give the linear adduct. The prolonged reaction period at higher temperatures induces the allylic rearrangement of (6) to (7), resulting in the formation of the branched adduct.

Alkylating Reagents.

Monoalkylation of ketones is accomplished by reaction of trialkylboranes with a-bromo ketones under the influence of Potassium t-Butoxide in THF.29 For example, a-bromocyclohexanone reacts with Et3B to give a-ethylcyclohexanone (eq 16).29 The reaction involves formation of the anion of the a-bromo ketone, formation of the boron ate complex, and rearrangement of Et from boron to the a-carbon. The use of potassium 2,6-di-t-butylphenoxide as a base, instead of t-BuOK, provides better results.30 a-Bromoacetone, chloroacetonitrile, ethyl bromoacetate, and ethyl dibromoacetate are alkylated using this hindered base and R3B.30 The reaction of Et3B with ethyl 4-bromocrotonate in the presence of one equiv of the new base affords ethyl 3-hexenoate (79% trans).31 Monoalkylation of dichloroacetonitrile with Et3B is achieved in 89% yield, and the dialkylation is carried out by using 2 equiv of base and 2 equiv of Et3B (97% yield).32

Trialkylcarbinols are prepared by the reaction of trialkylboranes with carbon monoxide in diglyme followed by oxidation with Hydrogen Peroxide (eq 17).1b Alternatively, trialkylcarbinols are obtained by the reaction of trialkylboranes with Chlorodifluoromethane (or Dichloromethyl Methyl Ether) under the influence of lithium triethylmethoxide,1b,33 or by the cyanidation reaction of trialkylboranes with Sodium Cyanide-Trifluoroacetic Anhydride followed by oxidation.1b,34 Bromination of triethylborane under irradiation in the presence of water followed by oxidation gives 3-methyl-3-pentanol in 88% yield (eq 18).35 In order to effect successful a-bromination-migration, slow addition of bromine is important to avoid polybromination. The use of N-Bromosuccinimide in the presence of water increases the yield in eq 18 to 97%.36 The bromination-migration reaction is applicable to simple trialkylboranes and dialkylborinic acids. The cross-coupling reaction of B-alkyl-9-borabicyclo[3.3.1]nonanes (B-R-9-BBN) with 1-halo-1-alkenes or haloarenes (RŽX) in the presence of a catalytic amount of Dichloro[1,1Ž-bis(diphenylphosphino)ferrocene]palladium(II) and bases, such as NaOH and K2CO3, gives the corresponding alkenes or arenes (R-RŽ).37 The use of catalytic amounts of Cl2Pd[PPh3]2 in combination with Bis(acetylacetonato)zinc(II) effects carbonylative coupling of trialkylboranes with aryl iodides to give unsymmetrical ketones in 60-80% yields (eq 19).38

Alkynes are easily synthesized by the reaction of iodine with alkyne ate complexes, readily formed in situ from R3B and lithium acetylides (eq 20).1b Treatment of the alkyne ate complexes with mild electrophiles E+ results in b-attack on the triple bond and a migration of the organic group R from boron to carbon (eq 20).1b The protonation reaction with HX yields a mixture of cis- and trans alkenes, and mixtures of alkene isomers are also obtained in reactions involving MeI, MeOTs, allyl bromide, and oxirane. However, a single stereoisomer results from the reactions with other electrophiles.

Stereochemical Control Element.

Triethylborane acts as a stereo- and regiocontrol element in certain carbanionic reactions; several examples have been demonstrated in eqs 10, 11, and 13-15. Triethylborane-mediated epimerization of a 1a-methylcarbapenem intermediate proceeds with high stereoselectivity to give the 1b-methyl diastereomer (eq 21).39 The 1b-methyl derivative is also obtained via alkylation of an 2-azetidinon-4-ylacetic acid derivative by using LDA-Et3Al-MeI.39 The deuteration of a-lithiobenzyl methyl sulfoxide in the presence of Et3Al occurs with inversion, while the reaction in the absence of the additive occurs with retention; the use of Et3B gives a mixture of the retention and inversion product.40 The reagent RCu.BEt3, prepared in situ from RCu and BEt3 in ether at -70 °C, adds to a,b-alkynic carbonyl compounds with high stereospecificity, which cannot be achieved with conventional reagents such as R2CuLi (eq 22).41

Lewis Acids and Radical Reactions.

Methylenecyclopropanes react with 2-cyclopentenone in the presence of a Ni0 catalyst (such as Bis(1,5-cyclooctadiene)nickel(0)), Triphenylphosphine, and triethylborane to afford 6-methylenebicyclo[3.3.0]octan-2-ones (eq 23).42 Treatment of tantalum-alkyne complexes with dimethylhydrazones and Trimethylaluminum in a DME, benzene, and THF solvent system at 45 °C gives (E)-allylic hydrazines stereoselectively, although the use of Et3B results in formation of the product in very low yield.43

Trialkylboranes do not undergo facile addition reactions to carbonyl groups. However, rapid conjugate addition reactions occur with a,b-unsaturated carbonyl compounds, such as Acrolein and Methyl Vinyl Ketone (eq 24).1b The reaction proceeds through a radical mechanism. Trialkylboranes also participate in facile radical chain reactions with disulfides (e.g. Diphenyl Disulfide), producing the corresponding thioethers (RSPh).1b Triphenylgermane adds easily to alkynes (RC&tbond;CH) in the presence of Et3B to give (E)- or (Z)-alkenyltriphenylgermanes (RCH=CHGePh3) in good yields.44 The (Z)-isomers predominate at -78 °C, whereas the hydrogermylation at 60 °C favors the (E)-isomer. Similarly, Et3B is as efficient as Azobisisobutyronitrile for initiation of the hydrostannylation of alkynes, resulting in vinyltins.45 The reaction is sluggish in the absence of oxygen. Triethylborane can also initiate radical cyclization of unsaturated alkynes to vinylstannanes (eq 25).45 The 1,4-reduction of a,b-unsaturated ketones and aldehydes with Triphenylstannane or Tri-n-butylstannane proceeds in the presence of Et3B to give the corresponding saturated ketones and aldehydes in good yields, whereas the same reaction of a,b-unsaturated esters with Ph3SnH affords the tin hydride conjugate adduct.46 Thiols47a and perfluoroalkyl iodides47b undergo similar addition reactions to alkynes in the presence of catalytic amounts of Et3B. Treatment of 1-allyloxy-1-phenyl-2-bromo-1-silacyclopentanes with Bu3SnH in the presence of catalytic amounts of Et3B provides the cyclization products, which can be converted to 1,4,6-triol derivatives (eq 26).48 Alkoxymethyl radicals (2-oxahex-5-enyl or 2-oxahept-6-enyl radicals), generated conveniently from phenylseleno precursors upon treatment with AIBN or Et3B, cyclize to afford substituted tetrahydrofurans and tetrahydropyrans.49

Related Reagents.

B-Allyl-9-borabicyclo[3.3.1]nonane; Crotyldimethoxyborane; Di-n-butylboryl Trifluoromethanesulfonate; Lithium Triethylborohydride; Potassium Tri-s-butylborohydride.


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Yoshinori Yamamoto

Tohoku University, Sendai, Japan



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