Boron Tribromide1

BBr3

[10294-33-4]  · BBr3  · Boron Tribromide  · (MW 250.52)

(Lewis acid used for deprotection of OH and NH groups; cleaves ethers or esters to alkyl bromides; bromoborates allene and alkynes)

Physical Data: mp -45 °C; bp 91.7 °C; d 2.650 g cm-3.

Form Supplied in: colorless, fuming liquid; a 1.0 M solution in dichloromethane and hexane; BBr3.Me2S complex is available as either a white solid or a 1.0 M solution in dichloromethane.

Purification: by distillation.

Handling, Storage, and Precautions: BBr3 is highly moisture sensitive and decomposes in air with evolution of HBr. Store under a dry inert atmosphere and transfer by syringe or through a Teflon tube. It reacts violently with protic solvents such as water and alcohols. Ether and THF are not appropriate solvents.

Removal of Protecting Groups.

BBr3 is highly Lewis acidic. It coordinates to ethereal oxygens and promotes C-O bond cleavage to an alkyl bromide and an alkoxyborane that is hydrolyzed to an alcohol during workup (eq 1).2

BBr3 has been widely used to cleave ethers because the reaction proceeds completely under mild conditions. In a special case, BBr3 has been used to cleave acetals that cannot be deprotected by usual acidic conditions.3 Because alkyl aryl ethers are cleaved at the alkyl-oxygen bond to give ArOH and alkyl bromides, BBr3 has been most generally used for the demethylation of methyl aryl ethers,2,4 for example as the final step of zearalenone synthesis (eq 2).5 Problems are sometimes encountered in attempts to deprotect more than one nonadjacent methoxy group on one aromatic ring, and when stable chelates are formed.6 The presence of a carbonyl substituent facilitates the selective deprotection of polymethoxyaryl compounds (eq 3).7

The cleavage of mixed dialkyl ethers occurs at the more substituted carbon-oxygen bond. Methyl ethers of secondary or tertiary alcohols give methanol and secondary or tertiary alkyl bromides selectively by the reaction with BBr3,8 although the addition of Sodium Iodide and 15-Crown-5 ether can change this selectivity (eq 4).9 In contrast, methyl ethers of primary alcohols are generally cleaved at the Me-O bond, as demonstrated in Corey's prostaglandin synthesis (eq 5).10

BBr3 has been also used for the deprotection of carbohydrate derivatives11 and polyoxygenated intermediates in the synthesis of deoxyvernolepin,12 vernolepin,13 and vernomenin.13 Although one of the model compounds is deprotected cleanly (eq 6),14 application of BBr3 to more highly functionalized intermediates leads to cleavage of undesired C-O bonds competitively (eq 7).12,13

For the complete cleavage, 1 mol of BBr3 is required for each ether group and other Lewis-basic functional groups. Sometimes it is difficult to find reaction conditions for the selective cleavage of the desired C-O bond. Recently, modified bromoboranes such as B-Bromocatecholborane,15 dialkylbromoboranes,16 Bromobis(isopropylthio)borane,17 and 9-Bromo-9-borabicyclo[3.3.1]nonane,18 have been introduced to cleave C-O bonds more selectively under milder conditions. BBr3.SMe2 is also effective for ether cleavage and has the advantage of being more stable than BBr3. It can be stored for a long time and handled easily. However, a two- to fourfold excess of the reagent is necessary to complete the dealkylation of alkyl aryl ether.19

Amino acid protecting groups such as benzyloxycarbonyl and t-butoxycarbonyl groups are cleaved by BBr3. However, the hydrolysis of the ester function also occurs under the same reaction conditions.20 Debenzylation and debenzyloxymethylation of uracils proceed successfully in aromatic solvents, but demethylation is more sluggish and less facile (eq 8).21

Substitution Reactions.

BBr3 reacts with cyclic ethers to give tris(o-bromoalkoxy)boranes which provide o-bromoalkanols or o-bromoalkanals when treated with MeOH or Pyridinium Chlorochromate, respectively (eq 9).22 Unfortunately, unsymmetrically substituted ethers such as 2-methyltetrahydrofuran are cleaved nonregioselectively. Generally, ester groups survive under the reaction conditions for ether cleavage, but the ring opening of lactones occurs under mild conditions to give o-halocarboxylic acids in good yields (eq 10).23

In the reaction with methoxybenzaldehyde, bromination of the carbonyl group takes place more rapidly than demethylation; therefore benzal bromide formation is generally observed in the reaction with aromatic aldehydes.24 Cleavage of t-butyldimethylsilyl ethers or t-butyldiphenylsilyl ethers occurs at the C-O bond to give alkyl bromides.25 Alcohols can be converted to alkyl bromides by this method.

In a special case, BBr3 is used for the bromination of hydrocarbons. Adamantane is brominated by a mixture of Bromine, BBr3, and Aluminum Bromide to give 1,3-dibromoadamantane selectively.26 Tetrachlorocyclopropene27 and hexachlorocyclopentadiene28 are substituted to the corresponding bromides by BBr3 and, in the latter case, addition of AlBr3 and Br2 is effective to improve the result.29

Reduction of Sulfur Compounds.

Alkyl and aryl sulfoxides are reduced by BBr3 to the corresponding sulfides in good yields.30 Addition of Potassium Iodide and a catalytic amount of Tetra-n-butylammonium Iodide is necessary for the reduction of sulfonic acids and their derivatives.31

Transesterification of Esters or Conversion to Amides.

Transesterification reactions of carboxylic esters or conversion into the amides is promoted by a stoichiometric amount of BBr3.32

Removal of Methyl Sulfide from Organoborane-Methyl Sulfide Complexes.

Methyl sulfide can be removed from BrBR2.SMe2 or Br2BR.SMe2, which are prepared by the hydroboration reaction of alkenes or alkynes with BrBH2.SMe2 or Br2BH.SMe2, by using BBr3.33 The resulting alkenyldibromoboranes are useful for the stereoselective synthesis of bromodienes (eq 11).34

Bromoboration Reactions.

BBr3 does not add to isolated double bonds, but reacts with allene spontaneously even at low temperature to give (2-bromoallyl)dibromoborane,35 which provides stable (2-bromoallyl)diphenoxyborane by the addition of anisole.36 The diphenoxyborane derivative reacts with carbonyl compounds to give 2-bromohomoallylic alcohols in high yields (eq 12). Bromoboration of 1-alkynes provides (Z)-(2-bromo-1-alkenyl)dibromoboranes stereo- and regioselectively (eq 13),37 which are applied for the synthesis of trisubstituted alkenes,38 a,b-unsaturated esters,39 and g,d-unsaturated ketones,40 bromodienes,41 1,2-dihalo-1-alkenes,42 2-bromoalkanals,43 and b-bromo-a,b-unsaturated amides.44

Chiral Bromoborane Reagents.

Complexes made from chiral 1-alkyl-2-(diphenylhydroxymethyl)pyrrolidines and BBr3 are effective catalysts for asymmetric Diels-Alder reactions.45 Bromoboranes prepared from chiral 1,2-diphenyl-1,2-bis(arenesulfonamido)ethanes46,47 are used to prepare chiral allylic boranes,47,48 allenylic borane,49 propargylic boranes,49 and enolates.46,47,50 The B-bromodiazaborolidinene (1), prepared from 1,2-diphenyl-1,2-bis(p-toluenesulfonamido)ethane, is particularly effective in these applications. The reagents prepared from (1) are highly effective for the enantioselective synthesis of homoallylic alcohols (eq 14),48 homopropargylic alcohols (eq 15),49 propadienyl carbinols (eq 16),49 and aldol condensation products (eq 17).46


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Akira Suzuki & Shoji Hara

Hokkaido University, Sapporo, Japan



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