Boron Trichloride1

BCl3

[10294-34-5]  · BCl3  · Boron Trichloride  · (MW 117.17)

(Lewis acid capable of selective cleavage of ether and acetal protecting groups; reagent for carbonyl condensations; precursor of organoboron reagents)

Physical Data: bp 12.5 °C; d 1.434 g cm-3 (0 °C).

Solubility: sol saturated and halogenated hydrocarbon and aromatic solvents; solubility in diethyl ether is approximately 1.5 M at 0 °C; stable for several weeks in ethyl ether at 0 °C, but dec by water or alcohols.

Form Supplied in: colorless gas or fuming liquid in an ampoule; BCl3.SMe2 complex (solid) and 1 M solutions in dichloromethane, hexane, heptane, and p-xylene are available.

Handling, Storage, and Precautions: a poison by inhalation and an irritant to skin, eyes, and mucous membranes. Reacts exothermically with water and moist air, forming toxic and corrosive fumes. Violent reaction occurs with aniline or phosphine. All operations should be carried out in a well-ventilated fume hood without exposure to the atmosphere. The gas can be collected and measured as a liquid by condensing in a cooled centrifuge tube and then transferred to the reaction system by distillation with a slow stream of nitrogen.

Cleavage of Ethers, Acetals, and Esters.

Like many other Lewis acids, BCl3 has been extensively used as a reagent for the cleavage of a wide variety of ethers, acetals, and certain types of esters.2 Ether cleavage procedures involve addition of BCl3, either neat or as a solution in CH2Cl2, to the substrate at -80 °C. The vessel is then stoppered and allowed to warm to rt. Whereas the complexes of BCl3 with dimethyl ether and diethyl ether are rather stable at rt, they decompose to form ROBCl2 or (RO)2BCl with evolution of alkyl chloride upon heating to 56 °C.1 Diaryl ethers are unreactive. Mixed dialkyl ethers are cleaved to give the alkyl chloride derived from C-O bond cleavage leading to the more stable carbenium ion. The transition state is predominantly SN1 in character, as evidenced by partial racemization of chiral ethers1,2 and the rearrangement of allyl phenyl ethers to o-allylphenols.3 BCl3 can be used for the deprotection of a variety of methoxybenzenes including hindered polymethoxybenzenes and peri-methoxynaphthalene.1,2,4 When methoxy groups are ortho to a carbonyl group, the reaction is accelerated by the formation of a chelate between boron and the carbonyl oxygen atom (Scheme 1).4a-c

The reagent is less reactive than Boron Tribromide for ether cleavage; however, the type and extent of deetherification can be more easily controlled by the ratio of substrate to BCl3 as well as the reaction temperature and time. The transformation of (-)-b-hydrastine (1) to (-)-cordrastine II is efficiently achieved by selective cleavage of the methylenedioxy group in preference to aromatic methoxy groups.5 The demethylation of (-)-2-O-methyl-(-)-inositol in dichloromethane proceeds at -80 °C without cleavage of a tosyl ester group.6 Methyl glycosides are converted into glycosyl chlorides at -78 °C without effecting benzyl and acetyl protecting groups.7

One of the difficulties with the use of BCl3 arises from its tendency to fume profusely in air. The complex of BCl3 with dimethyl sulfide is solid, stable in air, and handled easily. By using a two- to fourfold excess of the reagent in dichloroethane at 83 °C, aromatic methoxy and methylenedioxy groups can be cleaved in good yields.8

Another application of BCl3 is for the cleavage of highly hindered esters under mild conditions. O-Methylpodocarpate (2) and methyl adamantane-1-carboxylate are cleaved at 0 °C.9 The highly selective displacement of the acetoxy group in the presence of other potentially basic groups in 2-cephem ester (3) provides the corresponding allylic chloride. On the other hand, treatment of (3) with an excess of BCl3 results in the cleavage of the acetoxy and t-butyl ester groups.10

Tertiary phosphines are cleaved at the P-C bond to give diphenylphosphine oxides. Workup with Hydrogen Peroxide provides diphenylphosphinic acids (eq 1).11

Condensation Reactions.

Boron trichloride converts ketones into (Z)-boron enolates at -95 °C in the presence of Diisopropylethylamine. These enolates react with aldehydes with high syn diastereoselectivity (eq 2).12 A similar condensation of imines with carbonyl compounds also provides crossed aldols in reasonable yields.13 The reaction was extended to the asymmetric aldol condensation of acetophenone imine and benzaldehyde by using isobornylamine as a chiral auxiliary (48% ee).14

(N-Alkylanilino)dichloroboranes (5), prepared in situ from N-alkylanilines and boron trichloride, are versatile intermediates for the synthesis of ortho-functionalized aniline derivatives (eqs 3-5).15 The regioselective ortho hydroxyalkylation can be achieved with aromatic aldehydes.16

The reaction of (5) with alkyl and aryl nitriles and Aluminum Chloride catalyst provides ortho-acyl anilines.16 When chloroacetonitrile is used, the products are ideal precursors for indole synthesis.17 Use of isocyanides instead of nitriles provides ortho-formyl N-alkylanilines.18 Although these reactions with BCl3 are restricted to N-alkylanilines, the use of Phenylboron Dichloride allows the ortho-hydroxybenzylation of primary anilines.19

Analogously, boron trichloride induces ortho selective acylation of phenols at rt with nitriles, isocyanates, or acyl chlorides (eq 6).20 The efficiency and regioselectivity of these reactions are best with BCl3 among the representative metal halides that have been examined. In both the aniline and phenol substitutions the boron atom acts as a template to bring the reactants together, leading to cyclic intermediates and exclusively products of ortho substitution. A similar ortho selective condensation of aromatic azides with BCl3 provides fused heterocycles containing nitrogen.21

Aldehydes and ketones condense with ketene in the presence of 1 equiv of boron trichloride to give a,b-unsaturated acyl chlorides.22 Aryl isocyanates are converted into allophanyl chlorides, which are precursors for industrially important 1,3-diazetidinediones (eq 7).23

Synthesis of Organoboron Reagents.

General method of synthesis of organoboranes consists of the transmetallation reaction of organometallic compounds with BX3.24 Boronic acid derivatives [RB(OH)2] are most conveniently synthesized by the reaction of B(OR)3 with RLi or RMgX reagents, but boron trihalides are more advantageous for transmetalation reactions with less nucleophilic organometallic reagents based on Pb,25 Hg,26 Sn,27 and Zr28 (eqs 8 and 9).

Redistribution or exchange reactions of R3B with boron trihalides in the presence of catalytic amounts of hydride provides an efficient synthesis of RBX2 and R2BX.29 Another convenient and general method for the preparation of organodichloroboranes involves treatment of alkyl, 1-alkenyl, and aryl boronates with BCl3 in the presence of Iron(III) Chloride (3 mol %).30 Organodichloroboranes are valuable synthetic reagents because of their high Lewis acidity, and their utility is well demonstrated in the syntheses of piperidine and pyrrolidine derivatives by the intramolecular alkylation of azides (eq 10)31 or the synthesis of esters by the reaction with Ethyl Diazoacetate.32 The various organoborane derivatives, R3B, R2BCl, and RBCl2, all react with organic azides and diazoacetates. However, especially facile reactions are achieved by using organodichloroboranes (RBCl2).

Dichloroborane and monochloroborane etherates or their methyl sulfide complexes have been prepared by the reaction of borane and boron trichloride.33 However, hydroboration of alkenes with these borane reagents is usually very slow due to the slow dissociation of the complex. Dichloroborane prepared in pentane from boron trichloride and trimethylsilane shows unusually high reactivity with alkenes and alkynes; hydroboration is instantaneous at -78 °C (eq 11).34

Direct boronation of benzene derivatives with BCl3 in the presence of activated aluminum or AlCl3 provides arylboronic acids after hydrolysis (eq 12).35 Chloroboration of acetylene with boron trichloride produces dichloro(2-chloroethenyl)borane.36 Similar reaction with phenylacetylene provides (E)-2-chloro-2-phenylethenylborane regio- and stereoselectively.37

The syntheses of thioaldehydes, thioketones, thiolactones, and thiolactams from carbonyl compounds are readily achieved by in situ preparation of B2S3 from bis(tricyclohexyltin) sulfide and boron trichloride (eq 13).38 The high sulfurating ability of this in situ prepared reagent can be attributed to its solubility in the reaction medium.

Related Reagents.

Bis(tricyclohexyltin) Sulfide-Boron Trichloride.


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Norio Miyaura

Hokkaido University, Sapporo, Japan



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