Boron Trifluoride Etherate

BF3.OEt2
(BF3.OEt2)

[109-63-7]  · C4H10BF3O  · Boron Trifluoride Etherate  · (MW 141.94) (BF3.MeOH)

[373-57-9]  · CH4BF3O  · Boron Trifluoride-Methanol  · (MW 99.85)

(BF3.OEt2: easy-to-handle and convenient source of BF3; Lewis acid catalyst; promotes epoxide cleavage and rearrangement, control of stereoselectivity; BF3.MeOH: esterification of aliphatic and aromatic acids; cleavage of trityl ethers)

Alternate Names: boron trifluoride diethyl etherate; boron trifluoride ethyl etherate; boron trifluoride ethyl ether complex; trifluoroboron diethyl etherate.

Physical Data: BF3.OEt2: bp 126 °C; d 1.15 g cm-3; BF3.MeOH: bp 59 °C/4 mmHg; d 1.203 g cm-3 for 50 wt % BF3, 0.868 g cm-3 for 12 wt % BF3.

Solubility: sol benzene, chloromethanes, dioxane, ether, methanol, THF, toluene.

Form Supplied in: BF3.OEt2: light yellow liquid, packaged under nitrogen or argon; BF3.MeOH is available in solutions of 10-50% BF3 in MeOH.

Preparative Methods: BF3.OEt2 is prepared by passing BF3 through anhydrous ether;1a the BF3.MeOH complex is formed from BF3.OET2 and methanol.

Purification: oxidation in air darkens commercial boron trifluoride etherate; therefore the reagent should be redistilled prior to use. An excess of the etherate in ether should be distilled in an all-glass apparatus with calcium hydroxide to remove volatile acids and to reduce bumping.1b

Handling, Storage, and Precautions: keep away from moisture and oxidants; avoid skin contact and work in a well-ventilated fume hood.

Addition Reactions.

BF3.OEt2 facilitates the addition of moderately basic nucleophiles like alkyl-, alkenyl-, and aryllithium, imines, Grignard reagents, and enolates to a variety of electrophiles.2

Organolithiums undergo addition reactions with 2-isoxazolines to afford N-unsubstituted isoxazolidines, and to the carbon-nitrogen double bond of oxime O-ethers to give O-alkylhydroxylamines.3 Aliphatic esters react with lithium acetylides in the presence of BF3.OEt2 in THF at -78 °C to form alkynyl ketones in 40-80% yields.4 Alkynylboranes, generated in situ from lithium acetylides and BF3.OEt2, were found to react with oxiranes5 and oxetanes6 under mild conditions to afford b-hydroxyalkynes and g-alkoxyalkynes, respectively. (1-Alkenyl)dialkoxyboranes react stereoselectively with a,b-unsaturated ketones7 and esters8 in the presence of BF3.OEt2 to give g,d-unsaturated ketones and a-acyl-g,d-unsaturated esters, respectively.

The reaction of imines activated by BF3.OEt2 with 4-(phenylsulfonyl)butanoic acid dianion leads to 2-piperidones in high yields.9 (Perfluoroalkyl)lithiums, generated in situ, add to imines in the presence of BF3.OEt2 to give perfluoroalkylated amines.10 Enolate esters add to 3-thiazolines under mild conditions to form thiazolidines if these imines are first activated with BF3.OEt2.11 The carbon-nitrogen double bond of imines can be alkylated with various organometallic reagents to produce amines.12 A solution of benzalaniline in acetone treated with BF3.OEt2 results in the formation of b-phenyl-b-anilinoethyl methyl ketone.13 Anilinobenzylphosphonates are synthesized in one pot using aniline, benzaldehyde, dialkyl phosphite, and BF3.OEt2;14 the reagent accelerates imine generation and dialkyl phosphite addition. Similarly, BF3.OEt2 activates the nitrile group of cyanocuprates, thereby accelerating Michael reactions.15

The reagent activates iodobenzene for the allylation of aromatics, alcohols, and acids.16 Allylstannanes are likewise activated for the allylation of p-benzoquinones, e.g. in the formation of coenzyme Qn using polyprenylalkylstannane.17

Nucleophilic silanes undergo stereospecific addition to electrophilic glycols activated by Lewis acids. The glycosidation is highly stereoselective with respect to the glycosidic linkage in some cases using BF3.OEt2. Protected pyranosides undergo stereospecific C-glycosidation with C-1-oxygenated allylsilanes to form a-glycosides.18,19 a-Methoxyglycine esters react with allylsilanes and silyl enol ethers in the presence of BF3.OEt2 to give racemic g,d-unsaturated a-amino acids and g-oxo-a-amino acids, respectively.20 b-Glucopyranosides are synthesized from an aglycon and 2,3,4,6-tetra-O-acetyl-b-D-glucopyranose.21 Alcohols and silyl ethers also undergo stereoselective glycosylation with protected glycosyl fluorides to form b-glycosides.22

BF3.OEt2 reverses the usual anti selectivity observed in the reaction of crotyl organometallic compounds (based on Cu, Cd, Hg, Sn, Tl, Ti, Zr, and V, but not on Mg, Zn, or B) with aldehydes (eq 1a) and imines (eq 1b), so that homoallyl alcohols and homoallylamines are formed, respectively.23-28 The products show mainly syn diastereoselectivity. BF3.OEt2 is the only Lewis acid which produces hydroxy- rather than halo-tetrahydropyrans from the reaction of allylstannanes with pyranosides.29 The BF3.OEt2 mediated condensations of g-oxygenated allylstannanes with aldehydes (eq 1c) and with activated imines (eq 1d) affords vicinal diol derivatives and 1,2-amino alcohols, respectively, with syn diastereoselectivity.30,31 The activated imines are obtained from aromatic amines, aliphatic aldehydes, and a-ethoxycarbamates. The reaction of aldehydes with a-(alkoxy)-b-methylallylstannanes with aldehydes in the presence of BF3.OEt2 gives almost exclusively syn-(E)-isomers.31

The reaction of a-diketones with allyltrimethylstannane in the presence of BF3.OEt2 yields a mixture of homoallylic alcohols, with the less hindered carbonyl group being allylated predominantly.32 The reaction between aldehydes and allylic silanes with an asymmetric ethereal functionality produces syn-homoallyl alcohols when Titanium(IV) Chloride is coordinated with the allylic silane and anti isomers with BF3.OEt2.33

Chiral oxetanes can be synthesized by the BF3.OEt2 catalyzed [2 + 2] cycloaddition reactions of 2,3-O-isopropylidenealdehyde-D-aldose derivatives with allylsilanes, vinyl ethers, or vinyl sulfides.34 The regiospecificity and stereoselectivity is greater than in the photochemical reaction; trans-2-alkoxy- and trans-2-phenylthiooxetanes are the resulting products.

2-Alkylthioethyl acetates can be formed from vinyl acetates by the addition of thiols with BF3.OEt2 as the catalyst.35 The yield is 79%, compared to 75% when BF3.OEt2 is used in conjunction with Mercury(II) Sulfate or Mercury(II) Oxide.

a-Alkoxycarbonylallylsilanes react with acetals in the presence of BF3.OEt2 (eq 2).36 The products can be converted into a-methylene-g-butyrolactones by dealkylation with Iodotrimethylsilane.

The cuprate 1,4-conjugate addition step in the synthesis of (+)-modhephene is difficult due to the neopentyl environment of C-4 in the enone, but it can occur in the presence of BF3.OEt2 (eq 3).37

The reagent is used as a Lewis acid catalyst for the intramolecular addition of diazo ketones to alkenes.38 The direct synthesis of bicyclo[3.2.1]octenones from the appropriate diazo ketones using BF3.OEt2 (eq 4) is superior to the copper-catalyzed thermal decomposition of the diazo ketone to a cyclopropyl ketone and subsequent acid-catalyzed cleavage.38

BF3.OEt2 reacts with fluorinated amines to form salts which are analogous to Vilsmeier reagents, Arnold reagents, or phosgene-immonium salts (eq 5).39 These salts are used to acylate electron-rich aromatic compounds, introducing a fluorinated carbonyl group (eq 6).

Xenon(II) Fluoride and methanol react to form Methyl Hypofluorite, which reacts as a positive oxygen electrophile in the presence of BF3 (etherate or methanol complex) to yield anti-Markovnikov fluoromethoxy products from alkenes.40,41

Aldol Reactions.

Although Titanium(IV) Chloride is a better Lewis acid in effecting aldol reactions of aldehydes, acetals, and silyl enol ethers, BF3.OEt2 is more effective for aldol reactions with anions generated from transition metal carbenes and with tetrasubstituted enol ethers such as (Z)- and (E)-3-methyl-2-(trimethylsilyloxy)-2-pentene.42,43 One exception involves the preparation of substituted cyclopentanediones from acetals by the aldol condensation of protected four-membered acyloin derivatives with BF3.OEt2 rather than TiCl4 (eq 7).44 The latter catalyst causes some loss of the silyl protecting group. The pinacol rearrangement is driven by the release of ring strain in the four-membered ring and controlled by an acyl group adjacent to the diol moiety.

The reagent is the best promoter of the aldol reaction of 2-(trimethylsilyloxy)acrylate esters, prepared by the silylation of pyruvate esters, to afford g-alkoxy-a-keto esters (eq 8).45 These esters occur in a variety of important natural products.

BF3.OEt2 can improve or reverse the aldehyde diastereofacial selectivity in the aldol reaction of silyl enol ethers with aldehydes, forming the syn adducts. For example, the reaction of the silyl enol ether of pinacolone with 2-phenylpropanal using BF3.OEt2 gives enhanced levels of Felkin selectivity relative to the addition of the corresponding lithium enolate.46,47 In the reaction of silyl enol ethers with 3-formyl-D2-isoxazolines, BF3.OEt2 gives predominantly anti aldol adducts, whereas other Lewis acids give syn aldol adducts.48 The reagent can give high diastereofacial selectivity in the addition of silyl enol ethers or silyl ketones to chiral aldehydes.49 In the addition of a nonstereogenic silylketene acetal to chiral, racemic a-thioaldehydes, BF3.OEt2 leads exclusively to the anti product.49

1,5-Dicarbonyl compounds are formed from the reaction of silyl enol ethers with methyl vinyl ketones in the presence of BF3.OEt2 and an alcohol (eq 9).50 a-Methoxy ketones are formed from a-diazo ketones with BF3.OEt2 and methanol, or directly from silyl enol ethers using iodobenzene/BF3.OEt2 in methanol.51

a-Mercurio ketones condense with aldehydes in the presence of BF3.OEt2 with predominant erythro selectivity (eq 10).52 Enaminosilanes derived from acylic and cyclic ketones undergo syn selective aldol condensations in the presence of BF3.OEt2.53

Cyclizations.

Arylamines can undergo photocyclization in the presence of BF3.OEt2 to give tricyclic products, e.g. 9-azaphenanthrene derivatives (eq 11).54

Substituted phenethyl isocyanates undergo cyclization to lactams when treated with BF3.OEt2.55 Vinyl ether epoxides (eq 12),56 vinyl aldehydes,57 and epoxy b-keto esters58 all undergo cyclization with BF3.OEt2.

b-Silyl divinyl ketones (Nazarov reagents) in the presence of BF3.OEt2 cyclize to give cyclopentenones, generally with retention of the silyl group.59 BF3.OEt2 is used for the key step in the synthesis of the sesquiterpene trichodiene, which has adjacent quaternary centers, by catalyzing the cyclization of the dienone to the tricyclic ketone (eq 13).60 Trifluoroacetic acid and trifluoroacetic anhydride do not catalyze this cyclization.

Costunolide, treated with BF3.OEt2, produces the cyclocostunolide (2) and a C-4 oxygenated sesquiterpene lactone (3), 4a-hydroxycyclocostunolide (eq 14).61

Other Condensation Reactions.

BF3.MeOH and BF3.OEt2 with ethanol are widely used in the esterification of various kinds of aliphatic, aromatic, and carboxylic acids;62 the reaction is mild, and no rearrangement of double bonds occurs. This esterification is used routinely for stable acids prior to GLC analysis. Heterocyclic carboxylic acids,63 unsaturated organic acids,64 biphenyl-4,4-dicarboxylic acid,65 4-aminobenzoic acid,63 and the very sensitive 1,4-dihydrobenzoic acid65 are esterified directly.

The dianion of acetoacetate undergoes Claisen condensations with tetramethyldiamide derivatives of dicarboxylic acids to produce polyketides in the presence of BF3.OEt2 (eq 15).66 Similarly, 3,5-dioxoalkanoates are synthesized from tertiary amides or esters with the acetoacetate dianion in the presence of BF3.OEt2 (eq 16).66

Aldehydes and siloxydienes undergo cyclocondensation with BF3.OEt2 to form pyrones (eq 17).67 The stereoselectivity is influenced by the solvent.

BF3.OEt2 is effective in the direct amidation of carboxylic acids to form carboxamides (eq 18).68 The reaction is accelerated by bases and by azeotropic removal of water.

Carbamates of secondary alcohols can be prepared by a condensation reaction with the isocyanate and BF3.OEt2 or Aluminum Chloride.69 These catalysts are superior to basic catalysts such as pyridine and triethylamine. Some phenylsulfonylureas have been prepared from phenylsulfonamides and isocyanates using BF3.OEt2 as a catalyst; for example, 1-butyl-3-(p-tolylsulfonyl)urea is prepared from p-toluenesulfonamide and butyl isocyanate.70 BF3.OEt2 is an excellent catalyst for the condensation of amines to form azomethines (eq 19).71 The temperatures required are much lower than with Zinc Chloride.

Acyltetrahydrofurans can be obtained by BF3.OEt2 catalyzed condensation of (Z)-4-hydroxy-1-alkenylcarbamates with aldehydes, with high diastereo- and enantioselectivity.72 Pentasubstituted hydrofurans are obtained by the use of ketones.

Isobornyl ethers are obtained in high yields by the condensation of camphene with phenols at low temperatures using BF3.OEt2 as catalyst.73 Thus camphene and 2,4-dimethylphenol react to give isobornyl 2,4-dimethylphenyl ether, which can undergo further rearrangement with BF3.OEt2 to give 2,4-dimethyl-6-isobornylphenol.73

The title reagent is also useful for the condensation of allylic alcohols with enols. A classic example is the reaction of phytol in dioxane with 2-methyl-1,4-naphthohydroquinone 1-monoacetate to form the dihydro monoacetate of vitamin K1 (eq 20), which can be easily oxidized to the quinone.74

BF3.OEt2 promotes fast, mild, clean regioselective dehydration of tertiary alcohols to the thermodynamically most stable alkenes.75 11b-Hydroxysteroids are dehydrated by BF3.OEt2 to give D9(11)-enes (eq 21).76,77

Epoxide Cleavage and Rearrangements.

The treatment of epoxides with BF3.OEt2 results in rearrangements to form aldehydes and ketones (eq 22).78 The carbon a to the carbonyl group of an epoxy ketone migrates to give the dicarbonyl product.79 The acyl migration in acyclic a,b-epoxy ketones proceeds through a highly concerted process, with inversion of configuration at the migration terminus.80 With 5-substituted 2,3-epoxycyclohexanes the stereochemistry of the quaternary carbon center of the cyclopentanecarbaldehyde product is directed by the chirality of the 5-position.81 Diketones are formed if the b-position of the a,b-epoxy ketone is unsubstituted. The 1,2-carbonyl migration of an a,b-epoxy ketone, 2-cycloheptylidenecyclopentanone oxide, occurs with BF3.OEt2 at 25 °C to form the cyclic spiro-1,3-diketone in 1 min (eq 23).82

The migration of the carbonyl during epoxide cleavage is used to produce hydroxy lactones from epoxides of carboxylic acids (eq 24).83 a-Acyl-2-indanones,84 furans,85 and D2-oxazolines86 (eq 25) can also be synthesized by the cleavage and rearrangement of epoxides with BF3.OEt2. The last reaction has been conducted with sulfuric acid and with tin chloride, but the yields were lower. g,d-Epoxy tin compounds react with BF3.OEt2 to give the corresponding cyclopropylcarbinyl alcohols (eq 26).87

Remotely unsaturated epoxy acids undergo fission rearrangement when treated with BF3.OEt2. Hence, cis and trans ketocyclopropane esters are produced from the unsaturated epoxy ester methyl vernolate (eq 27).88

Epoxy sulfones undergo rearrangement with BF3.OEt2 to give the corresponding aldehydes.89 a-Epoxy sulfoxides, like other negatively substituted epoxides, undergo rearrangement in which the sulfinyl group migrates and not the hydrogen, alkyl, or aryl groups (eq 28).89

a,b-Epoxy alcohols undergo cleavage and rearrangement with BF3.OEt2 to form b-hydroxy ketones.90 The rearrangement is stereospecific with respect to the epoxide and generally results in anti migration. The rearrangement of epoxy alcohols with b-substituents leads to a,a-disubstituted carbonyl compounds.91

The BF3.OEt2-induced opening of epoxides with alcohols is regioselective, but the regioselectivity varies with the nature of the substituents on the oxirane ring.92 If the substituent provides charge stabilization (as with a phenyl ring), the internal position is attacked exclusively. On the other hand, terminal ethers are formed by the regioselective cleavage of the epoxide ring of glycidyl tosylate.92

A combination of cyanoborohydride and BF3.OEt2 is used for the regio- and stereoselective cleavage of most epoxides to the less substituted alcohols resulting from anti ring opening.93 The reaction rate of organocopper and cuprate reagents with slightly reactive epoxides, e.g. cyclohexene oxide, is dramatically enhanced by BF3.OEt2.94 The Lewis acid and nucleophile work in a concerted manner so that anti products are formed.

Azanaphthalene N-oxides undergo photochemical deoxygenation reactions in benzene containing BF3.OEt2, resulting in amines in 70-80% yield;95 these amines are important in the synthesis of heterocyclic compounds. Azidotrimethylsilane reacts with trans-1,2-epoxyalkylsilanes in the presence of BF3.OEt2 to produce (Z)-1-alkenyl azides.96 The cis-1,2-epoxyalkylsilanes undergo rapid polymerization in the presence of Lewis acids.

Other Rearrangements.

BF3.OEt2 is used for the regioselective rearrangement of polyprenyl aryl ethers to yield polyprenyl substituted phenols, e.g. coenzyme Qn.97 The reagent is used in the Fries rearrangement; for example, 5-acetyl-6-hydroxycoumaran is obtained in 96% yield from 6-acetoxycoumaran using this reagent (eq 29).98

Formyl bicyclo[2.2.2]octane undergoes the retro-Claisen rearrangement to a vinyl ether in the presence of BF3.OEt2 at 0 °C (eq 30), rather than with HOAc at 110 °C.99

BF3.OEt2 is used for a stereospecific 1,3-alkyl migration to form trans-2-alkyltetrahydrofuran-3-carbaldehydes from 4,5-dihydrodioxepins (eq 31), which are obtained by the isomerization of 4,7-dihydro-1,3-dioxepins.100 Similarly, a-alkyl-b-alkoxyaldehydes can be prepared from 1-alkenyl alkyl acetals by a 1,3-migration using BF3.OEt2 as catalyst.101 Syn products are obtained from (E)-1-alkenyl alkyl acetals and anti products from the (Z)-acetals.

The methyl substituent, and not the cyano group, of 4-methyl-4-cyanocyclohexadienone migrates in the presence of BF3.OEt2 to give 3-methyl-4-cyanocyclohexadienone.102 BF3.OEt2-promoted regioselective rearrangements of polyprenyl aryl ethers provide a convenient route for the preparation of polyprenyl-substituted hydroquinones (eq 32), which can be oxidized to polyprenylquinones.103

The (E)-(Z) photoisomerization of a,b-unsaturated esters,104 cinnamic esters,105 butenoic esters,106 and dienoic esters106 is catalyzed by BF3.OEt2 or Ethylaluminum Dichloride. The latter two reactions also involve the photodeconjugation of a,b-unsaturated esters to b,g-unsaturated esters. The BF3.MeOH complex is used for the isomerization of 1- and 2-butenes to form equal quantities of cis- and trans-but-2-enes;107 the BF3.OEt2-acetic acid complex is not as effective.

The complex formed with BF3.OEt2 and Epichlorohydrin in DMF acts as a catalyst for the Beckmann rearrangement of oximes.108 Cyclohexanone, acetaldehyde, and syn-benzaldehyde oximes are converted into ε-caprolactam, a mixture of N-methylformamide and acetamide, and N-phenylacetamide, respectively.

The addition of BF3.OEt2 to an a-phosphorylated imine results in the 1,3-transfer of a diphenylphosphinoyl group, with resultant migration of the C-N=C triad.109 This method is less destructive than the thermal rearrangement. The decomposition of dimethyldioxirane in acetone to methyl acetate is accelerated with BF3.OEt2, but acetol is also formed.110 Propene oxide undergoes polymerization with BF3.OEt2 in most solvents, but isomerizes to propionaldehyde and acetone in dioxane.111

Hydrolysis.

BF3.OEt2 is used for stereospecific hydrolysis of methyl ethers, e.g. in the synthesis of (±)-aklavone.112 The reagent is also used for the mild hydrolysis of dimethylhydrazones.113 The precipitate formed by the addition of BF3.OEt2 to a dimethylhydrazone in ether is readily hydrolyzed by water to the ketone; the reaction is fast and does not affect enol acetate functionality.

Cleavage of Ethers.

In aprotic, anhydrous solvents, BF3.MeOH is useful for the cleavage of trityl ethers at rt.114 Under these conditions, O- and N-acyl groups, O-sulfonyl, N-alkoxycarbonyl, O-methyl, O-benzyl, and acetal groups are not cleaved.

BF3.OEt2 and iodide ion are extremely useful for the mild and regioselective cleavage of aliphatic ethers and for the removal of the acetal protecting group of carbonyl compounds.115,116 Aromatic ethers are not cleaved, in contrast to other boron reagents. BF3.OEt2, in chloroform or dichloromethane, can be used for the removal of the t-butyldimethylsilyl (TBDMS) protecting group of hydroxyls, at 0-25 °C in 85-90% yield.117 This is an alternative to ether cleavage with Tetra-n-butylammonium Fluoride or hydrolysis with aqueous Acetic Acid.

In the presence of BF3.OEt2, dithio-substituted allylic anions react exclusively at the a-carbons of cyclic ethers, to give high yields of the corresponding alcohol products (eq 33).118 The dithiane moiety is readily hydrolyzed with Mercury(II) Chloride to give the keto derivatives.

Inexpensive di-, tri-, and tetramethoxyanthraquinones can be selectively dealkylated to hydroxymethoxyanthraquinones by the formation of difluoroboron chelates with BF3.OEt2 in benzene and subsequent hydrolysis with methanol.119 These unsymmetrically functionalized anthraquinone derivatives are useful intermediates for the synthesis of adriamycin, an antitumor agent. 2,4,6-Trimethoxytoluene reacts with cinnamic acid and BF3.OEt2, with selective demethylation, to form a boron heterocycle which can be hydrolyzed to the chalcone aurentiacin (eq 34).120

Reductions.

In contrast to hydrosilylation reactions catalyzed by metal chlorides, aldehydes and ketones are rapidly reduced at rt by Triethylsilane and BF3.OEt2, primarily to symmetrical ethers and borate esters, respectively.121 Aryl ketones like acetophenone and benzophenone are converted to ethylbenzene and diphenylmethane, respectively. Friedel-Crafts acylation-silane reduction reactions can also occur in one step using these reagents; thus Benzoyl Chloride reacts with benzene, triethylsilane, and BF3.OEt2 to give diphenylmethane in 30% yield.121

BF3.OEt2 followed by Diisobutylaluminum Hydride is used for the 1,2-reduction of g-amino-a,b-unsaturated esters to give unsaturated amino alcohols, which are chiral building blocks for a-amino acids.122 a,b-Unsaturated nitroalkenes can be reduced to hydroxylamines by Sodium Borohydride and BF3.OEt2 in THF;123,124 extended reaction times result in the reduction of the hydroxylamines to alkylamines. Diphenylamine-borane is prepared from sodium borohydride, BF3.OEt2, and diphenylamine in THF at 0 °C.125 This solid is more stable in air than BF3.THF and is almost as reactive in the reduction of aldehydes, ketones, carboxylic acids, esters, and anhydrides, as well as in the hydroboration of alkenes.

Bromination.

BF3.OEt2 can catalyze the bromination of steroids that cannot be brominated in the presence of HBr or sodium acetate. Hence, 11a-bromoketones are obtained in high yields from methyl 3a,7a-diacetoxy-12-ketocholanate.126 Bromination (at the 6a-position) and dibromination (at the 6a- and 11a-positions) of methyl 3a-acetoxy-7,12-dioxocholanate can occur, depending on the concentration of bromine.127

A combination of BF3.OEt2 and a halide ion (tetraethylammonium bromide or iodide in dichloromethane or chloroform, or sodium bromide or iodide in acetonitrile) is useful for the conversion of allyl, benzyl, and tertiary alcohols to the corresponding halides.128,129

Diels-Alder Reactions.

BF3.OEt2 is used to catalyze and reverse the regiospecificity of some Diels-Alder reactions, e.g. with peri-hydroxylated naphthoquinones,130 sulfur-containing compounds,131 the reaction of 1-substituted trans-1,3-dienes with 2,6-dimethylbenzoquinones,132 and the reaction of 6-methoxy-1-vinyl-3,4-dihydronaphthalene with p-quinones.133 BF3.OEt2 has a drastic effect on the regioselectivity of the Diels-Alder reaction of quinoline- and isoquinoline-5,8-dione with piperylene, which produces substituted azaanthraquinones.134 This Lewis acid is the most effective catalyst for the Diels-Alder reaction of furan with methyl acrylate, giving high endo selectivity in the 7-oxabicyclo[2.2.1]heptene product (eq 35).135

a-Vinylidenecycloalkanones, obtained by the reaction of Lithium Acetylide with epoxides and subsequent oxidation, undergo a Diels-Alder reaction at low temperature with BF3.OEt2 to form spirocyclic dienones (eq 36).136

Other Reactions.

The 17-hydroxy group of steroids can be protected by forming the THP (O-tetrahydropyran-2-yl) derivative with 2,3-dihydropyran, using BF3.OEt2 as catalyst;137 the yields are higher and the reaction times shorter than with p-toluenesulfonic acid monohydrate.

BF3.OEt2 catalyzes the decomposition of b,g-unsaturated diazomethyl ketones to cyclopentenone derivatives (eq 37).138,139 Similarly, g,d-unsaturated diazo ketones are decomposed to b,g-unsaturated cyclohexenones, but in lower yields.140

BF3.OEt2 is an effective reagent for debenzyloxycarbonylations of methionine-containing peptides.141 Substituted 6H-1,3-thiazines can be prepared in high yields from BF3.OEt2-catalyzed reactions between a,b-unsaturated aldehydes, ketones, or acetals with thioamides, thioureas, and dithiocarbamates (eq 38).142

a-Alkoxy ketones can be prepared from a-diazo ketones and primary, secondary, and tertiary alcohols using BF3.OEt2 in ethanol.143 Nitrogen is released from a solution of a-Diazoacetophenone and BF3.OEt2 in ethanol to give a-ethoxyacetophenone.143

Anti-diols can be formed from b-hydroxy ketones using Tin(IV) Chloride or BF3.OEt2.144 The hydroxy ketones are silylated, treated with the Lewis acid, and then desilylated with Hydrogen Fluoride. Syn-diols are formed if Zinc Chloride is used as the catalyst.

BF3.OEt2 activates the formal substitution reaction of the hydroxyl group of g- or d-lactols with some organometallic reagents (M = Al, Zn, Sn), so that 2,5-disubstituted tetrahydrofurans or 2,6-disubstituted tetrahydropyrans are formed.145

A new method of nitrile synthesis from aldehydes has been discovered using O-(2-aminobenzoyl)hydroxylamine and BF3.OEt2, achieving 78-94% yields (eq 39).146

Carbonyl compounds react predominantly at the a site of dithiocinnamyllithium if BF3.OEt2 is present, as the hardness of the carbonyl compound is increased (eq 40).147 The products can be hydrolyzed to a-hydroxyenones.

Optically active sulfinates can be synthesized from sulfinamides and alcohols using BF3.OEt2.148 The reaction proceeds stereospecifically with inversion of sulfinyl configuration; the mild conditions ensure that the reaction will proceed even with alcohols with acid-labile functionality.

Related Reagents.

See entries for other Lewis acids, e.g. Zinc Chloride, Aluminum Chloride, Titanium(IV) Chloride; also see entries for Boron Trifluoride (and combination reagents), and combination reagents employing boron trifluoride etherate, e.g. n-Butyllithium-Boron Trifluoride Etherate, Cerium(III) Acetate-Boron Trifluoride Etherate, Lithium Aluminum Hydride-Boron Trifluoride Etherate, Methylcopper-Boron Trifluoride Etherate


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Veronica Cornel

Emory University, Atlanta, GA, USA



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