Boron trifluoride tetrahydrofuran

Aqueous mineral acids react with BF to yield the hydrates of BF or the hydroxyfluoroboric acids, fluoroboric acid, or boric acid. Solution in aqueous alkali gives the soluble salts of the hydroxyfluoroboric acids, fluoroboric acids, or boric acid. Boron trifluoride, slightly soluble in many organic solvents including saturated hydrocarbons (qv), halogenated hydrocarbons, and aromatic compounds, easily polymerizes unsaturated compounds such as butylenes (qv), styrene (qv), or vinyl esters, as well as easily cleaved cycHc molecules such as tetrahydrofuran (see Furan derivatives). Other molecules containing electron-donating atoms such as O, S, N, P, etc, eg, alcohols, acids, amines, phosphines, and ethers, may dissolve BF to produce soluble adducts. 

A suspension of lithium aluminum deuteride (1.6 g) in dry tetrahydrofuran (60 ml) is added dropwise to a stirred and cooled (with ice-salt bath) solution of 5a-androst-l4-ene-3j3,17j3-diol (179, 1.6 g) and boron trifluoride-etherate (13.3 g) in dry tetrahydrofuran (60 ml). The addition is carried out in a dry nitrogen atmosphere, over a period of 30 min. After an additional 30 min of cooling the stirring is continued at room temperature for 2 hr. The cooling is resumed in a dry ice-acetone bath and the excess deuteriodiborane is destroyed by the cautious addition of propionic acid. The tetrahydrofuran is then evaporated and the residue is dissolved in propionic acid and heated under reflux in a nitrogen atmosphere for 8 hr. After cooling, water is added and the product extracted with ether. The ether... 

To a suspension of 73.9 g of 1 -methyl-5-nitro-3-phenylindole-2-carbonitrile in 1.5 liters of dry tetrahydrofuran Is added dropwise a solution of 126 g of boron trifluoride etherate in 220 ml of dry tetrahydrofuran with stirring for 2 hours. After addition, stirring is continued for an additional 3 hours. To the reaction mixture Is added dropwise 370 ml of water and then 370 ml of concentrated hydrochloric acid with stirring under ice-cooling. 

In addition to the boron trifluoride-diethyl ether complex, chlorotrimcthylsilanc also shows a rate accelerating effect on cuprate addition reactions this effect emerges only if tetrahydrofuran is used as the reaction solvent. No significant difference in rate and diastereoselectivity is observed in diethyl ether as reaction solvent when addition of the cuprate, prepared from butyllithium and copper(I) bromide-dimethylsulfide complex, is performed in the presence or absence of chlorotrimethylsilane17. If, however, the reaction is performed in tetrahydrofuran, the reaction rate is accelerated in the presence of chlorotrimethylsilane and the diastereofacial selectivity increases to a ratio of 88 12 17. In contrast to the reaction in diethyl ether, the O-silylated product is predominantly formed in tetrahydrofuran. The alcohol product is only formed to a low extent and showed a diastereomeric ratio of 55 45, which is similar to the result obtained in the absence of chlorotrimethylsilane. This discrepancy indicates that the selective pathway leading to the O-silylated product is totally different and several times faster than the unselective pathway" which leads to the unsilylated alcohol adduct. A slight further increase in the Cram selectivity was achieved when 18-crown-6 was used in order to increase the steric bulk of the reagent. 

The alkynyl reagent 9 was recently introduced for the dia stereoselective synthesis of tertiary propargylic alcohols144. 9 can be prepared as a solid 1 1 complex with tetrahydrofuran by treatment of 9-methoxy-9-borabicyclo[3.3.1]nonane with (trimethylsilylethynyl)lithium, followed by addition of boron trifluoride-diethyl ether complex. The nucleophilic addition of reagent 9 to (R)-2-methoxy-2-methylhexanal (10) afforded a mixture of the diastereomers 11 with a considerable preference to the nonchelation-controlled (3S,4R)-isomer144. 

The use of boron trifluoride-diethyl ether complex as the Lewis acid in these reactions promotes silyl group migration and gives rise to the formation of tetrahydrofurans with excellent stereoselectivity82. 

Stannane 6a underwent facile transmetalation in tetrahydrofuran at — 78 °C on treatment with butyllithium to afford 6b. Addition of the lithium reagent 6b to a solution of 1.1 equivalents of copper(I) bromide-dimethyl sulfide in 1 1 diisopropyl sulfide/tetrahydrofuran at — 78 °C gave the copper reagent 6c, which reacted with methyl vinyl ketone at —78 "C in the presence of boron trifluoride-diethyl ether65, producing 7 in 55% yield65. 

A boron analog - sodium borohydride - was prepared by reaction of sodium hydride with trimethyl borate [84 or with sodium fluoroborate and hydrogen [55], and gives, on treatment with boron trifluoride or aluminum chloride, borane (diborane) [86. Borane is a strong Lewis acid and forms complexes with many Lewis bases. Some of them, such as complexes with dimethyl sulfide, trimethyl amine and others, are sufficiently stable to have been made commercially available. Some others should be handled with precautions. A spontaneous explosion of a molar solution of borane in tetrahydrofuran stored at less than 15° out of direct sunlight has been reported [87]. 

Sodium borohydride does not reduce the free carboxylic group, but borane prepared from sodium borohydride and boron trifluoride etherate in tetrahydrofuran converts aliphatic acids to alcohols at 0-25° in 89-100% yields... 

Tetrahydrofuran itself can be opened using either the stoichiometric or the catalytic version of arene-promoted lithiation, but both cases need the activation by boron trifluoride. The catalytic reaction was performed by treating the solvent THF 324 with the complex boron trifluoride-etherate and a catalytic amount (4%) of naphthalene. The intermediate 325 was formed. Further reaction with carbonyl compounds and flnal hydrolysis yielded the expected 1,5-diols 326 (Scheme 95), which could be easily cyclized to the corresponding substituted tetrahydropyrans under acidic conditions (concentrated FlCl). 

A. (S)-Phenylalanol. A dry, 3-L, three-necked flask is equipped with a mechanical stirrer and a reflux condenser connected to a mineral oil bubbler. The flask Is loaded with 165 g (1.00 mol) of (S)-phenylalanlne (Note 1), then equipped with a 250-mL pressure-equalized addition funnel capped with a rubber septum through which is Inserted a nitrogen-inlet needle. The flask Is swept with nitrogen and filled with 500 id. of anhydrous tetrahydrofuran, and the addition funnel is charged with 123 mL (1,00 mol) of freshly distilled boron trifluoride etherate via cannula (Note 2). The boron trifluoride etherate Is added dropwlse to the phenylalanine slurry over a 30-m1n period with stirring, and the mixture is heated at reflux for 2 hr, resulting in a... 

Reagent grade tetrahydrofuran (Fisher Scientific Company) was either freshly distilled from sodium metal and benzophenone or dried for at least 24 hr over activated Linde 4 A molecular sieves. Boron trifluoride etherate was redistilled prior to use. Fresh bottles of redistilled boron trifluoride etherate purchased from Aldrich Chemical Company, Inc., also usually give good results. 

Alkyl nitrites can also be used in anhydrous media and, for example, 4-hydroxyben-zenediazonium tetrafluoroborate is isolated in 89% yield after diazotization with isopcntyl nitrite, hydrogen fluoride and boron trifluoride in ethanol/diethyl ether.96 Diazotization can also be performed in dichloromethane or ethers (diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane) with terl-butyl nitrite and boron trifluoride-diethyl ether complex which generates nitrosyl fluoride in situ.229 Excess boron trifluoride is used to trap water and tert-butyl alcohol, so that the reaction can be considered as being performed under complete anhydrous conditions. Yields are higher in dichloromethane, but 1,2-dimethoxyethane is preferred for less soluble amines. This procedure has been successfully applied to the synthesis of mono-and difluorobenzo[c]phcnanthrenes.230... 

Synthesis of racemic naproxene Friedel-Crafts acylation (aluminum chloride - nitrobenzene) of p-naphthol methyl ether affords 2-acetyl-6-methoxy naphthalene, which, when treated with either dimethyl sulfonium or dimethylsulfoxonium methylide, gives 2-(6-methoxynaphthalen-2-yl)propylene oxide. Treatment of the latter with boron trifluoride etherate in tetrahydrofuran gives 2-(6-methoxynaphthalen-2-yl)propionaldehyde, which is oxidized using Jones reagent (4 M chromic acid) to yield the racemic 2-(6-methoxynaphthalen-2-yl)propionic acid. 

The ring expansion of 2-f-butyloxetanes to tetrahydrofurans in the presence of a Lewis catalyst has been reported. Treatment of the oxetane (341) with boron trifluoride etherate in diethyl ether leads to the ring expanded product (342). It is suggested that an intermediate carbocation is formed (Scheme 92) (79CC382). 

Borane-Sodium borohydride, 42 Borane-Tetrahydrofuran, 42 Boron tribromide, 43 Boron trichloride, 43 Boron trifluoride, 44 Boron trifluoride etherate, 3, 6, 10, 13, 43, 82, 99, 193, 200, 211, 306, 308, 321, 322... 

Borane can be prepared in situ as described in Expts 5.44 and 5.89. Alternatively, a separate solution of borane in tetrahydrofuran can be prepared by adding a solution of sodium borohydride to boron trifluoride-etherate and sweeping the resulting borane into tetrahydrofuran with the aid of a nitrogen gas stream. 

Borane, as a solution in tetrahydrofuran or generated in situ by the reaction of a metal hydride with boron trifluoride etherate, adds readily to alkenes to yield trialkylboranes. With a terminal alkene the reaction is highly (though not completely) regioselective and gives a primary trialkylborane, since the mode of addition results from the electrophilic character of the boron atom. 

Tetrahydrofuran (350 cm3), sodium borohydride (14.1 g) and (la,5a,6a)-3-N-benzyl-6-nitro-2,4-dioxo-3-azabicyclo[3.1.0]hexane (35.0 g, mmol) obtained above were stirred under nitrogen for 0.25 h and then treated dropwise with boron trifluoride-THF complex containing 21.5% BF3 (44.9 cm3) so that the exotherm was controlled to <40°C. After addition was completed, the reaction mixture was stirred for 3 h at 40°C, quenched slowly with water/THF 1 1 (70 cm3) to avoid excessive foaming, and stirred for 0.5 h at 50°C to ensure that the quench of unreacted diborane generated in situ was completed. The quench formed a salt slurry which was filtered and washed with THF (140 cm3) the combined filtrate was partially concentrated, diluted with water (350 cm3) and further concentrated to remove most of the THF, and extracted with ethyl acetate (140 cm3). The resulting ethyl acetate solution was concentrated to afford the (la,5a,6a)-3-N-benzyl-6-nitro-3-azabicyclo[3.1.0]hexane as a clear oil (30.6 g, 97%). 

After filtration, add slowly boron trifluoride etherate, and then the solution of the tetrahydrofuran intermediate in CH2CI2 (3 mL). Stir for 1 h. 

The dropping funnel is washed with small portions of tetrahydrofuran to remove all traces of boron trifluoride etherate and then is charged with a solution containing 10.57 g. (0.176 mole) of dry ethylenediamine in 100 ml. of tetrahydrofuran. Commercial ethylenediamine (Eastman 98%) is dried by careful distillation from sodium behind a safety shield in a hood or by the procedure described in reference 11. This solution is added dropwise (about 2-2 hours) and the reaction mixture warmed with stirring to room temperature. 

A suspension prepared from 4.25 g. of 95% sodium borohydride (0.11 mole) and 150 ml. of tetrahydrofuran is cooled in an ice-water bath and stirred while a solution containing 17 ml. (0.13 mole) of boron trifluoride-diethylether in 60 ml. of tetrahydrofuran is added dropwise over a period of 45 minutes. Thirty grams (0.11 mole) of triphenylphosphine is dissolved in 130 ml. of tetrahydrofuran, and this solution is added through a dropping funnel to the cooled suspension (1 hour). The mixture is allowed to warm to room temperature. Solids are collected by filtration, and the crude product is recovered by evaporation of the solvent from the filtrate in vacuo. Yield is 32 g. (100% theory). 

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