Tetrahydrofuran reaction with -butyllithium

Analogous reaction with the adduct 11 of thiophene 1,1-dioxide gave only a very poor yield of the substituted cycloheptatriene 12. The latter could be converted to l//-cyclopropabenzene (13) in 11% yield by reaction with titanium(III) chloride and lithium aluminum hydride in tetrahydrofuran, or in 50% yield by reaction with butyllithium in hexane. 

Subsequently, Kametani and coworkers observed a similar allylic sulfoxide-sulfenate-sulfoxide rearrangement. These authors reported the exceptionally facile ringopening reaction of condensed cyclobutenes facilitated by arylsulfinyl carbanion substituents. For example, treatment of sulfoxide 68 with butyllithium in tetrahydrofuran at — 30°C for 10 min, followed by normal workup, results in the formation of product 71, which can be explained by the intervention of a double [2,3]-sigmatropic rearrangement of the initial product 69 via 70 (equation 32). A similar double [2,3]-sigmatropic rearrangement of 1,4-pentadienylic sulfoxides has also been reported by Sammes and coworkers. ... 

Strong base treatment of the spiro salt 49 gives a benzyne (107) from which the isolated products were produced by further reaction. For example, with n-butyllithium and furan in tetrahydrofuran, 108 is produced after hydrogenation and acid treatment via 109. Reaction with phenyllithium gives 110 (R == Ph and Me) by subsequent addition of phenyl or methyl anion to the benzyne, respectively, and 110 (R = I) by subsequent reaction with iodine anion. Similarly the 9,9-diphenyl salt 111 gives 112 with phenyllithium. Pyrolysis of the spiro salt 49 gives 50. 

Although tetrahydrofuran is commonly used as a solvent in organometallic chemistry, it does undergo reaction with n-butyllithium. Proton-lithium exchange at an a-position is followed by cleavage to ethylene and the enolate anion of acetaldehyde. The half-life of a-lithio-THF is 10 min at 35°C (Scheme 55) (72JOC560). 

Efficient methods for the preparation of pentadienyl compounds of the alkali metals have now been developed. Treatment of 1,4-dienes with butyllithium in the presence of tetrahydrofuran (thf) at —78° yields deep orange solutions which contain pentadienyllithiums (36,37). Any excess butyllithium may be destroyed by its reaction with thf by allowing the mixture to warm up briefly to room temperature (38). Similar results are obtained using potassium amide in liquid ammonia (39). 1,3-Dienes, however, do not yield pentadienyl anions under these conditions, unless the diene is conjugated with a phenyl (40), vinyl (41), trimethylsilyl (48), or similar stabilizing group. Unfortunately, 1,4-dienes are not very readily accessible. However, 1,3- as well as 1,4-dienes can be metallated using a 1 1 mixture of butyllithium and potassium tm-butoxide (49). Trimethylsilylmethylpotassium is also effective (44). 

In Scheme 1.3, hexanal on reaction with 1,3-propanedithiol gives the 1,3-dithiane derivative 1.8. A strong base such as u-butyllithium abstracts the proton to give the corresponding 2-lithio-1,3-dithiane 1.9, which reacts with 1-bromopentane to give alkylated product 1.10. Treatment of 1.10 with FIgO and BF3 (boron trifluoride) in aqueous THF (tetrahydrofuran) yields the dipentyl ketone (the corey-seebach reaction ). Thus, dithianyllithium (2-lithio-1,3-dithiane) 1.9 is an acyl anion synthetic equivalent. 

Treatment of 2-deoxy-3,4 5,6-di-O-isopropylidene-D-arahtno-hex-ose diethyl dithioacetal (128a) with butyllithium in tetrahydrofuran produced a carbanion that is stable by virtue of having no electronegative substituent at C-2 this anion subsequently reacted with iodo-methane to afford255" l,3-dideoxy-4,5 6,7-di-O-isopropylidene-D-arabino-heptulose diethyl dithioacetal (128b) in 82% yield (see Section 11,5). This reaction provides a useful route to 1,3-dideoxy-2-ketoses. 

Reaction of 2-chloro-l,l-dicyclopropylethene (35, prepared from dicyclopropyl ketone by chloroolefination) with butyllithium in tetrahydrofuran between — 110°C and + 20 °C affords dicyclopropylethyne (36) in 83% yield together with some 1,1-dicyclopropylhex-l-ene (37,10% yield). Hydrogenation of 36 over a Lindlar catalyst proceeded almost quantitatively and stereospecifically to give (Z)-l,2-dicyclopropylethene (38). 

In most cases the reaction has been performed using a solution of the 1,1-dihalocyclopro-pane kept at or below 0 °C, to which is added butyllithium, which gives the cyclopropyllithium intermediate, followed by chlorotrimethylsilane. In the best cases the 1-bromo-l-trimethylsilyl-cyclopropane, e. g. 1 (Table 22), is formed in close to 90% yield. Thus, when 2-benzyIoxymethyl-1,1 -dibromocyclopropane was reacted first with butyllithium in tetrahydrofuran at — 95 "C and then with chlorotrimethylsilane, 2-benzyloxymethyl-l -bromo-1 -trimethylsilylcyclopropane (le) was obtained in 75% yield as a 1 1 isomeric mixture. An analogous reaction with 1,1-dibro-mo-2-ethoxycyclopropane gave l-bromo-2-ethoxy-l-trimethylsilylcyclopropane (Ij) in 87% yield.Under similar conditions 7,7-dibromobicyclo[4.1.0]heptane was converted to a 97 3 mixture of exo- and cn o-7-bromo-7-trimethylsilylbicyclo[4.1.0]heptane (Im) in 80% yield. 

The only product isolated from the reaction of 5,5,10,10-tetrabromotricyclo[7.1.0.0 ]decane (61) with methyllithium was naphthalene, but cyclodecahexaene was probably an intermediate. The same substrate 61 reacted efficiently with butyllithium in tetrahydrofuran when promoted by ultrasound, and a good yield of the cyclic bisallene 62 was obtained in only a few minutes. ... 

Dimethyl-4,8-dioxaspiro[2.5]oct-l-ene is a synthetically useful precursor for cyclopropenones because of its stability and ready availability. The sodium derivative 1 of the cyclopropenone acetal in liquid ammonia reacted with alkyl halides giving alkyl-substituted cyclopropenone acetals 3. The lithiated cyclopropenone acetal 4 was generated by treating the cyclopropenone acetal with one equivalent of butyllithium in tetrahydrofuran. Reaction of the lithium carbanion 4 with alkyl halides proceeded cleanly in the presence of two equivalents of hexamethylphosphoric triamide (Table 1, entries 1-4). The lithium compound underwent nucleophilic addition to carbonyl compounds smoothly at — 70 C giving hydroxymethyl derivatives 5 (Table 1, entries 5-10). 

The catalyst was prepared by treating in situ NMAP pellets with butyllithium in tetrahydrofuran. The oxophorone derivative 148 was added at — 70 °C followed by the Michael acceptor and some hexamethylphosphoramide the reaction requires 10-18 h at room temperature. The domino Michael reaction of the kinetic enolate of 148 with an electron-poor carbon-carbon double bond furnished stereoselectively the enc/o-bicyclo[2.2.2]octane derivative 149 (Scheme 3.44). 

For compounds in which the -carbon of the enolate is sterically hindered, this problem can normally be eliminated by the use of diethyl ether as the solvent. In several cases a switch from exclusive O-acylation in tetrahydrofuran to complete C-acylation in ether has been observed, and the conversion of 7 into 8 provides a typical illustration. When 3-methyl-2-cyclohexen-1-one 9 is converted into 10 by the addition of lithium dimethyl cuprate followed by in situ reaction with methyl cyanoformate, however, enol carbonate 11 accounts for 6% of the products. This can be avoided if the intermediate enolate is trapped as the enol trimethylsilyl ether and the enolate reliberated by treatment with butyllithium (note that the traditional reagent, methyllithium, Is Ineffective in ether as a solvem), but the overall yield is reduced. 

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