Butyl Lithium-based Alkylation Reactions

Buchachenko (1974) has advanced another theory. He based his reasoning on the absence of the CIDNP signals for the reaction of //-butyl iodide with t-butyl lithium conducted in ether at -70°C. The halogen and metal quickly exchange under these conditions, but the C—C bond does not form. In contrast to the preceding scheme, Buchachenko s theory assumes that the radicals produced form complexes with the alkyl lithium associates. Alkyl... 

The phosphonium ylide needed for a particular synthesis is obtained by an Sn2 reaction between triphenylphosphine and an alkyl halide with the appropriate number of carbon atoms. A proton on the carbon adjacent to the positively charged phosphorus atom is sufficiently acidic (p/fa = 35) to be removed by a strong base such as butyl-lithium (Section 12.11). 

An c ff-unsaturated sulphoxide (72) is the final product isolated when cis-1,2-diphenylthiiran 5-oxide (70) is treated with butyl-lithium, followed by alkylation. The lithio-thiiran 5-oxide (71) is a presumed intermediate. A number of papers have dealt with the reactions of alkyl-lithiums or other strong bases with c S-un-saturated sulphoxides. The reactions observed include (a) or-deprotonation, affording a-sulphinylvinyl anions, which turn out to be surprisingly configuration-... 

Use of the methylsulphinyl carbanion as base is recommended for the synthesis of ethers from alcohols and alkyl halides. The catalysed formation of dimethyl ether from hydrogen and carbon dioxide has been reported. Carey has described the use of the silicon-modified organolithium reagent (73) in the preparation of vinyl thioethers (Scheme 151). In order to extend the scope of this reaction to include vinyl ethers themselves, an attempt was made to metalate trimethylsilylmethyl ether use of n-buty 1-lithium resulted in nucleophilic attack on silicon, whereas t-butyl-lithium abstracted the wrong proton, as shown in Scheme 151. 

C-Alkylation of weakly activated methylpyridines to yield the isopropyl and tert-butyl derivatives (35-40%), which normally requires the use of strong bases, such alkyl lithiums, is earned out effectively using a phase-transfer catalyst and aqueous sodium hydroxide on the /V-methylpyridinium salts. The pyridines are regenerated by reaction with sodium acetate or sodium 4-toluenethiolate [134]. 3-Methylpyridine fails to react under these conditions and the synthesis of 2-ethylpyridines by this procedure is also unsuccessful. 

The stereoreactivity of the methylene protons of er -butyl (4-methylphenylsulfinyl)acetate is in sharp contrast with the highly stereospecific behavior of the methylene protons of benzyl methyl sulfoxide. An NMR study of phenylsulfinylacetic acid showed that the reactivity of these two diastereotopic protons is comparable83. These protons are even magnetically equivalent in deuterium oxide solution. The diastereoselectivity of the alkylation of a-sulfinyl carboxylic esters is poor, moreover, the reaction proceeds only when butyllithium, ferz-butyllithium or lithium diethylamide is used as the base in the preparation of the carbanion82. 

The treatment of thiazole with n-butyl- or phenyllithium leads to exclusive deprotonation at C-2. When the 2-position is blocked, deprotonation occurs selectively at C-5. However, if the substituent at C-2 is an alkyl group, the kinetic acidities of the protons at the a-position and at the 5-position are similar. The reaction of 2,4-dimethylthiazole with butyllithium at -78°C yields the 5-lithio derivative (289) as the major product but if the reaction is carried out at higher temperature the thermodynamically more stable 2-lithiomethyl derivative (290) is obtained (Scheme 37). The metallation at these two positions is also dependent on the strength and bulk of the base employed (74JOC1192) lithium diisopropylamide is preferred for selective deprotonations at the 5-position. 

Michael additions. Gerlach and Kiinzler report that the lithium enolate of S-t-butyl thioacetate undergoes 1,4-addition to cyclopentenone. They have extended this Michael reaction to a synthesis of methyl jasmonate (5), based on the similar conjugate addition of the trimethylsilyl enolate 1 promoted by tetra-n-butylam-monium fluoride. The adduct 2 was alkylated by l-bromo-2-pentyne in the presence of tetra-n-butylammonium fluoride to give 3 in rather low yield. Remaining steps to 5 were methanolysis and partial hydrogenation of the triple bond. 

The application of strong bases to hydrocarbons which contain a sp3 hybridized carbon and a conjugated system may abstract a proton and form a fully conjugated carbanion. This reaction has several synonyms such as deprotonation, proton abstraction or metalation reactions. The most common bases are alkyl lithium derivatives, e.g., butyl lithium21 24). Sometimes the addition of tetramethylethylenediamine (TMEDA) or potassium ferf-butoxide is required especially when dianions and polyanions are prepared 24e,f). Ether solvents or hydrocarbon solvents are most common. This process can be demonstrated by the preparation of anthraene dianion 22 from 9,10-dihydroanthracene (1)25). The metalation reaction can also be carried out in the NMR tube. 

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