Aryllithium basicity

Support-bound C,F I-acidic compounds, such as acetoacetamides, react with isocyanates under basic conditions to yield amides through C-carbamoylation [71]. Similarly, polystyrene-bound aryllithium compounds can be converted into benzamides by treatment with isocyanates [111]. These reactions are closely related to C-thiocarbamoyla-tion, which has been used for the solid-phase synthesis of thioamides (see Section 13.9). Amides have also been prepared by C-alkylation of resin-bound N-acylaminals with allyltrimethylsilane or diethylzinc (Entry 11, Table 13.7). 

Both aryllithium and vinyllithium cyclisations onto alkenes are successful despite the associated increase in organolithium basicity, and the first vinyllithium cyclisation was demonstrated by Chamberlin, who cyclised the Shapiro-derived 227 onto a terminal alkene to... 

It might be expected that strongly basic alkyllithium reagents (RLi) would deprotonate an arene (ArH) directly to form the aryllithium (ArLi) and the alkane (RH). Although this reaction does occur, it is usually extremely slow and side reactions may compete. In addition, deprotonation of most substituted benzenes will probably occur in a random manner rather than at a particular position in the benzene ring. 

BF3 Et20 facilitates the addition of moderately basic nucleophiles like alkyl-, alkenyl-, and aryllithium, imines, Grignard reagents, and enolates to a variety of electrophiles. 

A convenient synthetic method for the conversion of aryl bromides to phenols is the reaction of the corresponding organometalUc reagents with molybdenum peroxide-pyridine-hexamethylphosphoramide (MoOs-Py-HMPA = MoOPH)". This method provides a mild one-pot reaction sequence for the synthesis of phenols under basic conditions. Phenols are obtained in good to excellent yields with several prototype compounds. Other strongly basic carbanions have been hydroxylated with MoOPH, including aryllithium derivatives" . Table 2 shows some examples of this type of reaction" . ... 

With the more strongly basic aryllithium compounds, the tendency of further reaction to symmetrical ketones is increased ... 

Carboxylic acids can be obtained in good to excellent yields by rapidly introducing C02 at low temperatures into THF solutions of RLi, unless RLi is too strongly basic (i.e. aryllithiums, formation of R2C(OLi)2) or unless the acid to be prepared... 

Comparative experiments with aryllithium compounds (phenyllithium and para-fluorophenyllithium), however, resulted in low yields of the methyl esters in spite of the fact that a 300 % excess of chloroformic ester had been used. Reactions of C1COOR with lithio derivatives of heterocycles containing an azomethine function (e.g. lithiated thiazole, imidazole, pyridine) cannot succeed, since the excess of chloroformate will react with the basic nitrogen atom. A comparable situation arises if the organolithium intermediate has been generated by means of LDA reaction of C1COOR with the diisopropylamine liberated in the metallation will provide HC1 which will of course inactivate the organolithio compound. 

Aryllithiums give much lower yields of w-terphenyls. This is probably because aryllithiums are more basic than the corresponding Grignard reagents, and remove aryl protons from the trihalobenzenes, leading to other products. 

In the second step, deprotonation can again take place next to the methoxymethyl group. Two equivalents of BuLi are needed because the most acidic proton is in fact one of the protons of the methyl group a benzyllithium forms first, and then a more reactive aryllithium. When the electrophile (DMF) is added, it reacts only with the last formed, more basic anion. 

The bicyclo[2.2.0]but-l(3)-enes belong to the latter class. As systematic investigations by Gunter Szeimies have disclosed, tricyclo[4.1.0.0 ]hept-l(7)-ene acts as a turntable in the reactions of alkyl- and aryllithiums with 1-chlorotricyclo[4.1.0.0 ]heptanes (Scheme 1-219). Lithium aziridine is basic enough to sustain such a sequence of metaiation, elimination, and nucleophilic addition. The A-tricycloheptylaziridine thus formed thermolyses at 150 °C to cyclohex-2-ene-l-carbonitrile. The weekly basic lithium benzenethiolate requires the assistence of LITMP to accomplish the deprotonation step before it can add smoothly to give the intermediate 276 (Scheme 1-219). Dienes rather than nucleophiles may be also used to trap strained bicyclo[2.2.0]but-l(3)-enes like 276. Such species may also be generated from l-bromo-7-(trimethylsilyl)tricyclo[4.1.0.0 ]heptanes and cesium fluoride in DMSO at +25 °C. At elevated temperatures (about +100 °C), the bicyclobutene 276 isomerizes rapidly to 1,3,5-cycloheptatriene by [2+2]-cycloelimination. ... 

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