Arenes catalytic lithiation

Since different reactivity is observed for both the stoichiometric and the catalytic version of the arene-promoted lithiation, different species should be involved in the electron-transfer process from the metal to the organic substrate. It has been well-established that in the case of the stoichiometric version an arene-radical anion [lithium naph-thalenide (LiCioHg) or lithium di-ferf-butylbiphenylide (LiDTBB) for using naphthalene or 4,4 -di-ferf-butylbiphenyl (DTBB) as arenes, respectively] is responsible for the reduction of the substrate, for instance for the transformation of an alkyl halide into an alkyllithium . For the catalytic process, using naphthalene as the arene, an arene-dianion 2 has been proposed which is formed by overreduction of the corresponding radical-anion 1 (Scheme 1). Actually, the dianionic species 2 has been prepared by a completely different approach, namely by double deprotonation of 1,4-dihydronaphthalene, and its X-ray structure determined as its complex with two molecules of N,N,N N tetramethylethylenediamine (TMEDA). ... 

Allylic and benzylic ethers can also be cleaved using an arene-catalyzed lithiation, so the corresponding organohthium intermediates could be generated. Thus, different benzylic ethers 49 were hthiated using a catalytic amount of naphthalene (5%) to yield the expected intermediates 50, which after reaction with electrophiles and final hydrolysis gave products 51 (Scheme 16) . ... 

There are many examples of /3-amido and /3-oxido functionalized organolithium compounds, which were prepared mainly using the stoichiometric version of the arene-promoted lithiation ". In this section, the preparation of the same type of intermediates by halogen-or sulfur-lithium exchange will be considered, using the catalytic version of the mentioned lithiation. 

Lithium homoenolates derived from carboxylic acids were generated from the corresponding /3-chloro acids by means of an arene-catalyzed lithiation. Chloro acids 186 were deprotonated with n-butyllithium and lithiated in situ with lithium and a catalytic amount of DTBB (5%) in the presence of different carbonyl compounds to yield, after hydrolysis, the expected hydroxy acids (187). Since the purification of these products is difficult, they were cyclized without isolation upon treatment with p-toluenesulfonic acid (PTSA) under benzene reflux, into substituted y-lactones 188 (Scheme 64) . 

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). 

Dioxanes can be opened by an arene-catalyzed lithiation only if the carbon-oxygen bond to be cleaved occupies an allylic or benzylic position. This is the case of the vinyl-dioxane 416, which reacted with lithium and a catalytic amount of DTBB in THE at 0 °C, and the allylic intermediate 417 generated reacted at the y -position with tridecyl iodide to yield the compound 418, used in the synthesis of plasmenyl-type lipids (Scheme 117) . 

Also in this case, the use of the chloro thioether 479 allowed the introduction of two different electrophiles in a sequential process. Using lithium naphthalene (the stoichiometric version of the arene-promoted lithiation) in THF at — 78°C, only a chlorine-lithium exchange occurred, so the first electrophile R R CO was introduced (—78 to —50°C). Then the second lithiation (sulfur-lithium exchange) takes place under catalytic conditions (naphthalene) and the second electrophile R R CO was introduced. After final hydrolysis, differently substituted 1,5-diols 476 were isolated (Scheme 134) °. 

Simple enamines cannot be deprotonated directly at the a-position due to their low acidity, but starting from a-chloroenamines 685, a-lithioenamines 686991 have been prepared by chlorine-lithium exchange using an arene-catalyzed lithiation992. The treatment of compounds 685 with an excess of lithium and a catalytic amount of 4,4 -di-tert-butylbiphenyl (DTBB) in THF at —90 °C allowed the preparation of intermediates 686, which were trapped with a variety of electrophiles (Scheme 177). For aldol reactions, the arene-catalyzed lithiation has to be performed in the presence of aldehydes (Barbier conditions) at —40 °C. These adducts were transformed into a-hydroxy ketones after acid hydrolysis with hydrochloric acid or silica gel. 

Cyclic alkyl aryl ethers lead also to functionalized organolithium compounds by reductive carbon-oxygen bond cleavage in arene-catalyzed lithiation process. Thus, the treatment of 2,3-dihydrobenzofuran (47) with an excess of lithium in the presence of a catalytic amount of DTBB in THF at 0°C gives the dianion (48) which after reaction with different carbonyl compounds and final hydrolysis with water leads to... 

The corresponding catalytic version of this reaction was performed using either naphthalene- or biphenyl-supported polymers 594 or 595, respectively, which were prepared by cross-coupling copolymerization of 2-vinylnaphthalene or 4-vinylbiphenyl with vinyl-benzene and divinylbenzene promoted by AIBN in THF and polyvinyl alcohoP . These polymers have been used as catalysts (10%) in lithiation reactions involving either chlorinated functionalized compounds or dichlorinated materials in THF at —78°C and were re-used up to ten times without loss of activity, which is comparable to the use of the corresponding soluble arenes. 

On the basis of the catalytic roles of calix[4]arene derived model 18-[Zn"]2 (99JOC3896) and cis-diaqua Cu complexes for cleavage of phosphate diesters, Reinhoudt designed a calix[4]arene derivative 66-[Cu ]2 functionalized with two ds-diaqua Cu° centers at the distal positions of the upper rim as a model for dinuclear metalloenzymes that catalyze chemical transformations of phosphate esters. It was synthesized from Cu(C104)2 and 5,17-bis(bis(l-methylimidazol-2-yl)hydroxy-methyl)-25,26,27,28-tetrakis(2-ethoxyethoxy)calix[4]arene which was conveniently obtained from the precursor diester and lithiated 1-methyl-imidazole. In this model, the two Cu° centers are well organized on the calixarene scaffold for performing S5mergistic action. 

A 1,2 or 1,3 unsymmetrically disubstituted arene is prochi-ral and therefore the corresponding chromium tricarbonyl compounds are chiral. (Substituted arene) complexes with amine, carboxyl, and formyl groups at the ortho position are resolved into optically active chromium complexes through corresponding diastereomeric adducts (eq 25). Biocatalysts also perform the kinetic resolution of racemic chromium complexes (eq 26). The optically active chromium complexes can be prepared by di-astereoselective ortho lithiation of the chiral benzaldehyde or acetophenone acetal complexes, and diastereoselective chromium complexation of the chiral ort/io-substituted benzaldehyde am-inals (eq 27). Catalytic asymmetric cross-coupling of meso (1,2-haloarene)chromium complex produces chiral monosubstituted complexes. The chiral (arene)chromium complexes can be used as ligands in asymmetric reactions. ... 

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