Naphthalene catalyzed lithiation

The naphthalene-catalyzed (10%) lithiation of iV-allylic or iV-benzylic pivalamides 66 in the presence of an electrophile at —78 or 0 °C, respectively, gave, after hydrolysis, the expected products 20 (Scheme 25) °. 

The reaction shown in Scheme 25 has been successfully used to deprotect Al-benzylic carboxamides using water as the quenching reagent, after the naphthalene-catalyzed lithiation . 

The application of the naphthalene-catalyzed (10%) lithiation to benzylic ureas 69 under Barbier-type conditions in THF at —78 or — 30°C led to the formation of the expected products 35, after hydrolysis (Scheme 28) °. 

The naphthalene-catalyzed (8%) lithiation of phenyl sulfones 80 under Barbier conditions in THF at temperatures ranging between —78 and 20 °C led, after hydrolysis, to the formation of the corresponding products 20 (Scheme 33). ... 

The naphthalene-catalyzed (3%) lithiation of carbamoyl or thiocarbamoyl chlorides 91 in the presence of carbonyl componnds or imines as electrophiles in THF at temperatnres ranging between —78 to 20 °C led to the expected fnnctionalized amides or thioamides 92 after hydrolysis (Scheme 39) . ... 

Another type of acyllithium synthons was generated in situ from chloroimines. The naphthalene-catalyzed (4%) lithiation of chloroimines 93 in THF at —78 °C was followed by filtration of the excess of lithium, being then treated with an electrophile and finally hydrolyzed, to yield functionalized imines 94 (Scheme 40) . ... 

A naphthalene-catalyzed (<10%) lithiation of a,a-dibromo esters 152 in THF at —78°C was used to generate ester dianions 153, which by warming at 0°C gave lithium ynolates 154. These intermediates were trapped by carbonyl compounds, for instance benzophenone, to give, after final hydrolysis with water, a,/3-unsaturated acids 155 (Scheme 55)" ... 

Naphthalene-catalyzed (5%) lithiation of the chlorinated thioether 203 in the presence of pivalaldehyde gave, after hydrolysis, the product 204 in which, together with the... 

Naphthalene-catalyzed (5%) lithiation of the diiodinated ketal 205 afforded directly the cyclobutane derivative 206, a i5-iodinated organoUthium compound probably being involved (Scheme 71). In this case, a 5-elimination of lithium iodide is preferred to a y- or 5-elimination of lithium aUcoxide. 

The naphthalene-catalyzed (3-12%) lithiation of deprotonated chloro phenols and anilides 236 performed with n-butylUthium in THF at 0 or —78 °C, respectively, gave the corresponding functionalized aryllithium intermediates 237 which, by reaction with electrophiles and final hydrolysis, yielded the corresponding polyfunctionalized molecules 238 (Scheme 79) . 

The naphthalene-catalyzed (2.5%) lithiation of phthalan 330 (or its substituted derivatives ) in THF at room temperature allowed the preparation of the functionalized benzyllithium intermediate 331, which reacted with electrophiles at —78°C to give, after hydrolysis, the corresponding functionalized benzyl alcohols 332 (Scheme 97). When carbon dioxide was used as the electrophilic reagent, the corresponding 5-lactone was directly obtained . When carbonyl compounds were used as electrophiles, the cyclization of the resulting products 332 under acidic conditions (85% H3PO4) allows the synthesis of substituted isochromans. 

The only way to introduce two different electrophilic fragments in compounds such as 508 is to have a starting material with different halogens. This is the case with 510, which could be lithiated (bromide-lithium exchange) with t-butyllithium in THF at — 100°C giving intermediates 511, which reacted with a carbonyl compound R R CO and, after naphthalene-catalyzed lithiation, gave the new functionalized organolithium intermediate 512. Final reaction with 3-pentanone followed by hydrolysis yielded mixed products 513 (Scheme 142) °. 

Gomez, C. Ruiz, S. Yus, M. Polymer Supported Naphthalene-Catalyzed Lithiation Reactions, Tetrahedron Lett. 1998, 39, 1397. 

Metalhalogen exchange of 2-, 3-, and 4-chloropyridines, and 2-chloroquinoline can be effected by naphthalene-catalyzed reductive lithiation using lithium powder in the presence of catalytic quantities of naphthalene in THF at 78 C <2000T4043>. 

Although this method is convenient in the laboratory, t- and i-BnLi are somewhat expensive and shonld be handled carefnlly, especially in a large scale. A more practical method for the synthesis of ynolates is the rednctive lithiation method. The dibromo esters 43 are treated with lithinm naphthalenide to give the ynolates 44 in good yield. Naphthalene-catalyzed reductive lithiation of the dibromo esters can also be performed, providing the ynolates more efficiently (equation 17) . 

Naphthalene-catalyzed lithiation of l,3-dimethyl-2-phenylimidazolidine leads to cleavage of the benzylic carbon-nitrogen bond, with formation of an intermediate dianion. The dianion could be trapped with several electrophiles, including primary and secondary alkyl halides, as well as enolizable and nonenolizable carbonyl derivatives, affording diamines 485 in satisfactory yields (Scheme 112) <2005T3177>. 

Reductive cleavage of imidazolidines 641 was implicated in the one-pot synthesis of N,N,N -trisubstituted ethylenediamines 643 from V,V -disubstituted ethylene diamines and an aldehyde R CHO. Presumably the intermediate iminium ion 642 is reduced by NaBH4 (Scheme 154) <2003SC3193>. Naphthalene-catalyzed lithiation of l,3-dimethyl-2-phenylimidazoline 644 leads to benzylic C-N bond cleavage. The intermediate dianion can be trapped with electrophiles (HjO, alkyl halides, ketones, and aldehydes) to afford diamines 645 <2005T3177>. 

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) . ... 

An alternative to the use of pivalamides 66 is the lithiation of triflamides 67 catalyzed by naphthalene (4%) in the presence of different electrophiles at temperatures ranging between —78 and 0 °C, so after hydrolysis the expected products 20 were isolated (Scheme 26). ... 

Fig. 16.11. Nickel-catalyzed arylation of Grignard compounds. The Grignard compound can be prepared via a substituent-directed peri-lithia-tion of a substituted naphthalene (see Section 5.3.1 for the analogous ortho-lithiation) and subsequent transmetalation with MgBr2 (for the method cf.

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