Lithiation of arenes

In addition to the examples described in the previous section, various azaallyl Michael donors, successfully used in diastereoselective 1,4-additions, may be obtained by lithiation of arene acetonitriles117l llS, protected cyanohydrins 1 19 - 12 1,385, and a-amino-122 123 and a-phosphi-... 

Reactions and Applications TABLE 8.28. LITHIATION OF ARENES BY EVE-HMPA"... 

TABLE 8.27 LITHIATION OE OXAZOLINYLFERROCENE 439 AND TRAPPING WITH TMSCl, 457 TABLE 8.28 LITHIATION OF ARENES BY EVL-HMPA, 459... 

Ortho lithiation of arenes directed by CONRj, OCONRj, OMOM, or NHCOR (Eq. 5), or the halogen-lithium exchange reaction (Eq. 6) provides various aryllithiums regioselectively. In situ treatment of these lithium intermediates with trimethyl- or tri(isopropyl) borate gives variously functionalized arylboronic acids. Trapping aryl-lithium or aryl-magnesium intermediates with trimethylchlorosilane, followed by transmetallation to BClj or is a convenient alterna-... 

SCHEME 26.15 Asymmetric lithiation of arene complexes bearing a sugar residue. 

Dialkoxymethyllithium compounds, for example 2-lithio-l,3-dioxan (311), are generated in situ as shown in equation 69, either by reductive lithiation of a phenyl thioether with a lithium arene or by transmetallation of the corresponding trialkylstannyl compound. Subsequent quenching with electrophiles leads to the usual alkylated or functionalized species ... 

What is clearer is that, if two lithiation-directing groups are placed meta to one another, lithiation nearly always occurs between them. The only exceptions are when the resulting polysubstituted arene ring would be exceptionally hindered lithiation then takes place ortho to the better of the two directing groups. For example, lithiation of 633 gives 634 by lithiation at the 5- rather than the 2-position (Scheme 246) . 

As shown in the last section, the arene-catalyzed lithiation of mesylates has the limitation that it only proceeds for allylic and benzylic substrates. This drawback has been... 

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). 

Concerning the arene-catalyzed lithiation of 4-77-chromene 386, the process is not of synthetic interest as compared to the same process applied to 2,3-benzofuran 348 because both alkyl-and aryl-oxygen cleavage took place using DTBB (5%) as the electron-carrier... 

Another two polymers, which have been used for the same type of arene-catalyzed lithiation reactions, are compounds 596 and 597, which were prepared by ring-opening metathesis polymerization (ROMP) starting from the corresponding aryl norbonenes 598. ... 

Sulfonic acids are prone to reduction with iodine [7553-56-2] in the presence of triphenylphosphine [603-35-0] to produce the corresponding iodides. This type of reduction is also facile with alkyl sulfonates (16). Aromatic sulfonic acids may also be reduced electrochemicaUy to give the parent arene. However, sulfonic acids, when reduced with iodine and phosphorus [7723-14-0]y produce thiols (qv). Amination of sulfonates has also been reported, in which the carbon—sulfur bond is cleaved (17). Ortho-lithiation of sulfonic acid lithium salts has proven to be a useful technique for organic syntheses, but has litde commercial importance. Optically active sulfonates have been used in asymmetric syntheses to selectively O-alkylate alcohols and phenols, typically on a laboratory scale. Aromatic sulfonates are cleaved, ie, desulfonated, by uv radiation to give the parent aromatic compound and a coupling product of the aromatic compound, as shown, where Ar represents an aryl group (18). 

Figure 4.1. Lithiation of polystyrene-bound arenes and heteroarenes [1,8-10],...

Since trimethylsilylarenes can be prepared by metallation of the arene followed by treatment with chlorotrimethylsilane, this provides an alternative route into a range of difficult substitution patterns. For example, the ortho/para directing effects of the methoxy groups in 1,3-dimethoxybenzene 75 direct the electrophile to the 4-position. However, lithiation of 1,3-dimethoxybenzene takes place at the 2-position. Reaction with chlorotrimethylsilane then gives the 2-trimethylsilyl compound 76, which undergoes ipso substitution with the electrophile to give the 1,2,3-trisubstituted product 77 (equation 39)101,102. 

Further derivatives of amines in which the a-C,H groups are sufficiently acidic to enable metalation are carbamates [235,238-240] (Scheme 5.26), imides[241], N-nitroso amines [59,242], ureas [201,243], some N-phosphorus derivatives [212, 214, 226, 244, 245], N-(2-pyridyl)amines (Scheme 5.26), and isonitriles [59]. A potential side reaction in the examples in Scheme 5.26 is the lithiation of the arene this is, in fact, observed with an isomeric dipyridopyrazine (last reaction, Scheme5.26). 

Gibson and coworkers have examined the possibility of using chiral base methodology to enantioselectively lithiate the benzylic position of arene complexes (Scheme 46). (R,R)-3 has been used in combination with LiCl and followed by quenching with... 

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