Metalation with lithium arenes

Various effective synthetic routes can be based on metallation of organic substrates with lithium arenes, obtained in situ from metallic lithium and an arene present in substoichio-metric amounts. Immediate quenching of the lithiated intermediates may be considered as a reduction reaction of the original substrate. Otherwise, further functionalization may be attained when using diverse electrophiles. Various examples of such processes follow (see also equation 69 in section VI.B.l). 

As shown by the last reaction in Scheme 5.23, the metalation of benzamides is complicated by several potential side reactions (Scheme 5.24). Thus, benzamides can also undergo ortho-metalation [181, 217-222] or metalation at benzylic positions [223-225], Ortho-metalation seems to be promoted by additives such as TMEDA, and benzylic metalation can be performed selectively with lithium amide bases [217,224], which are often not sufficiently basic to mediate ortho- or a-amino metalation. If deprotonation of the CH-N group succeeds, the resulting product might also undergo cydization by intramolecular attack at the arene [214, 216] (see also Ref. [226] and Scheme 5.27) instead of reacting intermolecularly with an electrophile. That this cydization occurs, despite the loss of aromatidty, shows how reactive these intermediates are. 

Although not a catalytic reaction, the reduction of arenes with electropositive metals like lithium, zinc or aluminium in chloroaluminate... 

Deoxygenation of phenols. The reduction of enol phosphates to alkenes by titanium metal (8,482) has been extended to reduction of aryl diethyl phosphates to arenes. Yields are in the range 75-95% reduction with lithium in liquid ammonia (1, 248) usually proceeds in low yield. 

Use of Lithium Naphthalenide. Lithium arene radical anion complexes are mild and highly effective reagents for the reductive desulfonylation process of functionalized sulfones. These reagents have only rarely been used with vinylic and allylic sulfones. In addition to high yields and their operational simplicity, metal arene radical anion complexes demonstrate high chemoselectivity (Eq. 67).123... 

In other systems, N—cleavage gives bis(/i-nitrido)dimetal diamond cores as the products of N2 cleavage. A reduced niobium complex of calix[4]arene reduces N2 in the presence of sodium metal, and a number of intermediates can be isolated. A related tridentate aryloxide ligand also splits N2 to give a diamond core with lithium ions bound to the nitrides. A vanadium diamidoamine complex reacts with N2 to give a product with a similar core structure, which may be further reduced by potassium graphite to a compound with one unpaired electron. This... 

Among the arene-metal reagents, lithium 4,4 -di(f-butyl)biphenyl (LiDBB) i has been used in a series of transformations as a catalyst for SET reactions. With carbonyl groups, according to the conditions, the reaction product is either the ketyl radical anion or the dianion. 

Another interesting application of arene group activation by chromium complex formation is found in the facile metallation of coordinated arene moieties with lithium, the lithiated complex being activated towards subsequent substitutions by electrophilic reagents. This principle has been applied to the synthesis of anthracyclone analogues [5e]. 

Heterosubstituted Arenes. As a rule of thumb, the super-basic n-BuLi/f-BuOK reagent having coordinatively saturated lithium preferentially deprotonates such positions where charge excess is most efficiently stabilized. This may result in a different regiochemical behavior with respect to simple organolithium reagents exploiting the so-called optional site-selective metalation. Some representative examples of n-butyllithium/potassium ferf-butoxide metalations of heterosubstituted arenes are shown in Table 5. 

Other Metal Substitutions.—Substituted arenes react with diborane (in THF) in the presence of Li (best), Na, K, or Ca to give aryl-boranes by transmetallation. Yields are superior to those of the two-step process via reaction between the pre-formed lithium aryl and diborane.T1(03SCF3)3 is a more reactive thalla-ting agent than the trifluoroacetate, and may be prepared effectively in situ by... 

In a related reaction, heating ketones in the presence of TlClsOTf leads to 1,3,5-trisubstituted arenes. " Nitriles react with 2 mol of acetylene, in the presence of a cobalt catalyst, to give 2-substituted pyridines. " Triketones fix nitrogen gas in the presence of TiCU and lithium metal to form bicyclic pyrrole derivatives. " ... 

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). ... 

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