Deprotonative metalation benzene

In the case of benzene, the large kinetic barrier does not allow the reaction to proceed. The latter is possible, however, in the presenee of TMEDA. The role of this chelate ligand is first to break the hexamerie eluster in hexane by complexation of the Li+ eation, which strongly polarizes the Li-C bond. The addition of benzene or ferrocene then rapidly leads to deprotonation-metallation of the aromatic derivative, because the n-C4H9 anion is rendered more basie onee it is disengaged from the covalent bond with Li. 

Sn6garoff K, Komagawa S, Chevallier F et al (2010) Deprotonative metalation of substituted benzenes and heteroaromatics using amino/alkyl mixed lithium-zinc combinations. Chem Eur J 16 8191-8201. doi 10.1002/chem.201000543... 

Kyba and eoworkers prepared the similar, but not identical compound, 26, using quite a different approach. In this synthesis, pentaphenylcyclopentaphosphine (22) is converted into benzotriphosphole (23) by reduction with potassium metal in THF, followed by treatment with o "t/20-dichlorobenzene. Lithium aluminum hydride reduction of 23 affords l,2-i>/s(phenylphosphino)benzene, 24. The secondary phosphine may be deprotonated with n-butyllithium and alkylated with 3-chlorobromopropane. The twoarmed bis-phosphine (25) which results may be treated with the dianion of 24 at high dilution to yield macrocycle 26. The overall yield of 26 is about 4%. The synthetic approach is illustrated in Eq. (6.16), below. 

Conversion of tight ion pairs into crown ether-separated ion pairs leads in many cases to increased basicity. For example, Dietrich and Lehn (1973) have shown that a homogeneous solution of sodium t-amyloxide in benzene is unable to deprotonate triphenylmethane, whereas the reaction occurs rapidly in the presence of [2.2.2]-cryptand [37]. In THF or diethyl ether, alkali metal enolates do not react with triphenyl- or diphenylmethane (Pierre et al.,... 

The violence of superbasic slurries towards functionalized organic molecules means that they are at their most effective with simple hydrocarbons they also tolerate ethers and fluoro substituents. LiCKOR will deprotonate allyUc, benzylic, vinylic, aromatic and cyclopropane C—H bonds with no additional assistance. From benzene, for example, it forms a mixture of mono and dimetallated compounds 617 and 618 (Scheme 241) . ( Li/K indicates metallation with a structurally ill-defined mixture of lithium and potassium.)... 

Imines derived from macrocyclic ketones (C10 to C 15 ) and (- )-(S)-a-(methoxymcthyl)benzene-ethanamine are successfully deprotonated using LDA ( —25 JC. THF. 1 h)9. In contrast to azaenolates of C0- to C8-membered cyclic ketones, which show only E geometry, Z-isomers are observed with macrocyclic imines. As evident from H-NMR data, azaenolates of cyclodecanone imines generated under these conditions are a mixture of E- and Z-isomers (33 66), whereas azaenolates of cyclododecanone and cyclopenladecanone imines arc formed as the pure. E-isomers (see Table 3). Upon heating the solutions of metalated imines to reflux for 1 hour, complete isomerization to the thermodynamically more stable Z-isomers occurs. 

A peculiar complex is formed by if coordination of Os(II) ammine complex to one of the double bonds of benzene rings, rather than rf coordination, and the coordinated benzene rings show interesting reactivity [82]. For example, Os(II) coordinates regioselectively to the 2,3-double bond of anisole to form the complex 333, and hence localization of the remaining 7r-electrons occurs. As a result, at 20 °C an electrophile attacks easily at C(4) due to electron-donation of the methoxy group. The 4H-cationic intermediate 334 is stabilized by backdonation from the metal, and the monosubstitution product 334 is formed without deprotonation. The / ara-substituted anisole 335 is... 

Arenes cannot usually be deprotonated with LDA alone, but require mixtures of organosodium [365] or organolithium compounds and tertiary amines [181, 218, 219]. These amines, for instance TMEDA, lead to a partial dissociation of oligomeric BuLi-solvent aggregates and thereby to more powerful metalating reagents [366, 367]. Thus, although benzene cannot be deprotonated with BuLi alone, a mixture of BuLi and TMEDA leads to quantitative lithiation [181]. 

The preferred site of deprotonation of di- or polysubstituted arenes is not easy to predict. In 1,3-disubstituted benzenes in which both substituents facilitate ortho-metalation, deprotonation will usually occur between these two groups [181, 365, 408, 416-419] (Scheme 5.45). Dialkylamino groups, however, can sometimes deactivate ortho positions (fourth reaction, Scheme 5.45), but this does not always happen [181, 420], 3-Chloroanisole [411] and 3-fluoroanisole [421] are deprotonated by organolithium compounds between the two functional groups, but the lithiated arenes dimerize readily at -78 °C, presumably via intermediate aryne formation (last example, Scheme 5.45). 

The synthesis of the derivatives (339)-(346) was carried out as shown in Scheme 28. Metalation of the acetal (336), followed by thiolation and alkylation, gave the ester derivative (337). Acetal deprotection to form (338) and subsequent treatment under Knoevenagel conditions with piper-idinium acetate in benzene afforded the desired ester (339). Reduction of compound (339) gave alcohol (340), which was converted to aldehyde (341) and protected as its acetal (342) under standard conditions. Deprotonation was effected by Bu"Li in THF at — 78 °C and subsequent conversion to the sulfonyl chloride was carried out by sequential treatment with sulfur dioxide and A-chloro-succinimide. Treatment of the sulfonyl chloride (343) with concentrated NH4OH in acetone provided the sulfonamide (344), which was deprotected (345) and subjected to reductive amination to provide compounds in the aminomethyl sulfonamide series (346). 

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