Organolithium with arenes

Coordination of the chromium tricarbonyl group onto an arene enhances the kinetic acidity of the aryl C—bonds. In order to avoid nucleophilic attack of the organolithium reagent onto a CO ligand, the reaction has to be run at low temperature. The reaction is regioselective as ortholithiation is observed with arene substituted by OCH3, F, Cl. 

Acyclic and cyclic sp -hybridized ketal-containing y-functionalized organolithium compounds can be generated using an arene-catalyzed Uthiation at low temperature. In the case of acyclic precursors 171 (R = H) it was necessary to lower the temperature to -90 °C in the Uthiation step under DTBB catalysis (4%) in order to avoid decomposition of intermediates 172. Final electrophilic substitution reaction of these intermediates with electrophiles occurred with retention of configuration at temperatures ranging between... 

Several chapters deal with the synthesis of and the synthetic applications of organolithium compounds such as orthometallation, arene catalysed lithiation, addition to carbon-carbon double bonds, their reaction with oxiranes, and asymmetric deprotonation with lithium (-)-sparteine. We gratefully acknowledge the contributions of ah the authors of these chapters. 

Benzyl methyl ether or allyl methyl ethers can be selectively metalated at the benzylic/allylic position by treatment with BuLi or sBuLi in THF at -40 °C to -80 C, and the resulting organolithium compounds react with primary and secondary alkyl halides, epoxides, aldehydes, or other electrophiles to yield the expected products [187, 252, 253]. With allyl ethers mixtures of a- and y-alkylated products can result [254], but transmetalation of the lithiated allyl ethers with indium yields y-metalated enol ethers, which are attacked by electrophiles at the a position (Scheme 5.29). Ethers with ft hydrogen usually undergo rapid elimination when treated with strong bases, and cannot be readily C-alkylated (last reaction, Scheme 5.29). Metalation of benzyl ethers at room temperature can also lead to metalation of the arene [255] (Section 5.3.11) or to Wittig rearrangement [256]. Epoxides have been lithiated and silylated by treatment with sBuLi at -90 °C in the presence of a diamine and a silyl chloride [257]. 

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]. 

Polystyrene-bound silanes are usually prepared by reaction of organolithium compounds with resin-bound silyl chlorides [12, 13]. The C-Si bonds of aryl-, heteroaryl-, vinyl-, and allylsilanes are stable towards alcoholates or weak reducing agents, but can be cleaved under mild conditions by treatment with acids or fluoride to yield a hydrocarbon and a silyl ester or silyl fluoride. Several linkers of this type have been tested and have proven useful for the preparation of unfunctionalized arenes and alkenes upon cleavage from insoluble supports. 

Another approach for the preparation of either symmetrical or unsymmetrical iodonium salts used organolithium or organomercury compounds and (dichloroiodo)arenes [12]. The problem of the formation of unwanted isomers during reactions involving aromatic electrophilic substitution may also be overcome by the condensation of iodosylarenes with iodylarenes [12]. Several iodonium triflates were prepared in high yield from activated or mildly deactivated arenes with iodosylbenzene and triflic anhydride or triflic acid [13,14] or sulphur trioxide [15]. Some of these compounds are shown in Table 8.2. 

Desymmetrisation by enantioselective ortholithiation has been achieved with ferrocenylcarboxamides 434,187 and also (with chiral lithium amide bases) a number of chromium-arene complexes.188 The chromium arene complex 435, on treatment with s-BuLi-(-)-sparteine, gives 436 enantioselectively, and reaction with electrophiles leads to 437. However, further treatment with r-BuLi generates the doubly lithiated species 438, in which the new organolithium centre is more reactive than the old, which still carries the (-)-sparteine ligand. Reaction of 438 with an electrophile followed by protonation therefore gives ent-431.m... 

Among unsolvated organolithium compounds only the alkyllithiums are soluble in noncoordinating solvents such as alkanes and arenes. Their states of aggregation depend on the structure close to lithium. Thus primary, tertiary and secondary alkyllithiums, all unsolvated, assemble into respectively hexamers, tetramers and equilibrium mixtures of hexamers and tetramers. Most organolithium compounds dissolve in and coordinate with donor compounds such as ethers and tertiary amines. The actual structures depend critically on the nature of the donor. Thus, diethyl ether solvates tend to be mainly cubic tetramers (with some dimers) while THF favors mixtures of monomers and dimers. Tertiary vicinal diamines such as TMEDA and 1,2-di-Af-piperidinoethane, DPE, favor bidentated coordinated dimers. Finally, in the presence of triamines such as pentamethyl-triethylenediamine PMDTA and l,4,7-trimethyl-l,4,7-triazacyclononane TMTAN, many organolithium compounds form tridentately complexed monomers. 

As the methylene protons of the cycloproparenes are formally benzylic, the compounds should be at least as acidic as the corresponding methyl arenes. Simple extended Huckel calculations concur and predict some stabilization of 6 from charge delocalization the cycloproparenyl anion (6) is expected to be accessible. Indeed, treatment of 1 with butyl-lithium at -78 °C provides an organolithium that has been characterized by NMR and shown to be monomeric in solution. Both the H NMR (H(d 1.91, H(2/s) 5.83, H(3/4) 6.13 ppm, respectively) and NMR (C(,) 31.3, C(,a/5a) 149.0, 99.1, C(3/4) 120.4 ppm, respec-... 

C. Mixed-Metal Organolithium Compounds with Unsaturated (Alkene, Arene) Uganda... 

This amphiphilic conjugate alkylation has been used successfully for nucleophilic alkylation of electron deficient arenes, on the basis of the unprecedented conjugate addition of organolithiums to aromatic aldehydes and ketones by complexation with ATPH [136], Thus, initial complexation of benzaldehyde or acetophenone with ATPH and subsequent addition of organolithiums affords 1,6 adducts with high selectivity, as illustrated in Sch. 99. 

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