Polylithiation

Maercker, A., Theis, M. Some Aspects of the Chemistry of Polylithiated Aliphatic Hydrocarbons, 138, 1-61 (1986). 

Synthesis of Periphery-Functionalized Dendritic Molecules Using Polylithiated Dendrimers as Starting Material, P. 

Mulvaney and coworkers reported a polylithiation of a non-terminal acetylene for the first time, more exactly the formation of CeHsCBLiB and CeH4LiC3Li3 from 1-phenylpropyne and n-butyllithium in hexane" . Stimulated by their work. West and Gornowicz prepared and investigated new polylithium compounds from phenylpropynes and their polysilicon derivatives . The structures of several of them were analysed by IR spectroscopy. 

The authors noticed that polylithiated phenylallenes have a vibrational behaviour similar to that of polylithiated propynes and butynes (Table 8) . The monolithium compounds from terminal acetylenes were found to have acetylenic structures (2050 cm ), whereas the monolithium derivatives of non-terminal acetylenes could exist in either acetylenic (2000 cm ) or allenic (1870-1850 cm ) forms (Table 8) °. The polylithium... 

However, several years later Priester and coworkers revised the interpretation of the IR spectra of polylithiated acetylenes in terms of propargylide and allenic anions (Table 11) ". They divided the compounds into two categories those that can directly form lithioacetyUdes (the terminal acetylenes) and those that must undergo hydrogen or alkyl shifts to form acetylides (the internal acetylenes). 

While the mono- and dianions of internal acetylenes stiU have allenic structures, polylithiation of terminal acetylenes results in anions having a different structure, as previously reported (Scheme 9). 

Benzenechromium tricarbonyl 371 is deprotonated by BuLi in EtiO-THF at —40 °C in a reaction that needs carefnl control for good yields . The prodnct 372 can be sily-lated to give 373 in 60% yield (Scheme 158). Toluenechrominm tricarbonyl lithiates non-regioselectively on the ring (bnt at the benzylic position with Na or K bases). Excess base can lead to polylithiation . 

A less well developed, but potentially less intrusive alternative is to block acidic sites with deuterium and to use the kinetic isotope effect to prevent lithiation If the substrate can be polylithiated, the use of dianions (with the last-formed anion being likely to be the most reactive) may give the required selectivity. 

Moreover, in deprotonation reactions with common alkyllithium bases (e.g. butyl-lithium), no side-products are formed, that increase the solubility of the polylithium compound. Also, product mixtures are only rarely observed with this method. Thus, the resulting polylithium compound can be isolated or crystallized more easily. This is why—in addition to Section II. E—only this section presents many visualizations of successful X-ray structural analyses of polylithiated compounds. 

Ferrocene can be polylithiated, by treatment with several equivalents of n-butyllithium in hexane-benzene solvent at 100° or in the presence of a chelating tertiary diamine (TMED). Addition of trimethylchlorosilane to the product so obtained affords a mixture containing FeC10H10-B (SiMe3) (n = 1-7) compounds. The tetrakis derivative (n = 4) was isolated as a pure substance other members of the series were identified only by gas chromatography and mass spectrometry (65). 

Polylithiation at both the 2- and 5-positions gives access to 1,2,5-trisubstituted imidazoles in yields dependent on the ability of the 2-anion to further deprotonate at C-5 (83JCR(S)i96). As the 5-anion is the more reactive, sequential quenching by different electrophiles becomes possible (84JCS(Pi)48l). 

C-Alkylation of polypeptides. Seebach et al.1 report that selective C-alkylation of a sarcosine (N-methylglycine) unit in a tri- or hexapeptide with an N-protected terminal group is possible if polylithiation is eifected with excess LDA in THF with addition of LiCl (5-6 equiv.) to provide a homogeneous mixture. In some cases, addition of an aprotic dipolar solvent (DMPU) or of BuLi can improve the yield. Under these conditions, epimerization and N-alkylation are slight. The new center introduced by alkylation of Sar tends to have the (R)-configuration when the configuration at the other centers is (S). In the methylation of the tripeptide formulated in equation (I), the yield is particularly high because the Sar unit is flanked by an N-methylamino acid. In this case, aldehydes can also serve as electrophiles. Alkylation and benzylation are also possible in the presence of added DMPU. 

The backbone modification of dedicated peptides through the regio- and stereoselective alkylation of their polylithiated enolates was essentially addressed by Seebach s group200,481 483. Critical to the success of this procedure was the ability to solubilize the peptides and their polylithio derivatives in THF by the addition of lithium salts. 

Mono- and polylithiation of TTFs at —78°C constitutes the most significant route for the preparation of TTF derivatives. Treatment of unsubstituted TTF 16 with LDA followed by addition of /)-toluenesulfonyl cyanide (TsCN) afforded derivatives 691 (75%), 692 (4%), and 693 (69%) (Scheme 101). The formation of the small amount of 692 presumably occurred due to a disproportionation of the monoanion. The hydrolysis of 691 using excess sodium ethoxide in ethanol gave the 4-amido-TTF 694 in 65% yield, whilst the reaction with dicyanodiamide under basic conditions afforded the diaminotriazine derivative 695 in 66% yield (Scheme 102) <1995S1411>. 

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