Functionalized Organolithium Compounds

Vinyllithium derivatives 128-131 have been generated through a bromine-lithium exchange with t-BuLi. In the case of 128, used in the synthesis of (-)-wode-shiol, a deprotonation of the alcohol functionality was performed prior lithiation [107]. Intermediates 129 were also used in the synthesis of triquinanes [102,108], meanwhile 130 acted as an intermediate in a synthetic route to (-i)-pericosine B [109]. Dianionic species 131 showed an unexpected intramolecular carbometalla-tion upon addition of TMEDA to give dilithiated dihydropyrroles, which finally reacted with different electrophiles [110]. 

Organolithium compounds with a functional group at the / position can be represented by a great number of general structures (XI-XX) depending on the hybridization of the carbon atoms bearing both the lithium and the functional group. 

Functionalized organolithium compounds of type XI can be accessible through a large number of methodologies. They are accessible by halogen-, sulfur-, or selenium-lithium exchange, tin-lithium transmetallation, reductive opening of four-membered heterocycles and also by carbolithiation of cinnamyl systems. 

The allylic intermediate 157 was prepared by deprotonation with LDA and reacted with 1,2-dialkyloxiranes in the synthesis of parasorbic acid [132], Direct deprotonation of silyl ally] ether with s-BuLi gave the allylic compound 158, which reacted with electrophiles at the y-position [133]. Tin-lithium transmetallation of a 3-stannylated enamine led to the intermediate 159, which after reaction with electrophiles and acidic hydrolysis gave 3-funcionalized cyclohexenones [134], The chiral mdo-aminoallyllithium 160 was also prepared by tin-lithium transmetallation of the corresponding O-methylprolinol derivative, and alkylated to give after hydrolysis /3-alkylated ketones [135]. Direct deprotonation with t-BuLi of N-methal-lylaniline gave the dianionic intermediate 161, of type XIV [136]. 

Iron-catalyzed carbolithiation of the internal alkyne 186, bearing an alkoxy group at the homopropargylic position, led to the vinyllithium compound 187, 

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A study of the state of association of the functionalized organolithium compounds 204a-d was carried out by multinuclear ( H, Li, Li, C, N and P) NMR spectroscopy, using Li- and N-enriched species. Spectral evidence, supported in part by XRD crystallographic evidence, points to compounds 204a-c being dimerically associated in etheric solutions in three different forms (205-207). The interconversion among these three... 

V. FUNCTIONALIZED ORGANOLITHIUM COMPOUNDS BY HALOGEN-LITHIUM OR SULFUR-LITHIUM EXCHANGE... 

The reaction shown in Scheme 39 was also performed starting from a chiral carbamoyl chloride (91, Y = O) derived from (f )-iV-methyl-iV-(l-phenylethyl)amine, in order to study the possible asymmetric induction using prochiral carbonyl compounds. Thus, with pivalaldehyde or benzaldehyde the mixture of diastereomers obtained was ca 1 1. This behavior was also observed with other chiral functionalized organolithium compounds ". ... 

There are many examples of /3-amido and /3-oxido functionalized organolithium compounds, which were prepared mainly using the stoichiometric version of the arene-promoted lithiation ". In this section, the preparation of the same type of intermediates by halogen-or sulfur-lithium exchange will be considered, using the catalytic version of the mentioned lithiation. 

Oxido functionalized organolithium compounds of type 128 or 131 are also accessible by sulfur-lithium exchange using the arene-catalyzed lithiation technology. 

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... 

For aU the chiral intermediates above mentioned (253, 257 and 258) the reaction with prochiral electrophiles (aldehydes or differently substituted ketones) gave a c 1 1 mixture of diastereomers so, as occurred in other chiral functionalized organolithium compounds, the asymmetric induction is practically non-existent. 

Y = O) or —90°C (Y = NMe, S) gave the corresponding intermediates 427 resulting from a carbon-sulfur cleavage. Further reaction of these functionalized organolithium compounds with different electrophiles at the same temperature, followed by hydrolysis with water, yielded products 428 (Scheme 120) . 

C. Najera, M. Yus, Functionalized Organolithium Compounds New Synthetic Adventures, Curr. Org. Chem. 2003, 7, 867-926. 

Najera, C. Yus, M. Functionalized organolithium compounds New synthetic adventures. Current Organic Chemistry 2003, 7(9), 867-926. 

B. Reductive Opening of Heterocycles as a Source of Functionalized Organolithium Compounds... 

Cyclic alkyl aryl ethers lead also to functionalized organolithium compounds by reductive carbon-oxygen bond cleavage in arene-catalyzed lithiation process. Thus, the treatment of 2,3-dihydrobenzofuran (47) with an excess of lithium in the presence of a catalytic amount of DTBB in THF at 0°C gives the dianion (48) which after reaction with different carbonyl compounds and final hydrolysis with water leads to... 

Functionalized organolithium compounds in total synthesis 05T3139. 

Bachki A, Foubelo F, Yus M (1996) Chiral Epoxides as a Source of Chiral (3-Oxido-Functionalized Organolithium Compounds Reaction with Electrophiles. Tetrahedron Asymm 7 2997... 

There are several examples of a-oxygen- and nitrogen-functionalized organolithium compounds with sp and sp hybridization in acyclic and cyclic systems of general structures I-IV. These compounds show a tendency to undergo a-elim-ination processes to generate carbene intermediates. 

As commented above, this kind of functionalized organolithium compounds can also be prepared through deprotonation processes. The deprotonation can be also performed in a diastereoselective way, for instance, in the presence of (-)-sparteine [24]. Treatment of 0-alkyl carbamate 27 with s-BuLi in the presence of (-)-sparteine at -78 °C gave the organolithium compound 28 with high ee, which upon carboxylation and acidic hydrolysis led to (J )-pantolactone 29 (Scheme 2.5) [25],... 

As has been described before, one of the most important problems to be overcome in the preparation of sp -hybridized /3-functionalized organolithium compounds is their decomposition by a /3-elimination process to give olefins. Advantage of this reaction can be taken to prepare olefins starting from organomercur-ials, chlorohydrins and epoxides by performing the lithiation process at higher temperatures [92]. 

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