Lithium organolithium species

Due to the high interest in metalation reactions with lithium amide or alkyllithiums, an indicator scale of lithium ion pairs in THF has been developed119. Aggregation studies have indicated that organolithium species exist predominantly, if not exclusively, as monomers in the 10-3-10-4 M concentration range. Particular attention has been devoted to the lithium and caesium ion-pair acidities of diphenylamine in THF120 that, at 25 °C, have been found to be 19.05 and 24.20, respectively. 

Ahlbrecht and coworkers showed that tin-lithium exchange can be used to lithiate enamines of 2-methoxymethylpyrrolidine, as shown in Scheme 46. A 50 50 mixture of diastereomers is transmetalated, and the resultant organohthium(s) alkylated to give, after enamine hydrolysis, a 98 2 ratio of ketone enantiomers. In this system, the low barrier to inversion allows equilibration to a single organolithium species, which alkylates by an S 2inv mechanism. 

Transmetallation of allyltributyltin with organolithium species has been used for the generation of allyllithium solutions free of the coupling byproducts which often result from reduction of allylic halides with lithium metal. These solutions may then be used directly for the preparation of Gilman reagents and other reactive modifications of the parent allyllithium. 

In the Suzuki strategy 138 was treated with trityl chloride to afford amine 139 in 84% yield (Scheme 4.29) (Todo et al., 2000). Metal-halogen exchange of 5-bromoisoindoline 139 was achieved using w-butyl lithium at — 65°C to deliver an intermediate organolithium species that was trapped with triisopropylborate to afford the boronic acid upon work-up. Further treatment of the boronic acid with diethanolamine gave diethanolamine boronic ester 140 (Hayashi et al., 2002). Presumably, the diethanolamine boronic ester was formed for stability reasons, as a given diethanolamine boronic ester tends to be less... 

Related pyrrolidines 149 and 150 are produced from organolithium species which readily undergo cyclization onto suitably positioned alkenes <20030BC2111>. The amino-stannane starting material undergoes tin-lithium exchange at low temperatures followed by cyclization on warming to produce two stereoisomers in a 4 1 ratio (Equation 51). The major product formed was found to be the stereoisomer 149, contrary to expectation from model studies. 

The high propensity of organolithium compounds to form mixed complexes with other organolithium species in solution has been utilized successfully in synthesis using chiral lithium amides. Either the chiral lithium amides have been added to organolithium reagents in an effort to achieve asymmetry in addition reactions, or various additives have been introduced to alter the reactivity or selectivity of the chiral lithium amides themselves, e.g. in deprotonation reactions. 

Theoretical calculations of organolithium species have received considerable attention. The low atomic number of lithium is suitable for the most sophisticated molecular orbital methods. Although much debate exists over the degree of covalency within lithium carbon-bonding interactions, the presence of some covalent character in Li bonds of alkyllithinm componnds is widely accepted. 

With tetrameric lithium hydride as a model substance for ab initio calculations of oligomeric organolithium species it was possible to obtain first structural information [6] about the complexation and insertion of the CO molecule But the insertion turned out to be a sligthly exothermic partial reaction, which is hard to believe. 

Since HLiCO and LiCOH are intramolecular solvated organolithium species - in contrast to LiH - it is a question of interest, whether oligomerization is still a strongly exothermic process. Therefore again ab initio calculations on HF/6-3 IG level of theory are used to explore geometries and reaction enthalpies of dimers and tetramers, when the lithium to carbon monoxide ratio is 1 1. 

Sparteine 7 is also an excellent chiral ligand for the asymmetric Michael addition of chirally fixed organolithiums (Eq. (12.8)) [25]. The choice of ligand for the lithium cation provides control of 1,2- vs 1,4-addition of organolithium species to cycloalkenones. Furthermore, in these addition reactions, two contiguous stereocenters were constructed with high diastereo- and enantioselectivities. 

Sparteine 2 is also an excellent chiral diamine hgand in stoichiometric amounts as shown by the hgand-directed conjugate addition of chirally fixed organolithium species. The choice of ligand for lithium can provide control of 1,2-vs 1,4-addition of organohthium species to a,P-unsatuxated carbonyl substrates... 

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