Solvation lithium enolates

FIGURE 2. Molecular arrangement of methanol solvated lithium enolate of 1,3-cyclohexanedione (LiCHD)224... 

Finally, the alkylation of the hexameric di-solvated lithium enolate of methyl 3-amino-butyrate with benzyl bromide in THF shows a conversion-dependent deceleration attributed to the formation of LiBr (this is relevant for NMR results). Interestingly, the side dibenzylated product results from the alkylation of the enolate formed by deprotonation of the syn isomer (km/kan,i = 7)288. Kinetic studies performed under pseudo-first-order conditions reveal approximate first-order dependencies in THF (n = 1.3) and enolate. The idealized rate law implicates a direct alkylation of the hexamer without deaggregation. Moreover, the hypothesis of an anti alkylation taking place at either end of the open form of the hexamer (Scheme 81), although unusual, was not excluded by MNDO calculations. 

Exactly 10 years after the previous statement appeared, the first lithium enolate crystal structures were published as (5) and (6). Thus, structural information derived from X-ray diffraction analysis proved the tetrameric, cubic geometry for the THF-solvated, lithium enolates derived from r-butyl methyl ketone (pinacolone) and from cyclopentanone. Hence, the tetrameric aggregate characterized previously by NMR as (7) was now defined unambiguously. Moreover, the general tetrameric aggregate (7) now became embellished in (5) and (6) by the inclusion of coordinating solvent molecules, i.e. THE. A representative quotation from this 1981 crystal structure analysis is given below. 

Figure 3.2 (a) Structure of dimeric THF-solvated lithium enolate of p-fluorophenyl benzyl ketone. Copied from Ref [7]. (b) Structure of a c/s-configured magnesium enolate of t-butyl ethyl ketone. Copied from Ref [8a]. 

The effect of solvation in CH2=CHOLi was studied in detail. Earlier studies at the B3LYP/6-31+G level suggested that the lowest energy minima correspond to isolated bridged lithium enolate 2a, rather than the open-chain strnctnre 2b this is attributed to the interaction of the lithium cation with the enolate anion (Fignre 3). 

Wen and Grutzner used, among other NMR parameters, the QSC of the lithium enolate of acetaldehyde to deduce that it exists as tetramers of different solvation in THF and THF/n-hexane solvent systems . However, the most thorough study of Li QSC and the most interesting in the present context was reported by Jackman and coworkers in 1987167 -pjjg effects on the QSC values of both aggregation and solvation in a number of organolithium systems was studied in this paper, i.e. different arylamides, phenolates, enolates, substituted phenyllithium complexes and lithium phenylacetylide. 

As most organometallic compounds, lithium enolates are highly polar entities susceptible to combine in various types of (eventually solvated) aggregates that undergo dynamic equilibria in solution. This phenomenon explains why enolate solutions are difficult to describe by the classical spectroscopic, physicochemical or theoretical methods, a difficulty enhanced by the sensitivity of these equilibria to many physicochemical factors such as the concentration, the temperature or the presence of complexing additives (lithium halides, amides, amines, HMPA,. ..). The problems due to dynamics are avoided in the solid state where many clusters of lithium enolates, alone or co-crystallized with exogenous partners, have been identified by X-ray crystallography. 

The mixed (heterogeneous) complexes of a lithium amide (LDA or LiTMP) and a ketone lithium enolate (acetone, cyclohexanone or diisopropyl ketone) have been examined by semiempirical methods (MNDO) by Romesberg and Collum48. If the stabilization associated with these mixed complexes was not determined, the solvation (by THF and HMPA) of the mixed cyclic dimers and trimers was calculated to be generally exothermic (but decreasingly with the steric demand of the enolate) and led to disolvated entities. A set of solvated dimers, trimers and tetramers, cyclic or not, has thus been identified... 

The structure of mixed aggregates involving ester enolates is also of major interest to macromolecular chemists, since ionic additives are often introduced in the polymerization medium. The more stable arrangement between lithium 2-methoxyethoxide and MIB lithium enolate was thus calculated (at the DFT level) to be a 5 1 hexagonal complex with similar O—Li lateral coordinations212. The same team has recently extended this study to complexes formed between the same enolate in THF and a-ligands such as TMEDA, DME, 12-crown-4 and cryptand-2,1,1213. Only in the case of the latter ligand could a separate ion pair [(MIB-Li-MIB),2 THF]-, Li(2,l,l)+ be found as stable, still at the DFT level, as the THF solvated dimer [(MIB-Li)2,4 THF]. 

It has, for instance, been shown with these methods that the dependence of the p Ka of the lithium enolate of o-methoxyacetophenone on the concentration in diluted THF was a consequence of its aggregation, and that an important internal solvation effect of the lithium cation by the oxygen of the methoxy appendage was taking place in the dimer249. 

Abbotto and Streitwieser have shown that the lithium enolate of p-phenylisobutyro-phenone (PhIBP) evolves from a monomer at high dilution (ca 10 4 M) to a tetramer at 10 2 M. Note that the monomer contribution is still in the 1-5% range in 0.1-1.0 M solutions251. The study of the influence of the ethereal solvent on the aggregation of this very enolate has led to the conclusion that it can be found as a pure monomer (in DME) or a pure tetramer (in MTBE), as well as a mixture of both (in THF)252. Upon addition of HMPA, the tetramer dissociates to monomers solvated by 1-2 molecules of HMPA253. 

A short O- - -H distance (1.9 A) was found by Boche and coworkers for the weak ammonium enolate (p.Kbh = 24.3 in acetonitrile) derived from r-butyl a-acetoacetate237, and recently, clearly well-shaped crystals of 1,3-cyclohexanedione lithium enolate (LiCHD) solvated by two molecules of methanol or 2,2,2-trifluoroethanol have been isolated by slow evaporation of a methanol solution of LiCHD. In the aggregate pattern, both oxygens have intramolecular contacts at all available syn or anti lone-pair positions (Figure 2)224. 

The solvent effect has long been recognized as an important factor in that it affects the lithium-oxygen bond polarization but also the electrophilic reagent380,398. The effect on aggregation was evaluated by measurement and comparison of the reactivities of monomeric, dimeric and tetrameric forms of LiPhIBP and LiPhAT or LiPhIBP in various ethers252. In the less polar solvent methyl-tert-butyl ether, lithium enolates are tetrameric and do not react with benzyl bromide. On the contrary, with added HMPA the dissociation of the tetrameric LiPhIBP is accompanied by solvation of each monomer by 1 -2... 

Abbotto, Streitwieser and Schleyer performed an exhaustive study, using the B3LYP /6-31-bG //PM3 calculation level, on the effect of dimethyl ether solvation on aggregated forms of the lithium enolate of acetaldehyde (CH2=CH0Li) (Me20) c. 

Pratt and Streitwieser performed ab initio (HF/6-31G and HF/6-311-FG ) calculations to examine the formation of mixed dimer and trimer aggregates between the lithium enolate of acetaldehyde (lithium vinyloxide, LiOVi) and lithium chloride, lithium bromide and lithium amides. Gas-phase calculations showed that in the absence of solvation effects, the mixed trimer (LiOVi)2 LiX (20) was the most favored species. 

Solvation of lithium enolates in ether solvents was modeled by a combination of specific coordination of dimethyl ether ligands on each lithium and dielectric solvation ... 

Recent studies have suggested that coordination with a lithium cation may be responsible for the stereochemical outcome in Meyers-type enolate alkylations . In fact, the hypothesis that the diastereofacial selectivity observed in these reactions might result from specific interactions with a solvated lithium cation was already proposed in 1990 . Nevertheless, the potential influence exerted by solvation and lithium cation coordination was not supported by a series of experimental results reported by Romo and Meyers , who stated that it would appear that neither the aggregation state of the enolate nor the coordination sphere about lithium plays a major role in the observed selectivity. This contention is further supported by recent theoretical studies of Ando , who carried out a detailed analysis of the potential influence of solvated lithium cation on the stereoselective alkylation of enolates of y-butyrolactones. The results showed conclusively that complexation with lithium cation had a negligible effect on the relative stability of the transition states leading to exo and endo addition. The stereochemical outcome in the alkylation of y -butyrolactones is determined by the different torsional strain in the endo and exo TSs. 

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