Solutions lithium enolate structure

A more detailed representation of the reaction requires more intimate knowledge of the enolate structure. Studies of ketone enolates in solution indicate that both tetrameric and dimeric clusters can exist Tetrahydrofliran, a solvent in which many synthetic reactions are performed, favors tetrameric structures for the lithium enolate of isobutyr-ophenone, for example. ... 

Experimentally, x values for gaseous lithium halides were determined as early as 1949 by molecular beam resonance experiments In solution, the quadrupolar interaction of ethyUithium and of t-butyllithium were investigated in 1964 . It was found that tetrameric and hexameric aggregates have different interactions. In the solid state x of tetrameric methyl- and ethyUithium was determined in 1965 and 1966 , and for lithium formate in 1972 . However, it was not untU Jackman started his investigations of lithium enolates and phenoxides in solution that the quadrupolar interaction was used in a systematic fashion to obtain structural information . 

It is known that the chemistry of enolates depends on the nature of the metal. Moreover, the metals are an integral part of the structures of enolates. Lithium enolates are most frequently employed, and in the solid state the lithium cations definitely are associated with the heteroatoms rather than with the carbanionic C atoms. Presumably the same is true in solution. The bonding between the heteroatom and the lithium may be regarded as ionic or polar covalent. However, the heteroatom is not the only bonding partner of the lithium cation irrespective of the nature of the bond between lithium and the heteroatom ... 

L. M. Jackman, J. Bortiatynski, Structures of Lithium Enolates and Phenolates in Solution, in Advances in Carbanion Chemistry (V Snieckus, Ed.), Vol. 1, 45, Jai Press Inc, Greenwich, 1992. 

The position of the lithium cation in the enolates has been the object of much debate. It is now well established that the cations of the strongly electropositive metals of groups I, II and III stand closer to the oxygen than to the carbon atom while this metalotropy is more balanced with transition metal enolates. The structure of the lithium enolates in vacuum, in the solid state as well as in solution is discussed in detail in the next section of this chapter. 

The degree of aggregation of organolithium compounds (alkyl-, aryl-, and alkynyl-lithium compounds as well as lithium enolates) in dilute tetrahydrofuran solution at —108 °C has been determined by means of cryoscopic [289] and NMR spectroscopic measurements [290] for a review on the solution structure of Hthium enolates and phenolates, see reference [406]. 

The quadrupole splitting constant, QSC, of Li has been used by Jackman et al. [151] and Johnels [152] as an empirical parameter to obtain structural information on lithium enolates in solution. Tlie QSC is given by equation (11). 

Before commencing this discussion, it is appropriate to consider briefly the issue of kinetic versus thermodynamic control in the reactions of preformed Group I and Group II enolates and to summarize the structure-stereoselectivity generalizations that have emerged to date. It is now welt established that preformed lithium, sodium, potassium and magnesium enolates react with aldehydes in ethereal solvents at low temperatures (typically -78 °C) with a very low activation barrier. For example, reactions can often be quenched within seconds of the addition of an aldehyde to a solution of a lithium enolate. ... 

The alkylation reactions of enolate anions of both ketones and esters have been extensively utilized in synthesis. Both stable enolates, such as those derived from 6-ketoesters, 6-diketones, and malonate esters, as well as less stable enolates of monofunctional ketones, esters, nitriles, etc., are reactive. Many aspects of the relationships among reactivity, stereochemistry, and mechanism have been clarified. The starting point for the discussion of these reactions is the structure of the enolates. Studies of ketone enolates in solution indicate that both tetrameric and dimeric clusters can exist. THF, a solvent in which many synthetic reactions are performed, favors tetrameric structures for the lithium enolate of isobutyrophenone, for example. ... 

Since the start of investigations into asymmetric reactions with enolates it has been known that the reactivity and selectivity observed in enolate chemistry is influenced not only by the base employed, but also by the use of cosolvents such as HMPA, and the addition of metal salts or Lewis acids. [2-4, 11] Lithium enolates, in particular, tend to form aggregates by self-assembly. [3, 4] Decisive contributions to the explanation of this phenomenon and its consequences have been made by Seebach et al. by crystal structure analyses of crystalline lithium enolates [12] up to suggestions regarding the structure of the complexes in solution (Scheme 5). [3, 4, 13]... 

Any discussion of enolate geometry must include the structure of the enolate. It is well known that metal enolates exist as dimers a or other aggregates in ether solvents S (see Section 9.2.C. for a discussion of aggregate formation with LDA).28d Jackman and Szeverenyi suggested that the lithium enolate of isobutyro-phenone exists as a tetramer (31) in THF solution but exists as a dimer (32) in DME. o Such aggregates were proposed by House et ah,3 who found that ketone enolates of groups 1 (lA), 2 (llA), and 3 (lllA) metals... 

Lithium enolates of ketones exist as aggregates in solution.29-3l,34d,35 Mixed aggregates between the enolate anion and the amide base are also possible. In 1981, Seebach and co-workers confirmed by X-ray crystallography that the lithium enolates of pinacolone and cyclopentanone form a tetrameric aggregate in the solid state, and it was assumed that a similar species exited in solution. A THF solvated tetramer of lithium pinacolonate is shown (see 33), as it was reported by Seebach. Williard et al. reported the X-ray structure of... 

Lithium enolates exist as large aggregates and their approach to the electrophile is restricted by steric and electronic considerations, as well as by the relative geometry of the molecule. Despite the structural complexity remarkably good predictions for reactivity and diastereoselectivity can be made based on the steric requirements that would be present in a monomeric system. For example, in most reactions of enolate anions the electrophile will be delivered to the less hindered face of the enolate to give the major product. In all models used to describe reactivity (secs. 9.5.A.iii-9.5.A.v), a monomeric enolate will be shown but the facial and orientational bias of the enolate is clearly influenced by the state of aggregation in solution. 

Some solutions to the problem of the formation of a specific enolate from an unsymmetrical ketone were discussed above. Another solution makes use of the structurally specific enol acetates or enol silanes (silyl enol ethers). Treatment of a trimethylsilyl enol ether with one equivalent of methyllithium affords the corresponding lithium enolate (along with inert tetramethylsilane). Equilibration of the... 

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