Crystal lithium enolates

Fig. 1.1. Crystal structure of lithium enolate of methyl -butyl ketone in a structure containing four Li+, two enolates, and one HMDA anions, one bromide ion, and two TMEDA ligands. Reproduced from Angew. Chem. Int. Ed. Engl., 35, 1322 (1996), by permission of Wiley-VCH.

Notably, the lithium enolates have the planar methylenecyclopropane-type structure56, but give C-alkylation products49"52. X-ray structure analysis of the lithium enolate56 and bicyclobutyllithium57 TMEDA complexes revealed that both crystallize as lithium bridging dimers. 

Be this as it may, lithium attempts to bind to several bonding partners the structural consequences for the enolates of a ketone, an ester, and an amide are shown in Figure 13.2 In contrast to the usual notation, these enolates are not monomers at all The heteroatom that carries the negative charge in the enolate resonance form is an excellent bonding partner such that several of these heteroatoms are connected to every lithium atom. Lithium enolates often result in tetramers if they are crystallized in the absence of other lithium salts and in the absence of other suitable neutral donors. The lithium enolate of fert-butyl methyl ketone, for example, crystallizes from THF in the form shown in Figure 13.3. 

Fig. 13.2. X-ray single crystal structures of lithium enolates. TMEDA, tetramethylethylenedi-amine.

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. 

Seebach, Dunitz and coworkers reported, in 1981226, the first crystal structures of lithium enolates of simple ketones, obtained in THF from pinacolone (3,3-dimethyl-2-butanone) and cyclopentanone. Both were arranged as tetrasolvated cubic tetramers, one THF molecule capping each lithium cation (Scheme 58A). Note that pinacolone enolate can also be crystallized, from heptane at — 20 °C, as a prismatic unsolvated hexamer exhibiting an approximate S6 symmetry and six slight it-cation interactions227,228 (Scheme 58B) or as a dimer in the presence of 2 molecules of TriMEDA29. Similarly,... 

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. 

Alkylations of the Lithium Enolates. Treatment of the reagents with Lithium Diisopropylamide (LDA) generates the enolates (2) or ent- 2) (crystal structure of rac-TBDMS-(2) ) which can be alkylated to give, for instance, (/ )-a-methyl-dopa (3) or triacetyl (S)-a-methyl-dopa. ... 

S)-4-(l-Methylethyl)-5,5-diphenyl-2-oxazolidinone (3), whose preparation is described here, has several advantages over Evans original auxiliaries i) Derivatives of 3 are more likely to crystallize. In many cases the separation and purification of diastereoisomers can be achieved by simple recrystallization rather than by expensive and time-consuming chromatography, ii) Acylation of 3 can be carried out at 0°C (instead of-78°C for 4 and 5) by deprotonation with BuLi, followed by treatment with an activated carboxylic acid derivative, iii) Lithium enolates of N-acyl derivatives of 3 can be obtained directly by treatment with BuLi at -78°C, in comparison to 4 and 5 when the more expensive... 

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. 

Seebach, Dunitz and cowoikers fust described the THF-solvated tetrameric aggregates obtained from THF solutions of 3,3-dimethyl-2-butanone (pinacolone) and cyclopentanone lithium enolates. These are represented as (137). The pinacolone enolate also crystallizes as the unsolvated hexamer (138) from hydrocarbon solution, but this hexamer rearranges instantaneously to the tetramer (137) in the presence of THF. Williard and Carpenter completed the characterization of both the Na+ and the K+ pinacolone enolates.Quite unexpectedly the Na pinacolone enolate is obtained from hydrocarbon/THF solutions as the tetramer (139) with solvation of the Na atoms by unenolized ketone instead of by THF. Hie potassium pinacolone enolate is a hexameric THF solvate depicted as (140) and described as a hexagonal prism. A molecular model of (140) reveals slight chair-like distortions of the hexagonal faces in (140) so that the solvating THF molecules nicely fit into the holes between the pinacolone residues. 

The pinacolone lithium enolate condensation product with pivaldehyde (147) has been characterized as the tetrameric aggregate (148).However, an attempted condensation reaction of pinacolone with itself as shown in Scheme 8 led to crystallization of a product derived from subsequent dehydration and reenolization, i.e. (149). This dienolate (149) was characterized as the dimer (150) solvated by ditnethyl-propyleneurea (DMPU). ... 

Few ester enolate crystal structures have been described. The lack of structural information is no doubt due to the fact that the ester enolates undergo a-elimination reactions at or below room temperature. A good discussion of the temperatures at which lithium ester enolates undergo this elimination is presented in the same paper with the crystal structures of the lithium enolates derived from r-butyl propionate (163), r-butyl isobutyrate (164) and methyl 3,3-dimethylbutanoate (165). It is significant Aat two of the lithium ester enolates derived from (163) and (165) are both obtained with alkene geometry such that the alkyl group is trans to the enolate oxygen. It is also noteworthy that the two TMEDA-solvated enolates from (163) and (164) are dimeric, while the THF-solvated enolate from (165) exists as a tetramer. 

The lithium enol derived from lV,lV-dimethylcycloheptatrienecarboxainide (172) crystallizes as the bis-THF-solvated dimer (173). Neither the amide nitrogens nor the extended ir-system participates in complexation to the lithium atoms in this complex. 

Two lithium enolates (174) and (175) derived from the vinylogous urethanes (176) and (177) have been crystallized and subjected to X-ray diffraction analysis.Although the individual enolate units combine to form different aggregates, they are very nearly identical in conformation, i.e. s-trans around the 2,3-bond however, both the aggregation state and the diastereoselectivity of the enolates differ. The enolate (175) is obtained from benzene solution as a tetramer and (174) is obtained from THF solution as a dimer. The origin of the diastereoselectivity shown by these enolates is subtle. 

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