Lithium enolates

A further improvement utilizes the compatibility of hindered lithium dialkylamides with TMSC1 at —78 °C. Deprotonation of ketones and esters with lithium dialkylamides in the presence of TMSC1 leads to enhanced selectivity (3) for the kinetically generated enolate. Lithium t-octyl-t-butyl-amide (4) appears to be superior to LDA for the regioselective generation of enolates and in the stereoselective formation of (E) enolates. 

Enolates, lithium salts, aldol condensation with, 54, 49 Enol esters, preparation, 52,... 

To obtain complete conversion of ketones to enolates, it is necessary to use aprotic solvents so that solvent deprotonation does not compete with enolate formation. Stronger bases, such as amide anion ( NH2), the conjugate base of DMSO (sometimes referred to as the dimsyl anion),2 and triphenylmethyl anion, are capable of effecting essentially complete conversion of a ketone to its enolate. Lithium diisopropylamide (LDA), which is generated by addition of w-butyllithium to diisopropylamine, is widely used as a strong... 

The addition of Grignard reagents or organolithiums (alkenyl, alkyl, alkynyl, allyl or aryl) to nitroenamines (281)213 was reported by Severin to afford P-substituted-a-nitroalkenes.214 b Similarly, ketone enolates (sodium or potassium), ester enolates (lithium) and lactone enolates (lithium) react to afford acr-nitroethylidene salts (294) which, on hydrolysis with either silica gel or dilute acid, afford 7-keto-a,(3-unsaturated esters or ketones (295)2l4c-d or acylidene lactones (296).214 Alternatively, the salts (294, X s CH2) can be converted to -y-ketoketones (297) with ascorbic acid and copper catalyst. 

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 ... 

Hydrolysis and decarboxylation in the usual way lead to keto-esters or keto-acids. Of the more common metals used to form enolates, lithium is the most likely to give good C-acylation as it> like magnesium, forms a strong O-Li bond. It is possible to acylate simple lithium enolates with enoliz-able acid chlorides,... 

Na, and K) enolates. Lithium enolates are not ideal nucleophiles for thermodynamically controlled conjugate addition. Better results are... 

SCHEME 59. Various types of solid-state mixed aggregates involving ketone lithium enolates (A) pinacolone enolate/lithium amide [LiHMDS/CH2C(OLi)Bu-i, 2 DME]230 (B) pentan-3-one enolate/2 chiral lithium amide232 (C) pinacolone enolate/lithium amide/LiBr [LiHMDS/2 Cl HCtOI.ijBu-f/LiBr, 2 TMEDA]235... 

It is not essential to have two anion-stabilizing groups for successful conjugate addition and it is even possible with simple alkali metal (Li, Na, and K) enolates. Lithium enolates are not ideal nucleophiles for thermodynamically controlled conjugate addition. Better results are often observed with sodium or potassium enolates, which are more dissociated and thus more likely to revert. Lithium binds strongly to... 

No aldol reaction is possible until the LDA is consumed and a second carbonyl compound is added. This procedure is a convenient way to do crossed aldol reactions in a controlled fashion. When there is a choice, LDA forms the more accessible, less substituted enolate. Lithium diisopropylamide is a large, sterically encumbered base and removes a proton from the sterically less hindered position to give what is called the kinetic enolate. Notice that this reaction can be used to generate two new stereocenters adjacent to each other. This procedure is very useful and has received considerable attention in the past 30 years. 

The influence of the coordination of lithium and sodium enolates on the stereochemical outcome of their aldol reactions has been reviewed. The alkylation of the ambident enolates of a methyl glycinate Schiff base with ethyl chloride have been studied at B3LYP and MP2 levels. The transition states for the alkylation of the free ( )/(Z)-enolate with ethyl chloride have energy barriers of 13kcalmol However, with a lithium ion, the ( )-enolate behaves as an ambident enolate and makes a cyclic lithium complex in bidentate pattern, which is more stable by 11-23 kcal mor than the (Z)-enolate-lithium complexes. The results suggest that the alkylation of ambident enolates proceeds with stable cyclic bidentate complexes in the presence of metal ion and solvent. 

Dvofanek, L. and Vlcek, P. (1994) Anionic polymerization of acrylates. 8. Kinetics of the anionic polymerization of butyl acrylate initiated with the complex initiatOT lithium ester enolate/lithium rcr(-hutoxide. Macromolecules, 27,4881 885. 

Scheme 3.3 Preparation methods and structure of lithium enolate-lithium halide aggregates 5.

---