Enolates with alkyl halides

Alkylation of Enolates (condensation of enolates with alkyl halides and epoxides) Comprehensive Organic Synthesis 1991, vol. 3, 1. 

Optically active, a-branched lactams 30 have been built by means of Meyers chiral auxiliaries [ 10]. The key step included the diastereoselective a-alkylations of the initially formed co-i -sulfonamido oxazolines 26. The R or S configuration in the product 27 was obtained reacting the appropriately configured intermediate aza enolates with alkyl halides, high diastereoselectivities have been reported. Several attempts to achieve a complete ring closure to the lactams 30 (via 29) by an acidic cleavage of the oxazolines 27 failed. Varying mixtures of... 

Seebach and Naef1961 generated chiral enolates with asymmetric induction from a-heterosubstituted carboxylic acids. Reactions of these enolates with alkyl halides were found to be highly diastereoselective. Thus, the overall enantioselective a-alkyla-tion of chiral, non-racemic a-heterosubstituted carboxylic acids was realized. No external chiral auxiliary was necessary in order to produce the a-alkylated target molecules. Thus, (S)-proline was refluxed in a pentane solution of pivalaldehyde in the presence of an acid catalyst, with azeotropic removal of water. (197) was isolated as a single diastereomer by distillation. The enolate generated from (197) was allylated and produced (198) with ad.s. value >98 %. The substitution (197) ->(198) probably takes place with retention of configuration 196>. 

The reaction of these lithium enolates with alkyl halides is one of the most important C-C bondforming reactions in chemistry. Alkylation of lithium enolates Works with both acyclic and cyclic ketones as well as with acyclic and cyclic esters (lactones). The general mechanism is shown below, alkylation of an ester enolate alkylation of a ketone enolate... 

Various substitutions of hydrogen at positions 3 and 4 in -lactams can be performed with electrophilic reagents. The 3-position is activated by the carbonyl group. Alkylation at the 3-position is readily executed via the enolate with alkyl halides, aldehydes, ketones, carbon dioxide, etc. A carboxyl group at C(4) as in 79 does not interfere, the dilithium salt being alkylated at C(3) with excellent stereocontrol, giving the /ra j-disubstituted lactams 80. Hydrolysis leads to -alkyl aspartic acids 81. 

Reaction of stabilized carbanions (enolates) with alkyl halides (enolate alkylation)... 

The condensation of enolates with alkyl halides or other carbonyl derivatives allows a wide variety of synthetic and functional group transformations in the carbon-carbon bond-forming process. Enolates are, therefore, among the most powerful synthetic intermediates known. In addition to generating a new carbon-carbon bond, the reaction proceeds with high diastereoselectivity in most cases, making it even more useful. 

In conclusion, the reaction of enolates with alkyl halides and carbonyl compounds provides one of the most powerful and useful of all carbon-carbon bond-forming processes. Not only are a variety of synthetic products available, but the reaction can be made to proceed with excellent diastereoselectivity. In conjunction with the reactions of carbanions, nucleophilic methods constitute the largest single type of methodology for making new carbon-carbon bonds. 

Reductive alkylation of enones. Tin(IV) enolates are formed via the ketyls, which are derived from enones and BujSnH. Reaction of the enolates with aldehydes furnishes aldols. Quenching the enolates with alkyl halides in the presence of HMPA gives a-alkylated products. ... 

Deprotonation and Alkylation Reactions. Reaction of the title compound with LDA and trapping of the resulting ester enolate with alkyl halides leads to mixtures of the a- and p-alkylated products (eq 1), the ratio of which can be strongly influenced by the presence or absence of Cul. Related studies have been carried out on the dianion derived from the precursor acid, and one product of such processes exploited in the synthesis of the racemic modification of the diterpene trixagol. ... 

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