Reactions Involving Enolates

The alkylation of enolates constitutes a very powerful method for the formation of C-C bonds. Several methods have been developed in order to control the stereoselectivity of this process. First applications of carbohydrate auxiliaries in stereoselective alkylations of ester enolates were described by Heathcock et al. [152] in 1981. 

To obtain highly stereoselective alkylation reactions of auxiliary linked ester or amide enolates some conditions have to be kept  

The enolate must be formed with high ( )- or (Z)-selectivity. 

The stereotopic faces of the enolate double bond must be efficiently differentiated by the auxiliary. 

SCHEME 10.68 Silyl enol-ethers bearing sugar-derived auxiliaries can be generated with high E selectivity using LTMP as a base where no E/Z selectivity is realized using LHMDS. 

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For examples of this coupling reaction involving enol triflates derived from ketones, see Takai, K. Taga-shira, M. Kuroda, T. Oshima, K. Utimoto, K. Nozaki, H. J. Am. Chem. Soc. 1986, 108, 6048. 

NUCLEOPHILIC REACTIONS INVOLVING ENOLATE ANIONS Table 10.1 Keto-enoL equiLibria... 

We have seen many examples of chemical reactions involving enolate anions, and should now realize just how versatile they are in chemical synthesis (see Chapter 10). We have also seen several examples of how equivalent reactions are utilized in nature. For the triose phosphate isomerase mechanism above, we did not actually invoke a distinct enolate anion intermediate in the enolization process, but proposed that there was a smooth flow of electrons. For other reactions, we shall also need to consider whether enolate anions are actually involved, or whether a more favourable alternative exists. The aldol-type reaction... 

Considerable effort has been devoted to finding Lewis acid or other catalysts that could induce high enantioselectivity in the Mukaiyama reaction. As with aldol addition reactions involving enolates, high diastereoselectivity and enantioselectivity requires involvement of a transition state with substantial facial selectivity with respect to the electrophilic reactant and a preferred orientation of the nucleophile. Scheme 2.4 shows some examples of enantioselective catalysts. 

The most advanced synthetic methods involve chiral directors that have C2 symmetry. These are discussed first for x-chloro boronic esters (Section 1.1.2.1.2.1.) and then for the bromo analogs, which are better in reactions involving enolates (Section 1.1.2.1.2.2.). The first syntheses of secondary alcohols utilized pinanediol as chiral director (Section 1.1.2.1.2.3.). The method is marginally successful for some tertiary alcohols (Section 1.1.2.1.2.4.). 

Returning to the main theme in this section, another case where chelation to a metal centre controls reactions involving enolates is seen in complexes of amino acid derivatives. Amino acids are commonly found in metal complexes as the chelated anions in which the carboxylate oxygen and the amino group are co-ordinated to the metal. The co-ordinated amino acid anion could be in the keto (5.6) or enolate (5.7) form. 

Beagley, B. Betts, M. J. Pritchard, R. G. Schofield, A. Stoodley, R. J. Vohra, S. Hidden axial chirality as a stereodirecting element in reactions involving enol(ate) intermediates. Part 1. Cyclization reactions of methyl (4R)-3-(2-diazo-3-oxobutanoyl)thiazolidine-4-carboxyl-ate and related compounds. J. Chem. Soc. Perkin Trans. 1 1993, 1761-1770. 

Reactions Involving Enols or Enolic Derivatives.—Reviews on the use of... 

Other reactions involving enols and enolate ions. 176... 

Revision of Chapters 9 and 14 and a start on mechanisms for chemical reactions involving enolization. 

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