Geometry of enolates

Diastereoselective aldol condensations and related reactions. The geometry of enolates... 

The origin of the third diastereomer produced, complex 12, is of particular mechanistic interest. The configuration at Ca of 12 is opposite to that of the other two products 10 and 11 indicating that the opposite face of the enolate 6 has been approached by the epoxide. Two possible alterations of the geometry of enolate 6 inay be invoked to account for this, adoption of the 5yn- -conformer or adoption of the anti-Z-conformer. Examination of the different structures shown reveals that the observed minor product 12 could arise from a matched reaction pair of the ivn-E-enolate and epoxide (Newman Projection G) or from a mismatched reaction pair of the anti-Z-enolate and epoxide (Newman projection I). The absence of diastereomer 13 strongly suggests that the minor product 12 arises from reaction of the. ryn- -enolate, underscoring the extreme reluctance of iron-acyl complexes to form Z-enolates on deprotonation (see scheme on p 955). 

Figure 8.7 Stereoselective preparation of key intermediates in the syntheses of syn- or anti-1, 5-dimethylalkanes, by control of the geometry of enolate precursors.

Notice that the double bond in this enol could be either Eor Z. It is drawn as Zhere, but in reality is probably a mixture of both— though this is irrelevant to l e reaction. We shall not be concerned with the geometry of enols in this chapter, but there are some reactions that you will meet in later chapters where it is important, and you need to appreciate that the issue exists. 

TABLE 2. Relative energies (in kcalmoD ) of the three optimized geometries of enolates [PH2CH=CH—0] M+ (M = Li, Na)... 

The availibility of three geometric isomers of our artificial enzyme lets us examine other reactions that can show bifunctional catalysis. Enolization of a ketone— and its addition to an aldehyde group in an aldol condensation—are two cases examined so far in which an isomer of our catalyst is preferred that is not the one that was best in the ribonuclease mimic. The geometric preference indicates something novel about the geometry of enolization reactions. 

Breslow, R., and Graft, A. (1993) Geometry of Enolization Using a Bifunctional Cyclodextrin Based Catalyst, J. Am. Chem. Soc. 115, 10988-9. 

Breslow, R. and Graff, A., Geometry of enolization using a bifunctional cyclodextrin-based catalyst, /. Am. Chem. Soc., 1993,115,10988-10989. 

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