Stereochemical leakage

The reaction of 3-ketoacids with allyl carboxylates is also believed to proceed via a palladium enolate intermediate.126 Less than complete stereospecificity is also observed in these reactions (equation 163). Interestingly, the bicyclic lactone substrate employed to ascertain the stereointegrity of this reaction, in addition to being incapable of any syn-anti isomerization, cannot epimerize the starting material by car-boxylate attack at the metal. The observed stereochemical leakage could be due to epimerization of the intermediate allyl complex (equation 164) or reductive elimination of an allylpalladium enolate (retention) (equation 165). 

A methodology developed for the synthesis of cyclopropyl ketones from THFs (51) has been shown to suffer from stereochemical leakage resulting from the unexpected cleavage of a benzoate ester by potassium r-butoxide and the subsequent participation of the resulting hydroxyl group in the adjacent substitution reactions.90 This prob- lem has been solved, however, by the discovery of a simpler, more direct cascade reaction for the synthesis of single enantiomers of cyclopropanes with predictable stereochemistry.90 The mechanism of the reactions has been discussed. 

This particular reaction was studied when analytical methods were not available to measure the probably small degree to which each isomer gave some of the other alkene, either by a different mechanism or by incomplete stereospecificity in the E2 reaction itself. No matter how much stereochemical leakage there is, as long as the diastereoisomer ratio is greater than 50 50, the reaction is still stereospecific. It is not helpful to use the word stereospecific to mean 100% stereoselective, as many people thoughtlessly do—a useful distinction is lost, and understanding suffers. 

Tables 6 and 7 summarize results from stereochemical equilibration studies performed over the past decade by MaryanofT et al. (22,23), and Vedejs et al. (20, 21c, 39-42). A few other convincing examples are included to expand the scope of the systems covered. Table 6 lists those examples where control experiments establish at least 90% retention of stereochemistry from intermediates-to alkene products. As already discussed, the percentage of equilibration represents the upper limit for loss of stereochemistry from all possible pathways in the control experiments. No attempt has been made to determine whether the minor levels of stereochemical leakage in Table 6 occur at the stage of oxaphosphetanes, betaines, or other potential intermediates. Table 6 includes entries corresponding to all of the principal families of Wittig reagents nonstabilized ylides (entries 1-12, 24, 25, 29, and 30), benzylic ylides (entries 13-17 and 28), allylic ylides (entries 22, 23, 26, and 27), and ester-stabilized ylides (entries 18-21). The corresponding Wittig reactions must take place under dominant kinetic control.

Let us close this section with a gold- and palladium-cocatalyzed carbostannylation of substituted propiolates 89 by vinylstannanes 90 (Scheme 45) [81]. The Au(I) electrophilic activation of the triple bond is said to promote the oxidative addition of the Pd(0) to the alkyne. Next, a transmetallation of the vinylstannane across one of the Pd-C bonds puts the reaction back on a Stille-type track. Several a-stannylated dienic esters such as 91 were thus prepared in medium to good yields. The stereocontrol is similar to that observed in the Stille coupling (high syn selectivity for the addition and stereospecificity with respect to the vinylstannane), albeit some stereochemical leakage was observed with bulky Z-stannanes. 

The stereochemical structure was clarified with the use of X-ray crystallography by Iitake et at. (75). As for mode of action of tetranactin, Ando et at. (76) observed that tetranactin is an uncoupler in cockroach mitochondria and supposed that the antibiotic caused the leakage of alkali cations such as K+ through the lipid layer of the biomembrane in mitochondria, followed by uncoupling. 

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