Z-alkene formation

Kishi and coworkers noted the importance of the phosphonate structure in the synthesis of monensin, where a methyl phosphonate was used to maximize (Z)-alkene formation. These observations were expanded upon in the synthesis of rifamycin Several interesting Wittig reactions from this synthesis are presented in Table 14. 

An aldehyde with a-ether functionality was used in the synthesis of N-acetylneuraminic acid by Danishefsky (equation 37). A series of cis- and trans-alkenes with a-oxygen functionality were synthesized by Cinquinin and coworkers. Of the examples generated, the HWE reaction proceeded in the expected ( )-selective manner (164), while the trifluoroethyl phosphonate was used to form the (Z)-al-kenes (163) selectively (Scheme 26). Interestingly, 18-crown-6 was not used for (Z)-alkene formation. 

Increasing the steric bulk of the silyl group enhances the ratios of (Z)> to (E)-alkene isomers. The size of the ester group can also affect the ( ) (Z) ratios of alkenes. An example is the synthesis of but-enolides (360) by Peterson alkylation of a-keto acetals (359 equation 8S). Increasing the ester from methyl to isopropyl and r-butyl resulted in a corresponding increase in (Z)-alkene formation. 

The Cope elimination has been used to synthesize a variety of acyclic alkenes. 1,2-Disubstituted acyclic alkenes are usually obtained with the ( )-stereochemistry because of steric hindrance to (Z)-alkene formation. The stereochemistry of trisubstituted alkenes is determined by the configuration of the starting amine oxide and is not usually affected by subsequent isomerization. ... 

The observations summarized in Table 8 have important preparative consequences. To achieve the highest possible ( )-alkene selectivity in a system that is capable of stereochemical equilibration, it is essential to provide sufficient time for oxaphosphetane equilibration below the decomposition temperature. This is best done by monitoring the diastereomer mixture using NMR methods to establish the temperature thresholds for diastereomer equilibration as well as for alkene formation from the more reactive cis-diastereomer. Once these temperatures are known, equilibration can be allowed to proceed below the temperature for (Z)-alkene formation until the optimum ratio of trans-cis oxaphosphetanes is obtained. Subsequent warming completes the optimized E-selective alkene synthesis in an equilibrating system (Table 7). 

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