Epoxide formation from sulfur ylide

Whereas phosphonium ylides normally react with carbonyl compounds to give alkenes, dimethylsulfonium methylide and dimethylsulfoxonium methylide yield epoxides. Instead of a four-center elimination, the adducts from the sulfur ylides undergo intramolecular displacement of the sulfur substituent by oxygen. In this reaction, the sulfur substituent serves both to promote anion formation and as the leaving group. 

A number of attempts have been made to use optically active sulfur ylides to transfer the chirality of sulfur to carbon in the formation of epoxides and cyclopropanes. The results were somewhat disappointing. Thus, virtually no asymmetric induction was observed with the ylide (1) [475]. With the stabilized ylides (2), e.e. values in the range 7-43% were reported [476]. Better results were obtained with sulfonium ylides derived from Eliel oxathiane [477]. Optically active diaryl epoxides could be prepared under PTC in high yields and good e.e. values. 

Despite efficient conversions, a major drawback from practical and safety considerations is the use of (potentially) explosive diazo compounds. Consequently, the application was limited to small (mmol)-scale. Thus, replacement of the direct use of the diazo compound by suitable precursors which form the desired diazo compound in situ would be much more favorable. A remarkable improvement addressing this issue was recently achieved by the Aggarwal group [223, 224]. The key step was in-situ formation of the diazo compound starting from the tosylhydra-zone salt 222 under conditions (phase-transfer catalysis at 40 °C) compatible with the sulfur-ylide type epoxidation [223], The concept of this improved method is shown in Scheme 6.100. 

Several groups have investigated the use of complex sulfur ylide reagents for a key carbon-carbon bond formation step in leukotriene synthesis (equation 4). For example, tetraene (6) reacted with methyl S-oxopentanoate to give an 8S% yield of the desired epoxides as a mixture of cis and trans isomers. Significantly, only small amounts of by-products resulting from elimination or rearrangement of the sulfonium salt were observed. 

In order to account for the origin of the enantioselectivity and diastereoselectivity of benzylidene transfer, it is necessary know whether the sulfur ylide reactions are under kinetic or thermodynamic control. From cross-over experiments it was found that the addition of benzylsulfonium ylide to aldehydes was remarkably finely balanced (Scheme 9) [28]. The trans-epoxide was derived directly from irreversible formation of the anti-betaine 4 and the cis-epoxide was derived from partial reversible formation of the syn-betaine 5. The higher transselectivity observed in reactions with aromatic aldehydes compared to aliphatic aldehydes was due to greater reversibility in the formation of the syn-betaine. 

The addition of a diazocarbonyl compound to an alkene with metal catalysis is an effective method for the formation of cyclopropanes, as discussed above. However, direct addition to aldehydes, ketones or imines is normally poor. Epoxide or aziridine formation can be promoted by trapping the carbene with a sulfide to give an intermediate sulfur ylide, which then adds to the aldehyde or imine. For example, addition of tetrahydrothiophene to the rhodium carbenoid generated from phenyldiazomethane gave the ylide 131, which adds to benzaldehyde to give the trans epoxide 132 in high yield (4.104). On formation of the epoxide, the sulfide is released and hence the sulfide (and the rhodium complex) can be used in substoichiometric amounts. 

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