Reactions of sulfur ylides

An alternative to the synthesis of epoxides is the reaction of sulfur ylide with aldehydes and ketones.107 This is a carbon-carbon bond formation reaction and may offer a method complementary to the oxidative processes described thus far. The formation of sulfur ylide involves a chiral sulfide and a carbene or carbenoid, and the general reaction procedure for epoxidation of aldehydes may involve the application of a sulfide, an aldehyde, or a carbene precursor as well as a copper salt. This reaction may also be considered as a thiol acetal-mediated carbene addition to carbonyl groups in the aldehyde. 

Some organic reactions can be accomplished by using two-layer systems in which phase-transfer catalysts play an important role (34). The phase-transfer reaction proceeds via ion pairs, and asymmetric induction is expected to emerge when chiral quaternary ammonium salts are used. The ion-pair interaction, however, is usually not strong enough to control the absolute stereochemistry of the reaction (35). Numerous trials have resulted in low or only moderate stereoselectivity, probably because of the loose orientation of the ion-paired intermediates or transition states. These reactions include, but are not limited to, carbene addition to alkenes, reaction of sulfur ylides and aldehydes, nucleophilic substitution of secondary alkyl halides, Darzens reaction, chlorination... 

The reactions are normally limited to the use of electron deficient alkenes as substrates. However, there have been some reports of copper-catalyzed reactions of sulfur ylides with simple alkenes, as exemplified in equation (16).147... 

The reaction of sulfur ylides with carbonyl compounds such as ketones or the related imines leads to the corresponding epoxides or aziridines. 

The reaction of sulfur ylides with enones gives cyclopropanes. 

The reaction of sulfur ylides with aldehydes and ketones was first reported by Johnson in 1961, but is for some reason better known as the Corey-Chaykovsky reaction. The reaction between sulfur ylides and an electrophilic carbon atom of a C=0 gives a betaine intermediate. The favoured reaction path is therefore an internal Sn2 process which furnishes an epoxide with regeneration of the sulfide (Scheme 3.28). 

The reaction of sulfur ylides e.g. Me2S -CH2) with carbonyl compounds is a useful route to epoxides. 

SCHEME 7.44 Reactions of sulfur ylides with lactols. 

Frechou, C, Dheilly, L, Beaupere, D, Demailly, R U, Reaction of sulfur ylides on reducing sugars application to the synthesis of hydroxymethyl C-glycosides, Tetrahedron Lett, 33, 5067-5070, 1992. 

There is striking difference in the mode of reaction of sulfur ylides and phosphorus ylides (Wittig reagent) with aldehydes and ketones. The former ylides lead to epoxides, whereas the Wittig reagent furnishes alkenes, pointing to the low affinity of sulfur toward oxygen compared to that of phosphorus. 

Chiral epoxides frequently play a key role as intermediates in organic synthesis and the development of methods for the catalytic asymmetric synthesis of such compounds therefore remains an area of intensive research. Methods have focused principally on the asymmetric electrophilic oxidation of alkenes and good enantioselectivity has been achieved [1]. An alternative to oxidative processes for the synthesis of epoxides is the reaction of sulfur ylides with aldehydes and ketones [2,3,4,5,6]. Sulfur ylide epoxidation is a carbon-carbon bond forming reaction and is complementary to oxidative methods. The standard conditions for this reaction utilize the original Corey method treatment of a sulfonium salt with a strong base in the presence of or followed by the addition of an aldehyde... 

An alternate approach, pioneered by Kunz and MacMillan, proceeds by reaction of sulfur ylides with a,(3-unsaturated iminium ions, formed by reaction of a,p-enals with enantiomerically pure amines. In this approach the sulfur ylide (9.87) reacts with a range of (3-aryl- and P-alkyl-substituted enals, including (9.88), in the presence of the dihydroindole (9.89) to give the cyclopropane with ees ranging from 89 to 96%. More recently, it has been shown that replacement of the carboxylate functional group in (9.89) with an isosteric tetrazolic acid gives an improved catalyst that effects cyclopropanation with 99% ees in all cases studied. 

DFT calculations have been used to obtain mechanistic insights into the reaction of sulfur ylides PhHC (S+Me2) with dienals and enones by identifying all key transition states and intermediates along the reaction pathway for the 1,2-, 1,4-, and 1,6-nucleophilic attacks at PhCH=CHCH=CHCH=0 and for the 1,2- and 1,4-attacks at MeCH=CHCOMe. The final outcome of the reaction with both substrates has been found to be decided by the interplay between kinetic and thermodynamic factors. Thus, addition of a semi-stabilized ylide to conjugated carbonyl compounds prefers the 1,4-pathway under thermodynamic conditions, in consonance with the experimental reports. However, the formation of epoxides via a 1,2-addition pathway is equally competitive and could be favoured under kinetic conditions. The 2,3-trans cyclo-propanecarbaldehyde is the major product of the 1,4-addition pathway. The enone also prefers the 1,4-addition. ... 

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