Ylide compounds epoxide generation

The sulfur ylide-mediated epoxidation of aldehydes has been thoroughly investigated [70, 71]. The chiral sulfur ylides reported by Aggarwal have been most broadly applicable, and a catalytic, asymmetric process yielding aromatic transepoxides has been developed [72]. In this process, the sulfur ylides are produced in situ from diazo compounds, generated in turn from tosylhydrazone salts (Scheme 9.15) [73],... 

In 2001, a modified procedure for sulfur ylide-catalyzed epoxidation, aziridination and cyclopropanation was introduced by Aggarwal and co-workers that utilized the generation of the diazo compounds in situ from tosyl hydrazone salts at 40 °C in the presence of a phase-transfer catalyst [46, 79]. (For experimental details see Chapter 14.12.1). Using this modified protocol, sulfide 4 was shown to be effective for epoxidation and aziridination (see Sections 10.2.1.4 and 10.3), but was not an effective cyclopropanation catalyst (see Table 10.3). Sulfide 28 was tried instead as it had been shown in achiral studies [96] that six-membered sulfides were more effective than five-membered analogues. This change gave rise to... 

In the catalytic cycle itself, ylides A are generated in situ in the presence of carbonyl compounds in a reaction between a sulfide and a carbenoid B, which in turn is generated from a diazo compound C and a metal catalyst D. At the same time, ylides A react with carbonyl compounds to give trans-(S,S)-epoxides and are simultaneously regenerated to... 

Dimethylsulfonium methylide is both more reactive and less stable than dimethylsulfoxonium methylide, so it is generated and used at a lower temperature. A sharp distinction between the two ylides emerges in their reactions with a, ( -unsaturated carbonyl compounds. Dimethylsulfonium methylide yields epoxides, whereas dimethylsulfoxonium methylide reacts by conjugate addition and gives cyclopropanes (compare Entries 5 and 6 in Scheme 2.21). It appears that the reason for the difference lies in the relative rates of the two reactions available to the betaine intermediate (a) reversal to starting materials, or (b) intramolecular nucleophilic displacement.284 Presumably both reagents react most rapidly at the carbonyl group. In the case of dimethylsulfonium methylide the intramolecular displacement step is faster than the reverse of the addition, and epoxide formation takes place. 

Common reactions of the ylide include (i) [2,3]-sigmatropic rearrangement of allylic, propargylic, and allenic ylides (ii) [l,2]-shift (Stevens rearrangement) (iii) 1,3-dipolar cycloaddition of the ylide generated from carbonyl compounds or imines with dipolarophiles, usually G=G or C=C bonds and (iv) nucleophilic addition/elimination, leading to the formation of epoxides or cyclopropanes (Figure 2). 

Typical Procedure for Sulfur Ylide Epoxidation via In Situ Diazo Compound Generation [52] (p. 361)... 

The reactions of carbonyl compounds with benzyltrialkylstibonium ylides have been investigated (Scheme 9).39 The products are either benzyl alcohols (52) or mixtures of alkenes and epoxides depending on the base used to generate the ylide. A mechanism is suggested for the formation of (52). 

Initial studies of solvent effects, on the reactions of triarylarsonium benzoylylides with p-nitrobenzaldehyde in N, A-dimethylformamide, dimethyl sulphoxide or methanol, indicated little solvent effect in these cases" ", but later studies of the more finely balanced reactions of semi-stabilized ylides have provided examples of strong influences due to the effect of different base and solvent when the ylide is generated in the presence of a carbonyl compound ". Thus, when benzyltriphenylarsonium bromide or p-chloroben-zyltriphenylarsonium bromide were treated with sodium hydride in benzene in the presence of a variety of p-substituted benzaldehydes the products were alkenes, but if sodium ethoxide in ethanol was used the isolated products were epoxides ". Likewise, when triphenylarsonium benzylylide was generated by phenyllithium in the presence of either benzaldehyde or acetaldehyde, the preponderant product was the epoxide whereas use of sodium amide as base provided mostly the alkene . Similar results were obtained when an allyltriphenylarsonium salt was deprotonated using different hexamethyldisilaz-... 

Condensation with carbonyl compounds. Formation of epoxides from aldehydes by reaction with sulfonium ylides is subject to asymmetric induction. The latter species have been generated from 91, 92, and 93, and also those derived from monoterpenes, e.g., 94 " and 95.- Of course the ylides can be obtained in situ by deprotonation of sulfonium salts or copper-catalyzed decomposition of diazoalkanes (with the carbenoids trapped by the sulfides). 

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. 

As mentioned previously, the Aggarwal group has utilized the Bamford-Stevens reaction as a method to in situ generate diazo compounds 33 and further trap out these in a subsequent reaction. This in situ concept was initially tested on the sulfur-ylide 37 mediated epoxidation of aldehydes 39. "... 

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