Sulfur Ylide-mediated Epoxidation

Until this work, the reactions between the benzyl sulfonium ylide and ketones to give trisubstituted epoxides had not previously been used in asymmetric sulfur ylide-mediated epoxidation. It was found that good selectivities were obtained with cyclic ketones (Entry 6), but lower diastereo- and enantioselectivities resulted with acyclic ketones (Entries 7 and 8), which still remain challenging substrates for sulfur ylide-mediated epoxidation. In addition they showed that aryl-vinyl epoxides could also be synthesized with the aid of a,P-unsaturated sulfonium salts lOa-b (Scheme 1.4). 

Epoxy Esters, Amides, Acids, Ketones, and Sulfbnes 1.2.3.1 Sulfur Ylide-mediated Epoxidation... 

In general sulfur ylide-mediated epoxidation cannot be used to form an epoxide with an adjacent anion-stabilizing group such as an ester, as the requisite ylide is too stable and does not react with aldehydes [23], With the less strongly electron-withdrawing amide group, however, the sulfur ylide possesses sufficient reactivity for epoxidation. The first example of an asymmetric version of this reaction was by... 

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],... 

There are four main factors that control the enantioselectivity in the sulfur ylide-mediated epoxidation (1) selectivity for one sulfide lone pair (2) control of ylide conformation (3) control of facial selectivity and (4) the reversibility of anti-betaine formation. 

Aggarwal VK, Winn CL. Catalytic, asymmetric sulfur ylide-mediated epoxidation of carbonyl compounds scope, selectivity, and applications in synthesis. Acc. Chem. Res. 2004 37 611-620. Li A-H, Dai L-X, Aggarwal VK. Asymmetric ylide reactions epoxidation, cyclopropanation, aziridination, olefination, and rearrangement. Chem. Rev. 1997 97 2341-2372. 

Origins of enantio- and diastereocontrol in sulfur ylide-mediated epoxidation reactions 03CC2644. 

Scope, selectivity, and applications in the synthesis of catalytic, asymmetric sulfur ylide-mediated epoxidation of carbonyl compounds 04ACR611. 

Aggarwal, V.K., Richardson, J. The complexity of catalysis origins of enantio-and diasteieocontrol in sulfur ylide mediated epoxidation reactions. Chem. Com-mun. 2003, 2644-2651. 

In the design of chiral sulfides for sulfur ylide-mediated asymmetric epoxidation of aldehydes, two factors are important. First, a single sulfur ylide should be produced. Otherwise, the diastereomeric sulfur ylides may react with aldehydes in different ways and thus cause a drop in stereoselectivity. This may be achieved by choosing a rigid cyclic structure to make one of the lone pairs more accessible than the other. Second, the structure should be amenable to structural modification in order to study the electronic and steric effects of the sulfur on the enantioselectivity of the epoxidation reaction. 

It should be mentioned at this stage that in addition to the catalytic version, numerous sulfur-ylide mediated asymmetric diastereoselec-tive epoxidations which require the use of stoichiometric amounts of the sulfur-ylide were reported. In these cases, the sulfonium salts had to be prepared in a first step, and were used in a subsequent diastereoselective epoxidation step. For some selected references for this type of stoichiometric asymmetric two-step epoxidation, see (a) T. Durst, L. Breau, R. N. 

Most studies on sulfur ylide-mediated asymmetric epoxidation have concentrated on the development of the methodology. The usefulness of this approach has been demonstrated in the synthesis of a number of biologically interesting compounds. Furaldehyde-derived epoxides can be oxidized to produce glycidic esters that are versatile intermediates in several syntheses (see Scheme 10.9) [46]. The... 

Highly enantioselective ylide-type covalent catalysis has been achieved with sulfides, phosphines, tertiary amines, selenides, and teUurides, and the reported reaction types include epoxidation, aziridination, cyclopropanation, and other cyclization reactions. So far, the sulfur ylide-mediated reactions are the best... 

Catalytic asymmetric epoxidation and aziridination mediated by sulfur ylides 98SL329. 

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. 

AggarwaU, V. K. Catalytic Asymmetric Epoxidation and Aziridination Mediated by Sulfur Ylides. Evolution of a Project, Synlett 1998, 329-336. 

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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