Sulfonium yhdes

The generation of sulfonium yhdes relies mostly on three strategies (Scheme 78). The classic variant uses sulfide alkylation to the sulfonium salts 316 which can be deprotonated to dehver the desired yhdes 317 [180,181]. A related method involves silane 320 as the alkylating agent to allow for regioselective ylide generation via fluoride ion induced desilylation [182]. Finally, the action of carbenes 319 or metal-bound carbenoids offers a direct means for ylide generation [183,184]. 

Thus far, discussion has centered around the reaction of alkenes with a source of electrophilic oxygen as a route to epoxides [the C=C + O protocol]. However, a second general approach is represented by the reaction of carbonyl compounds with amphophilic carbon centers [the C=0 + C protocol]. For example, sulfonium yhdes are known to convert aldehydes and ketones to epoxides much recent work has focused on asymmetric induction using this methodology, a topic which has been the subject of a concise review in the past year <04ACR611>. As an illustration, the D-mannitol derived chiral sulfide 42 serves as a useful chiral auxiliary in the sulfonium methylide epoxidation of aldehydes to provide terminal monosubstituted oxiranes (e.g., 44) in fair to excellent yield and good enantiomeric excess <04CC1076>. 

Dimethylsulfonium methylide and dimethylsulfoxonium methylide also differ in their reachons with a,p-unsaturated carbonyl compounds. The sulfonium ylide reacts at the carbonyl group to form an epoxide, but with the sulfoxonium ylide a cyclopropane derivative is obtained by Michael addihon to the carbon-carbon double bond. The difference is again due to the fact that the kinehcally favoured reachon of the sulfonium yhde with the carbonyl group is irreversible, whereas the corresponding reaction with the sulfoxonium yhde is reversible, allowing preferenhal formahon of the thermodynamically more stable product from the Michael addihon. For example, the cyclopropane 112 is obtained from the reaction of dimethylsulfoxonium methylide with the enone 111 (1.105). Other methods for the formahon of cyclopropanes include carbene and Simmons-Smith-type... 

The additional electronegative oxygen atom in the sulfoxonium salts stabilizes these yhdes considerably, relative to the sulfonium yhdes." ... 

This process follows the mechanistic pattern of a 1,3-elimination and formally corresponds to a (1 + 2)-cycloaddition of the ylidic (carbene-like) CH2 group to the carbonyl group. It should be mentioned that a, fi-unsaturated ketones like benzalacetophenone react with sulfonium yhdes to give oxiranes, but with sulfoxonium ylides to give cyclopropanes [13]. 

The camphor-derived P-hydroxyl-sulfonium yhde proved to be unusually efficient for the cyclopropanation of electron-deficient alkenes. For example, the reaction of salt 21b with a,P-unsaturated nitrile affords the desired cyclopropane in 61% yield and 96% ee. In comparison, the corresponding tetrahydrothiophene and dimethyl sulfide-derived sulfonium salts (23 and 24), which lack the hydroxyl group, only gave a trace amount of the desired cyclopropane (Scheme 20.21). 

As a C - C bond-forming process, [2,3]-sigmatropic rearrangements of sulfonium ylides merit particular interest. Indeed, since their discovery in the late 1960s [172-176], this type of yhde rearrangement has become the most extensively studied and applied. This activity is well dociunented in a niunber of excellent review articles, many of them published quite recently [9,177-179]. This demonstrates a vivid interest by the scientific community in these rearrangements which is strongly related to the advent of asymmetric and catalytic variants, as will be discussed later. 

The preformed benzyl sulfonium salt produced the oxirane in nearly the same yield and optical purity as the direct use of the sulfide, indicating that the one-pot reaction proceeds via initial formation of the sulfonium salt, which is subsequently deprotonated to generate the yhde in situ (Scheme 20.4). The sulfide is finally released upon epoxide ring closure. 

Selenium and tellurium ylides other than sulfonium have also been reported to be useful for the cyclopropanation. Selenium ylides were smdied by Kataoka and coworkers, and cyclopropane formation was observed. Diphenyl vinyl or allenyl selenium triflate serves as an electron-deficient alkene, and selenium ylides can be generated by the conjugate addition. The resulting yhdes underwent cyclopropane formation by an MIRC reaction (Scheme 1.31) [54]. 

Sulfide 2a was later employed by Tang and coworkers in the reaction of 4-chlorobenzaldehyde with 3-trimethylsilylallyl bromide for the synthesis of viny-loxiranes. In the presence of 20mol% of 2a, the trans vinyl epoxide was obtained as the major diastereoisomer in 40% yield and 37% ee [21]. Higher concentrations of both aldehyde and aUyUc bromide were found to be beneficial to the yields, because the high concentration of aUyHc bromide favors the formation of the sulfonium salt and the high concentration of aldehyde could probably allow capture of the sulfur yhde before the [2,3]-sigmatropic rearrangement (Scheme 20.6). This reaction with thiolane (THT) as a catalyst could also be carried out without solvent, but the yield was lower than that in t-BuOH. 

When compared with phosphonium and sulfonium ylides, the corresponding selenonium and telluronium yhdes frequently exhibit better reactivity and nucle-ophilicity, while the use of selenides and tellurides in catalytic yUde reactions is far less reported. In 2001, Metzner and coworkers reported an asymmetric epoxi-dation reaction of aldehydes using a C2-symmetric selenide 42 resembling their sulfide catalyst (Scheme 20.32). High yields (65-97%) and enantioselectivity (76-94% ee) were obtained with a range of aromatic aldehydes and cinnamalde-hydes. However, no diastereoselectivity (trans cis = 1 1) was observed in these reactions, while the corresponding sulfide gave around 80% diastereoselectivities, which could be rationalized as the formation of a less diastereoselective early transihon state with the more reactive selenonium ylides. The reactions of more electron-deficient aryl aldehydes (p-Cl and p-CFs) were less enantioselective (76% ee and 83% ee, respectively) [58]. 

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