Corey’s ylide

The Corey-Chaykovsky reaction entails the reaction of a sulfur ylide, either dimethylsulfoxonium methylide (1, Corey s ylide, sometimes known as DMSY) or dimethylsulfonium methylide (2), with electrophile 3 such as carbonyl, olefin, imine, or thiocarbonyl, to offer 4 as the corresponding epoxide, cyclopropane, aziridine, or thiirane. ... 

Corey s ylide (1), as the methylene transfer reagent, has been utilized in ring expansion of epoxide 75 and arizidine 77 to provide the corresponding oxetane 76 and azetidine 78, respectively. 

An ingenious application of Corey s ylide (1) was discovered by the Shea group in 199 7 51,52 ugjj g trialkylboranes as initiator/catalyst and 1 as the monomer, a living... 

Stoichiometric sulfur ylide epoxidation was first reported by A.W. Johnson [23] in 1958, and subsequently the method of Corey and Chaykovsky has found widespread use [24-26]. The first enantioselective epoxidations using stoichiometric amounts of ylide were reported in 1968 [27, 28]. In another early example, Hiyama et al. used a chiral phase-transfer catalyst (20 mol%) and stoichiometric amounts of Corey s ylide to effect asymmetric epoxidation of benzaldehyde in moderate to good enantiomeric excess (ee) of 67 to 89% [29]. Here, we will focus on epoxidations using catalytic amounts of ylide [30-32]. A general mechanism for sulfur ylide epoxidation is shown in Scheme 10.2, whereby an attack by the ylide on a carbonyl group yields a betaine intermediate which collapses to yield... 

Corey s sulfonium ylide methodology32 was then adopted. As shown in Scheme 7-51, conversion of ketone 161 to spiroepoxide 165 proceeded with high yield, and a Lewis acid-induced epoxide opening gave the desired allylic alcohol 164 with perfect yield. 

Oxidation of p-hydroxy ketones. Reaction of the Corey-Kim reagent with these substrates can result in dimethylsulfonium dicarbonylmethylides in 80-98% yield. These S-ylides are desulfurized to p-diketones by zinc in acetic acid, p-... 

Dimethylsulfoxonium methylide (DMSY, also referred to as Corey s reagent) is a convenient methylene transfer reagent. It appears to be the most used sulfur ylide and a Tetrahedron Report [455] covers most of its chemistry (345 references). In contrast to dimethylsulfonium methylide, which must be used as soon as it is formed, DMSY is much more stable and can be stored for several days at room temperature. It is the reagent of choice in many instances. However, with a,(3-unsaturated ketones the two reagents react in different ways, as shown for cyclohexenone. 

Corey s procedures for the conversion of ketones into epoxides using sulfonium or oxosulfonium ylides have found widespread use in organic synthesis. An attempt to apply the method to methyl 2-benzoylbenzoate, however, gave 4-phenylisocoumarin in 52% yield when dimethyloxosulfonium methylide was used. 

For the synthesis of cyclopropyl amino acids, Williams has used an oxazinone auxiliary (cf. Scheme 3.12) as an electrophilic component in a sulfur ylide cyclopropanation using Johnson s sulfoximines, as illustrated in Scheme 6.41 [148]. Surprisingly, the sulfur ylide approaches from the P face the authors speculate that there may be some sort of 7t-stacking between the phenyls on the oxazinone ring and the phenyl in the sulfoximine to account for this [149]. With Corey s [147] dimethylsulfonium methylide, the diastereoselectivity was only about 75%, but with Johnson s sulfoximines (used in racemic form), only one diastereomer could be detected for most substrates studied (with the exception of R = H, [149]). Dissolving metal reduction afforded moderate yields of the cyclopropyl amino acids. 

It is likely that the ( )-alkene selective reactions of anionic ylides are due to equlibration of the betaine lithium halide adduct as discussed earlier. However, the balance is delicate and small structural changes can have surprising consequences. Thus, Corey s stereospecific trisubstituted alkene synthesis via /3-oxido ylides (Table 10) is clearly under dominant kinetic control, even though lithium ion is present and aromatic aldehydes can be used as the substrates (54,55). The only obvious difference between the intermediates of Table 10 and oxido ylide examples such as entry 11 in Table 21 is that the latter must decompose via a disubstituted oxaphosphetane while the stereospecific reactions in Table 10 involve trisubstituted analogues. Apparently, the higher degree of oxaphosphetane substitution favors decomposition relative to equilibration. There are few easy and safe generalizations in this field. Each system must be evaluated in detail before rationales can be recommended. 

In this synthesis, S-ylide nucleophiles derived from trialkylsulfonium or trialkylsulfoxonium halides are made to react with carbonyl compounds (Corey 1962) [7], e.g. ... 

Homopropargyl cyclohexanone reacts with the S-ylide from trimethyl sulfoxonium iodide in a Corey synthesis (cf p 21). The resulting spiroepoxide A can be subjected to a 5-exo-cyclization catalyzed by titanocene (Cp2TiCl2) in the presence of a stoichiometric amount of Mn yielding a product B in 90% yield. 

Alkoxysulphonium Ylides.—Alkoxysulphonium ylides are thought to be involved in the oxidation of alcohols with DMSO-related reagents, as demonstrated for the deuteriated form of Corey s iV-chlorosuccinimide-dimethyl sulphide reagent (23). Chlorosulphonium or chloro-oxosulphonium reagents Ra (0) -... 

Corey s seminal investigations of the chemistry of trimethylsulfoxonium ylide established a powerful method for the generation of cyclopropanes from enones [19, 21, 73, 74). In a typical experiment, treatment of enones such as carvone (121) with Me3S(0)I/NaH in DMSO leads to the formation of 122 in 82% yield as a single diastereomer (Equation 19) [74]. 

The echoes of Corey s seminal discovery with sulfonium and sulfoxonium ylides have found considerable resonance in modern investigations of enan-tioselective cyclopropanation reactions. Shibasaki showed that treatment of pyrrole amides such as 126 with trimethylsulfoxonium ylide was effectively promoted by the La-Li-(biphenyldiolate) catalyst 127 to give the cyclopropane adduct 128 in 98% ee (Equation 20) [78]. Key to the success of the transformation was the use of Nal as an additive. The investigators speculated that exchange of Li for Na occurs in 127 to some extent to give an active cyclopropanation catalyst that is more enantioselective. The observation underscored the versatility of such bifunctional heterobimetallic catalysts, the properties of which can be fine-tuned in a multitude of ways by variation of the ligand and the nature of the metals employed [79]. 

In Corey and Chaykovsky s initial investigation, a cyclic ylide 79 was observed from the reaction of ethyl cinnamate with ylide 1 in addition to 32% of cyclopropane 53. In a similar fashion, an intermolecular cycloaddition between 2-acyl-3,3-bis(methylthio)acrylnitrile 80 and 1 furnished 1-methylthiabenzene 1-oxide 81. Similar cases are found in transformations of ynone 82 to 1-arylthiabenzene 1-oxide 83 and N-cyanoimidate 84 to adduct ylide 85, which was subsequently transformed to 1-methyl-lX -4-thiazin-l-oxide 86. ... 

In a synthesis of PGEt reported by Corey 89) for the preparation of the 0,S-acetal-protected dienol thioether aldehyde 122, the ylide generated from phosphonium salt 119 was used as an electrophile in the alkylation of 118. The following Wittig reaction of the resulting phosphonium salt 120 with the thioenolether aldehyde 121 in the presence of phenyllithium as the base gave intermediate 122 in 35% yield. 

Katayama, S., Watanabe, T., Yamauchi, M. Convenient synthesis of stable sulfur ylides by reaction of active methylene compounds with Corey-Kim reagent. Chem. Pharm. Bull. 1990, 38, 3314-3316. 

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