Sulfur ylides carbonyl compounds

It is well known that aziridination with allylic ylides is difficult, due to the low reactivity of imines - relative to carbonyl compounds - towards ylide attack, although imines do react with highly reactive sulfur ylides such as Me2S+-CH2-. Dai and coworkers found aziridination with allylic ylides to be possible when the activated imines 22 were treated with allylic sulfonium salts 23 under phase-transfer conditions (Scheme 2.8) [15]. Although the stereoselectivities of the reaction were low, this was the first example of efficient preparation of vinylaziridines by an ylide route. Similar results were obtained with use of arsonium or telluronium salts [16]. The stereoselectivity of aziridination was improved by use of imines activated by a phosphinoyl group [17]. The same group also reported a catalytic sulfonium ylide-mediated aziridination to produce (2-phenylvinyl)aziridines, by treatment of arylsulfonylimines with cinnamyl bromide in the presence of solid K2C03 and catalytic dimethyl sulfide in MeCN [18]. Recently, the synthesis of 3-alkyl-2-vinyl-aziridines by extension of Dai s work was reported [19]. 

The addition reaction of enolates and enols with carbonyl compounds is of broad scope and of great synthetic importance. Essentially all of the stabilized carbanions mentioned in Section 1.1 are capable of adding to carbonyl groups, in what is known as the generalized aldol reaction. Enolates of aldehydes, ketones, esters, and amides, the carbanions of nitriles and nitro compounds, as well as phosphoms- and sulfur-stabilized carbanions and ylides undergo this reaction. In the next section we emphasize the fundamental regiochemical and stereochemical aspects of the reactions of ketones and aldehydes. 

Whereas phosphonium ylides normally react with carbonyl compounds to give alkenes, dimethylsulfonium methylide and dimethylsulfoxonium methylide yield epoxides. Instead of a four-center elimination, the adducts from the sulfur ylides undergo intramolecular displacement of the sulfur substituent by oxygen. In this reaction, the sulfur substituent serves both to promote anion formation and as the leaving group. 

Efforts to realize an intramolecular version of the above reactions met with limited success when monocyclic 4-thio-substituted (3-lactams were used. Cu(acac)2-catalyzed decomposition of diazoketone 358 produced the epimeric carbapenams 359 a, b together with the oxapenam derivative 360 341 these compounds correspond to the C4/S insertion products obtained in intermolecular reactions. Oxapenams were obtained exclusively when the acrylate residue in 359 was replaced by an aryl or heteroaryl substituent 275 342). The different reaction mode of diazoketones 290a, b, which furnish mainly or exclusively carbonyl ylide rather than sulfur ylide derived products, has already been mentioned (Sect. 5.2). 

Sulfur ylides are a classic reagent for the conversion of carbonyl compounds to epoxides. Chiral camphor-derived sulfur ylides have been used in the enantioselective synthesis of epoxy-amides <06JA2105>. Reaction of sulfonium salt 12 with an aldehyde and base provides the epoxide 13 in generally excellent yields. While the yield of the reaction was quite good across a variety of R groups, the enantioselectivity was variable. For example benzaldehyde provides 13 (R = Ph) in 97% ee while isobutyraldehyde provides 13 (R = i-Pr) with only 10% ee. These epoxy amides could be converted to a number of epoxide-opened... 

The chemical behavior of heteroatom-substituted vinylcarbene complexes is similar to that of a,(3-unsaturated carbonyl compounds (Figure 2.17) [206]. It is possible to perform Michael additions [217,230], 1,4-addition of cuprates [151], additions of nucleophilic radicals [231], 1,3-dipolar cycloadditions [232,233], inter-[234-241] or intramolecular [220,242] Diels-Alder reactions, as well as Simmons-Smith- [243], sulfur ylide- [244] or diazomethane-mediated [151] cyclopropanati-ons of the vinylcarbene C-C double bond. The treatment of arylcarbene complexes with organolithium reagents ean lead via conjugate addition to substituted 1,4-cyclohexadien-6-ylidene complexes [245]. 

Durst [478, 479] has shown that the sulfonium ylide (3) transfers its benzylidene group to some carbonyl compounds with e.e. values approaching enantiomeric purity, although the reaction was not yet amenable to synthetic utility (low overall yields, side reaction). However, an interpretation of the difference of behaviour of (3) and (4) towards PhCHO (e.e. values, respectively, 96% and less than 3%) led the authors to propose a [2 + 2] cycloaddition mechanism rather than the commonly accepted nucleophilic antiperiplanar addition for the reaction of a sulfur ylide with a carbonyl compound [479]. Clearly, more work is needed in this area. 

The comparison between the reactions of a carbonyl compound with a phosphorus ylide (Wittig s reagent) on one hand and a sulfur ylide on the other shows clearly the complementarity of these reagents in the strategy of synthesis. 

Ylides based upon sulfur are the most generally useful in these cyclopropane-forming reactions.133 Early work in this area was done with the simple dimethyloxysulfonium methylide (9) derived from dimethyl sulfoxide. The even simpler dimethylsulfonium methylide (10) was studied at the same time as a reagent primarily for the conversion of carbonyl compounds into epoxides.134 Somewhat later, other types of sulfur ylides were developed, among which the nitrogen-substituted derivatives such as (11) are... 

Ylides of other elements have been used much less commonly than sulfur ylides in cyclopropanations. Rather, other ylides are better known for their uses in other types of reactions, the best example being the use of phosphonium ylides in the Wittig reaction with carbonyl compounds to give alkenes. Nonetheless, some cases of cyclopropanations have been reported with phosphonium ylides and the related arsenic derivatives. Examples are given in Table 9. 

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

Finally, Sato and co-workers have added a twist to the known preparation of epoxides from the action of sulfur ylides on carbonyl compounds. In this version, the requisite sulfur ylides are formed by desilylation of [(trimethylsilyl)methyI]sulfonium salts (e.g., 45) in DMSO. This avoids the strongly basic conditions typically encountered in the preparation of sulfur ylides [95SYN649],... 

The intermediacy of such oxaspiropentanes has been proposed in the addition of diazomethane to ketonesi0) and in the reaction of dimethyloxosulfonium methylide with a-haloketones55). In contrast to phosphorous ylides, sulfur ylides usually condense with carbonyl compounds to yield epoxides, thus reaction of the N,N-dimethylaminophenyloxosulfonium cyclopropylide 99 with cyclohexanone produced the dispiroepoxide 100 which rearranged to the spiro [3.5] nonan-l-one 101 upon isolation by gas chromatography, Eq. (29) S6). 

The formation of a minor side product 172 was observed which, if moisture was not rigorously excluded, could become a major product in this reaction (Scheme 36). The formation of compound 172 can be rationalized by protonation of the sulfur ylide 166, followed by deprotonation of one of the readily accessible methyl hydrogens to give the ylide 169, which then reacts at the carbonyl center to give the seven-membered ring intermediate 170. The methyl sulfide is then displaced by the alkoxide to give the oxirane 171, which upon addition of sodium azide, opens up to the azido alcohol 172 <1999T10659>. 

The reaction requires the addition of base (conunonly triethylamine) and results in the formation of an ylide (2 Scheme 3), which collapses intramolecularly to the carbonyl compound. - Further siqiportive evidence for ylide formation lies in the observation that sulfonium salts lacking a hydrogen a to the sulfur do not break down to form the carbonyl compound." ... 

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

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. 

The high nucleophilicity of a-selenoalkyllithiums towards carbonyl conqiounds, even those that are the most hindered or enolizable, such as 2,2,6-trimethyl- and 2,2,6,6-tetramethyl-cyclohexanone (Schemes 113 and 164), di-t-butyl ketone, pennethylcyclobutanone, peimethylcyclopenta-none (Schemes 113 and 187) °- and deoxybenzoin (Schemes 115, 116 and i65y 4 49 23 iqws the synthesis of related alkenes, epoxides and rearranged ketones which are not available from the same carbonyl compounds on reaction with phosphorus or sulfur ylides - or diazoalkanes. ... 

The reaction between sulfur ylides and carbonyl compounds entails attack of the ylide on the carbonyl to form a betaine, which then collapses with expulsion of the neutral sulfide or sulfoxide (Scheme 1 X = R2S ). - - a theoretical study of this mechrmism has appeared. Ylides belonging to the general classes of (1) and (2) differ in stability and in the relative rates of the two mechanistic steps. Specifically, the more stable (2) reacts reversibly with carbonyl groups, whereas (1) undergoes a kinetic addition to the substrate followed by a rapid collapse of the betaine to an epoxide. Differences in chemoselectivity and stereoselectivity between Ae ylides are attributed to this key difference. - - ... 

The few published attempts at the asymmetric epoxidation of carbonyl compounds with chiral sulfur ylides have been reviewed. Thus far, such processes have not been very useful synthetically. For example, reaction of benzaldehyde with an optically pure sulfoximine ylide only afforded an qioxide in 20% enantiomeric excess. More recently, chiral sulfur methylides have provided tra/i -stilbene oxides in up to 83% ee An example of optical induction observed in reactions t ng place with a chiral phase transfer reagent was reported, but later disputed. ... 

Arsonium ylides were discovered near the turn of the century, but their reactions with carbonyl compounds did not become elucidated until the 1960s. In a broad sense, arsonium ylides are midway in chemical behavior between ylides of phosphorus and those of sulfur. Stabilized arsonium ylides react with carbonyl compounds to afford alkenes, whereas the unstabilized analogs give rise to epoxides. More subtly, the nature of the substituents on either the ylide arsenic or carbon atom can alter the course of the reaction the choice of solvent can exert a similar effect. ... 

Deprotonadon of thioanisole and addition of a carbonyl compound affords an isolable hydroxy sulfide which can then be alkylated (Scheme 7). Treatment with base generates the same betaine that would have been formed using the sulfur ylide approach, and effects the intramolecular displacement reaction. The addition of methylthiomethyllithium to 2-cyclohexenone exclusively provides the 1,2-addition prod-uct the dianions derived from phenylmethanethiol or allylthiol react in a similar manner. In one case a 6-keto steroidal substrate was found to undergo smooth methylenation using this procedure. 

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