Sulfur ylides reactions with carbonyl compounds

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. 

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. ... 

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. 

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

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

The reaction of the sulfur ylides with carbonyl compounds provides a valuable synthetic route to a wide range of epoxides. For instance, benzophenone (20) reacts smoothly with... 

In the case of the sulfur analogues, the reaction of sulfiir ylides with carbonyl compounds, known as the Corey-Chaykovsky reaction, is a well-established procedure for the synthesis of oxiranes This reaction is usually considered to involve the formation of an a/ift -betaine (205) followed by a back side attack of an oxido anion on the p-carbon. (Scheme 3.29)... 

DFT calculations have been used to obtain mechanistic insights into the reaction of sulfur ylides PhHC (S+Me2) with dienals and enones by identifying all key transition states and intermediates along the reaction pathway for the 1,2-, 1,4-, and 1,6-nucleophilic attacks at PhCH=CHCH=CHCH=0 and for the 1,2- and 1,4-attacks at MeCH=CHCOMe. The final outcome of the reaction with both substrates has been found to be decided by the interplay between kinetic and thermodynamic factors. Thus, addition of a semi-stabilized ylide to conjugated carbonyl compounds prefers the 1,4-pathway under thermodynamic conditions, in consonance with the experimental reports. However, the formation of epoxides via a 1,2-addition pathway is equally competitive and could be favoured under kinetic conditions. The 2,3-trans cyclo-propanecarbaldehyde is the major product of the 1,4-addition pathway. The enone also prefers the 1,4-addition. ... 

There is an important difference between the reactions of these sulfur ylides and the analogous phosphorus ylides with carbonyl compounds. Whereas phosphorus ylides react with aldehydes and ketones to yield alkenes, dimethylsulfonium methylide and dimethyloxosulfonium methylide yield epoxides. Instead of a four-center elimination in the zwitterionic intermediate, intramolecular nucleophilic displacement by oxygen occurs. 

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]. 

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... 

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