Sulfur ylides preparation

Sulfur ylides 1 and 2 are usually prepared by treatment of either trimethylsulfoxonium... 

In addition, NaOMe, and NaNH2, have also been employed. Applieation of phase-transfer conditions with tetra-n-butylammonium iodide showed marked improvement for the epoxide formation. Furthermore, many complex substituted sulfur ylides have been synthesized and utilized. For instance, stabilized ylide 20 was prepared and treated with a-D-a/lo-pyranoside 19 to furnish a-D-cyclopropanyl-pyranoside 21. Other examples of substituted sulfur ylides include 22-25, among which aminosulfoxonium ylide 25, sometimes known as Johnson s ylide, belongs to another category. The aminosulfoxonium ylides possess the configurational stability and thermal stability not enjoyed by the sulfonium and sulfoxonium ylides, thereby are more suitable for asymmetric synthesis. 

Isolated carbonyls always give epoxides from the Corey-Chaykovsky reaction. Take the aldehyde substrate as an example. Spiro epoxide 30 was produced from the reaction of trisnorsqualene aldehyde 28 (R20 represents the polyene side-chain with 20 carbons) with substituted sulfur ylide 29, prepared in situ from cyclopropyldiphenylsulfonium tetrafluoroborate and KOH. " For the epoxidation of ketones, the Corey-Chaykovsky reaction works well for diaryl- (31), arylalkyl- (32), ... 

Since cbiral sulfur ylides racemize rapidly, they are generally prepared in situ from chiral sulfides and halides. The first example of asymmetric epoxidation was reported in 1989, using camphor-derived chiral sulfonium ylides with moderate yields and ee (< 41%) Since then, much effort has been made in tbe asymmetric epoxidation using sucb a strategy without a significant breakthrough. In one example, the reaction between benzaldehyde and benzyl bromide in the presence of one equivalent of camphor-derived sulfide 47 furnished epoxide 48 in high diastereoselectivity (trans cis = 96 4) with moderate enantioselectivity in the case of the trans isomer (56% ee). ... 

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]. 

Sulfur ylides have several applications as reagents in synthesis.282 Dimethylsul-fonium methylide and dimethylsulfoxonium methylide are particularly useful.283 These sulfur ylides are prepared by deprotonation of the corresponding sulfonium salts, both of which are commercially available. 

Cyclic dinuclear ylide complexes have also been prepared with sulfur ylides. The reactions of (dppm)(AuCl)2 or (dppe)(AuCl)2 with trimethylsulfoxonium tetrafluoroborate and base under phase-transfer conditions gave the products shown in Scheme 42. Auration of the dppm ligand leads to the byproducts.27... 

The utility of sulfur ylides in organic synthesis demands methods for the efficient preparation of the precursor sulfonium salts.2 Among the... 

A -Unsubstituted 1,2,4-diazaphospholes (4) undergo A -alkylation by reaction with alkyl vinyl ether, sulfur ylides, and diazo compounds <95HAC403>. They react with acyl chlorides in a 2 1 molar ratio to give a mixture of the A -acylated diazaphosphole and the diazaphosphole hydrochloride. Preparative A -acyclation is achieved in presence of a tertiary amine. Sulfonyl chlorides and phosphorus trichloride also give A -substitution reactions (Scheme 2) <87TH 422-01 >. 

The reduction of trifluoromethylimines with Mg(0) affords A-silyl difluoroena-mines." These synthons are very interesting for the preparation of difluoro- S-amino alcohols and of difluoro amino acids (cf. Chapter 4). They can also add onto radicals, react with sulfur ylides to afford difluoromethylaziridines, or even undergo intramolecular ene reactions (Figure 2.26)." ... 

The carbon fragment used in this approach can also be provided by sulfur yUdes. In this arena, Metzner and co-workers <99JCS(P1)731> developed a novel asymmetric variant employing (+)-(2/J,5/J)-2,5-dimethylthiolane (53) as the chiral auxiliary to prepare rrons-(S,S)-stilbene oxide (56). Chiral epoxides have also been prepared from aldehydes using sulfur ylides derived from the products of Baker s yeast reductions <99SL1328>. 

These reactions rapidly found wide use and success, and many other sulfur ylides have been prepared and exploited [194, 195, 203, 204]. Various experimental procedures are to be found in the detailed monograph by Trost and Melvin [204] for sulfonium salts, ylides, epoxidations and cyclopropanations. 

A number of attempts have been made to use optically active sulfur ylides to transfer the chirality of sulfur to carbon in the formation of epoxides and cyclopropanes. The results were somewhat disappointing. Thus, virtually no asymmetric induction was observed with the ylide (1) [475]. With the stabilized ylides (2), e.e. values in the range 7-43% were reported [476]. Better results were obtained with sulfonium ylides derived from Eliel oxathiane [477]. Optically active diaryl epoxides could be prepared under PTC in high yields and good e.e. values. 

Both reagents transfer a methylene group in efficient and selective pathways. So it is not surprising that sulfur ylides have been widely used as synthetic tools for the preparation of epoxides. The reactions can make use of sulfonium salts under phase transfer catalytic conditions, and the cheap and easily accessible trimethyl sulfonium methyl sulfate and triethylsulfonium ethyl sulfate were found to show a high reactivity under such conditions [450]. 

Nucleophilic addition of sulfur ylides to C=0 double bonds is an important means of synthesis of epoxides [198], Because optically active epoxides are widely applied as versatile intermediates in the preparation of, e.g., pharmaceuticals, the asymmetric design of this sulfur ylide-based reaction has attracted much interest [199, 200, 212, 213], One aspect of this asymmetric organocatalytic process which has been realized by several groups is shown in Scheme 6.87A. In the first step a chiral sulfur ylide of type 204 is formed in a nucleophilic substitution reaction starting from a halogenated alkane, a base, and a chiral sulfide of type 203 as organocata-... 

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. 

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],... 

An interesting variant on the Darzens reaction has been reported featuring an in situ prepared sulfur ylide <07OL1745>. The reaction of an a-bromo amide with tetrahydrothiophene provides the sulfur ylide in situ. This sulfur ylide then undergoes the usual epoxidation reaction with a ketoamide to provide a spiroepoxide in excellent yield and diastereoselectivity. 

Sulfur ylides can also be prepared by the reaction of a carbene with a sulfide. 

Trost showed that the sulfur ylide 3.68 prepared by the deprotonation of 3.67 with n-butlyllithium (n-BuLi) on reaction with benzaldehyde under the same reaction conditions gave styrene oxide 3.69 as a racemic mixture. 

Preparation of aziridines using sulfur ylides and imines... 

Sulfur ylides, like the phosphorus ylides of Chapter 21, are useful intermediates in organic synthesis, as shown in Problem 21.79. Methyl frans-chrysanthemate, an intermediate in the synthesis of the insecticide pyrethrin I (the chapter-opening molecule), can be prepared from diene A and a sutfur ylide. Draw a stepwise mechanism for this reaction. 

In addition to the utility of phosphonate anions and phosphorus ylides in the preparation of C-glycosides, a discussion of the related chemistry surrounding sulfur ylides is warranted. Unlike phosphorus ylides, sulfur ylides deliver methylene groups to carbonyls, thus forming epoxides. As shown in Scheme 7.44, Frechou et al. [152] exploited this chemistry in the formation... 

Compounds with the oxirane rings are special cases which, beside this general methodology, are also prepared by a number of other methods (direct epoxidation, reaction with sulfur ylides, Darzens reaction, etc.) [1]. 

The high tendency of a-selenoalkyllithiums, even those that bear alkyl substituents on the carbanionic center, to add at the C-1 site of enones allows the high yield synthesis of vinyl oxiranes (Schemes 132, 134 and 166). These cannot be prepared from sulfur ylides since they add across the carbon-carbon double bond of enones to produce cyclopropyl ketones (Scheme 200). ... 

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