Ylides, sulfur

Sulfonium ylides and suHoxonium ylides are useful reagents for converting ketones and aldehydes into epoxides. 

Examine electrostatic potential maps for dimethylsulfonium and dimethylsulfoxonium ylides. Which contains the more negatively-charged carbon Do either or both of the ylides incorporate a fully formed 7U bond Compare bond distances involving methylene and methyl carbons. Also examine the highest-occupied molecular orbital (HOMO) for evidence of 7U bonding. 

McsSO and OHT react to form an ylide, but Me3S+ and OHT do not react. 

Electrostatic potential map for dimethylsulfoxonium ylide shows negatively-charged regions (in red) and positively-charged regions (in blue). 

HOMO of dimethylsulfonium ylide describes the extent to which a 7i bond is present. 

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Sulfur ylides contain a carbanion, which is stabilizea oy an adjacent positively-charged sulfur. Ylides derived from alkylsulfonium salts are usually generated and utilized at low temperatures. Oxosulfonium ylides are, however, stable near room temperature. The most common method of ylide formation is deprotonation of a sulfonium salt. What has been said... 

In contrast reaction with aprotic nucleophiles, e.g. alkoxides, LiAlILt and sulfur ylides (Z ), yields amino acid derivatives (341), resulting from sp C—N bond scission. The third possible way of ring opening, namely at the C—C bond, has also been observed in certain cases, i.e. (342) -> (343) (67TL5033). 

A versatile oxirane synthesis via (64) is the sulfur ylide approach (B-75MI50504, cf. 76TL457), which in effect inserts a CR2 group into a carbonyl group (Scheme 71). Older, less generally useful versions of this insertion utilize diazomethane or dibromomethane-butyllithium. 

Ring expansion of activated aziridines (43) with sulfur ylides also provides a synthesis of azetidines (75JOC2990, 58BSF345, 81CC417). The highly reactive sulfonium methylide (44 R = R = H) undergoes further reaction with the azetidines (46), but the reaction is satisfactory for substituted methylides. The less reactive sulfoxonium methylide (45 R = R = H)... 

Cyclization of the diazo compound (108) with a copper catalyst affords the clavulanic acid derivatives (110) and (111), possibly via rearrangement of the sulfur ylide (109) (80H(14)1999). Similar reactions have been reported in the recent literature (80H(14)1967, 81H(16)1305, 80TL31). 

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. ... 

Similar to phosphur ylides, sulfur ylides 1 and 2 possess the nucleophilic site at the carbon atom and the pendant leaving group at the heteroatom (sulfur). Different from the Wittig reaction, the Corey-Chaykovsky reaction does not lead to olefins. 

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), ... 

Stereoselective epoxidation can be realized through either substrate-controlled (e.g. 35 —> 36) or reagent-controlled approaches. A classic example is the epoxidation of 4-t-butylcyclohexanone. When sulfonium ylide 2 was utilized, the more reactive ylide irreversibly attacked the carbonyl from the axial direction to offer predominantly epoxide 37. When the less reactive sulfoxonium ylide 1 was used, the nucleophilic addition to the carbonyl was reversible, giving rise to the thermodynamically more stable, equatorially coupled betaine, which subsequently eliminated to deliver epoxide 38. Thus, stereoselective epoxidation was achieved from different mechanistic pathways taken by different sulfur ylides. In another case, reaction of aldehyde 38 with sulfonium ylide 2 only gave moderate stereoselectivity (41 40 = 1.5/1), whereas employment of sulfoxonium ylide 1 led to a ratio of 41 40 = 13/1. The best stereoselectivity was accomplished using aminosulfoxonium ylide 25, leading to a ratio of 41 40 = 30/1. For ketone 42, a complete reversal of stereochemistry was observed when it was treated with sulfoxonium ylide 1 and sulfonium ylide 2, respectively. ... 

In transforming bis-ketone 45 to keto-epoxide 46, the elevated stereoselectivity was believed to be a consequence of tbe molecular shape — tbe sulfur ylide attacked preferentially from tbe convex face of the strongly puckered molecule of 45. Moreover, the pronounced chemoselectivity was attributed to tbe increased electropbilicity of the furanone versus the pyranone carbonyl, as a result of an inductive effect generated by tbe pair of spiroacetal oxygen substituents at tbe furanone a-position. ... 

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). ... 

Reagent-controlled asymmetric cyclopropanation is relatively more difficult using sulfur ylides, although it has been done. It is more often accomplished using chiral aminosulfoxonium ylides. Finally, more complex sulfur ylides (e.g. 64) may result in more elaborate cyclopropane synthesis, as exemplified by the transformation 65 66 ... 

In the initial report by Corey and Chaykovsky, dimethylsulfonium methylide (2) reacted smoothly with benzalaniline to provide an entry to 1,2-diphenylaziridine 67. Franzen and Driesen reported the same reaction with 81% yield for 67. In another example, benzylidene-phenylamine reacted with 2 to produce l-(p-methoxyphenyl)-2-phenylaziridine in 71% yield. The same reaction was also carried out using phase-transfer catalysis conditions.Thus aziridine 68 could be generated consistently in good yield (80-94%). Recently, more complex sulfur ylides have been employed to make more functionalized aziridines, as depicted by the reaction between A -sulfonylimine 69 with diphenylsulfonium 3-(trimethylsilyl)propargylide (70) to afford aziridine 71, along with desilylated aziridine 72. ... 

Catalytic asymmetric epoxidation and aziridination mediated by sulfur ylides 98SL329. 

Cycloaddition of 2-nitrosopyridine 48 with nitrile oxides can give either di-A -oxides such as 49 or 3-mono-A -oxides such as 50 (93JHC287). In general, greater electron withdrawing character in the aromatic substituent appears to favor formation of the di-A -oxides. Sulfur ylides such as compound 51 are obtained from aryl isothiocyanates and l-amino-2-methylthiopyridinium iodides (84JCS(P1)1891) nitrogen ylides can be obtained from a similar reaction (86H(24)3363). 

The ylides have been classified on the basis of the heteroalom covalently bonded to the carbanion. Accordingly, they can be differentiated into nitrogen ylide (Scheme 2), sulfur ylide Scheme 3, phosphorus ylide Scheme 4, arsenic ylide Scheme 5, antimony ylide (Scheme 6), bismuth ylide (Scheme 7) and thallium ylide (Scheme 8). 

A comparative study on ylide stability as a function of the heteroatom type was carried out by Doering et al. [3,4]. They concluded that the phosphorus and sulfur ylides are the most stable ones. The participation of three-dimensional orbitals in the covalency determines the resonance stabilization of the phosphorus and sulfur ylides [5-8]. The nitrogen ylides are less stable from this point of view. The only stabilization factor involves electrostatic interactions between the two charges localized on adjacent nitrogen and carbon atoms [9]. 

Recently, in connection with the use of sulfur ylides in polymerization, Kondo and his coworkers [64] attempted to use diphenylsulfonium bis(methoxycarbo-nyl)methylide (DPSY) (Schemes 27, 29) methylphen-ylsulfonium bis-(methoxycarbonyl)methylide (MPSY) (Scheme 30) and dimethylsulfonium bis (methoxycar-bonyl) methylide (DMSY) (Scheme 31) as photoinitiators for the polymerization of MMA and styrene. They concluded that DPSY and MPSY are effective photoini-... 

Until this work, the reactions between the benzyl sulfonium ylide and ketones to give trisubstituted epoxides had not previously been used in asymmetric sulfur ylide-mediated epoxidation. It was found that good selectivities were obtained with cyclic ketones (Entry 6), but lower diastereo- and enantioselectivities resulted with acyclic ketones (Entries 7 and 8), which still remain challenging substrates for sulfur ylide-mediated epoxidation. In addition they showed that aryl-vinyl epoxides could also be synthesized with the aid of a,P-unsaturated sulfonium salts lOa-b (Scheme 1.4). 

The first attempt at a catalytic asymmetric sulfur ylide epoxidation was by Fur-ukawa s group [5]. The catalytic cycle was formed by initial alkylation of a sulfide (14), followed by deprotonation of the sulfonium salt 15 to form an ylide 16 and... 

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