Ketones sulfur ylides

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. ... 

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). 

Epoxy Esters, Amides, Acids, Ketones, and Sulfbnes 1.2.3.1 Sulfur Ylide-mediated Epoxidation... 

Sulfur ylides can also transfer substituted methylene units, such as isopropylidene (Entries 10 and 11) or cyclopropylidene (Entries 12 and 13). The oxaspiropentanes formed by reaction of aldehydes and ketones with diphenylsulfonium cyclopropylide are useful intermediates in a number of transformations such as acid-catalyzed rearrangement to cyclobutanones.285... 

An alternative to the synthesis of epoxides is the reaction of sulfur ylide with aldehydes and ketones.107 This is a carbon-carbon bond formation reaction and may offer a method complementary to the oxidative processes described thus far. The formation of sulfur ylide involves a chiral sulfide and a carbene or carbenoid, and the general reaction procedure for epoxidation of aldehydes may involve the application of a sulfide, an aldehyde, or a carbene precursor as well as a copper salt. This reaction may also be considered as a thiol acetal-mediated carbene addition to carbonyl groups in the aldehyde. 

The source of the latter from the appropriate ketone 194 using cyclopropyl sulfur ylide chemistry is apparent. The ultimate starting material is the well known diketone 195 which is easily available in optically active form. 

Sulfur ylides behave similarly to phosphorus ylides, but the final products are different. Figure 10-31 shows the mechanism for the prepciration of a sulfur ylide and the reaction of the sulfur ylide with a carbonyl group. Notice that the mechanism for the formation of the sulfur ylide is similar to the formation of a phosphorus ylide. However, the last step in the sulfur ylide mechanism is an internal S, 2 reaction, which eliminates the original thioether (dimethyl sulfide). The reaction of a sulfur ylide with a ketone yields epoxides, whereas the product of a phosphorus ylide with a ketone is an alkene. 

Sulfur ylides react with aldehydes and ketones to form epoxides (oxiranes) ... 

Aldehydes and ketones can be converted to epoxides756 in good yields with the sulfur ylides dimethyloxosulfonium methylide (72) and dimethylsulfonium methylide (73).757 For most purposes, 72 is the reagent of choice, because 73 is much less stable and ordinarily must be... 

The generally accepted mechanism for the reaction between sulfur ylides and aldehydes or ketone is... 

Addition of sulfur ylides or diazomethane to aldehydes or ketones 9-63 Bimolecular reduction of aldehydes or ketones... 

A sulfur ylide is formed with base which then abstracts the a proton, generating dimethylsulfide and the aldehyde or ketone. 

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. 

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

The reaction of sulfur ylides with aldehydes and ketones was first reported by Johnson in 1961, but is for some reason better known as the Corey-Chaykovsky reaction. The reaction between sulfur ylides and an electrophilic carbon atom of a C=0 gives a betaine intermediate. The favoured reaction path is therefore an internal Sn2 process which furnishes an epoxide with regeneration of the sulfide (Scheme 3.28). 

In the Swern oxidation, the reaction of oxalyl chloride with DMSO may generate chlorodimethylsulfonium chloride (A), which reacts with the alcohol to give alkoxysulfonium ion intermediate B. The base, typically triethylamine, deprotonates the alkoxysulfonium ion B to give the sulfur ylide C, which decomposes to give DMS and the desired aldehyde or ketone (Scheme 7.7). The temperature of this reaction is kept near —60 to -78°C. 

Nakayama and co-workers established that carbonyl-stabilized sulfur ylide (83) reacted with elemental selenium to afford 1,3-oxaselenole (85) in good yield (85TL2201). The reaction was presumed to proceed through the intermediacy of selenal (84). Subsequently, support for this mechanism has come from the isolation of adduct 86 when the reaction is performed in the presence of dimethylbutadiene (87TL4423). Other Diels-Alder reactions of intermediate a-oxoseleno-aldehydes and -ketones were also found... 

The use of sulfur in place of the phosphorus brings about a different mode of decomposition of the intermediate betaine. Two sulfur ylides, dimethylsulfonium methylide (Scheme 3.49a) and dimethylsulfoxonium methylide (Scheme 3.49b), have been used. Both ylides react with ketones to give epoxides, but the stereochemistry may differ. 

The dehydrogenation of bis(a-bromobenzyl) sulfide (41) with Fe2(CO)9 in the presence of furan affords (43). The iron-stabilized sulfur ylide (42) has been proposed as intermediate. Reaction of C -di-phenylnitrone (44) with l,2-bis(methylene)-3,3.4,4,5,5-hexamethylcyclopentane (45) in benzene at 80 C gives a [4 -I- 3] cycloadduct (46 18%), along with some other products. Landor et al. have shown that the dehydrobromination of allenyl bromide (47) in the presence of furan affords bicyclic ketone (49) in 9% yield. Apparently, a strain alkyne intermediate reacts with r-butyl alcohol to afford an enol ether (48), which is then converted to (49) (Scheme 11). 

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 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). ... 

The most commonly used reagents to effect the addition of a methylene group to an aldehyde or ketone are sulfur ylides such as dimethylsulfonium methylide (1) or dimethyloxosulfonium methylide (2) (Corey-Chaykovsky reaction). This reaction is well reviewed in standard treatises of organic synthesis - and several useful monographs. - This update will concentrate on progress attained from 1975. The reader is also encouraged to consult reviews on the chemistry of the related sulfoximine-derived ylides such as (3). -"... 

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