Sulfur ylides, chiral

The sulfur ylide-mediated epoxidation of aldehydes has been thoroughly investigated [70, 71]. The chiral sulfur ylides reported by Aggarwal have been most broadly applicable, and a catalytic, asymmetric process yielding aromatic transepoxides has been developed [72]. In this process, the sulfur ylides are produced in situ from diazo compounds, generated in turn from tosylhydrazone salts (Scheme 9.15) [73],... 

The aldehyde structures and the tosylhydrazone salts were varied in an extensive study of scope and limitations, with use of both achiral and chiral sulfur ylides [73]. Aromatic aldehydes were excellent substrates in the reaction with benzaldehyde-derived ylides, whereas aliphatic aldehydes gave moderate yields and transxis ratios. 

When ot, 3-unsaturated aldehydes were employed, vinylepoxides were obtained with excellent transxis ratios but in poor yields. When benzaldehyde was treated with a, 3-unsaturated tosylhydrazone salts, the yields of vinylepoxides were improved but the transxis ratios dropped. When chiral sulfides were utilized, the ees were high with a, 3-unsaturated aldehydes, whereas unsaturated, chiral sulfur ylides gave moderate ees, poor yields, and modest transxis ratios. 

A very convenient asymmetric synthesis of cyclopropane or epoxide systems developed by Johnson (184) is based on the use of chiral sulfur ylides as the agents that induce optical activity. Generally, this method consists of the asymmetric addition of a chiral sulfur ylide to the C=C or C=0 bond and subsequent cyclization of the addition product to form a chiral cyclopropane or epoxide system together with chiral sulfinamide. A wide range of chiral... 

The required chiral sulfur ylide of type 59 is formed in a reaction with a diazo compound in the presence of an achiral metal catalyst. Subsequently, asymmetric reaction of the chiral ylide 59 with the C=N double bond of the imine proceeds diastereoselectively and enantioselectively, giving the optically active aziridine 57. The chiral sulfide catalyst released is then used for the next catalytic cycle. The cat-alytically active species in the asymmetric process is the sulfide, so this concept can also be regarded as an organocatalytic reaction. 

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-... 

A variation of the [C + C=N] pathway involves the addition of sulfur ylides to imines and this method has been effectively used to access a wide range of substituted aziridines under mild reaction conditions. Although high enantiomeric excesses can be achieved by using a chiral sulfur ylide (up to 98%), the m//rstepwise mechanism via a betaine intermediate . Sulfur ylides can be conveniently generated in situ from alkyl halides and chiral sulfides thus, benzyl bromide and tosyl imine in the presence of a camphor-derived chiral sulfide mediator provide aziridine 4 in practically quantitative yield as a 3 1 mixture of /Z-isomers and in 92% ee (A-isomer) (Scheme 8) <2001TL5451>. 

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. ... 

Chiral aminosulfoxonium ylides react with electron-deficient alkenes, e.g. a,p-unsaturated ketones and esters, to cyclopropanes in moderate to high yields (56-94%) and up to 34% ee The chiral sulfur ylides A, and were reacted with various Michael acceptors, whereby enantioselectivities up to 53% were achieved. 

The use of sulfur ylides as versatile reactants in these domino reactions was also reported by Briere and co-workers [53]. They developed a highly diastereoselective synthesis of spiro epoxyoxindoles from reaction between in s/Yw-generated sulfur ylides and isatin derivatives. Moderate enantioselectivity (30% ee) could be achieved with a C2-symmetrical chiral sulfur ylide. 

Aggarwal and Fang utilized the chiral sulfur ylide 212 to impart chirality on the allylborane 214 that underwent smooth allylboration with aldehydes to provide the corresponding homoallylic alcohol 215 (Scheme 25.33). ... 

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 ... 

Aziridination remains less well developed than epoxidation. Nevertheless, high selectivity in inline aziridination has been achieved through the use of chiral sulfi-nimines as auxiliaries. Highly successful catalytic asymmetric aziridination reactions employing either sulfur ylides or diazo esters and chiral Lewis acids have been developed, although their scope and potential applications in synthesis have yet to be established. 

Metzner and co-workers reported a one-pot epoxidation reaction in which a chiral sulfide, an allyl halide, and an aromatic aldehyde were allowed to react to give a trons-vinylepoxide (Scheme 9.16c) [77]. This is an efficient approach, as the sulfonium salt is formed in situ and deprotonated to afford the corresponding ylide, and then reacts with the aldehyde. The sulfide was still required in stoichiometric amounts, however, as the catalytic process was too slow for synthetic purposes. The yields were good and the transxis ratios were high when Ri H, but the enantioselectivities were lower than with the sulfur ylides discussed above. 

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... 

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. 

In the design of chiral sulfides for sulfur ylide-mediated asymmetric epoxidation of aldehydes, two factors are important. First, a single sulfur ylide should be produced. Otherwise, the diastereomeric sulfur ylides may react with aldehydes in different ways and thus cause a drop in stereoselectivity. This may be achieved by choosing a rigid cyclic structure to make one of the lone pairs more accessible than the other. Second, the structure should be amenable to structural modification in order to study the electronic and steric effects of the sulfur on the enantioselectivity of the epoxidation reaction. 

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>. 

The enantiomeric synthesis of rranj-3,4-disubstituted tetrahydrothiophenes using a sulfur ylide cycloaddition has been reported <990L1667>. The sulfur ylide derived from the action of cesium fluoride on sulfide 111 underwent an asymmetric cycloaddition with chiral a,p-unsaturated camphorsultam amide 112 giving tetrahydrothiophene 113 (80% de). The configuration was confirmed by cleavage of the chiral auxiliary followed by reductive desulfurization with Raney-Ni which gave known carboxylic acid 114. 

Chiral cyclopropanes. Carrie el al.b l have developed a highly enantioselective synthesis of cyclopropanes from the aldehyde 2, in which the butadiene group is protected as the iron tricarhonyl complex. The complex (2) is resolved by the method of Kelly and Van Rheenan (5, 289-290), and the two optical isomers arc then converted separately into a cyclopropanealdehyde (5a and 5b) as formulated. A sulfur ylide such as (CH3)2S=CHCOOCH3 can be used in place of diazomethane for cyclopropanation. Optical yields are > 90%,... 

Chiral compounds (Continued) epoxy alcohols, 141 formulas, xiii xvii hydroxystannanes, 318 liquid crystals, 350 molecular lattics, 347 natural, 1 NMR spectra, 282 olefins, 173 oxetanones, 326 phenols, 287 see also Binaphthol phenylbutenes, 172 protonating agents, 324 sulfoxides, 159 sulfur ylides, 328 synthesis, I... 

Some organic reactions can be accomplished by using two-layer systems in which phase-transfer catalysts play an important role (34). The phase-transfer reaction proceeds via ion pairs, and asymmetric induction is expected to emerge when chiral quaternary ammonium salts are used. The ion-pair interaction, however, is usually not strong enough to control the absolute stereochemistry of the reaction (35). Numerous trials have resulted in low or only moderate stereoselectivity, probably because of the loose orientation of the ion-paired intermediates or transition states. These reactions include, but are not limited to, carbene addition to alkenes, reaction of sulfur ylides and aldehydes, nucleophilic substitution of secondary alkyl halides, Darzens reaction, chlorination... 

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. 

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