Cyclopropanations using sulfur ylides

Scheme 10.22 Catalytic asymmetric cyclopropanation using sulfur ylides via an alkylation/deprotonation route.

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 ... 

The first catalytic asymmetric cyclopropanation using an ylide as catalyst was reported by Aggarwal et al. in 1997 [95, 96]. Phenyl diazomethane was added slowly to a mixture containing sulfide 12, an enone and Rh2(OAc)4 (1 mol%). A sulfur ylide was generated in situ from the sulfide and phenyl diazomethane in the presence of the transition-metal catalyst (see Scheme 10.20), as in the epoxidations discussed earlier (see Section 10.2.1.3). 

In addition to sulfur ylides, examples are known of cyclopropanations using other ylides containing group V or group VI elements. Among these, triphenylphosphonium ylides have most frequently been studied. Some examples are collected in Table 19. The products obtained in entries 1-3 and 10 of Table 19 are suitable precursors for chrysanthemic acid. An enantioselec-tive synthesis of cyclopropanes was achieved by using electron-deficient alkenes substituted with an optically pure oxazolidine or acetonide function. When the alkene is stabilized by a ketone or nitro function instead of an ester function, the yield dropped considerably. 

The electron-deficient double bond in 2-phenylsulfonyI-l,3-dienes underwent regioselective cyclopropanation with sulfur ylides in very good yield, e.g. cyclopropanation of 13, 14 and 15 with sulfur ylides.On the other hand, the use of zinc-copper couple and diiodomethane afforded a 83 17 mixture of vinylcyclopropanes 16 and 17 from 2-(phenylsulfonyl)cyclohexa-1,3-diene (15) in moderate yield. The reaction at the electron-deficient double bond rather than at the expected electron-rich double bond shows that the Simmons-Smith carbenoid is fairly nucleophilic in character. 

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... 

Sulfur ylides are among the most interesting carbon nucleophiles and their synthetic importance has been recently reviewed.One especially interesting use of these ylides is their application to the synthesis of cyclopropane derivatives using unsaturated oxazolones. For example, stabilized sulfur yhdes react with unsaturated oxazolones 629 via a Michael reaction to give oxazolone spirocyclopropanes 630 as shown in Scheme 7.202 and Table 7.46 (Fig. 7.57), whereas the less stabilized sulfur ylides give ring-opened products 631 as the major compounds (Scheme 7.202). ... 

Double-bond compounds that undergo the Michael reaction (5-17) can be converted to cyclopropane derivatives with sulfur ylides.1068 Among the most common of these is di-methyloxosulfonium methylide (108),l,l6, which is widely used to transfer CH2 to activated... 

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%,... 

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. 

Kinetic control and thermodynamic control account, respectively, for epoxide formation and cyclopropanation [204]. Various Michael acceptors have been converted to cyclopropane derivatives with sulfur ylides. Some of the reagents used to transfer CHCOR [456], CHCOOR [457], CHMe... 

A limited number of other anionic species have been employed as Michael donors in tandem vicinal difunctionalizations. In a manner similar to sulfur ylides described above, phosphonium ylides can be used as cyclopropanating reagents by means of a conjugate addition-a-intramolecular alkylation sequence. Phosphonium ylides have been used with greater frequency261-263 than sulfur ylides and display little steric sensitivity.264 Phosphorus-stabilized allylic anions can display regiospecific 7-1,4-addition when used as Michael donors.265... 

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... 

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. 

In this chapter, we will review the use of ylides as enantioselective organocata-lysts. Three main types of asymmetric reaction have been achieved using ylides as catalysts, namely epoxidation, aziridination, and cyclopropanation. Each of these will be dealt with in turn. The use of an ylide to achieve these transformations involves the construction of a C-C bond, a three-membered ring, and two new adjacent stereocenters with control of absolute and relative stereochemistry in one step. These are potentially very efficient transformations in the synthetic chemist s arsenal, but they are also challenging ones to control, as we shall see. Sulfur ylides dominate in these types of transformations because they show the best combination of ylide stability [1] with leaving group ability [2] of the onium ion in the intermediate betaine. In addition, the use of nitrogen, selenium and tellurium ylides as catalysts will also be described. 

Stoichiometric ylide cyclopropanations have been known for some time, with asymmetric variants using aminosulfoxonium ylides having been reported as early as 1968 [27]. Since then, procedures using stoichiometric amounts of sulfur, nitrogen, and tellurium ylides to achieve asymmetric cyclopropanations have been reported [16, 22, 86, 92-94]. The catalytic analogues of these reactions are discussed in the following sections. 

In 2001, a modified procedure for sulfur ylide-catalyzed epoxidation, aziridination and cyclopropanation was introduced by Aggarwal and co-workers that utilized the generation of the diazo compounds in situ from tosyl hydrazone salts at 40 °C in the presence of a phase-transfer catalyst [46, 79]. (For experimental details see Chapter 14.12.1). Using this modified protocol, sulfide 4 was shown to be effective for epoxidation and aziridination (see Sections 10.2.1.4 and 10.3), but was not an effective cyclopropanation catalyst (see Table 10.3). Sulfide 28 was tried instead as it had been shown in achiral studies [96] that six-membered sulfides were more effective than five-membered analogues. This change gave rise to... 

Recently, Tang, Wu and co-workers have reported the synthesis of vinylcyclopro-panes using an alternative catalytic cycle for sulfur ylide-catalyzed cyclopropanation (see Scheme 10.22) [98]. Sulfonium salt 41a or 41b was deprotonated by CS2CO3 to form an ylide which then reacted with chalcones 37 to form cyclopropanes and a sulfide. The sulfonium salt was regenerated in situ through reaction... 

Alkenes susceptible to Michael additions react with sulfur ylides to form cyclopropanes. Examples of typical ylides used in the cyclopropanation reaction of Michael acceptors are presented in Scheme 4. Best results were obtained with stabilized ylides, i.e. ylides of type C, D or E, and yields were enhanced with increase of the electron-withdrawing capacity of the anion stabilizing group in the alkene. The mechanism of the cyclopropanation reaction (Scheme 5) is known, and proceeds in a nonstereospecific manner. The E/Z geometry of the alkene is frequently retained in the product and a high degree of asymmetric induction can be achieved with optically active Michael acceptors or ylides. 

Starting from (2-oxoalkylidene)sulfur-5, triacylcyclopropanes are often the dominant products, regardless of the decomposition mode of the sulfonium ylide. . In fact, no example of an efficient alkene cyclopropanation using these synthetic equivalents of oxocar-benes is yet known. The photochemical decomposition (2> 300nm) of (2-oxo-2-phenylethylidene)sulfur-5" in cyclohexene yielded only a minor amount of 7-benzoyl-bicyclo[4.1.0]heptane (2, 5%) in addition to tranj-l,2,3-tribenzoylcyclopropane (3, 40%), acetophenone (37%), bicyclohex-2-enyl (38%), and propiophenone (3%). In an inert solvent (benzene, chloroform) without an additional trapping reagent,, 2,3-tribenzoylcyclo-... 

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