Aminosulfoxonium ylide

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. 

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. ... 

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 ... 

Fig. 1.3.6 Structure of the allyl aminosulfoxonium ylide 30 according to ab-initio calculations. Rel. energy 0.0 kcal mob Ca—S 163 pm, a ZCa 356 °.

Scheme 1.3.17 Asymmetric synthesis of homopropargyl alcohols via a-elimination of alkylidene aminosulfoxonium ylides.

The methylation of sulfoximines 45 with Me30BF4 proceeded readily and gave the corresponding cyclic aminosulfoxonium salts 46 in quantitative yields. Upon treatment with LiN(H)t-Bu first at-78 °C and then at room temperature, salts 46 delivered the enantio- and diastereomerically pure bicyclic 2,3-dihydrofurans 50 cleanly in high overall yields. It is proposed that the reactions of the aminosulfoxonium salts 40 and 46 with the lithium amide at low temperatures afford the vinyl aminosulfoxonium ylides 41 and 47, respectively. These alkylidene carbenoids eliminate sulfinamide 35 at higher temperatures with formation of the alkylidene carbenes 42 and 48, respectively. Subsequently, the alkylidene... 

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. 

Johnson et al. were the first to prepare enantiomerically pure aminosulfoxonium ylide 3.73 from 3.72, which on reaction with benzaldehyde gave (P)-styrene oxide (3.69) in 20% ee. The reaction of aminosulfoxonium ylide 3.74 with heptaldehyde gave the corresponding epoxide 3.75 with opposite enantioselectivity (39% ee, S) as expected. 

A two-step mechanism (Scheme 3.34) for epoxidation was proposed in which intermediate betaine A and B are obtained from the carbonyl compound and sulfonium ylides irreversibly and from aminosulfoxonium ylide reversibly (step 1). Betaine (A or B) then undergoes ring closure (step 2) irreversibly. 

Asymmetric ylide cyclopropanations have been studied since 1960 and have been intensively discussed and documented in the literature. Besides chiral aminosulfoxonium ylides, chiral sulfonium as well as chiral sulfoxonium ylides have been examined in reagent-controlled asymmetric cyclopropanations. However, asymmetric ylide cyclopropanations with alkenes bearing the chiral inductor proved to be more efficient. 

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. 

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