Sulfonium ylides alkylation/deprotonation

Thia-[2,3]-Wittig sigmatropic rearrangement of lithiated carbanions 47, obtained by deprotonation of the S-allylic sulfides 46, affords the thiols 48 or their alkylated derivatives 49. The corresponding sulfonium ylides 51, prepared by deprotonation of the sulfonium salts 50 also undergoes a [2,3]-sigmatropic shift leading to the same sulfides 49 [36,38] (Scheme 13). As far as stereochemistry is concerned, with crotyl (R R =H,R =Me) and cinnamyl (R, R =H,R =Ph) derivatives, it has been shown that the diastereoselectivity depends on the nature of the R substituent and on the use of a carbanion or an ylide as intermediate. 

Sulfonium ylides can also be generated by in situ alkylation with diazo compounds. The alkylation can be carried out by reaction of a diazo compound with HBF4 and DBU.281 The reagents are added alternately in small portions and the reaction presumably proceeds by trapping of the carbocation generated by dediazonization and deprotonation. 

In the first step of this reaction sequence, the primary alcohol 21 is oxidized to the corresponding aldehyde 38 in a Parikh-Doering oxidation which is related to the Swern oxidation. In general, this type of oxidation is conveniently carried out by addition of a solution of pyridine-SOs complex in DMSO to a mixture of the alcohol, DMSO and NEts. It can be assumed that dimethyl sulfoxide and sulfur trioxide react to form 0-dimethylsulfoxonium sulfate 40, which then further reacts with primary alcohol 39 to give 0-alkyl dimethylsulf-oxonium intermediate 41. Then, sulfonium salt 42 is formed and subsequently deprotonated by NEts to give sulfonium ylide 43. Finally, an intramolecular p-elimination occurs to provide the desired aldehyde 44 and dimethyl sulfide. 

In catalytic epoxidation reactions an alternative to the ylide generation method via alkylation/deprotonation is the transition metal-mediated carbene transfer from diazo compounds to sulfide catalysts. In 1994, Aggarwal and coworkers employed this method in the enantioselective catalytic epoxidation of aldehydes [25]. Using 20mol% of non-racemic sulfide 17 and lmol% of Rh2(OAc)4 together with the slow addition of PhCHN2, a 58% yield and 11% ee were obtained in the epoxidation of benzaldehyde (Scheme 20.10). The enantioselectivity was similar to the results obtained by Breau and Durst using preformed sulfonium salts [26]. 

Tang and co-workers report a catalytic asymmetric cyclopropanation method where the sulfide reacts with an activated alkyl bromide to afford the sulfonium intermediate [163], This is deprotonated by base to generate the sulfur ylide that reacts with electrondeficient alkenes via Michael-addition and S -attack of the enolate formed to give the cyclopropane and to regenerate the sulfide (alkylation-deprotonation. Scheme 7.35). 

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... 

The generation of sulfonium yhdes relies mostly on three strategies (Scheme 78). The classic variant uses sulfide alkylation to the sulfonium salts 316 which can be deprotonated to dehver the desired yhdes 317 [180,181]. A related method involves silane 320 as the alkylating agent to allow for regioselective ylide generation via fluoride ion induced desilylation [182]. Finally, the action of carbenes 319 or metal-bound carbenoids offers a direct means for ylide generation [183,184]. 

Sulfur ylides are primarily synthesized by deprotonation of a sulfonium salt, which in turn is usually prepared by alkylation of a sulfrde. Branched chain sulfonium salts are not generally preparable by simple sulfrde displacement, although some can be made by other routes. - While ylide solutions are most commonly prepared and used immediately, frozen stock solutions of the more stable (2) can be stored for several months in DMSO at -20 C. ... 

An alternative procedure for generation of S-allyl oxathianone ylides is illustrated by the silver triflate induced alkylation of 22 with allyl halides119. Deprotonation of the resulting sulfonium triflates 23 results in formation of the rearranged products 24 with excellent control of simple and induced diastereoselection. An essentially identical product mixture (18) is obtained from alkylation of 22 with either (E)- or (Z)-l-bromo-2-butene, suggesting that an equilibration of olefin geometry precedes rearrangement. 

Sulfonium and ammonium salts are prepared readily by alkylation of sulfides or amines. For example, allylation of the amine 318 gave the intermediate ammonium salt 319 (3.205). Deprotonation to the ylide with sodium hydride was followed by [2,3]-sigmatropic rearrangement at room temperature to give the peni-cilhn derivative 320. In a synthesis of y-cyclocitral, the sulfonium salt 321 was prepared by alkylation of 1,3-dithiane and was converted to the ylide 322 and hence the rearranged product 323 (3.206). 

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