Pummerer rearrangement vinylic sulfoxides

Kita et al. have reported an asymmetric Pummerer rearrangement of optically active sulphoxides, induced by ethoxy vinyl esters (EVE). In particular ethoxy vinyl acetate 50 was used to effect the Pummerer rearrangement of sulfoxides 51a-b in good yields and high enantioselectivity. 

An intramolecular version of enolate Michael addition to enantiomerically pure vinylic sulfoxides is represented by reaction of a cyclopentenone sulfoxide with dichloroketene (Scheme 5)90 this type of additive Pummerer rearrangement has been developed by Marino and coworkers91 into a highly effective way of constructing variously substituted lactones in very high enantiomeric purity (equation 43). 

Vinyl sulfoxides (221), which are aldehyde a-cation equivalents, and vinylthiolium ions (230), which are a.jj-unsaturated carbonyl 3-cation equivalents, are also suitable acceptors for silyl ketene acetals and enol silyl ethers (Scheme 36). Kita reports that the bulky r-butyldimethylsilyl ketene acetals and tri-methylsilyl ketene acetals form 1 1 adducts (224) and 1 2 adducts (225) with (221), respectively 91 mechanistically, these additions proceed via an initial Pummerer rearrangement The vinylthiolium ion additions are notable for their synthetic flexibility for example, additions to the ketene dithioacetal (229) proceed with higher diastereoselectivity than the corresponding enolate additions to a,3-unsaturated esters.9 lc,91d... 

The reaction of phenyl vinyl sulfoxide 234 with isobutene, in the presence of trifluoroacetic anhydride, yielded the to-alkylated product 238 (Scheme 59).128 It was suggested that this reaction proceeded by a different mechanism than the usual additive Pummerer mechanism. The alkene reacts with the electrophilic sulfur atom of intermediate 235, giving, after loss of a trifluoroacetate ion and a proton, the sulfonium ion 236. Thio-Claisen rearrangement of the ion then gives the thonium ion 237 which reacts with a further molecule of isobutene to give the product 238. 

The Pummerer-type rearrangement of vinyl sulfoxide has been named an additive Pummerer rearrangement because both the addition to the double bond and the... 

Vinylic sulfoxides can undergo additive Pummerer rearrangement when they are treated with trichlo-roacetyl chloride and a zinc/copper couple in refluxing ether giving opticdly pure 7-butyrolactone... 

A simple and straightforward application was outlined in the synthesis of hydrohydrastinine as depicted in Scheme 10. Michael addition of 3,4-methyle-nedioxyphenylmethyl amine to vinyl sulfoxide 36 took place smoothly in refluxing methanol. Pummerer rearrangement in acetic anhydride afforded acetoxysulfide 37 in 90% yield and this was then cyclized to 38 with BF3 etherate in 93 % yield. Sulfide 38, which was rather unstable, was desulfurized with Raney nickel in 80 % yield. Hydrolysis of the acetyl group followed by reductive methy-lation afforded hydrohydrastinine (39) in good yield [24]. 

Dithiole-2-one (60), which can be readily transformed into its thio- or seleno-carbonyl derivatives, is a key intermediate for the synthesis of tetrathiafulvalene (Scheme 13)[31]. We first anticipated that compound 57, a Michael addition product of xanthate 54 to vinyl sulfoxide, might be an ideal intermediate for the synthesis of 60 via cyclization under Pummerer rearrangement conditions. However, although Michael addition of dithiocarbamate 53 to vinyl sulfoxide proceeded smoothly to yield compound 55, the addition reaction with xanthate 54 failed. We then turned to the alkylation approach. Xanthate 54 was alkylated smoothly with 56, which served as the synthetic equivalent of the vinyl sulfoxide, in ethanol under sonication in 90% yield [32]. Cyclization of 57 under Pummerer rearrangement conditions in the presence of trifluoroacetic acid afforded 58 in 79% yield. Sodium metaperiodate oxidation gave the unstable sulfoxide 59 which underwent thermal elimination to yield 60 in refluxing benzene in moderate yield. 

In summary, vinyl sulfoxide (or its equivalent 56) was adopted as a two-carbon synthon for the syntheses of alkaloids (39,43ab,45ab), furans (51), pyrroles (52), and l,3-dithiole-2-one (60). Our overall strategy is summarized in Scheme 14. Michael addition of Nu1 to the vinyl sulfoxide followed by intramolecular trapping of the presumed sulfenium ion Pummerer rearrangement intermedia-... 

At a later stage, since nitroethylene itself is difficult to produce on a large scale, a second procedure using the adducts derived from phenyl vinyl sulfone was developed. This involved oxidation to the sulfoxide followed by Pummerer rearrangement with trifluoroacetic anhydride and finally mild alkaline hydrolysis (Scheme 34)... 

Pummerer rearrangement of the optically active sulfoxide (64) to the 1,3-benzoxathiinone (65) occurs with moderate to good transfer of enantiomeric excess when the reaction is promoted by ethoxy vinyl esters <97TA303>. 

A new route to pyrroles which begins by conjugate addition of p-ketoesters to phenyl vinyl sulfoxide was developed. <94JCS(P1)2355> The adducts are subjected to Pummerer rearrangement which generates 2-phenylthio-dihydrofurans as intermediates. Treatment with amines and HgClj leads to formation of the pyrroles. 

Williams has demonstrated the use of 1-phenylsulfinyl-l-trimethylsilylethene (164) and phenyl vinyl sulfoxide as effective ketene equivalents for the Diels-Alder reaction [142,143], important as it is known that ketenes do not undergo satisfactory [4+2] cycloadditions. The initial cycloadduct (165), derived from the Diels-Alder reaction between 1-phenylsulfinyl-l-trimethylsilylethene (164) and cyclopentadiene, undergoes a facile sila-Pummerer rearrangement to give the thioacetal (166), which yields the product (167) upon hydrolysis (Scheme 5.55) [142]. 

So far, the more common ways to use Pummerer chemistry have been described (i.e., 24 26 and 24 25, Scheme 20.7T However, even if it usually is the A fragment fScheme 20.7 of the sulfoxide which is the inportant component of the target, some researchers have used the classical Pummerer reaction to obtain thiols or complex vinyl sulfides (24 28 or 24 27, Scheme 20.7). Clearly, the convenience of using Pummerer chemistry in the synthesis of thiols is closely related to the structure of the desired product. Sinple thiols can be obtained by Pummerer reactions, but in most cases, other shorter and cheaper methods are available. Consequently, the use of the Pummerer rearrangement to produce thiol products is most favorable in the s)mthesis of very complex thiols. 

Acid anhydrides and/or acids are employed in the majority of synthetic applications of the Pummerer reaction. However, there are a number of other reagents which activate the sulfoxide oxygen in the Pummerer reaction. The use of organosilicon reagents is discussed in Sections 4.7.3.3,4.7.3.S and 4.7.3.7 in connection with the preparation of trimethylsiloxy sulfides and vinyl sulfides. Recently it was shown that the trimethylsilyl ester of polyphosphoric acid also promotes the Pummerer rearrangement. 

The Pummerer reaction of sulfinyl compounds involves the formation of an a-functionalized sulfide [244, 245] from a sulfoxide. Acetic anhydride is commonly used as the electrophile, which adds to the sulfoxide to yield a sulfonium salt, and the rearrangement occurs through successive formations of an ylide (rate-determining step) and an alkylidene sulfonium, trapped by a nucleophile, or stabilized by a proton loss with formation of a vinyl sulfide. 

Vinyl chloroformate might find interesting applications in Pummerer related rearrangements. Thus, VOC-CI reacts with sulfoxides to yield a-chlorosulfides as shown in scheme 108 (Ref. 161). In this type of reaction, VOC-Q is more... 

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