Sulfonium salts rearrangement

Two reports [93,94] have shown that allyl vinyl sulfonium salts rearranged readily to form thionium salts, which were subsequently transformed into a thioacetal (Scheme9.16). It is noteworthy that the initial investigation was made in the context of a possible path for an indole alkaloid biosynthesis [93]. The rearrangement of an allyl aryl dithiacation was also shown to proceed by an analogous route [95]. 

Two efficient syntheses of strained cyclophanes indicate the synthetic potential of allyl or benzyl sulfide intermediates, in which the combined nucleophilicity and redox activity of the sulfur atom can be used. The dibenzylic sulfides from xylylene dihalides and -dithiols can be methylated with dimethoxycarbenium tetrafiuoroborate (H. Meerwein, 1960 R.F. Borch, 1968, 1969 from trimethyl orthoformate and BFj, 3 4). The sulfonium salts are deprotonated and rearrange to methyl sulfides (Stevens rearrangement). Repeated methylation and Hofmann elimination yields double bonds (R.H. Mitchell, 1974). 

Ylides 2 can be prepared in situ from the sulfonium salts 1 with sodium hydride. These ylides 2 react with electrophiles, for example, acetylenes, to give the new stable ylides 3, for R1 =R2 = Me as a mixture of the cis- and trans-isomer, otherwise as the trans-isomer only. Compounds 3 are stable in refluxing tetrahydrofuran for 1 hour, but heating without solvent at 170-200r C for 3 to 5 minutes results in a 1,4-rearrangement to give thiaazulenes 4 quantitatively, with the exception of R1 = R2 = Et, where the yield is 25%.98... 

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. 

Similar to the well-known thio-Claisen rearrangement of allyl aryl sulfides and sulfonium salts, the thio-Claisen rearrangement of allyl aryl sulfoxides has also been reported. For example, heating of allyl 2-naphthyl sulfoxide (147) at 120 °C for 2h in dimethylformamide resulted in quantitative isomerization to the dihydronaphthothio-... 

Allylic sulfonium ylides readily undergo [2,3]-sigmatropic rearrangement.280 The ylides are usually formed by deprotonation of the S-allyl sulfonium salts. 

Shimizu and co-workers reported that thermal decomposition of A4-thiabenzenes ylides afforded both thienofuran and thiophene derivatives in addition to the expected alkyl-rearranged products. A plausible mechanism was proposed with a [3.1.0] bicyclic sulfonium salt 9 as the key reactive intermediate <2001J(P1)2269>. Warren and co-workers, in their study of stereospecific phenysulfanyl migrations, found that [l,4]-sulfanyl participation could compete with the usual [l,2]-sulfanyl participation <1999SL1211>. Rearrangement of alcohol 18 with TsCl in pyridine gave an inseparable mixture of isomeric chlorides, 19 and 20, in a ratio of 52 48, as shown in Equation (3). 

It is interesting to note that asymmetric induction was also observed (308) during generation of ylide 288 from achiral sulfonium salt 287a by means of chiral lithium 2,2,2-trifluoromethyl-a-phenylethoxide. The [2,3]sigmatropic rearrangement of the chiral ylide 288 obtained in situ in this way leads to optically active sulfide 289 of 5% optical purity. 

The [44-2] cycloadditions of the sulfonium salt, derived by loss of CP from 2-chlorodihydrobenzothiazine 248 with a diene, followed by a rearrangement give product 73 (Scheme 37) <1997J(P 1)309, 1998J(P1)1569>. 

Chiral bis-lithium amide bases have been used for enantiotopic deprotonation of the sulfonium salt of 1,4-oxathiane 86. The anion undergoes an enantioselective thia-Sommelet rearrangement to afford the 3-substituted-1,4-oxathiane 87. Only bis-lithium amide bases were effective, giving products with high diastereoselectivity and with low to moderate enantioselectivity (Equation 13) <2003TL8203>. 

The reaction of 1,3-dibromopropane with methyl methylsulfanylmethyl sulfoxide in the presence of base gave cyclobutanone via the intermediate formation of ftve-membered cyclic sulfonium salt 6, which was finally converted to 1-methylsulfinyl-l-methylsulfanylcyclobutane (7 a) by a Stevens-type rearrangement in 70% yield which on acid hydrolysis gave cyclo-butanone.142... 

Cleavage of sulfonium compounds 8 22 Rearrangement of sulfonium salts... 

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. 

Lucchini, Pasquato, and co-workers have obtained stereoisomeric 2,3-disubstituted 1-methylthiiranium ions, reported characterization (1H and 13C NMR, X-ray crystallography), and studied their anionotropic rearrangements. The synthesis was performed by reacting methylbis(methylthio)sulfonium salts with alkenes184,185 (Scheme 4.7). 

Reaction of (2-aminophenyl)-(4-bromophenyl)-methanone with methylsulfanylacetic acid ethyl ester and tert-butyl hypochlorite gives a corresponding sulfonium salt. This salt was transformed to initially to the betaine. Electrocyclic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid. Internal ester-amine interchange leads then to 4-bromophenyl-(3-(methylthio)indolin-7-yl)methanone. The thiomethyl group is then removed with Raney nickel to give 4-bromophenyl-(indolin-7-yl)methanone. Saponification of this intermediate affords the (2-amino-3-(4-bromobenzoyl)-phenyl)-acetic acid (Bromfenac). 

A cyclic sulfonium salt undergoes a thia-Sommelet rearrangement which results in dearomatization and production of the 2-substituted tetrahydrothiopyran 471 in a diastereoselective fashion (Equation 156) <1998JA841>. 

The first step is just the SN2 displacement of Cl- by RS that you have already seen. The second step actually involves chlorination at sulfur (you have also seen that sulfides are good soft nucleophiles for halogens) to form a sulfonium salt. Now a remarkable thing happens. The chlorine atom is transferred from the sulfur atom to the adjacent carbon atom by the Pummerer rearrangement. 

The generally accepted mechanism6 of Pummerer rearrangement is the one in which there is an initial attack on the sulfoxide oxygen atom by an electrophilic species, e.g., protonation or acylation. Acylation is followed by proton abstraction by a base from the a-carbon atom of the sulfoxide to form an ylide, which rapidly eliminates an acetate anion to form the a-sulfonium salt. Addition of acetate anion to the sulfonium intermediate completes the formation of the a-functionalized sulfide. Ylide formation from sulfoxonium salts is well recognized, and this aspect... 

The a nature of the LUMO level in sulfonium salts is, we believe, the fundamental scientific reason for their unique photochemical behavior. For example, photolysis of 1-naphthylmethyl-substituted alkyl sulfonium salts produce molecular rearrangement and photosolvolysis [90] as shown. The HOMO level is jr in character localized on naphthalene and the LUMO is cr localized on the... 

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