Pummerer elimination

The resulting 6-(methylthio)hexanoic acid is easily separable by aqueous extraction or by filtration through silica gel and can be reoxidized to 1873 with sodium metaperiodate in 97% yield. Low temperature (—60 °C) NMR spectrometry has been used to examine the intermediates of this Swem process. The results indicate that any residual unoxidized alcohol is generated during Pummerer elimination of the alkoxysulfonium intermediate and can be minimized by prolonged exposure to triethylamine at —40 °C. Reaction of the potassium salt of 1873 with cross-linked chloromethyl polystyrene affords a polymer-bound reagent that quantitatively oxidizes bomeol to camphor when used in two-fold excess [1394]. 

All of these ehimnddon reacdons contain fi-carbonyl groups in the nltro compounds Of course, masked carbonyl groups are also frequently employed for such fi-elimination of HNO, as shown in Eq 7131, Eq 7 133, and Eq 7 133In these cases, the sulfinylmethyl or hydroxymethyl group is converted into the carbonyl group by the Pummerer rearrangement or by simple oxidation... 

A very interesting approach to optically active sulphoxides, based on a kinetic resolution in a Pummerer-type reaction with optically active a-phenylbutyric acid chloride 269 in the presence of /V,A -dimethyIaniline, was reported by Juge and Kagan332 (equation 149). In contrast to the asymmetric reductions discussed above, this procedure afforded the recovered sulphoxides in optical yields up to 70%. Chiral a, /1-unsaturated sulphoxides 270 were prepared via a kinetic resolution elaborated by Marchese and coworkers333. They found that elimination of HX from racemic /i-halogenosulphoxides 271 in the presence of chiral tertiary amines takes place in an asymmetric way leading to both sulphoxides 270 and 271, which are optically active (optical yields up to 20%) with opposite configurations at sulphur (equation 150). 

The Pummerer reaction346 of conformationally rigid 4-aryl-substituted thiane oxides with acetic anhydride was either stereoselective or stereospecific, and the rearrangement is mainly intermolecular, while the rate-determining step appears to be the E2 1,2-elimination of acetic acid from the acetoxysulfonium intermediates formed in the initial acetylation of the sulfoxide. The thermodynamically controlled product is the axial acetoxy isomer, while the kinetically controlled product is the equatorial isomer that is preferentially formed due to the facile access of the acetate to the equatorial position347. The overall mechanism is illustrated in equation 129. 

Zwanenburg and Wagenaar148 have reported the rather unusual rearrangement of sulfone 81 to 82, after standing overnight at 0°, and suggested an elimination-addition mechanism, via initial isomerization of A3 to the A2-thiazoline-oxide with subsequent elimination and readdition of sulfmic acid, followed by spontaneous loss of water in a Pummerer-type aromatization reaction. 

DMSO or other sulfoxides react with trimethylchlorosilanes (TCS) 14 or trimefhylsilyl bromide 16, via 789, to give the Sila-Pummerer product 1275. Rearrangement of 789 and further reaction with TCS 14 affords, with elimination of HMDSO 7 and via 1276 and 1277, methanesulfenyl chloride 1278, which is also accessible by chlorination of dimethyldisulfide, by treatment of DMSO with Me2SiCl2 48, with formation of silicon oil 56, or by reaction of DMSO with oxalyl chloride, whereupon CO and CO2 is evolved (cf also Section 8.2.2). On heating equimolar amounts of primary or secondary alcohols with DMSO and TCS 14 in benzene, formaldehyde acetals are formed in 76-96% yield [67]. Thus reaction of -butanol with DMSO and TCS 14 gives, via intermediate 1275 and the mixed acetal 1279, formaldehyde di-n-butyl acetal 1280 in 81% yield and methyl mercaptan (Scheme 8.26). Most importantly, use of DMSO-Dg furnishes acetals in which the 0,0 -methylene group is deuter-ated. Benzyl alcohol, however, affords, under these reaction conditions, 93% diben-zyl ether 1817 and no acetal [67]. 

The influence of the classical anomeric effect and quasi-anomeric effect on the reactivity of various radicals has been probed. The isomer distribution for the deu-teriation of radical (48) was found to be selective whereas allylation was non-selective (Scheme 37). The results were explained by invoking a later transition state in the allylation, thus increasing the significance of thermodynamic control in the later reactions. Radical addition to a range of o -(arylsulfonyl)enones has been reported to give unexpected Pummerer rearrangement products (49) (Scheme 38).A mechanism has been postulated proceeding via the boron enolate followed by elimination of EtaBO anion. 

Samarium(II) iodide, 46, 3 Sandmeyer reaction, 2, 7 Schiemann reaction, 5, 4 Schmidt reaction, 3, 8, 9 Selenium dioxide oxidation, 5, 8 24, 4 Seleno-Pummerer reaction, 40, 3 Selenoxide elimination, 44, 1 Shapiro reaction, 23, 3 39, 1 Silanes ... 

The one-pot reaction of the a-(difluoromethyl)-p-sulfinylenamine 70 with trifluoroacetic anhydride in CHCI3, followed by treatment with silica gel affords 4-(difluoromethyl)-5-p-tolylthio-2(3//)-oxazolone 74 (Fig. 5.18). This reaction proceeds via a Pummerer-type rearrangement, followed by [l,3]-proton shift and the simultaneous elimination of trifluoroacetic acid and benzyl alcohol. ... 

The best available methods for synthesis of the parent heterocycles are clearly (a) Pummerer rearrangement of thiane 1-oxide, followed by elimination, affording the 3,4-dihydro compound and (b) dehydration of thian-4-ol to give the 3,6-dihydro system (78JHC289). Preparation of the benzannelated compounds is covered in reviews (75AHC(18)59, 80AHC(26)115>. 

Thiopyrans are readily available by manipulation of dihydrothiopyrans, either by elimination of water, amines or halogens, or via Pummerer reaction of the S-oxide (79LA784). Elimination reactions are of course particularly facile in the benzo fused systems and may be used to specifically make 2H- or AH-1- benzothiopyrans. On the other hand, extrusion reactions are relatively unknown, though an example has been reported which produces 1H-2-benzothiopyran 2,2-dioxides (equation 110) (72US(A)(2)287), but sadly its scope appears to be rather restricted. 

Substituted 2H- and AH- thiopyrans are largely confined to alkylated systems, and are usually derived by reduction of corresponding thiopyrylium salts, or by manipulation of dihydro systems either by elimination reactions or Pummerer reactions. The heteroatom substituted compounds which have been reported have usually been made by a [4 + 2] process such as that shown in equations (104) and (111) (71TL2241), and the range of examples is limited. 

Treatment of the isomeric dihydroselenines 93 containing electron-withdrawing groups in both the 2- and 6-positions with w-chloroperbenzoic acid also leads to formation of Pummerer-type oxidation products, the 4H-selenines 94 and the corresponding w-chlorobenzoate ester by-products (Equation 39) <1999J(P1)1155>. The esters could be converted to the corresponding 477-selenines by treatment with polyphosphoric acid trimethylsilyl ester (PPSE), a useful reagent for eliminations under neutral conditions. These 4/7-selenines were key intermediates in the synthesis of selenabenzenes. 

The reaction of arylsulfonyl-substituted sulfines (175) with diazomethane gives A3-l,3,4-thiadiazoline 1-oxides (176) which, however, are unstable and rearrange via an isomerization of the A3- to the A-thiadiazoline oxide. This is followed by an elimination and readdition of sulfinic acid and loss of water in a Pummerer-type aromatization to give the rearranged thiadiazole (177 Scheme 24) (73TL5009). 

The ease of oxidation depends on the electron availability on the sulfur. In quinoline and pyrimidine analogues of (459) the rate of the reaction is decreased, and in these betaine systems sulfone formation is not observed using peracids in the oxidations. A 2-carboxy group as in (463 R = H) promotes the Pummerer-type rearrangement. The initially formed hemimercaptal mainly eliminates water to give the thiazole (464) a minor product (465) may be formed by ring opening (81H(15)1349). 

Thioethers of azines are generally oxidizable to sulfones. By analogy (466) can be oxidized to its sulfone and the intermediate sulfoxide may be isolated. The latter, when subjected to the Pummerer rearrangement, yields the 2-acetoxy derivative (467), which on acid catalysis eliminates acetic acid to form the thiazole (79CPB1207). 

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... 

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