A Pummerer rearrangement

Heating of the sulfoxide 31 causes a Pummerer rearrangement generating the ylide 32, which could be trapped with dimethyl acetylenedicarboxylate (DMAD) giving the dihydrothiophene derivative 33 <06HC648>. 

Pyrrolo[2,l-c][l,4]benzothiazepine 297 (R=Ph) has been prepared by an intramolecular nucleophilic displacement of acetyl derivative 296 (Scheme 64 (1992H51)). The same compound and its aryl (R = Ar (1992H51)) and carboethoxy or cyano (R = C(30Et or CN (1990H1291)) analogs can also be obtained by a Pummerer rearrangement-cyclization of sulfinyl precursor 298. 

Further elaboration of the sulfur cycloadducts could be achieved by the use of a Pummerer rearrangement in the syntheses of 5-(hydroxymethyl)prolines. Oxidation of adduct 298 to sulfoxide 299, followed by treatment with TEA in DCM and quenching with either methanol or benzyl alcohol, delivered the Pummerer products 300 in 57% yield for R = Me and 38% for R = Bn as single diastereoisomers. Raney Ni desulfurization and Pearlman s catalyst mediated hydrogenolysis, for R = Bn furnished the final enantiopure proline derivative (Scheme 3.99). 

Dihydrofurans can be prepared efficiently by a Michael addition of (3-ketoesters to alkenyl sulfoxides followed by a Pummerer rearrangement (Scheme 36) (92JCS(Pi)945). 

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>. 

This form of activated DMSO is stable below —30°C, but suffer a Pummerer rearrangement above this temperature, resulting in the formation of methylthio-methyl trifluoroacetate (23). In fact, compound 23 reacts with alcohols in the presence of an amine, resulting in a very quick trifluoroacetylation. However, this trifluoroacetylation pathway is not operative in a properly perfonned Omura-Sharma-Swem oxidation, because alcohols are previously transfonned in afkoxy-dimethylsulfonium salts 24. 

A Pummerer rearrangement features in two approaches to 1,3-oxathiins. Refluxing y,8-unsaturated sulfinyl compounds (26) in xylene containing TsOH effects conversion to the 3,1-benzoxathiin (27) via a sulfonium ion intermediate (95CC1197), whilst 2-(hydroxymethyl)phenyl sulfoxides (28), readily cyclise to the benzoxathiin (95T6819). 

A Pummerer rearrangement has been shown to occur on the sulfoxide 150 anchored onto Cso-fuHerene < 1999TL1543>. 

CcHiimon by-products in these reactions are (methylthio)methyl ethers (3) formed by a Pummerer rearrangement which occurs via an alternative breakdown of (2), as shown in Scheme 3. The proportion of the Pummerer rearrangement derived product varies with the electrophilic activator used. 

On warming above -30 C the mixture clears and a Pummerer rearrangement occurs to form (methyl-thio)methyl trifluoracetate (13). However the extent of this by-product formation is minimized at Ae lower temperature, and the reaction with alcohols gives high yields of carbonyl products over short reaction times. This makes trifluoroacetic anhydride one of the better activators for dimethyl sulfoxide oxidations. 

Synthesis of P-Keto Sulfoxides. Optically active p-keto sulfoxides are very useful building blocks (eq 4) because they can be stereoselectively reduced to afford either diastereomer of the corresponding p-hydroxy sulfoxide under appropriate conditions (Diisobutylaluminum Hydride or Zinc ChloridefDlBALf and thus give access to a wide variety of compounds chiral carbinols by desulfurization with Raney Nickel or LithiumJethyhmme ini the case of allylic alcohols epoxides via cyclization of the derived sulfonium salt butenolides by alkylation of the hydroxy sulfoxide 1,2-diols via a Pummerer rearrangement followed by reduction of the intermediate. ... 

Note that treatment of (1) with acetic anhydride gives a 3,l-bcnzoxathiane-4-one (3) via a Pummerer rearrangement in good yield. ... 

Iverything is set up for a Pummerer rearrangement - the sulfoxide, the acidic hydrogens on one .de, the anhydride - so we must first react the oxygen of the sulfoxide with the anhydride and make -he Pummerer cation. 

Alkyl aryl sulfides, when oxidized in HOAc-Ac20-NaOAc, produce the corresponding sulfoxides and the a-acetoxy derivatives [102]. The formation of the latter compounds was ascribed to a Pummerer rearrangement of the initially formed sulfoxide. These compounds normally are obtained by heating sulfoxides with Ac O at elevated temperature, and it seemed attractive to perform the electrolyses in the boiling solvent to form the a-acetyoxy derivatives as the sole product. This approach was shown to be adequate, and yields are given in Eq. (54) [102]. 

These trihydroxy sulfoxides are useful molecules in total synthesis because of the possible transformation of the sulfoxide into aldehyde by a Pummerer rearrangement. Homoallylic 3-hydroxy sulfoxides have also been prepared from 3-epoxy sulfoxides, readily obtained from methyl monochloroacetate (Scheme 61a). ... 

A beautiful application of two consecutive 2,3-sigmatropic shifts was provided by Corey (equation 69). In a one-pot operation he elaborated sulfoxide (203) into sulfoxide (204), which gave an a,p,y,8-unsaturated aldehyde by a Pummerer rearrangement (for a similar application see ref. 135). 

Upon treatment of 48 with Bri under photochemical conditions [36], the primary bromide was generated and subsequently displaced with thiophenoxide to give product 49 (Scheme 8). Periodate oxidation of 49 followed by a Pummerer rearrangement [37] fixmished adduct 50 as a mixture of diastereomers (1 2). 

Bonjoch, J., Catena, J., Vails, N. Total Synthesis of ( )-Deethylibophyllidine Studies of a Fischer Indolization Route and a Successful Approach via a Pummerer Rearrangement/Thionium Ion-Mediated Indole Cyclization. J. Org. Chem. 1996, 61, 7106-7115. 

Scheme 16.7 Li s safety-catch system including a Pummerer rearrangement.

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