Pummerer rearrangement cyclization

Cyclization of the sulfoxide 1248 with TMSOTf 20/DlPEA affords a 4 1 mixture of the tetrahydroquinolines 1249 and 1250, in 97% yield, and HMDSO 7 [49]. On heating of the sulfoxide 1251 to 80 °C Brook rearrangement then Sila-Pummerer rearrangement-cyclization gives, via 1252, 17% 1253 [50] (Scheme 8.19). 

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. 

Thieno[2,3-c]furans have also been prepared in situ by the Pummerer-rearrangement cyclization reaction (96JOC6166). For transient generation of thieno[2,3-c]furans see also Kuroda et al. [91JCS(CC)1635]. These compounds proved to be reactive intermediates for inter- and intramolecular Diels-Alder reactions (see Section IV). 

A Pummerer rearrangement cyclization was next achieved hy treating indole 242 with trifluoroacetic anhydride in dichloromethane. The indole-nine product was then reduced with sodium cyanoborohydride and desulfurized with Raney nickel to furnish lactam 243. It is interesting to note that in contrast to the Pummerer cychzation of the acetamide 242, which undergoes cyclization to the indole 3-position as shown, photocyclization of... 

Pummerer cyclization. Pummerer rearrangement of 4-(phenylsulfinyl)butyric acids (1) catalyzed by TsOH results in 4-phenylthio-4-butanolides (2). Oxidation followed by thermolysis results in either 3 or 4, depending on the substitution pattern. 

The cyclization of the Pummerer rearrangement product 30 derived from o-methylsulfinyl-difluorostyrene 29 leads to 2-fluorobenzo[ ]thiophene 31 (Scheme 7) <1997CC1537>. Treatment of thiol 32 with NaH affords 2-fluoro-4,5-dihydrothiophene 33 by a cyclization <2000CC1887>. 

A combination of the Pummerer rearrangement and the Ritter reaction occurs in the reaction of acetonitrile with methyl phenyl sulfoxide (equation 25) in a mixture of irifluoroacetic acid and its anhydride, although a substantial amount of the nonnal a-acetoxylation also occurs. Participation by amido groups is also possible, the interest here being largely in the construction of lactams via the intramolecular cycli-zation mode. Whereas Wolfe and his coworkers were unable to find conditions for the cyclization of S-phenylcysteinamide sulfoxides under Pummerer conditions, Kaneko found that variously substituted... 

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. ... 

The total synthesis of (+)-deethylibophyllidine was accomplished by J. Bonjoch and co-workers, who applied a regioselective Fischer indole synthesis as one of the key steps to obtain octahydropyrrolo[3,2-c]carbazoles. The indole formation was followed by a tandem Pummerer rearrangement-thionium ion cyclization to generate the quaternary spiro stereocenter. 

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. 

Pummerer rearrangement and cyclization, completed the construction of the aspidospermidine ring system, and (+)-aspidospermidine was finally obtained by appropriate reduction procedures (Scheme 54) (296). 

We view acetylenic sulfoxide 1 as a two-carbon synthon in alkaloid synthesis. Our general approach, as depicted in Scheme 4, called for a Michael addition of Nu1 to the terminal acetylenic position followed by a cyclization by Nu2 (an intramolecular second Michael addition). This Michael addition cyclization step will build up the basic skeleton of the alkaloid system and at the same time control the absolute stereochemistry of the newly created chiral center through asymmetric induction of the chiral sulfoxide moiety. Finally, the sulfoxide can be transformed to another functional group (X) or used to promote the formation of another bond with Nu3 via trapping of the sulfenium ion intermediate under Pummerer rearrangement conditions (Scheme 4). 

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]. 

Pummerer rearrangement of the Michael adducts would produce reactive sul-fenium ion intermediates 49 susceptible to a second nucleophile attack intramolecular trapping by the enol oxygen would then give the cyclized products (50). This two-step transformation was achieved directly in good yield by treatment of 48 with trichloroacetic acid and acetic anhydride in refluxing toluene. MCPBA oxidation of sulfide 50 followed by spontaneous elimination afforded furan 51 in good overall yield (Table 6). 

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. 

By the Pummerer rearrangement, jS-oxosulfoxides may be converted under acidic conditions into a-oxoaldehydes (cf. Houben Weyl, Vol. Ell, pp 872-884), and thus be used for cyclizations with orf/io-diamino compounds. Pyridine-3,4-diamines reacting in this way with a-aroylsulfox-ides in the presence of acetic acid give the corresponding 2-arylpyrido[3,4-/)]pyrazines 17.122... 

During these explorations, the Pummerer rearrangement of sulfoxide 235 was found to undergo cyclization only to the indole nitrogen to yield thioaminal 236. Protection of the indole nitrogen also did not lead to any... 

Upon exposure to LiAl(O Bu)3H (2.5 equiv) in refluxing toluene, ketone 26.103 smoothly rearranged to a 10 1 mixture of 26.105 and 26.106 via the intermediate alkoxide 26.104. The tricyclic ether 26.105 was then converted to Schore s ketone 26.76, thereby completing a formal total synthesis of racemic furanether B (18.8). In addition, de Groot et al. explored an alternative conversion of 26.76 to 18.8 via the isomeric lactaranolides 26.97 and 26.110, which could be obtained in fair yield using the Pummerer-induced cyclization reaction of sulfoxide 26.108 as a key reaction (Scheme 36). 

The Pummerer rearrangement has been employed in tandem with other reactions to enable complex transformations to be carried out efficiently and in a one-pot manner. Studies of these have been reported mainly by Padwa who has utilized such transformations in the syntheses of natural products. A particularly intriguing cascade sequence involving the Pummerer rearrangement was employed in the synthesis of the alkaloid jamtine, 57. " Padwa et al. synthesized the bromo-enamide 55 in a 4 1 (Z/ ) mixture of isomers. Treatment of the isomeric mixture with camphorsulfonic acid caused the the sulfoxide to undergo a Pummerer/Mannich ion cyclization, which was then followed by a spontaneous Pictet-Spengler reaction to furnish the isoquinoline core. Although a 5 2 1 1 mixture of diastereoisomers was obtained, the desired diastereoisomer 56 was formed preferentially. This was attributed to a 4 r-Nazarov-type conrotatory electrocyclisation which controls the direction of closure from the a-acylthionium ion intermediate. 

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