Cyclizations Pummerer

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. 

Milder conditions (SnC, room temperature) suffice for a-chloro-a-thio-methylacetanilides, implying that it is the ionization of the halogen that is the difficult step in the chloroacetanilide cyclization[18,19]. Pummerer conditions can also be used for the cyclization of a-sulfinylacetanilides[19,20]. 

Nucleophilic Substitutions and Cyclizations via Sila-Pummerer Reactions... 

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). 

Acetalization or ketalization with silylated glycols or 1,3-propanediols and the formation of thioketals by use of silylated 1,2-ethylenedithiols and silylated 2-mer-captoethylamines have already been discussed in Sections 5.1.1 and 5.1.5. For cyclizations of ketones such as cyclohexanone or of benzaldehyde dimethyl acetal 121 with co-silyl oxyallyltrimethylsilanes 640 to form unsaturated spiro ethers 642 and substituted tetrahydrofurans such as 647, see also Section 5.1.4. (cf. also the reaction of 654 to give 655 in Section 5.2) Likewise, Sila-Pummerer cyclizations have been discussed in Chapter 8 (Schemes 8.17-8.20). 

The intramolecular Pummerer reaction has been applied to the synthesis of simple quinolizidine alkaloids like lupinine <2000JOC2368>, and also to arenoquinolizine alkaloids. Thus, the 2-(2-piperidyl)indole 284 was converted to indolo[2,3- ]quinolizidine 287 following a protocol that has as the key step the regioselective cyclization onto the indole 3-position of a thionium ion generated by Pummerer reaction from the appropriately substituted compound... 

The synthesis of the tetracyclic dibromophakellstatin 362 has been successfully accomplished in 45% yield through an NBS-mediated cyclization of 361 (Equation 97) <2002TL5135>. Another noteworthy approach utilizes a similar precursor, but the cyclization is carried out through an extended Pummerer reaction <20050L929>. 

An effective synthesis of 2-methylthio-5-amidofurans 71 involves a Pummerer induced cyclization of imidodithioacetals, which can be prepared by a mixed aldol reaction of the N-... 

Finally, saturated oxazolo[3,2-tf]pyridine derivatives can also be accessed via a Pummerer cyclization-deprotona-tion-cycloaddition cascade from imidosulfoxides <1999JOC2038> or by a [3+2] cycloaddition of nonstabilized... 

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. 

Pummerer reaction conditions was followed by cycUzation to isomilnchnone 292 and hence to cycloadduct 293, which loses water to form a-pyridone 294. Subsequent manipulation involving deoxygenation and debenzylation completed the synthesis. In similar fashion, the azaanthraquinone alkaloid dielsiquinone was synthesized for the first time. Also, the quinolizidine alkaloids ( )-lupinine and ( )-anagyrine, and the ergot alkaloid ( )-costaclavine were synthesized using this Pummerer cyclization-cycloaddition cascade of imidosulfoxides and isomiinch-nones. 

Improved methods for preparing isoquinolines through ring closure at the C4-aryl bond were reported (Scheme 9). The Pummerer reaction induces cyclization of the iV-formylbenzylamine sulfoxide 40 by treatment with TFAA or BFj OEt/TFAA <99H(51)119>. The unactivated titanium-mediated cyclization of the Schiff base 41 to 6-methoxyisoquinoline is effected through intermediacy of the Ai"-ethylcarbamate-aminophosphate derivative 42 <99SC1617>. 

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). 

Feldman KS, Skoumbourdis AP (2005) Extending Pummerer Reaction Chemistry. Synthesis of ( )-Dibromophakellstatin by Oxidative Cyclization of an Imidazole Derivative. Org Lett 7 929... 

DFIT-induced fluoro-Pummerer reactions of N-substituted-2-(phenylsul-fanyl)acetamides have also been reported (Scheme 37) [107]. With some amides, cyclization of the Pummerer intermediate was competitive with fluorination, and in other cases, fluorination was preempted by sulfoxide formation. 

A new synthesis of ethyl 7-methoxyindole-3-acetate was accomplished by reductive cyclization of the o-nitrobenzyl cyanide 22a. The indole was then elaboarated to the tetracycle 22d by an intramolecular Pummerer reaction. <95JHC947> ch2co2c2h5... 

The pioneer in phenolate radical coupling was Pummerer. In 1925 he showed1 that one electron oxidation of />-cresol using potassium ferricyanide afforded a nicely crystalline ketonic dimer of the radical in up to 25 % yield. Pummerer s ketone, as it became known, was considered to result from the coupling of two p-cresol radicals to give the dienone 1. This then underwent spontaneous cyclization to furnish 2. As proof of the structure... 

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