Heterocycles Pummerer rearrangements

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>. 

Methods for the construction of the thieno[2,3-c]pyridine skeleton based on the formally simultaneous formation of both the pyridine and thiophene rings were documented. Under the Pummerer rearrangement conditions, ( -s ul liny lain idc 222 underwent a cascade transformation into 223, which was oxidized to fused lactam 224 in low yield (1999JOC2038). Data on the use of cascade transformations, including the Pummerer rearrangement - cycloaddition sequence, in the synthesis of complex heterocyclic systems were summarized in a review (1997S1353). 

The previous reaction describes the synthesis of a novel class of heterocycles by the name of [l,2,3]thiadiazolo[4,5- /]-pyrimidines. Visibly, a redox process is involved, whereby the initial hydrazine derivative becomes an R-N=N-R system and, at the same time, the sulfur atom in thionyl chloride is converted to an azo-sulfide. The transfer of oxidaton level from sulfur—as sulfoxide—to the neighboring atom is a well documented process in sulfur chemistry that is called the Pummerer rearrangement. In essence, it involves the treatment of sulfoxides with an electrophile such as acetic anhydride to yield an a-acetoxy sulfide, according to the following sequence (see Scheme 26.1) ... 

Trifluoroacetic acid Heterocyclics from / -ketosulfoxides via Pummerer rearrangement... 

The second set of examples involves the use of thionium ions as electrophiles in inter- and intramolecular processes to obtain a-substituted sulfides (see 24 25, Scheme 20.7T which is the most common type of Pummerer reaction. Applications of this classical Pummerer rearrangement are exemplified in the synthesis of trans-solamin, the synthesis of indolizidine alkaloids, and the synthesis of the CDE ring of erinacine E. The first exanple fScheme 20.10 uses Pummerer chemistry in the generation of a thionium ion, which reacts in an intermolecular tin-mediated ene reaction the second one fScheme 20.11 uses Pummerer chemistry to introduce a nitrogen-containing heterocycle by intramolecular addition to form the coniceine core and the third example fScheme 20.12 is an intramolecular silicon-induced Pummerer reaction with oxygenated nucleophiles applied to the synthesis of a precursor of erinacine. Details of these Pummerer-based strategies are discussed below. 

Scheme 20.2S describes the work published by Kawasaki s group where they used a combination of dimethylsulfoxide and trifluoroacetic anhydride as source of trifluoroacetylated sulfonium ion 109 which reacted with 108 generating the new sulfonium salt 110 that underwent the loss of the sulfur-containing moiety promoted by nucleophilic attack. The nucleophile could be an alcohol, thiol, amine or organometallic species, or even another heterocyclic substrate. In cases where the nucleophile was a sulfoxide, the reaction led to an overall CH2 oxidation (Scheme 20.2S). Kawasaki s results suggest that this transformation, based on an interrupted Pummerer rearrangement, could be applied in the synthesis of biologically active tetrahydrocarbazoles and analogues fFigure 20.2T...

Glycoside and nucleoside derivatives of 3-aniino-3-deoxy-4.-thio-DL-threofuranose have been synthesized starting from the thiane diol (H). Thus the 4-thioglycoside (15) was prepared from the heterocycle (16), itself obtained from (H) in seven steps, via a Pummerer rearrangement of the intermediate sulphoxide as shown in Scheme 9 Intramolecular cyclization of D-threose dithianes... 

Pummerer-type rearrangements in synthesis of heterocycles 97YZ282, 98MI62. 

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