Pummerer heterocyclics

Application of Pummerer reaction in the synthesis of complex carbo- and heterocycles 97S1353. 

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

For further Pummerer reactions with silylated heterocyclic bases see Refs. 414a—414i in Handbook of Nucleoside Synthesis , H. Vorbruggen, C. Ruh-Pohlenz, Wiley-Inter-science. New York, 2001... 

Oxygen at the heterocyclic sulfur atom has been functionalized in two ways (1) by a TMSOTf-catalyzed Pummerer reaction in the presence of a silyl enol ether (Scheme 95) <1998TL9131> or (2) by reductive removal of the oxygen using Ac20/Zn/cat. 4-dimethylaminopyridine (DMAP) <1996SL885>. The formation of 1,3-dithiane from 1,3-dithiane 1-oxide proceeds efficiently in 95% yield (Equation 70). 

These unusual sulfur heterocycles (310 R = H,Ph) have been generated in situ by Pummerer dehydration of the sulfoxides 312 (R = H, Ph). Isolation of the betaines has not been achieved, but they are trapped in high yield by A -phenylmaleimide giving the exo adducts (313 R = H, Ph, R = This is in sharp contrast to the corresponding nitrogen... 

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). 

Ozonation of carbohydrate-based heterocycles containing selenium 111 (or sulfur) afford the corresponding selenoxides 113 (or sulfoxides) <2006JA227>. Low-temperature treatment of the initially formed ozonation products leads to Pummerer-like reactions affording interesting selenosugars 114 (Scheme 7). Thiosugars are formed from the... 

BTIB can be utilized in conjunction with trifluoroacetic acid(TFA) for interrupted Pummerer reactions leading to heterocyclic products. This is illustrated in Scheme 27 with BTIB-induced conversions of the benzylsulfanylalkenamides and -benzamides 89 and 91 to the isothiazolones 90 and 92 via N-S bond formation (01MI3, 01H1231). Similar treatment of the l-(2-alkylthiophenyl)pyrroles 93 affords the pyrrolo[2,l-Z>]benzothiazoles 94, in this case by C-S bond formation (Scheme 28) (99H1437). 

The finding that thionium ions may serve as electrophiles in electrophilic substitution chemistry has greatly extended the synthetic range of the Pummerer reaction. Padwa and Kuethe used intramolecular versions of this process in the preparation of nitrogen-containing heterocycles. Vinyl amido sulfoxide 217 underwent an additive Pummerer reaction, on treatment with triflic anhydride, to yield product 220 (Scheme 56).123 The critical step in this transformation involves a... 

The asymmetric version of an intramolecular Pummerer-type cyclization is quite useful for the synthesis of optically active heterocyclic compounds. Only a few examples of these types of reactions have been reported, and the ee yields were low. An example of an asymmetric intramolecular Pummerer cyclization was reported... 

Participation by aromatic rings is also possible and there are now several examples of electro M]ic aromatic substitution involving Pummerer intermediates. Equation (20), the alkylation of benzene with dimethyl sulfoxide in trifluoroacetic anhydride, illustrates the process in its inq>lest foim. As widi al-kenes, reaction with aromatics has been more widely exploit in intramolecular versions for the construction of carbocycles and heterocycles. In many cases the sulfoxide precursor is of the keto variety, thus ensuring regiospecificity in the point of cyclization. Equation (21) (formation of a six-monber carbocycle), equation (22) (formation of a six-membered sulfur heterocycle), equation (23) (formation of a six-membered nitrogen heterocycle) and equation (24) (formation of a seven-membered nitrogen, sulfur heterocycle) provide illustrations of the versatility of diis form of intramolecular aromatic alkylation. 

A fluorous phase Pummerer reaction was introduced by Procter. This report was based on the need to address problems associated with difficulties in optimization and monitoring of solid-phase processes. Good to excellent yields of heterocyclic scaffolds, mainly oxindoles, were reported after the development of a high-throughput fluorous phase synthesis strategy. 

Sarkar and coworkers reported a route from which heterocyclic analogs of 1-arylnaphthalene lignans were synthesized via a sequential Pummerer-Diels-Alder pathway, featuring furo[3,4-c]pyridines as intermediates. An example is depicted below <03JOC6919>. 

Pericyclic reactions in the synthesis of heterocycles 87YGK60. Pummerer reaction in the synthesis of heterocycles 89KGS1299. Retro-Diels-Alder strategy in the synthesis of heterocycles 87S207. Solid-phase synthesis of heterocycles 89BSF237. 

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) ... 

Padwa, A. Heterocyclic synthesis using the Pummerer reaction. Phosphorus, Sulfur Silicon Relat. Elem. 1999, 153-154, 23-40. 

Padwa, A., Waterson, A. G. Synthesis of nitrogen heterocycles using the intramolecular Pummerer reaction. Curr. Org. Chem. 2000,4, 175-203. 

Padwa, A., Kuethe, J. T. Additive and Vinylogous Pummerer Reactions of Amido Sulfoxides and Their Use in the Preparation of Nitrogen Containing Heterocycles. J. Org. Chem. 1998, 63, 4256-4268. 

Syntheses of A-heterocycles by the linked Pummerer-Mannich ion cyclization 02SL851. 

Alkanesulfonic acids can be prepared from the thiols or disulfides and air using cocatalytic DMSO and HBr.f The use of aqueous DMSO in the absence of air, but in the presence of a halogen or hydrogen halide catalyst, readily converts most aliphatic, aromatic, and heterocyclic thiols or disulfides to the corresponding sulfonic acid. In effect, DMSO oxidizes the hydrohalide to the molecular halogen, which then reacts with the organosulfur substrates. Water serves as a proton and oxygen source, and inhibits the Pummerer-type decomposition of the DMSO. 

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