Pummerer-type processes

However, a Pummerer-type process is involved in the introduction of two fluorine atoms into phenylsulphanated lactams [52] (Figure 3.5b, p. 52). 

An improved route has been described for the synthesis of 5 -5-aryl (or alkyl)-5 -thionucleosides,7 and it has been shown that the S-aryl compounds can be oxidized directly to 5 -fluoro-5 -thionucleoside derivatives using XeP2, in addition to the two-stage process involving oxidation to the sulfoxide and then treatment with DAST to induce a Pummerer-type process (see Vol. 22, p.212). Further oxidation of the a-fluorosulfides gives sulfones such as (9l).li3 Another reference to the use of such intermediates was discussed earlier, and there has been a further report on the preparation of 5 -(fluoromethylthio)adenosine and 5 -fluoro-5 -methylthioadenosine from the methylsulfinyl derivative and DAST (see Vol. 23, p.216)H - 5 -(Di- and trifluoromethylthio)adenosine have been prepared by alkylation with the appropriate chlorofluoromethane,H as have fluorinated 5-ethyl compounds of type (92),115.ll6 and the 5-(3-fluoropropyl)analogue.H9 The cyclic... 

Another anionic pericyclic domino process is a Pummerer-type rearrangement/... 

In the synthesis of a-amino acids [290] through addition of the carbanion of MMTS to nitriles the overall process involves three other steps frequently encountered in sulfur-mediated chemistry a Pummerer-type rearrangement, with a less common migration of a methylthio group, and a Raney nickel desulfurization following transesterification of the thioester function. 

Asymmetric Pummerer rearrangement is a very attractive reaction as previously described. In particular, the reactions induced by SKA work well, and may be synthetically exploited in many cases. The results described here demonstrate that the stereoselective a-deprotonation of the sulfoxide is a prerequisite process for asymmetric induction in the Pummerer reaction. Since many kinds of synthetic and enzymatic preparative methods of optically pure sulfoxides have been developed, the present Pummerer-type reaction will be applicable to many other chiral sulfoxides with one a-substituent, chiral vinylsulfoxides and chiral co-carbamoylsulfox-ides, thus leading to enantioselective syntheses of many new bioactive compounds in the near future. 

This novel anodic methoxylation may proceed via the intermediacy of fluorosulfonium ion G by way of a Pummerer-type mechanism as shown in Scheme 17. In this route, the sulfide cation radical F is trapped by fluoride ion, a process which suppresses potentially complicating side reactions (such as dimerization and nucleophilic attack on an aromatic ring) of this intermediate. Because fluoride ion is a much weaker nucleophile than methoxide, it is reasonable that methoxylation predominates in methanol. Thus, fluoride ions are not incorporated into the products yet they promote the anodic methoxylation, playing the role of a mediator. 

A final type of oxidative carbon-carbon bond forming dearomatization process involves electrophile-induced dearomatization. The most common variant of this reaction entails activation of an alkyne or alkene moiety with an electrophilic halide source to initiate intramolecular dearomatization accompanied by formal arene oxidation (Scheme 15.26) [72]. Proper positioning of an electron-donating methoxy group is crucial for success of this transformation. Other examples of halocyclization-dearomatization reactions involving appropriately substituted arenes tethered to alkynes and alkenes have been reported, along with an intramolecular Pummerer-type dearomatization initiated by an electrophilic thionium ion [73, 74]. 

The chapter is divided into six different sections The first four describe the five types of Pummerer reactions, then a few exanples of cascades or tandem processes with the participation of the Pummerer reaction are presented. Section 20.6 is used to highlight recent applications in selenium-Pummerer variants, and finally, a summary and outlook is provided. The exanples presented herein showcase the enormous variety of structures that can be obtained by Pummerer chemistry, while highlighting that, even though this reaction has been known for more than one hundred years, there is still much work to be done. 

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. 

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