Vinylogous Pummerer reactions

The vinylogous Pummerer reaction of an amido-substituted sulfoxide has been used for the preparation of tetrahydroisoquinoline 83 <95JOC(60)7082>. 

The aryl ketones 8 arise from an initially formed thietane followed by photochemical fission of the C-S bond and then by hydrolysis of an imine during chromatographic work-up <95JCS(P1)2931>. A 2-alkylation of a furan was effected by a vinylogous Pummerer reaction of the amido-substituted sulfoxide 9 <95JOC7082>. 

The vinylogous Pummerer reaction of an amido-substituted sulfoxide produces the tetrahydroisoquinoline (Equation 62) <1995JOC7082>. Benzoyltetrahydroisoquinolinones have also been synthesized under Pummerer-type conditions on polymer support <2005H(65)1881>. Additional later examples highlighted the same reaction incorporating a fluorous-phase cyclative-capture method <2005AGE452>. 

The Pummerer rearrangement of sulfoxides with acid anhydrides has been extensively utilized as a method for the synthesis of a-substituted sulfides. When a,(3-unsaturated sulfoxides are used, the initial formed oxysulfonium ion may undergo two different pathways the additive Pummerer reaction or the vinylogous Pummerer reaction. The following sections will consider examples from both pathways. 

For the intramolecular vinylogous Pummerer reaction pathway, an electrophilic thionium ion intermediate (222) is formed by y-proton loss from 221 followed by sulfoxide S-O bond scission. This unsaturated thionium ion (222) is then intercepted by a nucleophile at the y-position to yield a vinyl sulfide product (223) (Fig. 11). 

Padwa and Kuethe have also used vinylogous Pummerer reactions of amido sulfoxides in the preparation of nitrogen-containing heterocycles. Vinyl amido sulfoxide (224) underwent an additive Pummerer reaction, on treatment with trifluoroacetic anhydride, to yield product 226 (Scheme 57).123 The a-thiocarbo-cation 225 generated from the Pummerer reaction of N-methyl-N-phenyl-2-[2-(toluene-4-sulfinyl)phenyl]acetamide (224) underwent a Friedel-Crafts reaction at the y-carbon with the tethered aromatic ring. Reductive removal of the... 

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. 

Scheme 20.17 nylogous Pummerer hydroxylatinn in the synthesis nf ent-hyperforin. Scheme 20.18 Optimization studies on selectivity for vinylogous Pummerer reaction. Scheme 20.19 Oridine alkaloids from a common intermediate.

Some of the most important applications of this reaction have been toward the synthesis of oridine-derived alkaloids. These routes have been extensively studied by Feldman s team and received special attention in previous reviews. In this chapter, we will focus on three more recent applications of the vinylogous Pummerer reaction and also on one recent report highlighting an unejq)ected and potentially useful result. 

Scheme 20,18 Optimization studies on selectivity for vinylogous Pummerer reaction.

Cycloadditions of thiocarbonyl compounds to dienes, or of vinyl thiocarbonyl derivatives to dienophiles, have received particular attention. Thus, A -dihydro-thiopyrans, e.g. (28), have been obtained by the addition of diphenyl thioketone to 1,3-dienes. Oxidation of (28), followed by a vinylogous Pummerer reaction, gave the 2i/-thiopyran (29). ... 

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