Tandem reactions Pummerer rearrangement

Cycloadditions of dienes with oxyallyl offer the opportunity to prepare seven-membeted ring systems. This reaction has also proved to be of importance in Ae furan series. A few examples may illustrate the value of this methodology. A tandem Pummerer rearrangement and intramolecular [4-i3]-cycloaddition with a fiiran derivative has been reported <99TL545>. For a similar reaction see <99T13999>. 

Substituted benzo[ ]thiophene derivatives have been prepared in excellent yields by a tandem Pummer rearrange-ment/Diels-Alder reaction of the intermediate furan with maleic anhydride or A -phenylmaleimide (Equation 87) <1996JOC6166>. 

Tandem, cascade, and other kinds of combined chemical transformations have been shown to be extremely useful in the synthesis of conplex structures. The Pummerer rearrangement can also be combined with different known reactions in order to produce structures more conplex than the usual Pummerer products. Here, we describe two recent applications of Pummerer chemistry in combination strategies. 

The Pummerer rearrangement has been employed in tandem with other reactions to enable complex transformations to be carried out efficiently and in a one-pot manner. Studies of these have been reported mainly by Padwa who has utilized such transformations in the syntheses of natural products. A particularly intriguing cascade sequence involving the Pummerer rearrangement was employed in the synthesis of the alkaloid jamtine, 57. " Padwa et al. synthesized the bromo-enamide 55 in a 4 1 (Z/ ) mixture of isomers. Treatment of the isomeric mixture with camphorsulfonic acid caused the the sulfoxide to undergo a Pummerer/Mannich ion cyclization, which was then followed by a spontaneous Pictet-Spengler reaction to furnish the isoquinoline core. Although a 5 2 1 1 mixture of diastereoisomers was obtained, the desired diastereoisomer 56 was formed preferentially. This was attributed to a 4 r-Nazarov-type conrotatory electrocyclisation which controls the direction of closure from the a-acylthionium ion intermediate. 

In a similar fashion, the Pummerer rearrangement has been used to generate mesoionic dipoles which can then undergo cycloaddition reactions to afford azapolycyclic ring systems. This is illustrated in the reaction of imidosulfoxide 58 which, when treated under Pummerer reaction conditions, underwent a tandem Pummerer-induced cyelization-isomunehnone dipolar... 

The Pummerer rearrangement can also be carried in tandem with a Diels-Alder reaction. This sequence has been utilized in the syntheses of the arylnaphthalene lignan natural products. Sulphoxide 64 in acetic anhydride was slowly added to a solution of dimethyl maleate in acetic anhydride under reflux, resulting in cycloadduct 65 in 85% yield. 

In their studies towards the synthesis of polycyclic natural products such as pseudolaric acid A, Bai et al. reported the tandem Pummerer rearrangement and intramolecular [4 + 3] cycloaddition of sulfoxide 104." The reaction constitutes the overall [4 + 3] cycloaddition of a fully... 

Finally, two syntheses of desethyl-ibophyllidine (674), by Bosch and collaborators, may be described. In the first of these (396,397), the tetracyclic tetrahydrocarbazole derivative 739 was constructed, as outlined in Scheme 112. The 6,7-bond was then formed by a tandem Pummerer re-arrangement-cyclization reaction, the phenylthio group was removed from the product 740 by hydrogenolysis, and the synthesis was completed by photochemical rearrangement of the methoxycarbonyl group. 

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