Pummerer Cascade Reactions

Other ji-bonds were also found to efficiently participate in the Pummerer/Mannich cascade. For example, allylsilane 303 gave bicycle 304 in 61% yield when heated with /7- l sO11 (equation (7)). The terminal alkene present in 305 cyclized to give 306, 

As part of their investigations dealing with N,S-fused polycyclic ring systems, Daich and coworkers reported the use of a tandem Pummerer/W-acyliminium ion 

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A Pummerer-initiated cascade reaction has also been used as a method for generating isomiinchnones for further use in cycloaddition chemistry. For example, treatment of sulfoxide 23 with acetic anhydride first resulted in the formation of a reactive thionium ion that reacted with the distal amide carbonyl group to produce isomunchnone 24 (Scheme 6) (99JOC2038). Exposure of 24 to a dipolarophile, such as iV-phenylmaleimide, resulted in 1,3-dipolar cycloaddition to give 25 as a single diastereomer in 85% yield. 

Pummerer reaction conditions was followed by cycUzation to isomilnchnone 292 and hence to cycloadduct 293, which loses water to form a-pyridone 294. Subsequent manipulation involving deoxygenation and debenzylation completed the synthesis. In similar fashion, the azaanthraquinone alkaloid dielsiquinone was synthesized for the first time. Also, the quinolizidine alkaloids ( )-lupinine and ( )-anagyrine, and the ergot alkaloid ( )-costaclavine were synthesized using this Pummerer cyclization-cycloaddition cascade of imidosulfoxides and isomiinch-nones. 

Finally, there is also only a single report descrihing the sequential formation of the rings A, B, and C of the erythrinane framework in one step. Starting from the complex homoveratrylimide derivative 191 this triple cascade process involves - apart from the initial Pummerer reaction 191 —1192 - the Diels-Alder reaction 192 —> 193 as well as the final acyliminium ion cyclization 194 —1195 providing the erythrinane 195 in 83% yield. This in turn could be converted to ( )-erysotramidine (73) by a sequence already reported (76) (Scheme 34). The requisite educt 191 has been smoothly prepared through six steps in 45% overall yield (80). 

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. 

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. 

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