Synthesis of Nitrogen Heterocycles Using the Intramolecular Pummerer Reaction

Albert      Padwa; Alex   G.   Waterson

doi:10.2174/1385272003376300

Abstract

The Pummerer rearrangement has been widely studied and has received considerable attention as a synthetically useful process. a-Acyl thionium ions generated from a-acyl sulfoxides under Pummerer conditions are powerful electrophiles, reacting efficiently with nucleophilic carbon species. Bimolecular addition of the cation to various carbon-carbon double bonds is well known. In the realm of natural product synthesis, most success has been achieved using intramolecular Friedel-Crafts cyclization of the Pummerer thionium ion intermediate. Interception of the Pummerer intermediate by heteronucleophiles represents an extremely important variation which has been used for the synthesis of numerous nitrogen containing heterocycles. The present article also describes various applications of the domino Pummerer (slash) N-acyliminium ion cyclization cascade. The successful synthesis of a number of alkaloids by this sequence of reactions reveals the usefulness and importance of this unique domino cascade.XXXYYYZ ZZ

Keywords: Intramolecular Pummerer Reaction, Cyclization, Heteroaromatic Nucleophiles, Pyrrole cyclization, Target syntheses, Pummerer Intermediates, Additive, Vinylogous pummerer chemistry, Tandem cyclization of pumerer intermediates, Intramolecular heteroatom trapping, Diels Alder cyclizations, Dipolar cycloaditions