Ammonium Ylides as Building Blocks for Alkaloid Synthesis

Abstract

Q1 A significant number of the organic compounds isolated from Nature consist of nitrogenheterocycles.These compounds represent amajority ofimportantmedicinal agents also found in nature. The development of new synthetic methods for the preparationofsuchheterocyclesandtheapplicationofthesemethods tothesynthesis ofalkaloidscontinuetobeanactiveandexcitingareaofresearchinorganicchemistry. In particular, cyclization and cycloaddition reactions of various ammonium ylides have been used in recent years for the construction of a wide assortment of different alkaloidskeletons.Oneoftheattractivefeaturesofthecycloadditionchemistryisthat there are numerous ylides to employ, and these provide, after reaction with a p-system, a diverse array of substituted heterocycles, often in high yield. Since Huisgen developed the mechanistic understanding and classification of 1,3-dipolar reactions, the number of molecular architectures accessed through these cycloadditions has expanded rapidly. Cycloaddition reactions of ammonium 1,3ylides (i.e., 1,3-dipoles) such as azomethine ylides and mesoionic isom€ betaines, by virtue of allowing the regio- and stereoselective construction of new rings, occupy a leading position among the tools available to the synthetic chemist. From simple pyrrolizidine, indolizidine, and quinolizidine alkaloids to the more complex frameworks found in Erythrina, Aspidosperma, and Amaryllidaceae alkaloids, dipolar cycloadditions have been deployed as a key strategic element in a wide variety of synthetic efforts. The rearrangement of ammonium 1,2-ylides has also proven to be particularly powerful in the synthesis of biologically relevant molecules. Because ammonium 1,2-ylidesareeasilyformedbyavarietyofmethods,thesereactiveintermediateshave been extensively employed for the synthesis of a variety of important alkaloid