AMMONIUM YLIDES AS BUILDING BLOCKS FOR ALKALOID SYNTHESIS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 428

13
AMMONIUM YLIDES AS
BUILDING BLOCKS FOR
ALKALOID SYNTHESIS

CHAPTER

SCOTT BUR and ALBERT PADWA
Department of Chemistry, Emory University, Atlanta, Georgia, USA

13.1. INTRODUCTION

A significant number of the organic compounds isolated from nature consist of
nitrogen heterocycles. These compounds represent a majority of important medicinal
agents also found in nature. The development of new synthetic methods for the
preparation of such heterocycles and the application of these methods to the synthesis
of alkaloids continue to be an active and exciting area of research in organic chemistry.
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
alkaloid skeletons. One of the attractive features of the cycloaddition chemistry is that
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
1,3-ylides (i.e., 1,3-dipoles) such as azomethine ylides and mesoionic isomunchnone
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-ylides are easily formed by a variety of methods, these reactive intermediates have