DOMINO REACTIONS IN THE ENANTIOSELECTIVE SYNTHESIS OF BIOACTIVE NATURAL PRODUCTS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 268

9
DOMINO REACTIONS IN THE
ENANTIOSELECTIVE SYNTHESIS
OF BIOACTIVE NATURAL
PRODUCTS

CHAPTER

LUTZ F. TIETZE, SCOTT G. STEWART, and
ALEXANDER D ¨ FERT
Institut f¨r Organische und Biomolekulare Chemie, Universitat Gottingen, Gottingen,
Germany

9.1. INTRODUCTION

A wide range of bioactive molecules from natural sources or medicinal chemistry
and pharmaceutical programs are viable synthetic targets. The development of new
powerful synthetic methods has allowed the construction of rather complicated
molecules. Moreover, the introduction of the domino concept has greatly improved
the efficiency of syntheses, since it not only allows the short synthesis of complex
compounds from simple substrates but has also ecological and economical
advantages [1]. Thus, it helps to minimize waste and saves labor as well as our
resources. Domino reactions are defined as two or more bond forming transformations
under identical reaction conditions, in which the latter transformations take place at
the functionalities formed in the former bond forming reactions. Clearly, the more
bonds are formed in a domino process with an increase in complexity, the more
valuable it is. In this chapter, we will mainly deal with domino reactions in the
enantioselective synthesis of natural products with interesting biological properties
and bioactive compounds such as drugs, in which one or more stereogenic centers are
created during the domino process. Special focus will be placed on transformations
that start from achiral substrates to give enantioenriched products. As in the case of
our earlier publications dealing with a collection of domino reactions, in this chapter
also we have for clarity classified these transformations according to the mechanism
of the single steps in the domino process. For this purpose, we make the distinction as