METATHESIS-BASED SYNTHESIS OF COMPLEX BIOACTIVES - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 153

5
METATHESIS-BASED SYNTHESIS
OF COMPLEX BIOACTIVES

CHAPTER

JEAN-ALEXANDRE RICHARD, SIN YEE NG, and
DAVID Y.-K. CHEN
Department of Chemistry, Seoul National University, Seoul, South Korea

5.1. INTRODUCTION

Total synthesis of complex molecular architectures has witnessed a new paradigm
with the recent advent of powerful synthetic technologies and innovative synthetic
strategies. Among these the abilities to construct carbon-carbon bonds in an efficient
and selective manner continue to be the center of any successful synthetic campaign.
Over the last decade, the landmark discovery of metathesis reactions has substantially
broadened the repertoire of synthetic arsenals and revolutionized the way organic
chemists conceive their synthetic strategies [1,2]. Derived from the ancient Greek
words meta (change) and thesis (position), this serendipitous discovery from the
industrial sector has evolved into a powerful synthetic transformation that unifies
two unsaturated carbon termini with astonishing substrate scope and efficiency.
Mechanistic understanding of the metathesis reaction culminated nearly two decades
of intensive research and debates, where the initial proposal put forward by Chauvin
and coworkers was ultimately validated by Casey and Burkhardt, Katz andMcGinnis,
and Grubbs et al. through a series of detailed kinetics and isotopic labeling studies [3].
More important, this mechanistic proposal involving a propagating metal carbene
species in the catalytic cycle enabled the rational design and preparation of more
effective initiators for the metathesis process. As a result, the transition from a
multicomponent catalyst system to single metal carbene initiators marked the
beginning of a new era in catalyst design, and the search for more active metal
carbene catalysts with greater functional group tolerance became the center of
attention. The first significant advance in this context came from the Schrock group
with the introduction of molybdenum catalyst , which demonstrated greatly

improved metathesis activity and functional group compatibility compared to pre-
viously described catalysts [4]. However, the sensitivity of catalyst

1

1 toward oxygen