THE NEGISHI CROSS-COUPLING IN THE SYNTHESIS OF NATURAL PRODUCTS AND BIOACTIVE MOLECULES - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 33

2
THE NEGISHI CROSS-COUPLING
IN THE SYNTHESIS OF NATURAL
PRODUCTS AND BIOACTIVE
MOLECULES

CHAPTER

EVELINA COLACINO, JEAN MARTINEZ, and
FR ´ D ´ RIC LAMATY
Institut des Biomol´cules Max Mousseron, Universit´ Montpellier 2, Montpellier, France

2.1. INTRODUCTION

The palladium-catalyzed cross-coupling reaction of an organometal with an organic
electrophile (Scheme 2.1) has become one of the most efficient ways to construct
carbon-carbon bonds. In 2010, Ei-ichi Negishi and Akira Suzuki together with
Richard F. Heck were awarded the Nobel Prize in Chemistry for discovering and
developing this synthetic methodology. Because of its simplicity, this reaction has
known a lot of developments [1]. Various metals can be involved, including Zn, Al, B,
Cu Zr, Sn, Mg, etc and so on, together with many organic electrophiles [2]. Recently,
the palladium-catalyzed cross-coupling reaction has become a major tool in the
synthesis of complex molecules because of its efficiency and functional group
tolerance. Furthermore, by bringing a LEGO game approach, retrosyntheses have
become much more straightforward.
Among the metals, zinc was shown to be particularly useful in palladium-
catalyzed transformations [3]. The so-calledNegishi coupling isusuallyvery selective,
fast, performed at lowor room temperature, and as such has become a tool of choice for
the synthesis of complex molecules. To illustrate the efficacy of the Negishi coupling,
this chapter will present some applications in the synthesis of various natural products
as well as in the large-scale synthesis of bioactive molecules.

Dedicated to Professor Ei-ichi Negishi, 2010 Nobel Prize in Chemistry Awardee.