Chemistry Reference
In-Depth Information
4
ASYMMETRIC SYNTHESIS THROUGH
C- H ACTIVATION
HUW M. L. DAVIES AND J Ø RN HANSEN
Department of Chemistry, Emory University, Atlanta, GA
4.1. INTRODUCTION
Transition metal-catalyzed activation of carbon-hydrogen bonds in organic molecules
for the purpose of functionalization (formation of C- C, C - O, C -N, or C-B bonds) has
been subject to extensive investigation by the chemical community for the past 25 years
[1-22]. Due to the ubiquity of C-H bonds in organic molecules, such transformations
constitute an attractive approach for the direct synthesis of complex molecules, such as
pharmaceuticals, natural products, and other industrially relevant targets, from simple
starting materials [19]. However, since high-energy species are required to activate the
relatively strong C-H bond, the issue of selective activation becomes of concern [18].
Much effort has been made to achieve practical, catalytic, and selective methods for
C-H functionalization [13,14,18-20]. However, these remain major challenges. Two
major directions have evolved (Fig. 4.1): (i) direct C-H activation, involving oxidative
addition of the C-H bond onto an active metal center, which in turn can result in func-
tionalization of the bond; and (ii) insertion of transition metal-coordinated carbenes or
nitrenes into the C-H bond to afford functionalized products directly [23,24].
Direct activation of the C-H bond via oxidative addition to a suitable metal complex
has been investigated at length by the organometallic community [4,5,13,15,17-21].
Many approaches have been described, but a major challenge has been to regenerate a
catalytically active species and thereby achieve a catalytic process. While this has been
developed in recent years, selectivity still remains a problem. Kakiuchi and Murai
described the use of a coordinating moiety to direct the metal to the desired site of
insertion [25]. Such directing groups can be a suitable heteroatomic moiety in the
substrate. Oxidative addition usually forms a fi ve -
or
six - membered
metallacycle
