Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 72

Senanayake and co-workers recently developed a biarylmonophosphine
ligand with only phosphorus and carbon central chirality and applied it to
asymmetric Suzuki-Miyaura reactions. 223 High yields and enantioselectivities
were observed in reactions of arylboronic acids and aryl bromides bearing o-
acyloxazolidinones. They also demonstrated the utility of this transformation
using a similar ligand in the syntheses of axially chiral biaryl natural products
korupensamine A and B and michellamine B (Figure 2.70). 224
Garc ´ a-Fortanet and Buchwald accomplished the asymmetric intra-
molecular Pd-catalyzed a-arylation of aldehydes 225 using a phox ligand, 226 a
ligand family which features only carbon central chirality (Figure 2.71).
The phox family of ligands can also promote highly enantioselective Heck
reactions, 204 as demonstrated by Pfaltz and co-workers (Figure 2.72). 227
Lee and Hartwig investigated the Pd-catalyzed intramolecular a-arylation
of amides to form oxindoles. 228 Having observed disappointing enantio-
selectivities with available chiral phosphines, they turned to chiral NHC
ligands to enhance the enantioselectivities up to 70% (Figure 2.73).
Several groups have since reported efforts in the asymmetric formation of
oxindoles. 229 The first highly enantioselective example was reported by
K¨ndig et al. using imidazolium iodide ligand precursors (Figure 2.74). 230
2.4 Outlook
Clearly, the development and understanding of new ligands and how they
affect individual steps in catalytic reactions have been crucial to the ad-
vancement of the field, leading to the 2010 Nobel Prize-winning work and
beyond. 1 The sheer number of transformations that can be accomplished
today by modern cross-coupling technology is indeed vast, but not limitless.
For instance, many challenging reductive elimination processes limit the
scope of coupling partners that can be used. In fact, only recently have Pd-
catalyzed trifluoromethylation 176,231 and fluorination 177 been achieved and
more challenging processes such as catalytic aryl trifluoromethoxylation
have not yet been realized. 232 Additionally, cross-coupling reactions have
traditionally been limited to aryl halide/pseudohalide (primarily sulfonate)
electrophiles. Efforts are intensifying to expand the scope of the electrophilic
partners that can be employed. Accordingly, exciting results have been re-
ported recently in which relatively inert C-X (X ¼ N, O) bonds have been
activated in cross-coupling reactions, primarily with Ni catalysts. 233 Also of
significant interest is the ability to functionalize C-H bonds selectively, a
mode of reactivity that obviates the need to use prefunctionalized coupling
partners such as aryl halides. Over the past several years, this dream is
rapidly becoming a reality and despite the fact that this area is still in its
infancy, a wide scope of literature exists on this topic. Beginning with the
groundbreaking work of Lkeiman and Dubeck in 1963 up to the ever-
advancing state-of-the-art driven by the work of the groups of Fagnou, White,
Du Bois, Gaunt, Hartwig, Miura, Sanford, Yu and others, the area is pro-
gressing by leaps and bounds and the reader is directed to Chapter 12,