Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 67

A more detailed discussion on NHC ligands in Pd-catalyzed cross-coupling
reactions can be found in Chapter 4.

2.3.6 Chiral Ligands Used in Asymmetric Transformations
Compared with the breadth of ligands available for non-asymmetric cross-
coupling reactions, the number of chiral ligands commonly used is signifi-
cantly lower. This is likely because asymmetric transformations are typically
limited to the generation of enantioenriched axially chiral biaryl structures,
a-arylcarbonyl compounds that contain a quaternary chiral center and
products of asymmetric Heck reactions. The pioneering work of Hayashi and
co-workers in asymmetric Kumada-Corriu coupling reactions, however,
demonstrated the feasibility of this concept. 201 Using a P,N ligand con-
taining carbon central chirality [(S)-Phephos], axially chiral biaryls were
synthesized in high yield (77-87%) with enantiomeric excesses (ees) ranging
from 84 to 93% from ditriflates (Figure 2.62).
Since this early report, several prominent ligand types have emerged that
promote highly enantioselective cross-coupling processes. BINAP (either
racemic or non-racemic), 99 which was introduced earlier as a broadly useful
ligand for non-asymmetric reactions, is also used as a supporting ligand in
several enantioselective processes in its optically active forms. Since the
earliest examples of asymmetric Heck reactions were reported independently
by the groups of Shibasaki 202 and Overman, 203 Pd/BINAP systems are still
the most broadly used in enantioselective Heck reactions. 204 Buchwald and
co-workers showed that a Pd/(S)-BINAP catalyst can give reasonable enan-
tioselectivity in the a-arylation of ketone enolates, 205,206 and a BINAP/Ni
catalyst can give high enantioinduction in a-arylation reactions of g-
butyrolactones (Figure 2.63). 207
Hartwig and co-workers showed that both Pd and Ni catalysts of BINAP
and the BINAP-related difluorphos 208 ligand can give excellent enantios-
electivities in the a-arylation of cyclic ketones with aryl/heteroaryl chlor-
ides 209 and aryl triflates (Figure 2.64). 210
Kwong, Chan and co-workers reported asymmetric arylations of ketone
enolates with mainly aryl bromides using an Ni/(R)-P-Phos catalyst sys-
tem, 211 a chiral bisphosphine ligand developed by Chan and co-workers
(Figure 2.65). 212
Asymmetric Suzuki-Miyaura reactions 213 have also been reported using
BINAP as a supporting ligand; however, the enantioselectivities were typi-
cally modest-moderate. 214 Yin and Buchwald reported one of the earliest
processes for asymmetric Suzuki-Miyaura coupling using a monophosphine
containing the axially chiral binaphthyl backbone (Figure 2.66). 215 This new
ligand, named KenPhos, was used in combination with Pd 2 (dba) 3 to give
biaryls in high yield (74-98%) with high enantiocontrol (up to 92% ee).
Pd/KenPhos-based catalysts (or similarly related ligands) have since been
used by Buchwald and co-workers to improve upon asymmetric arylation 216
and vinylation 217

of ketone enolates, expand the scope of asymmetric