Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 57

important Pd-arene interactions involving the non-phosphine-containing
aryl ring of the ligand. 161b,162 Substitution in the ortho-position on the
non-phosphine-containing aryl ring also prevents cyclometallation via C-H
activation of the lower ring, a process shown to occur with non-ortho-
substituted (lower aryl ring) biarylphosphines. 163
The ligand library that has resulted is vast, and catalysts based on many of
these ligands promote several challenging transformations. Several of the
most prominent and widely used are shown in Figure 2.45.
XPhos, introduced in 2003, featured significant advances over the existing
technology. 164 The scope of aryl amination was broadened, the first
amidation of aryl sulfonates was achieved and amination reactions were
conducted in water with no cosolvent for the first time (Figure 2.46).
XPhos would prove not only to be useful in C-N bond-forming processes, 165
but also would become one of the most versatile ligands in the biarylphos-
phine family. Examples include challenging Suzuki-Miyaura, 158a,c-f,166
Negishi, 158b Kumada-Corriu, 167 Stille, 168 a-arylation 169 and Miyaura boryla-
tion 170 reactions. In the following year, SPhos was introduced as a new ligand
which allowed for unprecedented reactivity in Suzuki-Miyaura reactions to
generate highly hindered biaryls with low Pd loadings, as low as 0.0005 mol%,
even at room temperature (Figure 2.47). 171
An X-ray structure of an (SPhos)Pd(dba) complex was obtained, 171b and an
Z 1 interaction 172 between the Pd and ipso-carbon of the non-phosphine-
containing ring was observed. It was again postulated that this interaction
may be important to the catalyst stability. With the aid of detailed computa-
tional studies, Pd-arene interactions were identified in catalytic intermedi-
ates, thereby further underlining their importance to catalyst stability/
longevity (Figure 2.48). 161b,162
SPhos-based catalysts have been widely used for various C-C 173 and
C-N 174 bond-forming reactions. Additional key breakthrough ligands have
been reported over the past several years. For example, RuPhos, originally
developed for challenging Negishi couplings, 175 has been shown to be an
extremely useful ligand for aryl aminations with secondary amines, 157a and
BrettPhos 157e is highly selective for monoarylation of primary amines, 157a,e
including methylamine. 157e Taken together, catalysts based on either
RuPhos or BrettPhos cover an extremely broad scope of aryl amination
reactions. 157a Furthermore, these ligands can operate in concert with one
another. 157b Starting with either a RuPhos precatalyst 165a and additional
BrettPhos or vice versa, a catalyst system equivalent to (or better than) both
ligands was observed (for a more detailed discussion of palladacycle
precatalysts, see Chapter 3). This was demonstrated by the ''multiligand''
reactions of 3-bromoanisole with morpholine or octylamine as shown in
Figure 2.49.
Thus, primary and secondary amines can both be coupled eciently from
a single catalyst system based on both ligands. Mechanistic evidence was
provided that showed ligand exchange to be facile under the reaction con-
ditions (480 1C). Ligand exchange was shown to occur at both the Pd(0)