Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 45

R

Pd 2 (dba) 3 /BINAP
NaO t -Bu
toluene, 80 °C

PPh 2
PPh 2

Br

N

R'

HN(R)R'

R R

65 - 98%

BINAP

Figure 2.27 Amination of aryl bromides using Pd/BINAP.

catalyst loadings (many examples at 0.05 mol% Pd), including the use of
triisopropylsilanethiol [TIPS-SH] as an H 2 S equivalent. This methodology
was then later extended to include aryl bromides and iodides. 98
In a 1996 report, Buchwald and co-workers described the use of both ra-
cemic and non-racemic BINAP [2,2 0 -bis(diphenylphosphino)-1,1 0 -binaph-
thyl] 99 in successful C-N cross-coupling reactions of aryl bromides with
primary and secondary amines (Figure 2.27). 100 Catalyst loadings as low as
0.05% Pd could be employed in some cases. It was also demonstrated that
this catalyst combination was more active and selective for monoarylation of
a primary amine than other chelating bisphosphine ligands such as dppe
and dppf.
A more detailed study of Pd/BINAP-catalyzed amination of aryl bromides
followed a few years later, 101 and it was proposed that the smaller bite angle
of BINAP (92.71) 102 in comparison with dppf (99.11) 74 coupled with the rigid
nature of the ligand backbone provides a tight chelate, which disfavors the
ligand from adopting a monodentate coordination mode and accessing the
b-hydride elimination pathway. The high selectivity for monoarylation of
primary amines was attributed to the steric demand of BINAP. Buchwald and
co-workers also reported the first amination of a heteroaryl chloride using
the Pd/BINAP system. Similarly, the same catalyst system has also been
successfully used for amination reactions of aryl triflates, 103 iodides 104 and
chloropyridines 91b by the same group, and benzophenone imine, 105 benzo-
phenone hydrazone 106 and a-chiral amines 107 have been used as nitrogen
nucleophiles. Importantly, for intermolecular N-arylation of optically active
a-chiral amines, the use of ( )-BINAP as a supporting ligand was essential in
providing perfect stereochemical fidelity; analogous reactions using other
ligands such as P(o-tol) 3 led to the erosion of optical purity. The loss of
enantiopurity with monodentate phosphines was determined to be due to an
off-cycle b-hydride elimination/reinsertion pathway, a pathway which was
shut down by the tight chelating ability of the BINAP (Figure 2.28). 107
BINAP has also been shown to be a very useful ligand for many other C-N
cross-coupling reactions 108 and also others including C-O cross-coupling 109
and a-arylation reactions of amides, 110 ketone enolates 111 and aldehydes. 112
However, a major limitation with the use of BINAP is the general inability to
utilize aryl chloride substrates owing to the more dicult oxidative addition.