Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 32

Koie 1998

N

Pd 2 (dba) 3 / P( t -Bu) 3
or Pd(OAc) 2 / P( t -Bu) 3
NaO t -Bu

H
N

X

N

R

N
H

o -xylene, 105 - 120 °C

R

(or heteroaryl − X)

X = I, Br, Cl

22 - 94 %

Br

R

N

Pd(OAc) 2 / P( t -Bu) 3
NaO t -Bu

Me

R

N Me

o -xylene, 120 °C

80 - 92 %

Figure 2.9 Koie's amination reactions with Pd/P(t-Bu) 3 .

Fu 1998

Cl B(OH) 2

Pd 2 (dba) 3 / P( t -Bu) 3
Cs 2 CO 3

R

R'

R

R'

dioxane, 80 - 90 °C

86 - 91 %

Figure 2.10 Suzuki-Miyaura reactions of aryl chlorides using Pd/P(t-Bu) 3 .

ligands such as P(mesityl) 3 or P(n-Bu) 3 were employed, highlighting the
significance of the electron richness in concert with the steric bulk of the
tert-butyl groups to make the ligand exceptionally unique.
Concurrently, Littke and Fu reported that both Pd/PCy 3 and Pd/P(t-Bu) 3
combinations provided highly active catalysts for Suzuki-Miyaura cross-
coupling reactions, with the latter being marginally more active
(Figure 2.10). 40 This breakthrough represented one of the first general SMC
reactions with unactivated aryl chlorides. The authors found a Pd : ligand
ratio of near 1 : 1 to be optimal, hence they suggested the active catalytic
species to be a mono-ligated Pd species. Furthermore, they observed that no
coupling took place when less electron-rich triarylphosphines were em-
ployed as ligands. This led to the assumption that ''the steric bulk and the
electron-richness of P(t-Bu) 3 are critical for this unprecedented reactivity.'' 40
This study sparked significant interest in the use of P(t-Bu) 3 (and also other
highly electron-rich and sterically demanding phosphines) as a ligand in
coupling reactions. Even today, Pd in combination with P(t-Bu) 3 remains the
most widely used system in cross-coupling. 1k