Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 52

PCy 2

Br

Br B(OH) 2 1) Pd(PPh 3 ) 4 ,

1) Na 2 CO 3 , MeI

I

H 2 N Me 2 N

2) n -BuLi, then B(O i Pr) 3

2) n -BuLi, then ClPCy 2
29 % Overall

Me 2 N
DavePhos

Pd 2 (dba) 3 (2.5 mol %)
DavePhos (7.5 mol %)
NaO t Bu

O

Cl

HN

N

O

DME, rt
96 %

NC

NC

Pd(OAc) 2 (2 mol %)
DavePhos (3 mol %)
CsF

B(OH) 2

Cl

dioxane, rt
92 %

MeO

MeO

Figure 2.37 Synthesis (top) and applications (bottom) of DavePhos.

aryl amination reactions of unactivated aryl chlorides. 143 Noteworthy is that
this work preceded Littke and Fu's studies using trialkylphosphines. 40
DavePhos was originally prepared in four steps from commercially avail-
able 2-bromoaniline in 29% overall yield (Figure 2.37). This ligand was in-
spired by the authors' ''reasonable success'' in the amination of a
chloroarene using electron-rich 2,2 0 -bis(dicyclohexylphosphino)-1,1 0 -
binaphthyl coupled with their previous success using Hayashi-type ''biden-
tate'' monophosphine PPFA and PPF-OMe ligands, 144,145 prompting the
installation of the dicyclohexylphosphino group and dimethylamino group,
respectively, on the biaryl backbone (Figure 2.38). The resulting Pd/
DavePhos-based catalyst was highly active as it promoted room temperature
amination reactions of aryl bromides and also the unprecedented room
temperature amination of aryl chlorides, and it was the first general catalyst
system for room temperature Suzuki-Miyaura couplings of aryl chlorides. It
was believed at that time that coordination of the dimethylamino group to
palladium was important to the catalysis as other electron-rich monodentate
phosphines (Cy 3 P, PhPCy 2 ) gave significantly diminished reactivity.
In subsequent studies of Suzuki-Miyaura reactions, 146 aryl amination
reactions 146a,147 and C-O cross-coupling reactions 148 with phenols, it was
found in many instances that the desamino derivatives of DavePhos (John-
Phos, CyJohnPhos) were equally ecient as supporting ligands for many
transformations with loadings as low as 0.000001% Pd (Figure 2.39). They
were prepared in good yield in one step from commercial 2-bromobiphenyl
by a Grignard reaction (JohnPhos) or lithium-halogen exchange (CyJohn-
Phos) and subsequent reaction with the appropriate chlorodialkylphosphine