Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 41

Pd(dba) 2 (2 mol %)
dtbpf (1 mol %)
NaO t -Bu

O

O

R'

ArX

R' R

THF or Dioxane
25 - 100 °C

R

Ar

(X = Br, Cl) 70 −− 99 %

Figure 2.21 a-Arylation of ketones using Pd/dtbpf.

O Me

Me

O

(dtbpf)PdCl 2 (2 mol %)
NaO t -Bu (1.1 equiv)
Dioxane, 100 °C

Cl

Me

Me

Me

95 %

Figure 2.22 Arylation of ketone enolates using preformed (dtbpf)PdCl 2 .

binding (k 1 versus k 2 ), an array of ketone enolates and malonates were
monoarylated with bromo- and chloroarenes (Figure 2.21). 47 It was hy-
pothesized that the steric bulk of the ligand promotes the formation of the
active low-coordinate Pd(0) species and that the alkyl groups are more re-
sistant to migration relative to aryl groups, thus leading to the observed
higher turnover numbers.
Grasa and Colacot later demonstrated that the preformed
(dtbpf)PdCl 2 48,83 complex was successful in the a-arylation of ketone eno-
lates. 29,84 Using this precatalyst, a-arylation reactions of various ketones
were achieved with a broad range of aryl bromides and chlorides
(Figure 2.22).
Lu and co-workers developed a modification of the Larock indole syn-
thesis utilizing o-bromo- and o-chloroanilines and internal alkynes
(Figure 2.23). 85 Several ligands, including PCy 3 ,P(t-Bu) 3 , dppf, and bi-
aryldialkylphosphines (Buchwald ligands), were evaluated in this process
and dtbpf was optimal in terms of both yield and regioselectivity as 2,3-di-
substituted indoles were formed in 60-97% yield.
Hamman and Hartwig examined the effects of systematic variation of
bidentate ligands in aryl amination (Buchwald-Hartwig) reactions, with
particular attention to dppf analogs. 86 Interestingly, they observed that
electron-rich, bulky ligands with small bite angles ( 901) gave the best

selectivities over hydrodehalogenation of the aryl halides. Additionally, they
found a similar trend with respect to selectivity for monoarylation of primary
amines; bulky, electron-rich ligands promoted monoarylation. A subsequent
study identified dtbpf as a highly active ligand in amination reactions of aryl
halides and the first amination of an aryl tosylate. 87 Also described in this
paper was the use of Solvias's Josiphos-based chelating ligands in aryl
amination reactions, a family of ligands initially developed for asymmetric
reduction reactions (Figure 2.24). 88

B