Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 62

P(t-Bu) 2

P(t-Bu) 2 Pd(OAc) 2 (5 mol %)

NaO t -Bu

Fe

Ph Ph

Fe

PhCl

25 - 110 °C

Ph Ph

85 %

Ph

Q-Phos

Figure 2.52 Q-Phos synthesis via perphenylation of FcP(t-Bu) 2 .

Br O t -Bu

Pd(dba) 2 /Q-Phos (5 mol %)
NaO t -Bu

Ph t -BuOH Ph

Toluene, rt
98 %

O O

Br O t -Bu

Pd(dba) 2 /Q-Phos (5 mol %)
NaO t -Bu

t -BuOH

MeO MeO

Toluene, 80 °C
67 %

Figure 2.53 Synthesis of aryl ethers using Pd/Q-Phos.

some unusual observations: (1) whereas the catalytic reactions of aryl halides
with PhONa proceeded in high yield with Pd(dba) 2 and PFc(t-Bu) 2, stoi-
chiometric reductive elimination reactions gave much lower yield and (2) in
the catalytic reactions a significant induction period was observed and aryl
halide was initially consumed without the generation of aryl ether prod-
uct. 181 Mechanistic studies were carried out to find an explanation for these
phenomena and it was ultimately established that the FcP(t-Bu) 2 ligand was
being catalytically perphenylated 182 on the unsubstituted cyclopentadienyl
ring, thus forming a significantly more active catalyst system (Figure 2.52).
The combination of Pd(dba) 2 and the modified ligand, named Q-Phos, 48,183
was demonstrated to be an ecient catalyst for the mild (r.t.-80 1C)
formation of aryl ethers from aryl chlorides and bromides, as shown in
Figure 2.53.
Q-Phos has also been shown by Hartwig and co-workers to be an ecient
ligand in various Pd-catalyzed C-C, C-N and C-O cross-coupling re-
actions, 183 including the arylation of malonates and cyanoacetate 184 and the
a-arylation of azalactones, 61 zinc amide enolates 185 and aldehydes. 186
Colacot and co-workers showed that (p-crotyl)Pd(Q-Phos)Cl is an effective
and convenient precatalyst for a variety of C-C and C-N cross-coupling re-
actions. 72 Lautens and co-workers described an interesting carbohalogena-
tion reaction using Pd(Q-Phos) 2 48 as a precatalyst (Figure 2.54). 187 The key
step in these transformations is an unusual C-I reductive elimination.
A more detailed account of this transformation can be found in Chapter 7.