Chemistry Reference
In-Depth Information
6.2.2.1 Palladium-Catalyzed Cross-Coupling Reactions of Aryl
Halides With Primary and Secondary Alcohols
The general structures of the ligands that have been developed for pal-
ladium-catalyzed carbon-oxygen cross-coupling between aryl halides and
primary or secondary alcohols are shown in Scheme 6.4. Most of the these
systems were developed in Buchwald's laboratory
38-41
whereas the inter-
esting bispyrazole ligand 17 was developed by Beller and co-workers.
42
Currently, the most general ligand for aryl halide couplings with aliphatic
alcohols is the bulky, substituted biphenyl compound 18.
43
The obvious
structural similarity amongst these ligands is the binaphthyl or biphenyl
aromatic scaffolds. The aromatic moiety is thought to assist in the stabil-
ization of highly reactive, unsaturated palladium species.
44
Catalysts em-
ploying these ligands have been developed for cross-couplings between aryl
bromides and aryl chlorides and primary and secondary alcohols, producing
the corresponding alkyl aryl ethers (Scheme 6.5).
O
R
2
R
2
Pd
ligand
X
HO
R
+
R
1
R
R
1
(CH
3
)
4
P(tBu)
2
t
Bu
P(tBu)
2
N(CH
3
)
2
P(tBu)
2
P(tBu)
2
i
Pr
9
13
14
15
(both)
OCH
3
Ph
(CH
3
)
4
Ph
N
P(tBu)
2
P(tBu)
2
N
P(tBu)
2
tBu
i
Pr
i
Pr
i
Pr
i
Pr
N
N
Ph
P(1-Ad)
2
i
Pr
i
Pr
16
17
5
18
(both)
Scheme 6.4
catalyst
ArX
+
ROH
ArOR
Ar
X
R
Catalyst
Yield (%)
p
-CH
3
OC
6
H
4
Br
n
-C
4
H
9
[Pd(allyl)Cl]
2
/
18
80
p
-PhOC
6
H
4
Cl
CF
3
CH
2
[Pd(allyl)Cl]
2
/
18
83
o
-CH
3
OC
6
H
4
Br
n
-C
4
H
9
[Pd(allyl)Cl]
2
/
18
84
p
-
n
BuC
6
H
4
Br
sec
-C
4
H
9
Pd(OAc)
2
/
15
72
m
-CH
3
OC
6
H
4
Br
sec
-C
4
H
9
Pd(OAc)
2
/
15
63
m
-CF
3
C
6
H
4
Br
sec
-C
4
H
9
Pd(OAc)
2
/
15
80
Scheme 6.5
Search WWH ::
Custom Search