Chemistry Reference
In-Depth Information
3
-allyl)Cl]
2
(0.5 mol %)
35
(2 mol %)
KO
t
-Bu, PTS (2 wt %)
H
2
O, rt, 4 h
[Pd(
η
N
Br
H
2
N
Ph
Ph
O
O
+
P(
t
-Bu)
2
O
O
Cl
Cl
35
99%
Scheme 14.34
Br
29
(0.5 mol %)
Zn, TMEDA
Brij-30 (4 wt %), H
2
O
rt, 48 h
EtO
2
C
Br
+
EtO
2
C
CO
2
Et
67%
CO
2
Et
Scheme 14.35
O
(HO)
2
B
OH
O
Pd/C (2 mol %)
PPh
3
(2 mol %)
Pd(PPh
3
)
4
(2 mol %)
n
-BuNH
2
, NMP
60 °C, 2 h
TBAB, Na
2
CO
3
THF/H
2
O, 20 h
Br
75%
E-factor: 89.2
94%
O
I
OH
O
(HO)
2
B
Br
36
Pd(Davephos)Cl
2
(2.5 mol%)
CuI
TPGS-750 M (5 wt %)
H
2
O, Et
3
N, 30 °C, 5 h
Br
OH
95%
E-factor: 11.9
Pd(dtbpf)Cl
2
(2.5 mol %)
TPGS-750-M (5 wt %)
H
2
O, Et
3
N, rt, 5 h
60%
OH
Scheme 14.36
eciently. A few examples of Buchwald-Hartwig aminations of amines or
enolates in aqueous reaction media have been reported. Amine arylation
occurs eciently using a Pd/cBRIDP catalyst system in water-PTS
(Scheme 14.34).
109
Ketone a-arylation catalyzed by Pd/Pt-Bu
3
also proceeds
eciently in water-PTS.
110
More notably, Negishi couplings of aryl bromides
and alkyl iodides, which react with zinc in situ to give organozinc reagents, are
eciently coupled using PTS on water.
111
Although benzyl halides can be
coupled on water, less reactive alkyl iodides gave low yields in the absence of a
surfactant. For less reactive alkyl bromides, Brij-30 (dodecyl tetraglyme) gave
better results than PTS or TPGS-750-M (Scheme 14.35).
112
Brij-30 provides
larger micelles than other nonionic surfactants. Larger micelles are thought to
provide a larger payload of alkyl halide upon collision with heterogeneous zinc
particles, which increases the rate of organozinc formation.
Comparison of aqueous-micellar catalysis with traditional organic-
phase reactions show significant improvement in reaction eciency for
Suzuki, Heck and Sonogashira couplings.
6a
Researchers at Johnson and
Johnson reported the synthesis of intermediate 36 by a sequential pal-
ladium-catalyzed cross-coupling approach under traditional organic solvent
conditions (Scheme 14.36).
113
The reported process had an E-factor of 89.2
kg waste kg
1
product when including the aqueous workup. In contrast, an
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