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CuCl/bpy (20 mol %) adsorbed in
O
10 mol % TEMPO-(Gly)
3
-
OH
O
20 mol %
D
-Pro-Tyr(
t-
Bu)-Phe-
OH
(7.15)
air, DMF, rt, 24 h
Tris-HCl buffer
(pH 7.8)
0 °C, 24 h
NO
2
NO
2
70
71
, 73%, ee: 85%
The transformation of an alcohol C-O single bond to a nitrile C
N triple
bond was accomplished through a sequential multistep dehydrogenation
reaction. Huang and co-workers disclosed such a process using a catalytic
CuI-bpy-TEMPO system.
43
The alcohol was first oxidized by this catalytic
system to form the corresponding aldehyde, which reacted with aqueous
ammonia affording an imine intermediate. The aerobic oxidation of the
latter with the CuI-bpy-TEMPO system produced the desired nitrile. The
robustness of this methodology was demonstrated by using KU-0063794 72,
a specific inhibitor of the mammalian target of rapamycin,
44
as substrate to
produce the corresponding nitrile analog 73 (Equation 7.16).
O
O
N
N
N
N
CuI/bpy (5 mol %)
TEMPO (5 mol %)
N
N
O
N
N
O
(7.16)
aq NH
3
(2 equiv)
EtOH, O
2
(1 atm)
rt, 24 h
N
N
MeO
OH
MeO
CN
72
73
Simultaneously, Cook and co-workers also described similar copper
catalysts to perform the oxidation of aldehydes to produce nitriles using
aqueous ammonia and air as oxidant at room temperature. In only one ex-
ample, the authors demonstrated that the reaction proceeded eciently
starting from 1-octanol 74 at 50 1C (Equation 7.17).
45
The corresponding
octanenitrile 75 was isolated in quantitative yield.
Cu(MeCN)
4
PF
6
/bpy (10 mol %)
TEMPO (10 mol %)
OH
(7.17)
Me
Me
CN
6
6
aq NH
3
(2.5 equiv)
MeCN, 50 °C, air, 24 h
74
75
, 100%
Supported ruthenium hydroxide was also reported by Mizuno and co-
workers as a heterogeneous complex to catalyze a similar oxidative synthesis
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