.
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demonstrated reactivity for the oxidation of benzyl alcohol
without an N-oxide, albeit under stoichiometric conditions.
bases had different effects. While strong Brønsted bases, such
[16]
as DBU, DABCO, or NiPr Et, were ineffective, (Table 1,
2
Recent success in mimicking the catalytic reactivity of
entries 2–4), aromatic amines, such as pyridine, NMI, or
DMAP, had beneficial effects (entries 5–7). Of these, DMAP-
based systems showed the highest reactivity, providing 1-
tyrosinase with N,N’-di-tert-butyl-ethylenediamine (DBED)
[
17]
and [Cu(CH CN) ]PF ,
prompted us to consider the
3
4
6
[18,19]
aerobic oxidation of alcohols without an N-oxide co-catalyst,
with the potential to achieve complementary selectivity over
existing methods by employing a dramatically different
octanal in 92% yield after 3 h.
While optimized con-
ditions employ one atmosphere of O , the reaction can also be
2
conducted in air, albeit with longer reaction times (Table 1,
entry 8). DBED is a unique diamine ligand, as evidenced by
the lack of reactivity with 2,2’-bipyridine or 1,10-phenanthro-
line, which are commonly employed in Cu/TEMPO-catalyzed
aerobic oxidations (Table 1, entries 8–14). Furthermore, no
aldehyde was observed when DMAP was used in the absence
of DBED (Table 1, entry 16). These results demonstrate the
high reactivity of the Cu /O adducts that were formed with
mechanism for O activation and substrate oxidation. Here
2
we report the successful investigation of this approach, which
led to a practical Cu catalyst for the aerobic oxidation of
a diverse range of activated and unactivated alcohols. This
system also shows complementary selectivity to TEMPO-
based oxidations, with preferential oxidation of activated
secondary over primary alcohols.
2
2
[
10a,13a]
As a starting point, we examined the aerobic oxidation of
this ligand,
and underscores the unique ability of the
1
-octanol under previously optimized conditions for the
Cu/DBED catalyst system to affect the rapid oxidation of
unactivated alcohols without the use of any external radical
co-oxidant.
[
17a]
oxygenation of phenols,
observed in the presence of 4 mol% [Cu(CH CN) ]PF and
but no significant reaction was
3
4
6
5
mol% DBED (Table 1, entry 1). The addition of nitrogen
Our optimized conditions proved to be efficient for the
oxidation of linear non-activated alcohols bearing common
functional groups to the corresponding aldehydes or ketones
Table 1: Optimization of reaction conditions for the oxidation of
-octanol.
(
Scheme 2). The functional groups that were tolerated by the
reaction include alkenes (2d), alkyl halides (2k), nitro groups
2e), aryl and alkyl ethers (2c,g), protected alcohols (2 f), and
1
(
protected amines (2m). We observed a decreased reactivity
for sterically encumbered substrates with b-alkyl branches,
but some activity could be regained by increasing the reaction
Entry
Ligand
Additive
Yield
%]
[
[
a]
1
2
3
4
5
6
7
8
DBED
DBED
DBED
DBED
DBED
DBED
DBED
DBED
–
2
–
–
8
17
62
92
84
DBU
DABCO
NiPr Et
pyridine
NMI
DMAP
DMAP
2
[
b]
9
1
DMAP
4
0
1
2
DMAP
6
1
1
DMAP
DMAP
6
–
1
1
3
4
DMAP
DMAP
–
–
1
1
5
6
DMAP
DMAP
18
–
–
Scheme 2. Oxidation of primary and secondary unactivated alcohols.
For standard reaction conditions, see Table 1, entry 7, 6 h. [a] 20 h.
[b] [Cu(CH CN) ]PF (0.05 mmol), DBED (0.05 mmol), 0.20 mmol
Reaction conditions: alcohol (0.5 mmol), [Cu(CH CN) ]PF
6
3
4
(
0.025 mmol), ligand (0.025 mmol), additive (0.1 mmol), 4 ꢁ molecular
3
4
6
sieves (100 mg), CH Cl (4 mL), O (1 atm), 3 h. Yield determined by
DMAP. [c] 40 h. [d] Yield determined by NMR analysis with benzyl
benzoate as internal standard. [e] Catalyst reported in Ref. [5e]:
[Cu(CH CN) ]OTf (0.025 mmol), 2,2’bipyridine (0.025 mmol), NMI
2
2
2
1
H NMR spectroscopy with benzyl benzoate as internal standard. [a] No
molecular sieves added, [Cu(CH CN) ]PF (0.02 mmol). [b] Conducted
3
4
6
3
4
under air for 20 h.
(0.05 mmol), TEMPO (0.025 mmol), CH CN (4 mL), 20 h, O (1 atm).
3
2
2
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 5
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