Selective aerobic oxidation of alcohols to aldehydes, carboxylic acids, and imines catalyzed by a Ag-NHC complex

Article abstract of DOI:10.1021/ol501353q

Silver NHC catalysts have been developed for the selective oxidation of alcohols to aldehydes or carboxylic acids in the presence of BnMe₃NOH or KOH under dry air. The aerobic oxidation conditions are mild, and the yield is excellent. Further tandem catalysis enables the one-pot synthesis of imines in excellent yield. Only 0.1 mol % of the catalyst is required.

Full text of DOI:10.1021/ol501353q

Letter
pubs.acs.org/OrgLett
Selective Aerobic Oxidation of Alcohols to Aldehydes, Carboxylic
Acids, and Imines Catalyzed by a Ag-NHC Complex
Lei Han,† Ping Xing,† and Biao Jiang*,†,‡
†CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Road, Shanghai, 200032, China
‡Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Shanghai 201210, China
S
* Supporting Information
ABSTRACT: Silver NHC catalysts have been developed for the
selective oxidation of alcohols to aldehydes or carboxylic acids in
the presence of BnMe3NOH or KOH under dry air. The aerobic
oxidation conditions are mild, and the yield is excellent. Further
tandem catalysis enables the one-pot synthesis of imines in
excellent yield. Only 0.1 mol % of the catalyst is required.
Scheme 1. Silver NHC Complexes
etal N-heterocyclic carbene (NHC) complexes have
Mbeen widely studied for their intriguing structural
properties and numerous applications.1 Ag-NHC complexes
are the most studied metal-NHC complexes due to their facile
preparation using Ag2O.2 Although many Ag-NHC complexes
have been reported because of their ease of synthesis, their
catalytic properties have scarcely been investigated. Applica-
tions have primarily included NHC ligand transmetalation from
silver to other late-transition metals.3 Peris and Fernandez first
reported the use of a Ag-NHC catalyst in alkene diboration
reactions.4 A combination of NHC and AgOTf has been
successfully utilized for the hydrosilylation of aldehydes.5 Ag-
NHC complexes have also been tested in the ring-opening
polymerization of L-lactides.6 Ag-NHC catalysis has been
recently applied to carbometalation,7 the silylcyanation of
imines,8 and cross-coupling.9 However, their potential in
aerobic oxidation has not been fully elucidated. A number of
anaerobic10 and aerobic11catalytic methods have been explored
for alcohol oxidation. Noble metal catalysts (Ru,10a−f Rh,10g
Ir,10h,i and Pd11a−c) were developed in the presence of external
or internal oxidants. A Co(PNP) complex,10j a cheap metal
catalyst, was reported for acceptorless dehydrogenation,
whereas the CuI/TEMPO system11d−g was also considered as
a promising methodology. Silver oxide is a classic, mild
oxidizing agent for the oxidation of aldehydes to carboxylic
acids. We envision that Ag-NHC complexes could serve as a
catalyst for aerobic oxidation. In this report, we describe the
mild selective oxidation of benzylic and allylic alcohols to
aldehydes, carboxylic acids, or imines in high yields catalyzed by
Ag-NHC complexes.
of KOH and 0.1% mol of Ag-1 to give an almost 1:1 ratio of the
corresponding aldehyde and acid, whereas the reaction gave a
65% yield of the aldehyde as the only product with t-BuOK
(entries 1−2). Using BnMe3NOH (BTMAH) as a base in the
aerobic oxidation afforded a moderate yield of aldehyde (entry
3). Thus, various Ag-NHC complexes were tested for aerobic
oxidation using BTMAH as a base (Scheme 1, Table 1).
The silver NHC catalysts bearing unsaturated NHC ligands
(Ag-1/3, entries 3 and 5) performed better than their
analogues bearing a saturated NHC ligand (Ag-2/4, entries 4
and 6), whereas sterically constrained complexes (Ag-3/4,
entries 5 and 6) gave lower yields than their more flexible
counterparts (Ag-1/2, entries 3 and 4). Ag-5, a silver NHC
complex containing a sulfur atom, which might poison the
reactive metal center, gave a low yield of aldehyde (entry 7).
The catalytic activity of Ag(I)-NHC complexes bearing pyridyl
groups was also examined, and product specificity was
maintained. Ag-7, bearing a symmetrically N,N′-pyridyl NHC
ligand, showed excellent catalytic activity and gave an excellent
yield of aldehyde (98% yield, entry 9) whereas Ag-6, bearing an
Ag(I)-NHC (Ag-1) was initially tested with different bases
and at different reaction temperatures (Scheme 1). It was found
that a base is necessary for Ag(I)-NHC catalyzed aerobic
oxidation (Table 1). The reaction was carried out with 2 equiv
Received: February 24, 2014
© XXXX American Chemical Society
A
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Organic Letters
Letter
Table 1. Optimization of the Ag(I)-NHC Catalyzed Aerobic
Oxidation
Table 2. Ag(I)-NHC Catalyzed Aerobic Oxidative
Preparation of Aldehydes and Carboxylic Acids
a
d
entry
Ag cat. (mol %) base (equiv) T (°C) t (h) 2a/3a yield (%)
be
,
1
Ag-1 (0.1), KOH (2.0)
Ag-1 (0.1), t-BuOK (2.0)
Ag-1 (0.1), BTMAH (1.1)
Ag-2 (0.1), BTMAH (1.1)
Ag-3 (0.1), BTMAH (1.1)
Ag-4 (0.1), BTMAH (1.1)
Ag-5 (0.1), BTMAH (1.1)
Ag-6 (0.1), BTMAH (1.1)
Ag-7 (0.1), BTMAH (1.1)
Ag-7 (0.1), KOH (2.0)
Ag-7 (0.1), KOH (6.0)
rt, 12
rt, 12
rt, 12
rt, 12
rt, 12
rt, 48
rt, 12
rt, 12
rt, 12
rt 12
48/49
65/−
70/−
57/−
62/−
53/−
18/5
be
,
2
bce
, ,
3
ce
,
4
a
a
ce
,
entry
1
2 yield (%)
3 yield (%)
5
ce
,
1
p-O2NC6H4CH2OH (1b)
p-FC6H4CH2OH (1c)
96 (2b)
94 (2c)
99 (2d)
98 (2e)
99 (2f)
97 (2g)
95 (2h)
89 (2i)
94 (2j)
90 (2k)
86 (2l)
92 (2m)
96 (2n)
80 (2o)
− (3b)
− (3c)
98 (3d)
98 (3e)
99 (3f)
96 (3g)
93 (3h)
88 (3i)
95 (3j)
− (3k)
80 (3l)
92 (3m)
95 (3n)
−
6
ce
,
2
7
ce
,
3
p-ClC6H4CH2OH (1d)
p-BrC6H4CH2OH (1e)
p-MeOC6H4CH2OH (1f)
m-MeOC6H4CH2OH (1g)
o-MeOC6H4CH2OH (1h)
o-HOC6H4CH2OH (1i)
o-H2NC6H4CH2OH (1j)
2-furanmethanol (1k)
8
54/−
98/−
65/34
−/99
ce
,
4
9
cf
,
5
10
11
cf
,
6
60, 24
a
7
The mixture of 1a, Ag-NHC catalyst, base, and 4 Å MS was stirred
b
under dry air or pure oxygen and monitored by 1H NMR. The
oxidation reaction was carried out under pure oxygen. The oxidation
reaction was carried out under dry air. Isolated yield. In toluene (0.1
M). In DME (2.0 M).
8
c
9
d
e
10
11
12
13
14
f
2-pyridinemethanol (1l)
2-thiophenemethanol (1m)
cinnamyl alcohol (1n)
geraniol (1o)
unsymmetrically N, N′-pyridyl NHC ligand, showed lower
performance (54% yield, entry 8). Although performing the
oxidation with 2 equiv of KOH could still result in a high
conversion but poor specificity with Ag-7 (entry 10), we
attempted direct oxidation of the alcohol to the carboxylic acid
by increasing the amount of base. When the reaction was
performed with 6 equiv of KOH in dimethoxyethane with heat,
Ag-7 could efficiently catalyze the oxidation of the alcohol into
the carboxylic acid in nearly quantitative yield (entry 11). We
also performed control experiments to demonstrate that the
Ag(I)-NHC catalysts were necessary.11h
a
1
Reactions were monitored by H NMR.
Imines, also known as Schiff bases, are an important class of
nitrogen compounds in chemistry. Due to the high reactivity of
their CN double bonds, they are important nitrogen sources
and key intermediates in biological, pharmaceutical, industrial,
and natural product synthetic applications. Therefore, devel-
oping methods for the preparation of imines is an important
challenge.12 Tandem catalysis that enables a one-pot multistep
reaction shows great potential for increasing the efficiency of
chemical synthesis. Because mild conditions were used for the
selective oxidation of alcohols, a cascade reaction was
attempted for the one-pot oxidative tandem synthesis of imines
from alcohols and amines (Table 3). We found that benzyl
alcohol 1a could react efficiently with aliphatic, aromatic, and
steric amines (4a−d) to afford the corresponding imines in
high yields (entries 1−4). Amines 4a/d likewise reacted with
benzyl alcohols 1b−j with electron-donating and -withdrawing
substituents (entries 5−13), heterobenzyl alcohols 1k−m
(entries 14−16), and allyl alcohols 1n−o (entries 17−18).
No obvious electronic effect contributing to the yield of imine 5
(entries 19−23) was found when para-substituted amines 4e−i
bearing electron-deficient or -rich groups were used as a
substrate. Comparative experiments on para-, meta-, and ortho-
methoxyaniline (4i/j/k) identified that steric hindrance more
or less influences the yields of the imines (entries 23−25).
In addition, the mechanism of the mild oxidation process was
explored.13 When ethyl sulfide or TEMPO was added, the yield
of aldehyde 2a was dramatically decreased and the catalytic rate
was slower, respectively. TEMPO could trap radical inter-
mediates and interrupt the catalytic cycle (Scheme 2, entry 1).
The sulfide may coordinate with silver and poison the active
metal center (entry 2). Electron paramagnetic resonance (EPR)
experiments clearly showed that radicals were present in the
reaction solution, indicating a direct molecular oxygen
activation process. AgOTf was used as a substitute for Ag-7
but failed to catalyze the reaction (entry 3), indicating the
importance of the NHC ligands. Basic luminol and K3[Fe-
With the optimized conditions in hand, Ag-7 was chosen as
the universal catalyst and utilized with various alcohol
substrates to test the breadth of substrates tolerated in the
oxidation (Table 2). In the selective oxidations, para-
substituted benzyl alcohols 1 listed reacted efficiently and
universally to afford the corresponding aldehydes 2 in almost
quantitative yields, regardless of whether the substituents were
electron-rich or -deficient (entries 1−5). The reaction of para-,
meta-, or ortho-methoxybenzyl alcohols 1f−1h under standard
conditions showed no obvious effect of steric hindrance on the
aldehyde yields (entries 5−7). Active hydrogen substrates such
as 1i and 1j were also tested and afforded high yields (entries
8−9), whereas the high yield of salicyl aldehyde 2i indicated
that our oxidative method was chemoselective for alcohols over
phenols. Similar to benzyl alcohols, heterobenzylic counterparts
1k−1m reacted efficiently to afford moderate to high yields of
the heterobenzylic aldehydes 2k−2m (entries 10−12). For
some allylic alcohols, a high yield of cinnamyl aldehyde 2n and
cinnamyl acid 3n were obtained from cinnamyl alcohol 1n
(entry 13). A cis−trans isomeric citral mixture 2o (E/Z = 1:1)
could be afforded in moderate yield from geraniol 1o (entry
14). In addition, the optimized conditions for cascade catalysis
produced carboxylic acids 3 in high yields from most alcohol
substrates. Fluoro- and nitro-substrates (1b/c) were intolerant
of the concentrated base, and the furyl structure 1k was
sensitive to heat. We also tried to afford carboxylic acid 3o
under the standard conditions, but the crude reaction solution
became complex.
B
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Organic Letters
Letter
Table 3. Ag(I)-NHC Catalyzed Aerobic Oxidative
Preparation of Imines from Alcohols and Amines
Scheme 2. Experiments for Proposed Mechanism
a
entry
1
4
5 yield (%)
1
1a
1a
1a
1a
1b
1c
1d
1e
1f
PhNH2 (4a)
n-C3H7NH2 (4b)
cyclo-C6H11NH2 (4c)
BnNH2 (4d)
4a/4d
92
2
99
3
97
4
98
5
95/95
94/94
98/97
98/98
99/97
96/94
94/92
88/87
96
6
4a/4d
7
4a/4d
8
4a/4d
9
4a/4d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
1g
1h
1i
4a/4d
4a/4d
4a/4d
1j
4d
1k
1l
4a/4d
83/85
80/82
91/90
94/96
84/75
83
4a/4d
1m
1n
1o
1a
1a
1a
1a
1a
1a
1a
4a/4d
4a/4d
4a/4d
p-O2NC6H4NH2 (4e)
p-FC6H4NH2 (4f)
p-ClC6H4NH2 (4g)
p-BrC6H4NH2 (4h)
p-MeOC6H4NH2 (4i)
m-MeOC6H4NH2 (4j)
85
90
91
93
86
amine. This method has great potential for the preparation of
imines because it tolerates a wide range of substrates and is high
yielding.
o-MeOC6H4NH2 (4k)
82
a
1
Reactions were monitored by H NMR.
ASSOCIATED CONTENT
* Supporting Information
Full experimental details, spectroscopic data, and computational
data. This material is available free of charge via the Internet at
http://pubs.acs.org.
(CN)6] solutions were added to the reaction mixture, and
purple chemiluminescence was immediately observed, which
suggests that peroxide species were present.
■
S
A plausible mechanism of molecular oxygen activation for the
selective oxidation was proposed based on previous experi-
ments and in situ ESI-MS. Alkoxide-coordinated silver NHC
complex 6 activates molecular oxygen to afford a triplet AgII
complex 7 bearing a peroxy radical (ΔG = 5.6 kcal/mol). The
peroxy radical then removes a benzyl hydrogen via a six-
membered-ring transition state (TS, ΔΔG‡ = 15.9 kcal/mol)
without the assistance of exogenous radicals (e.g., TEMPO),
which is followed by a spin flip to singlet complex 8 (ΔG =
−9.9 kcal/mol). Complex 8 dissociates into aldehyde 2a and
peroxide 9 (ΔG = −20.6 kcal/mol). Finally, the catalytic cycle
is completed by metathesis of the anion to regenerate complex
6, and peroxide decomposes into oxygen and hydroxide under
basic conditions. In addition, theoretical computations of the
catalytic cycle were performed for both the mono- and bis-
NHC silver complexes. Ligand disassociation of the bis-NHC
complex 6′ is facile and nearly thermoneutral (ΔG = −1.5 kcal/
mol), but mono-NHC complex 6 activates molecular oxygen
more efficiently than does 6′.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: jiangb@sioc.ac.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Basic Research
Program of China (973-2010CB833200 and 973-
2010CB833300), the National Natural Science Foundation of
China (20832007 and 21102167), the Science and Technology
Commission of Shanghai Municipality (12DZ1930902), and
the Knowledge Innovation Program of the Chinese Academy of
Sciences.
In conclusion, a robust and effective Ag catalyst for the
aerobic oxidation of a variety of alcohols has been discovered
and studied. Using BTMAH or KOH, the oxidation can be
carried out aerobically to selectively afford aldehydes or
carboxylic acids in excellent yield. In addition, tandem catalysis
was explored for the one-pot synthesis of imines from an
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