General, green, and scalable synthesis of imines from alcohols and amines by a mild and efficient copper-catalyzed aerobic oxidative reaction in open air at room temperature

Article abstract of DOI:10.1002/adsc.201200574

A general, green, and scalable synthesis of the useful imines and a,b-unsaturated imines is successfully achieved by a low-loading and powerful, mild and efficient copper-catalyzed aerobic oxidative reaction of alcohols and amines in the open air at room temperature under base- and dehydrating reagent-free conditions. This practical reaction can use air as the economic and green oxidant, tolerates a wide range of substrates, can afford high yields of the target imines on a large scale, and produces water as the only by-product, and thus being the best imination method as yet using alcohols and amines directly.

Full text of DOI:10.1002/adsc.201200574

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DOI: 10.1002/adsc.201200574
General, Green, and Scalable Synthesis of Imines from Alcohols
and Amines by a Mild and Efficient Copper-Catalyzed Aerobic
Oxidative Reaction in Open Air at Room Temperature
Haiwen Tian,a Xiaochun Yu,a Qiang Li,a Jianxin Wang,a and Qing Xua,*
a
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang 325035, Peopleꢀs Republic of
China
Fax : (+86)-577-8668-9300; phone: (+86)-138-5774-5327; e-mail: qing-xu@wzu.edu.cn
Received: June 30, 2012; Published online: September 28, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200574.
Abstract: A general, green, and scalable synthesis
of the useful imines and a,b-unsaturated imines is
successfully achieved by a low-loading and power-
ful, mild and efficient copper-catalyzed aerobic oxi-
dative reaction of alcohols and amines in the open
air at room temperature under base- and dehydrat-
ing reagent-free conditions. This practical reaction
can use air as the economic and green oxidant, tol-
erates a wide range of substrates, can afford high
yields of the target imines on a large scale, and pro-
duces water as the only by-product, and thus being
the best imination method as yet using alcohols and
amines directly.
one-pot oxidative condensation of alcohols and
amines is apparently a more appealing approach. Sev-
eral methods have been reported, but severe draw-
backs still remain and many challenges have not yet
been effectively addressed.[7–9] For example, the early
methods require the use of large excess amounts of
oxidants such as MnO2 or PhIACHTNUTRGNE(NUG OAc)2, which may
result in many problems such as waste disposal.[7] The
recently-developed dehydrogenative methods were
catalytically carried out under oxidant-free conditions
and proceed with comparatively high atom efficien-
cy.[8] However, since dihydrogen generation is a ther-
modynamically unfavourable process and thus requir-
ing a high temperature heating (up to 1638C), the re-
actions suffer from the use of sophisticated, poorly
available, expensive, and not easily handled noble
metal catalysts such as Ru and Os complexes,[8a–c]
inert atmosphere protection, long reaction time and
high base loadings,[8d] special equipments,[8e] formation
of by-products under the reductive conditions, and
Keywords: aerobic oxidative reaction; alcohols;
amines; copper catalysis; imine synthesis
Imines, also known as the Schiff bases,[1] are a class of low yields of the products.[8] On the other hand, the
nitrogen compounds of high significance in chemis- presently available aerobic oxidative methods[9] usual-
try.[1–4] Due to the high reactivity of the C=N double ly require noble metal catalysts, pure oxygen as the
bonds, they are both important nitrogen sources and oxidant, large amounts of base, and high temperature
key intermediates in different types of reactions that heating (up to 1458C);[9a–e] otherwise, the reactions
can be further elaborated in biological, pharmaceuti- would not be efficient.[9f–h] Although a mild Pd-cata-
cal, industrial, and natural chemical synthesis.[2–4] lyzed method was recently reported, it uses expensive
Therefore, developing new methods for imine prepa- Pd catalysts and large amounts of ligands and bases,
ration still represents an important challenge in cur- and requires a long reaction time.[9h] Besides, low tol-
rent imine chemistry.[5–9]
erance or low reactivity of the substrates was inevita-
Despite the recent progress in amine oxidation[5] ble in the known methods.[7–9] All these drawbacks
and aza-Wittig reactions,[6] the traditional condensa- make them still far from practicable for synthetic pur-
tion of aldehydes or ketones with amines[1] is most poses. Therefore, a general and green, mild and effi-
often the method of choice.[1–3] Since aldehydes and cient, and practical method that can compete with the
ketones are usually obtained from alcohols by stoi- traditional condensation reaction is still highly desira-
chiometric oxidation, and alcohols are generally ble today.
greener than the carbonyl compounds, such as being
Recently, several groups also reported a few transi-
wider in scope, more readily available, more stable, tion metals (TM)-catalyzed aerobic oxidative reac-
cheaper, less toxic, and easier to handle,[10] the direct tions of alcohols (Scheme 1): (a) esterification of two
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Scheme 1. TM-catalyzed aerobic oxidative transformations of alcohols.
alcohols,[11] (b) amidation of alcohols and amines,[12]
(c) alcohol oxidation,[13a] and (d) an air-promoted de-
hydrative alkylation method.[14] Herein we report an-
other advance in the field by disclosing a powerful
low-loading copper-catalyzed practical and scalable
synthesis of the useful imines directly from alcohols
and amines that can tolerate a wide range of sub-
strates and efficiently afford high yields of the prod-
ucts under neutral conditions in the open air at room
temperature [Scheme 1 (e)].
Copper catalysts have exhibited broad utilities in
both academy and industry for their many advantag-
es,[4,13–16] especially in the aerobic oxidative reactions
recently.[4,13,16] Surprisingly, although copper com-
pounds have been known as effective catalysts for
aerobic alcohol oxidations,[13] an efficient and practi-
cal Cu-catalyzed imination method using directly al-
cohols and amines has not been successfully achieved
as yet.[9] Based on our Cu-catalyzed aerobic alkylation
reactions,[14d,-e] we envisioned that copper might be su-
perior to other metal catalysts for the aerobic oxida-
tive imination reaction. Thus, in our hands,
Table 1. Screening and optimization of the reaction condi-
tions.[a]
Run
[Cu]
Solvent
T, t
3aa [%][b]
[e]
1[c,d]
2[d]
3
4
5
Cu
Cu
Cu
N
–
1208C, 12 h
1208C, 6 h
1208C, 6 h
r.t., 12 h
r.t., 6 h
r.t., 6 h
62
94
94
84
toluene
toluene
toluene
toluene
CH3CN
CuI
CuI
97
>99 (94)
6
[a]
Unless otherwise noted, the mixture of 1a (2.2 mmol,
1.1 equiv.), 2a (2 mmol), [Cu] (1 mol%), 2,2’-bipyridine
(1 mol%), and TEMPO (2 mol%) in a commercial sol-
vent (0.5 mL) was stirred under air and then monitored
by GC-MS. Room temperature (r.t.): ca. 25–308C.
GC yields (isolated yields in parenthesis) based on 2a.
The reaction was carried out using 4 equiv of 1a (neat
conditions) without the addition of the ligand, TEMPO,
and solvent.
[b]
[c]
CuACHTUNGTRENNUNG(OAc)2·H2O was initially investigated in the model
reaction of benzyl alcohol 1a and benzylamine 2a
(Table 1). When the reaction was heated at 1208C by
using 1 mol% of [Cu], 20 mol% of K2CO3, 4 equiv. of
1a under excess air, it afforded a moderate yield of
the product 3aa (run 1). Then, 2,2’-bipyridine and
TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxyl), the
[d]
[e]
20 mol% K2CO3 was added as the base.
Cu
ACHTUNGTRENNUNG
available and abbreviated as CuAHCNUTGTRENNUNG
ligand and cocatalyst frequently used in aerobic alco- tivities in the reaction (CuBr, 6 h, 67%; CuCl, 6 h,
hol oxidations,[13] were found to promote the reaction 77%; CuBr2, 6 h, 89%; CuCl2·2H2O, 6 h, 78%; CuSO4,
greatly, giving a high product yield in a shorter time 12 h, 32%; CuO, 12 h, 0%), among which CuI was
(run 2). By using toluene as the solvent, the loading found to be the best one, giving the highest yield
could be reduced to only 1 equiv. (run 2). It seemed (97%) of the product in only 6 h (run 5). The solvent
that the base did not affect the reaction at all that its effect was also investigated by directly using the com-
use can be totally avoided (run 3). This catalytic mercial solvents (xylene, C6H6, CH2Cl2, THF, dioxane,
system was found to be very active so that the reac- EtOAc, DMF, DMSO, etc., used without any pre-
tion can even be conducted at room temperature, treatment). It seemed these solvents are all acceptable
giving still a good yield of the product (run 4). Cu cat- for giving generally high yields of the product (91–
alyst, bipyridine, and TEMPO were all crucial for the 99%). In comparison, acetonitrile is the best one (run
reaction that their combination gave the best results; 6), in which full conversion of the substrates was ob-
vice versa, the reactions with neither of them were served in only 6 h, and 94% isolated yield of 3aa
not effective at all under the same conditions. Various could be obtained.
Cu catalysts were then screened, showing varying ac-
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General, Green, and Scalable Synthesis of Imines from Alcohols and Amines
Table 2. Cu-catalyzed aerobic oxidative imine preparation
Table 2. (Continued)
from alcohols and amines.[a]
Run
Alcohol
Amine
3
1
2
[%][b]
[(S)- 91
22
1a
2h]
(2i)
(2j)
(82)
Run
Alcohol
Amine
3
92
(81)
23[e]
24
1a
1a
1
2
[%][b]
74
(62)
>99
(94)
1
2
3
4
(1a)
(1b)
(1c)
(1d)
(2a)
2a
91
(83)
94
(87)
25
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
(2k)
(2l)
>99
(89)
78
(71)
2a
26
96
(87)
85
(76)
2a
27
(2m)
(2n)
(2o)
(2p)
(2q)
(2r)
(2s)
(2t)
60
(54)
92
(80)
28
5
(1e)
2a
74
(63)
98
(90)
29
6
(1f)
(1g)
(1h)
(1i)
2a
2a
2a
2a
85
(76)
87
(80)
30[c,f]
31[c]
32[c]
33[c]
34[c,f]
7
96
(90)
80
(70)
8
84
(70)
9[c]
61
(49)
96
(87)
98
(82)
10
11
(1j)
2a
2a
51
(42)
(1k)
44
(30)
12[c,d]
13[d]
(1l)
2a
2a
66[g]
66
(50)
35[c,d]
(2u)
(1m)
64[g]
[a]
Unless otherwise noted, the mixture of 1 (2.2 mmol,
1.1 equiv.), 2 (2 mmol), CuI (1 mol%), 2,2’-bipyridine
(1 mol%), and TEMPO (2 mol%) in CH3CN (0.5 mL)
was stirred in open air at room temperatutr (r.t., ca. 25–
308C) for 12 h, monitored by GC-MS, and then isolated
by column chromatography.
Unless otherwise noted, GC yields (isolated yields in pa-
renthesis) were based on 2.
1.5 equiv. of 1 and 2 mol% of pyrrolidine added.
At 30–358C for 24 h.
Yields based on 1 by using 1.5 equiv. of 2.
At 508C.
>99
(88)
>99
(91)
>99
(89)
>99
(89)
>99
(92)
>99
(92)
>99
(93)
14
1a
(2b)
(2c)
(2d)
2d
15
1a
16[e]
17[e]
18[e]
19[e]
20[e]
1a
[b]
(1n)
1a
[c]
[d]
[e]
[f]
(2e)
(2f)
(2g)
1a
[g]
These imines could not be isolated in pure form at pres-
ent, making it difficult to calculate the isolated yields.
See ref.[17]
1a
98
(88)
21
1a
(2h)
The optimized conditions were then applied to vari-
ous alcohols and amines to extend the scope of the
method. As shown in Table 2, various electron-defi-
cient and electron-rich benzylic alcohols 1a–i (runs 1–
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Table 3. Preparation of a,b-unsaturated imines from allylic
9), including the sterically more hindered ortho-sub-
stituted ones (runs 3, 8, 9) and those with reactive
functional groups such as chloro, bromo, nitro and
amino (runs 2–5, 9), reacted efficiently with 2a to
afford the corresponding imines in good to high iso-
lated yields (70–94%). In the case of o-aminobenzyl
alcohol 1i, addition of 2 mol% of pyrrolidine could
promote the reaction to some extent (run 9). Like
benzylic alcohols, heterobenzylic alchols 1j and 1k
also gave good results under the same conditions
(runs 10 and 11). This method is also suitable for ali-
phatic alcohols, but in these cases, the addition of pyr-
rolidine or running the reactions at slightly higher
temperatures (30–358C) was more preferable, giving
moderate yields of the products (runs 12 and 13).
However, these imines could not be isolated in the
pure form at present.[17]
and propargylic alcohols and amines.[a]
Run
Alcohol 1
Amine 2
3 [%][b]
(2a) 83 (75)
(2c) 97 (88)
1
(1o)
2
1o
3[c]
4[c]
1o
1o
(2d) >99 (87)
(2g) >99 (90)
The reactions of various aliphatic amines 2a–i with
1a were then investigated (Table 2, runs 14–23). These
amines, including a heterobenzylamine 2b, the steri-
cally more bulky cyclo-hexylamine 2g and 1-phenyl-
5[c]
6[d]
1o
1o
(2i) 93 (86)
(2j) 77 (69)
ACHTUNGTRENNUNG
7
(1p)
(2a) 88[e]
ACHTUNGTRENNUNG
8[c]
9[c]
1p
1p
(2d) 94[e]
hol 1n also afforded a high yield of the product (run
17). It is worth noting that, under the mild conditions,
optically active (S)-1-phenylethylamine 2h could also
be efficiently converted to the corresponding chiral
imine in high yields without racemization (run 22).[18]
This method could also be applied to a series of
electron-deficient and electron-rich aromatic and het-
eroaromatic amines 2j–u (Table 2, runs 24–35). Be-
cause these amines are less basic and less nucleophilic
than the aliphatic ones, they were seldom successfully
used as substrates in previous methods, and the reac-
tions usually require large amounts of bases and heat-
ing at high temperatures.[7–9] In contrast, as shown in
Table 2, these amines, including the sterically more
hindered ortho-substituted ones (runs 27, 29, 33), all
reacted effectively under the mild and base-free con-
ditions, giving usually moderate to high yields of the
(2g) 97 (80)
10[c]
1p
1p
(2i) 97 (82)
11[d]
(2j) >99 (90)
[a]
See Table 2 for conditions.
Unless otherwise noted, GC yields (isolated yields in pa-
renthesis) were based on 2.
Yields based on 1 by using 1.5 equiv. of 2.
1.5 equiv. of 1, 36 h.
These imines could not be isolated in pure form at pres-
ent, making it difficult to calculate the isolated yields.
See ref.[17]
[b]
[c]
[d]
[e]
products. Even though the results of the electron-defi- storage of the reactive and unstable acrylaldehydes
cient amines 2r–2u were inferior, giving only low to and propiolaldehydes.[3] As shown in Table 3, cinnam-
moderate yields of the corresponding imines (run 32– yl alcohol 1o and 3-phenylpropargyl alcohol 1p react-
35), these results (runs 24–35) clearly revealed the ad- ed efficiently with various aliphatic and aromatic
vantages of the present Cu-catalyzed reaction (vide amines under the optimized conditions to give gener-
infra) over the known methods.[7–9]
ally high yields of the a,b-unsaturated imines (runs 1–
Moreover, preliminary studies on the reactions of 11). The reactions with aniline 2j were slower, but
allylic and propargylic alcohols also revealed that could still afford good to high yields of the products
they can also be effectively employed to prepare the in longer reaction time (runs 6 and 11).
useful a,b-unsaturated imines (Table 3). Alkenyl- and
The reaction was then carried out on a much larger
alkynylimines, also known as aza-dienes and aza- scale to examine the practicality and synthetic poten-
enynes, are another class of imines playing important tial of the Cu-catalyzed imination reaction. Thus, as
roles in synthetic chemistry.[3] In comparison with the shown in Eq. (1), a 100-mmol scale reaction of 1a and
usual imines,[2] developments regarding the a,b-unsa- 2a successfully afforded 89% (78% isolated) yield of
turated imines are apparently bottle-necked by their 3aa under the standard conditions. In addition, it
low availability due to the difficult preparation and seems that a dehydrating reagent that was in many
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General, Green, and Scalable Synthesis of Imines from Alcohols and Amines
both in the Cu-catalyzed aerobic alcohol oxidation re-
actions[13] and in the metal-catalyzed aerobic oxidative
imination reactions.[9] This finding also reveals anoth-
er advantage of using copper as the catalyst in the
aerobic oxidative imination reactions because, in the
reported methods using other metal catalysts,[7–9] the
cases used in conventional condensation reactions[2,3] substrate amines cannot promote the target reaction.
is not required at all in the present method. All the
Moreover, as predicted by Crabtree[10b] and as in
above results clearly revealed the generality, practical- our metal-catalyzed aerobic N-alkylation reactions,[14]
ity and synthetic potential of the present method. To the Cu catalyst was again found to promote the con-
the best of our knowledge, this is the first general and densation of benzaldehyde 4a and aniline 1j [Eq. (2)],
green, mild and efficient, practical and scalable imine which may account for the higher reaction efficiencies
preparation method that can directly use alcohols and of the less basic and less nucleophilic aromatic and
amines under mild conditions.[7–9]
heteroaromatic amines under the present Cu-cata-
Preliminary mechanistic studies of the reaction lyzed mild and base-free conditions than under other
were also conducted. In the alcohol oxidation step conditions.[7–9] Therefore, the present Cu-catalyzed
(Table 4), surprisingly, almost no reaction occurred in
the absence of the amines (run 1), which is a great
contrast to the efficient standard imination reaction
(Table 1, run 6) and the reported Cu-catalyzed aero-
bic alcohol oxidation reactions.[13] On the contrary,
unreacted 1a decreased in degrees when 10–
100 mol% of 2a were added (runs 2–5), affording
quantitative yields of 3aa (if based on 2a added) and
less than 10% yields of 4a (based on 1a). These inter- aerobic oxidative imination reaction most probably
esting results clearly implied that amines can facilitate proceeds via an amine-promoted Cu-catalyzed aero-
the Cu-catalyzed aerobic alcohol oxidation step, bic alcohol oxidation reaction and a Cu-promoted de-
which, to the best of our knowledge, is a new finding hydrative condensation of aldehydes 4 and amines 2
(Scheme 2).
Table 4. Cu-Catalyzed aerobic alcohol oxidation in the pres-
ence of an amine.[a]
Scheme 2. Proposed simplified reaction path for Cu-cata-
lyzed aerobic oxidative imine synthesis from alcohols and
amines.
Run 2a[b]
1a [%] (unreacted)[c] 4a [%][d] 3aa [%][e]
1
2
3
4
5
–
>98
~85
~74
~41
<2
~5
~6
~9
<1
–
~10
~20
~50
~10 (>99)
~20 (>99)
~50 (>99)
>99
In summary, we have developed a general and
green, mild and efficient, powerful low-loading Cu-
catalyzed practical and scalable synthesis of imines
and a,b-unsaturated imines directly from alcohols and
~100 <1
[a]
[b]
[c]
The mixture of 1a (2 mmol) and different loadings of 2a
(mol%) in CH3CN (0.5 mL) was stirred under the stan- amines that can be readily carried out in the open air
dard condition for 12 h, and then monitored by GC-MS.
Since 2a (mol%) was added using a microsyringe, its
amounts might not be exactly accurate but approximately
the amount indicated.
Calculated based on GC analysis and the yields of 4a and
3aa.
at room temperature under base- and dehydrating re-
agent-free conditions. This method is of high potential
in imine preparation for it tolerates a wide range of
substrates, can afford efficiently high yields of the
imines and operate on a large scale. Due to the many
advantages of the Cu catalysts, the importance of the
useful imines, and the green features of the method,
this reaction should find wide interest and numerous
utilities in many fields. Further extension and applica-
tions of this Cu-catalyzed method are underway.
[d]
[e]
GC yields based on 1a.
Yields based on 1a (the yields in parenthesis were based
on 2a added). As shown by GC spectra, no unreacted 2a
was observed, indicating that GC yields of 3aa are all
100% (quantitative yields) if based on 2a.
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Experimental Section
Chem. Rev. 2011, 111, 1713–1760; t) J. Adrio, J. C. Car-
retero, Chem. Commun. 2011, 47, 6784–6794; u) C. S.
Marques, A. J. Burke, ChemCatChem 2011, 3, 635–645;
v) T. R. Ramadhar, R. A. Batey, Synthesis 2011, 1321–
1346; w) M. Nielsen, D. Worgull, T. Zweifel, B.
Gschwend, S. Bertelsen, K. A. Jøgensen, Chem.
Commun. 2011, 47, 632–649.
Typical Procedure for Cu-Catalyzed Aerobic
Oxidative Synthesis of Imines from Alcohols and
Amines
The mixture of benzyl alcohol 1a (0.23 mL, 2.2 mmol,
1.1 equiv.), benzylamine 2a (0.22 mL, 2 mmol), CuI
(0.0038 g, 0.02 mmol, 1 mol%), 2,2’-bipyridine (0.0031 g,
0.02 mmol, 1 mol%), TEMPO (0.0063 g, 0.04 mmol,
2 mol%) was stirred in the open air at room temperature
(ca. 25–308C) and monitored by TLC and/or GC-MS. The
mixture was then, without any work-up, directly purified by
column chromatography on neutral alumina gel (petroleum
ether/ethyl acetate/triethylamine 100:10:1) to afford 3aa in
94% isolated yield. The alumina gel was preneutralized with
1% (v/v) of triethylamine in petroleum ether before pack-
ing.
[3] a) M. Shimizu, I. Hachiya, I. Mizota, Chem. Commun.
2009, 874–889; b) B. Groenendaal, E. Ruijter, R. V. A.
Orru, Chem. Commun. 2008, 5474–5489; c) J.-C. M.
Monbaliu, K. G. R. Masschelein, C. V. Stevens, Chem.
Soc. Rev. 2011, 40, 4708–4739.
[4] a) C.-J. Li, Z. Li, Pure Appl. Chem. 2006, 78, 935–945;
b) C.-J. Li, Acc. Chem. Res. 2009, 42, 335–344; c) C. J.
Scheuermann, Chem. Asian J. 2010, 5, 436–451.
[5] a) M. Largeron, M.-B. Fleury, Angew. Chem. 2012, 124,
5505–5508; Angew. Chem. Int. Ed. 2012, 51, 5409–5412;
b) X. Lang, H. Ji, C. Chen, W. Ma, J. Zhao, Angew.
Chem. 2011, 123, 4020–4023; Angew. Chem. Int. Ed.
2011, 50, 3934–3937; c) R. D. Patila, S. Adimurthy, Adv.
Synth. Catal. 2011, 353, 1695–1700; d) G. Jiang, J. Chen,
J.-S. Huang, C.-M. Che, Org. Lett. 2009, 11, 4568–4571;
e) C. S. Yi, D. W. Lee, Organometallics 2009, 28, 947–
949; f) H. Choi, M. P. Doyle, Chem. Commun. 2007,
745–747; g) J. S. M. Samec, A. H. ꢆll, J.-E. Bꢃckvall,
Chem. Eur. J. 2005, 11, 2327–2334.
Acknowledgements
We thank NNSFC (No. 20902070), SRF for ROCS of SEM,
NSF (No. Y4100579) and QJTP of Zhejiang Province (No.
QJD0902004) for financial support. H.T. thanks the Post-
graduate Innovation Foundation of Wenzhou University (No.
31606036010142).
[6] a) F. Palacios, C. Alonso, D. Aparicio, G. Rubiales,
J. M. de Los Santos, Tetrahedron 2007, 63, 523–575;
b) P. M. Fresneda, P. Molina, Synlett 2004, 1–17.
[7] a) L. Blackburn, R. J. K. Taylor, Org. Lett. 2001, 3,
1637–1639; b) A. S. Medvedeva, A. V. Mareev, A. I.
Borisova, A. V. Afonin, ARKIVOC, 2003, 13, 157–165;
c) M. S. Yusubov, K.-W. Chi, J. Y. Park, R. Karimovc,
V. V. Zhdankinc, Tetrahedron Lett. 2006, 47, 6305–6308.
[8] a) B. Gnanaprakasam, J. Zhang, D. Milstein, Angew.
Chem. 2010, 122, 1510–1513; Angew. Chem. Int. Ed.
2010, 49, 1468–1471; b) A. Maggi, R. Madsen, Organo-
metallics 2012, 31, 451–455; c) M. A. Esteruelas, N.
Honczek, M. Olivꢇn, E. Onate, M. Valencia, Organo-
metallics 2011, 30, 2468–2471; d) R. Cano, D. J. Ramꢂn,
M. Yus, J. Org. Chem. 2011, 76, 5547–5557; e) Y. Shir-
aishi, M. Ikeda, D. Tsukamoto, S. Tanaka, T. Hiraia,
Chem. Commun. 2011, 47, 4811–4813; f) J. W. Rigoli,
S. A. Moyer, S. D. Pearce, J. M. Schomaker, Org.
Biomol. Chem. 2012, 10, 1746–1749.
[9] a) M. S. Kwon, S. Kim, S. Park, W. Bosco, R. K. Chi-
drala, J. Park, J. Org. Chem. 2009, 74, 2877–2879; b) H.
Sun, F.-Z. Su, J. Ni, Y. Cao, H.-Y. He, K.-N. Fan,
Angew. Chem. 2009, 121, 4454–4457; Angew. Chem. Int.
Ed. 2009, 48, 4390–4393; c) J. W. Kim, J. He, K. Yama-
guchi, N. Mizuno, Chem. Lett. 2009, 38, 920–921; d) W.
He, L. Wang, C. Sun, K. Wu, S. He, J. Chen, P. Wu, Z.
Yu, Chem. Eur. J. 2011, 17, 13308–13317; e) Q. Kang,
Y. Zhang, Green Chem. 2012, 14, 1016–1019; f) S.
Kegnæs, J. Mielby, U. V. Mentzel, C. H. Christensen, A.
Riisager, Green Chem. 2010, 12, 1437–1441; g) S. Si-
thambaram, R. Kumar, Y.-C. Son, S. L. Suib, J. Catal.
2008, 253, 269–277; h) L. Jiang, L. Jin, H. Tian, X.
Yuan, X. Yu, Q. Xu, Chem. Commun. 2011, 47, 10833–
10835.
References
[1] a) H. Schiff, Justus Liebigs Ann. Chem. 1864, 131, 118–
119; b) M. M. Sprung, Chem. Rev. 1940, 26, 297–338;
c) R. W. Layer, Chem. Rev. 1963, 63, 489–510.
[2] a) S. Patai, The Chemistry of the Carbon-Nitrogen
Double Bond (Chemistry of Functional Goups), Wiley-
Interscience, New York, 1970; b) J. P. Adams, J. Chem.
Soc. Perkin Trans. 1 2000, 125–139; c) J. A. Ellman,
T. D. Owens, T. P. Tang, Acc. Chem. Res. 2002, 35, 984–
995; d) A. E. Taggi, A. M. Hafez, T. Lectka, Acc.
Chem. Res. 2003, 36, 10–19; e) A. Cꢂrdova, Acc. Chem.
Res. 2004, 37, 102–112; f) J.-A. Ma, Chem. Soc. Rev.
2006, 35, 630–636; g) A. Dçmling, Chem. Rev. 2006,
106, 17–89; h) A. Erkkilꢃ, I. Majander, P. M. Pihko,
Chem. Rev. 2007, 107, 5416–5470; i) J. Gawronski, N.
Wascinska, J. Gajewy, Chem. Rev. 2008, 108, 5227–
5252; j) K.-I. Yamada, K. Tomioka, Chem. Rev. 2008,
108, 2874–2886; k) P. Merino, E. Marquꢄs-Lꢂpez, R. P.
Herrera, Adv. Synth. Catal. 2008, 350, 1195–1208; l) M.
OrdꢂÇez, H. Rojas-Cabrera, C. Cativiela, Tetrahedron
2009, 65, 17–49; m) S. F. Martin, Pure Appl. Chem.
2009, 81, 195–204; n) P. de Armas, D. Tejedor, F. Garꢅa-
Tellado, Angew. Chem. 2010, 122, 1029–1032; Angew.
Chem. Int. Ed. 2010, 49, 1013–1016; o) C.-J. Li, Acc.
Chem. Res. 2010, 43, 581–590; p) V. R. Akhmetova,
G. R. Khabibullina, E. B. Rakhimova, R. A. Vagapov,
R. R. Khairullina, Z. T. Niatshina, N. N. Murzakova,
Mol. Diversity 2010, 14, 463–471; q) B. Yin, Y. Zhang,
L.-W. Xu, Synthesis 2010, 3583–3595; r) S. Kobayashi,
Y. Mori, J. S. Fossey, M. M. Salter, Chem. Rev. 2011,
111, 2626–2704; s) J.-H. Xie, S.-F. Zhu, Q.-L. Zhou,
[10] a) A. J. A. Watson, J. M. J. Williams, Science 2010, 329,
635–636; b) G. E. Dobereiner, R. H. Crabtree, Chem.
2676
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 2671 – 2677

General, Green, and Scalable Synthesis of Imines from Alcohols and Amines
Rev. 2010, 110, 681–703; c) G. Guillena, D. J. Ramꢂn,
M. Yus, Chem. Rev. 2010, 110, 1611–1641; d) E. Emer,
R. Sinisi, M. G. Capdevila, D. Petruzziello, F. De Vin-
centiis, P. G. Cozzi, Eur. J. Org. Chem. 2011, 647–666.
[11] a) S. Gowrisankar, H. Neumann, M. Beller, Angew.
Chem. 2011, 123, 5245–5249; Angew. Chem. Int. Ed.
2011, 50, 5139–5143; b) C. Liu, J. Wang, L. Meng, Y.
Deng, Y. Li, A. Lei, Angew. Chem. 2011, 123, 5250–
5254; Angew. Chem. Int. Ed. 2011, 50, 5144–5148; c) Y.
Endo, J.-E. Bꢃckvall, Chem. Eur. J. 2011, 17, 12596–
12601; d) F. Luo, C. Pan, J. Cheng, F. Chen, Tetrahe-
dron 2011, 67, 5878–5882; e) H. Miyamura, T. Yasuka-
wa, S. Kobayashi, Green Chem. 2010, 12, 776–778.
[12] a) K. Yamaguchi, H. Kobayashi, T. Oishi, N. Mizuno,
Angew. Chem. 2012, 124, 559–562; Angew. Chem. Int.
Ed. 2012, 51, 544–547; b) J.-F. Soule, H. Miyamura, S.
Kobayashi, J. Am. Chem. Soc. 2011, 133, 18550–18553;
c) Y. Wang, D. Zhu, L. Tang, S. Wang, Z. Wang,
Angew. Chem. 2011, 123, 9079–9083; Angew. Chem.
Int. Ed. 2011, 50, 8917–8921.
[14] a) S. L. Feng, C. Z. Liu, Q. Li, X. C. Yu, Q. Xu, Chin.
Chem. Lett. 2011, 22, 1021–1024; b) C. Liu, S. Liao, Q.
Li, S. Feng, Q. Sun, X. Yu, Q. Xu, J. Org. Chem. 2011,
76, 5759–5773; c) X. Yu, C. Liu, L. Jiang, Q. Xu, Org.
Lett. 2011, 13, 6184–6187; d) Q. Li, S. Fan, Q. Sun, H.
Tian, X. Yu, Q. Xu, Org. Biomol. Chem. 2012, 10,
2966–2972; e) S. Liao, K. Yu, Q. Li, H. Tian, Z. Zhang,
X. Yu, Q. Xu, Org. Biomol. Chem. 2012, 10, 2973–2978.
[15] a) S. V. Ley, A. W. Thomas, Angew. Chem. 2003, 115,
5558–5607; Angew. Chem. Int. Ed. 2003, 42, 5400–5449;
b) G. Evano, N. Blanchard, M. Toumi, Chem. Rev.
2008, 108, 3054–3131; c) D. Ma, Q. Cai, Acc. Chem.
Res. 2008, 41, 1450–1460; d) F. Monnier, M. Taillefer,
Angew. Chem. 2009, 121, 7088–7105; Angew. Chem.
Int. Ed. 2009, 48, 6954–6971; e) H. Rao, H. Fu, Synlett
2011, 745–769.
[16] a) A. E. Wendlandt, A. M. Suess, S. S. Stahl, Angew.
Chem. 2011, 123, 11256–11283; Angew. Chem. Int. Ed.
2011, 50, 11062–11087; b) C. Liu, H. Zhang, W. Shi, A.
Lei, Chem. Rev. 2011, 111, 1780–1824; c) M. Kluss-
mann, D. Sureshkumar, Synthesis 2011, 353–369; d) Z.
Shao, F. Peng, Angew. Chem. 2010, 122, 9760–9762;
Angew. Chem. Int. Ed. 2010, 49, 9566–9568; e) H. A.
Stefani, A. S. Guarezemini, R. Cella, Tetrahedron 2010,
66, 7871–8918.
[17] Despite many attempts, these imines cannot be isolated
in pure form due to their easy decomposition during
purification. Unlike other imines, they have seldom
been isolated successfully and clearly characterized
even employing the conventional condensation
method. Therefore, these imines were mostly reported
in GC yields. See: a) P. A. Burland, D. Coisson,
H. M. I. Osborn, J. Org. Chem. 2010, 75, 7210–7218.
For other methods, see: b) A. V. Lee, L. L. Schafer, Or-
ganometallics 2006, 25, 5249–5254; c) C. Li, R. K.
Thomson, B. Gillon, B. O. Patrick, L. L. Schafer, Chem.
Commun. 2003, 2462–2463; d) L. Monnereau, D. Sꢄ-
meril, D. Matt, Green Chem. 2010, 12, 1670–1673.
[18] See the Supporting Information for details.
[13] a) During the preparation of this work, Stahl and co-
workers reported an efficient CuACHTUNTRGNEUNG(OTf)-catalyzed aero-
bic alcohol oxidation reaction: J. M. Hoover, S. S. Stahl,
J. Am. Chem. Soc. 2011, 133, 16901–16910. For earlier
reports, see: b) M. F. Semmelhack, C. R. Schmid, D. A.
Cortes, C. S. Chou, J. Am. Chem. Soc. 1984, 106, 3374–
3376; c) I. E. Markꢂ, P. R. Giles, M. Tsukazaki, S. M.
Brown, C. J. Urch, Science 1996, 274, 2044–2046; d) P.
Gamez, I. W. C. E. Arends, J. Reedijk, R. A. Sheldon,
Chem. Commun. 2003, 2414–2415; e) P. Gamez,
I. W. C. E. Arends, R. A. Sheldon, J. Reedijk, Adv.
Synth. Catal. 2004, 346, 805–811; f) E. T. T. Kumoulai-
nen, A. M. P. Koskinen, Chem. Eur. J. 2009, 15, 10901–
10911; g) L. Liang, G. Rao, H.-L. Sun, J.-L. Zhang,
Adv. Synth. Catal. 2010, 352, 2371–2377; h) L. Cheng, J.
Wang, M. Wang, Z. Wu, Inorg. Chem. 2010, 49, 9392–
9399; i) P. Belanzoni, C. Michel, E. J. Baerends, Inorg.
Chem. 2011, 50, 11896–11904.
Adv. Synth. Catal. 2012, 354, 2671 – 2677
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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