Cooperative catalysis with aldehydes and copper: Development and application in aerobic oxidative C-H amination at room temperature

Article abstract of DOI:10.1002/adsc.201200944

A conceptually new cooperative catalytic system via a synergistic combination of aldehyde and copper catalysis has been established based on systemic mechanistic studies. This new cooperative catalysis has been successfully applied in the direct aerobic oxidative C-H amination of azoles at room temperature, which was previously realized under harsh conditions. Mechanistic studies including isotopic labeling experiments and kinetic isotope effect (KIE) experiments support a reaction pathway that involves formation of an aminal, hydrolysis of the aminal to generate the copper-amide species, subsequent C-H amination and re-oxidation of copper(I) to copper(II) by oxygen. It not only provides an efficient method to realize the oxidative C-H amination of benzoxazoles with free amines at room temperature, but also paves the way for establishing new C-N bond formation reactions by using this efficient cooperative catalysis. Copyright

Full text of DOI:10.1002/adsc.201200944

FULL PAPERS
DOI: 10.1002/adsc.201200944
Cooperative Catalysis with Aldehydes and Copper: Development
À
and Application in Aerobic Oxidative C H Amination at Room
Temperature
Yinjun Xie,a Bo Qian,a Pan Xie,a and Hanmin Huanga,*
a
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese
Academy of Sciences, Lanzhou 730000, Peopleꢀs Republic of China
Fax : (+86)-931-496-8129; e-mail: hmhuang@licp.cas.cn
Received: October 26, 2012; Revised: December 5, 2012; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200944.
Abstract: A conceptually new cooperative catalytic aminal to generate the copper-amide species, subse-
À
system via a synergistic combination of aldehyde and quent C H amination and re-oxidation of copper(I)
copper catalysis has been established based on sys- to copper(II) by oxygen. It not only provides an effi-
À
temic mechanistic studies. This new cooperative cat- cient method to realize the oxidative C H amination
alysis has been successfully applied in the direct of benzoxazoles with free amines at room tempera-
À
À
aerobic oxidative C H amination of azoles at room ture, but also paves the way for establishing new C
temperature, which was previously realized under N bond formation reactions by using this efficient
harsh conditions. Mechanistic studies including iso- cooperative catalysis.
topic labeling experiments and kinetic isotope effect
(KIE) experiments support a reaction pathway that Keywords: aldehydes; C H amination; cooperative
involves formation of an aminal, hydrolysis of the catalysis; copper; room temperature reaction
À
Introduction
recently been made in the direct amination of aromat-
ic C H bonds by using transition metal complexes as
À
Transition metal and organocatalyst combined coop- catalysts.[5,6] However, harsh conditions (high temper-
erative catalysis is emerging as a valuable and power- ature) are usually required, which is generally as-
ful strategy in synthetic organic chemistry.[1] It pro- cribed to the difficult C H bond activation in these
À
vides new ways to activate molecules by mutual acti- transformations. While in some cases, high tempera-
vation and preorganization of reactants, which is con- ture still remained necessary even though the C H
ceptually different from the catalysis promoted by bond cleavage is a facile process, which might result
metal catalysts or organocatalysts alone.[1d] In this from the difficulty in formation of metal-amide spe-
context, the establishment of new cooperative cataly- cies. Up to now, comparatively less attention was di-
sis and discovery of new active modes that feature rected to developing new strategies for the generation
higher catalytic activity and selectivity is highly desir- of metal-amide species, which were previously ob-
À
able for exploring new reactions.
tained by using pre-activated amino precursors[6] or
À
Transition metal-catalyzed aromatic C N bond for- stoichiometric amounts of strong bases to promote
mation reactions have evolved into remarkable syn- the corresponding aminometalation,[2] thus dramati-
thetic tools enabling the efficient construction of com- cally decreasing the atom economy of such transfor-
plex amines,[2] which are prevalent in bioactive mole- mations. Hence, the discovery of efficient strategies
cules and functional materials. The direct C H amina- for the transformation of simple amines to the corre-
tion of simple arenes or heteroarenes is a particularly sponding metal-amide species is crucial for C H ami-
À
À
attractive subset of this chemistry, as it avoids pre- nation to be realized under mild conditions.
functionalization of the starting aromatic molecules.[3]
In the area of organocatalysis, secondary amines
To achieve this transformation efficiently, efficient have proven to be outstanding catalysts for the activa-
À
strategies for activation of inert C H bonds and con- tion of aldehydes or other carbonyl-containing com-
venient methods for the generation of metal-amide pounds in amino catalytic cycles, in which the catalyt-
species are generally required.[4] Notable progress has ic formation of iminium ions or enamines has been
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Scheme 1. New strategy for the oxidative C H amination
identified as a key step.[7] However, taking a reversed in acid condition at room temperature, might act as
consideration, the N H group of the amines was si- a surrogate for the iminium ions.[9] To test our hypoth-
À
multaneously activated by the aldehyde in these esis, the reaction of benzoxazole 1a with aminal 2a
transformations. In this context, we envisioned that catalyzed by a copper catalyst in the presence of
aldehydes might act as a catalyst for the facile activa- 1 atm of O2 at room temperature was examined. The
À
tion of secondary amines via formation of iminium desired C H amination reaction did indeed occur at
À
ions or aminals. Merging this perspective of N H acti- room temperature albeit in low yield (Table 1,
À
vation with the metal-catalyzed C H activation pro- entry 1), when CuBr2 (10 mol%) was used as catalyst.
cess might establish an efficient approach to realize Other copper sources, including CuBr, CuCl2,
À
C N bond formation reactions. Herein, we report Cu
(OAc)2, Cu
E
N
a conceptually new cooperative catalysis via a syner- ined and led to the observation that CuBr2 was the
gistic combination of copper and aldehyde catalysis best choice (Table 1, entries 2–6). The solvent screen-
À
for the aerobic oxidative C H amination of benzoxa- ing proved to be fruitful and we found that the yield
zoles at room temperature.[8]
of the desired 3aa was dramatically increased when
Our initial design is exemplified in Scheme 1, we CH2Cl2 was used as solvent (Table 1, entry 8). It is in-
hypothesized that exposure of amines to a catalytic teresting to note that both of the two amino moieties
amount of aldehyde would form the aminal A. Be- contained in the aminal could be incorporated into
cause the aminal is known to be a reactive compound, the product and the reaction could be performed
it would react with the metal to afford the corre- smoothly with CuBr2 as catalyst in the absence of li-
sponding metal-amide species B via hydrolysis under gands. The addition of BHT or 1,1-diphenylethylene
appropriate conditions.[9] Once formed the metal- has no deleterious effect on the reaction, which ex-
amide species B would further react with arenes via cludes the existence of propagating radical species.
À
C H activation under oxidative conditions, and so the Acid was not essential for this reaction, albeit a rela-
catalytic direct oxidative C H amination could be re- tive lower yield was obtained in the absence of acid.
À
alized. On the way towards the envisioned coopera- No conversion was observed when the reaction was
tive catalysis, we first need to identify a catalytic C H conducted in the absence of Cu catalyst (Table 1,
amination reaction for adopting this catalytic system entry 13). The C H amination reaction failed to go to
and investigating whether the aminal A could act as completion when it was conducted in the presence of
a nitrogen group source for C N bond formation re- a catalytic amount of CuBr2 (10 mol%) under anaero-
actions.
À
À
À
bic conditions and the desired product was obtained
with lower yield (5% yield, Table 1, entry 14). To un-
derstand the role that O2 plays during the process,
control experiments with different amounts of CuBr2
were conducted in the absence of O2 (Table 1, en-
Results and Discussion
Previously, we have reported on a Cu-catalyzed C H tries 15 and 16).[12] The amination product was ob-
amination of azoles with tertiary amines using oxygen tained with 9% and 21% yield in the presence of 20%
as sole oxidant.[10] A detailed mechanistic study re- and stoichiometric amount of CuBr2, respectively.
À
vealed that the iminium-type species, generated via White precipitates were observed at the end of the re-
3
À
cleavage of the sp C H bond of the tertiary amine, action when the reactions were conducted in the ab-
was involved as a key intermediate.[11] Encouraged by sence of an O2 atmosphere. The precipitates were iso-
these results, we conceived that the proposed cooper- lated by filtration and were characterized by XPS
ative catalysis could be applied in the Cu-catalyzed analysis (Table 1, entries 15 and 16, see the Support-
À
C H amination reaction since the proposed aminal ing Information), indicating that CuBr was produced.
A, which would be converted to iminium ions easily These observations revealed that O2 was not likely in-
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Cooperative Catalysis with Aldehydes and Copper: Development and Application
Table 1. Optimization of the reaction conditions.[a]
Entry
CuXn
Solvent
Acid
Yield [%][b]
1
2
3
4
5
6
7
8
CuBr2
CuBr
CuCl2
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
CH3CN
CH2Cl2
THF
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
PhCOOH
–
27
15
12
<1
3
Cu
Cu
Cu
U
<1
42
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
–
CuBr2
CuBr2
CuBr2
78 (73)[f]
34
9
10
11
12
13
14[c]
15[c,d]
16[c,e]
DMF
10
55
62
<1
5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
HOAc
HOAc
–
9
21
–
[a]
Reaction conditions: CuXn (0.05 mmol), 1a (0.6 mmol), 2a (0.25 mmol), acid (0.1 mmol), solvent (1.0 mL), O2 (1 atm), at
room temperature for 18 h, unless otherwise noted.
GC yield based on the conversion of amine moiety.
In an argon atmosphere.
20 mol% CuBr2 was used.
100 mol% CuBr2 was used.
[b]
[c]
[d]
[e]
[f]
Isolated yield.
À
À
volved in the steps of C H bond cleavage and C N involved in the rate-limiting step. However, the
bond formation, but may just play a role for the re- higher KIE value (kH/D =2.0) was detected for the
À
oxidation of CuBr to CuBr2.
After establishing this new Cu-catalyzed oxidative the azole was significant with respect to the rate-limit-
C H amination and identifying the aminals could act ing step. To further elucidate how the C N bond of
benzoxazole, which indicated that C H cleavage of
À
À
À
as nitrogen source in the C N bond formation reac- the aminal was cleaved to generate the copper-amide
tion, we were interested in elucidating the mechanis- species, isotopic labeling experiments with 18O2 or
tic features of this reaction. The first question we H218O were conducted by employing the benzalde-
needed to address is whether the amidine 5a, which hyde-derived aminal 2b as the amine source under
could form in situ from morpholine and benzoxazole the standard conditions. As illustrated in Scheme 2,
at room temperature,[8h,i] is involved as a key inter- PhCH18O was detected in the reaction of 1a with 2b
mediate in this reaction. As shown in Scheme 2, the by using 16O2 as the oxidant in the presence of H218O.
intermediate 5a was not observed when the standard While using 18O2 as the oxidant in the presence of
reaction proceeded in the absence of oxygen under H216O instead, only Ph-CH16O was observed. Further
otherwise identical conditions. Furthermore, replacing isotopic labeling experiments with 18O2 as the oxidant
O2 with PhIACHTUNGTRENNUNG(OAc)2 caused the reaction to shut down. in the absence of H2O showed that the oxygen atom
These results seem to suggest that the formation of in- from 18O2 was incorporated into the benzaldehyde.
termediate 5a could be excluded and the correspond- These results indicated that O2 was converted to H2O
À
ing copper amide species is most likely involved in in the reaction system and the H2O promoted the C
this reaction.
N bond cleavage (Scheme 2).
The intermolecular kinetic isotope effects (KIEs)
As the proposed design was partially realized by
for both coupling partners were then investigated successful employment of aminal A as nitrogen group
À
under the standard conditions. As shown in Scheme 2, source for the C H amination, we wanted to further
no kinetic isotope effect (kH/D =1.0) was observed for investigate whether the cooperative catalysis via the
À
the aminal, suggesting that the C H bond of the combination of aldehyde and copper catalysis could
aminal is not cleaved or that the C H cleavage is not promote the desired C H amination with free secon-
À
À
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Scheme 2. Control experiments for mechanistic studies.
dary amines as nitrogen group sources. To our delight, product 3aa was obtained in 39% yield (Table 2,
À
when benzaldehyde was introduced to the C H ami- entry 1). Only a trace amount of the desired product
nation reaction performed with 1a and 4a, the desired was obtained in the absence of aldehyde (Table 2,
[a]
À
Table 2. Cooperative catalysis for the C H amination.
Entry
RCHO
Solvent
Yield [%][d]
1[b]
2[b]
3[c]
4
5
6
Ph-CHO
–
dioxane
dioxane
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
39
<5
37
77
72
82
78
70
Ph-CHO
Ph-CHO
4-Me-C6H4-CHO
2,3-Cl2-C6H3-CHO
t-Bu-CHO
–
7
8
[a]
Reaction conditions: 1a (0.6 mmol), 4a (0.5 mmol), CuBr2 (0.05 mmol), HOAc (0.1 mmol), RCHO (0.1 mmol), solvent
(1.0 mL), O2 (1 atm), at room temperature for 18 h, unless otherwise noted.
1a (0.5 mmol), 4a (1.0 mmol), RCHO (0.5 mmol).
1a (0.5 mmol), 4a (1.0 mmol), RCHO (0.1 mmol).
Yield was determined by GC with biphenyl as internal standard.
[b]
[c]
[d]
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Cooperative Catalysis with Aldehydes and Copper: Development and Application
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Figure 1. Kinetic reaction profiles for the oxidative C H amination of 1a with 4a in 1,4-dioxane (investigation the effect of
aldehyde): (a) 1a/4a/benzaldehyde=1.2/1/0.5, (b) 1a/4a/benzaldehyde=1.2/1/0, (c) 1a/4a/benzaldehyde=1/2/1, (d) 1a/4a/
benzACHTUNGTRENNUNGaldehyde=1/2/0.
entry 2). When CH2Cl2 served as solvent, the reaction than 14% yield was found when the reaction was con-
could be performed in presence of a catalytic amount ducted in the absence of aldehyde under the same
of aldehyde (Table 2, entry 3). Furthermore, the yield conditions (reaction b). Furthermore, on changing the
was improved to 77% by changing the ratio of 1a to ratio of 1a/4a from 1.2/1 to 1/2, the reaction was in-
4a (1a/4a=1.2/1, Table 2, entry 4).[13] Further studies hibited completely in the absence of benzaldehyde
indicated that other aldehydes including both aromat- (reaction d). However, the reaction went smoothly in
ic aldehydes and aliphatic aldehydes could catalyze the presence of aldehyde under the same conditions
this reaction and the aromatic aldehydes with an elec- (reaction c). These results indicated that the aldehyde
tron-withdrawing group gave better results (Table 2, acted as a catalyst for this reaction and accelerated
entries 4–7). The acid was also not essential for this the reaction rate.
reaction (see the Supporting Information). As the
On the basis of the above-mentioned results and
aminal could be facilely generated via the reaction of those obtained previously,[8a,10] a cooperative catalysis
a secondary amine with CH2Cl2,[14] we supposed that of aldehyde and copper in the aerobic oxidative C H
À
good results could also be obtained in the absence of amination could be established and a plausible de-
aldehyde when CH2Cl2 served as solvent. Indeed, tailed reaction pathway is shown in Figure 2. Initially,
a 70% yield was obtained when the reaction was con- the aminal A or iminium species C may be generated
ducted in CH2Cl2 without addition of aldehyde under in situ through reaction of the secondary amine with
the otherwise identical conditions (Table 2, entry 8). aldehyde or CH2Cl2.[14] The aminal A then reacts with
Subsequent analysis of the gas phase of the reaction CuBr2, generating the copper-amide intermediate B
mixture (Table 2, entry 8) by using MS indicated that and iminium C. The iminium C further quickly reacts
HCHO was produced (see the Supporting Informa- with CuBr2 via hydrolysis to afford copper-amide in-
tion), which revealed that CH2Cl2 played the same termediate B and regenerate the aldehyde to com-
role as formaldehyde.
plete the aldehyde catalytic cycle. The intermediate B
The catalytic effect of aldehyde was further demon- reacts with benzoxazole to generate organocopper in-
strated by the kinetic reaction profiles shown in termediate D via abstraction of the hydrogen atom of
Figure 1. Obviously, the rate of the reaction was ac- benzoxazole, which is the rate-determining step of the
celerated by aldehyde even when the reaction was reaction. Subsequent reductive elimination to provide
performed in dioxane. For example, more than 40% the product 3aa releases the Cu(I),[15] which is oxi-
yield was obtained when the reaction was conducted dized by O2 to afford Cu(II) and complete the copper
with a 1.2/1 ratio of 1a/4a in the presence of 0.5 equiv. catalytic cycle.
of benzaldehyde for 4 h (reaction a). However, less
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Figure 2. Plausible reaction mechanism.
Several additional experiments and analyses provid- more, the substrates with internal or terminal alkene
ed further support for this mechanistic proposal. In functionality were also well-tolerated (3ai and 3an).[17]
the cooperative catalytic system, a higher KIE value
(kH/D =2.4) was observed for the benzoxazole (see the
À
Supporting Information), which suggested that C H Conclusions
cleavage of the benzoxazole contributed to the rate-
determining step during the process. Labeling experi- In summary, we have successfully developed a concep-
ments using 18O2 as oxidant for the cooperative catal- tually new cooperative catalytic system via the syner-
ysis in the absence of HOAc showed that the oxygen gistic combination of aldehyde and copper catalysis
atom from 18O2 was incorporated into the recovered and successfully applied it in the aerobic oxidative C
À
catalytic amount of benzaldehyde (see the Supporting H amination of benzoxazoles. The ability of aldehyde
Information).[16] These results revealed that the ben- to activate the N H bond of amines enabled the reac-
zaldehyde did indeed participate in the catalytic cycle tion to be conducted under mild conditions. This
À
and acted as a catalyst.
study not only provides an efficient method to realize
À
This cooperative catalysis of aldehyde and copper the oxidative C H amination of benzoxazoles with
has shown its power by realizing the aerobic oxidative free amines at room temperature, but also paves the
À
À
C H amination of benzoxazole at room temperature. way for establishing new C N bond formation reac-
To further confirm the generality of this cooperative tions by using this efficient cooperative catalysis. Fur-
catalysis, more substrates were tested in this oxidative ther exploration of this powerful strategy in establish-
À
À
C H amination by using a range of secondary amines ing new C N bond formation reactions is currently
and benzoxazoles (Table 3). An array of benzoxazoles being pursued in our laboratory.
with different electronic and steric properties was
À
found to be effective for this room-temperature C H
amination via this cooperative catalysis in the pres- Experimental Section
ence of 1 atm of O2. Both electron-donating substitu-
ents and electron-withdrawing substituents were toler- General procedure
ated, providing the coupling products 3aa–3ga in good
Benzoxazole 1a (0.6 mmol), morpholine 4a (0.5 mmol), 2,4-
yields. Acyclic as well as cyclic secondary amines
dichlorobenzaldehyde
(0.1 mmol,
20 mol%),
CuBr2
À
were proved to be effective in this oxidative C H
(0.05 mmol, 10 mol%), HOAc (6 mL, 20 mol%) and CH2Cl2
(1 mL) were added to a 25-mL Young-type tube. The result-
ing mixture was degassed by the freeze-thaw method and
supplied with 1 atm of O2. The mixture was stirred at room
temperature for 18 h, then washed with water, and extracted
with diethyl ether for three times. The organic layer was
dried over anhydrous Na2SO4 and concentrated under re-
duced pressure. The residue was purified by flash column
chromatography on silica gel and eluted with EtOAc/hex-
anes (1/50–1/5) to afford the desired product.
amination reaction. For example, the five-membered
and six-membered cyclic amines also gave the corre-
sponding tertiary amines in high yields. The Boc-pro-
tected amine was also well-tolerated in this reaction
(3ad). For secondary acyclic amines with long aliphat-
ic chain groups, a relatively higher temperature
(458C) was required to smoothly promote the corre-
À
sponding C H amination to afford the desired prod-
ucts in 62–75% yields. The functional group tolerance
of this reaction was demonstrated by 3ai–3an. Reac-
tions using substrates with benzyl groups and hetero-
cyclic groups such as pyridine and furan also afford
the desired tertiary amines in 52–76% yields. Further-
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Cooperative Catalysis with Aldehydes and Copper: Development and Application
Table 3. Oxidative C-H amination via the cooperative catalysis.[a]
[a]
Reaction conditions: 1 (0.6 mmol), 4 (0.5 mmol), CuBr2 (0.05 mmol), HOAc
(0.1 mmol), 2,3-Cl2-C6H3-CHO (0.1 mmol), CH2Cl2 (1.0 mL), O2 (1 atm), at
room temperature for 18 h; isolated yield; yield in parentheses was obtained in
the absence of aldehyde, unless otherwise noted.
[b]
At 458C.
Ma, Q. Cai, Acc. Chem. Res. 2008, 41, 1450; d) D. S.
Acknowledgements
Surry, S. L. Buchwald, Chem. Sci. 2011, 2, 27.
À
[3] For reviews on C H amination: a) P. Mꢂller, C. Fruit,
This work was supported by the Chinese Academy of Scien-
ces and the National Natural Science Foundation of China
(21222203, 21172226 and 21133011).
Chem. Rev. 2003, 103, 2905; b) P. Dauban, R. H. Dodd,
Synlett 2003, 1571; c) F. Collet, R. H. Dodd, P. Dauban,
Chem. Commun. 2009, 5061; d) P. Thansandote, M.
Lautens, Chem. Eur. J. 2009, 15, 5874; e) A. Armstrong,
J. Collins, Angew. Chem. 2010, 122, 2332; Angew.
Chem. Int. Ed. 2010, 49, 2282; f) J. Wencel-Delord, T.
Drçge, F. Liu, F. Glorius, Chem. Soc. Rev. 2011, 40,
4740; g) S. H. Cho, J. Y. Kim, J. Kwak, S. Chang, Chem.
Soc. Rev. 2011, 40, 5068.
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W.-Y. Yu, Org. Lett. 2012, 14, 272; e) C. Grohmann, H.
Wang, F. Glorius, Org. Lett. 2012, 14, 656.
[9] For the reactivity of aminal: a) H. Heaney, G. Papa-
georgiou, R. F. Wilkins, Tetrahedron 1997, 53, 2941;
b) B. Hatano, K. Nagahashi, T. Kijima, J. Org. Chem.
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Przybyla, R. W. Nagorski, Tetrahedron Lett. 2010, 51,
6031.
[10] S. Guo, B. Qian, Y. Xie, C. Xia, H. Huang, Org. Lett.
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[11] a) J. S. Tian, T. P. Loh, Angew. Chem. 2010, 122, 8595;
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Loh, Chem. Commun. 2011, 47, 5458; c) J. S. Tian,
K. W. J. Ng, J. R. Wong, T. P. Loh, Angew. Chem. Int.
Ed. 2012, 51, 9105.
[12] For obtaining a pure CuBr sample and because acid
was not essential for this reaction, the reactions were
conducted in the absence of HOAc to avoid producing
CuOAc.
[13] Other copper sources, including Cu
ACHTUGTNERNNUG(OAc)2, CuACHTUNGTRENNUNG(OTf)2
and Cu(acac)2 were also examined and almost no de-
AHCTUNGTRENNUNG
sired product was observed, suggesting anion, such as
[7] a) A. Erkkilꢃ, I. Majander, P. M. Pihko, Chem. Rev.
2007, 107, 5416; b) S. Mukherjee, J. W. Yang, S. Hoff-
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Int. Ed. 2009, 48, 1360; d) S. Bertelsen, K. A. Jørgen-
sen, Chem. Soc. Rev. 2009, 38, 2178.
OAcÀ and OTfÀ, may not act as base to cleavage the
À
N H bond in this reaction.
[14] Aminals can be easily formed by stirring a solution of
secondary amine in CH2Cl2 at room temperature, see:
J. E. Mills, C. A. Maryanoff, D. F. McComsey, R. C.
Stanzione, L. Scott, J. Org. Chem. 1987, 52, 1857.
À
[8] Although some examples of C H amination of azoles
[15] For disproportionation of Cu(II) to CuACTHUNRTGNEUNG(III) and Cu(I),
had been reported, harsh reaction conditions, stoichio-
metric metals or additional additives were generally re-
quired: a) D. Monguchi, T. Fujiwara, H. Furukawa, A.
Mori, Org. Lett. 2009, 11, 1607; b) Q. Wang, S. L.
Schreiber, Org. Lett. 2009, 11, 5178; c) S. H. Cho, J. Y.
Kim, S. Y. Lee, S. Chang, Angew. Chem. 2009, 121,
9291; Angew. Chem. Int. Ed. 2009, 48, 9127; d) J. Y.
Kim, S. H. Cho, J. Joseph, S. Chang, Angew. Chem.
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e) T. Kawano, N. Matsuyama, K. Hirano, T. Satoh, M.
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M. Wang, W. Su, M. Hong, Adv. Synth. Catal. 2010,
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C. Duan, J. Org. Chem. 2011, 76, 5444; h) S. Wertz, S.
Kodama, A. Studer, Angew. Chem. 2011, 123, 11713;
see: a) A. E. King, T. C. Brunold, S. S. Stahl, J. Am.
Chem. Soc. 2009, 131, 5044; b) A. E. King, L. M. Huff-
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Huang, Z. Yu, Y.-F. Gao, J. Org. Chem. 2012, 77, 4414.
[16] We have confirmed that O atom of H2O and benzalde-
hyde almost cannot exchange in the absence of acid,
thus the incorporation of 18O into the aldehyde can
only proceed from the hydrolysis of the aminal in the
absence of HOAc. For details, see the Supporting Infor-
mation.
[17] Unfortunately, benzthiazoles and benzimidazoles were
not applicable in this reaction under the current reac-
tion conditions.
8
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FULL PAPERS
Cooperative Catalysis with Aldehydes and Copper:
9
À
Development and Application in Aerobic Oxidative C H
Amination at Room Temperature
Adv. Synth. Catal. 2013, 355, 1 – 9
Yinjun Xie, Bo Qian, Pan Xie, Hanmin Huang*
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
9
ÞÞ
These are not the final page numbers!