Highly efficient copper-catalyzed hydroacylation reaction of aldehydes with azodicarboxylates

Article abstract of DOI:10.1016/j.tetlet.2011.08.165

The hydroacylation reaction of aldehydes with azodicarboxylates catalyzed by copper(II) acetate monohydrate has been reported. The reaction of various aldehydes gave the corresponding hydroacylation products in 60-98% yields under mild conditions. The met

Full text of DOI:10.1016/j.tetlet.2011.08.165

Tetrahedron Letters 52 (2011) 5880–5883
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Highly efficient copper-catalyzed hydroacylation reaction of aldehydes
with azodicarboxylates
⇑
Yuancheng Qin, Qiang Peng , Jinsheng Song, Dan Zhou
School of Environmental and Chemical Engineering, Nanchang Hangkong University, Nanchang 330063, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The hydroacylation reaction of aldehydes with azodicarboxylates catalyzed by copper(II) acetate mono-
hydrate has been reported. The reaction of various aldehydes gave the corresponding hydroacylation
products in 60–98% yields under mild conditions. The method is simple, economical, and has practical
advantages for the construction of the carbon–nitrogen bonds.
Received 7 April 2011
Revised 27 August 2011
Accepted 30 August 2011
Available online 2 September 2011
Crown Copyright Ó 2011 Published by Elsevier Ltd. All rights reserved.
Keywords:
Hydroacylation
Copper catalyst
Azo compounds
Aldehydes
Formation of C–N bond is considered to be an important strat-
egy that finds wide applications in the synthesis of many sub-
stances such as drugs, materials, and natural products.1 During
the last few decades, the enormous progress has been made in
the application of polar, pericyclic, and radical reactions in such
bond construction.1,2 Dialkyl azodicarboxylates, with a central
azo functionality flanked by two carboalkoxy groups, are excellent
electrophiles and can readily participate in the zwitterion forma-
tion. They are commercially available. So, over the last few dec-
mild conditions to provide the hydrazine imides.8 However, rela-
tively low yields were obtained when the aromatic aldehydes were
used as the substrates for this method. In addition, very costly
Table 1
Optimization of the reaction condition for benzaldehyde with diisopropyl
azodicarboxylatea
ades,
a very efficient reaction, which involves the use of
O
O
O
N
Cu(OAc)2 H2O
O
azodicarboxylates as electrophiles, has been successfully used for
such carbon–nitrogen bond formation. There are many types of
reactions involving azodicarboxylates that have been studied
extensively for the formation of C–N bond, such as the zwitterion
+
CHO
N
O
O
N
O
N
H
O
solvent, r.t., 48 h
O
1
Entry
Solvent
Cu (mol %)
Yieldb (%)
intermediate reactions,3
the C–H activation at the
a
-amination of carbonyl compounds,4
-position of amines and ethers,5 and
1
2
3
4
5
6
7
8
9
EtOAc
MeCN
MeOH
THF
CH2Cl2
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
20
20
20
20
20
0
10
15
30
20
20
98
90
72
60
52
a
the ene-type reaction with olefins.6 But the direct hydroacylation
reaction, which involves aldehydes has not been studied
extensively.7
<5
84
Hydroacylation reaction with the direct functionalization of the
aldehydic C–H to form a variety of hydrazine imides is a highly effi-
cient synthetic methodology to form a carbon–nitrogen bond. But
they often result in low yields and only a narrow scope of the sub-
strates can be used under photolytic or thermal conditions.7 The
transition-metal catalyst, rhodium acetate, has proven to be an
effective catalyst for the hydroacylation reaction involving aliphatic
saturated or unsaturated aldehydes with azodicarboxylates under
87
98c
90d
82e
10
11
a
Reaction conditions: diisopropyl azodicarboxylate (0.5 mmol), benzaldehyde
(1 mmol), catalyst, solvent (5 mL), rt, 48 h.
b
Isolated by silica gel column chromatography and based on diisopropyl
azodicarboxylate.
c
The reaction time was 36 h.
The ratio of benzaldehyde to diisopropyl azodicarboxylate was 1.5:1.
The ratio of benzaldehyde to diisopropyl azodicarboxylate was 1.2:1.
d
⇑
Corresponding author. Tel./fax: +86 07913953369.
E-mail address: qiangpengjohnny@yahoo.com (Q. Peng).
e
0040-4039/$ - see front matter Crown Copyright Ó 2011 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.08.165

Y. Qin et al. / Tetrahedron Letters 52 (2011) 5880–5883
5881
Table 2
Hydroacylation of aldehydes with azobicarboxylatesa
O
R
O
O
Cu(OAc)
2 H2O
EtOAct, r.t.
O
N
O
R CHO+
N
O
O
N
O
N
H
O
Entry
1
Aldehyde
CHO
Time (h)
Product
Yieldb (%)
O
O
O
N
48
24
98
86
N
H
O
O
1
H3CO
O2N
Br
H3CO
O2N
Br
CHO
O
O
O
2
3
4
O
N
N
H
O
O
2
CHO
O
O
96
48
O
N
67
82
N
H
O
3
CHO
O
O
O
N
N
H
O
O
4
N
CHO
N
O
O
5
96
60
O
S
N
N
H
O
O
5
S
O
CHO
O
O
O
N
6
7
72
16
72
97
N
H
O
O
O
6
S
S
O
CHO
O
N
N
H
O
7
n-C12H25
C12H25
S
S
O
O
N
CHO
8
48
86
80
O
N
N
H
O
O
O
8
O
O
CHO
9
36
12
N
H
O
O
O
9
C11H23
O
O
O
N
N
H
O
10
n-C11H23-CHO
97
10
(continued on next page)

5882
Y. Qin et al. / Tetrahedron Letters 52 (2011) 5880–5883
Table 2 (continued)
Entry
Aldehyde
Time (h)
20
Product
Yieldb (%)
CHO
O
O
O
O
O
O
N
11
N
N
H
O
11
12
96
O
O
CHO
O
N
H
O
O
8
99
98
12
O
C6H13
O
N
N
H
13
n-C6H13-CHO
10
O
13
a
Reaction conditions: diisopropyl azodicarboxylate (0.5 mmol), aldehyde (1 mmol), copper(II) acetate monohydrate (0.1 mmol), EtOAc (5 mL), rt.
Isolated by silica gel column chromatography and based on diisopropyl azodicarboxylate.
b
precious metalsare used. Ni et al. have demonstrated that the hydro-
9). The effect of the ratio of benzaldehyde to diisopropyl azodicar-
boxylate was also investigated. Lower ratio of benzaldehyde to
diisopropyl azodicarboxylate led to lower reaction yield (Table 1,
entries 10 and 11).
acylation reaction can be carried out successfully in the presence of
the ionic liquid, 1-n-butyl-3-methylimidazolium bis(trifluorome-
thane sulfonyl)imide without the use of a catalyst9a and they also re-
ported that the reaction can be carried out successfully in water
without the use of a catalyst.9b However, the reaction gives rela-
tively low yields and requires a long time when the aromatic alde-
hydes are used as the substrates. Therefore, it is highly desirable to
develop a more efficient procedure while broadening the scope of
the substrates without the use of an expensive catalyst.
Copper stands out as a convenient alternative to costly precious
metals, because copper salts are often cheap and environmentally
benign. Copper catalysts have been proved to be active and versa-
tile in many types of reactions.10 To the best of our knowledge,
there has been no general study on the hydroacylation reaction be-
tween aldehydes and azodicarboxylates catalyzed by the copper
catalysts. We report here that the copper-catalyzed hydroacylation
between aldehydes and azodicarboxylates can provide the hydra-
zine imides in moderate to excellent yields under mild and li-
gand-free conditions.
Initially, the hydroacylation reaction between benzaldehyde
with diisopropyl azodicarboxylate was selected as a model reac-
tion for optimizing the reaction conditions. Firstly, we studied
the effect of various solvents for the hydroacylation reaction. As
shown from the results summarized in Table 1, the reaction pro-
ceeded smoothly in conventional organic solvents, such as MeOH,
CH3CN, and EtOAc. The isolated yields were significantly influ-
enced by the solvent employed. Among the solvents tested, EtOAc
was proven to be the best compared to the others (Table 1, entry
1). When MeCN was used as the solvent, the desired hydroacyla-
tion product was obtained in high yields, 90% (Table 1, entry 2).
Methanol and THF could also provide relatively good yields of
the desired hydroacylation products (Table 1, entries 3 and 4). Rel-
atively low yields were obtained when dichloromethane was used
as a solvent (Table 1, entry 5).
The effect of catalyst loading on the cross-coupling reaction is
shown in Table 1. Poor yields were obtained without the use of a
catalyst (Table 1, entry 6).9 The amount of the copper(II) acetate
monohydrate employed in the reaction is of importance. When
the catalyst loading was less than 15 mol %, the yield of the corre-
sponding product was relatively lower (Table 1, entries 7 and 8). A
yield of 98% was obtained when 20 mol % Cu(OAc)2 was applied
(Table 1, entry 1), and the yield was not apparently improved fur-
ther when the catalyst loading was more than 30 mol %. Only dif-
ferent reaction rate was observed for the reaction (Table 1, entry
Under our optimized reaction conditions, the scope of this
hydroacylation reaction was then explored. A variety of aldehydes
were examined for the hydroacylation reactions. As shown in Table
2, most of the hydroacylation reactions afforded the hydroacylation
products in good to excellent yields. Aromatic aldehydes were good
substrates for this reaction and afforded the hydroacylation prod-
ucts in good to excellent yields. The hydroacylation reactions with
benzaldehyde provided the desired products 1 in excellent yields
(Table 2, entry 1). To our knowledge, this is the highest yields re-
ported so far. The aromatic aldehydes, bearing either electron-with-
drawing or electron-donating groups, gave the hydroacylation
products 2–4 in good yields (Table 2, entries 2–4). These results
are superior to that obtained by Lee8 and Ni,9 in which rhodium ace-
tate catalyst and ionic liquid are used. To broaden the scope of the
reaction, heterocyclic aldehydes were used in the reaction and also
gave the desired products in good to excellent yields (72–97%, Table
2, entries 6–8). Especially the hydroacylation reaction with thio-
phene-3-carbaldehyde provided the desired product 7 in excellent
yield (Table 2, entry 7). The trans-cinnamaldehyde also provided
the desired product in good yield (Table 2, entry 9). The aliphatic
saturated aldehydes, with either linear or branched substituents
were treated with diisopropyl azodicarboxylated to give the desired
products in excellent yields (96–99%, Table 2, entries 10–13).
At present, the mechanism for the hydroacylation reaction is still
not clear. It was described in previous studies that the hydroacyla-
tion of aldehydes with azodicarboxylate considered to proceed by a
radical intermediate mechanism.7–10 In a radical mechanism, cop-
per initiates the radical chain process by transferring its one elec-
tron in previous studies.11,12 Therefore, we assume that the
hydroacylation reaction still proceed via a radical mechanism
(Scheme 1). This radical mechanism is supported by a complete
inhibition of the reaction when it was run with as low as 4 mol %
of radical scavenger (hydroquinone). When 0.5, 1, 2, or 3 mol % rad-
ical scavenger was applied, the yields were 61%, 52%, 16%, and 10%.
In conclusion, we have developed a highly efficient copper-cat-
alyzed hydroacylation reaction of aldehydes with azobicarboxy-
lates, the corresponding target products were obtained in good to
excellent yields, and an array of functional groups are tolerated un-
der the mild conditions with respect to the aldehydes. The protocol
used inexpensive copper(II) acetate monohydrate as the catalyst,
no additional ligand and additive were required, so the method

Y. Qin et al. / Tetrahedron Letters 52 (2011) 5880–5883
5883
O
References and notes
1. (a) Nair, V.; Biju, A. T.; Mathew, S. C.; Babu, B. P. Chem. Asian J. 2008, 3, 810; (b)
Nair, V.; Menon, R. S.; Sreekanth, A. R.; Abhilash, N.; Biju, A. T. Acc. Chem. Res.
2006, 39, 520.
R'
H
2. (a) Shen, B.; Makley, D. M.; Johnston, J. N. Nature 2010, 465, 1027; (b)
Thansandote, P.; Chong, E.; Feldmann, K.; Lautens, M. J. Org. Chem. 2010, 75,
3495; (c) Shen, H.; Xie, Z. J. Am. Chem. Soc. 2010, 132, 11473; (d) Mantel, M. L.
H.; Lindhardt, A. T.; Lupp, D.; Skrydstrup, T. Chem. Eur. J. 2010, 16, 5437; (e)
Wang, S.; Wang, Z.; Zheng, X. Chem. Commun. 2009, 7372.
3. (a) Nair, V.; Biju, A. T.; Mohanan, K.; Suresh, E. Org. Lett. 2006, 8, 2213; (b) Otte,
R. D.; Sakata, T.; Guzei, I. A.; Lee, D. Org. Lett. 2005, 7, 495; (c) Nair, V.; Biju, A. T.;
Abhilash, K. G.; Menon, R. S.; Suresh, E. Org. Lett. 2005, 7, 2121; (d) Nair, V.; Biju,
A. T.; Vinod, A. U.; Suresh, E. Org. Lett. 2005, 7, 5139.
O
R
R
N
NH
R'
O
R
N N R
R'
4. (a) Zhu, R.; Zhang, D.; Wu, J.; Liu, C. Tetrahedron: Asymmetry 2007, 1655, 18; (b)
Mashiko, T.; Hara, K.; Tanaka, D.; Fujiwara, Y.; Kumagai, N.; Shibasaki, M. J. Am.
Chem. Soc. 2007, 129, 11342; (c) Thomassigny, C.; Prim, D.; Greck, C.
Tetrahedron Lett. 2006, 47, 1117; (d) Liu, X.; Li, H.; Deng, L. Org. Lett. 2005, 7,
167; (e) Marigo, M.; Juhl, K.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2003, 42,
1367; (f) Erdik, E. Tetrahedron 2004, 60, 8747; (g) Greck, C.; Drouillat, B.;
Thomassigny, C. Eur. J. Org. Chem. 2004, 1377.
5. (a) Doleschall, G. Tetrahedron Lett. 1978, 19, 2131; (b) Abarca, B.; Ballesteros, R.;
Gonzalez, E.; Sancho, P.; Sepulveda, J.; Soriano, C. Heterocycles 1990, 31, 1811;
(c) Reliquet, A.; Besbes, R.; Reliquet, F.; Meslin, J. C. Phosphorus, Sulfur Silicon
Relat. Elem. 1992, 70, 211; (d) Denis, A.; Renou, C. Tetrahedron Lett. 2002, 43,
4171.
O
R
R
N
N
O
R'
H
R'
Scheme 1. Mechanism for the hydroacylation reaction.
6. (a) Hoffmann, H. M. R. Angew. Chem., Int. Ed. Engl. 1969, 8, 556; (b) Stephenson,
L. M.; Mattern, D. J. Org. Chem. 1976, 41, 3614; (c) Grigg, R.; Kemp, J. J. Chem.
Soc., Chem. Commun. 1977, 125; (d) Dang, H. S.; Davies, A. G. J. Chem. Soc., Perkin
Trans. 2 1991, 721; (e) Leblanc, Y.; Zamboni, R.; Bernstein, M. A. J. Org. Chem.
1991, 56, 1971; (f) Brimble, M. A.; Heathcock, C. H. J. Org. Chem. 1993, 58, 5261;
(g) Kinart, W. J. J. Chem. Res., Synop. 1994, 486; (h) Sarkar, T. K.; Ghorai, B. K.;
Das, S.; Grangopadhyay, P.; Rao, S. Tetrahedron Lett. 1996, 37, 6607; (i) Aly, A.
A.; Ehrhardt, S.; Hopf, H.; Dix, I.; Jones, P. G. Eur. J. Org. Chem. 2006, 335; (j)
Biswas, A.; Sharma, B. K.; Willett, J. L.; Erhan, S. Z.; Cheng, H. N. Green Chem.
2008, 10, 298.
7. (a) Schenck, G. O.; Formaneck, H. Angew. Chem. 1958, 70, 505; (b) Alder, K.;
Noble, T. Ber. Dtsch. Chem. Ges. 1943, 54; (c) Huisgen, R.; Jakob, F. Liebigs Ann.
Chem. 1954, 590, 37; (d) González-Rosende, M. E.; Lozano-Lucia, O.; Zaballos-
Garcia, E.; Sepúlveda-Arques, J. J. Chem. Res., Synop. 1995, 260; (e) Zaballos-
García, E.; González-Rosende, M. E.; Jorda-Gregori, J. M.; Sepúlveda-Arques, J.;
Jennings, W. B.; O’Leary, D.; Twomey, S. Tetrahedron 1997, 53, 9313.
8. (a) Lee, D.; Otte, R. D. J. Org. Chem. 2004, 69, 3569; (b) Kim, Y. J.; Lee, D. Org. Lett.
2004, 6, 4351.
is simple, economical, and has practical advantages for the con-
struction of the carbon–nitrogen bonds.
Acknowledgments
The work was financially supported by the Natural Science
Foundation of China (Grant No. 20802033), Program for New Cen-
tury Excellent Talents in University (Grant No. NCET-10-0170),
Yong Scientist of Jing Gang Zhi Xing Project of Jiangxi Province
(Grant No. 2008DQ00700) and Natural Science Foundation of
Jiangxi Province (Grant No. 2010GZH0110).
9. (a) Ni, B.; Zhang, Q.; Garre, S.; Headley, A. D. Adv. Synth. Catal. 2009, 351, 875;
(b) Zhang, Q.; Parker, E.; Headley, A. D.; Ni, B. Synlett 2010, 2453.
10. Chudasama, V.; Fitzmaurice, R. J.; Caddick, S. Nature Chem. 2010, 2, 592.
11. Metzger, J. O.; Mahler, R. Angew. Chem., Int. Ed. Engl. 1995, 34, 902.
12. Ranu, B. C.; Saha, A.; Jana, R. Adv. Synth. Catal. 2007, 349, 2690.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.08.165.