Cu(II)-catalyzed synthesis of naphthalene-1,3-diamine derivatives from haloalkynes and amines

Article abstract of DOI:10.1021/ol302486h

An efficient procedure for the preparation of naphthalene-1,3-diamine derivatives by copper-catalyzed haloalkynes with amines has been reported. The reaction was supposed to proceed through a coupling reaction followed by the dimerization of ynamines.

Full text of DOI:10.1021/ol302486h

ORGANIC
LETTERS
2012
Vol. 14, No. 21
5385–5387
Cu(II)-Catalyzed Synthesis of
Naphthalene-1,3-diamine Derivatives from
Haloalkynes and Amines
Zhengwang Chen,†,‡ Wei Zeng,† Huanfeng Jiang,*,† and Liangxian Liu‡
School of Chemistry and Chemical Engineering, South China University of Technology,
Guangzhou 510640, People’s Republic of China, and Key Laboratory of
Organo-Pharmaceutical Chemistry of Jiangxi Province, Gannan Normal University,
Ganzhou 341000, People’s Republic of China
jianghf@scut.edu.cn
Received September 10, 2012
ABSTRACT
An efficient procedure for the preparation of naphthalene-1,3-diamine derivatives by copper-catalyzed haloalkynes with amines has been
reported. The reaction was supposed to proceed through a coupling reaction followed by the dimerization of ynamines.
Transition-metal-catalyzed reactions are vital tools for
constructing carbonÀcarbon and carbonÀheteroatom
bonds in organic synthesis, and substantial advances have
been made during the past decades.1 In particular, copper
catalyst systems have been widely applied as a powerful
tool in various synthetic areas, such as for the preparation
of heterocyclic compounds, natural products, pharmaceu-
ticals, and molecular organic materials.2 The field of
ynamide chemistry has experienced rapid development in
the past decade;3 particularly, copper-catalyzed reactions
for the preparation of ynamides have provided efficient,
straightforward, and reliable access to useful building
blocks.4 On the contrary, although ynamine chemistry
has a long history,5 the high reactivity caused much dif-
ficulty in the experimental preparation and general hand-
ling of ynamines and rendered ynamine chemistry inac-
cessible.6 Hence it is a challenge to develop new methods
for preparation and application of ynamines.
Haloalkynesare useful intermediates and versatilebuild-
ing blocks.7 Several mild and convenient methods have been
developed and thus have increased the attractiveness of this
† South China University of Technology.
‡ Gannan Normal University.
(1) For selective reviews, see: (a) Alonso, F.; Beletskaya, I. P.; Yus, M.
Chem. Rev. 2004, 104, 3079. (b) Nakamura, I.; Yamamoto, Y. Chem.
Rev. 2004, 104, 2127. (c) Punniyamurthy, T.; Velusamy, S.; Iqbal, J.
Chem. Rev. 2005, 105, 2329. (d) Beletskaya, I.; Moberg, C. Chem. Rev.
2006, 106, 2320. (e) Willis, M. C. Chem. Rev. 2010, 110, 725. (f) Bellina,
F.; Rossi, R. Chem. Rev. 2010, 110, 1082. (g) Beletskaya, I. P.; Ananikov,
V. P. Chem. Rev. 2010, 110, 725. (h) Wu, W.; Jiang, H. Acc. Chem. Res.
2012, 45, 1736.
(2) For selective reviews on copper-catalyzed cross-couplings, see:
(a) Liu, Y.; Wan, J.-P. Chem. Asian J. 2012, 7, 1488. (b) Rao, H.; Fu, H.
Synlett 2011, 745. (c) Monnier, F.; Taillefer, M. Angew. Chem., Int. Ed.
2009, 48, 6954. (d) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev.
2008, 108, 3054. (e) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem.
Rev. 2004, 248, 2337. (f) Ley, S. V.; Thomas, A. W. Angew. Chem., Int.
Ed. 2003, 42, 5400. (g) Kunz, K.; Scholz, U.; Ganzer, D. Synlett 2003,
2428.
(4) For selective examples, see: (a) Frederick, M. O.; Mulder, J. A.;
Tracey, M. R.; Hsung, R. P.; Huang, J.; Kurtz, K. C. M.; Shen, L.;
Douglas, C. J. J. Am. Chem. Soc. 2003, 125, 2368. (b) Dunetz, J. R.;
Danheiser, R. L. Org. Lett. 2003, 5, 4011. (c) Zhang, Y.; Hsung, R. P.;
Tracey, M. R.; Kurtz, K. C. M.; Vera, E. L. Org. Lett. 2004, 6, 1151.
(d) Zhang, X.; Zhang, Y.; Huang, J.; Hsung, R. P.; Kurtz, K. C. M.;
Oppenheimer, J.; Petersen, M. E.; Sagamanova, I. K.; Shen, L.; Tracey,
M. R. J. Org. Chem. 2006, 71, 4170. (e) Dooleweerdt, K.; Birkedal, H.;
Ruhland, T.; Skrydstrup, T. J. Org. Chem. 2008, 73, 9447. (f) Jouvin, K.;
Couty, F.; Evano, G. Org. Lett. 2010, 12, 3272. (g) Coste, A.; Karthi-
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(5) (a) Bode, J. Liebigs Ann. Chem. 1892, 267, 268. (b) Zaugg, H. E.;
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(3) For recent reviews on ynamides, see: (a) Evano, G.; Coste, A.;
Jouvin, K. Angew. Chem., Int. Ed. 2010, 49, 2840. (b) DeKorver, K. A.;
Li, H.; Lohse, A. G.; Hayashi, R.; Lu, Z.; Zhang, Y.; Hsung, R. P. Chem.
Rev. 2010, 110, 5064. (c) Zificsak, C. A.; Mulder, J. A.; Hsung, R. P.;
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Organischen Chemie (Houben-Weyl); Kropf, H., Schaumann, E., Eds.;
Georg Thieme Verlag: Stuttgart, 1993; p 3267. (b) Collard-Motte, J.;
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r
10.1021/ol302486h
2012 American Chemical Society
Published on Web 10/18/2012

class of compounds in organic synthesis.8,9 Recently, our
group has reported transition-metal-catalyzed bond for-
mation reactions, nucleophilic additions, and homocou-
pling reactions of haloalkynes.10 As part of our continuing
project in the functionalization of haloalkynes, here we
wish to report the first copper-catalyzed one-pot domino
synthesis of naphthalene derivatives from haloalkynes and
amines. Theynaminewasconsidered to be the intermediate
in this transformation process. It is important to note that,
very recently, Skrydstrup’s group reported an unprece-
dented dimerization reaction of ynamides in the presence
of gold(I) catalysis.11 The aryl-substituted ynamides could
be transformed into a mixture of three kinds of products,
and the naphthalene derivatives were one of the products.
Therefore, the development of new strategies for con-
structing naphthalene derivatives with expedient condi-
tions and high efficiency remains an extremely attractive
task for organic chemists.
effective (Table 1, entries 6À9). To our delight, Cu(BF4)2
3
6H2O was superior to any other copper catalyst so far tested
and could afford the desired product with 88% isolated yield,
and the side product was mainly the 1,3-diyne from the
homocoupling of phenylethynyl bromide with 10% isolated
yield (Table 1, entry 10). Only trace product was detected
using KBF4 as the catalyst instead (Table 1, entry 11). Then
Cu(BF4)2 6H2O was used as the catalyst of choice. The
3
reaction showed a strong solvent dependence. Except for
the corresponding amine, other organic solvent and water
were proven to be inappropriate for the reaction (Table 1,
entries 12À16). The lower temperature disfavored the reac-
tion (Table 1, entry 17). After some attempts, we considered
that the optimized reaction conditions are as follows: 1a
(1 mmol) with amine (1 mL) and Cu(BF4)2 6H2O (5 mol %)
at 80 °C for 6 h (Table 1, entry 10).
3
The reaction of phenylethynyl bromide (1a) with diethy-
lamine (2a, 1 mL) was chosen as the model reaction. First,
four different commonly used metal salts were used as the
catalyst to conduct this reaction. We found that CuI could
afford the naphthalene-1,3-diamine in 36% yield (Table 1,
entry 4). The reaction did not proceed without copper salt
(Table1, entry5). Different copperspecieswerealsotested.
Cu(OAc)2, CuO, CuBr2, and Cu(CF3SO3)2 were also less
Scheme 1. Copper-Catalyzed Synthesis of Naphthalene-1,3-
diamine Derivativesa
Table 1. Optimization of Reaction Conditions for the Synthesis
of Naphthalene-1,3-diaminea
entry
catalyst
Pd(OAc)2
solvent
yieldb (%)
1
NHEt2
NHEt2
NHEt2
NHEt2
NHEt2
NHEt2
NHEt2
NHEt2
NHEt2
NHEt2
NHEt2
CH3CN
DMF
np
np
np
36
2
AgBF4
FeCl3
CuI
3
4
5c
6
np
51
Cu(OAc)2
CuO
7
40
8
CuBr2
20
9
Cu(CF3SO3)2
46
10
11
12d
13
14
15
16
17e
Cu(BF4)2 6H2O
88
3
KBF4
trace
43
Cu(BF4)2 6H2O
3
Cu(BF4)2 6H2O
13
3
Cu(BF4)2 6H2O
toluene
DMSO
water
52
3
Cu(BF4)2 6H2O
27
3
Cu(BF4)2 6H2O
trace
45
3
Cu(BF4)2 6H2O
NHEt2
3
a Reaction conditions: phenylethynyl bromide (1.0 mmol), solvent
(1.0 mL), and catalyst (5 mol %) at 80 °C for 6 h. b Isolated yield.
c Without catalysis. d Reactions were reacted with other organic solvent
or water (1.0 mL) and diethylamine (3.0 mmol) in entries 12À16. e Room
temperature.
a Reaction conditions: haloalkyne (1.0 mmol), the corresponding amine
(1.0 mL), and Cu(BF4)2 6H2O (5 mol %) at 80 °C for 6 h. Isolated yields.
3
5386
Org. Lett., Vol. 14, No. 21, 2012

With the success in finding the optimum reaction con-
ditions (Table 1, entry 10), the scope and the utility of this
method with other haloalkynes and amines under the
standard conditions were then investigated in detail. As
summarized in Scheme 1, aromatic alkynyl bromides or
iodides with either an electron-donating or electron-with-
drawing group on the benzene ring were able to generate
the corresponding products in moderate to good yields,
and alkynyl bromides gave naphthalene-1,3-diamine deri-
vatives in better yields as compared to the corresponding
alkynyl iodides (3aÀo). Clearly, the electronic effect plays
an important role, as electron-rich substituents on the
benzene ring favored the transformation. The reaction
conditions were compatible with alkyl, alkyloxy, fluoro,
chloro, bromo, and trifluoromethyl groups (3eÀo). It is
noteworthy that the aryl bromides and chlorides could
further realize varieties of transformations under transition-
metal-catalyzed conditions (3l, 3m, and 3n). Interestingly,
for the meta-substituted aromatic 1-bromoalkynes, the
reaction could afford the corresponding products regios-
pecifically (3g and 3m). Unfortunately, substitution
at the ortho-position of the aromatic ring was ineffec-
tive in the reaction conditions. On the other hand, the
structure of the amine was important for the reaction.
Scheme 2. Formation of 2-Substituted 1,1-Ethenediamine
Derivatives
The alkyl-substituted secondary amines could afford the
corresponding products successfully.
Subsequently, 2-trifluoromethyl- and 3,5-bis(trifluoro-
methyl)-substituted phenylethynyl bromides were reacted
under the standard conditions (Scheme 2). However, we
were surprised that the 2-substituted 1,1-ethenediamine
derivatives were formed in good yields instead of naphtha-
lene-1,3-diamine derivatives. 1,1-Enediamines, also called
ketene N,N-acetals or ketene aminals, are useful intermedi-
ates in organic synthesis.12 However, their exceptional
reactivity renders their preparation, storage, and handl-
ing difficult, which accounts for how seldom they have
beeninvestigatedinorganicsynthesis. Here, the CF3 onthe
benzene ring contributed to the delocalization of the pairs
on the double bond and strengthened the stability of
ynamine intermediates and ketene aminal products.
In summary, we have described the first example of
copper-catalyzed synthesis of naphthalene-1,3-diamine
derivatives. This reaction appears to involve two consecu-
tive processes, the formation of ynamines from haloalky-
nes with amines and the dimerization of ynamines. The
mild reaction conditions, simple substrate preparation,
and one-pot operation of this procedure are attractive
aspects for organic synthesis. Although some disadvan-
tages exist in the transformation, such as limited scope and
use of a large excess of amine, the reaction is an important
application of haloalkynes and paves a way for the devel-
opment of ynamine chemistry. Further studies on this new
process are currently underway in our laboratory.
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Acknowledgment. The authors thank the NSFC(21162001,
20932002, and 21172076), National Basic Research Pro-
gram of China (973 Program) (2011CB808600), NSF of
Jiangxi Province (20114BAB213006), and the NSF of
Jiangxi Provincial Education Department (GJJ12579)
for financial support.
€
(11) Kramer, S.; Odabachian, Y.; Overgaard, J.; Rottlander, M.;
Supporting Information Available. Typical experimen-
tal procedure and characterization for all products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
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The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 21, 2012
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