Copper(I)-catalyzed reaction of diaryl buta-1,3-diynes with cyclic amines: An atom-economic approach to amino-substituted naphthalene derivatives

Article abstract of DOI:10.1016/j.tetlet.2011.06.046

1,4-Diaryl-1,3-butadiynes react with cyclic amines, such as pyrrolidine, piperidine, and morpholine in the presence of a catalytic amount of CuCl to afford amino-substituted naphthalene derivatives with good to high yields. The new catalytic procedure pro

Full text of DOI:10.1016/j.tetlet.2011.06.046

Tetrahedron Letters 52 (2011) 4408–4411
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Tetrahedron Letters
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Copper(I)-catalyzed reaction of diaryl buta-1,3-diynes with cyclic amines:
an atom-economic approach to amino-substituted naphthalene derivatives
Hongbin Sun b, Xiaoli Wu b, Ruimao Hua a,c,
⇑
a Department of Chemistry, Tsinghua University, Beijing 100084, China
b Department of Chemistry, Northeastern University, Shenyang 110004, China
c State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
a r t i c l e i n f o
a b s t r a c t
Article history:
1,4-Diaryl-1,3-butadiynes react with cyclic amines, such as pyrrolidine, piperidine, and morpholine in the
presence of a catalytic amount of CuCl to afford amino-substituted naphthalene derivatives with good to
high yields. The new catalytic procedure provides an atom-economic, one-pot synthetic method for the
synthesis of naphthalene derivatives from easily available 1,4-diaryl-1,3-butadiynes.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 2 May 2011
Revised 5 June 2011
Accepted 10 June 2011
Available online 17 June 2011
Keywords:
Cuprous chloride
Cyclic amine
Diaryl buta-1,3-diyne
Naphthalene derivatives
The attractive advantages of the cycloaddition using alkyne as
reaction partner to afford functionalized cyclic compounds are its
high-atom efficiency, one-pot procedure, and easily available start-
ing materials.1 The selective activation of C–H bond of aromatic
compounds by the effect of ortho-substituent and its intramolecular
cyclization to benzo-fused cyclic compounds is a very interesting
process to organic chemists since not only the chemoselectivity of
reaction is expectable, but also the structures of products are highly
designable. As part of our ongoing research program on the
development of cycloaddition reactions of alkynes synthesizing car-
bocyclic and heterocyclic compounds,2 we are interested in devel-
oping the atom-economic and one-pot reaction to construct the
functionalized naphthalene derivatives, and we design a new syn-
thetic route involving the selective intermolecular hydro-hetero-
functionalization affording enyne intermediate and its subsequent
intramolecular hydroarylation to afford naphthalenes having E
groups (Scheme 1, E: heteroatom groups, such as R2N, R3Si, R3Sn,
etc.). In this Letter, we would like to report the first example of the
formation of amino-substituted naphthalene derivatives by this
new protocol from the reaction of 1,4-diaryl-1,3-butadiynes with
cyclic amines.3
R
R
intermolecular hydro-
heterofunctionalization
E
R'
+
H E
H
enyne
E
R'
intramolecular
hydroarylation
R
E = NR'2, SiR3, SnR3, etc.
R'
Scheme 1. Strategy for funtionalized napthalene derivatives.
Therefore, we conducted the reaction of 1,4-diphenyl-1,3-but-
adiyne (1a)6 with secondary amines, such as Bu2NH, Et2NH, and
pyrrolidine under different reaction conditions, and found that
the use of Bu2NH and Et2NH resulted in no catalytic reaction, but
pyrrolidine (2a), a cyclic amine showed reactivity to give a cyclic
compound. As concluded in Table 1, when a solution of 1a, 2a
(4.0 equiv), and CuCl (5 mol %) in toluene in an air atmosphere in
a sealed tube was heated at 60, 80, and 100 °C for 6 h, the conver-
sion of 1a was in a range of 8–20% by GC analyses of the reaction
mixture (Table 1, entries 1–3). The formation of a new compound
with a molecular weight of 342 was determined by GC–MS analy-
sis, its structure was assigned as 1-phenyl-2,4-bis(N-pyrrolidi-
nyl)naphthalene (3a) by its 1H-, 13C-NMR, mass spectroscopy,
elemental analysis, and further confirmed by X-ray crystallography
(Fig. 1).7
We decided to use cuprous halides as catalysts to investigate
such type of reaction, since cuprous halides have greatly attracted
interests as versatile catalysts in diverse organic synthesis4 and
showing high catalytic activity for the hydroamination of alkynes.5
⇑
Corresponding author. Fax: +86 10 62771149.
E-mail address: ruimao@mail.tsinghua.edu.cn (R. Hua).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.06.046

H. Sun et al. / Tetrahedron Letters 52 (2011) 4408–4411
4409
Table 1
Copper-catalyzed reaction of 1,4-diphenyl-1,3-butadiyne (1a) with pyrrolidine (2a)a
N
Ph
cat. (5 mol%)
air, 6 h
+
NH
N
1a
2a
3a
Entry
Catalyst
Solvent
Pyrrolidine (equiv)
Temp (°C)
Conv. of 1ab (%)
1
2
3
4
5
6
7
8
9
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuBr
CuI
Toluene
Toluene
Toluene
THF
DMF
DMSO
4.0
4.0
4.0
4.0
4.0
60
80
100
80
80
80
80
80
80
80
8
12
20
7
9
6
>99 (83)
>99
>99
4.0
30.0
30.0
30.0
30.0
10
CuCl2
>99 (86)
a
Unless otherwise noted, reactions were carried out using 1.0 mmol of 1a and 2.0 mL of solvent if used.
Conversion was determined by GC, and numbers in parentheses are isolated yields of 3a.
b
NR2
H
R2NH
CuCl
Ph
H
1a
A
Ph
NR2
NR2
R2NH
2H
Cl
Cu
Cl
Cu
H
R2N
B
C
Ph
Ph
R2N
NR2
CuCl
NR2
NR2
Cu
Ph
D
3
Ph
Cl
Scheme 2. Proposed mechanism for naphthalenes formation.
with one molecule of 1a, accompanied with the elimination of
two protons. Therefore, on the basis of the new protocol shown
in Scheme 1, a slightly modified possible mechanism for the forma-
tion of naphthalene derivatives 3 is shown in Scheme 2. It involves
the intermolecular hydroamination of 1a with amine 2 to give en-
amine intermediate A, the coordinated copper to selectively acti-
vate the ortho-C–H bond of benzene ring forming intermediate B,
which reacts with other amine to afford Cu-NR2 intermediate C,
subsequent intramolecular amination of C–C triple bond and
reductive elimination of C–C bond furnishing 3. Although, at pres-
ent we do not have any straightforward experimental results to
support the formation of these proposed intermediates, the follow-
ing known copper chemistry is useful for understanding the pro-
posed mechanism: (1) both Cu(I) and Cu(II) have been confirmed
to be the efficient catalysts for the hydroamination of alkynes5;
(2) there are many reports on the CuH-catalyzed organic transfor-
mations8; (3) the examples of copper compounds having copper-
nitrogen bond9 and Cu(III) compounds10 have appeared; (4) Ar-
Cu(III)-(NR2)(X) was proposed as the intermediate in the cop-
per(I)-promoted C–N bond formation.11
Figure 1. Molecular structure of 3a.
Repeating the same reaction under other solvents, such as THF,
DMF, and DMSO was not effective either (Table 1, entries 4–6). For-
tunately, we found that the reaction proceeded smoothly when
much more excess amount of 2a (30.0 equiv) was used as the reac-
tion partner as well as solvent to afford 3a in 83% isolated yield
(entry 7). In addition to CuCl, CuBr, and CuI have the similar cata-
lytic activity (Table 1, entries 8 and 9), and CuCl2 also shows high
catalytic activity for the formation of 3a (Table 1, entry 10). It
should be noted that under a nitrogen atmosphere the present
cyclization could also efficiently occur.
Since the expected structure of naphthalene derivative has only
one amino group from the cyclization of one molecule of 1,3-diyne
with one molecule of amine via the reaction route as shown in
Scheme 1, thus it is apparent that the formation of 3a having dia-
mino groups resulted from the reaction of two molecules of 2a
In the presence of CuCl, several 1,4-diaryl-1,3-butadiynes with
electron-donating or electron-withdrawing groups in benzene ring

4410
H. Sun et al. / Tetrahedron Letters 52 (2011) 4408–4411
were examined. As shown in Table 2, by slightly modifying the
reaction conditions, 1,3-butadiynes having both electron-rich and
electron-deficient groups underwent the present cyclization with
2a or piperidine (2b) providing the corresponding naphthalene
derivatives in good yields. With the purpose of introducing the
amino group which can be further easily transferred, so as to ex-
tend the application of products in organic synthesis, we then
chose morpholine (2c) as the cyclic amine to successfully introduce
morpholinyl groups in the naphthalene ring. It is expected that
morpholinyl-substituted naphthalenes are much more useful com-
pounds in organic synthesis via the cleavage of C–O bond.
When unsymmetrical 1,4-diaryl-1,3-diynes were employed,
two isomers of naphthalenes were usually formed. For example,
the cyclization of 1-(4-methoxyphenyl)-4-phenyl-1,3-butadiyne
with 2a afforded a mixture of two isomers (3h) in 78% total yields,
but each isomer could not be obtained in their analytic purity by
column chromatography or preparative TLC separation.
1,4-diaryl-1,3-diynes and the cheap catalyst made the presented
procedure an unequivocal alternative synthetic method for func-
tionalized naphthalene derivatives, which are not easily prepared
by traditional known organic transformations. Further studies on
the cyclization of arylated 1,3-butadiyne in the reactions with
other hydrogen–heteroatom bonds are ongoing in our laboratory.
A typical experimental procedure for the reaction of 1,4-diphe-
nyl-1,3-butadiyne (1a) with pyrrolidine (2a) affording 1-phenyl-
2,4-bis(N-pyrrolidinyl)naphthalene (3a) (Table 1, entry 7): into a
thick-walled Pyrex screw-cap tube (10 mL) equipped with a mag-
netic stirring bar was placed 1,4-diphenyl-1,3-butadiyne (202.0
mg, 1.0 mmol), pyrrolidine (2.5 mL, 2.1 g, 30.0 mmol), and CuCl
(5.0 mg, 0.05 mmol), the tube was capped and the mixture was
stirred at 80 °C for 6 h. After the reaction mixture was cooled to
room temperature, CH2Cl2 (15.0 mL) was added and the insoluble
materials were filtrated out, and then mesitylene (30.0 mg,
0.25 mmol) was added as the internal standard for GC analysis.
After GC and GC–MS analyses, removing volatiles under reduced
pressure and the residue was subjected to column chromatography
isolation (silica gel, eluted with a mixture solvents of petroleum
ether and ethyl acetate (10:1)) to give 3a as a white solid (283.4
mg, 0.83 mmol, 83%). GC analysis of the reaction mixture revealed
that the conversion of 1a was more than 99%. Data for 3a: white
solid, mp 158.3–159.4 °C (recrystallization with CH2Cl2 and cyclo-
hexane). 1H-NMR (300 MHz, CDCl3) d 8.08 (d, J = 8.6 Hz, 1H), 7.41–
7.31 (m, 6H), 7.22–7.14 (m, 2H), 6.78 (s, 1H), 3.38 (t, J = 5.8 Hz, 4H),
2.96 (t, J = 5.9 Hz, 4H), 2.02 (t, J = 5.8 Hz, 4H), 1.70 (t, J = 5.8 Hz, 4H).
13C-NMR (75 MHz, CDCl3) d 147.7, 145.4, 141.2, 135.9, 132.7, 127.9,
126.3, 125.8, 124.8, 124.5, 122.3, 120.5, 116.4, 103.6, 52.8, 51.0,
25.8, 24.8. GC–MS m/z (% rel inten.) 342 (M+, 100), 313 (7), 265
(14), 238 (9), 265 (15), 202 (13), 128 (15). Anal. Calcd for
In conclusion, we have designed a new synthetic route for ac-
cess to functionalized naphthalene derivatives by the reaction of
arylated 1,3-butadiyne with hydrogen–heteroatom bond, which
has been proven to be practical by the reaction of 1,4-diaryl-
1,3-diynes with cyclic amines catalyzed by CuCl affording
diamino-substituted naphthalenes. The easy availability of the
Table 2
CuCl-catalyzed formation of amino-substituted naphthalenesa
O
N
N
N
N
O
C24H26N2: C, 84.21; H, 7.60; N, 8.18. Found: C, 84.03; H, 7.69; N,
8.12.
3b 80% (100 oC, 36 h)
3c 89% (120 oC, 36 h)
Acknowledgment
This project was supported by the National Natural Science
Foundation of China (20972084, 20873073, 21032004).
N
N
Me
N
MeO
N
Supplementary data
Supplementary data (general method, characterization data,
charts of 1H-, 13C-NMR for all products and the full X-ray diffrac-
tion data for 3a are concluded) associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2011.06.046.
Me
MeO
3d 78% (80 oC, 24 h)
3e 80% (100 oC, 24 h)
O
N
N
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F
N
MeO
N
O
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4411
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