Iron-promoted electrophilic annulation of aryl enynes with disulfides or diselenides leading to polysubstituted naphthalenes

Article abstract of DOI:10.1002/adsc.201400070

An iron-promoted electrophilic annulation of aryl enynes with disulfides or diselenides has been developed. In the presence of iron(III) chloride (FeCl₃) and iodine (I₂,), a variety of trifluoromethyl-containing aryl enynes underwent electrophilic annulation with various disulfides or diselenides successfully to afford the corresponding polysubstituted naphthalenes in moderate to excellent yields.

Full text of DOI:10.1002/adsc.201400070

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DOI: 10.1002/adsc.201400070
Iron-Promoted Electrophilic Annulation of Aryl Enynes with
Disulfides or Diselenides Leading to Polysubstituted
Naphthalenes
Zhi-Jun Yang,a Bo-Lun Hu,a Chen-Liang Deng,a and Xing-Guo Zhanga,*
a
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, Peopleꢀs Republic of China
Fax : (+86)-577-8668-9615; phone: (+86)-577-8668-9615; e-mail: zxg@wzu.edu.cn
Received: January 19, 2014; Revised: March 6, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400070.
Abstract: An iron-promoted electrophilic annula-
tion of aryl enynes with disulfides or diselenides has
been developed. In the presence of ironACTHNUTRGNE(NUG III) chlo-
ride (FeCl3) and iodine (I2,), a variety of trifluoro-
methyl-containing aryl enynes underwent electro-
philic annulation with various disulfides or disele-
nides successfully to afford the corresponding poly-
substituted naphthalenes in moderate to excellent
yields.
naphthalene derivatives using a similar electrophilic
cyclization, and as part of our continuing interest in
trifluoromethylated aromatics,[9] we herein report
a simple and efficient protocol for the synthesis of
polysubstituted naphthalenes via iron-promoted elec-
trophilic annulation of aryl enynes with disulfides or
diselenides in the presence of iodine (Scheme 1).
The reaction between 1,4-diphenyl-2-trifluorome-
thylbut-1-en-3-yne 1a[10] and 1,2-diphenyldisulfane 2a
was selected as a model reaction to optimize the reac-
tion conditions, and the results are summarized in
Table 1. The reaction was initially carried out with
our previously reported catalytic systems (PdCl2 com-
bined with I2), but only afforded the target product in
36% yield (entry 1). Low yields were also observed
Keywords: aryl enynes; diselenides; disulfides; elec-
trophilic annulation; naphthalenes
using PdACHTNUGTRENNUG(OAc)2 or CuACHUTNGTRENN(UGN OAc)2 as catalyst (entries 2
Naphthalenes are an important class of aromatic com- and 3). Iron catalysts were more effective for the elec-
pounds in medicinal chemistry and materials science trophilic annulation and provided the product in mod-
due to their remarkable biological activities,[1] and erate yields (entries 4–7). Treatment of substrate 1a
photo-/electro-chemical properties.[2] Moreover, poly- with 1,2-diphenyldisulfane, iodine and 10 mol% of
substituted naphthalenes also have a wide range of FeCl3 in CH3NO2 at 1208C afforded the desired prod-
applications in the design of chiral catalysts and li-
gands.[3] As a consequence, considerable efforts have
been made to develop efficient strategies for the syn-
thesis of naphthalenes.[4] Most of these methodologies
focus on the Lewis acid-catalyzed benzannulation of
enynals with unsaturated compounds. For example,
Yamamoto and co-workers reported a variety of tran-
sition metal-catalyzed benzannulations of enynals
with alkynes or enols.[5] Lee and co-workers devel-
oped another approach to naphthalene derivatives via
platinum-catalyzed hydroarylation of aryl enynes.[6]
Recently, the electrophilic cyclization of arylalkynes
with electrophiles was a frequently utilized strategy
for the construction of heterocyclic and polycyclic ar-
omatics because of the atom-economical advantage.[7]
In our former study, we reported a palladium-cata-
lyzed electrophilic annulation of 2-(1-alkynyl)-biphen-
yls with disulfides for the preparation of phenan-
threnes.[8] To develop new method for the synthesis of Scheme 1. Synthesis of naphthalenes.
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Zhi-Jun Yang et al.
Table 1. Screening for reaction conditions.[a]
Entry
Catalyst
PdCl2
[I] source
Additive
Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
I2
I2
I2
I2
I2
I2
I2
NIS
–
–
–
–
–
–
–
–
–
–
–
–
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
DCE
36
25
35
48
43
40
41
34
9
trace
7
12
0
71
52
43
78
34
17
51
0
Pd
A
Cu
A
FeCl3
FeBr3
FeF3
Fe
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
–
9
PhI
ICl
I2
N
10
11
12
13
14
15
16
17
18[c]
19
20
21
I2
I2
I2
I2
I2
I2
I2
–
MeCN
DMSO
–
BPO (10%)
AIBN (10%)
TBHP (10%)
BPO (5%)
BPO (5%)
BPO (5%)
BPO (5%)
BPO (5%)
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
I2
–
–
[a]
Reaction conditions: 1a (0.2 mmol), 2a (0.2 mmol), catalyst (10 mol%), [I] source (2 equiv.) and additive (5 or 10 mol%)
in solvent (2 mL) under an N2 atmosphere at 1208C for 24 h.
Isolated yield.
1 equiv. of I2 was used.
[b]
[c]
uct 3 in 48% yield (entry 4). The structure of product
3 was confirmed by an X-ray single-crystal diffraction
analysis (Figure 1). Based on these results, various
iodine sources [NIS, PhIACHTNUTRGNENG(U OAc)2 and ICl] were exam-
ined, but all were less effective than I2 (entries 8–10).
During the examination of solvent effects, we found
that the cyclization reaction nearly did not proceed in
DCE, MeCN or DMSO (entries 11–13). Inspired by
some free radical-promoted cyclization reactions,[11]
we next investigated some radical initiators with the
aim of increasing the yield of the reaction (entries 14–
17). The results showed that benzoyl peroxide (BPO)
could promote the reaction and the reaction yield in-
creased sharply to 78% upon using 5 mol% of BPO
as additive (entry 17). It is worth noting that the reac-
tion yield decreased significantly using 1 equiv. of I2
or in the absence of I2, which suggested that iodine
played a critical role in this transformation (entries 18
and 19). The product 3 could be isolated in 51%
when the reaction was carried out in the absence of
FeCl3 (entry 20), but the reaction did not work in the
presence of BPO alone (entry 21).
With the optimized reaction conditions in hand, we
next surveyed the electrophilic annulation reaction of
Figure 1. X-ray crystallographic structure of compound 3.
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Iron-Promoted Electrophilic Annulation of Aryl Enynes
Table 2. Iron-promoted electrophilic annulation of aryl enynes with disulfides or diselenides.[a]
[a]
Reaction conditions: 1 (0.2 mmol), 2 (0.2 mmol), FeCl3 (10 mol%), I2 (2 equiv.) and BPO (5 mol%) in CH3NO2 (2 mL)
under an N2 atmosphere at 1208C for 24 h.
Isolated yield.
[b]
various types of aryl enynes with disulfides and disele- 41% yields, respectively. Aliphatic dimethyl disulfide
nides (Table 2). Firstly, the reactions between 1,4-di- and diethyl disulfide were also tolerated well to pro-
phenyl-2-trifluoromethylbut-1-en-3-yne 1a and vari- vide products 8 and 9 in moderate yields (57 and
ous disulfides were investigated under the standard 53%). Subsequently, we investigated the substrate
conditions. The results disclosed that both aryl disul- scope of aryl enynes by examining their reaction with
fides and alkyl disulfides are suitable substrates and diphenyl disulfide 2a under the standard conditions.
afforded the corresponding products in moderate to Methyl- or tert-butyl-substituted naphthalenes 10 and
good yields. For example, p-methylphenyl disulfide 11 were obtained in good yields (80 and 84%). Mod-
provided the product 4 in 77% yield and p-chloro- erate yields were observed when 2-chlorophenyl and
phenyl disulfide gave a 71% yield. Fluorinated phenyl 4-biphenyl enynes were used as substrates (12 and
disulfides afforded the products 6 and 7 in 62 and 13). Trisubstitued anthracene 14 was also obtained
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Zhi-Jun Yang et al.
successfully in an 89% yield from naphthalen-2-yl
enyne, whereas naphthalen-1-yl enyne provided the
corresponding phenanthrene 15 in a lower yield of
50%. 1-Tolyl-substituted naphthalenes 16–18 were ob-
tained in 44–72% yields. However, naphthalene 19
was observed only in a 22% yield when p-chlorophen-
yl-substituted enyne was used as substrate, presuma-
bly because of the strong electron-withdrawing effect
of the chloro group. Finally, the electrophilic annula-
tion reaction of aryl enynes with diselenides was ex-
amined. As expected, the reaction of substrate 1a
with 1,2-diphenyldiselane was conducted successfully
to produce the desired product 20 in 70% yield. Simi-
lar results were also obtained for tert-butyl-substituted
naphthalenes 21, whereas 4-biphenyl enyne provided
the corresponding phenanthrene 22 in a lower yield.
1-Tolyl-substituted naphthalenes 23 and 24 were ob-
tained in 60 and 51% yields, respectively. Notably, the
reaction between substrate 1a with 1,2-bis(2-nitrophe-
nyl)diselane, bearing a strong electron-withdrawing
group, proceeded smoothly to afford the target prod-
uct 25, albeit in a low yield (35%).
Scheme 2. Control experiments.
To probe the mechanism, the reaction of 1,4-di-
phenyl-2-trifluoromethylbut-1-en-3-yne
1a
with
2 equiv. of I2, FeCl3 and BPO was carried out in the
absence of disulfide under the standard conditions
[Eq. (1), Scheme 2]. The iodocyclization product 26
could not be detected and almost all of the starting
materials 1a were recovered. The results revealed that
the electrophilic annulation of aryl enynes with disul-
fides did not proceed through an iodocyclization pro-
Scheme 3. Possible mechanism.
cess. Considering the role of BPO, 1 equiv. of to alkyne 1 to produce a vinyl radical C, which then
TEMPO, a radical-trapping reagent, was added into undergoes an intramolecular cyclization to form radi-
the reaction of substrate 1a with 1, 2-diphenyldisul- cal D.[14] The following oxidation by I2 or FeCl3 produ-
fane under standard conditions [Eq. (2)]. Only a trace ces the corresponding carbocation, which loses a H+
amount of product 3 was observed, which suggested to yield desired products 3–22. A study of the detailed
that the reaction may proceed through a free-radical mechanism is in progress.
process.
In conclusion, we have developed a practical FeCl3-
On the basis of the present results and our previous promoted electrophilic annulation for the synthesis of
work,[12] a plausible mechanism was outlined as shown polysubstituted naphthalenes. The reaction proceeded
in Scheme 3. The electrophilic annulation still works with high selectivity to provide the 6-endo-dig cycliza-
in the absence of FeCl3 (entry 20 in Table 1) and the tion product and showed good functional group toler-
iodocyclization product could not be detected ance. A variety of 1,4-diaryl-2-trifluoromethylbut-1-
(Scheme 2). These results imply that the reaction of en-3-ynes underwent the electrophilic annulations
disulfide with iodine may take place to produce the successfully with various disulfides or diselenides to
active RSI in situ.[13] The presence of BPO promotes afford the corresponding polysubstituted naphtha-
the generation of free radical RSC which subsequently lenes in moderate to excellent yields. The utilization
reacted with I2 to form RSI [Eq. (3) and Eq. (4)]. The of inexpensive ferric chloride and commercially avail-
electrophilic addition of RSI to the triple bond of sub- able disulfides and diselenides as electrophiles are sig-
strate 1 affords intermediate A (Path 1). The Lewis nificant advantages for the usefulness of this reaction.
acid (FeCl3)-catalyzed intramolecular electrophilic The present process could facilitate the synthetic ap-
attack on the neighboring aryl group provides inter- plications of trifluoromethyl-containing building
mediate B, subsequent deprotonation yields the de- blocks, and also provides a new optional route for
sired products 3–22. However, a free radical pathway constructing naphthalene.
cannot be ruled out (Path 2), in view of the fact that
the product 3 can be isolated in 17% yield in the ab-
sence of I2 (entry 19 in Table 1). The addition of RSC
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Iron-Promoted Electrophilic Annulation of Aryl Enynes
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To a 10-mL flame-dried Schlenk tube with a magnetic stir-
ring bar were charged 1,4-diaryl-2-trifluoromethylbut-1-en-
3-yne 1 (0.2 mmol), disulfide (0.2 mmol), FeCl3 (3.2 mg,
0.02 mmol), I2 (101.6 mg, 0.4 mmol), BPO (2.4 mg,
0.01 mmol), and CH3NO2 (2 mL) under an N2 atmosphere.
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temperature and then poured into ethyl acetate, which was
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Phenyl[1-phenyl-3-(trifluoromethyl)naphthalen-2-yl]sul-
fane (3):[15] Yellow solid; yield: 59.3 mg (78%); mp 116.7–
1
117.48C; H NMR (500 MHz, CDCl3): d=8.39 (s, 1H), 8.00
(d, J=8.5 Hz, 1H), 7.63–7.60 (m, 1H), 7.48–7.46 (m, 1H),
7.41 (d, J=8.5 Hz, 1H), 7.34–7.31 (m, 1H), 7.28–7.25 (m,
2H), 7.04–6.97 (m, 5H), 6.73–6.71 (m, 2H); 13C NMR
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Acknowledgements
We thank the National Natural Science Foundation of China
(No. 21002070 and 21272177) for financial support.
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6 Iron-Promoted Electrophilic Annulation of Aryl Enynes
with Disulfides or Diselenides Leading to Polysubstituted
Naphthalenes
Adv. Synth. Catal. 2014, 356, 1 – 6
Zhi-Jun Yang, Bo-Lun Hu, Chen-Liang Deng,
Xing-Guo Zhang*
6
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