Triflic acid-catalyzed cascade cyclization of arenyl enynes via acetylene-cation cyclization and Friedel-Crafts type reaction

Article abstract of DOI:10.1016/j.tetlet.2010.10.094

A novel triflic acid-catalyzed cascade cyclization of arenyl 1,7-enynes through acetylene-cation cyclization followed by Friedel-Crafts reaction has been described. Various fused poly carbocycles can be obtained in good to high yields under mild reaction

Full text of DOI:10.1016/j.tetlet.2010.10.094

Tetrahedron Letters 52 (2011) 2069–2071
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Triflic acid-catalyzed cascade cyclization of arenyl enynes via
acetylene-cation cyclization and Friedel–Crafts type reaction
Tienan Jin a,b, , Junichi Uchiyama a, Masafumi Himuro a, Yoshinori Yamamoto a,b,
⇑
⇑
a Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
b Advanced Institute for Materials Research (WPI-AIMR), Tohoku University, Sendai 980-8577, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online 25 October 2010
A novel triflic acid-catalyzed cascade cyclization of arenyl 1,7-enynes through acetylene-cation cycliza-
tion followed by Friedel–Crafts reaction has been described. Various fused poly carbocycles can be
obtained in good to high yields under mild reaction conditions.
Keywords:
Triflic acid
Ó 2010 Elsevier Ltd. All rights reserved.
Arenyl enynes
Acetylene-cation cyclization
Friedel–Crafts type reaction
Fused carbocycles
Catalytic carbocyclization of alkynes with arenes has emerged
as a potentially important transformation for the construction of
carbocyclic and heterocyclic compounds in organic chemistry.1 In
general, the reaction of alkynes with arenes catalyzed by transition
metals proceeds via vinylidene complexes.1a,b Recently, Lewis
acidic gold and/or platinum catalysts have been demonstrated to
We recently reported that cyclic enynes 5 [n = 1, Eq. 2] undergo
triflic acid-catalyzed acetylene-cation cyclization to give various
spirocycles 6.4a Furthermore, we have demonstrated that
a
Brønsted acid catalyst promotes the cleavage of an entirely inactive
C(sp3)–H bond by the use of cyclic or acyclic enynes 7 [n = 2, Eq. 3]
as a substrate.4b Both of the reactions proceed through the forma-
tion of a vinyl cation B, that is, formed by Brønsted acid promoted
acetylene-cation cyclization, followed by reaction with H2O or ring
closure of the benzylidene cation B with an sp3-hybridized carbon.
We assumed that a C(sp2)–H would be more reactive than a
C(sp3)–H to undergo Friedel–Crafts type reaction with the benzyl-
idene cation.5
In order to investigate an effective catalyst, a brief optimiza-
tion was carried out for carbocyclization of arenyl 1,7-enyne 1a,
as shown in Table 1. Triflic acid exhibited the highest catalytic
activity, affording 2a in 93% yield (entry 1). Tf2NH catalyst was
also effective, although the yield was lower than that with triflic
acid (entry 2). p-TsOH and AgSbF6 were completely ineffective
coordinate in p-electrophilic manner to alkynes, triggering an elec-
trophilic substitution reaction with an arene.1c–h However, the
Brønsted acid-catalyzed cyclization of alkynes with arenes has
been rarely reported.2 Zhang and Kozmin reported the first
Brønsted acid-catalyzed cyclization of arene-siloxyalkyne,3a and
Hsung and co-workers reported a Brønsted acid-catalyzed arene–
ynamide cyclization;3b in both cases Brønsted acid was proposed
to activate the alkyne moiety. In this communication, we report
a novel triflic-catalyzed cascade cycloisomerization of arenyl 1,7-
enynes 1 via the formation of acetylene-cations and subsequent
Friedel–Crafts type reaction, affording fused polycyclic compounds
2 in good to high yields under mild reaction conditions [Eq. 1].
Ar
Ar
Ar
R1
cat. TfOH
R1
R1
ð1Þ
m
R2
m
m
R2
R2
1
2
(m = 0, 1)
⇑
Corresponding authors. Tel.: +81 22 795 3585; fax: +81 22 795 6784 (T.J.); tel.: +81 22 795 6581; fax: +81 22 795 6784 (Y.Y.).
E-mail addresses: tjin@m.tohoku.ac.jp (T. Jin), yoshi@m.tohoku.ac.jp (Y. Yamamoto).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.094

2070
T. Jin et al. / Tetrahedron Letters 52 (2011) 2069–2071
Table 1
Table 2
Optimization of catalystsa
TfOH-catalyzed cascade cyclization of arenyl enynesa
Ph
Ph
Ar
Ar
catalyst
R1
R2
10 mol % TfOH
(ClCH2)2, rt
(CH2Cl)2 or CH2Cl2, rt
R2
1a
2a
Yieldb (%)
1
2
Entry
Catalyst (mol %)
Solvent
t (h)
Entry
1
t
(h)
2
Yieldb
(%)
1
2
3
4
5
6
7
TfOH (10)
Tf2NH (10)
p-TsOH (10)
AgSbF6 (5)
AuClPPh3/AgSbF6 (5/5)
AuClP(o-Bip)(tBu)2/AgSbF6 (5/5)
AuClPPh3/AgOTf (5/5)
(CH2Cl)2
(CH2Cl)2
(CH2Cl)2
CH2Cl2
CH2Cl2
CH2Cl2
1
1
24
24
1
93
86
0c
Me
Ph
0c
Ph
82
70
28
Me
12
4
1
0.5
99
CH2Cl2
a
Reaction conditions: 1a (0.4 mmol), solvent (2 mL, 0.2 M), catalyst (5–
10 mol %), room temperature.
2b
1b
1c
b
Yield of the isolated product 2a.
Recovery of 1a.
p-Tol
p-Tol
c
2
3
1
93
68
(entries 3 and 4). Cationic gold catalysts having hexafluoroantim-
onate anion were also effective, giving 2a in good yields (entries
5 and 6) without formation of any by-products arising from or-
dinary alkyne activation,1e,6,7 while a cationic gold salt having tri-
flate anion gave a complex mixture of products containing a low
yield of 2a (entry 7). It is noteworthy that, in the presence of
triflic acid catalyst, other solvents, such as THF, toluene, and ace-
tonitrile, were almost ineffective; only DCE gave an excellent
result.
2c
Cl
Ph
Ph
Cl
Cl
0.5
2d
2e
1d
Cl
p-Tol
p-Tol
Ar
Ar
Ar
4
5
1
1
36
91
cat. TfOH
or Tf2NH
acetylene-
cation
m
m
n
n
n
m
1e
1f
cyclization
5 (m = 0, 1, 2, 3; n =1)
7 (m = 2, 3, 4, 5; n =2)
A
B
2-naphthyl
2-naphthyl
O
Ar
H2O
(2)
(3)
5
7
enynes
2f
m
Ph
6
Ar
Ph
enynes
C(sp3)-H bond
cleavage
6
7
1
3
74
m
8
2g
1g
1h
The scope of the TfOH-catalyzed cascade cyclization of various
substituted arenyl 1,7-enynes is summarized in Table 2.
Ph
Ph
Et
1
Substrates 1 having an electron-donating aromatic group, such as
p-toly at the alkynyl terminus or alkenyl moiety afforded the cor-
responding tricycles 2b and 2c in excellent yields (entries 1 and 2).
Cyclization of enynes substituted with an electron-withdrawing
aromatic ring at the olefin moiety gave the desired tricycles 2d
and 2e in moderate yields (entries 3 and 4). These reactivities sug-
gest that the ring closure of benzylidene cation with arene follows
Friedel–Crafts type process as shown in Scheme 1. Enynes 1 with a
naphthalene group either substituted at the alkynyl terminus or
olefin side produced the expected tricycle (2f) and tetracycle (2g)
in good to high yields (entries 5 and 6). The reaction also worked
well with the trisubstituted enyne 1h to give 2h in 91% yield at
40 °C (entry 7). The reaction of enyne 1i, with benzene ring
in the tether, gave the corresponding tetracycle 2i in 82% yield
91c
2h
a
Reaction conditions: 1 (0.4 mmol), TfOH (10 mol %), 1,2-dichloroethane (2 mL,
0.2 M), room temperature.
b
Yield of the isolated product.
c
The E and Z ratio in 1h is 1:10. Reaction temperature is 40 °C.
[Eq. 4]. It is noteworthy that enynes tethered with a shorter carbon
chain failed to give the desired products, instead resulting in the
decomposition of enynes.

T. Jin et al. / Tetrahedron Letters 52 (2011) 2069–2071
Ph
2071
Ph
A proposed reaction mechanism is shown Scheme 1. Proton-
ation of alkene moiety of the enyne 1a by triflic acid leads to the
stable tertiary carbocation 1A. Attack of the alkyne moiety at the
cation 1A affords the benzylidene cation 1B.4 Intramolecular Fri-
edel–Crafts type reaction of benzylidene cation with phenyl group
in 1B affords the corresponding product 2a and regenerates triflic
acid.
TfOH
2a
1a
OTf
Ph
Ph
In summary, we have developed a novel triflic acid-catalyzed
cascade cycloisomerization of arenyl 1,7-enynes through acety-
lene-cation cyclization and Friedel–Crafts type reaction. Various
fused poly carbocycles can be obtained under mild reaction condi-
tions in high yields. Application of the present Brønsted acid-cata-
lyzed cascade reactions to the construction of fused congested
carbon skeletons is in progress.
1B
OTf
1A
Scheme 1. Proposed mechanism of the TfOH-catalyzed cascade cyclization of
arenyl enynes.
Acknowledgment
Ph
This work was financially supported by a Grant-in Aid for Young
Scientists (B) from Japan Society for Promotion of Science (JSPS).
Ph
10 mol % TfOH
ð4Þ
Supplementary data
(ClCH2)2, rt, 2 h
Me
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.10.094.
1i
1i 82%
The cyclization reaction was extended to the cyclic enyne as
shown in Eq. 5. Interestingly, the TfOH-catalyzed reaction of eny-
nes 1j (containing 38% of 1,6-enyne 1j0)8 bearing a dihydro-benzo-
cycloheptene group gave the highly congested carbocycle 2j in 90%
yield without formation of a product deriving from the C(sp3)–H
bond cleavage pathway.4b The structure of 2j was unambiguously
confirmed by X-ray crystal analysis.9
References and notes
1. For selected recent reviews, see: (a) Nevado, C.; Echavarren, A. M. Synthesis
2005, 167; (b) Bandini, M.; Emer, E.; Tommasi, S.; Umani-Ronchi, A. Eur. J. Org.
Chem. 2006, 3527; (c) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180; (d) Fürstner,
A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 2; (e) Jiménez-Núu˜ez, E.;
Echavarren, A. M. Chem. Rev. 108, 3326.; (f) Li, Z.; Brouwer, C.; He, C. Chem. Rev.
2008, 108, 3239; (g) Patil, N. T.; Yamamoto, Y. Chem. Rev. 2008, 108, 3395; (h)
Yamamoto, Y.; Gridnev, I. D.; Patil, N. T.; Jin, T. Chem. Commun. 2009, 5075; (i)
Hashmi, A. S. K. Angew. Chem., Int. Ed. 2010, 49, 5232.
Ph
Ph
Ph
2. For a recent review on Brønsted acids, see: Akiyama, T. Chem. Rev. 2007, 107,
5744.
10 mol % TfOH
(ClCH2)2, rt, 1 h
3. (a) Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2004, 126, 10204; (b) Zhang, Y.;
Hsung, R. P.; Zhang, X.; Huang, J.; Slafer, B. W.; Davis, A. Org. Lett. 2005, 7, 1047.
4. (a) Jin, T.; Himuro, M.; Yamamoto, Y. Angew. Chem., Int. Ed. 2009, 48, 5893; (b)
Jin, T.; Himuro, M.; Yamamoto, Y. J. Am. Chem. Soc. 2010, 132, 5590.
5. (a) Lian, J.-J.; Chen, P.-C.; Lin, Y.-P.; Ting, H.-C.; Liu, R.-S. J. Am. Chem. Soc. 2006,
128, 11372; (b) Liu, L.; Zhang, J. Angew. Chem., Int. Ed. 2009, 48, 6093; (c) Yao, L.-
F.; Shi, M. Eur. J. Org. Chem. 2009, 4036.
1j
1j'
1j 1j'
:
2j
90%
= 3:2
ð5Þ
6. Michelet, V.; Toullec, P. Y.; Genet, J.-P. Angew. Chem., Int. Ed. 2008, 47, 4268.
7. Some other gold-catalyzed reactions have been proven to be also catalyzed by
strong acids: (a) Hashmi, A. S. K.; Schwarz, L.; Rubenbauer, P.; Blanco, M. C. Adv.
Synth. Catal. 2006, 348, 705; (b) Hashmi, A. S. K. Catal. Today 2007, 122, 211; (c)
Krater, C. M.; Hashmi, A. S. K.; Perpointner, M. ChemCatChem 2010, 2, 1226.
8. Concerning 1j0, only one isomer was formed, but its E or Z form was not
determined. See Supplementary data.
To our delight, when a methylene carbon atom was inserted be-
tween the aromatic ring and the alkene, the reaction still pro-
ceeded smoothly. Thus, enynes 1k–m were converted into the
corresponding six-membered tricycles 2k–m in good yields at
80 °C [Eq. 6].10
9. CCDC-778127 contains the supplementary crystallographic data for 2j. The
detailed data can be obtained free of charge from The Cambridge
Crystallographic Data Centre at www.ccdc.cam.ac.uk/data_request/cif.
10. A related tricyclic framework has been synthesized recently by gold catalysis:
(a) Hashmi, A. S. K.; Pankajakshan, S.; Rudolph, M.; Enn, E.; Bander, T.;
Rominger, F.; Frey, W. Adv. Synth. Catal. 2009, 351, 2855; (b) Hashmi, A. S. K.;
Rudolph, M.; Huck, J.; Frey, W.; Bats, J. W.; Hamzic, M. Angew. Chem., Int. Ed.
2009, 48, 5848.
R
Ph
Ph
10 mol % TfOH
(ClCH2)2, 80 o
R
C
Me
1k
2k
2l
R = H
63% (9 h)
1l R = Me
1m R = Cl
64% (3 h)
2m
59% (15 h)
ð6Þ