Synthesis of carbocyclic aromatic compounds using ruthenium-catalyzed ring-closing enyne metathesis

Article abstract of DOI:10.1021/jo900456g

(Chemical Equation Presented) General synthetic methods of substituted carbocyclic aromatic compounds are reported. Ring-closing enyne metathesis (RCEM)/dehydration of 1,5-octadien-7-yn-4-ols 6 and RCEM/tautomerization of 1,5-octadien-7-yn-4-ones 7 furnis

Full text of DOI:10.1021/jo900456g

Synthesis of Carbocyclic Aromatic Compounds Using
Ruthenium-Catalyzed Ring-Closing Enyne Metathesis
Hidetoshi Takahashi, Kazuhiro Yoshida,* and Akira Yanagisawa*
Department of Chemistry, Graduate School of Science, Chiba UniVersity, Yayoi-cho,
Inage-ku, Chiba 263-8522, Japan
kyoshida@faculty.chiba-u.jp; ayanagi@faculty.chiba-u.jp
ReceiVed March 2, 2009
General synthetic methods of substituted carbocyclic aromatic compounds are reported. Ring-closing
enyne metathesis (RCEM)/dehydration of 1,5-octadien-7-yn-4-ols 6 and RCEM/tautomerization of 1,5-
octadien-7-yn-4-ones 7 furnished a wide variety of substituted styrenes 4 and 4-vinylphenols 8, respectively.
Acyclic precursors 6 and 7 were readily prepared from ꢀ-halo-R,ꢀ-unsaturated aldehydes 9 or 3-halo-
2-propene-1-ols 13 by utilizing combinations of the Sonogashira coupling, allylation, and the Dess-Martin
oxidation. The RCEM/dehydration for the synthesis of 1,3,5-tris(1-phenylethenyl)benzene derivative 4r
and the RCEM/RCM/dehydration for the synthesis of 1,1′-binaphthyl derivative 19a are also presented
as applications of this method.
Introduction
catalyzed cross-coupling reaction of aryl halides,4 the Heck
reaction of aryl halides,5 and the elimination of aryl alcohols
to generate a double bond.6 However, there are a few reports7
of the construction of benzene rings of styrenes from acyclic
precursors despite the fact that unique styrenes can be obtained
with this entirely different procedure.
The construction of aromatic rings from acyclic precursors
using ruthenium-catalyzed ring-closing olefin metathesis (RCM)8,9
has recently emerged as an interesting and efficient strategy for
preparing aromatic compounds.10-12 One of the greatest ad-
vantages of this strategy is the flexible introduction of various
Substituted styrenes offer considerable utility as important
intermediates in organic chemistry.1,2 For instance, 4-vinylsty-
renes are well-known building blocks of pharmaceuticals,1c-g
polymer-supported catalysts,2b functional polymers,2c and
calixarenes.2d The development of highly reliable and flexible
synthetic methods of substituted styrenes is therefore an
important subject in organic synthesis. Commonly employed
methods for the preparation of styrenes are functional group
transformations on existing aromatic rings, such as the Wittig
olefination of aryl carbonyl compounds,3 the transition-metal-
(4) For recent examples, see: (a) Belema, M.; Nguyen, V. N.; Zusi, F. C.
Tetrahedron Lett. 2004, 45, 1693–1697. (b) Zeng, F.; Stehouwer, J. S.; Jarkas,
N.; Voll, R. J.; Williams, L.; Camp, V. M.; Votaw, J. R.; Owens, M. J.; Kilts,
C. D.; Nemeroff, C. B.; Goodman, M. M. Bioorg. Med. Chem. Lett. 2007, 17,
3044–3047. (c) Achmatowicz, M.; Chan, J.; Wheeler, P.; Liu, L.; Faul, M. M.
Tetrahedron Lett. 2007, 48, 4825–4829.
(5) For recent examples, see: (a) Kotoku, N.; Kato, T.; Narumi, F.; Ohtani,
E.; Kamada, S.; Aoki, S.; Okada, N.; Nakagawa, S.; Kobayashi, M. Bioorg.
Med. Chem. 2006, 14, 7446–7457. (b) Huang, W.-S.; Wang, Y.; Sundaramoorthi,
R.; Thomas, R. M.; Wen, D.; Liu, S.; Lentini, S. P.; Das, S.; Banda, G.; Sawyer,
T. K.; Shakespeare, W. C. Tetrahedron Lett. 2007, 48, 7388–7391.
(6) For recent examples, see: (a) Antane, S.; Caufield, C. E.; Hu, W.; Keeney,
D.; Labthavikul, P.; Morris, K.; Naughton, S. M.; Petersen, P. J.; Rasmussen,
B. A.; Singh, G.; Yang, Y. Bioorg. Med. Chem. Lett. 2006, 16, 176–180. (b)
Nakamura, S.; Sugano, Y.; Kikuchi, F.; Hashimoto, S. Angew. Chem., Int. Ed.
2006, 45, 6532–6535. (c) Sinha, A. K.; Sharma, A.; Joshi, B. P. Tetrahedron
2007, 63, 960–965.
To whom correspondence should be addressed. Tel: +81-43-290-2790. Fax:
+81-43-290-2789.
(1) For examples, see: (a) Fassina, V.; Ramminger, C.; Seferin, M.; Monteiro,
A. L. Tetrahedron 2000, 56, 7403–7409. (b) Fu¨rstner, A.; Thiel, O. R.; Kindler,
N.; Bartkowska, B. J. Org. Chem. 2000, 65, 7990–7995. (c) Winum, J.-Y.;
Baghdiguian, S.; Commes, T.; Leydet, A.; Montero, J.-L. Bioorg. Med. Chem.
Lett. 2002, 12, 3529–3532. (d) Perera, R. P.; Wimalasena, D. S.; Wimalasena,
K. J. Med. Chem. 2003, 46, 2599–2605. (e) Snider, B. B.; Grabowski, J. F.
Tetrahedron 2006, 62, 5171–5177. (f) Bo¨ehrsch, V.; Blechert, S. Chem. Commun.
2006, 1968–1970. (g) Nagarapu, L.; Paparaju, V.; Satyender, A. Bioorg. Med.
Chem. Lett. 2008, 18, 2351–2354.
(2) (a) For examples, see: Styrene Polymers in Encyclopedia of Polymer
Science and Engineering, 2nd ed.; Moore, E. R., Ed.; Wiley-Interscience: New
York, 1989; Vol. 16, and references therein. (b) Heckel, A.; Seebach, D. HelV.
Chim. Acta 2002, 85, 913–926. (c) Xu, L.; Yokoyama, E.; Satoh, M. Langmuir
2005, 21, 7153–7160. (d) Yordanova, S.; Miloshev, S.; Berlinova, I.; Diakovski,
B. J. Inclusion Phenom. Macrocycl. Chem. 2006, 56, 337–344.
(3) For recent examples, see: (a) Srikrishna, A.; Babu, R. R.; Ravikumar,
P. C. Synlett 2007, 655–657. (b) Tietze, L. F.; Brasche, G.; Grube, A.; Boehnke,
N.; Stadler, C. Chem.sEur. J. 2007, 13, 8543–8563.
(7) For examples, see: (a) Gevorgyan, V.; Yamamoto, Y. J. Organomet.
Chem. 1999, 576, 232–247. (b) Xi, Z.; Li, Z.; Umeda, C.; Guan, H.; Li, P.;
Kotora, M.; Takahashi, T. Tetrahedron 2002, 58, 1107–1117. (c) Gorin, D. J.;
Watson, I. D. G.; Toste, F. D. J. Am. Chem. Soc. 2008, 130, 3736–3737.
3632 J. Org. Chem. 2009, 74, 3632–3640
10.1021/jo900456g CCC: $40.75 2009 American Chemical Society
Published on Web 04/24/2009

Synthesis of Carbocyclic Aromatic Compounds
substituents to the aromatic rings. Since modern synthetic
organic chemistry offers sufficient flexibility to construct acyclic
compounds selectively, the formation of aromatic compounds
from acyclic precursors having various substituents makes it
possible to obtain a wide variety of aromatic compounds without
the formation of inseparable regioisomers.
In the past few years, we have devoted much of our effort to
this field13 and reported that benzenes 2 and styrenes 4 can be
obtained by RCM/dehydration of 1,4,7-octatrien-3-ols 1 (eq 1)13b
and ring-closing enyne metathesis (RCEM)14/elimination of
3-acetoxy-4,7-octadien-1-ynes 3 (eq 2),13f respectively. Although
various benzenes and styrenes could be synthesized without the
formation of regioisomers, these approaches were limited by
the difficulty of preparing 1 and 3. Further, in the styrene
synthesis, the requirement of acyl protection at the propargyl
hydroxyl group of the substrate was another disadvantage. Very
low conversions were observed in the RCEM with substrates
having a free propargyl hydroxyl group, which were the
precursors of 3.
derivatives of 3,13f we were unable to obtain 2-vinylphenols by
RCEM/tautomerization. However, taking into account that a
considerable number of the analogues of 7, which have a similar
conjugate (Z)-2-en-4-yn-1-one framework, have been reported
so far,15 we have every reason to expect that 7 would be
prepared and their conversion to 4-vinylphenols 8 would be
achieved.
In this paper, we report the synthesis of styrenes 4 by RCEM/
dehydration of 6 and the synthesis of 4-vinylphenols 8 by
RCEM/tautomerization of 7. We describe first the preparation
of enyne substrates 6 and 7, and then the synthesis of the
styrenes in detail. We also present applications of the RCEM/
dehydration to the synthesis of unique aromatic compounds,
1,3,5-tris(1-phenylethenyl)benzene derivative 4r and 1,1′-bi-
naphthyl derivative 19a.
(8) For a comprehensive review, see: (a) Handbook of Metathesis; Grubbs,
R. H., Ed; Wiley-VCH: Weinheim, Germany, 2003. For reviews, see: (b) Grubbs,
R. H.; Chang, S. Tetrahedron 1998, 54, 4413–4450. (c) Fu¨rstner, A. Angew.
Chem., Int. Ed. 2000, 39, 3012–3043. (d) Trnka, T. M.; Grubbs, R. H. Acc.
Chem. Res. 2001, 34, 18–29. (e) Hoveyda, A. H.; Zhugralin, A. R. Nature 2007,
450, 243–251.
(9) For reports on the pharmaceutical application of RCM in multi-kilogram
scale (>400 kg of cyclized product), see: (a) Nicola, T.; Brenner, M.; Donsbach,
K.; Kreye, P. Org. Process Res. DeV. 2005, 9, 513–515. (b) Yee, N. K.; Farina,
V.; Houpis, I. N.; Haddad, N.; Frutos, R. P.; Gallou, F.; Wang, X.-J.; Wei, X.;
Simpson, R. D.; Feng, X.; Fuchs, V.; Xu, Y.; Tan, J.; Zhang, L.; Xu, J.; Smith-
Keenan, L. L.; Vitous, J.; Ridges, M. D.; Spinelli, E. M.; Johnson, M.; Donsbach,
K.; Nicola, T.; Brenner, M.; Winter, E.; Kreye, P.; Samstag, W. J. Org. Chem.
2006, 71, 7133–7145. (c) Tsantrizos, Y. S.; Ferland, J.-M.; McClory, A.; Poirier,
M.; Farina, V.; Yee, N. K.; Wang, X.-J.; Haddad, N.; Wei, X.; Xu, J.; Zhang,
L. J. Organomet. Chem. 2006, 691, 5163–5171.
In 2008, we reported an improved and general synthetic
approach to the synthesis of benzenes 2 that adopted 1,5,7-
octatrien-4-ols 5 instead of 1 as the new acyclic precursors of
RCM/dehydration (eq 3).13e Because the synthetic routes to 1
show great generality in which cross-coupling with vinyl metal
reagents and allylation with allyl metal reagents were employed
as carbon-carbon bond forming reactions, a wide variety of
substituted benzenes 2 having various functionalities could be
synthesized. Based on this background, we expected that the
generality of the synthesis of styrenes might likewise be
improved by replacing enyne substrates 3 with 1,5-octadien-7-
yn-4-ols 6 (eq 4). The analogy of the basic structure of 6 to 5
is expected to lead to the easy and flexible preparation of 6. In
addition, acyl protection of the hydroxyl group of 6 may be
unnecessary because the hydroxyl group is not located at the
propargyl position of 6.
(10) For a review, see: Donohoe, T. J.; Orr, A. J.; Bingham, M. Angew.
Chem., Int. Ed. 2006, 45, 2664–2670.
(11) For reports on the direct synthesis of carbocyclic aromatic compounds
using RCM, see: (a) Iuliano, A.; Piccioli, P.; Fabbri, D. Org. Lett. 2004, 6, 3711–
3714. (b) Walker, E. R.; Leung, S. Y.; Barrett, A. G. M. Tetrahedron Lett. 2005,
46, 6537–6540. (c) Bonifacio, M. C.; Robertson, C. R.; Jung, J.-Y.; King, B. T.
J. Org. Chem. 2005, 70, 8522–8526. (d) Pelly, S. C.; Parkinson, C. J.; Van
Otterlo, W. A. L.; De Koning, C. B. J. Org. Chem. 2005, 70, 10474–10481. (e)
Collins, S. K.; Grandbois, A.; Vachon, M. P.; Coˆte´, J. Angew. Chem., Int. Ed.
2006, 45, 2923–2926. (f) Grandbois, A.; Collins, S. K. Chem.sEur. J. 2008,
14, 9323–9329. For reports using RCM/elimination protocol, see: (g) Evans, P.;
Grigg, R.; Ramzan, M. I.; Sridharan, V.; York, M. Tetrahedron Lett. 1999, 40,
3021–3024. (h) Huang, K. S.; Wang, E. C. Tetrahedron Lett. 2001, 42, 6155–
6157. (i) Chen, Y.; Dias, H. V. R.; Lovely, C. J. Tetrahedron Lett. 2003, 44,
1379–1382. (j) Chen, P.-Y.; Chen, H.-M.; Chen, L.-Y.; Tzeng, J.-Y.; Tsai, J.-
C.; Chi, P.-C.; Li, S.-R.; Wang, E.-C. Tetrahedron 2007, 63, 2824–2828. For
reports using the RCM/oxidation protocol, see: (k) Kotha, S.; Mandal, K.
Tetrahedron Lett. 2004, 45, 2585–2588. (l) Ma, S.; Yu, F.; Zhao, J. Synlett 2007,
583–586. (m) Kotha, S.; Shah, V. R.; Mandal, K. AdV. Synth. Catal. 2007, 349,
1159–1172. For reports using the RCM/tautomerization protocol, see: (n) van
Otterlo, W. A. L.; Ngidi, E. L.; Coyanis, E. M.; de Koning, C. B. Tetrahedron
Lett. 2003, 44, 311–313. (o) Toueg, J.; Prunet, J. Synlett 2006, 2807–2811.
(12) For selected recent reports on the synthesis of heterocyclic aromatic
compounds using RCM, see: (a) Arisawa, M.; Nishida, A.; Nakagawa, M. J.
Organomet. Chem. 2006, 691, 5109–5121. (b) Donohoe, T. J.; Fishlock, L. P.;
Procopiou, P. A. Chem.sEur. J. 2008, 14, 5716–5726.
(13) (a) Yoshida, K.; Imamoto, T. J. Am. Chem. Soc. 2005, 127, 10470–
10471. (b) Yoshida, K.; Kawagoe, F.; Iwadate, N.; Takahashi, H.; Imamoto, T.
Chem. Asian J. 2006, 1, 611–613. (c) Yoshida, K.; Horiuchi, S.; Iwadate, N.;
Kawagoe, F.; Imamoto, T. Synlett 2007, 1561–1564. (d) Yoshida, K.; Toyoshima,
T.; Imamoto, T. Chem. Commun. 2007, 3774–3776. (e) Yoshida, K.; Takahashi,
H.; Imamoto, T. Chem.sEur. J. 2008, 14, 8246–8261. (f) Yoshida, K.;
Shishikura, Y.; Takahashi, H.; Imamoto, T. Org. Lett. 2008, 10, 2777–2780. (g)
Yoshida, K.; Narui, R.; Imamoto, T. Chem.sEur. J. 2008, 14, 9706–9713. (h)
Yoshida, K.; Toyoshima, T.; Imamoto, T. Bull. Chem. Soc. Jpn. 2008, 81, 1512–
1517. (i) Yoshida, K.; Kawagoe, F.; Hayashi, K.; Horiuchi, S.; Imamoto, T.;
Yanagisawa, A. Org. Lett. 2009, 11, 515–518.
It should also be added that the synthesis of 4-vinylphenols
8 by RCEM/tautomerization of 1,5-octadien-7-yn-4-ones 7 is
possible (eq 5). Because of the instability of 4,7-octadien-1-
yn-3-ones that we tried to prepare by oxidation of the alcohol
J. Org. Chem. Vol. 74, No. 10, 2009 3633

Takahashi et al.
TABLE 1. Preparation of 1,5-Octadien-7-yn-4-ols 6, Precursors of
Styrenes 4, from ꢀ-Halo-r,ꢀ-unsaturated Aldehydes 9 by
Sonogashira Coupling and Allylationa
SCHEME 1
Results and Discussion
The retrosynthetic analysis of 6 and 7 is shown in Scheme
1. The route starts from the Sonogashira coupling16 between
terminal alkynes 10 and ꢀ-halo-R,ꢀ-unsaturated aldehydes 9,17,18
which are well-known and readily prepared building blocks.
Then, the allylation of resulting coupling products 11 with allyl
metal reagents 12 is expected to yield 6,19 which are the
precursors of styrenes 4. Further, the preparation of 7 for the
synthesis of 4-vinylphenols 8 is expected to be achieved by
oxidizing 6 at the alcohol position.
The results of the Sonogashira coupling between 9 and 10
and the allylation reaction of coupling products 11 with 12 to
yield 6 are summarized in Table 1. The Sonogashira coupling
was conducted with various 9 and 10 in the presence of
PdCl2(PPh3)2 (5 mol %), CuI (5 mol %), and NEt3 (3 equiv) in
THF, and the resulting coupling products 11 were obtained in
good yields after silica gel chromatography. The following
allylation of aldehydes 11 was conducted with readily available
allyl Grignard or allylborane reagents without any problems to
produce desired enyne substrates 6. In the case of the preparation
of 6k that has a terminal alkyne, the crude mixture of the
allylation of 11j was treated with K2CO3 in MeOH at room
temperature to cleave the C-Si bond (Table 1, entry 11).
For the preparation of 6, we also examined another synthetic
route starting from 3-halo-2-propen-1-ols 13 that were prepared
by reducing corresponding ꢀ-halo-R,ꢀ-unsaturated esters20
(Table 2). The route involves the Sonogashira coupling between
13 and 10, the oxidation of resulting coupling products 14 to
aldehydes 11 with Dess-Martin periodinane, and the allylation
of 11 with allyl metal reagents 12 to yield 6. All Sonogashira
coupling reactions were run at room temperature and desired
coupling products 14 were obtained in high yields. However, a
non-negligible amount of the (Z)-stereoisomer of 14a (E/Z )
10/1) was produced when the reaction of geometrically pure
(14) (a) Mori, M. Top. Organomet. Chem. 1998, 1, 133–154. (b) Poulsen,
C. S.; Madsen, R. Synthesis 2003, 1–18. (c) Diver, S. T.; Giessert, A. J. Chem.
ReV. 2004, 104, 1317–1382. (d) Mori, M. AdV. Synth. Catal. 2007, 349, 121–
135.
(15) (a) Kusumoto, T.; Nishide, K.; Hiyama, T. Chem. Lett. 1985, 1409–
1410. (b) Kobayashi, S.; Matsui, S.; Mukaiyama, T. Chem. Lett. 1988, 1491–
1494. (c) Liu, Y.; Zhong, Z.; Nakajima, K.; Takahashi, T. J. Org. Chem. 2002,
67, 7451–7456. (d) Jeong, I. H.; Jeon, S. L.; Kim, M. S.; Kim, B. T. J. Fluorine
Chem. 2004, 125, 1629–1638. (e) Irifune, T.; Ohashi, T.; Ichino, T.; Sakai, E.;
Suenaga, K.; Uemura, D. Chem. Lett. 2005, 34, 1058–1059. (f) Casey, C. P.;
Strotman, N. A. J. Org. Chem. 2005, 70, 2576–2581.
(16) For a review, see: Chinchilla, R.; Ne´jera, C. Chem. ReV. 2007, 107,
874–922.
a Sonogashira coupling was carried out with ꢀ-halo-R,ꢀ-unsaturated
aldehyde 9 and terminal alkyne 10 in the presence of PdCl2(PPh3)2 (5
mol %), CuI (5 mol %), and NEt3 (3 equiv) in THF at room temperature
for 17-49 h. Allylation was carried out with 11 and allyl metal reagent
12 under various conditions (see the Supporting Information for details).
b Yield of isolated product after silica gel chromatography. c The
reaction was carried out at refluxing temperature.
(17) 9a-f and 9j are known compounds, and 9g-i are commercially
available; see the Supporting Information.
(18) For a review, see: Brahma, S.; Ray, J. K. Tetrahedron 2008, 64, 2883–
2896.
(19) For similar synthetic approaches to the construction of the o-ethynyl(1-
hydroxy-3-butenyl)benzene framework, see: (a) Blanco-Urgoiti, J.; Casarrubios,
L.; Dom´ınguez, G.; Pe´rez-Castells, J. Tetrahedron Lett. 2001, 42, 3315–3317.
(b) Rosillo, M.; Dom´ınguez, G.; Casarrubios, L.; Amador, U.; Pe´rez-Castells, J.
J. Org. Chem. 2004, 69, 2084–2093. (c) Pe´rez-Serrano, L.; Dominguez, G.; Pe´rez-
Castells, J. J. Org. Chem. 2004, 69, 5413–5418. (d) Bajracharya, G. B.;
Nakamura, I.; Yamamoto, Y. J. Org. Chem. 2005, 70, 892–897. (e) Madu, C. E.;
Lovely, C. J. Org. Lett. 2007, 9, 4697–4700.
(Z)-13a with 10a was carried out (Table 2, entry 1). The
undesired (Z)-stereoisomer was removed by gel permeation
chromatography at the next oxidation step, because the separa-
(20) These are known compounds; see the Supporting Information.
3634 J. Org. Chem. Vol. 74, No. 10, 2009

Synthesis of Carbocyclic Aromatic Compounds
TABLE 2. Preparation of 1,5-Octadien-7-yn-4-ols 6, Precursors of Styrenes 4, from 3-Halo-2-propen-1-ols 13 by Sonogashira Coupling,
Oxidation with Dess-Martin Periodinane, and Allylationa
a Sonogashira coupling was carried out with 3-halo-2-propen-1-ol 13 and terminal alkyne 10 in the presence of PdCl2(PPh3)2 (5 mol %), CuI (5 mol
%), and NEt3 (3 equiv) in THF at room temperature for 12-65 h. Oxidation of 14 to 11 was carried out with Dess-Martin periodinane (2 equiv) and
pyridine (4 equiv) in CH2Cl2 at 0 °C for 30 min. Allylation was carried out by reacting 11 with allyl metal reagent 12 under various conditions (see the
Supporting Information for details). b Yield of isolated product after silica gel chromatography. c E/Z ratio (14a: E/Z ) 10/1, 14b-d: E/Z ) 1/>20).
d E/Z ratio (11m: E/Z ) 10/1, 11n-p: E/Z ) 1/>20). e The obtained isomers were separated by gel permeation chromatography at this step.
tion of the E/Z-stereoisomers of 14a was difficult by silica gel
chromatography. The oxidation of 14 with Dess-Martin pe-
riodinane and the allylation of 11 with allyl Grignard or allyl
borane reagents proceeded without any problems and desired 6
were obtained in high yields.
TABLE 3. Preparation of 1,5-Octadien-7-yn-4-ones 7, Precursors
of 4-Vinylphenols 8, from 1,5-Octadien-7-yn-4-ols 6 by Oxidation
with Dess-Martin Periodinanea
The Dess-Martin oxidation was employed for the conversion
of 6 into 7, the acyclic precursors of 4-vinylphenols 8 (Table
3). The reaction was carried out in CH2Cl2 at 0 °C in the
presence of Dess-Martin periodinane and pyridine. To our
delight, 7 proved to be stable and isolable, while we failed to
obtain 4,7-octadien-1-yn-3-ones by oxidation of the alcohol
derivatives of 3.13f
Next, we tried to synthesize substituted styrenes from a wide
variety of resulting acyclic precursors 6 and 7 by using RCEM
(Tables 4 and 5). Since ethylene often plays significant roles in
RCEM,21 we conducted all RCEM reactions under both nitrogen
and ethylene atmospheres and compared the difference between
the two reaction conditions.
entry
6
7
yieldb (%)
1
2
3
4
5
6
7
8
6a
6c
6d
6e
6f
6g
6i
6m
6n
6o
6p
6q
7a
7c
7d
7e
7f
7 g
7i
7m
7n
7o
7p
7q
82
72
45
59
73
69
60
26
89
63
63
78
As can be seen from Table 4, the RCEM/dehydration of 6
successfully furnished a wide variety of substituted styrenes 4
having various functionalities and the RCEM with Grubbs
9
10
11
12
(21) Mori and co-workers reported the beneficial effects of ethylene
atmosphere in RCEM. See: (a) Mori, M.; Sakakibara, N.; Kinoshita, A. J. Org.
Chem. 1998, 63, 6082–6083. For recent examples of the RCEM conducted under
ethylene gas, see: (b) Kim, B. G.; Snapper, M. L. J. Am. Chem. Soc. 2006, 128,
52–53. (c) Kaliappan, K. P.; Ravikumar, V. J. Org. Chem. 2007, 72, 6116–
6126. (d) Yang, Q.; Lai, Y.-Y.; Xiao, W.-J.; Alper, H. Tetrahedron Lett. 2008,
49, 7334–7336.
a The reaction was carried out with 1,5-octadien-7-yn-4-ol 6,
Dess-Martin periodinane (2 equiv), and pyridine (4 equiv) in CH2Cl2 at
0
°C for 0.5-1 h. b Yield of isolated product after silica gel
chromatography.
J. Org. Chem. Vol. 74, No. 10, 2009 3635

Takahashi et al.
TABLE 4. Synthesis of Styrenes 4 by RCEM/Dehydration of 6a
a Ring-closing enyne metathesis was carried out with 1,5-octadien-7-yn-4-ol 6 and ruthenium catalyst (15, 7.5 mol %) in toluene (0.01 M) for 2 h
under ethylene or nitrogen atmosphere (1 atm). The reaction mixture was treated with p-toluenesulfonic acid (10 mol %) at room temperature for 1 h.
b Yield of isolated product after silica gel chromatography. c For the dehydration, the reaction mixture after RCEM was treated with silica gel (SiO2;
excess) and stirred for 9 h at room temperature. d The reaction was carried out with freshly prepared ruthenium catalyst (15, 7.5 mol %). e Even if the
load of freshly prepared ruthenium catalyst was decreased to 1 mol %, the reaction still efficiently furnished 4h in 80% yield. f Recovered 6j and an
isomer that has the 2,5-octadien-7-yn-4-ol framework were obtained. g The reaction was carried out in the presence of ruthenium catalyst (15, 15 mol
%).
3636 J. Org. Chem. Vol. 74, No. 10, 2009

Synthesis of Carbocyclic Aromatic Compounds
TABLE 5. Synthesis of 4-Vinylphenols 8 by RCEM/Tautomerization of 7a
a Ring-closing enyne metathesis was carried out with 1,5-octadien-7-yn-4-one 7 and ruthenium catalyst (15, 7.5 mol %) in toluene (0.01 M) for 2 h
under ethylene or nitrogen atmosphere (1 atm). b Yield of isolated product after silica gel chromatography. c The reaction was carried out in the presence
of ruthenium catalyst (15, 15 mol %). d The reaction was carried out at substrate concentration of 0.1 M.
second-generation catalyst 1522 proceeded well without the acyl
protection of the hydroxyl group of 6.13f,23 The formation of
condensed styrenes having five- to eight-membered aliphatic
rings 4a-f (Table 4, entries 1-12), 4-vinylbenzothiophene 4g
(Table 4, entries 13 and 14), and 1-vinylnaphthalenes 4h and
4k (entries 15, 16, and 25-28) was achieved by the RCEM/
dehydration of corresponding enyne substrates 6. Further, the
construction of two rings simultaneously from 6l and 6m yielded
1,5-divinylanthracene 4l (Table 4, entries 29 and 30) and 1,4-
bis(1-phenylethenyl)benzene derivative 4m (Table 4, entries 31
and 32), respectively. Single-ring styrenes 4n-p were also
synthesized in good yields without any problems (Table 4,
entries 33-38). Applying the tandem RCEM/RCM to 6q that
has a second olefin functionality at the appropriate position led
to the construction of two rings and resulted in the formation
of 1,2-dihydronaphthalene 4q as the final product (Table 4,
entries 39 and 40).24
Comparing the difference between nitrogen and ethylene
atmospheres revealed that the reactions under ethylene gas
proceeded smoothly and gave products in high yields in most
runs. Striking differences were observed in the reactions of
substrates having an R3 substituent (Table 4, entries 5, 33 vs
entries 6, 34). Substrate 6i that had substituents at both R1 and
R2 positions could not be converted into corresponding product
(22) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1,
953–956. (b) Trnka, T. M.; Morgan, J. P.; Sanford, M. S.; Wilhelm, T. E.; Scholl,
M.; Choi, T.-L.; Ding, S.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2003,
125, 2546–2558.
(23) For acceleration effect of an allylic hydroxyl group on RCEM, see:
Imahori, T.; Ojima, H.; Yoshimura, Y.; Takahata, H. Chem.sEur. J. 2008, 14,
10762–10771.
(24) The sequence of the RCEM/RCM/dehydration/DDQ oxidation of 6q
provided 1-(3-chloropropyl)naphthalene in 49% isolated yield.
J. Org. Chem. Vol. 74, No. 10, 2009 3637

Takahashi et al.
SCHEME 2
SCHEME 3
4i at all under nitrogen or ethylene atmosphere (Table 4, entries
17-20). On the other hand, the reaction of 6k that has a methyl
group at R2 position and a terminal alkynyl group furnished
corresponding product 4k (Table 4, entries 25 and 26). In this
case, however, the yields were extremely low and the beneficial
effects of ethylene were not observed. Although slight improve-
ment in product yield was attained by lowering temperature and
increasing catalyst load, cross-metathesis product 4k′, which
has a phenyl group that was derived from catalyst 15, was
formed in a non-negligible amount and its amount increased as
the catalyst load increased (Table 4, entries 27 and 28).
Concerning the R1 position, the introduction of various alkyl
and aryl substituents was accomplished successfully. However,
substrate 6j that has a bulky trimethylsilyl group at R1 position
was found to be inactive to RCEM (Table 4, entries 21-24).
The results of RCEM/tautomerization of isolated 7 for the
synthesis of 4-vinylphenols 8 are summarized in Table 5. Similar
to styrenes 4, a wide variety of 8 having various functionalities,
such as a haloalkyl, a phthalimido, an ester, or a benzyloxy
group, were obtained due to the great functional group tolerance
of the catalyst. As we had anticipated, the reaction of 7i that
has a methyl group at R2 position did not proceed at all (Table
5, entries 13-16). The difference in the reactivity of 7 between
nitrogen and ethylene atmospheres showed the same tendency
as that of 6. In most runs, the reactions under ethylene gas gave
products in high yields and the differences were most prominent
in the reactions of substrates having an R3 substituent (Table 5,
entries 3, 19 vs entries 4, 20). One exception was the reaction
of 7o in which product 8o was obtained in lower yield under
ethylene gas than under nitrogen gas (Table 5, entry 21 vs entry
22). The reason for the low yield of the reaction under ethylene
gas is the formation of byproduct having structures that were
undefined and difficult to assign.
It can be assumed that the sluggishness of the reaction
between Ru-alkylidene intermediate 17 and acyclic substrate 6
or 7 in the ene-then-yne mechanism25 accounts for such a
decrease in reactivity under nitrogen gas (Scheme 2). In
particular, the presence of the R3 substituent would hinder this
step by steric interactions. In contrast, under ethylene gas, it is
possible to interpret that ethylene promotes the formation of
16 from 17 smoothly via 18, which must be advantageous for
the steric hindrance.
This procedure can be applied to the synthesis of highly useful
aromatic compounds. 1,3,5-Tris(1-phenylethenyl)benzene is an
attractive linking agent for the synthesis of branched polysty-
renes.26 The preparation of this compound was accomplished
by the Wittig olefination of 1,3,5-tris(benzoyl)benzene that was
prepared by the Friedel-Crafts reaction of benzene with 1,3,5-
SCHEME 4
benzenetricarbonyl trichloride. We envisaged that various 1,3,5-
tris(1-phenylethenyl)benzene derivatives could be synthesized
by the RCEM/dehydration strategy. In fact, the construction of
three benzene rings from 6r by the RCEM/dehydration strategy
led to the formation of desired 1,3,5-tris(1-phenylethenyl)ben-
zene derivative 4r in good yields (Scheme 3).
1,1′-Binaphthyl compounds constitute a class of compounds
employed in many research fields, e.g., asymmetric synthesis,
molecular recognition, and polydendrimer.27 Therefore, the
development of flexible synthetic methods of these compounds
continues to be an active area of research. Our next plan was
the synthesis of 1,1′-binaphthyl compounds using the RCEM/
dehydration strategy. The retrosynthetic analysis shown in
Scheme 4 revealed that 1,1′-binaphthyl compounds 19 could
be synthesized by the tandem RCEM/RCM of dienynes 21
followed by the double dehydration of resulting diols 20. To
our delight, combination of the tandem RCEM/RCM with the
dehydration of 21a that was prepared readily by allylation of
corresponding dicarboxyaldehyde successfully furnished desired
nonsymmetrically substituted 1,1′-binaphthyl derivative 19a
(Scheme 5).
Conclusion
We have synthesized a wide variety of styrenes 4 by the
RCEM/dehydration of acyclic precursors 6 that were readily
(25) (a) Lippstreu, J. J.; Straub, B. F. J. Am. Chem. Soc. 2005, 127, 7444–
7457. (b) Lloyd-Jones, G. C.; Margue, R. G.; de Vries, J. G. Angew. Chem., Int.
Ed. 2005, 44, 7442–7447.
(26) (a) Quirk, R. P.; Tsai, Y. Macromolecules 1998, 31, 8016–8025. (b)
Lee, J. S.; Quirk, R. P.; Foster, M. D. Macromolecules 2005, 38, 5381–5392.
(27) (a) Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345–50. (b) Pu,
L. Chem. ReV. 1998, 98, 2405–2494. (c) Kocovsky´, P.; Vyskocil, S.; Smrcina,
M. Chem. ReV. 2003, 103, 3213–3245. (d) Brunel, J. M. Chem. ReV. 2005, 105,
857–897.
3638 J. Org. Chem. Vol. 74, No. 10, 2009

Synthesis of Carbocyclic Aromatic Compounds
SCHEME 5
128.26, 131.24, 135.08, 149.31; HRMS (FAB) calcd for C20H23O
(M+ - H) 279.1749, found 279.1761.
Procedures for the Preparation of (E)-6-Benzyloxymethyl-3-
methyl-8-phenyl-1,5-octadien-7-yn-4-ol (6n). To a mixture of
dichlorobis(triphenylphosphine)palladium (54.7 mg, 0.078 mmol)
and ally alcohol 13a (478 mg, 1.57 mmol) in THF (22 mL) was
added triethylamine (660 µL, 4.74 mmol). After the mixture was
stirred for 10 min at room temperature, terminal acetylene 10a (241
mg, 2.37 mmol) and copper iodide (15.0 mg, 0.079 mmol) were
added. The resulting mixture was stirred at room temperature for
12 h. The reaction mixture was diluted with saturated aq NH4Cl
and extracted with ethyl acetate three times. The organic layers
were combined, washed with brine, and dried over Na2SO4. After
filtration, the filtrate was evaporated under reduced pressure. The
residue was purified by silica gel column chromatography (hexane/
EtOAc ) 3/1) to give (E)-3-benzyloxymethyl-5-phenyl-2-penten-
prepared from ꢀ-halo-R,ꢀ-unsaturated aldehydes 9 or 3-halo-
2-propen-1-ols 13 by utilizing highly reliable transformations
at all steps. Employing the RCEM/dehydration enabled us to
introduce various functionalities to the styrene framework with
perfect regiocontrol. Moreover, we could obtain 4-vinylstyrenes
8 by the RCEM/tautomerization of 7 that were prepared by
oxidizing 6. Because the RCEM/tautomerization does not
involve any elimination steps, it is a 100% atom-economical
process. Obtained 8 are markedly useful building blocks whose
hydroxyl and vinyl groups are convertible in many ways. In
addition, we have presented the application of the method to
the synthesis of unique aromatic compounds, 1,3,5-tris(1-
phenylethenyl)benzene derivative 4r and 1,1′-binaphthyl deriva-
tive 19a. We are currently extending the scope of the methods
to the synthesis of other important aromatic compounds and
the catalytic asymmetric synthesis of biaryl compounds, includ-
ing 1,1′-binaphthyl derivatives, by employing homochiral Ru-
alkylidene catalysts.
1
4-yn-1-ol (14a) (405 mg,1.46 mmol, 93% yield, brown oil): H
NMR (CDCl3) δ 1.61 (br s, 1H), 4.13 (d, J ) 1.2 Hz, 2H), 4.51 (t,
J ) 6.4 Hz, 2H), 4.55 (s, 2H), 6.24 (tt, J ) 6.8, 1.6 Hz, 1H),
7.24-7.47 (m, 10H). To a stirred suspension of Dess-Martin
periodinane (1.24 g, 2.92 mmol) in dichloromethane (18 mL) and
pyridine (500 µL, 5.80 mmol) was added 14a (406 mg, 1.46 mmol)
at 0 °C. The reaction mixture was warmed to room temperature
and stirred for 30 min. The mixture was then diluted with Et2O
and passed through Celite. The residual solid was washed with Et2O
thoroughly. The filtrate was concentrated under reduced pressure.
Purification by silica gel flash column chromatography (hexane/
EtOAc ) 6/1) gave (E)-3-benzyloxymethyl-5-phenyl-2-penten-4-
ynal (11m) (E/Z ) 9/1 mixture: 323 mg, 1.17 mmol, 80% yield,
yellow oil). The single isomer was obtained by gel permeation
1
chromatography: H NMR (CDCl3) δ 4.30 (d, J ) 1.9 Hz, 2H),
4.64 (s, 2H), 6.57 (dt, J ) 8.3, 1.9 Hz, 1H), 7.30-7.44 (m, 8H),
7.48-7.52 (m, 2H), 10.26 (d, J ) 8.6 Hz, 1H); 13C NMR (CDCl3)
δ 71.29, 72.91, 82.93, 101.25, 121.39, 127.68, 127.98, 128.52,
128.56, 129.75, 131.92, 132.27, 132.29, 137.22, 143.02, 192.26;
HRMS (FAB) calcd for C19H17O2 (M+ + H) 277.1229, found
277.1237. To a stirred solution of 11m (59.2 mg, 0.214 mmol) in
THF (20 mL) was added crotylmagnesium chloride (0.50 M solution
in THF, 860 µL, 0.430 mmol) at 0 °C and the mixture stirred for
30 min. The mixture was then quenched by addition of saturated
aq NH4Cl, extracted with EtOAc three times, and washed with brine.
The organic layers were dried over Na2SO4 and concentrated under
reduced pressure. The residue was purified by silica gel column
chromatography (hexane/EtOAc ) 3/1) to give (E)-6-benzyloxym-
ethyl-3-methyl-8-phenyl-1,5-octadien-7-yn-4-ol (6n) (diastereomeric
mixture: 69.8 mg, 0.210 mmol, 98% yield, colorless oil). The
following data are for a mixture of two diastereomers (0.5/0.5): 1H
NMR (CDCl3) δ 1.08 (d, J ) 7.0 Hz, 1.5H), 1.11 (d, J ) 7.0 Hz,
1.5H), 1.93 (br s, 0.5H), 1.99 (br s, 0.5H), 2.37 (sextet, J ) 7.0
Hz, 0.5H), 2.54 (sextet, J ) 7.0 Hz, 0.5H), 4.13 (t, J ) 1.2 Hz,
1.0H), 4.15 (t, J ) 1.5 Hz, 1.0H), 4.53-4.62 (m, 0.5H), 4.58 (d, J
) 1.8 Hz, 1.0H), 4.59 (d, J ) 2.1 Hz, 1.0H), 4.68 (t, J ) 7.1 Hz,
0.5H), 5.11-5.19 (m, 2.0H), 5.81-5.89 (m, 1.0H), 6.02 (q, J )
1.2 Hz, 0.5H), 6.03 (q, J ) 1.5 Hz, 0.5H), 7.27-7.46 (m, 10.0H);
13C NMR (CDCl3) δ 14.90, 16.07, 43.76, 44.49, 72.04, 72.09, 72.12,
73.42, 85.33, 95.29, 95.47, 116.57, 122.51, 122.86, 122.89, 127.70,
127.75, 128.33, 128.38, 128.49, 131.53, 138.01, 138.54, 139.75,
140.12; HRMS (FAB) calcd for C23H23O (M+ - OH) 315.1749,
found 315.1755.
Experimental Section
Procedures for the Preparation of 1-((Z)-2-Phenylethynyl-1-
cyclooctenyl)-3-buten-1-ol (6a). To a mixture of dichlorobis(triph-
enylphosphine)palladium (210.6 mg, 0.300 mmol) and ꢀ-halo-R,ꢀ-
unsaturated aldehyde 9a (1.30 g, 5.99 mmol) in THF (43 mL) was
added triethylamine (1.70 mL, 12.2 mmol). After the mixture was
stirred for 10 min at room temperature, terminal acetylene 10a (1.30
mL, 11.8 mmol) and copper iodide (22.9 mg, 0.120 mmol) were
added. The resulting mixture was stirred at room temperature for
17 h. The reaction mixture was diluted with saturated aq NH4Cl
and extracted with ethyl acetate three times. The organic layers
were combined, washed with brine, and dried over Na2SO4. After
filtration, the filtrate was evaporated under reduced pressure. The
residue was purified by silica gel column chromatography (hexane/
EtOAc ) 20/1) to give (Z)-2-phenylethynyl-1-cyclooctenecarbal-
1
dehyde (11a) (1.15 g, 4.83 mmol, 80% yield, pale yellow oil): H
NMR (CDCl3) δ 1.46-1.60 (m, 6H), 1.80-1.90 (m, 2H), 2.45-2.52
(m, 2H), 2.65-2.68 (m, 2H), 7.33-7.39 (m, 3H), 7.46-7.50 (m,
2H), 10.33 (s, 1H); 13C NMR (CDCl3) δ 23.48, 25.81, 26.38, 28.86,
29.72, 33.96, 86.73, 98.96, 122.28, 128.38, 128.99, 131.61, 142.89,
145.77, 192.40; HRMS (FAB) calced for C17H19O (M+ + H)
239.1436, found 239.1425. To a stirred solution of 11a (842 mg,
3.53 mmol) in Et2O (20 mL) was added allylmagnesium bromide
(1.07 M solution in Et2O, 7.60 mL, 7.06 mmol) at 0 °C and the
mixture stirred for 30 min. The mixture was then quenched by
addition of saturated aq NH4Cl, extracted with EtOAc three times,
and washed with brine. The organic layers were dried over Na2SO4
and concentrated under reduced pressure. The residue was purified
by silica gel column chromatography (hexane/EtOAc ) 10/1) to
give 1-((Z)-2-phenylethynyl-1-cyclooctenyl)-3-buten-1-ol (6a) (852
Procedures for the Preparation of 1-((Z)-2-Phenylethynyl-1-
cyclooctenyl)-3-buten-1-one (7a). To a stirred suspension of
Dess-Martin periodinane (632 mg, 1.49 mmol) in dichloromethane
(5 mL) and pyridine (260 µL, 3.02 mmol) was added 6a (209 mg,
0.746 mmol) at 0 °C. The reaction mixture was warmed to room
temperature and stirred for 30 min. The mixture was then diluted
with Et2O and passed through Celite. The residual solid was washed
with Et2O thoroughly. The filtrate was concentrated under reduced
pressure and purified by silica gel flash column chromatography
(hexane/EtOAc ) 10/1) to give 1-((Z)-2-phenylethynyl-1-cycloocte-
1
mg, 3.04 mmol, 86% yield, colorless oil): H NMR (CDCl3) δ
1.45-1.73 (m, 8H), 1.88 (s, 1H), 2.29-2.46 (m, 6H), 5.12 (dt, J
) 1.9, 1.0 Hz, 1H), 5.14-5.16 (m, 1H), 5.19-5.21 (m, 1H), 5.89
(ddt, J ) 17.3, 10.2, 7.1 Hz, 1H), 7.28-7.33 (m, 3H), 7.39-7.42
(m, 2H); 13C NMR (CDCl3) δ 26.00, 26.15, 26.64, 28.44, 31.12,
31.53, 40.48, 73.70, 89.19, 93.41, 117.69, 119.21, 123.74, 127.82,
J. Org. Chem. Vol. 74, No. 10, 2009 3639

Takahashi et al.
nyl)-3-buten-1-one (7a) (171 mg, 0.614 mmol, 82% yield, pale
yellow oil): H NMR (CDCl3) δ 1.48-1.55 (m, 4H), 1.63-1.68
Procedures for the Preparation of (1-(5,6,7,8,9,10-Hexahydro-
1-hydroxy-4-benzocyclooctenyl)vinyl)benzene (8a). Under Ethyl-
ene Atmosphere. To a solution of 7a (84.3 mg, 0.303 mmol) in
toluene (30.3 mL, 0.01 M) was added 7.5 mol % of catalyst 15
(19.3 mg, 0.0227 mmol) in one portion under nitrogen, and then
the system was evacuated carefully and filled with ethylene gas in
three cycles. The reaction mixture was heated to 80 °C and stirred
for 2 h. The mixture was concentrated under reduced pressure and
purified by PTLC on silica gel (hexane/EtOAc ) 5/1) to give (1-
(5,6,7,8,9,10-hexahydro-1-hydroxy-4-benzocyclooctenyl)vinyl)ben-
zene (8a) (82.7 mg, 0.297 mmol, 98% yield, colorless oil). Under
Nitrogen Atmosphere. To a solution of 7a (53.2 mg, 0.191 mmol)
in toluene (19.1 mL, 0.01 M) was added 7.5 mol % of catalyst 15
(12.2 mg, 0.022 mmol) in one portion under nitrogen. After being
stirred for 2 h at 80 °C, the mixture was concentrated under reduced
pressure and purified by PTLC on silica gel (hexane/EtOAc ) 5/1)
to give (1-(5,6,7,8,9,10-hexahydro-1-hydroxy-4-benzocycloocte-
nyl)vinyl)benzene (8a) (39.4 mg, 74% yield, colorless oil): 1H NMR
(CDCl3) δ 1.27-1.39 (m, 6H), 1.65-1.73 (m, 2H), 2.56-2.61 (m,
2H), 2.81-2.85 (m, 2H), 4.64 (s, 1H), 5.14 (d, J ) 1.7 Hz, 1H),
5.75 (d, J ) 1.7 Hz, 1H), 6.67 (d, J ) 8.3 Hz, 1H), 6.93 (d, J )
8.1 Hz, 1H), 7.20-7.31 (m, 5H); 13C NMR (CDCl3) δ 24.31, 26.11,
26.44, 28.92, 29.43, 30.91, 112.39, 114.77, 126.44, 127.30, 127.42,
128.15, 128.60, 134.21, 140.83, 141.42, 149.47, 152.32; HRMS
(FAB) calcd for C20H22O (M+) 278.1671, found 278.1671.
1
(m, 2H), 1.75-1.79 (m, 2H), 2.48-2.51 (m, 2H), 2.57-2.60 (m,
2H), 3.84 (dt, J ) 7.1, 1.2 Hz, 2H), 5.14 (dq, J ) 17.2, 1.5 Hz,
1H), 5.17 (dq, J ) 9.8, 1.6 Hz, 1H), 6.05 (ddt, J ) 17.3, 10.2, 6.8
Hz, 1H), 7.26-7.36 (m, 3H), 7.42-7.45 (m, 2H); 13C NMR
(CDCl3) δ 26.18, 26.38, 28.45, 28.96, 30.30, 34.39, 47.19, 90.19,
97.42, 118.12, 122.92, 128.40, 128.56, 128.68, 131.38, 131.57,
146.61, 202.56; HRMS (FAB) calcd for C20H23O (M+ + H)
279.1749, found 279.1739.
Procedures for the Preparation of 5,6,7,8,9,10-Hexahydro-1-(1-
phenylvinyl)benzo[8]annulene (4a). Under Ethylene Atmosphere.
To a solution of 6a (61.7 mg, 0.220 mmol) in toluene (22.0 mL,
0.01 M) was added 7.5 mol % of catalyst 15 (14.0 mg, 0.0227
mmol) in one portion under nitrogen, and then the system was
evacuated carefully and filled with ethylene gas in three cycles.
The reaction mixture was heated to 80 °C and stirred for 2 h. After
being cooled to room temperature, the reaction mixture was treated
with p-toluenesulfonic acid (4.2 mg, 0.022 mmol) and stirred for
1 h at room temperature. The mixture was concentrated under
reduced pressure and purified by PTLC on silica gel (hexane) to
give 5,6,7,8,9,10-hexahydro-1-(1-phenylvinyl)benzo[8]annulene
(4a); (42.8 mg, 0.163 mmol, 74% yield, colorless oil). Under
Nitrogen Atmosphere. To a solution of 6a (78.1 mg, 0.279 mmol)
in toluene (27.9 mL, 0.01 M) was added 7.5 mol % of catalyst 15
(17.7 mg, 0.0209 mmol) in one portion under nitrogen. After being
stirredfor 2 h at 80 °C, the reaction mixture was treated with
p-toluenesulfonic acid (5.3 mg, 0.028 mmol) and stirred for 1 h at
room temperature. The mixture was concentrated under reduced
pressure and purified by PTLC on silica gel (hexane) to give
5,6,7,8,9,10-hexahydro-1-(1-phenylvinyl)benzo[8]annulene (4a) (57.2
Acknowledgment. We appreciate the financial support from
the Mitsubishi Chemical Corporation Fund and a Grant-in-Aid
for Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
1
mg, 0.218 mmol, 78% yield, colorless oil): H NMR (CDCl3) δ
1.23-1.40 (m, 6H), 1.68 (m, 2H), 2.59-2.62 (m, 2H), 2.75-2.79
(m, 2H), 5.16 (d, J ) 1.2 Hz, 1H), 5.78 (d, J ) 1.5 Hz, 1H), 7.04
(dd, J ) 7.3, 2.0 Hz, 1H), 7.09-7.17 (m, 2H), 7.21-7.27 (m, 5H);
13C NMR (CDCl3) δ 25.89, 26.28, 28.18, 30.80, 32,39, 32,77,
114.58, 125.71, 126.38, 127.47, 128.19, 128.26, 128.59, 138.59,
141.05, 141.39, 142.23, 149.52; HRMS (FAB) calcd for C20H23
(M+ + Η) 263.1800, found 263.1803.
Supporting Information Available: Experimental details,
1
1H NMR and 13C NMR spectra of new compounds, and H
NMR spectra of known compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO900456G
3640 J. Org. Chem. Vol. 74, No. 10, 2009