Enantioselective intramolecular [2 + 2 + 2] cycloaddition of enediynes for the synthesis of chiral cyclohexa-1,3-dienes

Article abstract of DOI:10.1021/jo070762d

(Chemical Equation Presented) The enantioselective intramolecular [2 + 2 + 2] cycloaddition of various enediynes, where two acetylenic moieties are connected by a trans-olefinic moiety, gave chiral tricyclic cyclohexa-1,3-dienes using Rh-H₈-BIN

Full text of DOI:10.1021/jo070762d

Enantioselective Intramolecular [2 + 2 + 2] Cycloaddition of
Enediynes for the Synthesis of Chiral Cyclohexa-1,3-dienes
Takanori Shibata,* Hiroshi Kurokawa, and Kazumasa Kanda
Department of Chemistry and Biochemistry, School of AdVanced Science and Engineering,
Waseda UniVersity, Shinjuku, Tokyo, 169-8555, Japan
tshibata@waseda.jp
ReceiVed April 11, 2007
The enantioselective intramolecular [2 + 2 + 2] cycloaddition of various enediynes, where two acetylenic
moieties are connected by a trans-olefinic moiety, gave chiral tricyclic cyclohexa-1,3-dienes using Rh-
H8-BINAP catalyst. In the case of carbon-atom-tethered enediynes, enantioselectivity was generally good-
to-high regardless of the substituents on their alkyne termini. In contrast, with heteroatom-tethered
enediynes, appropriate substituents were required to induce the oxidative coupling of alkyne and alkene
moieties before that of two alkyne moieties, which would be important for highly enantioselective
intramolecular cycloaddition.
SCHEME 1. Types of Intramolecular [2 + 2 + 2]
Cycloadditions
Introduction
The transition-metal-catalyzed [2 + 2 + 2] cycloaddition of
C2-unsaturated motifs, such as alkynes and alkenes, is a
powerful and reliable method for the synthesis of a six-
membered carbon skeleton.1 There are several types of cycload-
ditions, including intermolecular and intramolecular reactions.
Among the latter reactions (Scheme 1), the cycloaddition of
triynes is a well-known protocol for the synthesis of substituted
benzene derivatives (type A), and various transition-metal
complexes including those of Rh,2 Ni,3 Pd,4 Ru,5 Co,6 Mo,7 and
Fe8 have been shown to be efficient catalysts. Three examples
(1) Recent reviews: (a) Yamamoto, Y. Curr. Org. Chem. 2005, 9, 503-
509. (b) Kotha, S.; Brahmachary, E.; Lahiri, K. Eur. J. Org. Chem. 2005,
4741-4761. (c) Chopade, P. R.; Louie, J. AdV. Synth. Catal. 2006, 348,
2307-2327.
(2) (a) Grigg, R.; Scott, R.; Stevenson, P. J. Chem. Soc., Perkin Trans.
1 1988, 1357-1364. (b) Ojima, I.; Vu, A. T.; McCullagh, J. V.; Kinoshita,
A. J. Am. Chem. Soc. 1999, 121, 3230-3231. (c) Witulski, B.; Alayrac, C.
Angew. Chem., Int. Ed. 2002, 41, 3281-3284. (d) Kinoshita, H.; Shinokubo,
H.; Oshima, K. J. Am. Chem. Soc. 2003, 125, 7784-7785.
(3) Bhatarah, P.; Smith, E. H. J. Chem. Soc., Perkin Trans. 1 1992,
2163-2168.
(4) (a) Negishi, E.; Harring, L. S.; Owczarczyk, Z.; Mohamud, M. M.;
Ay, M. Tetrahedron Lett. 1992, 33, 3253-3256. (b) Yamamoto, Y.;
Nagata, A.; Arikawa, Y.; Tatsumi, K.; Itoh, K. Organometallics 2000,
19, 2403-2405. (c) Yamamoto, Y.; Nagata, A.; Nagata, H.; Ando, Y.;
Arikawa, Y.; Tatsumi, K.; Itoh, K. Chem.-Eur. J. 2003, 9, 2469-2483.
(d) Pla-Quintana, A.; Roglans, A.; Torrent, A. Organometallics 2004, 23,
2762-2767.
(5) (a) Peters, J.-U.; Blechert, S. Chem. Commun. 1997, 1983-1984.
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K. J. Am. Chem. Soc. 2003, 125, 12143-12160.
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M. J. Org. Chem. 1998, 63, 4046-4050. (b) Son, S. U.; Paik, S.-J.; Lee, S.
I.; Chung, Y. K. J. Chem. Soc., Perkin Trans. 1 2000, 141-143. (c)
Sugihara, T.; Wakabayashi, A.; Nagai, Y.; Takao, H.; Imagawa, H.;
Nishizawa, M. Chem. Commun. 2002, 576-577. (d) Teply´, F.; Stara´, I.
G.; Stary´, I.; Kolla´rovicˇc, A.; Sˇaman, D.; Vyskocˇil, Sˇ.; Fiedler, P. J. Org.
Chem. 2003, 68, 5193-5197.
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10.1021/jo070762d CCC: $37.00 © 2007 American Chemical Society
Published on Web 07/18/2007
J. Org. Chem. 2007, 72, 6521-6525
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Shibata et al.
SCHEME 2. Enantioselective [2 + 2 + 2] Cycloaddition of
(E)-Enediynes
of an enantioselective reaction have also been reported: a
helically chiral compound was obtained using a chiral Ni
catalyst,9 ortho-diarylbenzenes with two axial chiralities were
provided using a chiral Ir catalyst,10 and planar chiral metacy-
clophanes were obtained using a chiral Rh catalyst.11 Compared
with the abundant information regarding triynes, there are few
examples of enediynes, including yne-ene-ynes (type B) and
yne-yne-enes (type C).12 Yamamoto and co-workers reported
the Pd-catalyzed reaction of an oxygen-tethered yne-ene-yne,
which gave a mixture of cyclohexa-1,3- and 1,4-dienes.13 Pd
catalyst could also be used in the cycloaddition of yne-yne-
enes.13 While the cobalt-mediated reaction of yne-yne-enes,14
including a diastereoselective version,15 has been reported, to
the best of our knowledge the catalytic and enantioselective
cycloaddition of enediynes remains unexplored.16,17
TABLE 1. Screening of Various Chiral Ligands
entry
ligand
time/h
yield/%
ee/%
Recently, Roglans and co-workers reported a Rh-catalyzed
intramolecular [2 + 2 + 2] cycloaddition, where macrocyclic
enediynes with an E-olefinic moiety gave dl cycloadducts and
those with a Z-olefinic moiety gave meso cycloadducts.18
Therefore, the enantioselective cycloaddition of an acyclic
enediyne with an E-olefinic moiety using a chiral catalyst would
give a tricyclic cyclohexa-1,3-diene with two chiral carbon
centers via a bicyclic metallacyclopentene (Scheme 2). If a
symmetrical substrate (R ) R′) were used, a C2 symmetrical
compound would be obtained.
1
2
(S)-BINAP
24
24
1/4
3
59
15
75
NR
NR
19
1
76
(S)-tolBINAP
(S)-H8-BINAP
(S,S)-BDPP
3
4a
5a
(S,S)-MeDUPHOS
3
a DCE was used as solvent, and the reaction temperature was gradually
raised to reflux.
pathway via alkyne-alkene coupling and that via alkyne-
alkyne coupling are also discussed.
We report here that the cationic Rh-H8-BINAP complex
catalyzes an enantioselective [2 + 2 + 2] cycloaddition of
symmetrical and unsymmetrical (E)-enediynes. The different
enantioselectivities of this cycloaddition between a reaction
Results and Discussion
We chose carbon-atom-tethered symmetrical enediyne 1a as
a model substrate and used it in the reaction using cationic
rhodium complexes with various chiral diphosphine ligands in
dichloromethane (DCM) at room temperature (Table 1).19 When
BINAP was used, [2 + 2 + 2] cycloadduct 2a was obtained as
a dl isomer, as expected; however, its enantiomeric excess was
low (entry 1). In the case of tolBINAP, which was an efficient
chiral ligand for the enantioselective intermolecular [2 + 2 +
2] cycloaddition of enynes with alkynes,20 the reaction proceeded
sluggishly, and almost no enantioselectivity was observed (entry
2). In contrast, H8-BINAP was found to be an appropriate ligand
for the present reaction: enediyne 1a was consumed within 15
min and cycloadduct 2a was obtained in good yield and ee (entry
3). Rh-MeDUPHOS and -BDPP complexes showed almost no
catalytic activity (entries 4 and 5).
(8) Saino, N.; Kogure, D.; Okamoto, S. Org. Lett. 2005, 7, 3065-3067.
(9) Stara´, I. G.; Stary´, I.; Kolla´rovicˇ, A.; Teply´, F.; Vyskocˇil, Sˇ.; Sˇaman,
D. Tetrahedron Lett. 1999, 40, 1993-1996.
(10) Shibata, T.; Tsuchikama, K.; Otsuka, M. Tetrahedron: Asymmetry
2006, 17, 614-619.
(11) Tanaka, K.; Sagae, H.; Toyoda, K.; Noguchi, K.; Hirano, M. J. Am.
Chem. Soc. 2007, 129, 1522-1523.
(12) Carbonylative carbocyclization of yne-yne-enes was already re-
ported: Ojima, I.; Lee, S.-Y. J. Am. Chem. Soc. 2000, 122, 2385-2386.
(13) Yamamoto, Y.; Kuwabara, S.; Ando, Y.; Nagata, H.; Nishiyama,
H.; Itoh, K. J. Org. Chem. 2004, 69, 6697-6705.
(14) Slowinski, F.; Aubert, C.; Malacria, M. AdV. Synth. Catal. 2001,
343, 64-67.
(15) (a) Slowinski, F.; Aubert, C.; Malacria, M. Tetrahedron Lett. 1999,
40, 5849-5852. (b) Slowinski, F.; Aubert, C.; Malacria, M. J. Org. Chem.
2003, 68, 378-386.
(16) A pioneering work of Co-mediated cycloaddition of two alkynes
and an alkene for the synthesis of cyclohexa-1,3-dienes: Wakatsuki, T.;
Kuramitsu, T.; Yamazaki, H. Tetrahedron Lett. 1974, 15, 4549-4552.
(17) Catalytic intermolecular [2 + 2 + 2] cycloadditions of two alkyne
and an alkene moieties for the synthesis of cyclohexa-1,3-dienes: (a)
Kezuka, S.; Tanaka, S.; Ohe, T.; Nakaya, Y.; Takeuchi, R. J. Org. Chem.
2006, 71, 543-552. (b) Wu, M.-S.; Rayabarapu, D. K.; Cheng, C.-H.
Tetrahedron 2004, 60, 10005-10009. (c) Sambaiah, T.; Li, L.-P.; Huang,
D.-J.; Lin, C.-H.; Rayabarapu, D. K.; Cheng, C.-H. J. Org. Chem. 1999,
64, 3663-3670. (d) Yamamoto, Y.; Kitahara, H.; Ogawa, R.; Kawaguchi,
H.; Tatsumi, K.; Itoh, K. J. Am. Chem. Soc. 2000, 122, 4310-4319. (e)
Ikeda, S.; Kondo, H.; Mori, N. Chem. Commun. 2000, 815-816. (f) Mori,
N.; Ikeda, S.; Sato, Y. J. Am. Chem. Soc. 1999, 121, 2722-2727. (g)
Yamamoto, Y.; Kitahara, H.; Hattori, R.; Itoh, K. Organometallics 1998,
17, 1910-1912. (h) Yamamoto, Y.; Kitahara, H.; Ogawa, R.; Itoh, K. J.
Org. Chem. 1998, 63, 9610-9611. (i) Ikeda, S.; Watanabe, H.; Sato, Y. J.
Org. Chem. 1998, 63, 7026-7029. (j) Ikeda, S.; Mori, N.; Sato, Y. J. Am.
Chem. Soc. 1997, 119, 4779-4780. (k) Balaich, G. J.; Rothwell, I. P. J.
Am. Chem. Soc. 1993, 115, 1581-1583. (l) Zhou, Z.; Costa, M.; Chiusoli,
G. P. J. Chem. Soc., Perkin Trans. 1 1992, 1399-1406. (m) Zhou, Z.;
Battaglia, L. P.; Chiusoli, G. P.; Costa, M.; Nardelli, M.; Pelizzi, C.; Predieri,
G. J. Chem. Soc., Chem. Commun. 1990, 1632-1634. (n) Suzuki, H.; Itoh,
K.; Ishii, Y.; Simon, K.; Ibers, J. A. J. Am. Chem. Soc. 1976, 98, 8494-
8500.
When a preliminarily isolated chiral rhodium complex, [Rh-
(cod){(S)-H8-binap}]BF4, was used, slight increases in yield and
ee were observed (Table 2, entry 1). Under these reaction
conditions, carbon-atom-tethered symmetrical (E)-enediynes
with various substituents on their termini were examined.21 In
the case of methoxycarbonyl- and benzyloxymethyl-substituted
(19) Tanaka reported cationic Rh-BINAP derivative complexes as
efficient catalysts for intermolecular [2 + 2 + 2] cycloaddition of alkynes.
See: Tanaka, K.; Shirasaka, K. Org. Lett. 2003, 5, 4697-4699.
(20) (a) Evans, P. A.; Lai, K. W.; Sawyer, J. R. J. Am. Chem. Soc. 2005,
127, 12466-12467. (b) Shibata, T.; Arai, Y.; Tahara, Y. Org. Lett. 2005,
7, 4955-4957.
(21) When (Z)-enediyne 1a was examined under the same reaction
conditions, an ene-type product derived from the enyne moiety was a major
product and [2 + 2 + 2] cycloadduct could not be detected. For
enantioselective ene-type reaction of 1,6-enynes with (Z)-olefinic moiety
using chiral Rh catalysts, see: (a) Cao, P.; Zhang, X. Angew. Chem., Int.
Ed. 2000, 39, 4104-4106. (b) Lei, A.; He, M.; Zhang, X. J. Am. Chem.
Soc. 2002, 124, 8198-8199. (c) Lei, A.; Waldkirch, J. P.; He, M.; Zhang,
X. Angew. Chem., Int. Ed. 2002, 41, 4526-4529.
(18) Torrent, A.; Gonza´lez, I.; Pla-Quintana, A.; Roglans, A. J. Org.
Chem. 2005, 70, 2033-2041.
(22) Only a trace amount of cycloadduct 2d was detected at room
temperature for 24 h.
6522 J. Org. Chem., Vol. 72, No. 17, 2007

[2 + 2 + 2] Cycloaddition of Enediynes
TABLE 2. [2 + 2 + 2] Cycloaddition of Carbon-Tethered
Symmetrical Enediynes
SCHEME 3. Possible Explanation of Asymmetric Induction
and the Structure of H8-BINAP
entry
R
time/h
yield/%
ee/%
1
2
3
H
1a
1b
1c
1d
1e
1f
1/4
1
6
24
24
24
81 (2a)
72 (2b)
63 (2c)
81 (2d)
48 (2e)
41 (2f)
78
98
98
97
91
95
CO2Me
CH2OBn
Me
Br
Ph
SCHEME 4. Possible Explanation for the Different
Enantioselectivity
4a
5a
6a,b
a DCE was used as solvent at 60 °C. b The amount of the catalyst was
20 mol %.
enediynes 1b and 1c, the reaction proceeded at room temperature
and the enantioselectivity was extremely high (entries 2 and
3). Me-substituted enediyne 1d was less reactive than enediynes
1b and 1c, and a higher reaction temperature was required;22
however, the ee of cycloadduct 2d was still extremely high
(entry 4). On the basis of the reaction temperature and time,
the reactivity of enediynes depending on the substituents of their
alkyne termini was in the order methoxycarbonyl > benzy-
loxymethyl > methyl. Bromo-substituted enediyne 1e also
underwent the cycloaddition, and 2,3-dibromocylcohexa-1,3-
diene 2e was obtained (entry 5). A phenyl substituent retarded
the cycloaddition and harsher conditions were required, but
cycloadduct 2f was obtained in high ee (entry 6).
the corresponding cycloadduct 2h was obtained in good yield
and extremely high ee (eq 2).
Next, we examined enediyne 1g which has geminal phenyl-
sulfonyl groups on its tethers (eq 1): in contrast to enediyne
1a (Table 2, entry 1), extremely high ee was achieved despite
the lack of a substituent on its alkyne termini. Moreover,
cycloadduct 2g was determined to be an (R,R)-isomer by X-ray
crystallographic measurements (Supporting Information).
Next, we examined nitrogen-tethered enediyne 1i with
methoxycarbonyl groups on its termini, which gave the best
enantioselectivity in the case of carbon-tethered enediynes
(Table 2, entry 2): the substrate was completely consumed
within 30 min and the corresponding cycloadduct 2i was
obtained, but its enantiomeric excess was very low (eq 3).
Scheme 3 shows a possible explanation for the asymmetric
induction of the (R,R)-isomer by the Rh-(S)-H8-BINAP catalyst.
Two asymmetric carbon atoms would be induced at the
formation of metallacyclopentene derived from an enyne moiety
of enediyne. Because of the equatorial phenyls on phosphorus
atoms of H8-BINAP, the first and third quadrants are congested.
As a result, metallacyclopentene A, where the R substituent is
located at the fourth quadrant, is more favorable than metalla-
cyclopentene B, where steric repulsion between R and phenyl
groups exists.
We assumed that the different enantioselectivity depending
on the structure of tethers derives from the reaction pathway
(Scheme 4): π-complexation of the metal catalyst to the enyne
moiety of enediyne would be the beginning of the present cyclo-
addition. In the case of carbon-tethered enediyne, the oxidative
coupling would proceed with high enantioselectivity to give
bicyclic metallacyclopentene C, where two chiral carbon centers
are generated. The subsequent intramolecular alkyne insertion
along with reductive elimination gives a tricyclic cyclohexa-
1,3-diene. In contrast, in the case of nitrogen-tethered enediyne,
the oxidative coupling of two distant alkyne moieties would
proceed before that of the enyne moiety to give a bicyclic
Unsymmetrical enediyne 1h, which has methoxycarbonyl and
methyl groups on its termini, was also a good substrate, and
J. Org. Chem, Vol. 72, No. 17, 2007 6523

Shibata et al.
TABLE 3. [2 + 2 + 2] Cycloaddition of Nitrogen-Tethered
Enediynes
TABLE 4. [2 + 2 + 2] Cycloaddition of Unsymmetrical Enediynes
with Carbon and Nitrogen Tethers
entry
R
R′
time/h
yield/%
ee/%
entry
R
R′
time/h
yield/%
ee/%
1
2
3
4
5
H
H
H
1m
1n
1o
1p
1q
1/4
1
1/4
1/4
1/2
41 (2m)
55 (2n)
66 (2o)
68 (2p)
>99 (2q)
15
64
91
91
97
1
2
3
CH2OBn
Me
CH2OBn
CH2OBn
Bu
1j
1k
1l
2
2
4
75 (2j)
71 (2k)
90 (2l)
51
71
89
Me
Me
Ph
CO2Me
CO2Me
Me
Bu
Me
metallacyclopentadiene D because nitrogen tether activates the
alkynes more than carbon tether. The enantioselectivity of the
subsequent intramolecular alkene insertion is expected to be very
low, and the corresponding cycloadduct would be obtained in
poor ee.
To ascertain the validity of the above speculation, we
subjected cyclic enediyne 3 with an E-olefinic moiety18 to
enantioselective [2 + 2 + 2] cycloaddition, where oxidative
coupling of a diyne moiety would proceed predominantly before
that of an enyne moiety. Under the same reaction conditions as
those of acyclic enediynes, tetracyclic cyclohexa-1,3-diene 4
was obtained in good yield, but its enantiomeric excess was
very low, as expected (eq 4).
oselectivity was improved (entry 2). When a methoxycarbonyl
group was introduced to the alkyne terminus of the carbon tether,
the oxidative coupling of two alkyne moieties could be further
impaired and the ee of cycloadduct 2o exceeded 90% (entries
3 and 4). Nitrogen-tethered enynes are generally more reactive
than carbon-tethered enynes, but the introduction of an ester
functionality increased the reactivity of alkyne and oxidative
coupling would mainly occur at the carbon-tethered enyne moi-
eties in enediynes 1o and 1p. Methyl groups at alkyne termini
sufficiently interfered with alkyne-alkyne oxidative coupling,
and extremely high enantioselectivity was achieved (entry 5).
Enediyne 1r with carbon and oxygen tethers could also be
transformed into the corresponding chiral tricyclic product 2r
in high ee (eq 5).
Conclusions
We here developed an enantioselective intramolecular [2 +
2 + 2] cycloaddition of various enediynes using Rh-H8-BINAP
catalyst. The reaction of carbon-tethered enediynes proceeded
with high enantioselectivity to give tricyclic cyclohexa-1,3-
dienes. In the case of nitrogen-tethered enediynes, the choice
of substituents on the alkyne termini is very important for high
enantioselectivity to prevent alkyne-alkyne oxidative coupling
of enediynes prior to alkyne-alkene coupling. Unsymmetrical
enediynes with carbon and heteroatom tethers were also
transformed into [2 + 2 + 2] cycloadducts in high ee.
These results imply that the selective formation of metalla-
cyclopentene from an enyne moiety of an enediyne would
induce high enantioselectivity. To suppress the oxidative
coupling of two alkyne moieties, we introduced appropriate
substituents to the alkyne termini of enediyne, which would
decrease the reactivity of alkyne moieties (Table 3). When
enediyne 1j with benzyloxymethyl groups was used, enantio-
meric excess of cycloadduct 2j was drastically increased (entry
1). The introduction of alkyl group(s) further improved the
enantioselectivity (entries 2 and 3): in the case of enediyne 1l
with two butyls on its alkyne termini, the enantiomeric excess
reached almost 90%.23
Experimental Section
We further examined unsymmetrical enediynes possessing
carbon and nitrogen tethers (Table 4). In the case of enediyne
1m with unsubstituted alkyne termini, enantioselectivity was
low, probably because terminal alkynes are very reactive and
the oxidative coupling of two alkyne moieties would proceed
predominantly before that of the enyne moiety (entry 1). In fact,
the introduction of a methyl group decreased the reactivity of
the alkyne of the nitrogen-tethered enyne moiety and enanti-
General. Anhydrous DCM and 1,2-dichloroethane (DCE) are
commercially available, and they were dried over molecular sieves
4 Å (MS 4 Å) and degassed by argon bubbling before use. All
reactions were examined under an argon atmosphere. NMR spectra
were measured using TMS as an internal standard, and CDCl3 was
used as a solvent.
Typical Experimental Procedure for the Enantioselective
Intramolecular [2 + 2 + 2] Cycloaddition of Enediyne 1a (Table
2, Entry 1). Under an atmosphere of argon, [Rh(cod)(H8-binap)]-
BF4 (10.0 mg, 0.010 mmol) was stirred in DCM (1.0 mL) at room
temperature. The flask was purged with hydrogen gas, and the
solution was stirred for a further 30 min. After the solvent and
(23) We examined enediyene 1l with two butyls because an enediyene
with two methyls on its alkyne termini gave insoluble products and their
structures could not be determined.
6524 J. Org. Chem., Vol. 72, No. 17, 2007

[2 + 2 + 2] Cycloaddition of Enediynes
hydrogen were excluded under reduced pressure, argon gas was
introduced. To the flask was added DCM (0.2 mL), and the solution
was stirred; then enediyne 1a (39.2 mg, 0.10 mmol) in DCM (0.8
mL) was added, and the mixture was stirred at ambient temperature
for 15 min. The solvent was removed under reduced pressure, and
the resulting crude products were purified by thin-layer chroma-
tography to give pure cycloadduct 2a (31.8 mg, 0.081 mmol, 81%).
(E)-Tetramethyldodec-6-ene-1,11-diyne-4,4,9,9-tetracarboxy-
late (1a): White solid. mp 102 °C (hexane/Et2O); IR (CH2Cl2) 3286,
37.9, 40.0, 44.5, 52.8, 52.8, 59.6, 117.3, 140.6, 172.0, 172.0; Anal.
Calcd for C20H24O8: C, 61.22; H, 6.16. Found: C, 61.23; H, 6.16.
[R]25 42.0° (c 1.36, CHCl3, 78% ee). The ee was determined by
D
HPLC analysis using a chiral column (Daicel Chiralcel Doubly
Arrayed OD-H: 4 × 250 mm, 254 nm UV detector, rt, eluent:
5% 2-propanol in hexane, flow rate: 1.0 mL/min, retention time:
21 min for minor isomer and 23 min for major isomer).
Acknowledgment. We thank Takasago International Corp.
for the gift of H8-BINAP. This research was supported by a
Grant-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
1
2956, 1737, 1201, 690 cm-1; H NMR δ ) 2.02 (t, J ) 2.7 Hz,
2H), 2.76-2.78 (m, 8H), 3.74 (s, 12H), 5.40-5.44 (m, 2H); 13C
NMR δ ) 22.6, 35.3, 52.8, 56.8, 71.5, 78.8, 128.6, 170.1; Anal.
Calcd for C20H24O8: C, 61.22; H, 6.16. Found: C, 61.31; H, 6.27.
trans-Tetramethyl-1,3,6,8,8a,8b-hexahydro-as-indacene-2,2,7,7-
tetracarboxylate (2a): White solid. mp 81 °C (hexane/Et2O); IR
Supporting Information Available: Spectral data for all new
compounds and CIF file. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
(CH2Cl2) 2954, 1731, 1280, 1218, 764 cm-1; H NMR δ ) 1.92
(dd, J ) 11.0, 13.1 Hz, 2H), 2.38-2.44 (m, 2H), 2.67 (dd, J )
5.5, 13.1 Hz, 2H), 2.91 (d, J ) 17.7 Hz, 2H), 3.16 (d, J ) 17.7
Hz, 2H), 3.72 (s, 6H), 3.74 (s, 6H), 5.79 (s, 2H); 13C NMR δ )
JO070762D
J. Org. Chem, Vol. 72, No. 17, 2007 6525