Asymmetric Heck reaction-carbanion capture process. Catalytic asymmetric total synthesis of (-)-Δ(9(12))-capnellene

Article abstract of DOI:10.1021/ja9609359

An asymmetric Heck reaction-carbanion capture process was realized for the first time, making possible the catalytic asymmetric synthesis of various functionalized bicyclo[3.3.0]octane derivatives 6 in up to 94% ee. Sodium bromide had interesting effects

Full text of DOI:10.1021/ja9609359

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J. Am. Chem. Soc. 1996, 118, 7108-7116
Asymmetric Heck Reaction-Carbanion Capture Process.
Catalytic Asymmetric Total Synthesis of (-)-∆9(12)-Capnellene
Takashi Ohshima, Katsuji Kagechika, Midori Adachi, Mikiko Sodeoka, and
Masakatsu Shibasaki*
Contribution from the Faculty of Pharmaceutical Sciences, UniVersity of Tokyo,
Hongo, Bunkyo-ku, Tokyo 113, Japan
ReceiVed March 22, 1996X
Abstract: An asymmetric Heck reaction-carbanion capture process was realized for the first time, making possible
the catalytic asymmetric synthesis of various functionalized bicyclo[3.3.0]octane derivatives 6 in up to 94% ee.
Sodium bromide had interesting effects on this asymmetric Heck reaction-carbanion capture process, and these
effects were useful for improving the enantiomeric excess. Furthermore, the catalytic asymmetric synthesis of (-)-
∆
9(12)-capnellene (7) was achieved for the first time, using 6b as a key intermediate and a radical cyclization as a
key step.
Introduction
Scheme 1
The synthesis of optically active compounds is extremely
important because enantiomer recognition plays an important
role in many biological systems. Many methods are known
for catalytic asymmetric reductions and oxidations,1 but several
successful catalytic asymmetric C-C bond-forming reactions2
have been reported only recently. The development of new
methods for catalytic asymmetric C-C bond formation is now
a major interest of many synthetic chemists.
The first examples of the asymmetric Heck reaction were
reported in 1989, by ourselves3a and later by Overman and co-
workers.3b Since then, we4 and others5 have demonstrated that
this type of catalytic asymmetric C-C bond-forming reaction
is useful for the synthesis of various optically active compounds.
In 1991, using alkenyl triflate 1 as a prochiral substrate, we
also succeeded in demonstrating the first example of an
asymmetric Heck reaction-acetate anion capture process to give
2 with 80% ee and an amine capture process to give 3 with
81% ee (Scheme 1).6 Compound 2 was successfully converted
to ∆9(12)-capnellene-3â,8â,10R-triol and ∆9(12)-capnellene-3â,8â,-
10R,14-tetrol. To extend the usefulness of the above reactions,
we decided to further examine the reaction of 1 with various
carbanions.7 The features of this asymmetric Heck reaction-
carbanion capture process are that a one-pot cascade C-C bond-
forming reaction occurs readily and various functionalized
carbon chains can be introduced to the bicyclic π-allyl-Pd(II)
complex 5 in a regio- and stereocontrolled manner to give 6
(Scheme 2). We describe here the catalytic asymmetric
cyclization of triflate 1 in the presence of a variety of carbanions
and the successful conversion of 6b, one of the cyclization
products, to (-)-∆9(12)-capnellene (7) (Figure 1). We also
discuss the effects of additives such as sodium bromide on the
asymmetric Heck reaction-carbanion capture process.
X Abstract published in AdVance ACS Abstracts, July 1, 1996.
(1) Noyori, R. Asymmetric Catalyst in Organic Synthesis; John Wiley
& Sons, Inc.: New York, 1994.
(2) (a) Narasaka, K. Synthesis 1991, 1. (b) Mikami, K.; Shimizu, M.
Chem. ReV. 1992, 92, 1021. (c) Maruoka, K.; Yamamoto, H. J. Synth.
Org. Chem., Jpn. 1993, 51, 1074. (d) Corey, E. J.; Loh, T.; Roper, T. D.
J. Am. Chem. Soc. 1992, 114, 8290. (e) Ito, Y.; Sawamura, M.; Hayashi,
T. J. Am. Chem. Soc. 1986, 108, 6405. (f) Oguni, N.; Omi, T.; Yamamoto,
Y.; Nakamura, A. Chem. Lett. 1983, 841. (g) Shindo, M.; Koga, K.;
Tomioka, K. J. Am. Chem. Soc. 1992, 114, 8732. (h) Shibasaki, M.; Sasai,
H. J. Synth. Org. Chem., Jpn. 1993, 51, 972. (i) Sakai, N.; Mano, S.;
Nozaki, K.; Takaya, H. J. Am. Chem. Soc. 1993, 115, 7033. (j) Trost, B.
M.; Vranken, D. L. V. Angew. Chem., Int. Ed. Engl. 1992, 31, 228. (k)
Aratani, T. Pure Appl. Chem. 1985, 57, 1839. (l) Pfaltz, A. Acc. Chem.
Res. 1993, 26, 339. (m) Doyle, M. P.; van Overen, A.; Westrum, L. J.;
Protopopova, M. N.; Clayton, T. W., Jr. J. Am. Chem. Soc. 1991, 113, 8982.
(3) (a) Sato, Y.; Sodeoka, M.; Shibasaki, M. J. Org. Chem. 1989, 54,
4738. (b) Carpenter, N. E.; Kucera, D. J.; Overman, L. E. J. Org. Chem.
1989, 54, 5846.
(4) (a) Sato, Y.; Sodeoka, M.; Shibasaki, M. Chem. Lett. 1990, 1953.
(b) Sato, Y.; Watanabe, S.; Shibasaki, M. Tetrahedron Lett. 1992, 33, 2589.
(c) Sato, Y.; Honda, T.; Shibasaki, M. Tetrahedron Lett. 1992, 33, 2593.
(d) Shibasaki, M.; Sato, Y.; Kagechika, K. J. Synth. Org. Chem., Jpn. 1992,
50, 826. (e) Kondo, K.; Sodeoka, M.; Mori, M.; Shibasaki, M. Tetrahedron
Lett. 1993, 34, 4219. (f) Nukui, S.; Sodeoka, M.; Shibasaki, M. Tetrahedron
Lett. 1993, 34, 4965. (g) Takemoto, T.; Sodeoka, M.; Sasai, H.; Shibasaki,
M. J. Am. Chem. Soc. 1993, 115, 8477. (h) Kondo, K.; Sodeoka, M.; Mori,
M.; Shibasaki, M. Synthesis 1993, 920. (i) Koga, Y.; Sodeoka, M.;
Shibasaki, M. Tetrahedron Lett. 1994, 35, 1227. (j) Sato, Y.; Nukui, S.;
Sodeoka, M.; Shibasaki, M. Tetrahedron 1994, 50, 371. (k) Kurihara, Y.;
Sodeoka, M.; Shibasaki, M. Chem. Pharm. Bull. 1994, 42, 2357. (l)
Shibasaki, M.; Sodeoka, M. J. Synth. Org. Chem., Jpn. 1994, 52, 956. (m)
Ohrai, K.; Kondo, K.; Sodeoka, M.; Shibasaki, M. J. Am. Chem. Soc. 1994,
116, 11737. (n) Nukui, S.; Sodeoka, M.; Sasai, H.; Shibasaki, M. J. Org.
Chem. 1995, 60, 398. (o) Sato, Y.; Mori, M.; Shibasaki, M. Tetrahedron:
Asymmetry 1995, 6, 757. (p) Kondo, K.; Sodeoka, M.; Shibasaki, M. J.
Org. Chem. 1995, 60, 4322. (q) Kondo, K.; Sodeoka, M.; Shibasaki, M.
Tetrahedron: Asymmetry 1995, 6, 2453.
(5) (a) Brunner, H.; Kramler, K. Synthesis 1991, 1121. (b) Ozawa, F.;
Kubo, A.; Hayashi, T. J. Am. Chem. Soc. 1991, 113, 1417. (c) Hayashi,
T.; Kubo, A.; Ozawa, F. Pure Appl. Chem. 1992, 64, 421. (d) Ozawa, F.;
Kubo, A.; Hayashi, T. Tetrahedron Lett. 1992, 33, 1485. (e) Ozawa, F.;
Hayashi, T. J. Organomet. Chem. 1992, 428, 267. (f) Sakamoto, T.; Kondo,
Y.; Yamanaka, H. Tetrahedron Lett. 1992, 33, 6845. (g) Ashimori, A.;
Overman, L. E. J. Org. Chem. 1992, 57, 4571. (h) Ashimori, A.; Matsuura,
T.; Overman, L. E.; Poon, D. J. Org. Chem. 1993, 58, 6949. (i) Ozawa,
F.; Kobatake, Y.; Hayashi, T. Tetrahedron Lett. 1993, 34, 2505. (j) Ozawa,
F.; Kubo, A.; Matsumoto, Y.; Hayashi, T. Organometallics 1993, 12, 4188.
(k) Tietze, L. F.; Schimpf, R. Angew. Chem., Int. Ed. Engl. 1994, 33, 1089.
(l) Sakuraba, S.; Awano, K.; Achiwa, K. Synlett 1994, 291. (m) Ozawa,
F.; Kobatake, Y.; Kubo, A.; Hayashi, T. J. Chem. Soc., Chem. Commun.
1994, 1323. (n) Moinet, C.; Fiaud, J.-C. Tetrahedron Lett. 1995, 36, 2051.
(6) (a) Kagechika, K.; Shibasaki, M. J. Org. Chem. 1991, 56, 4093. (b)
Kagechika, K.; Ohshima, T.; Shibasaki, M. Tetrahedron 1993, 49, 1773.
(7) For Heck reaction-anion capture process, see: (a) Grigg, R.;
Sridharan, V.; Xu, L.-X. J. Chem. Soc., Chem. Commun. 1995, 1903 and
references cited therein. (b) Ma, S.; Negishi, E. J. Am. Chem. Soc. 1995,
117, 6345 and references cited therein.
S0002-7863(96)00935-3 CCC: $12 00 © 1996 American Chemical Society

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Asymmetric Heck Reaction-Carbanion Capture Process
J. Am. Chem. Soc., Vol. 118, No. 30, 1996 7109
Table 1. Effects of Solvents on the Asymmetric Synthesis of 6aa
entry
solvent
time (h)
yield (%)
ee (%)
68
1
2
3
4
5
6
7
DMSO
HMPA
DMF
1.0
1.0
21.5
29.0
2.5
1.0
25.0
77
trace
61
11
79
69
40
14
31
<5
15
NMP
Figure 1.
MeCN
diglyme
THF
Scheme 2
16
a Reactions were carried out using Pd(OAc)2 (5 mol %), (S)-BINAP
(6.3 mol %), and the sodium enolate of dimethyl malonate (2.0 equiv)
at rt.
Table 2. Effects of Ligands on the Asymmetric Synthesis of 6aa
entry
solvent
(S)-BINAP
(S)-BINAPO
time (h)
yield (%)
ee (%)
1
2
3
4
5
6
7
1.0
1.0
0.5
65.0
1.5
0.5
77
69
77
trace
62
70
67
68
<5
<5
(R,R)-DIOP
(S,S)-CHIRAPHOS
(-)-NORPHOS
(R,R)-BPPM
<5
30b
27
(S,R)-BPPFA
0.5
Results and Discussion
a Reactions were carried out using Pd(OAc)2 (5 mol %), ligand (6.3
mol %), and the sodium enolate of dimethyl malonate (2.0 equiv) in
DMSO at rt. b The mirror image enantiomer was formed.
Improved Synthesis of Prochiral Triflate 1. As a key step
in an earlier paper,6 triflate 1 was prepared via selective
acetalization of triketone 88 by Noyori’s method9 using 1,2-
bis((trimethylsilyl)oxy)ethane. However, isomerization of 9 to
10 sometimes occurred in a large-scale reaction. To overcome
this problem, we undertook selective acetalization with 2,3-bis-
((trimethylsilyl)oxy)butane instead of 1,2-bis((trimethylsilyl)-
oxy)ethane, which we expected to prevent the isomerization of
acetal, to produce 11 in a high yield even in a large-scale
reaction. In fact, treatment of 8 (3.37 g scale) with 2,3-bis-
((trimethylsilyl)oxy)butane (dl:meso ) ca. 3:1) in the presence
of TMSOTf (trimethylsilyl trifluoromethanesulfonate) at -78
°C gave only 11 in 95% yield. Using this method, triflate 1
was readily prepared in 57% overall yield starting from 8, as
shown in Scheme 3.
Table 3. Effects of Carbanions on the Asymmetric Cyclization
of 1a
Preliminary Results of Asymmetric Heck Reaction-
Carbanion Capture Process. Treatment of 1 with Pd(OAc)2
(5 mol %), (S)-BINAP10 (6.3 mol %), and the sodium enolate
of dimethyl malonate (2 equiv) in DMSO at 20 °C for 2 h gave
the cyclic product 6a in 68% ee and 77% yield as the sole
product. The structure of 6a was determined by NOE experi-
ments and the 1H-NMR spectrum, which showed Jab ) ∼0 Hz.
The absolute configuration of 6a was determined as follows.
The allylic acetate 2 (80% ee), the absolute configuration of
which had been determined previously,6 was treated with [Pd-
(allyl)Cl]2 (2.5 mol %), 1,4-bis(diphenylphosphino)butane (6
mol %), and the sodium enolate of dimethyl malonate (2 equiv)
in DMSO at 20 °C for 16 h to give 6a in 68% yield with double
inversion of the configuration.11 The sign of the optical rotation
of the former sample of 6a (above) was consistent with that of
the latter, and the absolute configuration of 6a was established
unequivocally. Moreover, the enantiomeric excess of 6a was
determined by means of the 1H-NMR spectrum using Eu(hfc)3
(Scheme 4).
a Reactions were carried out using Pd(OAc)2 (5 mol %), (S)-BINAP
(6.3 mol %), and carbanion (2.0 equiv) in DMSO at rt. b Reaction was
carried out using [Pd(allyl)Cl]2 (5 mol %), (S)-BINAP (12 mol %),
methyl 4-chloro-3-oxobutyrate (2.0 equiv), and NaN(SiMe3)2 (2.0 equiv)
in DMSO at rt. c A mixture of 6e and 24 was obtained.
attempts, we eventually found that DMSO and BINAP gave
the best results as shown in Tables 1 and 2. Furthermore, other
carbanions such as lithium enolate of dimethyl malonate had
little effect on the asymmetric induction.
Asymmetric Heck Reactions Using Various Carbanions.
Considering this interesting result, the reaction of 1 with Pd-
(OAc)2 (5 mol %), (S)-BINAP (6.3 mol %), and various sodium
enolates (2 equiv) in DMSO was further investigated (Table
3). All of these reactions gave various functionalized cyclic
products 6 in high chemical yields (up to 91%) and in moderate
to good optical yields (up to 80% ee). However, the optical
yields of 6 were slightly lower than those of 2 and 3. In a
previous paper,6 the asymmetric Heck reaction of alkenyl iodide
16 in the absence of a silver salt provided cyclic product 20
with only low ee (Scheme 5), which is consistent with the
hypothesis that the asymmetric Heck reaction proceeded via a
16-electron Pd+ intermediate (like 4) but not via neutral
palladium intermediates such as 18 and 19 to give products with
To obtain a much higher enantiomeric excess, solvent effects
as well as ligand effects were carefully examined. After several
(8) Boyce, C. B. C.; Whitehurst, J. S. J. Chem. Soc. 1959, 2022. Hajos,
Z. G.; Parrish, D. R. J. Org. Chem. 1974, 39, 1612.
(9) Tsuda, T.; Suzuki, M.; Noyori, R. Tetrahedron Lett. 1980, 21, 1357.
(10) Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345.
(11) Trost, B. M.; Weber, L. J. Am. Chem. Soc. 1975, 97, 1611. Trost,
B. M.; Weber, L.; Strege, P. E.; Fullerton, T. J.; Dietsche, T. J. Am. Chem.
Soc. 1978, 100, 3416. Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc.
1978, 100, 3435. Hayashi, T.; Hagihara, T.; Konishi, M.; Kumada, M. J.
Am. Chem. Soc. 1983, 105, 7767. Hayashi, T.; Konishi, M.; Kumada, M.
J. Chem. Soc., Chem. Commun. 1984, 107.

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7110 J. Am. Chem. Soc., Vol. 118, No. 30, 1996
Scheme 3a
Ohshima et al.
a Reaction conditions: (a) 1,2-bis((trimethylsilyl)oxy)ethane (1.13 equiv), TMSOTf (0.1 equiv), CH2Cl2, -78 °C (77%); (b) 2,3-bis((trimeth-
ylsilyl)oxy)butane (1.13 equiv), TMSOTf (0.1 equiv), CH2Cl2, -78 °C (95%); (c) NaBH4 (1.2 mol equiv), MeOH, 0 °C to rt; (d) TsCl (4.3 equiv),
DMAP (0.3 equiv), pyridine, 0 °C to rt; (e) DBU (4 equiv), toluene, reflux (three steps 90%); (f) TSOH‚H2O (1.7 mol %), acetone, rt (94%); (g)
LDA (1.2 equiv), PhNTf2 (1.3 equiv), THF, -78 °C to rt (71%).
Table 5. Effects of Carbanions on the Asymmetric Cyclization
of 1a
Scheme 4
Table 4. Effects of Additives on the Asymmetric Synthesis of 6da
entry
additive
yield (%)
ee (%)
1
2
3
4
5
6
94
79
74
73
81
61
70
78
83
78
73
74
NaCl
NaBr
NaI
NaClO4
Na2SO4
a Reactions were carried out using [Pd(allyl)Cl]2 (2.5 mol %), (S)-
BINAP (6.3 mol %), sodium enolate of methyl acetoacetate (2.0 equiv),
and additive (2.0 equiv) in DMSO at rt.
high ee3-6. These results appeared to indicate that counteranion
exchange occurred between the hard triflate anion and the soft
enolate anion (4 f 22 and/or 23) to result in the formation of
6 with a slightly lower enantiomeric excess, as shown in Scheme
6.
a Reactions were carried out using [Pd(allyl)Cl]2 (2.5 mol %), (S)-
BINAP (6.3 mol %), NaBr (2.0 equiv), and carbanion (2.0 equiv) in
DMSO at rt.
on the reaction (entries 5 and 6). If even partial counteranion
exchange occurred between a triflate anion and a bromide anion,
the enantiomeric excess of the products 6 would decrease.4a,j
Thus, it appears that sodium bromide prevents counteranion
exchange between the triflate anion and the enolate anion by
complexing with sodium enolate (Scheme 8). The reaction of
1 with [Pd(allyl)Cl]2 (2.5 mol %), (S)-BINAP (6.3 mol %), NaBr
(2 equiv), and various sodium enolates (2 equiv) in DMSO was
further investigated (Table 5). These studies showed that the
addition of NaBr improved the optical yields (up to 94% ee,
entry 3) without decreasing the chemical yield in all cases. The
possible transition states leading to 6 are shown in Scheme 9.
The transition state (R)-4 is notable for the high probability of
severe steric repulsion between the cyclopentadiene moiety and
a bezene ring of the BINAP ligand, a factor which is not present
in the transition state (S)-4; this may account for the predomi-
nance of the (S)-5 enantiomer in the product.
Quite interestingly, the use of methyl 4-chloro-3-oxobutyrate
instead of methyl 3-oxobutyrate increased the optical yield from
74% to 80% ee (Table 3, compare entries 4 and 5). As soon as
sodium enolate of methyl 4-chloro-3-oxobutyrate was generated,
partial dimerization occurred to give dimer 24 and sodium
chloride (Scheme 7). Therefore, it was presumed that sodium
chloride affected the undesired counteranion exchange. Thus,
we next examined the effects of additivies such as sodium
chloride on counteranion exchange in this reaction (1 f 6d).
Effects of Additives. We first found that, as expected,
addition of 2 equiv of NaCl (1 equiv to carbanion) to the reaction
mixture (Table 4, compare entries 1 and 2) increased the optical
yield of 6d from 70% to 78% ee. Encouraged by this result,
we then examined the effects of a variety of sodium salts (entries
3-6). NaBr had the greatest effect and gave 6d in 83% ee
(entry 3). Since the addition of 5 equiv of NaBr gave the same
optical yield, an excess of NaBr was not required in this reaction
system. In contrast, NaClO4 and Na2SO4 had almost no effects
Catalytic Asymmetric Total Synthesis of (-)-∆9(12)-Cap-
nellene (7) from Bicyclic Compound (+)-(S,S,S)-6b. Having

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Asymmetric Heck Reaction-Carbanion Capture Process
Scheme 5
J. Am. Chem. Soc., Vol. 118, No. 30, 1996 7111
Scheme 6
Scheme 7
Scheme 8
Decarboxylation of diester (+)-(S,S,S)-6b (87% ee) produced
monoester 26 in 84% yield. Reduction of 26 with diisobutyl-
aluminum hydride in CH2Cl2 gave alcohol 27 in 96% yield,
which was protected as its benzoyl ester to afford 28 quanti-
tatively. Deprotection of the TBDPS (tert-butyldiphenylsilyl)
ether 28 was achieved by treatment with tetrabutylammonium
fluoride in THF to give alcohol 29 in 97% yield, and 29 was
successively treated with methanesulfonyl chloride and trieth-
ylamine in CH2Cl2 and NaI in acetone to furnish iodide 31
quantitatively from 29. Radical cyclization of 31 was performed
with tributyltin hydride and 2,2′-azobis(isobutyronitrile) in
refluxing benzene to give the tricyclic compound 32, which was
then treated with NaOH in methanol to give alcohol 33 in 96%
yield from 31. Exocyclic olefin 33 was treated with excess
diethylzinc and diiodomethane in toluene at 60 °C to give
cyclopropane 34 in 95% yield. Subsequent hydrogenation of
34 with a catalytic amount of PtO2 in acetic acid under a
achieved the catalytic asymmetric synthesis of bicyclic com-
pound 6a-h with high ee, we then sought to demonstrate the
usefulness of this class of compounds as asymmetric building
blocks. We planned to transform the key intermediate 6b into
natural (-)-∆9(12)-capnellene (7). (-)-∆9(12)-Capnellene (7) is
found in the soft coral Capnella imbricata and is believed to
be the biosynthetic precursor to the capnellane family of
nonisoprenoid sesquiterpenes.12a These compounds display
biological activities similar to those of their terrestrial counter-
parts, the hirsutanes, which possess antibacterial and antitumor
properties.12b Capnellanes appear to serve as chemical defense
agents within the coral reef biomass toward algae and microbial
growth and to prevent larvae settlement.13 Interest in these
substances has inspired several synthetic studies.14 However,
despite the efficient asymmetric syntheses of (+)-715a and (-)-
7,15b the catalytic asymmetric total synthesis of (-)-7 has not
yet been achieved.
(14) (a) Little, R. D.; Carroll, G. L. Tetrahedron Lett. 1981, 22, 4389.
Little, R. D.; Carroll, G. L.; Peterson, J. L. J. Am. Chem. Soc. 1983, 105,
928. (b) Stevens, K. E.; Paquette, L. A. Tetrahedron Lett. 1981, 22, 4393.
Paquette, L. A.; Stevens, K. E. Can. J. Chem. 1984, 62, 2415. (c) Birch,
A. M.; Pattenden, G. Tetrahedron Lett. 1982, 23, 991. Birch, A. M.;
Pattenden, G. J. Chem. Soc., Perkin Trans. 1 1983, 8, 1913. (d) Fujita, T.;
Ohtsuka, T.; Shirahama, H.; Matsumoto, T. Tetrahedron Lett. 1982, 23,
4091. (e) Oppolzer, W.; Battig, K. Tetrahedron Lett. 1982, 23, 4669. (f)
Huguet, J.; Karpf, M.; Dreiding, A. S. HelV. Chim. Acta 1982, 65, 2413.
(g) Mehta, G.; Reddy, D. S.; Murty, A. N. J. Chem. Soc., Chem. Commun.
1983, 824. Mehta, G.; Murty, A. N.; Reddy, D. S.; Verra, A. J. Am. Chem.
Soc. 1986, 108, 3443. (h) Piers, E.; Karunaratne, V. Can. J. Chem. 1984,
62, 629. (i) Crisp, G. T.; Scott, W. J.; Stille, J. K. J. Am. Chem. Soc. 1984,
106, 7500. (j) Liu, H. J.; Kulkarni, M. G. Tetrahedron Lett. 1985, 26,
4847. (k) Curran, D. P.; Chen, M.-H. Tetrahedron Lett. 1985, 26, 4991.
(m) Stille, J. R.; Grubbs, R. H. J. Am. Chem. Soc. 1986, 108, 855. Stille,
J. R.; Santarsiero, B. D.; Grubbs, R. H. J. Org. Chem. 1990, 55, 843. (n)
Iyoda, M.; Kushida, T.; Kitami, S.; Oda, M. J. Chem. Soc., Chem. Commun.
1987, 1607. (o) Uyehara, T.; Furuta, T.; Akamatsu, M.; Kato, T.;
Yamamoto, Y. J. Org. Chem. 1989, 54, 5411. (p) Mukherjee, Y. W. D.;
Birney, D.; Houk, K. N. J. Org. Chem. 1990, 55, 4504. (q) Ihara, M.;
Suzuki, T.; Katogi, M.; Taniguchi, N.; Fukumoto, K. J. Chem. Soc., Chem.
Commun. 1991, 646.
(12) (a) Ayanoglu, E.; Gebreyesus, T.; Beechan, C. M.; Djerassi, C.;
Kaisin, M. Tetrahedron Lett. 1978, 1671. (b) Takeuchi, T.; Linuma, H.;
Iwanagam, J.; Takahashi, S.; Takita, T.; Umezawa, H. J. Antibiot. 1969,
22, 215. (b) Takeuchi, T.; Takahashi, S.; Linuma, H.; Takita, T.; Maeda,
K.; Umezawa, H. J. Antibiot. 1971, 24, 631.
(13) (a) Burkolder, P. R.; Burkolder, L. M. Science 1958, 127, 1174.
Cierzsko, L. S. Trans. N. Y. Acad. Sci. 1962, 24, 502. (b) Cierzsko, L. S.
In Biology and Geology of Coral Reefs; Jones, O. A., Endean, R., Eds.;
Academic Press: New York, 1972; Vol. II, Chapter 6.
(15) (a) Meyers, A. I.; Bienz, S. J. Org. Chem. 1990, 55, 791. (b)
Sonawane, H. R.; Nanjundian, B. S.; Shah, V. G.; Kulkarni, D. G.; Ahuja,
J. R. Tetrahedron Lett. 1991, 32, 1107.

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7112 J. Am. Chem. Soc., Vol. 118, No. 30, 1996
Ohshima et al.
Scheme 9
Scheme 10a
a Reaction conditions: (a) LiCl (2 equiv), H2O (1 equiv), DMSO, reflux (84%); (b) DIBALH (3 equiv), CH2Cl2 -78 °C to rt (96%); (c) BzCl
(2 equiv), DMAP (0.1 equiv), pyridine, CH2Cl2, 0 °C to rt (quantitative) (d) TBAF (1 equiv), THF, rt (97%); (e) MsCl (10 equiv), Et3N (15 equiv),
CH2Cl2, -23 to 0 °C; (f) NaI (5 equiv), acetone, rt (quantitative); (g) Bu3SnH (2 equiv), AIBN (0.2 equiv), benzene, reflux; (h) NaOH, MeOH, rt
(two steps 96%); (i) Et2Zn (5 eq), CH2I2 (10 equiv), toluene, 60 °C (95%); (j) PtO2 (0.2 equiv), H2 (1 atm), AcOH, rt (80); (k) 2-nitrophenyl
selenocyanate (3 equiv), Bu3P (3 equiv), pyridine, rt; (l) H2O2, K2CO3 (10 equiv), THF, rt (two steps 78%).
hydrogen atmosphere gave 35 in 80% yield. The last stage in
this synthesis was transformation of the primary alcohol of 35
to the exocyclic olefin 7. This was realized through the
oxidation of a selenenyl compound. Alcohol 35 was treated
with 2-nitrophenyl selenocyanate16 and tributylphosphine in
pyridine to give 36, and 36 was oxidized with aqueous hydrogen
peroxide solution in THF in the presence of potassium carbonate
to give the title compound 7 in 78% yield from 35 without
isomerization of exocyclic olefin to endocyclic olefin (Scheme
10). The spectral data were identical to those previously
-120, 87% ee) was well within the limits of polarimetric error
for the reported value12 of the natural product ([R]D -145).
Conclusions
We have developed a new method for the catalytic asym-
metric synthesis of bicyclo[3.3.0]octane derivatives 6 with
excellent asymmetric induction (up to 94% ee) using the first
example of an asymmetric Heck reaction-carbanion capture
process. Using (+)-(S,S,S)-6b as an asymmetric building block,
we have achieved the first catalytic asymmetric total synthesis
of (-)-∆9(12)-capnellene (7) in 19 steps and in 20% overall yield
from commercially available starting material 8. Furthermore,
we have found that sodium bromide has interesting effects on
this asymmetric Heck reaction-carbanion capture process.
reported.12 The optical rotation of the synthetic product ([R]26
D
(16) Grieco, P. A.; Gilman, S.; Nishizawa, M. J. Org. Chem. 1976, 41,
1485. Grieco, P. A.; Jaw, J. Y.; Claremon, D. A.; Nicolaou, K. C. J. Org.
Chem. 1981, 46, 1215.

+
+
Asymmetric Heck Reaction-Carbanion Capture Process
J. Am. Chem. Soc., Vol. 118, No. 30, 1996 7113
5-Methyl-5-(3-oxobutyl)cyclopentadiene (15). To a solution of 14
(132.9 mg, 0.598 mmol) in acetone (1.2 mL) was added TsOH‚H2O
(2.3 mg, 0.01 mmol), the reaction mixture was stirred at rt for 48 h
and diluted with hexane, and most of the acetone was evaporated under
reduced pressure. This hexane solution was purified by silica gel
column chromatography (Et2O-hexane, 1:15) to give 156 (84.1 mg,
94%) as a colorless oil.
General Procedure for the Asymmetric Heck Reaction-Car-
banion Capture Process. [Pd(allyl)Cl]2 (3.79 mg, 10.4 µmol), (S)-
BINAP (16.24 mg, 26.1 µmol), and NaBr (85 mg, 0.828 mmol) were
added to a solution of 1 (116.8 mg, 0.414 mmol) in DMSO (1.5 mL).
After degassing, the sodium enolate of diethyl (2-((tert-butyldiphenyl-
silyl)oxy)ethyl)malonate17 (0.33 M, in DMSO, 2.5 mL, 0.83 mmol)
was gradually added to the mixture. The reaction mixture was stirred
at rt for 1 h, diluted with Et2O, washed with 1 N aqueous HCl and
brine, dried (Na2SO4), and concentrated. The residue was purified by
silica gel column chromatography (Et2O-hexane, 1:50) to give 6b
(183.0 mg, 77%, 87% ee) as colorless needles.
(1S,4S,5S)-4-(Bis(methoxycarbonyl)methyl)-1-methyl-6-methyl-
enebicyclo[3.3.0]oct-2-ene (6a): [R]22D -13.3 (c 1.23, CHCl3) (70%
ee); IR (neat) 1738, 1249, 1151 cm-1; 1H-NMR (CDCl3) δ 5.56-5.52
(m, 2 H), 4.90-4.84 (m, 2 H), 3.77 (s, 3 H), 3.74 (s, 3 H), 3.31 (d, J
) 10.0 Hz, 1 H), 3.21 (br-d, J ) 10.0 Hz, 1 H), 2.40 (br-s, 1 H),
2.32-2.16 (m, 2 H), 1.71 (ddd, J ) 12.5, 7.0, 3.0 Hz, 1 H), 1.50 (ddd,
J ) 12.5, 11.0, 7.5 Hz, 1 H), 1.20 (s, 3 H); 13C-NMR (CDCl3) δ 168.86
(s), 168.64 (s), 157.47 (s), 141.38 (d), 129.33 (d), 105.86 (t), 57.88
(d), 57.29 (s), 56.53 (d), 55.10 (d), 52.36 (q), 52.29 (q), 38.37 (t), 33.19
(t), 27.60 (q); MS m/z (relative intensity) 265 (M+ + H, 14), 205 (14),
132 (100). Anal. Calcd for C15H20O4: C, 68.16; H, 7.63. Found: C,
68.46; H; 7.47.
Experimental Section
Infrared (IR) spectra were recorded on a JASCO A-300 diffraction
grating infrared spectrometer. NMR spectra were measured in JEOL
JNM-EX 270 spectrometer, operating at 270 MHz, for 1H and 68 MHz
for 13C NMR. Chemical shifts were reported in the δ scale relative to
1
CHCl3 as an internal reference (7.26 ppm for H and 77.00 ppm for
13C). Mass spectra (MS) were measured on a JEOL JMS-DX303 or
JEOL JMN-SX-102A instruments. Optical rotation was measured on
a JASCO DIP-140 polarimeter. Thin layer chromatography (TLC)
analyses were performed on commercial glass plates bearing 0.25 mm
layer of Merck silica gel 60 F254 (Merck Art. No. 5715). Column
chromatography was carried out with silica gel, Merck Type 60 (70-
325 mesh ASTM) or Merck Type 60 (230-400 mesh ASTM). HPLC
was carried out on a JASCO HPLC system consisting of the follow-
ing: pump, 880-PU; detector, 875-UV, measured at 245 nm; column,
DAICEL CHIRALPAK AS, AD, OD; mobile phase, hexane-2-
propanol; flow rate, 0.5-1.0 mL/min. In general, reactions were carried
out in dry solvents under an argon atmosphere, unless otherwise
mentioned. IR, NMR, and MS data were obtained on all intermediates
described herein using chromatographically homogeneous samples.
Tetrahydrofuran (THF) and diethyl ether (Et2O) were distilled from
sodium benzophenone ketyl. Dichloromethane was distilled from
calcium hydride.
2-(3,3-(1,2-Dimethylethylenedioxy)butyl)-2-methyl-1,3-cyclopen-
tanedione (11). To a solution of 88 (3.37 g, 18.5 mmol) and 2,3-
bis((trimethylsilyl)oxy)butane (4.90 g, 20.9 mmol) in CH2Cl2 (19 mL)
was gradually added TMSOTf (0.36 mL, 1.85 mmol) at -78 °C. The
reaction mixture was stirred for 40 h at the same temperature, quenched
by the addition of pyridine (2.2 mL), poured into saturated aqueous
NaHCO3 solution with vigorous stirring (-78 °C f room temperature
(rt)), and extracted with Et2O. The organic extracts were dried (Na2-
SO4) and concentrated. The residue was purified by silica gel column
chromatography (EtOAc-hexane, 1:5) to give 11 (4.47 g, 95%) as a
colorless oil: IR (neat) 2978, 1724, 1378, 1244, 1094 cm-1; 1H-NMR
(CDCl3) δ 3.61 (dq, J ) 8.6, 5.9 Hz, 1 H), 3.47 (dq, J ) 8.6, 5.9 Hz,
1 H), 2.75 (s, 4 H), 1.81-1.69 (m, 2 H), 1.57-1.49 (m, 2 H), 1.29 (s,
3 H), 1.20 (d, J ) 5.9 Hz, 3 H), 1.19 (d, J ) 5.9 Hz, 3 H), 1.10 (s, 3
H); 13C-NMR (CDCl3) δ 216.05 (s, 2 C), 108.32 (s), 78.71 (d), 78.00
(d), 55.92 (s), 34.88 (t, 2 C), 34.48 (t), 29.40 (t), 25.23 (q), 18.74 (q),
17.05 (q), 16.35 (q); MS m/z (relative intensity) 255 (M+ + H, 0.4),
239 (26), 115 (100); HR-MS calcd for C14H22O4 254.1519, found
254.1506. Anal. Calcd for C14H22O4: C, 66.12; H, 8.72. Found: C,
65.84; H; 8.63.
(1S,4S,5S)-4-(1,1-Bis(ethoxycarbonyl)-3-((tert-butyldiphenylsilyl)-
oxy)propyl)-1-methyl-6-methylenebicyclo[3.3.0]oct-2-ene (6b): [R]24
D
+8.68 (c 1.32, CHCl3) (87% ee); IR (KBr) 2956, 1724, 1225, 1108,
704 cm-1; 1H-NMR (CDCl3) δ 7.67-7.62 (m, 4 H), 7.45-7.35 (m, 6
H), 5.63 (dd, J ) 5.6, 2.3 Hz, 1 H), 5.42 (dd, J ) 5.6, 2.3 Hz, 1 H),
4.77-4.73 (br-s, 2 H), 4.09 (dq, J ) 10.2, 7.0 Hz, 2 H), 4.03 (dq, J )
10.2, 6.3 Hz, 2 H), 3.74 (ddd, J ) 10.1, 9.0, 6.2 Hz, 1 H), 3.67 (ddd,
J ) 10.1, 9.0, 6.2 Hz, 1 H), 3.21 (dt, J ) 3.4, 2.3 Hz, 1 H), 2.51 (d,
J ) 3.4 Hz, 1 H), 2.38-2.08 (m, 4 H), 1.65 (ddd, J ) 12.0, 7.3, 2.1
Hz, 1 H), 1.39 (td, J ) 12.0, 6.9 Hz, 1 H), 1.16 (t, J ) 7.0 Hz, 3 H),
1.14 (t, J ) 7.0 Hz, 3 H), 1.10 (s, 3 H), 1.03 (s, 9 H); 13C-NMR (CDCl3)
δ 170.80 (s), 170.63 (s), 157.36 (s), 140.04 (d), 135.53 (d, 4 C), 133.78
(s, 2 C), 129.69 (d), 129.51 (d, 2 C), 127.57 (d, 4 C), 104.78 (t), 60.90
(t), 60.77 (t), 60.40 (t), 59.26 (s), 59.00 (d), 56.89 (s), 53.89 (d), 39.25
(t), 35.49 (t), 33.35 (t), 27.50 (q), 26.78 (q, 3 C), 19.12 (s), 13.96 (q),
13.87 (q); MS m/z (relative intensity) 574 (M+, 0.1), 559 (0.1), 517
(15), 385 (12), 227 (6), 199 (20), 133 (100); mp 85 °C. Anal. Calcd
for C35H46O5Si: C, 73.13; H, 8.07. Found: C, 73.00; H, 8.13; The
enantiomeric excess was determined by HPLC analysis (DAICEL
CHIRALPAK AD+AD, hexane-2-propanol, 99.5:0.5, 0.5 mL/min,
retention time: 19 min (-), 21 min (+)).
(1S,4S,5S)-1-Methyl-6-methylene-4-(bis(phenylsulfonyl)methyl)-
bicyclo[3.3.0]oct-2-ene (6c): [R]26D +0.942 (c 1.72, CHCl3) (94% ee);
IR (KBr) 1321, 1154 cm-1; 1H-NMR (CDCl3) δ 8.06-7.88 (m, 4 H),
7.70-7.53 (m, 6 H), 5.62 (dd, J ) 5.5, 2.6 Hz, 1 H), 5.23 (dd, J )
5.5, 2.2 Hz, 1 H), 4.73-4.69 (m, 2 H), 4.63-4.60 (br-s, 1 H), 3.47
(ddd, J ) 5.5, 2.6, 2.2 Hz, 1 H), 3.09 (d, J ) 5.5 Hz, 1 H), 2.35-2.20
(m, 2 H), 1.48-1.64 (m, 2 H), 1.26 (s, 3 H); 13C-NMR (CDCl3) δ
156.06 (s), 142.26 (d), 140.40 (s), 137.50 (s), 134.52 (d), 134.11 (d),
129.72 (d, 2 C), 129.20 (d, 2 C), 129.09 (d, 2 C), 128.81 (d, 2 C),
124.49 (d), 105.43 (t), 86.27 (d), 59.43 (d), 56.96 (s), 53.32 (d), 39.37
(t), 33.41 (t), 26.09 (q); MS m/z (relative intensity) 429 (M+ + H,
0.1), 287 (66), 145 (78), 57 (100); HR-MS (M+ + H) calcd for
C23H25O4S2 429.1194, found 429.1201; mp 145 °C; The enantiomeric
5-(3,3-(1,2-Dimethylethylenedioxy)butyl)-5-methylcyclopentane-
diene (14). To a stirred solution of 11 (593 mg, 2.33 mmol) in MeOH
(4 mL) was added NaBH4 (106 mg, 2.80 mmol) at 0 °C, and the reaction
mixture was stirred at 0 °C for 30 min and at rt for 30 min, quenched
by the addition of acetone, and diluted with H2O (0.4 mL) and excess
Et2O. The mixture was filtered through a silica gel pad and concen-
trated to give crude 12. To the residual oil was added pyridine (3.8
mL, 46.6 mmol), TsCl (1.91 g, 10.0 mmol), and DMAP (8.5 mg, 0.7
mmol) at 0 °C. The reaction mixture was stirred at rt for 42 h, quenched
by the addition of EtOH (1.2 mL) at 0 °C, diluted with CH2Cl2, and
successively washed with saturated aqueous CuSO4 solution, saturated
aqueous NaHCO3 solution, and brine. The CH2Cl2 layer was dried
(Na2SO4) and concentrated. The residue was purified by silica gel
column chromatography (EtOAc-hexane, 1:3) to give diastereo mixture
of 13 as a pale yellow oil. A solution of this mixture and DBU (1.4
mL, 9.3 mmol) in toluene (4 mL) was refluxed with stirring for 40 h.
The reaction mixture was poured into saturated aqueous NH4Cl solution
and extracted with Et2O. The organic extracts were dried (Na2SO4)
and concentrated. The residue was purified by silica gel column
chromatography (EtOAc-hexane, 1:20) to give 14 (446.0 mg, three
steps 90%) as a colorless oil: IR (neat) 2970, 1376, 1100, 753 cm-1
;
1H-NMR (CDCl3) δ 6.19 (s, 4 H), 3.63 (dq, J ) 8.6, 5.9 Hz, 1 H),
3.53 (dq, J ) 8.6, 5.9 Hz, 1 H), 1.74-1.62 (m, 2 H), 1.51-1.43 (m,
2 H), 1.29 (s, 3 H), 1.22 (d, J ) 5.9 Hz, 3 H), 1.21 (d, J ) 5.9 Hz, 3
H), 1.15 (s, 3 H); 13C-NMR (CDCl3) δ 145.32 (d, 2 C), 128.63 (d, 2
C), 109.20 (s), 78.74 (d), 77.97 (d), 55.73 (s), 35.65 (t), 29.92 (t), 25.59
(q), 20.72 (q), 17.13 (q), 16.52 (q); MS m/z (relative intensity) 222
(M+, 17), 185 (15), 149 (100), 115 (90); HR-MS calcd for C14H22O2
222.1620, found 222.1614.
(17) Diethyl (2-((tert-butyldiphenylsilyl)oxy)ethyl)malonate was prepared
as follows. Hydrogenolysis (10% Pd/C catalyst, H2, EtOH) of diethyl (2-
(benzyloxy)ethyl)malonate (Padgett, H. C.; Csendes, I. G.; Rapoport, H. J.
Org. Chem. 1974, 39, 1612.) gave the crude alcohol, which was redissolved
in dichloromethane and treated directly with tert-butyldiphenylsilyl chloride,
triethylamine, and 4-(dimethylamino)pyridine. After aqueous workup, the
crude product was further treated with chlorotrimethylsilane in order to
facilitate the removal from the target molecule of traces of tert-butyldi-
phenylsilanol, which had formed during the silylation step.

+
+
7114 J. Am. Chem. Soc., Vol. 118, No. 30, 1996
Ohshima et al.
excess was determined by HPLC analysis (DAICEL CHIRALPAK AD,
hexane-2-propanol, 90:10, 1.0 mL/min, retention time: 15 min (+),
19 min (-)).
(br-s, 0.5 H), 2.29-2.19 (m, 2 H), 2.19-2.15 (br-s, 0.5 H), 1.74-1.64
(m, 1 H), 1.53-1.39 (m, 1 H), 1.19 (s, 1.5 H), 1.14 (s, 1.5 H), 1.11 (s,
4.5 H), 1.10 (s, 4.5 H); 13C-NMR (CDCl3) δ 203.56, 203.34 (s), 168.48,
168.37 (s), 157.52, 157.34 (s), 141.22, 141.08 (d), 135.53 (d, 4 C),
135.53, 132.35, 132.31 (s, 2 C), 129.97 (d, 2 C), 129.74, 129.38 (d),
127.84 (d, 4 C), 106.09, 106.02 (t), 69.92, 69.88 (t), 60.29, 59.91 (d),
57.20, 56.82 (s), 57.07, 56.28 (d), 54.74, 54.07 (d), 52.24, 52.11 (q),
38.35 (t), 33.19 (t), 27.64 (q), 26.63 (q, 3 C), 19.16 (s); MS m/z (relative
intensity) 445 (M+ - tBu,2), 385 (1), 313 (15), 133 (100). Anal. Calcd
for C31H38O4Si: C, 74.06; H, 7.62. Found: C, 73.78; H, 7.66. The
enantiomeric excess was determined by its conversion to methyl
((1S,4R,5R)-4-hydroxy-5-methyl-8-methylene-R-oxobicyclo[3.3.0]oct-
2-en-2-yl)acetate. See ref 18.
(1S,4S,5S)-4-(1-(Methoxycarbonyl)-2-oxopropyl)-1-methyl-6-meth-
ylenebicyclo[3.3.0]oct-2-ene (6d): IR (neat) 2952, 1746, 1716, 1160
cm-1; 1H-NMR (CDCl3) δ 5.53 (s, 1 H), 5.52 (dd, J ) 5.5, 2.2 Hz, 0.5
H), 5.46 (dd, J ) 5.5, 2.2 Hz, 0.5 H), 4.88-4.85 (m, 2 H), 3.77 (s, 1.5
H), 3.73 (s, 1.5 H), 3.41 (d, J ) 6.5 Hz, 0.5 H), 3.38 (d, J ) 6.0 Hz,
0.5 H), 3.27-3.23 (m, 1 H), 2.30-2.28 (m, 1 H), 2.27 (s, 1.5 H), 2.24
(s, 1.5 H), 2.25-2.21 (m, 2 H), 1.73-1.68 (m, 1 H), 1.58-1.42 (m, 1
H), 1.22 (s, 1.5 H), 1.20 (s, 1.5 H); 13C-NMR (CDCl3) δ 202.07 (s),
169.07, 169.02 (s), 157.48, 157.32 (s), 141.44, 141.19 (d), 129.49,
129.11 (d), 106.02, 105.95 (t), 66.43, 66.17 (d), 57.27, 57.18 (s), 56.62,
56.34 (d), 54.92, 54.63 (d), 52.29, 52.22 (q), 38.24 (t), 33.14 (t), 29.62,
29.35 (q), 27.6 (q); MS m/z (relative intensity) 248 (M+, 0.5), 205 (36),
189 (20), 173 (16), 145 (22), 132 (100); HR-MS (M+ - Ac) calcd for
C13H17O2 205.1229, found 205.1224; The enantiomeric excess was
determined by its conversion to methyl ((1S,4R,5R)-4-hydroxy-5-
(1S,4S,5S)-4-(Dibenzoylmethyl)-1-methyl-6-methylenebicyclo-
[3.3.0]oct-2-ene (6h): [R]25D +69.3 (c 1.01, CHCl3) (80% ee); IR (neat)
1
2949, 1698, 1596, 1448 cm-1; H-NMR (CDCl3) δ 8.02-7.97 (m, 4
H), 7.59-7.38 (m, 6 H), 5.54-5.47 (m, 2 H), 5.23 (d, J ) 10.6 Hz, 1
H) 4.90-4.87 (br-s, 1 H), 4.85-4.82 (br-s, 1 H), 3.77 (br-d, J ) 10.6
Hz, 1 H), 2.36-2.33 (br-s, 1 H), 2.30-2.14 (m, 2 H), 1.76-1.67 (m,
1 H), 1.54-1.40 (m, 1 H), 1.31 (s, 3 H); 13C-NMR (CDCl3) δ 195.06
(s), 194.57 (s), 157.50 (s), 140.99 (d), 136.95 (s), 136.89 (s), 133.46
(d, 2 C), 130.75 (d), 128.95 (d, 4 C), 128.84 (d, 4 C), 106.51 (t), 64.62
(d), 57.34 (d), 57.00 (d), 56.84 (s), 38.21 (t), 33.23 (t), 27.85 (q); MS
m/z (relative intensity) 356 (M+, 0.2), 279 (0.3), 251 (63), 132 (50),
105 (100: HR-MS (M+ - PhCO) calcd for C18H19O 251.1436, found
251.1440. The enantiomeric excess was determined by HPLC analysis
(DAICEL CHIRALPAK OD+OD, hexane-2-propanol, 99.5:0.5, 1.0
mL/min, retention time: 45 min (-), 50 min (+)).
methyl-8-methylene-R-oxobicyclo[3.3.0]oct-2-en-2-yl)acetate: [R]24
D
-101 (c 0.40, CHCl3) (83% ee); IR (neat) 3418, 2956, 1738, 1681,
1152 cm-1; 1H-NMR (CDCl3) δ 6.96-6.93 (br-s, 1 H), 5.10-5.07 (br-
s, 1 H), 4.96-4.91 (br-s, 1 H), 4.79-4.75 (br-s, 1 H), 3.89 (s, 3 H),
3.59-3.55 (br-s, 1 H), 2.43-2.34 (m, 2 H), 2.30-2.15 (br-s, 1 H),
1.89-1.78 (m, 1 H), 1.64-1.43 (m, 1 H), 1.16 (s, 3 H); 13C-NMR
(CDCl3) δ 183.29 (s), 162.64 (s), 150.66 (s), 150.24 (d), 142.17 (s),
109.45 (t), 83.27 (d), 59.43 (d), 55.58 (s), 52.74 (q), 37.47 (t), 33.17
(t), 20.13 (q); MS m/z (relative intensity) 236 (M+, 18), 205 (18), 177
(60), 149 (78), 94 (100); HR-MS (M+) calcd for C13H16O4 236.1048,
found 236.1055. The enantiomeric excess was determined by HPLC
analysis (DAICEL CHIRALPAK AS, hexane-2-propanol, 90:10, 1.0
mL/min, retention time: 10 min (+), 13 min (-)). See ref 18.
(1S,4S,5S)-4-(3-Chloro-1-(methoxycarbonyl)-2-oxopropyl)-1-methyl-
6-methylenebicyclo[3.3.0]oct-2-ene (6e). A mixture of 6e and 24 was
(1S,4S,5S)-4-(3-((tert-Butyldiphenylsilyl)oxy)-1-(ethoxycarbonyl)-
propyl)-1-methyl-6-methylenebicyclo[3.3.0]oct-2-ene (26). A solu-
tion of 6b (280.7 mg, 0.488 mmol), LiCl (41.4 mg, 0.977 mmol), and
H2O (8.8 µL, 0.488 mmol) in DMSO (0.81 mL) was refluxed with
stirring for 6 h. After being cooled, the reaction mixture was diluted
with H2O, extracted with Et2O, dried (Na2SO4), and concentrated. The
residue was purified by silica gel column chromatography (EtOAc-
hexane, 1:50) to give 26 (205.1 mg, 84%) as a colorless oil: IR (neat)
1
obtained: IR (neat) 1673, 1443, 1343, 1213 cm-1; H-NMR (CDCl3)
δ 5.58-5.40 (m, 2 H), 4.91-4.85 (m, 2 H), 4.28-4.23 (m, 2 H), 3.78
(s, 1.5 H), 3.74 (s, 1.5 H), 3.66 (d, J ) 10.3 Hz, 1 H), 3.30 (d, J )
10.3 Hz, 1 H), 2.39-2.35 (br-s, 1 H), 2.28-2.20 (m, 2 H), 1.75-1.66
(m, 1 H), 1.54-1.42 (m, 1 H), 1.23 (s, 1.5 H), 1.21 (s, 1.5 H); MS m/z
(relative intensity) 284 (M+ (37Cl), 0.2), 284 (M+ (35Cl), 0.3), 267 (4),
239 (3), 205 (42), 132 (100). The enantiomeric excess was determined
by its conversion to 6d.
1
2954, 1731, 1428, 1173, 1112, 702 cm-1; H-NMR (CDCl3) δ 7.69-
7.63 (m, 4 H), 7.46-7.34 (m, 6 H), 5.58 (dd, J ) 5.6, 2.3 Hz, 0.4 H),
5.51-5.47 (m, 1 H), 5.41 (dd, J ) 5.6, 2.3 Hz, 0.6 H), 4.81-4.78
(br-s, 1 H), 4.76-4.72 (br-s, 0.4 H), 4.71-4.69 (br-s, 0.6 H), 4.20-
4.00 (m, 2 H), 3.76-3.58 (m, 2 H), 2.81-2.74 (m, 1 H), 2.66-2.55
(m, 1 H), 2.42-2.37 (br-s, 1 H), 2.35-2.15 (m, 2 H), 2.02-1.73 (m,
2 H), 1.73-1.64 (m, 1 H), 1.54-1.41 (m, 1 H), 1.22 (t, J ) 7.1 Hz,
1.8 H), 1.21 (t, J ) 7.1 Hz, 1.2 H), 1.20 (s, 1.2 H), 1.19 (s, 1.8 H),
1.05 (s, 9 H); 13C-NMR (CDCl3) δ 175.11, 174.99 (s), 158.54, 158.51
(s), 140.41, 140.16 (d), 135.54 (d, 4 C), 133.82, 133.76 (s, 2 C), 130.05,
129.94 (d), 129.56 (d, 2 C), 127.60 (d, 4 C), 104.94, 104.55 (t), 62.01
(t), 60.11 (t), 58.56, 58.26 (d) 57.27, 57.05 (s), 56.77, 56.19 (d), 48.23,
47.26 (d), 38.83, 38.73 (t), 33.43, 33.30 (t), 33.05, 32.98 (t), 27.64 (q),
26.81 (q, 3 C), 19.19 (s), 14.27 (q); MS m/z (relative intensity) 502
(M+, 0.1), 445 (84), 227 (34), 133 (100); HR-MS (M+) calcd for
C32H42O3Si 502.2903, found 502.2919.
(1S,4S,5S)-4-(3-((tert-Butyldiphenylsilyl)oxy)-1-(hydroxymethyl)-
propyl)-1-methyl-6-methylenebicyclo[3.3.0]oct-2-ene (27). To a
stirred solution of 26 (60.7 mg, 0.121 mmol) in CH2Cl2 (1.2 mL) was
added a solution of DIBALH (0.98 M, in hexane, 0.37 mL, 0.38 mmol)
at -78 °C. After gradually being warmed to 0 °C and 15 min further
of stirring, the reaction mixture was quenched by the addition of
saturated aqueous NH4Cl solution at the same temperature and excess
Et2O was added. The mixture was stirred at rt for 15 h, extracted with
Et2O, dried (Na2SO4), and concentrated. The residue was purified by
silica gel column chromatography (EtOAc-hexane, 1:10) to give 27
(53.3 mg, 96%) as a colorless oil: IR (neat) 3410, 2931, 1717, 1428,
1362, 701 cm-1; 1H-NMR (CDCl3) δ 7.71-7.66 (m, 4 H), 7.48-7.36
(m, 6 H), 5.54-5.49 (m, 1 H), 5.49-5.44 (m, 1 H), 4.78-4.75 (br-s,
1 H), 4.74-4.70 (br-s, 0.4 H), 4.70-4.66 (br-s, 0.6 H), 3.87-3.59 (m,
4 H), 2.94-2.84 (br-s, 0.4 H), 2.84-2.71 (br-s, 0.6 H), 2.64-2.55 (m,
1 H), 2.37-2.13 (m, 3 H), 1.82-1.53 (m, 4 H), 1.53-1.40 (m, 1 H),
1.18 (s, 1.2 H), 1.17 (s, 1.8 H), 1.07 (s, 9 H); 13C-NMR (CDCl3) δ
159.28, 159.07 (s), 139.71, 139.62 (d), 135.60 (d, 4 C), 133.24 (s, 2
C), 130.82, 130.64 (d), 129.76 (d, 2 C), 127.73 (d, 4 C), 104.15, 103.99
(t), 65.16, 64.82 (t), 63.18 (t), 58.11, 57.88 (d), 57.04, 57.00 (s), 56.89,
(1S,4S,5S)-4-[1,3-Bis(methoxycarbonyl)-2-oxopropyl]-1-methyl-
6-methylenebicyclo[3.3.0]oct-2-ene (6f):19 IR (neat) 2952, 1744, 1436,
1
1244, 1162 cm-1; H-NMR (CDCl3) δ 5.56-5.47 (m, 2 H), 5.22 (s,
0.1 H), 5.17 (s, 0.1 H), 4.95-4.75 (m, 2 H), 3.76, 3.75, 3.73, 3.72,
3.71 (s, 6 H), 3.65-3.51 (m, 2.4 H), 3.29-3.26 (m, 0.5 H), 3.25-3.22
(m, 0.5 H), 2.99 (d, J ) 10.6 Hz, 0.1 H), 2.93 (d, J ) 10.6 Hz, 0.1 H),
2.38-2.20 (m, 3 H), 1.76-1.65 (m, 1 H), 1.56-1.40 (m, 1 H), 1.21,
1.20, 1.19 (s, 3 H); 13C-NMR (CDCl3) δ 196.55, 196.44 (s), 168.52,
168.43 (s), 166.94, 166.81 (s), 157.39, 157.25 (s), 141.71 (d), 129.09,
128.90 (d), 106.27, 106.16 (t), 65.59, 65.37 (d), 57.34 (s), 56.59, 56.37
(d), 55.06, 54.66 (d), 52.53, 52.47, 52.36 (q, 2 C), 48.52, 48.20 (t),
38.30 (t), 33.19 (t), 27.60 (q); MS m/z (relative intensity) 306 (M+,
0.4), 205 (58), 132 (100). Anal. Calcd for C17H22O5: C, 66.65; H,
7.24. Found: C, 66.54; H, 7.54. The enantiomeric excess was
determined by its conversion to methyl ((1S,4R,5R)-4-hydroxy-5-
methyl-8-methylene-R-oxobicyclo[3.3.0]oct-2-en-2-yl)acetate. See ref
18.
(1S,4S,5S)-4-(3-((tert-Butyldiphenylsilyl)oxy)-1-(methoxycarbon-
yl)-2-oxopropyl)-1-methyl-6-methylenebicyclo[3.3.0]oct-2-ene (6g):
IR (neat) 2952, 1723, 1113, 758, 702 cm-1; 1H-NMR (CDCl3) δ 7.68-
7.62 (m, 4 H), 7.49-7.36 (m, 6 H), 5.56 (dd, J ) 5.6, 2.1 Hz, 0.5 H),
5.51 (dd, J ) 5.6, 1.5 Hz, 0.5 H), 5.45 (dd, J ) 5.5, 1.6 Hz, 0.5 H),
5.27 (dd, J ) 5.5, 2.2 Hz, 0.5 H), 4.96-4.92 (br-s, 0.5 H), 4.91-4.87
(br-s, 0.5 H), 4.87-4.83 (m, 1 H), 4.31 (d, J ) 12.5 Hz, 0.5 H), 4.29
(d, J ) 13.0 Hz, 0.5 H), 4.27 (d, J ) 12.5 Hz, 0.5 H), 4.24 (d, J )
13.0 Hz, 0.5 H), 3.78 (d, J ) 9.2 Hz, 0.5 H), 3.69 (d, J ) 10.3 Hz, 0.5
H), 3.68 (s, 1.5 H), 3.65 (s, 1.5 H), 3.33-3.23 (m, 1 H), 2.42-2.38
(18) Ohshima, T.; Sodeoka, M.; Shibasaki, M. Tetrahedron Lett. 1993,
34, 8509.
(19) 6f was obtained as an equilibrium mixture of the keto form and
2,3-enol form (ca. 8:2).

+
+
Asymmetric Heck Reaction-Carbanion Capture Process
J. Am. Chem. Soc., Vol. 118, No. 30, 1996 7115
56.44 (d), 44.35, 43.78 (d), 39.12, 39.07 (t), 33.43 (t), 33.07, 32.96 (t),
27.66, 27.59 (q), 26.79 (q, 3 C), 19.09 (s); MS m/z (relative intensity)
461 (M+ + H, 0.2), 443 (0.7), 403 (4), 385 (3), 373 (20), 325 (22),
199 (80), 133 (100). Anal. Calcd for C30H40O2Si: C, 78.21; H, 8.75.
Found: C, 77.97; H, 8.81.
2.70 (m, 1 H), 2.46-2.41 (br-s, 1 H), 2.33-2.20 (m, 2 H), 2.15-1.93
(m, 3 H), 1.74-1.64 (m, 1 H), 1.56-1.42 (m, 1 H), 1.24 (s, 1.8 H).
1.21 (s, 1.2 H); 13C-NMR (CDCl3) δ 166.50 (s), 158.74, 158.58 (s),
140.54 (d), 133.01 (d), 130.08, 129.70 (s), 129.56 (d, 3 C), 128.43 (d,
2 C), 104.60, 104.51 (t), 65.73, 65.21 (t), 57.34, 56.98 (d), 57.14, 57.07
(s), 56.62, 56.57 (d), 43.51, 43.15 (d), 38.94 (t), 34.29, 33.98 (t), 33.43,
33.35 (t), 27.59, 27.51 (q), 4.75, 4.57 (t); MS m/z (relative intensity)
436 (M+, 0.2), 421 (0.1), 314 (28), 299 (12), 187 (43), 159 (53), 105
(100). Anal. Calcd for C21H25IO2: C, 57.81; H, 5.77. Found: C,
57.57; H, 5.75.
(1S,4S,5S)-4-(1-((Benzoyloxy)methyl)-3-((tert-butyldiphenylsilyl)-
oxy)propyl)-1-methyl-6-methylenebicyclo[3.3.0]oct-2-ene (28). To
a solution of 27 (53.3 mg, 0.116 mmol) in CH2Cl2 (1.6 mL) were added
pyridine (0.038 mL, 0.464 mmol), BzCl (0.027 mL, 0.232 mmol), and
DMAP (1.4 mg, 0.012 mmol) at 0 °C. After being stirred at rt for 16
h, the reaction mixture was diluted with Et2O, washed with 1 N aqueous
HCl and saturated aqueous NaHCO3 solution, dried (Na2SO4), and
concentrated. The residue was purified by silica gel column chroma-
tography (EtOAc-hexane, 1:20) to give 28 (65.1 mg, quant.) as a
colorless oil: IR (neat) 2953, 1721, 1272, 1112 cm-1; 1H-NMR (CDCl3)
δ 8.04-7.09 (m, 2 H), 7.70-7.64 (m, 4 H), 7.59-7.52 (m, 1 H), 7.46-
7.32 (m, 8 H), 5.55 (dd, J ) 5.6, 2.1 Hz, 1 H), 5.50 (dd, J ) 5.6, 1.5
Hz, 1 H), 4.81-4.78 (br-s, 0.6 H), 4.77-4.73 (br-s, 1 H), 4.71-4.68
(br-s, 0.4 H), 4.40 (dd, J ) 11.3, 5.0 Hz, 0.4 H), 4.33 (dd, J ) 11.3,
5.2 Hz, 0.6 H), 4.28 (dd, J ) 11.3, 5.3 Hz, 0.6 H), 4.27 (dd, J ) 11.3,
5.5 Hz, 0.4 H), 3.89-3.76 (m, 2 H), 2.77-2.71 (m, 1 H), 2.46-2.41
(br-s, 1 H), 2.33-2.00 (m, 3 H), 1.92-1.63 (m, 3 H), 1.56-1.43 (m,
1 H), 1.22 (s, 1.8 H), 1.21 (s, 1.2 H), 1.06 (s, 9 H); 13C-NMR (CDCl3)
δ 166.56, 166.52 (s), 158.99, 158.81 (s), 139.91 (d), 135.53 (d, 4 C),
133.80, 133.76 (s, 2 C), 132.76 (d), 130.37 (s), 130.28, 130.19 (d),
129.56 (t, 2 C), 129.52 (d, 2 C), 128.30 (d, 2 C), 127.62 (d, 4 C),
104.35, 104.22 (t), 66.74, 65.95 (t), 61.98, 61.87 (t), 57.85, 57.59 (d),
57.05, 56.93 (s), 56.89, 56.68 (d), 39.21, 38.96 (d), 39.09, 39.01 (t),
33.48, 33.41 (t), 32.83, 32.19 (t), 27.64, 27.53 (q), 26.85 (q, 3 C), 19.14
(1S,2S,6S,8S)-11-(Hydroxymethyl)-6-methyl-3-methylenetricyclo-
[6.3.0.02,6]undecane (33). To a solution of 31 (61.4 mg, 0.141 mmol)
in benzene (7 mL) at reflux was added a solution of Bu3SnH (0.076
mL, 0.282 mmol) and AIBN (4.6 mg, 0.028 mmol) in benzene (3.5
mL) in 10 portions at 30 min intervals. Reflux was continued for 30
min, and after cooling to rt, KF‚2H2O (80 mg) in CH2Cl2 (0.7 mL)
was added and the mixture was stirred for 2 h, dried (Na2SO4), and
concentrated. The residue was purified by silica gel column chroma-
tography (hexane f EtOAc-hexane, 1:20) to give crude benzoate 32.
To this crude benzoate was added a solution of NaOH (0.7%, in MeOH,
5.6 mL), and the reaction mixture was stirred at rt for 22 h. The reaction
mixture was neutralized with saturated NH4Cl solution, extracted
EtOAc, dried (Na2SO4), and concentrated. The residue was purified
by silica gel column chromatography (EtOAc-hexane, 1:5) to give 33
(27.8 mg, two steps 96%) as a colorless oil: IR (neat) 3318, 2944,
1
1456, 1025, 878 cm-1; H-NMR (CDCl3) δ 4.89-4.84 (m, 1.2 H),
4.83-4.78 (m, 0.8 H), 3.84 (dd, J ) 11.3, 9.0 Hz 0.6 H), 3.69 (dd, J
) 11.3, 6.0 Hz, 0.6 H), 3.61 (dd, J ) 10.5, 6.2 Hz, 0.4 H), 3.48 (dd,
J ) 10.5, 7.8 Hz, 0.4 H), 2.80-2.29 (m, 3.6 H), 2.18-1.79 (m, 4.2
H), 1.78-1.52 (m, 2.4 H), 1.46-1.08 (m, 4.8 H), 1.06 (s, 1.2 H), 0.97
(s, 1.8 H); 13C-NMR (CDCl3) δ 158.76, 158.44 (s), 105.86, 105.00 (t),
66.54, 63.85 (t), 63.42, 58.44 (d), 57.00, 52.47 (d), 53.92, 52.89 (s),
49.67, 46.85 (d), 47.23, 46.98 (t), 43.74, 42.57 (d), 37.47, 35.55 (t),
32.62, 32.10 (t), 31.88, 30.82 (t), 30.17, 26.70 (t), 26.76, 25.36 (q);
MS m/z (relative intensity) 206 (M+, 13), 191 (100), 173 (30); HR-
MS (M+) calcd for C14H22O 206.1671, found 206.1664.
t
(s); MS m/z (relative intensity) 507 (M+ - Bu, 3), 385 (4), 303 (46),
187 (60), 133 (70), 105 (100). Anal. Calcd for C37H44O3Si: C, 78.68;
H, 7.85. Found: C, 78.70; H, 7.71.
(1S,4S,5S)-4-(1-((Benzoyloxy)methyl)-3-hydroxypropyl)-1-meth-
yl-6-methylenebicyclo[3.3.0]oct-2-ene (29). To a stirred solution of
28 (211.3 mg, 0.392 mmol) in THF (2 mL) was added a solution of
TBAF (1.0 M, in THF, 0.40 mL, 0.38 mmol) at rt, and the resulting
mixture was stirred at rt for 2 h. The mixture was poured into 1 N
aqueous HCl, extracted with Et2O, dried (Na2SO4), and concentrated.
The residue was purified by silica gel column chromatography (EtOAc-
hexane, 1:5) to give 29 (118.8 mg, 97%) as a colorless oil: IR(neat)
(1S,2S,6S,8S)-3,3-Ethylene-11-(hydroxymethyl)-6-methyltricyclo-
[6.3.0.02,6]undecane (34). To a stirred solution of 33 (19.9 mg, 0.0964
mmol) in toluene (2.4 mL) was added a solution of Et2Zn (1.0 M, in
hexane, 0.48 mL, 0.48 mmol) at rt. After warming to 60 °C, the
reaction mixture was treated dropwise with CH2I2 (0.078 mL, 0.964
mmol) and stirred for 15 h at the same temperature. The reaction
mixture was diluted with Et2O, washed with 1 N aqueous HCl and
saturated NaHCO3 solution, dried (Na2SO4), and concentrated. The
residue was purified by silica gel column chromatography (EtOAc-
hexane, 1:10) to give 34 (20.2 mg, 95%) as a colorless oil: IR (neat)
1
3420, 2949, 1719, 1273 cm-1; H-NMR (CDCl3) δ 8.05-8.00 (m, 2
H), 7.59-7.52 (m, 1 H), 7.47-7.40 (m, 2 H), 5.61-5.49 (m, 2 H),
4.80-4.70 (m, 2 H), 4.44 (dd, J ) 11.4, 5.0 Hz, 0.4 H), 4.36 (d, J )
5.5 Hz, 1.2 H), 4.33 (d, J ) 11.4, 5.7 Hz, 0.4 H), 3.84-3.75 (m, 2 H),
2.78-2.72 (m, 1 H), 2.46-2.41 (br-s, 1 H), 2.33-2.16 (m, 2 H), 2.09-
1.94 (m, 1 H), 1.89-1.60 (m, 4 H), 1.55-1.42 (m, 1 H), 1.21 (s, 1.8
H), 1.20 (s, 1.2 H); 13C-NMR (CDCl3) δ 166.70 (s), 158.94, 158.83
(s), 140.14 (d), 132.94 (d), 130.21 (s), 130.05 (d), 129.52 (d, 2 C),
128.39 (d, 2 C), 104.35 (t), 66.61, 66.22 (t), 61.17, 60.99 (t), 57.97,
57.76 (d), 57.11, 57.04 (s), 56.71, 56.48 (d), 39.43, 39.37 (d), 39.03
(t), 33.46, 33.41 (t), 32.85, 32.63 (t), 27.51 (q); MS m/z (relative
intensity) 326 (M+, 0.1), 311 (0.2), 308 (0.1), 303 (0.2), 204 (29), 189
(32), 145 (46), 133 (47), 105 (100). Anal. Calcd for C21H26O3: C,
77.27; H, 8.03. Found: C, 76.91; H, 8.19.
1
3341, 2939, 2863, 1458, 1024 cm-1; H-NMR (CDCl3) δ 3.59 (dd, J
) 10.2, 6.6 Hz, 0.6 H), 3.58 (dd, J ) 10.5, 5.4 Hz, 0.4 H), 3.45 (dd,
J ) 10.2, 7.8 Hz, 0.6 H), 3.38 (dd, J ) 10.5, 7.8 Hz, 0.4 H), 2.75-
2.44 (m, 1.4 H), 2.09-1.23 (m, 13.6 H), 1.21 (s, 1.2 H), 1.17 (s, 1.8
H), 0.58-0.32 (m, 4 H); 13C-NMR (CDCl3) δ 66.40, 64.94 (t), 65.05,
59.28 (d), 54.25 (s), 53.95, 51.97 (d), 49.51, 46.38 (d), 49.29, 48.20
(t), 44.49, 44.15 (d), 40.06, 39.23 (t), 35.80, 35.67 (t), 31.39, 30.77 (t),
29.47 (s), 28.45 (q), 28.25 (t), 16.53, 15.67 (t), 7.19, 6.81 (t); MS m/z
(relative intensity) 220 (M+, 4), 205 (43), 191 (55), 107 (100); HR-
MS (M+) calcd for C15H24O 220.1827, found 220.1836.
(1S,4S,5S)-4-(1-((Benzoyloxy)methyl)-3-iodopropyl)-1-methyl-6-
methylenebicyclo[3.3.0]oct-2-ene (31). To a solution of 29 (107.0
mg, 0.328 mmol) in CH2Cl2 (6.6 mL) was added Et3N (0.68 mL, 4.92
mmol) and MsCl (0.25 mL, 3.28 mmol) at -23 °C, and the reaction
mixture was stirred at the same temperature for 2 h and at 0 °C for 1
h. The reaction mixture was quenched by the addition of ice cold H2O
at 0 °C, extracted Et2O, dried (Na2SO4), and concentrated to give crude
mesylate 30. A solution of this mesylate and NaI (246 mg, 1.64 mmol)
in acetone (3.3 mL) was stirred at rt for 24 h. The reaction mixture
was diluted with H2O, extracted with Et2O, dried (Na2SO4), and
concentrated. The residue was purified by silica gel column chroma-
tography (EtOAc-hexane, 1:50) to give 31 (143.8 mg, quantitative)
as a pale yellow oil: IR (neat) 2949, 1721, 1451, 1271, 1113, 711
(1S,2S,6S,8S)-11-(Hydroxymethyl)-3,3,6-trimethyltricyclo[6.3.0.02,6]-
undecane (35). A mixture of 34 (22.4 mg, 0.102 mmol) and PtO2
(4.6 mg, 0.020 mmol) in acetic acid (2.0 mL) was hydrogenated at rt
under atmospheric pressure for 3 days. The reaction mixture was
filtered through a Celite pad, neutralized with saturated NaHCO3
solution, extracted with EtOAc, dried (Na2SO4), and concentrated. The
residue was purified by silica gel column chromatography (EtOAc-
hexane, 1:10) to give 35 (18.0 mg, 80%) as a colorless oil: IR (neat)
1
3374, 2935, 1028 cm-1; H-NMR (CDCl3) δ 3.72 (dd, J ) 10.5, 6.7
Hz, 0.6 H), 3.68 (dd, J ) 10.8, 4.2 Hz, 0.4 H), 3.54 (dd, J ) 10.5, 7.9
Hz, 0.6 H), 3.42 (dd, J ) 10.8, 7.1 Hz, 0.4 H), 2.66-2.40 (m, 1.4 H),
2.18-1.32 (m, 13.6 H), 1.22 (s, 1.2 H), 1.17 (s, 1.8 H), 1.00 (s, 1.2
H), 0.98 (s, 1.8 H), 0.95 (s, 1.8 H), 0.92 (s, 1.2 H); 13C-NMR (CDCl3)
δ 67.57, 61.92 (d), 66.87, 65.41 (t), 53.62, 53.35 (s), 50.74, 49.40 (d),
49.72, 48.84 (t), 48.79, 46.90 (d), 46.40, 45.50 (d), 42.37, 42.16 (s),
41.42, 41.39 (t), 40.70, 40.63 (t), 32.20 (q), 31.23, 31.04 (t), 30.73,
1
cm-1; H-NMR (CDCl3) δ 8.06-8.01 (m, 2 H), 7.61-7.53 (m, 1 H),
7.48-7.41 (m, 2 H), 5.58-5.51 (m, 2 H), 4.82-4.77 (br-s, 1 H), 4.77-
4.73 (br-s, 0.6 H), 4.73-4.70 (br-s, 0.4 H), 4.45 (dd, J ) 11.5, 4.0 Hz,
0.4 H), 4.39 (dd, J ) 11.0, 4.0 Hz, 0.6 H), 4.28 (dd, J ) 11.0, 5.0 Hz,
0.6 H), 4.26 (dd, J ) 11.5, 5.0 Hz, 0.4 H), 3.44-3.21 (m, 2 H), 2.78-

+
+
7116 J. Am. Chem. Soc., Vol. 118, No. 30, 1996
Ohshima et al.
30.30 (q) 29.56, 28.54 (t), 26.00, 25.68 (q); MS m/z (relative intensity)
222 (M+, 14), 207 (8), 166 (56), 151 (54), 135 (100): HR-MS (M+)
calcd for C15H26O 222.1983, found 222.1975.
(c 0.325, CHCl3) (87% ee); IR (neat) 3068, 2934, 2864, 1650, 1456,
1
1382, 1372, 1364, 874 cm-1; H-NMR (CDCl3) δ 4.91-4.88 (br-s, 1
H), 4.80-4.77 (br-s, 1 H), 2.68-2.62 (m, 1 H), 2.60-2.30 (m, 3 H),
1.78-1.64 (m, 3 H), 1.56-1.42 (m, 5 H), 1.20 (dd, J ) 13.2, 9.5 Hz,
1 H), 1.15 (s, 3 H), 1.05 (s, 3 H), 0.98 (s, 3 H); 13C-NMR (CDCl3) δ
158.98 (s), 104.96 (t), 69.06 (d), 53.32 (s), 52.27 (d), 47.89 (t), 45.99
(d), 42.32 (s), 41.66 (t), 40.56 (t), 31.81 (q), 31.50 (t), 30.80 (q), 29.02
(t), 26.04 (q).
(-)-∆9(12)-Capnellene (7). A solution of 35 (17.0 mg, 0.0764 mmol)
in pyridine (0.8 mL) containing 2-nitrophenyl selenocyanate (52 mg,
0229 mmol) was treated dropwise with Bu3P (0.057 mL, 0.229 mmol)
at rt. After being stirred for 20 h, the reaction mixture was quenched
by the addition of H2O, diluted with Et2O, washed with 1 N aqueous
HCl and saturated NaHCO3 solution, dried (Na2SO4), and concentrated
to give crude 36. To the residual yellow solid were added THF (1.5
mL), K2CO3 (105 mg, 0.764 mmol), and 30% H2O2 (0.31 mL) at rt.
The reaction mixture was stirred at rt for 20 h and directly filtered
through a silica gel pad. This crude products were purified by silica
gel column chromatography (EtOAc-hexane, 1:10) to give (-)-
capnellene (7) (12.2 mg, two steps 78%) as a colorless oil: [R]26D -120
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