A new method for installation of aryl and alkenyl groups onto a cyclopentene ring and synthesis of prostaglandins

Article abstract of DOI:10.1021/jo020375y

To construct a new strategy for synthesis of cyclopentanoids, the transition metal-catalyzed coupling reaction of cis 4-cyclopentene-1,3-diol monoacetate 1 with hard nucleophiles, R^T-m, was investigated (eq 1 in Chart 1). Although preliminary experiments using PhZnCl, PhSnMe₃, [Ph-B(Me)(OCH-(Me)CH(Me)O)]-Li⁺ (6a) (derived from boronate ester 4a (R^T = Ph) and MeLi) in the presence of a palladium or a nickel catalyst resulted in production of unidentified compounds, enone 16, and/or ketone 17 or recovery of 1, a new borate 5a (derived from 4a and n-BuLi) in the presence of a nickel catalyst (NiCl₂(PPh₃)₂) in THF at room temperature furnished the trans coupling products 2a (R^T = Ph) and 3a (R^T = Ph) in high combined yield, but with a low product ratio of 0.9:1. The ratio was improved to 13:1 by addition of t-BuCN and NaI into the reaction mixture. This is the first successful example of the reaction of 1 with a hard nucleophile, and the increase in the ratio, realized with the additives, is unprecedented. This reagent system (borate 5 (1.2-1.8 equiv), NiCl₂-(PPh₃)₂ (5-10 mol%), t-BuCN (2-5 equiv), NaI (0.5-1 equiv), THF, room temp) was further investigated with aryl borates 5b-g and alkenyl borates 5h-n to afford 2b-n in moderate to good yields (52-89%) with practically acceptable levels of the regioselectivity (5 ～ 21:1), thus establishing the generality of the reaction (Table 2, eqs 6 and 7). Starting with the products of the coupling reaction, syntheses of the prostaglandin intermediates 13 and 14 (for 11-deoxy-PGE₂ and PGA₂) and Δ⁷-PGA₁ methyl ester (15) were accomplished efficiently. During these investigations, LDA, LiCA, and LHMDS were found to be equally efficient bases for aldol reaction at the α′ (α prime) position of cyclopentenones 39, 40, and 41 (Table 3).

Full text of DOI:10.1021/jo020375y

A New Meth od for In sta lla tion of Ar yl a n d Alk en yl Gr ou p s on to a
Cyclop en ten e Rin g a n d Syn th esis of P r osta gla n d in s
Yuichi Kobayashi,* Modachur G. Murugesh, Miwa Nakano, Eisuke Takahisa,
Shahid B. Usmani, and Takayuki Ainai
Department of Biomolecular Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho,
Midori-ku, Yokohama 226-8501, J apan
ykobayas@bio.titech.ac.jp
Received J une 3, 2002
To construct a new strategy for synthesis of cyclopentanoids, the transition metal-catalyzed coupling
reaction of cis 4-cyclopentene-1,3-diol monoacetate 1 with hard nucleophiles, RT-m, was investigated
(eq 1 in Chart 1). Although preliminary experiments using PhZnCl, PhSnMe3, [Ph-B(Me)(OCH-
(Me)CH(Me)O)]-Li+ (6a ) (derived from boronate ester 4a (RT ) Ph) and MeLi) in the presence of a
palladium or a nickel catalyst resulted in production of unidentified compounds, enone 16, and/or
ketone 17 or recovery of 1, a new borate 5a (derived from 4a and n-BuLi) in the presence of a
nickel catalyst (NiCl2(PPh3)2) in THF at room temperature furnished the trans coupling products
2a (RT ) Ph) and 3a (RT ) Ph) in high combined yield, but with a low product ratio of 0.9:1. The
ratio was improved to 13:1 by addition of t-BuCN and NaI into the reaction mixture. This is the
first successful example of the reaction of 1 with a hard nucleophile, and the increase in the ratio,
realized with the additives, is unprecedented. This reagent system (borate 5 (1.2-1.8 equiv), NiCl2-
(PPh3)2 (5-10 mol %), t-BuCN (2-5 equiv), NaI (0.5-1 equiv), THF, room temp) was further
investigated with aryl borates 5b-g and alkenyl borates 5h -n to afford 2b-n in moderate to
good yields (52-89%) with practically acceptable levels of the regioselectivity (5 ∼ 21:1), thus
establishing the generality of the reaction (Table 2, eqs 6 and 7). Starting with the products of the
coupling reaction, syntheses of the prostaglandin intermediates 13 and 14 (for 11-deoxy-PGE2 and
PGA2) and ∆7-PGA1 methyl ester (15) were accomplished efficiently. During these investigations,
LDA, LiCA, and LHMDS were found to be equally efficient bases for aldol reaction at the R′ (R
prime) position of cyclopentenones 39, 40, and 41 (Table 3).
In tr od u ction
surprising to learn that only a few types of reactions have
successfully been applied to 1. These are the Claisen
rearrangement,2b,c,4 the intramolecular radical reaction,5
the palladium-initiated intramolecular reaction,6 and the
palladium-catalyzed reaction with soft nucleophiles fur-
nishing cis 1,4-products.7-11 We were interested in reac-
Installation of a “carbon-based nucleophile” onto a
preexisting cyclopentene (or -ane) ring is a key step in
building complex molecules in which the cyclopentane
ring acts as a major component of the compound (cyclo-
pentanoids). Cyclopentanone, 2-cyclopenten-1-one, and
derivatives possessing a functional group on these com-
pounds have been utilized most frequently as starting
substrates. Efficient reactions with these compounds and
methodologies therefrom have been developed with great
success and exploited in synthesis of the cyclopentanoids.1
These achievements, however, certainly imply the dif-
ficulty in planning a conceptually new strategy for
synthesis of the cyclopentanoids, and thence we felt it
necessary to find a new reaction using another starting
substrate. Monoacetate of cis 4-cyclopentene-1,3-diol (i.e.,
1) is one such compound as the convenient methods to
obtain both the enantiomers (>95% ee) have been pub-
lished.2,3 Moreover, monoacetate 1 is of excellent chemical
(1) (a) Collins, P. W.; Djuric, S. W. Chem. Rev. 1993, 93, 1533-1594.
(b) Crimmins, M. T. Tetrahedron 1998, 54, 9229-9272. (c) Noyori, R.;
Suzuki, M. Angew. Chem., Int. Ed. Engl. 1984, 23, 847-876. (d) Noyori,
R.; Suzuki, M. Science 1993, 259, 44-45. (e) Harre, M.; Raddatz, P.;
Walenta, R.; Winterfeldt, E. Angew. Chem., Int. Ed. Engl. 1982, 21,
480-492.
(2) (1R,3S)-1: (a) Sugai, T.; Mori, K. Synthesis 1988, 19-22. (b)
Laumen, K.; Schneider, M. P. J . Chem. Soc., Chem. Commun. 1986,
1298-1299. (1S, 3R)-1: (c) Laumen, K.; Schneider, M. Tetrahedron
Lett. 1984, 25, 5875-5878. (d) Wang, Y.-F.; Chen, C.-S.; Girdaukas,
G.; Sih, C. J . J . Am. Chem. Soc. 1984, 106, 3695-3696. Related
literatures: ref 2 of ref 12.
(3) (a) Certainly, acetylation and desilylation of enantiomerically
enriched 4-silyloxy-2-cyclopenten-1-ol3b-d would afford the enantiomers
of monoacetate 1. (b) Bhuniya, D.; DattaGupta, A.; Singh, V. K. J . Org.
Chem. 1996, 61, 6108-6113. (c) Asami, M.; Inoue, S. Tetrahedron 1995,
51, 11725-11730. (d) Asami, M. Bull. Chem. Soc. J pn. 1990, 63, 1402-
1408.
(4) Nara, M.; Terashima, S.; Yamada, S. Tetrahedron 1980, 36,
3161-3170.
(5) (a) Stork, G.; Sher, P. M.; Chen, H.-L. J . Am. Chem. Soc. 1986,
108, 6384-6385. (b) Keck, G. E.; Burnett, D. A. J . Org. Chem. 1987,
52, 2958-2960. (c) Larock, R.; Lee, N. H. J . Org. Chem. 1991, 56,
6253-6254. (d) Busato, S.; Tinembart, O.; Zhang, Z.; Scheffold, R.
Tetrahedron 1990, 46, 3155-3166.
(6) Larock, R.; Lee, N. H. J . Am. Chem. Soc. 1991, 113, 7815-7816.
(7) Deardorff, D. R.; Linde, R. G., II; Martin, A. M.; Shulman, M. J .
J . Org. Chem. 1989, 54, 2759-2762.
stability, thus allowing easy handling. However, it was
10.1021/jo020375y CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/11/2002
7110
J . Org. Chem. 2002, 67, 7110-7123

Installation of Aryl and Alkenyl Groups
CHART 1. Equ a tion 1: Th e P u r p ose of th e
P r esen t In vestiga tion . Regioselective a n d
Ster eosp ecific F or m a tion of 2 Ha ve Been Atta in ed
by Usin g Mod ified Bor a tes 5 in th e P r esen ce of
t-Bu CN a n d Na I in THF . Equ a tion 2: P r ep a r a tion
of th e Mod ified a n d Or igin a l Bor a tes 5 a n d 6
F IGURE 1. Plausible intermediates and products.
tion with hard nucleophiles RT-m (RT: transfer group)
(eq 1 of Chart 1) because it is, in principle, possible to
install a wide range of RT (especially sp2-carbon) on the
cyclopentene ring, and in the trans orientation.12 The
reaction was, however, suffering from low efficiency
because of, at least, two reasons pointed out in the next
paragraph.
On the basis of the general consideration for the
intermediates produced from allylic acetates and transi-
tion metal complexes,13 π-allylmetal complex 7 would be
a plausible intermediate generated from 1 (Figure 1).
Since a soft nucleophile (Nu) attacks the π-allyl moiety
from the outside, the steric repulsion of the hydroxyl
group results in the regioselective formation of cis 1,4-
isomer 8 as is observed in practice.7,8 On the contrary, a
hard nucleophile (RT-m) reacts with the central metal
of 7 to produce the advanced π-allylmetal complex 9, in
which the hydroxyl group is placed on the opposite side
of the ring, and thence a mixture of regioisomers 2 and
3 would be produced with low regioselectivity, but with
high trans stereoselectivity. In addition to this expecta-
tion, â-hydride elimination of the π-allylmetal complex
7 is a likely process to furnish enol 10 which undergoes
tautomerization to ketone 11. In fact, a poor regioselec-
tivity and facile production of ketone 11 have been
reported in the palladium-catalyzed reaction with cyclo-
pentadiene monoepoxide (12) where a similar π-allylpal-
ladium is formed from the monoepoxide.14,15 Although
these results and the above consideration contradict the
proposed reaction (Chart 1, eq 1), we dared to start an
investigation with the hope that an unauthorized inter-
mediate and/or an unexpected conformational bias in the
transient complex(s) may control the regioselectivity.
Herein, we report the installation of aryl and alkenyl
groups, for the first time, by using new reagents, the
lithium borates 5 shown in eq 2 of Chart 1. A practical
level of the regioselectivity in obtaining 1,4-isomers 2 is
realized by the addition of t-BuCN and NaI, the additive
effect being unprecedented.16 Moreover, synthesis of the
prostaglandin intermediates (for 11-deoxy-PGE2 and
PGA2) and ∆7-PGA1 methyl ester was achieved efficiently
by using the products of this reaction (Figure 2). Regard-
ing the latter synthesis, a significant advancement in
aldol reaction was made as well.
(8) (a) Knight, S. D.; Overman, L. E.; Pairaudeau, G. J . Am. Chem.
Soc. 1995, 117, 5776-5788. (b) Deardorff, D. R.; Savin, K. A.; J ustman,
C. J .; Karanjawala, Z. E.; Sheppeck, J . E., II.; Hager, D. C.; Aydin, N.
J . Org. Chem. 1996, 61, 3616-3622.
Resu lts a n d Discu ssion
(9) Recently, the asymmetric reaction of the 4-cyclopentene-1,3-diol
diacetate with soft nucleophiles in the presence of a palladium catalyst
and a chiral ligand has been reported: (a) Yoshizaki, H.; Satoh, H.;
Sato, Y.; Nukui, S.; Shibasaki, M.; Mori, M. J . Org. Chem. 1995, 60,
2016-2021. (b) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J . Am.
Chem. Soc. 1992, 114, 9327-9343. (c) Mori, M.; Nukui, S.; Shibasaki,
M. Chem. Lett. 1991, 1797-1800.
A. Exa m in a tion of Or ga n om eta llics. On the basis
of the high reactivity in the coupling reaction with
secondary allylic substrates, RTZnX/ Pd or Ni cat.,17 RT-
SnR3/ Pd cat.,14,18 and the lithium borate (6)/ Ni cat.19
were chosen for the present investigation. The last
reagent, developed by us, is prepared in situ from the
boronate ester 4 and MeLi (eq 2). Initially, phenylation
(10) (a) The same products have been synthesized by the palladium-
catalyzed reaction of cyclopentadiene monoepoxide (12) with soft
nucleophiles.10b-d However, the methods suffer from
a chemical
instability of 12. (b) Trost, B. M.; Molander, G. A. J . Am. Chem. Soc.
1981, 103, 5969-5972. (c) Deardorff, D. R.; Shulman, M. J .; Sheppeck,
J . E., II. Tetrahedron Lett. 1989, 30, 6625-6628. (d) Mazo´n, A.; Na´jera,
C.; Ezquerra, J .; Pedregal, C. Tetrahedron Lett. 1997, 38, 2167-2170.
(11) Surman, M. D.; Mulvihill, M. J .; Miller, M. J . J . Org. Chem.
2002, 67, 4115-4121.
(14) (a) Echavarren, A. M.; Tueting, D. R.; Stille, J . K. J . Am. Chem.
Soc. 1988, 110, 4039-4041. (b) Tueting, D. R.; Echavarren, A. M.,
Stille, J . K. Tetrahedron 1989, 45, 979-992.
(15) Suzuki, M.; Oda, Y.; Noyori, R. J . Am. Chem. Soc. 1979, 101,
1623-1625.
(12) Recently, we have succeeded in alkylation: Ito, M.; Matsuumi,
M.; Murugesh, M. G.; Kobayashi, Y. J . Org. Chem. 2001, 66, 5881-
5889.
(16) Preliminary works: (a) Kobayashi, Y.; Takahisa, E.; Usmani,
S. B. Tetrahedron Lett. 1998, 39, 597-600. (b) Usmani, S. B.; Takahisa,
E.; Kobayashi, Y. Tetrahedron Lett. 1998, 39, 601-604. (c) Kobayashi,
Y. Murugesh, M. G.; Nakano, M. Tetrahedron Lett. 2001, 42, 1703-
1707.
(17) (a) Matsushita, H.; Negishi, E. J . Chem. Soc., Chem. Commun.
1982, 160-161. (b) Hayashi, T.; Yamamoto, A.; Hagihara, T. J . Org.
Chem. 1986, 51, 723-727.
(13) (a) Tsuji, J . Palladium Reagents and Catalysts; Wiley: New
York, 1995. (b) Frost, C. G.; Howarth, J .; Williams, J . M. J . Tetrahedron
Asymm. 1992, 3, 1089-1122. (c) Trost, B. M. Chem. Rev. 1996, 96,
395-422. (d) Numata, S.; Kurosawa, H. J . Organomet. Chem. 1977,
131, 301-308.
J . Org. Chem, Vol. 67, No. 20, 2002 7111

Kobayashi et al.
TABLE 1. Ad d itive Effect on th e Ra tio of 2a a n d 3a
entry
additivea
ratio of 2a :3a b
yield, %c
1
2
3
4
5
6
7
t-BuCN
MeCN
6.6:1
5.2:1
4.0:1
6.0:1
4.9:1
13:1
-
-
PhCN
-
AIBNd
-
-
84
81
NaIe
t-BuCN + NaI
t-BuCN + KI
11:1
a
b
THF (solvent): additive ) 10:1 (2-6 equiv). Determined by
1H NMR spectroscopy. c Not determined in entries 1-5. Uniden-
d
tified products were coproduced. e 1 equiv.
submitted to the reaction under the same conditions
mentioned above. Among them, borate 5a with the n-Bu
ligand did provide 2a and 3a with 82% combined yield,
for the first time. However, the product ratio of 2a /3a
was miserably 0.9:1.
F IGURE 2. Target compounds synthesized from the products
To improve the product ratio of 2a /3a , other ligands
for NiCl2 were investigated. However, ligands such as
dppf, dppp, dppe, PBu3, and AsPh3 did not provide better
results. Next, aprotic polar compounds and inorganic
salts were added into the THF solution. While the
reaction did not proceed with bipyridine and TMEDA,
unifunctional compounds such as DMF, DMSO, NEt3,
pyridine, quinoline, t-BuCN, and even H2O increased the
selectivity for the 1,4-isomer 2a . Among them, t-BuCN
(2 equiv) furnished the highest selectivity of 6.6:1 for 2a /
3a (Table 1, entry 1).
of the coupling reaction (eqs 6 and 7).
of racemic acetate 120 was investigated. Reactions run
with PhZnCl (prepared from PhLi and ZnCl2) in the pre-
sence of Pd(PPh3)4, PdCl2(PPh3)2, NiCl2(PPh3)2, or NiCl2-
(dppf) in THF at room temperature furnished less than
5% of the desired coupling products 2a and/or 3a (RT )
Ph). Similar results were also obtained in Et2O and with
PhZnCl prepared from PhMgBr and ZnCl2. Attempted
palladium-catalyzed reaction with PhSnMe3 in the pres-
ence of PdCl2(MeCN)2 in DMF and H2O at 50 °C for 20 h
resulted in recovery of 1. These conditions were once used
by Stille in the reaction of cyclopentadiene monoepoxide
(12) with PhSnMe3, giving 2a and 3a with a 1.7:1 ratio.14
The result of Stille and our finding presented in later
paragraphs are discussed in subsection D.
However, other nitriles such as MeCN, EtCN, PhCN,
and AIBN resulted in lower ratios (entries 2-4). As for
inorganic salts such as LiCl, LiBr, NaBr, and NaI, the
best result of 4.9:1 was provided by NaI (1 equiv) (entry
5). To the best of our knowledge, the enhancement we
encountered is unprecedented for the nickel catalyst.23
Since a deeper shade of brown was observed in entry 5,
the independent roles of t-BuCN and NaI were inferred,
prompting the cooperative effect of t-BuCN and NaI on
the ratio. In fact, a higher ratio of 13:1 was observed with
84% isolated yield when the reaction was run with
t-BuCN and NaI (entry 6). A similar result was also
obtained with KI and t-BuCN (entry 7).
Next, lithium phenylborate 6a (RT ) Ph, R ) Me) was
tested in THF in the presence of a Ni(0) species, derived
from NiCl2(PPh3)2 and MeLi, at room temperature to
produce 2-cyclopenten-1-one (16) and 3-phenylcyclopen-
tan-1-one (17) with a combined yield of <50%. Enone 16
must be the isomerization product of 11, and the forma-
tion of 17 is a result of a nickel-catalyzed 1,4-addition of
the remaining borate 6a to enone 16.21,22 The above result
clearly indicates that the transmetalation of the supposed
intermediate 7 of M ) Ni (Figure 1) with 6a is a slower
process than the â-hydride elimination to 11,15 thus
suggesting that use of a borate with a more electron-
donating alkyl ligand (R) than the methyl ligand would
alter the reaction pathway in the desired direction. New
borates possessing the n-Bu, TMSCH2, or t-Bu group as
the alkyl ligand were prepared from boronate ester 4a
and the corresponding alkyllithium according to eq 2 and
B. Scop e a n d Lim ita tion of th e New Bor a tes. To
determine the efficiency (the reactivity and the regiose-
lectivity) of the reaction conditions found above for the
phenylation, different kinds of aryl and alkenyl borates
5b-n were submitted to the reaction, and the results are
summarized in Table 2. For comparison, the result of the
phenylation mentioned above is listed again in entry 1.
The boronate esters 4b-i were synthesized19,24 by esteri-
fication of the corresponding boronic acids which in turn
were prepared by the method of Brown.24a Boronate
esters 4j-l, the PG ω-chains, were synthesized from
(18) (a) Sheffy, F. K.; Godschalx, J . P.; Stille, J . K. J . Am. Chem.
Soc. 1984, 106, 4833-4840. (b) Kang, S.-K.; Yamaguchi, T.; Kim, J .-
S.; Choi, S.-C. Synth. Commun. 1997, 27, 1267-1271.
(19) Kobayashi, Y.; Mizojiri, R.; Ikeda, E. J . Org. Chem. 1996, 61,
5391-5399.
(20) (a) Deardorff, D. R.; Myles, D. C.; MacFerrin, K. D. Tetrahedron
Lett. 1985, 26, 5615-5618. (b) Deardorff, D. R.; Myles, D. C. In Organic
Syntheses; Freeman, J . P., Ed.; Wiley: New York, 1993; Collect. Vol.
8, pp 13-16.
(23) Acceleration of the reaction rate with inorganic salts in the
palladium-catalyzed coupling of aryl and alkenyl halides with orga-
nostannanes (sp2-sp2 coupling): (a) Echavarren, A. M.; Stille, J . K.
J . Am. Chem. Soc. 1987, 109, 5478-5486. (b) Farina, V.; Krishnan, B.
J . Am. Chem. Soc. 1991, 113, 9585-9595. (c) Farina, V.; Krishnan,
B.; Marshall, D. R.; Roth, G. P. J . Org. Chem. 1993, 58, 5434-5444.
(d) Farina, V.; Krishnamurthy, V.; Scott, W. J . In Organic Reactions;
Paquette, L. A., Ed.; Wiley: New York, 1997; Vol. 50, pp 1-652.
(24) (a) Brown, H. C.; Cole, T. E. Organometallics 1983, 2, 1316-
1319. (b) For 4e-g, see ref 19. (c) For 4h , see Kobayashi, Y.;
Nakayama, Y.; Mizojiri, R. Tetrahedron 1998, 54, 1053-1062.
(21) The 1,4-addition reaction was confirmed by an experiment
separately examined with enone 16 as a substrate under the same
reaction conditions.
(22) Related reactions: (a) Takaya, Y.; Ogasawara, M.; Hayashi, T.;
Sakai, M.; Miyaura, N. J . Am. Chem. Soc. 1998, 120, 5579-5580. (b)
Grisso, B. A.; J ohnson, J . R.; Mackenzie, P. B. J . Am. Chem. Soc. 1992,
114, 5160-5165.
7112 J . Org. Chem., Vol. 67, No. 20, 2002

Installation of Aryl and Alkenyl Groups
TABLE 2. Cou p lin g of 1, 29, a n d 30 w ith Bor a tes 5a -n a
boronate esters. Other boronate esters 4m 25 and 4n were
derived from acetylenes 21 and 22, respectively, through
hydroborations (eqs 4 and 5). Since we were aware of the
stability of borate 5a toward H2O (vide supra), we
deduced the same propensity toward the hydroxyl group
in monoacetate 1. Consequently, 1.2-1.8 equiv of borates
per 1 were used for the investigation and found to be
sufficient: a given boronate ester 4 and NiCl2(PPh3)2 (5-
10 mol %) were converted into the corresponding borate
5 and a Ni(0) species by addition of n-BuLi (0 °C to rt,
15-30 min, THF), and the coupling reaction was carried
out with racemic monoacetate 1 at room temperature in
the presence of 2-5 equiv of t-BuCN and 0.5-1 equiv of
NaI. For comparison, the inherent regioselectivities,
elucidated in most cases by running the reactions without
the additives, are also given in the table.
First, tolylborates 6b-d were examined. In all three
cases, addition of t-BuCN and NaI furnished good regi-
oselectivities (entries 2-4). However, reaction did not
complete with 6b (entry 2), indicating a substituent at
the ortho position is not compatible with the coupling
reaction. On the other hand, the methyl groups at the
meta and para positions, respectively, did not interfere
the efficiency (entries 3 and 4). Regarding the regiose-
lectivity recorded with the additives, 5d furnished a bet-
ter result than 5b and 5c. Next investigated were meth-
oxyborates 5e and 5f. A similar tendency for the reactiv-
ity and the regioselectivity was observed (entries 5 and
6). Furyl coupling was also successful as shown in entry
7.
a
Reactions were carried out with NiCl2(PPh3)2 (5-10 mol %)
in the presence or absence of additives (t-BuCN (2-5 equiv) and
b
NaI (0.5-1 equiv)) for 3-10 h. Racemic substrates were used.
c Ratios were determined by 1H NMR spectroscopy. Ratios given
d
in entries 15 and 16 are for MOM ethers of 2a /3a and 2h /3h , and
those in entries 17 and 18 are for TBS ethers of 2a /3a and 2h /3h ,
respectively. e Recovered 1 in 24% yield. f Not determined.
iodides 18-20 (eq 3) in a way similar to that for the above
Regarding the alkenyl coupling, as expected from the
aryl coupling shown above, good yields with moderate to
good regioselectivities were obtained (entries 8-14). In
the case of the simple alkenyl borates 5h and 5i, the
olefinic geometry did not reflect upon either the yield or
the regioselectivity (entries 8 and 9), and the regioselec-
tivities are among the lowest of those in Table 2.
The regioselectivity obtained with the alkenyl borate
5j, the ω-chain of the primary PGs, is especially note-
worthy (entry 10). Even without the additives, a moder-
(25) (a) Although the procedure25b,c ((i) (Ipc)2BH; (ii) MeCHO; (iii)
butanediol) furnished an inseparable mixture of 4m and IpcOH in our
hand, the method of Hoffmann25d cleanly afforded 4m as shown in eq
4. (b) Moriya, T.; Suzuki, A.; Miyaura, N. Tetrahedron Lett. 1995, 36,
1887-1888. (c) Kamabuchi, A.; Moriya, T.; Miyaura, N.; Suzuki, A.
Synth. Commun. 1993, 23, 2851-2859. (d) Hoffmann, R. W.; Dresely,
S. Synthesis 1988, 103-106.
J . Org. Chem, Vol. 67, No. 20, 2002 7113

Kobayashi et al.
ate selectivity of 5.4:1 for 2j was observed and was raised
to 15:1 by the addition of the additives. Such an unex-
pectedly high regioselectivity was also observed with 5k
and 5l (entries 11 and 12), while 5m and 5n showed
somewhat lower selectivities (entries 13 and 14) than 5j-
l.
where 2j and the related compounds had been synthe-
sized as racemic forms from cyclopentadiene monoepoxide
(12).
Next, the regioselectivity for MOM ether 29 and TBS
ether 30 was investigated. Although moderate to good
To check the relationship between the regioselectivity
and the chiral center present in borates 5j-l, reactions
of (S)-5j with (1R,3S)-1 or (1S,3R)-1 were examined un-
der the conditions used in entry 10 of Table 2. The enan-
tiomerically enriched boronate ester (S)-4j, the precursor
of borate (S)-5j, was prepared from the TBS ether (S)-18
of (S,E)-1-iodo-1-octen-3-ol26 (> 99% ee) according to eq
3, and converted into (S)-5j. Without isolation, reaction
with (1R,3S)-12a,b (95% ee by the MTPA method) and
(1S,3R)-1,2c,d (> 95% ee), furnished 24 and 26 as major
products as shown in eqs 6 and 7, respectively, with sim-
levels of the selectivities were obtained with phenyl- and
heptenyborates 5a and 5h (Table 2, entries 15-18), we
found no synthetic advantage in using these ethers
because chromatographic separation of the regioisomers
was unsuccessful due to the same mobilities and thence
we did not continue further investigations with these
ethers.
1
C. Deter m in a tion of th e Ster eoch em istr y. The H
NMR spectra of the 1,4-isomers 2a and 2j were consistent
with the data reported by Stille14b and Marino,27a,c who
have elucidated the stereochemistry of 2a ,j on the basis
of the difference in chemical shift between the geminal
protons at the C(5) position. In general, the differences
established for trans and cis isomers are <0.3 ppm and
>1 ppm, respectively.28 As for other major products 2b-
i, 2k -n , the trans stereochemistry was determined by
this principle (<0.25 ppm). On the other hand, the
stereochemistry of the minor products 3a -n was as-
signed by consideration of the stereochemistry of the
major products 2.
D. Mer its of th e P r esen t Rea ction . Some of cyclo-
pentenes 2 with an aryl or alkenyl group as RT have been
synthesized from cyclopentadiene monoepoxide (12) by
using RTSnMe3/ Pd catalyst,14b RTHgCl/PdCl2,29 RTCu-
(CN)Li,27a,c (RT)(RR)CuLi,27d and, recently, the reagent
derived from (RT)2Te and (2-Th)Cu(CN)Li2.27e The regi-
oselectivities, however, were < 2:1 for 2a /3a (RT
)
Ph),14b,27a,29 4:1 for 2j/3j (RT ) (E)-CHdCH-CH(OTBS)-
C5H11),27a 1.2:1 for 2/3 of RT ) -CHdCH2,14b 1.35:1 for
2/3 of RT ) (E)-CHdCH-CH(OTBS)(CH2)6CO2Me,14b
<
2.5:1 for 2/3 of RT ) -C(CH(OEt)2)dCH2,27d and < 3.6:1
for 2/3 of RT ) (Z)-CHdCHR.27e In addition to these low
regioselectivities, monoepoxide 12 suffers from a chemical
instability. Recently, asymmetric synthesis of 12 has been
reported with moderate to high enantiomeric excesses.30
These reactions, however, seem unattractive as a starting
compound due to the disadvantages mentioned above. On
the contrary, the present reaction (eq 1 with borates 5)
furnishes good regioselectivity and stereospecificity and
ilar ratios and yields to those obtained with racemic 1
and 5j (Table 2, entry 10). Consequently, it is obvious to
generalize that optically active alkenyl groups of the
general structure 28 with either the R or S configuration
(26) Kitano, Y.; Matsumoto, T.; Wakasa, T.; Okamoto, S.; Shimazaki,
T.; Kobayashi, Y.; Sato, F.; Miyaji, K.; Arai, K. Tetrahedron Lett. 1987,
28, 6351-6354.
(27) (a) Marino, J . P.; Ferna´ndez de la Pradilla, R.; Laborde, E. J .
Org. Chem. 1987, 52, 4898-4913. (b) Marino, J . P.; Ferna´ndez de la
Pradilla, R.; Laborde, E. J . Org. Chem. 1984, 49, 5279-5280. (c)
Marino, J . P.; Kelly, M. G. J . Org. Chem. 1981, 46, 4389-4393. (d)
Marino, J . P.; Farina, J . S. J . Org. Chem. 1976, 41, 3213-3215. (e)
Tucci, F. C.; Chieffi, A.; Comasseto, J . V.; Marino, J . P. J . Org. Chem.
1996, 61, 4975-4989.
(28) Trost, B. M.; Verhoeven, T. R. J . Am. Chem. Soc. 1980, 102,
4730-4743.
(29) Larock, R. C.; Ilkka, S. Tetrahedron Lett. 1986, 27, 2211-2214.
(30) (a) Chang, S.; Heid, R. M.; J acobsen, E. N. Tetrahedron Lett.
1994, 35, 669-672. (b) Mikame, D.; Hamada, T.; Irie, R.; Katsuki, T.
Synlett 1995, 827-828. (c) Zaidlewicz, M.; Krzeminski, M. Tetrahedron
Lett. 1996, 37, 7131-7134.
will be installed onto the ring of 1 with a practically high
level of the regioselectivity (∼ 15:1), and that a series of
artificial prostaglandins can be synthesized as optically
active forms from 2 by using the methods described later,
or the methods previously reported by other groups27a-c
7114 J . Org. Chem., Vol. 67, No. 20, 2002

Installation of Aryl and Alkenyl Groups
SCHEME 1a
a
Reagents and conditions: (a) MeC(OEt)3, PhOH (0.2 equiv),
80%; (b) LiOH, H2O/MeOH, 73%; (c) KI3, NaHCO3, 83%; (d)
Bu3SnH, AIBN, 81%; (e) AgOAc, DMSO, 82%.
to 9 is a competitive process with the transmetalation to
34, eventually producing a mixture of 2 and 3. Similar
competitive reactions are likely for 33 which is produced
from acetate 1 and Ni(0) in the absence of NaI. Among
the key intermediates 32 and 33 with the iodo and the
acetoxy ligands, respectively, it is quite reasonable to
think that transmetalation of 32 to 34 takes place faster
than that of 33. As for t-BuCN, it is probable that t-BuCN
simply accelerates the transmetalation of 32 as well as
33 to 34.
F IGURE 3. Plausible intermediates giving 2 and/or 3.
is applicable to synthesis of the enantiomerically enriched
compounds 2 as are demonstrated in eqs 6 and 7. From
a synthetic point of view, the use of 1.2-1.8 equiv of
borates 5 per monoacetate 1 is convenient, especially in
the case that boronate precursors 4 are prepared by
multistep procedures. In addition, boronate esters 4 are
also chemically stable. Regarding purification of the 1,4-
products 2, separation of the minor 1,2-isomers 3 is easily
accomplished by routine chromatography on silica gel (∆
Rf ) ca. 0.2, hexane/Et2O or EtOAc).
The higher regioselectivity observed with the PG
borates 5j-l can be understood similarly (Table 2, entries
10-12). Thus, the inherent selectivity built in 5j-l is
increased furthermore by the additives in the manner
described above. The origin for the inherent high regi-
oselectivity is, however, not clear at the moment.
F . Syn th esis of th e P r osta gla n d in In ter m ed ia tes.
As an extension of the present investigation, synthesis
of 1334 and 14,35 which are the intermediates of 11-deoxy-
PGE2 and PGA2, respectively (Figure 2), was explored
by a route summarized in Scheme 1 starting with 24,
which is the product of eq 6. The J ohnson-Claisen
rearrangement 24 and subsequent hydrolysis afforded
acid 36 which, upon iodolactonization with KI3 and
NaHCO3, furnished lactone 37 in good overall yield from
24. Deiodination of 37 with Bu3SnH and AIBN produced
E. Con sid er a tion of th e Regioselectivity. Since the
hydroxyl group on the ring does not seem to influence
the favoring of compound 2, the raise in the regioselec-
tivity is best understood by introducing new complexes,
[Ni‚I]-Na+ (31) and σ-allylnickel iodide 32, to the well-
established catalytic cycle that consists of π-allylnickels
7 and 9 (Figure 1, M ) Ni). The critical steps involving
these species are compiled in Figure 3. Although the
formation of 31 from Ni(0) species and NaI is speculation
from [Pd‚I]-Na+ (ref 31), the deeper brown color observed
with NaI indirectly suggests the formation of 31. The
participation of the σ-allyl species (palladium32 and
rhodium33 species) has recently been argued to explain
the results obtained in the coupling reaction of allylic
compounds with soft nucleophiles. Accordingly, the key
σ-allylnickel 32 initially formed from acetate 1 and
complex 31 undergoes transmetalation with borate 5 to
afford the advanced σ-allylnickel 34, which then produces
1,4-isomer 2 regioselectively. On the other hand, conver-
sion of σ-allylnickel 32 to the π-allylnickel 35 and then
lactone 13 ([R]21 ) +4.4 (c 0.95, CHCl3) in 81% yield,
D
while reaction with AgOAc afforded olefin 14 ([R]21
)
D
+159 (c 0.85, CHCl3); lit.35b [R]22D ) +161.5 (c 2.8, CHCl3))
in 82% yield.
Previously, 13 was synthesized as a mixture of the
diastereomers.34 However, application of the method to
synthesis of the optically active 13 seems difficult. As for
14, the asymmetric synthesis reported previously35 is
lengthy and less efficient than the present synthesis.
G. Syn th esis of ∆7-P GA1 Meth yl Ester . The artificial
prostaglandin 15 (Figure 2) synthesized by the Noyori
(31) Negishi, E.; Takahashi, T.; Akiyoshi, K. J . Chem. Soc., Chem.
Commun. 1986, 1338-1339.
(32) (a) Fiaud, J . C.; Malleron, J . L. Tetrahedron Lett. 1981, 22,
1399-1402. (b) Trost, B. M.; Bunt, R. C. J . Am. Chem. Soc. 1996, 118,
235-236.
(34) Dixon, A. J .; Taylor, R. J . K.; Newton, R. F. J . Chem. Soc.,
Perkin Trans. 1 1981, 1407-1410.
(33) (a) Evans, P. A.; Nelson, J . D. J . Am. Chem. Soc. 1998, 120,
5581-5582. (b) Evans, P. A.; Nelson, J . D. Tetrahedron Lett. 1998,
39, 1725-1728. Cf. (c) Evans, P. A.; Robinson, J . E.; Nelson, J . D. J .
Am. Chem. Soc. 1999, 121, 6761-6762.
(35) (a) Chapleo, C. B.; Finch, M. A. W.; Lee, T. V.; Roberts, S. M.;
Newton, R. F. J . Chem. Soc., Perkin Trans. 1 1980, 2084-2087. (b)
Newton, R. F.; Reynolds, D. P.; Davies, J .; Kay, P. B.; Roberts, S. M.;
Wallace, T. W. J . Chem. Soc., Perkin Trans. 1 1983, 683-685.
J . Org. Chem, Vol. 67, No. 20, 2002 7115

Kobayashi et al.
SCHEME 2 a
The investigation was initiated with enone 39, which,
after treatment with convenient amides such as LDA,
LiCA (LiN(i-Pr)(c-C6H11)), and LHMDS (LiN(TMS)2) at
-78 °C for 20-30 min in THF, was submitted to an aldol
reaction with aldehyde 42a (R2 ) (CH2)2Ph) at the same
temperature (eq 8). The enone disappeared completely
and furnished a mixture of the anti and syn aldols 43a
and 46a in reasonable yields (Table 3, entries 1-3). The
aldols were separated easily by routine chromatography.
It should be noted that longer reaction times (>60 min)
and/or higher temperatures (>-50 °C) for the anion
generation decreased the yield of the aldols. These results
suggest a somewhat unstable nature of the enolate
derived from 39, and account for a failure in alkylation
with MeI at a higher temperature of 0 °C. The anti and
syn stereochemistries for the major and minor aldols 43a
and 46a were determined, respectively, on the basis of
the coupling constants between Ha and Hb of 43a (J a,b
group36 has attracted much attention not only because
of its unique structure but also because of its antitumor
activity.37 The key structure responsible for the biological
activity, according to the group, is the alkylidene cyclo-
pentenone chromophore,38,39 which is constructed by the
1,4-addition of organo copper reagents onto 4-silyloxy-2-
cyclopenten-1-one followed by aldol reaction with the R
chain-aldehyde and the subsequent dehydration.36
Another method we have planned for synthesis of the
R-alkylidene core structure 38 is shown in Scheme 2,
which involves oxidation of alcohol 26 (the product of eq
7) to the enone and subsequent installation of the C(1)-
C(7) side chain by aldol reaction at the R′ (R prime)
position of the enone. Although the R′ enolates from
cyclohexenones have been explored well,40 a few reports
related to our investigation have been published. That
is reactions with unsubstituted cyclopentenone 41 (R1 )
H).41 What is worse, the conditions elucidated for the
enolate preparation are different. For example, Brown
used LDA to prepare the enolate from 41,41a while
Shibasaki found that Zr(O-i-Pr)4 is a better base than
LDA though the yield was moderate in his case.41b
Consequently, we undertook an investigation of the aldol
reaction of substituted enones 39 (R1 ) (E)-CHdCHC5H11)
and 40 (R1 ) Ph) with several aldehydes 42a -d in order
to find suitable conditions for synthesis of 15 (eq 8). These
1
) 8.7 Hz) and 46a (J a,b ) 3 Hz) in the H NMR spectra.42
In addition, the selective production of the anti isomer
43a was consistent with the chairlike cyclic transition
state involving the lithium R′ enolate and aldehyde 42a .
Since the yields of entries 1-3 in Table 3 are compa-
rable to each other, the conditions of entry 1 were applied
to the aldol reaction with other aldehydes, 42b (R2
)
i-Pr), 42c (R2 ) Ph), and 42d (R2 ) (E)-CHdCHPh), and
all of the reactions uniformly furnished anti aldols as the
major products in reasonable yields after chromatography
(entries 4-6). The stereochemistry of the aldols was
determined by the method described above: anti isomers
43b-d , J a,b ) 9.0-9.6 Hz; syn isomers 46b-d , J a,b ) ca.
3 Hz.43 The aldol products were fairly stable and the
corresponding dehydration-products were not detected by
1
either TLC or H NMR spectroscopy even in the cases of
the products of entries 5 and 6.
Next, aldol reaction of enone 40 (R1 ) Ph) with
aldehydes 42a -c (R2 ) (CH2)2Ph, i-Pr, Ph) was examined
under the conditions of entry 1 and found to furnish
similar anti/syn ratios and yields (entries 7-9).43 The
unsubstituted enone 41 (R1 ) H) also produced aldols
45a -c and 48a -c with similar ratios and yields (entries
10-12).43
In conclusion, LDA, LiCA, and LHMDS were found to
be equally practical bases for formation of the R′ enolates
from the cyclopentenones. Although the R′ enolates were
found to be somewhat unstable, aldol reactions were
conducted successfully (Table 3).
(40) For example: (a) Trost, B. M.; Krische, M. J . J . Am. Chem. Soc.
1999, 121, 6131-6141. (b) Spitzner, D.; Engler, A. In Organic
Syntheses; Freeman, J . P., Ed.; Wiley: New York, 1993; Collect. Vol.
8, pp 219-222. (c) Gesson, J .-P.; J acquesy, J .-C.; Renoux, B. Tetrahe-
dron 1989, 45, 5853-5866.
enones were prepared by PCC oxidation of 2h and 2a in
71% and 65% yields, respectively.
(41) (a) Brown, D. W.; Campbell, M. M.; Taylor, A. P.; Zhang, X.
Tetrahedron Lett. 1987, 28, 985-988. (b) Sasaki, H.; Kirio, Y.;
Shibasaki, M. J . Org. Chem. 1990, 55, 5306-3508. Cf: (c) Wender, P.
A.; Nuss, J . M.; Smith, D. B.; Sua´rez-Sobrino, A.; Vagberg, J .; Decosta,
D.; Bordner, J . J . Org. Chem. 1997, 62, 4908-4909. (d) Roulland, E.;
Monneret, C.; Florent, J .-C. J . Org. Chem. 2002, 67, 4399-4406.
(42) (a) House, H. O.; Crumrine, D. S.; Teranishi, A. Y.; Olmstead,
H. D. J . Am. Chem. Soc. 1973, 95, 3310-3324. (b) Mukaiyama, T.;
Banno, K.; Narasaka, K. J . Am. Chem. Soc. 1974, 96, 7503-7509.
(43) The aldol products and the coupling constants measured are
as follows: 43a , 8.7 Hz; 46a , 3 Hz; 43b, 9.3 Hz; 46b, ca. 3 Hz; 43c, 9.6
Hz; 46c, 3 Hz; 43d , 9.0 Hz; 46d , 3 Hz; 44a , 8.4 Hz; 47a , 3 Hz; 44b, 9.0
Hz; 47b, ca. 3 Hz; 44c, 9.6 Hz; 47c, ca. 3 Hz. However, coupling
constants of 45a -c and 48a -c could not be determined because of
overlap of the diagnostic signals.
(36) (a) Sugiura, S.; Toru, T.; Tanaka, T.; Hazato, A.; Okamura, N.;
Bannai, K.; Manabe, K.; Kurozumi, S.; Noyori, R. Chem. Pharm. Bull.
1984, 32, 4658-4661. (b) Suzuki, M.; Morita, Y.; Koyano, H.; Koga,
M.; Noyori, R. Tetrahedron 1990, 46, 4809-4822.
(37) (a) Kato, T.; Fukushima, M.; Kurozumi, S.; Noyori, R. Cancer
Res. 1986, 46, 3538-3542. (b) Noyori, R.; Suzuki, M. Science 1993,
259, 44-45. (c) Suzuki, M.; Kiho, T.; Tomokiyo, K.; Furuta, K.;
Fukushima, S.; Takeuchi, Y.; Nakanishi, M.; Noyori, R. J . Med. Chem.
1998, 41, 3084-3090.
(38) Suzuki, M.; Mori, M.; Niwa, T.; Hirata, R.; Furuta, K.; Ishikawa,
T.; Noyori, R. J . Am. Chem. Soc. 1997, 119, 2376-2385.
(39) Noyori, R.; Koyano, H.; Mori, M.; Hirata, R.; Shiga, Y.; Kokura,
T.; Suzuki, M. Pure Appl. Chem. 1994, 66, 1999-2005.
7116 J . Org. Chem., Vol. 67, No. 20, 2002

Installation of Aryl and Alkenyl Groups
TABLE 3. Ald ol Rea ction betw een En on es 39-41 a n d Ald eh yd es 42a -d a
entry enone R1 for 39-41, 43-48
base
aldehyde R2 for 42, 43-48 products anti,synb,c total yield, % ratiod anti/syn
1
2
3
4
5
6
7
8
39
39
39
39
39
39
40
40
40
41
41
41
(E)-CHdCH-C5H11
LDA
42a
42a
42a
42b
42c
42d
42a
42b
42c
42a
42b
42c
(CH2)2Ph
(CH2)2Ph
(CH2)2Ph
i-Pr
43a ,46a
43a ,46a
43a ,46a
43b,46b
43c,46c
43d ,46d
44a ,47a
44b,47b
44c,47c
45a ,48a
45b,48b
45c,48c
85
88
86
66
75
65
83
72
74
72
75
77
2:1
4.8:1
(E)-CHdCH-C5H11
LiCAe
LHMDSf
LDA
(E)-CHdCH-C5H11
3.5:1
(E)-CHdCH-C5H11
>20:1g
1.6:1
(E)-CHdCH-C5H11
LDA
LDA
LDA
LDA
LDA
LDA
LDA
LDA
Ph
(E)-CHdCH-C5H11
(E)-CHdCHPh
(CH2)2Ph
i-Pr
Ph
(CH2)2Ph
i-Pr
1.7:1
Ph
Ph
Ph
H
H
H
4.2:1
>20:1g
2.5:1
9
10
11
12
2.4:1
13:1g
1.5:1g
Ph
a
b
At -78 °C for 15-30 min in THF. The stereochemistry of the aldol isomers 43a -d , 46a -d , 44a -c, and 47a -c was determined by
the coupling constants between Ha and Hb of the isomers (see ref 43 in detail), while that of 45a -c and 48a -c was speculated on the
basis of chemical shifts of Hb and mobilities on TLC. c Both stereoisomers were separated easily by silica gel chromatography (∆ Rf ) ca.
d
0.2). Calculated from the isolated yields unless otherwise noted. e LiN(i-Pr)(c-C6H11). f LiN(TMS)2. g Determined by 1H NMR spectroscopy.
SCHEME 3 a
mesylate 54 in 89% yield and, concomitantly, the sub-
sequent product 55 () 38 of Scheme 2) in 11% yield. After
several trials,45 elimination of the mesylates 53 and 54
46
was effected cleanly with Al2O3 to produce 55 in good
yields in both cases. Finally, deprotection47 of the TBS
group with NBS48 in aqueous DMSO furnished the target
compound 15 in 80% yield: [R]26D ) +165 (c 0.13, CHCl3).
The 1H NMR spectrum of the synthetic PG 15 was
identical with that of the enantiomer reported by
Suzuki.37b
Con clu sion s
We have presented a new reaction for installation of
aryl and alkenyl groups onto the readily available
monoacetate 1 using lithium borates 5 and the nickel
catalyst in the presence of t-BuCN and NaI to afford
trans 1,4-isomers 2 with practically acceptable levels of
regioselectivity (eq 1 in Chart 1 and Table 2). Among the
(44) Suzuki, M.; Kawagishi, T.; Yanagisawa, A.; Suzuki, T.; Oka-
mura, N.; Noyori, R. Bull. Chem. Soc. J pn. 1988, 61, 1299-1312. Cold
MeOH was added to an ice-cold mixture of 1-methoxy-1-cycloheptene
and pyridine (0.3 equiv), and the MeOH solution (1.2 M) was submitted
to ozonolysis at -78 °C to afford aldehyde 50 in 91% yield.
(45) Although Et3N in CH2Cl2 furnished the desired olefin iii from
a model syn mesylate i efficiently, anti mesylate ii with Et3N produced
iii and iv with different ratios depending on the conditions employed.
Other amines did not improve the result.
a
Reagents and conditions: (a) PCC, 91%; (b) LDA, -78 °C, 20
min; 51 (73%), 52 (15%); (c) MsCl, Et3N, CH2Cl2; 53 (85%) from
51; 54 (89%) and 55 (11%) from 52; (d) Al2O3, CH2Cl2; 92% from
53, 88% from 54; (e) NBS, DMSO/H2O, 80%.
With the above results in mind, synthesis of prostag-
landin 15 was investigated and the successful result is
presented in Scheme 3. Oxidation of 26 with PCC
afforded enone 49 in 91% yield and subsequent aldol
reaction with aldehyde 5044 under the conditions men-
tioned above (Table 3, entry 1) produced a mixture of anti
aldol 51 and syn aldol 52 in 73% and 15% yields,
respectively, after chromatography. Mesylation of 51
under the usual conditions furnished 53 in good yield.
On the other hand, the same reaction with 52 produced
(46) (a) We used Alumina N - Super I from ICN: Posner, G. H.;
Gurria, G. M.; Babiak, K. A. J . Org. Chem. 1977, 42, 3173-3180. (b)
Yamada, K.; Arai, T.; Sasai, H.; Shibasaki, M. J . Org. Chem. 1998,
63, 3666-3672.
(47) Attempted desilylation with Bu4NF in THF resulted in produc-
tion of several unidentified compounds.
(48) Batten, R. J .; Dixon, A. J .; Taylor, R. J . K.; Newton, R. F.
Synthesis 1980, 234-236.
J . Org. Chem, Vol. 67, No. 20, 2002 7117

Kobayashi et al.
1H NMR δ 0.069 (s, 3 H), 0.074 (s, 3 H), 0.88 (s, 9 H), 1.59 (dt,
J ) 14, 5 Hz, 1 H), 2.03 (s, 3 H), 2.79 (dt, J ) 14, 7 Hz, 1 H),
4.70 (tm, J ) 6 Hz, 1 H), 5.45 (tm, J ) 7 Hz, 1 H), 5.87 (dt, J
) 6, 2 Hz, 1 H), 5.96 (dt, J ) 6, 2 Hz, 1 H). Anal. Calcd for
Calcd for C13H24O3Si: C, 60.89; H, 9.43. Found: C, 61.12; H,
9.36.
entries of Table 2, a series of borates corresponding to
the PG ω chain of the natural and artificial forms
furnished 2 with the unexpectedly high levels of the
regioselectivity. Then, syntheses of the PG intermediates
and ∆7-PGA1 methyl ester were accomplished quite
efficiently starting with the coupling products. The aldol
reaction of cyclopentenones at the R′ position proceeded
efficiently under the conditions we have found and was
applied successfully to the synthesis of ∆7-PGA1 methyl
ester. We would like to emphasize that the convenient
availability of 2, which had previously been inaccessible,
was all which led to the success in efficient synthesis of
these target molecules. It is no doubt that new strategies
for synthesis of other cyclopentanoids such as egregi-
achloride E, hitachimycin, hybridalactone, coronatine,
etc., will be proposed with compounds 2 and derivatives
thereof quite easily.
4,5-Dim eth yl-2-(2-m eth ylp h en yl)-1,3,2-d ioxa bor ola n e
(4b). To a solution of 2-bromotoluene (5.50 mL, 45.7 mmol)
and bipyridine (ca. 10 mg) in THF (50 mL) was added n-BuLi
(18.0 mL, 2.5 M in hexane, 45 mmol) at -78 °C. After being
stirred at -78 °C for 4 h, B(O-i-Pr)3 (10.5 mL, 45.5 mmol)
dissolved in Et2O (10 mL) was added slowly. The solution was
allowed to warm to room-temperature slowly, stirred over-
night, and poured into a mixture of EtOAc and 3 N HCl with
vigorous stirring. After separation of the organic layer, the
aqueous layer was extracted with EtOAc twice, and the
combined extracts were dried (MgSO4) and concentrated. To
the crude boronic acid in benzene (100 mL) were added 2,3-
butanediol (4.1 mL, 45.5 mmol) and MgSO4 (10 g), and the
resulting mixture was stirred at room temperature and filtered
through
a pad of Celite with benzene. The filtrate was
Exp er im en ta l Section
concentrated to leave an oil, which was purified by chroma-
Gen er a l In for m a tion . Infrared (IR) spectra are reported
in wavenumbers (cm-1). Unless otherwise noted, 1H NMR (300
MHz) and 13C NMR (75 MHz) spectra were measured in CDCl3
using SiMe4 (δ ) 0 ppm) and the center line of CDCl3 triplet
(δ ) 77.1 ppm) as internal standards, respectively. The 13C
NMR spectra of the boronate esters 4a -n were, however, not
measured because they are a mixture of dl- and meso-isomers
concerning the diol ligand and because the signals correspond-
ing to the carbon bearing the boron atom are not identified
due to the boron quadrapole.49 The following solvents were
distilled before use: THF (from Na/benzophenone), Et2O (from
Na/benzophenone), and CH2Cl2 (from CaH2). Racemic acetate
tography to afford 4b (6.87 g, 79%): Bp 145 °C (2 Torr); IR
(neat) 1601, 1082, 899 cm-1 1H NMR δ 1.29 and 1.36 (2d, J
:
) 6 and 6 Hz, 6 H (7:1)), 2.54 (s, 3 H), 4.15-4.22 and 4.62-
4.75 (2m, 2 H (1:7)), 7.04-7.38 (m, 3 H), 7.79 (d, J ) 8 Hz, 1
H). Anal. Calcd for C11H15BO2: C, 69.52; H, 7.96. Found: C,
69.78; H, 7.83.
4,5-Dim eth yl-2-(3-m eth ylp h en yl)-1,3,2-d ioxa bor ola n e
(4c). According to the above procedure, the title compound 4c
was prepared from 3-bromotoluene (5.5 mL, 45.3 mmol) in 72%
yield: Bp 140 °C (2 Torr); IR (neat) 1608, 1585, 1223, 1207,
1103, 1083 cm-1 1H NMR δ 1.30 and 1.40 (2d, J ) 6 and 6
:
Hz, 6 H (10:1)), 2.36 (s, 3 H), 4.14-4.23 and 4.64-4.76 (2m, 2
H (1:10)), 7.27-7.30 (m, 2 H), 7.58-7.66 (m, 2 H). Anal. Calcd
for C11H15BO2: C, 69.52; H, 7.96. Found: C, 69.83; H, 7.91.
1,20 (1R,3S)-12a,b ([R]20 ) +75 (c 1.02, CHCl3)) of 95% ee
D
(checked by the MTPA method) for eq 6, (1S,3R)-12c,d ([R]20
D
) -74 (c 1.03, CHCl3)) of >95% ee for eq 7 and of >99% ee for
Scheme 3, and the boronate esters 4a ,19 4e,19 4g,19 and 4h 24c
were prepared according to the procedures indicated. (S,E)-
1-Iodo-1-octen-3-ol of > 99% ee, the precursors of (S)-4j, was
kindly provided by Professor F. Sato.26 Routinely, organic
extracts were concentrated by using a rotary evaporator, and
residues were purified by chromatography on silica gel.
(1R*,4S*)-4-Meth oxym eth oxy-2-cyclop en ten yl Aceta te
(29). A solution of acetate 1 (1.71 g, 12.1 mmol), MOMCl (1.84
mL, 24.2 mmol), and i-Pr2NEt (10.5 mL, 60.3 mmol) in CH2-
Cl2 (15 mL) was stirred at room temperature for 6 h and
poured into a mixture of saturated NaHCO3 and Et2O. The
mixture was stirred for 30 min vigorously, the layers were
separated, and the aqueous layer was extracted with Et2O.
The combined extracts were dried (MgSO4) and concentrated
to leave a residual oil, which was purified by chromatography
to afford MOM ether 29 (2.05 g, 91%): Bp 95 °C (1.5 Torr); IR
4,5-Dim eth yl-2-(4-m eth ylp h en yl)-1,3,2-d ioxa bor ola n e
(4d ). According to the preparation of 4b, the title compound
4d was prepared from 4-bromotoluene (5.5 mL, 44.7 mmol) in
76% yield: Bp 130 °C (2 Torr); IR (neat) 1612, 1221, 1095 cm-1
;
1H NMR δ 1.29 and 1.39 (2d, J ) 6 and 6 Hz, 6 H (6:1)), 2.37
(s, 3 H), 4.12-4.21 and 4.63-4.74 (2m, 2 H (1:6)), 7.20 (d, J )
8 Hz, 2 H), 7.71 (d, J ) 8 Hz, 2 H). Anal. Calcd for C11H15BO2:
C, 69.52; H, 7.96. Found: C, 69.46; H, 7.88.
4,5-Dim e t h yl-2-(4-m e t h oxyp h e n yl)-1,3,2-d ioxa b or o-
la n e (4f). According to the preparation of 4b, the title
compound 4f was prepared from 4-bromoanisole (5.63 mL, 45.0
mmol) in 78% yield. The 1H NMR spectrum of 4f was identical
with that reported.19
(Z)-4,5-Dim eth yl-2-(1′-h epten yl)-1,3,2-dioxabor olan e (4i).
To a solution of (Z)-1-iodoheptene (3.39 g, 15.1 mmol) and
bipyridine (ca. 10 mg) in Et2O (30 mL) was added t-BuLi (18.3
mL, 1.64 M in pentane, 30 mmol) at -78 °C slowly. The
solution was stirred at -78 °C for 3 h and B(O-i-Pr)3 (3.50
mL, 15.2 mmol) was added to it. The solution was warmed to
0 °C slowly, stirred overnight, and poured into 1 N HCl with
EtOAc. The mixture was extracted with EtOAc three times,
and the combined extracts were dried (MgSO4) and concen-
trated to furnish the corresponding boronic acid, which was
used for the next reaction without further purification.
1
(neat) 3068, 1738, 1240, 1043 cm-1; H NMR δ 1.74 (dt, J )
14, 4 Hz, 1 H), 2.06 (s, 3 H), 2.80 (dt, J ) 14, 7 Hz, 1 H), 3.39
(s, 3 H), 4.54-4.60 (m, 1 H), 4.71 (s, 2 H), 5.48-5.54 (m, 1 H),
6.00 (dm, J ) 6 Hz, 1 H), 6.12 (dm, J ) 6 Hz, 1 H). Anal.
Calcd for C9H14O4: C, 58.05; H, 7.58. Found: C, 57.74; H, 7.57.
(1R*,4S*)-4-[(ter t-Bu tyld im eth ylsilyl)oxy]-2-cyclop en -
ten yl Aceta te (30). A solution of acetate 1 (1.42 g, 10.0 mmol),
TBSCl (1.81 g, 12.0 mmol), and imidazole (1.16 g, 17.0 mmol)
in DMF (10 mL) was stirred at room temperature for 3 h and
poured into a mixture of saturated NaHCO3 and hexane. The
resulting mixture was stirred for 1 h vigorously, and the
phases were separated. The aqueous phase was extracted with
hexane twice. The combined extracts were dried (MgSO4) and
concentrated to leave a residue, which was purified by chro-
matography to afford silyl ether 30 (2.35 g, 92%): Bp 155-
A mixture of the above boronic acid, 2,3-butanediol (1.38
mL, 15.5 mmol), and MgSO4 (ca. 5 g) in benzene (30 mL) was
stirred overnight and filtered through a pad of Celite. The
filtrate was concentrated to leave an oil, which was purified
by chromatography to furnish 4i (1.92 g, 65%): Bp 85 °C (0.5
1
Torr); IR (neat) 1630, 1261, 1074, 760 cm-1; H NMR δ 0.88
165 °C (0.5 Torr); IR (neat) 3066, 1738, 1250, 837, 777 cm-1
.
(t, J ) 7 Hz, 3 H), 1.07-1.44 (m, 12 H), 2.39 (dq, J ) 1, 7.5
Hz, 2 H), 3.98-4.08 and 4.52-4.60 (2m, 2 H (2:7)), 5.34 (dt, J
) 13, 1 Hz, 1 H), 6.46 (dt, J ) 13, 7.5 Hz, 1 H). Anal. Calcd for
(49) Pergament, I.; Srebnik, M. Tetrahedron Lett. 2001, 42, 8059-
8062.
C
11H21BO2: C, 67.38; H, 10.79. Found: C, 67.33; H 10.78.
7118 J . Org. Chem., Vol. 67, No. 20, 2002

Installation of Aryl and Alkenyl Groups
(E)-2-(3′-[(ter t-Bu tyld im eth ylsilyl)oxy]-1′-octen yl)-4,5-
d im eth yl-1,3,2-d ioxa bor ola n e (4j). To a solution of racemic
iodide 1850 (3.65 g, 9.92 mmol) and bipyridine (ca. 10 mg) in
THF (33 mL) was added n-BuLi (6.40 mL, 2.33 M in hexane,
14.9 mmol) at -78 °C dropwise. The solution was stirred for
30 min at -78 °C, and B(O-i-Pr)3 (3.66 mL, 15.9 mmol) was
added to it. The resulting solution was gradually warmed to 0
°C, stirred overnight and poured into an ice-cold mixture of
saturated NH4Cl and EtOAc. The resulting mixture was
stirred vigorously for 30 min. The layers were separated, and
the aqueous layer was extracted twice. The combined extracts
were dried (MgSO4) and concentrated to give the corresponding
boronic acid, which was used for the next reaction without
further purification.
was added. The resulting solution was stirred at room-
temperature overnight and concentrated to afford a residue,
which was purified by chromatography to afford 4m (1.10 g,
66%): Bp 130 °C (2 Torr); IR (neat) 1645, 1072, 837, 779 cm-1
;
1H NMR δ 0.04 (s, 6 H), 0.89 (s, 9 H), 1.18 and 1.28 (2d, J )
6 and 6 Hz, 6 H (9:7)), 3.95-4.04 and 4.46-4.59 (2m, 2 H (7:
9)), 4.21-4.25 (m, 2 H), 5.74 (dt, J ) 18, 2 Hz, 1 H), 6.66 (dt,
J ) 18, 4 Hz, 1 H). Anal. Calcd for C13H27BO3Si: C, 57.78; H,
10.07. Found: C, 58.04; H, 9.53.
3-Bu tyl-1-h ep tyn e (23).52 A solution of 1-heptyne (22) (1.36
mL, 10.4 mmol) and n-BuLi (8.42 mL, 2.72 M in hexane, 22.9
mmol) in Et2O (20 mL) was stirred at 0 °C for 5 h and n-BuBr
(1.11 mL, 10.3 mmol) was added. The resulting solution was
stirred at the same temperature overnight and poured into a
mixture of brine and EtOAc with vigorous stirring. The layers
were separated and the aqueous layer was extracted with
EtOAc. The combined extracts were dried (MgSO4) and
concentrated to leave an oil, which was distilled to afford
acetylene 23 (1.02 g, 65%): Bp 110 °C (22 Torr); IR (neat) 3311,
A mixture of the above boronic acid, 2,3-butanediol (1.0 mL,
11 mmol), and MgSO4 (20 g) in Et2O (200 mL) was stirred at
room temperature for 2 h and filtered through a pad of Celite
with EtOAc. Evaporation of the filtrate and chromatography
of the residue afforded boronate ester 4j (3.12 g, 92%): Bp
1
2112 cm-1; H NMR δ 0.90 (t, J ) 7 Hz, 6 H), 1.2-1.6 (m, 12
1
130-140 °C (1 Torr); IR (neat) 1645, 1072, 837, 779 cm-1; H
H), 2.03 (d, J ) 2.4 Hz, 1 H), 2.24-2.36 (m, 1 H); 13C NMR δ
NMR δ 0.005 (s, 3 H), 0.022 (s, 3 H), 0.86 (t, J ) 7 Hz, 3 H),
0.88 (s, 9 H), 1.1-1.5 (m, 14 H), 3.98-4.05 and 4.48-4.60 (2m,
2 H) (4:7)), 4.11-4.19 (m, 1 H), 5.59 (d, J ) 18 Hz, 1 H), 6.58
(d, J ) 18 Hz, 1 H). Anal. Calcd for C18H37BO3Si: C, 63.52; H,
10.96. Found: C, 63.26; H, 10.87.
88.3, 68.8, 34.6, 31.4, 29.4, 22.5, 13.9. Anal. Calcd for C11H20
C, 86.76; H, 13.24. Found: C, 86.99; H, 13.26.
:
(E)-2-(3′-Bu tyl-1′-h epten yl)-4,5-dim eth yl-1,3,2-dioxabor o-
la n e (4n ). To an ice-cold solution of acetylene 23 (3.65 mL,
19.7 mmol) in CH2Cl2 (40 mL) was added Br2BH‚SMe2 (19.7
mL, 1 M in CH2Cl2, 19.7 mmol). The solution was stirred at
room temperature for 6 h and poured into an ice-cold mixture
of H2O (3.55 mL, 197 mmol) and Et2O (10 mL) with vigorous
stirring. The layers were separated and the organic layer was
dried (MgSO4) and concentrated. To this boronic acid were
added benzene (150 mL), 2,3-butanediol (2.67 mL, 29.3 mmol),
and MgSO4 (10 g). The mixture was stirred at room temper-
ature overnight and filtered through a pad of Celite. The
filtrate was concentrated, and distillation of the crude product
afforded 4n (3.11 g, 62%): Bp 110 °C (2 Torr); IR (neat) 1638,
1075, 1000, 924 cm-1; 1H NMR δ 0.85 (t, J ) 7 Hz, 6 H), 1.1-
1.5 (m, 18 H), 1.94-2.07 (m, 1 H), 3.94-4.04 and 4.50-4.58
(2m, 2 H (2:5)), 5.36 (d, J ) 18 Hz, 1 H), 6.37 (dd, J ) 18, 9
Hz, 1 H). Anal. Calcd for C15H29BO2: C, 71.44; H, 11.59.
Found: C, 71.37; H, 11.50.
Gen er a l P r oced u r e for th e Nick el-Ca ta lyzed Cou p lin g
Rea ction of Mon oa ceta te 1 a n d Lith iu m Bor a te 5. To an
ice-cold suspension of the boronate ester 4 (1.2-1.8 equiv),
NiCl2(PPh3)2 (10 mol %), and NaI (0.5-1 equiv) in THF was
added n-BuLi (1.2-1.8 equiv, ca. 2 M in hexane) dropwise.
The cooling bath was removed, and the mixture was stirred
for 15-30 min at room temperature. Then t-BuCN (2-5 equiv)
and monoacetate 1 (50-100 mg, 0.352-0.704 mmol) were
added. The resulting mixture was stirred at room temperature
for several hours or overnight and poured into saturated
NaHCO3 solution. The product was extracted with EtOAc or
Et2O several times and the combined extracts were dried
(MgSO4) and concentrated to give an oil, which was subjected
to chromatography on silica gel. The regioisomer 3 and the
major product 2 were eluted in this order.
(E)-2-(3′-[(ter t-Bu tyld im eth ylsilyl)oxy]-3′-cycloh exyl-1′-
p r op en yl)-4,5-d im eth yl-1,3,2-d ioxa bor ola n e (4k ). Accord-
ing to the above procedure, iodide 1951 (1.20 g, 3.15 mmol) was
converted into the corresponding boronic acid by using THF
(15 mL), n-BuLi (1.73 mL, 2.72 M in hexane, 4.71 mmol) (-78
°C, 30 min), and B(O-i-Pr)3 (1.09 mL, 4.72 mmol) (-78 °C to
room temperature, 4 h). The boronic acid thus prepared was
esterified with 2,3-butanediol (0.43 mL, 4.7 mmol) and MgSO4
(5 g) in benzene (50 mL) overnight to afford 4k (701 mg,
63%): Bp 150 °C (2 Torr); IR (neat) 1642, 1075, 838, 777 cm-1
;
1H NMR δ 0.00 (s, 3 H), 0.03 (s, 3 H), 0.92 (s, 9 H), 0.95-1.43
(m, 12 H), 1.60-1.80 (m, 5 H), 3.88-3.96 (m, 1 H), 3.98-4.08
and 4.51-4.63 (2m, 2 H (3:4)), 5.57 (dt, J ) 18, 4.5 Hz, 1 H),
6.58 (dm, J ) 18 Hz, 1 H). Anal. Calcd for C19H37BO3Si: C,
64.76; H, 10.58. Found: C, 64.77; H, 10.56.
(E)-2-(3′-[(ter t-Bu tyld im eth ylsilyl)oxy]-4′-p h en yloxy-1′-
bu ten yl)-4,5-d im eth yl-1,3,2-d ioxa bor ola n e (4l). According
to the preparation of 4j, iodide 2051 (1.0 g, 2.47 mmol) was
converted into the corresponding boronic acid by using THF
(10 mL), n-BuLi (1.31 mL, 2.72 M, 3.56 mmol) (-78 °C, 30
min), and B(O-i-Pr)3 (0.72 mL, 3.1 mmol) (-78 °C to room
temperature, 3 h). The acid was esterified with 2,3-butanediol
(0.32 mL, 3.5 mmol) and MgSO4 (5 g) in benzene (50 mL) to
afford 4l (604 mg, 65%): Bp 240 °C (2 Torr); IR (neat) 1638,
1075, 838, 777 cm-1 1H NMR δ 0.09 (s, 6 H), 0.92 (s, 9 H),
;
1.23 and 1.36 (2d, J ) 7 and 7 Hz, 6 H (7:2)), 3.79-3.95 (m, 2
H), 4.01-4.08 and 4.50-4.64 (2m, 2 H (2:7), 5.88 (dm, J ) 18
Hz, 1 H), 6.72 (dd, J ) 18, 4 Hz, 1 H), 6.84-6.97 (m, 3 H),
7.23-7.32 (m, 2 H). Anal. Calcd for C20H33BO4Si: C, 63.82;
H, 8.84. Found: C, 63.73; H, 8.77.
(E)-2-(3′-[(ter t-Bu t yld im et h ylsilyl)oxy]-1′-p r op en yl)-
4,5-d im eth yl-1,3,2-d ioxa bor ola n e (4m ). To an ice-cold mix-
ture of BH3‚SMe2 (3.23 mL, 2 M in THF, 6.46 mmol) and DME
(10 mL) was added cyclohexene (1.31 mL, 12.9 mmol). After
15 min, the ice bath was removed, and the solution was stirred
at room temperature for 1.5 h to give a white precipitate of
(c-C6H11)2BH. The mixture was cooled to 0 °C and acetylene
21 (1.00 g, 5.87 mmol) was added. Stirring was continued for
3 h during which time the solid ((c-C6H11)2BH) disappeared.
To this solution was added a solution of anhydrous Me3N-O
in CHCl3 (11.8 mL, 1 M, 11.8 mmol). After an exothermic
reaction ceased, the solution was stirred at room temperature
for further 1 h and then 2,3-butanediol (0.53 mL, 5.85 mmol)
The yields and the regioselectivities of the products syn-
thesized by this procedure are listed in Table 2, while their
spectral and physical data are presented below.
(1S*,4S*)-4-P h en yl-2-cyclopen ten -1-ol (2a). Entry 1: The
1H NMR spectra of 2a and regioisomer 3a were identical with
those reported.14b
(1S*,4S*)-4-(2′-Meth ylp h en yl)-2-cyclop en ten -1-ol (2b).
Entry 2: IR (neat) 3336, 1489, 1025, 754 cm-1; 1H NMR δ 1.6
(br s, 1 H), 1.98 (ddd, J ) 14, 7, 6 Hz, 1 H), 2.32 (ddd, J ) 14,
8, 2.5 Hz, 1 H), 2.36 (s, 3 H), 4.36 (ddd, J ) 8, 6, 2 Hz, 1 H),
5.03 (d, J ) 7 Hz, 1 H), 6.07 (br s, 2 H), 6.97-7.18 (m, 4 H);
13C NMR δ 143.0, 138.8, 135.6, 134.1, 130.2, 126.20, 126.17,
125.5, 77.5, 46.1, 42.8, 19.8.
(50) Luo, F.-T.; Negishi, E. J . Org. Chem. 1985, 50, 4762-4766.
(51) Kobayashi, Y.; Shimazaki, T.; Taguchi, H.; Sato, F. J . Org.
Chem. 1990, 55, 5324-5335.
(52) Bhanu, S.; Khan, E. A.; Scheinmann, F. J . Chem. Soc., Perkin
Trans. 1 1976, 1609-1612.
J . Org. Chem, Vol. 67, No. 20, 2002 7119

Kobayashi et al.
Regioisomer 3b: IR (neat) 3369, 1052 cm-1; 1H NMR δ 1.8
(br s, 1 H), 2.35 (br d, J ) 17 Hz, 1 H), 2.45 (s, 3 H), 2.79 (ddq,
J ) 17, 7, 2.5 Hz, 1 H), 4.03 (br s, 1 H), 4.22-4.29 (m, 1 H),
5.78 (dq, J ) 6, 2 Hz, 1 H), 5.96 (dq, J ) 6, 2 Hz, 1 H), 6.97-
7.24 (m, 4 H); 13C NMR δ 140.1, 136.4, 132.1, 130.4, 129.7,
126.4, 126.13, 126.06, 80.0, 57.2, 41.7, 20.1.
(dq, J ) 6, 2 Hz, 1 H), 5.87 (dq, J ) 6, 2 Hz, 1 H), 6.01 (d, J
) 3 Hz, 1 H), 6.29 (dd, J ) 3, 2 Hz, 1 H), 7.34 (dd, J ) 2, 1 Hz,
1 H).
(1S*,4R*,1′E)-4-(1′-H ep t en yl)-2-cyclop en t en -1-ol (2h ).
1
Entry 8: IR (neat) 3336, 3055, 1024 cm-1; H NMR δ 0.90 (t,
J ) 7 Hz, 3 H), 1.1-1.5 (m, 7 H), 1.78-1.97 (m, 4 H), 3.47 (q,
J ) 7 Hz, 1 H), 4.85-4.91 (m, 1 H), 5.22 (dd, J ) 15, 8 Hz, 1
H), 5.44 (dt, J ) 15, 7 Hz, 1 H), 5.82 (br s, 2 H); 13C NMR δ
139.3, 133.1, 132.8, 130.2, 77.1, 47.0, 41.2, 32.2, 31.2, 29.0, 22.4,
13.9. Anal. Calcd for C12H20O: C, 79.94; H, 11.18. Found: C,
79.79; H, 11.24.
(1S*,4S*)-4-(3′-Meth ylp h en yl)-2-cyclop en ten -1-ol (2c).
Entry 3: IR (neat) 3350, 1606, 1111, 1030 cm-1 1H NMR δ
;
1.82 (br s, 1 H), 2.09 (ddd, J ) 14, 7, 6 Hz, 1 H), 2.27 (ddd, J
) 14, 8, 3 Hz, 1 H), 2.32 (s, 3 H), 4.07-4.14 (m, 1 H), 5.02-
5.07 (m, 1 H), 5.96-6.06 (m, 2 H), 6.91-7.22 (m, 4 H); 13C NMR
δ 144.8, 139.3, 138.2, 133.9, 128.5, 127.9, 127.1, 124.1, 77.4,
49.7, 43.9, 21.3. Anal. Calcd for C12H14O: C, 82.72; H, 8.10.
Found: C, 82.51; H, 8.07.
Regioisomer 3h : IR (neat) 3386, 1610, 1510 cm-1; 1H NMR
δ 0.87 (t, J ) 7 Hz, 3 H), 1.1-1.5 (m, 6 H), 1.70 (br d, J ) 5
Hz, 1 H), 1.97 (q, J ) 7.0 Hz, 2 H), 2.26 (br d, J ) 17 Hz, 1 H),
2.68 (ddq, J ) 17, 7, 2 Hz, 1 H), 3.09-3.18 (m, 1 H), 4.10-
4.18 (m, 1 H), 5.32 (dd, J ) 15, 8 Hz, 1 H), 5.49 (dt, J ) 15, 7
Hz, 1 H), 5.61 (dq, J ) 6, 2 Hz, 1 H), 5.70 (dq, J ) 6, 2 Hz, 1
H).
(1S*,4R*,1′Z)-4-(1′-Hepten yl)-2-cyclopen ten -1-ol (2i). En-
try 9: IR (neat) 3367, 1595, 1232 cm-1; 1H NMR δ 0.91 (t, J )
7 H, 3 H), 1.2-1.5 (m, 6 H), 1.6 (br s, 1 H), 1.85 (ddd, J ) 14,
7, 5 Hz, 1 H), 2.01 (ddd, J ) 14, 8, 2.5 Hz, 1 H), 2.08 (q, J )
7 Hz, 2 H), 3.78-3.89 (m, 1 H), 4.86-4.94 (m, 1 H), 5.09 (tt, J
) 10, 1.5 Hz, 1 H), 5.38 (dt, J ) 10, 7 Hz, 1 H), 5.80 (dd, J )
5.5, 2 Hz, 1 H), 5.87 (dt, J ) 5.5, 2 Hz, 1 H); 13C NMR δ 140.0,
133.1, 132.5, 130.4, 77.2, 41.9, 41.4, 31.3, 29.3, 27.3, 22.4, 13.9.
Anal. Calcd for C12H20O: C, 79.94; H, 11.18. Found: C, 79.81;
H, 10.97.
Regioisomer 3i: IR (neat) 3390, 1594 cm-1; 1H NMR δ 0.90
(t, J ) 7 Hz, 3 H), 1.2-1.5 (m, 6 H), 1.7 (br s, 1 H), 2.14 (q, J
) 7 Hz, 2 H), 2.30 (br d, J ) 17 Hz, 1 H), 2.72 (ddq, J ) 17, 7,
2 Hz, 1 H), 3.44-3.55 (m, 1 H), 4.11-4.19 (m, 1 H), 5.11 (t, J
) 11 Hz, 1 H), 5.47 (dt, J ) 11, 7 Hz, 1 H), 5.55 (dq, J ) 6, 2
Hz, 1 H), 5.72 (dq, J ) 6, 2 Hz, 1 H).
(1S*,4S*,1′E)-4-[{3′-(ter t-Bu tyld im eth ylsilyl)oxy}-1′-oc-
ten yl]-2-cyclop en ten -1-ol (2j). Entry 10: The IR and 1H
NMR spectra of 2j and the regioisomer 3j were identical with
those reported.27a The 13C NMR spectrum of the optically active
2j (i.e. 24 and 26) are presented below. Anal. Calcd for
Regioisomer 3c: IR (neat) 3344, 1606, 1051 cm-1; 1H NMR
δ 1.96 (br s, 1 H), 2.33 (s, 3 H), 2.37 (br d, J ) 17 Hz, 1 H),
2.80 (ddq, J ) 17, 7, 2 Hz, 1 H), 3.72 (m, 1 H), 4.22-4.36 (m,
1 H), 5.76 (dq, J ) 6, 2 Hz, 1 H), 5.89 (dq, J ) 6, 2 Hz, 1 H),
6.92-7.26 (m, 4 H); 13C NMR δ 142.6, 138.3, 132.4, 129.4,
128.6, 128.2, 127.4, 124.4, 81.0, 60.6, 41.2, 21.3.
(1S*,4S*)-4-(4′-Meth ylp h en yl)-2-cyclop en ten -1-ol (2d ).
Entry 4: IR (neat) 3338, 1041, 889 cm-1; 1H NMR δ 1.96-2.17
(br peak, 1 H), 2.11 (ddd, J ) 14, 7, 5 Hz, 1 H), 2.29 (ddd, J )
14, 8, 3 Hz, 1 H), 2.32 (s, 3 H), 4.08-4.14 (m, 1 H), 5.02-5.08
(m, 1 H), 5.99-6.06 (m, 2 H), 7.03 (d, J ) 8 Hz, 2 H), 7.10 (d,
J ) 8 Hz, 2 H); 13C NMR δ 141.8, 139.3, 135.9, 133.8, 129.2,
126.9, 77.3, 49.4, 44.0, 20.8. Anal. Calcd for C12H14O: C, 82.72;
H, 8.10. Found: C, 82.54; H, 8.14.
1
Regioisomer 3d : IR (neat) 3350, 1513, 1052, 811 cm-1; H
NMR δ 1.84 (br s, 1 H), 2.36 (s, 3 H), 2.37 (br d, J ) 17 Hz, 1
H), 2.79 (ddq, J ) 17, 6, 2 Hz, 1 H), 3.71-3.76 (m, 1 H), 4.21-
4.31 (m, 1 H), 5.77 (dq, J ) 6, 2 Hz, 1 H), 5.89 (dq, J ) 6, 2
Hz, 1 H), 7.05-7.16 (m, 4 H).
(1S*,4S*)-4-(3′-Meth oxyp h en yl)-2-cyclop en ten -1-ol (2e).
1
Entry 5: IR (neat) 3383, 1601, 1047 cm-1; H NMR δ 1.92 (br
s, 1 H), 2.10 (ddd, J ) 14, 7, 5 Hz, 1 H), 2.27 (ddd, J ) 14, 8,
3 Hz, 1 H), 3.79 (s, 3 H), 4.08-4.16 (m, 1 H), 5.01-5.08 (m, 1
H), 6.04 (br s, 2 H), 6.66-6.79 (m, 3 H), 7.21 (t, J ) 8 Hz, 1
H); 13C NMR δ 159.9, 146.6, 139.0, 134.2, 129.6, 119.5, 112.9,
111.5, 77.4, 55.1, 49.8, 43.9. Anal. Calcd for C12H14O2: C, 75.76;
H, 7.42. Found: C, 75.41; H, 7.12.
C
19H36O2Si: C, 70.31; H, 11.18. Found: C, 70.30; H, 11.28.
(1S*,4S*,1′E)-4-[{3′-(ter t-Bu tyld im eth ylsilyl)oxy}-3′-cy-
cloh exyl-1′-p r op en yl]-2-cyclop en ten -1-ol (2k ). Entry 11:
IR (neat) 3421, 835, 775 cm-1; 1H NMR δ -0.03 (s, 3 H), 0.003
(s, 3 H), 0.87 (s, 9 H), 1.05-1.88 (m, 12 H), 1.88-2.04 (m, 2
H), 3.46-3.56 (m, 1 H), 3.69 (dt, J ) 2, 7 Hz, 1 H), 4.84-4.94
(m, 1 H), 5.31 (dd, J ) 15, 7 Hz, 1 H), 5.38 (dd, J ) 15, 7 Hz,
1 H), 5.83-5.89 (m, 2 H); 13C NMR δ 138.8, 138.6, 133.60,
133.56, 133.51, 132.1, 78.1, 77.18, 77.15, 46.7, 44.4, 41.0, 40.9,
29.0, 28.6, 28.5, 26.6, 26.17, 26.12, 25.8, 18.1, -4.1, -4.9. Anal.
Calcd for C20H36O2Si: C, 71.37; H, 10.78. Found: C, 71.40; H,
10.55.
Regioisomer 3k : IR (neat) 3367, 1595, 1252 cm-1; 1H NMR
δ -0.035, -0.021, 0.003 and 0.011 (4s, 6 H), 0.865 and 0.874
(2s, 9 H), 1.0-1.9 (m, 12 H), 2.27 (d, J ) 17 Hz, 1 H), 2.69
(dm, J ) 17 Hz, 1 H), 3.14-3.20 (m, 1 H), 3.70-3.75 (m, 1 H),
4.11-4.18 (m, 1 H), 5.34-5.49 (m, 2 H), 5.59-5.65 (m, 1 H),
5.72-5.77 (m, 1 H).
Regioisomer 3e: IR (neat) 3390, 3055, 1601, 1583, 1049
1
cm-1; H NMR δ 1.98 (br s, 1 H), 2.36 (dm, J ) 17 Hz, 1 H),
2.80 (ddq, J ) 17, 7, 2 Hz, 1 H), 3.71-3.76 (m, 1 H), 3.80 (s, 3
H), 4.21-4.33 (m, 1 H), 5.77 (dq, J ) 6, 2 Hz, 1 H), 5.89 (dq,
J ) 6, 2 Hz, 1 H), 6.71-6.82 (m, 3 H), 7.23 (t, J ) 8 Hz, 1 H).
(1S*,4S*)-4-(4′-Meth oxyp h en yl)-2-cyclop en ten -1-ol (2f).
Entry 6: IR (neat) 3365, 1610, 1511, 1248 cm-1 1H NMR δ
;
1.95 (br peak, 1 H), 2.06 (ddd, J ) 14, 7, 5 Hz, 1 H), 2.26 (ddd,
J ) 14, 8, 3 Hz, 1 H), 3.80 (s, 3 H), 4.08-4.17 (m, 1 H), 5.04
(d, J ) 7 Hz, 1 H), 6.02 (s, 2 H), 6.82 (d, J ) 8 Hz, 2 H), 7.02
(d, J ) 8 Hz, 2 H); 13C NMR δ 158.2, 139.4, 136.9, 133.7, 128.0,
113.9, 77.3, 55.2, 49.0, 44.1. Anal. Calcd for C12H14O2: C, 75.76;
H, 7.42. Found: C, 75.53; H, 7.63.
Regioisomer 3f: IR (neat) 3404, 1510, 1248 cm-1; 1H NMR
δ 1.84 (br peak, 1 H), 2.26-2.40 (m, 1 H), 2.72-2.82 (m, 1 H),
3.68-3.75 (m, 1 H), 3.80 (s, 3 H), 4.22 (dt, J ) 7, 4 Hz, 1 H),
5.75 (dq, J ) 6, 2 Hz, 1 H), 5.87 (dq, J ) 6, 2 Hz, 1 H), 6.82 (d,
J ) 8 Hz, 2 H), 7.10 (d, J ) 8 Hz, 2 H).
(1S*,4S*,1′E)-4-[{3′-(ter t-Bu tyldim eth ylsilyl)oxy}-4′-ph en -
yloxy-1′-bu ten yl]-2-cyclop en ten -1-ol (2l). Entry 12: IR
1
(neat) 3346, 1601, 1496, 1248 cm-1; H NMR δ 0.09 (s, 6 H),
(1S*,4S*)-4-(2′-F u r yl)-2-cyclop en ten -1-ol (2g). Entry 7:
IR (neat) 3410, 3055, 1601, 779, 696 cm-1; 1H NMR δ 1.57 (br
s, 1 H), 2.16 (ddd, J ) 14, 8, 3 Hz, 1 H), 2.32 (ddd, J ) 14, 7,
5 Hz, 1 H), 4.16-4.23 (m, 1 H), 4.99-5.06 (m, 1 H), 5.97-6.06
(m, 3 H), 6.28 (dd, J ) 3, 2 Hz, 1 H), 7.31 (dd, J ) 2, 1 Hz, 1
H); 13C NMR δ 157.5, 141.5, 136.0, 134.7, 110.3, 104.2, 77.1,
43.4, 40.3. Anal. Calcd for C9H10O2: C, 71.98; H, 6.71. Found:
C, 71.80; H, 6.68.
Regioisomer 3g: IR (neat) 3340, 1645, 1595, 837 cm-1; H
NMR δ 1.94 (br s, 1 H), 2.36 (dm, J ) 17 Hz, 1 H), 2.80 (dm,
J ) 17 Hz, 1 H), 3.82-3.88 (m, 1 H), 4.43-4.52 (m, 1 H), 5.75
0.90 (s, 9 H), 1.87-2.06 (m, 3 H), 3.56 (q, J ) 6 Hz, 1 H), 3.84
(d, J ) 6 Hz, 2 H), 4.46 (q, J ) 6 Hz, 1 H), 4.88-4.91 (m, 1 H),
5.55 (dd, J ) 15, 6 Hz, 1 H), 5.63 (ddd, J ) 15, 6, 2 Hz, 1 H),
5.83-5.91 (m, 2 H), 6.87-6.95 (m, 3 H), 7.24-7.31 (m, 2 H);
13C NMR δ 158.9, 138.23, 138.20, 134.95, 134.91, 133.8, 129.4,
129.06, 129.03, 120.6, 114.5, 76.90, 76.89, 72.2, 71.67, 71.63,
46.62, 46.59, 40.77, 40.74, 25.7, 18.2, -4.77, -4.83. Anal. Calcd
for C21H32O3Si: C, 69.95; H, 8.94. Found: C, 69.49; H, 8.84.
Regioisomer 3l: IR (neat) 3369, 1595 cm-1; 1H NMR δ 0.08
(s, 6 H), 0.89 (s, 9 H), 1.72 (br s, 1 H), 2.27, (d, J ) 17 Hz, 1
H), 2.69 (dd, J ) 17, 6 Hz, 1 H), 3.17-3.25 (m, 1 H), 3.84 (d,
1
7120 J . Org. Chem., Vol. 67, No. 20, 2002

Installation of Aryl and Alkenyl Groups
J ) 6 Hz, 2 H), 4.13-4.20 (m, 1 H), 4.48 (q, J ) 6 Hz, 1 H),
5.56-5.79 (m, 4 H), 6.84-6.97 (m, 3 H), 7.22-7.32 (m, 2 H).
Hz, 1 H), 5.72 (dq, J ) 6, 2 Hz, 1 H), 5.85 (dq, J ) 6, 2 Hz, 1
H), 7.15-7.35 (m, 5 H).
(1S*,4S*,1′E)-4-[{3′-(ter t-Bu tyldim eth ylsilyl)oxy}-1′-pr o-
p en yl]-2-cyclop en ten -1-ol (2m ). Entry 13: IR (neat) 3369,
1255, 837, 775 cm-1; 1H NMR δ 0.06 (s, 6 H), 0.89 (s, 9 H), 1.5
(br s, 1 H), 1.87-2.03 (m, 2 H), 3.49-3.59 (m, 1 H), 4.12 (d, J
) 4.5 Hz, 1 H), 4.84-4.93 (m, 1 H), 5.48 (dd, J ) 16, 7 Hz, 1
H), 5.56 (dt, J ) 16, 4.5 Hz, 1 H), 5.87 (br s, 2 H); 13C NMR δ
138.7, 133.6, 133.5, 128.9, 77.1, 63.7, 46.6, 40.9, 25.9, 18.3,
-5.3. Anal. Calcd for C14H26O2Si: C, 66.09; H, 10.30. Found:
C, 66.12; H, 10.30.
(1S,4S,1′E,3′S)-4-[{3′-(ter t-Bu t yld im et h ylsilyl)oxy}-1′-
octen yl]-2-cyclop en ten -1-ol (24). The TBS ether (S)-18 was
prepared from (S,E)-1-iodo-1-octen-3-ol26 (>99% ee) and then
converted into the boronate ester (S)-4j according to the
procedure described for preparation of racemic 4j. According
to the procedure for the coupling reaction, reaction of (1R,3S)-1
(95% ee, 200 mg, 1.41 mmol) and (S)-4j (575 mg, 1.69 mmol)
with NiCl2(PPh3)2 (92 mg, 0.141 mmol), NaI (212 mg, 1.41
mmol), THF (6 mL), n-BuLi (0.85 mL, 2.5 M in hexane, 2.13
mmol), and t-BuCN (0.78 mL, 7.06 mmol) at room temperature
for 4 h gave a 19:1 mixture of 24 and the regioisomer 25 by
1H NMR spectroscopy. Chromatography of the mixture af-
forded 25 (19 mg, 4%) first and then 24 (360 mg, 79%). The
Regioisomer 3m : IR (neat) 3398, 837, 775 cm-1; 1H NMR δ
3.15-3.22 (m, 1 H), 5.57-5.66 (m, 3 H), 5.72-5.77 (m, 1 H).
(1S*,4R*,1′E)-4-(3′-Bu tyl-1′-h ep ten yl)-2-cyclop en ten -1-
1
ol (2n ). Entry 14: IR (neat) 3350, 3055, 1022 cm-1; H NMR
1
IR and H NMR spectra of 24 and 25 were superimposed with
δ 0.86 (t, J ) 7 Hz, 6 H), 1.1-1.4 (m, 12 H), 1.64 (br s, 1 H),
1.77-1.88 (m, 1 H), 1.90 (ddd, J ) 14, 7, 5 Hz, 1 H), 1.98 (ddd,
J ) 14, 8, 3 Hz, 1 H), 3.44-3.52 (m, 1 H), 4.86-4.92 (m, 1 H),
5.07-5.21 (m, 2 H), 5.82-5.88 (m, 2 H); 13C NMR δ 139.4,
134.8, 133.0, 132.5, 77.1, 47.1, 42.5, 41.3, 34.98, 34.92, 29.3,
22.64, 22.62, 13.9. Anal. Calcd for C16H28O: C, 81.29; H, 11.94.
Found: C, 81.10; H, 11.73.
Regioisomer 3n : IR (neat) 3365, 3057 cm-1; 1H NMR δ 0.87
(t, J ) 7 Hz, 6 H), 1.1-1.4 (m, 12 H), 1.62-1.92 (m, 2 H), 2.25
(dm, J ) 17 Hz, 1 H), 2.68 (ddq, J ) 17, 6, 3 Hz, 1 H), 3.09-
3.16 (m, 1 H), 4.13 (dt, J ) 6, 3 Hz, 1 H), 5.18 (dd, J ) 15, 8
Hz, 1 H), 5.24 (dd, J ) 15, 7 Hz, 1 H), 5.62 (dq, J ) 6, 2 Hz,
1 H), 5.72 (dq, J ) 6, 2 Hz, 1 H).
those of the diastereomeric mixtures 2j and 3j, respectively,
which were synthesized from the racemic partners 1 and 4j.
Additional data of 24: [R]20D ) -153 (c 0.98, CHCl3); 13C NMR
δ 138.7, 133.53, 133.46, 132.5, 77.1, 73.4, 46.6, 40.9, 38.2, 31.6,
25.8, 24.9, 22.5, 18.1, 13.9, -4.3, -4.9.
(1R,4R,1′E,3′S)-4-[{3′-(ter t-Bu tyld im eth ylsilyl)oxy}-1′-
octen yl]-2-cyclop en ten -1-ol (26). According to the procedure
for the coupling reaction, (1S,3R)-1 (> 95% ee, 50 mg, 0.352
mmol), NiCl2(PPh3)2 (23 mg, 0.035 mmol), NaI (53 mg, 0.353
mmol), (S)-4j (143 mg, 0.420 mmol), n-BuLi (0.21 mL, 2.5 M
in hexane, 0.53 mmol), t-BuCN (0.19 mL, 1.76 mmol), and THF
(2 mL) at room temperature for 3 h afforded the regioisomer
27 (4 mg, 3.6%) and the desired product 26 (87 mg, 76%) after
(1S *,4S *)-1-Me t h oxym e t h oxy-4-p h e n yl-2-cyclop e n -
ten e (MOM Eth er of 2a ). Entry 15: IR (neat) 3060, 3026,
1
chromatography (26: 27 ) 21:1). The IR and H NMR spectra
of 26 and 27 were superimposed with those of the diastereo-
meric mixtures 2j and 3j, respectively. Additional data of 26:
1
1043 cm-1; H NMR δ 2.05 (ddd, J ) 14, 7, 5 Hz, 1 H), 2.38
(ddd, J ) 14, 8, 3 Hz, 1 H), 3.39 (s, 3 H), 4.08-4.16 (m, 1 H),
4.70 (d, J ) 7 Hz, 1 H), 4.72 (d, J ) 7 Hz, 1 H), 4.88-4.94 (m,
1 H), 6.03-6.10 (m, 2 H), 7.11-7.33 (m, 5 H); 13C NMR δ 145.0,
139.8, 132.3, 128.7, 127.2, 126.5, 95.8, 82.9, 55.3, 49.9, 41.3.
Anal. Calcd for C13H16O2: C, 76.44; H, 7.89. Found: C, 76.43;
H, 7.89.
[R]21 ) +152 (c 0.728, CHCl3); 13C NMR δ 138.7, 133.53,
D
133.51, 132.5, 77.2, 73.5, 46.6, 41.0, 38.2, 31.7, 25.8, 24.9, 22.5,
18.1, 13.9, -4.3, -4.9.
Ca r boxylic Acid 36. A solution of 24 (300 mg, 0.926 mmol),
MeC(OEt)3 (1.16 mL, 6.33 mmol), and phenol (17 mg, 0.18
mmol) in xylene (7 mL) was stirred at 140 °C for 2 h and
diluted with EtOAc. The resulting solution was washed with
1 N NaOH, dried (MgSO4), and concentrated. The residual oil
was purified by chromatography to furnish the ethyl ester of
Regioisomer (MOM ether of 3a ): IR (neat) 3059, 3028, 1045
cm-1; 1H NMR δ 2.43 (dm, J ) 17 Hz, 1 H), 2.79 (ddq, J ) 17,
7, 2 Hz, 1 H), 3.30 (s, 3 H), 3.88-3.93 (m, 1 H), 4.21 (dt, J )
7, 4 Hz, 1 H), 4.65 (s, 2 H), 5.74 (dq, J ) 6, 2 Hz, 1 H), 5.90
(dq, J ) 6, 2 Hz, 1 H), 7.18-7.38 (m, 5 H).
36 (292 mg, 80%): IR (neat) 3053, 1738, 835, 775 cm-1 1H
;
NMR δ -0.003 (s, 3 H), 0.02 (s, 3 H), 0.87 (s, 12 H), 1.1-1.6
(m, 11 H), 2.10-2.22 (m, 2 H), 2.30-2.58 (m, 3 H), 2.76-2.82
(m, 1 H), 4.01 (q, J ) 6 Hz, 1 H), 4.13 (q, J ) 7 Hz, 2 H), 5.39
(dd, J ) 16, 7 Hz, 1 H), 5.56 (dd, J ) 16, 6 Hz, 1 H), 5.64-5.75
(m, 2 H); 13C NMR δ 172.9, 134.0, 133.2, 132.8, 130.3, 73.6,
60.1, 48.1, 47.9, 38.7, 38.3, 31.7, 25.8, 25.0, 22.5, 18.1, 14.1,
13.9, -4.3, -4.9.
(1S*,4R*,1′E)-4-(1′-Hep ten yl)-1-m eth oxym eth oxy-2-cy-
clop en ten e (MOM Eth er of 2h ). Entry 16: IR (neat) 3053,
1043 cm-1; 1H NMR δ 0.88 (t, J ) 7 H, 1 H), 1.2-1.4 (m, 6 H),
1.84 (ddd, J ) 14, 7, 5 Hz, 1 H), 1.97 (q, J ) 7 Hz, 1 H), 2.08
(ddd, J ) 14, 8, 3 Hz, 1 H), 3.37 (s, 3 H), 3.40-3.51 (m, 1 H),
4.67 (d, J ) 7 Hz, 1 H), 4.69 (d, J ) 7 Hz, 1 H), 4.73-4.79 (m,
1 H), 5.24 (dd, J ) 15, 8 Hz, 1 H), 5.44 (dt, J ) 15, 7 Hz, 1 H),
5.84-5.92 (m, 2 H); 13C NMR δ 139.9, 132.9, 131.2, 130.3, 95.7,
82.6, 55.2, 47.1, 38.4, 32.3, 31.3, 29.1, 22.4, 14.0. Anal. Calcd
for C14H24O2: C, 74.95; H, 10.78. Found: C, 74.71; H, 10.49.
A mixture of the above ester (250 mg, 0.634 mmol) and 1 N
LiOH (3.2 mL, 3.2 mmol) in MeOH (5 mL) was stirred at 40
°C overnight and poured into the phosphate buffer (pH 3.6),
which had been prepared by mixing Na2HPO4‚12H2O (2.31 g)
and citric acid (1.31 g) in H2O (98.6 g). Ethyl acetate was added
to it and the resulting mixture was stirred for 30 min
vigorously. The organic layer was separated and the aqueous
layer was extracted with EtOAc. The combined extracts were
dried (MgSO4) and concentrated to give an oil, which was
purified by chromatography to furnish acid 36 (170 mg, 73%):
Regioisomer (MOM ether of 3h ): IR (neat) 3057, 1047 cm-1
;
1H NMR δ 0.88 (t, J ) 7 H, 1 H), 1.2-1.5 (m, 6 H), 1.99 (q, J
) 7 Hz, 1 H), 2.33 (dm, J ) 17 Hz, 1 H), 2.67 (ddq, J ) 17, 7,
2 Hz, 1 H), 3.22-3.32 (m, 1 H), 3.37 (s, 1 H), 4.08 (dt, J ) 7,
4 Hz, 1 H), 4.66 (d, J ) 7 Hz, 1 H), 4.69 (d, J ) 7 Hz, 1 H),
5.37 (dd, J ) 15, 8 Hz, 1 H), 5.50 (dt, J ) 15, 7 Hz, 1 H), 5.59
(dq, J ) 6, 2 Hz, 1 H), 5.70 (dq, J ) 6, 2 Hz, 1 H).
[R]20 ) +33 (c 0.94, CHCl3); IR (neat) 3404, 1709, 835, 775
D
cm-1
;
1H NMR δ 0.01 (s, 3 H), 0.03 (s, 3 H), 0.88 (s, 12 H),
(1S*,4S*)-1-[(ter t-Bu tyld im eth ylsilyl)oxy]-4-p h en yl-2-
cyclop en ten e (TBS Eth er of 2a ). Entry 17: IR (neat) 3060,
1.2-1.6 (m, 8 H), 2.13-2.30 (m, 2 H), 2.31-2.60 (m, 3 H),
2.76-2.85 (m, 1 H), 4.01 (q, J ) 7 Hz, 1 H), 5.42 (dd, J ) 15,
7 Hz, 1 H), 5.56 (dd, J ) 15, 8 Hz, 1 H), 5.65-5.77 (m, 2 H),
10.5 (br peak, 1 H); 13C NMR δ 179.5, 134.3, 132.9, 132.5,
130.7, 73.6, 48.0, 47.7, 38.7, 38.5, 38.3, 31.7, 25.8, 25.0, 22.5,
18.2, 13.9, -4.3, -4.9. Anal. Calcd for C21H38O3Si: C, 68.80;
H, 10.45. Found: C, 68.63; H, 10.39.
Iod ola cton e 37. An ice-cold mixture of acid 36 (150 mg,
0.409 mmol) and NaHCO3 (0.5 mL) in Et2O (4 mL) and THF
(4 mL) was stirred for 20 min, and then iodine (125 mg, 0.493
mmol) was added to it. The resulting dark brown mixture was
1
3028, 1603, 1053 cm-1; H NMR δ 0.16 (s, 6 H), 0.98 (s, 9 H),
2.12 (ddd, J ) 14, 7, 5 Hz, 1 H), 2.30 (ddd, J ) 14, 8, 3 Hz, 1
H), 4.15-4.23 (m, 1 H), 5.09-5.19 (m, 1 H), 5.97 (dt, J ) 6, 2
Hz, 1 H), 6.03 (dd, J ) 6, 2 Hz, 1 H), 7.11-7.39 (m, 5 H); 13C
NMR δ 145.4, 137.5, 134.6, 128.5, 127.1, 126.2, 77.8, 50.0, 44.1,
25.9, 18.2, -4.7. Anal. Calcd for C17H26OSi: C, 74.39; H, 9.55.
Found: C, 74.52; H, 9.19.
Regioisomer (TBS ether of 3a ): IR (neat) 3059, 3028, 1254
cm-1; 1H NMR δ -0.12 (s, 6 H), 0.84 (s, 9 H), 2.30-2.41 (m, 1
H), 2.64-2.76 (m, 1 H), 3.69-3.78 (m, 1 H), 4.21 (dt, J ) 7, 5
J . Org. Chem, Vol. 67, No. 20, 2002 7121

Kobayashi et al.
stirred at room temperature for 24 h. Aqueous Na2S2O3 was
added to the mixture and the product was extracted with Et2O
three times. The combined ethereal solutions were dried
(MgSO4) and concentrated. The residue was purified by
temperature for 1 h. 40: IR (neat) 3028, 1712 cm-1; 1H NMR
δ 2.32 (dd, J ) 19, 2.5 Hz, 1 H), 2.88 (dd, J ) 19, 7 Hz, 1 H),
4.17 (dq, J ) 7, 2.5 Hz, 1 H), 6.32 (dd, J ) 6, 2 Hz, 1 H), 7.10-
7.38 (m, 5 H), 7.66 (dd, J ) 6, 2.5 Hz, 1 H); 13C NMR δ 210.1,
166.8, 141.5, 134.1, 129.1, 127.3, 127.2, 46.6. 43.9. Anal. Calcd
for C11H10O: C, 83.51; H, 6.37. Found: C, 83.85; H, 6.53.
chromatography to afford iodolactone 37 (167 mg, 83%): [R]20
D
1
) -14 (c 1.30, CHCl3); IR (neat) 1788, 1155 cm-1; H NMR δ
-0.01 (s, 3 H), 0.02 (s, 3 H), 0.87 (s, 12 H), 1.1-1.5 (m, 8 H),
2.01 (dt, J ) 13, 10 Hz, 1 H), 2.16-2.30 (m, 1 H), 2.37 (d, J )
16 Hz, 1 H), 2.54-2.76 (m, 3 H), 3.98-4.07 (m, 1 H), 4.13 (ddd,
J ) 10, 7, 3 Hz, 1 H), 5.13 (q, J ) 3.5 Hz, 1 H), 5.43-5.55 (m,
2 H); 13C NMR δ 175.5, 136.2, 128.3, 94.0, 72.7, 49.1, 45.7,
44.7, 38.1, 33.5, 31.6, 25.8, 24.8, 22.5, 21.4, 18.1, 13.9, -4.4,
-4.9.
Gen er a l P r oced u r e for th e Ald ol Rea ction : Rea ction
betw een 39 (R1 ) -CHdCHC5H11) a n d Dih yd r ocin n a m a -
ld eh yd e (42a ) (R2 ) -(CH2)2P h ). To an ice-cold solution of
i-Pr2NH (0.079 mL, 0.56 mmol) in THF (4 mL) was added
n-BuLi (0.17 mL, 2.47 M in hexane, 0.42 mmol) dropwise. The
solution was stirred at 0 °C for 15 min and cooled to -78 °C.
To this solution was added enone 39 (50 mg, 0.28 mmol)
dissolved in THF (1 mL). The solution was stirred further 30
min at -78 °C and then aldehyde 42a (0.050 mL, 0.38 mmol)
was added dropwise. After 30 min at -78 °C, the solution was
poured into an ice-cold mixture of Et2O and saturated NH4Cl
with vigorous stirring. The ethereal solution was separated
and the aqueous layer was extracted with Et2O twice. The
combined extracts were dried (MgSO4) and concentrated to
give a stereoisomeric mixture of the aldols, which was sepa-
rated by chromatography (hexane/EtOAc) to afford anti aldol
43a (49 mg, 57%) and syn aldol 46a (25 mg, 28%). Anti aldol
43a : IR (neat) 3855, 3469, 1689, 972 cm-1; 1H NMR δ 0.87 (t,
J ) 7 Hz, 3 H), 1.14-2.41 (m, 6 H), 1.75-2.10 (m, 4 H), 2.17
(dd, J ) 8.7, 2.7 Hz, 1 H), 2.61-2.94 (m, 2 H), 3.16 (dq, J ) 8,
2.5 Hz, 1 H), 3.68-3.80 (m, 1 H), 4.25 (br s, 1 H), 5.35 (ddt, J
) 15, 8, 2 Hz, 1 H), 5.59 (dt, J ) 15, 6 Hz, 1 H), 6.16 (dd, J )
6, 2 Hz, 1 H), 7.10-7.34 (m, 5 H), 7.51 (dd, J ) 6, 2.5 Hz, 1
H); 13C NMR δ 213.2, 167.8, 142.2, 134.0, 132.8, 128.74, 128.68,
128.5, 125.9, 71.4, 56.3, 48.1, 37.2, 32.4, 31.3, 31.1, 28.8, 22.4,
14.0. Anal. Calcd for C21H28O2: C, 80.73; H, 9.03. Found: C,
80.44; H, 9.32. The Ha signal for syn isomer 46a : δ 2.24 (t, J
) 3 Hz).
In ter m ed ia te of 11-Deoxy-P GE2 (13). A solution of 37
(150 mg, 0.305 mmol), Bu3SnH (265 mg, 0.911 mmol), and a
catalytic amount of AIBN in benzene (10 mL) was stirred at
80 °C for 1 h and concentrated to give an oil, which was diluted
with Et2O and saturated aqueous NaF. The resulting mixture
was stirred vigorously at room temperature, the layers were
separated, and the aqueous layer was extracted with Et2O.
The combined extracts were dried (MgSO4) and concentrated
to give an oil, which was purified by chromatography to furnish
lactone 13 (91 mg, 81%): [R]21 ) +4.4 (c 0.95, CHCl3); IR
D
(neat) 1776, 835, 775 cm-1; 1H NMR δ -0.02 (s, 3 H), 0.01 (s,
3 H), 0.86 (s, 12 H), 1.18-1.54 (m, 8 H), 1.82-2.02 (m, 2 H),
2.10-2.30 (m, 3 H), 2.33 (dd, J ) 18, 2 Hz, 1 H), 2.36-2.47
(m, 1 H), 2.70 (dd, J ) 18, 9 Hz, 1 H), 3.96-4.05 (m, 1 H),
4.94 (dt, J ) 3, 7 Hz, 1 H), 5.36-5.50 (m, 2 H); 13C NMR δ
177.2, 134.8, 130.3, 85.8, 73.1, 48.5, 45.2, 38.2, 33.9, 31.8, 31.6,
31.5, 25.7, 24.9, 22.5, 18.1, 13.8, -4.4, -4.9. The above IR and
1H NMR spectra were identical with those reported previ-
ously.34
In ter m ed ia te of P GA2 (14). A mixture of 37 (150 mg, 0.305
mmol) and AgOAc (76 mg, 0.455 mmol) in DMSO (10 mL) was
stirred at 140 °C for 1 h and poured into brine with Et2O. The
product was extracted with Et2O three times. The combined
ethereal solutions were dried (MgSO4) and concentrated to
leave an oil, which was purified by chromatography to afford
(4S,1′E,3′S)-4-[3′-{ter t-Bu tyld im eth ylsilyl}oxy]-1′-octe-
n yl]-2-cyclop en ten -1-on e (49). A mixture of alcohol 26 (234
mg, 0.721 mmol), Celite (233 mg), and PCC (233 mg, 1.08
mmol) in CH2Cl2 (4 mL) was stirred vigorously at room
temperature for 1 h, and diluted with hexane. The resulting
mixture was filtered through a pad of Celite with hexane and
Et2O. The filtrate was washed with water and the aqueous
layer was extracted with hexane twice. The combined organic
solutions were dried (MgSO4) and concentrated to give an oil,
which was purified by chromatography (hexane/EtOAc) to
afford enone 49 (211 mg, 91%): [R]22D ) +143 (c 0.66, CHCl3);
14 (91 mg, 82%): [R]21D ) +159 (c 0.85, CHCl3); lit.35b [R]22
)
D
+161.5 (c 2.8, CHCl3): IR (neat) 1780, 835, 775 cm-1; 1H NMR
δ -0.01 (s, 3 H), 0.02 (s, 3 H), 0.87 (s, 12 H), 1.15-1.55 (m, 8
H), 2.36-2.43 (m, 1 H), 2.70-2.88 (m, 2 H), 3.18-3.22 (m, 1
H), 3.98-4.06 (m, 1 H), 5.43 (m, 2 H), 5.51 (dt, J ) 7, 2 Hz, 1
H), 5.91, (dt, J ) 6, 2 Hz, 1 H), 5.97 (dd, J ) 6, 2.5 Hz, 1 H);
13C NMR δ 176.9, 140.3, 135.0, 130.0, 129.2, 89.0, 73.0, 55.1,
42.8, 38.1, 34.9, 31.6, 25.7, 24.7, 22.5, 18.1, 13.9, -4.4, -4.9.
The above IR and 1H NMR spectra were identical with those
reported previously.35a Anal. Calcd for C21H36O3Si: C, 69.18;
H, 9.95. Found: C, 69.23; H, 9.88.
1
IR (neat) 1718, 1254, 835, 775 cm-1; H NMR δ -0.001 (s, 3
H), 0.026 (s, 3 H), 0.87 (br s, 12 H), 1.19-1.58 (m, 8 H), 2.10
(dd, J ) 19, 2 Hz, 1 H), 2.64 (dd, J ) 19, 7 Hz, 1 H), 3.52-3.61
(m, 1 H), 4.05 (q, J ) 6 Hz, 1 H), 5.44 (dd, J ) 16, 7 Hz, 1 H),
5.55 (dd, J ) 16, 6 Hz, 1 H), 6.18 (dd, J ) 6, 2 Hz, 1 H), 7.53
(dd, J ) 6, 3 Hz, 1 H); 13C NMR δ 209.8, 166.8, 135.9, 134.1,
129.1, 73.0, 43.7, 41.3, 38.2, 31.8, 25.9, 24.9, 22.6, 18.2, 14.0,
-4.3, -4.8. Anal. Calcd for C19H34O2Si: C, 70.75; H, 10.62.
Found: C, 70.47; H, 10.87.
(E)-4-(1′-Hep ten yl)-2-cyclop en ten -1-on e (39). To a mix-
ture of racemic alcohol 2h (936 mg, 5.19 mmol) and Celite (1.7
g) in CH2Cl2 (26 mL) was added PCC (1.68 g, 7.75 mmol) in
portions. The mixture was stirred vigorously at room temper-
ature for 1 h, and diluted with hexane. The resulting mixture
was filtered through a pad of Celite with hexane. The filtrate
was washed with water and the aqueous layer was extracted
with hexane twice. The combined organic solutions were dried
(MgSO4) and concentrated to give an oil, which was purified
by chromatography (hexane/EtOAc) to afford enone 39 (660
mg, 71%): Bp 90 °C (1 Torr); IR (neat) 1716, 1180, 970, 785
Ald ol Rea ction betw een En on e 49 a n d Ald eh yd e 50.
A solution of LDA in THF was prepared from i-Pr2NH (0.054
mL, 0.38 mmol), n-BuLi (0.14 mL, 2.26 M in hexane, 0.32
mmol), and THF (7.4 mL) as usual, and enone 49 (95.0 mg,
0.295 mmol) dissolved in THF (2 mL) was added to it at -78
°C. The solution was stirred for 10 min at -78 °C and then
aldehyde 50 (56 mg, 0.37 mmol) was injected. After 20 min at
-78 °C, the solution was poured into an ice-cold mixture of
Et2O and saturated NH4Cl with vigorous stirring. The organic
layer was separated and the aqueous layer was extracted with
Et2O twice. The combined extracts were dried (MgSO4) and
concentrated to afford an anti and syn aldol mixture, which
was separated by chromatography (hexane/EtOAc) to furnish
anti aldol 51 (103 mg, 73%) and syn aldol 52 (21 mg, 15%).
1
cm-1; H NMR δ 0.87 (t, J ) 7 Hz, 3 H), 1.18-1.42 (m, 6 H),
2.00 (q, J ) 7 Hz, 2 H), 2.11 (dd, J ) 19, 2.5 Hz, 1 H), 2.61
(dd, J ) 19, 7 Hz, 1 H), 3.49-3.57 (m, 1 H), 5.30 (ddt, J ) 15,
8, 1.5 Hz, 1 H), 5.55 (ddt, J ) 15, 1.5, 7 Hz, 1 H), 6.15 (dd, J
) 6, 2 Hz, 1 H), 7.52 (dd, J ) 6, 3 Hz, 1 H); 13C NMR δ 210.1,
167.5, 133.7, 132.9, 129.6, 44.2, 41.6, 32.4, 31.3, 28.9, 22.5, 14.0.
Anal. Calcd for C12H18O: C, 80.85; H, 10.18. Found: C, 80.68;
H, 10.32.
4-P h en yl-2-cyclop en ten -1-on e (40). According to the
above procedure, racemic alcohol 2a (161 mg, 1.00 mmol) was
transformed into enone 40 (103 mg, 65%) by using Celite (324
mg), PCC (324 mg, 1.50 mmol), and CH2Cl2 (5 mL) at room
Major aldol 51: [R]22 ) +117 (c 0.35, CHCl3); IR (neat)
D
3483, 1739, 1693, 836, 775 cm-1
;
1H NMR δ 0.007 (s, 3 H),
0.036 (s, 3 H), 0.88 (br s, 12 H), 1.2-1.7 (m, 16 H), 2.10 (dd, J
) 9, 3 Hz, 1 H), 2.30 (t, J ) 8 Hz, 2 H), 3.19-3.27 (m, 1 H),
7122 J . Org. Chem., Vol. 67, No. 20, 2002

Installation of Aryl and Alkenyl Groups
3.66 (s, 3 H), 3.68-3.76 (m, 1 H), 4.04-4.13 (m, 2 H, C(15)-H
and OH), 5.49 (dd, J ) 16, 8 Hz, 1 H), 5.60 (dd, J ) 16, 6 Hz,
1 H), 6.18 (dd, J ) 6, 2 Hz, 1 H), 7.52 (dd, J ) 6, 2 Hz, 1 H);
13C NMR δ 212.9, 174.4, 167.1, 136.8, 133.2, 128.2, 72.8, 72.1,
56.4, 51.5, 47.7, 38.2, 35.5, 34.0, 31.8, 29.1, 25.9, 24.87, 24.83,
22.6, 18.2, 14.0, -4.3, -4.8. Anal. Calcd for C27H48O5Si: C,
67.45; H, 10.06. Found: 67.52; H, 10.20.
137.0, 136.9, 134.9, 127.1, 73.0, 51.5, 46.8, 38.2, 33.9, 31.8, 28.9,
28.8, 28.2, 25.8, 24.8, 24.7, 22.6, 18.2, 14.0, -4.3, -4.8. Anal.
Calcd for C27H46O4Si: C, 70.08; H, 10.02. Found: C, 69.85; H,
9.97.
From alcohol 52 (syn aldol): According to the procedure
described above, alcohol 52 (20 mg, 0.042 mmol) was submitted
to mesylation with MsCl (0.024 mL, 0.31 mmol) and Et3N
(0.059 mL, 0.42 mmol) in CH2Cl2 (1 mL) at 0 °C for 1.5 h to
produce mesylate 54 (21 mg, 89%) and enone 55 (2 mg, 11%)
after chromatography. Mesylate 54: 1H NMR δ 0.88 (br s, 12
H), 1.1-1.7 (m, 16 H), 2.26-2.33 (m, 3 H), 2.86 (s, 3 H), 3.66
(s, 3 H), 3.65-3.75 (m, 1 H), 4.05-4.15 (m, 1 H), 5.06-5.14
(m, 1 H), 5.49 (ddd, J ) 15, 8, 1 Hz, 1 H), 5.66 (dd, J ) 15, 6
Hz, 1 H), 6.22 (dd, J ) 6, 2 Hz, 1 H), 7.56 (dd, J ) 6, 3 Hz, 1
H). Next, mesylate 54 (14 mg, 0.027 mmol) was transformed
to enone 55 (11 mg, 88%) with Al2O3 (50 mg X 2) in CH2Cl2 (1
mL) at room temperature for 2.5 h. The 1H NMR spectrum
and Rf value on TLC were identical with those of 55 obtained
from mesylate 53.
Minor aldol 52: IR (neat) 3462, 1739, 1712, 837, 775 cm-1
;
1H NMR δ 0.005 (s, 3 H), 0.033 (s, 3 H), 0.88 (br s, 12 H), 1.1-
1.7 (m, 16 H), 1.84-1.90 (m, 1 H), 2.17 (t, J ) 3 Hz, 1 H), 2.30
(t, J ) 8 Hz, 2 H), 3.66 (s, 3 H), 3.58-3.70 (m, 1 H), 4.07 (q, J
) 6 Hz, 1 H), 4.12-4.24 (m, 1 H), 5.50 (dd, J ) 15, 8 Hz, 1 H),
5.60 (dd, J ) 15, 6 Hz, 1 H), 6.18 (dd, J ) 6, 2 Hz, 1 H), 7.55
(dd, J ) 6, 3 Hz, 1 H); 13C NMR δ 211.0, 174.4, 167.6, 136.4,
133.7, 129.1, 73.0, 70.4, 57.6, 51.5, 44.9, 38.2, 34.8, 34.0, 31.8,
28.9, 25.87, 25.81, 24.88, 24.82, 22.6, 18.2, 14.0, -4.3, -4.8.
a n ti Mesyla te 53. To an ice-cold solution of alcohol 51 (46
mg, 0.096 mmol) and Et3N (0.13 mL, 0.96 mmol) in CH2Cl2 (1
mL) was added MsCl (0.055 mL, 0.71 mmol). After 40 min at
the same temperature, the solution was poured into EtOAc
and saturated NaHCO3. The product was extracted with
EtOAc several times. The combined extracts were dried
(MgSO4) and concentrated. The residue was purified by
chromatography (hexane/EtOAc) to furnish mesylate 53 (47
mg, 85%): IR (neat) 1738, 1712, 1174, 837, 777 cm-1; 1H NMR
δ -0.005 (s, 3 H), 0.025 (s, 3 H), 0.87 (br s, 12 H), 1.2-1.9 (m,
16 H), 2.29 (t, J ) 8 Hz, 2 H), 2.58 (dd, J ) 4, 3 Hz, 1 H), 2.99
(s, 3 H), 3.58-3.63 (m, 1 H), 3.65 (s, 3 H), 4.08 (q, J ) 6 Hz,
1 H), 4.97-5.04 (m, 1 H), 5.50 (dd, J ) 15, 8 Hz, 1 H), 5.63
(dd, J ) 15, 6 Hz, 1 H), 6.15 (dd, J ) 6, 2 Hz, 1 H), 7.55 (dd,
J ) 6, 2 Hz, 1 H); 13C NMR δ 206.5, 174.2, 166.4, 137.0, 133.7,
127.8, 81.3, 72.8, 54.9, 51.5, 46.5, 38.6, 38.1, 33.8, 31.8, 31.0,
28.6, 25.9, 25.4, 24.8, 24.6, 22.6, 18.2, 14.0, -4.3, -4.8.
En on e 55 () 38). From anti mesylate 53: To a solution of
mesylate 53 (33 mg, 0.058 mmol) in CH2Cl2 (2 mL) was added
Al2O3 (50 mg). The mixture was stirred at room temperature
for 16 h, during which time additional Al2O3 (2 × 50 mg) was
added after 4 and 12 h. After the reaction, the mixture was
filtered through a pad of Celite with EtOAc. The filtrate was
concentrated and the residue was purified by chromatography
(hexane/EtOAc) to afford enone 55 (25 mg, 92%): [R]27D ) +156
(c 0.31, CHCl3); IR (neat) 1741, 1707, 1655, 837, 775 cm-1; 1H
NMR δ -0.006 (s, 3 H), 0.024 (s, 3 H), 0.87 (br s, 12 H), 1.1-
1.7 (m, 14 H), 2.21 (q, J ) 8 Hz, 2 H), 2.30 (t, J ) 8 Hz, 2 H),
3.66 (s, 3 H), 4.00 (d, J ) 8 Hz, 1 H), 4.06 (q, J ) 7 Hz, 1 H),
5.32 (ddd, J ) 16, 8, 1 Hz, 1 H), 5.64 (ddd, J ) 16, 7, 1 Hz, 1
H), 6.33 (dd, J ) 6, 2 Hz, 1 H), 6.60 (t, J ) 8 Hz, 1 H), 7.35
(ddd, J ) 6, 3, 1 Hz, 1 H); 13C NMR δ 196.8 174.2, 160.5, 137.2,
∆7-P GA1 Meth yl Ester (15). To a solution of enone 55 (25
mg, 0.054 mmol) in DMSO/H2O (19:1, 1 mL) was added NBS
(13 mg, 0.073 mmol). The solution was stirred at room-
temperature overnight and poured into a mixture of Et2O and
the phosphate buffer of pH 3.6. The mixture was extracted
with Et2O twice, and the combined extracts were dried
(MgSO4) and concentrated to leave an oil, which, upon
purification by chromatography (hexane/EtOAc), afforded 15
1
(15 mg, 80%). The H NMR (300 MHz) spectrum of synthetic
15 was identical with that (270 MHz) reported for the
enantiomer of 15.37c An additional data of 15: [R]26 ) +165
D
(c 0.13, CHCl3).
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research from the Ministry
of Education, Science, Sports, and Culture, J apan, and
the Kurata Foundation. S.B.U. is grateful to the Sasaka-
wa Scientific Research Grant. We thank Professor
Fumie Sato of Tokyo Institute of Technology for the
generous gift of (S,E)-1-iodo-1-octen-3-ol and Professor
M. Shibasaki for providing us an information about
supply of Al2O3.
Su p p or tin g In for m a tion Ava ila ble: Experimental data
for aldol reaction and 1H NMR spectra of compounds lacking
elemental analyses (2b, 37, 52, and 53). This material is
available free of charge via the Internet at http://pubs.acs.org.
J O020375Y
J . Org. Chem, Vol. 67, No. 20, 2002 7123