Plant bioregulators, 2. Syntheses of (±)- and (+)-sorgolactone, the germination stimulant from Sorghum bicolor

Article abstract of DOI:10.1002/(sici)1099-0690(199909)1999:9<2183::aid-ejoc2183>3.0.co;2-4

Syntheses of (±)-2a, the racemate of the structure proposed for sorgolactone, and its three racemic stereoisomers have been accomplished with confirmation of the stereostructures of the intermediate (±)-10 and the final product (±)-2a by X-ray analysis. Its optically active form, (3aR,8S,8bS,2'R)-(+)-2a, has also been prepared from (S)-(-)-citronellal by employing radical cyclization of 18 to 19 as the key step. Spectroscopic properties of the synthetic products are compared with those reported for natural sorgolactone. Bioassays using clover broomrape (Orobanche minor) seeds have revealed that all the stereoisomers strongly stimulate their germination.

Full text of DOI:10.1002/(sici)1099-0690(199909)1999:9<2183::aid-ejoc2183>3.0.co;2-4

FULL PAPER
Plant Bioregulators, 2[°]
Syntheses of (؎)- and (؉)-Sorgolactone, the Germination Stimulant from
Sorghum bicolor
Junichi Matsui,[a][°°] Masahiko Bando,[b] Masaru Kido,[b] Yasutomo Takeuchi,[c]
and Kenji Mori*[a]
Keywords: Ecology / Lactones / Phytochemistry / Radical reactions / Sorgolactone
Syntheses of (±)-2a, the racemate of the structure proposed
for sorgolactone, and its three racemic stereoisomers have
been accomplished with confirmation of the stereostructures
of the intermediate (±)-10 and the final product (±)-2a by X-
ray analysis. Its optically active form, (3aR,8S,8bS,2ЈR)-(+)-
2a, has also been prepared from (S)-(–)-citronellal by
employing radical cyclization of 18 to 19 as the key step.
Spectroscopic properties of the synthetic products are
compared with those reported for natural sorgolactone.
Bioassays using clover broomrape (Orobanche minor) seeds
have revealed that all the stereoisomers strongly stimulate
their germination.
Parasitic weeds of the genera Striga, commonly known deavor in this area is still remarkable[12][13] and a gram-scale
as “witchweed”, and Orobanche cause severe yield losses in preparation of (ϩ)-strigol reported in the accompanying
grains and legumes in Africa, Asia, and the U.S.A.[1][2] The paper[14] has heralded a new stage in research concerning
seeds of such weeds remain dormant in soil until exudates the problem of parasitic weeds.
from their host plants induce germination. (ϩ)-Strigol (1,
In 1992, Hauck et al. isolated a second strigolactone, na-
Scheme 1) was first isolated from cotton (a non-host plant) mely sorgolactone, from Sorghum bicolor, a genuine host
root exudates and was shown to be a strong stimulant for plant for Striga asiatica and Striga hermonthica, as the po-
the germination of such seeds.[3] It was later isolated from tent germination stimulant for the parasitic weeds.[5] They
1
the host plants of Striga, such as maize, proso millet, and proposed 2a as the structure of sorgolactone based on H-
sorghum.[4] To date, four stimulants have been isolated from NMR and MS analysis in combination with a comparison
the host plants of the parasitic weeds[5Ϫ7] and have been of its CD spectrum with that of (ϩ)-strigol.[5][15] The ex-
given the general name strigolactones.[8]
tremely limited amount of material (5 µg) available at the
time of isolation, coupled with the fact that the natural
sample is no longer available, prompted chemists to devise
a synthesis of sorgolactone. Two attempted syntheses of 2a
have been reported.[16][17] We recently reported the syn-
thesis and biological evaluation of (±)-2aϪ(±)-2d[18] and
the synthesis of (ϩ)-2a from (S)-(Ϫ)-citronellal[19] as pre-
liminary communications, while Zwanenburg and co-work-
ers synthesized (ϩ)-2a and ent-(Ϫ)-2b together with the
four racemates.[20] This paper gives full accounts of the syn-
thesis and bioassay of racemic and optically active 2aϪ2d,
as well as a detailed comparison of their spectroscopic data
with those published for natural sorgolactone.
Scheme 1. Structures of strigol and sorgolactone
Early syntheses of (±)- and (ϩ)-strigol by Sih[9] and of
(±)-strigol by Raphael[10] prompted much interest in the
chemistry of germination stimulants, which culminated in
the determination of the absolute configuration of naturally
occurring (ϩ)-strigol by X-ray analysis.[11] The synthetic en-
Synthesis of (±)-2a؊(±)-2d
[°] Part 1: G. Audran, K. Mori, Eur. J. Org. Chem. 1998, 57Ϫ62.
In order to check the validity of the proposed structure
2a, we first synthesized (±)-2a and its three racemic stereo-
isomers (±)-2b, (±)-2c and (±)-2d as outlined in Scheme 1.
Phenylselenenylation of 4,[21] prepared by alkylation of
methyl 2-oxo-1-cyclopentanecarboxylate (3) with methyl
bromoacetate, was followed by oxidative removal of the
phenylselenyl group with aqueous hydrogen peroxide to af-
ford α,β-unsaturated ketone 5. Following the procedure of
To˜ ke et al.,[22] employing ethyl 1-methoxycarbonyl-2-oxocy-
[a]
Department of Chemistry, Faculty of Science, Science Univer-
sity of Tokyo,
Kagurazaka 1Ϫ3, Shinjuku-ku, Tokyo 162Ϫ8601, Japan
Fax: (internat.) ϩ 81-3/3235-2214
[b]
Otsuka Pharmaceutical Co., Ltd.,
Kawauchi, Tokushima 771-0192, Japan
Weed Science Center, Utsunomiya University,
[c]
Mine-machi 350, Utsunomiya, Tochigi 321-8505, Japan
[°°] Research fellow on leave from Kanebo Co., Ltd. (1996Ϫ1998).
Present address: Cosmetics Laboratory, Kanebo Co., Ltd., Ko-
tobuki-cho 5-3-28, Odawara, Kanagawa 250-0002, Japan.
Eur. J. Org. Chem. 1999, 2183Ϫ2194
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1434Ϫ193X/99/0909Ϫ2183 $ 17.50ϩ.50/0
2183

J. Matsui, M. Bando, M. Kido, Y. Takeuchi, K. Mori
FULL PAPER
clopent-3-en-1-ylacetate, 5 was converted to a racemic and
diastereomeric mixture of dioxo acid 6. The sodium salt of
6 was reduced with sodium tetrahydroborate in the presence
of cerium(III) chloride[23] to give, after acidification, a ra-
cemic and diastereomeric mixture of the hydroxylactone 7.
Treatment of
7 with carbon tetrabromide and tri-
phenylphosphane yielded a racemic and diastereomeric
mixture of the unstable bromolactone 8, which was immedi-
ately reduced with zinc-copper couple (Zn/Cu ϭ 91:5,
Kanto Chemical Co.)[24] and acetic acid in THF to furnish
a crude reduction product, presumably a stereoisomeric
mixture of dienoic acids, cf. ref.[24] This was dissolved in
chloroform and stirred for 60 h at room temperature in or-
der to bring about lactone formation by 1,4-addition of the
carboxyl group to the diene system.[24] The product was
further purified by MPLC [Lobar LiChroprep Si 60
(40Ϫ63 µm)] to give an oily fast-moving diastereomer and
a crystalline slow-moving one. The latter (m.p. 43Ϫ46°C)
was submitted to X-ray analysis, which revealed its struc-
ture to be (±)-10, with a cis relationship between the 8-
methyl group and the lactone ring. Its computer-generated
perspective view is shown in Figure 1. The oily lactone must
therefore be (±)-9, which gives rise to (±)-2a. The 1H-NMR
spectrum of (±)-9 recorded in CDCl3 solution features a
1 H doublet at δ ϭ 5.47, which is in agreement with the
published data for sorgolactone (δ ϭ 5.5),[5] whereas (±)-10
gives a signal at δ ϭ 5.31.
Scheme 2. Synthesis of (±)-2aϪ(±)-2d; reagents: (a) BrCH2CO2Me,
The two stereoisomeric lactones (±)-9 and (±)-10 were
processed separately to give (±)-2a and its three stereoiso- EtOAc/THF (61%); (c) NaOH, NaBH4, CeCl3·7H2O, CH2Cl2/H2O
mers. Formylation of (±)-9 with ethyl formate and sodium
K2CO3, acetone (98%); (b) 1. PhSeCl, HCl, EtOAc; 2. H2O2,
(67%); (d) CBr4, Ph3P, CH2Cl2 (87%); (e) 1. Zn/Cu, AcOH, THF;
2. CHCl3, stirring [40% as the mixture of (±)-9 and (±)-10]; 3.
hydride gave (±)-11 (a tautomeric mixture of the aldehyde
and the enol; m.p. 114Ϫ116°C). Treatment of (±)-11 with
(±)-4-bromo-2-methyl-2-buten-4-olide [(±)-13][10] in the
presence of potassium carbonate gave a mixture of (±)-2a
and (±)-2b, which could be separated by silica-gel chroma-
tography to give two crystalline products. The structure of
one of the products with m.p. 127Ϫ129°C was solved by
X-ray analysis, and its perspective view is shown in Figure
1. This product was thus identified as (±)-2a, while the
other, with m.p. 117Ϫ119°C, was evidently (±)-2b. Simi-
larly, the stereoisomeric lactone (±)-10 was converted to
(±)-2c, m.p. 131Ϫ133°C, and (±)-2d, m.p. 116Ϫ118°C. The
stereostructures of (±)-2c and (±)-2d were tentatively as-
signed on the basis of their m.p. and Rf values.[25]
MPLC separation; (f) NaH, HCO2Et, Et2O (quant.); (g) K2CO3,
N-methylpyrrolidone; 2) SiO2 chromatog. [42% of (±)-2a, 41% of
(±)-2b, 39% of (±)-2c and 45% of (±)-2d]
The 1H-NMR spectra of (±)-2aϪ(±)-2d were recorded in
CDCl3 or C6D6 solutions and compared with copies (sent
by Dr. C. Hauck) of the spectra of the natural sorgolactone
(Tables 1 and 2). Although the spectrum of (±)-2a was al-
Figure 1. Perspective views of (±)-10 and (±)-2a
most identical to that of the natural product, deviations in strongly dependent on their structures, including their rela-
the chemical shifts of some signals were apparent (Table 2). tive and absolute stereochemistries.[26Ϫ28] In particular, a C/
Since Dr. HauckЈs spectra of sorgolactone were unfortu- D-ring moiety is considered to be essential for high activity.
nately of rather poor quality due to the extremely limited Bioassays of the four final racemic products were therefore
amount of material available and the presence of impurities, carried out using seeds of clover broomrape (Orobanche
confirmation of the validity of the proposed structure sim- minor) as a test parasitic weed seed[29] (Table 3). All of the
ply by comparison of the 1H-NMR spectra of the synthetic four products with a C/D-ring moiety were effective in sti-
products and the natural material was difficult.
mulating the germination of the Orobanche minor seeds, and
The bioactivities of strigol and its stereoisomers or struc- the order of the stimulant activity was (±)-strigol ഠ (±)-2b
tural analogs as germination stimulants are known to be Ն (±)-2d > (±)-2a > (±)-2c.
2184
Eur. J. Org. Chem. 1999, 2183Ϫ2194

Plant Bioregulators, 2
Table 1. Comparison of the H-NMR spectra (500 MHz, CDCl3) of (±)-2aϪ(±)-2d with that of natural sorgolactone
FULL PAPER
1
(±)-2a
(±)-2b
(±)-2c
(±)-2d
Natural
sorgolactone[a]
8-Me
7-CH2
6-CH2
5-CH2
4Ј-Me
4-H
1.06 (3 H)
1.24, 1.56 (2 H)
1.70, 1.78 (2 H)
1.94 (2 H)
2.03 (1 H)
2.34 (1 H)
2.38 (1 H)
2.75 (1 H)
3.63 (1 H)
5.49 (1 H)
6.15 (1 H)
6.92 (1 H)
7.41 (1 H)
1.04 (3 H)
1.23, 1.55 (2 H)
1.68, 1.77 (2 H)
1.93 (2 H)
2.01 (1 H)
2.32 (1 H)
2.36 (1 H)
2.73 (1 H)
3.60 (1 H)
5.48 (1 H)
6.14 (1 H)
6.93 (1 H)
7.42 (1 H)
1.13 (3 H)
1.35, 1.55 (2 H)
1.72 (2 H)
1.92, 2.00 (2 H)
2.03 (1 H)
2.37 (1 H)
2.32 (1 H)
2.70 (1 H)
3.62 (1 H)
5.35 (1 H)
6.14 (1 H)
6.92 (1 H)
7.41 (1 H)
1.13 (3 H)
1.35, 1.54 (2 H)
1.74 (2 H)
1.91, 2.00 (2 H)
2.03 (1 H)
2.33 (1 H)
2.31 (1 H)
2.68 (1 H)
3.60 (1 H)
5.37 (1 H)
6.13 (1 H)
6.93 (1 H)
7.42 (1 H)
1.1 ( 3 H)
2.02 ( 3 H)
2.37 ( 1 H)
8-H
4-HЈ
3a-H
8b-H
2Ј-H
3Ј-H
9-H
2.75 ( 1 H)
3.63 ( 1 H)
5.51 ( 1 H)
6.13 ( 1 H)
6.92 ( 1 H)
7.45 ( 1 H)
[a] Ref.[15], 500 MHz.
Table 2. Comparison of the H-NMR spectra (500 MHz, C6D6) of (±)-2aϪ(±)-2d with that of natural sorgolactone
1
(±)-2a
(±)-2b
(±)-2c
(±)-2d
Natural
sorgolactone[a]
8-Me
7-CH2
4Ј-Me
6-H
0.94 (3 H)
1.02, 1.32 (2 H)
1.35 (3 H)
1.44 (1 H)
1.53 (1 H)
1.61 (1 H)
1.70 (1 H)
2.27 (1 H)
2.33 (1 H)
2.41 (1 H)
3.19 (1 H)
5.09 (1 H)
5.31 (1 H)
5.81 (1 H)
7.48 (1 H)
0.95 (3 H)
1.22 (3 H)
1.22 (3 H)
0.88 ( 3 H)
1.31 ( 3 H)
0.99, 1.22 (2 H)
1.34 (3 H)
1.16, 1.27 (2 H)
1.30 (3 H)
1.15, 1.23 (2 H)
1.31 (3 H)
1.36 (1 H)
1.43Ϫ1.56 (3 H)
1.48 (2 H)
1.38Ϫ1.47 (3 H)
6Ј-H
5-H
1.55 (1 H)
1.71 (1 H)
2.19 (1 H)
2.05 (1 H)
2.33 (1 H)
3.13 (1 H)
4.81 (1 H)
5.01 (1 H)
5.65 (1 H)
7.32 (1 H)
5Ј-H
4-H
8-H
4-HЈ
3a-H
8b-H
2Ј-H
3Ј-H
9-H
1.55 (1 H)
2.17 (1 H)
2.05 (1 H)
2.27 (1 H)
3.19 (1 H)
4.86 (1 H)
4.99 (1 H)
5.66 (1 H)
7.31 (1 H)
2.24(1 H)
2.33 (1 H)
2.36 (1 H)
3.24 (1 H)
5.13 (1 H)
5.22 (1 H)
5.77 (1 H)
7.43 (1 H)
2.13 ( 1 H)
2.30 ( 1 H)
3.06 ( 1 H)
4.93 ( 1 H)
4.96 ( 1 H)
5.65 ( 1 H)
7.23 ( 1 H)
[a] Ref.[15], 600 MHz.
Table 3. Germination-stimulating activity of (±)-2aϪ(±)-2d on Our own plan for the synthesis of (3aR,8S,8bS,2ЈR)-2a was
Orobanche minor seeds
to convert methyl (S)-(Ϫ)-citronellate (14) to the optically
active (3aR,8S,8bS)-9, and then to couple this with (±)-13
Concen-
tration
Relative germination of Orobanche minor seeds[a] (%)
in the same manner as described for the racemate, thereby
affording a separable mixture of 2a and 2b. As the key step,
we envisaged a radical cyclization[31] of 18 to 19 to give an
optically active A-ring building block.
(±)-2a
(±)-2b
(±)-2c
(±)-2d
(±)-strigol
10Ϫ5
10Ϫ6
10Ϫ7
10Ϫ8




82, 90
77, 65
40, 51
21, 23
95, 95
93, 93
90, 90
84, 87
70, 57
12, 18
7, 3
92, 95
90, 93
87, 78
80, 70
Ϫ, Ϫ
Ϫ, Ϫ
94, 94
86, 85
Scheme 3 summarizes the synthesis of 9 and 10. (S)-(Ϫ)-
Citronellal (97.0% ee, Takasago) was converted to methyl
(S)-citronellate (14),[32] which furnished the hydroxy ester
15 after epoxidation, periodate cleavage, and reduction. The
hydroxy ester 15 was converted to the corresponding iodo
ester 16 in 2 steps. Ethynylation of 16 with lithium acetylide
ethylenediamine complex gave the acetylenic ester 17 in
3, 0
[a] Control, 2, 0%.
Synthesis of (؉)-2a and Its Three Optically
Active Stereoisomers
Next, (3aR,8S,8bS,2ЈR)-2a and its three optically active moderate yield, which furnished the phenylselenenylated es-
stereoisomers were synthesized to allow comparison of their ter 18. The pivotal cyclization reaction was accomplished
CD spectra with that of natural sorgolactone, as well as by treatment of 18 with tri-n-butyltin hydride and AIBN in
their biological evaluation. ZwanenburgЈs strategy for the benzene at 80°C to generate the desired 19 as an insepar-
synthesis of 2a involved resolution of the A/B/C-tricyclic able mixture with methyl (S)-3-methyl-7-octenoate, an
precursor (±)-9 with an optically active D-ring precursor acyclic reduction product. Bromination of the mixture gave
corresponding to 13.[20] Welzel and co-workers devised a dibromide 20 (m.p. 37Ϫ39°C). Alkylation of dimethyl ma-
similar strategy also applicable to the synthesis of 2a.[30] lonate with the allylic bromide generated in situ from 20
Eur. J. Org. Chem. 1999, 2183Ϫ2194
2185

J. Matsui, M. Bando, M. Kido, Y. Takeuchi, K. Mori
FULL PAPER
was followed by Dieckmann-type cyclization, demethoxyca- and dimethyl malonate afforded the β-oxo ester 23. Hy-
rbonylation, and alkylation of the resulting sodium enolate drolysis and decarboxylation of 23 produced 24. Attempted
of the β-oxo ester with methyl bromoacetate to give a dia- alkylation of its RAMP-hydrazone 25 with methyl bromo-
stereomeric mixture of diester 21. Acid hydrolysis of 21 with acetate or tert-butyl bromoacetate led to complex reaction
concomitant decarboxylation gave oxo acid 22 as a dia- mixtures containing 25, a double-bond isomer of 25, and
stereomeric mixture. Attempts to separate the mixture at only trace amounts of the alkylated product.
this stage by means of recrystallization, asymmetric pro-
tonation of the enolate of 22, or diastereomeric salt forma-
tion with chiral bases such as (R)-(ϩ)-1-phenylethylamine,
(R)-(ϩ)-1-(1-naphthyl)ethylamine, cinchonine, quinine, bru-
cine dihydrate, and (1S,2R)-(ϩ)-2-amino-1,2-diphenyl-
ethanol, were unsuccessful. The oxo acid 22 was thus re-
duced under Luche conditions,[23] and the resulting hydroxy
acid was lactonized. As in the case of the racemates, the
mixture of 9 and 10 could be separated by MPLC [Lobar
LiChroprep Si 60 (40Ϫ63 µm)] to give pure (ϩ)-9 [oil,
24.6
[α]D
ϭ ϩ3.0 (c ϭ 0.60, CHCl3)] and (Ϫ)-10 [m.p.
26.0
1
45Ϫ47°C, [α]D
ϭ Ϫ68.4 (c ϭ 0.40, CHCl3)]. The H-
NMR spectra of the products were identical to those of (±)-
9 and (±)-10. The matching of the NMR data was sufficient
to establish the stereostructures of (ϩ)-9 and (Ϫ)-10 as (±)-
10 had been submitted to X-ray analysis.
Scheme 4. Preparation of RAMP-hydrazone 25; reagents: (a) 1.
NaOMe, CH2(CO2Me)2, MeOH; 2. AcOH (93%); (b) 6  HCl,
AcOH (72%); (c) RAMP, heating (93%)
The lactones (ϩ)-9 and (Ϫ)-10 were converted to 2a, 2b
1
and 2c, 2d, respectively (Schemes 5 and 6), the H-NMR
spectra of which were identical to those of the racemates.
The final products (ϩ)-2a, (Ϫ)-2c and (Ϫ)-2d were obtained
as colorless crystals and recrystallization from hexane/ethyl
acetate improved their enantiomeric purities to > 99.9% ee
(as determined by HPLC, Chiralcel OD). The enantiom-
eric purity of (ϩ)-2b, obtained as an amorphous powder,
was 99.9% ee. The CD spectrum of (ϩ)-2a is almost ident-
ical to that of (ϩ)-strigol[34] and the positive Cotton effect
at 232 nm (∆ε ϭ 21) of (ϩ)-2a is in accord with similar
observations reported for the natural (236 nm)[5] and the
synthetic (230 nm)[20] materials.
Scheme 3. Synthesis of (ϩ)-9 and (Ϫ)-10; reagents: (a) mCPBA,
CH2Cl2; (b) HIO4 · 2 H2O, THF/Et2O; (c) NaBH4, MeOH (91%, 3
steps); (d) TsCl, C5H5N; (e) NaI, acetone (82%, 2 steps); (f)
LiCϵCH·EDA, THF/DMSO (37%); (g) 1. LDA (2 equiv.), THF;
2. PhSeBr; 3. dil. HCl (69%); (h) nBu3SnH, AIBN, C6H6; (i)
Scheme 5. Synthesis of (ϩ)-2a and (ϩ)-2b; reagents: (a) NaH,
HCO2Et, Et2O (quant.); (g) 1. K2CO3, (±)-13, N-methylpyrroli-
done; 2. SiO2 chromatography [38% of (ϩ)-2a and 46% of (ϩ)-2b]
C5H5N·HBr · Br2, CHCl3 (37%,
2
steps); (j) 1. NaH,
CH2(CO2Me)2, THF; 2. BrCH2CO2Me (98%); (k) 6  HCl, AcOH
(96%); (l) 1. NaBH4, CeCl3 · 7 H2O, MeOH, then dil. HCl; 2.
MPLC separation [21% of (ϩ)-9 and 30% of (Ϫ)-10]
The bioactivities of the optically active stereoisomers
With a view to achieving a more efficient synthesis of 2aϪ2d were evaluated in a similar manner as for the racem-
(ϩ)-9, we attempted asymmetric alkylation[33] of the α,β- ates (Table 4). All stereoisomers were found to exhibit
unsaturated ketone 24. The preparation of 24 is summar- strong activity, which decreased in the order 2d > 2a > 2b ഠ
ized in Scheme 4. Acetic acid quenching of the sodium enol- 2c. It should be noted that 2a was not the strongest stimu-
ate generated by treatment of 20 with sodium methoxide lant for Orobanche minor seeds.
2186
Eur. J. Org. Chem. 1999, 2183Ϫ2194

Plant Bioregulators, 2
FULL PAPER
Methyl 1-Methoxycarbonyl-2-oxocyclopent-1-ylacetate (4): To
a
stirred mixture of methyl 2-oxo-1-cyclopentanecarboxylate (3,
2.84 g, 0.020 mol) and K2CO3 (13.8 g, 0.10 mol) in acetone
(100 mL) was added methyl bromoacetate (3.06 g, 0.020 mol). The
mixture was refluxed for 2 h and then concentrated under reduced
pressure. The residue was diluted with water and extracted with
diethyl ether. The combined ethereal layers were washed with brine
and dried with MgSO4. Evaporation of the solvent gave a crude
product, which was purified by silica-gel column chromatography
(hexane/ethyl acetate, 5:1) to furnish 4.02 g (98%) of the oxo diester
4[24] as a colorless oil. An analytical sample was purified by distil-
lation; b.p. 101Ϫ103°C/3 Torr. Ϫ IR (film): ν˜ ϭ 1760 cmϪ1 (s, Cϭ
O), 1740 (s, CϭO), 1730 (s, CϭO), 1635 (w, enolic CϭC), 1200 (s,
1
CϪO). Ϫ H NMR (270 MHz, CDCl3): δ ϭ 1.98Ϫ2.20 (m, 3 H,
4-CH2 and 5-H), 2.44 (m, 2 H), 2.60 (m, 1 H), 2.80 and 2.97 (AB,
1 H each, JAB ϭ 17.2 Hz, ϪCH2CO2Ϫ), 3.65 and 3.70 (2 s, 3 H
each, 2 ϫ OMe). Ϫ 13C NMR (67.8 MHz, CDCl3): δ ϭ 19.0, 32.6,
36.9, 37.3, 51.1, 52.1, 56.8, 170.1, 170.5, 213.1.
Scheme 6. Synthesis of (Ϫ)-2c and (Ϫ)-2d; reagents: (a) NaH,
HCO2Et, Et2O (quant.); (g) 1. K2CO3, (±)-13, N-methylpyrroli-
done; 2) SiO2 chromatography [33% of (Ϫ)-2c and 48% of (Ϫ)-2d]
Methyl 1-Methoxycarbonyl-2-oxocyclopent-3-en-1-ylacetate (5): To
a stirred solution of the oxo diester 4 (655 mg, 3.1 mmol) in ethyl
acetate (30 mL) containing a few drops of conc. HCl, phenylse-
lenenyl chloride (703 mg, 3.7 mol) was added in one portion. After
stirring for 24 h at room temperature, the resulting slightly pale-
yellow solution was diluted with water and extracted with ethyl
acetate. The combined organic layers were washed with water, satd.
NaHCO3 solution and brine, and then dried with MgSO4. The sol-
vent was evaporated under reduced pressure and the residue was
chromatographed on silica gel (hexane/ethyl acetate, 9:1) to give a
diastereomeric mixture of the selenide (1.01 g) as a yellowish vis-
cous oil. This was used for the next transformation without further
purification. To an ice-cooled, stirred solution of the above selenide
(812 mg, 2.2 mmol) in ethyl acetate/THF (2:1, 30 mL) was slowly
added ca. 35% hydrogen peroxide solution (0.64 mL, ca. 6.6 mmol).
After stirring for 30 min at 0°C and for a further 1 h at room tem-
perature, the excess oxidant was reduced with satd. Na2S2O3 solu-
tion. The mixture was then extracted with diethyl ether, and the
combined organic layers were washed with water and satd.
NaHCO3 solution, dried with MgSO4, and concentrated under re-
duced pressure. The residue was chromatographed on silica gel
(hexane/ethyl acetate, 9:1) to give 97 mg of the saturated oxo diester
4 and 254 mg (61% over 2 steps based on the consumed 4) of the
enone 5 as a colorless oil. Distillation of the oil afforded an analyti-
cal sample, b.p. 130Ϫ131°C/2.5 Torr. Ϫ nD24 ϭ 1.4802. Ϫ IR (film):
ν˜ ϭ 1740 cmϪ1 (s, CϭO), 1735 (s, CϭO), 1710 (s, CϭO), 1590 (m,
Table 4. Germination-stimulating activity of 2aϪ2d on Orobanche
minor seeds
Concen-
tration
Relative germination of Orobanche minor seeds[a] (%)
(ϩ)-2a
(ϩ)-2b
(Ϫ)-2c
(Ϫ)-2d
10Ϫ5
10Ϫ6
10Ϫ7
10Ϫ8




97, 89
91, 67
78, 58
37, 34
81, 75
65, 36
13, 0
98, 63
62, 22
7, 0
98, 98
98, 95
89, 87
88, 72
12, 0
3, 0
[a] Control, 2, 0%.
In conclusion, we have accomplished syntheses of the ra-
cemate and the optically active form of the structure pro-
posed for sorgolactone, and of their stereoisomers. Al-
though the spectroscopic properties of (ϩ)-2a are largely
in agreement with those reported for natural sorgolactone,
1
differences seen in the H-NMR spectra do not lead us to
the conclusion that the proposed structure is perfectly cor-
rect. Bioassays do not offer any clues as to the structure of
sorgolactone. Since at present we have no access to the
natural product itself, we conclude that reisolation of pure
sorgolactone must be attempted in order to resolve this un-
certainty. The isolation of sorgolactone from Sorghum bi-
color is currently being performed by Prof. T. Yokota at
Teikyo University. GC-MS analysis[7] of reisolated sorgo-
lactone and our synthetic samples should make it clear
whether the proposed structure is correct or not.
1
CϭC), 1190 (s, CϪO). Ϫ H NMR (270 MHz, CDCl3): δ ϭ 2.59
and 3.25 (AB, 1 H each, JAB ϭ 17.5 Hz, ϪCH2CO2Ϫ), 2.78 (dt, 1
H, J ϭ 19.5, JЈ ϭ 2.3 Hz, 5-H), 3.50 (dt, 1 H, J ϭ 19.5, JЈ ϭ
2.6 Hz, 5-HЈ), 3.69 and 3.71 (2 s, 3 H each, 2 ϫ OMe), 6.21 (dt, 1
H, J ϭ 5.9, JЈ ϭ 2.3 Hz, 3-H), 7.86 (dt, 1 H, J ϭ 5.9, JЈ ϭ 2.6 Hz,
4-H). Ϫ 13C NMR (67.8 MHz, CDCl3): δ ϭ 38.0, 40.3, 51.9, 53.0,
55.4, 131.2, 164.8, 169.6, 171.2, 203.7. Ϫ C10H12O5 (212.2): calcd.
C 56.60, H 5.70; found C 56.52, H 5.80.
Experimental Section
General: Boiling points and melting points (Yanaco MP-S3): Un-
corrected values. Ϫ IR: Shimadzu FT-IR 8100 or Jasco IRA-102.
7-Methyl-1,4-dioxo-2,3,4,5,6,7-hexahydroinden-2-ylacetic Acid (6):
According to the procedure of To˜ke et al.,[22] which used ethyl 1-
methoxycarbonyl-2-oxocyclopent-3-en-1-ylacetate in place of the
Ϫ
1H NMR: Jeol JNM-EX 90A (90 MHz), Jeol JNM-EX 270L
(270 MHz), Bruker DPX 300 (300 MHz), Jeol JNM-LA 400
(400 MHz), or Jeol JNM-LA 500 (500 MHz) (TMS at δH ϭ 0.00; methyl ester 5, 5 was converted to a diastereomeric mixture of the
CHCl3 at δH ϭ 7.26; C6H6 at δH ϭ 7.15 as internal standards).
dioxo acid 6 (54%, 3 steps). This acid 6 was unstable and aromat-
ized in the presence of air to give an acid with the phenolic ring
Ϫ
13C NMR: Jeol JNM-EX 270L (67.8 MHz), Bruker DPX 300
(75.5 MHz), Jeol JNM-LA 400 (100.4 MHz), or Jeol JNM-LA 500 A.[22] It was thus used immediately for the next reaction; m.p.
(125.7 MHz) (CDCl3 at δC ϭ 77.0 as internal standard). Ϫ MS: 135Ϫ137°C (diethyl ether) [ref.[22] 141Ϫ142°C]. Ϫ IR (KBr): ν˜ ϭ
Jeol JMX-DX 303 (70 eV). Ϫ Optical rotation: Jasco DIP-1000. Ϫ
CD: Jasco J-720. Ϫ CC: Merck Kieselgel 60 Art 1.07734. Ϫ TLC: O), 1630 (m, CϭC), 1400 (m, OϪH), 1290 (m, CϪO). Ϫ 1H NMR
3000 cmϪ1 (m, OϪH), 1740 (s, CϭO), 1690 (s, CϭO), 1685 (s, Cϭ
0.25 mm Merck silica gel plates (60F-254).
(300 MHz, CDCl3): δ ϭ 1.25 and 1.26 (2 d, 3 H total, J ϭ 7.1 Hz,
Eur. J. Org. Chem. 1999, 2183Ϫ2194
2187

J. Matsui, M. Bando, M. Kido, Y. Takeuchi, K. Mori
7-Me), 1.88 (m, 1 H, 6-H), 2.22 (m, 1 H, 6-HЈ), 2.28Ϫ2.94 (m, 7 tography (hexane/ethyl acetate, 5:1), the individual isomers could
FULL PAPER
H), 3.00 (m, 1 H), 7.82 (s, 1 H, OH). Ϫ 13C NMR (100.4 MHz,
CDCl3): δ (major isomer) ϭ 17.0, 26.5, 29.7, 30.4, 34.3, 36.0, 42.4,
156.5, 157.0, 176.1, 199.1, 209.6; δ (minor isomer) ϭ 16.9, 26.5,
29.6, 30.3, 34.6, 35.6, 42.0, 156.5, 157.2, 176.1, 199.1, 210.0.
not be characterized since they quickly epimerized and then decom-
posed. Ϫ IR (film): ν˜ ϭ 1770 cmϪ1 (s, CϭO), 1170 (s, CϪO). Ϫ
1H NMR (90 MHz, CDCl3): δ ϭ 1.12, 1.15 and 1.20 (3 d, 3 H
total, J ϭ 6.8 Hz, 8-Me), 1.46Ϫ1.88 (m, 2 H, 7-CH2), 1.94Ϫ3.30
(m, 8 H), 4.72 (m, 1 H, 5-H), 5.31 and 5.50 (2 d, 1 H total, J ϭ
7.3, 7.0 Hz, 8b-H).
5-H ydroxy-8-methyl-3,3a,4,5,6,7,8,8b-octahydroindeno[1,2-b]-
furan-2-one (7): A stirred suspension of the dioxo acid 6 (178 mg,
0.80 mmol) in water (8.5 mL) was neutralized with 1  NaOH
(±)-(3aR*,8S*,8bS*)- and (±)-(3aS*,8S*,8bR*)-8-Methyl-3,3a,
4,5,6,7,8,8b-octahydroindeno[1,2-b]furan-2-one [(±)-9 and (±)-10]:
To zinc-copper couple (Zn/Cu ϭ 91:5, Kanto Chemical Co., 2.13 g,
32 mmol) at room temperature under argon, a solution of the
bromolactone 8 (867 mg, 3.2 mmol) in dry THF (50 mL) was ad-
ded, followed by acetic acid (0.17 mL). The mixture was stirred for
(0.94 mL). To the resulting orange solution,
a solution of
CeCl3 · 7 H2O (298 mg, 0.80 mmol) in water (0.85 mL) was added
at room temperature, followed by CH2Cl2 (3.4 mL). After cooling
to 0°C, a solution of NaBH4 (182 mg, 4.8 mmol) in water
(0.85 mL) was added dropwise. The resulting mixture was stirred
for 2 h at 0°C. The excess reductant was then destroyed by the 1 h at room temperature, and then the excess zinc-copper couple
addition of 6  HCl, and the mixture was extracted with CH2Cl2.
The combined organic layers were washed with brine, dried with
MgSO4, and concentrated under reduced pressure. The residue was
was filtered off. The residue obtained upon evaporation of the sol-
vent under reduced pressure was redissolved in CHCl3 (100 mL).
The resulting colorless solution was stirred for 60 h at room tem-
chromatographed on silica gel (benzene/ethyl acetate, 6:1) to give perature, then diluted with water and extracted with CHCl3. The
111 mg (67%) of the hydroxylactone 7 as a diastereomeric mixture organic layer was washed with brine, dried with MgSO4, and con-
of the four possible racemates, which was employed directly in the centrated under reduced pressure. The slightly pale-yellow residue
next transformation. Separation by silica-gel column chromatogra-
phy (hexane/ethyl acetate, 5:1) furnished two pairs of dia-
stereomers, the more polar isomers (Rf ϭ 0.23, hexane/ethyl acet-
ate, 1:2) in a ratio of ca. 3.9:1 (as determined by 1H-NMR analysis)
as a colorless paste, and the less polar ones (Rf ϭ 0.29, hexane/
ethyl acetate, 1:2) in a ratio of ca. 3.1:1 (1H NMR) as colorless
needles. Ϫ More Polar Diastereomers: IR (film): ν˜ ϭ 3440 cmϪ1
(m, OϪH), 1760 (s, CϭO), 1170 (m, CϪO), 1000 (m, CϪO). Ϫ 1H
NMR (300 MHz, CDCl3): δ (for major isomer) ϭ 1.09 (d, 3 H,
J ϭ 7.1 Hz, 8-Me), 1.43 (m, 1 H, 7-H), 1.67Ϫ2.00 (m, 4 H, 6-CH2,
7-HЈ and OH), 2.17 (dd, 1 H, J ϭ 16.4, JЈ ϭ 2.2 Hz, 4-H), 2.28
was chromatographed on silica gel (hexane/ethyl acetate, 8:1) to
give a ca. 1:1 mixture (as determined by HPLC, silica gel) of the
debrominated lactones (±)-9 and (±)-10 (247 mg, 40%). The mix-
ture was separated by medium-pressure liquid chromatography
[Lobar LiChroprep Si 60 (40Ϫ63 mm), hexane/iPrOH, 49:1] to
furnish a fast-moving diastereomer (±)-9 as a pale-yellow oil and
a slow-moving one (±)-10 as a white solid. The latter was recrys-
tallized from hexane to afford colorless crystals suitable for X-ray
20
analysis. Ϫ The Oily Lactone (±)-9: nD ϭ 1.5088. Ϫ IR (film):
ν˜ ϭ 1765 cmϪ1 (s, CϭO), 1670 (w, CϭC), 1170 (s, CϪO). Ϫ 1H
NMR (300 MHz, CDCl3): δ ϭ 1.04 (d, 3 H, J ϭ 7.0 Hz, 8-Me),
(dd, 1 H, J ϭ 18.4, JЈ ϭ 5.7 Hz, 3-H), 2.32 (m, 1 H, 8-H), 2.84 1.25 (m, 1 H, 7-H), 1.50Ϫ1.85 (m, 3 H, 6-CH2 and 7-HЈ), 1.96 (m,
(dd, 1 H, J ϭ 18.4, JЈ ϭ 10.4 Hz, 3-HЈ), 2.98 (ddd, 1 H, J ϭ 16.4,
JЈ ϭ 8.2, JЈЈ ϭ 2.7 Hz, 4-HЈ), 3.10 (m, 1 H, 3a-H), 4.17 (m, 1 H,
5-H), 5.48 (d, 1 H, J ϭ 7.4 Hz, 8b-H), δ (characteristic signals of
minor isomer) ϭ 1.07 (d, 3 H, J ϭ 7.0 Hz, 8-Me), 4.22 (m, 1 H, 5-
2 H, 5-CH2), 2.13 (d, 1 H, J ϭ 16.6 Hz, 4-H), 2.29 (dd, 1 H, J ϭ
18.3, JЈ ϭ 5.7 Hz, 3-H), 2.36 (m, 1 H, 8-H), 2.66 (ddd, 1 H, J ϭ
16.5, JЈ ϭ 8.2, JЈЈ ϭ 1.5 Hz, 4-HЈ), 2.82 (dd, 1 H, J ϭ 18.3, JЈ ϭ
10.6 Hz, 3-HЈ), 3.05 (m, 1 H, 3a-H), 5.47 (d, 1 H, J ϭ 7.4 Hz, 8b-
H), 5.32 (d, 1 H, J ϭ 7.1 Hz, 8b-H). Ϫ Less Polar Diastereomers: H). Ϫ MS (EI, 70 eV): m/z (%) ϭ 192 (71) [Mϩ], 177 (31), 148 (39),
M.p. 109Ϫ110°C (diethyl ether). Ϫ IR (KBr): ν˜ ϭ 3420 cmϪ1 (m,
OϪH), 1765 (s, CϭO), 1175 (m, CϪO), 1010 (m, CϪO). Ϫ 1H
NMR (300 MHz, CDCl3): δ (major isomer) ϭ 1.16 (d, 3 H, J ϭ tone (±)-10: M.p. 43Ϫ46°C (hexane). Ϫ IR (KBr): ν˜ ϭ 1755 cmϪ1
133 (100), 131 (66), 117 (32), 105 (72), 91 (72). Ϫ HRMS: calcd.
for C12H16O2: 192.1150; found 192.1159. Ϫ The Crystalline Lac-
7.1 Hz, 8-Me), 1.49 (m, 2 H, 7-CH2), 1.68Ϫ1.86 (m, 3 H, 6-CH2
and OH), 2.29 (m, 1 H, 8-H), 2.38 (dd, 1 H, J ϭ 18.3, JЈ ϭ 4.6 Hz,
3-H), 2.54 (m, 1 H, 4-H), 2.62 (dd, 1 H, J ϭ 8.5, JЈ ϭ 3.3 Hz, 4-
HЈ), 2.82 (dd, 1 H, J ϭ 18.3, JЈ ϭ 10.3 Hz, 3-HЈ), 3.10 (m, 1 H,
3a-H), 4.13 (br. d, 1 H, J ϭ 4.8 Hz, 5-H), 5.32 (d, 1 H, J ϭ 7.5 Hz,
8b-H); δ (characteristic signals of minor isomer) ϭ 1.05 (d, 3 H,
J ϭ 7.0 Hz, 8-Me), 1.30 (m, 1 H, 7-H), 1.91 and 2.05 (2 m, 1 H
each, 6-CH2), 2.33 (dd, 1 H, J ϭ 18.4, JЈ ϭ 6.0 Hz, 3-H), 2.48 (m,
1 H, 4-H), 2.68 (dd, 1 H, J ϭ 8.7, JЈ ϭ 3.5 Hz, 4-HЈ), 2.84 (dd, 1
H, J ϭ 18.4, JЈ ϭ 10.6 Hz, 3-HЈ), 5.47 (d, 1 H, J ϭ 7.7 Hz, 8b-H).
Ϫ C12H16O3 (208.3): calcd. C 69.21, H 7.74; found C 69.27, H 7.72.
(s, CϭO), 1170 (m, CϪO). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ
1.10 (d, 3 H, J ϭ 7.1 Hz, 8-Me), 1.34 and 1.57 (2 m, 1 H each, 7-
CH2), 1.75 (m, 2 H, 6-CH2), 1.97 (m, 2 H, 5-CH2), 2.17 (dt, 1 H,
J ϭ 16.6, JЈ ϭ 1.7 Hz, 4-H), 2.31 (m, 1 H, 8-H), 2.34 (dd, 1 H,
J ϭ 18.2, JЈ ϭ 4.4 Hz, 3-H), 2.61 (ddt, 1 H, J ϭ 16.6, JЈ ϭ 8.7,
JЈЈ ϭ 1.5 Hz, 4-HЈ), 2.80 (dd, 1 H, J ϭ 18.2, JЈ ϭ 10.3 Hz, 3-HЈ),
3.03 (m, 1 H, 3a-H), 5.31 (d, 1 H, J ϭ 7.1 Hz, 8b-H). Ϫ C12H16O2
(192.3): calcd. C 74.97, H 8.39; found C 74.70, H 8.39.
(±)-(3aR*,8S*,8bS*)-3-H ydroxymethylene-8-methyl-3,3a,4,5,
6,7,8,8b-octahydroindeno[1,2-b]furan-2-one [(±)-11]: To a stirred
suspension of NaH (ca. 60% oil suspension, 31 mg, ca. 0.78 mmol)
in dry diethyl ether (2.0 mL) at room temperature under argon, was
added a solution of the lactone (±)-9 (50 mg, 0.26 mmol) in dry
diethyl ether (2.0 mL), followed by ethyl formate (0.25 mL, ca.
3 mmol). After stirring for 24 h, the mixture was acidified with 1 
5-Bromo-8-methyl-3,3a,4,5,6,7,8,8b-octahydroindeno[1,2-b]furan-2-
one (8): To a stirred solution of the hydroxylactone 7 (156 mg,
0.75 mmol) in dry CH2Cl2 (5.0 mL) were added solutions of tri-
phenylphosphane (354 mg, 1.35 mmol) in dry CH2Cl2 (10 mL) and
of carbon tetrabromide (672 mg, 2.03 mmol) in dry CH2Cl2 HCl and then extracted with ethyl acetate. The combined organic
(10 mL). The resulting mixture was stirred for 15 min at room tem-
perature and then concentrated under reduced pressure. The yel-
layers were washed with water (twice) and brine, and dried with
MgSO4. Evaporation of the solvent left a pale-yellow solid, which
lowish residue was chromatographed on silica gel (hexane/ethyl was washed several times with ice-cooled diethyl ether to give
acetate, 4:1) to give 205 mg (quant.) of a diastereomeric mixture of
the bromolactone 8 as an almost colorless oil [three spots upon
TLC analysis (hexane/ethyl acetate, 1:1), Rf ϭ 0.64, 0.57 and 0.49].
Although the mixture was separated by silica-gel column chroma-
57 mg (quant.) of the formylated lactone (±)-11 as a tautomeric
mixture of the enol and the aldehyde (ca. 2.4:1, as determined by
1H-NMR analysis), which was used directly in the subsequent
transformation without further purification; m.p. 114Ϫ116°C. Ϫ
2188
Eur. J. Org. Chem. 1999, 2183Ϫ2194

Plant Bioregulators, 2
FULL PAPER
IR (KBr): ν˜ ϭ 3500Ϫ2800 cmϪ1 (m, OϪH), 2750 (m, OCϪH),
1715 (s, CϭO), 1690 (s, CϭO), 1635 (s, CϭC), 1385 (m, OCϪH),
1205 (s, CϪO), 1080 (s, CϪO). Ϫ H NMR (300 MHz, CDCl3): δ
1.53 (2 m, 1 H each, 6-CH2), 1.61 and 1.70 (2 m, 1 H each, 5-CH2),
2.27 (dd, 1 H, J ϭ 16.5, JЈ ϭ 3.6 Hz, 4-H), 2.33 (m, 1 H, 8-H),
2.41 (dd, 1 H, J ϭ 16.5, JЈ ϭ 8.5 Hz, 4-HЈ), 3.19 (m, 1 H, 3a-H),
1
(for the enol) ϭ 1.06 (d, 3 H, J ϭ 7.1 Hz, 8-Me), 1.28 (m, 1 H, 7- 5.09 (d, 1 H, J ϭ 8.0 Hz, 8b-H), 5.31 (t, 1 H, J ϭ 1.5 Hz, 2Ј-H),
H), 1.49Ϫ1.85 (m, 3 H, 6-CH2 and 7-HЈ), 1.95 (m, 2 H, 5-CH2),
2.20 (d, 1 H, J ϭ 17.2 Hz, 4-H), 2.48 (m, 1 H, 8-H), 2.70 (dd, 1 H,
J ϭ 17.2, JЈ ϭ 8.4 Hz, 4-HЈ), 3.57 (m, 1 H, 3a-H), 5.58 (dd, 1 H,
J ϭ 7.8, JЈ ϭ 1.2 Hz, 8b-H), 7.07 (s, 1 H, 9-H), 10.41 (br s, 1 H,
OH); δ (characteristic signals of the aldehyde) ϭ 2.12 (d, 1 H, J ϭ
5.81 (t, 1 H, J ϭ 1.5 Hz, 3Ј-H), 7.48 (d, 1 H, J ϭ 2.5 Hz, 9-H). Ϫ
13C NMR (75.5 MHz): δ (in CDCl3) ϭ 10.7, 18.5, 20.6, 26.0, 27.8,
31.1, 36.4, 41.3, 88.0, 100.4, 114.3, 135.8, 137.2, 141.0, 141.3, 150.1,
170.2, 171.8; δ (in C6D6) ϭ 10.2, 18.6, 21.0, 26.2, 28.2, 31.3, 36.7,
41.5, 87.3, 101.0, 114.6, 135.2, 137.9, 140.6, 140.7, 151.0, 169.9,
16.8 Hz, 4-H), 3.38 (d, 1 H, J ϭ 6.6 Hz, 3-H), 3.50 (m, 1 H, 3a- 171.0. Ϫ MS (EI, 70 eV): m/z (%) 316 (50) [Mϩ], 219 (28), 201 (65),
H), 5.48 (d, 1 H, J ϭ 7.4, 8b-H), 9.86 (s, 1 H, CHO).
191 (10), 173 (32), 159 (5), 145 (11), 131 (19), 115 (10), 105 (14),
97 (100), 91 (37), 77 (17), 69 (27). Ϫ C18H20O5 (316.4): calcd. C
68.34, H 6.37; found C 68.12, H 6.44. Ϫ (±)-2Ј-Episorgolactone
[(±)-2b]: M.p. 117Ϫ119°C (hexane/ethyl acetate). Ϫ IR (KBr): ν˜ ϭ
2940 cmϪ1 (m), 2855 (m), 1785 (s, CϭO), 1745 (s, CϭO), 1685 (s,
CϭC), 1445 (m), 1380 (m), 1335 (s), 1210 (m), 1180 (s, CϪO), 1090
(s), 1025 (s, CϪO), 955 (s), 930 (w), 870 (w), 750 (m), 740 (m). Ϫ
1H NMR (500 MHz): δ (in CDCl3) ϭ 1.04 (d, 3 H, J ϭ 7.0 Hz, 8-
Me), 1.23 and 1.55 (2 m, 1 H each, 7-CH2), 1.68 and 1.77 (2 m, 1
H each, 6-CH2), 1.93 (m, 2 H, 5-CH2), 2.01 (t, 3 H, J ϭ 1.5 Hz,
4Ј-Me), 2.32 (d, 1 H, J ϭ 16.5 Hz, 4-H), 2.36 (m, 1 H, 8-H), 2.73
(dd, 1 H, J ϭ 15.0, JЈ ϭ 9.0 Hz, 4-HЈ), 3.60 (m, 1 H, 3a-H), 5.48
(d, 1 H, J ϭ 7.5 Hz, 8b-H), 6.14 (s, 1 H, 2Ј-H), 6.93 (t, 1 H, J ϭ
1.5 Hz, 3Ј-H), 7.42 (d, 1 H, J ϭ 3.0 Hz, 9-H); δ (in C6D6) ϭ 0.95
(d, 3 H, J ϭ 7.0 Hz, 8-Me), 0.99 and 1.22 (2 m, 1 H each, 7-CH2),
1.34 (br. s, 3 H, 4Ј-Me), 1.36 (m, 1 H, 6-H), 1.43Ϫ1.56 (m, 3 H, 5-
CH2 and 6-HЈ), 2.24 (d, 1 H, J ϭ 16.5 Hz, 4-H), 2.33 (m, 1 H, 8-
H), 2.36 (dd, 1 H, J ϭ 16.5, JЈ ϭ 8.5 Hz, 4-HЈ), 3.24 (m, 1 H, 3a-
H), 5.13 (d, 1 H, J ϭ 8.0 Hz, 8b-H), 5.22 (m, 1 H, 2Ј-H), 5.77 (br.
s, 1 H, 3Ј-H), 7.43 (br s, 1 H, 9-H). Ϫ 13C NMR (75.5 MHz,
CDCl3): δ ϭ 10.7, 18.6, 20.6, 26.0, 27.8, 31.1, 36.4, 41.4, 88.0,
100.6, 114.4, 135.7, 137.1, 141.1, 141.5, 150.4, 170.3, 171.8. Ϫ
C18H20O5 (316.4): calcd. C 68.34, H 6.37; found C 68.30, H 6.42.
(±)-(3aS*,8S*,8bR*)-3-H ydroxymethylene-8-methyl-3,3a,4,5,
6,7,8,8b-octahydroindeno[1,2-b]furan-2-one [(±)-12]: In the same
manner as described for (±)-11, the lactone (±)-10 (50 mg,
0.26 mmol) was formylated using NaH (ca. 60% oil suspension,
50 mg, ca. 0.26 mmol) and ethyl formate (0.25 mL, ca. 3 mol) in
dry diethyl ether (4.0 mL) to afford 58 mg (quant.) of the formy-
lated lactone (±)-12 as a tautomeric mixture of the enol and the
aldehyde (ca. 2.0:1, as determined by 1H-NMR analysis). Again,
this was employed without purification in the next step. White
solid, m.p. 118Ϫ119°C. Ϫ IR (KBr): ν˜ ϭ 3600Ϫ2800 cmϪ1 (m,
OϪH), 2740 (m, OCϪH), 2680 (m, OCϪH), 1710 (s, CϭO), 1660
(s, CϭO), 1600 (m, CϭC), 1380 (m, OCϪH), 1355 (m, OCϪH),
1200 (s, CϪO) 1100 (m, CϪO). Ϫ 1H NMR (300 MHz, CDCl3): δ
(for the enol) ϭ 1.12 (d, 3 H, J ϭ 7.0 Hz, 8-Me), 1.38 (m, 1 H, 7-
H), 1.50Ϫ1.83 (m, 3 H, 6-CH2 and 7-HЈ), 2.00 (m, 2 H, 5-CH2),
2.25 (d, 1 H, J ϭ 17.2 Hz, 4-H), 2.32 (m, 1 H, 8-H), 2.73 (dd, 1 H,
J ϭ 17.2, JЈ ϭ 7.7 Hz, 4-HЈ), 3.55 (m, 1 H, 3a-H), 5.45 (d, 1 H,
J ϭ 8.0 Hz, 8b-H), 7.06 (s, 1 H, 9-H), 10.43 (br s, 1 H, OH); δ
(characteristic signals of the aldehyde) ϭ 1.10 (d, 3 H, J ϭ 6.1 Hz,
8-Me), 2.18 (d, 1 H, J ϭ 16.8 Hz, 4-H), 3.50 (m, 1 H, 3a-H), 5.34
(d, 1 H, J ϭ 6.5 Hz, 8b-H), 9.84 (s, 1 H, CHO).
(±)-(3aR*,8S*,8bS*,2ЈR*)- and (3aR*,8S*,8bS*,2ЈS*)-3-[(E)-2Ј,5Ј-
Dihydro-4Ј-methyl-5Ј-oxo-2Ј-furanyloxymethylene]-8-methyl-3,3a,4,
5,6,7,8,8b-octahydroindeno[1,2-b]furan-2-one [(±)-Sorgolactone and
(±)-(3aS*,8S*,8bR*,2ЈS*)- and (3aS*,8S*,8bR*,2ЈR*)-3-[(E)-2Ј,5Ј-
Dihydro-4Ј-methyl-5Ј-oxo-2Ј-furanyloxymethylene]-8-methyl-3,3a,4,
(±)-2Ј-Episorgolactone, (±)-2a and (±)-2b]: To a stirred mixture of 5,6,7,8,8b-octahydroindeno[1,2-b]furan-2-one [(±)-8-Episorgo-
the hydroxymethylene lactone (±)-11 (55 mg, 0.25 mmol) and lactone and (±)-2Ј,8-Diepisorgolactone, (±)-2c and (±)-2d]: In the
K2CO3 (69 mg, 0.50 mmol) in anhydrous N-methylpyrrolidone same manner as described for (±)-2a and (±)-2b, the hydroxymeth-
(2.0 mL) at room temperature under argon, was added (±)-4-
bromo-2-methyl-2-buten-4-olide [(±)-13][10] (75 mg, 0.43 mmol).
ylene lactone (±)-12 (50 mg, 0.23 mmol) was alkylated with the
bromobutenolide (±)-13 (68 mg, 0.39 mmol) in the presence of
After stirring for 24 h at room temperature, the reaction mixture K2CO3 (63 mg, 0.45 mmol) in anhydrous N-methylpyrrolidone
was poured into 1  HCl (5 mL) and extracted with ethyl acetate.
The organic layer was washed with water (twice) and brine, and
dried with MgSO4. Evaporation of the solvent under reduced press-
ure gave a slightly pale-yellow oil, which was chromatographed on
silica gel (hexane/ethyl acetate, 6:1) to give first 33 mg (42%) of (±)-
(1.5 mL). Silica-gel column chromatography (hexane/ethyl acetate,
6:1) gave first 28 mg (39%) of (±)-8-episorgolactone [(±)-2c] as col-
orless crystals (Rf ϭ 0.41, hexane/ethyl acetate, 1:1) and then 32 mg
(45%) of (±)-2Ј,8-diepisorgolactone [(±)-2d] as colorless crystals
(Rf ϭ 0.33, hexane/ethyl acetate, 1:1). Ϫ (±)-8-Episorgolactone [(±)-
sorgolactone [(±)-2a] as colorless crystals (Rf ϭ 0.41, hexane/ethyl 2c]: M.p. 131Ϫ133°C (hexane/ethyl acetate). Ϫ IR (KBr): ν˜ ϭ
acetate, 1:1) and then 32 mg (41%) of (±)-2Ј-episorgolactone [(±)-
2935 cmϪ1 (m), 1790 (s, CϭO), 1740 (s, CϭO), 1685 (s, CϭC), 1340
2b] as colorless crystals (Rf ϭ 0.34, hexane/ethyl acetate, 1:1). The (m), 1210 (w), 1180 (m, CϪO), 1095 (s), 1020 (s, CϪO), 955 (s),
stereostructures of (±)-2a and (±)-2b were deduced from an X-ray
analysis of (±)-2a. Ϫ (±)-Sorgolactone [(±)-2a]: M.p. 127Ϫ129°C
(hexane/ethyl acetate). Ϫ IR (KBr): ν˜ ϭ 2930 cmϪ1 (m), 2860 (w),
1790 (s, CϭO), 1745 (s, CϭO), 1730 (s, CϭO), 1680 (s, CϭC), 1350
750 (w). Ϫ 1H NMR (500 MHz): δ (in CDCl3) ϭ 1.13 (d, 3 H, J ϭ
7.0 Hz, 8-Me), 1.35 and 1.55 (2 m, 1 H each, 7-CH2), 1.72 (m, 2
H, 6-CH2), 1.92 and 2.00 (2 m, 1 H each, 5-CH2), 2.03 (t, 3 H, J ϭ
1.5 Hz, 4Ј-Me), 2.32 (m, 1 H, 8-H), 2.37 (d, 1 H, J ϭ 16.5 Hz, 4-
(m), 1340 (m), 1180 (s, CϪO), 1095 (s), 1020 (s, CϪO), 955 (s), 930 H), 2.70 (ddd, 1 H, J ϭ 16.5, JЈ ϭ 9.5, JЈЈ ϭ 3.4 Hz, 4-HЈ), 3.62
(w), 750 (w). Ϫ 1H NMR (500 MHz): δ (in CDCl3) ϭ 1.06 (d, 3 (m, 1 H, 3a-H), 5.35 (d, 1 H, J ϭ 7.5 Hz, 8b-H), 6.14 (t, 1 H, J ϭ
H, J ϭ 7.0 Hz, 8-Me), 1.24 and 1.56 (2 m, 1 H each, 7-CH2), 1.70
1.5 Hz, 2Ј-H), 6.92 (t, 1 H, J ϭ 1.5 Hz, 3Ј-H), 7.41 (d, 1 H, J ϭ
and 1.78 (2 m, 1 H each, 6-CH2), 1.94 (m, 2 H, 5-CH2), 2.03 (t, 3 2.5 Hz, 9-H); δ (in C6D6) ϭ 1.16 (m, 1 H, 7-H), 1.22 (d, 3 H, J ϭ
H, J ϭ 1.5 Hz, 4Ј-Me), 2.34 (d, 1 H, J ϭ 16.5 Hz, 4-H), 2.38 (m,
1 H, 8-H), 2.75 (dd, 1 H, J ϭ 15.0, JЈ ϭ 9.0 Hz, 4-HЈ), 3.63 (m, 1
H, 3a-H), 5.49 (d, 1 H, J ϭ 8.0 Hz, 8b-H), 6.15 (t, 1 H, J ϭ 1.5 Hz,
7.5 Hz, 8-Me), 1.27 (m, 1 H, 7-HЈ), 1.30 (t, 3 H, J ϭ 1.5 Hz, 4Ј-
Me), 1.48 (m, 2 H, 6-CH2), 1.55 and 1.71 (2 m, 1 H each, 5-CH2),
2.05 (m, 1 H, 8-H), 2.19 (d, 1 H, J ϭ 16.5 Hz, 4-H), 2.33 (ddd, 1
2Ј-H), 6.92 (t, 1 H, J ϭ 1.5 Hz, 3Ј-H), 7.41 (d, 1 H, J ϭ 3.0 Hz, 9- H, J ϭ 16.5, JЈ ϭ 8.8, JЈЈ ϭ 3.0 Hz, 4-HЈ), 3.13 (m, 1 H, 3a-H),
H); δ (in C6D6) ϭ 0.94 (d, 3 H, J ϭ 7.0 Hz, 8-Me), 1.02 and 1.32
(2 m, 1 H each, 7-CH2), 1.35 (t, 3 H, J ϭ 1.5 Hz, 4Ј-Me), 1.44 and
4.81 (d, 1 H, J ϭ 7.5 Hz, 8b-H), 5.01 (t, 1 H, J ϭ 1.5 Hz, 2Ј-H),
5.65 (t, 1 H, J ϭ 1.5 Hz, 3Ј-H), 7.32 (m, 1 H, 9-H). Ϫ 13C NMR
Eur. J. Org. Chem. 1999, 2183Ϫ2194
2189

J. Matsui, M. Bando, M. Kido, Y. Takeuchi, K. Mori
FULL PAPER
(75.5 MHz, CDCl3): δ ϭ 10.7, 19.9, 20.2, 26.2, 30.0, 31.6, 36.8,
41.3, 90.8, 100.4, 114.4, 135.8, 136.5, 141.0, 142.8, 149.7, 170.3,
171.8. Ϫ C18H20O5 (316.4): calcd. C 68.34, H 6.37; found C 68.42,
H 6.34. Ϫ (±)-2Ј,8-Diepisorgolactone [(±)-2d]: M.p. 116Ϫ118°C
(hexane/ethyl acetate). Ϫ IR (KBr): ν˜ ϭ 2930 cmϪ1 (w), 1790 (s,
CϭO), 1735 (s, CϭO), 1730 (s, CϭO), 1685 (s, CϭC), 1340 (m),
1205 (w), 1180 (s, CϪO), 1090 (s), 1020 (s, CϪO), 955 (s), 930 (w),
2830 cmϪ1 (m, OCϪH), 2730 (w, OCϪH), 1740 (s, CϭO), 1725 (s,
CϭO), 1205 (m, CϪO), 1165 (m, CϪO). Ϫ H NMR (400 MHz,
1
CDCl3): δ ϭ 0.96 (d, 3 H, J ϭ 6.8 Hz, 3-Me), 1.54 and 1.71 (2 m,
1 H each, 4-CH2), 2.00 (m, 1 H, 3-H), 2.19 (dd, 1 H, J ϭ 15.1,
JЈ ϭ 7.5 Hz, 2-H), 2.31 (dd, 1 H, J ϭ 15.1, JЈ ϭ 6.3 Hz, 2-HЈ),
2.47 (dtd, 2 H, J ϭ 8.9, JЈ ϭ 6.2, JЈЈ ϭ 1.6 Hz, 5-CH2), 3.68 (s, 3
H, OMe), 9.78 (t, 1 H, J ϭ 1.6 Hz, CHO). Ϫ To an ice-cooled
solution of the above aldehyde (ca. 0.31 mol) in methanol
(700 mL), NaBH4 (12.5 g, 0.33 mol) was carefully added in several
1
870 (w), 755 (w). Ϫ H NMR (500 MHz): δ (in CDCl3) ϭ 1.13 (d,
3 H, J ϭ 7.0 Hz, 8-Me), 1.35 and 1.54 (2 m, 1 H each, 7-CH2),
1.74 (m, 2 H, 6-CH2), 1.91 and 2.00 (2 m, 1 H each, 5-CH2), 2.03 portions. After stirring for 1 h at 0°C, the mixture was diluted with
(t, 3 H, J ϭ 1.5 Hz, 4Ј-Me), 2.31 (m, 1 H, 8-H), 2.33 (d, 1 H, J ϭ
16.5 Hz, 4-H), 2.68 (ddd, 1 H, J ϭ 16.5, JЈ ϭ 9.5, JЈЈ ϭ 3.3 Hz, 4-
HЈ), 3.60 (m, 1 H, 3a-H), 5.37 (d, 1 H, J ϭ 7.5 Hz, 8b-H), 6.13 (t,
water, concentrated to remove most of the methanol, and extracted
with diethyl ether. The organic layer was washed with brine and
dried with MgSO4. Evaporation of the solvent gave a crude prod-
1 H, J ϭ 1.5 Hz, 2Ј-H), 6.93 (t, 1 H, J ϭ 1.5 Hz, 3Ј-H), 7.42 (d, 1 uct, which was purified by silica-gel column chromatography (hex-
H, J ϭ 2.5 Hz, 9-H); δ (in C6D6) ϭ 1.15 and 1.23 (2 m, 1 H each,
7-CH2), 1.22 (d, 3 H, J ϭ 7.0 Hz, 8-Me), 1.31 (t, 3 H, J ϭ 1.5 Hz,
4Ј-Me), 1.38Ϫ1.47 (m, 3 H, 5-H and 6-CH2), 1.55 (m, 1 H, 5-HЈ),
ane/ethyl acetate, 10:1) to afford 43.8 g (91% from 14 over 3 steps)
of the alcohol 15[35] as a colorless oil. Distillation furnished an
analytical sample, b.p. 99Ϫ100°C/24 Torr. Ϫ IR (film): ν˜ ϭ
2.05 (m, 1 H, 8-H), 2.17 (d, 1 H, J ϭ 16.5 Hz, 4-H), 2.27 (ddd, 1 3600Ϫ3200 cmϪ1 (m, OϪH), 1735 (s, CϭO), 1200 (m, CϪO), 1160
1
H, J ϭ 16.5, JЈ ϭ 9.0, JЈЈ ϭ 3.0 Hz, 4-HЈ), 3.19 (m, 1 H, 3a-H),
4.86 (d, 1 H, J ϭ 8.0 Hz, 8b-H), 4.99 (t, 1 H, J ϭ 1.5 Hz, 2Ј-H),
(m, CϪO), 1055 (m, CϪO). Ϫ H NMR (300 MHz, CDCl3): δ ϭ
0.92 (d, 3 H, J ϭ 6.6 Hz, 3-Me), 1.23 and 1.38 (2 m, 1 H each, 4-
5.66 (t, 1 H, J ϭ 1.5 Hz, 3Ј-H), 7.31 (d, 1 H, J ϭ 2.5 Hz, 9-H). Ϫ CH2), 1.56 (m, 2 H, 5-CH2), 1.91Ϫ2.03 (m, 2 H, 3-H and OH),
13C NMR (75.5 MHz, CDCl3): δ ϭ 10.7, 20.0, 20.2, 26.2, 30.1,
31.6, 36.7, 41.4, 90.9, 100.6, 114.4, 135.7, 136.4, 141.1, 142.9, 150.0,
170.3, 171.8. Ϫ C18H20O5 (316.4): calcd. C 68.34, H 6.37; found C
68.04, H 6.40.
2.12 (dd, 1 H, J ϭ 14.9, JЈ ϭ 6.4 Hz, 2-H), 2.19 (dd, 1 H, J ϭ 14.9,
JЈ ϭ 7.3 Hz, 2-HЈ), 3.60 (t, 2 H, J ϭ 6.5 Hz, 6-CH2), 3.64 (s, 3 H,
23.0
OMe). Ϫ [α]D
ϭ Ϫ6.6 (c ϭ 2.50, CHCl3).
Methyl (S)-6-Iodo-3-methylhexanoate (16): To a stirred, ice-cooled
mixture of the alcohol 15 (51.0 g, 0.32 mol) and pyridine (50 mL)
in CH2Cl2 (200 mL), p-toluenesulfonyl chloride (92 g, 0.48 mol)
was added portionwise. The resulting mixture was stirred for 19 h
at 5°C, then diluted with water, and poured into dilute aq. HCl.
Methyl (S)-Citronellate (14): Methyl (S)-citronellate was prepared
from (S)-citronellal (97.0% ee, Takasago) by JonesЈ CrO3 oxidation
and esterification with K2CO3 and methyl iodide (65% over the 2
steps), b.p. 104°C/24 Torr. Ϫ IR (film): ν˜ ϭ 1745 cmϪ1 (s, CϭO),
1
1200 (m, CϪO), 1160 (m, CϪO). Ϫ H NMR (90 MHz, CDCl3): This mixture was extracted with diethyl ether and the combined
δ ϭ 0.94 (d, 3 H, J ϭ 6.4 Hz, 3-Me), 1.05Ϫ1.46 (m, 2 H, 4-CH2),
1.59 (s, 3 H, 7-Me), 1.68 (d, 3 H, J ϭ 0.9 Hz, 7-Me), 1.74Ϫ2.41 NaHCO3 solution and brine, and dried with MgSO4. Evaporation
(m, 5 H, 2-CH2, 3-H and 5-CH2), 3.66 (s, 3 H, OMe), 5.08 (t, 1 H, of the solvent gave a crude product, which was purified by silica-
ϭ Ϫ7.6 (c ϭ 2.50, CHCl3) {ref.[32] gel column chromatography (hexane/ethyl acetate, 25:1) to afford
organic layers were successively washed with dilute aq. HCl, satd.
26.0
J ϭ 7.0 Hz, 6-H). Ϫ [α]D
22
[α]D ϭ Ϫ6.70 (c ϭ 2.28, CHCl3)}.
the corresponding tosylate as a colorless oil. This was used for the
subsequent transformation without further purification. Ϫ IR
(film): ν˜ ϭ 1740 cmϪ1 (s, CϭO), 1600 (m, Ar), 1500 (w, Ar), 1360
(s, sulfonate), 1190 (s, sulfonate), 1180 (s, sulfonate), 970 (m,
SϪOϪC), 920 (m, SϪOϪC), 660 (s, Ar). Ϫ 1H NMR (90 MHz,
CDCl3): δ ϭ 0.90 (d, 3 H, J ϭ 6.4 Hz, 3-Me), 1.05Ϫ2.03 (m, 5 H,
3-H, 4-CH2 and 5-CH2), 2.05Ϫ2.38 (m, 2 H, 2-CH2), 2.45 (s, 3 H,
3-Me), 3.65 (s, 3 H, OMe), 4.02 (t, 2 H, J ϭ 6.3 Hz, 6-CH2), 7.34
(d, 2 H, J ϭ 8.4 Hz, Ar), 7.79 (d, 2 H, J ϭ 8.4 Hz, Ar). Ϫ A
mixture of the above tosylate (ca. 0.32 mol) and sodium iodide
(62.4 g, 0.42 mol) in acetone (950 mL) was refluxed for 2 h and
then diluted with water. The resulting mixture was then concen-
trated to remove most of the acetone and extracted with diethyl
ether. The combined organic layers were successively washed with
water, satd. Na2S2O3 solution, satd. NaHCO3 solution and brine,
and dried with MgSO4. Evaporation of the solvent gave a crude
product, which was purified by silica-gel column chromatography
(hexane/diethyl ether, 80:1) to afford 71.1 g (81% from 15 over 2
steps) of the iodide 16 as a colorless oil. Distillation of the oil gave
an analytical sample, b.p. 109Ϫ110°C/10 Torr. Ϫ nD24 ϭ 1.4940. Ϫ
IR (film): ν˜ ϭ 1745 cmϪ1 (s, CϭO), 1200 (s, CϪO). Ϫ 1H NMR
(90 MHz, CDCl3): δ ϭ 0.94 (d, 3 H, J ϭ 6.1 Hz, 3-Me), 1.11Ϫ1.54
Methyl (S)-6-Hydroxy-3-methylhexanoate (15): To an ice-cooled
mixture of the methyl ester 14 (57.0 g, 0.31 mol) and NaHCO3
(28.6 g, 0.34 mol) in CH2Cl2 (1 L), m-chloroperbenzoic acid
(mCPBA, 84.0 g, 0.34 mol) was carefully added in several portions.
The resulting mixture was stirred for 30 min at 0°C, quenched by
the addition of Na2S2O3 solution, and then extracted with CH2Cl2.
The organic layer was successively washed with satd. NaHCO3
solution, water and brine, and dried with MgSO4. Evaporation of
the solvent gave a crude product, which was purified by silica-gel
column chromatography (hexane/ethyl acetate, 20:1) to afford
62.0 g of a diastereomeric mixture of the epoxide as a colorless oil.
This was used for the next transformation without further purifi-
cation. Ϫ IR (film): ν˜ ϭ 2960 cmϪ1 (s, CϪH), 1740 (s, CϭO), 1250
(m, epoxide), 1205 (m, CϪO), 1165 (m, CϪO), 1120 (m, CϪO). Ϫ
1H NMR (90 MHz, CDCl3): δ ϭ 0.97 (d, 3 H, J ϭ 6.4 Hz, 3-Me),
1.26 and 1.30 (2 s, 3 H each, 2 ϫ Me), 1.47Ϫ1.67 (m, 4 H, 4-CH2
and 5-CH2), 1.82Ϫ2.43 (m, 3 H, 2-CH2 and 3-H), 2.70 (t, 1 H, J ϭ
6.7 Hz, 6-H), 3.67 (s, 3 H, OMe). Ϫ To an ice-cooled solution of
HIO4 · 2 H2O (74.2 g, 0.34 mol) in THF (800 mL), an ethereal solu-
tion (600 mL) of the above epoxide (ca. 0.31 mol) was added drop-
wise over a period of 1 h. After stirring for 30 min at 0°C, the
mixture was diluted with water and extracted with diethyl ether.
The combined organic layers were successively washed with water,
satd. NaHCO3 solution and brine, and dried with MgSO4. Evapor-
ation of the solvent gave a crude product, which was purified by
silica-gel column chromatography (hexane/ethyl acetate, 15:1) to af-
ford the aldehyde as a colorless oil. This was employed in the next
transformation without further purification. Ϫ IR (film): ν˜ ϭ
(m, 2 H), 1.55Ϫ2.39 (m, 5 H), 3.16 (t, 2 H, J ϭ 6.8 Hz, 6-CH2),
24.0
3.66 (s, 3 H, OMe). Ϫ [α]D
ϭ Ϫ12.6 (c ϭ 2.00, CHCl3). Ϫ
C8H15IO2 (270.1): calcd. C 35.57, H 5.60; found C 35.54, H 5.58.
Methyl (S)-3-Methyl-7-octynoate (17): To a solution of the iodide
16 (21.6 g, 80 mmol) in dry THF/DMSO (2:1, 120 mL) under ar-
gon at 5°C was slowly added a suspension of ca. 90% lithium ace-
tylide ethylenediamine complex (9.8 g, 96 mmol) in dry THF/
2190
Eur. J. Org. Chem. 1999, 2183Ϫ2194

Plant Bioregulators, 2
DMSO (2:1, 120 mL). After stirring for 15 min at 5°C, water was CH). Ϫ MS (EI, 70 eV): m/z ϭ 168 [Mϩ], 153, 136, 125, 109, 108,
FULL PAPER
added to the resulting dark-orange suspension. The mixture was
extracted with diethyl ether and the combined organic layers were
washed with water and brine, and dried with MgSO4. Evaporation
of the solvent gave a crude product, which was chromatographed
on silica gel (pentane/diethyl ether, 250:1) to afford 4.97 g (37%) of
93, 79, 67, 55.
Methyl (6S)-2-Bromo-2-bromomethyl-6-methylcyclohexane-1-car-
boxylate (20): To a mixture of 19 and methyl (S)-3-methyl-7-oc-
tenoate (32 mg), obtained as described above, in CHCl3 (1.5 mL),
ca. 90% pyridinium hydrobromide perbromide (77 mg, ca.
0.22 mmol) was added portionwise at Ϫ60°C. After stirring for 3
h at this temperature, the reaction mixture was extracted with
CHCl3. The organic layer was washed twice with water and dried
with MgSO4. Evaporation of the solvent left a crude product,
which was purified by silica-gel column chromatography (hexane/
diethyl ether, 100:1) affording 49 mg (37% from 18) of the dibro-
mide 20 as colorless rods, m.p. 42Ϫ43°C (pentane). Ϫ IR (KBr):
ν˜ ϭ 1735 cmϪ1 (s, CϭO), 1195 (m, CϪO), 1150 (s, CH2Br). Ϫ H
NMR (90 MHz, CDCl3): δ ϭ 0.86Ϫ1.12 (m, 1 H), 0.93 (d, 3 H,
J ϭ 6.2 Hz, 6-Me), 1.64Ϫ2.35 (m, 5 H), 2.50 (d, 1 H, J ϭ 10.8 Hz,
1-H), 3.75 (s, 3 H, OMe), 3.84 and 4.10 (AB, 1 H each, JAB
10.4 Hz, ϪCH2Br). Ϫ [α]D
24
17 as a colorless oil, b.p. 86Ϫ89°C/16 Torr. Ϫ nD ϭ 1.4411. Ϫ
IR (film): ν˜ ϭ 3300 cmϪ1 (m, ϵCϪH), 2130 (w, CϵC), 1740 (s,
CϭO), 1200 (s, CϪO), 1155 (m, CϪO). Ϫ 1H NMR (300 MHz,
CDCl3): δ ϭ 0.92 (d, 3 H, J ϭ 6.6 Hz, 3-Me), 1.20Ϫ1.62 (m, 4 H,
4-CH2 and 5-CH2), 1.92 (t, 1 H, J ϭ 2.6 Hz, 8-H), 1.96 (m, 1 H,
3-H), 2.11 (dd, 1 H, J ϭ 14.8, JЈ ϭ 8.0 Hz, 2-H), 2.16 (td, 1 H,
J ϭ 7.0, JЈ ϭ 2.6 Hz, 6-CH2), 2.29 (dd, 1 H, J ϭ 14.8, JЈ ϭ 6.1 Hz,
2Ј-H), 3.64 (s, 3 H, OMe). Ϫ 13C NMR (75.5 MHz, CDCl3): δ ϭ
18.4, 19.5, 25.8, 29.9, 35.6, 41.4, 51.3, 68.2, 84.2, 173.4. Ϫ MS (EI,
1
70 eV): m/z ϭ 153 [Mϩ Ϫ Me], 139, 127, 114, 109, 101, 95, 87, 81,
25.2
74, 59. Ϫ [α]D
ϭ Ϫ10.0 (c ϭ 1.10, CHCl3). Ϫ Due to the high
ϭ
volatility of 17, correct elemental analytical data could not be ob-
tained.
25.5
ϭ ϩ12.1 (c ϭ 0.15, CHCl3). Ϫ
C10H16Br2O2 (328.0): calcd. C 36.61, H 4.92; found C 36.73, H
5.02.
Methyl (3S)-3-Methyl-2-phenylselenenyl-7-octynoate (18): To
a
stirred solution of lithium diisopropylamide (LDA, 7.39 mmol),
prepared from diisopropylamine (1.14 mL, 8.13 mmol) and n-bu-
tyllithium (1.66  hexane solution, 4.45 mL, 7.39 mmol), in dry
THF (14 mL), was added a solution of the ester 17 (564 mg,
3.36 mmol) in THF (14 mL) at Ϫ78°C under argon. The resulting
white suspension was stirred for 1 h at Ϫ78°C, allowed to warm to
Ϫ30°C over a period of 1 h, and then cooled to Ϫ78°C once more.
A solution of phenylselenenyl bromide (1.21 g, 3.86 mmol) in THF
(8 mL) was added to the mixture at Ϫ78°C and stirring was con-
tinued for 1 h. The resulting dark-orange solution was slowly al-
lowed to warm to room temperature, poured into 1  HCl, and
extracted with diethyl ether. The ethereal layer was washed with
water (twice) and brine, and dried with MgSO4. Evaporation of
the solvent followed by silica-gel column chromatography (hexane/
diethyl ether, 100:1) afforded a diastereomeric mixture of the selen-
ide 18 (748 mg, 69%) as a yellowish oil, which was used without
further purification in the next step. Ϫ IR (film): ν˜ ϭ 3250 cmϪ1
(w, ϵCϪH), 2120 (vw, CϵC), 1735 (s, CϭO), 1575 (m, Ar), 1210
(s, CϪO), 1200 (s, CϪO), 1150 (m, CϪO), 740 (s, Ar). Ϫ 1H NMR
(90 MHz, CDCl3): δ ϭ 0.97 and 1.17 (2 d, 3 H total, J ϭ 6.2,
6.6 Hz, 3-Me), 1.25Ϫ1.70 (m, 4 H, 4-CH2 and 5-CH2), 1.97 (m, 1
H, 8-H), 2.02Ϫ2.44 (m, 3 H, 3-H and 6-CH2), 3.53 (m, 1 H, 2-H),
3.64 and 3.69 (2 s, 3 H each, 2 ϫ OMe), 7.36 (m, 3 H, Ar), 7.64
(m, 2 H, Ar).
Methyl (7S)-2-Methoxycarbonyl-7-methyl-1-oxo-2,3,4,5,6,7-hexa-
hydroinden-2-ylacetate (21): To a stirred suspension of NaH (ca.
60% oil suspension, 288 mg, 7.21 mmol) in dry THF (25 mL) at
Ϫ10°C under argon, was added dimethyl malonate (0.40 mL,
3.47 mmol). After stirring for 10 min at Ϫ10°C, a solution of the
dibromo ester 20 (659 mg, 2.07 mmol) in dry THF (5 mL) was ad-
ded dropwise. The resulting pale-yellow suspension was stirred for
28 h at room temperature and then methyl bromoacetate (665 mg,
4.35 mmol) was added. The dark-orange mixture was stirred for a
further 43 h at room temperature, then quenched by the addition
of water, and extracted with diethyl ether. The combined organic
layers were washed with 5% Na2CO3 solution, water and brine, and
dried with MgSO4. Evaporation of the solvent left a crude product,
which was chromatographed on silica gel (hexane/ethyl acetate,
11:1) to afford a diastereomeric mixture (ca. 1:1, as determined by
1H-NMR analysis) of 21 (550 mg, 98%) as a yellowish viscous oil.
This was used directly for the next transformation without further
purification. Ϫ IR (film): ν˜ ϭ 1740 cmϪ1 (s, CϭO), 1705 (s, Cϭ
1
O), 1645 (m, CϭC), 1215 (m, CϪO), 1200 (m, CϪO). Ϫ H NMR
(300 MHz, CDCl3): δ ϭ 1.08 and 1.09 (2 d, 3 H total, J ϭ 7.0 Hz,
7-Me), 1.43 (m, 1 H, 6-H), 1.58Ϫ1.86 (m, 3 H, 5-CH2 and 6-HЈ),
2.19Ϫ2.58 (m, 3 H, 4-CH2 and 7-H), 2.45 and 3.29 (AB, 1 H each,
J
AB ϭ 17.1 Hz), 2.47 and 3.24 (AB, 1 H each, JAB ϭ 17.4 Hz), 3.66
and 3.67 (2 s, 3 H total, OMe), 3.69 (s, 3 H, OMe).
Methyl (2S)-2-Methyl-6-methylenecyclohexane-1-carboxylate (19):
To a stirred mixture of the selenide 18 (3.88 g, 12 mmol) and 2,2Ј-
(7S)-7-Methyl-1-oxo-2,3,4,5,6,7-hexahydroinden-2-ylacetic
Acid
azobisisobutyronitrile (AIBN) (0.20 g, 1.2 mmol) in dry benzene (22): A solution of the diester 21 (28 mg, 0.10 mmol) in 6  HCl
(400 mL) under reflux,
a
solution of tri-n-butyltin hydride
(0.5 mL) and glacial acetic acid (0.5 mL) was refluxed for 2.5 h. It
was then diluted with water and extracted with ethyl acetate. The
combined organic layers were washed with brine and dried with
MgSO4. Evaporation of the solvent followed by silica-gel column
(6.45 mL, 24 mmol) in dry benzene (50 mL) was added dropwise
over a period of 15 min. The resulting pale-pink solution was re-
fluxed for a further 1 h and then cooled to room temperature.
Evaporation of the solvent left a dark-yellow residue, which was
purified by silica-gel column chromatography (pentane/diethyl
ether, 250:1) and distillation (b.p. 84Ϫ88°C/20 Torr) to afford an
chromatography (hexane/ethyl acetate, 2:1) afforded
a dia-
stereomeric mixture [ca. 1:1, as determined by HPLC (Chiralcel
OD)] of 22 (20 mg, 96%) as a pale-yellow paste, which was em-
inseparable mixture (1.11 g) of 19 and methyl (S)-3-methyl-7-oc- ployed in the next transformation without further purification. Ϫ
tenoate, the acyclic reduction product, as a colorless oil. This mix-
ture was used directly for the next transformation. Ϫ IR (film): ν˜ ϭ
3240 cmϪ1 (w, CϭCϪH), 1740 (s, CϭO), 1640 (m, CϭC), 1200 (m,
CϪO), 1160 (s, CϪO), 910 (m, ϭCH2). Ϫ 1H NMR (300 MHz,
CDCl3): δ (for 19) ϭ 0.94 (d, 3 H, J ϭ 6.5 Hz, 2-Me), 1.12Ϫ1.52
(m, 3 H, 3-CH2 and 4-H), 1.78 (m, 1 H, 4-HЈ), 1.91Ϫ2.10 (m, 2 H,
IR (film): ν˜ ϭ 3600Ϫ2800 cmϪ1 (m, OϪH), 1730 (s, CϭO), 1695
(s, CϭO), 1420 (m, OϪH), 1310 (m, CϪO), 1205 (m, CϪO), 920
(m, CO2H). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 1.10 (d, 3 H, J ϭ
7.0 Hz, 7-Me), 1.45 (m, 1 H, 6-H), 1.60Ϫ1.84 (m, 3 H, 5-CH2 and
6-HЈ), 2.19Ϫ2.33 (m, 3 H, 2-H and ϪCH2CO2Ϫ), 2.40 and 2.43 (2
dd, 1 H total, J ϭ 16.2, JЈ ϭ 6.6 Hz and J ϭ 16.3, JЈ ϭ 6.2 Hz, 3-
5-CH2), 2.34 (m, 1 H, 2-H), 2.74 (d, 1 H, J ϭ 9.6 Hz, 1-H), 3.74 H), 2.52 (m, 1 H, 7-H), 2.66Ϫ2.90 (m, 2 H, 4-CH2), 2.86 (2 dd, 1
(s, 3 H, OMe), 4.52 (d, 1 H, J ϭ 1.2 Hz, ϭCH), 4.81 (s, 1 H, ϭ
Eur. J. Org. Chem. 1999, 2183Ϫ2194
H total, J ϭ 16.2, JЈ ϭ 5.1 Hz and J ϭ 16.3, JЈ ϭ 5.5 Hz, 3Ј-H).
2191

J. Matsui, M. Bando, M. Kido, Y. Takeuchi, K. Mori
FULL PAPER
(3aR,8S,8bS)- and (3aS,8S,8bR)-8-Methyl-3,3a,4,5,6,7,8,8b-octa-
hydroindeno[1,2-b]furan-2-one (9 and 10): A mixture of the oxo acid
22 (300 mg, 1.44 mmol) and CeCl3 · 7 H2O (1.07 g, 2.88 mmol) in
methanol (22 mL) was treated with NaBH4 (219 mg, 5.76 mmol) at
0°C. After stirring for 45 min at room temperature, the mixture
was acidified with 20% H2SO4 and then extracted with ethyl acet-
ate. The combined organic layers were washed with satd. NaHCO3
solution and brine, and dried with MgSO4. Evaporation of the sol-
vent gave a crude product, which was purified by silica-gel column
7-H). Ϫ MS (EI, 70 eV): m/z ϭ 150 [Mϩ], 135, 122, 117, 108, 93,
79. Ϫ HRMS: calcd. for C10H14O: 150.1045; found 150.1017.
(S)-7-Methyl-1-oxo-2,3,4,5,6,7-hexahydroindene RAMP-Hydrazone
(25):
A mixture of the α,β-unsaturated ketone 24 (50 mg,
0.32 mmol) and (R)-(ϩ)-1-amino-2-(methoxymethyl)pyrrolidine
(RAMP, 216 mg, 1.65 mmol) was heated at 90°C for 20 h. The mix-
ture was then diluted with CH2Cl2, washed with water and brine,
and dried with MgSO4. Evaporation of the solvent left a yellowish
crude product, which was chromatographed on silica gel (hexane/
diethyl ether, 9:1) to afford the RAMP-hydrazone 25 (81 mg, 93%)
as a yellowish paste. This was employed in the subsequent alky-
lation reaction without further purification. Ϫ IR (film): ν˜ ϭ
2940 cmϪ1 (s, CϪH), 1700 (m, CϭN), 1645 (m, CϭN), 1620 (m,
CϭC), 1130 (s, CϪO). Ϫ 1H NMR (90 MHz, CDCl3): δ ϭ 1.10
(d, 3 H, J ϭ 6.8 Hz, 7-Me), 1.40Ϫ2.80 (m, 17 H), 3.05Ϫ3.62 (m, 3
H), 3.34 (s, 3 H, OMe).
chromatography (hexane/ethyl acetate, 7:1) to afford
a dia-
stereomeric mixture of the tricyclic lactones 9 and 10. The mixture
was separated by medium-pressure liquid chromatography [Lobar
LiChroprep Si 60 (40Ϫ63 mm), hexane/2-propanol, 33:1] to fur-
nish a fast-moving diastereomer 9 (59 mg, 21%) as a pale-yellow
oil and a slow-moving one 10 (83 mg, 30%) as a white solid. The
latter was recrystallized from hexane to afford colorless needles. Ϫ
(؉)-9: 97.2% ee {determined by GC [column: Chirasil-Dex CB ,
0.25 mm ϫ 25 m, 100°C (1 min) to 210°C (5°C/min); carrier gas:
He (120 kPa); detector: FID]; (Ϫ)-9: tR ϭ 21.48 min (1.4%) and
(ϩ)-9: tR ϭ 21.68 min (98.6%)}. Ϫ Its IR and 1H-NMR spectra
(3aR,8S,8bS)-3-Hydroxymethylene-8-methyl-3,3a,4,5,6,7,8,8b-octa-
hydroindeno[1,2-b]furan-2-one (11): In the same manner as de-
scribed for (±)-11, the lactone 9 (29 mg, 0.15 mmol) was formylated
using NaH (ca. 60% oil suspension, 18 mg, ca. 0.45 mmol) and
ethyl formate (0.15 mL, ca. 2 mmol) in dry diethyl ether (4.0 mL)
to afford 33 mg (quant.) of the formylated lactone 11 (a tautomeric
mixture of the enol and the aldehyde in a ca. 2.1:1 ratio, as deter-
mined by 1H-NMR analysis) as a slightly yellow solid. This was
employed in the subsequent step without further purification; m.p.
113Ϫ115°C. Ϫ IR (KBr): ν˜ ϭ 3600Ϫ3000 cmϪ1 (m, OϪH), 2730
(m, OCϪH), 1715 (s, CϭO), 1680 (m, CϭO), 1640 (m, CϭC), 1415
25
24.6
were identical to those of (±)-9. Ϫ nD ϭ 1.4991. Ϫ [α]D
ϭ
ϩ3.0 (c ϭ 0.60, CHCl3). Ϫ (؊)-10: > 99.9% ee {determined by GC
[column: Chirasil-Dex CB , 0.25 mm ϫ 25 m, 100°C (1 min) to
210°C (5°C/min); carrier gas: He (120 kPa); detector: FID]; (Ϫ)-
10: tR
ϭ 16.55 min (> 99.9%); (ϩ)-10: tR ϭ 16.77 min
(undetectable)}; m.p. 45Ϫ47°C (hexane). Ϫ IR (KBr): ν˜
ϭ
1765 cmϪ1 (s, CϭO), 1170 (s, CϪO). Ϫ Its 1H-NMR spectrum was
26.0
identical to that of (±)-10. Ϫ [α]D
ϭ Ϫ68.4 (c ϭ 0.40, CHCl3).
(w, OCϪH), 1200 (s, CϪO), 1080 (m, CϪO). Ϫ Its 1H-NMR spec-
Ϫ C12H16O2 (192.3): calcd. C 74.97, H 8.39; found C 74.78, H 8.26.
24.8
trum was identical to that of (±)-11. Ϫ [α]D
ϭ ϩ144.3 (c ϭ
Methyl (7S)-7-Methyl-1-oxo-2,3,4,5,6,7-hexahydroindene-2-car-
0.30, CHCl3).
boxylate (23): To a solution of sodium methoxide, prepared from
sodium (217 mg, 9.44 mmol) and methanol (10 mL), was added di-
methyl malonate (1.31 g, 9.91 mmol). The resulting mixture was
cooled in an ice bath and stirred for 15 min. At this temperature,
a solution of the dibromide 20 (583 mg, 1.78 mmol) in methanol
(30 mL) was added dropwise. The mixture was stirred at room tem-
perature for 14.5 h and then refluxed for 2 h. The resulting orange
solution was acidified with acetic acid and extracted with ethyl
acetate. The organic layer was washed with NaHCO3 solution,
water and brine, and dried with MgSO4. Evaporation of the solvent
gave a crude product, which was chromatographed on silica gel
(hexane/ethyl acetate, 16:1) to afford a diastereomeric mixture of
the β-oxo ester 23 (342 mg, 93%) as a yellowish paste. This was
employed in the subsequent step without further purification. Ϫ
IR (film): ν˜ ϭ 1740 cmϪ1 (s, CϭO), 1705 (s, CϭO), 1640 (s, Cϭ
C), 1215 (m, CϪO), 1160 (s, CϪO). Ϫ 1H NMR (300 MHz,
CDCl3): δ ϭ 1.09 (d, 3 H, J ϭ 7.0 Hz, 7-Me), 1.45 (m, 1 H, 6-H),
1.63Ϫ1.83 (m, 3 H, 5-CH2 and 6-HЈ), 2.33 (m, 2 H, 4-CH2), 2.52
(m, 1 H, 7-H), 2.67 (dd, 1 H, J ϭ 18.1, JЈ ϭ 5.5 Hz, 3-H), 2.88 (d,
1 H, J ϭ 18.0 Hz, 3-HЈ), 3.40 (m, 1 H, 2-H), 3.76 (s, 3 H, OMe).
(3aS,8S,8bR)-3-Hydroxymethylene-8-methyl-3,3a,4,5,6,7,8,8b-octa-
hydroindeno[1,2-b]furan-2-one (12): In the same manner as de-
scribed for (±)-11, the lactone 10 (33 mg, 0.17 mmol) was formy-
lated using NaH (ca. 60% oil suspension, 20 mg, ca. 0.51 mmol)
and ethyl formate (0.16 mL, ca. 2 mmol) in dry diethyl ether
(3.0 mL) to afford 30 mg (quant.) of the formylated lactone 12 (a
tautomeric mixture of the enol and the aldehyde in a ca. 1.1:1 ratio,
as determined by 1H-NMR analysis) as a white solid. This was
employed in the subsequent step without further purification; m.p.
143Ϫ145°C. Ϫ IR (KBr): ν˜ ϭ 3300Ϫ2800 cmϪ1 (s, OϪH), 2750
(m, OCϪH), 1710 (s, CϭO), 1680 (m, CϭO), 1600 (m, CϭC), 1430
1
(m, OCϪH), 1205 (s, CϪO). Ϫ Its H-NMR spectrum was ident-
24.4
ical to that of (±)-12. Ϫ [α]D
ϭ Ϫ232.2 (c ϭ 0.30, CHCl3).
(3aR,8S,8bS,2ЈR)- and (3aR,8S,8bS,2ЈS)-3-[(E)-2Ј,5Ј-Dihydro-4Ј-
methyl-5Ј-oxo-2Ј-furanyloxymethylene]-8-methyl-3,3a,4,5,6,7,8,8b-
octahydroindeno[1,2-b]furan-2-one (Sorgolactone and 2Ј-Episorgol-
actone, 2a and 2b): In the same manner as described for (±)-2a and
(±)-2b, the hydroxymethylene lactone 11 (33 mg, 0.15 mmol) was
coupled with the bromobutenolide (±)-13 (53 mg, 0.30 mmol) in
(S)-7-Methyl-1-oxo-2,3,4,5,6,7-hexahydroindene (24): A solution of the presence of K2CO3 (41 mg, 0.30 mmol) in anhydrous N-methyl-
the β-oxo ester 23 (198 mg, 0.95 mmol) in 6  HCl/glacial acetic
pyrrolidone (2.5 mL). Silica-gel column chromatography (hexane/
acid (4:1, 2.5 mL) was refluxed for 1 h under argon. The reaction
ethyl acetate, 6:1) gave first 18 mg (38%) of sorgolactone (2a) as
mixture was then diluted with water and extracted with diethyl colorless needles (Rf ϭ 0.41, hexane/ethyl acetate, 1:1) and then
ether. The combined organic layers were washed with water and
brine, and dried with MgSO4. Evaporation of the solvent left a
yellowish residue, which was chromatographed on silica gel (pen-
tane/diethyl ether, 9:1) to afford the α,β-unsaturated ketone 24
22 mg (46%) of 2Ј-episorgolactone (2b) as an amorphous powder
(Rf ϭ 0.33, hexane/ethyl acetate, 1:1). Ϫ Sorgolactone [(؉)-2a]:
>
99.9% ee determined by HPLC (column: Chiralcel OD,
4.6 mm ϫ 25 cm; solvent: hexane/2-PrOH, 4:1; flow rate: 0.5 mL/
min; detector: 205 nm); (Ϫ)-2a: tR ϭ 24.7 min (undetectable); (ϩ)-
2a: tR ϭ 24.8 min (> 99.9%)]. Ϫ M.p. 145Ϫ147°C (hexane/ethyl
24
(103 mg, 72%) as a pale-yellow oil, nD ϭ 1.4841. Ϫ IR (film):
ν˜ ϭ 2950 cmϪ1 (s, CϪH), 1695 (s, CϭO), 1645 (s, CϭC), 1250 (m,
CϪO). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 1.10 (d, 3 H, J ϭ acetate). Ϫ IR (KBr): ν˜ ϭ 2925 cmϪ1 (m), 2865 (w), 1780 (s, Cϭ
7.2 Hz, 7-Me), 1.43 (m, 1 H, 6-H), 1.58Ϫ1.82 (m, 3 H, 5-CH2 and
6-HЈ), 2.28 (m, 2 H), 2.35 (m, 2 H), 2.45 (m, 2 H), 2.52 (m, 1 H,
O), 1765 (s, CϭO), 1740 (s, CϭO), 1680 (s, CϭC), 1400 (w), 1350
(m), 1335 (m), 1215 (w), 1180 (s, CϪO), 1100 (s), 1055 (m), 1020
2192
Eur. J. Org. Chem. 1999, 2183Ϫ2194

Plant Bioregulators, 2
FULL PAPER
1
(s, CϪO), 970 (s), 930 (m), 875 (m), 750 (w). Ϫ Its H-NMR spec- tions collected, 840 reflections with I > 3.0σ(I) were used for the
trum was identical to that of (±)-2a. Ϫ [α]D24.8 ϭ ϩ285.2 (c ϭ 0.26,
CHCl3). Ϫ CD (CH3CN, 43.4 µ): λmax (∆ε) ϭ 205 nm (Ϫ16.3),
230 (ϩ26.8), 263 (Ϫ2.1). Ϫ C18H20O5 (316.4): calcd. C 68.34, H
structure determination and refinement. The structure was solved
by direct methods using the TEXSAN crystallographic software
package.[36] All non-H atoms were located in a Fourier map. All H
6.37; found C 68.09, H 6.18. Ϫ 2Ј-Episorgolactone [(؉)-2b]: 99.9% atoms were calculated at geometrical positions and were not re-
ee determined by HPLC (column: Chiralcel OD, 4.6 mm ϫ 25 cm; fined. Atomic parameters were refined by full-matrix least-squares
solvent: hexane/2-PrOH, 4:1; flow rate: 0.5 mL/min; detector:
205 nm); (ϩ)-2b: tR ϭ 22.0 min (99.95%); (Ϫ)-2b: tR ϭ 25.7 min
(0.05%)]. Ϫ IR (KBr): ν˜ ϭ 2930 cmϪ1 (m), 1780 (s, CϭO), 1745 (s,
methods, using anisotropic temperature factors for all non-H
atoms. The final refinement converged with R ϭ 0.058 and Rw
0.072 for 127 parameters. The minimum and maximum peaks in
ϭ
CϭO), 1680 (s, CϭC), 1340 (m), 1210 (m), 1185 (s, CϪO), 1095 the final difference Fourier map were Ϫ0.27 and 0.18 eAϪ3. Atomic
˚
(s), 1020 (s, CϪO), 955 (s), 930 (w), 875 (w), 775 (w). Ϫ Its 1H-
NMR spectrum was identical to that of (±)-2b. Ϫ [α]D23.4 ϭ ϩ109.5 Crystallography”.[37] Supplementary material available includes
scattering factors were taken from “International Tables for X-ray
(c ϭ 0.10, CHCl3). Ϫ CD (CH3CN, 31.8 µ): λmax (∆ε) ϭ 218 nm
lists of atomic coordinates for the non-H atoms, the bond lengths
(Ϫ5.0), 245 (ϩ4.3). Ϫ C18H20O5 (316.4): calcd. C 68.34, H 6.37; and angles in (±)-10, with their e.s.d.s in parentheses.[38]
found C 68.26, H 6.37.
X-ray Analysis of (±)-2a: Crystal size, 0.3 ϫ 0.4 ϫ 0.5 mm. All data
were obtained with a Rigaku AFC-5S automated four-circle dif-
fractometer using graphite-monochromated Mo-Kα radiation. Fi-
nal lattice parameters were obtained from a least-squares refine-
ment using 25 reflections. Crystal data: C18H20O5, Mr ϭ 316.35,
(3aS,8S,8bR,2ЈS)- and (3aS,8S,8bR,2ЈR)-3-[(E)-2Ј,5Ј-Dihydro-4Ј-
methyl-5Ј-oxo-2Ј-furanyloxymethylene]-8-methyl-3,3a,4,5,6,7,8,8b-
octahydroindeno[1,2-b]furan-2-one (8-Episorgolactone and 2Ј,8-Di-
episorgolactone, 2c and 2d): In the same manner as described for
monoclinic, space group P21/n, a ϭ 6.957(3), b ϭ 17.541(3), c ϭ
(±)-2a and (±)-2b, the hydroxymethylene lactone 12 (36 mg,
3
˚
˚
13.777(4) A, β ϭ 97.78(3)°, V ϭ 1665.8(9) A , Z ϭ 4, DX ϭ 1.261 g/
cm3, F(000) ϭ 672, µ(Mo-Kα) ϭ 0.86 cmϪ1. The intensities were
measured using ω/2θ scans up to 45°. Three standard reflections
were monitored every 150 measurements. The data were corrected
for Lorentz and polarization factors. An absorption correction was
applied, but not a decay correction. Of the 2285 independent reflec-
tions collected, 1248 reflections with I > 3.0 σ(I) were used for the
structure determination and refinement. The structure was solved
by direct methods using the TEXSAN crystallographic software
package.[36] All non-H atoms were located in a Fourier map. All H
atoms were calculated at geometrical positions and were not re-
fined. Atomic parameters were refined by full-matrix least-squares
methods, using anisotropic temperature factors for all non-H
0.16 mmol) was coupled with the bromobutenolide (±)-13 (57 mg,
0.32 mmol) in the presence of K2CO3 (44 mg, 0.32 mmol) in anhy-
drous N-methylpyrrolidone (2.0 mL). Silica-gel column chromatog-
raphy (hexane/ethyl acetate, 6:1) gave first 17 mg (33%) of 8-episor-
golactone (2c) as colorless crystals (Rf ϭ 0.41, hexane/ethyl acetate,
1:1) and then 25 mg (48%) of 2Ј,8-diepisorgolactone (2d) as color-
less crystals (Rf ϭ 0.33, hexane/ethyl acetate, 1:1). Ϫ 8-Episorgolac-
tone [(؊)-2c]: > 99.9% ee determined by HPLC (column: Chiralcel
OD, 4.6 mm ϫ 25 cm; solvent: hexane/2-PrOH, 4:1; flow rate:
0.5 mL/min; detector: 205 nm); (ϩ)-2c: tR ϭ 30.3 min (undetect-
able); (Ϫ)-2c: tR ϭ 39.8 min (> 99.9%)]. Ϫ m.p. 178Ϫ179°C (hex-
ane/ethyl acetate). Ϫ IR (KBr): ν˜ ϭ 2930 cmϪ1 (m), 1780 (s, Cϭ
O), 1765 (s, CϭO), 1740 (s, CϭO), 1680 (s, CϭC), 1400 (m), 1345
(m), 1340 (s), 1220 (w), 1183 (s, CϪO), 1100 (s), 1055 (m), 1020 (s,
atoms. The final refinement converged with R ϭ 0.056 and Rw
ϭ
1
0.063 for 208 parameters. The minimum and maximum peaks in
CϪO), 965 (s), 925 (w), 880 (w), 755 (w), 745 (w). Ϫ Its H-NMR
˚
24.6
the final difference Fourier map were Ϫ0.24 and 0.25 eAϪ3. Atomic
spectrum was identical to that of (±)-2c. Ϫ [α]D
ϭ Ϫ354.8 (c ϭ
scattering factors were taken from “International Tables for X-ray
Crystallography”.[37] Supplementary material available includes
lists of atomic coordinates for the non-H atoms, the bond lengths
and angles in (±)-2a, with their e.s.d.s in parentheses.[38]
0.20, CHCl3). Ϫ CD (CH3CN, 40.5 µ): λmax (∆ε) ϭ 206 nm
(ϩ16.5), 229 (Ϫ26.5), 263 (ϩ2.8). Ϫ C18H20O5 (316.4): calcd. C
68.34, H 6.37; found C 68.24, H 6.24. Ϫ 2Ј,8-Diepisorgolactone
[(؊)-2d]: > 99.9% ee determined by HPLC (column: Chiralcel
OD, 4.6 mm ϫ 25 cm; solvent: hexane/2-PrOH, 4:1; flow rate:
0.5 mL/min; detector: 205 nm); (ϩ)-2d: tR ϭ 26.8 min (undetect-
able); (Ϫ)-2d: tR ϭ 29.6 min (> 99.9%)]. Ϫ M.p. 136Ϫ137°C (hex-
ane/ethyl acetate). Ϫ IR (KBr): ν˜ ϭ 2930 cmϪ1 (m), 1775 (s, Cϭ
O), 1750 (s, CϭO), 1740 (s, CϭO), 1675 (s, CϭC), 1350 (m), 1340
(s), 1180 (s, CϪO), 1090 (s), 1020 (s, CϪO), 955 (s), 930 (w), 870
Bioassays:[29] Seeds of Orobanche minor were harvested at the river-
side of Watarase river in Tochigi in 1994 and 1995, dried, and
stored in a refrigerator. Compounds to be tested were dissolved in
a 10Ϫ4  solution of gibberelin A3. For preconditioning, the seeds
were spread on glass fibre filter paper (5 mm diameter), wetted with
a 10Ϫ4  solution of gibberelin A3, and stored in the dark for 10 d
at room temperature. The seeds were then treated with the test solu-
tions. After incubation in the dark for 6 d, the germination rate
was determined under a microscope. In each series of tests, a
10Ϫ4  solution of gibberelin A3 was used as a negative control
and (±)-strigol was used as a positive control. Tests were replicated
4 times.
(w), 750 (w). Ϫ Its 1H-NMR spectrum was identical to that of (±)-
23.4
2d. Ϫ [α]D
ϭ Ϫ185.0 (c ϭ 0.20, CHCl3). Ϫ CD (CH3CN, 41.1
µ): λmax (∆ε) ϭ 217 nm (ϩ8.6), 245 (Ϫ2.9). Ϫ C18H20O5 (316.4):
calcd. C 68.34, H 6.37; found C 68.31, H 6.35.
X-ray Analysis of (±)-10: Crystal size, 0.2 ϫ 0.5 ϫ 0.8 mm. All data
were obtained with a Rigaku AFC-5S automated four-circle dif-
fractometer using graphite-monochromated Mo-Kα radiation. Fi-
nal lattice parameters were obtained from a least-squares refine-
ment using 25 reflections. Crystal data: C12H16O2, Mr ϭ 192.26,
Acknowledgments
monoclinic, space group P21/a, a ϭ 9.020(6), b ϭ 7.494(6), c ϭ
3
˚
˚
15.673(3) A, β ϭ 96.26(3)°, V ϭ 1053.1(8) A , Z ϭ 4, DX ϭ 1.213 g/
cm3, F(000) ϭ 416, µ(Mo-Kα) ϭ 0.756 cmϪ1. The intensities were We thank Dr. C. Hauck (Novartis, Basel) for kindly sending us a
measured using ω/2θ scans up to 45°. Three standard reflections
were monitored every 150 measurements. The data were corrected
for Lorentz and polarization factors. An absorption correction was
applied, but not a decay correction. Of the 1521 independent reflec-
copy of his doctoral dissertation, in which 1H-NMR spectra of
sorgolactone are recorded. (S)-(Ϫ)-Citronellal was a gift from Tak-
asago International Corporation. This work was financially sup-
ported by Kanebo Co., Ltd.
Eur. J. Org. Chem. 1999, 2183Ϫ2194
2193

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Received February 23, 1999
[O99108]
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Eur. J. Org. Chem. 1999, 2183Ϫ2194