Stereoselective Syntheses of (+)-Goniotriol, (+)-8-Acetylgoniotriol, (+)-Goniodiol, (+)-9-Deoxygoniopypyrone, (+)-Altholactone, and (-)-Goniofupyrone

Article abstract of DOI:10.1021/jo970725u

The γ-lactone intermediate (-)-7, derived from (+)-tricarbonyl(η⁶-o-(trimethylsilyl)benzaldehyde)chromium(0) complex, was efficiently converted into the corresponding δ-lactone intermediate (-)-11. This second intermediate has been shown to be a versatile compound for stereoselective syntheses of natural styryllactones possessing a six-membered lactone moiety, isolated from Goniothalamus giganteus, by transforming it into (+)-goniotriol, (+)-8-acetylgoniotriol, (+)-goniodiol, (+)-9-deoxygoniopypyrone, (+)-altholactone, and (-)-goniofupyrone.

Full text of DOI:10.1021/jo970725u

J . Org. Chem. 1997, 62, 6619-6626
6619
Ster eoselective Syn th eses of (+)-Gon iotr iol, (+)-8-Acetylgon iotr iol,
(+)-Gon iod iol, (+)-9-Deoxygon iop yp yr on e, (+)-Alth ola cton e, a n d
(-)-Gon iofu p yr on e
Chisato Mukai,* Syuichi Hirai, and Miyoji Hanaoka*
Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, Kanazawa 920, J apan
Received April 23, 1997
The γ-lactone intermediate (-)-7, derived from (+)-tricarbonyl(η6-o-(trimethylsilyl)benzalde-
hyde)chromium(0) complex, was efficiently converted into the corresponding δ-lactone intermediate
(-)-11. This second intermediate has been shown to be a versatile compound for stereoselective
syntheses of natural styryllactones possessing a six-membered lactone moiety, isolated from
Goniothalamus giganteus, by transforming it into (+)-goniotriol, (+)-8-acetylgoniotriol, (+)-goniodiol,
(+)-9-deoxygoniopypyrone, (+)-altholactone, and (-)-goniofupyrone.
In tr od u ction
Recent publications from McLaughlin’s group1 have
disclosed isolation and characterization of a number of
novel so-called styryllactones from Goniothalamus gi-
ganteus, which were found to be marginally to signifi-
cantly cytotoxic against human tumors.1,2 Because of
their antitumor activities, much effort2-11 has so far been
centered on the development of methodology for the
synthesis of these styryllactones. These styryllactones
can be mainly classified into two groups according to their
structural features, especially the size of the lactone ring.
The first group consists of styryllactones with a five-
membered lactone moiety involving (+)-goniofufurone,
(+)-goniobutenolide A, and (-)-goniobutenolide B, and
the second group is made up of styryllactones having a
Abstract published in Advance ACS Abstracts, August 15, 1997.
(1) (a) El-Zayat, A. A. E.; Ferrighi, N. R.; McKenzie, T. G.; Byrn, S.
F igu r e 1.
R.; Cassady, J . M.; Chang, C.-J .; McLaughlin, J . L. Tetrahedron Lett.
1985, 26, 955. (b) Alkofahi, A.; Ma, W.-W.; Mckenzie, A. T.; Byrn, S.
R.; McLaughlin, J . L. J . Nat. Prod. 1989, 52, 1371. (c) Fang, X.-P.;
Anderson, J . E.; Chang, C.-J .; Fanwick, P. E.; McLaughlin, J . L. J .
Chem. Soc., Perkin Trans. 1 1990, 1655. (d) Fang, X.-P.; Anderson, J .
E.; Chang, C.-J .; McLaughlin, J . L.; Fanwick, P. E. J . Nat. Prod. 1991,
54, 1034.(e) Fang, X.-P.; Anderson, J . E.; Chang, C.-J .; McLaughlin,
J . L. Tetrahedron 1991, 47, 9751. (f) Fang, X.-P.; Anderson, J . E.; Qiu,
X.-X.; Kozlowski, J . F.; Chang, C.-J .; McLaughlin, J . L. Tetrahedron
1993, 49, 1563.
(2) (a) Tadano, K.; Ueno, Y.; Ogawa, S. Chem. Lett. 1988, 111. (b)
Ueno, Y.; Tadano, K.; Ogawa, S.; McLaughlin, J . L.; Alkofahi, A. Bull.
Chem. Soc. J pn. 1989, 62, 2328.
(3) Shing, T. K. M.; Tsui, H.-C.; Zhou, Z.-H. J . Org. Chem. 1995,
60, 3121 and references cited therein.
(4) Yang, Z.-C.; Zhou, W.-C. Heterocycles 1997, 45, 367 and refer-
ences cited therein.
(5) Gesson, J .-P.; J acquesy, J .-C.; Mondon, M. Tetrahedron 1989,
45, 2627 and references cited therein.
(6) Kang, S.-H.; Kim, W.-J . Tetrahedron Lett. 1989, 30, 5915.
(7) (a) Honda, T.; Kametani, T.; Kanai, K.; Tatsuzaki, Y.; Tsubuki,
M. J . Chem. Soc., Perkin Trans. 1 1990, 1733. (b) Tsubuki, M.; Kanai,
K.; Honda, T. J . Chem. Soc., Chem. Commun. 1992, 1640. (c) Tsubuki,
M.; Kanai, K.; Honda, T. Synlett 1993, 653. (d) Tsubuki, M.; Kanai,
K.; Honda, T. Heterocycles 1993, 35, 281.
six-membered lactone functionality. Some representa-
tives of the latter are shown in Figure 1.
In the course of our program directed toward stereo-
selective total syntheses of all types of antitumor styryl-
lactones, we have recently completed the total syntheses
of the γ-lactone natural products12 (+)-goniofufurone, (+)-
goniobutenolide A, and (-)-goniobutenolide B from the
(+)-t r ica r bon yl(η6-o-(t r im et h ylsilyl)ben za ldeh yde)-
chromium(0) complex13 via the common key intermediate
(-)-7. Compound 7 has not only a carbon framework
required for all types of styryllactones but also four
hydroxy groups with different protecting groups. There-
fore, our next endeavor focused on successful modification
of the intermediate 7 for synthesis of six-membered
lactone natural products 1-6 (Figure 1). This paper
describes a highly stereoselective transformation of the
intermediate 7 to styryllactones possessing the δ-lactone
moiety.
(8) Somfai, P. Tetrahedron 1994, 50, 11315.
(9) (a) Surivet, J .-P.; Gore´, J .; Vate`le, J . M. Tetrahedron Lett. 1996,
37, 371. (b) Surivet, J .-P.; Vate`le, J .-M. Tetrahedron Lett. 1996, 37,
4373. (c) Surivet, J .-P.; Gore´, J .; Vate`le, J . M. Tetrahedron 1996, 52,
14877. (d) Surivet, J .-P.; Volle, J .-N.; Vate`le, J .-M. Tetrahedron:
Asymmetry 1996, 7, 3305. (e) Surivet, J .-P.; Vate`le, J .-M. Tetrahedron
Lett. 1997, 38, 819.
(10) (a) Saito, S.; Harunari, T.; Shimamura, N.; Asahara, M.;
Morikawa, T. Synlett 1992, 325. (b) Murphy, P. J . J . Chem. Soc., Chem.
Commun. 1992, 1096. (c) Prakash, K. R. C.; Rao, S. P. Tetrahedron
1993, 49, 1505. (d) Prakash, K. R. C.; Rao, S. P. Synlett 1993, 123. (e)
Ye, J .; Bhatt, R. K.; Falck, J . R. Tetrahedron Lett. 1993, 34, 8007.
(11) (a) Xu, D.; Sharpless, K. B. Tetrahedron Lett. 1994, 35, 4685.
(b) Ko, S. Y.; Lerpiniere, J . Tetrahedron Lett. 1995, 36, 2101. (c) Kotora,
M.; Negishi, E. Tetrahedron Lett. 1996, 37, 9041.
Resu lts a n d Discu ssion
The first concern and most significant requirement for
our synthetic plan of the δ-lactone natural products 1-6
(12) (a) Mukai, C.; Kim, I. J .; Hanaoka, M. Tetrahedron Lett. 1993,
34, 6081. (b) Mukai, C.; Hirai, S.; Kim, I. J .; Kido, M.; Hanaoka, M.
Tetrahedron 1996, 52, 6547.
(13) (a) Mukai, C.; Cho, W. J .; Hanaoka, M. Tetrahedron Lett. 1989,
30, 7435. (b) Mukai, C.; Cho, W. J .; Kim, I. J .; Kido, M.; Hanaoka, M.
Tetrahedron 1991, 47, 3007.
S0022-3263(97)00725-1 CCC: $14.00 © 1997 American Chemical Society

6620 J . Org. Chem., Vol. 62, No. 19, 1997
Mukai et al.
Sch em e 1a
Sch em e 2a
aReaction conditions: (a) TMS-imidazole, CH2Cl2, 97%; (b)
DIBALH, Et2O, -78 °C; (c) tBuOK, THF, -70 °C; (d) PDC, AcONa,
CH2Cl2; (e) 10% HCl, MeOH, 69% from 8.
from the intermediate 7 was an efficient transformation
of the γ-lactone moiety of the latter to the corresponding
δ-lactone derivative. Direct conversion of 7 into 11 under
acidic or basic conditions, however, gave decomposed
products and/or recovery of a starting material. Kita-
zume14 and co-workers have recently reported on a useful
method for ring transformation of butenolide derivatives
into pentenolide ones through lactol intermediates with
migration of the silyl group (Scheme 1). By taking
advantage of Kitazume’s procedure,14 we tried to convert
7 into 11. The secondary hydroxy group of (-)-7 was first
protected with the TMS group to give 8 in 97% yield.
Because of its instability, 8 was immediately reduced
with DIBALH to afford the five-membered lactol 9, which
on exposure to potassium tert-butoxide at -70 °C under-
went ring transformation accompanied with silyl group
migration producing the desired six-membered lactol 10
predominantly. Oxidation of a mixture of 9 and 10 with
PDC was followed by hydrolysis with 10% hydrochloric
acid to provide the δ-lactone derivative (-)-11 in 69%
overall yield from 8 together with a small amount of 7
(5%).
aReaction conditions: (a) PPh3, DEAD, p-NO2C6H4CO2H, C6H6,
12 (96%), 19 20 (49%); (b) 1% aq K2CO3, THF, 74%; (c)
NaI, BF3‚OEt2, CM3CN, 0 °C, (ii) TiCl4, CH2Cl2, 65%; (d) Ac2O,
DMAP, CH2Cl2, 13 14 (96%), 11 16 (100%); (e) TBAF-HF,
THF, 86%; (f) TiCl4, CH2Cl2, 15 2 (77%), 22 4 (96%); (g) Zn-
Hg, satd HCl in Et2O, -20 °C, 88%; (h) DBU, THF, 90%; (i) NaI,
BF3‚OEt2, CM3CN, 0 °C, 97%; (j) (i) 1 N LiOH, THF, (ii) TFA, THF,
(iii) DBU, THF, 84%.
11
[R]21D +118 (c 0.1, MeOH)] [ lit.1b mp 170 °C, [R]25D +121
(MeOH) ] in 65% yield.
On the other hand, 13 was acetylated with acetic
anhydride to give the acetate (+)-14 in 96% yield. It was
predicted that the C2′-hydroxy functionality or its anion
of 14 would intramolecularly attack the acetyl group on
the C4-position resulting in formation of 15, a precursor
of 2 under suitable conditions. Thus 14 was treated with
tetra-n-butylammonium fluoride (TBAF) in THF (basic
condition), however, to give only decomposed products.
When the reaction medium was changed from basic to
acidic conditions, 14 was again exposed to TBAF in the
presence of hydrofluoric acid in THF (ca. pH 5) to provide
the acyl group migrated product (+)-15 in 86% yield.
Acetyl group migration was easily confirmed by compari-
son of the 1H NMR spectra of 14 and 15, especially
chemical shift consideration. C4-H of 14 appeared at δ
5.27 as a doublet and C2′-H resonated at δ 4.96 as a
Syn t h eses of (+)-Gon iot r iol, (+)-8-Acet ylgon io-
tr iol, (+)-Gon iod iol, a n d (+)-9-Deoxygon iofu p yr on e.
With the potential δ-lactone intermediate 11 for target
natural products in hand, we completed the syntheses
of monocyclic natural products 1, 2, and 3 as well as
dioxabicyclo[3.3.1]nonanone one 4. Inversion of the
allylic hydroxy functionality of 11 was carried out under
standard Mitsunobu conditions15 using p-nitrobenzoic
acid to furnish the p-nitrobenzoate (+)-12 in 96% yield,
which was subsequently hydrolyzed with 1% aqueous
potassium carbonate to produce (+)-13 in 74% yield with
inverted stereochemistry at the allylic position (Scheme
2). Successive desilylation and debenzylation was real-
16
ized by treatment with (i) sodium iodide/BF3•OEt2 and
17
(ii) TiCl4 to afford (+)-goniotriol (1) [mp 169-170 °C,
1
doublet. In the H NMR spectrum of 15, both diagnostic
a higher field shift of C4-H (δ 5.27 to 4.39-4.34) and a
lower field shift of C2′-H (δ 4.96 to 6.08) were observed.
(14) Yamazaki, T.; Mizutani, K.; Kitazume, T. J . Org. Chem. 1993,
58, 4346.
(15) (a) Mitsunobu, O. Synthesis 1981, 1. (b) Martin, S. F.; Dodge,
J . A. Tetrahedron Lett. 1991, 32, 3017. (c) Ina, H.; Kibayashi, C. J .
Org. Chem. 1993, 58, 52. (d) Barks, J . M.; Knight, D. W.; Weingarten,
G. G. J . Chem. Soc., Chem. Commun. 1994, 719.
Finally (+)-8-acetylgoniotriol (2) [mp 159-161 °C, [R]24
D
+37.0 (c 0.4, EtOH)][ lit.1c mp 158-159 °C, [R]22 +30 (c
D
0.4 EtOH)] was obtained in 77% yield from 15 under
debenzylation conditions with TiCl4. Synthetic (+)-
goniotriol (1) and (+)-8-acetylgoniotriol (2) were identical
(16) Vankar, Y. D.; Rao, C. T. J . Chem. Res. Synop. 1985, 232.
(17) Hori, H.; Nishida, Y.; Ohrui, H. J . Org. Chem. 1989, 54, 1346.

Syntheses of Styryllactones
J . Org. Chem., Vol. 62, No. 19, 1997 6621
with natural compounds by comparison with spectral as
well as physical data.
made when we started out this program. Therefore, our
effort was directed toward transformation of the dioxa-
bicyclo[4.3.0]nonenone derivative (+)-24 into the pro-
posed structure for goniofupyrone, thereby the absolute
stereochemistry would be established unambiguously.
Stereochemical outcome for introduction of the hydroxy
functionality to the R,â-unsaturated moiety of 24 was
first worked out by employing racemic 24. cis-Dihy-
droxylation of (()-24 with osmium tetraoxide20 afforded
the diol (()-25 in 79% yield, acetylation of which provided
the diacetate (()-26 in 94% yield. NOE experiment of
(()-26 revealed 4.5% enhancement between C4-H and C9-
H. This observation strongly indicated that dihydroxy-
lation occurred from the R-face (convex face) resulting
in formation of 26 exclusively. Furthermore, X-ray
crystallographic analysis21 of (()-26 unambiguously con-
firmed the relative stereochemistry of 26 as depicted in
Scheme 3.25
In order to convert the intermediate 11 to (+)-goniodiol
(3) and (+)-9-deoxygoniopypyrone (4), removal of the C4-
hydroxy group was essential. Treatment of 11 with acetic
anhydride afforded (-)-16 quantitatively, which was then
exposed to zinc amalgam18 in Et2O in the presence of
hydrogen chloride at -20 °C to furnish the dehydrox-
ylated product (+)-17 accompanied with double-bond
migration in 88% yield. Isomerization of the â,γ-
unsaturated lactone structure of 17 to the corresponding
R,â one was easily achieved by DBU treatment at room
temperature to leave (+)-18 in 90% yield, deprotection
of which was undertaken according to the procedure
described for conversion of 13 into 1 to produce (+)-
goniodiol (3) [[R]21 +72.7 (c 0.3, CHCl3)] [lit.1d [R]22
D
D
+74.4 (c 0.3 CHCl3)] in 97% yield via 19.
Synthesis of (+)-9-deoxygoniopypyrone (4) required
inversion of the alcohol moiety at the benzylic position
of 19. Although Mitsunobu reaction15 of 19 under several
typical conditions was examined, the condition that
provided a satisfactory chemical yield is not established
yet. The best result so far obtained is production of (-)-
20 in 49% yield when 19 was treated with triphenylphos-
phine, diethyl azodicarboxylate (DEAD), and p-nitroben-
zoic acid in benzene at room temperature. Hydrolysis
of 20 with 1 N lithium hydroxide in THF at room
temperature unexpectedly gave fairly polar compounds
which might arise from removal of the p-nitrobenzoate
moiety and concomitant cleavage of the δ lactone ring.
On treatment with trifluoroacetic acid, the plausible
dihydroxy acid derivatives underwent ring closure to
provide (-)-22 in 59% yield along with 21 in 31% yield.
Compound 21 was shown to be easily converted into 22
in 80% yield when treated with DBU. Thus, 22 was
formed in 84% overall yield from 20. (+)-9-Deoxygo-
By analogy to conversion of racemic 24 into 25 in a
model study, we prepared (+)-25 from (+)-24 in 75%
yield. Selective removal of the C4-OH group of 25 was
undertaken by samarium diiodide22 in the presence of
ethylene glycol to furnish (+)-27 in 62% yield. It should
be mentioned that no reaction took place when methanol
was used instead of ethylene glycol and 25 was com-
pletely recovered. Debenzylation of 27 with SnCl4 yielded
(-)-6 [[R]18 -6.9 (c 0.15, CHCl3)] [lit.1e [R]25 -5.0 (c 0.1
D
D
CHCl3)] in 80% yield. Spectral data and the specific
rotation of (-)-6 were unexpectedly in good accordance
with those of natural (-)-goniofupyrone. The diacetate
(-)-28, derived from 6, again exhibited similar spectral
data to those1e of the diacetate derivative of natural
goniofupyrone. Thus, it was at this stage that we noticed
that natural (-)-goniofupyrone should have the relative
as well as absolute configuration shown in (-)-6 rather
than 31.
In order to confirm that unambiguously, we completed
a synthesis of 31. A direct and straightforward method
such as Mitsunobu reaction and SN2 type displacement
for inversion of the C5-hydroxy group of 27 was unsuc-
cessful. These negative results could be tentatively
rationalized in terms of (i) the â-hydroxy carbonyl
structure of 27 leading to easy â-elimination (ii) and/or
steric hindrance associated with approach of the nucleo-
phile from the concave face. Therefore, the lactone
moiety of 27, on treatment with DIBALH, was first
converted into the lactol derivative, which was subse-
quently transformed into the corresponding methyl acetal
29 as a mixture of diastereoisomers (ca. 1:1 mixture) in
77% yield. The acetal 29 was oxidized with tetra-n-
propylammonium perruthenate (TPAP)23 to give the C5-
carbonyl derivative, reduction of which with lithium
niopypyrone (4) [mp 201-204 °C, [R]16 +12.0 (c 0.10,
D
EtOH)] [lit.1d mp 203-204 °C, [R]22 +12 (c 0.1 EtOH)]
D
was synthesized in 96% yield from 22 by TiCl4 treatment.
Synthetic (+)-goniodiol and (+)-9-deoxygoniopypyrone
were identical with natural compounds, respectively, by
comparison with spectral and physical data.
Syn t h eses of (+)-Alt h ola ct on e a n d (-)-Gon io-
fu p yr on e.19 The allylic alcohol of the key intermediate
11 was tosylated by conventional procedures to give the
tosylate (-)-23 in 96% yield. Desilylation of 23 with
TBAF brought about spontaneous ring closure to provide
the dioxabicyclo[4.3.0]nonenone derivative (+)-24 in 89%
yield, which was subsequently exposed to SnCl417 produc-
ing (+)-altholactone (5) [mp 108-109 °C, [R]25 +182 (c
D
0.10, EtOH)][ lit.1a mp 110 °C, [R]25D +184.7 (c 0.1 EtOH)]
in 98% yield.
(-)-Goniofupyrone was isolated from the stem bark of
G. giganteus grown in Thailand in 1991.1e Its structure
was deduced as (1R*,5R*,6R*,8S*, 9S*)-5,9-dihydroxy-
8-phenyl-2,7-dioxabicyclo[4.3.0]nonan-3-one (31) on the
basis of its spectroscopic analysis involving comparison
with H NMR data of the related compound, altholactone
(5). No reports on synthesis and determination of
absolute stereochemistry of (-)-goniofupyrone had been
(20) (a) Hanessian, S.; Murray, P. J . J . Org. Chem. 1987, 52, 1170.
(b) Keck, G. E.; Romer, D. R. J . Org. Chem. 1993, 58, 6083. (c) Naruse,
M.; Aoyagi, S.; Kibayashi, C. J . Org. Chem. 1994, 59, 1358.
(21) Crystal data: C24H24O8, M ) 440.45, triclinic, a ) 10.846(2) Å,
b ) 11.527(2) Å, c ) 10.190(2) Å, R ) 114.14(1)°, â ) 102.64(2)°, γ )
71.33(2)°, V ) 1095.8 (4) Å3, Z ) 2, Dc ) 1.335 g/cm3, space group P1
(No. 2), µ(Mo KR) ) 0.94 cm-1. A colorless prisms crystal, ca. 0.7 × 0.7
× 0.5 mm, was mounted on a glass fiber. All measurements were made
on a Rigaku AFC5R diffractometer. The cell dimensions and intensities
were refined by the least-squares method, using 25 reflections on the
diffractometer with Mo KR radiation with ω-scan mode for 2θ less than
55.1°. The structure was solved by direct method (MITHRIL method).
The final cycle of full-matrix least-squares refinement was based on
3018 observed reflections. The final R value was 0.043.
1
(18) (a) Felkin, I. E.; Sarda, P. Tetrahedron Lett. 1972, 725. (b)
Corey, E. J .; Pyne, S. G.; Su, W.-g. Tetrahedron Lett. 1983, 24, 4883.
(c) Honda, T.; Kametani, T.; Kanai, K.; Tatsuzaki, Y.; Tsubuki, M. J .
Chem. Soc., Perkin Trans. 1 1990, 1733.
(19) A part of the work on a synthesis of (-)-goniofupyrone was
published in a preliminary communication: Mukai, C.; Hirai, S.; Kim,
I. J .; Hanaoka, M. Tetrahedron Lett. 1996, 37, 5389.
(22) (a) Molander, G. A.; Hahn, G. J . Org. Chem. 1986, 51, 1135.
(b) Kusuda, K.; Inanaga, J .; Yamaguchi, M. Tetrahedron Lett. 1989,
30, 2945. (c) Reed, A. D.; Hegedus, L. S. J . Org. Chem. 1995, 60, 3787.
(23) Ley, S. V.; Norman, J .; Griffith, W. P.; Marsden, S. P. Synthesis
1994, 639.

6622 J . Org. Chem., Vol. 62, No. 19, 1997
Mukai et al.
Sch em e 3a
and (-)-goniofupyrone. In addition, synthesis of (-)-
goniofupyrone elucidated its absolute stereochemistry. In
connection with previous efforts on total syntheses of (+)-
goniofufurone, (+)-goniobutenolide A, and (-)-goniobuteno-
lide B from our laboratory, we have now accomplished
syntheses of all types of alicyclic antitumor styryllactone
natural products except for eight-membered ones, gonio-
heptolides A and B from optical active tricarbonyl(η6-o-
(trimethylsilyl)benzaldehyde)chromium(0) complex via
two significant intermediates in a stereoselective manner.
Exp er im en ta l Section
Melting points are uncorrected. IR spectra were measured
in CHCl3 unless otherwise mentioned. 1H NMR spectra were
taken in CDCl3 unless otherwise indicated. CHCl3 (7.26 ppm)
was used as an internal standard for silyl compounds. TMS
was employed as an internal standard for other compounds.
13C NMR spectra were recorded in CDCl3 with CDCl3 (77.00
ppm) as an internal standard. CH2Cl2 was freshly distilled
from phosphorus pentoxide and THF from sodium diphenyl
ketyl, prior to use. Silica gel (silica gel 60, 230-400 mesh,
Merck) was used for chromatography. Organic extracts were
dried over anhydrous Na2SO4.
(-)-(1′S,2′R,4R,5R)-5-(1′-(Ben zyloxy)-2′-((ter t-b u t yld i-
m et h ylsilyl)oxy)-2′-p h en ylet h yl)-4-h yd r oxy-2-p en t en -5-
olid e (11). To a solution of (-)-7 (395 mg, 0.87 mmol) in
CH2Cl2 (8.7 mL) was added TMS-imidazole (0.15 mL, 1.04
mmol) at rt. After being stirred for 10 h, the reaction mixture
was washed with water and brine, dried, and concentrated to
leave the residual oil, which was passed through a short pad
of silica gel with hexane-AcOEt (20:1) to give 8 (444 mg,
97%): IR 1755 (CO) cm-1; 1H NMR δ 7.33-7.25 (m, 8H), 7.16-
7.14 (m, 2H), 6.89 (dd, 1H, J ) 5.9, 1.5 Hz), 6.02 (dd, 1H, J )
5.9, 2.0 Hz), 5.19 (ddd, 1H, J ) 4.9, 2.0, 1.5 Hz), 4.91 (d, 1H,
J ) 4.9 Hz), 4.48 (d, 1H, J ) 11.2 Hz), 4.29 (t, 1H, J ) 4.9
Hz), 4.24 (d, 1H, J ) 11.2 Hz), 3.59 (t, 1H, J ) 4.9 Hz), 0.91
(s, 9H), 0.09 (s, 3H), 0.07 (s, 9H), -0.13 (s, 3H); 13C NMR δ
172.97, 154.18, 141.89, 137.72, 128.19, 128.10, 127.66, 126.86,
122.53, 85.14, 83.38, 74.83, 74.32, 74.13, 25.84, 18.17, 0.78,
-4.58, -4.72. DIBALH (1.0 M hexane solution; 1.0 mL, 1.0
mmol) was added to a solution of 8 (444 mg, 0.85 mmol) in
dry Et2O (8.5 mL) at -78 °C. The reaction mixture was kept
at the same temperature for 10 min, then quenched by addition
of a saturated Na2SO4 solution, passed through a short pad of
Celite, dried, and concentrated to dryness. The crude 9 was
dissolved in THF (17 mL), to which KOBut (258 mg, 2.11 mmol)
was added at -60 °C. The reaction mixture was stirred at
the same temperature for 5 h, diluted with a saturated NH4Cl
solution, and extracted with AcOEt. The organic layer was
dried and evaporated off to give a crude mixture of 9 and 10,
which was dissolved in CH2Cl2 (8.5 mL). AcONa (777 mg, 8.5
mmol), 4 Å molecular sieves (1.7 g), and PDC (318 mg, 0.85
mmol) were added to a mixture of 9 and 10 in CH2Cl2. The
reaction mixture was stirred at rt for 4 h, passed through a
short pad of Florisil, and concentrated to dryness. To a
solution of the residue in MeOH (7.8 mL) was added a 10%
HCl solution (1.0 mL) at rt. After being stirred 30 min, the
reaction mixture was neutralized with a saturated NaHCO3
solution and extracted with AcOEt. The organic layer was
washed with water and brine, dried, and concentrated to leave
the residual oil which was chromatographed with hexane-
AcOEt (10 :1) to afford (-)-11 (266 mg, 69% from 8) and (-)-7
(19.6 mg, 5% from 8). (-)-11: colorless crystals; mp 183-184
aReaction conditions: Reaction conditions: (a) TsCl, DMAP,
CH2Cl2, 96%; (b) TBAF-HF THF, 89%; (c) SnCl4, CH2Cl2, 40 °C,
24
5 (98%), 27
6 (80%), 30
31 (74%); (d) cat. OsO4, NMO,
26 (94%), 6
32 (89%); (f) SmI2, ethylene glycol, THF 62%; (g)
acetone-H2O, 75%; (e) Ac2O, DMAP, CH2Cl2, 25
28 (76%), 31
(i) DIBALH, Et2O, -78 °C, (iii) p-TsOH, MeOH, 77%; (h) (i) TPAP,
NMO, MS4Å, CH3CN, (ii) LAH, THF, -20 °C, (iii) BF3‚OEt2,
m-CPBA, CH2Cl2, 40 °C, 61%.
aluminum hydride (LAH) was followed by exposure to
24
m-CPBA in the presence of BF3‚OEt2 regenerating the
lactone moiety to leave (-)-30 in 61% overall yield from
29 along with (-)-27 (14%). Debenzylation of 30 with
SnCl4 afforded (-)-31 [[R]18D -59.2 (c 0.1, CHCl3)] in 74%
yield. Acetylation of 31 under the standard conditions
gave (-)-32. Comparison of spectral and physical data
of 31 and 32 with those of natural goniofupyrone and its
diacetate, respectively, disclosed obvious differences not
only in chemical shift and coupling constant for some
protons but also in specific rotation. Thus, we concluded
that (-)-goniofupyrone possesses the (1S,5R,6S,8R,9R)-
5,9-dihydroxy-8-phenyl-2,7-dioxabicyclo[4.3.0]nonan-3-
one (6) structure as depicted in Scheme 3.
Con clu sion
We have succeeded in an efficient transformation of
the previously prepared γ-lactone intermediate 7 to the
δ-lactone compound 11. The latter intermediate 11 has
been found to be a useful key compound for stereoselec-
tive syntheses of (+)-goniotriol, (+)-8-acetylgoniotriol, (+)-
goniodiol, (+)-9-deoxygoniopypyrone, (+)-altholactone,
°C (MeOH); [R]25 -36.3 (c 0.40, CHCl3); IR 3600, 1730 (CO)
D
cm-1; 1H NMR δ 7.53-7.51 (m, 2H), 7.41-7.31 (m, 6H), 7.12-
7.10 (m, 2H), 6.70 (dd, 1H, J ) 10.3, 2.0 Hz), 5.88 (dd, 1H, J
) 10.3, 2.0 Hz), 4.97 (d, 1H, J ) 8.8 Hz), 4.56 (dd, 1H, J )
10.3, 1.5 Hz), 4.32 (m, 1H), 4.01 (d, 1H, J )11.7 Hz), 3.65 (dd,
1H, J ) 8.8, 1.5 Hz), 3.36 (d, 1H, J ) 11.7 Hz), 0.97 (d, 1H, J
) 3.0 Hz), 0.83 (s, 9H), 0.05 (s, 3H), -0.21 (s, 3H); 13C NMR δ
162.81, 150.43, 142.70, 137.49, 128.92, 128.57, 128.34, 128.25,
128.02, 127.73, 119.60, 80.50, 79.18, 73.35, 72.43, 62.91, 25.71,
17.94, -4.58, -5.16; CIMS m/ z (%) 455 (M+ + 1, 45), 348 (6),
(24) Greico, P. A.; Oguri, T.; Yokoyama, Y. Tetrahedron Lett. 1978,
419.
(25) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, U.K.

Syntheses of Styryllactones
J . Org. Chem., Vol. 62, No. 19, 1997 6623
323 (100), 305 (8), 221 (15), 91 (7). Anal. Calcd for
C26H34O5Si: C, 68.69; H, 7.54. Found: C, 68.42; H, 7.48.
1, 12), 233 (47), 215 (12), 137 (36), 119 (13), 107 (62), 97 (100).
Anal. Calcd for C13
H, 5.91.
H14O5: C, 62.39; H, 5.64. Found: C, 62.20;
(+)-(1′S,2′R,4S,5S)-5-(1′-(Ben zyloxy)-2′-((ter t-b u t yld i-
m eth ylsilyl)oxy)-2′-p h en yleth yl)-4-((p-n itr oben zoyl)oxy)-
2-p en ten -5-olid e (12). DEAD (0.06 mL, 0.37 mmol) was
added to a solution of (-)-11 (55.6 mg, 0.12 mmol), triphen-
ylphosphine (96.4 mg, 0.37 mmol), and p-nitrobenzoic acid
(61.8 mg, 0.37 mmol) in dry benzene (2.4 mL). After being
stirred for 5 h at rt, the reaction mixture was diluted with
water and extracted with AcOEt, which was washed with a
saturated NaHCO3 solution, water, and brine, dried, and
concentrated to dryness. The residue was chromatographed
with hexane-AcOEt (20:1) to afford (+)-12 (70.9 mg, 96%) as
(+)-(1′S,2′R,4S,5S)-4-Acetoxy-5-(1′-(ben zyloxy)-2′-((ter t-
b u t yld im e t h ylsilyl)oxy)-2′-p h e n yle t h yl)-2-p e n t e n -5-
olid e (14). A solution of (+)-13 (6.3 mg, 0.01 mmol) and
4-N,N-dimethylaminopyridine (DMAP) (3.5 mg, 0.03 mmol)
and Ac2O (one drop) in CH2Cl2 (0.2 mL) was stirred at rt for
10 min, diluted with water, and extracted with CH2Cl2. The
organic layer was washed with water and brine, dried, and
concentrated to dryness. Chromatography of the residue with
hexane-AcOEt (20:1) gave (+)-14 (6.6 mg, 96%) as a colorless
1
oil: [R]24 +139 (c 0.10, CHCl3); IR 1735 (CO) cm-1; H NMR
D
a colorless oil; [R]26D +135 (c 0.33, CHCl3); IR 1730 (CO) cm-1
;
δ 7.34-7.22 (m, 10H), 6.92 (dd, 1H, J ) 9.8, 4.9 Hz), 6.07 (d,
1H, J ) 9.8 Hz), 5.27 (dd, 1H, J ) 4.9, 3.4 Hz), 4.96 (d, 1H, J
) 4.4 Hz), 4.81 (dd, 1H, J ) 6.4, 3.4 Hz), 4.68 (d, 1H, J ) 11.2
Hz), 4.35 (d, 1H, J ) 11.2 Hz), 3.91 (dd, 1H, J ) 6.4, 4.4 Hz),
1.69 (s, 3H), 0.90 (s, 9H), 0.08 (s, 3H), -0.11 (s, 3H); 13C NMR
δ 169.52, 162.46, 141.34, 140.75, 137.93, 128.30, 128.25,
127.98, 127.62, 127.53, 126.49, 124.28, 82.32, 78.29, 74.97,
74.25, 63.16, 25.86, 20.11, 18.19, -4.76, -4.90; FABMS m/ z
(%) 497 (M+ + 1,11), 323 (50), 305 (39), 289 (26), 221 (100),
209 (27), 193 (28), 181 (52), 165 (23), 154 (38), 136 (50), 117
(33), 115 (26), 107 (35), 105 (53), 91 (100), 73 (100). Anal. Calcd
for C28H36O6Si: C, 67.71; H, 7.31. Found: C, 67.49; H, 7.33.
1H NMR δ 8.12 (d, 2H, J ) 8.2 Hz), 7.80 (d, 2H, J ) 8.2 Hz),
7.32-7.14 (m, 7H), 7.09 (dd, 1H, J ) 9.8, 5.9 Hz), 7.01 (t, 2H,
J ) 7.3 Hz), 6.88 (t, 1H, J ) 7.3 Hz), 6.20 (d, 1H, J ) 9.8 Hz),
5.46 (dd, 1H, J ) 5.9, 2.9 Hz), 5.04 (d, 1H, J ) 3.9 Hz), 4.96
(dd, 1H, J ) 6.4, 2.9 Hz), 4.69 (d, 1H, J ) 11.2 Hz), 4.47 (d,
1H, J ) 11.2 Hz), 4.01 (dd, 1H, J ) 6.4, 3.9 Hz), 0.90 (s, 9H),
0.09 (s, 3H), -0.10 (s, 3H); 13C NMR δ 150.55, 141.01, 140.02,
137.63, 133.68, 130.76, 128.25, 127.96, 127.67, 127.28, 125.88,
125.21, 123.15, 82.27, 78.53, 74.92, 74.02, 64.13, 25.84, 18.17,
-4.85, -4.90; CIMS m/ z (%) 604 (M+ + 1, 11), 472 (19), 439
(74), 437 (36), 331 (12), 329 (23), 323 (11), 307 (100), 237 (15),
221 (34), 215 (21), 168 (10), 147 (11), 138 (53), 133 (31), 107
(74), 91 (22). Anal. Calcd for C33H37O8NSi: C, 65.65; H, 6.18;
N, 2.32. Found: C, 65.65; H, 6.50; N, 2.31.
(+)-(1′R ,2′R ,4S ,5R )-5-(2′-Ace t oxy-1′-(b e n zyloxy)-2′-
p h en yleth yl)-4-h yd r oxy-2-p en ten -5-olid e (15). To a solu-
tion of (+)-14 (33.3 mg, 0.07 mmol) in THF (1.4 mL) was added
a solution of TBAF-hydrofluoric acid (0.7 mL; prepared from
1.0 M TBAF in a THF solution and 47% hydrofluoric acid, ca.
pH 5 solution) at rt. The reaction mixture was stirred for 3.5
h at the same temperature, diluted with water, and extracted
with AcOEt. The organic layer was washed with water and
brine, dried, and concentrated to dryness. Chromatography
of the residue with hexane-AcOEt (3:1) gave (+)-15 (22.2 mg,
86%). (+)-15: colorless crystals; 125-127 °C (hexane-
MeOH); [R]22D +17.5 (c 0.10, CHCl3); IR 3400 (OH), 1730 (CO)
(+)-(1′S,2′R,4S,5R)-5-(1′-(Ben zyloxy)-2′-((ter t-b u t yld i-
m et h ylsilyl)oxy)-2′-p h en ylet h yl)-4-h yd r oxy-2-p en t en -5-
olid e (13). To a solution of (+)-12 (6.8 mg, 0.01 mmol) in THF
(1.0 mL) was added a 1% K2CO3 solution (0.5 mL) at 0 °C.
The reaction mixture was stirred at rt for 4 h, diluted with
water, and extracted with AcOEt. The organic layer was
washed with water and brine, dried, and concentrated to
dryness. The residue was chromatographed with hexane-
AcOEt (10:1) to afford (+)-13 (3.8 mg, 74%). (+)-13: colorless
crystals; mp 175-176 °C (MeOH); [R]28D +62.8 (c 0.25, CHCl3);
IR 3450 (OH), 1730 (CO) cm-1; 1H NMR δ 7.47-7.33 (m, 5H),
7.25-7.23 (m, 3H), 7.04-7.01 (m, 2H), 6.93 (dd, 1H, J ) 9.8,
5.9 Hz), 6.10 (d, 1H, J ) 9.8 Hz), 4.98 (d, 1H, J ) 7.8 Hz),
4.74 (t, 1H, J ) 3.4 Hz), 4.38 (m, 1H; D2O; dd, J ) 5.9, 3.4
Hz), 4.25 (d, 1H, J )10.3 Hz), 3.92 (dd, 1H, J ) 7.8, 3.4 Hz),
3.74 (d, 1H, J ) 10.3 Hz), 3.42 (d, 1H, J ) 4.9 Hz), 0.84 (s,
9H), 0.06 (s, 3H), -0.20 (s, 3H); 13C NMR δ 163.13, 144.28,
141.56, 136.82, 128.43, 128.32, 128.25, 127.98, 127.62, 122.61,
83.83, 78.04, 74.54, 73.59, 62.52, 25.75, 18.03, -4.54, -5.01;
CIMS m/ z (%) 455 (M+ + 1, 15), 323 (100), 221 (12), 215 (6),
91 (7). Anal. Calcd for C26H34O5Si: C, 68.69; H, 7.54. Found:
C, 68.62; H, 7.57.
1
cm-1; H NMR δ 7.49-7.22 (m, 10H), 6.90 (dd, 1H, J ) 9.8,
5.4 Hz), 6.09 (d, 1H, J ) 9.8 Hz), 6.08 (d, 1H, J ) 5.4 Hz),
4.61 (d, 1H, J ) 11.2 Hz), 4.39-4.34 (m, 3H), 4.22 (t, 1H, J )
5.4 Hz), 2.95 (brs, 1H), 2.06 (s, 3H); 13C NMR δ 170.12, 162.57,
143.58, 137.32, 136.37, 128.79, 128.55, 128.43, 128.39, 128.14,
127.96, 122.82, 79.64, 79.59, 75.13, 74.18, 61.22, 21.10; CIMS
m/ z (%) 383 (M+ + 1, 22), 323 (100), 307 (16), 233 (12), 215
(31), 107 (31), 91 (19). Anal. Calcd for C22H22O6: C, 69.10;
H, 5.80. Found: C, 68.90; H, 5.85.
(+)-(1′R,2′R,4S,5R)-5-(2′-Acetoxy-1′-h yd r oxy-2′-p h en yl-
et h yl)-4-h yd r oxy-2-p en t en -5-olid e [8-a cet ylgon iot r iol
(2)]: colorless crystals (77%); mp 159-161 °C (hexane-
AcOEt); [R]24 +37.0 (c 0.40, EtOH) [lit.1c mp 158-159 °C
D
(hexane-AcOEt), [R]22 +30 (c 0.4, EtOH)]; IR (KBr) 3550
D
(OH), 3400 (OH), 1725 (CO), 1695 (CO) cm-1; 1H NMR(acetone-
d6) δ 7.50-7.28 (m, 5H), 7.01 (dd, 1H, J ) 9.8, 5.4 Hz), 6.01
(d, 1H, J ) 9.8 Hz), 5.86 (d, 1H, J ) 7.3 Hz), 4.57 (dd, 1H, J
) 5.4, 3.4 Hz), 4.49 (t, 1H, J ) 3.4 Hz), 4.46 (dd, 1H, J ) 7.3,
3.4 Hz), 2.84 (brs, 2H), 2.00 (s, 3H); 13C NM(acetone-d6) δ
170.06, 163.84, 145.50, 139.64, 129.39, 129.14, 123.38, 78.72,
75.07, 74.03, 63.57, 21.36; EIMS m/ z (%) 292 (M+, 0.3), 149
(34), 143 (25), 126 (80), 120 (10), 107 (100), 97 (51), 91 (43).
Anal. Calcd for C15H16O6: C, 61.64; H, 5.52. Found: C, 61.76;
H, 5.77.
(+)-(1′R ,2′R ,4S ,5R )-4-H yd r oxy-5-(1′,2′-d ih yd r oxy-2′-
p h en yleth yl)-2-p en ten -5-olid e [Gon iotr iol (1)]. To a solu-
tion of (+)-13 (48.4 mg, 0.11 mmol) and NaI (49.6 mg, 0.33
mmol) in dry CH3CN (1.0 mL) was added BF3‚OEt2 (1.0 M
CH3CN solution; 0.30 mL, 0.30 mmol) slowly at 0 °C. After
20 min, the reaction mixture was diluted with a saturated
Na2S2O3 solution and extracted with CH2Cl2. The organic
layer was washed with water and brine, dried, and concetrated
to leave the residual oil, which was taken up in CH2Cl2 (5.0
mL). TiCl4 (1.0 M CH2Cl2 solution; 1.0 mL, 1.0 mmol) was
addded to the above CH2Cl2 solution and the reaction mixture
was stirred at rt for 30 min, diluted with a saturated NaHCO3
solution, and extracted with CH2Cl2. The organic layer was
washed with water and brine, dried, and concentrated to give
the crude solids which were recrystallized from hexane-AcOEt
to afford (+)-1 (17.2 mg, 65%). (+)-1 (goniotriol): colorless
crystals; mp 169-171 °C (hexane-EtOH); [R]21D +118 (c 0.10,
(-)-(1′S,2′R,4R,5S)-4-Acetoxy-5-(1′-ben zyloxy-2′-((ter t-
b u t yld im e t h ylsilyl)oxy)-2′-p h e n yle t h yl)-2-p e n t e n -5-
olid e (16): colorless needles (100%); mp 106-108 °C (hexane);
[R]21 -78.1 (c 0.50, CHCl3); IR 1735 (CO) cm-1 1H NMR δ
;
D
7.48-7.46 (m, 2H), 7.38-7.29 (m, 3H), 7.22-7.20 (m, 3H),
6.93-6.90 (m, 2H), 6.69 (dd, 1H, J ) 9.8, 2.9 Hz), 6.03 (dd,
1H, J ) 9.8, 1.5 Hz), 5.46 (ddd, 1H, J ) 7.3, 2.9, 1.5 Hz), 4.97
(dd, 1H, J ) 7.3, 1.5 Hz), 4.90 (d, 1H, J ) 9.3 Hz), 3.68 (d, 1H,
J ) 10.8 Hz), 3.56 (d, 1H, J ) 10.8 Hz), 3.51 (dd, 1H, J ) 9.3,
1.5 Hz), 2.10 (s, 3H), 0.86 (s, 9H), 0.08 (s, 3H), -0.20 (s, 3H);
13C NMR δ 169.76, 161.87, 142.70, 142.30, 136.86, 128.36,
128.23, 128.07, 127.87, 127.21, 122.59, 82.03, 78.31, 74.16,
72.56, 64.78, 25.73, 20.85, 17.99, -4.51, -5.19; CIMS m/ z (%)
497 (M+ + 1, 63), 365 (100), 329 (38), 305 (19), 221 (16), 215
MeOH) [lit.1b mp 170 °C, [R]25 +121 (MeOH)]; IR (KBr) 3400
D
(OH), 1735 (CO) cm-1; 1H NMR (CD3OD) δ 7.47-7.25 (m, 5H),
7.01 (dd, 1H, J ) 9.8, 5.9 Hz), 6.08 (d, 1H, J ) 9.8 Hz), 4.73
(d, 1H, J ) 7.8 Hz), 4.59 (dd, 1H, J ) 3.9, 2.9 Hz), 4.43 (dd,
1H, J ) 5.9, 2.9 Hz), 4.17 (dd, 1H, J ) 7.8, 3.9 Hz); 13C NMR
(CD3OD) δ 166.03, 146.41, 143.37, 129.14, 128.83, 128.73,
122.96, 80.26, 75.63, 73.91, 63.47; CIMS m/ z (%) 251 (M+
+

6624 J . Org. Chem., Vol. 62, No. 19, 1997
Mukai et al.
(27), 147 (10), 133 (19), 107 (23), 91 (26). Anal. Calcd for
C28H36O5Si: C, 67.71; H, 7.31. Found: C, 67.51; H, 7.30.
(+)-(1′S,2′R,5R)-5-(1′-(Ben zyloxy)-2′-((ter t-bu tyld im eth -
ylsilyl)oxy)-2′-p h en yleth yl)-3-p en ten -5-olid e (17). Zn(Hg)
(1.5 g) was added to a solution of (-)-16 (307 mg, 0.62 mmol)
in dry Et2O (7.5 mL). The reaction mixture was cooled to -20
°C, to which a solution of saturated hydrogen chloride in Et2O
(3.0 mL) was added dropwise. The reaction mixture was
stirred at the same temperature for 30 min, washed with a
saturated NaHCO3 solution, water, and brine, dried, and
concentrated to dryness. Chromatography of the residue with
hexane-AcOEt (30:1) gave (+)-17 (238 mg, 88%): colorless
crystals (49%); mp 87-89 °C (MeOH-hexane); [R]16 -2.9 (c
D
0.60, CHCl3); IR 1735 (CO) cm-1
;
1H NMR δ 8.30-8.17 (m,
4H), 7.55-7.52 (m, 2H), 7.41-7.33 (m, 3H), 7.29-7.21 (m, 5H),
6.79 (ddd, 1H, J ) 9.8, 6.4, 2.4 Hz), 6.52 (d, 1H, J ) 7.3 Hz),
5.94 (ddd, 1H, J ) 9.8, 2.4, 1.0 Hz), 4.77 (d, 1H, J ) 11.2 Hz),
4.74 (d, 1H, J ) 11.2 Hz), 4.22 (dt, 1H, J ) 12.2, 3.4 Hz), 3.96
(dd, 1H, J ) 7.3, 3.4 Hz), 2.68 (ddt, 1H, J ) 18.1, 12.2, 2.4
Hz), 2.11 (dddd,1H, J ) 18.1, 6.4, 3.4, 1.0 Hz); 13C NMR δ
163.43, 163.02, 150.60, 144.73, 137.29, 136.64, 130.73, 128.95,
128.46, 128.03, 127.92, 127.31, 123.61, 121.12, 82.07, 78.13,
77.20, 75.49, 25.82; CIMS m/ z (%) 474 (M+ + 1, 63), 444 (22),
325 (11), 307 (92), 219 (13), 217 (26), 138 (48), 127 (19), 120
(14), 107(100), 91(27). Anal. Calcd for C27H23O7N: C, 68.49;
H, 4.90; N, 2.96. Found: C, 68.13; H, 4.83; N, 3.08.
crystals; mp 67-69 °C (hexane-AcOEt); [R]20 +187 (c 0.51,
D
CHCl3); IR 1730 (CO) cm-1
;
1H NMR δ 7.44-7.42 (m, 2H),
7.34-7.27 (m, 3H), 7.20-7.18 (m, 3H), 6.88-6.85 (m, 2H), 5.85
(s, 2H), 5.40 (s, 1H), 4.82 (d, 1H, J ) 9.3 Hz), 3.91 (d, 1H, J )
10.3 Hz), 3.54 (d, 1H, J ) 10.3 Hz), 3.38 (d, 1H, J ) 9.3 Hz),
2.93-2.90 (m, 2H), 0.87 (s, 9H), 0.10 (s, 3H), -0.18 (s, 3H);
13C NMR δ 169.43, 142.57, 137.48, 128.07, 128.01, 127.84,
127.75, 127.60, 127.55, 124.06, 123.59, 85.28, 77.90, 75.06,
72.76, 30.80, 25.75, 18.01, -4.54, -5.12; CIMS m/ z (%) 439
(M+ + 1, 86), 381 (15), 307 (100), 221 (53). Anal. Calcd for
C26H34O4Si: C, 71.19; H, 7.81. Found: C, 71.17; H, 7.90.
(+)-(1′S,2′R,5R)-5-(1′-(Ben zyloxy)-2′-((ter t-bu tyld im eth -
ylsilyl)oxy)-2′-p h en yleth yl)-2-p en ten -5-olid e (18). DBU
(one drop) was added to a solution of (+)-17 (120 mg, 0.27
mmol) in THF (2.7 mL). The reaction mixture was allowed to
stand at rt for 26 h, diluted with saturated NH4Cl, and
extracted with AcOEt. The organic layer was washed with
water and brine, dried, and concentrated to dryness. Chro-
matography of the residue hexane-AcOEt (30:1) gave (+)-18
(108 mg, 90%) along with 17 (6.6 mg, 5%). (+)-18: colorless
crystals; mp 133-134 °C (hexane); [R]20D +70.8 (c 0.51, CHCl3);
(1′R,2′S,5R)-5-(1′-(Ben zyloxy)-2′-h ydr oxy-2′-ph en yleth yl)-
2-p en ten -5-olid e a n d (-)-(1R,5R,7S,8R)-8-Ben zyloxy-7-
p h en yl-2,6-d ioxa bicyclo[3.3.1]n on a n -3-on e (21 a n d 22).
To a solution of (+)-20 (15.3 mg, 0.03 mmol) in THF (4.5 mL)
was added a 1 N LiOH solution (0.5 mL). The reaction mixture
was stirred at rt for 1 h and then cooled to 0 °C, to which
trifluoroacetic acid (2.5 mL) was added. The mixture was
gradually warmed to rt and then allowed to stand overnight.
The reaction mixture was diluted with saturated NaHCO3 and
extracted with AcOEt. The organic layer was washed with
water and brine, dried, and concentrated to dryness. Chro-
matography of the residue with hexane-AcOEt (10:1) gave 21
(3.2 mg, 31%) and (-)-22 (6.2 mg, 59%). DBU (one drop) was
added to a solution of 21 (3.2 mg, 0.01 mmol) in THF (0.6 mL).
The reaction mixture was stirred at rt for 24 h, diluted with a
saturated NH4Cl solution, and extracted with AcOEt. The
organic layer was washed with water and brine, dried, and
concentrated to dryness. Chromatography of the residue with
hexane-AcOEt (10:1) gave (-)-22 (2.6 mg, 80%; total amount
of 22 is 8.8 mg, 84% overall yield from 20). 21 was a colorless
1
IR 1720 (CO) cm-1; H NMR δ 7.48-7.45 (m, 2H), 7.37-7.18
1
(m, 6H), 7.02-7.00 (m, 2H), 6.86 (ddd, 1H, J ) 9.8, 6.4, 2.4
Hz), 5.98 (dd, 1H, J ) 9.8, 2.4 Hz), 4.99 (d, 1H, J ) 8.3 Hz),
4.90 (ddd, 1H, J ) 12.7, 3.4, 2.0 Hz), 3.78 (s, 2H), 3.39 (dd,
1H, J ) 8.3, 2.0 Hz), 2.57 (ddt, 1H, J ) 18.6, 12.7, 2.4 Hz),
2.01 (ddd, 1H, J ) 18.6, 6.4, 3.4 Hz), 0.83 (s, 9H), 0.06 (s, 3H),
-0.20 (s, 3H); 13C NMR δ 163.88, 145.59, 142.66, 137.38,
128.32, 128.18, 127.76, 127.64, 121.08, 83.88, 77.20, 76.35,
74.39, 72.69, 26.02, 25.75, 17.99, -4.58, -5.08; CIMS m/ z (%)
439 (M+ + 1, 100), 381 (8), 332 (8), 307 (64), 221 (6). Anal.
Calcd for C26H34O4Si: C, 71.19; H, 7.81. Found: C, 71.32; H,
7.77.
oil: IR 1735 (CO) cm-1; H NMR δ 7.44-7.21 (m, 10H), 6.87
(ddd, 1H, J ) 9.8, 6.5, 2.9 Hz), 6.00 (ddd, 1H, J ) 9.8, 2.9, 1.0
Hz), 5.08 (d, 1H, J ) 4.4 Hz), 4.67 (d, 1H, J ) 11.2 Hz), 4.57
(d, 1H, J ) 11.2 Hz), 4.39 (dt, 1H, J ) 12.7, 4.4 Hz), 3.70 (t,
1H, J ) 4.4 Hz), 2.74 (ddt, 1H, J ) 18.6, 12.7, 2.9 Hz), 2.70
(brs, 1H), 2.27 (dddd, 1H, J ) 18.6, 6.5, 4.4, 1.0 Hz); 13C NMR
δ 163.61, 145.30, 141.13, 137.32. 128.59, 128.48, 128.25,
128.10, 127.94, 126.33, 121.08, 83.43, 77.70, 75.31, 72.85,
25.88; EIMS m/ z (%) 324 (M+, 1), 233 (43), 218 (67), 174 (22),
127 (64), 109 (13), 107 (69), 105 (16), 97 (14), 91 (100).
HREIMS calcd for C20H20O4 324.1361, found 324.1358. (-)-
22: colorless crystals; mp 126-127 °C (hexane-AcOEt); [R]17
(+)-(1′R,2′R,5R)-5-(1′-(Ben zyloxy)-2′-h yd r oxy-2′-p h en yl-
D
-40.8 (c 0.15, CHCl3); IR 1735 (CO) cm-1; H NMR δ 7.40-
1
eth yl)-2-p en ten -5-olid e (19): colorless crystals (100%); mp
120-122 °C (hexane-AcOEt); [R]20 +106 (c 0.50, CHCl3); IR
7.30 (m, 5H), 7.26-7.19 (m, 3H), 6.96-6.92 (m, 2H), 4.92 (d,
1H, J ) 2.0 Hz), 4.75 (tt, 1H, J ) 3.9, 2.0 Hz), 4.53 (m, 1H),
4.02 (s, 2H), 3.65 (t, 1H, J ) 2.0 Hz), 2.95 (dd, 1H, J ) 19.5,
1.5 Hz), 2.84 (dd, 1H, J ) 19.5, 4.9 Hz), 2.63 (ddt, 1H, J )
14.2, 4.4, 2.0 Hz), 1.83 (dd, 1H, J ) 14.2, 3.9 Hz); 13C NMR δ
169.31, 137.63, 137.11, 128.30, 128.23, 127.87, 127.78, 126.61,
75.04, 73.73, 73.60, 70.42, 65.95, 36.33, 24.57; EIMS m/ z (%)
324 (M+, 2), 233 (100), 127 (30), 107 (41), 91 (88). Anal. Calcd
for C20H20O4: C, 74.05; H, 6.22. Found: C, 74.36; H, 6.26.
( +) -( 1 R , 5 R , 7 S , 8 R ) -8 -H y d r o x y -7 -p h e n y l -2 , 6 -
d ioxa bicyclo[3.3.1]n on a n -3-on e [9-d eoxygon iop yp yr on e
(4)]: colorless crystals(96%); mp 201-204 °C (hexane-AcOEt);
D
3400 (OH), 1720 (CO) cm-1
;
1H NMR δ 7.49-7.47 (m, 2H),
7.40-7.26 (m, 6H), 7.14-7.11 (m, 2H), 6.85 (ddd, 1H, J ) 9.8,
6.4, 2.4 Hz), 5.98 (dd, 1H, J ) 9.8, 2.4 Hz), 5.11 (dd, 1H, J )
7.8, 3.4 Hz), 4.79 (dt, 1H, J ) 12.2, 3.4 Hz), 4.17 (d, 1H, J )
11.2 Hz), 4.14 (d, 1H, J ) 11.2 Hz), 3.54 (dd, 1H, J ) 7.8, 3.4
Hz), 2.66 (br-d, 1H, J ) 3.4 Hz), 2.63 (ddt, 1H, J ) 18.1, 12.2,
2.4 Hz), 2.04 (ddd, 1H, J ) 18.1, 6.4, 3.4 Hz); 13C NMR δ
163.77, 145.57, 141.53, 137.20, 128.54, 128.36, 128.32, 128.10,
127.98, 127.01, 120.92, 82.12, 77.20, 73.89, 72.06, 25.81; CIMS
m/ z (%) 325 (M+ + 1, 100), 307 (14), 218 (8), 107 (7). Anal.
Calcd for C20H20O4: C, 74.05; H, 6.22. Found: C, 73.75; H,
6.22.
[R]16 +12.0 (c 0.10, EtOH) [lit.1d mp 203-204 °C (hexane-
D
AcOEt), [R]22 +12 (c 0.1, EtOH)]; IR (KBr) 3450 (OH), 1715
(+)-(1′R,2′R,5R)-5-(1′,2′-Dih yd r oxy-2′-p h en ylet h yl)-2-
D
(CO) cm-1; 1H NMR δ 7.43-7.33 (m, 5H), 4.97 (d, 1H, J ) 1.0
Hz), 4.89 (tt, 1H, J ) 3.9, 2.0 Hz), 4.54 (m, 1H), 3.95 (dd, 1H,
J ) 3.9, 1.0 Hz), 2.99 (dt, 1H, J ) 19.5, 2.0 Hz), 2.88 (dd, 1H,
J ) 19.5, 5.4 Hz), 2.61 (ddt, 1H, J ) 14.2, 3.9, 2.0 Hz), 1.86
(dd, 1H, J ) 14.2, 3.9 Hz), 1.60 (s, 1H); 13C NMR δ 169.16,
136.66, 128.91, 128.34, 126.11, 74.65, 70.50, 68.27, 66.09,
36.32, 23.97; EIMS m/ z (%) 234 (M+, 58), 177 (13), 144 (13),
128 (38), 120 (13), 107 (100), 105 (30), 91 (51). Anal. Calcd
for C13H14O4: C, 66.65; H, 6.02. Found: C, 66.49; H, 6.02.
(-)-(1′S,2′R,4R,5S)-5-(1′-(Ben zyloxy)-2′-((ter t-b u t yld i-
m eth ylsilyl)oxy)-2′-ph en yleth yl)-4-(p-tolu en esu lfon yloxy)-
2-p en ten -5-olid e (23). To a solution of (-)-11 (377 mg, 0.83
mmol) in CH2Cl2 (8.3 mL) were added DMAP (305 mg, 2.49
mmol) and TsCl (236 mg, 0.83 mmol). The reaction mixture
was stirred for 1.5 h, washed with water and brine, dried, and
p en ten -5-olid e [gon iod iol (3)]: colorless oil (97%); [R]21
D
+72.7 (c 0.32, CHCl3) [lit.1d [R]22 +74.4 (c 0.3, CHCl3)]; IR
D
3600 (OH), 3420 (OH), 1725 (CO) cm-1; 1H NMR δ 7.42-7.30
(m, 5H), 6.93 (ddd, 1H, J ) 9.8, 6.4, 2.0 Hz), 6.01 (ddd, 1H, J
) 9.8, 2.9, 1.0 Hz), 4.95 (d, 1H, J ) 7.3 Hz), 4.80 (ddd, 1H, J
) 12.7, 3.9, 2.0 Hz), 3.73 (dd, 1H, J ) 7.3, 2.0 Hz), 2.80
(dddd,1H,J ) 18.6, 12.7, 2.9, 2.0Hz), 2.55 (s, 1H), 2.27 (brs,
1H), 2.19 (dddd,1H,J ) 18.6, 6.4, 3.9, 1.0 Hz); 13C NMR δ
163.65, 146.11, 140.74, 128.77, 128.32, 120.61, 76.77, 75.02,
73.73, 26.06; FABMS m/ z (%) 235 (M+ + 1, 19), 217 (14), 154
(100), 136 (81), 120 (13), 107 (33), 105 (11), 97 (14); CIMS m/ z
(%) 235 (M+ + 1, 100), 217 (86), 173 (17), 107 (23); HRFABMS
calcd for C13H15O4 (M+ + 1) 235.0970, found 235.0964.
(-)-(1′S ,2′S ,5R )-5-(1′-(B e n zy lo x y )-2′-((p -n it r o b e n -
zoyl)oxy)-2′-p h en yleth yl)-2-p en ten -5-olid e (20): colorless

Syntheses of Styryllactones
J . Org. Chem., Vol. 62, No. 19, 1997 6625
concentrated to dryness. Chromatography of the residue with
137.25, 128.77, 128.54, 128.16, 127.76, 125.80, 90.24, 85.41,
84.37, 74.59, 72.74, 68.81, 66.25, 20.69, 20.43; EIMS m/ z (%)
440 (M+, 7), 397 (16), 338 (9), 243 (69), 183 (11), 144 (5), 113
(16), 91 (100), 79 (6), 77 (5). Anal. Calcd for C24H24O8: C,
65.45; H, 5.49. Found: C, 65.25; H, 5.45.
hexane-AcOEt (10:1) gave (-)-23 (485 mg, 96%) as a colorless
oil: [R]27 -58.1 (c 0.65, CHCl3); IR 1740 (CO) cm-1;1H NMR
D
δ 7.77-7.75 (m, 2H), 7.43-7.22 (m, 10H), 6.95-6.92 (m, 2H),
6.49 (dd, 1H, J ) 10.3, 3.4 Hz), 6.01 (dd, 1H, J ) 10.3, 1.5
Hz), 5.22 (m, 1H), 5.01 (d, 1H, J ) 6.9 Hz), 4.85 (d, 1H, J )
8.8 Hz), 3.77 (d, 1H, J ) 10.7 Hz), 3.50 (d, 1H, J ) 8.8 Hz),
3.43 (d, 1H, J ) 10.7 Hz), 2.46 (s, 3H). 0.83 (s, 9H), 0.04 (s,
3H), -0.22 (s, 3H); 13C NMR δ 161.02, 145.71, 142.14, 140.61,
137.23, 133.35, 130.23, 128.28, 128.14, 128.00, 127.85, 127.73,
123.47, 82.14, 78.55, 73.68, 72.58, 70.57, 25.73, 17.97, -4.54,
-5.19; CIMS m/ z (%) 609 (M+ + 1, 0.9), 437 (94), 341 (14),
329 (36), 323 (55), 287 (100), 215 (73), 147 (14), 133 (17), 107
(27), 97 (28), 91 (19). Anal. Calcd for C33H40O7SSi: C, 65.10;
H, 6.62. Found: C, 65.40; H, 6.86.
(+)-(1S,5R,6S,8R,9R)-9-(Ben zyloxy)-5-h yd r oxy-8-p h en -
yl-2,7-d ioxa bicyclo[4.3.0]n on a n -3-on e (27). To a solution
of (+)-25 (9.3 mg, 0.03 mmol) in THF (0.5 mL) were succes-
sively added SmI2 (0.1 M THF solution; 0.9 mL, 0.09 mmol)
and ethylene glycol (10% THF solution; 0.06 mL, 0.10 mmol)
at rt. The reaction mixture was stirred for 10 min, diluted
with a saturated NaHCO3 solution, and extracted with AcOEt.
The organic layer was washed with water and brine, dried,
and concentrated to dryness. Chromatography of the residue
with hexane-AcOEt (4:1) gave (+)-27 (5.5 mg, 62%) as a
(+)-(1 S ,6 S ,8 R ,9 R )-9 -(B e n z y l o x y )-8 -p h e n y l -2 ,7 -
d ioxa bicyclo[4.3.0]n on -4-en -3-on e (24): colorless crystals
colorless oil; [R]23 +39.0 (c 0.09, CHCl3); IR 3400 (OH), 1740
D
(CO) cm-1; H NMR δ 7.36-7.26 (m, 10H), 5.06 (dd, 1H, J )
1
(89%); 84-86 °C (MeOH); [R]28 +151.9 (c 0.53, CHCl3); IR
4.4, 2.0 Hz), 4.82 (d, 1H, J ) 5.9 Hz), 4.68 (d, 1H, J ) 11.7
Hz), 4.57 (d, 1H, J ) 11.7 Hz), 4.47 (m, 1H), 4.33 (t, 1H, J )
4.4 Hz), 4.10 (dd, 1H, J ) 5.9, 2.0 Hz), 2.92 (dd, 1H, J ) 7.1,
3.9 Hz), 2.68 (dd, 1H, J ) 7.1, 5.4 Hz), 2.34 (brs, 1H); 13C NMR
δ 168.57, 138.11, 136.82, 128.66, 128.48, 128.39, 128.07,
127.78, 126.06, 90.39, 84.91, 84.28, 72.63, 65.81, 35.19; EIMS
m/ z (%) 340 (M+, 6), 249 (61), 145 (12), 115 (7), 107 (96), 105
(10), 97 (15), 91 (100), 79 (26), 77 (16). Anal. Calcd for
C20H20O5: C, 70.57; H, 5.92. Found: C, 70.18; H, 5.95.
(-)-(1S ,5R ,6S ,8R ,9R )-5,9-D ih y d r o x y -8-p h e n y l-2,7-
d ioxa bicyclo[4.3.0]n on a n -3-on e [gon iofu p yr on e (6)]: col-
orless oil (80%); [R]18D -6.9 (c 0.15, CHCl3) [lit.1e [R]25D -5.0 (c
0.10, CHCl3)]; IR 3400 (OH), 1735 (CO) cm-1; 1H NMR δ 7.37-
7.29 (m, 5H), 4.96 (dd, 1H, J ) 5.4, 2.4 Hz), 4.70 (d, 1H, J )
6.4 Hz), 4.44 (dt, 1H, J ) 5.9, 3.9 Hz), 4.36 (ddd, 1H, J ) 5.4,
3.9, 1.0 Hz),4.29 (dd, 1H, J ) 6.4, 2.4 Hz), 3.31 (brs, 1H), 2.91
(dd, 1H, J ) 16.6, 3.9 Hz), 2.78 (brs, 1H), 2.68 (ddd, 1H, J )
16.6, 5.9, 1.0 Hz); 13C NMR δ 169.29, 137.93, 128.72, 128.46,
126.00, 86.76, 85.72, 83.65, 76.37, 65.82, 35.08; EIMS m/ z (%)
250 (M+, 36), 160 (18), 144 (44), 133 (30), 120 (50), 117 (29),
115 (13), 107 (93), 105 (48), 97 (17), 91 (100), 79 (43), 77 (45),
73 (33), 71 (25). Anal. Calcd for C13H14O5: C, 62.39; H, 5.64.
Found: C, 62.03; H, 5.64.
D
1735 (CO) cm-1; 1H NMR δ 7.34-7.28 (m, 10H), 7.00 (dd, 1H,
J ) 9.8, 5.4 Hz), 6.25 (d, 1H, J ) 9.8 Hz), 5.01 (dd, 1H, J )
4.9, 1.5 Hz), 4.86 (d, 1H, J ) 5.4 Hz), 4.68 (d, 1H, J ) 11.7
Hz), 4.61 (d, 1H, J ) 11.7 Hz), 4.58 (dd, 1H, J ) 5.4, 4.9 Hz),
4.24 (dd, 1H, J ) 5.4, 1.5 Hz); 13C NMR δ 160.95, 139.46,
138.22, 136.84, 128.61, 128.50, 128.30, 128.09, 127.78, 126.18,
124.26, 90.76, 85.30, 84.22, 72.76, 68.70; EIMS m/ z (%) 322
(M+, 8), 231 (14), 216 (8), 107 (45), 105 (8), 91 (100), 79 (16).
Anal. Calcd for C20H18O4: C, 74.52; H, 5.63. Found: C, 74.18;
H, 5.65.
(+)-(1S ,6S ,8R ,9R )-9-H y d r o x y -8-p h e n y l-2,7-d io x a -
bicyclo[4.3.0]n on -4-en -3-on e [a lth ola cton e (5)]: colorless
crystals (98%); mp 108-109 °C (EtOH-benzene); [R]25D +182.0
(c 0.10, EtOH) [lit.1a mp 110 °C; [R]25D +184.7 (EtOH)]; IR 3400
(OH), 1730 (CO) cm-1; 1H NMR δ 7.36-7.30 (m, 5H), 7.00 (dd,
1H, J ) 9.9, 5.0 Hz), 6.21 (d, 1H, J ) 9.9 Hz), 4.92 (dd, 1H, J
) 5.0, 2.3 Hz), 4.73 (d 1H, J ) 5.6 Hz), 4.63 (t, 1H, J ) 5.0
Hz), 4.44 (dd, 1H, J ) 5.6, 2.3 Hz), 3.37 (s, 1H); 13C NMR δ
161.35, 140.38, 138.10, 128.64, 128.36, 126.11, 123.61, 86.42,
85.99, 83.67, 68.16; EIMS m/ z (%) 232 (M+, 43), 136 (45), 126
(21), 107 (78), 97 (100), 95 (80), 91 (43), 79 (41), 77 (45). Anal.
Calcd for C13H12O4Si: C, 67.23; H, 5.21. Found: C, 66.96; H,
5.40.
(-)-(1R ,5R ,6S ,8R ,9R )-5,9-D ia c e t o x y -8-p h e n y l-2,7-
(()-(1R,4R,5S,6R,8S,9S)-9-(Ben zyloxy)-4,5-d ih yd r oxy-
8-p h en yl-2,7-d ioxa b icyclo[4.3.0]n on a n -3-on e (25). To a
solution of (()-24 (21.0 mg, 0.07 mmol) and N-methylmorpho-
line N-oxide (NMO) (11.7 mg, 0.10 mmol) in acetone (1.0 mL)
and water (0.5 mL) was added a 4% solution of osmium
tetraoxide in water (0.1 mL, 0.02 mmol) dropwise. The
reaction mixture was stirred at rt for 1.5 h and then a
saturated NaHSO3 solution was added. After being stirred
for 30 min, the reaction mixture was extracted with AcOEt,
which was washed with water and brine, dried, and concen-
trated to dryness. Chromatography of the residue with
hexane-AcOEt (1:1) gave (()-25 (18.4 mg, 79%). (()-25:
colorless crystals; mp 155-158 °C (hexane-AcOEt); IR 3550
(OH), 1745 (CO) cm-1; 1H NMR δ 7.37-7.26 (m, 10), 5.19 (dd,
1H, J ) 4.9, 2.4 Hz), 4.81 (d, 1H, J ) 6.4 Hz), 4.71 (d, 1H, J
) 11.7 Hz), 4.58-4.55 (m, 3H), 4.54 (dd, 1H, J ) 2.9, 2.0 Hz),
4.04 (dd, 1H, J ) 6.4, 2.4 Hz), 3.41 (s, 1H), 2.85 (s, 1H); 13C
NMR δ 172.15, 137.83, 136.62, 128.68, 128.50, 128.43, 128.10,
127.80, 125.80, 90.33, 85.82, 84.24, 76.30, 72.62, 68.50, 68.36;
EIMS m/ z (%) 356 (M+, 7), 265 (79), 107 (81), 91 (100), 79
(20), 77 (10); HREIMS calcd for C20H20O6 356.1260, found
356.1254. Similar treatment of (+)-24 (126 mg, 0.39 mmol)
afforded (+)-(1S,4S,5R,6S,8R,9R)-9-(benzyloxy)-4,5-dihydroxy-
8-phenyl-2,7-dioxabicyclo[4.3.0]nonan-3-one (25) (104 mg, 75%).
(+)-25: colorless crystals; mp 116-117 °C (hexane-AcOEt);
d ioxa bicyclo[4.3.0]n on a n -3-on e (28). Colorless oil (76%);
1
[R]21 -116.4 (c 0.15, CHCl3); IR 1750 (CO) cm-1; H NMR δ
D
7.38-7.30 (m, 5H), 5.49 (q, 1H, J ) 3.9 Hz), 5.34 (dd, 1H, J )
3.9, 1.0 Hz), 4.96 (dd, 1H, J ) 3.9, 1.0 Hz), 4.94 (d, 1H, J )
3.9, Hz), 4.36 (t, 1H, J ) 3.9 Hz), 3.03 (dd, 1H, J ) 17.6, 3.9
Hz), 2.75 (ddd, 1H, J ) 17.6, 3.9, 1.0 Hz), 2.15 (s, 3H), 2.13 (s,
3H); 13C NMR δ 169.42, 169.27, 166.18, 137.07, 128.75, 128.61,
126.16, 86.00, 83.36, 82.89, 73.80, 66.67, 31.97, 20.85, 20.78;
CIMS m/ z (%) 335 (M+ + 1, 100), 275 (76), 215 (15); FABMS
m/ z (%) 335 (M+ + 1, 18), 215 (21), 181 (10), 154 (23), 149
(16), 144 (10), 136 (29), 115 (14), 107 (19), 105 (20), 97 (11), 95
(16), 91 (100). HRFABMS calcd for C17H19O7 (M+ + 1)
335.1131, found 335.1138.
(-)-(1S,5S,6S,8R,9R)-9-(Ben zyloxy)-5-h yd r oxy-8-p h en -
yl-2,7-d ioxa bicyclo[4.3.0]n on a n -3-on e (30). DIBALH (1.0
M hexane solution; 0.15 mL, 0.15 mmol) was added to a
solution of (+)-27 (42.6 mg, 0.13 mmol) in dry Et2O (2.4 mL)
at -78 °C. The reaction mixture was kept at the same
temperature for 10 min, then quenched by addition of a
saturated Na2SO4 solution, passed through a short pad of
Celite, dried, and concentrated to dryness. The residue was
dissolved in MeOH (2.5 mL), to which p-TsOH‚H2O (2.0 mg,
0.01 mmol) was added. The reaction mixture was stirred at
rt for 15 h, neutralized with a saturated NaHCO3 solution,
and extracted with AcOEt. The organic layer was washed with
water, dried, and concentrated to dryness. The residue was
passed through a short column with hexane-AcOEt (5:1) to
afford 29 (32.6 mg, 77%) as a mixture of two diastereoisomers.
To a solution of 29 (12.7 mg, 0.04 mmol) in dry CH3CN (1.0
mL) were successively added 4 Å molecular sieves (250 mg),
NMO (8.3 mg, 0.08 mmol), and TPAP (4.0 mg, 0.01 mmol) at
rt. The reaction mixture was stirred for 30 min, diluted with
AcOEt, and passed through a short pad of Celite. The filtrate
was concnetrated to dryness. LAH (3.8 mg, 0.10 mmol) was
added to a solution of the residue in THF (1.0 mL) at -20 °C.
[R]23 +33.4 (c 0.19, CHCl3). Anal. Calcd for C20H20O6: C,
D
67.40; H, 5.66. Found: C, 67.32; H, 5.67.
(()-(1R,4R,5R,6R,8S,9S)-4,5-Dia cetoxy-9-(ben zyloxy)-8-
p h en yl-2,7-d ioxa bicyclo[4.3.0]n on a n -3-on e (26): colorless
prisms (94%); 127-128 °C (hexane-AcOEt); IR 1760 (CO)
cm-1; 1H NMR δ 7.39-7.26 (m, 10H), 5.83 (d, 1H, J ) 2.9 Hz),
5.74 (t, 1H, J ) 2.9 Hz), 5.11 (dd, 1H, J ) 5.4, 2.4 Hz), 4.82 (d,
1H, J ) 6.8 Hz), 4.69 (d, 1H, J ) 11.7 Hz), 4.56 (d, 1H, J )
11.7 Hz), 4.49 (dd, 1H, J ) 5.4, 2.9 Hz), 4.10 (dd, 1H, J ) 6.8,
2.4 Hz), 2.19 (s, 3H), 2.16 (s, 3H); 13C NMR δ 169.24, 164.76,

6626 J . Org. Chem., Vol. 62, No. 19, 1997
Mukai et al.
After being stirred for 20 min at the same temperature, the
reaction mixture was quenched by addition of water, passed
through a short pad of Celite, dried, and concentrated to give
the residual oil. The residue was taken up in CH2Cl2 (1.0 mL),
to which m-CPBA (19.4 mg, 0.09 mmol) and BF3‚OEt2 (1.0 M
CH2Cl2 solution; 0.15 mL, 0.15 mmol) were added successively.
The reaction mixture was stirred at rt for 1.5 h, diluted with
CH2Cl2, and washed with a saturated Na2S2O3 solution. The
organic layer was washed with water and brine, dried, and
concentrated to dryness. Chromatography of the residue with
hexane-AcOEt (5:1) gave 27 (1.7 mg, 14%) and (-)-30 (7.4
mg, 61%). (-)-30: colorless needles; mp 133-134 °C (hexane-
(-)-(1R ,5S ,6S ,8R ,9R )-5,9-D ia c e t o x y -8-p h e n y l-2,7-
d ioxa bicyclo[4.3.0]n on a n -3-on e (32): colorless oil (89%);
[R]21 -74.2 (c 0.09, CHCl3); IR 1740 (CO) cm-1 1H NMR δ
;
D
7.36-7.26 (m, 5H), 5.40 (ddd, 1H, J ) 11.2, 5.9, 2.9 Hz), 5.31
(dd, 1H, J ) 3.4, 1.0 Hz), 4.94 (d, 1H, J ) 3.4 Hz), 4.85 (dd,
1H, J ) 2.9, 1.0, Hz), 4.63 (t, 1H, J ) 2.9 Hz), 3.03 (dd, 1H, J
) 17.1, 11.2 Hz), 2.91 (dd, 1H, J ) 17.1, 5.9 Hz), 2.14 (s); 13C
NMR δ 170.13, 169.25, 166.45, 137.18, 128.77, 128.61, 126.24,
86.16, 83.13, 82.77, 73.86, 65.46, 31.32, 20.88, 20.78; CIMS
m/ z (%) 335 (M+ + 1, 100), 275 (47), 215 (9), 144 (14); FABMS
m/ z (%) 335 (M+ + 1, 46), 307 (12), 289 (12), 215 (29), 165
(10), 163 (12), 154 (100), 152 (14), 144 (16), 136 (92), 124 (12),
120 (18), 115 (13), 107 (39), 105 (22), 91 (35). HRFABMS calcd
for C17H19O7 (M+ + 1) 335.1131, found 335.1109.
AcOEt); [R]17 -8.0 (c 0.10, CHCl3); IR 1750 (CO) cm-1 1H
;
D
NMR δ 7.39-7.24 (m, 10H), 4.93 (dd, 1H, J ) 5.4, 2.4 Hz),
4.86 (d, 1H, J ) 6.8 Hz), 4.68 (d, 1H, J ) 11.7 Hz), 4.56 (d,
1H, J ) 11.7 Hz), 4.49 (dd, 1H, J ) 5.4, 3.9 Hz), 4.37 (m, 1H),
4.16 (dd, 1H, J ) 6.8, 2.4 Hz), 2.90 (dd, 1H, J ) 16.1, 7.8 Hz),
2.67 (dd, 1H, J ) 16.1, 3.9 Hz), 2.62 (d, 1H, J ) 5.4 Hz); 13C
NMR δ 168.39, 137.70, 136.80, 128.73, 128.63, 128.46, 128.05,
127.75, 126.27, 90.32, 84.24, 74.92, 72.74, 63.69, 34.95; EIMS
m/ z (%) 340(M+, 4), 249 (38), 143 (10), 133 (6), 107 (73), 97
(13), 91 (100), 79 (21), 77 (10). Anal. Calcd for C20H20O5: C,
70.57; H, 5.92. Found: C, 70.17; H, 5.95.
Ack n ow led gm en t. The authors thank Professor J .
L. McLaughlin, Purdue University, for generous supply
1
of H and 13C NHR spectra of natural (+)-8-acetylgo-
niotriol. This work was supported by a Grant-in-Aid
for Scientific Research from the Ministry of Education,
Science and Culture of J apan, to which the authors’
thanks are due.
(-)-(1S ,5S ,6S ,8R ,9R )-5,9-D ih y d r o x y -8-p h e n y l-2,7-
d ioxa b icyclo[4.3.0]n on a n -3-on e [5-ep i-gon iofu p yr on e
(31)]: colorless crystals (74%); mp 124-125 °C (CHCl3); [R]18
D
Su ppor tin g In for m ation Available: Procedures for prepa-
ration of compounds (+)-2, (+)-3, (+)-4, (+)-5, (-)-6, (-)-16,
(+)-19, (-)-20, (+)-24, (()-26, (-)-28, (-)-31, and (-)-32, 13C
NMR spectra for compounds (+)-3, 21, (()-25, 28, (-)-31, and
(-)-32, and ORTEP drawing of (()-26 (9 pages). This material
is contained in libraries on microfiche, immediately follows this
article in the microform version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
-59.2 (c 0.10, CHCl3); IR 3400 (OH), 1745 (CO) cm-1; 1H NMR
δ 7.40-7.34 (m, 5H), 4.88 (dd, 1H, J ) 6.4, 3.9 Hz), 4.76 (d,
1H, J ) 7.3 Hz), 4.49 (dd, 1H, J ) 6.4, 3.9 Hz), 4.38-4.35 (m,
2H), 2.91 (dd, 1H, J ) 16.6, 7.8 Hz), 2.63 (dd, 1H, J ) 16.6,
3.4 Hz), 2.58 (brs, 1H); 13C NMR δ, 168.88, 137.43, 128.79,
128.72, 126.25, 85.93, 84.57, 83.31, 74.11, 63.67, 34.83; CIMS
m/ z (%) 251 (M+ + 1, 100), 233 (8), 144 (9); FABMS m/ z (%)
251 (M+ + 1, 15), 165 (10), 154 (100), 149 (16), 136 (88), 124
(10), 120 (17), 115 (12), 107 (38), 91 (40). HRFABMS calcd
for C13H15O5 (M+ + 1) 251.0920, found 251.0920.
J O970725U