Total synthesis of dysidiolide

Article abstract of DOI:10.1021/ja973023v

The cdc25A protein phosphatase inhibitor dysidiolide (1) has been synthesized enantioselectively, starting from the enantiomerically pure ketal enone 2 and using a cationic rearrangement as the key step to produce the fully substituted bicyclic core of th

Full text of DOI:10.1021/ja973023v

VOLUME 119, NUMBER 51
DECEMBER 24, 1997
© Copyright 1997 by the
American Chemical Society
Total Synthesis of Dysidiolide
E. J. Corey* and Bryan E. Roberts
Contribution from the Department of Chemistry and Chemical Biology, HarVard UniVersity,
Cambridge, Massachusetts 02138
ReceiVed August 27, 1997
Abstract: The cdc25A protein phosphatase inhibitor dysidiolide (1) has been synthesized enantioselectively, starting
from the enantiomerically pure ketal enone 2 and using a cationic rearrangement as the key step to produce the fully
substituted bicyclic core of the natural product. Once the central portion of 1 was established, elaboration of the
side chains was accomplished expediently via steps that included (1) vinyl cuprate displacement of an iodide to
complete the C-1 side chain, (2) a highly diastereoselective oxazaborolidine-catalyzed (CBS) reduction to form carbinol
11, and (3) photochemical oxidation of 11 to generate the γ-hydroxybutenolide functionality of 1. Additionally, this
synthesis proves the absolute stereochemistry of dysidiolide (1).
Described herein (Scheme 1) is the first enantioselective total
synthesis of the marine sponge metabolite dysidiolide (1), the
structure of which was reported by Gunasekera, Clardy, and
colleagues in 1996.1 Isolated from the Caribbean sponge
Dysidea etheria de Laubenfels, dysidiolide is the first naturally
derived inhibitor of the cdc25A protein phosphatase, one of three
homologues (cdc25A, -B, -C) of a signaling enzyme shown to
activate the G2/M transition of the cell cycle.2 Dysidiolide
exhibits micromolar activity against A-549 human lung carci-
noma and P388 murine leukemia cancer cell lines. This in Vitro
antitumor activity, which is probably due to inhibition of cdc25A
by dysidiolide, may be a good lead in the search for improved
agents in the treatment of cancer and other proliferative
disorders. Dysidiolide is a γ-hydroxybutenolide of the rear-
ranged sesterterpene class whose [4.4.0] bicyclic nucleus and
appendant side chains define a type of structure not previously
encountered in a natural product. A key step of our synthesis
of 1 is a controlled, biomimetic carbocation rearrangement which
simultaneously creates the unusual quaternary center at C-1 and
the endocyclic double bond within the highly substituted bicyclic
core. The synthesis also proves the absolute stereochemistry
of dysidiolide, which was not determined in the original1 X-ray
crystallographic analysis.
The synthesis of 1 commenced from the enantiomerically pure
bicyclic ketal enone 2, which is readily available in three steps
starting from 2-methyl-1,3-cyclohexanedione and ethyl vinyl
ketone.3 Reduction of 2 with 4 equiv of lithium and 1 equiv of
H2O in liquid ammonia-tetrahydrofuran (THF) at -40 °C for
10 min, followed by reaction of the excess lithium with 4 equiv
of isoprene (-78 °C, 15 min) and enolate alkylation with excess
allyl bromide (gradual warming and -35 °C for 30 min),
provided allyl ketone 3 (82% yield) as a single diastereomer.4
Conversion of 3 to the corresponding R,â-enone (69% yield
and 21% recovered 3) was accomplished by a three-step
sequence:5 (1) deprotonation of 3 with 2 equiv of lithium
diisopropylamide in hexamethylphosphoramide (HMPA)-THF
(23 °C, 20 min), followed by phenylsulfenation with 3 equiv
of diphenyl disulfide (23 °C, 20 min); (2) oxidation of the
resulting R-phenylthio ketone with excess m-chloroperbenzoic
acid in dichloromethane (CH2Cl2, -78 °C, 2 h); and (3)
elimination of the resulting R-phenylsulfinyl ketone by heating
at reflux in benzene (13 h) in the presence of excess trimethyl
phosphite to form the R,â-unsaturated analogue of 3. Slow
(3) Hagiwara, H.; Uda, H. J. Org. Chem. 1988, 53, 2308.
(4) Allyl ketone 3 has been described previously: Hagiwara, H.; Inome,
K.; Uda, H. J. Chem. Soc. Perkin Trans. I 1995, 757.
(5) Trost, B. M.; Salzmann, T. N.; Hiroi, K. J. Am. Chem. Soc. 1976,
98, 4887.
(6) Still, W. C. J. Org. Chem. 1976, 41, 3063. A more reliable procedure
to prepare trimethylsilyl lithium has been detailed: Hudrlik, P. F.; Waugh,
M. A.; Hudrlik, A. M. J. Organomet. Chem. 1984, 271, 69.
X Abstract published in AdVance ACS Abstracts, December 15, 1997.
(1) Gunasekera, G. P.; McCarthy, P. J.; Kelly-Borges, M.; Lobkovsky,
E.; Clardy, J. J. Am. Chem. Soc. 1996, 118, 8759-8760.
(2) Millar, J. B. A.; Russell, P. Cell 1992, 68, 407.
S0002-7863(97)03023-0 CCC: $14.00 © 1997 American Chemical Society

12426 J. Am. Chem. Soc., Vol. 119, No. 51, 1997
Corey and Roberts
Scheme 1a
a Reagents (a) Li-NH3, THF, -40 °C, 10 min, then isoprene, -78 °C, 15 min; allyl bromide, -78 to -35 °C, then -35 °C for 30 min (82%
yield). (b) LDA, PhSSPh, HMPA-THF, 23 °C, 20 min; m-CPBA, CH2Cl2, -78 °C, 2 h; (MeO)3P, C6H6, 80 °C, 13 h (69% yield and 21%
recovered 3). (c) TMSLi, HMPA-Et2O, -78 °C, 3 h (64% yield). (d) KH, DMSO, Ph3PCH3Br, 23 °C, 2 h (97% yield). (e) (DHQD)2PYDZ,
K2OsO4‚2H2O, K2CO3, K3Fe(CN)6, MeSO2NH2, 1:1 t-BuOH-H2O, 0 °C, 4 h (97% yield). (f) NaIO4, 4:1 THF-H2O, 23 °C, 30 min. (g) NaBH4,
6:1 THF-EtOH, 0 °C, 20 min (94% yield for two steps). (h) PPTS, 4:1 acetone-H2O, 65 °C; 2 h (100% yield). (i) TBDPSCl, DMAP, 2,6-lutidine,
CH2Cl2, 23 °C, 1.5 h (96% yield). (j) (Ph3P)3RhCl, H2 (1000 psi), C6H6, 65 °C, 23 h (76% yield). (k) allylMgBr, Et2O, -78 to 23 °C, 10 min (99%
yield). (l) BH3-DMS, Et2O, 23 °C, 2.5 h; EtOH, NaOH, H2O2, 23 °C, 3.5 h (95% yield). (m) TBSCl, DMAP, 2,6-lutidine, CH2Cl2, 23 °C, 12 h
(97% yield). (n) BF3 (g), CH2Cl2, -78 °C, 3 h. (o) PPTS, EtOH, 55 °C, 2.5 h (70% yield for two steps). (p) I2, Ph3P, imidazole, CH2Cl2, 23 °C,
10 min (97% yield). (q) 2-bromopropene, t-BuLi, CuI, Et2O, -30 to 0 °C, 30 min (97% yield). (r) TBAF, THF, 23 °C, 8.5 h (96% yield). (s)
Dess-Martin periodinane, pyridine, CH2Cl2, 23 °C, 1 h (94% yield). (t) 3-bromofuran, n-BuLi, THF, -78 °C, 30 min (98% yield, 1:1 11-epi-11).
(u) O2, hν, Rose Bengal, i-Pr2EtN, CH2Cl2, -78 °C, 2 h (98% yield). (v) CBS catalyst 13, BH3-DMS, toluene, -30 °C, 15 h (91% yield).
addition of this R,â-enone to excess trimethylsilyl (TMS)
lithium6 in HMPA-diethyl ether (Et2O) at -78 °C effected
conjugate addition to form exclusively the axial â-TMS ketone
4 (64% yield).7 Wittig methylenation of ketone 4 with excess
methylenetriphenylphosphorane in dimethyl sulfoxide
(Ph3PCH3Br, KCH2SOCH3, 23 °C, 2 h, 97% yield)8 was
followed by conversion of the allyl appendage to a 2-hydroxy-
ethyl group to produce 5 by the following three-step sequence:
(1) position-selective dihydroxylation of the vinyl group by the
Sharpless reagent system (0.05 equiv of DHQD2-PYDZ, 0.01
equiv of K2OsO4‚2H2O, 3.5 equiv of K2CO3, 3.5 equiv of
K3Fe(CN)6, 1 equiv of MeSO2NH2, 1:1 t-butanol-H2O, 0 °C,
4 h)9 to form the corresponding 1,2-diol; (2) glycol cleavage
with 5 equiv of NaIO4 in 4:1 THF-H2O (23 °C, 30 min); and
(3) reduction of the aldehyde with 3 equiv of NaBH4 in 6:1
THF-EtOH (0 °C, 20 min) to provide alcohol 5 in 91% overall
yield. Deketalization of 5 using 1 equiv of pyridinium p-
toluenesulfonate (PPTS) in 4:1 acetone-H2O (65 °C, 2 h, 100%
yield), protection of the hydroxyl functionality as the t-
butyldiphenylsilyl (TBDPS) ether [3 equiv of TBDPSCl, 1 equiv
of 4-(dimethylamino)pyridine (DMAP), CH2Cl2, 23 °C, 1.5 h,
96% yield], and hydrogenation using Wilkinson’s catalyst10
[0.15 equiv of (Ph3P)3RhCl, 1000 psi H2, benzene, 65 °C, 23
h, 76% yield], followed by silica gel radial chromatography,
gave diastereomerically pure 6.11,12
(7) Slow addition of the R,â-enone to the TMSLi was necessary in order
to minimize the formation of dimeric side products.
(8) Sampath, V.; Lund, E. C.; Knudsen, M. J.; Olmstead, M. M.; Schore,
N. E. J. Org. Chem. 1987, 52, 3595.
(9) For reviews of the Sharpless catalytic asymmetric dihydroxylation,
see (a) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. ReV.
1994, 94, 2483; (b) Corey, E. J.; Noe, M. C. J. Am. Chem. Soc. 1996, 118,
11038. The cinchona alkaloid ligand (DHQD2-PYDZ), with its well-defined
structural characteristics, afforded enhanced selectivity for dihydroxylation
of the monosubstituted double bond relative to the 1,1-disubstituted
exocyclic double bond. This strategy has been used previously: Corey, E.
J.; Roberts, B. E.; Dixon, B. R. J. Am. Chem. Soc. 1995, 117, 193. The
diastereoselection of the attack on the monosubstituted double bond was
only moderate, as expected9b (2.6:1).
Although attempted nucleophilic addition of the 4-methyl-
(10) (a) Jardine, F. H.; Wilkinson, G. J. Chem. Soc. C, 1960, 270. (b)
Piers, E.; Waal, W.; Britton, R. W. J. Am. Chem. Soc. 1971, 93, 5113.
(11) The crude reaction mixture also contained the 6S diastereomer of 6
(21%), which was removed during silica gel radial chromatography.
(12) Efforts to improve the diastereoselectivity of the hydrogenation were
unproductive. It appears that the cyclohexyl ring containing the exocyclic
olefin is distorted out of the usual chair conformation as a result of steric
interactions between the 1,3-diaxial methyl groups. As a result, the two
faces of the olefin are nearly equally accessible to hydrogenation.

Total Synthesis of Dysidiolide
J. Am. Chem. Soc., Vol. 119, No. 51, 1997 12427
Figure 2. (S)-B-methyl CBS catalyst (13).
periodinane, 3.8 equiv of pyridine, CH2Cl2, 23 °C, 10 min, 100%
yield) and (2) oxazaborolidine-catalyzed (CBS) reduction19 using
CBS catalyst 13 (Figure 2) (2 equiv of 13, 2 equiv of BH3‚DMS,
toluene, -30 °C, 15 h) to give 11 in 91% yield.20 The recycling
of epi-11 allows for an overall 95% yield for the transformation
of 10 to 11. Photochemical oxidation21 of 11 (O2, Rose Bengal,
10 equiv of i-Pr2EtN, CH2Cl2, -78 °C, 2 h) furnished dysid-
iolide (1, 98% yield), [R]2D3 -10.8 (c 0.60, 1:1 CH2Cl2-
MeOH),22 as a white solid. The infrared, 1H and13C NMR, and
MS/HRMS spectra were identical to those recorded previ-
ously, and comparison of synthetic 1 with an authentic sample
of 1 by thin-layer chromatography showed them to be identi-
cal.23
A number of peripheral findings from our studies should be
mentioned. First, the presence of the trimethylsilyl group in 7
was essential for successful rearrangement to form 8. The
analogues of 7 with H or C6H5(CH3)2Si instead of (CH3)3Si
afforded little, if any, of the desired rearrangement under a
variety of conditions. In the case of the latter substrate, the
major reaction pathway was that in which the axial tertiary
hydroxyl attacked silicon to give after workup the analogue of
7 with HO(CH3)2Si replacing (CH3)3Si. Second, the 4-methyl-
4-pentenyl appendage could not be introduced directly since
its presence interferes with the cationic rearrangement step (step
n), which is disfavored relative to direct cation-olefin cycliza-
tion (without rearrangement) to form a new spiro ring. Finally,
attempted Mitsunobu reaction to convert epi-11 to 11 proceeded
with only partial (ca. 3:1) inversion at carbon. Oxidation of
epi-11 to ketone 12 followed by reduction with L-Selectride,
NaBH4, or LiBH4 also provided diastereomeric mixtures of
alcohols with epi-11 predominating. On the other hand, CBS
reduction of ketone 12 was highly diastereoselective and
afforded 11 in excellent yield, as described above.
Figure 1. X-ray crystal structure of the bis(3,5-dinitrobenzoate)
derivative of 8. The two 3,5-dinitrobenzoate functional groups have
been removed for improved clarity.
4-pentenyl lithium, magnesium, and cerium reagents to the
carbonyl group of 6 simply returned starting material, addition
of allylmagnesium bromide in Et2O (4 equiv, -78 to 23 °C, 10
min) to this substrate occurred smoothly and stereospecifically
to afford the axial tertiary alcohol in 99% yield. Hydroboration
of the vinyl group with excess BH3‚DMS in Et2O (23 °C, 2.5
h) and subsequent treatment with excess EtOH, NaOH, and
H2O2 (23 °C, 3.5 h) gave a primary-tertiary diol (95% yield),
which was then selectively protected at the primary hydroxyl
by reaction with 3 equiv of t-butyldimethylsilyl (TBS) chloride
(1 equiv of DMAP, CH2Cl2, 23 °C, 12 h) to provide 7 in 97%
yield. Treatment of 7 with 6 equiv of BF3(g) (CH2Cl2, -78
°C, 3 h) and subsequent selective cleavage of the TBS ether13
(1 equiv of PPTS, EtOH, 55 °C, 2.5 h) furnished alcohol 8 (70%
yield over two steps), which contains the fully substituted
bicyclic core of dysidiolide (1).14 The relative stereochemistry
of 8 was confirmed by single-crystal X-ray diffraction analysis
of its bis(3,5-dinitrobenzoate) derivative (Figure 1).15 In the
rearrangement of 7 to form 8, the trimethylsilyl (TMS) group
facilitates the migration of methyl to the cationic carbon
generated by C-O heterolysis of 7 (by â-hyperconjugation of
TMS in TMSC-C+). In addition, the very facile elimination
of that TMS group guarantees the location of the double bond.
The next stage of the synthesis involved the elaboration of
the two ring appendages of 8 to generate the complete
dysidiolide structure 1. The C-1 side chain was emplaced via
a two-step sequence: (1) iodination16 of alcohol 8 (I2, Ph3P,
imidazole, CH2Cl2, 23 °C, 10 min) and (2) iodide displacement
with the vinyl cuprate derived from 2-lithiopropene (10 equiv
of 2-bromopropene, 21 equiv of t-BuLi, 5 equiv of CuI, Et2O,
-30 to 0 °C, then 0 °C for 30 min) to afford 9 in 94% overall
yield. Cleavage of the TBDPS ether in 9 with excess tetrabu-
tylammonium fluoride (THF, 23 °C, 8.5 h, 96% yield) and
subsequent oxidation (Dess Martin periodinane,17 pyridine,
CH2Cl2, 23 °C, 1 h, 94% yield) provided aldehyde 10.
Treatment of 10 with excess 3-lithiofuran18 (3-bromofuran,
n-BuLi, THF, -78 °C, 30 min) afforded a 1:1 mixture (98%
yield) of the diastereomeric carbinols 11 and epi-11, which were
readily separated by silica gel chromatography. Undesired epi-
11 was efficiently converted to 11 by a two-step sequence: (1)
oxidation of epi-11 to ketone 12 (1.5 equiv of Dess-Martin
In conclusion, the research described above demonstrates the
first synthesis of dysidiolide (1), a C25 isoprenoid antimitotic
agent possessing exceptional bioactivity and an unusual rear-
ranged structure.24
Experimental Section
Chemical shifts for NMR spectra are reported as δ in units of parts
per million (ppm) downfield from tetramethylsilane (δ 0.0) using the
residual solvent signal as an internal standard: chloroform-d (1H NMR
δ 7.26, singlet; 13C NMR δ 77.0, triplet) or DMSO-d6 (1H NMR δ
(19) (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987,
109, 5551. (b) Corey, E. J.; Bakshi, R. K.; Shibata, S.; Chen, C. P.; Singh,
V. K. J. Am. Chem. Soc. 1987, 109, 7925. (c) Corey, E. J.; Bakshi, R. K.
Tetrahedron Lett. 1990, 31, 611. (d) Corey, E. J. Pure Appl. Chem. 1990,
62, 1209.
(20) For other examples of diastereoselective CBS reductions, see (a)
Corey, E. J.; Helal, C. J. Tetrahedron Lett., in press (Cicaprost ω-side chain);
(b) Rao, M. N.; McGuigan, M. A.; Zhang, X.; Shaked, Z.; Kinney, W. A.;
Bulliard, M.; Laboue, B.; Lee, N. E. J. Org. Chem. 1997, 62, 4541 (steroidal
side chains); (c) Tschaen, D. M.; Abramson, L.; Cai, D.; Desmond, R.;
Dolling, U.-H.; Frey, L.; Karady, S.; Shi, Y.-J.; Verhoeven, T. R. J. Org.
Chem. 1995, 60, 4324 (MK-0499).
(13) Prakash, C.; Saleh, S.; Blair, I. A. Tetrahedron Lett. 1989, 30, 19.
(14) Approximately 7% of a minor (nonrearranged) product derived from
elimination of the initially formed carbocation of 7 was isolated from this
reaction. After TBS ether cleavage, this product was separated from 8 by
silica gel radial chromatography.
(15) We are indebted to Dr. Marcus Semones for carrying out the X-ray
crystallographic analysis. Detailed X-ray crystallographic data are available
from the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge, CB2 1EZ, U.K.
(16) Garegg, P. J.; Samuelsson, B. J. Chem. Soc., Perkin Trans. I 1980,
2866.
(17) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155. An
improved procedure for the preparation of the Dess Martin periodinane has
been reported: Ireland, R. E.; Liu, L. J. Org. Chem. 1993, 58, 2899.
(18) Ihara, M.; Suzuki, S.; Taniguchi, N.; Fukumoto, K. J. Chem. Soc.,
Perkin Trans. 1 1993, 2251.
(21) Kernan, M. R.; Faulkner, D. J. J. Org. Chem. 1988, 53, 2773.
(22) Reported rotation of dysidiolide [R]2D3 -11.1 (c 0.60, 1:1
CH2Cl2-MeOH).1
(23) Obtained from Dr. Sarath P. Gunasekera, Harbor Branch Oceano-
graphic Institute, Fort Pierce, FL.
(24) This research was assisted financially by a grant from the National
Institutes of Health.

12428 J. Am. Chem. Soc., Vol. 119, No. 51, 1997
Corey and Roberts
2.49, quintet; 13C NMR δ 39.5, septet). Analytical thin-layer chroma-
tography was performed using Merck 60 F254 precoated silica gel plates
(0.25 mm thickness). Subsequent to elution, ultraviolet illumination
at 254 nm allowed for visualization of UV active material. Staining
with Verghn’s reagent followed by warming of the silica gel plate
allowed for further visualization. Verghn’s reagent was prepared by
dissolving ammonium molybdate (40 g) and ceric sulfate (1.6 g) in
10% aqueous H2SO4 (800 mL). Radial chromatography was performed
on a Harrison Research Chromatotron 7924 and silica gel plates (no.
7749, Kieselgel 60 PF254, Merck).
0.45; product, 0.38 (3:1 hexanes-EtOAc, Verghn’s). Spectroscopic
data for the R,â-enone: [R]D23 +28.0 (c 1.00, MeOH); FTIR (film)
2979, 1668, 1446, 1186, 1066, 914 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.03 (d, 1 H, J ) 10.3 Hz), 5.93 (d, 1 H, J ) 10.3 Hz), 5.55-5.65
(m, 1 H), 4.99-5.04 (m, 2 H), 3.93-4.04 (m, 4 H), 2.65 (dd, 1H, J )
5.6 and 13.9 Hz), 2.45-2.48 (m, 1 H), 2.12 (dd, 1 H, J ) 9.1 and 13.9
Hz), 1.42-1.74 (m, 6 H), 1.27 (s, 3 H), 1.07 (s, 3 H); 13C NMR (101
MHz, CDCl3) δ 203.8, 155.3, 134.6, 127.3, 117.6, 111.8, 65.0, 64.8,
47.8, 45.2, 43.3, 41.6, 29.5, 22.5, 21.9, 20.3, 19.2; HRMS (EI, Pos)
m/z calcd for [C17H24O3]+, 276.1725; found, 276.1728.
(4aS,5S,8aS)-(+)-3,4,4a,7,8,8a-Hexahydro-5,8a-dimethyl-5-(2-
propenyl)naphthalene-1,6(2H,5H)-dione 1-(Ethylene Acetal) (3). To
a solution of lithium (519 mg, 74.8 mmol, 4.3 equiv) in liquid ammonia
(100 mL) at -40 °C was added a solution of 23 (4.09 g, 17.32 mmol,
1.0 equiv, azeotropically dried with benzene) and water (337 µL, 0.867
mmol, 1.08 equiv) in dry THF (70 mL).25 After the mixture was stirred
for 10 min at -40 °C, isoprene (7.5 mL, 74.8 mmol, 4.3 equiv) was
added, and the dark suspension was cooled to -78 °C and treated with
allyl bromide (16.2 mL, 187 mmol, 10.8 equiv). The suspension was
slowly warmed to -35 °C over 1 h, and after 0.5 h at -35 °C it was
cooled to -78 °C and treated with water (5 mL, dropwise). The mixture
was warmed to 23 °C over 2 h, diluted with water (200 mL), and
extracted with Et2O (3 × 200 mL). The combined organic fractions
were dried (MgSO4) and concentrated in Vacuo. Flash chromatography
(200 g of SiO2; eluent, 5% Et2O-hexanes; product, fractions 12-18;
125 mL/fraction) afforded 34 (3.96 g, 14.2 mmol, 82% yield) as a clear
oil: Rf starting material, 0.24; product, 0.48 (3:1 hexanes-EtOAc,
Verghn’s); [R]2D3 +19.4 (c 1.00, MeOH); FTIR (film) 2947, 2880,
(4aS,5S,8S,8aS)-(+)-3,4,4a,7,8,8a-Hexahydro-5,8a-dimethyl-5-(2-
propenyl)-8-trimethylsilylnaphthalene-1,6(2H,5H)-dione 1-(Ethylene
Acetal) (4). Methyllithium (10.2 mL, 14.3 mmol, 1.4 M in Et2O, 9.0
equiv) and Et2O (20 mL) were sequentially added to frozen hexam-
ethyldisilane (3.26 mL, 15.9 mmol, 10.0 equiv) in HMPA (5 mL) at
-78 °C.25 The mixture was warmed to 0 °C and stirred vigorously
for several minutes. The resulting red solution was cooled to -78 °C,
and a solution of R,â-enone (440 mg, 1.59 mmol, 1.0 equiv) in Et2O
(150 mL) was added dropwise via cannula at -78 °C over 2.5 h. After
30 min, methanol (5 mL) and water (5 mL) were added to the yellow
solution, and the mixture was warmed to 23 °C and diluted with 1:1
Et2O-hexanes (300 mL). The combined organic fractions were washed
with water (2 × 100 mL), dried (MgSO4), and concentrated in Vacuo.
Flash chromatography (50 g of SiO2; eluent, 7% Et2O-hexanes for
fractions 1-20 and 15% Et2O-hexanes thereafter; product, fractions
20-34; 10 mL/fraction) afforded 4 (357 mg, 1.02 mmol, 64% yield)
as a clear oil: Rf starting material, 0.38; product, 0.60 (3:1 hexanes-
EtOAc, Verghn’s); [R]2D3 +55.9 (c 1.00, MeOH); FTIR (film) 2952,
1710, 1451, 1380, 1250, 1119, 857 cm-1; 1H NMR (400 MHz, CDCl3)
δ 4.60-4.70 (m, 1 H), 4.94-5.04 (m, 2 H), 3.90-4.01 (m, 4 H), 2.77
(dd, 1 H, J ) 11.1 and 13.4 Hz), 2.26-2.33 (m, 2 H), 2.10 (dd, 1 H,
J ) 7.6 and 13.8 Hz), 1.84 (dd, 1 H, J ) 4.0 and 11.0 Hz), 1.43-1.55
(m, 6 H), 1.25 (s, 1 H), 1.17 (s, 3 H), 1.00 (s, 3 H), 0.06 (s, 9 H); 13
NMR (101 MHz, CDCl3) δ 217.4, 134.1, 117.7, 113.4, 64.4, 63.7, 47.4,
45.4, 44.9, 37.4, 29.7, 28.7, 28.3, 22.3, 22.1, 18.7, 18.2, 0.9; HRMS
(CI, NH3) m/z calcd for [C20H34O3Si]+NH4 368.2621; found, 368.2621.
Wittig Methylenation of 4. Dimethyl sulfoxide (20 mL) was slowly
added to potassium hydride (628 mg, 15.66 mmol, 6.1 equiv, washed
thoroughly with hexanes) at 23 °C, and the resulting mixture was stirred
until gas evolution ceased.25 After 20 min, Ph3PCH3Br (6.43 g, 18.0
mmol, 7.0 equiv, azeotropically dried with toluene) was added, and
the yellow suspension was stirred for 15 min, after which it was added
via cannula into neat 4 (900 mg, 2.57 mmol, 1.0 equiv) at 23 °C. After
2 h, the red solution was cooled to 0 °C and diluted with water (10
mL), and the mixture was extracted with Et2O (3 × 100 mL). The
combined organic fractions were diluted with CH2Cl2 (200 mL), dried
(Na2SO4), and concentrated in Vacuo. Flash chromatography (50 g of
SiO2; eluent, 3% Et2O-hexanes; product, fractions 7-21; 10 mL/
fraction) afforded the diene (869 mg, 2.50 mmol, 97% yield) as a clear
oil: Rf starting material, 0.54; product, 0.68 (5:1 hexanes-EtOAc,
Verghn’s); [R]2D3 +61.4 (c 1.00, CHCl3); FTIR (film) 2951, 2869,
1380, 857, 833 cm-1; 1H NMR (400 MHz, CDCl3) δ 5.70-5.79 (m, 1
H), 4.90-5.00 (m, 2 H), 4.85 (s, 1 H), 4.70 (s, 1 H), 3.86-3.98 (m, 4
H), 2.48 (ddd, 1 H, J ) 1.0, 9.7, and 13.7 Hz), 2.25 (dd, 1 H, J ) 3.2
and 13.7 Hz), 2.10 (s, 1 H), 2.08 (s, 1 H), 1.86 (dd, 1 H, J ) 3.2 and
11.8 Hz), 1.37-1.64 (m, 6 H), 1.26 (s, 1 H), 1.16 (s, 3 H), 0.95 (s, 3
H), 0.06 (s, 9 H); 13C NMR (101 MHz, CDCl3) δ 153.5, 135.5, 116.5,
113.7, 108.1, 64.3, 63.5, 46.6, 46.3, 46.0, 41.7, 31.6, 29.0, 28.1, 22.5,
22.4, 21.3, 19.1, 1.7; HRMS (CI, NH3) m/z calcd for [C21H36O2Si]+H,
349.2563; found, 349.2561.
1
1703, 1439, 1184, 1047, 910 cm-1; H NMR (400 MHz, CDCl3) δ
5.60-5.71 (m, 1 H), 4.95-5.04 (m, 2 H), 3.84-3.96 (m, 4 H), 2.48-
2.57 (m, 2 H), 2.32 (ddd, 1 H, J ) 3.5, 5.8, and 16.0 Hz), 2.12 (dd, 1
H, J ) 3.5 and 12.7 Hz), 1.88-2.01 (m, 2H ), 1.60-1.70 (m, 3 H),
1.50-1.58 (m, 1 H), 1.35-1.45 (m, 3 H), 1.19 (s, 3 H), 1.02 (s, 3 H);
13C NMR (101 MHz, CDCl3) δ 215.8, 135.2, 117.4, 112.9, 65.3, 64.9,
50.9, 44.3, 42.6, 42.4, 35.0, 30.3, 28.9, 22.7, 21.8, 21.4, 16.4; HRMS
(EI, Pos) m/z calcd for [C17H26O3]+, 278.1882; found, 278.1877.
Conversion of 3 to the Corresponding r,â-Enone. A solution of
34 (1.1 g, 3.95 mmol, 1.0 equiv, azeotropically dried with benzene) in
dry THF (10 mL) was added to a solution of lithium diisopropylamide
(2.35 equiv of n-BuLi, 2.40 equiv of diisopropylamine) in THF (4 mL)
at -78 °C.25 HMPA (6 mL) was added, and the yellow solution was
warmed to 0 °C. After 20 min, the red solution was warmed to 23 °C
for 20 min, cooled to 0 °C, and treated with a solution of diphenyl
disulfide (2.58 g, 11.8 mmol, 3.0 equiv, azeotropically dried with
benzene) in THF (6 mL). The purple solution was warmed to 23 °C
and, after 20 min, was poured into saturated aqueous NaHCO3 (250
mL) and Et2O (250 mL). The organic fraction was washed sequentially
with saturated aqueous NaHCO3 (100 mL) and brine (100 mL), diluted
with CH2Cl2 (300 mL), and then dried (Na2SO4) and concentrated in
Vacuo. The crude R-phenylthio ketone was azeotropically dried with
benzene and used immediately in the next reaction.
A solution of m-chloroperbenzoic acid (4.0 g, 19.8 mmol, 5.0 equiv)
in dry CH2Cl2 (200 mL) was added dropwise via cannula over 30 min
to a suspension of the crude R-phenylthio ketone and NaH2PO4 (3.9 g,
27.7 mmol, 7.0 equiv) in CH2Cl2 (100 mL) at -78 °C over 30 min.25
After 1.5 h, trimethyl phosphite (3.26 mL, 27.7 mmol, 7.0 equiv) was
added, and after 5 min, the suspension was poured into saturated
aqueous NaHCO3 (250 mL). The organic fraction was washed
sequentially with saturated aqueous NaHCO3 (100 mL), brine (100 mL),
and water (100 mL) and then dried (Na2SO4) and concentrated in Vacuo.
The crude sulfoxide was used immediately in the next reaction.
A solution of the crude sulfoxide and trimethyl phosphite (1.86 mL,
15.8 mmol, 4.0 equiv) in dry benzene (130 mL) was heated to reflux
(oil bath, 90 °C).25 After 13 h, the reaction solution was cooled to 23
°C and concentrated in Vacuo. Flash chromatography (200 g of SiO2;
eluent, 10% Et2O-hexanes for fractions 1-20, 15% Et2O-hexanes
for fractions 21-40, 20% Et2O-hexanes for fractions 41-60 and 25%
Et2O- hexanes thereafter; product, fractions 54-78; 25 mL/fraction)
afforded pure R,â-enone (747 mg, 2.70 mmol, 69% yield) and recovered
3 (232 mg, 0.83 mmol, 21% yield) as clear oils: Rf starting material,
C
(4aS,5S,8S,8aS)-(+)-3,4,4a,5,6,7,8,8a-Octahydro-5-(2-hydroxyethyl)-
6-methenyl-5,8a-dimethyl-8-trimethylsilylnaphthalen-1(2H)-one
1-(Ethylene Acetal) (5). A solution of DHQD2-PYDZ9b (91 mg, 0.13
mmol, 0.05 equiv), potassium ferricyanide (2.96 g, 9.0 mmol, 3.5 equiv),
potassium carbonate (1.24 g, 9.0 mmol, 3.5 equiv) and methanesulfona-
mide (238 mg, 2.5 mmol, 1.0 equiv) in t-butyl alcohol-water (1:1, 30
mL) at 23 °C was added to the diene (860 mg, 2.5 mmol, 1.0 equiv).
The resulting solution was cooled to 0 °C with vigorous stirring. After
15 min, potassium osmate (VI) dihydrate (9 mg, 0.03 mmol, 0.01 equiv)
was added to the biphasic mixture, which was stirred for 4 h. The
suspension was treated with excess Na2SO3 and water (20 mL), and
the mixture was extracted with EtOAc (3 × 100 mL). The combined
(25) This reaction was conducted under an atmosphere of dry nitrogen.

Total Synthesis of Dysidiolide
J. Am. Chem. Soc., Vol. 119, No. 51, 1997 12429
1
organic fractions were dried (Na2SO4) and concentrated in Vacuo. Flash
chromatography (60 g of SiO2; eluent, 40% EtOAc-hexanes for 1-10
and 60% EtOAc-hexanes thereafter; product, fractions 13-34; 10 mL/
fraction) afforded the 1,2-diol (925 mg, 2.42 mmol, 97% yield) as a
2.6:1 mixture of diastereomers and a clear oil: Rf starting material,
0.80; product, 0.26 (1:1 hexanes-EtOAc, Verghn’s); FTIR (film) 3405,
(film) 2942, 1710, 1472, 1428, 1247, 1112, 863 cm-1; H NMR (400
MHz, CDCl3) δ 7.63-7.66 (m, 4 H), 7.35-7.42 (m, 6 H), 4.63 (s, 1
H), 4.50 (s, 1 H), 3.72 (ddd, 1 H, J ) 4.7, 10.2, and 10.2 Hz), 3.41
(ddd, 1 H, J ) 5.9, 10.2, and 10.2 Hz), 2.55-2.63 (m, 1 H), 2.26 (dd,
1 H, J ) 14.1 Hz), 2.08 (dd, 2 H, J ) 4.7 and 14.1 Hz), 1.83-1.93
(m, 2 H), 1.57-1.74 (m, 2 H), 1.38-1.42 (m, 1 H), 1.20-1.30 (m, 3
H), 1.23 (s, 3 H), 1.03 (s, 9 H), 1.00 (s, 3 H), -0.05 (s, 9 H); 13C
NMR (101 MHz, CDCl3) δ 214.6, 153.1, 135.6, 134.0, 133.9, 129.5,
127.7, 127.6, 106.3, 59.7, 53.7, 52.5, 42.5, 41.3, 37.7, 31.6, 31.2, 31.1,
27.2, 26.9, 24.5, 21.4, 16.9, -0.2; HRMS (FAB, NaI) m/z calcd for
[C34H50O2Si2]+Na, 569.3247; found, 569.3264.
1
2948, 1443, 1247, 1067, 834 cm-1; H NMR (400 MHz, CDCl3) δ
4.98 (s, 1 H, major), 4.97 (s, 1 H, major), 4.93 (s, 1 H, minor), 4.90 (s,
1 H, minor), 3.84-3.98 (m, 5 H), 3.30-3.44 (m, 2 H), 2.67 (br s, 1
H), 2.57-2.63 (m, 1 H, major), 2.47-2.53 (m, 1 H, minor), 2.34 (d,
1 H, J ) 13.4 Hz, major), 2.27 (d, 1 H, J ) 13.4 Hz, minor), 2.15 (br
s, 1 H), 1.87-1.90 (m, 1 H), 1.38-1.65 (m, 9 H), 1.16 (s, 3 H, minor),
1.13 (s, 3 H, major), 1.09 (s, 3 H, minor), 1.07 (s, 3 H, major), 0.06 (s,
9 H); HRMS (CI, NH3) m/z calcd for [C21H38O4Si]NH4+, 400.2883;
found, 400.2874.
Sodium periodate (2.6 g, 12.05 mmol, 5 equiv) was added to a
solution of the 1,2-diol (920 mg, 2.41 mmol, 1.0 equiv) in THF-water
(4:1; 40 mL) at 23 °C. After 30 min, the white suspension was diluted
with brine (40 mL), and the resulting mixture was extracted with CH2Cl2
(3 × 100 mL). The combined organic fractions were dried (Na2SO4)
and concentrated in Vacuo. The crude aldehyde was immediately
subjected to the next reaction.
Sodium borohydride (274 mg, 7.23 mmol, 3 equiv) was added to a
solution of the crude aldehyde in THF-ethanol (6:1; 30 mL) at 0 °C.25
After 20 min, the clear solution was diluted with water (50 mL), and
the resulting mixture was extracted with CH2Cl2 (3 × 100 mL). The
combined organic fractions were dried (Na2SO4) and concentrated in
Vacuo. Flash chromatography (60 g of SiO2; eluent, 40% Et2O-
hexanes for fractions 1-5, 70% Et2O-hexanes thereafter; product,
fractions 16-32; 30 mL/fraction) afforded 5 (795 mg, 2.25 mmol, 94%
yield) as a clear foam: Rf starting material, 0.26; aldehyde, 0.77;
product, 0.58 (1:1 hexanes-EtOAc, Verghn’s); [R]2D3 +37.9 (c 1.00,
CHCl3); FTIR (film) 3352, 2929, 1467, 1452, 1246, 1112, 1068, 1027,
855 cm-1; 1H NMR (500 MHz, CDCl3) δ 4.87 (s, 1 H), 4.83 (s, 1 H),
3.95-3.98 (m, 1 H), 3.86-3.92 (m, 3 H), 3.58-3.66 (m, 2 H), 2.53
(dd, 1 H, J ) 10.0 and 13.5 Hz), 2.28 (dd, 1 H, J ) 2.9 and 13.5 Hz),
1.83 (dd, 1 H, J ) 3.2 and 11.8 Hz), 1.40-1.70 (m, 10 H), 1.14 (s, 3
H), 1.03 (s, 3 H), 0.06 (s, 9 H); 13C NMR (101 MHz, CDCl3) δ 155.1,
113.6, 108.2, 64.3, 63.5, 59.6, 47.9, 46.3, 43.9, 40.9, 31.4, 29.0, 28.1,
22.6, 22.5, 21.0, 19.0, 1.7; HRMS (EI, Pos) m/z calcd for [C20H36O3Si]+,
352.2434; found, 352.2434.
(4aS,5R,6R,8S,8aS)-(-)-3,4,4a,5,6,7,8,8a-Octahydro-5-(2-t-butyl-
diphenylsiloxyethyl)-5,6,8a-trimethyl-8-trimethylsilylnaphthalen-
1(2H)-one (6). Tris(triphenylphosphonium)rhodium chloride (137 mg,
0.148 mmol, 0.15 equiv) was added to a solution of the TBDPS ether
(540 mg, 0.987 mmol, 1.0 equiv, azeotropically dried with benzene)
in dry benzene (18 mL) at 23 °C. The red suspension was placed in
a Parr high-pressure vessel which was purged and then filled with
hydrogen (1000 psi). After stirring for 23 h at 65 °C, the solution was
filtered through SiO2 (15 g, 300 mL of 10% Et2O-hexanes) and then
concentrated in Vacuo to afford a 3.67:1 mixture of 6 and a minor
diastereomer (6S configuration). Radial chromatography (2 × 4 mm
SiO2 plate; eluent, 250 mL of hexanes followed by 1% Et2O-hexanes;
product, fractions 88-110; 10 mL/fraction) afforded 6 (411 mg, 0.749
mmol, 76% yield) as a clear syrup: Rf starting material, 0.25; product
6, 0.23; 6S diastereomer, 0.28 (10:1 hexanes-Et2O, Verghn’s);
[R]2D3 -31.9 (c 1.00, CHCl3); FTIR (film) 2956, 2858, 1707, 1428,
1247, 1112, 1085, 835 cm-1; H NMR (400 MHz, CDCl3) δ 7.65-
1
7.68 (m, 4 H), 7.35-7.43 (m, 6 H), 3.66-3.70 (m, 2 H), 2.60-2.69
(m, 1 H), 2.04-2.14 (m, 2 H), 1.49-1.64 (m, 5 H), 1.20 (s, 3 H),
1.14-1.37 (m, 5 H), 1.03 (s, 9 H), 0.92 (s, 3 H), 0.71 (d, 3 H, J ) 7.0
Hz), -0.10 (s, 9 H); 13C NMR (101 MHz, CDCl3) δ 215.0, 135.6,
134.1, 134.0, 129.6, 129.5, 127.6, 60.1, 52.8, 51.2, 42.6, 38.4, 37.7,
35.9, 31.6, 27.7, 27.2, 26.9, 22.7, 22.3, 21.5, 20.4, 19.1, 17.5, 14.5,
14.1, -0.4; HRMS (FAB, NaI) m/z calcd for [C34H52O2Si2]+Na,
571.3404; found, 571.3403.
Allylation of 6. Allylmagnesium bromide (2.89 mL, 1.0 M in Et2O,
2.89 mmol, 4.0 equiv) was added to a solution of 6 (395 mg, 0.720
mmol, 1.0 equiv, azeotropically dried with benzene) in dry Et2O (40
mL) at -78 °C.25 The gray solution was stirred for 10 min and then
warmed to 23 °C. After 10 min, the reaction solution was cooled to
-78 °C and treated with saturated aqueous NH4Cl (5 mL, dropwise),
and the mixture was warmed to 23 °C. The mixture was partitioned
between brine (40 mL) and CH2Cl2 (40 mL), and the aqueous portion
was extracted with CH2Cl2 (2 × 100 mL). The combined organic
fractions were dried (Na2SO4) and concentrated in Vacuo. Flash
chromatography (40 g of SiO2; eluent, hexanes for fractions 1-10, 4%
Et2O-hexanes thereafter; product, fractions 12-17; 30 mL/fraction)
afforded the tertiary alcohol (420 g, 0.711 mmol, 99% yield) as a clear
syrup: Rf starting material, 0.55; product, 0.65 (5:1 hexanes-EtOAc,
Verghn’s); [R]2D3 -20.2 (c 0.79, CHCl3); FTIR (film) 3573, 2998,
Deketalization and Silylation of 5. Pyridinium p-toluenesulfonate
(564 mg, 2.24 mmol, 1.0 equiv) was added to a solution of 5 (790 mg,
2.24 mmol, 1.0 equiv) in acetone-water (4:1, 35 mL) at 23 °C. The
solution was heated to 65 °C for 2 h, cooled to 23 °C, and diluted with
brine (40 mL), and the mixture was extracted with CH2Cl2 (3 × 75
mL). The combined organic fractions were dried (Na2SO4) and
concentrated in Vacuo. Flash chromatography (50 g of SiO2; eluent,
60% Et2O- hexanes; product, fractions 6-24; 30 mL/fraction) afforded
the ketone (690 mg, 2.24 mmol, 100% yield) as a clear syrup: Rf
starting material, 0.58; product, 0.50 (1:1 hexanes-EtOAc, Verghn’s);
[R]2D3 -24.3 (c 0.82, CHCl3); FTIR (film) 3400, 2950, 1708, 1439,
1
2891, 1472, 1428, 1243, 1112, 1076, 1036, 859 cm-1; H NMR (400
1
1247, 1025, 862 cm-1; H NMR (400 MHz, CDCl3) δ 4.78 (s, 1 H),
MHz, CDCl3) δ 7.67-7.69 (m, 4 H), 7.36-7.44 (m, 6 H), 5.84-5.91
(m, 1 H), 5.14-5.19 (m, 2 H), 3.68-3.72 (m, 2 H), 2.63 (dd, 1 H, J
) 7.1 and 13.7 Hz), 2.41 (dd, 1 H, J ) 7.7 and 13.7 Hz), 1.65-1.83
(m, 2 H), 1.15-1.56 (m, 11 H), 1.04 (s, 12 H), 0.83 (s, 3 H), 0.76 (d,
3 H, J ) 6.8 Hz), 0.02 (s, 9 H); 13C NMR (101 MHz, CDCl3) δ 135.6,
135.0, 134.1, 129.5, 127.6, 118.7, 76.9, 60.4, 47.9, 44.0, 42.9, 37.4,
36.7, 35.9, 33.0, 28.4, 26.9, 22.8, 22.4, 21.8, 20.7, 19.1, 15.3, 15.0,
2.3; HRMS (FAB, NaI) m/z calcd for [C37H58O2Si2]+Na, 613.3873;
found, 613.3868.
(1S,4aS,5R,6R,8S,8aS)-(-)-Decahydro-1-[3-(t-butyldimethylsil-
oxy)propyl]-5-[2-(t-butyldiphenylsiloxy)ethyl]-1-hydroxy-5,6,8a-tri-
methyl-8-trimethylsilylnaphthalene (7). Borane-dimethyl sulfide
complex (360 µL, 10.0 M, 3.60 mmol, 5.4 equiv) was added to a
solution of the tertiary alcohol (397 mg, 0.672 mmol, 1.0 equiv) in dry
Et2O (50 mL) at -78 °C.25 The clear solution was warmed to 23 °C.
After 2.5 h, the solution was cooled to 0 °C, and ethanol (9 mL), NaOH
(9 mL, 3 M aqueous solution) and H2O2 (9 mL, 30% aqueous solution)
were added sequentially and dropwise (to control gas evolution). The
white mixture was warmed to 23 °C, stirred for 3.5 h, and partitioned
between brine (100 mL) and Et2O (50 mL). The aqueous portion was
4.68 (s, 1 H), 3.65-3.71 (m, 1 H), 3.46-3.53 (m, 1 H), 2.63-2.73
(m, 1 H), 2.30-2.36 (m, 1 H), 2.05-2.24 (m, 3 H), 1.74-1.84 (m, 4
H), 1.35-1.53 (m, 2 H), 1.22-1.30 (m, 2 H), 1.29 (s, 3 H), 1.08 (s, 3
H), -0.03 (s, 9 H); 13C NMR (101 MHz, CDCl3) δ 214.6, 153.6, 106.4,
58.8, 53.9, 52.6, 42.7, 41.3, 37.8, 31.6, 31.1, 27.2, 24.2, 21.8, 17.0,
-0.2; HRMS (CI, NH3) m/z calcd for [C18H32O2Si]+NH4, 326.2515;
found, 326.2514.
2,6-Lutidine (1.05 mL, 8.95 mmol, 4.0 equiv), t-butyldiphenylsilyl
chloride (1.74 mL, 6.71 mmol, 3.0 equiv), and DMAP (273 mg, 2.24
mmol, 1.0 equiv) were added sequentially to a solution of the ketone
(690 mg, 2.24 mmol, 1.0 equiv) in dry CH2Cl2 (25 mL) at 23 °C.25
After the mixture was stirred at 23 °C for 1.5 h, brine (20 mL) was
added, and the mixture was extracted with CH2Cl2 (3 × 150 mL). The
combined organic fractions were dried (Na2SO4) and concentrated in
Vacuo. Flash chromatography (80 g of SiO2; eluent, 2% Et2O-hexanes
for fractions 1-10, 4% Et2O-hexanes thereafter; product, fractions
7-37; 30 mL/fraction) afforded the TBDPS ether (1.18 g, 2.16 mmol,
96% yield) as a clear syrup: Rf starting material, 0.19; product, 0.72
(3:1 hexanes-EtOAc, Verghn’s); [R]2D3 -2.4 (c 1.00, CHCl3); FTIR

12430 J. Am. Chem. Soc., Vol. 119, No. 51, 1997
Corey and Roberts
extracted with Et2O (2 × 100 mL) and the combined organic fractions
were dried (MgSO4) and concentrated in Vacuo. Flash chromatography
(60 g of SiO2; eluent, 25% Et2O-hexanes for fractions 1-10, 40%
Et2O- hexanes thereafter; product, fractions 20-33; 30 mL/fraction)
afforded the primary-tertiary diol (390 mg, 0.640 mmol, 95% yield)
as a clear foam: Rf starting material, 0.65; product, 0.12 (5:1 hexanes-
EtOAc, Verghn’s); [R]2D3 -21.4 (c 1.00, CHCl3); FTIR (film) 3322,
X-ray Analysis Summary for the Bis(3,5-Dinitrobenzoate) De-
rivative of 8.15 Data was collected using a Siemens SMART CCD-
(charge-coupled device-) based diffractometer equipped with an LT-2
low-temperature apparatus at 213 K. A suitable crystal (crystallized
from ether at 4 °C as small colorless plates) was chosen and mounted
on a glass fiber using grease. Data was measured using Ω scans of
0.3 °/frame for 30 s, such that a hemisphere was collected. A total of
1271 frames were collected with a final resolution of 0.75 Å. Cell
parameters were retrieved using SMART software and refined using
SAINT on all observed reflections. Data reduction was performed using
SAINT software, which corrects for Lp and decay. The structure was
solved by the direct method using the SHELXS-90 program and refined
by the least-squares method on F2, SHELXL-93, incorporated in
SHELXTL-IRIX V 5.03. Summary of crystal parameters: formula,
C32H36N4O12; MW ) 668.65; a ) 9.7272 (18); b ) 11.997 (4); c )
15.216 (5); R ) 75.93 (3)°; â ) 72.45 (2)°; γ ) 74.952 (19)°; vol )
1608.5 (7) Å3; triclinic; P-1; Z ) 2; crystal size ) 0.11 × 0.05 × 0.12
mm; GOF ) 1.010; final R indices [I > 2σ(I)], R1 ) 6.25%, wR2 )
16.65%; R indices (all data), R1 ) 7.46%, wR2 ) 17.93%.
Iodination of 8. Iodine (255 mg, 1.00 mmol, 4 equiv) was added
to a solution of triphenyl phosphine (329 mg, 1.25 mmol, 5 equiv) and
imidazole (128 mg, 1.88 mmol, 7.5 equiv) in dry CH2Cl2 (10 mL) at
0 °C.25 After 10 min at 23 °C, the yellow suspension was treated with
2-methyl-2-butene (0.5 mL), stirred for 10 min, and added to a solution
of 8 (130 mg, 0.251 mmol, 1.0 equiv) in dry CH2Cl2 (2 mL) at 23 °C.
After 10 min, water (20 mL) and Et2O (50 mL) were added, and the
organic portion was washed with Na2S2O3 (20 mL, 0.1 N aqueous
solution), dilute H2O2 (20 mL, to remove excess triphenyl phosphine),
and water (30 mL). The organic fraction was diluted with hexanes
(50 mL), dried (Na2SO4), and concentrated in Vacuo. Flash chroma-
tography (20 g of SiO2; eluent, 4% Et2O-hexanes; product, fractions
3-13; 10 mL/fraction) afforded the iodide (153 mg, 0.243 mmol, 97%
yield) as a clear oil that was immediately subjected to the next
reaction: Rf starting material, 0.27; product, 0.68 (5:1 hexanes-EtOAc,
Verghn’s).
1
2950, 2867, 1462, 1381, 1238, 1119, 1075, 856 cm-1; H NMR (500
MHz, CDCl3) δ 7.66-7.68 (m, 4 H), 7.36-7.42 (m, 6 H), 3.67-3.71
(m, 4 H), 1.92-1.98 (m, 1 H), 1.49-1.82 (m, 8 H), 1.11-1.43 (m, 8
H), 1.04 (s, 9 H), 1.02 (s, 3 H), 0.83 (s, 3 H), 0.77 (d, 3 H, J ) 6.8
Hz), 0.01 (s, 9 H); 13C NMR (101 MHz, CDCl3) δ 135.6, 134.1, 129.5,
127.6, 77.1, 63.6, 60.4, 48.4, 44.2, 42.9, 37.5, 36.7, 32.5, 31.6, 28.4,
27.7, 26.9, 26.8, 22.7, 22.5, 21.3, 20.7, 19.1, 15.2, 15.1, 2.2; HRMS
(FAB, NaI) m/z calcd for [C37H60O3Si2]+Na, 631.3979; found, 631.3973.
2,6-Lutidine (614 µL, 5.27 mmol, 4.0 equiv), t-butyldimethylsilyl
chloride (595 mg, 3.95 mmol, 3.0 equiv), and DMAP (161 mg, 1.32
mmol, 1.0 equiv) were added sequentially to a solution of the primary-
tertiary diol (802 mg, 1.32 mmol, 1.0 equiv) in dry CH2Cl2 (30 mL) at
23 °C.25 After 12 h, brine (50 mL) was added, and the mixture was
extracted with CH2Cl2 (3 × 100 mL). The combined organic fractions
were dried (Na2SO4) and concentrated in Vacuo. Flash chromatography
(60 g of SiO2; eluent, 3% Et2O-hexanes; product, fractions 6-40; 30
mL/fraction) afforded 7 (914 mg, 1.27 mmol, 97% yield) as a clear
foam: Rf starting material, 0.12; product, 0.59 (5:1 hexanes-EtOAc,
Verghn’s); [R]2D3 -20.9 (c 1.00, CHCl3); FTIR (film) 3406, 2930,
1
2867, 1453, 1254, 1106, 834 cm-1; H NMR (500 MHz, CDCl3) δ
7.66-7.68 (m, 4 H), 7.37-7.41 (m, 6 H), 3.66-3.71 (m, 4 H), 1.91-
1.97 (m, 1 H), 1.76-1.82 (m, 1 H), 1.12-1.73 (m, 16 H), 1.04 (s, 9
H), 1.03 (s, 3 H), 0.92 (s, 9 H), 0.83 (s, 3 H), 0.76 (d, 3 H, J ) 6.9
Hz), 0.08 (s, 3 H), 0.07 (s, 3 H), 0.00 (s, 9 H); 13C NMR (101 MHz,
CDCl3) δ 135.5, 134.1, 129.4, 127.5, 77.1, 63.9, 60.4, 48.2, 44.0, 42.8,
37.4, 36.6, 32.3, 28.3, 28.1, 26.8, 26.7, 25.9, 22.6, 22.5, 21.2, 20.7,
19.0, 18.3, 15.2, 14.9, 14.0, 2.2, -5.3, -5.4; HRMS (FAB, NaI) m/z
calcd for [C43H74O3Si3]+Na, 745.4844; found, 745.4842.
(1S,4aS,5R,6R)-(-)-1,2,3,4,4a,5,6,7-Octahydro-5-[2-(t-butyldi-
phenylsiloxy)ethyl]-1-(4-methyl-4-pentenyl)-1,5,6-trimethylnaphtha-
lene (9). t-Butyllithium (3.1 mL, 5.27 mmol, 1.7 M in pentanes, 21.7
equiv) was added to a solution of 2-bromopropene (223 µL, 2.51 mmol,
10.3 equiv) in dry Et2O (5 mL) at -78 °C.25 After 30 min, the pale
yellow solution was warmed to 23 °C for 1 h, recooled to -78 °C, and
added to a gray suspension of copper (I) iodide (239 mg, 1.25 mmol,
5.15 equiv) in Et2O (5 mL) at -78 °C. The resulting white suspension
was stirred for 1 h at -40 to -50 °C, during which time it became a
gray, then black, suspension and then a dark green-yellow solution. A
solution of the iodide (153 mg, 0.243 mmol, 1.0 equiv) in Et2O (3
mL) at -78 °C was added, and the black-green solution was warmed
to 0 °C. After 30 min, 1:1 saturated aqueous NH4Cl-10% NH4OH (8
mL) was added, and the mixture was warmed to 23 °C with vigorous
stirring. After 20 min, water (50 mL) and Et2O (50 mL) were added,
the aqueous portion was extracted with Et2O (2 × 50 mL), and the
combined organic fractions were dried (MgSO4) and concentrated in
Vacuo. Flash chromatography (20 g of SiO2; eluent, 1% Et2O-hexanes;
product, fractions 3-9; 10 mL/ fraction) afforded 9 (128 mg, 0.236
mmol, 97% yield) as a clear oil: Rf starting material, 0.68; product,
0.75 (5:1 hexanes- EtOAc, Verghn’s); [R]2D3 -17.6 (c 1.00, CHCl3);
FTIR (film) 3071, 2930, 2858, 1725, 1462, 1111 cm-1; 1H NMR (400
MHz, CDCl3) δ 7.66-7.69 (m, 4 H), 7.36-7.42 (m, 6 H), 5.27 (dd,
1H, J ) 3.5 Hz), 4.64 (s, 1 H), 4.61 (s, 1 H), 3.69-3.73 (m, 2H),
1.44-1.88 (m, 12 H), 1.65 (s, 3 H), 1.06-1.30 (m, 6 H), 1.04 (s, 9 H),
0.95 (s, 3 H), 0.73 (s, 3 H), 0.70 (d, 3 H, J ) 6.8 Hz); 13C NMR (101
MHz, CDCl3) δ 146.1, 135.5, 134.1, 129.4, 127.5, 116.6 (br), 109.6,
60.8, 41.2 (br), 40.1 (br), 38.6, 37.2, 35.6, 33.1, 32.2, 31.5, 29.8, 26.8,
26.0, 25.3, 22.3, 22.2, 19.0, 17.2, 14.7, 14.0; HRMS (FAB, NaI) m/z
calcd for [C37H54OSi]+Na, 565.3842; found, 565.3837.
Cationic Rearrangement of 7. Anhydrous boron trifluoride gas
(55 mL, 2.28 mmol, 6.0 equiv) was added portionwise (11 × 5 mL)
via gastight syringe to a sealed solution of 7 (275 mg, 0.38 mmol, 1.0
equiv, azeotropically dried with benzene) in dry CH2Cl2 (75 mL) at
-78 °C.25 After 3 h, triethylamine (5 mL) and THF-water (1:1, 15
mL) were added at -78 °C, and the mixture was warmed to 23 °C.
Brine (50 mL) was added, and the aqueous portion was extracted with
CH2Cl2 (2 × 100 mL). The combined organic fractions were dried
(Na2SO4) and concentrated in Vacuo. Flash chromatography (20 g of
SiO2; eluent, hexanes for fractions 1-10, 3% Et2O-hexanes thereafter;
product, fractions 4-12; 10 mL/fraction) afforded an inseparable 9:1
mixture of the rearranged bicycle and an elimination product (244 mg)
as a clear syrup: Rf starting material, 0.41; product, 0.59 (10:1 hexanes-
EtOAc, Verghn’s). The mixture was immediately subjected to the next
reaction.
(1S,4aS,5R,6R)-(-)-1,2,3,4,4a,5,6,7-Octahydro-5-[2-(t-butyldi-
phenylsiloxy)ethyl]-1-(3-hydroxypropyl)-1,5,6-trimethylnaphtha-
lene (8). Pyridinium p-toluenesulfonate (96 mg, 0.38 mmol, 1.0 equiv)
was added to a solution of the above mixture of rearrangement and
elimination products (244 mg) in ethanol (15 mL) at 23 °C, and the
clear solution was heated to 55 °C. After 2.5 h, the solution was cooled
to 23 °C and treated with saturated aqueous NaHCO3 (50 mL), and
the mixture was extracted with CH2Cl2 (3 × 100 mL). The combined
organic fractions were dried (Na2SO4) and concentrated in Vacuo. Radial
chromatography (4 mm SiO2 plate; eluent, 10% Et2O-hexanes; product,
fractions 30-48; 10 mL/fraction) afforded 8 (136.2 mg, 0.263 mmol,
70% yield) as a clear syrup: Rf starting material, 0.74; product, 0.27
(5:1 hexanes-EtOAc, Verghn’s); [R]2D3 -31.7 (c 1.00, CHCl3); FTIR
(film) 3407, 3071, 3050, 2955, 2859, 1471, 1428, 1112, 1028, 908
cm-1; 1H NMR (400 MHz, CDCl3) δ 7.66-7.70 (m, 4 H), 7.36-7.44
(m, 6 H), 5.28 (dd, 1 H, J ) 3.4 Hz), 3.41-3.79 (m, 4 H), 1.85-2.00
(m, 3 H), 1.43-1.70 (m, 9 H), 1.03-1.33 (m, 5 H), 1.05 (s, 9 H), 0.97
(s, 3 H), 0.62-0.65 (m, 6 H); 13C NMR (101 MHz, CDCl3) δ 145.6
(br), 135.6, 135.5, 133.9, 133.8, 129.6, 129.5, 127.6, 127.5, 117.1 (br),
63.4, 61.2, 42.1 (br), 41.0 (br), 39.7 (br), 35.3, 33.2, 32.8, 31.5, 29.4
(br), 28.0, 26.8, 25.9, 22.6, 22.3, 22.0, 19.0, 14.6, 14.0; HRMS (FAB,
NaI) m/z calcd for [C34H50O2Si]+Na, 541.3478; found, 541.3471.
TBDPS Ether Cleavage of 9. Tetrabutylammonium fluoride (1.65
mL, 1.65 mmol, 1.0 M in THF, 9.0 equiv) was added to a solution of
9 (100 mg, 0.184 mmol, 1.0 equiv) in THF (6 mL) at 23 °C. After 8.5
h, water (40 mL) and EtOAc (40 mL) were added, the aqueous portion
was extracted with EtOAc (2 × 40 mL), and the combined organic
fractions were dried (Na2SO4) and concentrated in Vacuo. The yellow
oil was filtered through SiO2 (20 g; eluent, 150 mL of 15% EtOAc-

Total Synthesis of Dysidiolide
J. Am. Chem. Soc., Vol. 119, No. 51, 1997 12431
hexanes) to afford a mixture of the alcohol (54 mg, 0.177 mmol, 96%
yield) and TBDPSF as a clear oil. This mixture was generally subjected
to the next reaction without further purification; however, radial
chromatography (4 mm SiO2 plate; eluent, 5% EtOAc-hexanes;
product, fractions 31-43; 10 mL/fraction) affords an analytically pure
sample of the alcohol. Analytical data for the alcohol: Rf starting
material, 0.76; product, 0.38 (5:1 hexanes-EtOAc, Verghn’s); [R]D23
-54.2 (c 1.00, CHCl3); FTIR (film) 3374, 2955, 1428, 1113, 884, 821
cm-1; 1H NMR (400 MHz, CDCl3) δ 5.29 (dd, 1 H, J ) 3.4 Hz), 4.67
(s, 1 H), 4.66 (s, 1 H), 3.64-3.68 (m, 2 H), 1.94-1.98 (m, 2 H), 1.89
(d, 1 H, J ) 12.3 Hz), 1.49-1.74 (m, 8 H), 1.70 (s, 3 H), 1.06-1.37
(m, 7 H), 0.97 (s, 3 H), 0.85 (s, 3 H), 0.81 (d, 3 H, J ) 6.8 Hz); 13C
NMR (101 MHz, CDCl3) δ 146.8, 145.2 (br), 116.9 (br), 109.3, 59.7,
41.8 (br), 41.2 (br), 39.8 (br), 38.7, 37.2, 35.5, 32.9, 31.5 (br), 29.3,
29.0 (br), 26.0, 22.5, 22.4, 22.3, 14.8, 14.7; HRMS (CI, Pos) m/z calcd
for [C21H36O]+NH4, 322.3110; found, 322.3120.
A solution of Dess-Martin periodinane (10 mg, 0.024 mmol, 1.5 equiv)
and pyridine (5 µL, 0.062 mmol, 3.8 equiv) in dry CH2Cl2 (0.5 mL) at
0 °C was added to a solution of epi-11 (6 mg, 0.016 mmol, 1.0 equiv)
in CH2Cl2 (0.5 mL).25 The solution was warmed to 23 °C for 10 min,
hexanes (5 mL) were added, the resulting white suspension was filtered
through Celite, and the filtrate was concentrated in Vacuo. Flash
chromatography (3 g of SiO2; eluent, 7% Et2O-hexanes; product,
fractions 2-6; 10 mL/fraction) afforded 12 (6 mg, 0.016 mmol, 100%
yield) as a clear oil that was subjected to the next reaction: Rf starting
material, 0.46; product, 0.60 (5:1 hexanes-EtOAc, Verghn’s); 1H NMR
(400 MHz, CDCl3) δ 7.94 (s, 1 H), 7.39 (s, 1 H), 6.72 (s, 1 H), 5.33
(d, 1 H, J ) 3.7 Hz), 4.57 (s, 1 H), 4.55 (s, 1 H), 2.55-2.72 (m, 2 H),
1.59-1.94 (m, 10 H), 1.59 (s, 3 H), 1.05-1.43 (m, 6 H), 0.99 (s, 3 H),
0.97 (s, 3 H), 0.87 (d, 3 H, J ) 6.5 Hz).
(1S,4aS,5R,6R)-(-)-1,2,3,4,4a,5,6,7-Octahydro-5-[2R-2-hydroxy-
2-(3-furyl)ethyl]-1-(4-methyl-4-pentenyl)-1,5,6-trimethylnaphtha-
lene (11). A freshly prepared solution of borane-dimethyl sulfide (48
µL, 0.024 mmol, 0.5 M in toluene, 2.0 equiv) was added to a solution
of 12 (4.5 mg, 0.012 mmol, 1.0 equiv, azeotropically dried with
benzene) and (S)-B-methyl CBS catalyst 13 (470 µL, 0.024 mmol, 0.05
M in toluene, 2.0 equiv) at -78 °C.25 After the mixture was stirred
for 15 h at -30 °C, methanol (100 µL) was added, followed by water
(0.5 mL) and Et2O (2 mL), and the mixture was warmed to 23 °C.
Water (10 mL) and Et2O (10 mL) were added, and the aqueous portion
was extracted with Et2O (2 × 20 mL). The combined organic fractions
were dried (MgSO4) and concentrated in Vacuo. Flash chromatography
(3 g of SiO2; eluent, 8% Et2O-hexanes; product, fractions 12-22; 10
mL/ fraction) afforded 11 (4.1 mg, 0.011 mmol, 91% yield) as a clear
oil.
(1S,4aS,5R,6R)-1,2,3,4,4a,5,6,7-Octahydro-5-(formylmethyl)-1-(4-
methyl-4-pentenyl)-1,5,6-trimethylnaphthalene (10). A solution of
Dess-Martin periodinane (306 mg, 0.722 mmol, 5.0 equiv) and pyridine
(117 µL, 1.44 mmol, 10.0 equiv) in dry CH2Cl2 (5 mL) at 0 °C was
added to a solution of the alcohol (44 mg, 0.144 mmol, 1.0 equiv) in
CH2Cl2 (2 mL).25 After 1 h at 23 °C, hexanes (30 mL) were added,
the resulting white suspension was filtered through Celite, and the
filtrate was concentrated in Vacuo. Flash chromatography (10 g of
SiO2; eluent, 3% Et2O-hexanes; product, fractions 3-9; 10 mL/
fraction) afforded 10 (41 mg, 0.135 mmol, 94% yield) as a clear oil
that was immediately subjected to the next reaction: Rf starting material,
1
0.38; product, 0.61 (5:1 hexanes-EtOAc, Verghn’s); H NMR (500
MHz, CDCl3) δ 9.90 (dd, 1 H, J ) 3.1 Hz), 5.33 (m, 1 H), 4.67 (s, 1
H), 4.64 (s, 1 H), 2.33 (dd, 1 H, J ) 1.9 and 14.2 Hz), 2.24 (dd, 1 H,
J ) 3.4 and 14.2 Hz), 1.90-2.08 (m, 4 H), 1.77-1.82 (m, 1 H), 1.68
(s, 3 H), 1.51-1.74 (m, 6 H), 1.09-1.35 (m, 5 H), 1.07 (s, 3 H), 0.99
(s, 3 H), 0.84 (d, 3 H, J ) 6.5 Hz).
Dysidiolide (1). Rose Bengal (2 mg) was added to a solution of 11
(20 mg, 0.054 mmol, 1.0 equiv, azeotropically dried with benzene)
and diisopropylethylamine (94 µL, 0.541 mmol, 10.0 equiv) in dry
CH2Cl2 (30 mL) at 23 °C. The suspension was cooled to -78 °C and
anhydrous oxygen was bubbled in for 20 min, after which the
suspension was placed under an oxygen atmosphere and irradiated with
a 250-W tungsten filament lamp. After 2 h, irradiation was stopped,
the pink solution was warmed to 23 °C, and saturated aqueous oxalic
acid (2 mL) was added. After 30 min of vigorous stirring, water (10
mL) and CH2Cl2-methanol (3:1, 50 mL) were added to the colorless
mixture, and the aqueous portion was extracted with CH2Cl2-methanol
(3:1, 2 × 50 mL). The combined organic fractions were dried (MgSO4)
and concentrated in Vacuo. Flash chromatography (30 g of SiO2; eluent,
2% MeOH-CH2Cl2; product, fractions 9-20; 10 mL/fraction) afforded
1 (21.4 mg, 0.053 mmol, 98% yield) as a white solid: Rf product, 0.40
(1:1 hexanes-EtOAc, Verghn’s); [R]2D3 -10.8 (c 0.60, 1:1 CH2Cl2-
(1S,4aS,5R,6R)-(-)-1,2,3,4,4a,5,6,7-Octahydro-5-[2R-2-hydroxy-
2-(3-furyl)ethyl]-1-(4-methyl-4-pentenyl)-1,5,6-trimethylnaphtha-
lene (11). n-Butyllithium (727 µL, 1.64 M in hexanes, 1.19 mmol,
10.0 equiv) was added to a solution of 3-bromofuran (107 µL, 1.19
mmol, 10.0 equiv) in dry THF (2 mL) at -78 °C, and after 30 min,
the yellow solution was treated with a solution of 10 (36 mg, 0.119
mmol, 1.0 equiv) in THF (3 mL).25 After 30 min, saturated aqueous
NH4Cl (1 mL) and water (5 mL) were added, the mixture was warmed
to 23 °C, and water (20 mL) and Et2O (50 mL) were added. The
aqueous portion was extracted with Et2O (2 × 50 mL), and the
combined organic fractions were diluted with CH2Cl2 (100 mL), dried
(Na2SO4), and concentrated in Vacuo to give a 1:1 mixture of the two
alcohol diastereomers, 11 (desired) and epi-11. Flash chromatography
(20 g of SiO2; eluent, 5% Et2O-hexanes for fractions 1-20 and 8%
Et2O-hexanes thereafter; product epi-11, fractions 14-23, product 11,
fractions 29-40; 10 mL/ fraction) afforded the desired diastereomer
11 (22 mg, 0.059 mmol, 50% yield) and the undesired diastereomer
epi-11 (21 mg, 0.057 mmol, 48% yield) as clear oils: Rf starting
material, 0.75; product (11), 0.32; undesired diastereomer (epi-11), 0.46
(5:1 hexanes-EtOAc, Verghn’s). Spectroscopic data for 11: [R]D23
-36.9 (c 1.00, CHCl3); FTIR (film) 3397, 2930, 2863, 1444, 1024,
875 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.33 (s, 2 H), 6.38 (s, 1 H),
5.31 (s, 1 H), 4.84 (s, 1 H), 4.65 (s, 1 H), 4.58 (s, 1 H), 1.01-1.88 (m,
21 H), 1.64 (s, 3 H), 0.95 (s, 3 H), 0.87 (d, 3 H, J ) 6.5 Hz); 13C
NMR (101 MHz, CDCl3) δ 145.9 (br), 143.2, 138.4, 131.1, 117.1 (br),
109.7, 108.7, 64.0, 41.4 (br), 39.9 (br), 38.4, 37.0 (br), 36.3 (br), 33.4
(br), 31.6, 29.7 (br), 26.0, 23.4 (br), 22.3, 21.9, 14.9; HRMS (CI, NH3)
m/z calcd for [C25H38O2]+NH4, 388.3216; found, 388.3224.
MeOH; [R]2D3 -11.1); melting point: 179-181 °C; FTIR (film)
lit.
3387, 2925, 1744, 1643, 1581, 1444, 1375, 1131 cm-1; 1H NMR (500
MHz, CDCl3) δ 7.84 (d, 1 H, J ) 6.4 Hz), 6.09 (d, 1 H, J ) 6.4 Hz),
5.91 (br s, 1 H), 5.27, 5.18 (br s, 1 H), 4.64 (s, 1 H), 4.60 (s, 1 H),
4.50 (s, 1 H), 4.37 (dd, 1 H, J ) 8.4 Hz), 1.61 (s, 3 H), 1.51 (br s, 3
H), 0.93 (s, 3 H), 0.81 (d, 3 H, J ) 6.5 Hz); 13C NMR (101 MHz,
CDCl3) δ 172.0 (br), 170.4, 145.3, 142.2 (br), 118.3 (br), 116.2 (br),
110.0, 98.1 97.6, 63.8 (br), 41.2 (br), 37.9, 36.4 (br), 33.0, 31.2 (br),
29.7 (br), 26.6 (br), 25.9, 23.5 (br), 22.1, 21.7, 21.5 (br), 14.9; HRMS
(FAB, NaI) m/z calcd for [C25H38O4]+Na, 425.2668; found, 425.2663.
Supporting Information Available: Structure of dysidiolide
and five tables, showing crystallographic data, atom coordinates,
temperature factors, and bond lengths and angles (11 pages).
See any current masthead page for ordering and Internet access
instructions.
(1S,4aS,5R,6R)-1,2,3,4,4a,5,6,7-Octahydro-5-[2-keto-2-(3-fur-
yl)ethyl]-1-(4-methyl-4-pentenyl)-1,5,6-trimethylnaphthalene (12).
JA973023V