Synthesis of a CDE fragment of the insect antifeedant 12-hydroxyazadiradione

Article abstract of DOI:10.1021/jo961100j

A diastereoselective and versatile synthesis of the model insect antifeedant 23 related to 12-hydroxyazadiradione has been achieved in 11 steps starting from α-cyclocitral, 1. The key steps involve intramolecular 1,3-dipolar cycloaddition of a nitrile oxide and a Stille coupling reaction of a vinyl iodide with a stannylfuran.

Full text of DOI:10.1021/jo961100j

J . Org. Chem. 1996, 61, 9097-9102
9097
Syn th esis of a CDE F r a gm en t of th e In sect An tifeed a n t
12-Hyd r oxya za d ir a d ion e
Alfonso Ferna´ndez-Mateos,* Gustavo Pascual Coca, Rosa Rubio Gonza´lez, and
Carolina Tapia Herna´ndez
Universidad de Salamanca, Facultad de C. Quı´micas, Departamento de Quı´mica Orga´nica,
Plaza de los Caı´dos 1-5, 37008 Salamanca, Spain
Received J une 11, 1996X
A diastereoselective and versatile synthesis of the model insect antifeedant 23 related to
12-hydroxyazadiradione has been achieved in 11 steps starting from R-cyclocitral, 1. The key steps
involve intramolecular 1,3-dipolar cycloaddition of a nitrile oxide and a Stille coupling reaction of
a vinyl iodide with a stannylfuran.
Sch em e 1
In tr od u ction
The 12-hydroxy derivatives of the havanensin li-
monoids are promising compounds of interest not only
because of their bioactivity (anticancer, antifeedant)1 but
also because they are potential precursors2 of the C-seco
limonoids (salanin, azadirachtin), considered the most
active of the limonoid family.1b,3 However, despite these
interesting properties, no synthetic approach has been
made to this class of compounds and related CDE
molecular fragments. Here, we have developed a plan
for the synthesis of the CDE molecular fragments of 12-
hydroxyazadiradione which is sufficiently versatile to
access limonoids and pentacyclic analogs.
Resu lts a n d Discu ssion
The plan has been divided into four phases (Scheme
1). The first (A) consists of the intramolecular cycload-
dition of an unsaturated nitrile oxide, which builds up a
tricyclic compound precursor of the hydroxy ketone, a key
intermediate which will be obtained by heterocycle cleav-
age in the second phase (B). The third phase (C),
insertion of a furan ring into the indane nucleus, is based
on a novel Stille type coupling reaction. Finally the
fourth phase (D) involves the elaboration of the cyclo-
pentene inside the cyclopentenone.
The required isoxazoline 10 was obtained from the
R-cyclocitral by two parallel procedures through the
unsatured ester 3 (Scheme 2). Olefination of the R-cy-
clocitral (1)4 followed by selective hydrogenation of the
unsaturated ester 2 gave 3, which was quantitatively
reduced to the alcohol 4 with LAH. From this point
onward we followed two paths to the isoxazoline 10; one5
through the oxime 6 and the other6 through the nitroalk-
ene 9. The overall yield of the first route was 44% and
the second was 46%.7
The second phase of the synthetic plan involves the
cleavage of the heterocycle to the hydroxy ketone (Scheme
3). This transformation was accomplished by treatment
of 10 with Raney nickel in a mixture of methanol-
water-acetic acid8 to afford a mixture of the two epimeric
hydroxy ketones 11a and 11b in a 6:4 ratio, respectively.
Substitution of Raney nickel in acetic acid by Pd/C with
boric acid increased selectivity and avoided the epimer-
ization. The addition of sodium acetate to the reaction
mixture changed the product ratio of hydroxy ketones
11a and 11b to 4:6, respectively (Scheme 3). A simple
method to convert the hydroxy ketone 11a with the axial
hydroxyl group to the corresponding equatorial isomer
11b is based on the Meerwein-Ponford-Verley9 reaction
which after 48 h afforded a 6(ax):4(eq) ratio mixture
starting from pure axial isomer.
Insertion of the furan into the indan nucleus was first
attempted by nucleophilic addition of 3-furyllithium.10
The high acidity of cyclopentanones, the neopentylic
character of the carbonyl group, and the presence of other
oxygenated functions in the molecule are factors that
hinder the nucleophilic reaction. These considerations
led us to approach a more selective procedure compatible
X Abstract published in Advance ACS Abstracts, December 1, 1996.
(1) (a) Taylor, D. A. H. Prog. Chem. Org. Nat. Prod. 1984, 45, 1. (b)
Champagne, D. E.; Koul, O.; Isman, M. B.; Scudder, G. G. E.; Towers,
G. H. N. Phytochemistry 1992, 31, 377.
(2) (a) Mitra, C. R.; Garg, H. S.; Pandy, G. N. Tetrahedron Lett. 1970,
2761. (b) Siddiqui, S.; Siddiqui, B. S.; Faizi, S.; Mahmood, T. J . Nat.
Prod. 1988, 51, 30. (c) Reference (1a) pag. 34; (d) Rajab, M. S.; Bentley,
M. D.; Fort, R. C., J r. J . Nat. Prod. 1988, 51, 168.
(3) Kraus, W. Biologically active compounds from Meliaceae. In
Chemistry and Biotechnology of Biologically Active Natural Products;
Proceedings of the Second Internacional Conference; Budapest, 15-
19 August, 1983. Szantay, Cs., Ed.; Studies in Organic Chemistry. 17;
Elsevier: Amsterdam, 1984; pp 331-345.
(7) All compounds synthesized are racemic modifications, although
only one enantiomer is depicted.
(8) Curran, D. P. J . Am. Chem. Soc. 1983, 105, 5826.
(9) Eliel, E. L.; Ro, R. S. Stereoselective Reductions; Doyle, M. P.,
West, Ch. T., Eds.; Dowden, Hutchinson & Ross, Inc.: Pennsylvania,
1976; p 236.
(4) Gedye, R. N.; Aura, P. C.; Deck, K. Can. J . Chem. 1971, 49, 1764.
(5) Kozikowski, A. P.; Li, C.-S. J . Org. Chem. 1987, 52, 3541.
(6) Kozikowski, A. P.; Chen, Y.-Y.; Wang, B. C.; Xu, Z.-B. Tetrahe-
dron 1984, 40, 2345.
(10) (a) Fukuyama, Y.; Kawashima, Y.; Miwa, T.; Tokoroyama, T.
Synthesis 1974, 443. (b) Imamoto, T.; Sugiura, Y.; Takiyama, N.
Tetrahedron Lett. 1984, 25, 4233. (c) Renoud-Grappin, M.; Vanucci,
C.; Lhommet, G. J . Org. Chem. 1994, 59, 3902.
S0022-3263(96)01100-0 CCC: $12.00 © 1996 American Chemical Society

9098 J . Org. Chem., Vol. 61, No. 26, 1996
Fernandez-Mateos et al.
Sch em e 4
Sch em e 2a
Sch em e 5a
a
(a) (EtO)2POCH2CO2Et, NaH, benzene; (b) H2, Pd/C, Et2NH,
AcOEt; (c) LiAlH4, ether, 0 °C; (d) (COCl)2, DMSO, Et3N, CH2Cl2;
(e) NaOAc, NH2OH‚HCl, H2O; (f) TsCl, py, CH2Cl2; (g) NaI, DMF;
(h) NaNO2, DMF; (i) NaClO, CH2Cl2; (j) PhNCO, Et3N, benzene,
25 °C.
Sch em e 3
a
(a) LiCl, Pd(PPh3)4, Bu3(3-furyl)Sn, THF, reflux; (b) Ac2O, py;
(c) TBDMSCl, imidazole, DMF; (d) m-CPBA, CH2Cl2, -40 °C; (e)
BF3‚Et2O, CH2Cl2, 0 °C; (f) (i) LDA, PhSeBr, THF; (ii) H2O2 30%,
THF; (g) NBu4F, THF.
The usual procedure to transform a ketone into a vinyl
iodide is carried out through the corresponding hydrazone
and subsequent treatment with iodine.15 From both
ketones 11a and 11b, the hydrazones 12a and 12b were
obtained in nearly quantitative yield. The behavior of
each hydrazone with iodine in the presence of triethyl-
amine was very different: while the axial isomer 12a
gave the diiodo alcohol 13 exclusively in 80% yield, the
equatorial isomer 12b afforded the vinyl iodide 14b only
in 82% yield. Dehydrohalogenation of diiodo alcohol 13
to 14a was achieved in 36% yield after 24 h treatment
with DBU in xylene at 90 °C.
The coupling reaction of the vinyl iodides 14a and 14b
separately and 3-furylstannane was carried out in THF
under reflux using tetrakis(triphenylphosphine)pal-
ladium(0) as catalyst11 to give the furan derivatives 15a
and 15b in 60% and 81% yields, respectively (Scheme
5).
with the structural characteristics and functional groups
of the hydroxy ketone 11a . One method which could
fulfill our demands for the mild conditions, chemoselec-
tivity, and low steric requirements would be a Stille type
coupling reaction.11 One partner for the coupling reaction
would be tri-n-butyl(3-furyl)tin12 and the other a enol
triflate or, alternatively a vinyl iodide. Transformation
of the carbonyl group to the enol triflate group was
carried out by treatment with triflic anhydride and 2,6-
di-tert-butyl-4-methylpyridine13 in very low yield. The
McMurry14 procedure was unsuccessful. The discourag-
ing results obtained in the preparation of the enol
triflates prompted us to prepare the vinyl iodides 14a
and 14b (Scheme 4).
The last phase of the synthetic plan was attempted
first with acetates 16a and 16b. Stereoselective epoxi-
dation16 of 16a with m-CPBA in CH2Cl2 at -40 °C gave
(11) (a) Stille, J . K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b)
Scott, W. J .; Stille, J . K. J . Am. Chem. Soc. 1986, 108, 3033. (c) Yang,
Y.; Wong, H. N. C. Tetrahedron 1994, 50, 9583.
(12) Pinhey, J . T.; Roche, E. G. J . Chem. Soc., Perkin Trans. 1 1988,
2415.
(13) Harnish, W.; Morera, E.; Ortar, G. J . Org. Chem. 1985, 50, 1990.
(14) Mc Murry, J . E.; Scott, W. J . Tetrahedron Lett. 1983, 24, 979.
(15) Barton, D. H. R.; Bashiardes, G.; Fourrey, J . L. Tetrahedron
1988, 44, 147.
(16) Mateos, A. F.; de la Fuente, J . A. J . Org. Chem. 1990, 55, 1349.

Synthesis of a CDE Fragment of 12-Hydroxyazadiradione
J . Org. Chem., Vol. 61, No. 26, 1996 9099
spectra were recorded in CDCl3 solution at 200 and 50 MHz,
respectively. IR spectra were obtained as thin films. Mass
spectra were obtained on a VG-TS 250 instrument. All
reactions were carried out under an atmosphere of nitrogen
in glassware dried overnight and cooled under nitrogen.
Reactions were monitored by TLC. Flash column chromatog-
raphies were carried out using silica gel 60 (0.040-0.063 mm
Merck). Organic extracts were washed with saturated NaCl
solution, dried over Na2SO4, and concentrated under reduced
pressure with the aid of a rotary evaporator.
Eth yl 3-(2,6,6-Tr im eth yl-2-cycloh exen yl)-2-p r op en oa te
(2). A dry three-necked flask equipped with stirrer, condenser,
and dropping funnel was purged with dry nitrogen and
charged with a 68.6% dispersion of sodium hydride in mineral
oil (2.4 g, 69 mmol) and dry benzene (21 mL). To this stirred
mixture was added dropwise triethyl phosphonoacetate (14.2
mL, 72 mmol). During the addition period, the temperature
was maintained at 30-35 °C. A vigorous evolution of hydro-
gen was noted during this part of the reaction. After the
addition of triethyl phosphonoacetate had been completed, the
mixture was stirred for 1 h at room temperature to ensure
complete reaction. To this nearly clear solution was added
dropwise R-cyclocitral (1) (10 g, 65.8 mmol). The mixture was
stirred for an additional 1 h at room temperature and diluted
with ether, and water was then added dropwise. The organic
layer was separated, and the aqueous phase was extracted
with ether. The combined extracts were washed with brine
and dried (Na2SO4). Evaporation of the solvent left the
unsaturated ester 2 as a colorless oil (13.2 g, 90%): IR 1715
F igu r e 1.
the epoxide 17a in quantitative yield. An R configuration
was assigned to the oxiranic oxygen, assuming that the
â face is more sterically hindered to the peracid approach
(Scheme 5). This is consistent with the upfield shift in
the 13C NMR signal for the homoallylic carbon bearing
an axial proton cis to the oxygenated function in the
epoxide 17a (47.67 ppm) as compared to the unsaturated
precursor 16a (55.86 ppm).16
Treatment of epoxide 17a with boron trifluoride ether-
ate17 gave only the keto acetate 18a in 87% yield. The
assigned cis relationship to the angular methyl group and
furan is based on the Coxon18 mechanism for epoxide
rearrangement and to the diamagnetic shielding effect
caused in the methyl group by the furan which maintains
the chemical shift of the methyl group under 1.07 ppm
distant from 1.40 ppm for a trans methyl/furan relation.16
By the same procedure, acetate 16b was transformed into
the ketone 18b.
1
cm-1; H NMR δ 0.82 (3H, s), 0.89 (3H, s), 1.27 (3H, t, J ) 7
Hz), 1.53 (3H, s), 4.15 (2H, q, J ) 7 Hz), 5.45 (1H, br s), 5.76
(1H, d, J ) 15.5 Hz), 6.76 (1H, dd, J ) 15.5 Hz and J ′ ) 9.7
Hz); 13C NMR δ 166.10, 149.44, 131.56, 122.11, 122.01, 59.75,
53.65, 32.04, 30.79, 27.29, 26.41, 22.62, 22.37, 13.87; MS m/z
(relative intensity) 222 (11, M+), 177 (8), 166 (36), 93 (100),
77 (31). Anal. Calcd for C14H22O2: C, 75.63; H, 9.97. Found:
C, 75.68; H, 10.10.
Attempts at dehydrogenation of 18b to the correspond-
ing enone (23, R ) OAc) by the known sequence19 of
selenylation, oxidation, and selenoxide elimination were
unsuccessful. Fortunately, the change in the hydroxyl
protector group from acetyl to tert-butyldimethylsilyl
permitted the transformation of the alkene 15b into the
enone 23.
E t h yl 3-(2,6,6-Tr im et h yl-2-cycloh exen yl)p r op a n oa t e
(3). To a solution of 2 (5 g, 22.3 mmol) in ethyl acetate (45
mL) and diethylamine (5 mL) was added 1.25 g of 10% Pd/C.
This stirred mixture was blanketed with hydrogen (1 atm).
After 3 h the catalyst was removed by filtration, and the
filtrate was evaporated to give the ester 3 as a colorless oil (5
Silylation20 of alcohol 15b was achieved by treatment
with tert-butyldimethylsilyl chloride and imidazole in
DMF at 25 °C. The sequence described above for
acetates, epoxidation and epoxide rearrangement, was
applied to unsaturated silyl ether 19 to afford the ketone
21 in 42% yield. Dehydrogenation of the ketone 21 by
the reported procedure21 gave the enone 22. Deprotection
of the hydroxyl group with tetrabutylammonium fluoride
yielded the CDE fragment of 12-hydroxyazadiradione 23.
Stereochemical assignements were based on NOE stud-
ies. Some representative data are shown in the Figure
1.
1
g, 100%): IR 1738 cm-1; H NMR δ 0.86 (3H, s), 0.91 (3H, s),
1.24 (3H, t, J ) 7 Hz), 1.67 (3H, s), 2.33 (2H, t, J ) 10 Hz),
4.11 (2H, q, J ) 7 Hz), 5.32 (1H, br s); 13C NMR δ 173.68,
135.49, 120.88, 59.99, 48.45, 34.31, 32.44, 31.40, 27.45 (2),
25.73, 23.31, 22.88, 14.14; MS m/z (relative intensity) 224 (7,
M+), 195 (25), 177 (29), 123 (88.6), 95 (52), 55 (100). Anal.
Calcd for C14H24O2: C, 74.95; H, 10.78. Found: C, 74.91; H,
10.73.
3-(2,6,6-Tr im eth yl-2-cycloh exen yl)p r op a n ol (4). To a
slurry of LAH (3.4 g, 88.8 mmol) in dry ether (100 mL) at 0 °C
was added dropwise a solution of the ester 3 (10 g, 44.6 mmol)
in dry ether (150 mL). The mixture was vigorously stirred
for 10 min, after which it was quenched with Na2SO4‚10H2O.
The resulting mixture was filtered, and the filtrate was
concentrated in vacuo to give the alcohol 4 as a colorless oil
(7.8 g, 96%): IR 3374 cm-1; 1H NMR δ 0.86 (3H, s), 0.91 (3H,
s), 1.67 (3H, s), 3.58 (2H, m), 5.27 (1H, br s); MS m/z (relative
intensity) 178 (2, M+), 123 (7), 109 (23), 95 (26), 83 (21), 69
(78), 55 (100). Anal. Calcd for C12H22O: C, 79.06; H, 12.16.
Found: C, 79.10; H, 12.18.
Exp er im en ta l Section
Gen er a l Meth od s. Commercial reagents were used as
received. Dichloromethane, pyridine, diethylamine, diisopro-
pylamine, and dimethylformamide were distilled under nitro-
gen from calcium hydride or BaO. Ether and tetrahydrofuran
were distilled from sodium. Hexane and ethyl acetate were
distilled before use. Melting points were determined on a hot-
3-(2,6,6-Tr im eth yl-2-cycloh exen yl)p r op a n a l (5). A so-
lution of dimethyl sulfoxide (6.7 mL, 94.4 mmol) in CH2Cl2
(25 mL) was added dropwise to a stirred solution of oxalyl
chloride (4 mL, 47.2 mmol) in CH2Cl2 (155 mL) under N2 at
-60 °C. After 5 min, a solution of the alcohol 4 (7.8 g, 42.8
mmol) in CH2Cl2-DMSO (3:1, 62 mL) was added dropwise.
stage apparatus and are not corrected. The H and 13C NMR
1
(17) Mateos, A. F.; Lo´pez, A.; Pascual, G.; Rubio, R.; Tapia, C. Synlett
1995, 409.
(18) (a) Coxon, J . M.; Lim, C. E. Aust. J . Chem. 1977, 30, 1137. (b)
Blackett, B. N.; Coxon, J . M.; Hartshorn, M. P.; Richards, K. E. Aust.
J . Chem. 1970, 23, 2077.
(19) (a) Grieco, P. A.; Pogonowski, Ch. S.; Burke, S. J . Org. Chem.
1975, 40, 542.
(20) Ronald, R. C.; Lansinger, J . M.; Lillie, T. S.; Wheeler, C. J . J .
Org. Chem. 1982, 47, 2451.
The reaction mixture was stirred for
a further 20 min,
triethylamine (31 mL, 224 mmol) was added at -60 °C, and
stirring was continued for a further 10 min. Then, it was
allowed to warm to room temperature, and water was added.
The organic layer was separated, and the aqueous phase was
extracted with CH2Cl2. The combined extracts were washed
with water, dried (Na2SO4), and filtered. The solvent was
(21) Baraldi, P. G.; Barco, A.; Benetti, S.; Ferretti, V.; Pollini, G.
P.; Polo, E.; Zanirato, V. Tetrahedron 1989, 45, 1517.

9100 J . Org. Chem., Vol. 61, No. 26, 1996
Fernandez-Mateos et al.
1
removed to afford the aldehyde 5 as a colorless oil (7.7 g,
1370 cm-1; H NMR δ 0.78 (3H, s), 0.86 (3H, s), 1.21 (3H, s),
2.39 (2H, m), 4.23 (1H, dd, J ) 7.3 Hz and J ′ ) 8.7 Hz); 13C
NMR δ 20.26, 22.15, 25.46, 29.67 (2), 31.27, 31.57, 33.48, 50.14,
60.67, 84.10, 174.48; MS m/z (relative intensity) 193 (58, M+),
176 (33), 163 (68), 107 (71), 81 (56), 69 (89), 55 (100). Anal.
Calcd for C12H19NO: C, 74.57; H, 9.91; N, 7.24. Found: C,
74.51; H, 9.88; N, 7.23.
100%): IR 1726 cm-1 1H NMR δ 0.88 (3H, s), 0.95 (3H, s),
;
1.66 (3H, s), 2.47 (2H, m), 5.35 (1H, br s), 9.74 (1H, m). Anal.
Calcd for C12H20O: C, 75.74; H, 11.18. Found: C, 75.80; H,
11.20.
Oxim e of 3-(2,6,6-Tr im eth yl-2-cycloh exen yl)p r op a n a l
(6). A solution of hydroxylamine hydrochloride (30 g) in water
(110 mL) was added to a solution of the aldehyde 5 (7.7 g, 43
mmol) in ether (454 mL). The mixture was vigorously stirred
at room temperature, and a solution of sodium carbonate (46
g) in water (110 mL) was added dropwise. After the mixture
was stirred for an additional 10 min, the layers were sepa-
rated. The aqueous phase was extracted with ether. The
combined extracts were washed with brine, dried (Na2SO4),
filtered, and evaporated to give an oily product identified as a
P r oced u r e B. To a solution of the nitroalkene 9 (2.88 g,
13.6 mmol) in benzene (88 mL) was added phenyl isocyanate
(6 mL, 55.2 mmol) and a catalytic amount of triethylamine
(0.35 mL). The reaction mixture was stirred at room temper-
ature for 2 days. Aqueous ammonium hydroxide (10%) was
added to precipitate the urea which was filtered off. The
filtrate was concentrated in vacuo, and the residue was
purified by flash chromatography (eluent: hexane-ether, 1:1)
to afford the isoxazoline 10 (1.92 g, 73%).
Red u ction of Isoxa zolin e 10. P r oced u r e A. A solution
of the isozaxoline 10 (1.5 g, 7.77 mmol) in methanol (21 mL)
containing acetic acid (3 mL) was hydrogenated in presence
of Raney nickel W-2 for 12 h at room temperature and
atmospheric pressure. After filtration of the catalyst through
Celite, the solvent was removed in vacuo and the residue was
extracted with ether and washed with satured aqueous
NaHCO3. The dried organic phase was concentrated at reduce
pressure to give a residue which was chromatographed using
hexane-ether (7:3) as eluent.
The first fraction (731 mg, 48%) which was a crystalline
product was identified as the hydroxy ketone 11a : mp 68 °C;
IR 3479, 1738 cm-1; 1H NMR δ 0.86 (3H, s), 0.98 (3H, s), 1.19
(3H, s), 2.21 (2H, m), 3.62 (1H, dd, J ) 2.2 Hz and J ′ ) 3.0
Hz); 13C NMR δ 22.03, 23.56, 26.63, 27.25, 29.71, 31.66 (2),
37.30, 51.49, 53.27, 73.75, 225.15; ΜS m/z 196 (2, M+), 181
(14), 140 (53), 123 (15), 97 (100), 81 (22), 69 (15), 55 (24). Anal.
Calcd for C12H20O2: C, 73.43; H, 10.27. Found: C, 73.49; H,
10.31.
The second fraction (487 mg, 32%) was identified as the
hydroxy ketone 11b: IR 3455, 1728 cm-1; 1H NMR δ 0.91 (3H,
s), 1.10 (3H, s), 1.20 (3H, s), 2.39 (2H, m), 3.51 (1H, dd, J )
7.2 Hz and J ′ ) 10.6 Hz); 13C NMR δ 16.84, 22.23, 25.30, 28.92,
29.25, 31.56, 33.93, 36.56, 52.47, 55.01, 67.89, 222.92; MS m/z
(relative intensity) 196 (1, M+), 181 (10), 140 (7), 97 (100), 79
(8), 67 (11), 55 (22). Anal. Calcd for C12H20O2: C, 73.43; H,
10.27. Found: C, 73.40; H, 10.30.
P r oced u r e B. To a solution of the isoxazoline 10 (734 mg,
3.80 mmol) in a mixture of methanol-water (5:1, 21.8 mL)
was added boric acid (470 mg, 7.60 mmol) and Pd/C of 10%
(220 mg). The resulting mixture was hydrogenated for 12 h
at 50 °C and atmospheric pressure. After filtration of the
catalyst through Celite, the solvent was removed in vacuo.
Water was added to the residue which was extracted with
ether. The combined extracts were washed with brine, dried
(Na2SO4), and filtered. The solvent was evaporated to afforded
a product identified as the hydroxy ketone 11a (596 mg, 80%).
P r oced u r e C. To a solution of the isoxazoline 10 (1 g, 5.2
mmol) in methanol (10 mL) was added aqueous sodium
acetate-acetic acid (2 M, 1:1, 0.75 mL) and Pd/C of 10% (300
mg). The resulting mixture was hydrogenated for 1 h 15 min
at 50 °C and atmospheric pressure. After filtration of the
catalyst through Celite, the solvent was removed in vacuo and
the residue was extracted with ether and washed with satured
aqueous NaHCO3. The dried organic phase was concentrated
at reduce pressure to give a residue which was chromato-
graphed using hexane-ether (7:3) as eluent to afford the
hydroxy ketone 11a (300 mg, 30%) and the hydroxy ketone
11b (600 mg, 60%).
Ep im er iza tion of Hyd r oxy Keton e 11b. A mixture of
the hydroxy ketone 11a (1 g, 5.10 mmol), aluminum isopro-
poxide (1 g), acetone (1.5 mL), and 2-propanol (15 mL) was
refluxed under N2 with magnetic stirring for 2 days. Then, it
was cooled to room temperature, poured into aqueous HCl
(6%), and extracted with ether. The combined extracts were
washed with brine, dried (Na2SO4), and filtered. Removal of
solvent afforded a residue which was flash chromatographed
using hexane-ether (7:3) as eluent to give the hydroxy ketone
11a (540 mg, 54%) and the hydroxy ketone 11b (360 mg, 36%).
mixture of the oximes 6 (7.68 g, 92%): IR 3268, 1709 cm-1
;
1H NMR δ 0.87 (6H, s), 0.92 (3H, s), 0.93 (3H, s), 1.67 (6H, s),
5.32 (2H, br s), 6.72 (1H, t, J ) 5.9 Hz), 7.41 (1H, t, J ) 5.9
Hz); MS m/z (relative intensity) 195 (1, M+), 110 (7), 96 (21),
83 (27), 74 (44), 59 (41), 55 (100).
p-Tolu en esu lfon a te of 3-(2,6,6-Tr im eth yl-2-cycloh ex-
en yl)p r op a n ol (7). To a stirred solution of the alcohol 4 (5
g, 27.5 mmol) in pyridine (13.3 mL) at 0 °C was gradually
added p-toluenesulfonyl chloride (7.86 g, 41.5 mmol). After
12 h at 0 °C, the mixture was poured into ice-water and
stirred for an additional 30 min at room temperature. The
two-phase system was extracted with ether. The combined
ethereal extracts were washed with aqueous HCl (2 N),
NaHCO3 (5%), and brine, dried (Na2SO4), filtered, and evapo-
rated to yield the tosylate 7 as a viscous oil (8.1 g, 88%): IR
1362, 1177 cm-1 1H NMR δ 0.81 (3H, s), 0.82 (3H, s), 1.58
;
(3H, s), 2.43 (3H, s), 3.98 (2H, t, J ) 6.4 Hz), 5.26 (1H, br s),
7.32 (2H, d, J ) 8.2 Hz), 7.77 (2H, d, J ) 8.2 Hz).
3-(2,6,6-Tr im eth yl-2-cycloh exen yl)p r op yl Iod id e 8. A
mixture of the tosylate 7 (8.1 g, 24.1 mmol) and sodium iodide
(7.23 g, 48.2 mmol) in acetone (80 mL) was stirred under N2
at room temperature for 20 h. Then, the solvent was removed
in vacuo, and water was added to the residue which was
extracted with ether. The combined extracts were washed
with aqueous Na2SO3 (10%) and brine, dried (Na2SO4), and
filtered. Removal of the solvent afforded a yellow oily residue
identified as the iodide 8 (6.54 g, 93%): IR 2926, 2868, 1451,
1
1366, 1188, 1179 cm-1; H NMR δ 0.85 (3H, s), 0.92 (3H, s),
1.68 (3H, s), 3.16 (2H, t, J ) 7 Hz), 5.30 (1H, br s); MS m/z
(relative intensity) 292 (4, M+), 236 (83), 109 (33), 91 (24), 81
(100), 67 (65), 55 (36).
3-(2,6,6-Tr im eth yl-2-cycloh exen yl)n itr op r op a n e (9). A
mixture of the iodide 8 (6.54 g, 22.4 mmol) and sodium nitrite
(3.09 g, 44.8 mmol) in DMF (46 mL) was stirred under N2 at
room temperature for 6 h. The mixture was poured into ice
and allowed to warm to room temperature. It was extracted
with ether, and the combined extracts were washed with water
and brine, dried (Na2SO4), and filtered. Removal of the solvent
afforded a residue which was flash chromatographed using
hexane-ether (95:5) as eluent.
The first fraction (0.90 g, 19%) was a yellow oil identified
as the nitrite compound 9a : IR 1647 cm-1 1H NMR δ 0.87
;
(3H, s), 0.91 (3H, s), 1.67 (3H, s), 4.66 (2H, m), 5.31 (1H, br s).
The second fraction (3.1 g, 67%) was a viscous yellow oil
identified as the nitro alkene 9: IR 1553 cm-1; 1H NMR δ 0.86
(3H, s), 0.90 (3H, s), 1.66 (3H, s), 4.35 (2H, t, J ) 6.9 Hz), 5.33
(1H, br s); MS m/z (relative intensity) 211 (9, M+), 163 (7),
123 (18), 107 (24), 93 (47), 91 (53), 81 (80), 79 (93), 67 (51), 55
(100).
(4aSR,7RS,7aSR)-4,4,7a-Tr im eth ylper h ydr oin den e[1,7-
cd ]isoxa zolin e (10). P r oced u r e A. To a solution of the
oximes 6 (5 g, 25.6 mmol) and triethylamine (0.2 mL) in CH2-
Cl2 (50 mL) at 0 °C was added dropwise a solution of aqueous
sodium hypochlorite (10%, 46 mL) over a period of 15 min.
After the mixture was stirred for half an hour, it was added
water, and the organic layer was separated. The aqueous
phase was extracted with CH2Cl2. The combined organic
layers were washed with brine, dried (Na2SO4), and filtered.
The solvent was removed, and the residue was purified by flash
chromatography using hexane-ether (1:1) as eluent to yield
the isoxazoline 10 as colorless oil (2.5 g, 50%): IR 1450, 1390,

Synthesis of a CDE Fragment of 12-Hydroxyazadiradione
J . Org. Chem., Vol. 61, No. 26, 1996 9101
Syn t h esis of (4a SR,7RS,7a SR)-7-H yd r oxy-1-iod o-4,4,
7a-tr im eth yl-4,4a,5,6,7,7a-h exah ydr o-3H-in den e (14a). (A)
Hyd r a zon e P r ep a r a tion . A solution of the hydroxy ketone
11a (750 mg, 3.82 mmol) in ethanol (13.3 mL) was treated with
triethylamine (2.6 mL) and hydrazine hydrate (6.6 mL), and
the solution was heated under reflux for 24 h. The solvent
was evaporated, the residue was dissolved in dichloromethane,
and the solution was washed with water to neutrality. Then
the organic phase was dried (Na2SO4) and evaporated to give
the corresponding hydrazone 12a (765 mg, 95%): IR 3430,
(4a SR,7SR,7a SR)-1-(3-F u r yl)-4,4,7a -t r im et h yl-4,4a ,5,
6,7,7a -h exa h yd r o-3H-in d en -7-ol (15b). Vinyl iodide 14b
(780 mg) was treated the same manner as described above.
Flash chromatography (hexane-ether, 8:2) gave the alcohol
15b as a white solid (508 mg, 81%): mp 58-59 °C; IR 3416,
1
1456, 1161, 1047 cm-1; H NMR δ 0.92 (3H, s), 1.12 (3H, s),
1.33 (3H, s), 3.60 (1H, m), 5.90 (1H, m), 6.52 (1H, m), 7.38
(1H, m), 7.62 (1H, m); 13C NMR δ 18.19, 27.94, 29.46, 30.75,
32.15, 33.44, 34.57, 52.00, 59.59, 77.60, 110.69, 126.17 (2),
139.48, 142.34, 145.00; MS m/z (relative intensity) 246 (47,
M+), 231 (21), 147 (100), 131 (27), 115 (54), 91 (78), 77 (57), 55
(98). Anal. Calcd for C16H22O2: C, 78.01; H, 9.00. Found: C,
78.05; H, 9.07.
1469, 1110 cm-1 1H NMR δ 0.69 (3H, s), 0.86 (3H, s), 1.26
;
(3H, s), 3.47 (1H, m) ppm.
(B) Vin yl Iod id e 14a . A solution of the above hydrazone
12a (765 mg, 3.64 mmol) in THF (24.4 mL) and triethylamine
(5.1 mL) was treated with iodine until a slight excess was
present (cessation of nitrogen evolution, brown color not
discharged) and then was added diethyl ether. The ethereal
solution was washed successively with aqueous 2 N HCl, water
to neutrality, aqueous NaHSO3 (10%), water, saturated aque-
ous NaHCO3, and brine. The organic phase was then dried
(Na2SO4) and evaporated to give the diiodide 13 (1.26 g,
80%): 1H NMR δ 0.91 (3H, s), 0.93 (3H, s), 1.29 (3H, s), 4.75
(1H, m) ppm.
1-(3-F u r yl)-4,4,7a -t r im et h yl-4,4a ,5,6,7,7a -h exa h yd r o-
3H-in d en -7-yl Aceta te (16a ). A solution of 15a (75 mg, 0.31
mmol), pyridine (1 mL), DMAP (1 mg), and acetic anhydride
(1 mL) was stirred at room temperature for 7 days and poured
into water. The mixture was extracted with diethyl ether, and
the organic phase was washed successively with 2 N HCl and
aqueous NaHCO3. The organic layer was dried (Na2SO4) and
concentrated to afford 87 mg (100%) of the title compound 16a
1
as an oil: IR 1740 cm-1; H NMR δ 0.97 (3H, s), 1.11 (3H, s),
1.30 (3H, s), 1.86 (3H, s), 5.03 (1H, m), 5.89 (1H, m), 6.34 (1H,
m), 7.31 (2H, m). Anal. Calcd for C18H24O3: C, 74.97; H, 8.39.
Found: C, 74.88; H, 8.42.
To a solution of diiodide 13 (1.26 g, 2.98 mmol) in xylene
(6.8 mL) was added DBN (1.1 mL). The mixture was heated
at reflux for 24 h. Then, it was cooled and diluted with ether.
The resulting mixture was washed sucesively with aqueous
Na2CO3 (10%) and brine, dried (Na2SO4), and evaporated.
Chromatography of the residue on silica gel with pentane as
eluent gave the vinyl iodide 14a as a yellow oil (320 mg,
1-(3-F u r yl)-4,4,7a -t r im et h yl-4,4a ,5,6,7,7a -h exa h yd r o-
3H-in d en -7-yl Aceta te 16b. A solution of 15b (438 mg, 1.78
mmol), pyridine (1 mL), DMAP (1 mg), and acetic anhydride
(1 mL) was stirred at room temperature for 4 h and poured
into water. The mixture was extracted with diethyl ether, and
the organic phase was washed successively with 2 N HCl and
aqueous NaHCO3. The organic layer was dried (Na2SO4) and
concentrated to afford 514 mg (100%) of the title compound
16b as an oil: IR 1750 cm-1; 1H NMR δ 0.92 (3H, s), 1.13 (3H,
s), 1.41 (3H, s), 1.85 (3H, s), 4.37 (1H, m), 5.85 (1H, t, J ) 2.6
Hz), 6.41 (1H, m), 7.29 (1H, m), 7.41 (1H, m). Anal. Calcd
for C18H24O3: C, 74.97; H, 8.39. Found: C, 74.89; H, 8.37.
Syn th esis of th e Silyl Eth er 19. A mixture of the alcohol
15b (270 mg, 1.10 mmol), tert-butylchlorodimethylsilane (662
mg, 4.39 mmol), and imidazole (621 mg, 9.13 mmol) in dry
DMF (1 mL) was stirred overnight under N2 at room temper-
ature. This mixture was extracted with hexane. The com-
bined extracts were concentrated in vacuo, filtered through a
small pad of silica gel, and concentrated to yield the silyl ether
19 as a colorless oil (335 mg, 85%): IR 2934, 2864, 1562, 1351,
1
36%): IR 3488, 1670, 1384, 1015 cm-1; H NMR δ 0.94 (3H,
s), 1.06 (3H, s), 1.19 (3H, s), 3.46 (1H, m), 6.50 (1H, m) ppm.
Syn t h esis of (4a SR,7SR,7a SR)-7-H yd r oxy-1-iod o-4,4,
7a-tr im eth yl-4,4a,5,6,7,7a-h exah ydr o-3H-in den e (14b). (A)
Hyd r a zon e P r ep a r a tion . Hydroxy ketone 11b (750 mg) was
treated in essentially the same manner as described above
except the reaction was completed after 5 h to give the
corresponding hydrazone 12b (765 mg, 95%): IR 3374, 1460,
1
1074 cm-1; H NMR δ 0.87 (3H, s), 1.09 (3H, s), 1.21 (3H, s),
3.40 (1H, m) ppm; MS m/z (relative intensity) 210 (2, M+), 207
(6), 180 (3), 135 (6), 110 (7), 96 (20), 83 (30), 74 (54), 69 (42),
59 (55), 55 (100).
(B) Vin yl Iod id e 14b. A solution of the above hydrazone
12b (765 mg, 3.64 mmol) in THF (24.4 mL) and triethylamine
(5.1 mL) was treated with iodine until a slight excess was
present (cessation of nitrogen evolution, brown color not
discharged) and then was added diethyl ether. The ethereal
solution was washed successively with aqueous 2 N HCl, water
to neutrality, aqueous NaHSO3 (10%), water, saturated aque-
ous NaHCO3, and brine. The organic phase was then dried
(Na2SO4) and evaporated to give the vinyl iodide 14b as a
yellow oil (913 mg, 82%): IR 3381, 1651, 1458, 1053 cm-1; 1H
NMR δ 0.89 (3H, s), 1.07 (3H, s), 1.24 (3H, s), 3.65 (1H, m),
6.30 (1H, m) ppm; MS m/z (relative intensity) 306 (11, M+),
206 (24), 161 (30), 99 (37), 91 (33), 81 (100), 77 (71), 69 (15),
55 (48).
1
1209, 987 cm-1; H NMR δ -0.30 (3H, s), -0.03 (3H, s), 0.83
(9H, s), 0.87 (3H, s), 1.13 (3H, s), 1.37 (3H, s), 3.60 (1H, dd, J
) 3.7 Hz and J ′ ) 10.7 Hz), 5.86 (1H, t, J ) 6.7 Hz), 6.47 (1H,
m), 7.28 (1H, m), 7.52 (1H, m) ppm. Anal. Calcd for C22H36O2-
Si: C, 73.27; H, 10.06. Found: C, 73.33; H,9.89.
(1SR,2RS,4a SR,7RS,7a SR)-1-(3-Fu r yl)-4,4,7a -tr im eth yl-
1,2-ep oxyp er h yd r oin d -7-yl Aceta te (17a ). A solution of
m-chloroperoxybenzoic acid (157 mg, 0.91 mmol) in dry CH2-
Cl2 (8.7 mL) was added dropwise under N2 at -30 °C to a
solution of acetate 16a (87 mg, 0.31 mmol) in dry CH2Cl2 (2.6
mL), and the resulting mixture was stirred at this temperature
for an additional 30 min. A solution of Na2SO3 (10%) was
added, and the resulting heterogeneous mixture was stirred
and gradually warmed to room temperature. The organic
layer was separated, and the aqueous phase was extracted
with CH2Cl2. The combined extracts were washed with
NaHCO3 (5%), water, and brine, dried (Na2SO4), and filtered.
Removal of the solvent afforded the epoxy compound 17a as a
viscous oil (87 mg, 94%): IR 1730, 1255, 1027 cm-1; 1H NMR
δ 0.90 (3H, s), 1.04 (3H, s), 1.28 (3H, s), 1.93 (3H, s), 3.58 (1H,
s), 4.83 (1H, m), 6.26 (1H, m), 7.34 (1H, m), 7.41 (1H, m) ppm;
13C NMR δ 20.50, 21.32, 22.57, 28.59, 29.40, 30.67, 30.80,
31.07, 44.87, 47.67, 64.12, 65.79, 75.06, 109.73, 120.33, 140.94,
142.79, 169.90 ppm.
(4a SR,7RS,7a SR)-1-(3-F u r yl)-4,4,7a -t r im et h yl-4,4a ,5,
6,7,7a -h exa h yd r o-3H-in d en -7-ol (15a ). To a slurry of LiCl
(80 mg, 1.87 mmol) and Pd(PPh3)4 (14 mg, 2.0 mol %) in THF
(1.7 mL) was added a solution of vinyl iodide 14a (187 mg,
0.61 mmol) and 3-(tributylstannyl)furan (217 mg, 0.61 mmol)
in THF (4.5 mL). This mixture was heated under reflux for 2
days, cooled to room temperature, and diluted with pentane.
The resulting solution was washed sequentially with water,
10% ammonium hydroxyde, water, and brine. This solution
was dried (Na2SO4) and filtered. Removal of the solvent
afforded a residue which was flash chromatographed using
hexane-ether (9:1) as eluent to yield the alcohol 15a as a
colorless oil (90 mg, 60%): IR 3560, 1460, 1159, 1045 cm-1
;
1H NMR δ 0.95 (3H, s), 1.11 (3H, s), 1.30 (3H, s), 3.76 (1H, m),
6.13 (1H, m), 6.44 (1H, m), 7.39 (1H, m), 7.43 (1H, m); 13C NMR
δ 24.49, 24.82, 27.94, 29.74, 31.03, 31.45, 35.06, 52.20, 55.86,
71.11, 109.80, 122.00, 130.43, 138.07, 139.91, 142.82 ppm; MS
m/z (relative intensity) 246 (24, M+), 213 (21), 158 (100), 147
(39), 129 (12), 115 (22), 91 (27), 77 (23), 55 (40). Anal. Calcd
for C16H22O2: C, 78.01; H, 9.00. Found: C, 78.08; H, 8.89.
(1SR,2RS,4a SR,7SR,7a SR)-1-(3-Fu r yl)-4,4,7a -tr im eth yl-
1,2-ep oxyp er h yd r oin d -7-yl Aceta te (17b). Acetate 16b
(514 mg) was treated in essentially the same manner as
described above except the reaction was completed after 90
min to give the epoxy acetate 17b as a colorless solid (542 mg)
in 100% yield: mp 84-86 °C; IR 1738, 1373, 1248, 1032 cm-1
;
1H NMR δ 0.86 (3H, s), 1.08 (3H, s), 1.42 (3H, s), 1.54 (3H, s),

9102 J . Org. Chem., Vol. 61, No. 26, 1996
Fernandez-Mateos et al.
3.52 (1H, s), 4.62 (1H, m), 6.48 (1H, m), 7.32 (1H, m), 7.38
(1H, m) ppm; 13C NMR δ 16.03, 20.39, 24.34, 28.88, 29.67,
30.32, 31.24, 33.56, 45.58, 50.57, 60.02, 66.44, 74.35, 111.18,
120.98, 141.20, 142.33, 170.38 ppm. Anal. Calcd for
C18H24O4: C, 71.03; H, 7.95. Found: C, 71.09; H, 7.88.
(1SR,2RS,4a SR,7SR,7a SR)-7-(ter t-Bu tyld im eth ylsilyl)-
1-(3-fu r yl)-4,4,7a-tr im eth yl-1,2-epoxyper h ydr oin den e (20).
Compound 19 (320 mg) was treated in essentially the same
manner as described above to give the epoxy compound 20 as
dropwise a solution of the ketone 21 (75 mg, 0.20 mmol) in
THF (1.3 mL). After enolate formation was complete (30 min),
a solution of phenylselenyl bromide (198 mg, 0.84 mmol) in
THF (1 mL) was added dropwise at -78 °C. After an
additional 30 min, the reaction mixture was allowed to warm
to room temperature, quenched by addition of aqueous satu-
rated NH4Cl, and extracted with ether. The combined extracts
were dried (Na2SO4) and filtered. The solvent was removed
to afforded the phenylseleno ketone.
a colorless oil (217 mg, 65%): IR 2953, 2870, 1120, 898 cm-1
;
To a solution of above selenylated ketone in THF (2 mL) at
0 °C was added 30% hydrogen peroxide (0.2 mL). The reaction
mixture was stirred at room temperature for 5 min and diluted
with ether, and then water was added. The organic layer was
separated, and the aqueous phase was extracted with ether.
The combined extracts were washed with brine, dried (Na2-
SO4), and filtered. The solvent was removed to give a residue
which was flash chromatographed using hexane-ether (8:2)
as eluant to yield the indenone 22 (55 mg, 75%); IR 1699 1103
1H NMR δ -0.34 (3H, s), -0.07 (3H, s), 0.72 (9H, s), 0.84 (3H,
s), 1.07 (3H, s), 1.37 (3H, s), 3.58 (1H, s), 3.62 (1H, m), 6.45
(1H, m), 7.29 (1H, m), 7.40 (1H, m).
(1RS,4a SR,7RS,7a RS)-1-(3-F u r yl)-4,4,7a -t r im et h yl-2-
oxop er h yd r oin d -7-yl Aceta te (18a ). To a solution of the
epoxide 17a (87 mg, 0.28 mmol) in dry CH2Cl2 (10 mL) was
added boron trifluoride-diethyl ether (0.05 mL) at 0 °C, and
the reaction mixture was stirred for 5 min. Then, it was
diluted with ether, and water was added. The layers were
separated, and the organic phase was washed with NaHCO3
(5%) and brine and then dried (Na2SO4). Evaporation of the
solvent afforded a residue which was flash chromatographed
using hexane-ether (8:2) as eluent to give a white solid
identified as the ketone 18a (76 mg, 87%): mp 82-84 °C; IR
1
cm-1; H NMR δ 0.09 (3H, s), 0.10 (3H, s), 0.87 (9H, s), 1.04
(3H, s), 1.22 (3H, s), 1.25 (3H, s), 3.47 (1H, s), 3.59 (1H, dd, J
) 4.3 Hz and J ′ ) 10.7 Hz), 6.00 (1H, s), 6.19 (1H, m), 7.31
(1H, m), 7.34 (1H, m); 13C NMR δ 8.96 (2), 18.19, 25.97 (3),
26.71, 28.49, 31.03, 35.92, 38.51, 54.52, 57.20, 81.11, 112.09,
120.06, 126.98, 142.16 (2), 191.39, 207.13; MS m/z (relative
intensity) 374 (10, M+), 220 (36), 205 (100), 177 (11), 145 (14),
105 (11), 91 (28), 78 (39), 67 (21), 57 (69), 55 (47).
1
1738, 1238, 1021 cm-1; H NMR δ 0.95 (3H, s), 1.00 (3H, s),
1.07 (3H, s), 1.95 (3H, s), 3.23 (1H, s), 4.90 (1H, m), 6.18 (1H,
m), 7.23 (1H, m), 7.37 (1H, m) ppm; 13C NMR δ 20.83, 23.80,
24.22, 29.34, 29.89, 30.21, 32.15, 40.88, 45.25, 49.96, 55.11,
77.00, 111.23, 120.06, 140.99, 142.93, 170.12, 218.19 ppm; MS
m/z (relative intensity) 304 (14, M+), 244 (49), 229 (30), 203
(31), 160 (21), 139 (26), 121 (43), 108 (62), 91 (52), 79 (52), 69
(44), 55 (100). Anal. Calcd for C18H24O4: C, 71.03; H, 7.95.
Found: C, 71.06; H, 7.92.
(1RS,7SR,7aRS)-1-(3-Fu r yl)-7-h ydr oxy-4,4,7a-tr im eth yl-
2,4,5,6,7,7a -h exa h yd r o-1H-in d en -2-on e (23). A solution of
ketone 22 (30 mg, 0.08 mmol) and Bu4NF (76 mg, 0.24 mmol)
in THF (0.5 mL) was stirred at room temperature for 8 h.
Aqueous saturated solution NH4Cl was then added, and the
resulting mixture was extracted with ether. The combined
extracts were washed with brine, dried (Na2SO4), and filtered.
The solvent was removed to give a residue which was flash
chromatographed using hexane-ether (1:1) as eluant to yield
the indenone 23 as a crystalline solid (19 mg, 90%): mp 125
(1RS,4a SR,7SR,7a RS)-1-(3-F u r yl)-4,4,7a -t r im et h yl-2-
oxop er h yd r oin d -7-yl Aceta te (18b). Acetate 17b (542 mg)
was treated in essentially the same manner as described
above. Flash chromatography (hexane-ether, 8:2) gave the
ketone 18b as an oily product (471 mg, 87%): IR 1742, 1246,
1
°C; IR 3453, 1687, 1602, 1033 cm-1; H NMR δ 1.13 (3H, s),
1.27 (3H, s), 1.28 (3H, s), 3.16 (1H, s), 3.90 (1H, dd, J ) 4.4
Hz and J ′ ) 10.4 Hz), 6.13 (1H, s), 6.25 (1H, m), 7.35 (2H, m)
ppm; 13C NMR δ 18.04, 26.22, 26.87, 30.88, 37.77, 39.78, 53.83,
57.09, 77.42, 109.95, 124.80, 126.99, 140.71, 143.49, 191.78,
205.89 ppm; MS m/z (relative intensity) 260 (54, M+), 227 (76),
203 (44), 186 (70), 175 (39), 161 (61), 147 (24), 128 (34), 115
(50), 91 (82), 77 (100), 55 (51), 55 (94). Anal. Calcd for
C16H20O3: C, 73.82; H, 7.74. Found: C, 73.89; H, 7.77.
1
1013 cm-1; H NMR δ 0.91 (3H, s), 0.97 (3H, s), 1.10 (3H, s),
2.06 (3H, s), 3.30 (1H, s), 4.72 (1H, m), 6.15 (1H, m), 7.23 (1H,
m), 7.37 (1H, m) ppm; 13C NMR δ 20.05, 20.89, 23.58, 28.48,
29.94, 32.04, 32.80, 39.91, 45.83, 50.58, 54.91, 74.62, 110.74,
119.15, 140.77, 142.87, 170.38, 215.76 ppm; MS m/z (relative
intensity) 304 (20, M+), 244 (42), 203 (100), 162 (32), 139 (66),
121 (27), 107 (70), 91 (58), 79 (56), 67 (28), 55 (73). Anal. Calcd
for C18H24O4: C, 71.03; H, 7.95. Found: C, 71.10; H, 8.07.
(1RS,4a SR,7SR,7a RS)-7-(ter t-Bu tyld im eth ylsilyl)-1-(3-
fu r yl)-4,4,7a -tr im eth ylp er h yd r oin d en -2-on e (21). Com-
pound 20 (217 mg) was treated in essentially the same manner
as described above. Flash chromatography (hexane-ether,
9:1) gave an oily compound identified as the ketone 21 (139
Ack n ow led gm en t. Financial support of this work
by the Ministerio de Educacio´n y Ciencia of Spain
(DGICYT PB89-0399 and PB95-0943) and the J unta de
Castilla y Leo´n (SA 65/94) is gratefully acknowledged.
We also thank Universidad de Salamanca for the
fellowship to C.T.H.
1
mg, 64%): IR 1739, 1243, 1124 cm-1; H NMR δ 0.04 (3H, s),
0.05 (3H, s), 0.86 (3H, s), 0.89 (9H, s), 0.92 (3H, s), 1.10 (3H,
s), 3.42 (1H, s), 3.45 (1H, dd, J ) 4.8 Hz and J ′ ) 9.8 Hz), 6.15
(1H, m), 7.19 (1H, m), 7.36 (1H, m); MS m/z (relative intensity)
376 (2, M+), 319 (24), 225 (39), 197 (10), 171 (19), 105 (11), 91
(17), 77 (17), 75 (100), 69 (15), 59 (19), 55 (23).
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds 10, 13, 14a , 14b, 15a , 15b, 25a , 25b,
26a , 26b, 27a , 27b, 31, and 32 and the NOE experiment of
the compound 32 (32 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
(1RS,7SR,7a RS)-7-(ter t-Bu tyld im eth ylsilyl)-1-(3-fu r yl)-
4,4,7a -t r im et h yl-2,4,5,6,7,7a -h exa h yd r o-1H -in d en -2-on e
(22). To a solution of lithium diisopropylamide, prepared from
diisopropylamine (0.09 ml, 0.66 mmol) and 1.6 M butyllithium
in hexane (0.38 mL, 0.61 mmol) under N2 at -78 °C, was added
J O961100J