A synthesis of (±)-stemodinone: An application of organoiron chemistry to the construction of sterically congested quaternary carbon centers

Article abstract of DOI:10.1021/jo9705475

A synthesis of racemic stemodinone is described, using tricarbonyl(1-5- η-4-methoxy-1,3-dimethylcyclohexadienyl)iron(I) hexafluorophosphate (9) as an electrophile that is the A-ring precursor. Reaction of 9 with the tin enolate from 4,4-(ethylenedioxy)cyclohexanecarbaldehyde proceeded with excellent regioselectivity and high yield to generate an intermediate representing the A and C rings of the target molecule. The B ring was constructed by introducing a two-carbon electrophilic group onto the A ring, followed by ring closure using an intramolecular enolate alkylation. Installation of the D ring and manipulation to give the final product followed transformations precedented with this series of compounds.

Full text of DOI:10.1021/jo9705475

5284
J . Org. Chem. 1997, 62, 5284-5292
A Syn th esis of (()-Stem od in on e: An Ap p lica tion of Or ga n oir on
Ch em istr y to th e Con str u ction of Ster ica lly Con gested Qu a ter n a r y
Ca r bon Cen ter s
Anthony J . Pearson* and Xinqin Fang
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106
Received March 25, 1997X
A synthesis of racemic stemodinone is described, using tricarbonyl(1-5-η-4-methoxy-1,3-dimeth-
ylcyclohexadienyl)iron(I) hexafluorophosphate (9) as an electrophile that is the A-ring precursor.
Reaction of 9 with the tin enolate from 4,4-(ethylenedioxy)cyclohexanecarbaldehyde proceeded with
excellent regioselectivity and high yield to generate an intermediate representing the A and C
rings of the target molecule. The B ring was constructed by introducing a two-carbon electrophilic
group onto the A ring, followed by ring closure using an intramolecular enolate alkylation.
Installation of the D ring and manipulation to give the final product followed transformations
precedented with this series of compounds.
In tr od u ction
Stemodinone (1) is a tetracyclic diterpenoid, isolated
from the leaves of Stemodia maritimal L, a plant used
on the Carribean island of Curacao for the treatment of
venereal disease.1,2 The structural elucidation of stemo-
dinone was accomplished in 1973 by Manchand, White,
and their co-workers.1 This naturally occurring sub-
stance possesses an interesting arrangement of fused,
spiro, and bridged rings, and especially noteworthy is the
unique spiro center at C-9. Other natural diterpenoids1,2
of the stemodane-type have also been obtained, including
stemodin (3), 2-desoxystemodinone (4), and maritimol (5)
(Figure 1).
The diterpenoid tetraol aphidicolin (2), isolated from
Cephalosporium aphidicolia petch,3,4 shows activity against
Herpes simplex virus,5,6 as well as antimitotic and
antitumor activity.7 The structure and absolute config-
uration of aphidicolin were determined by X-ray crystal-
lographic analysis in 1973.3,4
Stemodinone and aphidicolin have similar tetracyclic
skeleta with a different stereochemical relationship of the
C and D rings. Owing to this structural resemblance, a
methodology developed for a synthesis of stemodinone
can be employed for synthesis of aphidicolin with some
modifications, and vice versa.
Because of their unique molecular framework and the
alleged medicinal properties of S. maritima L,1,2a stemo-
dinone and its derivatives have received considerable
F igu r e 1. Aphidicolin and stemodinone and its derivatives;
skeletal numbering of parent stemodane and aphidicolane.
X Abstract published in Advance ACS Abstracts, J uly, 15, 1997.
(1) Manchand, P. S.; White, J . D.; Wright, H.; Clardy, J . J . Am.
Chem. Soc. 1973, 95, 2705.
(2) (a) Hufford, C. D.; Guerrero, R. D.; Doorenbos, N. J . J . Pharm.
Sci. 1976, 65, 778. (b) Kelly, R. B.; Harley, M. L.; Alward, S. J .; Rej, R.
N.; Gowda, G.; Mukhopadhyay, A.; Manchard, P. S. Can. J . Chem.
1983, 61, 269.
(3) Brundret, K. M.; Dalziel, W.; Hesp, B.; J arvis, J . A. J .; Neidle,
S. J . Chem. Soc., Chem Commun. 1972, 1027.
(4) Dalziel, W.; Hesp, B.; Stevenson, K. M.; J avis, J . A. J . J . Chem.
Soc., Perkin Trans. 1 1973, 2841.
(5) Bucknall, R. A.; Moores, J .; Simms, R.; Hesp, B. Antimicrob.
Agents Chemother. 1973, 4, 294.
(6) (a) Starrett, A. N.; Loshiavo, S. R. Can. J . Microbiol. 1974, 20,
416. (b) Kawada, Y.; Katogiri, K.; Suzuki, A.; Tamura, S. Agric. Biol.
Chem. 1978, 42, 1611. (c) Ohashi, M.; Taguchi, T.; Ikegami, S. Biochem.
Biophys. Res. Commun. 1978, 82, 1084.
(7) (a) Ikegami, S.; Taguchi, T.; Ohashi, M.; Oguro, M.; Nagano, H.;
Mano, Y. Nature (London) 1978, 275, 458. (b) Pedrali-Noy, G.;
Belvedere, M.; Crepaldi, T.; Focher, F.; Spedari, S. Cancer Res. 1982,
42, 3810.
attention as challenging targets for synthesis;8 ap-
(8) (a) Corey, E. J .; Tius, M. A.; Das, J . J . Am. Chem. Soc. 1980,
102, 7612. (b) Van Tamelen, E. E.; Carlson, J . G.; Russell, R. K.;
Zawacky, S. R. J . Am. Chem. Soc. 1981, 103, 4615. (c) See ref 2b. (d)
Bettolo, R. M.; Tagliatesta, P.; Lupi, A.; Bravetti, D. Helv. Chim. Acta
1983, 66, 760. (e) White J . D.; Somers, T. C. J . Am. Chem. Soc. 1987,
109, 4424. (f) White, J . D.; Skeean, R. W.; Trammell. G. L. J . Org.
Chem. 1985, 50, 1939. (g) Piers, E.; Abeysekera, B. F.; Herbert, D. J .;
Suckling, I. D. J . Chem. Soc., Chem. Commun. 1982, 404. (h) Piers,
E.; Abeysekera, B. F.; Herbert, D. J .; Suckling, I. D. Can. J . Chem.
1985, 63, 3418. (i) Germanas, J .; Aubert, C.; Vollhardt, K. P. C. J . Am.
Chem. Soc. 1991, 113, 4006. (j) Toyota, M.; Seishi, T.; Yokoyama, M.;
Fukumoto, K.; Kabuto, C. Tetrahedron Lett. 1992, 33, 4581. (k) Iwata,
C.; Morie, T.; Maezaki, N.; Shimamura, H.; Tanaka, T.; Imanishi, T.
J . Chem. Soc., Chem. Commun., 1984, 930. (l) Hegarty, P.; Mann, J .
Synlett, 1993, 553. (m) White, J . D.; Somers, T. C. J . Am. Chem. Soc.
1994, 116, 9912. (n) Tanaka, T.; Murakami, K.; Kanda, A.; Patra, D.;
Yamamoto, S.; Satoh, N.; Kim, S-W.; Ishida, T.; In, Y.; Iwata, C.
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S0022-3263(97)00547-1 CCC: $14.00 © 1997 American Chemical Society

Synthesis of (()-Stemodinone
Sch em e 1
J . Org. Chem., Vol. 62, No. 16, 1997 5285
Sch em e 2
Sch em e 3
intermediates. Thus, reversible enolate formation
(NaOMe or KOBut base) from 8 would lead to internal
alkylation at C-15, to provide 6, having the stemodinone
BCD ring stereochemistry, while kinetically controlled
deprotonation (LiN(But)2) would occur at C-12, to give 7,
possessing aphidicolin stereochemistry. In this paper we
report an investigation into the construction of the
stemodinone ring system which uses the cyclohexadien-
yliron complex 9 as the A-ring precursor, coupled with
an enolate (see later) that corresponds to the D ring, the
remaining rings being elaborated by appropriate bond
connections between residues incorporated into each
subunit (Scheme 1).
In the synthetic direction, conversion of 7 into aphidi-
colin would require functionalization of the A-ring double
bond via hydroboration and oxidation, followed by ther-
modynamic enolate formation and hydroxymethylation.
This planned sequence is not shown here. The elabora-
tion of 6 into stemodinone might be achieved according
to Scheme II. It should be noted here that cuprate
addition to enone 10 has been reported as the final step
in a recently published synthesis of stemodinone,8n so
production of this intermediate would constitute a formal
synthesis of the natural product.
proaches to aphidicolin have also been intensively stud-
ied.9 One of the challenges associated with the construc-
tion of these molecules is the dense arrangement of
quaternary carbon centers. We have previously found
that the addition of nucleophiles to substituted cyclo-
hexadienyliron complexes provides methodology that is
well-suited to this task,10 and we report herein an
application of this chemistry to the synthesis of racemic
stemodinone.
At the synthetic planning stage, it was conceived that
both stemodinone and aphidicolin could be accessed from
a common intermediate (8) (Scheme 1). Simplifications
of 1 to 6 and 2 to 7 involve fuctional group removals
(FGR) and interconversions (FGI). The C-ring discon-
nections on both 6 and 7 as shown are based on Corey’s
synthesis8a,9d of aphidicolin and stemodinone from related
(9) (a) Trost, B. M.; Nishimura, Y.; Yamamoto, K.; McElvain, S. S.
J . Am. Chem. Soc. 1979, 101, 1328. (b) McMurry, J . E.; Andrus, A.;
Ksander, G. M.; Musser, J . H.; J ohnson, M. A. J . Am. Chem. Soc. 1979,
101, 1330. (c) Sum, F.-W.; Weiler, L. Can. J . Chem. 1979, 57, 1431.
(d) Corey, E. J .; Tius, M. A.; Das, J . J . Am. Chem. Soc. 1980, 102,
1742. (e) Ireland, R. E.; Godfrey, J . D.; Thaisrivongs, S. J . Am. Chem.
Soc. 1981, 103, 2446. (f) van Tamelen, E. E.; Zawacky, S. R.; Russell,
R. K.; Carlson, J . G. J . Am. Chem. Soc. 1983, 105, 142. (g) Bettollo, R.
M.; Tagliatesta, P.; Lupi, A.; Bravetti, D. Helv. Chem. Acta 1983, 66,
1922. (h) Holton, R. A.; Kennedy, R. M.; Kim, H.-B.; Krafft, M. E. J .
Am. Chem. Soc. 1987, 109, 1597. (i) Robichaud, A. J .; Meyers, A. I. J .
Org. Chem. 1991, 56, 2607. (j) Maity, S. K.; Mukherjee, D. Tetrahedron
1984, 40, 757. (k) Tanis, S. P.; Chuang, Y.-H.; Head, D. B. Tetrahedron
Lett. 1985, 26, 6147. (l) Tanis, S. P.; Chuang, Y.-H.; Head, D. B. J .
Org. Chem. 1988, 53, 4929. (m) van Tamelen, E. E.; Zawacky, S. R.
Tetrahedron Lett. 1985, 26, 2833. (n) Koyama, H.; Okawara, H.;
Kobayashi, S.; Ohno, M. Tetrahedron Lett. 1985, 26, 2685. (o) Cargill,
R. L.; Bushey, D. F.; Dalton, J . R.; Prasad, R. S.; Dyer, R. D.; Bordner,
J . J . Org. Chem. 1981, 46, 3389. (p) Bell, V. L.; Giddings, P. J .; Holmes,
A. B.; Mock, G. A.; Raphael, R. A. J . Chem. Soc., Perkin Trans. 1 1986,
1515. (q) Ireland, R. E.; Dow, W. C.; Godfrey, J . D.; Thaisrivongs, S.
J . Org. Chem. 1984, 49, 1001. (r) Bell, V. L.; Holmes, A. B.; Hsu, S.-
Y.; Mock, G. A.; Raphael, R. A. J . Chem. Soc., Perkin Trans. 1 1986,
1507. (s) Kametani, T.; Honda, T.; Shiratori, Y.; Matsumoto, H.;
Fukumoto, K. J . Chem. Soc., Perkin Trans. 1 1981, 1386. (t) Kelly, R.
B.; Lal, G. S.; Gowda, G.; Rej, R. N. Can. J . Chem. 1984, 62, 1930.
(10) (a) Pearson, A. J .; Heywood, G. C.; Chandler, M. J . Chem. Soc.,
Perkin Trans. 1 1982, 2631. (b) O'Brien, M. K.; Pearson, A. J .;
Pinkerton, A. A.; Schmidt, W.; Wilman, K. J . Am. Chem. Soc. 1989,
111, 1499. (c) Pearson, A. J .; O'Brien, M. K. J . Chem. Soc., Chem.
Commun. 1987, 1445.
Resu lts a n d Discu ssion
Our synthesis began with the known11 cyclohexadi-
enyliron complex 9, which represents the A ring of
stemodinone, and can be prepared on large scale (>200
g). We planned to connect the A and C rings of stemo-
dinone by tin enolate nucleophile addition to 9, and the
requisite enolate was prepared by standard methods as
follows (Scheme III). Reduction of ester 11 with lithium
aluminum hydride afforded alcohol 12, which was then
converted into aldehyde 13 by Swern oxidation. Trans-
formation of aldehyde 13 into silyl enol ether 14 was
accomplished by reaction with chlorotrimethylsilane in
the presence of triethylamine. Enolsilane 14 was purified
by fractional distillation under reduced pressure and
(11) Curtis, H.; J ohnson, B. F. G.; Stephenson, G. R. J . Chem. Soc.,
Dalton Trans. 1985, 1723.

5286 J . Org. Chem., Vol. 62, No. 16, 1997
Pearson and Fang
Sch em e 4
The coupling constants (J aa ) 8.8 Hz, J ae ) 2.8 Hz)
indicated that the allylic proton was in an axial position,
as required.
In order to construct the B ring on 23, it was necessary
to introduce a two-carbon unit onto the molecule. This
was achieved by converting allylic alcohol 23 into allyl
vinyl ether 25, followed by Claisen rearrangement to give
26, as shown in Scheme 6. In view of the degree of steric
hindrance in the substrate, this reaction was expected
to be problematic, as was indeed the case. Uncatalyzed
reaction in mesitylene at 165 °C gave only 8% yield of
the desired product. After experimenting with numerous
modifications of the procedure, we discovered that a
substantial yield improvement (to 32%) was obtained
when the reaction was conducted in the presence of
ammonium chloride.
In order to complete the B-ring construction, interme-
diate 30 was prepared from aldehyde 26 via a three-step
sequence (Scheme 6). Thus, reduction of 26, followed by
treatment of the resulting alcohol 27 with carbon tetra-
chloride and triphenylphosphine in dichloromethane16
cleanly generated chloride 28. Removal of the silyl
protecting group on 28 using tetra-n-butylammonium
fluoride released alcohol 29 in quantitative yield, which
was readily oxidized to aldehyde 30.
Ring closure of aldehyde-chloride 30 turned out to be
a very facile reaction.17 Thus, treatment of 30 with an
excess of potassium hydride (to ensure equilibration of
the product aldehyde to the thermodynamically more
stable epimer) in tetrahydrofuran at ambient tempera-
ture provided the spiro tricyclic aldehyde 31 in 98% yield!
The starting material was consumed in 1 h according to
thin layer chromatography of the reaction mixture. In
Corey’s total synthesis of aphidicolin10d and stemodinone,8a
only the thermodynamically more stable equatorial al-
dehydes were produced in both the cases, and the
formation of their C-8 epimers was not observed, thus
supporting our own stereochemical assignment.
In order to construct the tetracyclic skeleton of stemo-
dinone, one more cyclization was to be conducted upon
tricyclic keto-tosylate 8, which was obtained from alde-
hyde 31 by a three-step manipulation (Scheme 7). The
aldehyde was reduced to primary alcohol 32 by reaction
with sodium borohydride in a 1:1 mixture of ethanol and
THF. Treatment of alcohol 32 with p-toluenesulfonyl
chloride (4 equiv) and triethylamine (10 equiv) in chlo-
roform, in the presence of 4-(dimethylamino)pyridine (2
equiv),18 afforded the crude ketal tosylate, which was
hydrolyzed to 8 with dilute hydrochloric acid in THF (97%
yield over two steps). Corey’s earlier work had shown
that treatment of a similar keto-tosylate with sodium
methoxide in methanol at 0 °C led exclusively to the
product that has the BCD ring stereochemistry of ste-
modinone. Reaction of 8 with 10 equiv of sodium meth-
oxide in anhydrous methanol at 0 °C indeed afforded a
single cyclization product (6), which was assigned the
stemodinone stereochemistry based on Corey’s observa-
tions.
provided a convenient precursor to its tin enolate deriva-
tive. The in situ generation of enolstannane 16 from
enolsilane 14 was performed according to a modification
of the procedure12 described by Yamamoto (Scheme 4).
The reason for choosing a tin enolate as the nucleophile
was based on the earlier discovery10 made in our labora-
tory that these enolates react with dienyliron complexes
such as 9 with excellent regioselectivity at the methylated
terminus. Indeed, addition of tributyltin enolate 16 to
dimethyl-substituted dienyl complex 9 proceeded smoothly
to produce aldehyde 17 as a single product in high yield.
This reaction provides a method of joining two six-
membered rings at highly substituted positions, forming
contiguous quaternary centers, appropriate for synthesis
of the key intermediate 8. There are 20 carbon atoms in
both stemodane and aphidicolane skeleta (see Figure 1).
Intermediate 17 contributes 15 of these skeletal carbons.
Thus, a substantial portion of the stemodane and aphidi-
colane frameworks is set in place in a single nucleophile
addition step.
The presence of aldehyde functionality in complex 17
allowed us to incorporate the required pro-C ring carbon
unit at this stage, thus overcoming some of the problems
encountered in earlier approaches where this residue is
incorporated onto a later, sterically congested tricyclic
intermediate.9,10 Wittig methylenation in refluxing THF,
using n-BuLi as base, afforded a high yield of olefin 18,
which was converted into primary alcohol 19 upon
hydroboration/oxidation (Scheme 5); this intermediate
was protected as its tert-butyldiphenylsilyl (TBDPS)
ether 20 by treatment with tert-butyldiphenylsilyl chlo-
ride and imidazole in dimethylformamide.13 It is note-
worthy that a large number of synthetic transformations
can be carried out without detriment to the diene-
Fe(CO)3 moiety, which acts as a protecting group for the
masked A-ring enone.
Removal of the tricarbonyliron moiety from 20 was
effected by using a large excess of trimethylamine N-
oxide (10-15 equiv).14 The resulting diene 21 was
subjected to hydrolysis with aqueous oxalic acid in an
8:1 mixture of methanol and tetrahydrofuran, to give
enone 22. Cleavage of the ketal and silyl ether functions
was not observed when the pH of the initial reaction
mixture was around 2, and the reaction was permitted
to proceed for 18 min before immediate neutralization
with aqueous sodium bicarbonate solution.
Sodium borohydride reduction15 of enone 22 afforded
the allylic alcohol 23 via axial hydride delivery. The
stereochemistry of product 23 was supported by 1H NMR
spectroscopy of its benzoyl derivative 24, where the allylic
proton showed a doublet of doublets around 5.70 ppm.
Stereoselective addition of a methyl group to the
carbonyl group in ketone 6 also follows the precedent set
(12) Yamamoto, Y.; Yatagai, H.; Maruyama, K. J . Chem. Soc., Chem.
Commun. 1981, 162.
(13) Blanchette, M. A.; Kageyama, M.; Malamas, M. S.; Nantz, M.
H.; Roberts, J . C.; Somfai, P.; Tamura, T.; Whritenour, D. C.; Masam-
une, S. J . Org. Chem. 1989, 54, 2817.
(16) Boger, D. L.; Ishizaki, T.; Kitos, P. A.; Suntornwat, O. J . Org.
Chem. 1990, 55, 5823.
(17) This observation is in contrast to the corresponding aldehyde-
tosylate which did not give a reasonable cyclization yield under a
variety of reaction conditions.
(14) Shvo, Y.; Hazum, E. J . Chem. Soc., Chem. Commun. 1974, 336.
(15) Ficini, J .; d'Angelo, J . Tetrahedron Lett. 1976, 2441.
(18) Ho¨fle, G.; Steglich, W.; Vorbru¨ggen, H. Angew Chem., Int, Ed.
Engl. 1978, 17, 569.

Synthesis of (()-Stemodinone
J . Org. Chem., Vol. 62, No. 16, 1997 5287
Sch em e 5
Sch em e 6
Sch em e 7
the tertiary alcohols 34 and 35 was assigned by com-
parison of the observed chemical shifts of the carbinol
methyl groups with the data reported for Corey’s epimers.
It should be noted that some physical properties (Rf and
mp) of these four alcohols are quite comparable: the
desired isomers have higher Rf (less polar) and lower
melting points than their epimers (see Experimental
Section).
by Corey’s synthesis of stemodinone.8a Thus, reaction of
6 with 10 equiv of methylmagnesium bromide in diethyl
ether at 19 °C generated epimeric alcohols 34 and 35 as
a chromatographically separable 3:1 mixture, in favor of
the desired product (Scheme 7). The stereochemistry of
For generating the A-ring enone functionality from

5288 J . Org. Chem., Vol. 62, No. 16, 1997
Pearson and Fang
acid-free trityl solution was added, via cannula, to a solution
of the mixture of diene-iron complexes (138 g) in 200 mL of
CH2Cl2, with vigorous stirring. After the addition, the reaction
mixture was continually stirred at rt for 1 h and then poured
into 2 L of wet diethyl ether. The resulting precipitate was
collected and washed with wet ether and then with dry ether
and air-dried overnight. Recrystallization from methanol
twice provided 77 g (35%) of the desired dienyl-iron complex
9 as yellow needles: mp 206 °C (dec); IR (MeCN) 2100, 2050,
1250, 855-825 cm-1; 1H NMR (200 MHz, CD3CN) δ 5.74 (s, 1
H), 3.92-3.88 (dd, 1 H, J ) 6.4, 1.3 Hz), 3.66 (s 3 H), 2.98-
2.87 (ddd, 1 H, J ) 16, 6.4, 1.3 Hz), 2.61 (s, 3 H), 2.3-2.1 (m,
1 H), 1.70 (s, 3 H).
olefin 34, an allylic oxidation procedure described by
Salmond and co-workers19 was employed. Thus, treat-
ment of 34 with 20 equiv of 3,5-dimethylpyrazole/
chromium trioxide complex (CrO3‚DMP) in methylene
chloride for 5 h afforded the desired enone 10 (Scheme
7).
The stereochemistry of intermediate 10 is supported
by comparing its 1H and 13C NMR spectra with the
corresponding spectra of (+)-stemodinone.20 In the 1H
NMR spectrum of 10, the chemical shifts for the angular
methyl and the carbinol methyl are δ 1.09 and 1.14; for
authentic stemodinone, the two corresponding resonances
also occur at δ 1.09 and 1.14. In the 13C NMR spectrum
of 10, the chemical shift for the unique carbon atom
which carries a hydroxyl group is 72.16 ppm; for authen-
tic stemodinone, the corresponding carbon resonance is
at 72.15 ppm. Installation of the final methyl group, via
cuprate addition, to produce stemodinone proceeds in
very low yield, with poor conversion.8n A variety of
alternate conjugate addition methods21 were examined
in our laboratory without success. In summary, the
capability of dienyliron complexes for generating con-
gested quaternary carbon centers provides a relatively
straighforward route to the stemodinone and aphidicolin
ring structures (18 steps from complex 9). Since these
types of cyclohexadienyliron complexes can be obtained
optically pure,22 the methodology would also provide
access to stemodinone in its natural form.
Met h yl 4,4-(E t h ylen ed ioxy)cycloh exa n eca r b oxyla t e
(11). This compound was prepared according to a procedure
used earlier in our laboratory.24 A mixture of methyl 4-oxo-
cyclohexanecarboxylate (143 g, 0.917 mol), ethylene glycol (220
mL), and p-toluenesulfonic acid (2 g) in 500 mL of benzene
was agitated via overhead stirring at rt under nitrogen
atmosphere for 20 h (it was not necessary to heat or to use a
Dean-Stark apparatus for azeotropic removal of the water
formed during the reaction). After being poured into 2 L of
diethyl ether, the mixture was washed with water (1 L × 2),
dilute sodium bicarbonate solution (800 mL × 2), and brine.
The organic solution was dried over MgSO4, filtered, and
evaporated in vacuo to furnish 174 g (95%) of ketal 11 as a
colorless oil which gave a clean 1H NMR spectrum and was
not further purified: IR (CHCl3) 2955, 1729 cm-1 1H NMR
;
(200 MHz, CDCl3) δ 3.85 (s, 4 H), 3.58 (s, 3 H), 2.27 (m, 1 H),
1.9-1.3 (m, 8 H).
4,4-(Eth ylen ed ioxy)cycloh exa n em eth a n ol (12). To a
stirred solution of the ketal-ester 11 (5.88 g, 29.4 mmol) in
25 mL of diethyl ether was added 1 M solution of LiAlH4 in
diethyl ether (30 mL, 30 mmol) dropwise at such a rate as to
maintain a gentle reflux. After complete addition, the result-
ing white suspension was heated to reflux under nitrogen
atmosphere for 15 h. Upon cooling, the reaction was carefully
quenched by slowly adding water (20 mL) dropwise, followed
by addition of 15% aqueous sodium hydroxide (20 mL). After
the solution was stirred at rt for 1 h, 10 g of solid sodium
chloride was added in order to facilitate the subsequent
workup, and the mixture was then filtered through a pad of
cotton wool and washed through with diethyl ether. The
filtrate was extracted with diethyl ether. The combined
organic layers were washed with brine, dried over anhydrous
MgSO4, filtered, and concentrated in vacuo. The residue was
purified by flash chromatography on a silica gel column
(EtOAc/hexane, 50/50) to afford 4.58 g (91%) of alcohol 12 as
a colorless liquid: Rf 0.27 (EtOAc/hexane, 50/50); IR (neat)
Exp er im en ta l Section
General methods for purification and characterization of
reaction products are described elsewhere.23
Tr ica r bon yl(1-5-η-2-m eth oxy-3,5-d im eth ylcycloh exa -
d ien yl)ir on (I) h exa flu or o-p h osp h a te (9). This compound
was reported earlier by Curtis et al.11 We prepared 9 on large
scale using a somewhat different procedure: Di-n-butyl ether
was filtered through basic alumina prior to use. The 1,4-diene
resulting from Birch reduction of 2,4-dimethylanisole (91 g,
0.66 mol, prepared according to Curtis et al.11) was refluxed
with pentacarbonyliron (240 mL) in di-n-butyl ether (500 mL)
under argon for 5 days. After being cooled to rt, the reaction
mixture was filtered through a Celite pad, and the pad was
washed through with dibutyl ether. The filtrate was evapo-
rated on a rotary evaporator fitted with a dry ice-acetone
condenser, and the resulting residue was filtered through a
pad of silica gel eluting with diethyl ether. Evaporation to
near dryness gave a mixture of three isomeric diene-iron
complexes11 (138 g, 75%) as a clear orange oil, which, without
being separated, was used for hydride abstraction as follows.
Ph3C+PF6- (102 g, 0.25 mol) in 800 mL of methylene chloride
was stirred over solid K2CO3 (5 g) for 30 min prior to use. This
3640-3250 (br, OH), 2940, 2865 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 3.95 (s, 4 H), 3.50 (d, 2 H, J ) 6.4 Hz), 1.8-1.2 (m,
10 H); 13C NMR (75 MHz, CDCl3) δ 109.1, 67.3, 64.1, 39.0,
34.0, 26.6; HRMS calcd for C9H16O3 (M) 172.1010, found
172.1009.
4,4-(Eth ylen ed ioxy)cycloh exa n eca r ba ld eh yd e (13). To
a stirred solution of oxalyl chloride (16.1 mL, 182 mmol) in
185 mL of dichloromethane at -78 °C under a nitrogen
atmosphere was added dropwise, over a period of 30 min,
dimethyl sulfoxide (26.7 mL, 365 mmol). After 10 min, the
primary alcohol 12 (12.5 g, 72.7 mmol) in 100 mL of dichlo-
romethane was added dropwise over a period of 40 min. After
10 min the initially clear solution became white and cloudy.
The mixture was stirred at -78 °C for an additional hour.
Triethylamine (68 mL, 0.48 mol) was added dropwise while
the reaction temperature was maintained at -78 °C. Upon
complete addition, the reaction mixture was slowly warmed
to -10 °C in 2 h and then quenched by addition of 50 mL of
water. The organic layer (lower layer) was separated and
washed with water and brine. The aqueous layers were
combined and extracted with CH2Cl2. The combined organics
were dried over anhydrous MgSO4, filtered, and concentrated
in vacuo. The residual oil was purified by flash chromatog-
(19) (a) Salmond, W. G.; Barta, M. A.; Havens, J . L. J . Org. Chem.
1978, 43, 2057. (b) Schlessinger, R. H.; Wood, J . L.; Poss, A. J .; Nugent,
R. A.; Parsons, W. H. J . Org. Chem. 1983, 48, 1146 (footnote 11).
(20) We thank Prof. J . D. White for providing us with the 1H and
13C NMR spectra of authentic stemodinone.
(21) (a) Smith, A. B., III; J erris, P. J . J . Am. Chem. Soc. 1981, 103,
194. (b) J asperse, C. P.; Curran, D. P. J . Am. Chem. Soc. 1990, 112,
5601. (c) Cohen, T.; Bhupathy, M.; Matz, J . R. J . Am. Chem. Soc. 1983,
105, 520. (d) Corey, E. J .; J ardine, P. D. S.; Rohloff, J . C. J . Am. Chem.
Soc. 1988, 110, 3672. (e) Greene, A. E.; Charbonnier, F.; Luche, M.-J .;
Moyano, A. J . Am. Chem. Soc. 1987, 109, 4752. (f) Lipshutz, B. H.
Synthesis 1987, 325. (g) Yamamoto, Y.; Yamamoto, S.; Yatagai, H.;
Ishihara, Y.; Maruyama, K. J . Org. Chem. 1982, 47, 119. (h) Yama-
moto, Y.; Maruyama, K. J . Am. Chem. Soc. 1978, 100, 3240. (i) Corey,
E. J .; Boaz, N. W. Tetrahedron Lett. 1985, 26, 6019. (j) J ohnson, C. R.;
Marren, T. J . Tetrahedron Lett. 1987, 28, 27. (k) Overman, L. E.; Ricca,
D. J .; Tran, V. D. J . Am. Chem. Soc. 1993, 115, 2042.
(22) (a) Birch, A. J .; Raverty, W. D.; Stephenson, G. R. Organome-
tallics 1984, 3, 1075. (b) Howell, J . A. S.; Thomas, M. J . J . Organomet.
Chem. 1983, 247, C21. (c) Stephenson, G. R. Aust. J . Chem. 1981, 34,
2339.
(24) O’Brien, M. K. Ph.D. Dissertation, 1989, pp 176-177, Case
Western Reserve University. White, A. D. Unpublished results, 1988,
Case Western Reserve University.-
(23) Pearson, A. J .; O'Brien, M. K. J . Org. Chem. 1989, 54, 4663.

Synthesis of (()-Stemodinone
J . Org. Chem., Vol. 62, No. 16, 1997 5289
raphy on a silica gel column (EtOAc/hexane, 20/80) to give 12.4
g (99%) of aldehyde 13 as a pale yellow liquid: Rf 0.36 (EtOAc/
hexane, 25/75); IR (neat) 2925, 2855, 2706, 1720 cm-1; 1H NMR
(300 MHz, CDCl3) δ 9.58 (s, 1 H), 3.88 (s, 4 H), 2.19 (quintet,
1 H, J ) 4.5 Hz), 1.91-1.47 (m, 8 H); 13C NMR (75 MHz,
CDCl3) δ 203.9, 107.9, 64.2, 48.1, 33.2, 23.2; HRMS calcd for
C9H14O3 (M) 170.0943; found 170.0941.
oil: Rf 0.25 (EtOAc/hexane, 15/85); IR (neat) 2930, 2860, 2020,
1
1940, 1725 cm-1; H NMR (300 MHz, CDCl3) δ 5.46 (dd, 1 H,
J ) 17.6, 11.0 Hz), 5.28 (dd, 1 H, J ) 11.0, 1.5 Hz), 4.92 (dd,
1 H, J ) 17.6, 1.5 Hz), 3.90 (s, 4 H), 3.55 (s, 3 H), 3.20, (t, 1 H,
J ) 2.5 Hz), 2.49 (s, 1 H), 2.14 (s, 3 H), 1.91 (dd, 1 H, J ) 15.2,
2.5 Hz), 1.62-1.43 (m, 8 H), 1.28 (dd, 1 H, J ) 15.2, 3.1 Hz),
0.97 (s 3 H); 13C NMR (75 MHz, CDCl3) δ 212.1 141.3, 139.5,
116.2, 108.9, 85.1, 68.1, 64.1, 55.2, 46.7, 45.8, 43.8, 38.4, 31.2,
28.6, 27.5, 26.1, 17.5; HRMS calcd for C22H28FeO6 (M) 444.1235,
found 444.1230. Anal. Calcd for C22H28FeO6: C, 59.47; H,
6.35. Found: C, 58.98; H, 6.32.
1′-(((Tr im eth ylsilyl)oxy)m eth ylen e)-4,4-(eth ylen ed iox-
y)cycloh exa n e (14). Chlorotrimethylsilane (23.2 mL, 183
mmol) was added via syringe to a stirred solution of aldehyde
13 (12.4 g, 72.9 mmol) and triethylamine (51.0 mL, 365 mmol)
in N,N-dimethylformamide (150 mL) at rt under nitrogen
atmosphere. The reaction mixture was then heated to reflux
for 24 h. After cooling, the mixture was diluted with diethyl
ether (350 mL) and washed successively with saturated sodium
bicarbonate solution, cold 1 N hydrochloric acid (to remove the
triethylamine), and aqueous NaHCO3 again. The ethereal
layer was dried (MgSO4) and concentrated in vacuo. Frac-
tional distillation of the resultant residue at 80-85 °C/0.35
mmHg yielded 12.2 g (75%) of the expected product 14 as a
pale yellow liquid: Rf 0.75 (EtOAc/hexane, 25/75); IR (neat)
Tr ica r b on yl[5-[1-(2-h yd r oxye t h yl)-4,4-(e t h yle n e d i-
oxy)cycloh exyl]-2-m eth oxy-3,5-dim eth yl-1-4-η-cycloh exa-
1,3-d ien e]ir on (19). To a stirred solution of olefin 18 (6.40
g, 14.4 mmol) in 100 mL of dry tetrahydrofuran at 0 °C was
added a borane-tetrahydrofuran solution (1.0 M, 28.8 mL,
28.8 mmol) dropwise via a pressure-equalizing funnel. After
complete addition, the cooling bath was removed and the
reaction solution was continually stirred under nitrogen
atmosphere for 4 h. Water (60 mL), 15% aqueous NaOH (80
mL), and a 30% aqueous H2O2 solution (100 mL) were added
sequentially, and the resultant mixture was stirred for 2 h.
The mixture was filtered to remove some orange precipitate,
and the filtrate was extracted with diethyl ether. The ethereal
extracts were combined and dried over anhydrous MgSO4,
filtered, and concentrated in vacuo to give a vicous oil, which
was purified by flash chromatography on silica gel (EtOAc/
Hexane, 40/60) to afford 5.9 g (89%) of alcohol 19 as yellow
crystals: mp 124- 126 °C; Rf 0.13 (EtOAc/hexane, 50/50); IR
2970, 2850, 1710, 1660 cm-1 1H NMR (300 MHz, CDCl3) δ
;
6.04 (s, 1 H), 3.96 (s, 4 H,), 2.32 (t, 2 H, J ) 6.4 Hz), 2.11 (t,
2 H, J ) 6.3 Hz), 1.68-1.60 (m, 4 H), 0.16 (s, 9 H); 13C NMR
(75 MHz, CDCl3) δ 131.1, 119.4, 109.3, 64.2 (2 coincident), 36.1,
34.8, 27.2, 21.9, -0.6; HRMS calcd for C12H22O3Si (M) 242.1338,
found 242.1378.
Tr icar bon yl[5-(1-for m yl-4,4-eth ylen edioxy)cycloh exyl)-
2-m e t h oxy-3,5-d im e t h yl-1-4-η-cycloh e xa -1,3-d ie n e ]-
ir on (0) (17). To a stirred solution of silyl enol ether 14 (9.29
g, 9.0 mL, 38.39 mmol) in 40 mL of 1,2-dimethoxyethane under
a nitrogen atmosphere was added dropwise methyllithium
solution (1.4 M in diethyl ether, 27.42 mL, 38.39 mmol) over
a period of 15 min, and the resulting solution was continually
stirred at rt for 1 h. After the solution was cooled to -78 °C,
tri-n-butyltin chloride (10.42 mL, 38.39 mmol) was added via
syringe over a period of 3 min and the solution was stirred at
-78 °C for 90 min. The dienyl-iron salt 9 (16.20 g, 38.39
mmol) dissolved in 150 mL of dry acetonitrile was added via
cannula over a period of 20 min. After complete addition, the
reaction mixture was gradually warmed to -14 °C in 3 h and
then quenched by addition of 30 mL of 50% aqueous tetrahy-
drofuran. The resulting mixture was extracted with diethyl
ether (200 mL × 3). The combined organic extracts were
successively washed with a saturated aqueous ammonium
chloride solution, saturated sodium bicarbonate, and brine.
The organics were dried over anhydrous MgSO4, filtered, and
concentrated in vacuo to give a brown liquid. Flash chroma-
tography (twice) on silica gel (EtOAc/hexane, 35/65) afforded
15.1 g (88%) of the desired addition product 17 as an orange
viscous oil: Rf 0.78 (EtOAc/hexane, 50/50); IR (CHCl3) 2950,
(CHCl3) 3618, 2928, 2897, 2038, 1959, 1640 cm-1 1H NMR
;
(300 MHz, CDCl3) δ 3.92 (s, 4 H), 3.65 (t, 2 H, J ) 8.5 Hz),
3.55 (s, 3 H), 3.20 (t, 1 H, J ) 2.9 Hz), 2.55 (s, 1 H), 2.18 (s, 3
H), 1.91 (dd, 1 H, J ) 15.0, 2.8 Hz), 1.86 (s, 1 H), 1.8 - 1.3 (m,
10 H), 1.26 (dd, 1 H, J ) 15.0, 3.0 Hz), 1.03 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 212.1, 139.3, 108.5, 85.4, 77.2, 68.0, 64.2,
64.1, 60.3, 55.2, 45.5, 43.4, 41.5, 39.6, 35.0, 31.0, 26.6, 17.3;
HRMS calcd for C22H30FeO7 (M) 462.1341, found 462.1378.
Anal. Calcd for C22H30FeO7: C, 57.13; H, 6.54. Found: C,
57.05; H, 6.62.
Tr icar bon yl[5-(1-(2-((ter t-bu tyldiph en ylsilyl)oxy)eth yl)-
4,4-(eth ylen ed ioxy)cycloh exyl)-2-m eth oxy-3,5-d im eth yl-
1-4-η-cycloh exa -1, 3-d ien e]ir on (0) (20). To a stirred so-
lution of alcohol 19 (5.90 g, 12.8 mmol) in 100 mL of DMF
were added imidazole (2.60 g, 38.0 mmol) and tert-butylchlo-
rodiphenylsilane (6.70 mL, 25.6 mmol). The mixture was
stirred at rt under nitrogen for 24 h, then diluted with diethyl
ether (200 mL), and washed with water and brine. The organic
phase was dried over anhydrous MgSO4, filtered, and concen-
trated in vacuo. Flash chromatography of the residue on silica
gel (EtOAc/hexane, 15/85) gave 8.81 g (98%) of silyl ether 20
as a viscous yellow oil: Rf 0.24 (EtOAc/hexane, 15/85); IR
(CHCl3) 2036, 1966 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.73-
7.61 (m, 4 H), 7.46-7.36 (m, 6 H), 3.92 (s, 4 H), 3.64 (m, 2 H),
3.49 (s, 3 H), 3.11 (t, 1 H, J ) 2.8 Hz), 2.38 (br, 1 H), 2.2-1.1
(m, 12 H), 1.56 (s, 3 H), 1.03 (s, 9 H), 0.83 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 212.1, 135.5, 134.8, 133.8, 133.7, 129.7,
129.5, 127.7, 108.7, 73.5, 68.2, 64.2, 64.0, 61.5, 55.1, 45.6, 41.5,
39.7, 39.6, 30.9, 26.8, 26.5, 19.1, 17.2; HRMS calcd for
C27H44FeO6Si (M-CO): 548.2256, found 548.2260. The mo-
lecular ion was not observed.
1
2040, 1962, 1712 cm-1; H NMR (300 MHz, CDCl3) δ 9.55 (s,
1 H), 3.91 (s, 4 H), 3.56 (s, 3 H), 3.23 (t, 1 H, J ) 2.9 Hz), 2.48
(s, 1 H), 2.16 (s, 3 H), 2.10 (dd, 1 H, J ) 15.4, 2.8 Hz), 1.7-1.3
(m, 8 H), 1.28 (dd, 1 H, J ) 15.4, 3.0 Hz), 1.02 (s, 3 H); 13C
NMR (75 MHz, CDCl3) δ 211.5, 207.7, 139.5, 108.0, 84.9, 65.9,
64.2, 55.5, 55.4, 45.6, 43.4, 38.2, 31.7, 26.1, 25.3, 25.1, 17.3;
HRMS calcd for C21H26FeO7 (M) 446.1028, found 446.1035.
Anal. Calcd for C21H26FeO7: C, 56.52; H, 5.87. Found: C,
56.11; H, 5.64.
Tr ica r bon yl[5-(1-vin yl-4,4-(eth ylen ed ioxy)cycloh exyl)-
2-m e t h oxy-3,5-d im e t h yl-1-4-η-cycloh e xa -1,3-d ie n e ]-
ir on (0) (18). To a stirred mixture of methyltriphenylphos-
phonium bromide (6.73 g, 18.8 mmol, 5.05 equiv) in 60 mL of
THF under nitrogen atmosphere at rt, was added, dropwise,
n-butyllithium (1.29 M solution in hexanes, 14.6 mL, 18.6
mmol, 5.00 equiv). The resultant orange suspension was
stirred at rt for 40 min, and then aldehyde 17 (1.66g, 3.72
mmol) in 20 mL of THF was added dropwise. Upon complete
addition, the mixture was heated to reflux for 35 h. After
being cooled to rt, the mixture was poured into water (20 mL)
and extracted with diethyl ether (40 mL x 3), and the combined
organic extracts were washed with brine, dried over anhydrous
MgSO4, filtered, and evaporated. The crude product was
purified by flash chromatography on silica gel column (EtOAc/
Hexane, 15/85) to give 1.45 g (88%) of olefin 18 as a yellow
2-Meth oxy-3,5-d im eth yl-5-[1-(2-((ter t-bu tyld ip h en ylsi-
lyl)oxy)eth yl)-4,4-(eth ylen e-d ioxy)cycloh exyl]cycloh exa -
1,3-d ien e (21). Trimethylamine N-oxide (12.4 g, 165 mmol)
was refluxed in 550 mL of dry benzene under a nitrogen
atmosphere until all the oxide was dissolved. After cooling,
the diene-iron complex 20 (7.71 g, 11.0 mmol) in 150 mL of
benzene was added via cannula, and the mixture was refluxed
for 18 h (the reaction was monitored by IR, and disappearance
of the Fe(CO)3 bands at 2036, 1966 cm-1 indicated its comple-
tion). After cooling, the mixture was diluted with diethyl ether
(200 mL) and washed with water and brine. The organic layer
was dried over anhydrous MgSO4, filtered through Celite, and
concentrated in vacuo to yield 5.01 g (91%) of crude diene 21
as an oil, which was used for the next step without further
purification: IR (CHCl3) 2959, 2860, 1727 cm-1; 1H NMR (200
MHz, CDCl3) δ 7.67 (m, 4 H), 7.36 (m, 6 H), 5.27 (s, 1 H), 4.30

5290 J . Org. Chem., Vol. 62, No. 16, 1997
Pearson and Fang
(dd, 1 H, J ) 7.0, 3.0 Hz), 3.90 (s, 4 H), 3.70 (m, 2 H), 3.45 (s,
3 H), 2.3-1.1 (m, 12 H), 1.54 (br, 3 H), 1.01 (s, 9 H), 0.78 (s, 3
H).
mmol) at rt under a nitrogen atmosphere. The mixture was
stirred at reflux for 3 h. After cooling, the mixture was diluted
with 20 mL of diethyl ether, washed with an aqueous sodium
thiosulfate solution (for removal of Hg(OAc)2), water, and
brine. The organics were dried over anhydrous sodium
carbonate, filtered through Celite, and concentrated in vacuo.
Column chromatography on basic alumina (this vinyl ether
underwent hydrolysis on silica gel) (EtOAc/hexane, 15/85)
provided 160 mg (85%) of allyl vinyl ether 25 as a viscous
liquid: Rf 0.78 (EtOAc/hexane, 25/75); 1H NMR (200 MHz,
CDCl3) δ 7.62-7.38 (m, 10 H), 6.23 (dd, 1 H, J ) 14.0, 6.5
Hz), 5.22 (s, br, 1 H), 4.26 (dd, 1 H, J ) 14.0, 1.4 Hz), 3.93 (dd,
1 H, J ) 6.5, 1.4 Hz), 3.90 (s, 4 H), 3.87-3.47 (m, 3 H), 2.15-
1.14 (m, 14 H), 1.54, (s, 3 H), 1.01 (s, 9 H), 0.81 (s, 3 H); HRMS
calcd for C36H50O4Si (M) 574.3478, found 574.3482.
4-[1-(2-((ter t-bu tyld ip h en ylsilyl)oxy)eth yl)-4,4-(eth yl-
en ed ioxy)cycloh exyl]-2,4-d i-m eth ylcycloh ex-2-en -1-on e
(22). To a solution of the dienyl methyl ether 21 (32.0 g, 57.1
mmol) in a mixture of THF (100 mL) and methanol (800 mL)
was added aqueous oxalic acid (18.1 g, 200 mmol, in 500 mL
of water). The resultant mixture was vigorously stirred via
overhead stirring at rt for 18 min and poured into water (1 L)
and immediately neutralized with aqueous sodium bicarbonate
solution. The mixture was extracted with diethyl ether. The
combined ethereal layers were dried over anhydrous MgSO4,
filtered through Celite, and evaporated. Purification of the
residual oil by column chromatography on silica gel (EtOAc/
Hexane, 25/75) afforded 21.2 g (68%) of the desired enone 22
as a foam: Rf 0.45 (EtOAc/hexane, 25/75); IR (CHCl3) 1667
cm-1; 1H NMR (300 MHz, CDCl3) δ 7.65-7.38 (m, 10 H), 6.50
(s, 1 H), 3.93 (br s, 4 H), 3.70 (t, 2 H, J ) 8.0 Hz), 2.38 (ddd,
1 H, J ) 17.0, 13.9, 5.4 Hz), 2.27 (ddd, 1 H, J ) 17.0, 5.2, 2.6
Hz), 1.86-1.25 (m, 12 H), 1.58 (s, 3 H), 1.04 (s, 9 H), 0.95 (s,
3 H); 13C NMR (75 MHz, CDCl3) δ 199.5, 152.3, 135.5, 133.7,
133.6, 132.7, 129.7, 127.7, 108.4, 64.2, 61.1, 41.7, 39.7, 34.3,
33.3, 30.9, 30.7, 29.3, 27.3, 26.9, 19.1, 19.0, 16.3; HRMS calcd
for C34H46O4Si (M) 546.3165, found 546.3160.
2,4-Dim eth yl-4-[1-(2-((ter t-bu tyldiph en ylsilyl)oxy)eth yl)-
4,4-(eth ylen ed ioxy)cycloh exyl]cycloh ex-2-en -1-ol (23). To
a stirred solution of enone 22 (190 mg, 0.347 mmol) in 6 mL
of 1:1 THF and methanol at 0 °C was added sodium borohy-
dride (20 mg, 0.529 mmol) in portions. After the solution was
stirred at 0 °C for 45 min, 5 mL of water was added, and the
resultant mixture was stirred for 5 min. The mixture was then
poured into 20 mL of ethyl acetate and washed with water
and brine. The aqueous layers were combined and extracted
with EtOAc. The combined organics were dried over anhy-
drous MgSO4, filtered, and evaporated to give a yellow oil.
Flash chromatography on silica gel (EtOAc/hexane, 25/75) and
subsequent recrystallization from chloroform provided 186 mg
(98%) of the desired allylic alcohol 23 as pale yellow rods: mp
152-153 °C; Rf 0.35 (EtOAc/hexane, 25/75); IR (CHCl3) 3609,
1663 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.66-7.38 (m, 10 H),
5.17 (s, 1 H), 3.9 (br s, 4H), 3.84-3.60 (m, 3 H), 1.9-1.1 (m,
15 H), 1.56 (s, 3 H), 1.04 (s, 9 H), 0.83 (s, 3 H); 13C NMR (75
MHz, CDCl3) δ 135.4, 134.6, 133.9, 133.8, 131.1, 129.5, 127.6,
108.7, 69.6, 64.0, 61.4, 41.0, 39.7, 33.5, 30.8, 30.7, 30.2, 28.8,
27.1, 26.8, 22.1, 19.2, 19.0; HRMS calcd for C34H48O4Si (M)
548.3322, found 548.3318.
2,4-D im e t h y l-3-(2-o x o e t h y l)-4-[1-(2-((t er t -b u t y ld i-
p h en ylsilyl)oxy)eth yl)-4,4-eth ylen ed ioxy)cycloh exyl]cy-
cloh exen e (26). To a degassed solution of allyl vinyl ether
25 (710 mg, 1.24 mmol) in 10 mL of mesitylene was added
ammonium chloride (67 mg, 1.24 mmol). The reaction mixture
was refluxed at 164 °C with stirring under
a nitrogen
atmosphere for 17 h (or until the starting material was
completely consumed according to TLC). The solvent was then
removed from the mixture on a rotary evaporator at 85 °C
(bath), and the residual oil was diluted with diethyl ether (50
mL) and filtered through Celite. The filtrate was washed with
water (10 mL) and brine (10 mL), dried over magnesium
sulfate, filtered, and concentrated in vacuo. Flash chroma-
tography on silica gel (EtOAc/hexane, 15/85) afforded 230 mg
(32%) of the expected aldehyde product 26 as an oil: Rf 0.18
1
(EtOAc/hexane, 15/85); IR (CHCl3) 1722 cm-1; H NMR (300
MHz, CDCl3) δ 9.71 (s, 1 H), 7.67-7.37 (m, 10 H), 5.38 (s br,
1 H), 3.91 (s, 4 H), 3.78 (m, 2 H), 2.55 (dd, 1 H, J ) 16.9, 6.8
Hz), 2.35 (dd, 1 H, J ) 16.9, 8.4 Hz), 1.9-1.1 (m, 15 H), 1.55
(s, 3 H), 1.05 (s, 9 H), 0.64 (s, 3 H); 13C NMR (75 MHz, CDCl3)
δ 202.8, 136.4, 135.5, 133.9, 129.6, 127.6, 123.4, 108.5, 64.1,
61.6, 46.4, 41.7, 40.9, 38.0, 33.6, 31.1, 30.9, 28.5, 28.2, 26.9,
23.1, 22.7, 21.3, 19.1, 14.0; HRMS calcd for C36H50O4Si (M)
574.3478, found 574.3484.
2,4-Dim et h yl-3-(2-h yd r oxyet h yl)-4-[1-(2-((ter t-b u t yl-
d ip h en ylsilyl)oxy)eth yl)-4-eth ylen ed ioxy)cycloh exyl]cy-
cloh exen e (27). To a cold (0 °C), stirred solution of aldehyde
26 (5.00 g, 8.70 mmol) in 100 mL of ethanol was added sodium
borohydride (0.795 g, 21.0 mmol) in small portions. After the
addition, the ice bath was removed, and the reaction mixture
was stirred at ambient temperature under a nitrogen atmo-
sphere for 50 min and then quenched with water (30 mL).
After being stirred for 5 min, the mixture was extracted with
diethyl ether. The combined extracts were washed with brine,
1-(Be n zoyloxy)-2,4-d im e t h yl-4-[1-(2-((t er t -b u t yld i-
p h en ylsilyl)oxy)eth yl)-4,4-(eth ylen ed ioxy)cycloh exyl]-2-
cycloh exen e (24). To a stirred solution of allylic alcohol 23
(50 mg, 0.091 mmol) and pyridine (22.1 µL, 0.373 mmol) in
dichloromethane (2 mL) at 0 °C under nitrogen atmosphere
was added benzoyl chloride (16.0 µL, 0.137 mmol) via syringe.
The reaction solution was stirred at 0 °C for 15 min, and then
at rt for 5 h. The mixture was transferred into a separatory
funnel, diluted with 15 mL of diethyl ether, and washed
successively with aqueous sodium bisulfate (0.15 N, 5 mL x
2), water, and saturated sodium bicarbonate. The organics
were dried over anhydrous MgSO4, filtered, and evaporated.
The resulting crude product was purified by column chroma-
tography on silica gel (EtOAc/hexane, 15/85) to afford 58 mg
(98%) of benzoyl derivative 24 as an oil: Rf 0.50 (EtOAc/
dried over anhydrous MgSO4
, filtered, and evaporated in
vacuo. The residual liquid was purified by flash chromatog-
raphy (EtOAc/hexane, 28/72) to provide 3.90 g (78%) of alcohol
27 as a clear oil: Rf 0.21 (EtOAc/hexane, 28/72); IR (CHCl3)
1
3618 (OH) cm-1; H NMR (300 MHz, CDCl3) δ 7.67-7.39 (m,
10 H), 5.34 (br s, 1 H), 3.91 (br s, 4 H), 3.74 (t, 2 H, J ) 8.4
Hz), 3.49 (t, 2 H, J ) 7.1 Hz), 2.0-1.1 (m, 18 H), 1.62 (s, 3 H),
1.04 (s, 9 H), 0.73 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 138.4,
135.4, 133.8, 129.5, 127.6, 122.4, 108.6, 63.9, 62.6, 61.6, 41.4,
41.2, 40.1, 34.4, 33.9, 31.6, 31.1, 31.0, 28.7, 27.9, 26.8, 23.6,
23.1, 22.1, 19.0; HRMS calcd for C36H52O4Si (M) 576.3635,
found 576.3633.
2,4-Dim et h yl-3-(2-ch lor oet h yl)-4-[1-(2-((ter t-b u t yld i-
p h en ylsilyl)oxy)eth yl)-4,4-eth ylen ed ioxy)cycloh exyl]-1-
cycloh exen e (28). To a solution of alcohol 27 (2.55 g, 4.42
mmol) and triphenylphosphine (2.32 g, 8.84 mmol, 2.0 equiv)
in 20 mL of methylene chloride at rt under nitrogen atmo-
sphere was added freshly distilled carbon tetrachloride (3.42
mL, 35.4 mmol, 8.0 equiv) via syringe. The reaction mixture
was stirred at ambient temperature (19 °C) for 24 h. After
removal of the solvent on a rotary evaporator, the residue was
directly purified by flash chromatography on silica gel, eluting
with 5% and then 8% EtOAc in hexane, to afford 2.04 g (76%)
of chloride 28 as a colorless oil: Rf 0.49 (EtOAc/hexane, 15/
1
hexane, 25/75); H NMR (300 MHz, CDCl3) δ 8.17-7.35 (m,
15 H), 5.70 (dd, J ) 8.8, 2.8 Hz, 1 H), 5.33, (br s, 1 H), 3.92 (br
s, 4 H), 3.77-3.68 (m, 2 H), 1.98 -1.18 (m, 14 H), 1.56 (s, 3
H), 1.04 (s, 9 H), 0.87 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ
166.3, 135.5, 134.5, 133.9, 133.2, 132.8, 130.5, 129.6, 128.9,
128.3, 127.7, 108.7, 72.9, 64.1, 61.5, 41.0, 39.7, 33.5, 30.9, 30.7,
29.7, 28.4, 27.3, 26.9, 26.3, 22.0, 19.4, 19.1; HRMS calcd for
C36H43O5Si (M - C4H9) 583.2880, found 583.2879. The mo-
lecular ion was not observed.
1-(Vin yloxy)-2,4-d im eth yl-4-[1-(2-((ter t-bu tyld ip h en yl-
silyl)oxy)eth yl)-4,4-(eth ylen ed ioxy)cycloh exyl]-2-cyclo-
h exen e (25). To a solution of allylic alcohol 23 (180 mg, 0.328
mmol) in 8 mL of n-butyl vinyl ether were added mercuric
acetate (210 mg, 0.656 mmol) and vinyl acetate (60.5 µL, 0.656
85); IR (CHCl3) 2959, 2933, 2890, 1589 cm-1 1H NMR (200
;
MHz, CDCl3) δ 7.65-7.36 (m, 10 H), 5.35 (t, br, 1 H, J ) 0.62
Hz), 3.89 (s, 4 H), 3.71 (t, br, 2 H, J ) 7.8 Hz), 3.33 (t, br, 2 H,

Synthesis of (()-Stemodinone
J . Org. Chem., Vol. 62, No. 16, 1997 5291
8.0 Hz), 1.9-1.2 (m, 17 H), 1.59 (d, 3 H, J ) 1.0 Hz), 1.02 (s,
9 H), 0.68 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 135.9, 135.1,
134.2, 130.0, 129.8, 128.0, 123.7, 109.0, 64.4, 61.9, 44.7, 42.1,
41.9, 41.7, 35.3, 34.4, 32.2, 31.5, 29.0, 28.4, 27.2, 26.9, 23.9,
23.4, 19.4; HRMS calcd for C36H51ClO3Si (M) 594.3296, found
594.3301.
C20H30O3 (M) 318.2195, found 318.2194. Anal. Calcd for
C20H30O3: C, 75.43; H, 9.50. Found: C, 75.88; H, 9.52.
Spir o[4,10-dim eth yl-8-(h ydr oxym eth yl)-∆3,4-tr a n s-deca-
lin -9,1′-(3,3′-(eth ylen edioxy)cycloh exan e] (32). To a stirred
solution of the aldehyde 31 (7.0 mg, 0.022 mmol) in 1.5 mL of
a 1:1 mixture of ethanol and tetrahydrofuran was added
sodium borohydride (8.3 mg, 0.22 mmol) in portions. The
reaction mixture was stirred at rt under a nitrogen atmosphere
for 50 min, followed by addition of water (2 mL) and extraction
with diethyl ether. The organic extracts were combined and
washed with brine, dried over anhydrous MgSO4, filtered, and
evaporated to give 9 mg of residue. Flash chromatography
on silica gel, eluting with 25% and then 50% ethyl acetate in
hexane, yielded 6.2 mg (88%) of the alcohol 32 as a clear oil:
2,4-Dim et h yl-3-(2-ch lor oet h yl)-4-[1-(2-h yd r oxyet h yl)-
4,4-(eth ylen ed ioxy)cycloh exyl]-1-cycloh exen e (29). To a
stirred solution of silyl ether 28 (1.79 g, 3.00 mmol) in 25 mL
of tetrahydrofuran at 0 °C under a nitrogen atmosphere was
added tetra-n-butylammonium fluoride (1.0 M solution in THF,
3.3 mL, 1.1 equiv) dropwise over 10 min. After the addition,
the ice bath was removed, and the reaction mixture was stirred
at ambient temperature (20 °C) for 5 h. Upon removal of the
solvent on a rotary evaporator, the residue was directly
subjected to flash chromatographic purification on silica gel,
eluting with 15% and then 50% ethyl acetate in hexane, to
yield 1.09 g (100%) of alcohol 29 as a colorless liquid: Rf 0.31
Rf 0.10 (EtOAc/hexane, 25/75); IR (CHCl3) 3616 (OH) cm-1
;
1H NMR (200 MHz, CDCl3) δ 5.30 (s, br, 1 H), 3.91 (s, 4 H),
3.76 (m, 2 H), 2.3-0.8 (m, 19 H), 1.60 (s, 3 H), 0.66 (s, 3 H);
13C NMR (75 MHz, CDCl3) δ 135.8, 120.9, 108.8, 64.2, 64.1,
63.0, 42.5, 40.6, 38.5, 38.1, 30.9, 30.2, 29.5, 25.9, 25.1, 23.6,
23.2, 21.8, 19.9, 14.9; HRMS calcd for C20H32O3 (M) 320.2351,
found 320.2348.
1
(EtOAc/hexane, 50/50); IR (CHCl3) 3618 (OH) cm-1; H NMR
(300 MHz, CDCl3) δ 5.47 (s, br, 1 H), 3.92 (s, 4 H), 3.83-3.71
(m, 2 H), 3.57 (dt, 1 H, J ) 17.2, 3.7 Hz), 3.50 (dt, 1 H, J )
17.2, 4.9 Hz), 2.10-1.21 (m, 17 H), 1.57 (s, 3 H), 0.93 (s, 3 H);
13C NMR (75 MHz, CDCl3) δ 137.4, 123.5, 108.5, 64.1, 63.7,
60.4, 44.6, 41.6, 35.0, 34.4, 32.0, 31.2, 28.6, 28.1, 23.7, 23.6,
23.2, 22.3; HRMS calcd for C20H33ClO3 (M) 356.2118, found
356.2121.
Sp ir o[4,10-d im e t h yl-8-((p a r a -t olu e n e su lfon yloxy)-
m eth yl)-∆3,4-tr a n s-d eca lin -9,1′-3′-oxocycloh exa n e] (8). To
a cold (0 °C) solution of the alcohol 32 (20.0 mg, 0.0625 mmol)
in 2 mL of chloroform, were successively added p-toluenesulfo-
nyl chloride (48 mg, 0.25 mmol, 4.0 equiv), triethylamine (87
µL, 0.625 mmol, 10 equiv), and 4-(dimethylamino)pyridine
(15.3 mg, 0.125 mmol, 2.0 equiv). After the addition, the
cooling bath was removed and the reaction mixture was stirred
under a nitrogen atmosphere at rt for 3 h. Aqueous sodium
bicarbonate (5%, 4 mL) was added to hydrolyze the unreacted
p-TsCl. After being stirred for 30 min, the mixture was
extracted with chloroform. The combined chloroform layers
were sequentially washed with a 0.15 N aqueous NaHSO4
solution, water, and a saturated NaHCO3 solution, dried over
anhydrous MgSO4, filtered, and concentrated in vacuo. The
resulting crude tosylate (36 mg) was, without further purifica-
tion, carried through to the next step as follows. To a solution
of this crude ketal tosylate in 5 mL of THF was added 1.5 mL
of 2 N hydrochloric acid. The resulting mixture was stirred
under a nitrogen atmosphere at ambient temperature for 16
h. After being diluted with brine (5 mL), the mixture was
extracted with diethyl ether. The extracts were combined and
washed with water and aqueous NaHCO3, dried over anhy-
drous MgSO4, filtered, and concentrated in vacuo. Flash
chromatography of the residual liquid on silica gel column
(EtOAc/hexane, 14/86) gave 26 mg (97% over two steps) of the
desired keto tosylate 8 as a pale yellow oil: Rf 0.30 (EtOAc/
2,4-Dim et h yl-3-(2-ch lor oet h yl)-4-[1-(2-oxoet h yl)-4,4-
(et h ylen ed ioxy)cycloh exyl]-1-cycloh exen e (30). To a
stirred solution of oxalyl chloride (814 µL, 9.18 mmol, 3.0
equiv) in 10 mL of dry methylene chloride at -78 °C under a
nitrogen atmosphere, was added, dropwise, dimethyl sulfoxide
(1.35 mL, 19.0 mmol, 6.2 equiv) in 4 mL of CH2Cl2 over 10
min. After the solution was stirred for an additional 10 min,
alcohol 29 (1.09 g, 3.06 mmol) in 8 mL of dichloromethane was
added dropwise over a period of 8 min, and the resulting
solution was continually stirred for 70 min. Triethylamine (4.5
mL) was added dropwise while the reaction temperature was
maintained at -78 °C. After the addition, the reaction mixture
was allowed to warm to -10 °C in 2 h, and then 5 mL of water
was added. The mixture was extracted with CH2Cl2, and the
combined organics were washed with brine, dried over anhy-
drous MgSO4, filtered, and evaporated. Flash chromatography
on silica gel (EtOAc/hexane, 25/75) furnished 0.998 g (92%) of
aldehyde 30 as a pale yellow oil: Rf 0.35 (EtOAc/hexane, 25/
75); IR (CHCl3) 1733 cm-1; 1H NMR (300 MHz, CDCl3) δ 9.95
(t, 1 H), 5.48 (s br, 1 H), 3.94 (s, 4 H), 3.53 (m, 1 H), 2.57 (dd,
1 H, J ) 15.8, 3.2 Hz), 2.45 (dd, 1 H, J ) 15.8, 3.2 Hz), 2.15-
1.25 (m, 16 H), 1.72 (s, 3 H), 0.94 (s, 3 H); 13C NMR (75 MHz,
CDCl3) δ 203.6, 137.2, 123.6, 108.1, 64.2, 44.6, 44.3, 42.0, 41.6,
34.9, 31.8, 31.3, 31.1, 30.9, 28.6, 28.2, 23.3, 23.1, 22.4; HRMS
calcd for C20H31ClO3 (M) 354.1962, found 354.1959.
Hexane, 25/75); IR (CHCl3) 1705, 1662 cm-1 1H NMR (200
;
MHz, CDCl3) δ 7.79 (d, 2 H, J ) 8.3 Hz), 7.34 (d, 2 H, J ) 8.3
Hz), 5.29 (s, br, 1 H), 4.4-4.1 (m, 2 H), 2.43 (s, 3 H), 2.3-0.8
(m, 18 H), 1.57 (s, 3 H), 0.65 (s, 3 H); 13C NMR (75 MHz, CDCl3)
δ 211.3, 135.0, 130.9, 129.9, 129.8, 128.8, 127.8, 127.0, 120.9,
71.0, 41.9, 41.0, 38.3, 37.1, 36.3, 36.0, 29.8, 29.3, 28.7, 27.3,
23.6, 22.9, 21.6, 19.4, 14.1; HRMS calcd for C25H34O4S (M)
430.2178, found 430.2181.
Sp ir o[4,10â-Dim eth yl-8r-for m yl-∆3,4-tr a n s-d eca lin -9,1′-
[3,3′-(eth ylen ed ioxy)cycloh exa n e] (31). Potassium hydride
(35 wt % dispersion in mineral oil, 122 mg, 1.06 mmol, 8.8
equiv) was placed in a 10 mL flask and washed with dry
pentane (0.5 mL × 2) and THF (0.5 mL) under a nitrogen
atmosphere before addition of 4 mL of dry tetrahydrofuran.
To this stirred KH suspension in THF was introduced a
solution of the aldehyde-chloride 30 (42 mg, 0.12 mmol) in
1.5 mL of THF via syringe over a period of 2 min. The reaction
mixture was stirred at ambient temperature (21 °C) under a
nitrogen atmosphere for 4 h and then carefully quenched with
an aqueous ammonium chloride solution (3 mL). The mixture
was extracted with diethyl ether, and the combined ethereal
extracts were washed with brine, dried over anhydrous
Na2SO4, filtered, and evaporated to give a white powder (44
mg). Flash chromatography on silica gel (EtOAc/hexane, 25/
75) and subsequent recrystallization from chloroform afforded
37 mg (98%) of the desired tricyclic aldehyde 31 as white
needles: mp 188-189 °C; Rf 0.39 (EtOAc/hexane, 25/75); IR
4,16-Nor -∆3,4-2-Desoxystem od in on e (6). To a stirred
solution of the keto-tosylate 8 (26 mg, 0.0625 mmol) in 4 mL
of anhydrous methanol at 0 °C under an argon atmosphere
was added 138 µL of sodium methoxide-methanol solution (25
wt % solution, 0.605 mmol, 10 equiv) via syringe. The
resulting yellowish solution was stirred at 0 °C for 15 h, and
the keto- tosylate was completely consumed according to TLC.
The reaction was then quenched by addition of a saturated
aqueous solution of ammonium chloride (2 mL). After being
transferred into a test tube, the mixture was extracted with
diethyl ether (3 mL × 3). The combined ethereal layers were
washed with a saturated aqueous NaCl solution (3 mL), dried
over anhydrous MgSO4, filtered, and evaporated in vacuo. The
crude product was purified by flash chromatography on silica
gel (EtOAc/hexane, 2/98 and 15/85) using a Pasteur pipet as
the column. This reaction gave a single cyclization product 6
(14 mg, 89%): mp 108-109 °C; Rf 0.37 (EtOAc/hexane, 15/
85); IR (CHCl3) 1710 cm-1; 1H NMR (300 MHz, CDCl3) δ 5.35
(s br, 1 H), 2.67 (m, 1 H), 2.46-2.33 (m, 2 H), 2.26-1.10 (m,
16 H), 1.62 (s, 3 H), 0.97 (s, 3 H); 13C NMR (75 MHz, CDCl3)
1
(CHCl3) 1705 cm-1; H NMR (300 MHz, CDCl3) δ 10.10 (s, 1
H), 5.32 (s br, 1 H), 3.96 (s, 4 H), 2.68 (dd, 1 H, J ) 5.1, 1.5
Hz), 2.29 (m, 2 H), 2.10-1.41 (m, 13 H), 1.59 (s, 3 H), 1.39-
1.15 (m, 2 H), 0.71 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 205.1,
135.5 120.9, 108.4, 64.3, 64.2, 45.8, 43.1, 41.6, 39.0, 31.2, 30.4,
28.7, 26.4, 24.5, 23.1, 21.6, 20.8, 20.3, 14.6; HRMS calcd for

5292 J . Org. Chem., Vol. 62, No. 16, 1997
Pearson and Fang
δ 215.2, 136.3, 120.8, 55.5, 51.2, 47.1, 40.2, 38.0, 37.2, 36.4,
35.3, 34.3, 32.2, 28.0, 23.2, 22.7, 21.5, 18.5; HRMS calcd for
C18H26O (M) 258.1984, found 258.1986.
mmol, 20 equiv) in 980 µL of dry methylene chloride at -20
°C under a dry argon atmosphere was added 3,5-dimeth-
ylpyrazole (71.6 mg, 0.744 mmol) in one portion. After the
solution was stirred at -20 °C for 15 min, the tetracyclic olefin
34 (10.2 mg, 0.0372 mmol) in 120 µL of dichloromethane was
introduced via syringe over a period of 3 min. Upon addition,
the reaction mixture was warmed to -15 °C and stirred at
this temperature for 5 h. An aqueous sodium hydroxide
solution (5 N, 500 µL) was added, the resulting mixture was
stirred at 0 °C for 1 h, and two layers were separated. After
being transferred into a test tube, the mixture was extracted
with dichloromethane. The combined organic layers were
washed with 1 N hydrochloric acid to remove the 3,5-dimeth-
ylpyrazole, then washed with water and saturated sodium
bicarbonate solution, dried over anhydrous Na2SO4, filtered,
and evaporated. Column chromatography of the residue on
silica gel (EtOAc/hexane, 15/85) yielded 7.8 mg (73%) of the
expected A-ring enone 10 as an off-white solid: mp 195-196
°C; Rf 0.22 (EtOAc/hexane, 50/50); IR (CHCl3) 3560, 3380, 1661
Tetr a cyclic Ter tia r y Alcoh ols 34 a n d 35. To a stirred
and precooled solution of the tetracyclic ketone 6 (10.0 mg,
0.039 mmol) in 1.2 mL of diethyl ether at 0 °C under an argon
atmosphere was added a methylmagnesium bromide solution
(3.0 M in Et2O, 130 µL, 0.39 mmol, 10 equiv) via syringe. After
the addition, the cooling bath was removed and the reaction
mixture was stirred at ambient temperature (19 °C) for 150
min. The reaction was quenched by addition of saturated
aqueous ammonium chloride (1 mL) and water (1 mL). After
being transferred into a test tube, the mixture was extracted
with diethyl ether. The organic extracts were combined and
washed with water (2 mL), dried over anhydrous MgSO4,
filtered, and evaporated on a rotary evaporator to give 12 mg
of residual solid. The TLC and 1H NMR of this residue
indicated it was a mixture of two epimeric alcohols, as
expected. Gravity chromatography on silica gel (EtOAc/
Hexane, 10/90) afforded the desired alcohol 34 (6.0 mg, white
solid), along with its epimer 35 (2.1 mg, white solid) in 76%
total yield 4-Nor -∆3,4-2-Desoxystem od in on e (34): mp 114-
115.5 °C; Rf 0.28 (EtOAc/hexane, 15/85); IR (CHCl3) 3571, 3421
cm-1; 1H NMR (300 MHz, CDCl3) δ 5.36 (s br, 1H), 2.18-1.20
(m, 20 H), 1.61 (s, 3 H), 1.13 (s, 3 H), 0.91 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 136.7, 120.7, 72.4, 47.6, 46.1, 39.1, 37.8,
36.5, 33.6, 31.9, 30.9, 30.7, 29.7, 28.6, 27.9, 23.4, 22.8, 21.4,
18.0; HRMS calcd for C19H30O (M) 274.2297, found 274.2280.
4-Nor -∆3,4-16-ep i-2-d esoxystem od in on e (35): mp 135-137
1
cm-1; H NMR (300 MHz, CDCl3) 5.81 (s, br, 1 H), 2.65-2.45
(m, 2 H), 2.30-1.20 (m, 16 H), 1.89 (s, 3 H), 1.14 (s, 3 H), 1.09
(s, 3 H); 13C NMR (75 MHz, CDCl3) δ 200.5, 162.2, 125.5, 72.16,
49.1, 48.1, 46.2, 40.8, 40.0, 39.8, 34.3, 34.1, 33.6, 33.0, 27.0,
26.5, 23.0, 21.9, 19.0; HRMS calcd for C19H28O2 (M) 288.2089,
found 288.2093.
Ack n ow led gm en t. We are grateful to the National
Science Foundation for financial support (CHE93-08105
and CHE96-16247).
°C; Rf 0.23 (EtOAc/hexane, 15/85); IR (CHCl3) 3569, 3426 cm-1
;
1H NMR (300 MHz, CDCl3) δ 5.33 (s, br, 1 H), 2.2-0.9 (m, 20
H), 1.60 (s, 3 H), 1.25 (s, 3 H), 0.89 (s, 3 H); 13C NMR (75 MHz,
CDCl3) δ 136.8, 120.6, 72.6, 48.2, 46.6, 39.7, 37.8, 34.6, 34.4,
33.4, 31.9, 29.7, 27.9, 27.3, 26.5, 23.4, 22.8, 21.4, 18.0; HRMS
calcd for C19H30O (M) 274.2297, found 274.2296.
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C NMR
spectra for all new compounds (43 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.
4-Nor -∆3,4-Stem od in on e (10). Chromium trioxide was
dried over P2O5 in a vacuum desiccator overnight prior to use.
To a stirred suspension of chromium trioxide (74.4 mg, 0.744
J O9705475