Studies directed to the synthesis of the antifungal antibiotic aleurodiscal. Enantioselective construction of an advanced β-D-xyloside congener

Article abstract of DOI:10.1055/s-1998-5921

The first synthesis of a highly functionalized congener of aleurodiscal is reported. An enantiocontrolled route to tricyclic ketone 8 was first developed by taking advantage of regiodirected tandem methylation and vinylation of a phenylsulfanyl precursor, as 23 → 24 → 8. These experiments formed the basis for the coupling of 8 to 30, in turn prepared from (4S)-(- )-tert-butyldimethylsiloxycyclopentenone, prior to oxy-anionic Cope rearrangement. Phenylselenenylation of the enolate ion generated in this manner ultimately led to a pair of dienone isomers, whose distinctively different chemistries were made apparent at several levels. Notable features of the overall approach include the introduction of stereogenic centers positioned remotely from each other across a medium-sized ring and stereoselective bond construction via a boatlike transition state following efficient conjoining of the two key segments.

Full text of DOI:10.1055/s-1998-5921

SYNTHESIS
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Studies Directed to the Synthesis of the Antifungal Antibiotic Aleurodiscal.
Enantioselective Construction of an Advanced â-D-Xyloside Congener
Leo A. Paquette,* Todd M. Heidelbaugh
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210, USA
Fax +1(614)2921685; E-mail: Paquette.1@osu.edu
Received 13 May 1997
Abstract: The first synthesis of a highly functionalized congener of
aleurodiscal is reported. An enantiocontrolled route to tricyclic
ketone 8 was first developed by taking advantage of regiodirected
tandem methylation and vinylation of a phenylsulfanyl precursor, as
23 → 24 → 8. These experiments formed the basis for the coupling
of 8 to 30, in turn prepared from (4S)-(-)-tert-butyldimethylsiloxycy-
clopentenone, prior to oxy-anionic Cope rearrangement. Phenylsele-
nenylation of the enolate ion generated in this manner ultimately led
to a pair of dienone isomers, whose distinctively different chemis-
tries were made apparent at several levels. Notable features of the
overall approach include the introduction of stereogenic centers
positioned remotely from each other across a medium-sized ring and
stereoselective bond construction via a boatlike transition state fol-
lowing efficient conjoining of the two key segments.
Key words: anionic sigmatropy, oxy-Cope reaction, chiral sulfox-
imine, cyclobutanones
In 1989, a team of researchers from three West German
universities reported on the isolation and characterization
of aleurodiscal (1), an antifungal antibiotic produced by
mycelial cultures of Aleurodiscus mirabilis collected
from the bark of Cinnamonum camphora endemic to Ja-
pan.1 Structure elucidation, accomplished by combined
application of spectroscopic and X-ray crystallographic
methods, revealed the substance to constitute a fundamen-
tally new type of sesterterpenoid. Hydrolysis of 1 in meth-
anolic hydrochloric acid released D-(+)-xylose, thereby
making possible the assignment of absolute configuration
as shown. Aleurodiscal, believed to be biogenetically relat-
ed to retigeranic acid (2),2,3 has structural components sim-
ilar to those found in precapnelladiene (3),4,5 albolic acid
(4) and related ophiobolins,6,7 as well as variecolin (5).8
conveniently obtained from commercially available (±)-
2,6-dimethylhept-5-enal (melonal) according to the proto-
cols developed by Snider10 and by Corey.3a,11 In order to
set the rather elusive trans intra-ring stereochemistry, 12
was subjected sequentially to stereoselective hydride re-
duction from the α-face, Mitsunobu inversion to generate
the α-allylic alcohol 13, and facially controlled hydroge-
nation of 13 in the presence of norbornadienerhodium(I)
diphosphine complex 14.12 This route, originally devised
by Engler,11,13 delivered 10 efficiently without evidence
of contamination from the more thermodynamically sta-
ble cis isomer (Scheme 2).
The novel structural framework and therapeutic potential
of 1 were among the considerations that prompted the de-
sign of a strategy for its de novo construction. In particu-
lar, the intention was to extend our earlier work involving
the synthesis of structurally complex targets by proper de-
ployment of oxy-anionic sigmatropy.9 Therefore, the
theme that will be developed in the present context is the
convergent coupling of optically pure cyclobutanone 8
with cyclopentenyllithium 9 of >98% ee as a means of es-
tablishing the central eight-membered ring (Scheme 1).
The primary initial concerns necessarily become those as-
sociated with the crafting of 8 and 9 from precursors such
as 10 and 11, respectively. Subsequently, consideration
will be given to the chemistry of 7 and related advanced
intermediates including, but not restricted to, dienones
such as 6.
In preparation for annulation of the cyclobutanone ring,
attention was given to the regiodirected dehydration of 10.
The most effective of the reagents examined proved to be
(methoxycarbonylsulfamoyl)triethylammonium hydrox-
ide inner salt.14 The elimination of 10, realized in hot
benzene solution, led uniquely to 15 as confirmed spectro-
scopically, in a reproducible 88% yield.
Advantage was taken of the face selectivity with which 12
is attacked by nucleophiles for resolution purposes. To
this end, this ketone was transformed by reaction with the
lithium salt of Johnson's (+)-(S)-sulfoximine15 into the
chromatographically separable 1,2-adducts 16 and 17
Discussion of Results
Enantiocontrolled Route to the Left Half. The starting
point for accessing 8 was the hydrindenone 12, which was

SYNTHESIS
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496
(Scheme 3). The absolute stereochemistry of 16 was de-
fined by X-ray crystallographic analysis (Figure 1). Re-
lease of the optical antipodes of 12 was readily
accomplished by heating 16 and 17 separately in toluene.
Since the less polar diastereomer 16 was more easily pu-
rified, the desired levorotatory enantiomer of 12 was rou-
tinely accessed in optically pure form, i.e., >99% ee.
Scheme 1
Scheme 3
Figure 1
After considerable experimentation, the [2+2] cycloaddi-
tion of dichloroketene to 15 was successfully implement-
ed by the slow addition of trichloroacetyl chloride to a
suspension of zinc–copper couple and the alkene in dieth-
yl ether at room temperature.16 These conditions gave rise
Scheme 2

SYNTHESIS
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497
to 19 (74%) with the proper regio- and stereochemistry as
deduced by NOE experiments (Figure 2) and X-ray crys-
1
tallography (Figure 3). High-field H NMR analysis re-
vealed the existence of W couplings between HQ and both
HL and HM. The vicinal coupling between HA and HC is
characteristic of a 90° dihedral angle relationship (J <
1 Hz). The relative positioning of the carbonyl in this ad-
duct follows from the chemical shifts of HA (α to carbon-
yl) and HB (α to CCl2). The most diagnostic NOE effect is
the 8% enhancement of the HB signal that arises from
irradiation of HQ.
Scheme 4
Although the [2+2] cycloaddition of vinyl ketenes to alk-
enes has been extensively exploited in synthesis,20 the use
of such reagents in the present context followed by C-
methylation would culminate in formation of the incorrect
stereoisomer of 8. These considerations demanded, there-
fore, that 20 or 21 serve as the appropriate precursor. As
our point of departure, 21 was subjected to kinetic depro-
tonation with LDA and the resulting enolate anion was
trapped with methyl iodide. However, these and related
conditions led to 22 (47%) alongside unreacted cyclobu-
tanone (Scheme 5). When 20 was found to respond to me-
thylation with the identical regiochemistry,21 recourse
was made instead to treatment of the kinetically (and ther-
modynamically) favored silyl enol ether of 21 with
phenylsulfenyl chloride.22 The phenylsulfanyl ketone 23
so obtained responded well to directed methylation, with
24 arising in 86% isolated yield following swamping with
methyl iodide at 25°C.23 Since 23 had given no evidence
of S-methylation after 5 h at room temperature in the pres-
ence of a vast excess of CH3I, the obviously slow bimo-
lecular rate eased concern about possible competing side
reactions during the conversion to 24. The methylation of
23 occurred exclusively from the β-face as confirmed by
NOE measurements.
Figure 2
Figure 3
Initial attempts to accomplish the reductive removal of the
chlorine atoms in 19 proved unsatisfactory (Scheme 4).
Powdered zinc in acetic acid gave the monochloro ketone
20 readily, but the prolonged heating (110°C, 2 h) re-
quired to bring about the second dechlorination caused
substantial decomposition and led to a poor yield of 21.
Neither were chromium(II) chloride in aqueous acetone,17
tributyltin hydride and AIBN in hexanes, or other pre-
scribed methods18 useful. In contrast, a mixture of
zinc–copper couple and ammonium chloride in hot
methanol19 resulted in clean, complete reduction to 21
(85%). Nonetheless, the optimum protocol for this con-
version was to effect initial monoreduction to 20 during 5
min at room temperature, since 20 proved much easier to
purify than 21. The final step was subsequently performed
for 1–2 h at the reflux temperature.
Of the several methods probed for the vinylation of 24,
that involving initial base-promoted condensation with
monomeric formaldehyde24 proved to be highly success-
ful. Removal of the phenylsulfanyl blocking group in 25
was again accomplished with zinc–copper couple. Oxida-
tion of 26 to oxo aldehyde 27 with pyridinium chlorochro-
mate on alumina25 set the stage for arrival at 8 via
chemoselective Wittig alkenation.
Assembly of the Right Hand Segment. With subtarget 8 in
hand, attention was directed to generation of enantiopure
nucleophile 9. Our approach exploited the ready avail-

SYNTHESIS
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498
ability of (–)-1126 and the excellent stereoselectivity with
which lithium dimethylcuprate undergoes conjugate ad-
dition to its enone chromophore (Scheme 6). Trapping of
the resulting enolate with N-(5-chloro-2-pyridyl)-
triflimide27 afforded 28, from which the vinylstannane 29
was secured by reaction with hexamethylditin in the pres-
ence of tetrakis(triphenylphosphine)palladium(0) and lith-
ium chloride.28 Bromide 30 was subsequently obtained by
titration of 29 with bromine in dichloromethane at
–78°C.29 NOE studies of 28–30 confirmed the trans ar-
rangement of the substituents.
The possibility of transmetalating 29 was skirted because
of the inherent difficulties of removing the tin byproducts
of this process. In contrast, the halogen–metal exchange
involving 30 and tert-butyllithium proceeded very effi-
ciently. When solutions of 9 generated in this manner
were quenched with methanol, 31 was isolated in 86%
yield.
Coupling of the Sectors. Arrival at the Aleurodiscal Core.
The anionic oxy-Cope reaction, with its ability to deliver
high levels of chirality transfer and regiocontrol under
mild conditions, is a powerful variant of the [3,3] sigma-
tropic rearrangement. When this transformation is ac-
companied by significant strain release, the process is
irreversible. In light of the ground state conformation
adopted by 8 (Scheme 7), the approach of cycloalkenyl-
lithium 9 to its carbonyl group is relegated exclusively to
β-face attack. With arrival at divinylcyclobutanoxide 32,
spontaneous rearrangement via a boat-like transition
state to deliver 33 was anticipated. As discussed else-
where,30 this transition state geometry is adopted to skirt
the introduction of a pair of trans double bonds in the
emerging eight-membered ring. Electrophilic capture by
33 proceeds from the molecular exterior to set the final
substituent syn to the three pre-existing tertiary hydro-
gens. The tetracyclic ketones 34a and 34b, obtained fol-
lowing the addition of water and phenylselenenyl
chloride, respectively, to 33, were securely identified on
the basis of NOE data (see Experimental Section). The
remarkable efficiency (91%) of the one-pot, four-step
process (including the lithiation of 30) leading to 34b is
noteworthy.
Scheme 5
With generous amounts of 34b now available, oxidative
elimination of the phenylseleno substituent was next pur-
sued. When exposed to 30% hydrogen peroxide in dichlo-
romethane containing pyridine, conversion to a 2.6:1
mixture of 35a and 36a was realized (Scheme 8). These
dienones, easily distinguished by 1H NMR spectroscopy,
are considered to be the end result of sterically controlled
intramolecular proton abstraction within the two selenox-
ide diastereomers. In order to test this operating assump-
tion, efforts were made to redirect the regioselectivity of
the process. Recourse to sodium periodate in metha-
nol–tetrahydrofuran–water (5:1:l) gave rise to solubility
problems as evidenced by the need for long reaction times
and the extensive recovery of 34b. Alternative use of 3-
chloroperbenzoic acid at –78°C and at –10°C surprisingly
had no effect on the originally observed distribution of
35a and 36a. In order to evaluate the role of the TBS
group on the regioselectivity of the elimination, the free
Scheme 6

SYNTHESIS
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499
Scheme 7
hydroxy selenide 37 was generated and subjected to per-
acid oxidation. Under these circumstances, 35b and 36b
were generated in a parallel 2.6:1 ratio. In contrast, the ox-
idation of diastereomer 38, prepared independently, gave
39 very predominantly.
Evaluation of End Game Tactics. The predominant
formation of 35a and 35b prompted initial investiga-
tion of their isomerization to 36a and 36b. Iodine in
benzene solution had no effect on either intermediate
at room temperature; heating to reflux induced decom-
position. However, the desired transformations were
accomplished instead with rhodium trichloride trihy-
drate in hot ethanol,31 but only modest yields
(32–35%) were realized in these conversions. Since
chromatographic separation of the isomers was
straightforward, this pathway was routinely used to
obtain quantities of 36a.
Scheme 8
One’s ability to accomplish epimerization α to the carbo-
nyl group rests on the relative positioning of the two dou-
ble bonds.32 Thus, stirring 36a with potassium carbonate
in a 2:1 mixture of methanol and tetrahydrofuran at room
temperature for 2 days resulted in conversion to the con-
jugated dienone 40 (Scheme 9). This isomerization can be
attributed to the substantial acidity of the doubly allylic
protons in 36a, a situation that does not exist in 35a. The
latter dienone is indeed amenable to conversion to its
more stable diastereomer 41, although refluxing condi-
tions were necessary to bring the configurational inver-
sion about in a reasonable timeframe (12 h).
Arrival at aleurodiscal (1) requires that several of its
unique structural features be addressed. The necessary
chemical transformations include epimerization at C-12,
oxidation of the allylic methyl group at position 25, instal-
lation of a methyl group (C-23) in the lower portion of the
eight-membered ring, and coupling to the xylose moiety.
Each of these changes has been accorded preliminary at-
tention.

SYNTHESIS
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500
The intra-ring activation available to 36a manifested itself
again during attempts to oxidize C-25 to the aldehyde lev-
el. For example, heating 36a with selenium dioxide, tert-
butyl hydroperoxide, and silica gel in dichloromethane33
for a few hours led to the isolation of 42a and 42b
(Scheme 10). Alternative radical-based methods involv-
ing N-bromosuccinimide or the chromium trioxide/3,5-
dimethylpyrazole reagent failed to give recognizable
products.
The final methyl group in aleurodiscal was installed by re-
action of 34a with methyllithium in tetrahydrofuran at
0°C. Strict attention must be paid to acid-free conditions
during workup in order to avoid cyclization with forma-
tion of a bridged ether.21 Exposure of 43 to thionyl chlo-
ride and pyridine led exclusively to the exocyclic double
bond isomer 44. Since 44 was not smoothly isomerized to
the desired internal diene following heating with rhodium
trichloride, the introduction of C-23 must be accom-
plished by an alternative route.
At this point, it was considered timely to investigate the
coupling of an activated xylose derivative with a represen-
tative aglycone. To this end, 44 was desilylated and the al-
cohol 45 so formed was brought into reaction with bromo
triacetate 4634 under catalysis by silver triflate35 in diethyl
ether at –50°C, with subsequent warming to room temper-
ature. Although this single experiment returned a large
amount (69%) of the acetate of 45, sufficient 47 (24%)
was obtained to permit full characterization. The ready
acetyl transfer operative under these conditions points up
Scheme 9
Scheme 10

SYNTHESIS
H NMR (300 MHz, CDCl ): δ = 6.66 (d, J = 10.2 Hz, 1 H), 5.84 (d,
J = 10.2 Hz, 1 H), 5.06 (t, J = 1.3 Hz, 1 H), 2.44–2.40 (m, 2 H),
2.00–1.92 (m, 3 H), 1.81–1.70 (m, 1 H), 1.65 (s, 3 H), 1.57 (s, 3 H),
1.48–1.41 (m, 2 H), 1.12 (s, 3 H).
April 1998
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1
the likelihood that a different protecting group may ulti-
mately be preferred.
3
13
C NMR (75 MHz, CDCl ): δ = 199.5, 159.1, 131.9, 127.3, 123.9,
3
Summary
40.9, 35.6, 34.1, 33.4, 25.6, 24.8, 22.8, 17.6.
Recourse to a 1,2-addition/anionic oxy-Cope reaction se-
quence provides a very concise route to the aleurodiscal
framework. The protocol allows for the direct introduc-
tion of six of the eight stereogenic centers resident in 1.
Proper absolute configuration is set at all of these sites. In
addition, several advanced intermediates are adequately
functionalized to permit arrival at 1 in principle. While
this has not yet been achieved, some useful and important
insight has been gained that should allow future imple-
mentation of a proper end game. Some of the key lessons
learned include (i) an appreciable kinetic bias exists for
selenoxide elimination to occur exocyclic to the cyclocte-
nyl core; (ii) epimerization at C-12 is thermodynamically
favored under the proper conditions; (iii) the central eight-
membered ring is prone to transannular effects and is
amenable to setting resident double bonds in conjugation;
(iv) the sensitivity of this medium-sized ring is such that
oxidation of C-25 to the aldehyde level will need to be ac-
complished indirectly; and (v) introduction of the allylic
methyl group at C-23 and its associated double bond must
be approached in a manner that skirts the dehydration of a
tertiary alcohol since the latter tactic is clearly conducive
to elimination in the exocyclic direction.
(+)-2,6-Dimethyl-2-(3-oxobutyl)hept-5-enal could be isolated in
yields up to 10% as a side product.
A single-necked flask was fitted with an addition funnel and charged
with the above ketone (80.0 g, 0.42 mol) and anhyd CH2Cl2 (2 L) at
10°C under N2. Ethylaluminum dichloride (660 mL of 1 M in hex-
anes, 0.66 mol) was transferred via cannula to the addition funnel and
added dropwise over 1.5 h. The clear yellow-orange solution was al-
lowed to react over 4 h at r.t., quenched with aq NH Cl (200 mL), di-
4
luted with Et2O (500 mL), and washed with H2O (300 mL) and sat.
NaHCO (2 × 200 mL). The aluminum salts were rinsed with Et2O.
3
The combined organic solutions were dried and concentrated, and the
residue was chromatographed on silica gel (elution with 10–15%
EtOAc in hexanes) to give racemic 12 as a colorless oil (60 g, 73%).
–1
IR (neat, cm ): ν = 1665, 1460, 1205.
1
H NMR (300 MHz, CDCl ): δ = 5.74 (s, 1 H), 2.82 (m, 1 H), 2.55
3
(m, 1 H), 2.35 (m, 1 H), 2.06–1.60 (m, 6 H), 1.46–1.30 (m, 1 H), 1.18
(s, 3 H), 0.98 (d, J = 6.8 Hz, 3 H), 0.72 (d, J = 6.8 Hz, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 199.6, 180.8, 120.4, 47.3, 43.3, 39.9,
3
35.9, 33.8, 29.4, 23.5, 22.6, 21.8, 16.4.
MS m/z (M ) calcd 192.1514, obsd 192.1505.
+
Pyrolysis of 16 as described below for the diastereomer gave (–)-12
exhibiting [α]D20 –153.4 (c = 0.78, CHCl3).
Anal. Calcd for C
10.51.
H O: C, 81.20; H, 10.48. Found: C, 81.21; H,
13 20
Finally, arrival at (–)-34b was accomplished from (–)-8 in
12 steps and 6.8% overall yield. It is hoped that the lessons
learned in this series of experiments can be applied to the
acquisition of aleurodiscal and bioactive analogs thereof.
(–)-(3R,5S,7aR)-5,6,7,7a-Tetrahydro-3-isopropyl-7a-methylin-
dan-5-ol (13):
Hydrindenone 12 (6.0 g, 36 mmol) was diluted with anhyd Et2O (40
mL) and added dropwise over 40 min to a solution of LiAlH4 (1.5 g,
39 mmol) in Et2O (50 mL) at –25°C. After 1.5 h of stirring, sat.
Most reactions were carried out under N2. Solvents were reagent
grade, and in most cases dried before use. Benzene, Et2O, THF, tolu-
ene, and dioxane were distilled from Na/benzophenone ketyl.
CH2Cl2, diisopropylamine, DMSO, DMF, Et3N, Hunig's base, and
most other reaction solvents were distilled from CaH2. MeOH was
distilled from the magnesium salt. Flash chromatography was per-
formed on silica gel (230–400 mesh, 60 Å) or Fluka silica gel H with
the indicated solvents. Mps were determined in open capillaries and
are uncorrected. HRMS (Kratos MS-30 or VG-70-2505) were record-
ed at The Ohio State University Chemical Instrumentation Center. El-
emental analyses were performed at the Scandinavian Micro-
analytical Laboratory, Herlev, Denmark or at Atlantic Microlab, Inc.,
Norcross, Georgia, USA.
NH Cl and Et2O were introduced and the aluminum salts were fil-
4
tered and rinsed (3 × 50 mL) with Et2O. The filtrate was dried and
concentrated, and the residue was purified on silica gel by elution
with 15% EtOAc in hexanes to give 5.7 g (95%) of the β-alcohol as a
waxy, white solid, mp 46–48°C.
–1
IR (neat, cm ): ν = 3340, 1560.
1Η NMR (300 MHz, CDCl3): δ = 5.21 (br s, 1 H), 4.33–4.07 (m, 1 H),
2.57–2.45 (m, 1 H), 2.02–1.14 (m, 10 H), 1.04 (s, 3 H), 0.92 (d, J =
6.8 Hz, 3 H), 0.68 (d, J = 6.8 Hz, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 153.9, 119.1, 68.8, 45.1, 41.9, 40.1,
3
36.1, 29.9, 28.6, 25.1, 22.2, 22.1, 15.9.
+
MS m/z (M ) calcd 194.1671, obsd 194.1670.
[α]D20 –89.0 (c = 2.61, CHCl3)
Anal. Calcd for C13H22O: C, 80.36; H, 11.41. Found: C, 80.11; H, 11.37.
The above alcohol (40 g, 21 mmol) was dissolved in anhyd Et2O (2 L)
along with Ph3P (55 g, 21 mmol) and benzoic acid (26.3 g, 22 mmol).
Diethyl azodicarboxylate (DEAD) (33 mL, 21 mmol) was added
dropwise via syringe and the yellow solution was stirred for 10 min
before a white precipitate developed. After another 20 min, the mix-
ture was concentrated, placed atop a column of silica gel, and filtered
through with 15% EtOAc in hexanes. The ester was concentrated and
hydrolyzed with 5% KOH in MeOH (900 mL) during 12 h at r.t.
NaHCO3 (40 g) was added, the solution was evaporated, and the
concentrate was dissolved in Et2O and washed with H2O prior to dry-
ing and solvent removal. Purification on silica gel by elution with
10% EtOAc in hexanes furnished 33 g (83%) of (–)-13 as a waxy
solid.
(–)-(3S,7aR)-7,7a-Dihydro-3-isopropyl-7a-methylindan-5(6H)-
one (12):
Melonal (80% tech. grade, 100 g, 0.57 mol) was heated to reflux under
N with pyrrolidine (127 mL, 1.52 mol) in benzene (3 L) for 40 h using
2
a Dean–Stark trap to separate the water (about 14 mL). The excess pyr-
rolidine and benzene were removed by simple distillation. After cool-
ing, anhyd benzene (2 L) was added to the solution followed by methyl
vinyl ketone (115 mL of 95% freshly distilled, 1.42 mol) in a solution
of anhyd benzene (200 mL) over 2 h. The mixture was heated for an ad-
ditional 15 h and cooled. Glacial HOAc (75 mL) and NaOAc (100 mL
of 4.3 M) were introduced and heating at reflux was resumed for 3 h.
The mixture was diluted with Et2O (750 mL), washed with 10% HCl
(2 × 200 mL) and sat. NaHCO3 (3 × 200 mL), dried, filtered, and evap-
orated. Purification was accomplished by distillation, bp 120°C at
0.5 mm Hg, to furnish 77.6 g (71%) of (±)-4-methyl-4-(4-methylpent-
3-enyl)cyclohex-2-en-1-one as a clear yellow oil.
–1
IR (neat, cm ): ν = 3350, 1010.
1
H NMR (300 MHz, CDCl ): δ = 5.40 (br s, 1 H), 4.20–4.15 (m, 1 H),
3
2.60–2.50 (m, 1 H), 2.08–1.15 (m, 10 H), 0.95 (d, J = 6.7 Hz, 3 H),
0.95 (s, 3 H), 0.70 (d, J = 6.7 Hz, 3 H).
–1
IR (neat, cm ): ν = 1680, 1610, 1450, 1375.

SYNTHESIS
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502
13
C NMR (75 MHz, CDCl ): δ =155.0, 117.5, 64.0, 45.1, 41.8, 40.0,
For 17: colorless crystals, mp 110–111°C.
3
–1
31.0, 28.4, 28.1, 23.6, 22.2, 22.0, 15.9.
IR (neat, cm ): ν = 3240, 2160, 1670, 1460, 1250.
1
[α]D20 –176.6 (c = 1.30, CHCl ).
H NMR (300 MHz, CDCl ): δ = 7.87–7.84 (m, 2 H), 7.62–7.55 (m,
3
3
3 H), 5.78 (s, 1 H), 3.27 (m, 2 H), 2.62 (s, 3 H), 2.60–2.56 (m, 1 H),
2.10–1.96 (m, 2 H), 1.85–1.45 (m, 6 H), 1.29–1.16 (m, 1 H), 1.04 (s,
3 H), 1.12–0.98 (m, 1 H), 0.94 (d, J = 6.7 Hz, 3 H), 0.74 (d, J = 6.7
(–)-(3S,5aS,5S,7aR)-Hexahydro-3-isopropyl-7a-methylindan-5-ol
(10):
Norbornadiene (1,4-bisdiphenylphosphinobutane)rhodium(I) tetra-
fluoroborate (14, 500 mg) and allylic alcohol (–)-13 (4.83 g,
25.2 mmol) were dissolved in THF (60 mL) and placed under H2 at-
mosphere of 900 psi in a bomb. The resulting suspension was filtered
through silica gel and purified on silica gel by elution with 20%
EtOAc in hexanes to give 4.73 g (97%) of (–)-10 as a white solid, mp
44–46°C.
Hz, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 153.0, 139.0 (2 C), 133.0, 129.5,
129.0 (2 C), 119.6, 72.1, 65.8, 44.9, 42.1, 40.1, 34.8, 34.5, 28.9, 28.5,
24.4, 22.1 (2 C), 15.7.
MS m/z (M ) calcd 361.2075, obsd 361.2037.
Anal. Calcd for C
8.72.
3
+
H O SN: C, 69.77; H, 8.64. Found: C, 69.55; H,
21 31 2
–1
IR (neat, cm ): ν = 3430, 1210, 740.
1
(+)-(3R,7aS)-7,7a-Dihydro-3-isopropyl-7a-methylindan-5(6H)-
one (18):
H NMR (300 MHz, CDCl ): δ = 4.08 (m, 1 H), 1.75–1.25 (m, 14 H),
3
0.89 (d, J = 6.7 Hz, 3 H), 0.80 (d, J = 6.7 Hz, 3 H), 0.74 (s, 3 H).
13
Sulfoximine 17 (20.15 g, 56.5 mmol) was dissolved in toluene
(200 mL) and heated to reflux. Progress of the reaction was followed
by TLC every 15 min. After 45 min, the mixture was cooled and the
toluene was removed on a rotary evaporator. The residue was chro-
matographed on silica gel, elution with 20% EtOAc in hexanes pro-
viding 10.3 g (95%) of ketone 18.
C NMR (75 MHz, CDCl ): δ = 66.9, 45.9, 42.8, 41.5, 39.2, 34.1,
3
32.8, 29.1, 29.0, 22.9, 22.1, 17.8, 16.7.
+
MS m/z (M ) calcd 196.1827, obsd 196.1828.
[α]D20 –61 (c = 1.01, CHCl ).
3
Anal. Calcd for C
12.37.
H
O: C, 79.35; H, 12.32. Found: C, 79.59; H,
13 24
[α]D20 +146.6 (c = 0.73, CHCl3).
(–)-(1S,3aR,7aS)-3a,4,7,7a-Tetrahydro-1-isopropyl-3a-methylin-
dan (15):
(–)-(2aS,3aR,6S,6aS,7aR)-2,2-Dichlorodecahydro-6-isopropyl-
3a-methyl-1H-cyclobut[f]inden-1-one (19):
Alcohol (–)-10 (9.0 g, 46 mmol) was diluted with benzene (250 mL)
and added to a solution of Burgess reagent (12.6 g, 53.0 mmol) in ben-
zene (50 mL). This solution was stirred for 3 h, heated to reflux over-
night, cooled, and diluted with Et2O (100 mL). The organic solution
was washed with brine (2 × 100 mL), and the aqueous solution was
extracted with Et2O (1 × 50 mL). The organic layer was dried, the sol-
vent was removed, and the residue was chromatographed on silica gel
with hexane elution to give 7.2 g (88%) of (–)-15 as a colorless oil.
Hydrindene 15 (10.8 g, 56.0 mmol) and zinc–copper couple (9.5 g,
146 mmol) were suspended in Et2O (200 mL). A solution of trichlo-
roacetyl chloride (7.5 mL, 67 mmol) in Et2O (90 mL) was added over
2 h and the suspension was stirred for an additional 2 h, filtered
through Celite with Et2O, concentrated to one-quarter volume, and di-
luted with pentane to the original volume. The viscous aqueous layer
was removed and extracted with Et2O (3 × 20 mL). The combined or-
–1
ganic phases were washed with brine, sat. NaHCO , and brine (25 mL
3
IR (neat, cm ): ν = 1460, 1375.
1
each), dried, filtered, and evaporated. Chromatography on silica gel
H NMR (300 MHz, CDCl ): δ = 5.64–5.60 (m, 2 H), 2.20–2.10 (m,
3
with 4% EtOAc in hexanes yielded 19 (13.0 g, 74%).
1 H), 1.97 (br s, 2 H), 1.77–1.48 (m, 5 H), 1.37–1.17 (m, 3 H), 0.91
–1
IR (neat, cm ): ν = 1800, 1500, 1380, 1265.
(d, J = 6.7 Hz, 3 H), 0.84 (d, J = 6.7 Hz, 3 H), 0.76 (s, 3 H).
1
13
H NMR (300 MHz, CDCl ): δ = 4.08 (t, J = 9.2 Hz, 1 H), 3.13–3.03
3
C NMR (75 MHz, CDCl ): δ = 126.7, 126.6, 47.5, 46.3, 41.0, 40.3,
3
(m, 1 H), 2.26–2.12 (m, 2 H), 1.75–0.92 (m, 9 H), 0.89 (d, J = 6.7 Hz,
39.2, 30.4, 28.4, 24.3, 21.8, 18.8, 18.1.
+
3 H), 0.80 (d, J = 6.7 Hz, 3 H), 0.75 (s, 3 H).
MS m/z (M ) calcd 178.1721, obsd 178.1708.
13
[α]D20 –116 (c = 4.74, CHCl ).
C NMR (75 MHz, CDCl ): δ = 195.7, 87.9, 53.9, 47.3, 46.4, 43.3,
3
3
40.9, 39.7, 38.5, 29.8, 23.7, 23.0, 21.7, 18.3, 17.1.
Anal. Calcd for C
12.47.
H
: C, 87.56; H, 12.44. Found: C, 87.75; H,
+
13 22
MS m/z (M ) calcd 288.1048, obsd 288.1056.
[α]D20 –110 (c = 0.9, CHCl3).
Anal. Calcd for C
7.66.
H OCl : C, 62.29; H, 7.66. Found: C, 62.19; H,
15 22 2
(S)-N-Methyl-S-phenyl-S-{[(3S,5R,7aR)-5,6,7,7a-tetrahydro-5-
hydroxy-3-isopropyl-7a-methyl-5-indanyl]methyl}sulfoximine
(16) and Diastereomer 17:
For the X-ray crystallographic analysis, see Figure 3.
A solution of Johnson’s (+)-(S)-sulfoximine (9.0 g, 53 mmol) in THF
(150 mL) was cooled to –5°C and treated with BuLi (34 mL, 1.58 M
in hexanes, 53 mmol). The anion solution, which formed over 25 min,
was cooled to –78°C before racemic 12 (10 g , 53 mmol) was added
slowly via cannula. After 20 min, the mixture was quenched with sat.
(–)-(2S,2aS,3aR,6S,6aS,7aR)-2-Chlorodecahydro-6-isopropyl-3a-
methyl-1H-cyclobut[f]inden-1-one (20):
Dichlorocyclobutanone 19 (200 mg, 0.69 mmol) was dissolved in a
3% solution of NH Cl in MeOH (20 mL) and mixed with a suspen-
4
sion of zinc–copper couple (300 mg). The reduction proceeded to
completeness nearly instantaneously at r.t. Et2O was added and the
suspension was filtered through Celite. Monochloro ketone 20
(195 mg, 88%) was recovered as a fine white crystalline compound
following chromatography on silica gel with elution by 5% EtOAc in
hexanes; mp 108–110°C.
NH Cl (50 mL). Hexanes (100 mL) were added and the separated or-
4
ganic phase was dried and evaporated. Chromatographic separation
on silica gel with 20% EtOAc in hexanes gave 6.4 g (34%) of 16 and
7.0 g (37%) of 17. Compound 16 was a white solid, mp 105–106°C.
–1
IR (neat, cm ): ν = 3310, 1450, 1370, 1225, 1150, 1110, 1005.
1
–1
H NMR (300 MHz, CDCl ): δ = 7.89–7.86 (m, 2 H); 7.65–7.54 (m,
3
IR (neat, cm ): ν = 1795, 1450.
1
3 H), 5.00 (s, 1 H), 3.28 (dd, J = 1.4, 2.5 Hz, 1 H), 3.11 (d, J = 14 Hz,
1 H), 2.84 (m, 1 H), 2.61 (s, 3 H), 2.58–2.51 (m, 1 H), 2.11–2.00 (m,
1 H), 1.87–1.70 (m, 3 H), 1.60–1.53 (m, 1 H), 1.46–1.39 (m, 2 H),
1.38–1.10 (m, 1 H), 1.06 (s, 3 H), 1.03–0.93 (m, 1 H), 0.88 (d, J =
H NMR (300 MHz, CDCl ): δ = 4.98 (dd, J = 9.0, 2.3 Hz, 1 H), 3.37 (t,
3
J = 8.7 Hz, 1 H), 2.96 (m, J = 9.4 Hz, 1 H), 2.17 (dd, J = 14.4, 4.5 Hz, 1
H), 1.94 (dd, J = 8.2, 14.5 Hz, 1 H), 1.76–1.51 (m, 2 H), 1.01–0.93 (m, 7
H), 0.89 (d, J = 6.7 Hz, 3 H), 0.80 (d, J = 6.7 Hz, 3 H), 0.77 (s, 3 H).
13
6.7 Hz, 3 H), 0.54 (d, J = 6.7 Hz, 3 H).
C NMR (75 MHz, CDCl ): δ = 200.9, 63.4, 53.0, 47.1, 46.0, 40.7,
3
13
C NMR (75 MHz, CDCl ): δ = 154.7, 139.1 (2 C), 133.1, 129.6,
3
38.5, 37.3, 29.7, 28.7, 23.7, 22.9, 21.8, 18.2, 17.1.
MS m/z (M ) calcd 254.1437, obsd 254.1438.
+
129.0 (2 C), 120.9, 72.7, 62.0, 44.7, 42.3, 40.0, 35.5, 31.9, 28.8, 28.5,
24.9, 22.0, 21.9, 15.8.
+
MS m/z (M ) calcd 361.2075, obsd 361.2059.
(–)-(2aR,3aR,6S,6aS,7aR)-Decahydro-6-isopropyl-3a-methyl-1H-
cyclobut[f]inden-1-one (21):
Dichlorocyclobutanone 19 (16 g, 55.4 mmol), zinc–copper couple
Anal. Calcd for C
8.71.
H O SN: C, 69.77; H, 8.64. Found: C, 69.27; H,
21 31 2
(10 g, 166 mmol), and solid NH Cl (15 g) were suspended in MeOH
For the X-ray crystallographic analysis, see Figure 1.
4

SYNTHESIS
IR (neat, cm–1): ν = 1770, 1580, 1450, 1385, 1085.
April 1998
503
(400 mL) and stirred for 1 h at r.t., and at reflux for 1 h. The mixture
was cooled, diluted with Et2O (300 mL), filtered through Celite, and
evaporated to dryness. Chromatography of the residue on silica gel
with 3% EtOAc in hexanes gave 10.3 g (85%) of 21 as a colorless to
slightly yellow oil.
1
H NMR (300 MHz, CDCl ): δ = 7.54–7.50 (m, 2 H), 7.49–7.28 (m,
3
3 H), 2.81–2.72 (m, 1 H), 2.40 (dd, J = 9.7, 3.4 Hz, 1 H), 2.23–2.04
(m, 2 H), 1.78–1.57 (m, 1 H), 1.57–1.26 (m, 5 H), 1.50 (d, J = 7.6 Hz,
3 H), 1.26–0.88 (m, 3 H), 0.83 (s, 3 H), 0.78 (d, J = 6.7 Hz, 3 H), 0.72
–1
IR (neat, cm ): ν = 1780, 1460, 1380, 1230, 1050.
(d, J = 6.7 Hz, 3 H).
1
13
H NMR (300 MHz, CDCl ): δ = 3.40 (t, J = 8.8 Hz, 1 H), 3.25–3.16
C NMR (75 MHz, CDCl ): δ = 210.3, 135.4 (2 C), 131.4, 128.9,
3
3
(m, 1 H), 2.67–2.54 (m, 1 H), 2.41–2.35 (m, 1 H), 2.21 (dd, J = 8.1,
5.2 Hz, 1 H), 2.10 (dd, J = 4.4, 9.4 Hz, 1 H), 1.74–1.50 (m, 3 H),
1.50–1.24 (m, 3 H), 1.22–0.92 (m, 3 H), 0.88 (d, J = 6.8 Hz, 3 H), 0.79
128.7 (2 C), 66.2, 63.4, 47.8, 47.6, 45.6, 42.1, 39.0, 32.6, 29.4, 24.0,
21.8, 18.6, 17.9.
MS m/z (M ) calcd 342.2017, obsd 342.2018.
+
(d, J = 6.8 Hz, 3 H), 0.76 (s, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 210.0, 58.0, 52.4, 47.4, 46.8, 44.2,
(2S,2aR,3aR,6S,6aS,7aS)-Decahydro-2-(hydroxymethyl)-6-iso-
propyl-2,3a-dimethyl-7a-(phenylsulfanyl)-1H-cyclobut[f]inden-
1-one (25):
3
41.7, 38.7, 29.7, 23.8, 23.3, 22.1, 21.8, 18.2, 17.1.
+
MS m/z (M ) calcd 220.1827, obsd 220.1827.
[α]D20 –57.7 (c = 4.00, CHCl3).
Methylcyclobutanone 24 (2.0 g, 5.8 mmol) in THF (100 mL) was
deprotonated with LDA (11.7 mL of 0.5 M solution in THF) over
45 min at –78°C. Excess monomeric formaldehyde (15 mL of form-
aldehyde solution in THF) was added quickly and the mixture was
stirred for 20 min at –78°C, quenched with H2O (30 mL) at –78°C,
and diluted with Et2O (20 mL) after warming to 20°C. The aqueous
layer was extracted with Et2O (3 × 15 mL) and the extracts were dried
and evaporated. Chromatography of the residue was performed on sil-
ica gel using 20% EtOAc in hexanes to give 25 (1.41g, 65%) as a
white solid.
Anal. Calcd for C
11.05.
H O: C, 81.76; H, 10.98. Found: C, 81.53; H,
15 24
(+)-(2aR*,3aR*,6S*,6aS*,7aR*)-Decahydro-6-isopropyl-3a,7a-
dimethyl-1H-cyclobut[f]inden-1-one (22):
Cyclobutanone 21 (0.050 g, 0.23 mmol) was dissolved in THF (4 mL)
at –78°C, and potassium hexamethyldisilazide (1.13 mL of 0.4 M in
toluene, 0.45 mmol) was added dropwise. The solution was stirred for
90 min before MeI (15 mL, 0.28 mmol) was slowly introduced. After
2 h at –78°C and overnight at r.t., H2O (3 mL) was added and the
products were extracted into Et2O. The organic layers were dried and
the residue was chromatographed on silica gel with 5% EtOAc in hex-
–1
IR (neat, cm ): ν = 3600–3100, 1770, 1440, 1390, 1030.
1
H NMR (300 MHz, CDCl ): δ = 7.55–7.50 (m, 2 H), 7.37–7.26 (m,
3
3 H), 4.03 (dd, J = 9.9, 8.5 Hz, 2 H), 2.50 (dd, J = 8.9, 2.8 Hz, 1 H),
2.15 (dd, J = 4.9, 9.2 Hz, 1 H), 1.96 (dd, J = 10.8, 2.7 Hz, 1 H),
1.76–1.66 (m, 1 H), 1.57–1.32 (m, 8 H), 1.17 (s, 3 H), 1.11–0.93 (m,
anes to give 25 mg (47%) of 22 as a colorless oil.
1
H NMR (300 MHz, CDCl ): δ = 3.50–3.41 (m, 1 H), 2.35 (dd, J =
3
2.4, 14.2 Hz, 1 H), 2.28–2.18 (m, 3 H), 1.76–1.56 (m, 3 H), 1.46–1.32
(m, 3 H), 1.31 (s, 3 H), 1.26–0.90 (m, 3 H), 0.88 (d, J = 6.7 Hz, 3 H),
1 H), 0.88 (s, 3 H), 0.78 (d, J = 6.7 Hz, 3 H), 0.71 (d, J = 6.7 Hz, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 211.1, 135.0 (2 C), 131.2, 128.9,
3
0.79 (d, J = 6.7 Hz, 3 H), 0.72 (s, 3 H).
128.7 (2 C), 70.3, 66.6, 64.5, 47.9, 47.7, 41.7, 39.3, 38.4, 37.1, 33.1,
29.6, 24.2, 21.8, 19.3, 18.0, 15.1.
13
C NMR (75 MHz, CDCl ): δ = 213.9, 62.7, 51.7, 47.7, 47.6, 45.0,
3
42.1, 38.7, 31.2, 30.4, 29.9, 25.9, 24.2, 21.8, 18.4, 17.6.
(–)-(2S,2aS,3aR,6S,6aS,7aR)-Decahydro-2-(hydroxymethyl)-6-
isopropyl-2,3a-dimethyl-1H-cyclobut[f]inden-1-one (26):
(+)-(2aR,3aR,6S,6aS,7aS)-Decahydro-6-isopropyl-3a-methyl-7a-
(phenylsulfanyl)-1H-cyclobut[f]inden-1-one (23):
Ketone 25 (1.15 g, 3.09 mmol) in MeOH (100 mL) with NH Cl
4
A solution of cyclobutanone 21 (3.25 g, 14.7 mmol) and hexamethyl-
disilazane (3.50 mL, 19.7 mmol) in pentane (325 mL) was cooled to
-50°C before iodotrimethylsilane (2.40 mL, 16.9 mmol) was added.
The mixture was stirred at r.t. overnight, cooled to –50°C, treated
with phenylsulfanyl chloride (3.1 mL), and warmed to r.t. with stir-
ring for 30 min. After dilution with CH2Cl2, the mixture was washed
with sat. Na2S2O3, dried, and concentrated. Chromatography of the
residue was performed on silica gel with elution by 3% Et2O in hex-
anes to furnish 3.40 g (70%, or 90% based on recovered starting ma-
terial) of 23 as a white solid, mp 50–51°C.
(1.25 g, 23.3 mmol) and zinc–copper couple (4 g, 62 mmol) was
stirred overnight at r.t. To this was added Et2O (80 mL) and the sus-
pension was filtered through Celite. Solvent was evaporated and the
residue was chromatographed on silica gel with 25% EtOAc in hex-
anes to give 26 (0.670 g, 82%) as a white solid, mp 73–74°C.
–1
IR (neat, cm ): ν = 3470, 1740, 1470, 1380, 1040.
1
H NMR (300 MHz, CDCl ): δ = 3.75 (br s, 2 H), 3.62 (dd, J = 9.9,
3
1.9 Hz, 1 H), 2.51–2.42 (m, 1 H), 2.13 (dd, J = 4.9, 9.1 Hz, 1 H), 1.87
(dd, J = 8.4, 4.8 Hz, 1 H), 1.76–1.56 (m, 3 H), 1.52–1.30 (m, 3 H),
1.27–1.12 (m, 3 H), 1.09 (s, 3 H), 1.05–0.92 (m, 1 H), 0.88 (d, J = 6.6
IR (neat, cm–1) ν = 1770, 1450, 1380, 1060.
Hz, 3 H), 0.80 (d, J = 6.6 Hz, 3 H), 0.76 (s, 3 H).
13
1H NMR (300 MHz, CDCl3): δ = 7.53–7.48 (m, 2H), 7.38–7.28 (m,
3H), 3.79 (dd, J = 16.3, 7.5 Hz, 1H), 2.50–2.28 (m, 3H), 2.13 (dd,
J = 13.9, 4.5 Hz, 1H), 1.77–1.54 (m, 1H), 1.53–1.31 (m, 5H),
1.14–0.86 (m, 3H), 0.80 (d, J = 6.5 Hz, 3 H), 0.79 (s, 3 H), 0.71 (d, J
C NMR (75 MHz, CDCl ): δ = 213.0, 69.1, 67.1, 54.8, 47.8, 47.1,
3
41.3, 38.9, 37.9, 29.8, 29.6, 23.9, 23.1, 21.8, 18.4, 17.2, 12.6.
+
MS m/z (M ) calcd 264.2089, obsd 264.2082.
[α]D20 –63 (c = 2.02, CHCl3).
= 6.5 Hz, 3 H).
Anal. Calcd for C
10.68.
H O : C, 77.23; H, 10.67. Found: C, 77.02; H,
17 28 2
13
C NMR (75 MHz, CDCl ): δ = 204.7, 135.2 (2 C), 131.2, 129.0,
3
128.7 (2 C), 69.4, 53.1, 47.7, 47.5, 45.0, 41.7, 38.4, 31.7, 30.5, 29.3,
23.8, 21.8, 17.8, 17.5.
+
MS m/z (M ) calcd 328.1861, obsd 328.1867.
(1S,2aR,3aS,4S,6aR,7aS)-Decahydro-4-isopropyl-1,6a-dimethyl-
2-oxo-1H-cyclobut[f]indene-1-carboxaldehyde (27):
[α]D20 +118 (c = 1.66, CHCl3).
Anal. Calcd for C
8.59.
H
OS: C, 76.79; H, 8.60. Found: C, 76.42; H,
Cyclobutanone 26 (420 mg, 1.52 mmol) was dissolved in CH2Cl2
(30 mL) and cooled to 0°C. Pyridinium chlorochromate on alumina
(1.6 g, 1.6 mmol) was added in one portion and the mixture was
stirred for 10 h at r.t. The suspension was filtered through silica gel
and eluted with 25% EtOAc in hexanes. Clear white crystals of 27
formed on standing: 357 mg (89%); mp 65–67°C.
21 28
(2R,2aR,3aR,6S,6aS,7aS)-Decahydro-6-isopropyl-2,3a-dimethyl-
7a-(phenylsulfanyl)-1H-cyclobut[f]inden-1-one (24):
A stock solution of LDA (15.0 ml of 0.5 M in THF, 7.50 mmol) was
added rapidly to a solution of 23 (1.52 g, 4.63 mmol) in THF
(200 mL) at 0°C and stirred for 1 h at r.t. MeI (10 ml, 160 mmol) was
added rapidly and the mixture was stirred for 30 min at r.t. before be-
ing washed with H2O (20 mL). The aqueous layer was extracted with
Et2O (2 × 20 mL) and the combined organic phases were dried and
evaporated. Chromatography of the residue was performed with 3%
Et2O in hexane to give 24 (1.36 g, 86%) as a colorless oil.
–1
IR (neat, cm ): ν = 1785, 1720, 1470.
1
H NMR (300 MHz, CDCl ): δ = 9.55 (s, 1 H), 3.69 (dd, J = 8.0, 3.1
3
Hz, 1 H), 3.03–2.93 (m, 1 H), 2.13 (dd, J = 4.8, 9.4 Hz, 1 H), 1.89 (dd,
J = 8.2, 5.0 Hz, 1 H), 1.74–1.37 (m, 5 H), 1.36 (s, 3 H), 1.34–0.94 (m,
4 H), 0.89 (d, J = 6.8 Hz, 3 H), 0.81 (d, J = 6.8 Hz, 3 H), 0.80 (s, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 201.3, 197.1, 79.9, 57.5, 47.5, 46.8,
3
41.2, 38.9, 37.3, 29.8, 28.5, 23.8, 22.8, 21.8, 18.3, 17.0, 10.9.

SYNTHESIS
Papers
504
+
+
MS m/z (M ) calcd 262.1933, obsd 262.1943.
MS m/z (M ) calcd 376.1244, obsd 376.1245.
Anal. Calcd for C H O : C, 77.80; H, 9.99. Found: C, 78.18; H, 9.74.
[α]D20 –34.8 (c = 1.73, CHCl ).
17 26
2
3
(–)-(2R,2aS,3aR,6S,6aR,7aR)-Decahydro-6-isopropyl-2,3a-di-
methyl-2-vinyl-1H-cyclobut[f]inden-1-one (8):
(+)-{[(1S,2S)-4-Bromo-2-methylcyclopent-3-en-1-yl]oxy}-tert-bu-
tyldimethylsilane (30):
To a solution of methyltriphenylphosphonium bromide (366 mg,
1.02 mmol) in anhyd Et2O (45 mL) at –70°C was added potassium
hexamethyldisilazide (2.05 mL, 1.5 M solution in toluene, 1.02 mmol)
and the mixture was stirred for 40 min. Oxo aldehyde 27 (257 mg,
0.98 mmol) dissolved in Et2O (10 mL) was added dropwise at –78°C.
After 45 min at r.t., the yellow mixture turned white and was quenched
Lithium chloride (192 mg, 4.55 mmol) was placed in a 50-mL round-
bottomed flask and dried under vacuum with a flame. Pd(PPh )
3 4
(90 mg, 0.078 mmol) was added and dissolved in THF (15 mL).
Hexamethylditin (210 mg, 0.64 mmol) was introduced followed by
28 (235 mg, 0.65 mmol) in THF (5 mL) . The mixture was stirred at
20°C for 30 min and heated to 75°C for 3 h. The stirring bar was re-
moved and the THF was evaporated to 1/3 volume. The remainder
was poured into hexanes (50 mL), filtered through a pad of Celite
with sat. NaHCO (15 mL). The separated organic phase was dried and
3
concentrated. Chromatography of the residue on silica gel with 5%
EtOAc in hexanes gave 8 (200 mg, 79%) as a colorless oil.
with 1% triethylamine in hexanes, washed with NaHCO (15 mL)
3
IR (neat, cm–1): ν = 1760, 1630, 1460, 1390.
and dried. The solvent was removed and the crude tin compound (204
mg) was redissolved in CH2Cl2 (10 mL). Br2 (96 mg, 0.60 mmol) was
added as a 0.1 M solution in CH2Cl2 (6 mL) at –78°C. After 5 min,
1
H NMR (300 MHz, CDCl ): δ = 5.98 (dd, J = 10.4, 6.9 Hz, 1 H), 5.08
3
(d, J = 17.5 Hz, 1 H), 5.05 (d, J = 10.5 Hz, 1 H), 3.66 (dd, J = 8.1, 2.5
Hz, 1 H), 2.58–2.48 (m, 1 H), 2.12 (dd, J = 4.8, 9.1 Hz, 2 H), 1.88 (dd,
J = 8.1, 5.2 Hz, 2 H), 1.73–1.53 (m, 3 H), 1.49–1.15 (m, 4 H), 1.13 (s,
the mixture was washed with 5 mL each of NH OH, H2O, and brine,
4
then dried and concentrated. Chromatography of the residue on silica
gel (elution with 2% Et2O in hexanes) furnished 30 as a colorless oil
(122 mg, 64%).
3 H), 0.89 (d, J = 6.7 Hz, 3 H), 0.80 (d, J = 6.7 Hz, 3 H), 0.76 (s, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 210.9, 142.1, 113.1, 67.8, 54.3, 47.6,
3
46.9, 41.3, 38.9, 38.0, 32.2, 29.8, 23.9, 22.8, 21.8, 18.4, 17.1, 15.2.
IR (neat, cm–1): ν = 1475, 1370, 1260, 1120.
+
1
MS m/z (M ) calcd 260.2140, obsd 260.2147.
H NMR (300 MHz, CDCl ): δ = 5.71 (t, J = 1.9 Hz, 1 H), 4.03–3.97
3
[α]D20 –92 (c = 0.715, CHCl3).
(m, 1 H), 2.87–2.78 (m, 1 H), 2.62–2.50 (m, 2 H), 1.05 (d, J = 7.1 Hz,
Anal. Calcd for C18H28O: C, 83.02; H, 10.84. Found: C, 82.77; H,
10.93.
3 H), 0.89 (s, 9 H), 0.065 (s, 3 H), 0.06 (s, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 134.7, 117.3, 79.7, 49.6, 48.8, 25.8
3
(3 C), 18.1, 17.9, –4.7, –4.8.
+
(3S,4S)-4-(tert-Butyldimethylsiloxy)-3-methylcyclopent-1-en-1-yl
Trifluoromethanesulfonate (28):
MS m/z (M ) calcd 290.0701, obsd 290.0710.
[α]D20 +50.3 (c = 6.2, CHCl3).
Copper(I) bromide–dimethyl sulfide complex (1.87 g, 9.1 mmol) was
dried under vacuum, suspended in THF (120 mL), cooled to –78°C
and treated with MeLi (12 mL, 18 mmol). The slightly yellow solu-
tion was stirred for 1 h before (–)-11 (1.75 g, 8.24 mmol) in cold
(–78°C) THF (40 mL) was added dropwise via cannula. After 15 min,
N-(5-chloro-2-pyridyl)triflimide (6.00 g, 15.2 mmol) dissolved in
THF (40 mL) was added via cannula at –50°C, and the mixture was
stirred at –50°C for 45 min and poured into 15% ammonium hydrox-
ide (100 mL). Hexanes (100 mL) were added followed by extraction
of the aqueous layer with Et2O (3 × 25 mL). The combined organic
layers were dried and evaporated, and the residue was chromato-
graphed on silica gel with 3% Et2O in hexanes to give 28 (1.99 g,
67%) as a clear light oil.
(2S,3S,3aR,6aS,7aR,10S,10aS,11aR,12aS)-2-(tert-Butyldimethyl-
siloxy)-2,3,3a,4,6a,7,7a,8,9,10,10a,11,11a,12a-tetradecahydro-10-
isopropyl-3,6,7a-trimethylcyclopenta[4,5]cyclooct[1,2-f]inden-
12(1H)-one (34a):
Vinyl bromide 30 (173 mg, 0.60 mmol) was placed in a flame-dried
flask with a stirring bar and anhyd THF (15 mL) at –78°C, and t-BuLi
(0.70 mL, 1.19 mmol) was added via syringe. After 45 min, a solution
of 8 (140 mg, 0.54 mmol) in THF (5 mL) was added via cannula at
–78°C. The mixture was stirred for 20 min, H2O (5 mL) was added,
and the solution was warmed to 20°C. Hexane (5 mL) was added, the
organic layer was separated, and the aqueous phase was extracted
with Et2O (2 × 10 mL), and dried. The residue was chromatographed
on TLC grade silica gel (elution with hexane to 2% Et2O in hexanes)
to give 34a (175 mg, 69%) as a colorless oil.
–1
IR (neat, cm ): ν = 1665, 1435, 1260, 1220, 1150.
1
H NMR (300 MHz, CDCl3): δ = 5.47 (br s, 1 H), 4.01 (m, 1 H),
–1
2.87–2.78 (m, 1 H), 2.71–2.61 (m, 1 H), 2.56–2.48 (m, 1 H), 1.50 (d,
IR (neat, cm ): ν = 1695, 1460, 1375, 1255, 1080.
1
J = 6.1 Hz, 3 H), 0.89 (s, 9 H), 0.71 (s, 3 H), 0.63 (s, 3 H).
H NMR (300 MHz, CDCl ): δ = 5.46 (m, 1 H), 4.13 (m, 1 H), 3.34
3
13
C NMR (75 MHz, CDCl3): δ = 145.5, 120.7, 45.9, 40.7, 25.7 (3 C),
(m, 1 H), 3.03 (m, 1 H), 2.51–2.28 (m, 2 H), 2.22–2.05 (m, 2 H),
1.90–1.84 (m, 5 H), 1.80 (s, 3 H), 1.78–1.23 (m, 8 H), 1.20–0.98 (m,
4 H), 0.91 (d, J = 7.2 Hz, 6 H), 0.89 (s, 6 H), 0.87 (s, 3 H), 0.78 (s, 3
H), 0.03 (s, 6 H).
18.0, –4.7, –4.8 (CF3 not detected).
+
MS m/z (M ) calcd 360.1038, obsd 360.1038.
[α]D20 –27.6 (c = 2.42, CHCl3).
(–)-[(3S,4S)-4-(tert-Butyldimethylsiloxy)-3-methylcyclopent-1-
en-1-yl]trimethylstannane (29):
Vinyl triflate 28 (312 mg, 0.87 mmol) was dissolved in THF (30 mL)
and treated in order with hexamethylditin (312 mg, 0.95 mmol), LiCl
(280 mg, 6.6 mmol; dried under vacuum and heated prior to addition),
and tetrakis(triphenylphosphine)palladium(0) (115 mg, 0.1 mmol).
The mixture was stirred at 20°C for 1 h and heated for 45 min at 65°C.
The product was isolated by adding hexanes (15 mL) and washing
with H2O (2 x 15 mL). The aqueous layer was extracted with hexanes
(2 × 5 mL) and the combined organic solutions were dried, filtered
and concentrated. Chromatography of the residue on silica gel with
2% Et2O in hexanes containing 1% Et3N gave 29 (260 mg, 78%) as a
colorless oil.
–1
IR (neat, cm ): ν = 1465, 1365, 1255, 1110.
1
H NMR (300 MHz, CDCl ): δ = 5.76–5.62 (m, 1 H), 4.00–3.94 (m,
3
1 H), 2.71–2.58 (m, 2 H), 2.34–2.26 (m, 1 H), 1.01 (d, J = 7.2 Hz, 3
H), 0.90 (s, 9 H), 0.11 (s, 6 H), 0.10–0.06 (m, 9 H).
13
C NMR (75 MHz, CDCl ): δ = 145.1, 140.5, 81.6, 50.3, 47.5, 25.9
3
(3 C), 18.2, 18.1, –4.5, –4.6, –10.2.

SYNTHESIS
April 1998
13
505
C NMR (75 MHz, CDCl ): δ = 219.4, 138.1, 126.0, 81.5, 52.9, 52.1,
7.2 Hz, 1 H), 3.01–2.92 (m, 1 H), 2.80–2.69 (m, 1 H), 2.28–2.13 (m,
1 H), 1.89–1.54 (m, 3 H), 1.63 (s, 3 H), 1.45–1.03 (m, 9 H), 0.97 (d,
J = 7.4 Hz, 3 H), 0.95–0.79 (m, 15 H), 0.77 (s, 3 H), 0.07 (s, 3 H), 0.06
3
46.2, 46.1, 44.4, 42.4, 41.9, 41.7, 41.3, 38.9, 38.2, 28.9, 28.2, 28.1,
27.1, 25.9 (3 C), 22.8, 22.1, 18.1, 17.6, 17.3, 13.4, –4.7 (2 C).
MS m/z (M ) calcd 472.3737, obsd 472.3728.
Anal. Calcd for C
11.12.
+
(s, 3 H).
13
H
O Si: C, 76.21; H, 11.08. Found: C, 76.26; H,
C NMR (75 MHz, CDCl ): δ = 205.7, 149.0, 139.6, 137.7, 125.2,
30 52
2
3
99.6, 82.8, 77.2, 46.9, 46.0, 45.8, 45.1, 44.5, 41.4, 40.8, 39.5, 36.2,
29.6, 26.9, 26.3, 25.9 (3 C), 25.8, 24.4, 23.3, 21.9, 18.3, 17.0, 14.9,
–4.6, –4.7.
(–)-(2S,3S,3aR,6aS,7aR,10S,10aS,11aR,12aR)-2-(tert-Butyldime-
thylsiloxy)-2,3,3a,4,6a,7,7a,8,9,10,10a,11,11a,12a-tetradecahy-
dro-10-isopropyl-3,6,7a-trimethyl-12a-
(phenylseleno)cyclopenta-[4,5]cyclooct[1,2-f]inden-12(1H)-one
(34b):
+
MS m/z (M ) calcd 470.3580, obsd 470.3592.
[α]D20 +34 (c = 0.31, CHCl ).
Anal. Calcd for C
10.72.
3
H
O Si: C, 76.53; H, 10.70. Found: C, 76.40; H,
30 50
2
Vinyl bromide 30 (175 mg, 0.60 mmol) in THF (20 mL) was cooled
to –78°C and reacted with tert-butyllithium (860 µL, 1.20 mmol) for
15 min. A solution of 8 (135 mg, 0.52 mmol) in THF (5 mL) was
cooled to –78°C and added dropwise via cannula. After the mixture
had been stirred for 40 min, a solution of phenylselenyl chloride
(33 mg, 0.173 mmol) in THF (3 mL) cooled to –78°C was added
dropwise via cannula. The mixture was stirred for 20 min, warmed to
–50°C, and quenched with H2O (5 mL). The aqueous portion was ex-
tracted with Et2O (2 × 10 mL) and the organic solution was dried and
concentrated. Chromatography of the residue on silica gel with 2%
Et2O in hexanes gave 297 mg (91%) of 34b as a white solid, mp
123–125°C.
For 36a:
–1
IR (neat, cm ): ν = 1650, 1450, 1360, 1240, 1100.
1
H NMR (300 MHz, CDCl ): δ = 5.47 (t, J = 8.5 Hz, 1 H), 3.90–3.86
3
(m, 1 H), 3.63 (t, J = 6.5 Hz, 1 H), 3.15 (dd, J = 7.1, 6.8 Hz, 1 H),
2.79–2.50 (m, 5 H), 1.83–1.11 (m, 11 H), 1.69 (s, 3 H), 1.07 (d, J =
7.2 Hz, 3 H), 0.88 (s, 9 H), 0.87 (d, J = 6.8 Hz, 3 H), 0.84 (d, J =
6.8 Hz, 3 H), 0.80 (s, 3 H), 0.05 (s, 3 H), 0.04 (s, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 207.7, 153.6, 140.5, 136.9, 127.7,
3
123.2, 77.9, 54.5, 49.0, 46.5, 44.5, 42.6, 41.8, 39.6, 39.3, 37.9, 29.4,
28.8, 28.5, 25.9 (3 C), 23.0, 22.1, 18.2, 18.1, 17.3, 15.9, –4.6, –4.8.
MS m/z (M ) calcd 470.3580, obsd 470.3579.
+
–1
Method B. Peracid Oxidation.
IR (neat, cm ): ν = 1680, 1420, 1120.
1
A solution of 34b (297 mg, 0.47 mmol) in CH2Cl2 (100 mL) cooled
to –5°C was treated with MCPBA (81 mg, 172 mmol) in one portion.
The mixture turned yellow and then almost clear before more peracid
was added at 45 minute intervals. The solution was washed with sat.
H NMR (300 MHz, C D ): δ = 7.62–7.59 (m, 2 H), 7.12–7.02 (m, 3
6
6
H), 5.18 (t, J = 7.8 Hz, 1 H), 3.85–3.73 (m, 2 H), 2.98–2.94 (m, 1 H),
2.81–2.73 (m, 2 H), 2.50 (dd, J = 3.7, 13.9 Hz, 2 H), 2.32–2.23 (m, 1
H), 2.22–2.16 (m, 2 H), 2.01–1.66 (m, 6 H), 1.62 (s, 3 H), 1.59–1.22
(m, 4 H), 1.06–0.86 (m, 18 H), 0.76 (s, 3 H), 0.02 (s, 3 H), –0.05 (s, 3
H).
NaHCO (2 × 10 mL) and the organic phase was dried and concen-
3
trated. Chromatography as before furnished both 35a (154 mg, 70%)
and 36a (59 mg, 27%).
13
C NMR (75 MHz, C D ): δ = 208.0, 143.5, 136.8, 129.9, 129.1,
6
6
129.0, 128.2, 128.1, 127.9, 123.9, 78.6, 64.2, 49.6, 47.3, 45.6, 44.5,
44.4, 42.2, 41.6, 41.5, 40.0, 36.9, 31.3, 29.2, 26.1, 25.8 (3 C), 24.2,
22.7, 22.5, 18.3, 17.5, 17.2, 13.7, –4.4, –4.8.
(2S,3S,3aR,6aS,7aR,10S,10aS,11aR,12aR)-2,3,3a,4,6a,7,7a,8,9,
10,10a,11,11a,12a-Tetradecahydro-2-hydroxy-10-isopropyl-
3,6,7a-trimethyl-12a-(phenylseleno)cyclopenta[4,5]cyclooct[1,2-
f]-inden-12(1H)-one (37):
+
MS m/z (M ) calcd 628.3215, obsd 628.3218.
[α]D20 –8.3 (c = 0.42, CHCl ).
3
A solution of 34b (30 mg, 0.048 mmol) in THF (10 mL) at –5°C was
reacted with tetrabutylammonium fluoride (60 µL, 0.06 mmol) in
THF over 10 min at r.t. Product 37 (20 mg, 82%) was isolated as a
white solid, mp 160°C, after chromatography on silica gel with 35%
EtOAc in hexanes.
Anal. Calcd for C
H, 9.01.
H
O SeSi: C, 68.87; H, 8.99. Found: C, 68.93;
36 56
2
–1
IR (neat, cm ): ν = 3440, 1630, 1420.
1
H NMR (300 MHz, C D ): δ = 7.57–7.53 (m, 2 H), 7.10–7.02 (m, 3
6
6
H), 5.10 (t, J = 8.1 Hz, 1 H), 3.85 (t, J = 7.3 Hz, 1 H), 3.56–3.48 (m,
1 H), 2.77–2.68 (m, 3 H), 2.44 (dd, J = 10.2, 3.6 Hz, 1 H), 2.33–2.13
(m, 3 H), 1.93–1.85 (m, 3 H), 1.82–1.74 (m, 1 H), 1.72–1.62 (m, 3 H),
1.63 (s, 3 H), 1.57–1.42 (m, 3 H) 1.40–1.18 (m, 2 H), 1.04–0.97 (m,
6 H), 0.93 (d, J = 6.9 Hz, 3 H), 0.75 (s, 3 H).
13
C NMR (75 MHz, C D ): δ = 208.5, 143.2, 136.2 (2 C), 130.2, 128.9,
6
6
128.6, 127.9, 123.9, 78.1, 64.4, 50.1, 47.3, 45.6, 44.5, 44.4, 42.3, 41.6,
41.5, 39.9, 37.1, 31.2, 29.1, 25.9, 24.4, 22.8, 22.5, 17.5, 17.2, 13.6.
MS m/z (M ) calcd 514.2350, obsd 514.2348.
+
(+)-(2R,3S,3aR,6aS,7aR,10S,10aS,11aR)-2-(tert-Butyldimethyl-
siloxy)-3,3a,4,6a,7,7a,8,9,10,10a,11,11a-dodecahydro-10-isopro-
pyl-3,6,7a-trimethylcyclopenta[4,5]cyclooct[1,2-f]inden-12(2H)-
one (35a) and (2S,3S,6aS,7aR,10S,10aS,11aR)-2-(tert-Butyldime-
thylsiloxy)-2,3,4,6a,7,7a,8,9,10,10a,11,11a-dodecahydro-10-iso-
propyl-3,6,7a-trimethylcyclopenta[4,5]cyclooct[1,2-f]inden-
12(1H)-one (36a):
Anal. Calcd for C
8.22.
H O Se: C, 70.15; H, 8.24. Found: C, 69.86; H,
30 42 2
(2R,3S,3aR,6aS,7aR,10S, 10aS,11aR)-3, 3a,4,6a,7,7a,8,9,10,10a,
11,11a-Dodecahydro-2-hydroxy-10-isopropyl-3,6,7a-trimethyl-
cyclopenta[4,5]cyclooct[1,2-f]inden-12(2H)-one (35b) and
(2S,3S,6aS,7aR, 10S,10aS,11aR)-2,3,4,6a,7,7a,8,9,10,10a,11,11a-
Dodecahydro-2-hydroxy-10-isopropyl-3,6,7a-trimethylcyclopen-
ta[4,5]cyclooct[1,2-f]inden-12(1H)-one (36b):
Compound 37 (12 mg, 0.024 mmol) was dissolved in CH2Cl2 (10 mL)
and cooled to –10°C. MCPBA (4.8 mg, 0.028 mmol) was added in
one portion and allowed to react for 1 h while being allowed to warm
Method A. Oxidation with Hydrogen Peroxide:
Oxo selenide 34b (40 mg, 0.064 mmol) was dissolved in CH2Cl2
(10 mL) and pyridine (0.4 mL). H2O2 (0.5 mL, 30% solution) was
added at 0°C and the mixture was allowed to warm to r.t. during 2 h.
H2O (5 mL) was added and the organic phase was washed with H2O
(2 × 5 mL). The organic layer was dried, freed of solvent, and chro-
matographed on silica gel with 2% Et2O in hexanes to furnish 35a (19
mg, 62%) and 36a (7 mg, 23%).
to r.t. The mixture was washed with sat. NaHCO (2 × 5 mL), dried,
3
filtered, and evaporated. Purification of the residue on silica gel with
elution by 40% EtOAc in hexanes furnished 35b (8.0 mg) and 36b
(3.1 mg) (96% combined).
For 35a:
–1
IR (neat, cm ): ν = 2960, 1675, 1610, 1460, 1370, 1250, 1040, 835.
1
H NMR (300 MHz, CDCl ): δ = 6.38 (t, J = 2.2 Hz, 1 H), 5.35 (t, J
For 35b: white solid, mp 148–151°C.
3
–1
= 8.6 Hz, 1 H), 4.29 (br s, 1 H), 3.69 (t, J = 7.5 Hz, 1 H), 3.47 (t, J =
IR (neat, cm ): ν = 3240, 1720, 1600, 1460, 1375.

SYNTHESIS
Papers
506
1
H NMR (300 MHz, CDCl ): δ = 6.46 (t, J = 2.4 Hz, 1 H), 5.33 (t, J
Hz, 3 H), 0.95–0.82 (m, 12 H), 0.79 (d, J = 6.8 Hz, 3 H), 0.08 (s, 6 H).
3
13
= 7.8 Hz, 1 H), 4.32 (m, 1 H), 3.70 (t, J = 7.4 Hz, 1 H), 3.50 (m, 1 H),
2.97 (m, 1 H), 2.85–2.70 (m, 1 H), 2.32–2.27 (m, 1 H), 2.24–2.16 (m,
1 H), 1.90–1.77 (m, 3 H), 1.71–1.65 (m, 2 H), 1.64 (s, 3 H), 1.62–1.53
(m, 2 H), 1.46–1.32 (m, 4 H), 1.26–1.20 (m, 1 H), 1.01 (d, J = 7.4 Hz,
C NMR (75 MHz, CDCl ): δ = 203.3, 146.9, 145.0, 139.7, 122.7,
3
81.1, 58.5, 50.4, 47.5, 45.8, 45.1, 42.9, 41.9, 38.9, 36.6, 29.1, 28.8,
28.4, 25.8 (3 C), 23.0, 21.9, 19.1, 18.9, 18.1, 17.6, 12.2, –4.5, –4.8.
+
MS m/z (M ) calcd 470.3580, obsd 470.3581.
3 H), 0.91 (d, J = 6.8 Hz, 3 H), 0.87 (d, J = 6.8 Hz, 3 H), 0.77 (s, 3 H).
[α]D20 +167 (c = 1.11, CHCl ).
3
13
C NMR (75 MHz, CDCl ): δ = 205.6, 150.2, 139.9, 136.8, 124.9,
3
82.4, 46.9, 46.3, 46.0, 45.2, 44.6, 41.5, 40.8, 39.5, 36.3, 29.7, 27.0,
26.3, 24.5, 23.5, 21.9, 18.4, 17.0, 14.8.
MS m/z (M ) calcd 356.2715, obsd 356.2714.
(2S,3S,7aS,10S,10aS)-2-(tert-Butyldimethylsiloxy)-2,3,7,7a,8,9,
10,10a,11,11a-decahydro-10-isopropyl-3,6,7a-trimethylcyclopen-
ta[4,5]cyclooct[1,2-f]inden-12(1H)-one (42a) and (2S,3S,7aS,
10S,10aS)-2,3,7,7a,8,9,10,10a,11,11a-Decahydro-2-hydroxy-10-
isopropyl-3,6,7a-trimethylcyclopenta[4,5]cyclooct[1,2-f]inden-
12(1H)-one (42b):
SeO2 on silica gel (260 mg, 0.11 mmol) was suspended in CH2Cl2
(5 mL) and tert-butyl hydroperoxide (20 mg, 0.22 mmol) was added.
After 10 min, 36a (35 mg, 0.074 mmol) in CH2Cl2 (5 mL) was intro-
duced at r.t. and stirred for 72 h. The mixture was heated to reflux and
more SeO2 on silica gel was added. Products 42a (9.6 mg, 27%) and
42b (6.6 mg, 19%) were collected following chromatography on sili-
ca gel with elution by 2% Et2O in hexanes.
+
Anal. Calcd for C
9.98.
H O : C, 80.85; H, 10.18. Found: C, 81.22; H,
24 36 2
For 36b: heavy, colorless oil.
–1
IR (neat, cm ): ν = 3420, 2930, 2780, 1640, 1440, 1370.
1
H NMR (300 MHz, C D ): δ = 5.38 (t, J = 7.7 Hz, 1 H), 3.88–3.85
6
6
(m, 1 H), 3.61 (t, J = 6.0 Hz, 1 H), 3.13 (dd, J = 8.4, 8.6 Hz, 1 H), 2.85
(dd, J = 5.9, 10.7 Hz, 1 H), 2.66–2.48 (m, 3 H), 2.36 (d, J = 6.6 Hz, 1
H), 1.79–1.57 (m, 2 H), 1.58 (s, 3 H), 1.56–1.03 (m, 9 H), 0.98 (d, J
= 7.3 Hz, 3 H), 0.93–0.82 (m, 1 H), 0.78 (d, J = 6.8 Hz, 3 H), 0.73 (d,
J = 6.8 Hz, 3 H), 0.70 (s, 3 H).
Rhodium Trichloride-Promoted Isomerizations.
Method A: To a solution of 35a (91 mg, 0.19 mmol) in EtOH (30 mL)
was added RhCl · 3H O (14 mg, 0.054 mmol) and the orange mix-
ture was heated to reflux for 20 h. The residue was purified by chro-
matography on silica gel with 30% EtOAc in hexanes to give 24 mg
(35%) of 36a.
For 42a: white solid, mp 160°C (dec).
–1
IR (neat, cm ): ν = 1680, 1510, 1410, 1300, 1150.
3
2
1
H NMR (300 MHz, CDCl ): δ = 6.35 (d, J = 12.3 Hz, 1 H), 6.05 (d,
3
J = 12.3 Hz, 1 H), 3.85 (m, 1 H), 3.37 (dd, J = 6.2, 17.1 Hz, 1 H), 3.10
(d, J = 5.8 Hz, 1 H), 2.89 (dd, J = 4.1, 17.1 Hz, 1 H), 2.79 (m, 1 H),
2.62 (d, J = 14 Hz, 1 H), 2.51 (td, J = 4.2, 12.4 Hz, 1 H), 2.36 (dd, J
= 12.9, 4.0 Hz, 1 H), 1.92 (m, 1 H), 1.75 (br d, J = 12.7 Hz, 2 H), 1.62
(s, 3 H), 1.57–1.22 (m, 4 H), 1.39 (s, 1 H), 1.19 (d, J = 6.7 Hz, 3 H),
1.19 (s, 1 H), 1.14 (d, J = 6.8 Hz, 3 H), 1.06 (d, J =7.2 Hz, 3 H), 0.92
Method B: A solution of 35b (7.7 mg, 0.022 mmol) in EtOH (10 mL)
was treated with rhodium trichloride (4.6 mg, 0.022 mmol) and the
solution was heated to reflux for 17 h. The EtOH was removed and
the residue was placed atop a column of silica gel and eluted with
20–25% EtOAc in hexanes to deliver 3 mg (35%) of 36b.
(s, 9 H), 0.78 (s, 3 H), 0.04 (s, 3 H), 0.02 (s, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 192.4, 148.6, 143.6, 138.4, 137.3,
3
131.1, 123.1, 77.4, 55.9, 49.1, 47.2, 46.1, 43.0, 42.1, 42.0, 38.6, 30.2,
26.1, 26.0 (3 C), 24.3, 22.0, 18.5, 18.2, 18.0, 17.9, 16.3, –4.4, –4.6.
MS m/z (M ) calcd 468.3424, obsd 468.3420.
(2S,3S,6aS,7aR,10S,10aS)-2-(tert-Butyldimethylsiloxy)-
2,3,6a,7,7a,8,9,10,10a,11,11a,12a-dodecahydro-10-isopropyl-
3,6,7a-trimethylcyclopenta[4,5]cyclooct[1,2-f]inden-12(1H)-one
(40):
+
For 42b: white solid, mp 158–159°C.
–1
IR (neat, cm ): ν = 3390, 2950, 1640, 1440, 1370, 1200.
1
Ketone 36a (4.3 mg, 9.1 mmol) was dissolved in a solution of K CO
H NMR (300 MHz, C D ): δ = 6.29 (d, J = 12.4 Hz, 1 H), 5.94 (d, J
2
3
6 6
(3 mg) in MeOH (3 mL) and THF (0.5 mL) and stirred for 48 h. The
mixture was concentrated, CH2Cl2 (10 mL) was added, and the organ-
ic solution was dried, filtered, and evaporated. The residue was puri-
fied on silica gel with elution by 1.5% Et2O in hexanes to furnish 40
= 12.4 Hz, 1 H), 3.54 (m, 1 H), 3.18 (dd, J = 5.7, 17.8 Hz, 1 H), 3.00
(d, J = 5.9 Hz, 1 H), 2.74 (d, J = 17.9 Hz, 1 H), 2.58 (m, 2 H),
2.50–2.40 (m, 1 H), 2.28 (m, 1 H), 1.87 (m, 1 H), 1.75–1.64 (m, 3 H),
1.58 (s, 3 H), 1.56–1.14 (m, 4 H), 1.12 (d, J = 6.8 Hz, 3 H), 1.13 (s, 1
H), 1.08 (d, J = 6.8 Hz, 3 H), 0.87 (d, J = 7.3 Hz, 3 H), 0.72 (s, 3 H).
(2.5 mg, 58%) as a white solid, mp 110–127°C.
1
13
H NMR (300 MHz, CDCl ): δ = 6.06 (t, J = 10.6 Hz, 1 H), 5.85 (m,
C NMR (75 MHz, C D ): δ = 192.5, 149.4, 143.2, 138.3, 137.3,
3
6 6
1 H), 3.91–3.88 (m, 1 H), 3.28 (dd, J = 0.5, 4.9 Hz, 1 H), 3.02 (dd, J
= 6.2, 8.0 Hz, 1 H), 2.77 (m, 1 H), 2.45 (dd, J = 9.0, 1.4 Hz, 1 H),
2.25–2.15 (m, 1 H), 2.12–2.05 (m, 1 H), 1.96–1.90 (m, 1 H),
1.80–1.10 (m, 10 H), 1.01 (d, J = 7.3 Hz, 3 H), 0.99–0.80 (m, 18 H),
0.75 (s, 3 H), 0.07 (s, 6 H).
131.0, 123.5, 75.3, 56.2, 49.2, 46.2, 43.0, 42.5, 42.1, 38.6, 30.2, 26.1,
24.3, 22.0, 18.6, 18.0, 17.9, 16.6.
MS m/z (M ) calcd 354.2559, obsd 354.2577.
+
13C NMR (75 MHz, CDCl ): δ = 205.1, 149.7, 145.8, 137.2, 124.7,
3
(2S,3S,3aR,6aS,7aR,10S,10aS,11aR,12S,12aS)-2-(tert-Butyldime-
thylsiloxy)-1,2,3,3a,4,6a,7,7a,8,9,10,10a,11,11a,12,12a-hexa-
decahydro-10-isopropyl-3,6,7a,12-tetramethylcyclopenta[4,5]-
cyclooct-[1,2-f]inden-12-ol (43):
53.9, 50.1, 46.2, 45.5, 45.0, 41.6, 41.4, 40.3, 39.0, 36.8, 29.0, 27.0,
25.9 (3 C), 23.1, 22.0, 18.6, 18.2, 17.8, 17.7, 16.8, –4.5, –4.8.
+
MS m/z (M ) calcd 470.3580, obsd 470.3590.
Ketone 34a (20 mg, 0.042 mmol) was dissolved in THF (5 mL) at 0°C
before MeLi (36.4 µL, 0.051 mmol) was added via syringe. The mix-
ture was stirred at 20°C for 30 min and quenched with brine (3 mL).
The separated organic phase was dried and concentrated. The crude
material was purified by chromatography on silica gel with 5%
EtOAc in hexanes to give 43 (21 mg, 99%) as a colorless oil.
(+)-(2R,3S,3aR,6aS,7aR,10S,10aS,11aS)-2-(tert-Butyldimethyl-
siloxy)-3,3a,4,6a,7,7a,8,9,10,10a,11,11a-dodecahydro-10-isopro-
pyl-3,6,7a-trimethylcyclopenta[4,5]cyclooct[1,2-f]inden-12(2H)-
one (41):
Ketone 35a (28 mg, 59 mmol) was dissolved in MeOH (10 mL),
K CO (5 mg) was added, and the suspension was stirred for 12 h at
–1
IR (neat, cm ): ν = 3320, 1470, 1370, 1260, 1090.
2
3
1
r.t. After an additional 12 h at 60°C, the MeOH was removed and
CH2Cl2 (3 mL) was added. The mixture was dried and concentrated,
and the residue was purified by chromatography on silica gel with
1.5% Et2O in hexanes to furnish 41 (15 mg, 53%) as a white solid, mp
H NMR (300 MHz, CDCl ): δ = 7.06 (br s, 1 H), 5.41 (br s, 1 H),
3
4.18–4.13 (m, 1 H), 3.84–3.73 (m, 1 H), 3.22 (br s, 1 H), 2.97–2.91
(m, 1 H), 2.56–2.04 (m, 4 H), 2.00–1.87 (m, 2 H), 1.83 (s, 3 H),
1.75–1.25 (m, 14 H), 1.05 (s, 3 H), 0.95 (d, J = 6.8 Hz, 3 H), 0.91 (s,
95–110°C.
3 H), 0.89 (s, 9 H), 0.81 (d, J = 6.8 Hz, 3 H), 0.04 (s, 6 H).
1
13
H NMR (300 MHz, CDCl ): δ = 6.58 (s, 1 H), 5.16 (br d, J = 7.2 Hz,
C NMR (75 MHz, CDCl ): δ = 141.4, 127.0, 85.2, 78.5, 76.8, 76.4,
3
3
1 H), 4.46 (d, J = 8.2 Hz, 1 H), 3.75–3.67 (m, 1 H), 3.45 (t, J = 3.3 Hz,
1 H), 2.48–2.25 (m, 3 H), 2.00–1.85 (m, 1 H), 1.80–1.60 (m, 4 H),
1.56 (s, 4 H), 1.52–1.30 (m, 4 H), 1.30–1.13 (m, 5 H), 1.10 (d, J = 7.0
52.5, 48.9, 48.4, 44.1, 41.7, 39.6, 39.1, 35.8, 31.6, 29.4, 28.1, 25.9 (3
C), 25.3, 24.5, 24.4, 23.9, 21.9, 18.2, 18.1, 13.4, –4.4, –4.7.
MS m/z (M ) calcd 488.4050, obsd 488.4047.
+

SYNTHESIS
April 1998
507
(–)-tert-Butyl{[(2S,3S,3aS,6aS,7aR,10S,10aS,11aR,12aR)-1,2,3,
3a,4,6a,7,7a,8,9,10,10a,11,11a,12,12a-hexadecahydro-10-isopro-
pyl-3,6,7a-trimethyl-12-methylenecyclopenta[4,5]cyclooct[1,2-
f]inden-2-yl]oxy}dimethylsilane (44):
MS m/z (M+) calcd 398.3185, obsd 398.3188.
[α]D20–38.1 (c = 0.75, CHCl3).
Also isolated was 4 mg (24%) of 47 as a thick, colorless oil.
1
H NMR (300 MHz, CDCl ): δ = 5.37–5.35 (t, J = 2.9 Hz, 1 H), 5.30
3
Alcohol 43 (50 mg, 0.103 mmol) was dissolved in CH2Cl2 (3 mL) and
pyridine (2 mL) and cooled to –78°C. SOCl2 (50 µL, 0.68 mmol) was
added via syringe and reaction was complete within 5 min. Ice (10 g)
was added followed by EtOAc (10 mL), and the mixture was allowed
to warm to r.t. The aqueous layer was extracted with EtOAc (3 ×
5 mL) and the combined organic phases were dried and concentrated.
The residue was purified by chromatography on silica gel with 1.5 to
2% Et2O in hexanes to deliver 44 (34 mg, 68%) as a heavy, colorless
oil.
(s, 1 H), 5.20 (t, J = 9.6 Hz, 1 H), 4.95–4.87 (m, 2 H), 4.89 (s, 1 H),
4.26–4.20 (m, 1 H), 4.13–4.09 (m, 1 H), 3.78 (dd, J = 5.8, 5.0 Hz, 1
H), 3.61–3.55 (m, 1 H), 3.60 (t, J = 10.6 Hz, 1 H), 2.77–2.74 (m, 1 H),
2.56–2.51 (m, 1 H), 2.40–2.45 (m, 1 H), 2.31–2.26 (m, 1 H), 2.11 (s,
3H), 2.10 (s, 3 H), 2.03 (s, 3 H), 2.05–1.81 (m, 2 H), 1.80–1.59 (m, 3
H), 1.74 (s, 3 H), 1.52–1.23 (m, 8 H), 1.02 (d, J = 7.5 Hz, 3 H), 0.91
(d, J = 6.8 Hz, 3 H), 0.89–0.80 (m, 2 H), 0.84 (d, J = 6.8 Hz, 3 H),
0.82 (s, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 183.1, 181.6, 177.0, 156.7, 144.1,
3
1
H NMR (300 MHz,C D ): δ = 5.48 (s, 1 H), 5.42 (dt, J = 3.1, 1.5 Hz,
6
6
140.7, 140.5, 125.3, 124.2, 101.1, 97.0, 88.5, 73.1, 70.8, 69.0, 57.8,
46.3, 45.5, 45.4, 44.9, 42.9, 42.4, 39.3, 31.6, 30.8, 28.4, 22.7(3 C),
22.3, 21.0, 20.8, 17.6, 17.5, 16.4, 14.1.
1 H), 5.11 (s, 1 H), 4.30–4.28 (m, 1 H), 2.86 (td, J = 3.1, 1.5 Hz, 1 H),
2.56–2.49 (m, 2 H), 2.49–2.37 (m, 1 H), 2.20–2.16 (m, 1 H),
2.15–1.77 (m, 3 H), 1.76 (s, 3 H), 1.74–1.05 (m, 8 H), 1.03 (d, J = 7.8
Hz, 3 H), 1.01 (s, 9 H), 0.95 (d, J = 6.8 Hz, 3 H), 0.90 (d, J = 6.7 Hz,
3 H), 0.88–0.80 (m, 3 H), 0.79 (s, 3 H), 0.12 (s, 3 H), 0.11 (s, 3 H).
T. M. H. served as a Department of Education Fellow 1990–1991.
This work was financially supported by the National Institutes of
Health and the Eli Lilly Company. We thank Dr. Kurt Loening for his
assistance with nomenclature.
13
C NMR (75 MHz, C D ): δ = 157.9, 138.9, 126.2, 112.2, 83.6, 50.0,
6
6
46.8, 46.7, 45.8 (2 C), 44.8, 43.5, 42.8, 42.6, 42.5, 39.6, 31.2, 28.9,
27.8, 27.5, 26.2 (3 C), 22.8, 22.7, 18.3, 17.8, 17.7, 16.3, –4.2, –4.6.
+
MS m/z (M ) calcd 470.3944, obsd 470.3953.
[α]D24 –15.0 (c = 2.34, CHCl ).
3
(1) Lauer, U.; Anke, T.; Sheldrick, W. S. J. Antibiotics 1989, 42,
875.
(2) Isolation: Kaneda, M.; Takahashi, R.; Itaka, Y.; Shibata, S.
Tetrahedron Lett. 1972, 4609.
Kaneda, M.; Itaka, Y.; Shibata, S. Acta Crystallogr. 1974, 30B,
358.
(3) Syntheses: (a) Corey, E. J.; Desai, M. C.; Engler, T. A. J. Am.
Chem. Soc. 1985, 107, 4339.
(2S,3S,3aS,6aS,7aR,10S,10aS,11aR,12aR)-1,2,3,3a,4,6a,7,7a,
8,9,10,10a,11,11a,12,12a-Hexadecahydro-10-isopropyl-3,6,7a-tri-
methyl-12-methylenecyclopenta[4,5]cyclooct[1,2-f]inden-2-ol
(45):
A solution of 44 (20 mg, 0.042 mmol) in THF (10 mL) was cooled to
0°C. TBAF (300 µL of a 1 M soln in THF) was added via syringe and
the solution was allowed to warm to 20°C and stirred for 8 h. The
(b) Wright, J.; Drtina, G. J.; Roberts, R. A.; Paquette, L. A. J.
Am. Chem. Soc. 1988, 110, 5806.
(c) Hudlicky, T.; Fleming, A.; Radesca, L. J. Am. Chem. Soc.
1989, 111, 6691.
mixture was quenched with sat. NaHCO (5 mL), and the organic lay-
3
er was dried and evaporated. Chromatography of the residue on silica
gel with 15% to 30% EtOAc in hexanes afforded 45 (11 mg, 70%) and
recovered 44 (11%).
(4) Isolation: Ayanoglu, E.; Gebreyesus, T.; Beechan, C. M.;
Djerassi, C. Tetrahedron 1979, 35, 1035.
(5) Syntheses: Kinney, W. A.; Coghlan, M. J.; Paquette, L. A.
J. Am. Chem. Soc. 1984, 106, 6868; 1985, 107, 7352.
Mehta, G.; Narayana Murty, A. J. Chem. Soc., Chem. Commun.
1984, 1058.
(6) Isolation: Rios, T.; Gomez, G. Tetrahedron Lett. 1969, 2969.
(7) Early synthetic studies: (a) Kato, N.; Tanaka, S.; Takeshita, H.
Bull. Chem. Soc. Jpn. 1989, 61, 3231.
For 45: white solid, mp 105–107°C.
1
H NMR (300 MHz, C D ): δ = 5.46 (s, 1 H), 5.41 (t, J = 7.8 Hz, 1
6
6
H), 5.02 (s, 1 H), 4.08–4.02 (m, 1 H), 2.79 (dt, J = 3.1, 3.0 Hz, 1 H),
2.54–2.43 (m, 2 H), 2.36–2.26 (m, 1 H), 2.17–2.02 (m, 1 H),
2.00–1.77 (m, 3 H), 1.76 (s, 3 H), 1.69–1.54 (m, 3 H), 1.50–1.27 (m,
4 H), 1.10 (t, J = 10.1 Hz, 1 H), 1.04–0.92 (m, 3 H), 0.96 (s, 3 H), 0.95
(d, J = 6.7 Hz, 3 H), 0.89 (d, J = 6.8 Hz, 3 H), 0.91–0.81 (m, 2 H),
0.78 (s, 3 H).
(b) Rowley, M.; Tsukamoto, M.; Kishi, Y. J. Am. Chem. Soc.
1988, 111, 2735.
13
C NMR (75 MHz, C D ): δ = 157.6, 138.8, 126.2, 112.4, 82.5, 50.0,
6
6
46.8, 46.6, 45.9, 45.8, 45.0, 43.1, 42.7, 42.6, 42.5, 39.6, 31.3, 28.9,
27.8, 27.4, 22.8, 22.6, 17.8, 17.7, 16.3.
(c) Boeckman, R. K., Jr.; Arvanitis, A.; Voss, N. H. J. Am.
Chem. Soc. 1989, 111, 2737.
(d) Paquette, L. A.; Wang, T.-Z.; Vo, N. H. J. Am. Chem. Soc.
1993, 115, 1676.
(8) Hensens, O. D.; Zink, D.; Williamson, J. M.; Lotti, V. J.; Chang,
R. S. L.; Goetz, M. A. J. Org. Chem. 1991, 56, 3399.
(9) Paquette L. A. Synlett 1990, 2, 67.
Paquette, L. A. Angew. Chem. Int. Ed. Engl. 1990, 29, 609.
Paquette, L. A. Tetrahedron 1997, 53, 13971.
(10) Snider, B. B.; Kirk, T. C. J. Am. Chem. Soc. 1983, 105, 2364.
Snider, B. B.; Rodini, D. J.; van Straten, J. J. Am. Chem. Soc.
1980, 102, 5872.
(11) Corey, E. J.; Engler, T. A. Tetrahedron Lett. 1984, 26, 149.
(12) Evans, D. A.; Morrissey, M. M. J. Am. Chem. Soc. 1984, 106,
3866.
(–)-(2S,3S,3aS,6aS,7aR,10S,10aS,11aR,12aS)-1,2,3,3a,4,
6a,7,7a,8,9,10,10a,11,11a,12,12a-Hexadecahydro-10-isopropyl-
3,6,7a-trimethyl-12-methylenecyclopenta[4,5]cyclooct[1,2-f]in-
den-2-yl â-D-Xylopyranoside Triacetate (47):
Molecular sieves (4 Å, 100 mg, dried under vacuum), alcohol 45
(10 mg, 0.028 mmol), and 46 (14 mg, 0.042 mmol) were suspended
in Et2O (10 mL) for 10 min before being cooled to –50°C. Silver tri-
flate (10 mg, 0.039 mmol) was added in one portion and the suspen-
sion was stirred for 1 h. The mixture was filtered and washed with
NaHCO3. The separated organic phase was dried, refiltered and evap-
orated. The residue was purified by chromatography on silica gel
(elution with 5–15% EtOAc in hexanes) to furnish 7.5 mg (69%) of
the acetate of 45 as a colorless oil.
(13) Engler, T. A. private communication.
(14) Burgess, E. M.; Penton, H. R.; Taylor, E. A. J. Org. Chem.
1973, 38, 26.
(15) Johnson, C. R.; Schroeck, C. W. J. Am. Chem. Soc. 1973, 95,
7418.
1
H NMR (300 MHz, C D ): δ = 5.43 (s, 1 H), 5.40–5.36 (m, 2 H),
6
6
5.06 (s, 1 H), 2.76 (t, J = 7.1 Hz, 1 H), 2.45–2.32 (m, 3 H), 2.28–1.78
(m, 5 H), 1.81–1.68 (m, 3 H), 1.75 (s, 3 H), 1.66–1.49 (m, 3 H),
1.48–1.23 (m, 5 H), 1.10 (d, J = 7.6 Hz, 3 H), 0.96 (d, J = 6.8 Hz, 3
H), 0.89 (d, J = 6.8 Hz, 3 H), 0.78 (s, 3 H).
Johnson, C. R.; Schroeck, C. W.; Shanklin, J. R. J. Am. Chem.
Soc. 1973, 95, 7424.
Johnson, C. R.; Haake, M.; Schroeck, C. W. J. Am. Chem. Soc.
1970, 92, 6594.
13
C NMR (75 MHz, C D ): δ = 170.1, 156.7, 139.1, 126.0, 113.5,
6
6
85.2, 50.0, 46.8, 46.1, 45.9, 45.4, 43.7, 42.9, 42.7, 42.5, 40.2, 39.6,
31.2, 28.8, 28.0, 27.3, 22.8, 22.7, 20.9, 17.8, 17.7, 16.0.

SYNTHESIS
(29) Barth, W.; Paquette, L. A. J. Org. Chem. 1985, 50, 2438.
(30) Paquette, L. A.; Andrews, D. R.; Springer, J. P. J. Org. Chem.
1983, 48, 1148.
Papers
508
(16) Depres, J.-P.; Greene, A. E. Org. Synth. 1989, 68, 41.
Lambert, J. B.; Koenig, F. R.; Hawersma, J. W. J. Org. Chem.
1971, 36, 2941.
(17) Takai, K. In Encyclopedia of Reagents for Organic Synthesis,
Paquette, L. A., Ed.; Wiley: Chichester; 1995, pp 1266–1269.
(18) Danheiser, R. L.; Savariar, S.; Cha, D. D. Org Synth. 1990, 68,
32.
Paquette, L. A.; Colapret, J. A.; Andrews, D. R. J. Org. Chem.
1985, 50, 201.
Paquette, L. A.; Learn, K. S.; Romine, J. L. Synth. Commun.
1987, 17, 114.
Ghosez, L.; Montaigne, R.; Roussel, A.; Vanlierde, H.; Mollet,
P. Tetrahedron 1971, 27, 615.
Paquette, L. A.; Learn, K. S.; Romine, J. L. Tetrahedron 1987,
43, 4989.
(19) Noyori, R.; Hayakawa, Y. J. Am. Chem. Soc. 1974, 96, 3336.
(20) Snider, B. B. Chem. Rev. 1988, 88, 793.
(21) Heidelbaugh, T. M. Ph.D. Thesis, The Ohio State University,
1996.
(22) Cohen, T.; Yu, L.-C.; Daniewski, W. M. J. Org. Chem. 1985,
50, 4596.
(31) Grieco, P. A.; Marinovic, N. Tetrahedron Lett. 1978, 29, 2545.
Grieco, P. A.; Nishizawa, M.; Marinovic, N. J. Am. Chem. Soc.
1976, 98, 7012.
(32) Attempts to effect the epimerization of 34b were expectedly
met by rapid deselenenylation. At longer reaction times, decom-
position was encountered.
(23) Fellmann, P.; Dubois, J.-E. Tetrahedron 1978, 34, 1349.
(24) Schlosser, M.; Jenny, T.; Guggisberg, Y. Synlett 1990, 704.
(25) Cheng, Y.-S.; Liu, W. L.; Chen, S.-H. Synthesis 1980, 223.
(26) Paquette, L. A.; Heidelbaugh, T. M. Org. Synth. 1996, 73, 44.
(27) Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 33, 6299.
Comins, D. L.; Dehghani, A.; Foti, C. J.; Joseph, S. P.; Ritter,
K. Synthesis 1993, 735.
(33) Chabra, B. R.; Hayano, K.; Ohtsuka, T.; Shirahama, H.; Matsu-
moto, T. Chem Lett. 1981, 1703.
(34) Lemieux, R. U. Methods in Carbohydr. Chem., Vol. II 1963, 55,
221.
Weygand, F. Methods in Carbohydr. Chem., Vol. I 1963, 55,
182.
(35) Sjolin, P.; Elofsson, M.; Kihlberg, J. J. Org. Chem. 1996, 61,
560.
(28) Scott, W. J.; Crisp, G. T.; Stille, J. K. J. Am. Chem. Soc. 1984,
106, 4630.
Toshima, K. J. Am. Chem. Soc. 1995, 117, 3717.
Scott, W. J.; McMurry, J. E. Acc. Chem. Res. 1988, 21, 47.