A direct route to angularly substituted hydrindanes. Formal synthesis of bakkenolide-A and synthesis of an advanced intermediate to umbellactal

Article abstract of DOI:10.1016/j.tet.2009.09.029

A direct route for the synthesis of highly functionalized angularly substituted hydrindanes has been developed. The key step involves RO-RCM of an appropriately functionalized norbornene derivative. The hydrindane derivative obtained in this way has been

Full text of DOI:10.1016/j.tet.2009.09.029

Tetrahedron 65 (2009) 9202–9210
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A direct route to angularly substituted hydrindanes. Formal synthesis of
bakkenolide-A and synthesis of an advanced intermediate to umbellactal
*
Soumitra Maity, Subrata Ghosh
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 July 2009
Received in revised form 4 September 2009
Accepted 4 September 2009
Available online 11 September 2009
A direct route for the synthesis of highly functionalized angularly substituted hydrindanes has been
developed. The key step involves RO–RCM of an appropriately functionalized norbornene derivative. The
hydrindane derivative obtained in this way has been used to accomplish a formal synthesis of bakke-
nolide-A. This protocol has also been extended for the synthesis of an advanced intermediate to the
synthesis of the diterpene umbellactal.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Hydrindanes
Metathesis
Spiro lactones
Terpenes
O
O
1. Introduction
O
O
O
O
O
Hydrindane ring system with an angular substituent is fre-
quently encountered in terpenoids. Representative examples in-
clude sesquiterpenes of the bakkanes family such as bakkenolide-A
(1),1 homogynolide-A (2),2 9-acetoxyfukinanolide (3),3 etc. Most of
the bakkanes also contain a spiro-fused
lactone moiety. The recently isolated diterpene umbellactal (4)4 is
also a cis-hydrindane derivative with an angularly fused -lactone.
Bakkenolide-A and umbellactal exhibit cytotoxicity toward several
carcinoma cell lines.5 The former also acts as an effective insect
antifeedant.6 The novel molecular architecture along with in-
teresting biological activities elicited considerable interest for the
synthesis of these compounds culminating in a number of elegant
approaches for the total synthesis of bakkanes.7 These approaches
include construction of hydrindanes by (i) annulation of a five-
membered ring onto a properly constructed cyclohexane deriva-
tive,7b–j (ii) ring contraction of decalin derivatives,7k,n and (iii)
intramolecular Diels–Alder reaction7l–m in appropriately designed
substrates. Among these approaches, only intramolecular Diels–
Alder route provides direct access to cis-hydrindane derivatives.
We thought of developing a route that not only allows direct
construction of cis-hydrindane derivatives with an angular sub-
stituent but at the same time introduces functionality at both the
rings of the resulting hydrindane system for elaboration to the
H
H
2
1
O
CHO
O
O
b-methylene g-butyro-
H
g
H
Me
HO
AcO
OH
4
3
highly functionalized bakkanes as well as umbellactal. Our retro-
synthetic plan is delineated in Scheme 1. The hydrindane derivative
5 was envisaged as the key intermediate for entry into bakkanes as
well as umbellactal. The vicinal ester units in 5 can be transformed
to methyl groups for bakkanes while they can be employed to
construct the angularly fused
g-lactone present in umbellactal.
Domino metathesis of norbornene derivatives and other strained
cycloalkenes involving ring opening–ring closing metathesis (RO–
RCM) has recently emerged as a powerful tool8 for the construction
of fused bicyclic rings including cis-hydrindanes.9 This protocol has
been employed successfully in the synthesis of natural products.10
Very recently, we have demonstrated that a sequence of RO–RCM of
norbornenes with multiple alkene chains leads to densely func-
tionalized bridged11 and linearly arrayed tricycles.12 Intrigued by
these observations, we visualized that a direct synthesis of the cis-
hydrindane derivative 5 could be achieved through RO–RCM of the
* Corresponding author. Tel.: þ91 33 2473 4971; fax: þ91 33 2473 2805.
E-mail address: ocsg@iacs.res.in (S. Ghosh).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.029

S. Maity, S. Ghosh / Tetrahedron 65 (2009) 9202–9210
9203
norbornene derivative 6. The latter can be obtained from allylation
of the diester 7, available from Diels–Alder adduct of itaconic an-
hydride with the cyclopentadiene derivative 8. Herein, we report13
results of the investigation toward the synthesis of bakkanes and
umbellactal based on the concept delineated in Scheme 1.
the cis-hydrindane derivative with C-1, C-2 substituents syn to each
other, the following protocol was adopted. The mixture of 13 and 14
was reduced with lithium aluminum hydride to produce a mixture
of the diols 15 and 16. The mixture of these diols was next trans-
formed to a mixture of the trans-lactone 17 and cis-lactone 18 in 70%
yield by two consecutive oxidation steps using IBX and followed by
Jones reagent. The angularly fused trans-lactone 17 appears to be
highly strained and hence energetically less stable. Thus, it should
be isomerizable to the cis-lactone 18. Indeed, a quantum mechanical
calculation17 revealed that cis-lactone 18 is more stable than the
trans-lactone 17 by 3.9 kcal/mol. Thus, the mixture of the cis- and
trans-lactones, when treated with DBU in benzene under reflux
afforded exclusively the cis-lactone 18 in 80% yield.
An alternative route to the cis-lactone 18 was also developed.
Reduction of the anhydride 9 with NaBH4 afforded known lactone
1918 in excellent yield. Alkylation of the lithium enolate of the
lactone 19 with the allyl bromide led to an inseparable mixture of
the lactones 20 and 21 in 4:1 ratio in 85% yield. Construction of
a Dreiding model of the lactone 19 revealed that allylation would
proceed preferentially from the face away from the ethylene bridge,
as the other face is blocked to some extent by the ethylene bridge to
produce lactone 20 as the major product. This structural assign-
ment to the lactones 20 and 21 was confirmed by their trans-
formation to the tricyclic lactones 17 and 18, respectively, as
follows: Treatment of the mixture of lactones 20 and 21 with the
catalyst 12 afforded a mixture of the hydrindane derivatives 17 and
18 prepared already in a different route as described above in 4:1
ratio in 70% yield. Comparison of 13C NMR spectral data of the
minor component of this mixture was found to be identical with
that of the cis-lactone 18. This confirmed the structure of the major
and minor allylated products as 20 and 21, respectively. The lactone
18 represents the core structure of umbellactal.
R1
R3
R2
H
CO2Me
CO2Me
R1
R1
5, R2=R3= CO2Me
6
R1
O
CO2Me
CO2Me
7
O
+
O
8, R1= OH /
latent OH group
Scheme 1.
2. Results and discussion
We initially chose the norbornene derivative 10 to establish the
efficacy of the concept. The dimethyl ester 10 was prepared14 from
the anhydride 915 obtained by Diels–Alder reaction of the itaconic
anhydride with the cyclopentadiene (Scheme 2). Alkylation of the
lithium enolate of the ester 10 with the allyl bromide afforded di-
ester 11 as a 2:1 chromatographically inseparable mixture in 90%
yield.
X
i
ii
CO2Me
CO2Me
CO2Me
CO2Me
O
O
9, X= O
19, X= H2
10
11
vi
iii
vii
R2
O
O
R1
R3
v
iii
2
1
8
O
R1
R2
6
R
4
H
H
O
20, R1= H, R2= allyl
17, R= β-H
18, R= α-H
13, R1=R3= CO2Me, R2= H
14, R1=R2= CO2Me, R3= H
15, R1=R3= CH2OH, R2= H
16, R1=R2= CH2OH, R3= H
viii
21, R1= allyl, R2= H
iv
Scheme 2. Reagents and conditions: (i) (a) TFA, THF/H2O (2:1), 60 ꢀC, (b) CH2N2, Et2O, 95%; (ii) LDA, allyl bromide, THF, ꢁ78 ꢀC, 90%; (iii) catalyst 12 (2 mol %), DCM, C2H4, rt, 5 h,
95%; (iv) LiAlH4, Et2O, 0 ꢀC, 90%; (v) (a) IBX, DMSO/acetone (1:4), rt, 1 h, (b) Jones reagent, acetone, 0 ꢀC, 80%; (vi) NaBH4, DMF, 0 ꢀC, 70%; (vii) LDA, allyl bromide, THF, ꢁ78 ꢀC, 85%;
(viii) DBU, C6H6, reflux, 2 h, 82%.
Treatment of the mixture of the diesters 11 with Grubbs’ catalyst
Cl2(PCy3)2Ru]CHPh 12,16 produced a mixture of hydrindanes 13
and 14 in near quantitative yield. The structures of 13 and 14 could
be easily ascertained from analysis of 1H and 13C NMR spectra.
Synthesis of bakkanes requires the hydrindane 14 in which C-1 and
C-2 esters are syn to each other. We thought that the C-2 carbo-
methoxy group in the diastereoisomer 13 in the mixture of 13 and 14
could be epimerized to produce the desired diester 14. However, the
C-2 ester in the mixture of 13 and 14 as obtained above when treated
with NaOMe in MeOH failed to undergo epimerization and the ratio
of 13 and 14 in the mixture remained unchanged. In order to make
We next focused on the transformation of the lactone unit to
dimethyl groups. The lactone 17 was reduced with LiAlH4 to afford
the diol 16 in 90% yield (Scheme 3). The diol 16 was transformed to
the dimesylate 22. Reduction of the dimesylate with LiAlH4 led to
monodeoxygenation leading to the formation of 23. Attempts for
deoxygenation of 22 with Zn/NaI or LiEt3BH afforded the same
product 23. The dimesylate 22 was next converted to the sulfide 24
on treatment with Na2S. The cyclic sulfide 24 was subjected to re-
duction with Raney Ni W-4. In this way deoxygenation of both the
mesyl groups in 22 could be achieved. But the reaction was ac-
companied with reduction of the double bonds also to afford the

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S. Maity, S. Ghosh / Tetrahedron 65 (2009) 9202–9210
S
R2
R1
H
iv
i
iii
18
H
H
16, R1=R2= CH2OH
24
25
ii
v
22, R1=R2= CH2OMs
23, R1= CH2OMs, R2= Me
S
OMs
vii
MsO
HO
HO
OH
HO
OH
iv
vi
22
OH
H
H
H
26
27
28
xi
O
O
O
O
viii
2
1
O
8
6
R
H
H
OR
H
29, R= TBDMS
30, R= H
32
33, R= H
34, R= CH3
ix
x
xii
31, R= COOEt
Scheme 3. Reagents and conditions: (i) LiAlH4, Et2O, 0 ꢀC, 92%; (ii) MsCl, Et3N, DCM, 0 ꢀC, 1 h, 90%; (iii) Na2S/DMF, 50 ꢀC, 3 h, 90%; (iv) Raney Ni W-4, THF, rt, 80%; (v) LiEt3BH, THF,
80%; (vi) OsO4, NMO, THF/H2O (4:1), rt, 12 h, 80%; (vii) Na2S/DMF, 50 ꢀC, 6 h, 85%; (viii) (a) TBDMSCl, DMAP, Et3N, DCM, rt, 95%, (b) DMP, DCM, rt, 90%; (ix) TBAF, THF, rt, 80%;
(x) ClCO2Et, DMAP, Py, DCM, 96%; (xi) NaIO4, THF/H2O (2:1), 0 ꢀC; (xii) (a) MeMgI, Et2O, 0 ꢀC, 90%, (b) DMP, DCM, rt, 96%.
hydrindane derivative 25 with the desired vicinal dimethyl groups.
Since the vinyl unit will be required for annulation of the spiro
lactone unit for bakkanes, we modified the above sequence as
follows: selective dihydroxylation of the dimesylate 22 with OsO4
produced the diol 26 in 80% yield. The dimesylate 26 was trans-
formed to cyclic sulfide 27. Reduction of cyclic sulfide 27 was ach-
ieved with Raney Ni W-4 to afford the dimethyl derivative 28 in 85%
yield. For construction of the spiro lactone unit, the compound 28
was converted to the hydroxy-ketone 30 through a three-step se-
quence involving silylation of the primary hydroxy group with
TBDMSCl followed by oxidation of the secondary hydroxy group
with Dess–Martin periodinane (DMP) and desilylation. The
hydroxy-ketone 30 was treated with ethylchloroformate to afford
the carbonate 31. It was anticipated that a carbanion generated at
C-8 would trigger an intramolecular nucleophilic reaction resulting
in the synthesis of the spiro lactone 32. However, attempted spi-
rolactonization of 31 with a variety of bases to afford 32 was un-
successful. The diol 28 was, thus, transformed to the ketone 34 in
the following way. Periodate cleavage of the diol unit in 28 afforded
aldehyde 33. Addition of MeMgI to the aldehyde 33 followed by
DMP oxidation gave ketone 34. The ketone 34 has already been
converted19 to bakkenolide-A in three steps. With the synthesis of
the ketone 34, a formal synthesis of bakkenolide-A is, thus,
achieved.
We next focused on synthesis of umbellactal. This required in-
troduction of an alkyl chain in the six-membered ring of the
hydrindane derivative 18. We thought that a hydrindane system
with a hydroxy group in the six-membered ring will enable in-
troduction of alkyl chain. Toward this end the enolate of the lactone
19 was allowed to react with acrolein (Scheme 4). A mixture of
adducts 35 and 36 along with their corresponding hydroxy epimers
was obtained in 83% yield, the ratio of the four isomers being about
5:2:2:1. Stereochemical assignment at the newly generated carbon
centers in 35 and 36 was based on analogy to the formation of 20
and 21 from 19. The stereochemistry at the centers bearing the
hydroxy groups in 35 and 36 was based on their transformation to
44 and 45 (Scheme 5), respectively. Metathesis of this mixture of
adducts with Grubbs’ catalyst 12 produced a mixture of tricycles 39
in poor yield (20%) along with 50% of unreacted norbornene
derivatives.
RCM of dienes bearing free hydroxy groups with Grubbs’ I cat-
alyst has occasionally been reported20 to proceed with low yields
possibly due to decomposition of the active ruthenium/methylene
catalyst generated after the first catalytic cycle. Protection of the
hydroxy groups generally improves the yield of metathesis product.
The hydroxy group in the above mixture of the adducts 35 and 36
was protected with CH2(OMe)2 to afford the corresponding MOM
protected ethers 37 and 38 along with the other two epimers at the
MOM bearing stereocenters. Metathesis of the MOM protected
derivatives 37 and 38 gave the tricycles 40 in significantly improved
yield (50%). However a substantial amount of the ring-opened
product 41 (25%) remained uncyclized under the above reaction
condition.
To enhance further the efficiency of the metathesis, the hydroxy
group in the above mixture of aldol adducts 35 and 36 was pro-
tected with TBDMSCl to give the silyl ethers 42 and 43, respectively.
Column chromatography of the silylated mixture afforded pure silyl
i
+
19
H
O
O
H
R
R
O
O
35, R= OH
36, R= OH
iii
37, R= OMOM
38, R= OMOM
OR
OMOM
O
O
H
H
ii
+
O
O
H
H
H
H
41
39, R= H
40, R= MOM
Scheme 4. Reagents and conditions: (i) LDA, acrolein, THF, ꢁ78 ꢀC, 83%; (ii) Grubbs’ I
(5 mol %), DCM, C2H4, rt, 23 h, 20% (for 39), 50% (for 40); (iii) CH2(OMe)2, BF3$OEt2,
DCM, 0 ꢀC, 75%.

S. Maity, S. Ghosh / Tetrahedron 65 (2009) 9202–9210
9205
4. Experimental section
4.1. General
i
35 + 36
+
H
O
O
H
R
R
O
O
Melting points were taken in open capillaries in sulfuric acid bath
and are uncorrected. Petroleum ether refers to the fraction having bp
60–80 ꢀC. A usual workup of the reaction mixture consists of ex-
traction with diethyl ether, washing with brine, drying over Na2SO4,
and removal of the solvent in vacuo. Column chromatography was
carried out with silica gel (60–120 mesh). Peak positions in 1H and
13C NMR spectra are indicated in parts per million downfield from
42 R= OTBDMS 43
ii
ii
OR
OR
4
O
O
H
O
H
v
3a
O
internal TMS in d units. NMR spectra were recorded in CDCl3 solution
H
H
at 300 MHz for 1H and 75 MHz for 13C on Bruker-Avance DPX300
instrument. 13C Peaks assignment is based on DEPT experiment. IR
spectra were recorded as liquid film for liquids and in KBr plate for
solids on Shimadzu FTIR-8300 instrument. Mass spectra were
measured in a QTOF I (quadrupole-hexapole-TOF) mass spectrom-
eter with an orthogonal Z-spray–electrospray interface on Micro
(YA-263) mass spectrometer (Manchester, UK). Unless otherwise
indicated, all reactions were carried out under a blanket of Ar.
H
H
45
44
R= TBDMS
iv
OH
iii
O
O
H
O
O
4.1.1. Methyl 2-(1-(methoxycarbonyl)but-3-enyl)bicyclo[2.2.1]hept-
5-ene-2-carboxylate 11. A solution of the ester 10 (2.0 g, 9.14 mmol)
in THF (20 mL) was added drop wise to a magnetically stirred so-
lution of LDA [prepared from diisopropyl amine (2.56 mL,
18.3 mmol) in anhydrous THF (20 mL) and nBuLi (10.3 mL,
16.5 mmol, 1.6 M in hexane)] at ꢁ78 ꢀC and the reaction mixture
was stirred at that temperature for 1 h. Freshly distilled allyl bro-
mide (1.6 mL, 18.2 mmol) was added drop wise to the reaction
mixture at the same temperature and was allowed to attain rt for
2 h. After quenching with saturated aqueous NH4Cl solution, the
reaction mixture was worked up in the usual way to afford, after
column chromatography (10% Et2O/petroleum ether), the ester 11
(2.2 g, 90%) as 2:1 diastereomeric mixture as colorless oil; Rf (20%
EtOAc/petroleum ether) 0.8; nmax (liquid film) 2976, 2950, 1732,
H
H
H
H
47
46
Scheme 5. Reagents and conditions: (i) TBDMSCl, DMAP, Im, Et3N, DCM, rt, 50% (for
42), 19% (for 43); (ii) Grubbs’ I (5 mol %), DCM, C2H4, rt, 12 h, 72% (for 44), 70% (for 45);
(iii) TBAF, THF, rt, 12 h, 85%; (iv) TBAF, THF, rt, 6 h, 75%; (v) DBU, C6H6, D, 1 h, 43% (45)
and 35% (46).
ethers 42 and 43 in 50% and 19% yields, respectively. Metathesis of
the silyl ether 42 under the above condition afforded, after
chromatography, the tricyclic compound 44 in 72% yield. Similarly,
metathesis of the silyl ether 43 provided the tricycle 45 in 70% yield.
The stereochemical assignment of the trans-lactone 44 (except the
C-4 center) is based on analogy to the formation of 17 from 20. To
determine the stereochemistry of the C-4 substituent, the lactone
44 was subjected to desilylation. The product isolated in 85% yield
was found to be exclusively 46 presumably arising from facile de-
hydration of the in situ generated corresponding hydroxy group.
This indicated that C-3a H and the C-4 silyloxy group in 44 were
anti to each other. In contrast, desilylation of 45 produced exclu-
sively the hydroxy-compound 47 (75%), which failed to undergo
dehydration under a variety of conditions indicating that C-3a H
and C-4 OH in 47 were syn to each other. This also confirmed the
stereochemical assignment of lactone 45. The stereochemical as-
signment of 44 was further confirmed when the latter was found to
isomerize to the cis-lactone 45 (43%) on treatment with DBU in
benzene under reflux. During isomerization of 44, the diene 46 was
also isolated in ca. 35% yield. The IR absorption of the lactone car-
bonyl was observed at an unusually higher frequency (nmax
1787 cmꢁ1) in 44 than that (nmax 1762 cmꢁ1) of 45 also indicated
the presence of a highly strained trans-lactone ring in 44. The silyl
ether 45 represents the highly functionalized tricyclic skeleton
present in umbellactal.
1435, 1334 cmꢁ1
; dH (300 MHz, CDCl3) (for major isomer from the
mixture) 6.18 (2H, br s, ]CH), 5.52–5.61 (1H, m, ]CH), 4.83–4.92
(2H, m, ]CH2), 3.62 (3H, s, OCH3), 3.61 (3H, s, OCH3), 2.73 (1H, s),
3.13 (1H, s), 2.36 (1H, dd, J 12.7, 3.8 Hz), 2.25–2.31 (1H, m), 2.07–
2.12 (2H, m), 1.42 (1H, d, J 8.7 Hz), 1.18 (1H, d, J 8.8 Hz), 0.96 (1H, dd,
J 12.4, 2.4 Hz); dC (75 MHz, CDCl3) (for major isomer) 175.6, 172.9,
139.1, 136.1, 134.5, 116.2, 57.5, 52.8, 51.9, 51.4, 49.7, 48.5, 41.8, 36.3,
32.8; (for minor isomer) 175.6, 173.8, 140.4, 135.9, 132.0, 116.5, 56.8,
54.0, 52.0, 51.5, 49.5, 47.9, 42.3, 35.0, 33.5; HRMS (ESI) (m/z):
[MþNa]þ, found 287.1256. C15H20O4Na requires 287.1259.
4.1.2. (2S
*
,3aR
*
,7aS )-Dimethyl 2,3,3a,4,5,7a-hexahydro-2-vinyl-1H-
*
indene-3a,4-dicarboxylates 13 and 14. To a solution of 11 (1.0 g,
3.8 mmol) in dry CH2Cl2 (100 mL) under ethylene atmosphere at rt
was added a solution of catalyst 12 (62 mg, 2 mol %) in CH2Cl2
(5 mL). After stirring for 5 h, the reaction mixture was concen-
trated. Column chromatography of the residue (10% Et2O/petro-
leum ether) gave a mixture of 13 and 14 (950 mg, 95%) as colorless
oil; Rf (20% EtOAc/petroleum ether) 0.7; nmax (liquid film) 2972,
2875, 1734, 1448, 1420 cmꢁ1
; dH (300 MHz, CDCl3) (for the mixture
of 13 and 14) 5.71–5.55 (3H, m, ]CH), 5.02–4.79 (2H, m, ]CH2),
3.69, 3.66, 3.64, 3.62 (total 6H, all s, OMe), 2.85–2.53 (3H, m), 2.39–
2.14 (4H, m), 1.44–1.38 (1H, m), 1.24–1.17 (1H, m); dC (75 MHz,
CDCl3) (for major isomer) 177.2, 174.0, 143.8, 131.7, 122.5, 112.7, 55.1,
52.3, 51.8, 44.2, 43.8, 40.9, 37.5, 34.3, 23.6; (for minor isomer) 176.7,
174.3, 141.6, 129.0, 123.4, 113.7, 52.0, 51.7, 51.1, 45.8, 44.1, 43.7, 42.5,
40.1, 26.0; HRMS (ESI) (m/z): [MþNa]þ, found 287.1256. C15H20O4Na
requires 287.1259.
3. Conclusion
We have demonstrated that RO–RCM of norbornene derivatives
can be employed efficiently to construct directly highly function-
alized angularly substituted hydrindane derivatives. This protocol
has been employed to accomplish a formal synthesis of bakkeno-
lide-A. The potential of this protocol toward the synthesis of the
biologically active diterpene umbellactal has also been explored
leading to the construction of an advanced intermediate.
4.1.3. (2S
*
,3aR
*
,7aS )-2,3,3a,4,5,7a-Hexahydro-3a,4-dihydroxy-
*
methyl-2-vinyl-1H-indenes 15 and 16. To a suspension of LiAlH4

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S. Maity, S. Ghosh / Tetrahedron 65 (2009) 9202–9210
(72 mg,1.9 mmol) in dry ether (5 mL) at 0 ꢀC was added a solution of
the diesters 13 and 14 (250 mg, 0.95 mmol) in dry ether (5 mL). The
reaction mixture was allowed to stir at that temperature for 1 h and
then quenched by sequential addition of water (0.08 mL), aqueous
NaOH solution (0.08 mL, 15%), and water (0.24 mL), and allowed to
attain rt. The resulting suspension was filtered and the filtrate was
dried and concentrated and the residual mass was purified by col-
umn chromatography (30% Et2O/petroleum ether) to give a mixture
of diols 15 and 16 (176 mg, 90%) as a colorless liquid; Rf (40% EtOAc/
petroleum ether) 0.5; nmax (liquid film) 3273, 3018, 2900, 1640,
afford, after column chromatography (10% Et2O/petroleum ether),
the lactones 20 and 21 (1.05 g, 85%) as colorless oil; Rf (30% EtOAc/
petroleum ether) 0.8; nmax (liquid film) 2968, 2873, 1774, 1639,
1448 cmꢁ1
; dH (300 MHz, CDCl3) (for the mixture of 20 and 21) 6.31–
6.25 (1H, m, ]CH), 6.06–6.03 (1H, m, ]CH), 5.83–5.69 (1H, m,
]CH), 5.14–5.02 (2H, m, ]CH2), 4.27–4.19 (1H, m, OCH2), 4.11–4.08
(1H, m, OCH2), 2.84 (1H, br s), 2.68 (1H, br s), 2.38–2.26 (2H, m), 2.23–
2.17 (1H, m),1.58–1.34 (3H, m),1.22–1.15 (1H, m); dC (75 MHz, CDCl3)
(for major isomer) 179.4, 139.9, 134.4, 133.8, 117.9, 78.0, 50.5, 50.3,
48.1, 47.6, 41.8, 34.2, 33.4; (for minor isomer) 178.3, 139.4, 134.3,
133.4, 117.7, 78.5, 50.4, 50.3, 47.5, 46.2, 44.2, 42.4, 32.4; HRMS (ESI)
(m/z): [MþNa]þ, found 227.1046. C13H16O2Na requires 227.1048.
1446 cmꢁ1
; dH (300 MHz, CDCl3) (for the mixture of 15 and 16) 5.74–
5.61 (2H, m, ]CH), 5.52–5.49 (1H, m, ]CH), 4.99–4.79 (2H, m,
]CH2), 3.81 (1H, dd, J 11.2, 2.1 Hz, OCH2), 3.62–3.34 (2H, m, OCH2),
3.15 (1H, d, J 11.3 Hz, OCH2), 2.63–2.42 (1H, m), 2.24–2.15 (2H, m),
1.98–1.75 (3H, m), 1.73–1.51 (2H, m), 1.26–1.12 (3H, m); dC (75 MHz,
CDCl3) (for major isomer) 144.0, 133.0, 123.0, 112.4, 68.3, 65.2, 49.4,
42.0, 41.9, 40.1, 38.1, 32.4, 25.3; (for minor isomer) 142.5,128.5,125.9,
113.0, 65.8, 62.4, 47.0, 45.6, 42.8, 42.4, 40.7, 39.6, 25.5; HRMS (ESI)
(m/z): [MþNa]þ, found 231.1365. C13H20O2Na requires 231.1361.
4.1.7. (2S
*
,3aR
*
,4S
*
,7aS )-2,3,3a,4,5,7a-Hexahydro-3a,4-bis(hydroxy-
*
methyl)-2-vinyl-1H-indene 16. Following the above described pro-
tocol a solution of the tricyclic lactone 18 (350 mg, 1.72 mmol) in
diethyl ether (5 mL) was reduced with LiAlH4 (78 mg, 2.06 mmol)
to afford, after column chromatography (30% Et2O/petroleum
ether), the diol 16 (328 mg, 92%) as viscous liquid; Rf (40% EtOAc/
petroleum ether) 0.5; nmax (liquid film) 3271, 2937, 2869, 1640,
* * *
4.1.4. (6aS ,8S ,9aR )-3a,4,6a,7,8,9-Hexahydro-8-vinylindeno[3a,4-c]-
1458 cmꢁ1
; dH (300 MHz, CDCl3) 5.79–5.57 (3H, m, ]CH), 4.95 (1H,
furan-3(1H)-ones 17 and 18. A mixture of dimethyl sulfoxide (3 mL),
acetone (12 mL), and o-iodoxybenzoic acid (1.27 g, 4.53 mmol) was
stirred for 1 h, and the resulting solution was added to the mixture
of diols 15 and 16 (787 mg, 3.78 mmol). After 1 h at rt, the reaction
mixture was quenched with water (10 mL) and filtered through
Celite. The filtrate was extracted with dichloromethane (3ꢂ10 mL),
washed with water, dried (Na2SO4), concentrated, and used for the
next step without further purification. The crude lactols (100 mg,
0.48 mmol) in acetone (2 mL) was immediately treated with Jones
reagent at 0 ꢀC until the color of the reagent persisted. Work up of
the reaction mixture with diethyl ether followed by purification of
the residue by column chromatography (10% Et2O/petroleum ether)
afforded an inseparable mixture of lactones 17 and 18 (79 mg, 80%)
as a liquid; Rf (30% EtOAc/petroleum ether) 0.7; nmax (liquid film)
d, J 17.1 Hz, ]CH), 4.86 (1H, d, J 10.2 Hz, ]CH), 3.76 (1H, dd, J 11.2,
1.8 Hz, OCH2), 3.61–3.56 (2H, m, OCH2), 3.14 (1H, d, J 11.2 Hz, OCH2),
2.51–2.49 (1H, m), 2.19–2.12 (2H, m), 1.99–1.86 (4H, m), 1.56–1.51
(1H, m), 1.29–1.16 (3H, m); dC (75 MHz, CDCl3) 142.5, 128.5, 125.9,
113.0, 65.7, 62.3, 46.9, 45.6, 42.8, 42.3, 40.7, 39.5, 25.5; HRMS (ESI)
(m/z): [MþNa]þ, found 231.1365. C13H20O2Na requires 231.1361.
4.1.8. (2S
*
,3aR
*
,4S
*
,7aS )-2,3,3a,4,5,7a-Hexahydro-3a,4-bis(methyl-
*
sulfonyloxymethyl)-2-vinyl-1H-indene 22. To a solution of the diol 16
(150 mg, 0.72 mmol) in CH2Cl2 (3 mL) were added triethylamine
(0.40 mL, 2.88 mmol) and mesylchloride (0.16 mL, 2.16 mmol) at
0 ꢀC. The resulting solution was stirred at that temperature for 1 h.
The reaction mixture was concentrated and the residue was purified
by column chromatography (50% Et2O/petroleum ether) to give the
dimesylate 22 (236 mg, 90%) as a white crystalline solid; Rf (50%
EtOAc/petroleum ether) 0.6; mp 105–107 ꢀC; nmax (KBr plate) 3026,
3020, 2935, 2869, 1780, 1639, 1446 cmꢁ1
; dH (300 MHz, CDCl3) (for
major isomer) 5.76–5.57 (2H, m, ]CH), 5.45 (1H, dd, J 9.9, 1.3 Hz,
]CH), 5.02–4.83 (2H, m, ]CH2), 4.19 (1H, d, J 8.3 Hz, OCH2), 3.99–
3.92 (1H, m, OCH2), 2.78–2.61 (1H, m), 2.55–2.43 (1H, m), 2.40–1.97
(2H, m), 1.87–1.79 (1H, m), 1.63–1.55 (1H, m), 1.45–1.37 (1H, m),
1.29–1.08 (2H, m); dC (75 MHz, CDCl3) (for major isomer) 176.4,
142.5, 133.5, 123.1, 113.4, 77.3, 50.8, 43.2, 41.8, 40.5, 36.1, 33.5, 20.5;
(for minor isomer) 178.5, 140.9, 131.4, 121.9, 114.0, 79.1, 47.9, 42.2,
42.1, 41.7, 40.6, 40.2, 20.9; HRMS (ESI) (m/z): [MþNa]þ, found
227.1045. C13H16O2Na requires 227.1048.
2939, 1641, 1329, 1174 cmꢁ1
; dH (300 MHz, CDCl3) 5.76–5.70 (3H, m,
]CH), 5.01 (1H, d, J 17.1 Hz, ]CH2), 4.93 (1H, d, J 10.1 Hz, ]CH2), 4.39
(1H, dd, J 9.8, 2.1 Hz, CH2OMs), 4.19 (1H, d, J 7.7 Hz, CH2OMs), 4.12
(1H, d, J 9.8 Hz, CH2OMs), 3.97 (1H, d, J 9.7 Hz, CH2OMs), 3.01 (6H, s,
OMs), 2.59–2.57 (1H, m), 2.31–2.22 (2H, m), 2.13–2.04 (2H, m), 2.02–
1.95 (2H, m),1.51–1.42 (1H, m),1.33–1.21 (1H, m); dC (75 MHz, CDCl3)
141.2, 128.2, 124.5, 114.0, 71.9, 71.2, 44.6, 44.1, 42.6, 41.4, 40.9, 39.5,
37.5 (2C), 26.0; HRMS (ESI) (m/z): [MþNa]þ, found 387.0911.
C15H24O6S2Na requires 387.0912.
4.1.5. (3aS
*
,6aS
*
,8S
*
,9aR )-3a,4,6a,7,8,9-Hexahydro-8-vinyl-
*
indeno[3a,4-c]furan-3(1H)-one 18. A mixture of the lactones 17 and
18 (250 mg, 1.2 mmol) and DBU (0.9 mL) in PhH (5 mL) was
refluxed for 2 h. The resulting slurry was worked up by washing
with 1 M HCl. Purification of the crude mixture by column chro-
matography (10% Et2O/petroleum ether) gave cis-lactone 18
(205 mg, 82%) as a colorless liquid; Rf (30% EtOAc/petroleum ether)
4.1.9. (2S
*
,3aR
*
,4S
*
,7aR )-2-Ethyl-octahydro-3a,4-dimethyl-1H-in-
*
dene 25. Na2S (43 mg, 0.54 mmol) was added to a solution of the
dimesylate 22 (100 mg, 0.27 mmol) in DMF (3 mL) and stirred at
50 ꢀC for 3 h. After addition of H2O, the resulting slurry was parti-
tioned between EtOAc/hexane and H2O. The combined organic
layers were washed thoroughly with brine, dried, and concentrated
in vacuo. Purification of the residual mass by column chromatog-
raphy (10% EtOAc/petroleum ether) gave 24 (51 mg, 90%) as a col-
orless oil; Rf (40% EtOAc/petroleum ether) 0.5; nmax (liquid film)
0.7; nmax (liquid film) 2927, 2858, 1778, 1639, 1458, 1370 cmꢁ1
; dH
(300 MHz, CDCl3) 5.74–5.68 (1H, m, ]CH), 5.66 (2H, br s, ]CH),
4.99 (1H, d, J 17.1 Hz, ]CH), 4.93 (1H, d, J 10.2 Hz, ]CH), 4.13 (1H, d,
J 8.5 Hz, OCH2), 3.99 (1H, d, J 8.5 Hz, OCH2), 2.53–2.45 (2H, m), 2.41–
2.39 (1H, m), 2.34–2.21 (2H, m), 1.85 (1H, dd, J 12.7, 6.0 Hz), 1.65–
1.57 (1H, t, J 12.4 Hz), 1.22–1.08 (2H, m); dC (75 MHz, CDCl3) 178.5,
140.9, 131.4, 121.9, 114.0, 79.1, 47.9, 42.2, 42.1, 41.7, 40.6, 40.2, 20.9;
HRMS (ESI) (m/z): [MþNa]þ, found 227.1047. C13H16O2Na requires
227.1048.
2926, 1639 cmꢁ1
; dH (300 MHz, CDCl3) 5.82–5.70 (1H, m, ]CH),
5.68 (2H, br s, ]CH), 4.99 (1H, d, J 17.1 Hz, ]CH2), 4.90 (1H, d, J
10.2 Hz, ]CH2), 3.01 (1H, dd, J 10.3, 5.1 Hz, SCH2), 2.81 (1H, d, J
10.1 Hz, SCH2), 2.67–2.61 (2H, m, SCH2), 2.42–2.38 (1H, m), 2.16–
2.12 (1H, m), 2.04–1.88 (3H, m), 1.33–1.13 (4H, m); dC (75 MHz,
CDCl3) 142.3, 129.6, 123.7, 113.2, 53.6, 45.4, 43.9, 42.8, 42.7, 41.9,
40.7, 35.8, 27.1. Without further characterization 24 was used di-
rectly for the next step.
4.1.6. Synthesis of spiro lactones 20 and 21. Following the above
described protocol a solution of the lactone 19 (1.0 g, 6.09 mmol) in
THF (10 mL) was allylated with allyl bromide (1.1 mL, 12.2 mmol) to
A mixture of the thioether 24 (50 mg, 0.24 mmol) and Raney Ni
W-4 (ca.100 mg) in THF (2 mL) was stirred at rt for 2 h. The reaction

S. Maity, S. Ghosh / Tetrahedron 65 (2009) 9202–9210
9207
mixture was filtered through Celite and washed with EtOAc. The
filtrate was concentrated in vacuo. Purification of the residual mass
by column chromatography (4% Et2O/petroleum ether) gave 25
(2C), 27.0, 26.9; HRMS (ESI) (m/z): [MþNa]þ, found 263.1082.
C13H20O2SNa requires 263.1082.
(35 mg, 80%) as a colorless oil; nmax (liquid film) 2956, 1483 cmꢁ1
;
4.1.13. 1-((2S
*
,3aR
*
,4S
*
,7aR )-Octahydro-3a,4-dimethyl-1H-inden-2-
*
dH (300 MHz, CDCl3) 1.65–1.58 (3H, m), 1.55–1.45 (4H, m), 1.42–1.25
(9H, m), 0.88–0.86 (2 H, m), 0.85 (3H, s, CH3), 0.76 (3H, d, J 6.6 Hz,
CH3); dC (75 MHz, CDCl3) 47.6, 45.5, 42.7, 38.9, 36.5, 35.9, 31.1, 29.8,
25.1, 21.7, 20.8, 16.6, 13.4; HRMS (ESI) (m/z): [MþNa]þ, found
203.1767. C13H24Na requires 203.1776.
yl)ethane-1,2-diol 28. Following the above described protocol a so-
lution of the cyclic thioether 27 (100 mg, 0.41 mmol) was reduced
with Raney Ni W-4 (ca. 500 mg) to afford, after column chromato-
graphy (40% Et2O/petroleum ether), the compound 28 (75 mg, 85%)
as a colorless oil; Rf (50% EtOAc/petroleum ether) 0.3; nmax (liquid
film) 3385, 2860, 1641, 1386 cmꢁ1
; dH (300 MHz, CDCl3) (for the
4.1.10. ((2S
*
,3aS
*
,4S
*
,7aS
*
)-2,3,3a,4,5,7a-Hexahydro-4-methyl-2-vi-
mixture) 3.67 (1H, d, J 10.4 Hz, CH2OH), 3.50–3.45 (1H, m, CH2OH),
3.42–3.36 (1H, m, CHOH), 2.79 (2H, br s, OH), 2.01–1.99 (2H, m),
1.73–1.67 (3H, m), 1.55–1.36 (7H, m), 1.14–1.01 (1H, m), 0.86 (3H, s,
CH3), 0.78, 0.75 (total 3H, two d, J 6.7 and 7.1 Hz, respectively, CH3);
dC (75 MHz, CDCl3) (for the mixture) 77.9 (2C), 66.2, 66.0, 47.4, 47.2,
43.5, 43.4, 41.7, 41.6, 39.7, 39.6, 35.8, 35.7, 33.0, 32.6, 31.1, 31.0, 24.8,
24.6, 21.6, 21.5, 20.6, 20.5, 16.6, 16.5; HRMS (ESI) (m/z): [MþNa]þ,
found 235.1675. C13H24O2Na requires 235.1674.
nyl-1H-inden-3a-yl)methyl methanesulfonate 23. LiEt3BH (1.5 mL,
1.5 mmol, 1.0 M solution in THF) was added drop wise to the
dimesylate 22 (140 mg, 0.38 mmol) in THF (3 mL) at 0 ꢀC and
the mixture was stirred at rt for 3 h. After the addition of 1.0 M HCl,
the resulting slurry was partitioned between EtOAc and H2O. The
combined organic layers were washed with saturated aqueous
NaHCO3, brine, dried (Na2SO4), and concentrated in vacuo. Purifi-
cation of the residue by column chromatography (10% Et2O/petro-
leum ether) gave 23 (83 mg, 80%) as a colorless oil; Rf (20% EtOAc/
petroleum ether) 0.6; nmax (liquid film) 3020, 2956, 1639,
4.1.14. 1-((2S
*
,3aR
*
,4S
*
,7aS )-Octahydro-3a,4-dimethyl-1H-inden-2-
*
yl)-2-(tert-butyl)dimethylsilyloxy ethanone 29. To a cooled (0 ꢀC)
solution of 28 (280 mg, 1.32 mmol) in CH2Cl2 (20 mL) were added
Et3N (0.2 mL), TBDMSCl (297 mg, 1.98 mmol), and DMAP (cat). The
mixture was stirred for 3 h and diluted with saturated brine. This
was extracted with CH2Cl2 (3ꢂ5 mL). The combined organic layers
were dried and concentrated in vacuo. The residue was purified by
column chromatography (5% Et2O/petroleum ether) to provide the
corresponding silyl ether (409 mg, 95%) as colorless oil; Rf (10%
EtOAc/petroleum ether) 0.8; nmax (liquid film) 3579, 3481, 2954,
1458 cmꢁ1
; dH (300 MHz, CDCl3) 5.73–5.61 (3H, m, ]CH), 4.92 (1H,
d, J 17.1 Hz, ]CH2), 4.83 (1H, d, J 10.2 Hz, ]CH2), 4.09 (1H, d, J
9.2 Hz, CH2OMs), 4.02 (1H, d, J 9.3 Hz, CH2OMs), 2.93 (3H, s, OMs),
2.50–2.45 (1H, m), 2.37–2.31 (1H, m), 1.99–1.89 (3H, m), 1.77–1.65
(2H, m), 1.36 (1H, d, J 10.6 Hz), 1.31 (1H, d, J 10.7 Hz), 0.92 (3H, d, J
6.5 Hz, CH3); dC (75 MHz, CDCl3) 142.1, 128.3, 125.7, 113.3, 72.2, 45.2,
43.0, 42.9, 41.5, 40.0, 37.2, 34.7, 31.2, 15.5; HRMS (ESI) (m/z):
[MþNa]þ, found 293.1183. C14H22O3SNa requires 293.1187.
1463, 1377 cmꢁ1
; dH (300 MHz, CDCl3) (for the mixture) 3.66–3.62
4.1.11. 1-((2S
*
,3aR
*
,4S
*
,7aS
*
)-2,3,3a,4,5,7a-Hexahydro-3a,4-dimethyl
(1H, m, CHOH), 3.44–3.31 (2H, m, CH2OH), 2.50 (1H, t, J 3.5 Hz),
methanesulfonate-1H-inden-2-yl)ethane-1,2-diol 26. To a solution
of the hydrindane derivative 22 (50 mg, 0.14 mmol) and NMO
(18 mg, 0.15 mmol) in THF (1 mL) and H2O (0.25 mL) was added
2.01–1.92 (1H, m), 0.06 (6H, br s, Me2Si), 1.81–1.75 (1H, m), 1.71–
1.59 (2H, m), 1.55–1.35 (9H, m), 0.89 (9H, br s, BuSi), 0.87, 0.86
t
(total 3H, two s, CH3), 0.78, 0.75 (total 3H, two d, J 7.4 and 7.3 Hz,
respectively, CH3); dC (75 MHz, CDCl3) (for the mixture) 77.1, 77.0,
66.7, 66.5, 47.4, 47.2, 42.6, 42.5, 41.6, 41.5, 39.4, 39.3, 35.6, 35.5, 33.0,
32.5, 31.0 (2C), 26.0 (6C), 24.9, 24.7, 21.6, 21.5, 20.6, 20.5, 18.4 (2C),
16.6, 16.5, ꢁ5.2, ꢁ5.3 (3C); HRMS (ESI) (m/z): [MþNa]þ, found
349.2537. C19H38O2SiNa requires 349.2539.
t
OsO4 (0.04 mL, 0.0034 mmol, 2.5 wt % in BuOH) at 0 ꢀC. The mix-
ture was stirred at rt for 12 h and the resulting slurry was
partitioned between EtOAc and H2O. The combined organic layer
was washed with brine, dried over Na2SO4, and concentrated in
vacuo. Purification of the crude mixture by column chromato-
graphy (90% EtOAc/petroleum ether) gave 26 (43 mg, 80%) as col-
To a magnetically stirred suspension of DMP (550 mg, 1.3 mmol)
in CH2Cl2 (10 mL) at 0 ꢀC, the silyl ether obtained as above (354 mg,
1.08 mmol) in CH2Cl2 (5 mL) was added drop wise. The reaction
mixture was stirred for 30 min and was quenched with 10%
Na2S2O3 solution (3 mL) doped with NaHCO3. The organic layer was
separated and the aqueous part extracted with diethyl ether
(2ꢂ10 mL). The combined organic layer was dried, concentrated,
and purified by column chromatography (3% Et2O/petroleum ether)
to afford 29 (316 mg, 90%) as colorless liquid; nmax (liquid film)
orless oil; nmax (liquid film) 3519, 3417, 2940, 1640 cmꢁ1
; dH
(300 MHz, CDCl3) (for the mixture) 5.68 (2H, br s, ]CH), 4.47–4.41
(1H, m, CH2OH), 4.15 (2H, d, J 7.8 Hz, OCH2), 3.94 (1H, d, J 9.8 Hz,
OCH2), 3.63 (1H, d, J 10.7 Hz, OCH2), 3.52–3.47 (1H, m, CH2OH),
3.50–3.41 (1H, m, CHOH), 3.02 (3H, s, OMs), 3.01 (3H, s, OMs), 2.32–
2.18 (3H, m), 2.10–1.91 (6H, m), 1.67–1.50 (1H, m), 1.23–1.18 (1H,
m); dC (75 MHz, CDCl3) (for the mixture) 128.3, 128.1, 124.6, 124.4,
75.8, 75.2, 72.2, 72.1, 71.5 (2C), 65.8 (2C), 44.6, 44.4, 43.8, 43.7, 40.8,
40.7, 40.1, 39.8, 37.5, 37.4 (2C), 37.3, 37.2, 36.9, 35.9, 35.3, 26.1 (2C);
HRMS (ESI) (m/z): [MþNa]þ, found 421.0965. C15H26O8S2Na re-
quires 421.0967.
2954, 2858, 1730, 1462, 1381, 1253 cmꢁ1
; dH (300 MHz, CDCl3) 4.23
(2H, s, CH2OTBDMS), 3.20–3.08 (1H, m, CHCO), 2.12–1.96 (2H, m),
1.76–1.65 (3H, m), 1.52–1.48 (3H, m), 1.45–1.34 (4H, m), 0.91 (9H, s,
tBuSi), 0.87 (3H, s, CH3), 0.75 (3H, d, J 6.5 Hz, CH3), 0.07 (6H, s,
Me2Si); dC (75 MHz, CDCl3) 212.8, 68.9, 47.5, 44.2, 43.2, 40.4, 33.4,
31.6, 30.8, 25.9 (3C), 24.4, 21.2, 20.1,18.5,16.6, ꢁ5.4 (2C); HRMS (ESI)
(m/z): [MþNa]þ, found 347.2386. C19H36O2SiNa requires 347.2382.
4.1.12. 1-((3aS
*
,6aS
*
,8S
*
,9aR )-1,3,3a,4,6a,7,8,9-Octahydroindeno[3-
*
a,4-c]thiophen-8-yl)ethane-1,2-diol 27. Following the above de-
scribed protocol a solution of the dimesylate 26 (500 mg,1.25 mmol)
in DMF (10 mL) was treated with Na2S (196 mg, 2.50 mmol) to afford,
after column chromatography (40% EtOAc/petroleum ether), the
cyclic thioether 27 (256 mg, 85%) as a colorless oil; Rf (50% EtOAc/
petroleum ether) 0.2; nmax (liquid film) 3390, 3016, 2931, 1666,
4.1.15. 1-((2S
*
,3aR
*
,4S
*
,7aR )-Octahydro-3a,4-dimethyl-1H-inden-2-
*
yl)-2-hydroxyethanone 30. Desilylation of the hydrindane de-
rivative 29 (285 mg, 0.88 mmol) in THF (5 mL) was accomplished
with tetrabutylammonium fluoride (277 mg, 0.88 mmol) at rt for
4 h. After addition of water, the resulting slurry was partitioned
between ether and water. The combined organic layers were
washed with brine, dried (Na2SO4), and concentrated in vacuo.
Purification of the residue by column chromatography (10% Et2O/
petroleum ether) afforded the hydroxy-ketone 30 (147 mg, 80%) as
colorless liquid; Rf (10% EtOAc/petroleum ether) 0.4; nmax (liquid
1454 cmꢁ1
; dH (300 MHz, CDCl3) (for the mixture) 5.58 (2H, br s,
]CH), 3.64–3.60 (1H, m, CHOH), 3.49–3.36 (2H, m, CH2OH), 3.25
(2H, br s, OH), 3.01–2.94 (1H, m, SCH2), 2.79–2.76 (1H, m, SCH2),
2.64–2.55 (2H, m, SCH2), 2.35 (1H, br s), 2.07–1.99 (4H, br s), 1.73–
1.66 (1H, m),1.43–1.35 (1H, m),1.26–1.08 (2H, m); dC (75 MHz, CDCl3)
(for the mixture) 129.5, 129.4,123.7, 123.6, 76.5, 76.4, 65.9 (2C), 53.5,
53.2, 43.3 (2C), 42.0, 41.9 (2C), 41.8, 41.3, 41.1, 41.0 (2C), 37.1, 36.7, 35.7

9208
S. Maity, S. Ghosh / Tetrahedron 65 (2009) 9202–9210
film) 3417, 2924, 2860, 1712, 1656, 1462, 1381 cmꢁ1
;
dH (300 MHz,
(75 MHz, CDCl3) 211.2, 49.6, 47.4, 43.0, 39.9, 33.6, 31.6, 30.8, 28.9,
24.4, 21.2, 20.0, 16.5; HRMS (ESI) (m/z): [MþNa]þ, found 217.1569.
C13H22ONa requires 217.1568.
CDCl3) 4.24 (2H, s, CH2OH), 3.19 (1H, br s, OH), 2.99–2.89 (1H, m,
CHCO), 2.06–1.97 (2H, m), 1.80–1.70 (2H, m), 1.56–1.54 (3H, m),
1.50–1.35 (4H, m), 1.09–1.04 (1H, m), 0.87 (3H, s, CH3), 0.75 (3H, d, J
6.4 Hz, CH3); dC (75 MHz, CDCl3) 212.4, 67.4, 47.5, 44.8, 43.2, 40.3,
33.6, 32.1, 30.7, 24.2, 21.1, 20.0, 16.5; HRMS (ESI) (m/z): [MþNa]þ,
found 233.1513. C13H22O2Na requires 233.1517.
4.1.18. Synthesis of hydroxy-lactones 35 and 36. A solution of the
lactone 19 (990 mg, 6.04 mmol) in THF (12 mL) was added drop
wise to a magnetically stirred solution of LDA (prepared from dii-
sopropyl amine (1.6 mL, 12.1 mmol) in anhydrous THF (12 mL) and
nBuLi (6.8 mL, 10.8 mmol, 1.6 M in hexane)) at ꢁ78 ꢀC and the re-
action mixture was stirred at that temperature for 1 h. Freshly
distilled acrolein (0.8 mL, 12.1 mmol) was added drop wise to the
reaction mixture at the same temperature and was allowed to stir
for 1 h. After quenching with saturated aqueous NH4Cl solution, the
reaction mixture was worked up in the usual way to afford, after
column chromatography (40% Et2O/petroleum ether), hydroxy-
lactones 35 and 36 and their corresponding hydroxy epimers (1.1 g,
83%) as colorless oil; Rf (30% EtOAc/petroleum ether) 0.5; nmax
4.1.16. Ethyl 2-((2S
*
,3aR
*
,4S
*
,7aR )-Octahydro-3a,4-dimethyl-1H-in-
*
den-2-yl)-2-oxoethyl carbonate 31. To a solution of the hydroxy-
ketone 30 (184 mg, 0.87 mmol) in CH2Cl2 (7 mL) at 0 ꢀC were added
DMAP (ca. 5 mg), pyridine (1.63 mL), and ethylchloroformate
(1.0 mL, 10.4 mmol), and the resulting mixture was quenched with
2 N aqueous HCl and extracted with EtOAc (2ꢂ10 mL). Combined
extracts were dried (Na2SO4), filtered, and concentrated in vacuo.
Purification of the residual mass by column chromatography (5%
Et2O/petroleum ether) gave the carbonate 31 (237 mg, 96%) as
colorless liquid; Rf (10% EtOAc/petroleum ether) 0.6; nmax (liquid
(liquid film) 3273, 2870, 1775, 1638, 1462 cmꢁ1
; dH (300 MHz,
film) 2929, 2873, 1755, 1732, 1463, 1373, 1263 cmꢁ1
;
dH (300 MHz,
CDCl3) (for major isomer) 6.33 (1H, dd, J 5.5, 3.1 Hz, ]CH), 6.08 (1H,
dd, J 5.3, 2.7 Hz, ]CH), 5.81–5.70 (1H, m, ]CH), 5.30 (1H, d, J
17.2 Hz, ]CH2), 5.20 (1H, d, J 10.4 Hz, ]CH2), 4.33 (1H, br s, OH),
4.26 (1H, d, J 8.9 Hz, OCH2), 4.10 (1H, d, J 8.9 Hz, OCH2), 3.11 (1H, d, J
7.8 Hz, CHOH), 2.83 (1H, br s), 2.69 (1H, br s), 2.44 (1H, d, J 4.1 Hz,
CHCO), 1.80 (1H, dd, J 12.6, 2.5 Hz), 1.54 (1H, d, J 8.8 Hz), 1.38 (1H,
dd, J 12.6, 3.4 Hz), 1.29 (1H, d, J 8.9 Hz); dC (75 MHz, CDCl3) (for
major isomer) 179.5, 140.4, 137.2, 133.7, 117.4, 79.2, 72.5, 53.4, 51.2,
48.7, 47.6, 41.9, 34.6; HRMS (ESI) (m/z): [MþNa]þ, found 243.0994.
C13H16O3Na requires 243.0997.
CDCl3) 4.68 (2H, s, OCH2CO), 4.20 (2H, q, J 6.9 Hz, OCH2), 3.02–2.90
(1H, m, CHCO), 2.10–2.04 (2H, m), 1.77–1.72 (2H, m), 1.51–1.47 (3H,
m), 1.42–1.37 (3H, m), 1.32–1.27 (4H, m), 1.08–1.02 (1H, m), 0.86
(3H, s, CH3), 0.74 (3H, d, J 6.5 Hz, CH3); dC (75 MHz, CDCl3) 205.8,
154.8, 69.8, 64.6, 47.5, 44.8, 43.2, 39.7, 33.3, 31.6, 30.7, 24.2, 21.0,
19.9, 16.5, 14.3; HRMS (ESI) (m/z): [MþNa]þ, found 305.1725.
C16H26O4Na requires 305.1729.
4.1.17. 1-((2S
*
,3aR
*
,4S
*
,7aR )-Octahydro-3a,4-dimethyl-1H-inden-2-
*
yl)ethanone 34. To a magnetically stirred ice-cold solution of the
diol 28 (100 mg, 0.47 mmol) in THF/water (4.5 mL, 2:1) was added
NaIO4 (201.6 mg, 0.94 mmol) in portions. The reaction mixture was
allowed to stir at 0 ꢀC for 30 min. The precipitated white solid was
filtered off after washing it thoroughly with diethyl ether. Usual
workup of the filtrate afforded the aldehyde 33, which was im-
mediately used for the next step without purification.
4.1.19. Synthesis of the compounds 37 and 38. To a magnetically
stirred solution of the mixture of alcohols 35 and 36 and their
epimers (440 mg,1.99 mmol) in CH2Cl2 (3 mL), dimethoxy methane
(0.53 mL, 6.0 mmol) and BF3$Et2O (0.3 mL, 2.4 mmol) were added
drop wise at 0 ꢀC. After complete addition, the reaction mixture
was stirred for 1 h at 0 ꢀC. After quenching with saturated aqueous
NaHCO3 solution, the reaction mixture was worked up in the usual
way to afford, after column chromatography (10% Et2O/petroleum
ether), the MOM ether derivatives 37 and 38 and their epimers
(422 mg, 80%) as colorless liquid; Rf (30% EtOAc/petroleum ether)
To a solution of the crude aldehyde 33 in dry ether (5 mL) was
added methylmagnesium iodide (3.0 M in Et2O, 0.37 mL, 1.1 mmol)
at 0 ꢀC. The mixture was stirred at that temperature for 1 h, and to
this was added saturated aqueous NH4Cl solution. After stirring it
for 15 min at rt, the mixture was extracted with ether (2ꢂ5 mL).
The combined organic layer was dried, concentrated in vacuo. The
resulting crude product was chromatographed (10% Et2O/petro-
leum ether) affording the corresponding methyl addition product
(83 mg, 90%) as colorless liquid; Rf (20% EtOAc/petroleum ether)
0.6; nmax (liquid film) 1774, 1642 cmꢁ1
; dH (300 MHz, CDCl3) (for
major isomer) 6.32 (1H, dd, J 5.5, 3.06 Hz, ]CH), 6.22 (1H, dd, J 5.5,
2.5 Hz, ]CH), 5.79–5.70 (1H, m, ]CH), 5.47 (1H, d, J 17.3 Hz,
]CH2), 5.42 (1H, d, J 10.5 Hz, ]CH2), 4.65 (1H, d, J 6.8 Hz, OCH2),
4.52 (1H, d, J 6.8 Hz, OCH2), 4.35 (1H, dd, J 8.6, 3.0 Hz, CHOMOM),
4.30 (1H, d, J 5.5 Hz, OCH2), 4.04 (1H, d, J 8.3 Hz, OCH2), 3.34 (3H, s,
OCH3), 2.90 (1H, br s), 2.87 (1H, br s), 2.31 (1H, d, J 3.0 Hz, CHCO),
1.94 (1H, dd, J 11.8, 3.7 Hz), 1.52 (1H, d, J 8.7 Hz), 1.39 (1H, d, J
9.0 Hz), 1.25–1.21 (1H, m); dC (75 MHz, CDCl3) (for major isomer)
177.0, 139.7, 134.6, 134.0, 121.4, 93.0, 79.2, 75.0, 55.7 (2C), 49.2, 47.5,
46.4, 46.0, 42.0; HRMS (ESI) (m/z): [MþNa]þ, found 287.1255.
C15H20O4Na requires 287.1259.
0.6; nmax (liquid film) 3364, 2928, 2870, 1460, 1375 cmꢁ1
; dH
(300 MHz, CDCl3) (for the mixture) 3.56–3.50 (1H, m), 1.95–1.87
(1H, m), 1.72–1.32 (13H, m), 1.14, 1.13 (total 3H, two d, J 6.2 and
6.1 Hz, respectively, CH3COH), 0.86 (3H, s, CH3), 0.76, 0.74 (total 3H,
two d, J 6.3 and 6.1 Hz, respectively, CH3); dC (75 MHz, CDCl3) (for
both diastereoisomers) 73.6, 73.4, 47.4 (2C), 45.4, 45.3, 42.7, 42.6,
42.0, 41.7, 35.7, 35.6, 33.1, 32.9, 31.0 (2C), 24.9, 24.7, 22.4 (2C), 21.6
(2C), 20.6 (2C), 16.5 (2C); HRMS (ESI) (m/z): [MþNa]þ, found
219.1725. C13H24ONa requires 219.1725.
4.1.20. (6aR
*
,8R
*
,9aS )-3a,4,6a,7,8,9-Hexahydro-4-hydroxy-8-vinyl-
*
To a solution of the hydroxy-compound thus obtained (56 mg,
0.28 mmol) in CH2Cl2 (3 mL) at rt was added DMP (144.6 mg,
0.34 mmol) portion wise and the reaction mixture was allowed to
stir for 1 h. The reaction mixture was quenched with 10% Na2S2O3
solution (2 mL) doped with NaHCO3 at ice-cold condition and
stirred vigorously until the organic layer became transparent. The
organic layer was washed with brine, dried over Na2SO4, and
concentrated in vacuo. Purification of the residue by column
chromatography (5% Et2O/petroleum ether) gave 34 (53 mg, 96%)
as colorless oil; Rf (10% EtOAc/petroleum ether) 0.7; nmax (liquid
indeno[3a,4-c]furan-3(1H)-one 39. To a solution of the mixture of
hydroxy-lactones 35 and 36 and their hydroxy epimers (80 mg,
0.36 mmol) in dry CH2Cl2 (30 mL) under ethylene atmosphere at rt
was added a solution of Grubbs’ catalyst 12 (17 mg, 5 mol %) in
CH2Cl2 (1 mL). After stirring for 30 h, the reaction mixture was
concentrated. Purification of the residue by column chromatogra-
phy (10% Et2O/petroleum ether) gave the tricyclic lactone 39 as
a diastereoisomeric mixture (16 mg, 20%) as colorless oil; Rf (40%
EtOAc/petroleum ether) 0.5; nmax (liquid film) 3470, 1760, 1645,
1469 cmꢁ1
; dH (300 MHz, CDCl3) (for major diastereoisomer) 5.86–
film) 2957, 2872, 1711, 1462 cmꢁ1
;
dH (300 MHz, CDCl3) 2.95–2.90
5.79 (3H, m, ]CH), 5.07–4.96 (2H, m, ]CH2), 4.45–4.41 (1H, m,
CHOH), 4.24 (1H, d, J 8.4 Hz, OCH2), 4.10–4.07 (1H, m, OCH2), 2.82
(1H, d, J 5.6 Hz), 2.53–2.39 (2H, m), 2.35–2.21 (1H, m), 2.03–1.91
(1H, m), 2.13 (3H, s, COCH3), 2.09–2.00 (2H, m), 1.82–1.72 (3H, m),
1.53–1.32 (7H, m), 0.87 (3H, s, CH3), 0.76 (3H, d, J 6.6 Hz, CH3); dC

S. Maity, S. Ghosh / Tetrahedron 65 (2009) 9202–9210
9209
(1H, m), 1.83–1.56 (2H, m), 1.14–1.02 (1H, m); dC (75 MHz, CDCl3)
(for major isomer of the mixture) 177.1, 139.8, 132.4, 128.7, 114.7,
80.6, 63.6, 48.9, 48.8, 42.4, 42.0, 41.9, 41.1; (for minor isomer of the
mixture) 178.5, 140.3, 133.0, 126.3, 114.5, 79.1, 64.5, 50.4, 47.3, 43.9,
43.2, 40.9, 39.9; HRMS (ESI) (m/z): [MþNa]þ, found 243.0995.
C13H16O3Na requires 243.0997.
atmosphere. The solvent was then removed by rotary evaporator
and the residue was purified by column chromatography (10% Et2O/
petroleum ether) to give 44 (58 mg, 72%) as a colorless oil; Rf (5%
EtOAc/petroleum ether) 0.5; nmax (liquid film) 2952, 2885, 1787,
1641, 1469, 1373 cmꢁ1
; dH (300 MHz, CDCl3) 5.80–5.66 (2H, m,
]CH), 5.59 (1H, dd, J 9.8, 1.9 Hz, ]CH), 4.95 (1H, d, J 16.8 Hz,
]CH2), 4.87 (1H, d, J 10.0 Hz, ]CH2), 4.53 (1H, br s, CHOSi), 4.21
(1H, d, J 8.2 Hz, OCH2), 3.89 (1H, dd, J 8.2, 1.9 Hz, OCH2), 2.59–2.55
(1H, m), 2.54 (1H, d, J 3.6 Hz), 2.53–2.51 (1H, m), 2.45 (1H, t, J
12.3 Hz), 2.26–2.21 (1H, m), 1.65 (1H, dd, J 13.1, 6.6 Hz), 1.40–1.35
(1H, m), 0.85 (9H, s, 3ꢂCH3), 0.16 (3H, s, CH3), 0.11 (3H, s, CH3); dC
(75 MHz, CDCl3) 173.5,142.5, 135.5,126.5,113.1, 77.4, 61.4, 49.7, 47.2,
44.1, 42.0, 37.0, 35.9, 25.7 (3C), 18.0, ꢁ4.4, ꢁ5.1; HRMS (ESI) (m/z):
[MþNa]þ, found 357.1857. C19H30O3SiNa requires 357.1862.
4.1.21. (6aR
*
,8R
*
,9aS )-3a,4,6a,7,8,9-Hexahydro-4-(methoxy-
*
methoxy)-8-vinylindeno[3a,4-c]furan-3(1H)-one 40. Following the
metathesis procedure described above, the mixture of lactones 37
and 38 and their epimers (90 mg, 0.34 mmol) in CH2Cl2 (35 mL)
was treated with the catalyst 12 (14 mg, 5 mol %) in ethylene at-
mosphere (17 h) to afford, after column chromatography (10% Et2O/
petroleum ether), the cyclized tricyclic lactone 40 as
a di-
astereoisomeric mixture (45 mg, 50%) as colorless liquid; Rf (30%
EtOAc/petroleum ether) 0.5; nmax (liquid film) 1772, 1641,
4.1.24. (3aS
*
,4S
*
,6aR
*
,8R
*
,9aS )-3a,4,6a,7,8,9-Hexahydro-4-(tert-bu-
*
1469 cmꢁ1
;
dH (300 MHz, CDCl3) (for major isomer) 5.82 (2H, br s,
tyl)dimethylsilyloxy-8-vinylindeno[3a,4-c]furan-3(1H)-one
45. Following the metathesis procedure described above, the lac-
tone 43 (70 mg, 0.21 mmol) in DCM (35 mL) was treated with the
catalyst 12 (8.6 mg, 5 mol %) for 12 h to afford, after column chro-
matography (10% Et2O/petroleum ether), the tricyclic lactone 45
(49 mg, 70%) as a colorless liquid; Rf (5% EtOAc/petroleum ether)
]CH), 5.74–5.66 (1H, m, ]CH), 5.00 (1H, d, J 17.7 Hz, ]CH2), 4.93
(1H, d, J 10.2 Hz, ]CH2), 4.74 (1H, d, J 6.7 Hz, OCH2), 4.70 (1H, d, J
6.8 Hz, OCH2), 4.44 (1H, br s, CHOMOM), 4.11 (1H, d, J 8.5 Hz, OCH2),
4.00 (1H, d, J 8.5 Hz, OCH2), 3.37 (3H, s, OCH3), 2.88 (1H, d, J 2.2 Hz),
2.54–2.44 (2H, m), 2.38–2.29 (1H, m), 2.05 (1H, t, J 12.5 Hz), 1.83
(1H, dd, J 12.7, 6.0 Hz), 1.34–1.24 (1H, m); dC (75 MHz, CDCl3) (for
major isomer) 176.0, 140.8, 134.5, 123.1, 114.2, 96.1, 79.2, 68.9, 55.7,
47.3, 47.1, 43.0, 41.6, 41.1, 40.0; HRMS (ESI) (m/z): [MþNa]þ, found
287.1256. C15H20O4Na requires 287.1259.
0.6; nmax (liquid film) 1762, 1645, 1469 cmꢁ1
; dH (300 MHz, CDCl3)
5.96–5.91 (1H, m, ]CH), 5.86 (1H, dd, J 9.9, 1.7 Hz, ]CH), 5.75–5.70
(1H, m, ]CH), 5.04 (1H, d, J 17.1 Hz, ]CH2), 4.96 (1H, d, J 10.3 Hz,
]CH2), 4.52 (1H, t, J 5.0 Hz, CHOSi), 4.17 (1H, d, J 7.1 Hz, OCH2), 4.09
(1H, d, J 7.7 Hz, OCH2), 2.49–2.45 (1H, m), 2.42–2.36 (1H, m), 2.22
(1H, d, J 4.6 Hz), 2.26–2.20 (1H, m), 2.09 (1H, dd, J 5.0, 1.2 Hz), 1.24–
1.15 (2H, m), 0.83 (9H, s, 3ꢂCH3), 0.06 (3H, s, CH3), 0.02 (3H, s, CH3);
dC (75 MHz, CDCl3) 177.7, 140.0, 134.3, 126.0, 114.5, 80.3, 63.4, 51.9,
48.4, 46.7, 41.8, 40.2, 40.0, 25.7 (3C), 17.9, ꢁ3.9, ꢁ5.2; HRMS (ESI)
(m/z): [MþNa]þ, found 357.1864. C19H30O3SiNa requires 357.1862.
4.1.22. Synthesis of silyl ether compounds 42 and 43. To a cooled
(0 ꢀC) solution of mixture of 35, 36 and its hydroxy epimers
(511 mg, 2.32 mmol) as obtained above in CH2Cl2 (20 mL) were
added Et3N (0.64 mL, 4.64 mmol), TBDMSCl (696 mg, 4.64 mmol),
and DMAP (cat). The mixture was stirred for 36 h and diluted with
saturated brine. This was extracted with CH2Cl2 (3ꢂ10 mL). The
combined organic layers were dried and concentrated in vacuo. The
residue was purified by column chromatography (5% Et2O/petro-
leum ether) to provide 42 (388 mg, 50%) and 43 (147 mg, 19%) as
the major hydroxy-lactones. Compound 42 as a colorless oil; nmax
4.1.25. (6aR
*
,8R
*
,9aS )-6a,7,8,9-Tetrahydro-8-vinylindeno[3a,4-c]fu-
*
ran-3(1H)-one 46. To a magnetically stirred solution of 44 (23 mg,
0.07 mmol) in THF (1 mL) was added TBAF (0.07 mL, 0.07 mmol,
1 M solution in THF) at 0 ꢀC. The mixture was stirred at rt for 3 h.
After addition of water, the resulting slurry was partitioned be-
tween diethyl ether and water. The combined organic layers were
washed with brine, dried (Na2SO4), and concentrated in vacuo.
Purification of the crude mass by column chromatography (10%
Et2O/petroleum ether) gave 46 (12 mg, 85%) as colorless oil; Rf (30%
EtOAc/petroleum ether) 0.5; nmax (liquid film) 1759, 1747, 1642,
(liquid film) 2940, 1778, 1643, 1462 cmꢁ1
; dH (300 MHz, CDCl3)
6.27–6.24 (1H, m, ]CH), 5.99–5.96 (1H, m, ]CH), 5.75–5.64 (1H,
m, ]CH), 5.14 (1H, d, J 17.4 Hz, ]CH2), 5.07 (1H, d, J 10.5 Hz, ]CH2),
4.69 (1H, d, J 2.1 Hz, CHOSi), 4.33 (1H, d, J 8.4 Hz, OCH2), 4.05 (1H, d,
J 8.4 Hz, OCH2), 2.76 (1H, s), 2.64 (1H, s), 2.20 (1H, s, CHCO), 2.17
(1H, dd, J 11.5, 2.7 Hz), 1.49 (1H, d, J 8.4 Hz), 1.34 (1H, dd, J 13.0,
3.4 Hz), 1.27 (1H, d, J 9.0 Hz), 0.86 (9H, s, 3ꢂCH3), 0.00 (3H, s, CH3),
ꢁ0.03 (3H, s, CH3); dC (75 MHz, CDCl3) 180.0, 140.0, 139.9, 133.7,
115.4, 79.5, 74.8, 54.3, 50.9, 49.3, 47.5, 41.9, 34.6, 25.9 (3C), 17.9,
ꢁ4.8, ꢁ5.0; HRMS (ESI) (m/z): [MþNa]þ, found 357.1863.
C19H30O3SiNa requires 357.1862. Compound 43 as a colorless oil;
1458 cmꢁ1
; dH (300 MHz, CDCl3) 6.85 (1H, d, J 5.1 Hz, ]CH), 6.08–
6.02 (1H, m, ]CH), 5.82 (1H, dd, J 9.4, 2.5 Hz, ]CH), 5.76–5.65 (1H,
m, ]CH), 5.04 (1H, d, J 17.1 Hz, ]CH2), 4.95 (1H, d, J 10.1 Hz, ]CH2),
4.29 (1H, d, J 8.3 Hz, OCH2), 3.85 (1H, dd, J 8.2, 1.3 Hz, OCH2), 2.83
(1H, s), 2.58–2.38 (2H, m),1.98 (1H, dd, J 12.4, 6.2 Hz),1.65–1.57 (2H,
m); dC (75 MHz, CDCl3) 170.2, 140.5, 138.0, 129.7, 127.4, 120.3, 114.5,
78.4, 47.7, 43.2, 42.2, 38.2, 37.7; HRMS (ESI) (m/z): [MþNa]þ, found
225.0895. C13H14O2Na requires 225.0892.
nmax (liquid film) 2877, 1776, 1645, 1460 cmꢁ1
; dH (300 MHz, CDCl3)
6.29–6.26 (1H, m), 6.18–6.15 (1H, m), 5.97–5.86 (1H, m, ]CH), 5.34
(1H, d, J 17.3 Hz, ]CH2), 5.22 (1H, d, J 10.2 Hz, ]CH2), 4.57 (1H, d, J
4.7 Hz, CHOSi), 4.45 (1H, d, J 7.7 Hz, OCH2), 4.01 (1H, d, J 7.7 Hz,
OCH2), 2.95 (1H, s), 2.85 (1H, s), 2.13 (1H, d, J 2.3 Hz, CHCO), 1.90
(1H, dd, J 11.7, 3.8 Hz), 1.50 (1H, d, J 8.34 Hz), 1.42 (1H, d, J 8.8 Hz),
1.13 (1H, d, J 12.1 Hz), 0.91 (9H, s, 3ꢂCH3), 0.05 (3H, s, CH3), 0.03
(3H, s, CH3); dC (75 MHz, CDCl3) 178.3, 139.9, 139.3, 135.4, 116.4,
80.2, 74.8, 57.7, 48.9, 47.8 (2C), 46.2, 41.6, 26.0 (3C), 18.2, ꢁ4.4, ꢁ4.9;
HRMS (ESI) (m/z): [MþNa]þ, found 357.1860. C19H30O3SiNa requires
357.1862.
4.1.26. (3aS
*
,4S
*
,6aR
*
,8R
*
,9aS )-3a,4,6a,7,8,9-Hexahydro-4-hydroxy-
*
8-vinylindeno[3a,4-c]furan-3(1H)-one 47. Following the procedure
described for desilylation of the tricycle 44, the silyl protected tri-
cycle 45 (20 mg, 0.06 mmol) in THF (1 mL) at 0 ꢀC was deprotected
using TBAF (0.06 mL, 0.06 mmol) to afford, after column chroma-
tography (30% Et2O/petroleum ether), the hydroxy-lactone 47
(10 mg, 75%) as a colorless liquid; Rf (30% EtOAc/petroleum ether)
0.4; nmax (liquid film) 3485, 3018, 2900, 1759, 1643, 1373,
4.1.23. (3aR
*
,4S
*
,6aR
*
,8R
*
,9aS
*
)-3a,4,6a,7,8,9-Hexahydro-4-(tert-bu-
1217 cmꢁ1
; dH (300 MHz, CDCl3) 5.90–5.79 (2H, m, ]CH), 5.76–5.65
tyl)dimethylsilyloxy-8-vinylindeno[3a,4-c]furan-3(1H)-one 44. The
catalyst 12 (10 mg, 5 mol %) was dissolved in CH2Cl2 (4 mL) and was
(1H, m, ]CH), 5.04 (1H, d, J 17.2 Hz, ]CH2), 4.98 (1H, d, J 10.3 Hz,
]CH2), 4.45–4.42 (1H, m, CHOH), 4.24 (1H, d, J 8.4 Hz, OCH2), 4.09
(1H, d, J 8.4 Hz, OCH2), 3.91 (1H, d, J 9.9 Hz, OH), 2.82 (1H, d, J 5.6 Hz,
CHCO), 2.55–2.43 (2H, m), 2.35–2.26 (2H, m), 1.93 (1H, dd, J 12.8,
5.5 Hz), 1.14–1.02 (1H, m); dC (75 MHz, CDCl3) 178.4, 139.9, 132.4,
added via syringe to
a solution of the lactone 42 (80 mg,
0.24 mmol) in degassed CH2Cl2 (40 mL). This solution was then
purged with ethylene and stirred at rt for 12 h under an ethylene

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T. J.; Nagaraju, S.; Sattigeri, J. A. Tetrahedron Lett. 1994, 35, 7841–7844;
(k) Mori, K.; Matsushima, Y. Synthesis 1995, 845–850; (l) Back, T. G.;
Payne, J. E. Org. Lett. 1999, 1, 663–665; (m) Back, T. G.; Nava-Salgado, V.
O.; Payne, J. E. J. Org. Chem. 2001, 66, 4361–4368; (n) Hayashi, K.; Na-
kamura, H.; Mitsuhashi, H. Chem. Pharm. Bull. 1973, 21, 2806–2807; (o)
Reddy, D. S. Org. Lett. 2004, 6, 3345–3347; (p) Constantino, M. G.; de
Oliveira, K. T.; Polo, E. C.; da Siva, G. V. J.; Brocksom, T. J. J. Org. Chem.
2006, 71, 9880–9883.
8. For reviews on RO–RCM reaction see: (a) Arjona, O.; Csaky, A. G.; Plumet, J. Eur.
J. Org. Chem. 2003, 611–622; (b) Blechert, S.; Holub, N. Chem. Asian J. 2007, 2,
1064–1082; For selected works see: (c) Stille, J. R.; Santarsiero, B. D.; Grubbs, R.
H. J. Org. Chem. 1990, 55, 843–862; (d) Arjona, O.; Csaky, A. G.; Murcia, M. C.;
Plumet, J. Tetrahedron Lett. 2000, 41, 9777–9779; (e) Weatherhead, G. S.; Ford, J.
G.; Alexanian, E. J.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122,
1828–1829; (f) Hagiwara, H.; Katsumi, T.; Endou, S.; Hoshi, T.; Suzuki, T. Tet-
rahedron 2002, 58, 6651–6654; (g) Arjona, O.; Csaky, A. G.; Medel, R.; Plumet, J.
J. Org. Chem. 2002, 67, 1380–1383; (h) Arjona, O.; Csaky, A. G.; Leon, V.; Medel,
R.; Plumet, J. Tetrahedron Lett. 2004, 45, 565–567; (i) Maechling, S.; Norman, S.
E.; Mckendrick, J. E.; Basra, S.; Koppner, K.; Blechert, S. Tetrahedron Lett. 2006,
47, 189–192; (j) Liu, Z.; Rainier, J. D. Org. Lett. 2006, 8, 459–462; (k) Carreras, J.;
Avenoza, A.; Busto, J. H.; Peregrina, J. M. Org. Lett. 2007, 9, 1235–1238; (l) Calvet,
G.; Blanchard, N.; Kouklovsky, C. Org. Lett. 2007, 9, 1485–1488.
128.7, 114.8, 80.7, 63.7, 48.9, 48.8, 42.5, 41.9, 41.8, 41.2; HRMS (ESI)
(m/z): [MþNa]þ, found 243.0992. C13H16O3Na requires 243.0997.
Acknowledgements
S.G. thanks the Department of Science and Technology, Gov-
ernment of India for a Ramanna Fellowship. S.M. thanks CSIR, New
Delhi for a Senior Research Fellowship.
Supplementary data
Supplementary data associated with this article can be found in
online version, at doi:10.1016/j.tet.2009.09.029.
References and notes
1. (a) Abe, N.; Onoda, R.; Shirahata, K.; Kato, T.; Woods, M. C.; Kitahara, Y. Tetra-
hedron Lett. 1968, 9, 369–373; (b) Shirahata, K.; Kato, T.; Kitahara, Y.; Abe, N.
Tetrahedron 1969, 25, 3179–3191 and 4671–4680; (c) Naya, K.; Takagi, I.; Hay-
ashi, M.; Nakamura, S.; Kobayashi, M.; Katsumura, S. Chem. Ind. (London) 1968,
318–320; (d) Naya, K.; Hayashi, M.; Takagi, I.; Nakamura, S.; Kobayashi, M. Bull.
Chem. Soc. Jpn. 1972, 45, 3673–3685.
9. Stragies, R.; Blechert, S. Synlett 1998, 169–170.
10. (a) Wrobleski, A.; Sahasrabudhe, K.; Aube, J. J. Am. Chem. Soc. 2004, 126, 5475–
5481; (b) Hart, A. C.; Phillips, A. J. J. Am. Chem. Soc. 2006, 128, 1094–1095.
11. Malik, C. K.; Ghosh, S. Org. Lett. 2007, 9, 2537–2540.
12. (a) Mondal, S.; Malik, C. K.; Ghosh, S. Tetrahedron Lett. 2008, 49, 5649–5651;
(b) Malik, C. K.; Yadav, R. N.; Drew, M. G. B.; Ghosh, S. J. Org. Chem. 2009, 74,
1957–1963; (c) Malik, C. K.; Hossain, Md. F.; Ghosh, S. Tetrahedron Lett. 2009,
50, 3063–3066; (d) Mondal, S.; Yadav, R. N.; Ghosh, S. Tetrahedron Lett. 2009,
50, 5277–5279.
13. A portion of this work appeared as a preliminary communication: Maity, S.;
Ghosh, S. Tetrahedron Lett. 2008, 49, 1133–1136.
14. (a) Sarkar, S.; Ghosh, S. Tetrahedron Lett. 1996, 37, 4809–4810; (b) Ghatak, A.;
Sarkar, S.; Ghosh, S. Tetrahedron 1997, 53, 17335–17342.
´
2. (a) Harmatha, J.; Samek, Z.; Synackova, M.; Novotny, L.; Herout, V.; Sorm, F.
Collect. Czech. Chem. Commun. 1976, 41, 2047–2058; (b) Jakupovic, J.; Grenz, M.;
Bohlmann, F. Planta Med. 1989, 55, 571–572.
3. Naya, K.; Kawai, M.; Naito, M.; Kasai, T. Chem. Lett. 1972, 241–244.
4. El-Gamal, A. A. H.; Wang, S. K.; Duh, C. Y. Tetrahedron Lett. 2005, 46, 6095–6096.
5. (a) Jamieson, G. R.; Reid, E. H.; Turner, B. P.; Jamieson, A. T. Phytochemistry 1976,
15, 1713–1715; (b) Kano, K.; Hayashi, K.; Mitsuhashi, H. Chem. Pharm. Bull. 1982,
30, 1198–1203.
15. Hill, R. K.; Auken, T. V. J. Org. Chem. 1958, 23, 626–627.
6. (a) Nawrot, J.; Bloszyk, E.; Harmatha, J.; Novotny, L. Z. Angrew. Entomol. 1984,
98, 394–398; (b) Hamatha, J.; Nawrot, J. Biochem. Syst. Ecol. 1984, 12, 95–98;
(c) Nawrot, J.; Harmatha, J.; Novotny, L. Biochem. Syst. Ecol. 1984, 12, 99–101;
(d) Nawrot, J.; Bloszyk, E.; Harmatha, J.; Novotny, L.; Drozdz, B. Acta Entomol.
Bohemoslov. 1986, 83, 327–335; (e) Nawrot, J.; Harmatha, J.; Bloszyk, E. 4th
International Conference on Stored-Product Protection, Tel-Aviv, Sept. 1986.;
(f) Kreckova, J.; Krecek, J.; Harmatha, J. Pr. Nauk. Inst. Chem. Org. Fiz. Politech.
Wroclaw. 1988, 33, 105–107; (g) Rosinski, G.; Bloszyk, E.; Harmatha, J.; Knapik,
A. Pr. Nauk. Inst. Chem. Org. Fiz. Politech. Wroclaw. 1988, 33, 91–94.
7. Forareviewonsynthesesofbakkanesandrelatedcompoundssee:(a)Silva, L. F., Jr.
Synthesis 2001, 671–689; For selected works see: (b) Evans, D. A.; Sims, C. L. Tet-
rahedronLett.1973,14, 4691–4694;(c) Evans, D. A.; Sims, C. L.; Andrews, G. C.
J. Am. Chem. Soc. 1977, 99, 5453–5461; (d) Greene, A. E.; Depre´s, J. P.;
Coelho, F.; Brocksom, T. J. J. Org. Chem. 1985, 50, 3943–3945; (e) Greene,
A. E.; Coelho, F.; Depres, J. P.; Brocksom, T. J. Tetrahedron Lett. 1988, 29,
5661–5662; (f) Hamelin, O.; Depres, J.-P.; Greene, A. E.; Tinant, B.; De-
clercq, J.-P. J. Am. Chem. Soc. 1996, 118, 9992–9993; (g) Hamelin, O.; Wang,
Y.; Depres, J.-P.; Greene, A. E. Angew. Chem., Int. Ed. 2000, 39, 4314–4316;
(h) Brocksom, T. J.; Coelho, F.; Depres, J.-P.; Greene, A. E.; Freire de Lima,
M. E.; Hamelin, O.; Hartmann, B.; Kanazawa, A. M.; Wang, Y. J. Am. Chem.
Soc. 2002, 124, 15313–15325; (i) Srikrishna, A.; Nagaraju, S.; Sharma, G. V.
R. J. Chem. Soc., Chem. Commun. 1993, 285–288; (j) Srikrishna, A.; Reddy,
16. Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446–452.
17. The ground state energy calculations for the lactones 11 and 12 were computed
by using DFT (B3LYP/6-31G) levels with GAUSSIAN software: Frisch, M. J.;
Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.;
Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.;
Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega,
N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.;
Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.;
Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts,
R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J.
W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.;
Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick,
D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul,
A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.;
Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong,
M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision B.01; Gaussian: Pittsburgh,
PA, 2003.
18. Haslouin, J.; Rouessac, F. Tetrahedron Lett. 1976, 17, 4651–4654.
19. See Ref. 7o.
20. Hyldtoft, L.; Madsen, R. J. Am. Chem. Soc. 2000, 122, 8444–8452.