Effect of ring fusion stereochemistry on double bond geometry. Unexpected formation of nine-membered cyclic ether with E-configurated double bond through RCM

Article abstract of DOI:10.1016/j.tet.2010.09.084

Formation of a nine-membered cyclic ether with E-configurated double bond was observed during construction of 5-9-5 tricycles through RCM of dienes. Ring fusion stereochemistry in the products oxonenes was found to have profound influence on the olefin geometry. cis-anti-cis 5-9-5 tricycle was obtained with Z-configurated olefin while cis-syn-cis 5-9-5 system was obtained with E- as well as Z-configurated double bond with the former predominating.

Full text of DOI:10.1016/j.tet.2010.09.084

Tetrahedron 66 (2010) 9159e9164
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Effect of ring fusion stereochemistry on double bond geometry. Unexpected
formation of nine-membered cyclic ether with E-configurated double bond
through RCM
*
Subrata Ghosh , Md. Firoj Hossain, Chanchal K. Malik, Soumitra Maity
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, West Bengal 700032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 August 2010
Received in revised form 27 September 2010
Accepted 27 September 2010
Available online 1 October 2010
Formation of a nine-membered cyclic ether with E-configurated double bond was observed during
construction of 5-9-5 tricycles through RCM of dienes. Ring fusion stereochemistry in the products
oxonenes was found to have profound influence on the olefin geometry. cis-anti-cis 5-9-5 tricycle was
obtained with Z-configurated olefin while cis-syn-cis 5-9-5 system was obtained with E- as well as
Z-configurated double bond with the former predominating.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
DielseAlder reaction
Oxygen heterocycles
Metathesis
Stereocontrol
1. Introduction
Ring closing metathesis (RCM)7 of acyclic precursors with ter-
minal alkene units has emerged as a powerful tool for direct syn-
Nine-membered cyclic ethers are present in a variety of marine
natural products. The bicyclic ethers isolaurallene 1,1 neolaurallene
2,2 polycyclic ethers3 brevetoxin-A, and ciguatoxins are represen-
tative examples. All of these compounds contain at least one nine-
membered ring with Z-configurated double bond within the ring.
Many of these compounds exhibit interesting biological activities.
Thus synthesis of medium-sized cyclic ethers has received con-
siderable attention.4 Construction of medium-sized rings (8e10)
through ring closure of the corresponding linear precursors is ex-
tremely difficult5 because of transannular interactions in the
transition state. A number of indirect but efficient methodologies6
have thus been developed for their synthesis.
thesis of cycloalkenes of different ring sizes. Generally in RCM
eight- and nine-membered carbo-, and hetero-cyclic rings are
obtained in high yields with Z-configurated olefin. To date there is
only one example reported8 in literature for the formation of trans-
cyclooctene through RCM. Although there are a number of reports
on the synthesis of nine-membered carbocycles9 and cyclic ethers10
through RCM, all of them produce carba-and oxa-cycles with
Z-configurated olefin.
1 O
1 O
R3
R4
R3
R4
R
R
H
H
O
O
O
O
O
O
RCM
R2
R2
H
H
O
O
H
O
4
O
H
1
2
3
4
3, a
R = R = R = β-H, R = vinyl
b R1= R2= α-H, R3= vinyl, R4= H
C
C
O
H
O
H
H
H
Br
Me
Br
Me
H
Br
Br
H
In continuation to our interest in the application of RCM re-
action in organic synthesis,11 we became interested in RCM of di-
enes 3. RCM of dienes 3 is expected to produce the tricycles 4 with
nine-membered cyclic ether having Z-olefinic geometry. We herein
present12 the results of RCM of the dienes 3 demonstrating that the
relative stereochemistry at the ring fusion at both ends of the
1
2
* Corresponding author. Tel.: þ91 33 2473 4971; fax: þ91 33 2473 2805; e-mail
address: ocsg@iacs.res.in (S. Ghosh).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.084

9160
S. Ghosh et al. / Tetrahedron 66 (2010) 9159e9164
central ring to be formed influences the olefin geometry signifi-
cantly resulting in the synthesis of nine-membered cyclic ether
with E-configurated double bond. To the best of our knowledge this
is the first example of the formation of oxonene with an E-olefinic
geometry through RCM.13
of the 5,6-acetonide moiety of the known glucofuranose derivative
1214 followed by periodate cleavage of the resulting vicinal diol
afforded the aldehyde 13. Addition of vinyl magnesium bromide to
the aldehyde 13 and subsequent oxidation of the carbinol afforded
the required enone 14. DielseAlder reaction of the enone 14 with
cyclopentadiene in the presence of anhydrous ZnCl2 as catalyst was
found to be highly diastereoselective producing exclusively the
adduct 15 in 92% isolated yield. Removal of PMB protecting group
afforded the hydroxy compound 16 as a crystalline solid, mp
112e114 ꢀC. The structure of the adduct 16 was established by
determination of X-ray crystal structure (Fig. 1).15 The crystal
structure of 16 clearly reveals that diene added to the Re-face of the
enone 14. With establishment of the structure of the adduct 15,
the structure of the DielseAlder adduct of the enone 9 was assigned
the structure as depicted in 10.
2. Results and discussion
For the synthesis of the dienes 3a and 3b, we planned to employ
ring opening metathesis of the appropriate norbornene derivatives
prepared from the dienophile 9. The dienophile 9 was prepared as
follows (Scheme 1). The hydroxyl group in diacetone glucose 5 was
transformed to the allyl ether 610f on reaction of its sodium salt
with allyl bromide. Selective removal of the 5,6-acetonide moiety
and periodate cleavage of the vicinal diol resulted in the known
aldehyde 7.10f Reaction of this aldehyde with vinyl magnesium
bromide afforded the carbinol 8 as a single diastereomer in 70%
yield. Assignment of stereochemistry to the newly created stereo-
centre in 8 was based on addition of vinyl magnesium bromide on
the face opposite to the allyloxy group as the other face of the al-
dehyde unit is blocked by the allyloxy group. DesseMartin peri-
odinane oxidation of the carbinol 8 produced the enone 9 in
excellent yield.
O
O
H
H
O
O
H
O
PMBO
O
i
O
PMBO
O
O
H
H
13
12
H
H
O
iii
O
ii
O
O
PMBO
O
O
H
O
O
H
O
O
H
O
RO
O
RO
ii
O
O
H
O
O
H
O
O
H
H
15
, R = PMB
14
iv
16
, R = H
7
5, R = H
6, R = CH2CH:CH2
Scheme 2. Reagents and conditions: (i) (a) 75% aq HOAc, 12 h, 80%, (b) NaIO4, CH3CN/
H2O (3:1), 2 h, 73%; (ii) (a) CH2¼CHMgBr, THF, ꢁ78 ꢀC to rt, 5h, 68%; (b) DMP, CH2Cl2,
1 h, 95%; (iii) cyclopentadiene, ZnCl2, CH2Cl2, ꢁ78 ꢀC, 5 h, 92%; (iv) DDQ, CH2Cl2/H2O
(18:1), 4 h, 87%.
i
Si
OH
H
H
O
Re
O
O
O
O
H
iii
iv
O
O
O
O
H
H
9
8
v
vi
H
H
O
O
O
O
O
O
O
O
O
O
H
H
11
10
Scheme 1. Reagents and conditions: (i) NaH, HMPA, THF, CH2¼CHCH2Br, rt, 83%; (ii)
(a) 75% aq HOAc, 12 h, 78%, (b) NaIO4, CH3CN/H2O (3:1), 2 h, 70%; (iii) CH2¼CHMgBr,
THF, ꢁ78 ꢀC to rt, 5 h, 70%, (iv) DMP, CH2Cl2, 1 h, 90%; (v) cyclopentadiene, ZnCl2,
CH2Cl2, ꢁ78 ꢀC, 5 h, 95%; (vi) cyclopentadiene, CH2Cl2, 0 ꢀC/rt, 5h, 81%.
DielseAlder reaction of the enone 9 with cyclopentadiene may
proceed from the Re-face as well as from the Si-face to produce
either the adduct 10 or 11. When the enone 9 was treated with
cyclopentadiene in the presence of anhydrous ZnCl2 as catalyst, the
reaction was found to be highly diastereoselective producing ex-
clusively the adduct 10 in 95% isolated yield as an oil. The overall
structure of the product could be discerned from NMR spectral
data. However, it was difficult to distinguish the structure 10 from
11 based on only NMR spectral data. At this stage we decided to
prepare an analogue of 10 as a crystalline solid so that the structure
could be solved by X-ray crystallography. Indeed a solid analogue
15 was prepared as follows (Scheme 2). Acid induced deprotection
Fig. 1. ORTEP diagram of compound 16.
It may be noted that the Re-face of the dienophile 9 is blocked by
the alkoxy group and DielseAlder reaction was expected to take
place by addition on the unhindered Si-face of the enone 9 to give
the adduct 11. It appeared that the catalyst played an important role
in dictating the facial selectivity. So we decided to carry out Diel-
seAlder reaction of the enone 9 with cyclopentadiene without
using any catalyst. To our delight a DielseAlder Adduct was
obtained as a liquid in 81% yield. This adduct was found to be dif-
ferent than the adduct 10 as revealed from NMR spectral data. This

S. Ghosh et al. / Tetrahedron 66 (2010) 9159e9164
9161
adduct was assigned the structure 11 arising out of the addition of
the diene on the unhindered Si-face. The change in facial selectivity
in presence of Lewis acid as catalyst may be attributed as follows.
Initially the enone 9 forms a metal co-ordinated species 17. Rotation
along the C4eC5 bond in the complex 17 forms a tight five-mem-
bered metal chelate 18. Chelate formation is probably the driving
force for this rotation. During this process the Re-face of the diene is
no longer blocked and addition took place through chelate 18
leading to the product 10.
on treating a dichloromethane solution with the Grubbs’ second
generation catalyst 23 at rt for 12 h. Careful chromatography of the
product led to isolation of the tricycles 20 (21%) and 21 (29%) along
with a dimeric compound (14%, not characterized). cis-Olefinic
geometry in 20 was confirmed by the coupling constant (J¼11 Hz)
between C6 and C7 H’s, which appeared at
d
5.45 (J¼0.6, 3.4, and
11.4 Hz) and 5.80 (J¼2.4, 9, and 11 Hz). The cis-olefinic geometry in
20 was further confirmed by analysis of its 2D NMR (HSQC, COSY,
and NOESY) spectra (Fig. 2). Analysis of 1H NMR spectra of 21
revealed that both the C6 and C7 olefinic protons appeared as an
overlapping multiplet at
d 5.63e5.71. It was difficult to determine
Zn2+
O
the coupling constant values for the ring olefinic protons from this
complex pattern. Thus we had to take resort to 2D NMR spectra.
While the COSY and NOESY (Fig. 2) spectra of 20 showed a strong
correlation between C6 and C7 protons, no such correlation was
observed between the ring alkene protons in its COSY and NOESY
spectra (Supplementary data). This confirmed that the nine-
membered cyclic ether in 21 contains an E-configurated olefin.
H
O
O
2+Zn
O
O
O
O
O
O
O
H
H
18
17
With the norbornene derivatives 10 and 11 ready in hand, we
focused on their ring opening metathesis (Scheme 3). The adduct
10 was first subjected to metathesis. Exposure of a dichloro-
methane solution of 10 with Grubbs’ first generation catalyst 22 in
the presence of ethylene at rt led complete consumption of the
starting material within 15 min and afforded, after purification
through column chromatography, mainly the triene 3a in 81% yield.
That the compound 3a is the ring opened product was easily
ascertained from the appearance of three olefinic methines at
O
H
H
H
H
O
O
H
O
O
H
H
O
O
H
H
H
H
H
H
O
O
H
H
H
O
H
H
H
H
COSY
d
133.3, 139.0, 141.9, and three methylenes at 113.6, 115.7, and 118.6
20
21
in its 13C NMR spectrum. Similarly treatment of the adduct 11 in
dichloromethane solution with Grubbs’ first generation catalyst at
rt in the presence of ethylene underwent smooth ring opening to
afford the triene 3b in 96% yield.
NOESY
Fig. 2. COSY and NOESY analysis of 20 and 21.
The diene 3a differs from 3b in the stereochemistry of the five-
membered ring fused to the nine-membered ring to be formed
during RCM. Remarkably this subtle difference in structures of the
diene precursors leads to the formation of thermodynamically less
stable E-alkene in the oxonene. Indeed DFT calculation16 of energy
associated with the cis-oxonene 19 formed from RCM of 3a shows it
be energetically much more stable by 5.62 Kcal/mol than its trans-
analogue. Thus as expected cis-oxonene 19 was formed. On the
other hand the trans-oxonene 21 is energetically more stable by
3.40 Kcal/mol over the cis-oxonene 20 both of which are obtained
by RCM of the diene 3b. In this case the energy difference between
20 and 21 is less compared to that between 19 and its trans-ana-
logue. Thus formation of trans-oxonene 21 competes favorably and
leads to a mixture of cis- and trans-oxonene 20 and 21, respectively.
O
O
1
H
H
H
H
H
O
O
O
O
O
O
i
10
H
H
H
H7
H
O
O
6
3a
19
O
O
H
H
H
H
O
O
O
O
O
O
ii
iii
11
H
H
H
O
O
3b
20
+
3. Conclusion
Mes N N Mes
Cl
We have demonstrated that nine-membered cyclic ether with
thermodynamically less stable E-configurated geometry13 can be
formed through RCM reaction of diene. It is not the strain energy
associated with incorporation of trans-alkene in the ring but
probably the overall stability of the resulting ring system that
dictates the olefin geometry. In the present example, cis-syn-cis
stereochemistry of the ring junction at both ends of the nine-
membered ring made E-configurated oxonene more stable than the
corresponding Z-analogue.
O
PCy3
Ru
PCy3
H
O
O
O
Cl
Cl
Ru
Ph
Ph
Cl
H
H
PCy3
23
O
22
21
Scheme 3. Reagents and conditions: (i) catalyst 22 (5 mol %), CH2Cl2, C2H4, rt, 6 h, 78%;
(ii) catalyst 22 (10 mol %), CH2Cl2, C2H4, rt, 1 h, 96%; (iii) catalyst 23 (6 mol %), CH2Cl2,
C2H4, rt, 12 h, 29% (for 21) and 21% (for 20).
The triene 3a on treatment with the catalyst 22 for 6 h at rt
afforded the tricycle 19 in 78% yield. Assignment of Z-olefinic ge-
ometry in the nine-membered ring in 19 could be easily made from
the coupling constant (J¼10.5 Hz) of the C6 and C7 olefinic protons
4. Experimental section
4.1. General
at
d
5.51 (dt, J¼4, 10.5 Hz) and 5.57 (dt, J¼2, 10.5 Hz). The triene 3b
failed to undergo ring closure with the catalyst 22 even after pro-
longed heating in toluene. However, the triene 3b could be cyclized
Melting points were taken in open capillaries in sulfuric acid
bath and are uncorrected. Petroleum ether refers to the fraction

9162
S. Ghosh et al. / Tetrahedron 66 (2010) 9159e9164
having bp 60e80 ꢀC. A usual work up of the reaction mixture
consists of extraction with diethyl ether, washing with brine, drying
over Na2SO4, and removal of the solvent in vacuo. Column chro-
matography was carried out with silica gel (60e120 mesh). Peak
positions in 1H and 13C NMR spectra are indicated in parts per
0.779 mmol) was added and stirred for 30 min followed by addition
of freshly distilled cyclopentadiene (78 mg, 1.18 mmol). After stir-
ring for 5 h, the reaction mixture was quenched with brine (0.2 mL)
and worked up in the usual way to afford, after column chroma-
tography (10% Et2O/petroleum ether), the adduct 10 (120 mg, 95%);
26
million downfield from internal TMS in
d
units. NMR spectra were
Rf (15% EtOAc/petroleum ether) 0.8; [
a]
ꢁ112 (c 0.28, CHCl3); IR
D
recorded in CDCl3 solution at 300, 500, and 600 MHz for 1H and 75,
125 MHz for 13C on Bruker-Avance DPX300, DPX500, DPX600 in-
struments. 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. Optical rotations were
nmax (liquid film) 2976, 2937, 1708, 1381 cmꢁ1
; dH (300 MHz, CDCl3)
6.12 (1H, dd, J 5.3, 3.1 Hz, ]CH), 6.05 (1H, d, J 3.6 Hz, OeCHeO),
5.83 (1H, dd, J 5.4, 2.2 Hz, ]CH), 5.79e5.74 (1H, m, ]CH),
5.27e5.16 (2H, m, ]CH2), 4.65 (1H, d, J 3.6 Hz, OeCHeCO), 4.54
(1H, d, J 3.8 Hz, OCH), 4.19 (1H, d, J 3.6 Hz, CHeOeCH2), 4.03 (1H, dd,
J 12.7, 5.3 Hz, OCH2), 3.94 (1H, dd, J 12.8, 5.8 Hz, OCH2), 3.39e3.33
(1H, m, CH), 3.23 (1H, br s, CH), 2.85 (1H, br s, CH), 1.82e1.74 (1H,
ddd, J 11.9, 8.9, 3.6 Hz), 1.45 (3H, s, CH3), 1.42e1.37 (2H, m), 1.31 (3H,
s, CH3), 1.28 (1H, m); dC (75 MHz, CDCl3) 208.1, 137.1, 133.7, 132.3,
118.2, 112.2, 105.7, 85.6, 83.1, 82.0, 71.4, 50.1, 48.7, 46.2, 42.8, 28.8,
26.9, 26.4; HRMS (ESI) (m/z): [MþNa]þ, found 343.1525.
C18H24O5Na requires 343.1521.
measured using Jasco P-1020 digital polarimeter and [a]D values are
given in units of 10ꢁ1 deg cm2 gꢁ1. Mass spectra were measured in
a QTOF I (quadrupole-hexapole-TOF) mass spectrometer 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.
4.1.1. 1-((3aR,5R,6S,6aR)-6-(Allyloxy)-tetrahydro-2,2-dimethylfuro
[2,3-d][1,3]dioxol-5-yl)prop-2-en-1-ol 8. To a magnetically stirred
solution of the known aldehyde 7 (900 mg, 3.95 mmol) in dry THF
(10 mL) at ꢁ78 ꢀC was added vinyl magnesium bromide (1.0 M
solution in THF, 5.9 mmol, 5.9 mL) dropwise. The reaction mixture
was stirred at that temperature for 1 h. The temperature of the
reaction mixture was slowly raised to rt. After stirring for 4 h at rt it
was quenched with saturated NH4Cl solution (1.0 mL). Usual work
up of the reaction mixture and purification of the crude residue by
column chromatography (25% Et2O/petroleum ether) afforded the
4.1.4. ((3aR,5S,6R,6aR)-6-(Allyloxy)-tetrahydro-2,2-dimethylfuro
[2,3-d][1,3]dioxol-5-yl)(bicyclo[2.2.1]hept-5-en-2-yl)methanone
11. To a stirred solution of the dienophile 9 (200 mg, 0.787 mmol)
in dry THF (5 mL) at 0 ꢀC, freshly distilled cyclopentadiene (156 mg,
2.36 mmol) was added dropwise. Stirring was continued for 1 h at
0
ꢀC and 6 h at rt. Solvent was removed in vacuo and the residue
was purified by column chromatography (12% Et2O/petroleum
ether) to afford the cycloadduct 11 (204 mg, 81%); Rf (20% EtOAc/
petroleum ether) 0.85; dH (300 MHz, CDCl3) 6.16 (1H, dd, J 5.5,
3.1 Hz, ]CH), 6.08 (1H, d, J 3.6 Hz, OeCHeO), 5.80e5.77 (1H, m,
]CH), 5.75e5.68 (1H, m, ]CH), 5.22e5.14 (2H, m, ]CH2), 4.56
(1H, d, J 3.5 Hz, OeCHeCO), 4.54 (1H, d, J 3.4 Hz, OCH), 4.15 (1H, d, J
3.5 Hz, CHeOCH2), 4.00 (1H, dd, J 12.9, 5.1 Hz, OCH2), 3.89 (1H, dd, J
12.7, 5.4 Hz, OCH2), 3.46e3.42 (1H, m, CHeCO), 3.41 (1H, br s, CH),
2.89 (1H, br s, CH), 1.72e1.64 (1H, m), 1.48 (3H, s, CH3), 1.42e1.37
(2H, m), 1.33 (3H, s, CH3), 1.27e1.22 (1H, m); dC (75 MHz, CDCl3)
209.2, 137.6, 133.7, 131.5, 117.8, 112.3, 106.1, 85.7, 84.0, 82.2, 71.7,
50.3, 48.9, 46.3, 43.0, 27.7, 27.0, 26.4; HRMS (ESI) (m/z): [MþNa]þ,
found 343.1524. C18H24O5Na requires 343.1521.
alcohol 8 (785 mg, 70%) as colorless oil; Rf (30% EtOAc/petroleum
24
ether) 0.7; [
a]
ꢁ41.96 (c 5.95, CHCl3); IR nmax (liquid film) 3477,
D
2987, 2935, 1737, 1643, 1454, 1427, 1375 cmꢁ1
; dH (300 MHz, CDCl3)
6.00e5.95 (1H, m, ]CH), 5.91 (1H, d, J 2.8 Hz, OeCHeO), 5.88e5.77
(1H, m, ]CH), 5.35 (1H, d, J 17.4 Hz, ]CH2), 5.25 (1H, d, J 17.4 Hz,
]CH2), 5.17 (2H, d, J 10.5 Hz, ]CH2), 4.49 (1H, d, J 3.5 Hz, CH), 4.43
(1H, d, J 5.1 Hz, CH), 4.11 (1H, dd, J 11.8, 5.21 Hz), 3.92e4.01 (3H, m),
2.99 (1H, br s, OH), 1.41 (3H, s, CH3), 1.25 (3H, s, CH3); dC (75 MHz,
CDCl3) 137.8, 133.5, 118.3, 115.9, 111.6, 105.1, 82.6, 81.9, 81.5, 71.1,
70.5, 26.7, 26.3; HRMS (ESI) (m/z): [MþNa]þ, found 279.1209.
C13H20O5Na requires 279.1208.
4.1.5. (3aR,5S,6S,6aR)-6-(4-Methoxybenzyloxy)-tetrahydro-2,2-
dimethylfuro[2,3-d][1,3]dioxole-5-carbaldehyde 13. A solution of the
acetonide 12 (2.0 g, 2.63 mmol) and aqueous acetic acid (75%,
10 mL) was stirred at rt for 12 h. The resulting solution was con-
centrated under reduced pressure and the residual mass was pu-
rified by column chromatography (40% EtOAc/petroleum ether) to
4.1.2. 1-((3aR,5S,6R,6aR)-6-(Allyloxy)-tetrahydro-2,2-dimethylfuro
[2,3-d][1,3]dioxol-5-yl)prop-2-en-1-one 9. A solution of the hydroxy
compound 8 (100 mg, 0.391 mmol) in anhydrous dichloromethane
(10 mL) was degassed by bubbling Ar and DMP (329 mg,
0.781 mmol) was added to it. The reaction mixture was stirred for
1 h and quenched by adding dropwise (1:1 mixture of saturated
aqueous sodium thiosulfate and saturated sodium bicarbonate) till
a transparent solution is obtained. The compound was extracted
with ether and concentrated under vacuum and purified by column
chromatography (15% Et2O/petroleum ether) to afford the enone 9
afford the corresponding diol (1.43 g, 80%) as colorless oil; Rf (50%
26
EtOAc/petroleum ether) 0.5; [
a
]
D
ꢁ32.7 (c 6.4, CHCl3); IR nmax
(liquid film) 3439, 2987, 2937, 1612, 1514, 1416, 1379 cmꢁ1
; dH
(300 MHz, CDCl3) 7.24 (2H, d, J 8.3 Hz, AreH), 6.85 (2H, d, J 8.4 Hz,
AreH), 5.88 (1H, d, J 3.5 Hz, OeCHeO), 4.62e4.55 (2H, m, CH2), 4.47
(1H, d, J 11.3 Hz, CH), 4.09e4.06 (2H, m), 3.98e3.97 (1H, m), 3.75
(4H, br s, OCH3), 3.64 (1H, dd, J 11.4, 5.2 Hz, CH), 3.08 (2H br s, OH),
1.45 (3H, s, CH3), 1.28 (3H, s, CH3); dC (75 MHz, CDCl3) 159.5, 129.5
(2C), 129.3, 114.0 (2C), 111.7, 105.1, 82.2, 81.5, 79.9, 71.8, 69.1, 64.2,
55.2, 26.7, 26.2; HRMS (ESI) (m/z): [MþNa]þ, found 363.1422.
C17H24O7Na requires 363.1420.
(89 mg, 90%) as colorless oil; Rf (20% EtOAc/petroleum ether) 0.8;
25
[
a]
ꢁ50.5 (c 1.36, CHCl3); IR nmax (liquid film) 2991, 2939, 1710,
D
1610, 1446, 1377 cmꢁ1
; dH (300 MHz, CDCl3) 6.76 (1H, dd, J 17.4,
10.6 Hz, ]CH), 6.29 (1H, d, J 17.3 Hz, ]CH2), 6.04 (1H, d, J 3.5 Hz,
OeCHeO), 5.68 (1H, dd, J 10.4, 1.4 Hz, ]CH2), 5.73e5.63 (1H, m,
]CH), 5.18e5.08 (2H, m, ]CH2), 4.74 (1H, d, J 3.5 Hz, OeCHeCO),
4.53 (1H, d, J 3.5 Hz, OeCH), 4.21 (1H, d, J 3.5 Hz, CHeOeCH2), 3.98
(1H, dd, J 12.8, 5.3 Hz, OCH2), 3.86 (1H, dd, J 12.9, 5.5 Hz, OCH2), 1.43
(3H, s, CH3), 1.28 (3H, s, CH3); dC (75 MHz, CDCl3) 196.0, 133.2, 132.2,
128.7, 117.8, 112.3, 105.8, 84.8, 83.4, 82.1, 71.3, 26.9, 26.3; HRMS (ESI)
(m/z): [MþNa]þ, found 277.1050. C13H18O5Na requires 277.1052.
To a magnetically stirred ice-cold solution of the diol (2.5 g,
7.35 mmol) obtained as above in acetonitrile/water (3:1, 24 mL) was
added NaIO4 (2.36 g, 11.03 mmol) in several portions. The reaction
mixture was allowed to stir at 0 ꢀC for 2 h. The precipitated white
solid was filtered off after washing it thoroughly with diethyl ether.
Usual work up of the filtrate afforded the title aldehyde 13 (1.60 g,
73%) as colorless liquid; IR nmax (liquid film) 2978, 2928, 1737, 1610,
4.1.3. ((3aR,5S,6R,6aR)-6-(Allyloxy)-2,2-dimethyltetrahydrofuro
[2,3-d][1,3]dioxol-5-yl)((1S,2S,4S)-bicyclo[2.2.1]hept-5-en-2-yl)
methanone10. To a magnetically stirred solution of the dienophile 9
(100 mg, 0.393 mmol) in DCM (5 mL) at ꢁ78 ꢀC, ZnCl2 (106 mg,
1587, 1514, 1373 cmꢁ1
; dH (300 MHz, CDCl3) 9.56 (1H, s, CHO), 7.10
(2H, d, J 8.5 Hz, AreH), 6.79 (2H, d, J 8.5 Hz, AreH), 6.03 (1H, d, J
3.4 Hz, OeCHeO), 4.55 (1H, d, J 3.4 Hz, CH), 4.48 (1H, br s, CH), 4.46

S. Ghosh et al. / Tetrahedron 66 (2010) 9159e9164
9163
(1H, d, J 11.6 Hz, CH2Ph), 4.33 (1H, d, J 11.6 Hz, CH2Ph), 4.24 (1H, d, J
3.7 Hz, CHeOPMB), 3.72 (3H, s, OMe), 1.39 (3H, s, CH3), 1.25 (3H, s,
CH3); dC (75 MHz, CDCl3) 200.1, 159.7, 129.6 (2C), 128.7, 114.0 (2C),
112.6, 106.3, 84.7, 83.3, 82.3, 72.2, 55.4, 27.1, 26.4; HRMS (ESI) (m/z):
[MþNa]þ, found 331.1156. C16H20O6Na requires 331.1158.
chromatographed on silica gel to give a white solid 16 (195 mg,
26
87%), mp 112e114 ꢀC; Rf (30% EtOAc/petroleum ether) 0.5; [
ꢁ146.21 (c 2.0, CHCl3); IR nmax (KBr plate) 3442, 2985, 2965, 1710,
1384, 1374 cmꢁ1
dH (300 MHz, CDCl3) 6.15 (1H, dd, J 5.4, 3.0 Hz,
a]
D
;
]CH), 6.07 (1H, d, J 3.5 Hz, OeCHeO), 5.84 (1H, dd, J 5.4, 2.6 Hz,
]CH), 4.69 (1H, d, J 3.0 Hz, OeCHeCO), 4.56 (1H, d, J 3.4 Hz, OCH),
4.52 (1H, br s, CHeOH), 3.41e3.35 (1H, m), 3.33 (1H, br s, CH), 3.10
(1H, br s, CH), 2.90 (1H, br s, CH), 2.10 (1H, br s, OH), 1.86e1.78 (1H,
m), 1.49 (3H, s, CH3), 1.47e1.43 (2H, m), 1.33 (3H, s, CH3); dC
(75 MHz, CDCl3)209.8; 137.6, 131.9, 112.1, 105.4, 86.0, 84.6, 76.1, 50.1,
49.6, 46.4, 42.8, 28.4, 27.0, 26.3; HRMS (ESI) (m/z): [MþNa]þ, found
303.1205. C15H20O5Na requires 303.1208.
4.1.6. 1-((3aR,5S,6R,6aR)-6-(4-Methoxybenzyloxy)-tetrahydro-
2,2-dimethylfuro[2,3-d][1,3]dioxol-5-yl)prop-2-en-1-one
14. Following the procedure described for 8, the aldehyde 13
(2.23 g, 7.2 mmol) in dry THF (15 mL) was reacted with vinyl
magnesium bromide (15 mL, 15 mmol, 1.0 M in THF) to afford the
corresponding carbinol (1.63 g, 68%) as colorless oil; Rf (30% EtOAc/
petroleum ether) 0.5; [
a
]
D
26 ꢁ42.6 (c 5.1, CHCl3); IR nmax (liquid film)
3498, 2987, 2935, 1612, 1585, 1514, 1463, 1375 cmꢁ1
;
dH (300 MHz,
4.1.9. Synthesis of the tricycle 19. Grubbs’ first generation catalyst
(15 mg, 0.018 mmol) was dissolved in degassed CH2Cl2 (2 mL) and
was added through a syringe to a solution of the norbornene de-
rivative 10 (200 mg, 0.62 mmol) in degassed CH2Cl2 (50 mL). This
solution was then purged with ethylene and stirred at rt for 15 min
under an ethylene atmosphere. The solvent was then removed by
rotary evaporation and purified by column chromatography (10%
Et2O/petroleum ether) to afford the compound 3a (176 mg, 81%) as
colorless oil; Rf (20% EtOAc/petroleum ether) 0.6; IR nmax (liquid
CDCl3) 7.22 (2H, d, J 7.6 Hz, AreH), 6.86 (2H, d, J 7.1 Hz, AreH), 5.96
(1H, d, J 2.6 Hz, CH), 5.84e5.73 (1H, m), 5.39 (1H, d, J 17.1 Hz), 5.17
(1H, d, J 10.6 Hz), 4.61e4.57 (2H, m), 4.47 (1H, t, J 5.9 Hz), 4.37 (1H,
d, J 11.3 Hz), 4.03e4.01 (1H, m), 3.90 (1H, br s), 3.77 (3H, s), 2.52 (1H,
br s, OH), 1.46 (3H, s), 1.30 (3H, s); dC (75 MHz, CDCl3) 159.5, 135.8,
129.6 (2C), 129.0, 116.9, 113.9 (2C), 111.8, 105.0, 83.1, 82.2, 82.1, 71.6,
70.9, 55.2, 26.8, 26.3; HRMS (ESI) (m/z): [MþNa]þ, found 359.1475.
C18H24O6Na requires 359.1471.
Following the procedure described for 9, the hydroxy compound
obtained as above (1.7 g, 5.06 mmol) in dry DCM (25 mL) was ox-
film) 2983, 2937,1707,1373 cmꢁ1
; dH (300 MHz, CDCl3) 6.03 (1H, d, J
3.5 Hz, OeCHeO), 5.88e5.66 (3H, m, ]CH), 5.26e5.17 (3H, m,
]CH2), 5.05e4.89 (3H, m, ]CH2), 4.73 (1H, d, J 3.8 Hz, OeCHeCO),
4.50 (1H, d, J 3.6 Hz, eOeCHe), 4.25 (1H, d, J 3.8 Hz, eOeCHe), 4.06
(1H, dd, J 12.6, 5.3 Hz, OCH2), 3.88 (1H, dd, J 12.7, 6.1 Hz, OCH2), 3.22
(1H, q, J 8.1 Hz), 2.91e2.80 (1H, m), 2.60e2.46 (1H, m), 1.98e1.79
(3H, m), 1.61e1.49 (1H, m), 1.44 (3H, s, CH3), 1.31 (3H, s, CH3); dC
(75 MHz, CDCl3) 205.9, 141.9, 139.0, 133.3, 118.6, 115.7, 113.6, 112.3,
105.7, 86.1, 82.8, 81.9, 71.1, 51.4, 48.0, 44.0, 39.6, 34.9, 27.1, 26.5.
A solution of the triene 3a (100 mg, 0.28 mmol) in dichloro-
methane (40 mL) was treated with Grubbs’ first generation catalyst
22 (12 mg, 0.014 mmol) under Ar atmosphere and stirred at rt for
6 h. The residual mass obtained after removal of solvent was
idized with DMP (2.6 g, 6.07 mmol) to afford the enone 14 (1.61 g,
25
95%) as colorless liquid; Rf (20% EtOAc/petroleum ether) 0.7; [a]
D
ꢁ52.8 (c 2.6, CHCl3); IR nmax (liquid film) 2988, 2936, 1698, 1612,
1514, 1403, 1383 cmꢁ1
dH (300 MHz, CDCl3) 7.1 (2H, d, J 8.5 Hz,
;
AreH), 6.82 (2H, d, J 8.7 Hz, AreH), 6.76e6.71 (1H, m, ]CH), 6.33
(1H, d, J 17.4 Hz, ]CH2), 6.07 (1H, d, J 3.5 Hz, OeCHeO), 5.68 (1H, d,
J 10.1 Hz, ]CH2), 4.78 (1H, d, J 3.6 Hz, OeCHeCO), 4.57 (1H, d, J
3.5 Hz, OCH), 4.47 (1H, d, J 11.6 Hz, OCH2Ar), 4.37 (1H, d, J 11.5 Hz,
OCH2Ar), 4.28 (1H, d, J 3.5 Hz, CHeOCH2Ar), 3.76 (3H, s, OMe), 1.45
(3H, s, CH3), 1.30 (3H, s, CH3); dC (75 MHz, CDCl3) 195.1, 159.5, 132.4,
129.5 (2C), 128.9, 128.6, 113.8 (2C), 112.3, 105.9, 84.9, 83.2, 82.2, 72.1,
55.3, 27.0, 26.4; HRMS (ESI) (m/z): [MþNa]þ, found 357.1314.
C18H22O6Na requires 357.1314.
chromatographed (12% Et2O/petroleum ether) to afford 19 (71 mg,
25
78%) as colorless liquid; Rf (15% EtOAc/petroleum ether) 0.85; [a]
D
ꢁ77.6 (c 2.4, CHCl3); IR nmax (liquid film) 2983, 2937, 1707,
1373 cmꢁ1
dH (500 MHz, CDCl3) 6.09 (1H, d, J 3.2 Hz, OeCHeO),
4.1.7. ((1S,2S,4S)-Bicyclo[2.2.1]hept-5-en-2-yl(3aR,5S,6R,6aR)-6-
(4-methoxybenzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-
5-yl)methanone 15. The enone 14 (270 mg, 0.81 mmol) was
allowed to react with cyclopentadiene (267 mg, 4.04 mmol) in
presence of ZnCl2 (120 mg, 0.882 mmol) to afford after column
;
5.85 (1H, tdd, J 18.0, 10.0, 7.2 Hz, ]CH), 5.57 (1H, dt, J 10.5, 2.0 Hz,
]CH), 5.51 (1H, dt, J 10.5, 4.0 Hz, ]CH), 5.06 (1H, d, J 17.1 Hz, ]
CH2), 4.96 (1H, d, J 10.3 Hz, ]CH2), 4.53 (1H, d, J 3.1 Hz, OeCHeCO),
4.40 (1H, d, J 15.0 Hz,), 4.33 (1H, d, J 2.3 Hz), 4.04 (1H, d, J 1.7 Hz),
4.00 (1H, q, J 9.6 Hz), 3.82 (1H, dd, J 15.0,10.6 Hz), 3.42 (1H, quintet, J
8.7 Hz), 2.56 (1H, sextet, J 8.6 Hz), 2.19 (1H, td, J 7.6, 6.4 Hz),1.82 (2H,
t, J 10.0 Hz), 1.48 (3H, s, CH3), 1.40e1.36 (1H, m), 1.33 (3H, s, CH3); dC
(75 MHz, CDCl3) 211.8, 141.7, 141.6, 125.2, 113.7, 112.8, 105.9, 86.3,
85.5, 84.3, 68.6, 51.1, 44.4, 41.2, 40.3, 35.8, 26.9, 26.5; HRMS (ESI)
(m/z): [MþNa]þ, found 343.1524. C18H24O5Na requires 343.1521.
chromatography the adduct 15 (297 mg, 92%); Rf (20% EtOAc/pe-
25
troleum ether) 0.8; [
a]
ꢁ88.4 (c 3.0, CHCl3); IR nmax (liquid film)
D
2972, 2938, 1705, 1612, 1585, 1514, 1456, 1375 cmꢁ1
; dH (300 MHz,
CDCl3) 7.12 (2H, d, J 8.5 Hz, AreH), 6.80 (2H, d, J 8.5 Hz, AreH), 6.04
(1H, dd, J 5.2, 3.1 Hz, ]CH), 6.00 (1H, d, J 3.6 Hz, OeCHeO), 5.70
(1H, dd, J 5.4, 2.4 Hz, ]CH), 4.62 (1H, d, J 3.6 Hz, OeCHeCO), 4.51
(1H, d, J 3.6 Hz, OCH), 4.47 (1H, d, J 11.6 Hz, OCH2Ar), 4.34 (1H, d, J
11.6 Hz, OCH2Ar), 4.20 (1H, d, J 3.60 Hz, CHeOeCH2Ar), 3.71 (3H, s,
OMe), 3.16e3.12 (1H, m, CHeCO), 3.10 (1H, br s, CH), 2.77 (1H, br s,
CH),1.72e1.64 (1H, m),1.39 (3H, s, CH3),1.37e1.27 (1H, m),1.25 (3H,
s, CH3), 1.18e1.13 (2H, m); dC (75 MHz, CDCl3) 207.5, 159.6, 137.1,
132.2, 129.7 (2C), 129.0, 113.9 (2C), 112.1, 105.6, 85.4, 82.8, 81.8, 72.0,
55.3, 50.0, 48.8, 46.2, 42.6, 28.6, 27.0, 26.4; HRMS (ESI) (m/z):
[MþNa]þ, found 423.1788. C23H28O6Na requires 423.1783.
4.1.10. ((3aR,5S,6R,6aR)-6-(Allyloxy)-2,2-dimethyltetrahydrofuro
[2,3-d][1,3]dioxol-5-yl)((1R,2R,4R)-2,4-divinylcyclopentyl)methanone
3b. To a solution of 11 (60 mg, 0.19 mmol) in dry CH2Cl2 (30 mL)
under ethylene atmosphere at rt was added a solution of the cat-
alyst 22 (15 mg, 0.018 mmol) in CH2Cl2 (2 mL). After stirring for 1 h,
the reaction mixture was concentrated. Column chromatography of
the residue (10% Et2O/petroleum ether) gave the ring opened
product 3b (59 mg, 96%) as colorless oil; Rf (20% EtOAc/petroleum
4.1.8. (Bicyclo[2.2.1]hept-5-en-2-yl)((3aR,6R,6aR)-tetrahydro-6-
hydroxy-2,2-dimethylfuro[2,3-d][1,3]dioxol-5-yl)methanone 16. To
a stirred solution of 15 (320 mg, 0.8 mmol) in DCM (8.1 mL) and
water (0.5 mL) was added DDQ (272 mg, 1.2 mmol) at rt. After 3 h
precipitated solid was removed by decantation and washed with
CH2Cl2 (5 mL). The combined CH2Cl2 solution was then washed
with saturated NaHCO3, water and saturated NaCl, and dried over
Na2SO4. Evaporation of the solvent in vacuo gave an oil, which was
ether) 0.7; nmax (liquid film) 2971, 1709, 1442 cmꢁ1
; dH (300 MHz,
CDCl3) 6.04 (1H, d, J 3.5 Hz, OeCHeO), 5.88e5.61 (3H, m), 5.21e5.13
(2H, m), 5.04e4.98 (2H, m), 4.92e4.87 (2H, m), 4.50 (1H, d, J 3.5 Hz,
OeCHeCO), 4.41 (1H, d, J 3.4 Hz, OCH), 4.14 (1H, d, J 3.4 Hz,
CHeOeCH2), 4.02e3.86 (2H, m), 3.71e3.62 (1H, m), 3.10 (1H,
quintet, J 8.5 Hz, CH), 2.55e2.46 (1H, m), 2.06e1.97 (1H, m),
1.91e1.62 (3H, m), 1.42 (3H, s, CH3), 1.31 (3H, s, CH3); dC (75 MHz,
CDCl3) 210.8, 142.2, 139.8, 133.8, 117.8, 114.9, 113.4, 112.3, 106.1, 85.9,

9164
S. Ghosh et al. / Tetrahedron 66 (2010) 9159e9164
€
2446e2452; (d) Nicolaou, K. C.; Yang, Z.; Ouellette, M.; Shi, G.-Q.; Gartner, P.;
Gunzner, J. L.; Agrios, K. A.; Huber, R.; Chadha, R.; Huang, D. H. J. Am. Chem.
Soc. 1997, 119, 8105e8106.
84.0, 82.1, 71.7, 52.6, 45.6, 43.5, 39.0, 33.6, 27.1, 26.6; HRMS (ESI)
(m/z): [MþNa]þ, found 371.1839. C20H28O5Na requires 371.1834.
7. For excellent accounts on RCM see: (a) Grubbs, R. H.; Miller, S. J.; Fu, G. C.
Acc. Chem. Res. 1995, 28, 446e452; (b) Furstner, A. Top. Catal. 1997, 4,
285e299; (c) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. 1997, 36,
2036e2056; (d) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413e4450;
€
4.1.11. Synthesis of tricycles 20 and 21. Following the metathesis
procedure described above, the ring opened product 3b (42 mg,
0.12 mmol) in CH2Cl2 (20 mL) was treated with the catalyst 23
(6 mg, 6 mol %) in argon atmosphere (12 h) to afford, after column
chromatography (35% Et2O/petroleum ether), the tricycles 20
(8 mg, 21%) and 21 (11 mg, 29%) as colorless oil. Compound 20; Rf
€
(e) Armstrong, S. K. J. Chem. Soc., Perkin Trans. 1 1998, 371e388; (f) Furstner,
A. Angew. Chem., Int. Ed. 2000, 39, 3012e3043; (g) Kotha, S.; Sreenivasachary,
N. Indian J. Chem. 2001, 40B, 763e780; (h) Deiters, A.; Martin, S. F. Chem. Rev.
2004, 104, 2199e2238; (i) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew.
Chem., Int. Ed. 2005, 44, 4490e4527; (j) Ghosh, S.; Ghosh, S.; Sarkar, N. J.
Chem. Sci. 2006, 118, 223e235; (k) Chattopadhyay, S. K.; Karmakar, S.; Biswas,
T.; Majumdar, K. C.; Rahaman, H.; Roy, B. Tetrahedron 2007, 63, 3919e3952
For recent works see: (l) Kotha, S.; Mandal, K. Chem.dAsian J. 2009, 4,
354e362; (m) Mehta, G.; Likhite, N. S. Tetrahedron Lett. 2009, 50,
5263e5266; (n) Srikrishna, A.; Pardeshi, V. H.; Satyanarayana, G. Tetrahedron:
Asymmetry 2010, 21, 746e750.
(30% EtOAc/petroleum ether) 0.35; [
a
]
27 ꢁ5.4 (c 1.2, CHCl3); IR nmax
D
(liquid film) 3076, 2986, 2935, 1726, 1641 cmꢁ1
;
dH (600 MHz,
CDCl3) 6.09 (1H, d, J 3.6 Hz, OeCHeO), 5.80 (1H, ddd, J 11, 9,
2.4 Hz, ]CHe), 5.82e5.74 (1H, m, ]CHe), 5.45 (1H, ddd, J 11.4, 3.4,
0.6 Hz, ]CHe), 5.06 (1H, td, J 17.1,1.8 Hz, ]CH2), 4.95 (1H, td, J 10.3,
1.2 Hz, ]CH2), 4.88 (1H, d, J 3.7 Hz, OCH), 4.58 (1H, d, J 3.7 Hz, OCH),
4.53 (1H, d, J 3.5 Hz, OCH), 4.38 (1H, td, J 15.5, 3.0 Hz, OCH2), 3.94
(1H, dd, J 15.4, 5.3 Hz, OCH2), 3.08e3.03 (1H, m), 2.89e2.80 (2H, m),
2.12e2.05 (2H, m),1.53 (1H, dd, J 11.4, 10.8 Hz), 1.47 (3H, s), 1.32 (3H,
s), 1.28e1.22 (1H, m); dC (125 MHz, CDCl3) 207.3, 140.9, 140.8, 124.6,
114.1, 112.4, 106.3, 87.7, 82.6, 78.4, 65.7, 50.6, 45.5, 45.4, 42.9,
36.8, 27.2, 26.5; HRMS (ESI) (m/z): [MþNa]þ, found 343.1523.
8. Bourgeois, D.; Pancrazi, A.; Ricard, L.; Prunet, J. Angew. Chem., Int. Ed. 2000, 39,
726e728.
9. (a) Paquette, L. A.; Edmondson, S. D.; Monck, N.; Rogers, R. D. J. Org. Chem. 1999,
64, 3255e3265; (b) Paquette, L. A.; Yang, J.; Long, Y. O. J. Am. Chem. Soc. 2002,
124, 6542e6543; (c) Rodriguez, J. R.; Castedo, L.; Mascarenas, J. L. Chem.dEur. J.
2002, 8, 2923e2930; (d) Yang, J.; Long, Y. O.; Paquette, L. A. J. Am. Chem. Soc.
2003, 125, 1567e1574; (e) Malik, C. K.; Yadav, R. N.; Drew, M. G. B.; Ghosh, S. J.
Org. Chem. 2009, 74, 1957e1963.
10. (a) Clark, J. S.; Kettle, J. G. Tetrahedron Lett. 1997, 38, 127e130; (b) Oishi, T.;
Nagumo, Y.; Hirama, M. Chem. Commun. 1998, 1041e1042; (c) Crimmins, M. T.;
Choy, A. L. J. Am. Chem. Soc. 1999, 121, 5653e5660; (d) Holt, D. J.; Barker, W. D.;
Jenkins, P. R.; Panda, J.; Ghosh, S. J. Org. Chem. 2000, 65, 482e493; (e) Crimmins,
M. T.; Emmitte, K. A.; Choy, A. L. Tetrahedron 2002, 58, 1817e1834; (f) Kaliappan,
K. P.; Kumar, N. Tetrahedron Lett. 2003, 44, 379e381.
C18H24O5Na requires 343.1521. Compound 21; Rf (30% EtOAc/pe-
26
troleum ether) 0.40; [
a
]
D
ꢁ21.4 (c 1.1, CHCl3); IR nmax (liquid film)
3077, 2984, 2938,1724,1641 cmꢁ1
; dH (600 MHz, CDCl3) 6.00 (1H, d,
J 3.6 Hz, OeCHeO), 5.82 (1H, ddd, J 17.4, 10.2, 7.2 Hz, ]CHe),
5.72e5.63 (2H, m, CH]CH), 5.06 (1H, td, J 17.4, 1.2 Hz, ]CH2), 4.97
(1H, ddd, J 10.3, 1.5, 0.6 Hz, ]CH2), 4.73 (1H, d, J 2.4 Hz, OCH), 4.65
(1H, d, J 2.4 Hz, OCH), 4.52 (1H, d, J 3.0 Hz, OCH), 4.24 (1H, dd, J 12.6,
6.0 Hz, OCH2), 3.86 (1H, dd, J 12.5, 9.5 Hz, OCH2), 3.52e3.42 (2H, m,
CHeCH2), 2.62e2.53 (1H, m), 2.23e2.16 (1H, m), 2.04e1.97 (1H, m),
1.93e1.83 (1H, m), 1.60e1.52 (1H, m), 1.54 (3H, s, CH3), 1.31 (3H, s,
CH3); dC (125 MHz, CDCl3) 205.9, 141.0, 140.6, 128.0, 114.2, 112.2,
104.8, 89.6, 87.3, 85.1, 68.9, 53.4, 44.1, 40.8, 39.7, 37.2, 27.0, 26.4;
HRMS (ESI) (m/z): [MþNa]þ, found 343.1525. C18H24O5Na requires
343.1521.
11. (a) Nayek, A.; Banerjee, S.; Sinha, S.; Ghosh, S. Tetrahedron Lett. 2004, 45,
6457e6460; (b) Banerjee, S.; Ghosh, S.; Sinha, S.; Ghosh, S. J. Org. Chem.
2005, 70, 4199e4202; (c) Ghosh, S.; Sinha, S.; Drew, M. G. B. Org. Lett. 2006,
8, 3781e3784; (d) Ghosh, S.; Bhaumik, T.; Sarkar, N.; Nayek, A. J. Org. Chem.
2006, 71, 9687e9694; (e) Maity, S.; Ghosh, S. Tetrahedron Lett. 2007, 48,
3355e3358; (f) Malik, C. K.; Ghosh, S. Org. Lett. 2007, 9, 2537e2540; (g)
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12. A portion of this work appeared as a preliminary communication: see Ref. 11.
13. Synthesis of a nine-membered lactone with E-olefinic geometry through RCM
has been reported recently. See: Ramirez-Fernandez, J.; Collado, I. G.; Her-
nandez-Galan, R. Synlett 2008, 3, 339e342.
Acknowledgements
14. Czernecki, S.; Gorson, G. Tetrahedron Lett. 1978, 19, 4113e4114.
15. Crystal data for compound 16: A plate shaped colorless crystal (0.3ꢂ0.24ꢂ0.08)
was analyzed. C15H20O5, Mr¼280.31, monoclinic, space group P2(1) (no. 4)
SG thanks the Department of Science and Technology (DST),
Government of India for a Ramanna Fellowship. MFH and CKM
thank CSIR, New Delhi for Research Fellowships. Financial support
from DST for National Single Crystal X-Ray Diffractometer facility at
Department of Inorganic Chemistry is gratefully acknowledged.
ꢀ
ꢀ
a¼10.337(4), b¼5.798(2), c¼13.054(5) A,
b
¼113.295(5), V¼718.6(5) A3,
T¼100 K, Z¼2. rcalcd¼1.295 g cmꢁ3. F(000)¼300,
l
(Mo K
a
)¼0.71073 A,
m Mo
s(I)) 187 pa-
ꢀ
K
a
/mmꢁ1¼0.097, 3193 reflections measured, 761 observed (I>2
rameters; Rint¼0.0345, R1¼0.0305; wR2¼0.0753 (I>2 (I)), R1¼0.0347; wR2¼0.
s
0780 (all data) with GOF¼1.045. X-ray single crystal data were collected using
ꢀ
Mo K
a
(l
¼0.7107 A) radiation on a SMART APEX diffractometer equipped with
CCD area detector. The structure was solved by direct method and refined in
a routine manner. Crystallographic data for compound 16 has been deposited
with the Cambridge Crystallographic Data Center as supplementary publication
no. CCDC 708798. Copies of the data can be obtained, free of charge, on ap-
plication to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK. Fax: þ44 1223
336033. e-mail: deposit@ccdc.cam.ac.uk.
Supplementary data
Supplementary data associated with this article can be found
online at doi:10.1016/j.tet.2010.09.084. These data include MOL
files and InChIKeys of the most important compounds described in
this article.
16. The ground state energy calculations for the oxonenes 19, 20 and 21 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,
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