[6+3] Cycloaddition of pentafulvenes with 3-oxidopyrylium betaine: a novel methodology toward the synthesis of 5-8 fused oxabridged cyclooctanoids

Article abstract of DOI:10.1016/j.tet.2006.04.017

Pentafulvenes undergo a facile [6+3] cycloaddition with 3-oxidopyrylium betaine, generated from the corresponding pyranulose acetate, leading to the formation of 5-8 fused oxabridged cyclooctanoids. The product is formed by a [6+3] cycloaddition, followed

Full text of DOI:10.1016/j.tet.2006.04.017

Tetrahedron 62 (2006) 5952–5961
[6+3] Cycloaddition of pentafulvenes with 3-oxidopyrylium
betaine: a novel methodology toward the synthesis
of 5–8 fused oxabridged cyclooctanoids
c
K. Syam Krishnan,a V. S. Sajisha,a S. Anas,a C. H. Suresh,b, Mohan M. Bhadbhade,
*
Gaurav V. Bhosekarc and K. V. Radhakrishnana,
*
aOrganic Chemistry Section of Chemical Sciences Division, Regional Research Laboratory (CSIR), Trivandrum 695 019, India
bComputational Modeling and Simulation Group, Regional Research Laboratory (CSIR), Trivandrum 695 019, India
cCenter for Materials Characterization, National Chemical Laboratory (CSIR), Pune 411008, India
Received 27 January 2006; revised 21 March 2006; accepted 6 April 2006
Available online 5 May 2006
Abstract—Pentafulvenes undergo a facile [6+3] cycloaddition with 3-oxidopyrylium betaine, generated from the corresponding pyranulose
acetate, leading to the formation of 5–8 fused oxabridged cyclooctanoids. The product is formed by a [6+3] cycloaddition, followed by a
1,5-hydrogen shift of the initially formed [6+3] adduct. The reaction was found to be general and a number of fulvenes with a wide range
of substituents at the exocyclic double bond, that is, at the C6 position followed a similar reactivity pattern. The [6+3] adduct, a 5–8 fused
oxabridged cyclooctanoid, is potentially amenable to a number of synthetic transformations due to the presence of an a,b-unsaturated ketone
and cyclopentadiene part. By selecting appropriately substituted fulvene and pyranulose acetates, it is possible to use this methodology for the
synthesis of a wide range of 5–8 fused cyclooctanoids. The experimental results have been rationalized on the basis of theoretical calculations.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
O
O
H
The synthesis of cyclooctanoids is of great importance in
organic chemistry due to their wide occurrence in many
biologically active natural products and synthetic com-
pounds.1 The interesting biological activities combined with
the synthetic challenges have served to make them target
molecules in a number of synthetic studies.2 Some of the
interesting cyclooctanoids are shown in Figure 1. Designing
efficient, short routes for the stereoselective construction
of cyclooctanoids is an interesting challenge in synthetic
organic chemistry. Among the various strategies for the syn-
thesis of eight-membered rings,3 higher order cycloadditions
that directly form eight-membered rings4 are attractive
because of their ability to produce complex molecules with
extensive functionality in a single step, with good control
over the creation of new stereocentres.
O
OH
HO
H
O
O
H
Dactylol
Spartidienedione Asteriscanolide
OH
HO
OH
O
H
OAc
OH
H
H
O
H
OH
H
Acetoxycrenulide
Cycloaraneosene
Kalmanol
Figure 1. Some of the biologically active cyclooctanoids.
Fragmentation of complex bicyclic systems, metal mediated
metathesis, and acyclic ring closures are the commonly
used methodologies.6 [3,3]-Sigmatropic rearrangements of
smaller rings to such skeletons have gained popularity be-
cause of the high stereoselectivity observed.6 Transition
metal mediated cycloadditions provide another interesting
route to cyclooctanoids.7
Eight-membered rings are notoriously difficult to prepare
because of unfavorable entropic and enthalpic effects as
well as the propensity for transannular interactions.5
Keywords: Fulvenes; Oxidopyrylium betaine; [6+3] Cycloaddition;
Oxabridged cyclooctanoids.
Fulvenes, cyclic molecules with an odd number of carbon
atoms in the ring, belong to the category of non-functionalized
* Corresponding authors. Tel.: +91 471 2515275; fax: +91 471 2491712;
e-mail: radhupreethi@rediffmail.com
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.04.017

K. S. Krishnan et al. / Tetrahedron 62 (2006) 5952–5961
5953
carbon–carbon double bonds.8 Among various fulvenes, pen-
Ph
Ph
Ph
Ph
tafulvenes represent a very attractive structural unit, not only
as a model for theoretical studies but also as a valuable build-
ing block to access polycyclic cyclopentanoids through a
diverse array of cyclizations.9 The development of efficient
and short routes for the stereoselective construction of poly-
cyclic molecules is currently one of the main challenges in
synthetic organic chemistry. Pentafulvenes have been the sub-
ject of great interest both from synthetic and theoretical points
because they exhibit different modes of cycloadditions. In
cycloadditions, pentafulvenes can participate as a 2p, 4p, or
6p component10 and have served as excellent synthons for
the synthesis of triquinanes, pyrindines, etc. Investigations
from our own laboratory have unraveled the interesting
reactivity profile of fulvenes in cycloaddition reactions.11
Barluengaandco-workershavereporteda[6+3]cycloaddition
of Fischer carbene complexes10l with fulvenes. Recent reports
from Hong and co-workers have shown that fulvenes can
undergo [6+3] cycloaddition with azomethine ylides leading
O
O
Et3N (Dry)
CHCl3(Dry)
O
3
AcO
O
O
O
1
4
2
70 %
1,5-H shift
Ph
Ph
O
O
1a
Scheme 1.
The product 1a was characterized on the basis of spec-
troscopic data. The IR spectrum showed characteristic
absorptions at 1691 cmꢀ1, indicating the presence of an
a,b-unsaturated carbonyl, and at 1077 cmꢀ1 indicative of
the ether linkage. In the 1H NMR spectrum, the two protons
at C1 appeared as a singlet at d 3.06 ppm. Two bridgehead
protons resonated as a singlet and doublet at d 4.88 and
5.36 ppm, respectively. The protons at C5 and C6 appeared
as a doublet and double doublet at d 5.76 and 5.99 ppm, re-
spectively. 13C NMR spectroscopy showed a characteristic
signal for a carbonyl group at d 194.5 ppm. The bridgehead
carbons appeared at d 76.6 and 74.9 ppm. Unambiguous
evidence for the structure and stereochemistry of the product
was obtained by single crystal X-ray analysis16 (Fig. 2). The
product 1a is formed by a [6+3] cycloaddition followed by
a 1,5-hydrogen shift.
12
to the formation of [2]pyrindines and other molecules of
biological importance.
3-Oxidopyrylium betaines13 have been well utilized in
the synthesis of cycloheptanoids.13,14 Hendrickson has re-
ported the generation and cycloaddition of oxidopyrylium
betaine with a few electrophilic alkenes leading to oxabi-
cyclo[3.2.1] systems.14 Later Sammes has demonstrated
the utility of oxidopyrylium betaines for the synthesis of
oxabicyclic systems by cycloaddition with electron rich
and electron deficient alkenes.13 Wender has exploited the
intermolecular cycloaddition of 4-methoxy and 4-silyloxy-
3-oxidopyrylium betaines in the construction of phorbol
framework.15 To the best of our knowledge, there is no re-
port on the cycloaddition of pentafulvenes with 3-oxido-
pyrylium betaines.
Similar reactivity was observed with different 6,6-diaryl ful-
venes and the results are summarized in Table 1. 6,6-Diaryl
fulvenes afforded [6+3] adducts on reaction with 3-oxido-
pyrylium betaines in good to excellent yield.
Recently, we have reported a [6+3] cycloaddition of penta-
fulvenes with 3-oxidopyrylium betaines.16 We have carried
out detailed investigation of the reported reaction with
a number of pentafulvenes having wide range of substituents
at the exocyclic double bond, that is, at the C6 position. The
theoretical calculations were carried out to rationalize the
results obtained. The details of our studies are presented in
the following section.
C22
C21
C16
C23
C20
C17
C15
2. Results and discussion
C18
C19
C12
2.1. [6+3] Cycloaddition of 6,6-diaryl fulvenes with
3-oxidopyrylium betaine
C14
C8
C13
The fulvenes selected for our studies were synthesized from
the corresponding ketone or aldehyde following Little’s pro-
cedure.17 The pyranulose acetates,18 precursors for 3-oxido-
pyrylium betaines, were synthesized from corresponding
furfuryl alcohol by oxidation with N-bromosuccinimide fol-
lowed by protection with acetic anhydride in the presence of
pyridine and DMAP.
C7
C10
C9
C6
C2
O1
C5
C11
C1
C4
C3
Our initial experiments involved the reaction of 6,6-diaryl-
fulvene 3 with 3-oxidopyrylium betaine 2. The reaction
proceeded smoothly affording the [6+3] adduct 1a in 70%
yield (Scheme 1).
O2
Figure 2. ORTEP plot for X-ray crystal structure of 1a.

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K. S. Krishnan et al. / Tetrahedron 62 (2006) 5952–5961
Table 1. [6+3] Cycloaddition of 6,6-diaryl fulvenes with 3-oxidopyrylium
betaines
Table 2. [6+3] Cycloaddition of 6,6-dimethyl fulvene with 3-oxidopyrylium
betaines
Entry Pyranulose
acetate
Fulvene
Product
Yield
[%]
Entry Pyranulose acetate
Fulvene
Product
Yield [%]
Me
Me
Me
Me
Me
Me
O
O
1
83
O
O
AcO
AcO
AcO
O
O
O
O
O
1
70
O
1b
AcO
AcO
O
O
Me
Me
O
O
O
Me
Me
O
1a
O
2
3
79
68
2b
Me
Me
2
62
O
O
O
O
2a
3b
Reaction conditions: fulvene (1.0 equiv), pyranulose acetate (1.2 equiv),
Et3N (1.2 equiv), CHCl3, 50 ꢁC, 6 h.
O
3
53
O
AcO
O
Table 3. [6+3] Cycloaddition of cycloalkyl fulvenes with 3-oxidopyrylium
betaines
3a
Entry
Pyranulose acetate
Fulvene
Product
Yield [%]
Cl
Cl
Cl
Cl
O
O
1
70
O
4
57
AcO
AcO
O
O
AcO
O
O
1c
O
O
O
4a
O
O
O
Reaction conditions: fulvene (1.0 equiv), pyranulose acetate (1.2 equiv),
Et3N (1.2 equiv), CHCl3, 50 ꢁC, 6 h.
2
3
4
60
58
59
O
2c
2.2. [6+3] Cycloaddition of 6,6-dimethyl fulvene with
3-oxidopyrylium betaines
O
6,6-Dimethyl fulvene showed a similar reactivity pattern and
the results are summarized in Table 2. The unsubstituted
3-oxidopyrylium betaine 2 on reaction with 6,6-dimethyl
fulvene afforded [6+3] adduct in 83% yield. 2-Methyl and
2-isopropyl substituted 3-oxidopyrylium betaine also
afforded [6+3] adducts in good yield.
AcO
AcO
AcO
O
O
3c
O
O
2.3. [6+3] Cycloaddition of cycloalkyl fulvenes with
3-oxidopyrylium betaines
O
4c
Cycloalkyl fulvenes (6,6-pentamethylene, hexamethylene,
and heptamethylene fulvenes), prepared from the corre-
sponding cyclic ketones, also followed a similar reaction
pathway and the results obtained with various substituted
betaines are summarized in Table 3.
O
5
O
52
O
O
5c
2.4. [6+3] Cycloaddition of 6-alkyl,6-aryl fulvenes and
6-aryl fulvenes with 3-oxidopyrylium betaines
Reaction conditions: fulvene (1.0 equiv), pyranulose acetate (1.2 equiv),
Et3N (1.2 equiv), CHCl3, 50 ꢁC, 6 h.
6-Alkyl,6-aryl fulvenes and 6-aryl fulvenes also underwent
smooth [6+3] cycloaddition leading to the functionalized
5–8 fused cyclooctanoids in good to excellent yield. The
results are summarized in Tables 4 and 5.
From the results summarized in Tables 1–5, it is clear that
pentafulvenes undergo facile [6+3] cycloaddition with
3-oxidopyrylium betaines leading to the regioselective for-
mation of 5–8 fused cyclooctanoids in good to excellent

K. S. Krishnan et al. / Tetrahedron 62 (2006) 5952–5961
Table 4. [6+3] Cycloaddition of 6-alkyl,6-aryl fulvenes with 3-oxidopyry-
lium betaines
5955
O
H
O
O
H
O
O
H
O
O
H
O
H
H
Entry Pyranulose
acetate
Fulvene
Product
Yield [%]
O
O
H
O
O
O
O
H
HO
O
H
O
H
OH
OH
H
Me
O
OH
O
O
O
Lancifodilactone G
Anti-HIV active
Me
Lancifodilactone E
1
67
O
AcO
AcO
AcO
O
O
O
O
1d
O
O
H
O
O
O
OH
O
H
H
O
H
O
OH
H
O
O
O
O
2
3
54
50
O
H
O
H
O
H
O
OH
H
O
O
H
O
H
O
H
OH
2d
O
Lancifodilactone B
Lancifodilactone C
Cl
Cl
Figure 3. Examples of oxabridged cyclooctanoid natural products.
Me
Me
amenable to a number of synthetic transformations. It is pre-
sumed that by using appropriately functionalized fulvenes
and oxidopyrylium betaines, the present methodology can
be utilized in the synthesis of fused oxabridged cycloocta-
noid natural products.
O
O
3d
Reaction conditions: fulvene (1.0 equiv), pyranulose acetate (1.2 equiv),
Et3N (1.2 equiv), CHCl3, 50 ꢁC, 6 h.
We have carried out theoretical calculations to rationalize
the results obtained and are discussed in the following
section.
Table 5. [6+3] Cycloaddition of 6-aryl fulvenes with 3-oxidopyrylium
betaines
Entry Pyranulose acetate
Fulvene
Product
Yield [%]
3. Theoretical calculations
H
O
H
O
All the molecular geometries were optimized at the DFT
level by using the Becke’s three-parameter exchange func-
tional (B3)20,21 in conjunction with the Lee–Yang–Parr cor-
relation functional (LYP)22 as implemented in the Gaussian
03 suite of programs.23 For H, C, and O, 6-31G(d) basis
functions were selected.24 Normal coordinate analysis has
been performed for all stationary points to characterize the
transition states and minimum structures. The calculated
Gibbs’ free energy changes were used throughout the text
for discussing the energetics.
1
65
AcO
AcO
O
O
1e
O
O
H
H
H
O
2
3
50
45
O
2e
H
O
Several modes of cycloaddition reactions between fulvene
and 3-oxidopyrylium betaine can be envisioned. At first,
using unsubstituted fulvene and the 3-oxidopyrylium betaine
shown in Figure 4, we have investigated the 18 different pos-
sible cycloaddition products. The structure and energetics of
these cycloadducts are depicted in Figure 5.
O
AcO
O
O
3e
Reaction conditions: fulvene (1.0 equiv), pyranulose acetate (1.2 equiv),
Et3N (1.2 equiv), CHCl3, 50 ꢁC, 6 h.
The optimized geometry of fulvene shows two localized
˚
double bonds of length 1.353 A each in the ring and another
yield. The reaction is applicable to a wide range of fulvenes
with substituents at C6 position, i.e., at the exocyclic double
bond.
˚
one of 1.344 A in the exo position (Fig. 4a). The exo double
bond is more localized than the ring double bonds, which is
consistent with the experimental geometry.25 In the case of
3-oxidopyrylium betaine, the C2–C3 and C3–C4 bonds are
significantly longer than other bonds (Fig. 4b) as well as
The adducts obtained may be transformed to fused eight-
membered rings, which is the main structural skeleton of
a number of natural products such as dactylol, asteriscano-
lide, cycloaraneosene, kalmanol, etc (Fig. 1). A survey of
the literature showed that some of the naturally occurring
oxabridged cyclooctanoids possess interesting biological
activity such as cytotoxicity and anti-HIV activity (Fig. 3).19
The presence of an a,b-unsaturated ketone, an oxabridge
and the cyclopentadiene functionality makes these adducts
˚
a typical C–C aromatic bond (1.400 A), which means that
the schematic structure given in Figure 4c is quite suitable
for this molecule. The dotted lines represent a 6p electron
conjugation, which includes two electrons from ring oxygen
as in the case of furan molecule. However, compared to furan
26
˚
where the C–O bond lengths are 1.369 A, the bonding
around the ring oxygen in the oxidopyrylium betaine

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K. S. Krishnan et al. / Tetrahedron 62 (2006) 5952–5961
O
O
(a)
(b)
(c)
(d)
Figure 4. Optimized structure of (a) fulvene and (b) 3-oxidopyrylium betaine. (c) Schematic structure of 3-oxidopyrylium betaine and (d) MESP painted on the
˚
van der Waals’ surface of betaine. Bond lengths in A. See text for details.
1
-22.2
2
-21.6
3
-17.4
4
-17.0
5
-15.7
6
-15.2
7
-13.3
8
-12.6
9
-4.6
10 -3.0
11 -2.4
12 0.1
13 0.9
14 1.8
15 3.3
16 5.7
17 6.5
18 9.5
Figure 5. Optimized geometries of various cycloadducts (values in italics are relative free energy in kcal/mol). The sum of the free energies of fulvene and
3-oxidopyrylium betaine is taken as 0.0 kcal/mol.

K. S. Krishnan et al. / Tetrahedron 62 (2006) 5952–5961
5957
is stronger. The molecular electrostatic potential (MESP)
analysis was carried out on the oxidopyrylium betaine to
understand its p-electron distribution.27 It is found that the
negative MESP is centered around the carbonyl oxygen
and no negative MESP is observed over the ring region
(Fig. 4d). This suggests a zwitterionic structure for this mol-
ecule wherein the carbonyl oxygen and the ring oxygen
would bear the negative and positive charges, respectively.
in Figure 7. Interestingly, 20 is more stable than 19 by
1.9 kcal/mol and as noted in the previous paragraph, this
can be attributed to the stereoelectronic effect of the phenyl
groups. The TSs TS4 and TS5 are also located for the forma-
tion of 19 and 20, respectively. TS5 is 11.7 kcal/mol lower
in energy than TS4, which further confirms the stereoselec-
tive formation of 20. Moreover, the activation barrier of
22.2 kcal/mol obtained from TS5 for the [6+3] cycloaddi-
tion is quite reasonable for a feasible reaction as compared
to a higher activation barrier of 33.9 kcal/mol obtained
from TS4. It may be noted that the steric effect is in favor
of the less stable TS TS4 because a closer approach of
the reactants is found in this TS as compared to TS5.
Therefore, the higher stability of TS5 and the corresponding
product 20 can be attributed mainly to the electronic effect.
The same conclusion can be obtained even from the unsub-
stituted systems as one can see a higher stability of 11.7 kcal/
mol for TS2 than TS1. This difference should come mainly
from the electronic effect because the steric effect is nearly
the same or negligible in both the TSs. Also obtained is a TS
TS6 for the 1,5-hydrogen shift starting from 20 and the
corresponding product 21 (Fig. 7). The activation energy
of 26.6 kcal/mol is predicted for this step of the reaction.
Among the 18 cycloadducts given in Figure 5, the structures
1, 2, 5, and 6 are formed as a result of [6+3] cycloaddition in
which the atoms C2 and C6 of both fulvene and 3-oxido-
pyrylium betaine are reacted. Compound 1 is formed from
endo-cycloaddition giving rise to C2(fulvene)–C6(betaine) and
C6(fulvene)–C2(betaine) bond formations while 2, also an
endo-cycloaddition product is formed by the C2(fulvene)
–
C2(betaine) and C6(fulvene)–C6(betaine) bond formations.
Similarly, 5 and 6 are obtained by the exo-cycloadditions.
Clearly, the endo-cycloaddition products are more stable
than exo- and all other cycloaddition products. The transition
states (TSs) TS1 and TS2 are also located for the cycloaddi-
tion corresponding to the formation of 1 and 2, respectively
(Fig. 6). A relative free energy of 19.1 kcal/mol is obtained
for TS1 while it is 7.4 kcal/mol for TS2. This suggests that
compound 2 is the most favored product in cycloaddition
step of the reaction. It may be noted that in the experiment,
predominantly only one product is formed and in the case of
the reaction of 6,6-diphenyl fulvene, the X-ray structure of
the product is also available (Fig. 2). This product can be
considered as formed from 2 (except for the substituent
phenyl groups) when it undergoes a 1,5-hydrogen shift of
the H atom, which was originally bonded to the C2 atom
of fulvene. For the 1,5-hydrogen shift starting from 2, a TS
TS3 is also located which gives an activation barrier of
16.7 kcal/mol for it (Fig. 6). Thus, the theoretical study using
the unsubstituted systems strongly support the stereoselec-
tive formation of the product shown in Figure 2. Since in
the calculation 1 is 0.6 kcal/mol more stable than 2, we
expect that in the experiment the stereoelectronic effect
exerted by the phenyl groups may give additional stability
to the cycloadduct 2 than 1. In order to understand this sub-
stituent effect, further modeling study is carried out for the
reaction of 6,6-diphenyl fulvene and the 3-oxidopyrylium
betaine.
4. Conclusion
In conclusion, we have unraveled a novel reactivity pattern
of pentafulvenes with 3-oxidopyrylium betaines. It offers
a useful methodology for the synthesis of 5–8 fused cyclo-
octanoids. The theoretical studies have confirmed a highly
stereospecific endo-cycloaddition giving rise to C2(fulvene)
–
C2(betaine) and C6(fulvene)–C6(betaine) bond formations. The
intermediate product thus formed (20) undergoes a facile
1,5-hydrogen shift at the five-membered ring of fulvene
unit to yield the cyclooctanoid system 21 (Fig. 6), which
is in complete agreement with the X-ray structure of the
product reported in Figure 2. The reaction was found to be
general and a number of fulvenes with a wide range of sub-
stituents at the exocyclic double bond, that is, at the C6
position followed similar reactivity pattern. The [6+3]
adduct, a 5–8 fused oxabridged cyclooctanoid, is potentially
amenable to a number of synthetic transformations due to the
presence of an a,b-unsaturated ketone and cyclopentadiene
part. By selecting appropriately substituted fulvene and pyr-
anulose acetate, it is possible to use this methodology for the
synthesis of a wide range of 5–8 fused cyclooctanoids.
The optimized geometry of the cycloadducts 19 and 20
which are similar to 1 and 2, respectively, are presented
TS1 19.1
TS2 7.4
TS3 16.7
Figure 6. Optimized geometries of transition states. TS1 and TS2 are for the formation of 1 and 2, respectively, and TS3 for the 1,5-hydrogen shift. The sum of
the free energies of fulvene and oxidopyrylium betaine is taken as 0.0 kcal/mol.

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K. S. Krishnan et al. / Tetrahedron 62 (2006) 5952–5961
TS4 33.9
19 -2.1
TS5 22.2
20 -4.0
TS6 26.6
21 -2.2
Figure 7. Optimized geometries of the TSs (TS4 and TS5) and products (19 and 20) for [6+3] cycloaddition as well as the TS (TS6) and product (21) for
1,5-hydrogen shift. Relative free energy values with respect to the sum of the free energies of 6,6-diphenyl fulvene and 3-oxidopyrylium betaine are given
in italics.
Further work to utilize this methodology toward the synthe-
sis of biologically active oxabridged cyclooctanoids is in
progress and will be reported in due course.
silica gel column chromatography. NMR spectra were
recorded at 300 (1H) and 75 (13C) MHz on a Brucker
¨
DPX-300 MHz spectrometer. Chemical shifts (d) were
reported relative to TMS (1H) and CDCl3 (13C) as the inter-
nal standards. Coupling constants (J) are reported in Hertz
(Hz). IR spectra were recorded on a Bomem MB Series
FTIR spectrophotometer. Melting points were recorded on
a Buchi melting point apparatus and are uncorrected.
Fulvenes were prepared according to the literature proce-
dure.17 Pyranulose acetates,18 precursors for 3-oxidopyry-
lium betaines, were prepared from corresponding furfuryl
alcohol by oxidation with N-bromosuccinimide followed
by protection with acetic anhydride in presence of pyridine
and DMAP. Commercial grade solvents were distilled prior
5. Experimental
5.1. General
All reactions were carried out in oven-dried glasswares
under an atmosphere of argon. Progress of reactions was
monitored by thin layer chromatography (Silica gel 60
F254, 0.25 mm, Merck) and purification was effected using

K. S. Krishnan et al. / Tetrahedron 62 (2006) 5952–5961
5959
to use. Triethylamine, chloroform and diethyl ether were
dried as per the standard procedures.
d 193.9, 147.6, 143.9, 140.5, 140.3, 134.4, 133.8, 133.6,
132.7, 131.5, 130.5, 130.3, 129.7, 128.9, 128.7, 128.6,
123.5, 74.7, 51.8, 40.8. HRMS (EI): m/z calcd for
C23H16O2Cl2: 394.0527. Found: (M+) 394.0509.
5.1.1. Details of a typical experiment are as follows.
Diphenyl fulvene (100 mg, 0.43 mmol), pyranulose acetate
(81 mg, 0.52 mmol) and dry triethylamine (52 mg,
0.52 mmol) were taken in anhydrous chloroform and stirred
at 50 ꢁC in a Schlenk tube for 6 h under nitrogen. The solvent
was removed under reduced pressure and the residue was
subjected to chromatography on a silica gel (60–120 mesh)
column using 5% ethyl acetate/hexane mixture as eluent
to afford the product as a pale yellow crystalline solid
(98 mg, 70%). The product 1a was recrystallized from
dichloromethane/hexane mixture.
5.2.5. Compound 1b. Yield 83%, pale yellow solid. Mp
:
110–112 ꢁC. Rf 0.45 (7:3 hexane/EtOAc). IR (KBr) nmax
2963, 2917, 1702, 1468, 1379, 1243, 1159, 1069, 896,
1
769 cmꢀ1. H NMR: d 1.13 (s, 3H), 1.43 (s, 3H), 2.79–
3.07 (m, 2H), 4.29 (d, 1H, J¼4.1 Hz), 4.74 (s, 1H), 5.92
(d, 1H, J¼10.2 Hz), 6.32 (d, 1H, J¼4.2 Hz), 6.41 (s, 1H),
6.97 (dd, 1H, J1¼4.1 Hz, J2¼10.2 Hz). 13C NMR: d 193.0,
147.4, 133.9, 131.5, 129.9, 129.7, 123.9, 77.0, 76.5, 40.5,
39.2, 29.3, 22.7. HRMS (EI): m/z calcd for C13H14O2:
202.0994. Found: (M+) 202.0999. Anal. Calcd for
C13H14O2: C, 77.20; H, 6.98. Found: C, 77.18; H, 7.35.
5.2. Spectroscopic data for new compounds
5.2.1. Compound 1a. Yield 70%, pale yellow crystalline
solid. Mp 173–175 ꢁC. Rf 0.50 (7:3 hexane/EtOAc). IR
(KBr) nmax: 3062, 2928, 1691, 1598, 1443, 1376, 1247,
5.2.6. Compound 2b. Yield 79%, pale yellow solid. Mp
:
124–126 ꢁC. Rf 0.51 (7:3 hexane/EtOAc). IR (KBr) nmax
2963, 2937, 1687, 1442, 1370, 1206, 1172, 1059, 902,
1
1
1160, 1077, 1036, 943 cmꢀ1. H NMR: d 3.06 (s, 2H),
770 cmꢀ1. H NMR: d 1.13 (s, 3H), 1.39 (s, 3H), 1.48 (s,
4.88 (s, 1H), 5.36 (d, 1H, J¼4.3 Hz), 5.76 (d, 1H,
J¼10.4 Hz), 5.99 (dd, 1H, J1¼4.3, J2¼10.4 Hz), 6.44 (d,
1H, J¼5.3 Hz), 6.56 (d, 1H, J¼5.3 Hz), 7.00–7.54 (m,
10H). 13C NMR: d 194.5, 148.5, 145.8, 142.3, 141.4,
133.9, 132.9, 132.3, 129.3, 129.0, 128.6, 128.4, 128.3,
128.2, 127.3, 126.4, 123.2, 76.6, 74.9, 52.7, 40.7. HRMS
(EI): m/z calcd for C23H18O2: 326.1307. Found: (M+)
326.1323. Anal. Calcd for C23H18O2: C, 84.64; H, 5.56.
Found: C, 84.37; H, 5.41.
3H), 2.75–3.04 (m, 2H), 4.31 (d, 1H, J¼4.2 Hz), 5.88 (d,
1H, J¼10.3 Hz), 6.28 (s, 1H), 6.39 (d, 1H, J¼10.7 Hz),
6.91 (dd, 1H, J1¼4.2 Hz, J2¼10.3 Hz). 13C NMR: d 196.4,
147.1, 133.9, 130.1, 124.1, 123.9, 123.7, 76.9, 76.1, 39.7,
38.4, 29.7, 22.7, 19.2. HRMS (EI): m/z calcd for
C14H16O2: 216.1150. Found: (M+) 216.1122.
5.2.7. Compound 3b. Yield 68%, pale yellow solid. Mp
:
178–180 ꢁC. Rf 0.56 (7:3 hexane/EtOAc). IR (KBr) nmax
2963, 2937, 1687, 1442, 1370, 1206, 1172, 1059, 902,
1
5.2.2. Compound 2a. Yield 62%, pale yellow crystalline
solid. Mp 213–215 ꢁC. Rf 0.48 (7:3 hexane/EtOAc). IR
(KBr) nmax: 3061, 2929, 1692, 1596, 1491, 1446, 1262,
770 cmꢀ1. H NMR: d 0.78 (d, 3H, J¼6.6 Hz), 0.88 (d,
3H, J¼6.6 Hz), 1.22 (s, 3H), 1.41 (s, 3H), 2.64–2.97 (m,
3H), 4.25 (d, 1H, J¼4.2 Hz), 5.81 (d, 1H, J¼10.3 Hz),
6.21 (s, 1H), 6.29–6.36 (m, 1H), 6.80–6.85 (dd, 1H,
J1¼4.2, J2¼10.3 Hz). 13C NMR: d 196.4, 146.8, 134.0,
131.4, 129.9, 125.3, 125.0, 85.1, 76.6, 39.5, 37.7, 30.9,
29.8, 23.6, 16.4, 16.3. HRMS (EI): m/z calcd for
C16H20O2: 244.1463. Found: (M+) 244.1469.
1
1157, 1069, 1024, 947 cmꢀ1. H NMR: d 1.56 (s, 3H),
2.98 (s, 2H), 5.35 (d, 1H, J¼4.2 Hz), 5.73 (d, 1H,
J¼10.3 Hz), 5.94 (dd, 1H, J1¼4.2, J2¼10.3 Hz), 6.42 (d,
1H, J¼5.1 Hz), 6.55 (d, 1H, J¼5.2 Hz), 7.00–7.57 (m,
10H). 13C NMR: d 196.1, 148.3, 146.2, 142.5, 141.4,
137.9, 132.9, 132.5, 129.5, 129.2, 128.8, 128.5, 128.3,
128.3, 128.2, 127.2, 126.4, 123.3, 79.6, 75.8, 52.6, 39.9,
20.4. HRMS (EI): m/z calcd for C24H20O2: 340.1463.
Found: (M+) 340.1490.
5.2.8. Compound 1c. Yield 70%, pale yellow viscous liquid.
Rf 0.53 (7:3 hexane/EtOAc). IR (KBr) nmax: 3067, 2953,
1702, 1620, 1455, 1377, 1157, 1128, 1067, 980, 940 cmꢀ1
.
1H NMR: d 0.88–1.26 (m, 8H), 2.89–2.99 (m, 2H), 4.34
(d, 1H, J¼4.1 Hz), 4.73 (s, 1H), 5.91 (d, 1H, J¼10.4 Hz),
6.36 (d, 1H, J¼5.2 Hz), 6.42 (d, 1H, J¼5.2 Hz), 6.93 (dd,
1H, J1¼4.1, J2¼10.4 Hz). 13C NMR: d 194.9, 146.8,
133.9, 130.5, 129.7, 123.8, 77.2, 74.5, 40.7, 32.9, 31.6,
26.0, 24.5. HRMS (EI): m/z calcd for C15H16O2: 228.1150.
Found: (M+) 228.1133.
5.2.3. Compound 3a. Yield 53%, pale yellow solid. Mp
:
193–195 ꢁC. Rf 0.43 (7:3 hexane/EtOAc). IR (KBr) nmax
2918, 2851, 1687, 1460, 1383, 1209, 1176, 1069, 900,
1
760 cmꢀ1. H NMR: d 0.70 (d, 3H, J¼6.8 Hz), 0.99 (d,
3H, J¼6.6 Hz), 2.58–2.68 (m, 1H), 2.95 (s, 2H), 5.38 (d,
1H, J¼4.3 Hz), 5.75 (d, 1H, J¼10.3 Hz), 5.95 (dd, 1H,
J1¼4.3, J2¼10.3 Hz), 6.43 (d, 1H, J¼5.3 Hz), 6.52 (d, 1H,
J¼5.3 Hz), 6.96–7.56 (m, 10H). 13C NMR: d 196.2, 147.8,
146.1, 142.7, 142.1, 137.1, 132.9, 132.3, 129.0, 128.4,
128.3, 128.1, 128.0, 127.9, 126.9, 126.1, 124.3, 84.8, 75.2,
39.4, 30.8, 16.3, 16.1. HRMS (EI): m/z calcd for
C26H24O2: 368.1776. Found: (M+) 368.1773.
5.2.9. Compound 2c. Yield 60%, pale yellow solid. Mp
125–127 ꢁC. Rf 0.50 (7:3 hexane/EtOAc). IR (KBr) nmax
:
3070, 2933, 1691, 1612, 1454, 1378, 1245, 1157, 1067,
996, 943 cmꢀ1. 1H NMR: d 1.25–1.79 (m, 10H), 2.81–3.07
(m, 2H), 4.71 (s, 1H), 4.84–4.87 (m, 1H), 5.94 (d, 1H,
J¼10.5 Hz), 6.29–6.34 (m, 1H), 6.39–6.47 (m, 1H), 6.96–
7.06 (m, 1H). 13C NMR: d 194.9, 147.2, 133.8, 130.2,
129.5, 123.8, 123.7, 76.5, 70.4, 40.6, 39.7, 36.4, 31.7,
25.7, 22.2, 22.1. HRMS (EI): m/z calcd for C16H18O2:
242.1307. Found: (M+) 242.1321. Anal. Calcd for
C16H18O2: C, 79.31; H, 7.49; O, 13.21. Found: C, 79.69;
H, 4.08.
5.2.4. Compound 4a. Yield 57%, pale yellow viscous liquid.
Rf 0.71 (7:3 hexane/EtOAc) IR (KBr) nmax: 2956, 2927,
1
1691, 1495, 1379, 1252, 1098, 1074, 1015, 906 cmꢀ1. H
NMR: d 3.07 (s, 2H), 4.88 (s, 1H), 5.28 (d, 1H, J¼4.3 Hz),
5.79 (d, 1H, J¼10.4 Hz), 6.02 (dd, 1H, J1¼4.3 Hz,
J2¼10.4 Hz), 6.47 (s, 2H), 6.89–7.47 (m, 8H). 13C NMR:

5960
K. S. Krishnan et al. / Tetrahedron 62 (2006) 5952–5961
5.2.10. Compound 3c. Yield 58%, pale yellow viscous liq-
uid. Rf 0.69 (7:3 hexane/EtOAc). IR (KBr) nmax: 2928, 2856,
J1¼4.2, J2¼10.3 Hz), 6.20 (d, 1H, J¼5.3 Hz), 6.47 (d, 1H,
J¼4.9 Hz), 7.10–7.29 (m, 4H). 13C NMR: d 194.0, 148.7,
134.3, 132.2, 129.8, 129.7, 124.0, 123.7, 121.4, 121.1,
78.3, 76.4, 41.7, 30.6, 27.3. HRMS (EI): m/z calcd for
C18H15ClO2: 298.0761. Found: (M+) 298.0788.
1
1697, 1459, 1377, 1248, 1161, 1068, 924, 733 cmꢀ1. H
NMR: d 1.29–1.81 (m, 12H), 2.89–3.07 (m, 2H), 4.71 (s,
1H), 4.84–4.87 (m, 1H), 5.94 (d, 1H, J¼10.5 Hz), 6.28–
6.34 (m, 1H), 6.39–6.48 (m, 1H), 6.97–7.07 (m, 1H). 13C
NMR: d 193.4, 147.7, 133.9, 131.2, 130.7, 124.0, 123.8,
77.3, 76.3, 43.7, 40.1, 38.7, 34.2, 31.3, 30.5, 23.9, 23.6.
HRMS (EI): m/z calcd for C17H20O2: 256.1463. Found:
(M+) 256.1451.
5.2.16. Compound 1e. Yield 65%, pale yellow crystalline
solid. Mp. 99–101 ꢁC. Rf 0.49 (7:3 hexane/EtOAc). IR
(KBr) nmax: 3065, 2928, 1692, 1605, 1492, 1377, 1248,
1154, 1069, 995, 944 cmꢀ1 1H NMR: d 2.82–3.21 (m,
.
2H), 3.57 (d, 1H, J¼8.7 Hz), 4.69 (d, 1H, J¼4.0 Hz), 4.93
(s, 1H), 5.96 (d, 1H, J¼10.4 Hz), 6.19 (d, 1H, J¼5.2 Hz),
6.42 (d, 1H, J¼4.8 Hz), 7.06 (dd, 1H, J1¼4.0, J2¼
10.4 Hz), 7.14–7.30 (m, 5H). 13C NMR: d 194.9, 146.9,
133.8, 132.6, 129.6, 128.9, 128.8, 127.9, 127.2, 123.9,
123.7, 76.6, 73.7, 42.9, 40.6. HRMS (EI): m/z calcd for
C17H14O2: 250.0994. Found: (M+) 250.0991.
5.2.11. Compound 4c. Yield 59%, pale yellow viscous liq-
uid. Rf 0.59 (7:3 hexane/EtOAc). IR (KBr) nmax: 3066, 2932,
2859, 1691, 1621, 1453, 1370, 1257, 1174, 1057, 938,
1
900 cmꢀ1. H NMR: d 1.35–1.70 (m, 13H), 2.84–3.05 (m,
2H), 4.89 (d, 1H, J¼4.3 Hz), 5.90 (d, 1H, J¼10.3 Hz),
6.40–6.46 (m, 2H), 6.97 (dd, 1H, J1¼4.3, J2¼10.3 Hz).
13C NMR: d 196.2, 148.0, 146.9, 133.6, 130.9, 130.4,
124.1, 76.5, 71.9, 40.3, 35.1, 33.2, 31.7, 26.3, 22.6, 22.3,
21.8. HRMS (EI): m/z calcd for C17H20O2: 256.1463.
Found: (M+) 256.1467.
5.2.17. Compound 2e. Yield 50%, pale yellow viscous liq-
uid. Rf 0.52 (7:3 hexane/EtOAc). IR (KBr) nmax: 2928, 2851,
1694, 1460, 1388, 1249, 1176, 1072, 909, 749 cmꢀ1
.
1H NMR: d 1.26 (s, 3H), 2.86–3.03 (m, 2H), 4.28–4.34
(m, 1H), 4.90–4.95 (m, 1H), 5.92 (d, 1H, J¼10.3 Hz), 6.12
(d, 1H, J¼5.3 Hz), 6.34–6.40 (m, 1H), 6.39–6.43 (m, 1H),
7.00–7.28 (m, 5H). 13C NMR: d 196.9, 146.9, 134.2,
132.8, 132.6, 129.6, 128.9, 128.8, 127.9, 127.2, 123.8,
123.7, 76.3, 74.0, 44.9, 40.5, 20.6. HRMS (EI): m/z calcd
for C18H16O2: 264.1150. Found: (M+) 264.1164.
5.2.12. Compound 5c. Yield 52%, pale yellow viscous liq-
uid. Rf 0.61 (7:3 hexane/EtOAc). IR (KBr) nmax: 2933, 2861,
1
1681, 1537, 1454, 1259, 1259, 1184, 1069, 749 cmꢀ1. H
NMR: d 0.79 (d, 3H, J¼6.8 Hz), 0.93 (d, 3H, J¼6.6 Hz),
1.25–1.59 (m, 10H), 2.55–2.59 (m, 1H), 2.86–3.07 (m,
2H), 4.87–4.90 (m, 1H), 5.89 (d, 1H, J¼10.3 Hz), 6.27 (s,
1H), 6.40–6.42 (m, 1H), 6.91–6.95 (m, 1H). 13C NMR:
d 196.9, 146.5, 133.6, 131.4, 130.2, 129.1, 125.2, 70.5,
39.5, 35.1, 32.9, 31.4, 25.6, 22.2, 21.9, 16.3, 15.9. HRMS
(EI): m/z calcd for C19H24O2: 284.1776. Found: (M+)
284.1776.
5.2.18. Compound 3e. Yield 45%, pale yellow viscous liq-
uid. Rf 0.47 (7:3 hexane/EtOAc). IR (KBr) nmax: 2969, 2928,
1
1692, 1460, 1388, 1249, 1176, 1074, 909, 749 cmꢀ1. H
NMR: d 0.86 (d, 3H, J¼7.0 Hz), 0.96 (d, 3H, J¼6.6 Hz),
2.66–2.73 (m, 1H), 2.97–3.05 (m, 2H), 4.35–4.38 (m, 1H),
4.94–4.98 (m, 1H), 5.93 (d, 1H, J¼10.3 Hz), 6.14 (d, 1H,
J1¼5.3 Hz), 6.31–6.36 (m, 1H), 6.39–6.43 (m, 1H), 7.05–
7.33 (m, 5H). 13C NMR: d 196.2, 147.8, 146.1, 142.7,
137.1, 132.9, 132.3, 129.0, 128.4, 128.3, 128.1 127.9,
126.9, 126.1, 124.3, 84.8, 75.2, 39.4, 30.8. HRMS (EI):
m/z calcd for C20H20O2: 292.1463. Found: (M+) 292.1464.
5.2.13. Compound 1d. Yield 67%, pale yellow viscous liq-
uid. Rf 0.51 (7:3 hexane/EtOAc). IR (KBr) nmax: 3063, 2927,
1693, 1602, 1490, 1370, 1240, 1116, 1072, 991, 940 cmꢀ1
.
1H NMR: d 1.84 (s, 3H), 3.12 (s, 2H), 4.51 (dd, 1H,
J1¼0.9, J2¼4.3 Hz), 4.83 (s, 1H), 5.78 (d, 1H,
J¼10.5 Hz), 6.08 (dd, 1H, J1¼4.3, J2¼10.5 Hz), 6.27 (d,
1H, J¼5.3 Hz), 6.46 (d, 1H, J¼5.3 Hz), 7.17–7.33 (m,
5H). 13C NMR: d 194.5, 148.6, 143.9, 140.9, 133.4, 133.0,
131.8, 128.7, 128.4, 127.9, 127.5, 127.2, 122.9, 77.4, 76.6,
44.5, 40.9, 26.5. HRMS (EI): m/z calcd for C18H16O2:
264.1150. Found: (M+) 264.1156.
Acknowledgements
K.S.K., V.S.S. and S.A. thank Council of Scientific and
Industrial Research (CSIR), New Delhi for Junior Research
Fellowship. The authors thank Dr. R. Luxmi Varma, Ms. S.
Viji, Ms. Saumini Mathew and Mr. Thirumalai Kumaran
for the NMR and high-resolution mass spectral analysis.
Thanks are due to CSIR, New Delhi for financial assistance
(Task force project (CMM-005) on specialty chemicals.
5.2.14. Compound 2d. Yield 54%, pale yellow solid. Mp
:
55–57 ꢁC. Rf 0.56 (7:3 hexane/EtOAc). IR (KBr) nmax
2963, 2937, 1687, 1442, 1370, 1206, 1172, 1059, 902,
1
770 cmꢀ1. H NMR: d 1.11–1.41 (m, 7H), 3.07–3.27 (m,
2H), 4.58 (d, 1H, J¼4.1 Hz), 4.78 (s, 1H), 5.73 (d, 1H,
J¼10.3 Hz), 6.00 (dd, 1H, J1¼4.1, J2¼10.3 Hz), 6.38 (d,
1H, J¼4.9 Hz), 6.49 (d, 1H, J¼4.9 Hz), 7.13–7.28 (m,
5H). 13C NMR: d 194.4, 148.8, 139.6, 139.5, 133.5, 131.9,
128.5, 127.9, 126.9, 122.8, 77.8, 76.4, 59.5, 45.3, 38.1,
31.2, 29.6, 26.6. HRMS (EI): m/z calcd for C21H20O2:
304.1463. Found: (M+) 304.1487.
References and notes
1. (a) Oishi, T.; Ohtsuks, Y. Studies in Natural Products Synthesis;
Atta-ur-Rahman, Ed.; Elsevier: Amsterdam, The Netherlands,
1989; Vol. 3, p 73; (b) Rigby, J. H. Studies in Natural
Products Synthesis; Atta-ur-Rahman, Ed.; Elsevier: Amster-
dam, The Netherlands, 1993; Vol. 12, p 233.
2. For reviews of the construction of cycloctanoid systems, see (a)
Mehta, G.; Singh, V. Chem. Rev. 1999, 99, 881; (b) Petasis,
N. A.; Petane, M. A. Tetrahedron 1992, 48, 5757.
5.2.15. Compound 3d. Yield 50%, pale yellow viscous liq-
uid. Rf 0.37 (7:3 hexane/EtOAc). IR (KBr) nmax: 2963, 2937,
1
1687, 1442, 1370, 1206, 1172, 1059, 902, 770 cmꢀ1. H
NMR: d 1.82 (s, 3H), 3.12 (s, 2H), 4.47 (d, 1H, J¼4.2 Hz),
4.83 (s, 1H), 5.80 (d, 1H, J¼10.3 Hz), 6.11 (dd, 1H,

K. S. Krishnan et al. / Tetrahedron 62 (2006) 5952–5961
5961
3. Molander, G. A. Acc. Chem. Res. 1998, 31, 603.
13. (a) Sammes, P. G.; Street, L. J. J. Chem. Soc., Perkin Trans. 1
1983, 1261; (b) Sammes, P. G. Gazz. Chim. Ital. 1986, 51,
1573.
14. Hendrickson, J. B.; Farina, J. S. J. Org. Chem. 1980, 45, 3359.
15. Wender, P. A.; Kogen, H.; Lee, H. Y.; Munger, J. D.;
Wilhelm, R. S., Jr.; Williams, P. D. J. Am. Chem. Soc. 1989,
111, 8957.
16. Radhakrishnan, K. V.; Krishnan, K. Syam; Bhadbhade, M. M.;
Bhosekar, G. V. Tetrahedron Lett. 2005, 46, 4785.
17. Stone, K. J.; Little, R. D. J. Org. Chem. 1984, 49, 1849.
18. Georgiadis, M. P.; Couladouros, E. A. J. Org. Chem. 1986, 51,
2725.
19. (a) Li, R. T.; Zhao, Q. S.; Li, S. H.; Han, Q. B.; Sun, H. D.; Lu,
Y.; Zhang, L. L.; Zheng, Q. T. Org. Lett. 2003, 5, 1023; (b) Li,
R. T.; Li, S. H.; Zhao, Q. S.; Lin, Z. W.; Sun, H. D.; Lu, Y.;
Wang, C.; Zheng, Q. T. Tetrahedron Lett. 2003, 44, 3531; (c)
Xiao, W. L.; Li, R. T.; Li, S. H.; Li, X. L.; Sun, H. D.;
Zheng, Y. T.; Wang, R. R.; Lu, Y.; Wang, C.; Zheng, Q. T.
Org. Lett. 2005, 7, 1263; (d) Li, R. T.; Xiang, W.; Li, S. H.;
Lin, Z. W.; Sun, H. D. J. Nat. Prod. 2004, 67, 94.
4. (a) Davis, R. E.; Dodds, T. A.; Hesu, T. H.; Wagnon, J. C.;
Devon, T.; Tancrede, J.; McKennis, J. S.; Pettit, R. J. Am.
Chem. Soc. 1974, 96, 7562; (b) Fischler, I.; Grevels, F.;
Leitich, J.; Ozkar, S. Chem. Ber. 1991, 124, 2857; (c)
Chaffee, K.; Sheridan, J. B.; Aistars, A. Organometallics
1992, 11, 18; (d) Wender, P. A.; Correa, A. G.; Sato, Y.;
Sun, R. J. Am. Chem. Soc. 2000, 122, 7815; (e) Wender,
P. A.; Gamber, G. G.; Hubbard, R. D.; Zhang, L. J. Am.
Chem. Soc. 2002, 124, 2876; (f) Wender, P. A.; Ihle, N. C.
J. Am. Chem. Soc. 1986, 108, 4678; (g) Wender, P. A.; Nuss,
J. M.; Smith, D. B.; Suarez-Sobrino, A.; Vagberg, J.;
Decosta, D.; Bordner, J. J. Org. Chem. 1997, 62, 4908; (h)
Ma, B.; Snyder, J. K. J. Org. Chem. 2001, 66, 6943; (i)
Evans, P. A.; Robinson, J. E.; Baum, E. W.; Fazal, A. N.
J. Am. Chem. Soc. 2002, 124, 8782; (j) Gilbertson, S. R.;
DeBoef, B. J. Am. Chem. Soc. 2002, 124, 8784; (k) Delgado,
A.; Castedo, L.; Mascarenas, J. L. Org. Lett. 2002, 4, 3091.
5. Iiiuminati, G.; Mandolini, L. Acc. Chem. Res. 1981, 14, 95.
6. Mehta, G.; Singh, V. Chem. Rev. 1999, 99, 881.
7. (a) Rigby, J. H.; Short, K. M.; Ateeq, H. S.; Henshil wood, J. A.
J. Org. Chem. 1992, 57, 5290; (b) Rigby, J. H.; Mann, L. W.;
Myers, B. J. Tetrahedron Lett. 2001, 42, 8773; (c) Wender,
P. A.; Correa, A. G.; Sato, Y.; Sun, R. J. Am. Chem. Soc.
2000, 122, 7815; (d) Wender, P. A.; Ihle, N. C. J. Am. Chem.
Soc. 1986, 108, 4678; (e) See Ref. 4j.
8. Neuenschwander, M. The Chemistry of Double Bonded Func-
tional Groups; Patai, S., Ed.; Wiley: Chichester, UK, 1989;
Vol. 2, p 1131.
20. Becke, A. D. Phys. Rev. A 1988, 38, 3098.
21. Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
22. Lee, C. T.; Yang, W. T.; Parr, R. G. Phys. Rev. B 1988, 37,
785–789.
23. 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.;
Bakken, V.; 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 C.02; Gaussian: Wallingford, CT, 2004.
24. Hariharan, P. C.; Pople, J. A. Mol. Phys. 1974, 27, 209.
25. Norman, N.; Post, B. Acta Crystallogr. 1961, 14, 503.
26. Fourme, R. Acta Crystallogr. Sect. B: Struct. Crystallogr.
Cryst. Chem. 1972, 28, 2984.
27. (a) Politzer, P.; Truhlar, D. G. Chemical Applications of Atomic
and Molecular Electrostatic Potentials; Plenum: New York,
NY, 1981; (b) Gadre, S. R.; Shirsat, R. N. Electrostatics of
Atoms and Molecules; Universities Press: Hyderabad, 2000;
(c) Suresh, C. H.; Gadre, S. R. J. Org. Chem. 1999, 64, 2505;
(d) Suresh, C. H.; Gadre, S. R. J. Am. Chem. Soc. 1998, 120,
7049; (e) Suresh, C. H.; Koga, N.; Gadre, S. R. J. Org.
Chem. 2001, 66, 6883.
9. Hong, B.-C.; Gupta, A. K.; Wu, M.-F.; Liao, J.-H. Tetrahedron
Lett. 2004, 45, 1663.
10. For [2+2], see (a) Imafuku, K.; Arai, K. Synthesis 1989, 501;
(b) Paquette, L. A.; Colapret, J. A.; Andrews, D. R. J. Org.
Chem. 1985, 50, 201; For [4+2] see (c) Harre, M.; Raddatz,
P.; Walenta, R.; Winterfeldt, E. Angew. Chem., Int. Ed. Engl.
1982, 21, 480; (d) Gleiter, R.; Borzyk, O. Angew. Chem., Int.
Ed. Engl. 1995, 34, 1001; For [2+4], see (e) Himeda, Y.;
Yamataka, H.; Ueda, I.; Hatanaka, M. J. Org. Chem. 1997,
62, 6529; For [6+4], see (f) Gupta, Y. N.; Doa, M. J.; Houk,
K. N. J. Am. Chem. Soc. 1982, 104, 7336; (g) Yoshida, Z.-I.;
Shibata, M.; Ogino, E.; Sugimoto, T. Angew. Chem., Int. Ed.
Engl. 1985, 24, 60; For [6+2] and [6+3], see (h) Hong, B.-C.;
Shr, Y. J.; Wu, J. L.; Gupta, A. K.; Lin, K. Org. Lett. 2002, 4,
2249; (i) Suda, M.; Hafner, K. Tetrahedron Lett. 1977, 2543;
(j) Wu, T. C.; Houk, K. N. J. Am. Chem. Soc. 1985, 107,
5308; (k) Hong, B.-C.; Sun, S. S.; Tsai, Y. C. J. Org. Chem.
1997, 62, 7717; (l) Barluenga, J.; Martinez, S.; Suarez-
Sobrino, A. L.; Tomas, M. J. Am. Chem. Soc. 2001, 123, 11113.
11. (a) Nair, V.; Nair, A. G.; Rahdakrishnan, K. V.; Nandakumar,
M. V.; Rath, N. P. Synlett 1997, 767; (b) Nair, V.; Anilkumar,
G.; Radhakrishnan, K. V.; Nandakumar, M. V.; Kumar, S.
Tetrahedron 1997, 53, 15903; (c) Nair, V.; Jayan, C. N.;
Radhakrishnan, K. V.; Anilkumar, G.; Rath, N. P. Tetrahedron
2001, 57, 5807.
12. (a) Hong, B.-C.; Gupta, A. K.; Wu, M.-F.; Liao, J.-H.
Tetrahedron Lett. 2004, 45, 1663; (b) Hong, B.-C.; Gupta,
A. K.; Wu, M.-F.; Liao, J.-H. Org. Lett. 2003, 5, 1689.