Synthesis of annulated oxa-triquinanes and oxa-diquinanes via cascade Michael addition-intramolecular alkylation involving α-halodicyclopentadienones

Article abstract of DOI:10.1016/j.tet.2017.01.003

Base Mediated Michael addition of 1,3-dicarbonyl compounds to α-halodicyclopentadienones followed by cyclization of the intermediate Michael adducts leads to novel annulated dihydrofurans as single diastereomers. Such fused dihydrofurans, which are also oxa-triquinanes and oxa-diquinanes, undergo retro-Diels-Alder reaction to give cyclopentadiene-eliminated products in excellent yield. Certain 1,3-dicarbonyl compounds exhibited a different reactivity profile with α-halodicyclopentadienones leading to spiro-cyclopropanes fused to dicyclopentadiene skeleton.

Full text of DOI:10.1016/j.tet.2017.01.003

Accepted Manuscript
Synthesis of annulated oxa-triquinanes and oxa-diquinanes via cascade Michael
addition-intramolecular alkylation involving α-halodicyclopentadienones
Sohan Lal, Irishi N.N. Namboothiri
PII:
S0040-4020(17)30003-0
10.1016/j.tet.2017.01.003
TET 28373
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 12 November 2016
Revised Date: 2 January 2017
Accepted Date: 3 January 2017
Please cite this article as: Lal S, Namboothiri INN, Synthesis of annulated oxa-triquinanes and oxa-
diquinanes via cascade Michael addition-intramolecular alkylation involving α-halodicyclopentadienones,
Tetrahedron (2017), doi: 10.1016/j.tet.2017.01.003.
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Synthesis of annulated oxa-triquinanes and oxa-diquinanes via cascade Michael addition-
intramolecular alkylation involving α-halodicyclopentadienones
Sohan Lal, Irishi N. N. Namboothiri*
Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400 076, India

ACCEPTED MANUSCRIPT
1
Tetrahedron
journal homepage: www.elsevier.com
Synthesis of annulated oxa-triquinanes and oxa-diquinanes via cascade Michael
addition-intramolecular alkylation involving α-halodicyclopentadienones
Sohan Lal, Irishi N. N. Namboothiri*
aDepartment of Chemistry, Indian Institute of Technology Bombay, Mumbai 400 076, India
ARTICLE INFO
ABSTRACT
Base Mediated Michael addition of 1,3-dicarbonyl compounds to α-halodicyclopentadienones
followed by cyclization of the intermediate Michael adducts leads to novel annulated
dihydrofurans as single diastereomers. Such fused dihydrofurans, which are also oxa-triquinanes
and oxa-diquinanes, undergo retro-Diels-Alder reaction to give cyclopentadiene-eliminated
products in excellent yield. Certain 1,3-dicarbonyl compounds exhibited a different reactivity
profile with α-halodicyclopentadienones leading to spiro-cyclopropanes fused to
dicyclopentadiene skeleton.
Article history:
Received
Received in revised form
Accepted
Available online
Keywords:
Halodicyclopentadienone
1,3-Dicarbonyl compounds
Michael addition
Dihydrofurans
2009 Elsevier Ltd. All rights reserved.
Oxa-triquinanes
1. Introduction
2,3-dihydrofuran fused enone moiety is part of
meroterpenoids8 and advanced intermediates in the synthesis
Functionalized and fused furans are remarkable structural
entities that are abundant in numerous natural products and
designed molecules of biological significance.1 The
dihydrofuran moiety, in particular, is an extremely useful
synthetic intermediate and is present in many plants and
marine organisms.2 Dihydrofurans are key substrates in the
preparation of functionalized tetrahydrofurans with high
stereoselectivity.3 Annulated 2,3-dihydrofurans have been
reported to function as flavoring agents and exhibit
insecticidal and fish antifeedant properties.4
of Maoecrystal9 and HIV protease inhibitors (Figure 1).10
Due to the presence of dihydrofuran moiety in bioactive
molecules, including natural products, considerable efforts
have been made towards the development of various
approaches to its construction from readily available
reactants and reagents. These approaches include
intramolecular cyclization of intermediates arising from
Michael addition,11 interrupted Feist-Benary reaction,12
nucleophilic ring opening,13 aldol condensation,5,14 radical
mediated coupling15 and other miscellaneous methods.16
From another perspective, endo-dicyclopentadiene is an
excellent substrate for the synthesis of triquinane terpenoids
such as hirsutene, coriolin etc possessing a cis-anti-cis fused
cyclopentane
framework.17
The
corresponding
dicyclopentadienone18 has also been employed in the
synthesis of sesquiterpenoids,19 pyranone based natural
product sibrinone,20 optically pure cross-conjugated
cyclopentadienones,21
and
polycarbocyclic
cage
compounds.22 Although the dienophilic reactivity of α-
halodicyclopentadienone has been investigated,23 the
possibility of its other annulation pathways remained
unexplored.24 In particular, a cascade Michael addition-
Figure 1. Selected dihydrofuran fused enone containing
bioactive compounds
The 2,3-dihydrofuran moiety is an integral part of bioactive
molecules such as histamine H4R antagonist,5 α-
chymotrypsin inhibitor6 and aflatoxins,7 to name a few. A
intramolecular
alkylation,
involving
α-
halodicyclopentadienone with various 1,3-dicarbonyl
compounds leading to fused dihydrofurans, remains
unreported, to our knowledge, despite its tremendous
1

ACCEPTED MANUSCRIPT
2
Tetrahedron
potential in the stereoselective synthesis of complex
cyclization (entry 7). Longer reaction time (48-50 h) and/or
polycycles.
lower yields (65-72%) were encountered with solvents such
as CH3CN and less polar solvents such as DCM and toluene
(entries 8-10). Finally, the optimization studies confirmed
that 2 equiv of Cs2CO3 as base in THF as solvent constitute
the best conditions for our reaction.
In the above scenario, we intended to investigate the
application of α-halodicyclopentadienones as key substrates
in the cascade Michael-alkylation with 1,3-dicarbonyl
compounds for the stereoselective synthesis of novel
annulated 2,3-dihydrofurans. Such 2,3-dihydrofurans,
extending to an oxa-polyquinane skeleton, due to extensive
ring fusion, are attractive intermediates for the synthesis of
complex molecules including natural products.
The scope of the above reaction was investigated first with
enone 1a as the representative acceptor and various cyclic
and open chain 1,3-dicarbonyls
2 as the donors (Table 2).
Besides dimedone 2a which delivered the highly
functionalized polycycle 3a in 98% yield, cyclohexanedione
2b reacted with 1a to afford the product 3b in 92% yield in 2
h. Acetylacetone 2d and ethylacetoacetate 2e also reacted
with 1a over 1-4 h and furnished the products 3d and 3e
respectively in good (67-72%) yield. Although
benzoylacetophenone 2g required long reaction time (5 d), it
too provided the corresponding fused polycycle 3g in
satisfactory (50%) yield. On the other hand,
hydroxynaphthaquinone 2i did not react with 1a under our
experimental conditions and also upon reflux for 2 days.
2. Results and discussion
We started the synthesis of dihydrofuran containing
polycycles via Michael addition of 1,3-dicarbonyl
compounds to halodicyclopentadienones under mild
conditions.
α
-Bromoenone 1a25 and dimedone 2a were
chosen as the model substrates (Table 1).
Table 1. Optimization of reaction conditionsa
Surprisingly, treatment of 1a with cyclopentan-1,3-dione 2c
Meldrum’s acid 2f and indan-1,3-dione 2h did not lead to
the expected fused product . Instead, the spiro compounds
4c 4f and 4h were formed in good to excellent yield (61-
93%).
,
3
,
entry
base (equiv)
solvent
time
% Yieldb
Table 2. Scope of 1,3-dicarbonyls
1
K2CO3 (2)
Cs2CO3 (2)
DABCO (2)
DMAP (2)
DBU (2)
THF
5 h
93
98
88
86
91
90
98c
94
65
72
2
THF
THF
15 min
22 h
24 h
50 min
48 h
48 h
50 h
48 h
50 h
3
4
THF
5
THF
6
NEt3 (2)
THF
7
Cs2CO3 (1)
Cs2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (2)
THF
8
CH3CN
DCM
Toluene
9
10
aThe reactions were carried out with 0.3 mmol of α-bromoenone 1a and
b
0.36 mmol of 1,3-dicarbonyl compound 2a. Yield after purification by
trituration with 5% EtOAc-petroleum ether. cα-Bromoenone 1a was
consumed within 30 min and the Michael adduct obtained was further
converted to final product 3a by adding an additional equiv of base.
To our delight, the reaction proceeded smoothly in THF at
room temperature with 2 equiv of K2CO3 as base affording
3a in 93% yield in 5 h (entry 1). The effect of base on the
rate of reaction and product yield was evaluated by
screening Cs2CO3 and amine bases such as DABCO, DMAP,
DBU and Et3N (entries 2-6). With 2 equiv of Cs2CO3 as base
the reaction was complete within 15 min to furnish the
product in 98% yield (entry 2). Among organic bases DBU
was superior both in terms of reaction time (50 min) and
product yield (91%, entry 5) while others required longer
time (22-48 h) and the yield remained ≤90% (entries 3-4 and
6). Having confirmed Cs2CO3 to be the best base, we
proceeded to investigate the quantity of base required and
the effect of solvent (entries 7-10). With one equiv of
Cs2CO3, the reaction stopped at the Michael addition stage
and an additional equivalent was required to complete the
aThe reactions were carried out with 0.3 mmol of α-bromoenone 1a and
b
0.36 mmol of 1,3-dicarbonyl compound
2. Yield after purification by
trituration with 5-10% EtOAc-petroleum ether or silica gel column
chromatography.
The diketone 1b 25-26
exceptionally well with dimedone 2a and afforded the fused
polycycle in 98% yield in just 10 min (Scheme 1).
,
derived from enone 1a, also reacted
5

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3
The yields of polycycles 8c
,
8d and 8f, derived from
iodoenone 7a and 1,3-dicarbonyl compounds 2d
,
2e and
curcumin analog 2j were also good (70%, 68% and 65%
respectively) although the reaction times were short (2 h and
6 h) for the formation of 8c and 8d and long (5 d) for the
formation of 8f
.
The reaction of 7a with
benzoylacetophenone 2g was also sluggish (5 d) delivering
the desired product 8e in moderate yield (45%). Further, the
reaction of iodoenone 7b with representative 1,3-dicarbonyl
compounds, viz dimedone 2a, cyclohexanedione 2b and
acetylacetone 2d was investigated. This led to the formation
Scheme 1
Subsequently, iododicyclopentadienones 7a-b were readily
prepared from known dicyclopentadienones 6a-b18,25
(Scheme 2).
of polycycles 8g, 8h and 8i in 98%, 90% and 75% yields
X
X
X
X
respectively. That the reaction pathway (fused dihydrofuran
vs spirocyclopropane) is sensitive to the nature of 1,3-
dicarbonyl compounds as observed in the case of enone 1a
K2CO3 , DMAP, I2
THF: H2O (1:1), RT
I
O
is reflected in the case of enone 7 as well. Thus the reaction
O
6a: X = H
6b: XX = OCH2CH2O
7a: 8 h, 86%
7b: 12 h, 71%
of 7a with indan-1,3-dione 2h afforded the
spirocyclopropane 9j in 85% yield.
Scheme 2. Preparation of iodoenones
The structure and stereochemistry of the fused products
and spiro products were unambiguously established by
single crystal X-ray analysis of representative compounds
The reactivity of 7a-b with various 1,3-dicarbonyl
compounds was then investigated (Table 3). Thus
2
3b, 4f and 8a (Table 4).
iodoenone 7a reacted smoothly with dimedone 2a and
cyclohexanedione 2b and afforded the corresponding fused
polycycles 8a and 8b in excellent yield (98% and 90%
respectively).
Table 4. Single crystal X-ray structures and selected data
for 3b
,
4f and 8a
Table 3. Scope of enone and 1, 3-dicarbonyls
3b
4f
8a
CCDC No
Empirical
formula
Formula weight
T [K]
1513035
C18H17BrO5
1513047
C18H17BrO7
1513046
C18H20O3
393.23
425.22
284.34
100(2) K
0.71073
monoclinic
P 1 21/n 1
10.1122(3)
22.0892(5)
21.5138(5)
90
150(2) K
0.71073
monoclinic
P 21/c
13.2374(5)
11.7385(5)
11.2250(4)
90
100(2) K
0.71070
monoclinic
P 1 21/c 1
9.126(2)
6.5778(15)
23.812(5)
90
λ [Å]
Crystal system
Space group
a [Å]
b [Å]
c [Å]
aThe reactions were carried out with 0.3 mmol of
7b and 0.36 mmol of 1,3-dicarbonyl compound
α
-bromoenone 7a or
bYield after
2.
purification by trituration with 2-5% EtOAc-petroleum ether or silica
gel column chromatography.
α [°]
β [°]
97.673
104.070(4)
92.039(4)
3

ACCEPTED MANUSCRIPT
4
Tetrahedron
γ [°]
90
4747(2)
12
1.645
2.615
90
90
Alder reaction of representative dihydrofurans 8a and 8d
V [Å3]
Z
1691.89(12)
4
1.669
2.469
864
3.236 to 24.996
-5<=h<=14,
-13<=k<=13,
-13<=l<=13
1428.5(5)
4
(Scheme 4). Thus refluxing pentacycle 8a in diphenyl ether
for 45 min led to the formation of fused tricycle 10a in
excellent yield. Under the same conditions, tetracycle 8d
afforded fused bicycle 10d in 85% yield.
ρcalcd [mg/m3]
ꢀ [mm-1]
F(000)
θ [°]
1.322
0.089
608
2400
3.02 to 29.18
-12<=h<=12,
-26<=k<=26,
-25<=l<=25
4.47 to 25.00
-10<=h<=10,
-7<=k<=7,
-28<=l<=28
Index ranges
Reflections
collected
74458
7873
16705
Independent
reflections
8360 [R(int) =
0.0852]
2960 [R(int) =
0.0294]
2493 [R(int) =
0.0432]
Completeness to 99.7 %
99.6 %
99.2 %
theta
Refinement
method
θ = 29.18°
Full-matrix least-
squares
θ = 24.996°
Full-matrix
least-squares on least-squares
θ = 25.00°
Full-matrix
2
2
2
on F
F
on F
Data / restraints / 8360 / 0 / 649
parameters
2960 / 0 / 243
2493 / 0 / 190
1.057
Goodness-of-fit
1.061
0.917
2
Scheme 4. Retro-Diels-Alder reaction
on F
Final R indices
[I>2sigma(I)]
R indices (all
data)
R1 = 0.0403,
wR2 = 0.1002
R1 = 0.0487, wR2
= 0.1060
R1 = 0.0249
wR2 = 0.0604
R1 = 0.0272
wR2 = 0.0621
0.346 and -
0.269
R1 = 0.0383,
wR2 = 0.0977
R1 = 0.0430,
wR2 = 0.1014
0.284 and -0.187
3. Conclusions
Largest diff. peak 10.835 and
-3 -5.520
and hole ([e Å ])
In conclusion, α-halodicyclopentadienones reacted with
various open chain and cyclic 1,3-dicarbonyl compounds
under basic conditions to afford dihydrofuran containing
linear tetracycles and pentacycles as single diastereomers in
good to excellent yields in most cases. The reaction
sequence involved Michael addition of the 1,3-dicarbonyl
compound to α-halodicyclopentadienone followed by
enolization and intramolecular nucleophilic substitution of
the halogen (O-alkylation). However, the reaction of α-
halodicyclopentadienones with 1,3-dicarbonyls such as
cyclopentan-1,3-dione, indan-1,3-dione and Meldrum’s acid
led to the formation of spirocyclopropanes. Selected
polycycles have been successfully transformed to fused and
functionalized oxadiquinanes through retro-Diels-Alder
reaction under thermal conditions.
A mechanism for the formation of fused dihydrofurans 3/8
and spiro-cyclopropanes 4/9 is proposed in Scheme 3. Thus,
base mediated 1,4-addition of β-dicarbonyl compound
enone 1/7 generates the intermediate Michael adduct whose
keto and enol forms and II, respectively, are in tautomeric
equilibrium. While intramolecular O-alkylation of in a 5-
2 to
I
I
exo-tet fashion delivers the fused product 3/8 through an
overall [3+2] annulation, intramolecular C-alkylation of II
in a 3-exo-tet fashion leads to cyclopropanes 4/9 in an
overall [2+1] annulation.
R
R
O
R
R
R
R
O
H
O
X
H
X
X
H
H
H
Base
Base
+
O
5-exo-tet
Cyclization
Michael
Addition
H
X
O
O
X
4. Experimental section
H
H
O
H
O
O
I
1/7
3/8
4.1. General experimental details.
R
R
O
H
R
X
R
X
O
H
H
Base
The melting points recorded are uncorrected. NMR spectra
1
1
1
(1H, H decoupled 13C, APT and H- H NOESY, COSY,
1H-13C HSQC) were recorded with TMS as the internal
standard. The coupling constants (J values are given in Hz).
High resolution mass spectra were recorded under ESI Q-
3-exo-tet
Cyclization
O
H
X
H
H
H
O
O
O
II
4/9
Scheme 3. Proposed mechanism
TOF conditions. X-ray data were collected on
a
diffractometer equipped with graphite monochromated Mo
Kα radiation. The structure was solved by direct methods
shelxs97 and refined by full-matrix least squares against F2
Although 2a and majority of other β-dicarbonyl compounds
exhibited 1,3-binucleophilic character and afforded fused
dihydrofurans 3/8, cyclopentanedione 2c, Meldrum’s acid 2f
and indanedione 2h displayed a different reactivity profile,
using shelxl97 software. α-Bromoenone 1a was synthesized
from readily available cyclopentanone in four steps as
reported by Chapman and co-workers.25 Diketone 1b was
synthesized in five steps from cyclopentanones as reported
in the literature.25,26 Enones 6a18 and 6b25,27 were also
prepared by literature procedures.
1,1-binucleophilic character, and delivered
spiro
compounds 4c 4f 4h and 9j. This is attributable to the
,
,
geometric constraints associated with the intermediate
Michael adducts to undergo oxa-Michael addition.
Finally, synthesis of fused and functionalized
oxadiquinanes was successfully carried out via retro-Diels-

ACCEPTED MANUSCRIPT
5
NMR (CDCl3, 125 MHz) δ 28.1, 29.2, 34.3, 37.8, 41.9, 48.6,
4.2. General procedure for the synthesis of α-iodoenones
(7a-b) 28
50.6, 51.5, 52.3, 65.9, 66.6, 68.5, 87.8, 112.0, 126.2, 133.6,
138.1, 176.0, 194.2, 216.0; HRMS calcd for C20H22BrO5 (MH+)
421.0645, found 421.0644.
.
To a solution of enone
6 (3.5 mmol, 1 equiv, 511 mg of 6a
or 714 mg of 6b) in THF: H2O (1:1, 20 mL) was added
K2CO3 (731 mg, 5.3 mmol, 1.5 equiv) and DMAP (128 mg,
1.05 mmol, 0.3 equiv) followed by molecular iodine (1.058
g, 4.2 mmol, 1.2 equiv). After completion of reaction (8 h
for 7a and 12 h for 7b), monitored by TLC), saturated
aqueous sodium sulfite (10 mL) was added and the aqueous
4.3.2.
10-Bromo-3,4,5a,6a,7,10,10a,10b-octahydro-1H-spiro
[7,10-methanoindeno[2,1-b]benzofuran-11,2'-[1,3]dioxolane]-
1,6(2H)-dione (3b). White solid; 108 mg, 92%; mp 248-249 °C;
IR (neat, cm-1) 2964 (m), 2947 (m), 2894 (m), 1749 (vs), 1650
(vs), 1630 (vs), 1392 (s), 1270 (s), 1148 (m), 1022 (w), 743 (w);
1H NMR (CDCl3, 500 MHz) δ 2.01 (m, 2H), 2.34-2.47 (m, 4H),
2.95-2.97 (m, 1H), 3.14 (m, 1H), 3.62 (d, J = 8.4 Hz, 1H), 3.72
(d, J = 9.5 Hz, 1H), 3.88-3.93 (m, 1H), 3.94-4.00 (m, 1H), 4.18-
4.25 (m, 2H), 4.44 (d, J = 9.5 Hz, 1H), 6.20 (dd, J = 6.5, 3.7 Hz,
1H), 6.32 (d, J = 6.5, 1.1 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ
21.7, 24.0, 37.0, 42.0, 48.6, 50.6, 52.4, 65.9, 66.6, 68.5, 87.5,
113.4, 126.2, 133.6, 138.1, 177.0, 194.9, 215.2; HRMS calcd for
C18H17BrNaO5 (MNa+) 415.0152, found 415.0151; Selected X-
ray data: C18H17BrO5, M = 393.23, Monoclinic, space group P 1
21/n 1, a = 10.1122(3) Å, b = 22.0892(5) Å, c = 21.5138(5) Å, α
=90°, β = 97.673 (4)°, γ = 90°, V = 4747(2) Å3, Z = 12, ρcald =
layer was extracted with ethyl acetate (5
×
50 mL). The
10 mL),
combined organic layer was washed with brine (2
×
dried over anhydrous Na2SO4 and concentrated in vacuo.
The residue was purified by silica gel column
chromatography by eluting with 2-10% EtOAc-petroleum
ether.
4.2.1. 2-Iodo-3a,4,7,7a-tetrahydro-1H-4,7-methanoinden-1-
one (7a). Yellow solid; 818 mg, 86%; mp 51-52 °C; IR
(neat, cm-1) 3059 (w), 2980 (s), 2937 (m), 2869 (w), 1712
(vs), 1566 (w), 1298 (m), 1285 (m), 1276 (m), 1123 (w),
1019 (w), 961 (w), 743 (s), 726 (s), 691 (s); 1H NMR
3
-1
,
1.645 mg/m , F(000) = 2400, λ = 0.71073 Å, ꢀ = 2.615 mm
total/unique reflections 74458/8360. Final indices
[I>2sigma(I)]: R1 = 0.0403, wR2 = 0.1002. R (all data): R1 =
0.0487, wR2 = 0.1060.
=
R
(CDCl3, 500 MHz) δ 1.59 (d,
8.6 Hz, 1H), 2.85 (t, = 5.1 Hz, 1H), 2.99-3.01 (unresolved
m, 1H), 3.23-3.25 (unresolved m, 1H), 3.41-3.43 (m, 1H),
J = 8.6 Hz, 1H), 1.72 (d, J =
J
5.81 (dd,
7.70 (d,
J
J
= 5.5, 2.9 Hz, 1H), 5.89 (dd,
J = 5.5, 2.9 Hz, 1H),
4.3.3. 2'-Bromo-1a',1b',2',5',5a',6a'-hexahydro-6'H-dispiro[cyclo
pentane-1,1'-[2,5]methanocyclo-propa[a]indene-7',2''-
= 2.8 Hz, 1H); 13C NMR (CDCl3, 125 MHz)
δ
44.5, 45.3, 47.3, 50.2, 52.0, 104.6, 132.9, 132.9, 170.2,
204.1; HRMS calcd for C10H9INaO (MNa+) 294.9590, found
294.9591.
[1,3]dioxolane]-2,5,6'-trione (4c). White solid; 105 mg, 93%; mp
269-270 °C; IR (neat, cm-1) 2913 (w), 1735 (s), 1714 (vs), 1359
(m), 1269 (s), 1148 (m), 1089 (m), 1021 (w), 899 (w), 738 (w),
710 (w); 1H NMR (CDCl3, 500 MHz) δ 2.65 (d, J = 5.6 Hz, 1H),
2.77 (d, J = 5.6 Hz, 1H), 2.79-2.96 (m, 4H), 2.97-2.99 (m, 1H),
3.18 (d, J = 6.6 Hz, 1H), 3.56 (t, J = 6.0 Hz, 1H), 3.90-3.95 (m,
1H), 3.99-4.02 (m, 1H), 4.14-4.21 (m, 2H), 6.08 (dd, J = 6.5 Hz,
3.6 Hz, 1H), 6.23 (d, J = 6.5 Hz, 1H); 13C NMR (CDCl3, 125
MHz) δ 35.4, 36.4, 46.2, 46.3, 47.2, 48.0, 50.3, 54.0, 65.8, 66.6,
68.0, 126.3, 131.5, 135.4, 207.7, 209.1, 210.0; HRMS calcd for
C17H15BrNaO5 (MNa+) 400.9995, found 400.9983.
4.2.2. 2-Iodo-3a,4,7,7a-tetrahydro-1H-spiro[4,7-methanoindene-
8,2'-[1,3]dioxolan]-1-one (7b). Yellow solid; 820 mg, 71%; mp
97-98 °C; IR (neat, cm-1) 2983 (w), 2887 (w), 1709 (vs), 1565
(w), 1297 (vs), 1266 (m), 1100 (s), 1072 (s), 1006 (m), 728 (m),
693 (s); 1H NMR (CDCl3, 500 MHz) δ 2.82-2.85 (m, 1H), 3.02 (t,
J = 5.0 Hz, 1H), 3.04-3.06 (m, 1H), 3.59 (td, J = 4.7, 2.9 Hz, 1H),
3.81-3.84 (m, 2H), 3.92-3.94 (m, 2H), 5.92, 5.98 (ABqd, J = 6.4,
3.3 Hz, 2H), 7.69 (d, J = 2.9 Hz, 1H); 13C NMR (CDCl3, 125
MHz) δ 44.5, 47.2, 48.8, 49.8, 64.7, 65.2, 106.4, 127.2, 131.1,
131.1, 168.7, 203.2; HRMS calcd for C12H11INaO3 (MNa+)
352.9645, found 352.9644.
4.3.4.
3-Acetyl-4-bromo-2-methyl-3b,4,7,7a-tetrahydro-3aH-
spiro[4,7-methanoindeno[2,1-b]furan-9,2'-[1,3]dioxolan]-8
(8aH)-one (3d). White solid; 76 mg, 67%; mp 130-131 °C; IR
(neat, cm-1) 2984 (m), 2964 (m), 2899 (m), 1748 (vs), 1668 (s),
1615 (vs), 1597 (vs), 1383 (m), 1267 (s), 1221 (s), 1140 (m),
1023 (s), 930 (m), 733 (s); 1H NMR (CDCl3, 400 MHz) δ 2.16 (s,
3H), 2.37 (s, 3H), 2.95-2.98 (m, 1H), 3.11-3.15 (m, 1H), 3.40 (d,
J = 8.4 Hz, 1H), 3.85 (d, J = 10.0 Hz, 1H), 3.88-4.02 (m, 2H),
4.15-4.24 (m, 2H), 4.32 (d, J = 10.0, 1H), 6.18 (dd, J = 6.2, 3.7
Hz, 1H), 6.31 (d, J = 6.2, 1H); 13C NMR (CDCl3, 100 MHz) δ
15.3, 30.1, 45.4, 48.3, 51.7, 52.1, 65.9, 66.7, 69.2, 85.3, 114.2,
126.1, 134.1, 137.6, 168.4, 194.5, 216.2; HRMS calcd for
C17H18BrO5 (MH+) 381.0332, found 381.0332.
4.3. General procedure for the synthesis of polycycles 3, 4, 5,
8 and 9.
To a solution of 1,3-diketone 2 (0.36 mmol, 1.2 equiv) and
Cs2CO3 (196 mg, 0.6 mmol, 2 equiv for 1 and 294 mg, 0.9 mmol,
3 equiv for 7) in THF (4 mL) was added to α- haloenone 1a, 1b,
7a or 7b (0.3 mmol, 1 equiv, 108 mg of 1a, 95 mg of 1b, 82 mg
of 7a or 99 mg of 7b) at room temperature. Then the reaction
mixture was stirred at ambient temperature (see Tables 2 and 3).
After completion of the reaction (monitored by TLC), the solvent
was evaporated in vacuo. The reaction mixture was then
extracted with ethyl acetate (3 × 20 mL), the combined organic
layer was dried over anhydrous Na2SO4 and concentrated in
vacuo. The residue was purified by trituration with 2-10% EtOAc
in petroleum ether or silica gel column chromatography by
eluting with 5-30% EtOAc in petroleum ether (gradient elution).
4.3.5. Ethyl-4-bromo-2-methyl-8-oxo-3b,4,7,7a,8,8a-hexahydro-
3aH-spiro[4,7-methanoindeno[2,1-b]furan-9,2'-[1,3]dioxolane]-
3-carboxylate (3e). White solid; 88 mg, 72%; mp 151-152°C; IR
(neat, cm-1) IR (neat, cm-1) 2979 (m), 2920 (m), 2905 (m), 1751
(s), 1698 (vs), 1638 (s), 1380 (w), 1324 (w), 1266 (s), 1222 (m),
1136 (s), 1079 (s), 1025 (m), 953 (w), 772 (m), 737 (m), 714 (m);
1H NMR (CDCl3, 400 MHz) δ 1.33 (t, J = 7.1 Hz, 3H), 2.16 (s,
3H), 2.94-2.96 (m, 1H), 3.10-3.14 (m, 1H), 3.51 (d, J = 8.5 Hz,
1H), 3.76 (d, J = 10.0 Hz, 1H), 3.88-3.97 (m, 1H), 3.98-4.01 (m,
1H), 4.15-4.28 (m, 4H), 4.31 (d, J = 10.0 Hz, 1H), 6.18 (dd, J =
6.5 Hz, 3.6 Hz, 1H), 6.30 (dd, J = 6.5, 1.2 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) δ 14.4, 14.8, 44.9, 48.4, 51.5, 52.0, 60.1, 65.9,
66.7, 69.0, 85.4, 103.9, 126.0, 133.8, 137.9, 165.1, 169.2, 216.7;
HRMS calcd for C18H19BrNaO6 (MNa+) 433.0257, found
433.0256.
4.3.1. 10-Bromo-3,3-dimethyl-3,4,5a,6a,7,10,10a,10b-octahydro-
1H-spiro[7,10-methanoindeno[2,1-b]benzofuran-11,2'-[1,3]
dioxolane]-1,6(2H)-dione (3a). White solid; 123 mg, 98%; mp
155-156 °C; IR (neat, cm-1) 2959 (s), 2895 (s), 1750 (vs), 1654
(vs), 1635 (vs), 1396 (s), 1267 (s), 1218 (s), 1155 (m), 1141 (s),
1028 (m), 982 (w), 904 (w), 735 (s); 1H NMR (CDCl3, 500 MHz)
δ 1.03 (s, 3H), 1.05 (s, 3H), 2.15-2.34 (m, 4H), 2.92-2.94 (m,
1H), 3.09-3.12 (m, 1H), 3.58 (d, J = 8.4 Hz, 1H), 3.73 (d, J = 9.5
Hz, 1H), 3.86-3.95 (m, 1H), 3.96-3.99 (m, 1H), 4.16-4.24 (m,
2H), 4.46 (d, J = 9.5 Hz, 1H), 6.17 (dd, J = 6.5, 3.6 Hz, 1H), 6.30
(d, J = 6.5 Hz, 1H), Confirmed by 1H-1H COSY experiment; 13C
4.3.6. 2'-Bromo-2,2-dimethyl-1a',1b',2',5',5a',6a'-hexahydro-6'H-
dispiro[[1,3]dioxane-5,1'-[2,5]-methanocyclopropa[a]indene-7',
2''-[1,3] dioxolane]-4,6,6'-trione (4f). White solid; 82 mg, 65%;
5

ACCEPTED MANUSCRIPT
6
Tetrahedron
mp 223-225 °C; IR (neat, cm-1) 2920 (m), 2900 (m), 1774 (m),
by 1H-1H COSY experiment; 13C NMR (CDCl3, 100 MHz) δ
28.1, 29.1, 34.4, 37.8, 43.2, 46.2, 47.2, 48.2, 51.4, 51.8, 53.3,
88.4, 113.6, 136.5 (×2), 176.2, 195.0, 217.4; HRMS calcd for
C18H20NaO3 (MNa+) 307.1305, found 307.1302; Selected X-ray
data: C18 H20O3, M = 284.34, Monoclinic, space group P 1 21/c 1
a = 9.126(2) Å, b = 6.5778(15) Å, c = 23.812(5) Å, α =90°, β =
1741 (vs), 1358 (w), 1269 (s), 1246 (m), 1159 (w), 1014 (w), 902
(w), 731 (m), 714 (s); 1H NMR (CDCl3, 500 MHz) δ 1.80 (s, 3H),
1.88 (s, 3H), 2.80 (d, J = 6.1 Hz, 1H), 2.97-2.99 (m, 1H), 3.00 (d,
J = 6.1 Hz, 1H), 3.22 (d, J = 6.8 Hz, 1H), 3.51 (t, J = 6.0 Hz,
1H), 3.91-3.95 (m, 1H), 3.96-4.03 (m, 1H), 4.14-4.21 (m, 2H),
6.18 (dd, J = 6.5, 3.6 Hz, 1H), 6.24 (d, J = 6.5 Hz, 1H), 13C NMR
(CDCl3, 125 MHz) δ 27.6, 27.8, 36.3, 45.1, 45.7, 48.0, 48.4, 55.2,
65.9, 66.6, 67.9, 105.9, 126.3, 133.4, 135.7, 164.2, 165.1, 207.7;
HRMS calcd for C18H17BrNaO7 (MNa+) 447.0050, found
3
92.039(4)°, γ = 90°, V = 1428.5(5) Å , Z = 4, ρcald = 1.322
mg/m , F(000) = 608, λ = 0.71070 Å, ꢀ = 0.089 mm
total/unique reflections 16705/2493, Final indices
3
-1
,
=
R
[I>2sigma(I)]: R1 = 0.0383, wR2 = 0.0977. R (all data): R1 =
0.0430, wR2 = 0.1014.
447.0054; Selected X-ray data: C18H17BrO7,
M = 425.22,
Monoclinic, space group P 21/c, a = 13.2374(5) Å, b =
11.7385(5) Å, c = 11.2250(4) Å, α = 90°, β =104.070(4)°, γ =
4.3.11.
10b-Octahydro-1H-7,10-methanoindeno[2,1-b]benzo
3
3,
90°, V =1691.89(12) Å , Z = 4, ρcald =1.669 mg/m F(000) =
furan-1,6 (2H) -dione (8b). White solid; 70 mg, 90%; mp 151-
864, λ = .71073 Å, ꢀ = 2.469 mm total/unique reflections =
152 °C; IR (neat, cm-1) 2945 (m), 2870 (m), 1744 (s), 1633 (vs),
1396 (s), 1171 (m), 1005 (m), 981 (m), 737 (m), 708 (m); H
-1,
1
7873/2960, Final R indices [I>2sigma(I)]: R1 = 0.0249, wR2 =
0.0604. R (all data): R1 = 0.0272, wR2 = 0.0621.
NMR (CDCl3, 500 MHz) δ 1.43 (d, J = 7.5 Hz, 1H), 1.56 (d, J =
7.5 Hz, 1H), 1.95-2.00 (m, 2H), 2.27-2.46 (m, 4H), 2.87 (dd, J =
8.3, 4.5 Hz, 1H), 3.23-3.27 (m, 2H), 3.31-3.32 (m, 1H), 3.43 (d,
J = 9.5 Hz, 1H), 4.45 (d, J = 9.5 Hz, 1H), 6.13 (dd, J = 5.3, 2.9
Hz, 1H), 6.31 (dd, J = 5.3, 2.9 Hz, 1H); 13C NMR (CDCl3, 125
4.3.7. 3-Benzoyl-4-bromo-2-phenyl-3b,4,7,7a-tetrahydro-3aH-
spiro[4,7-methanoindeno[2,1-b]furan-9,2'-[1,3]dioxolan]-8
(8aH)-one (3g). White solid; 75 mg, 50%; mp 207-208 °C; IR
(neat, cm-1) 3058 (m), 2985 (m), 2960 (m), 2897 (m), 1749 (vs),
MHz) δ 21.8, 24.1, 37.0, 43.4, 46.4, 47.3, 48.3, 51.9, 53.6, 88.2,
1
1623 (vs), 1594 (s), 1575 (m), 1358 (s), 1266 (s), 1225 (m), 1145
115.2, 136.5, 136.6, 177.2, 195.8, 217.5, Confirmed by H-13C
1
(m), 1099 (s), 1024 (s), 890 (m), 736 (vs), 698 (vs); H NMR
HSQC experiment; HRMS calcd for C16H16O3 (MH+) 257.1172,
found 257.1178.
(CDCl3, 500 MHz) δ 3.00-3.03 (m, 1H), 3.23-3.26 (m, 1H), 3.42
(d, J = 8.4 Hz, 1H), 3.88-3.94 (m, 1H), 3.88-3.99 (m, 1H), 4.16-
4.27 (m, 2H), 4.34 (d, J = 9.8 Hz, 1H), 4.55 (dd, J = 9.8, 1.2 Hz,
1H), 6.26 (dd, J = 6.5, 3.7 Hz, 1H), 6.40 (dd, J = 6.5, 1.2 Hz,
1H), 7.05 (t, J = 7.6 Hz, 2H), 7.11 (t, J = 7.6 Hz, 2H), 7.16-7.22
(m, 3H), 7.25-7.29 (m, 1H), 7.48 (dd, J = 8.3, 1.2 Hz, 2H); 13C
NMR (CDCl3, 125 MHz) δ 48.5, 48.6, 50.8, 52.2, 65.9, 66.6,
68.4, 84.9, 112.3, 126.2, 127.9, 128.0, 128.9, 129.2, 129.5, 130.7,
132.2, 133.7, 138.1, 138.5, 165.1, 192.6, 216.8; HRMS calcd for
C27H21BrNaO5 (MNa+) 527.0465, found 527.0463.
4.3.12. 3-Acetyl-2-methyl-3b,4,7,7a-tetrahydro-3aH-4,7-methano
indeno[2,1-b]furan-8(8aH)-one (8c). White solid; 51 mg, 70%;
mp 116-117 °C; IR (neat, cm-1) 2977 (m), 2968 (m), 1741 (s),
1614 (vs), 1387 (m), 1366 (m), 1225 (m), 1207 (m), 1172 (m),
1011 (m); H NMR (CDCl3, 500 MHz) δ 1.45 (d, J = 8.3 Hz,
1H), 1.56 (d, J = 8.3 Hz, 1H), 2.16 (s, 3H), 2.29 (s, 3H), 2.89 (dd,
J = 8.3, 4.8 Hz 1H), 3.03 (dd, J = 8.3, 3.8 Hz, 1H), 3.26 (d, J =
14.1 Hz, 2H), 3.49 (d, J = 10.0 Hz, 1H), 4.29 (d, J = 10.0 Hz,
1H); 6.13 (dd, J = 5.6, 2.9 Hz, 1H), 6.29 (dd, J = 5.6, 2.9 Hz,
1H); 13C NMR (CDCl3, 125 MHz) δ 15.3, 29.6, 47.0, 47.4, 48.2,
48.5, 51.9, 53.4, 86.0, 116.6, 136.3, 136.4, 167.4, 193.9, 217.5;
HRMS calcd for C15H16NaO3 (MNa+) 267.0992, found 267.0995.
1
4.3.8.
2'-Bromo-1a',1b',2',5',5a',6a'-hexahydro-6'H-dispiro
[indene-2,1'-[2,5]methanocyclopropa[a]-indene-7',2''-[1,3]
dioxolane]-1,3,6'-trione (4h). White solid; 102 mg, 80%; mp
232-233 °C; IR (neat, cm-1) 3055 (w), 2985 (w), 1732 (vs), 1656
1
(m), 1638 (m), 1265 (vs), 1245 (vs), 1046 (s), 737 (s); H NMR
4.3.13. Ethyl-2-methyl-8-oxo-3b,4,7,7a,8,8a-hexahydro-3aH-4,7-
metha noindeno[2,1-b]furan-3-carboxylate (8d). White solid; 56
mg, 68%; mp 71-72 °C; IR (neat, cm-1) 2977 (s), 2942 (m), 1746
(vs), 1700 (vs), 1645 (s), 1381 (m), 1339 (m), 1175 (m), 1132
(m), 1081 (s), 1016 (m), 770 (m), 738 (m), 707 (m); H NMR
(CDCl3, 400 MHz) δ 1.27 (t, J = 7.1 Hz, 3H), 1.41, 1.51 (ABq, J
= 8.5 Hz, 2H), 2.08 (s, 3H), 2.85 (dd, J = 8.5, 4.7 Hz, 1H), 3.11
(dd, J = 8.5, 4.1 Hz, 1H), 3.18 (d, J = 11.4 Hz, 2H), 3.40 (d, J =
10.0 Hz, 1H), 4.11- 4.21 (m, 2H), 4.25 (d, J = 10.0 Hz, 1H), 6.08
(dd, J = 5.6, 2.9 Hz, 1H), 6.25 (dd, J = 5.6, 2.9 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 14.3, 14.5, 46.3, 47.2, 48.1, 48.1,
51.8, 53.1, 59.8, 86.0, 105.4, 136.2, 136.3, 165.4, 168.0, 217.8;
HRMS calcd for C16H18NaO4 (MNa+) 297.1097, found 297.1096.
(CDCl3, 500 MHz) δ 2.70, 2.85 (ABq, J = 5.5 Hz, 2H), 2.86-
3.03 (m, 1H), 3.30 (d, J = 6.5 Hz, 1H), 3.72 (t, J = 6.5 Hz, 1H),
3.90-3.98 (m, 1H), 4.00-4.03 (m, 1H), 4.13-4.21 (m, 2H), 6.11
(dd, J = 6.5, 3.8 Hz, 1H), 6.28 (d, J = 6.5 Hz, 1H), 7.81-7.84 (m,
2H), 7.92-7.94 (m, 2H); 13C NMR (CDCl3, 125 MHz) δ 40.7,
43.6, 46.7, 47.2, 48.0, 53.9, 65.8, 66.5, 68.3, 123.0, 123.3, 126.3,
131.5, 135.5, 135.6, 135.7, 140.7, 142.9, 194.7, 195.4, 210.5;
Confirmed by 1H-1H COSY and 1H-13C HSQC experiments;
HRMS calcd for C21H15BrO5Na (MNa+) 448.9995, found
448.9995.
1
4.3.9.
10-Bromo-3,3-dimethyl-3,4,6a,7,10,10a-hexahydro-1H-
7,10-methanoindeno[2,1-b]benzofuran-1,6,11(2H,5aH,10bH)-
trione (5). White solid; 110 mg, 98%; mp 171-172 °C; IR (neat,
4.3.14. 3-Benzoyl-2-phenyl-3b,4,7,7a-tetrahydro-3aH-4,7-metha
noindeno[2,1-b]furan-8(8aH)-one (8e). White solid; 50 mg,
45%; mp 162-163; IR (neat, cm-1) 3059 (m), 2967 (s), 2937 (s),
2868 (m), 1746 (vs), 1614 (vs), 1595 (vs), 1576 (s), 1447 (m),
cm-1) 2986 (m), 1729 (vs), 1710 (vs), 1372 (m), 1255 (m), 1044
1
(m), 1025 (m); H NMR (CDCl3, 400 MHz) δ 1.06 (s, 3H), 1.07
(s, 3H), 2.20, 2.21 (ABq, J = 16.2 Hz, 2H), 2.26, 2.34 (ABq, J =
17.1 Hz, 2H), 3.12 (dd, J = 9.0, 3.9 Hz, 1H), 3.46-3.51 (m, 2H),
3.92 (d, J = 9.6 Hz, 1H), 4.51 (d, J = 9.6 Hz, 1H), 6.53 (dd, J =
6.8, 3.9 Hz, 1H), 6.61 (d, J = 6.8 Hz, 1H); 13C NMR (CDCl3, 125
MHz) δ 28.1, 29.2, 34.4, 37.8, 43.1, 47.1, 47.3, 49.4, 51.4, 62.6,
87.2, 110.7, 132.7, 137.1, 176.5, 192.2, 194.3, 213.8; HRMS
calcd for C18H18BrO4 (MH+) 377.0383, found 377.0384.
1360 (s), 1341 (m), 1265 (m), 1175 (m), 1100 (m), 1073 (m),
1
1002 (m), 890 (m), 769 (m), 732 (vs), 709 (vs), 696 (vs); H
NMR (CDCl3, 400 MHz) δ 1.46 (d, J = 8.5 Hz, 1H), 1.59 (d, J =
8.5 Hz, 1H), 2.99 (dd, J = 8.5, 4.6 Hz, 1H) 3.13 (dd, J = 8.0, 3.6
Hz, 1H), 3.31-3.32 (m, 2H), 4.05 (d, J = 9.6 Hz, 1H), 4.53 (d, J =
9.6 Hz, 1H), 6.20 (dd, J = 5.6, 3.0 Hz, 1H), 6.39 (dd, J = 5.6, 3.0
Hz, 1H), 7.02 (t, J = 7.7 Hz, 2H), 7.08 (t, J = 7.7 Hz, 2H), 7.14-
7.18 (m, 2H), 7.23-7.27 (m, 2H), 7.41-7.44 (m, 2H); 13C NMR
(CDCl3, 125 MHz) δ 46.9, 47.5, 48.4, 49.9, 52.1, 53.5, 85.5,
114.4, 127.8, 128.0, 128.2, 129.1, 129.2, 129.7, 130.6, 132.0,
136.6, 138.8, 165.3, 193.5, 218.2; HRMS calcd for C25H20NaO3
(MNa+) 391.1305, found 391.1307.
4.3.10. 3,3-Dimethyl-3,4,5a,6a,7,10,10a,10b-octahydro-1H-7,10-
methan oindeno[2,1-b]benzofuran-1,6(2H)-dione (8a). White
solid; 84 mg, 98%; mp 158-159 °C; IR (neat, cm-1) 2957 (s),
2870 (m), 1743 (vs), 1634 (vs), 1396 (s), 1343 (m), 1208 (w),
1
1160 (m), 1143 (m), 1031 (m), 974 (m), 744 (m), 708 (m); H
NMR (CDCl3, 400 MHz) δ 1.02 (s, 3H), 1.04 (s, 3H), 1.43, 1.54
(ABq, J = 8.5 Hz, 2H), 2.13-2.27 (m, 4H), 2.85 (dd, J = 8.5, 4.8
Hz, 1H), 3.22-3.30 (m, 3H), 3.46 (d, J = 9.6 Hz, 1H), 4.44 (d, J =
9.6 Hz, 1H), 6.12, 6.26 (ABqd, J = 5.6, 2.8 Hz, 2H); Confirmed
4.3.15. 3-(4-Methoxyphenyl)acryloyl)-2-((E)-4-methoxystyryl)-
3b,4,7,7a-tetrahydro-3aH-4,7-methanoindeno[2,1-b]furan-8
(8aH)-one (8f). Yellow solid; 94 mg, 65%; mp 196-198 °C; IR

ACCEPTED MANUSCRIPT
7
(neat, cm-1) 2956 (m), 2936 (m), 1746 (s), 1715 (m), 1601 (vs),
4.4. General procedure for the retro-Diels-Alder reaction of
polycycles (8a and 8d)
1575 (m) 1512 (s), 1306 (m), 1254 (vs), 1172 (s), 1030 (m), 969
(w), 829 (s), 735 (m); 1H NMR (CDCl3, 400 MHz) δ 1.49 (d, J =
7.8 Hz, 1H), 1.62 (d, J = 7.8 Hz, 1H), 2.90-3.01 (m, 1H), 3.11-
3.13 (m, 1H), 3.31 (d, J = 9.5 Hz, 2H), 3.81 (s, 6H), 3.85 (s, 1H);
4.45 (d, J = 9.5 Hz, 1H), 6.21-6.23 (unresolved m, 1H), 6.39-
6.41 (unresolved m, 1H), 6.86 (d, J = 7.8 Hz, 2H), 6.95 (d, J =
7.8 Hz, 2H), 6.98-7.01 (m, 1H), 7.33 (d, J = 15.5 Hz, 1H), 7.46-
7.50 (m, 3H), 7.57 (d, J = 7.8 Hz, 2H), 7.71 (d, J = 15.5 Hz, 1H);
13C NMR (CDCl3, 100 MHz) δ 47.1, 47.5, 48.0, 49.4, 52.0, 53.4,
55.5, 55.6, 85.8, 113.8, 114.4, 114.7, 116.0, 122.7, 127.9, 128.7,
129.6, 130.2, 136.0, 137.0, 139.4, 142.3, 161.1, 161.7, 164.4,
186.0, 217.1; HRMS calcd for C31H29O5 (MH+) 481.2010, found
481.2023.
A solution of polycycle 8a (568 mg, 2 mmol) or 8d (548 mg, 2
mmol) in diphenylether (5 mL) was refluxed for 45 min (the
progress of the reaction was monitored by TLC). After
completion of reaction, the reaction mixture was cooled to room
temperature and directly purified by silica gel column
chromatography by eluting with 5-20% EtOAc-petroleum ether.
4.4.1. 6,6-Dimethyl-5,6,7,8b-tetrahydro-3H-cyclopenta[b] benzo
furan-3,8(3aH)-dione (10a). Yellow liquid; 380 mg, 87%; IR
(neat, cm-1) 2960 (m), 2874 (m), 1722 (vs), 1635 (vs), 1579 (m),
1397 (s), 1213 (s), 1038 (m), 1003 (m), 889 (w), 825 (w), 791
(w), 640 (w); 1H NMR (CDCl3, 500 MHz) δ 1.00 (s, 3H), 1.06 (s,
3H), 2.16, 2.20 (ABq, J = 8.2 Hz, 2H), 2.26, 2.30 (ABq, J = 9.9
Hz, 2H), 4.29 (dd, J = 7.2, 1.8 Hz, 1H), 4.94 (d, J = 7.2 Hz, 1H),
6.20 (dt, J = 5.8, 1.8 Hz, 1H), 7.97-7.99 (m, 1H); 13C NMR
(CDCl3, 125 MHz) δ 28.6, 28.7, 34.5, 37.8, 46.4, 51.0, 83.3,
113.8, 132.7, 166.1, 176.9, 194.2, 202.9; HRMS calcd for
C13H14NaO3 (MNa+) 241.0835, found 241.0832.
4.3.16.
3,3-Dimethyl-3,4,5a,6a,7,10,10a,10b-octahydro-1H-
spiro[7,10-methanoindeno[2,1-b]benzofuran-11,2'-[1,3]
dioxolane]-1,6(2H)-dione (8g). White solid; 100 mg, 98%; mp
97-98 °C; IR (neat, cm-1) 2990 (m), 2955 (s), 2900 (m), 1746
(vs), 1640 (vs), 1395 (m), 1074 (m), 1029 (m), 974 (m), 753 (m);
1H NMR (CDCl3, 400 MHz) δ 1.02 (s, 3H), 1.04 (s, 3H), 2.13-
2.33 (m, 4H), 2.95-3.11 (m, 3H), 3.36-3.88 (unresolved m, 1H),
3.48 (d, J = 9.6 Hz, 1H), 3.77-4.92 (m, 4H), 4.43 (d, J = 9.6 Hz,
1H), 6.19-6.21 (unresolved m, 1H), 6.37-6.39 (unresolved m,
1H); 13C NMR (CDCl3, 125 MHz) δ 28.2, 29.1, 29.8, 34.4, 37.8,
42.8, 43.4, 50.9, 51.0, 51.4, 64.9, 65.3, 88.7, 113.3, 126.6, 134.2,
135.0, 176.0, 194.8, 217.0; HRMS calcd for C20H23O5 (MH+)
343.1540, found 343.1542.
4.4.2.
Ethyl-2-methyl-6-oxo-6,6a-dihydro-3aH-cyclopenta
[b]furan-3-carboxylate (10d). Yellow liquid; 354 mg, 85%; IR
(neat, cm-1) 2980 (m), 1723 (vs), 1704 (vs), 1643 (s), 1380 (m),
1
1341 (m), 1212 (s), 1082 (s), 1022 (m); H NMR (CDCl3, 400
MHz) δ 1.29 (t, J = 7.1 Hz, 3H), 2.16 (s, 3H), 4.15-4.24 (m, 2H),
4.28 (dd, J = 7.5, 1.4 Hz, 1H), 4.78 (d, J = 7.5 Hz, 1H), 6.25 (dd,
J = 5.8, 1.4 Hz, 1H), 7.99 (dd, J = 5.8, 2.6 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) 14.5 (×2), 49.5, 60.1, 80.8, 104.7, 132.9,
165.0, 167.0, 169.2, 203.9; HRMS calcd for C11H11O4 ([MH-
2H]+) 207.0652, found 207.0652.
4.3.17. 10b-Octahydro-1H-spiro[7,10-methanoindeno[2,1-b]ben
zofuran-11,2'-[1,3]dioxolane]-1,6(2H)-dione (8h). White solid;
85 mg, 90%; mp 163-164 °C; IR (neat, cm-1) 2958 (m), 2892 (m),
1745 (s), 1631 (vs), 1396 (s), 1296 (s), 1273 (m), 1227 (m), 1170
1
(m), 1101 (m), 1074 (m), 988 (m), 735 (s), 711 (m); H NMR
(CDCl3, 500 MHz) δ 2.00 (quint, J = 6.4 Hz, 2H), 2.33 (q, J = 6.4
Hz, 2H), 2.37-2.47 (m, 2H), 2.96-2.98 (m, 1H), 3.05-3.07 (m,
1H), 3.12-3.14 (m, 1H), 3.39 (dq, J = 4.4, 1.3 Hz, 1H), 3.46 (d, J
= 9.8 Hz, 1H), 3.78-3.94 (m, 4H), 4.43 (dd, J = 9.8, 1.2 Hz, 1H),
6.22, 6.40 (ABqd, J = 3.2, 1.0 Hz, 2H); NMR (CDCl3, 125 MHz)
δ 21.7, 23.9, 36.9, 42.9, 43.4, 50.9, 51.0, 51.1, 64.9, 65.3, 88.3,
114.7, 126.5, 134.1, 135.0, 176.9, 195.4, 216.9; HRMS calcd for
C18H18NaO5 (MNa+) 337.1046, found 337.1047.
Acknowledgements
INNN thanks SERB, DST India (EMR/2014/000395) for
financial assistance. SL thanks ISRO, DRDO and CSIR for
research fellowship. The authors also thank Prof. Arindrajit
Chowdhury, Department of Mechanical Engineering, IIT
Bombay, for his support and Ms. Deepa Nair, Mr. Gulzar
Ahmad Bhat and Mr. R. Saravanan, Department of
Chemistry, IIT Bombay, for the X-Ray data.
4.3.18. 3-Acetyl-2-methyl-3b,4,7,7a-tetrahydro-3aH-spiro[4,7-
methanoindeno[2,1-b]furan-9,2'-[1,3]dioxolan]-8(8aH)-one (8i).
Colourless liquid; 68 mg, 75%; IR (neat, cm-1) 2983 (m), 2893
Supplementary Material
(m), 1745 (vs), 1669 (m), 1617 (vs), 1426 (w), 1387 (m), 1297
1
(m), 1102 (m), 1076 (m), 925 (m), 736 (vs), 709 (s); H NMR
Copies of NMR spectra for all the new compounds.
Supplementary data associated with this article can be found in
the online version, at
(CDCl3, 500 MHz) δ 2.18 (s, 3H), 2.29 (s, 3H), 2.96-2.98 (m,
1H), 3.06-3.08 (m, 2H), 3.19 (dq, J = 4.4, 1.8 Hz, 1H), 3.53 (d, J
= 10.0 Hz, 1H), 3.80-3.94 (m, 4H), 4.26 (dd, J = 10.3, 1.2 Hz,
1H), 6.21, 6.39 (ABdq, J = 3.2, 1.0 Hz, 2H); 13C NMR (CDCl3,
125 MHz) δ 15.3, 29.5, 45.4, 46.4, 50.8, 50.9, 51.0, 64.8, 65.3,
86.1, 116.3, 126.5, 134.1, 134.8, 167.3, 193.8, 217.2; HRMS
calcd for C17H19O5 (MH+) 303.1227, found 303.1230.
Notes and references
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1a',1b',2',5',5a',6a'-Hexahydro-6'H-spiro[indene-2,1'-
M. X.; Meegan, M. J. In Comprehensive Heterocyclic Chemistry II
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[2,5]methan ocyclopropa[a]indene]-1,3,6'-trione (9j). White
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2991 (w), 2963 (w), 1723 (vs), 1713 (vs), 1359 (m), 1336 (m),
1254 (m), 1094 (m), 987 (m), 767 (m), 742 (m); 1H NMR
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1H), 3.41-3.44 (m, 1H), 6.07 (dd, J = 5.6, 2.8 Hz, 1H), 6.26 (dd,
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