Dimerization of conjugated 1-indanones

Article abstract of DOI:10.1139/v99-236

Conjugated 1-indanones dimerize under basic conditions to provide spirodimers. For example when 2-(E)-carbomethoxymethylene-1-indanone (5) was treated with Cs₂CO₃ in CH₃CN, two spirodimers, 6 and 7, were produced via two m

Full text of DOI:10.1139/v99-236

784
Dimerization of conjugated 1-indanones
Yves Leblanc, Claude Dufresne, Rajiv Dhawan, Jason Ollerenshaw, Adam Littke,
Laird A. Trimble, and Nancy N. Tsou
Abstract: Conjugated 1-indanones dimerize under basic conditions to provide spirodimers. For example when 2-(E)-
carbomethoxymethylene-1-indanone (5) was treated with Cs2CO3 in CH3CN, two spirodimers, 6 and 7, were produced
via two modes of reaction (mode A and mode B). With 2-(E)-cyanomethylene-1-indanone (9) only mode A dimerized
spiro products (10 and 11) were observed whereas with 2-chloromethylidene-1-indanone (12) a 1,2-dimer (13) was ob-
tained instead of the expected spirodimer.
Key words: dimerization, conjugated 1-indanones, spirodimers.
Résumé : Les 1-indanones dimérisent en présence d’une base pour donner des spirodimères. Par exemple, lorsqu’on
traite le 2-(E)-carbomethoxymethylène-1-indanone (5) avec Cs2CO3 dans CH3CN on obtient les spirodimères 6 et 7.
Ces deux dimères sont produits par deux modes de dimérisation (mode A et mode B). Dans le cas du 2-(E)-
cyanomethylène-1-indanone (9) uniquement la dimérization de type A a lieu pour produire les produits spiros 10 et 11
tandis qu’avec le 2-chloromethylidène-1-indanone (12) comme produit de départ on obtient un dimère de type 1,2 (13).
Mots clés : dimérisation, 1-indanones conjugués, spirodimères.
Leblanc et al. 790
Introduction
benzaldehyde in EtOH under acidic conditions. The mono-
mer 1c derives from oxidation of 1b with Oxone® in
CH2Cl2–MeOH. With monomers 1b and 1c (Table 1), the
reactions proceeded smoothly to provide the corresponding
dimers (Scheme 1). Moderate yields (60%) of the
spirodimers were obtained with Cs2CO3 as the base (entry 3
and 5, Table 1). In addition, it has been observed that in the
case where KHMDS was used as the base for substrate 1b,
the reaction took place very rapidly (5 min) at –78°C to pro-
vide the corresponding spirodimers 3b and 4b in high yields
(85%) (Table 1). The relative stereochemistry of the pre-
dominant dimers (3b and 3c) is the same as that observed
for the unsubstituted case (3a). In all cases the dimerization
gave, as the major product, the spirodimers with the phenyl
substituents on the convex face of the molecule.
In a previous report we presented our study on the dimeri-
zation of 2-benzylidene-1-indanone (1a, Scheme 1) (1). The
structure and the stereochemistry of the major spirodimer
(3a) obtained from this reaction had initially been estab-
lished by COSY, HMQC, HMBC, and NOESY NMR corre-
lation techniques. The structure was then confirmed by X-
ray crystallography (1). The stereochemistry assigned for
dimer 3a (Scheme 1) differs from previous reports (2, 3)
where X-ray crystallographic analysis was not used to prove
the stereochemistry. To the best of our knowledge no exam-
ples of this dimerization other than the benzylidene case
(1a) have been published. Herein we describe new results on
the dimerization of substituted benzylidene-1-indanones and
other conjugated 1-indanones to assess the generality of the
reaction.
The preceding results suggest that the electronic nature of
the substituents on the aromatic ring have little influence on
the outcome of the reaction. Following these results, we
turned our attention to other conjugated 1-indanones without
Results and discussion
a
phenyl ring. With 2-(E)-carbomethoxy-methylene-1-
For the benzylidene cases, the monomers 1b (X = SMe)
and 1c (X = SO2Me) were chosen as substrates to verify the
effect of the electronic nature of the aromatic substituents on
the outcome of the reaction. The monomer 1b was readily
prepared by condensation of 1-indanone with 4-thiomethyl-
indanone (5) as the substrate (Scheme 2), rapid dimerization
(0.5 h) was observed with Cs2CO3 in CH3CN (entry 1, Ta-
ble 2) providing two spirodimers, 6 and 7, in a 1:1 ratio. The
KHMDS reaction conditions (entry 2, Table 2) were also
applied to indanone 5 to afford dimers 6 and 7, also in a 1:1
Received May 6, 1999. Published on the NRC Research Press website on June 9, 2000.
This manuscript is dedicated to Professor Hanessian to underline his major achievements in organic chemistry.
Ce manuscrit est dédié au Professeur Hanessian dans le but de souligner son apport à la chimie organique.
Y. Leblanc,1 C. Dufresne, R. Dhawan, J. Ollerenshaw, A. Littke, and L.A. Trimble. Merck Frosst Centre for Therapeutic
Research, P.O. Box 1005, Pointe-Claire – Dorval, QC H9R 4P8, Canada.
N.N. Tsou. Merck & Co. Inc., 126 E. Lincoln Avenue, P.O. Box 2000, Rahway, NJ 07065–0900, U.S.A.
1Author to whom correspondence may be addressed. Telephone: (514) 428-3096. Fax: (514) 428-4900.
e-mail: yves_leblanc@merck.com
Can. J. Chem. 78: 784–790 (2000)
© 2000 NRC Canada

Leblanc et al.
785
Table 1. Reaction conditions and isolated yields for the dimerization of 1a–c to produce various spirodimers.
% Yield of
Entry
X
Indanone
Time
Condition
Dimer 2
Dimer 3
Dimer 4
Cs2CO3, CH3CN, rt
KHMDS, THF, –78°C
Cs2CO3, CH3CN, rt
KHMDS, THF, –78°C
Cs2CO3, CH3CN, rt
1
2
3
4
5
H
H
1a
1a
1b
1b
1c
18 h
5 min
50 h
5 min
16 h
0
0
0
0
0
93
81
52
80
57
4
6
8
5
3
SMe
SMe
SO2Me
Table 2. Reaction conditions for dimerization of compound 5.
Ratios
Yield
(%)
Entry
Conditions
Dimer 6
Dimer 7
Dimer 8
Cs2CO3, CH3CN, rt/30 minutes
KHMDS, THF, –78°C/4 minutes
(–)-spartine, THF, rt/18 h
DBU, THF, rt/18 h
1
2
3
4
85
80
83
60
1
1
1
3.6
1
1
2.2
2.8
—
—
—
1
Scheme 2.
Scheme 1.
ratio. In the case where the dimerization was achieved with
DBU as a base (entry 4, Table 2), a third dimer (8) was pro-
duced late in the reaction. This dimer is also formed from
dimer 7 using DBU which suggests that compound 8 is de-
rived by epimerization of 7. The dimerization of 5 can also
be achieved with (–)-spartine in THF to provide dimers 6
and 7 in a 1:2 ratio (entry 3, Table 2). Under these condi-
tions no enantioselectivity was observed for this
dimerization using chiral HPLC column for analysis. The
spirodimers 6 and 7 are easily separable by TLC. The more
mobile dimer 6 is produced by the same mode of
dimerization (mode A, see Scheme 3) as observed in the
benzylidene cases 1. The second dimer originates from a dif-
ferent mode of dimerization (mode B) providing the vicinal
diester 7. As described in Scheme 3, the latter dimer results
from the addition of the enolate 5a onto the β carbon of the
ester of second monomer (5), followed by an
a
intramolecular addition to the β carbon of the ketone. Ini-
tially, the structure and the stereochemistry of dimer 6 and
of dimer 7 were established by the same NMR techniques
used for the spirodimer 3a. To prove the structure of dimer
7, it was submitted for X-ray crystallographic analysis. As
depicted in Fig. 1, the X-ray structure is identical to the
structure derived from NMR.
When the dimerization of the cyano compound 9 was
studied, a similar reaction pattern to that obtained with the
corresponding ester 5 was expected. Using Cs2CO3 as a
base, the dimerization of 9 was completed within a few min-
utes and, in contrast to ester 5, two dimers 10 and 11 were
isolated that arose from a mode A type addition. No
© 2000 NRC Canada

786
Can. J. Chem. Vol. 78, 2000
Fig. 1. Stereoview of the ORTEP representation of 7.3 Non-hydrogen atoms are represented by ellipsoids corresponding to 30% proba-
bility.
Scheme 3.
Scheme 4.
formation of
a mode B type dimer was observed
Scheme 5.
(Scheme 4). Presumably, the cyano compound undergoes
only mode A dimerization because the addition onto the β
carbon of the nitrile would lead to an intermediate with a
negative charge α to the nitrile, and would thus make it less
stable than in the ester case. As was the case for ester 7,
treatment of dimer 10 under basic conditions (Cs2CO3–
CH3CN) resulted in the production of its epimer 11.
The last case studied was the chloromethylene analog 12
which was prepared according to a literature procedure (4).
Interestingly, when this monomer was subjected to basic
conditions (LiHMDS, THF, –78°C), none of the expected
spirodimer was produced; however, the 1,2-dimer 132 was
formed exclusively (Scheme 5). It appears that the electronic
nature of the substituent on the double bond has an effect on
the site of reactivity of both the cross conjugated enolate and
the monomer.
ionic cycloaddition (Scheme 6) which could explain the high
degree of diastereoselectivity observed in these reactions.
Experimental
2-(E)-p-thiomethylbenzylidene-1-indanone (1b)
In conclusion, conjugated 1-indanones provide spirodimers
when exposed to basic conditions. This allows the prepara-
tion of molecules containing five stereogenic centers from
achiral monomers in a single step. The only exception to this
statement so far is the chloromethylene analog 12. The for-
mation of the spirodimers is probably the result of either a
double Michael reaction as already proposed (1) or of an
To a mixture of 1-indanone (4.97 g, 37.6 mmol) and 4-
thiomethylbenzaldehyde (4.60 mL, 34.6 mmol) in EtOH (50 mL)
was added 25 drops of concentrated HCl. The resulting mix-
ture was refluxed at 80°C for 19 h and then allowed to cool
to room temperature to give a yellow solid. The solid was
filtered and washed with EtOH to provide 8.16 g (89%) of
1
the title compound 1b: mp 130–133°C (EtOH); H NMR
2 The stereochemistry of the double bond has not been established.
3 N.N. Tsou, R.G. Ball, C. Dufresne, and Y. Leblanc. Acta Cryst. C. (2000). In preparation.
© 2000 NRC Canada

Leblanc et al.
787
Scheme 6.
50 mL). The organic portions were combined, dried over
Na2SO4, filtered, and evaporated under reduced pressure.
The crude mixture was then purified by column chromatog-
raphy with 5% EtOAc in toluene followed by a preparative
plate purification (5% EtOAc in toluene) to yield 0.25 g
(52%) of pure dimer 3b and 0.040 g (8%) of isomer 4b.
Isomer 3b: mp 181–183°C (EtOH); 1H NMR (500 MHz,
benzene-d6, 27°C) δ : 7.78 (d, J = 7.1 Hz, 1H), 7.60 (d, J =
7.4 Hz, 1H), 7.23 (d, J = 8.3 Hz, 2H), 7.09 (d, J = 8.6 Hz,
2H), 7.01–6.91 (m, 3H), 6.89 (d, J = 1.6 Hz, 2H), 6.88 (d,
J = 1.6 Hz, 2H), 6.68 (t, J = 7.3 Hz, 1H), 6.60 (app. q, 2H),
4.31 (d, J = 11.0 Hz, 1H), 4.06 (dd, J = 9.0 Hz, 1H), 3.90 (d,
J = 11.0 Hz, 1H), 3.60 (dd, J = 9.0, 11.0 Hz, 1H), 2.79 (s,
2H), 1.80 (s, 3H), 1.79 (s, 3H). HRMS calcd. for
C34H29O2S2 [M + H]+: 533.1608, found: 533.1609. Elemen-
tal analysis calcd. for C34H28O2S2: C 76.60, H 5.30, S 12.05;
found: C 76.21, H 5.34, S 12.28.
1
Isomer 4b (oil): H NMR (500 MHz, benzene-d6, 70°C) δ :
8.00 (d, J = 7.5 Hz, 1H), 7.42 (d, J = 7.9 Hz, 1H), 7.13 (d,
J = 8.4 Hz, 2H), 7.06 (t, J = 7.7 Hz, 1H), 6.99 (d, J =
8.0 Hz, 2H), 6.97 (app. s, 1H), 6.92 (t, J = 7.7 Hz, 1H),
6.78–6.73 (m, 3H), 6.71 (d, J = 7.9 Hz, 1H), 6.60 (d, J =
8.3 Hz, 2H), 6.50 (d, J = 7.6 Hz, 1H), 4.20 (d, J = 4.4 Hz,
1H), 4.05 (app. t, J = 9.3 Hz, 1H), 3.67 (d, J = 10.3 Hz, 1H),
3.46 (dd, J = 4.2, 8.1 Hz, 1H), 2.79 (d, J = 17.6 Hz, 1H),
2.47 (d, J = 17.5 Hz, 1H), 2.07 (s, 3H), 1.84 (s, 3H). 13C
NMR (125 MHz, 27°C, acetone-d6) δ : 207.2, 205.9, 154.3,
152.5, 139.8, 139.5, 137.9, 137.8, 137.2 135.3, 134.0, 133.6,
132.2, 130.1, 129.2, 128.1, 128.0, 127.1, 126.9, 125.5, 123.9,
123.6, 68.1, 58.8, 58.7, 51.9, 49.1, 37.6, 15.2, 14.9. HRMS
calcd. for C34H29O2S2 [M + H]+: 533.1608, found: 533.1609.
(300 MHz, acetone-d6, 27°C) δ : 7.79 (d, J = 7.5 Hz, 1H),
7.72 (d, J = 8.5 Hz, 2H), 7.69–7.66 (m, 2H), 7.52 (t, J =
2.1 Hz, 1H), 7.49–7.44 (m, 1H), 7.38 (d, J = 8.5 Hz, 2H),
4.11 (d, J = 2.0 Hz, 2H), 2.56 (s, 3H). 13C NMR (125 MHz,
acetone-d6, 27°C) δ : 193.9, 150.7, 142.5, 138.9, 135.3,
133.2, 132.7, 132.0, 128.4, 127.4, 126.7, 124.4, 33.0, 14.8.
HRMS calcd. for C17H15OS [M + H]+: 267.0842, found:
267.0843. Elemental analysis calcd. for C17H14OS: C 76.66,
H 5.30, S 12.04; found: C 76.69, H 5.38, S 12.11.
2-(E)-p-methylsulfonebenzylidene-1-indanone (1c)
Dimerization of 2-(E)-p-methylsulfonebenzylidene-1-
indanone (1c) using Cs2CO3–CH3CN to afford 3c and 4c
To a stirring solution of 1c (0.10g, 0.35 mmol) in CH3CN
(1.8 mL) was added Cs2CO3 (0.13 g, 0.39 mmol). The re-
sulting mixture was stirred for 16 h at room temperature and
was then quenched by the addition of aqueous NH4OAc
(2 mL), followed by addition of ethyl acetate (10 mL). The
organic phase was separated and the aqueous phase was ex-
tracted twice more with ethyl acetate (2 × 10 mL). The or-
ganic portions were combined, dried over Na2SO4, filtered,
and evaporated under reduced pressure. Addition of a 70%
EtOAc in hexane solution to the crude mixture resulted in
the precipitation of the major isomer 3c as a white solid,
which was filtered and dried under vacuum for several
hours; to afford 0.05 g (51%). Purification of the filtrate by
preparative plate (7% EtOAc–hexane) yielded a further
0.006 g of isomer 3c (total mass obtained: 0.060 g, 57%),
and 0.002 g (3%) of isomer 4c.
To a solution of 1b (1.00 g, 3.75 mmol) in a mixture of
MeOH (53 mL) and CH2Cl2 (5 mL) was added dropwise a
suspension of OXONE® (10 g, 16.3 mmol) in water
(37 mL). The resulting mixture was stirred for 28 h and then
partitioned between H2O and CH2Cl2. The organic phase
was separated, dried over Na2SO4, filtered, and evaporated
under reduced pressure to yield a white solid. The crude
solid was stirred vigourously with Et2O for about 5 min, fil-
tered, and dried under vacuum for several hours to provide
0.97 g (87%) of the title compound 1c: mp 211–214°C
1
(EtOH); H NMR (300 MHz, acetone-d6, 27°C) δ : 8.06–
8.04 (m, 4H), 7.83 (d, J = 7.8 Hz, 1H),7.75–7.68 (m, 2H),
7.62 (t, J = 2.3 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 4.21 (d,
J = 2.1 Hz, 2H), 3.17 (s, 3H). 13C NMR (125 MHz, acetone-
d6, 27°C) δ : 193.9, 151.0, 142.5, 141.3, 139.4, 138.4, 135.9,
132.0, 131.4, 128.7, 128.6, 127.5, 124.7, 44.2, 32.8. HRMS
calcd. for C17H15O3S [M + H]+: 299.0740, found: 299.0741.
Isomer 3c: mp 249–251°C (EtOH); 1H NMR (500 MHz,
benzene-d6, 27°C) δ : 7.75 (d, J = 7.3 Hz, 1H), 7.56 (d, J =
8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 7.6 Hz,
1H), 7.24 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 7.9 Hz, 2H), 7.00
(t, J = 7.6 Hz, 1H), 6.96 (t, J = 7.6 Hz, 1H), 6.72 (d, J =
7.2 Hz, 1H), 6.59 (t, J = 7.6 Hz, 1H), 6.53 (t, J = 6.9 Hz,
1H), 6.38 (d, J = 7.6 Hz, 1H), 4.18 (d, J = 10.8 Hz, 1H),
3.95 (t, J = 9.4 Hz, 1H), 3.76 (d, J = 10.5 Hz, 1H), 3.47 (dd,
J = 8.9, 10.7 Hz, 1H), 2.52 (d, J = 17.5 Hz, 1H), 2.47 (d,
Dimerization of 2-(E)-p-thiomethylbenzylidene-1-
indanone (1b) using CS2CO3 as a base to yield 3b and 4b
To a stirring solution of 1b (0.65 g, 2.00 mmol) in
CH3CN (9.5 mL) was added Cs2CO3 (0.65 g, 2.00 mmol).
The resulting mixture was stirred for 50 h at room tempera-
ture and was then quenched by the addition of aqueous
NH4OAc (10 mL), followed by addition of ethyl acetate
(50 mL). The organic phase was separated and the aqueous
phase was extracted twice more with ethyl acetate (2 ×
© 2000 NRC Canada

788
Can. J. Chem. Vol. 78, 2000
J = 17.5 Hz, 1H), 2.10 (s, 3H), 2.07 (s, 3H). HRMS calcd.
for C34H29O6S2 [M + H]+: 597.1408, found: 597.1405. Ele-
mental analysis calcd. for C34H28O6S2: C 68.44, H 4.73, S
10.75; found: C 68.42, H 4.77, S 10.81.
J = 7.3 Hz, 1H), 6.84 (t, J = 7.3 Hz, 1H), 4.16 (t, J = 9.9 Hz,
1H), 3.78 (t, J = 9.4 Hz, 1H), 3.67 (d, J = 9.5 Hz, 1H), 3.30
(d, J = 10.1 Hz, 1H), 3.07 (d, J = 17.6 Hz, 1H), 2.83 (s, 3H),
2.79 (s, 3H), 2.77 (d, J = 16.6 Hz, 1H). 13C NMR
(125.6 MHz, acetone-d6, 22°C) δ : 203.8, 202.0, 171.0, 170.4,
154.5, 151.0, 137.0, 136.0, 135.0, 127.7, 127.6, 126.3,
126.0, 124.6, 124.4, 124.1, 63.4, 58.0, 53.5, 52.1, 51.1, 51.0,
45.0, 32.4. Elemental analysis calcd. for C24H20O6: C 71.28,
H 4.98; found: C 71.30, H 4.87. Mass spectrum m/z = 405.
1
Isomer 4c (oil): H NMR (500 MHz, benzene-d6, 70°C) δ :
7.91 (d, J = 7.7 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.39 (d,
J = 7.9 Hz, 2H), 7.34 (d, J = 8.1 Hz, 1H), 7.07 (d, J =
8.3 Hz, 2H), 6.99 (t, J = 7.6 Hz, 1H), 6.92 (t, J = 7.6 Hz,
1H), 6.87 (t, J = 7.6 Hz, 1H), 6.74 (t, J = 7.4 Hz, 1H), 6.71
(d, J = 8.5 Hz, 1H), 6.56 (d, J = 8.5 Hz, 2H), 6.26 (d, J =
7.8 Hz, 1H), 4.23 (d, J = 5.6 Hz, 1H), 3.96 (t, J = 9.3 Hz,
1H), 3.44 (d, J = 10.3 Hz, 1H), 3.36 (dd, J = 5.4, 8.7 Hz,
1H), 2.56 (d, J = 17.0 Hz, 1H), 2.34 (s, 3H), 2.31 (d, J =
17.0 Hz, 1H), 2.14 (s, 3H). HRMS calcd. for C34H29O6S2 [M
+ H]+: 597.1408, found: 597.1405.
1
Dimer 7: mp 170–171°C H NMR (500 MHz, benzene-d6,
22°C) δ : 7.68 (d, J = 6.7 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H),
7.10 (t, J = 7.8 Hz, 1H), 6.99 (d, J = 7.4 Hz, 1H), 6.82 (m,
3H), 6.48 (d, J = 7.4 Hz, 1H), 4.30 (dd, J = 4.4, 7.3 Hz, 1H),
3.77 (dd, J = 4.4, 7.9 Hz, 1H), 3.70 (d, J = 7.9 Hz, 1H), 3.63
(d, J = 17.0 Hz, 1H), 3.46 (d, J = 7.4 Hz, 1H), 3.35 (s, 3H),
3.22 (s, 3H), 2.97 (d, J = 17.0 Hz, 1H). 13C NMR
(125.6 MHz, acetone-d6), 298 K) δ : 204.7, 204.7, 173.0,
171.3, 151.7, 151.2, 137.7, 136.7, 134.8, 133.9, 127.0,
127.2, 126.6, 126.3, 124.2, 123.8, 60.4, 55.3, 55.2, 53.9,
51.9, 51.2, 47.7, 39.3. Elemental analysis calcd. for
C24H20O6: C 71.28, H 4.98; found: C 71.26, H 5.08. Mass
spectrum m/z = 405.
Dimerization of 2-(E)-p-thiomethylbenzylidene-1-
indanone (1b) using KN(SiMe3)2 to yield 3b and 4b
To a solution of 1b (0.15 g, 0.56 mmol) in THF (1.6 mL)
at –78°C was added dropwise via syringe a 0.5 M toluene
solution of KN(SiMe3)2 (1.2 mL, 0.60 mmol). The solution
was allowed to stir for one hour at –78°C and was then
quenched by addition of 3 mL of aqueous NH4OAc via sy-
ringe followed by immediate warming to room temperature.
The workup and purification procedure followed was the
same as that described for the dimerization of 1b using
Cs2CO3–CH3CN and yielded 0.12 g (80%) of isomer 3b and
0.005 g (5%) of isomer 4b.
Dimerization of 2-carbomethoxymethylene-1-indanones
(5) using KN(SiMe3)2 to yield 6 and 7
The indanone 5 (0.05 g, 0.25 mmol) was dissolved in
THF (1.5 mL) and cooled to –78°C for 5 min. This was fol-
lowed by the addition of a 0.05 M solution of KN(SiMe3)2
in toluene (0.10 eq, 50 µL). The crude deep purple mixture
was partitioned between ethyl acetate and 25% aqueous
NH4OAc. The organic layer was separated, dried over
MgSO4, and filtered through silica gel to provide the title
products 6 and 7 (0.04 g, 80% yield) in a 1:1 ratio.
Dimerization of 2-(E)-benzylidene-1-indanone (1a) using
KN(SiMe3)2 to yield 3a and 4a
The experimental procedure and workup followed was
that as described above for the dimerization of 1b using
KN(SiMe3)2. Quantities of reagents and solvents used:
2-(E)-benzylidene-1-indanone (0.10 g, 0.45 mmol); THF
1.1 mL; KN(SiMe3)2 (0.5 M, 0.92 mL, 0.460 mmol). Purifi-
cation was achieved by flash column chromatography (6%
EtOAc in toluene), which separated most of isomer 3a from
4a, followed by a preparative plate purification (6% EtOAc
in toluene) to separate the remaining fractions from the pre-
vious column. This procedure yielded 0.08 g (81%) of iso-
mer 3a and 0.006 g (6%) of isomer 4a. The isomers were
Dimerization of 2-carbomethoxymethylene-1-indanones
(5) using DBU to yield 6,7 and 8
To a solution of the indanone 5 (0.25 g, 1.24 mmol) in
THF (5 mL) was added DBU (0.18 mL, 6.20 mmol). The re-
sulting dark purple solution was allowed to react overnight
and this resulted in an additional dimeric product that was
more polar than those seen previously (6 and 7). The mix-
ture of dimers was purified to afford: 0.07 g (28.4%) of 6,
0.06 g (22.4%) of 7 and 0.008 g (8.0%) of 8: Dimer 8 mp
1
identified on the basis of their H NMR spectra, which were
identical to those reported previously (1).
1
198–200°C. H NMR (500 MHz, acetone-d6, 22°C) δ : 7.66
(t, J = 7.3 Hz, 1H), 7.62 (d, J = 7.7 Hz, 1H), 7.56 (d, J =
7.3 Hz, 1H), 7.30 (t, J = 7.5 Hz, 1H), 7.27 (t, J = 7.5 Hz,
1H), 7.23 (t, J = 7.5 Hz, 1H), 7.13 (d, J = 7.1 Hz, 1H), 6.91
(d, J = 7.5 Hz, 1H), 4.43 (d, J = 8.7 Hz, 1H), 4.02 (dd, J =
6.0, 11.5 Hz, 1H), 3.98 (d, J = 11.5 Hz, 1H), 3.89 (d, J =
17.5 Hz, 1H), 3.82 (d, J = 17.5 Hz, 1H), 3.77 (s, 3H), 3.50
(dd, J = 6.2, 9.0 Hz, 1H), 3.35 (s, 3H). 13C NMR
(125.6 MHz, acetone-d6, 22°C) δ : 206.4, 206.1, 175.2,
171.4, 153.5, 150.8, 138.4, 138.1, 135.9, 134.9, 129.3,
128.3, 127.2, 126.5, 124.0, 123.8, 60.1, 59.4, 55.8, 54.3,
52.6, 52.1, 46.5, 40.1. HRMS calcd. for C24H21O6 [M + H]+:
405.1339, found: 405.1338.
Dimerization of 2-carbomethoxymethylene-1-indanone
(5) using Cs2CO3–CH3CN to afford 6 and 7
To a solution of 2-carbomethoxymethylene-1-indanone (5)
(5) (0.50 g, 2.30 mmol) in CH3CN (22 mL) was added
Cs2CO3 (0.75 g, 2.30 mmol). The resulting mixture was
stirred at room temperature for 0.5 h. The reaction mixture
was partitioned between 25% aqueous NH4OAc and ethyl
acetate. The organic phase was separated, dried over
Na2SO4, and evaporated. The crude mixture was purified by
flash chromatography to afford dimer 6 (0.19 g, 43%) and
dimer 7 (0.19 g, 42%).
1
Dimer 6: mp 163–164°C. H NMR (500 MHz, benzene-d6,
22°C) δ : 7.79 (d, J = 7.7 Hz, 1H), 7.69 (d, J = 7.7 Hz, 1H),
7.51 (d, J = 7.7 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 7.04
(t, J = 7.3 Hz, 1H), 6.95 (d, J = 8.0 Hz, 2H), 6.92 (t,
Preparation of spirodimer 8 from dimer 7
To a solution of dimer 7 (0.02 g, 0.04 mmol) in THF
(0.40 mL) was added DBU (0.06 mL, 0.39 mmol). After a
© 2000 NRC Canada

Leblanc et al.
789
period of 72 h at room temperature, the reaction mixture was
partitioned between ethyl acetate and 25% aqueous
NH4OAc. The organic layer was separated, dried over
Na2SO4, filtered, and evaporated. After purification by flash
chromatography, dimer 8 was obtained (0.012 g, 75%).
J = 9.2 Hz, 1H), 3.07 (d, J = 10.1 Hz, 1H). 13C NMR
(125.6 MHz, acetone-d6, 22°C) δ : 201.9, 200.9, 153.0,
152.5, 137.9, 137.1, 136.4, 135.6, 130.5, 129.6, 128.0,
126.6, 125.3, 125.3, 117.9, 117.8, 64.5, 54.2, 48.1, 42.4,
37.8, 34.7. Calcd. for C22H14N2O2: C 78.09, H 4.17, N 8.28;
found: C 77.87, H 4.21, N 8.02. Mass spectrum m/z = 339
(M – H)–.
Preparation of 2-(1-oxo-1,3-dihydro-2H-inden-2-
ylidene)acetonitrile (9)
Dimer 11: 1H NMR (500 MHz, chloroform-d3, 22°C) δ :
7.90 (d, J = 7.7 Hz, 1H), 7.86 (d, J = 7.7 Hz, 1H), 7.79 (t,
J = 7.6 Hz, 1H), 7.75 (t, J = 7.9 Hz, 1H), 7.71 (d, J =
7.6 Hz, 1H), 7.59 (t, J = 7.5 Hz, 1H), 7.56 (d, J = 7.7 Hz,
1H), 7.51 (t, J = 7.4 Hz, 1H), 4.37 (t, J = 8.7 Hz, 1H), 3.77
(t, J = 9.8 Hz, 1H), 3.74 (d, J = 17.1 Hz, 1H), 3.62 (d, J =
8.7 Hz, 1H), 3.40 (d, J = 9.2 Hz, 1H), 3.25 (d, J = 17.3 Hz,
1H). 13C NMR (125.6 MHz, CD3CN, 22°C) δ : 202.6, 201.3,
153.7, 152.4, 137.9, 137.6, 135.7, 130.7, 129.8, 128.0,
127.2, 125.4, 125.1, 119.1, 117.8, 118.6, 63.6, 53.8, 48.4,
41.6, 39.6, 37.9. HRMS calcd. for C22H14N2O2 [M + H]+:
339.1332, found: 339.1333.
To a mixture of 2-carboxymethylene-1-indanone (6)
(0.50 g, 2.66 mmol) in dichloromethane (5.0 mL) was added
an excess of oxalyl chloride (1.0 mL, 11.5 mmol) and a cata-
lytic amount of dry DMF. This resulting mixture was al-
lowed to react for 1.5 h at room temperature. At this point,
the solvent was evaporated in vacuo and the excess of oxalyl
chloride co-evaporated with dichloromethane (3 × 5 mL).
The acid chloride was then dissolved in THF (10 mL) and
added to a cold solution of saturated NH4OAc (50 mL). The
ice cooled reaction mixture was then stirred for 30 min. The
aqueous phase was extracted with ethyl acetate and the or-
ganic layer was dried over MgSO4, filtered, and the solvent
evaporated under reduced pressure to provide 0.38 g (77%)
of a white solid. The acetamide was used to synthesize the
nitrile without further purification. To a 0°C solution of the
acetamide (0.16 g, 0.85 mmol) and pyridine (0.13 g,
1.70 mmol) in 1,4-dioxane was then added trifluoroacetic
anhydride (0.19 g, 0.94 mmol) over a period of 1 hour. The
slurry was kept at 0°C during the addition of the
trifluoroacetic anhydride. The reaction was stirred for an ad-
ditional 5 min and was then poured onto a cold NH4OAc
buffer solution. The aqueous layer was extracted with ethyl
acetate, dried over MgSO4, and the solvent evaporated in
vacuo to provide a crude brown solid. The compound was
purified by flash chromatography (20% ethyl acetate – hex-
anes) to provide 9 as a white crystalline material (0.10 g,
69%), mp 138–140°C. 1H NMR (500 MHz, acetone-d6,
22°C) δ : 7.83 (d, J = 7.8 Hz, 1H), 7.80 (t, J = 7.5 Hz, 1H),
7.71 (d, J = 7.7 Hz, 1H), 7.54 (t, J = 7.4 Hz, 1H), 6.50 (t,
J = 2.5 Hz, 1H), 4.10 (d, J = 2.3 Hz, 2H).13C NMR
(500 MHz, acetone-d6, 295 K) δ : 190.5, 156.6, 149.6, 137.5,
136.8, 129.0, 127.2, 124.8, 116.5, 101.0, 32.0. calcd. for
C11H7NO: C 78.09, H 4.17, N 8.28; found: C 78.18, H 4.02,
N 8.19. Mass spectrum m/z = 168 (M – 1).
Preparation of spirodimer 11 from dimer 10
To a solution of the dimer 10 (0.02 g, 0.06 mmol) in THF
(0.40 mL) was added DBU (0.03 mL, 0.19 mmol). After a
period of 72 h at room temperature, the reaction mixture was
partitioned between EtOAc and saturated NH4OAc. The or-
ganic layer was separated, dried over Na2SO4, filtered, and
evaporated. After purification by flash chromatography,
dimer 11 was obtained (0.006 g, 30%), with no trace of 10
in the reaction.
Dimerization of 2-chloromethylidene-1-indanone (12)
using LiHMDS to yield 13
To a solution of 2-chloromethylidene-1-indanone (12) (4)
(0.15 g, 0.84 mmol) in THF (4 mL) at –78°C was added
LiHMDS 500 µL of 1.0 M solution in THF, 0.50 mmol). Af-
ter a period of 5 min, followed by standard workup proce-
dure, the crude mixture was purified by flash
chromatography (20% ethyl acetate – hexanes). White crys-
talline, air sensitive material was isolated in 57% yield
(0.08 g). Compound 13 mp 90–110°C (decomposes). 1H
NMR (500 MHz, acetone-d6, 22°C) δ : 8.66 (s, 1H), 7.88 (d,
J = 7.5 Hz, 1H), 7.80 (td, J = 7.5, 0.9 Hz, 1H), 7.66 (d, J =
7.7 Hz, 1H), 7.56 (td, J = 7.2, 0.7 Hz, 1H), 7.41 (d, J =
7.4 Hz, 1H), 7.39 (dd, J = 6.9, 0.5 Hz, 1H), 7.36 (td, J = 7.1,
1.0 Hz, 1H), 7.29 (t, J = 7.8 Hz, 1H), 6.71 (t, J = 2.7 Hz,
1H), 4.03 (d, J = 21.1 Hz, 1H), 3.98 (d, J = 21.1 Hz, 1H),
3.89 (dd, J = 21.1, 2.2 Hz, 1H), 3.79 (dd, J = 21.1, 2.2 Hz,
1H). 13C NMR (125.6 MHz, acetone-d6, 22°C) δ : 194.1,
155.8, 150.8, 150.5, 149.5, 147.1, 140.3, 139.7, 137.3,
135.8, 130.3, 129.1, 128.5, 127.2, 125.8, 125.2, 118.5, 89.6,
37.5, 36.6. HRMS calcd. for C20H15Cl2O2 [M + H]+:
357.0448, found: 357.0449.
Dimerization of 2-(1-oxo-1,3-dihydro-2H-inden-2-
ylidene)acetonitrile (9) with Cs2CO3–CH3CN to yield 10
and 11
To a solution of the nitrile 9 (0.14 g, 0.89 mmol) in
acetonitrile (8 mL) was added Cs2CO3 (0.75 g, 2.30 mmol).
After a period of 10 min, followed by standard work up pro-
cedure, the crude mixture was purified on silica gel using
flash chromatography (40% ethyl acetate – hexanes followed
by 60% ethyl acetate – hexanes for the more polar com-
pound). This afforded one major dimer 10 (0.06 g, 43%) mp
>230°C and a minor dimer 11 (0.006 g, 4%) mp >230°C.
1
Dimer 10: H NMR (500 MHz, chloroform-d3, 22°C) δ :
7.86 (d, J = 7.8 Hz, 2H), 7.79 (t, J = 7.4 Hz, 1H), 7.78 (t,
J = 6.8 Hz, 1H), 7.68 (d, J = 7.9 Hz, 1H), 7.66 (d, J =
8.0 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.52 (t, J = 7.7 Hz,
1H), 4.35 (t, J = 9.7 Hz, 1H), 3.69 (d, J = 17.5 Hz, 1H), 3.67
(t, J = 8.8 Hz, 1H), 3.65 (d, J = 17.5 Hz, 1H), 3.35 (d,
Acknowledgements
The authors would like to thank Renata Oballa and Pat-
rick Roy for helpful discussions in the preparation of the
manuscript.
© 2000 NRC Canada

790
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© 2000 NRC Canada