Camps et al.
light yellow solid. On elution with hexane/AcOEt 90:10 to 80:20,
9d (271 mg, 21% yield) was separated as a light yellow solid.
Conclusions
Reaction of 1-indanones with aromatic aldehydes under
NaOEt base catalysis in THF affords spiro{cyclopenta[a]indene-
2,2′-indene}diones. The main diastereomer in this reaction arises
from two molecules of each starting compound with formation
of four new carbon-carbon bonds, leading to the construction
of a new five-membered ring that bears five contiguous
stereogenic centers with a well-defined relative configuration.
Different amounts of a minor epimer thereof and/or the
intermediate enones are also isolated from these reactions.
Although other mechanisms might be imagined, the reaction
leading to the spirocompounds from indanones 1/2 and alde-
hydes 3 seems to proceed through dimerization of the initially
formed 2-alkylidene-1-indanones 4/5, arising from the aldol
condensation reaction. The dimerization takes place through a
process involving an intermolecular Michael addition of the
carbanion obtained by C3-H deprotonation of the enone to a
second molecule of enone, followed by an intramolecular
Michael addition in the corresponding intermediate, and final
protonation of the resulting pyramidalized carbanion, which
accounts for the formation of the cis-fused pentacyclic system.
The experimental results can be explained on the basis of
the C3-H acidity in the intermediate enones: the more acidic
enones (i.e., those lacking the methoxy substituents on the
indanone ring and bearing a phenyl or 2-, 3-, or 4-pyridyl
substituent) give dimers under less drastic conditions. Enones
derived from pivalaldehyde failed to give dimers, probably for
steric reasons.
5d: mp 118-119 °C (MeOH) (described 113 °C).4 Rf 0.38 (SiO2,
hexane/AcOEt 4:1).
7d: mp 196-197 °C (MeOH). Rf 0.25 (SiO2, hexane/AcOEt 4:1).
IR (KBr): ν 3117, 3075, 3042, 2924, 2856, 1705 (CdO st), 1605
and 1590 (Ar-C-C st), 1466, 1285, 1013, 766, 747 cm-1. 1H NMR
(500 MHz, CDCl3): δ 3.03 (d, J ) 17.5 Hz, 1H, 3′-Ha), 3.13 (d,
J ) 17.5 Hz, 1H, 3′-Hb), 3.71 (d, J ) 10.5 Hz, 1H, 3-H), 3.74 (dd,
J ) 11.0 Hz, J′ ) 8.5 Hz, 1H, 8a-H), 3.90 (d, J ) 11.0 Hz, 1H,
1-H), 4.43 (dd, J ) 10.5 Hz, J′ ) 8.5 Hz, 1H, 3a-H), 6.15 [ddd, J
) 3.0 Hz, J′ ) J′′ ) 1.0 Hz, 1H, 3-H 3-(2-furyl)], 6.16 [dd, J )
3.5 Hz, J′ ) 2.0 Hz, 1H, 4-H 1-(2-furyl)], 6.19 [dd, J ) 3.0 Hz, J′
) 2.0 Hz, 1H, 4-H 3-(2-furyl)], 6.26 [ddd, J ) 3.5 Hz, J′ ) J′′ )
1.0 Hz, 1H, 3-H 1-(2-furyl)], 7.05 [dd, J ) 2.0 Hz, J′)1.0 Hz, 1H,
5-H 1-(2-furyl)], 7.17 [dd, J ) 2.0 Hz, J′ ) 1.0 Hz, 1H, 5-H 3-(2-
furyl)], 7.18 (ddd, J ) 7.5 Hz, J′ ) J′′ ) 1.0 Hz, 1H, 4′-H),
superimposes in part 7.258 (broad d, J ) 7.5 Hz, 1H, 4-H),
superimposes in part 7.260 (broad dd, J ) J′ ) 7.5 Hz, 1H, 6′-H),
7.42 (ddd, J ) J′ ) 7.5 Hz, J′′ ) 1.0 Hz, 1H, 5′-H), 7.44 (broad
dd, J ) J′ ) 7.5 Hz, 1H, 6-H), 7.55 (ddd, J ) J′ ) 7.5 Hz, J′′ )
1.5 Hz, 1H, 5-H), 7.71 (broad d, J ) 7.5 Hz, 1H, 7′-H), 7.78 (broad
d, J ) 7.5 Hz, 1H, 7-H). 13C NMR (75.4 MHz, CDCl3): δ 31.1
(CH2, C3′), 46.3 (CH, C3a), 47.8 (CH, C1), 52.6 (CH, C3), 53.1
(CH, C8a), 68.2 (C, C2), 107.9 [CH, C3 3-(2-furyl)], 108.1 [CH,
C3 1-(2-furyl)], 110.0 [CH, C4 1-(2-furyl)], 110.1 [CH, C4 3-(2-
furyl)], 123.8 (CH, C7′), 124.5 (CH, C7), 125.5 (CH, C4), 125.9
(CH, C4′), 127. 1 (CH, C6′), 128.5 (CH, C6), 134.6 (CH, C5′),
135.4 (CH, C5), 135.6 (C, C7a), 136.5 (C, C7a′), 141.9 [CH, C5
1-(2-furyl)], 142.2 [CH, C5 3-(2-furyl)], 151.7 [C, C2 3-(2-furyl)],
151.8 [C, C2 1-(2-furyl)], 152.7 (C, C3a′), 155.0 (C, C3b), 204.7
(C, C8), 205.9 (C, C1′). Elemental analysis calcd (%) for C28H20O4
(420.46): C, 79.98; H, 4.79. Found: C, 79.93; H, 4.78.
Experimental Section
9d: mp 185-186 °C (MeOH). Rf 0.19 (SiO2, hexane/AcOEt 4:1).
IR (KBr): ν 3147, 3103, 3070, 3028, 2939, 1704 (CdO st), 1606
and 1588 (Ar-C-C st), 1505, 1464, 1286, 1150, 1014, 734 cm-1
.
General Procedures for the Reaction of Indanones 1 or 2
with Aldehydes 3. A mixture of 5,6-dimethoxy-1-indanone (1, 1
mmol) or 1-indanone (2, 1 mmol), the aldehyde 3 (1.2 mmol), and
NaOEt (0.86 mmol) in THF (2.4 mL/mmol of 1 or 1.7 mL/mmol
of 2) was thoroughly stirred at room temperature (Method A) or
under reflux (Method B) for 16 h. Unless otherwise stated, the
resulting suspension was filtered in vacuo at room temperature,
the filtrate was concentrated under reduced pressure, and the
resulting residue was submitted to column chromatography through
silica gel to give the aldol condensation products 4 or 5 and/or the
dimerization products thereof 6/8 or 7/9.
General Procedure for the Dimerization of Enones 4 or 5
(Method C). A mixture of the enone 4 or 5 (1 mmol) and NaOEt
(0.86 mmol) in THF (4.7 mL) was heated under reflux for 16 h.
The resulting suspension was cooled to room temperature and
filtered in vacuo. Unless otherwise stated, the filtrate was concen-
trated under reduced pressure, and the resulting residue was
submitted to column chromatography through silica gel to give
products 6/8 or 7/9.
Reaction of Indanone 2 with Aldehyde 3d. Method A:
E-2-[(2-Furyl)methylene]indan-1-one (5d), (1RS,2RS,3SR,
3aSR,8aSR)-1,3-Di(2-furyl)-3a,8a-dihydrospiro{cyclopenta[a]-
indene-2,2′(1H,3′H)-indene}-1′,8(3H)-dione (7d) and (1RS,
2RS,3RS,3aSR,8aSR)-1,3-Di(2-furyl)-3a,8a-dihydrospiro-
{cyclopenta[a]indene-2,2′(1H,3′H)-indene}-1′,8(3H)-dione (9d).
This reaction was carried out from a mixture of indanone 2 (800
mg, 6.06 mmol), aldehyde 3d (0.60 mL, 696 mg, 7.25 mmol), and
NaOEt (374 mg, 5.22 mmol) in THF (10 mL). The resulting yellow
oily residue (1.67 g) was submitted to column chromatography (35-
70 µm of silica gel (167 g), hexane/AcOEt mixtures, gradient
elution). On elution with hexane/AcOEt 95:5, enone 5d (274 mg,
22% yield) was isolated as a light yellow solid. On elution with
hexane/AcOEt 90:10, 7d (612 mg, 48% yield) was isolated as a
1H NMR (500 MHz, CDCl3): δ 2.94 (d, J ) 17.5 Hz, 1H, 3′-Hb),
3.06 (d, J ) 17.5 Hz, 1H, 3′-Ha), 3.66 (dd, J ) 9.0 Hz, J′ ) 5.0
Hz, 1H, 8a-H), 4.15 (d, J ) 9.0 Hz, 1H, 3-H), 4.22 (d, J ) 5.0 Hz,
1H, 1-H), 4.52 (dd, J ) J′ ) 9.0 Hz, 1H, 3a-H), 5.63 [dd, J ) 3.0
Hz, J′ ) 1.0 Hz, 1H, 3-H 3-(2-furyl)], 6.01 [dd, J ) 3.0 Hz, J′ )
2.0 Hz, 1H, 4-H 3-(2-furyl)], 6.25 [ddd, J ) 3.0 Hz, J′ ) J′′ ) 1.0
Hz, 1H, 3-H 1-(2-furyl)], 6.31 [dd, J ) 3.0 Hz, J′ ) 2.0 Hz, 1H,
4-H 1-(2-furyl)], 6.75-6.80 (m, 1H, 4-H), 7.04 [dd, J ) 2.0 Hz, J′
) 1.0 Hz, 1H, 5-H 3-(2-furyl)], 7.261 (ddm, J ) J′ ) 7.5 Hz, 1H,
6′-H), 7.262 (dm, J ) 7.5 Hz, 1H, 4′-H), 7.33 [dd, J ) 2.0 Hz, J′
) 1.0 Hz, 1H, 5-H 1-(2-furyl)], 7.34-7.38 (complex signal, 2H,
5-H and 6-H), 7.47 (ddd, J ) J′ ) 7.5 Hz, J′′ ) 1.0 Hz, 1H, 5′-H),
7.57 (dm, J ) 7.5 Hz, 1H, 7′-H), 7.81-7.85 (m, 1H, 7-H). 13C
NMR (75.4 MHz, CDCl3): δ 37.1 (CH2, C3′), 45.4 (CH, C1), 47.6
(CH, C3a), 51.2 (CH, C3), 56.2 (CH, C8a), 65.7 (C, C2), 107.8
[CH, C3 1-(2-furyl)], 109.3 [CH, C3 3-(2-furyl)], 109.7 [CH, C4
3-(2-furyl)], 110.3 [CH, C4 1-(2-furyl)], 123.4 (CH, C7), 124.2 (CH,
C7′), 125.9 (CH, C4′), 126.8 (CH, C4), 127. 4 (CH, C6′), 127.7
(CH, C6), 133.6 (CH, C5), 134.6 (CH, C5′), 136.1 (C, C7a′), 138.4
(C, C7a), 141.6 [CH, C5 3-(2-furyl)], 141.9 [CH, C5 1-(2-furyl)],
150.9 [C, C2 3-(2-furyl)], 151.4 (C, C3a′), 153.0 (C, C3b), 154.9
[C, C2 1-(2-furyl)], 205.0 (C, C1′), 205.6 (C, C8). Elemental
analysis calcd (%) for C28H20O4 (420.46): C, 79.98; H, 4.79.
Found: C, 79.86; H, 4.82.
Acknowledgment. Financial support from Direccio´n General
de Investigacio´n of Ministerio de Ciencia y Tecnolog´ıa and
FEDER (Projects CTQ2005-02192 and BQU2002-01032) and
Comissionat per a Universitats i Recerca of the Generalitat de
Catalunya (Project 2005-SGR-00180) is gratefully acknowl-
edged.
3470 J. Org. Chem., Vol. 71, No. 9, 2006