Facile synthesis of indenones from indanones: A new procedure

Article abstract of DOI:10.1081/SCC-100000182

A two-step procedure for the conversion of indanones to indenones is described.

Full text of DOI:10.1081/SCC-100000182

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FACILE SYNTHESIS OF INDENONES FROM INDANONES:
A NEW PROCEDURE
Frank M. Hauser a , Maotang Zhou a & Yuanqiang Sun a
a Department of Chemistry, State University of New York at Albany, Albany, NY, 12222,
U.S.A.
Version of record first published: 09 Nov 2006
To cite this article: Frank M. Hauser, Maotang Zhou & Yuanqiang Sun (2001): FACILE SYNTHESIS OF INDENONES FROM
INDANONES: A NEW PROCEDURE, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 31:1, 77-80
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SYNTHETIC COMMUNICATIONS, 31(1), 77–80 (2001)
FACILE SYNTHESIS OF INDENONES FROM
INDANONES: A NEW PROCEDURE
Frank M. Hauser,∗ Maotang Zhou, and Yuanqiang Sun
Department of Chemistry, State University of New York at
Albany, Albany, NY 12222
ABSTRACT
A two-step procedure for the conversion of indanones to in-
denones is described.
In conjunction with our development of a route to prekinamycin (1). We
needed a brief and efficient route to the indenone 2a from the readily available
indanone 1a. Although the conversion of indanones to indenones would appear to
be straightforward, this has not proven to be the case. The only literature precedent
for this transformation were two examples reported by Bellamy and coworkers (2).
The four-step process involved bromination of the indanone, ketalization of the
α-bromoketone, dehydrohalogenation of the bromoketal with KOtBu, and, finally,
hydrolysis of the ketal with silica/HCl.
We decided to see if there was a shorter route for the conversion of indanones
to indenones. In developing a plan, an additional significant issue that had to be ad-
dressed: indenones, especially those lacking substituents at the 2- and 3-positions,
are notoriously unstable (3–5). It was clear that rapid formation of the indenone
under essentially neutral conditions would be required, and that any work-up
and purification would likewise have to be conducted under neutral conditions to
∗ To whom correspondence should be addressed.
77
Copyright ꢀ 2001 by Marcel Dekker, Inc.
www.dekker.com
C

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HAUSER, ZHOU, AND SUN
Scheme 1.
minimize loss of the product through conjugate addition or polymerization pro-
cesses. The Saegusa oxidation (6) of enol silylethers to α,β-unsaturated enones
appeared to meet these criteria. Moreover, this reaction can be worked-up under
essentially neutral conditions.
Reactionoftheindanone1awithTMSOTfandEt3Naffordedthetrimethylsi-
lyl enol ether intermediate, which without purification was reacted with Pd(OAc)2
in CH3CN for 1 h (Scheme 1). The crude product was filtered through a small plug
of silica, concentrated under reduced pressure, and immediately chromatographed
on silica to afford the pure indenone 2a in 75% yield. Encouraged with this result,
the generality of the protocol was established through analogous preparation of the
indenones 2b–g. As indicated in Scheme 1, application of the procedure uniformly
affords the corresponding indenones 2 in >65% yield, with the exception of 2g,
which proved to be very unstable and was isolated in only 17% yield.
In summary, we have developed a short and efficient route for the conversion
of indanones 1 to indenones 2 that should have wide applicability.
EXPERIMENTAL
General Procedure
To a solution of the indanone 1 (1.0 mmol) in dry PhH (10 mL) at 0◦C under
Ar was added successively Et3N (0.17 mL, 1.2 mmol) and TMSOTf (0.19 mL,
1.0 mmol). The mixture was warmed to room temperature and stirred for 10 min.
The reaction mixture was again cooled to 0◦C and diluted with ether (20 mL) and
NaHCO3 solution. The layers were separated and the aqueous phase was extracted
with ether (3 × 10 mL). The combined organic extracts were washed with brine,

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79
then dried (Na2SO4), filtered, and evaporated under reduced pressure to afford the
silyl enol ether as a light yellow oil.
The silyl enol ether was dissolved in CH2Cl2 (2 mL) and added dropwise to
an aluminum foil-wrapped flask containing a suspension of Pd(OAc)2 (220 mg,
1.0 mmol) in dry CH3CN (5 mL) under Ar. The mixture was stirred at room
temperature for 1 hr, then filtered through a short aluminum foil-wrapped column
of silica gel (CH2Cl2). The filtrate was evaporated under reduced pressure, and the
residue was chromatographed (aluminum foil-wrapped column, silica gel, 15g;
10% Et2O/hexanes) to afford the pure indenone 2. All of the indenones were
unstable and should be used immediately.
4-Methoxy-6-methylindenone (2a)
Indenone 2a was obtained in 75% yield as an unstable red solid with mp
1
60–61◦C. H NMR (CDCl3) δ 7.33 (d, J = 5.96 Hz, 1H), 6.90 (s, 1H), 6.74 (s,
1H), 5.70 (d, J = 5.96 Hz, 1H), 3.86 (s, 3H), 2.34 (s, 3H); 13C NMR (CDCl3) δ
198.89, 152.10, 147.22, 141.79, 131.92, 127.72, 124.03, 118.11, 116.79, 55.77,
21.89.
4-Methoxyindenone (2b)
Indenone 2b was obtained in 82% yield as an unstable yellow solid with mp
1
91–93◦C. H NMR (CDCl3) δ 7.77 (d, 1H, J = 6.0 Hz), 7.22 (m, 1H), 7.08 (m,
1H), 6.95 (m, 1H), 5.77 (d, 1H, 6.0 Hz), 3.88 (s, 3H); 13C NMR (CDCl3) δ 198.75,
152.44, 147.00, 131.77, 131.10, 130.75, 124.85, 118.06, 115.59, 55.78; IR (Nujol)
1708, 1596, 1514, 1273, 1243, 1177, 1107, 1047, 931, 841, 760, 690 cm−1
.
Indenone (2c)
1
Indenone 2c was obtained 72% yield as a yellow oil; H NMR (CDCl3) δ
7.55 (d, J = 6.0 Hz, 1H), 7.41 (d, J = 7.02 Hz, 1H), 7.33 (t, J = 7.42 Hz, 1H), 7.21
(t, J = 7.02 Hz, 1H), 7.04 (d, J = 7.14 Hz, 1H), 5.87 (d, J = 5.94 Hz, 1H); 13C
NMR (CDCl3) δ 198.09, 149.59, 144.39, 133.47, 130.16, 128.95, 126.97, 122.44,
122.09; IR (CDCl3) 3072, 1735, 1709, 1606, 1543, 1457, 1366, 1308, 1282, 1183,
1038, 910, 822, 767, 737 cm−1
.
5-Bromoindenone (2d)
Indenone 2d was obtained in 79% yield as a yellow solid with mp 116◦–
1
118◦C. H NMR (CDCl3) δ 7.54 (d, J = 6.0 Hz, 1H), 7.40 (dd, J1 = 7.6 Hz,
J2 = 1.6 Hz, 1H), 7.29 (d, J = 7.4 Hz, 1H), 7.22 (d, J = 1.6 Hz, 1H), 5.94
(d, J = 5.9 Hz, 1H); 13C NMR (CDCl3) δ 196.58, 148.30, 146.30, 131.71, 128.81,

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HAUSER, ZHOU, AND SUN
128.28, 128.22, 125.61, 123.70; IR (CDCl3) 3078, 1743, 1699, 1599, 1538, 1400,
1345, 1308, 1031, 908, 806 cm−1
.
6-Methoxyindenone (2e)
Indenone 2e was obtained in 68% yield as a yellow oil. 1H NMR (CDCl3) δ
7.51 (d, J = 6.03 Hz, 1H), 6.99 (d, J = 2.4 Hz, 1H), 6.92 (d, J = 7.89 Hz, 1H), 6.73
(dd, J1 = 7.89 Hz, J2 = 2.4 Hz, 1H), 5.75 (d, J = 5.88 Hz, 1H), 3.79 (s, 3H); 13
C
NMR (CDCl3) δ 197.83, 160.82, 150.38, 136.04, 132.20, 125.57, 122.79, 115.82,
110.59, 55.55; IR (CDCl3) 3078, 2940, 1707, 1613, 1536, 1481, 1432, 1280, 1222,
1039, 910, 827 cm−1
.
4,7-Dimethoxy-6-methylindenone (2f)
Indenone 2f was obtained in 67% yield as a red solid with mp 102◦–104◦C.
1H NMR (CDCl3) δ 7.62 (d, J = 5.91 Hz, 1H), 6.74 (s, 1H), 5.62 (d, J = 5.79 Hz,
1H), 3.93 (s, 3H), 3.79 (s, 3H), 2.18 (s, 3H); 13C NMR (CDCl3) δ 196.55, 150.72,
147.98, 145.71, 136.47, 129.30, 124.54, 120.89, 119.54, 61.47, 56.19, 16.62.
5,6-Dimethoxyindenone (2g)
The indenone (2g) was obtained in 17% yield as an extremely unstable red
solid; 1H NMR (CDCl3) δ 7.32 (d, J = 6.0 Hz, 1H), 6.99 (s, 1H), 6.60 (s, 1H), 5.68
(d, J = 5.9 Hz, 1H), 3.87 (s, 3H), 3.82 (s, 3H). This indenone was too unstable to
obtain either a reliable melting point or 13C NMR spectrum.
ACKNOWLEDGMENTS
This work was generously supported by the National Cancer Institute of the
National Institutes of Health under grant CA 18141.
REFERENCES AND NOTES
1. Hauser, F.M.; Zhou, M. J. Org. Chem. 1996, 61, 5722.
2. Bellamy, F.D.; Chazan, J.B.; Ou, K. Tetrahedron 1983, 39, 2803.
3. Marvel, C.S.; Hinman, C.W., J. Am. Chem. Soc. 1954, 76, 5453.
4. Lacy, P.H.; Smith, D.C.C. J. Chem. Soc. (C) 1971, 41.
5. Galatsis, P.; Manwell, J.J.; Blackwell, J.M., Can. J. Chem. 1994, 72, 1656.
6. Ito, Y.; Hirao, T.; Saegusa, T. J. Org. Chem. 1978, 43, 1011.

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