Synthesis and rearrangement of quinone-embedded epoxycyclopentenones: A new avenue to pyranonaphthoquinones and indenopyranones

Article abstract of DOI:10.1021/jo801961w

The epoxyquinones (e.g., 24), readily assembled in one step from the quinols (e.g., 27) by a simplified version of the Dowd oxidation, are shown to undergo rearrangement to pyranonaphthoquinones (e.g., 28) and their ring contracted homologues (e.g., 29) on flash vacuum pyrolysis at 450 °C and 0.01 Torr. The rearrangement has been demonstrated to be useful for a regiospecific synthesis of lambertellin (3). Similarly, the masked aziridinocyclopentanone 9 rearranges to 2-pyridone (37).

Full text of DOI:10.1021/jo801961w

Synthesis and Rearrangement of Quinone-Embedded
Epoxycyclopentenones: A New Avenue to Pyranonaphthoquinones
and Indenopyranones
Saroj R. De, Sujit K. Ghorai, and Dipakranjan Mal*
Department of Chemistry, Indian Institute of Technology, Kharagpur, India 721302
dmal@chem.iitkgp.ernet.in
ReceiVed September 10, 2008
The epoxyquinones (e.g., 24), readily assembled in one step from the quinols (e.g., 27) by a simplified
version of the Dowd oxidation, are shown to undergo rearrangement to pyranonaphthoquinones (e.g.,
2
8) and their ring contracted homologues (e.g., 29) on flash vacuum pyrolysis at 450 °C and 0.01 Torr.
The rearrangement has been demonstrated to be useful for a regiospecific synthesis of lambertellin (3).
Similarly, the masked aziridinocyclopentanone 9 rearranges to 2-pyridone (37).
Introduction
The thermal rearrangement of epoxycyclopentenones to
pyrones has been studied in detail from the mechanistic
1
,2
viewpoint. It is established that an uncommon pericyclic
3
reaction (
ketene intermediates, which in turn cyclize to 2-pyrones via a
process. The reaction, however, has not received any
π
4 a
+
2 a
π process) operates to form transient vinyl
4
π
s
+
2 s
π
4
attention from synthetic chemists. The inaccessibility of the
starting epoxides and the stringent reaction conditions have
probably hindered the advancement of the reaction. A few years
5
ago, we utilized the rearrangement as a means for the synthesis
of isocoumarins and benzoisocoumarins, and extended it to a
regiospecific total synthesis of coriandrin, a furoisocoumarin
6
natural product. Our continued interest in the synthesis of
7
quinonoids prompted us to explore the possibility of extending
FIGURE 1. Representative structures of pyranonaphthoquinones.
(
(
1) Ullman, E. F. J. Am. Chem. Soc. 1963, 85, 3529–3530.
the reaction to the synthesis of chemically sensitive pyranon-
2) (a) Dunston, J. W.; Yates, P. Tetrahedron Lett. 1964, 505–507. (b)
8,9
aphthoquinone natural products, 1-5 (Figure 1).
Klunder, A. J. H.; Bos, W. J.; Verlaak, M. M.; Zwanenburg, B. Tetrahedron
Lett. 1981, 22, 4553–4556.
The chemistry of pyrones, particularly fused ones, is of
(
3) (a) Morris, M. R.; Waring, A. J. Chem. Commun. 1969, 526–527. (b)
Trauner, D.; Malerich, J. P.; Maimone, T. J.; Elliott, G. L. J. Am. Chem. Soc.
005, 127, 6276–6283.
4) Houwen-Claassen, A. A. M.; Klunder, A. J. H.; Zwanenburg, B.
Tetrahedron 1989, 45, 7134–7148.
5) (a) Chapman, O. L.; Hess, T. C. J. Org. Chem. 1979, 44, 962–964. (b)
Undheim, K.; Nilson, B. P. Acta Chem. Scand. B 1975, 29, 503–506.
6) Mal, D.; Bandyopadhyay, M.; Ghorai, S. K.; Datta, K. Tetrahedron Lett.
000, 41, 3677–3680.
7) Mal, D.; Patra, A.; Pahari, P.; Roy, S. J. Org. Chem. 2005, 70, 9017–
020.
10
current interest and has recently been reviewed. Naphtho-
2
(
(8) (a) Armstrong, J. J.; Turner, W. B. J. Chem. Soc. C 1965, 5927–5930.
(b) Brown, P. M.; Krishnamoorthy, V.; Mathieson, J. W.; Thomson, R. H.
J. Chem. Soc. C 1970, 109–110. (c) Poulton, G. A.; Bushnell, G. W.; Li, Y. L.
Can. J. Chem. 1992, 70, 2688–2692. (d) Keniry, M. A.; Poulton, G. A. Magn.
Reson. Chem. 1991, 29, 46–48. (e) Jones, G. B.; Qabaja, G. J. Org. Chem. 2000,
65, 7187–7194.
(
(
2
(
(9) Rueping, M.; Sugiono, E.; Merino, E. Angew. Chem., Int. Ed. 2008, 47,
3046–3049.
9
1
598 J. Org. Chem. 2009, 74, 1598–1604
10.1021/jo801961w CCC: $40.75  2009 American Chemical Society
Published on Web 01/13/2009

Quinone-Embedded Epoxycyclopentenones
SCHEME 1. Proposed Thermal Rearrangement of Quinone-Embedded Epoxycyclopentenone
SCHEME 2. Rearrangement of Epoxide 6 to Naphthopyranone 7 and Indenopyranone 8
[
2,3-b]pyranones represented by lambertellin (3) and ꢀ-lapa-
examined. The mechanism of this reaction is well elucidated
in connection with the delineation of the mechanism of Vitamin
K action. However, it has not found any preparative use in
synthetic organic chemistry. Exposure of the quinol 13 to the
nonenzymatic conditions developed by Ham and Yoo, i.e.,
treatment with KH followed by bubbling of oxygen, provided
chone (4) are an important subgroup of biologically active
compounds. They exhibit a wide variety of biological activi-
ties. For example, ꢀ-lapachone displays (i) anticancer activity
including efficacy in pancreatic cancer treatment, (ii) antima-
larial activity, (iii) anti-inflammatory activity, and (iv)
trypanocidal activity. Lambertellin (3) is found to have
antifungal activity and is implicated in mycoparasitism. Herein,
we report a de novo strategy for the synthesis of the quinone-
embedded epoxycyclopentanones (e.g., 6) in a single step from
the respective quinols, and their rearrangement to naphtho-
1
1
12
1
9
1
3
14
1
5
16
(10) (a) Miller, A. K.; Trauner, D. Synlett 2006, 14, 2295–2316. (b) Sunazuka,
T.; Omura, S. Chem. ReV. 2005, 105, 4559–4580. (c) McGlacken, G. P.; Fairlamb,
I. J. S. Nat. Prod. Rep. 2005, 22, 369–385. (d) Donner, C. D.; Gill, M.; Tewierik,
L. M. Molecules 2004, 9, 498–512. (e) Brimble, M. A.; Nairn, M. R.; Prabaharan,
H. Tetrahedron 2000, 56, 1937–1992. (f) Claessens, S.; Verniest, G.; Jacobs, J.;
Van Hende, E.; Habonimana, P.; Van, T. N.; Van Puyvelde, L.; De Kimpe, N.
Synlett 2007, 829–850.
[
[
2,3-b]pyranones (e.g., 7) and ring-contracted analogues indeno-
1,2-b]pyranones (e.g., 8). We also report that such a rearrange-
(11) (a) Murakami, T.; Harada, N. Y.; Okuno, T.; Hashimoto, M. Biosci.
Biotechnol. Biochem. 2007, 71, 1230–1235. (b) Murakami, T.; Hashimoto, M.;
Okuno, T. Biorg. Med. Chem. Lett. 2005, 15, 4185–4188. (c) Murakami, T.;
Sasaki, A.; Fukushi, E.; Kawabata, J.; Hashimoto, M.; Okuno, T. Bioorg. Med.
Chem. Lett. 2005, 15, 2591–2594. (d) Murakami, T.; Sasaki, A.; Fukushi, E.;
Kawabata, J.; Hashimoto, M.; Okuno, T. Bioorg. Med. Chem. Lett. 2005, 15,
ment is applicable to an aziridinocyclopentanone (e.g., 9).
Results and Discussion
2
587–2590. (e) Murakami, T.; Takahashi, Y.; Fukushi, E.; Kawabata, J.;
Hashimoto, M.; Harada, T. Y. J. Am. Chem. Soc. 2004, 126, 9214–9220. (f)
Kumar, S.; Malachowski, W. P.; DuHadaway, J. B.; LaLonde, J. M.; Carroll,
P. J.; Jaller, D.; Metz, R.; Prendergast, G. C.; Muller, A. J. J. Med. Chem. 2008,
51, 1706–1718.
The synthetic strategy conceived is outlined in Scheme 1.
The rearrangement of epoxide 10 was envisaged to form
unstable vinyl ketene 11, which, in turn, would form both 1,4-
naphthoquinone 7 and 1,2-naphthoquinone 12, according to the
established mechanistic pathways. However, on the basis of the
energy minimization of the two structures at the B3LYP/6-31G
(
12) (a) Li, C. J.; Li, Y. U.S. Patent Appl. Publ. 2005,US 2005222246 A1
2
0051006. (b) Ough, M.; Lewis, A.; Bey, E. A.; Gao, J.; Ritchie, J. M.;
Bornmann, W.; Boothman, D. A.; Oberley, L. W.; Cullen, J. J. Cancer Biol.
Ther. 2005, 4, 95–102. (c) Ashwell, M.; Tandon, M.; Lapierre, J.-M.; Ali, S.;
Vensel, D.; Li, C. J. PCT Int. Appl. 2007,WO 2007139569 A1 20071206.
(
d) level and the reversibility of a pericyclic reaction, it was
(13) (a) de Andrade-Neto, V. F.; Goulart, M. O. F.; da Silva Filho, J. F.; da
further predicted that isomer 7, more stable by 2.9 kcal/mol
than 12, would exclusively be formed, and thus the rearrange-
ment would serve as a novel route to the lambertellins (e.g., 3).
Since the preparation of the precursor epoxide 10, unknown
Silva, M. J.; Pinto, M. F. R.; Pinto, A. V.; Zalis, M. G.; Carvalho, L. H.; Luzia,
H.; Krettli, A. U. Bioorg. Med. Chem. Lett. 2004, 14, 1145–1149. (b) Elisa,
P.-S.; Ana, E.-B.; Ravelo, A. G.; Yapu, D. J.; Turba, A. G. Chem. BiodiVersity
2
005, 2, 264–274.
(14) Moon, D.-O.; Choi, Y. H.; Kim, N.-D.; Park, Y.-M.; Kim, G.-Y. Int.
1
7
Immunopharmacol. 2007, 7, 506–514.
15) Salas, C.; Tapia, R. A.; Ciudad, K.; Armstrong, V.; Orellana, M.;
in the literature, proved to be a difficult task, we undertook
(
the preparation of its precursor 6 from the corresponding quinol
Kemmerling, U.; Ferreira, J.; Maya, D.; Morello, A. Bioorg. Med. Chem. 2008,
16, 668–674.
1
8
1
3 (Scheme 2), anticipating that compound 6 would form
(16) Murakami, T.; Morikawa, Y.; Hashimoto, M.; Okuno, T.; Harada, Y.
epoxide 10 via retro-Diels-Alder reaction. Accordingly, the key
Org. Lett. 2004, 6, 157–160.
quinol 13 was prepared in one step according to the literature
(17) Mal, D.; Hazra, N. K. Chem. Commun. 1996, 1181–1182.
1
8
(18) Ghorai, S. K.; Roy, H. N.; Bandopadhyay, M.; Mal, D. J. Chem. Res.
precedent from phthalide 14 with tricyclic enone 15. For the
19
(S) 1999, 30–31.
19) (a) Ham, S. W.; Yoo, J. S. Chem. Commun. 1997, 929–930. (b) Ham,
S. W.; Lee, G. H. Tetrahedron Lett. 1998, 39, 4087–4090.
conversion of the quinol 13 to the epoxide 6, Dowd oxidation,
a direct oxidation of a hydroquinone to its quinone oxide, was
(
J. Org. Chem. Vol. 74, No. 4, 2009 1599

De et al.
SCHEME 3. Synthesis and Rearrangement of the Epoxides 16 and 24
the desired epoxide 6 in one step but in low yield (<30%).
For establishing the generality of the rearrangement and
After extensive experimentation, we met the optimal conditions:
determining the structure of the unusual ring-contracted product
8, we examined the reactivity of a few substituted analogues of
the epoxide 6. As a second example, we chose to extend the
methodology to annularly substituted epoxyquinone 16 (Scheme
3), which was expected to provide a deoxy analogue of
lambertellin (3). The synthesis of the quinone, when patterned
after the synthesis of hexacyclic epoxide 6, called for the
synthesis of precursor quinol 17 and the corresponding tricyclic
enone 18. Although the preparation of the enone 18 seemed
trivial, it proved more problematic in practice than we had
2
O , 5% aq KOH in THF at rt under which the quinol 13
underwent smooth transformation to the epoxide 6 in 81% yield.
It was readily purified by silica gel chromatography. For the
proposed retro-Diels-Alder reaction, the hexacyclic quinone 6
was heated in refluxing diphenyl ether as well as o-dichloroben-
zene. In both cases, extensive decomposition of the ep-
oxyquinone took place. No tractable product was isolated. When
the epoxide 6 was subjected to flash vacuum pyrolysis (FVP)
at 450 °C/0.01 Torr, two products, 7 (41%) and 8 (53%)
(
Scheme 2), were identified. These structures were determined
hoped. Attempted C-methylation of enone 15 by LDA-CH
NaH-CH I, etc. resulted in the formation of an inseparable
mixture of products, which probably arose from thermal
3
I,
on the basis of spectroscopic evidence. Structure 12 was ruled
out as the structure of the product after completion of the total
synthesis of lambertellin (3) described below. Although the
formation of the pyranonaphthoquinone 7 was in accordance
with the proposed formation of epoxide 10 and its ring-opening
followed by recyclization, the other expected structure 12 was
not formed. On the contrary, the intriguing formation of
indenopyranone 8 was noted. All the spectroscopic data includ-
ing mass spectral data were consistent with the proposed
structure. On the basis of the NMR data as discussed later, two
alternative structures for 8, i.e., naphtho[1,2-b]furan-4,5-dione
and naphtho[2,3-b]furan-4,9-dione, were ruled out. The sup-
port for structure 7 was derived from the analysis of Dauson et
al. applied to R-lapachone and ꢀ-lapachone.
3
23
isomerization of the initial methylated product. In an alterna-
1
8
tive route, the pentacyclic quinol ether 19 was utilized for
access to the epoxyquinone 16. Reaction of dimethyl ether 19
with methyl iodide in the presence of LDA at - 78 °C produced
methyl-substituted product 20 in 81% yield. O-Demethylation
3
of compound 20 with BBr (20 equiv) in dichloromethane at 0
°C produced quinol 17 in 70% yield. Treatment of the quinol
with oxygen in the presence of 5% aq KOH solution in THF
yielded epoxide 16 (82%). FVP of the epoxide 16 at 450 °C/
0.01 Torr followed by chromatography of the pyrolysate yielded
two products: 21 (42%) and 22 (52%). Their structures were
assigned on the basis of spectroscopic data.
20
2
1
2
2
(
20) Sutton, D. C.; Gillan, F. T.; Susic, M. Phytochemistry 1985, 24, 2877–
(22) Dauson, B. A.; Girard, M.; Kindack, D.; Fillion, J.; Awang, D. V. C.
Magn. Reson. Chem. 1989, 27, 1176–1177.
(23) Lange, J. H. M.; Klunder, A. J. H.; Zwanenburg, B. Tetrahedron 1991,
1509–1524.
2
2
879.
(
008.
21) Hayashi, T.; Smith, F. T.; Lee, K.-H. J. Med. Chem. 1987, 30, 2005–
1
600 J. Org. Chem. Vol. 74, No. 4, 2009

Quinone-Embedded Epoxycyclopentenones
a
SCHEME 4. Probable Mechanism for the Formation of 28 and 29 from 24
a
Step 1: Initial retro-Diels-Alder reaction of epoxide 24. Step 2: Probable pathways of rearrangement of vinyl ketene intermediate 31a.
In a similar fashion as for 16, trimethoxy quinol ether 23
was elaborated to epoxyquinone 24. Compound 23 was
requisite structural features for retro [
4
π
a
+
2 a
π ] reaction, it
24a
undergoes the ring-opening to form vinyl ketene trione 31a.
The vinyl ketene intermediate 31a may then cyclize via paths
“a” and “b” to form pyranonaphthoquinones 28 and 32a,
respectively. The intermediate 32a, on decarbonylation followed
by radical combination, might lead to the formation of 29. It
may be noted that the thermal decarbonylation of quinones or
ketones, although uncommon, is reported to take place at high
2
4b,c
prepared by the Hauser annulation
5, followed by O-dimethylation of the resulting quinol with
Me SO -K CO in overall 83% yield. It was then submitted
to the sequence of C-methylation, O-demethylation, and Dowd
oxidation. C-Methylation of 9-methoxy derivative 23 with CH
produced compound 26 in 78% yield. Demethylation of 26 with
BBr in dichloromethane at 0 °C selectively generated quinol
7 in 72% yield. An attempted perdemethylation with excess
BBr resulted in a complex mixture rather than the desired
of enone 15 with phthalide
2
2
4
2
3
3
I
2
5
3
temperature (1100-1180 °C). Determination of the structure
2
of 28 was supported by the fact that with anhydrous AlCl , it
3
3
underwent O-demethylation to give lambertellin (3). The
hydroxyquinol. Treatment of the quinol 27 with oxygen in the
presence of 5% aq KOH solution in THF yielded epoxide 24
in 85% yield. The spectral data and the X-ray crystallographic
data were consistent with the structure. FVP of the epoxide at
spectroscopic data of the synthetic sample perfectly matched
1
6
with the reported values. The structure of the pyranonaph-
thoquinone 28 was also confirmed by its HMBC and HSQC
data (Table 1). The possibility of the formation of 29 from 28
was ruled out by a model experiment on structurally analogous
quinone 7. The attempted conversion of quinone 7 to 8 by FVP
under the conditions of its formation from 6 returned the starting
material (e.g., 7).
4
50 °C/0.01 Torr pressure yielded the rearrangement products
2
8 (44%) and 29 (51%). O-Methyllambertellin (28), on treat-
ment with anhydrous AlCl
3
in dichloromethane, yielded lam-
1
bertellin (3) (72%) (Scheme 3). To our delight, both H and
1
3
C NMR spectra of the synthetic sample agreed well with the
The alternative pathways for the formation of the ring
1
6
reported data.
contracted product 29 as well as other possible isomeric products
2
5
The rearrangement of 24 to 28 and 29 is rationalized on the
are outlined in Scheme 5. The loss of carbonyl “a” from the
1
2
6
basis of the earlier understanding of the thermal rearrangement
intermediate 31a followed by radical combination and sub-
sequent 6π electrocyclization would produce structure 31c.
of the simple epoxycyclopentenones and a probable mechanism
has been presented in Scheme 4. The cascade reaction is initiated
by thermally allowed extrusion of cyclopentadiene forming
epoxycyclopentenone 30. Since the epoxy intermediate 30 has
27
Decarbonylation of ketene carbonyl “b” from the intermediate
(
25) (a) Champlain, P. De.; Mayo, P. De. Can. J. Chem. 1972, 50, 270–273.
(
b) Amick, A. W.; Wakamiya, A.; Scott, L. T. J. Org. Chem. 2008, 5119–5122.
(26) Hoye, T. R.; Danielson, M. E.; May, A. E.; Zhao, H. Angew. Chem.,
(
24) (a) Mal, D.; Ghorai, S. K.; Hazra, N. K. Indian J. Chem. 2001, 40B,
94–996. (b) Mal, D.; Pahari, P. Chem. ReV. 2007, 107, 1892–1918. (c) Sperry,
J.; Gibson, J. S.; Sejberg, J. J. P.; Brimble, M. A. Org. Biomol. Chem. 2008, 6,
261–4270.
9
Int. Ed. 2008, 47, 9743–9746.
(27) Tseng, P. W.; Yeh, S. W.; Chou, C. H. J. Org. Chem. 2008, 73, 3481–
4
3485.
J. Org. Chem. Vol. 74, No. 4, 2009 1601

De et al.
TABLE 1. Summary of Key Information from HMBC Experiment for Compounds 22, 28, and 29
TABLE 2. Comparison of H and 13C NMR Data of Compounds 22, 29, and 34
1
a
b
c
compd 22
(J/Hz)
compd 29
(J/Hz)
compd 34
(J/Hz)
position
δ
H
δ
C
δ
H
δ
C
δ
H
δ
C
2
3
4
161.8
122.6
133.3
111.2
187.8
132.6
123.5
119.9
133.8
131.9
136.0
174.1
17.6
162.0
122.8
133.5
111.3
186.3
116.7
157.1
117.2
136.1
112.9
137.9
171.8
17.6
161.6
122.3
133.0
111.5
188.3
132.5
124.2
121.1
134.4
129.2
136.2
172.4
7.51-7.40 m
7.52-7.44 m
7.64-7.43 m
4
5
5
6
7
8
9
9
9
1
1
a
a
7.58 d (6.8)
7.51-7.40 m
7.51-7.40 m
7.51-7.40 m
7.64-7.43 m
7.64-7.43 m
7.64-7.43 m
7.64-7.43 m
7.02 d (8.6)
7.52-7.44 m
7.04 dd (7.2, 0.6)
a
b
0
1
2.17 s
2.17 s
4.0 s
56.1
a
1
13
b
1
13
c
1
Recorded at 400 MHz ( H) and 100 MHz ( C) in CDCl
3
.
Recorded at 200 MHz ( H) and 100 MHz ( C) in CDCl
3
.
Recorded at 300 MHz ( H)
13
and 75.5 MHz ( C) in d
6
-DMSO (ref 29).
SCHEME 5. Other Possibilities of Cyclization and Decarbonylation of Vinyl Ketene Intermediate 31a
3
1a should produce vinyl carbene 31d which, in turn, may
and 31h, isomeric with 29, were discarded due to mismatch in
HMBC data. In the HMBC spectra of 8, 22, and 29, there are
three bond couplings between the C-4 vinyl protons and the
carbonyl groups, which do not corroborate with the structures
cyclize in two possible ways to produce 31e and 31f. But both
structures were discarded on consideration of the upfield
chemical shifts of furan hydrogens of the reported furanonaph-
2
8
thoquinones. The probable loss of either carbonyl “c” or “d”
from 31a may lead to formation of 29 and 31h. However, the
spectroscopic data ( H, C, and HMBC) of the product
suggested that compound 29 was formed. The structures 31c
(
28) (a) Uno, H.; Murakami, S.; Fujimoto, A.; Yamaoka, Y. Tetrahedron
1
13
Lett. 2005, 46, 3997–4000. (b) Koyama, J.; Toyokuni, I.; Kino, A.; Tagahara,
K. Heterocycles 1998, 48, 1631–1638.
1
602 J. Org. Chem. Vol. 74, No. 4, 2009

Quinone-Embedded Epoxycyclopentenones
[
1,2-b]pyranones, and pyridone ring systems. It also demon-
strates that the polycyclic epoxy precursors can readily be
prepared by combined application of the Hauser annulation and
the Dowd oxidation. From the synthetic perspective, the
developed methodology has been employed in a total synthesis
of lambertellin (3). Development of an alternative to the FVP
technique as well as an independent synthesis of the indeno-
[
1,2-b]pyranones for the reconfirmation of the structures 8, 22,
FIGURE 2. Other probable structures of compounds 8 and 22.
and 29 is underway.
Experimental Section
General Procedure for Flash Vacuum Pyrolysis. A long (40
cm) high-quality glass tube open at both ends was fixed horizontally
in a pyrolytic chamber connected in series with a rheostat and an
ammeter. One end of the glass tube was closed, and a vial
containing the substance to be pyrolyzed was pushed inside until
it was adjacent to the heating coil. The open end was covered with
cotton plug and then connected to a high-vacuum pump. The
material in the vial was heated with a burner until it melted, then
was pushed inside the furnace after it reached 450-500 °C
FIGURE 3. Structure of (S)-N-benzoyl-3-(2,5-dioxo-2H,5H-indeno[1,2-
b]pyranyl-3)alanine methyl ester.
SCHEME 6. Synthesis and Rearrangement of
Aziridinocyclopentanone 9
(
monitored by a thermocouple). Heating was continued until all
the material was collected in the cold zone of the glass tube and
the rest was collected in a liquid N trap. After the tube was cooled
2
to the ambient conditions, the pyrolysate was dissolved in dichlo-
romethane. Finally, it was purified by column chromatography.
4b,10a-Epoxy-1,4,4a,4b,10a,11a-hexahydro-1,4-methano-11H-
benzo[b]fluoren-5,10,11-trione (6). To a solution of quinol 13 (450
mg, 16.2 mmol) in THF (20 mL) was added a solution of KOH
(
45 mg, 0.81 mmol in 5 mL of water). Oxygen was bubbled through
3
1c, 33e, and 33f. The structures of 8, 22, and 29 were also in
the resulting deep reddish solution for about 20 min, at which time
the color changed to green and finally pale yellow. The reaction
mixture was extracted with ethyl acetate (3 × 50 mL). The
agreement with the HMBC and HSQC data.
The alternative furanoquinone structures 33a, 33b, 33c, and
3
3d (Figure 2) for both 8 and 22 were ruled out on the basis of
combined extracts were washed with H
2
O (2 × 30 mL) and brine
28
the chemical shifts of the vinyl protons. Further, the structures
of indenopyranones 22 and 29 were supported from the
comparison of its spectroscopic data (Table 2) with those of 34
(
2 4
30 mL), dried (anhydrous Na SO ), and concentrated. The resulting
residue was purified by column chromatography on silica gel to
get pure product 6 (384 mg) as a white solid. Yield 81%; R 0.45
f
2
9
1
(
Figure 3).
(1:3 ethyl acetate/petroleum ether); mp 167-168 °C; H NMR (200
Next, we considered extension of the rearrangement to an
MHz, CDCl ) δ 8.04-7.94 (m, 2H), 7.81-7.71 (m, 2H), 6.12 (dd,
3
1
H, J ) 2.8, 5.5 Hz), 5.89 (dd, 1H, J ) 2.8, 5.6 Hz), 3.69-3.65
aziridinocyclopentanone system. Accordingly, we aimed at
preparing an aziridine by elaboration of enone 15. After several
(
m, 1H), 3.45-3.35 (m, 2H), 3.07-3.01 (m, 1H), 1.74-1.54
13
3
0
31
(m, 2H); C NMR (100 MHz, CDCl ) δ 200.5, 188.9, 186.7, 135.7,
3
unsuccessful attempts, we succeeded with the method of
Ikdea et al. involving the reaction of aminimides. Treatment of
tricyclic enone 15 with aminimide 35 prepared in situ from N,N-
dimethylhydrazine and propylene oxide in 2-propanol at 50 °C
furnished aziridinocyclopentanone 9 in 69% yield (Scheme 6).
As expected, FVP of the tetracyclic aziridine 9 under the same
1
5
1
34.9, 134.6, 134.1, 132.7, 131.6, 127.3, 127.2, 72.0, 62.2, 51.6,
-
1
0.9, 46.5, 44.1, 40.8; νmax (KBr, cm ) 1757, 1690, 1590, 1298,
+
12 4
168, 913, 717; HRMS (ES) calcd for C18H O (MH ) 292.0736,
found 292.0741.
H-Naphtho[2,3-b]pyran-2,5,10-trione (7). This compound was
2
prepared as a yellowish solid in 41% yield by flash vacuum
pyrolysis of 6 according to the described procedure. R 0.5 (1:1
ethyl acetate/petroleum ether); mp 217-219 °C; H NMR (400
MHz, CDCl
3
2
condition provided 2-pyridone (37) in 95% yield constituting
the first example of the aza-version of the rearrangement.
f
1
) δ 8.26-8.21 (m, 2H), 8.1 (d, 1H, J ) 9.6 Hz),
Methylation of compound 37 with CH
CO furnished N-methyl-2-pyridone in 85% yield as a yellow
oil, the spectral data of which matched well with the reported
3
I in the presence of
3
13
7
.87-7.83 (m, 2H), 6.71 (d, 1H, J ) 9.6 Hz); C NMR (100 MHz,
K
2
3
CDCl ) δ 180.3, 175.8, 157.5, 154.2, 138.2, 135.0, 134.7, 131.2,
130.9, 127.3, 127.0, 121.4, 118.7; νmax (KBr, cm ) 1752, 1678,
1
2
3
-
1
3
3
values.
+
620, 1420, 1312, 970; HRMS (ES) calcd for C13
27.0345, found 227.0343.
7 4
H O (MH )
Conclusion
2H-Indeno[1,2-b]pyran-2,5-dione (8). This compound was
prepared as a reddish yellow solid in 53% yield by flash vacuum
pyrolysis of 6 according to the described procedure. R 0.7 (1:1
ethyl acetate/petroleum ether); mp 179-180 °C; H NMR (400
MHz, CDCl ) δ 7.64-7.60 (m, 2H), 7.56-7.47 (m, 3H), 6.21 (d,
H, J ) 9.2 Hz); C NMR (100 MHz, CDCl
160.0, 137.5, 135.7, 134.0, 133.0, 132.6, 123.7, 120.5, 112.0, 110.8;
In conclusion, this study demonstrates that the thermal
rearrangement of the quinone-embedded epoxycyclopentenones
leads to the formation of naphtho[2,3-b]pyranones, indeno-
f
1
3
1
3
1
3
) δ 187.3, 176.8,
(29) Schof, M.; Svete, J.; Stanovnik, B. Heterocycles 1999, 51, 1051–1058.
(30) (a) Chebanov, V. A.; Zbruyev, A. I.; Desenko, S. M.; Orlov, V. D.;
-1
νmax (KBr, cm ) 1744, 1710, 1546, 1394, 1078; HRMS (ES) calcd
Yaremenko, F. G. Curr. Org. Chem. 2008, 12, 792–812. (b) Cromwell, N. H.;
Barker, N. G.; Wankel, R. A.; Vanderhorst, P. J.; Olson, F. W.; Anglin, H., Jr.
J. Am. Chem. Soc. 1951, 73, 1044.
+
7 3
for C12H O (MH ) 199.0396, found 199.0416.
(
(
31) Ikeda, I.; Machii, Y.; Okahara, M. Synthesis 1980, 650.
32) Hirano, S.; Toyota, S.; Toda, F. Heterocycles 2004, 64, 383–391.
(33) Ayer, W. A.; Hayatsu, R.; Mayo, P. D.; Reid, S. T.; Stothers, J. B.
Tetrahedron Lett. 1961, 648–653.
J. Org. Chem. Vol. 74, No. 4, 2009 1603

De et al.
1
4
b,10a-Epoxy-1,4,4a,4b,10a,11a-hexahydro-1,4-methano-9-
0.4 (1:1 ethyl acetate/petroleum ether); mp 250-251 °C; H NMR
methoxy-11a-methyl-11H-benzo[b]fluoren-5,10,11-trione (24).
This compound was prepared as a white solid from 27, according
to the same procedure for the preparation of compound 6. Yield
(400 MHz, CDCl ) δ 11.79 (s, 1H), 7.85 (s, 1H), 7.76-7.68 (m,
3
13
2H), 7.34 (d, 1H, J ) 4.2 Hz), 2.31 (s, 1H); C NMR (100 MHz,
CDCl ) δ 180.5, 179.9, 162.3, 159.2, 152.4, 137.4, 133.4, 133.1,
3
-
1
8
5%; R
f
0.58 (1:5 ethyl acetate/petroleum ether); mp 176-177 °C;
130.9, 125.3, 120.0, 119.9, 114.4, 17.7; νmax (KBr, cm ) 2930,
1
H NMR (400 MHz, CDCl
3
) δ 7.64 (t, 1H, J ) 8 Hz), 7.55 (d, 1H,
1748, 1642, 1576, 1282, 1058; HRMS (ES) calcd for C14
H
8
O
5
+
J ) 7.6 Hz), 7.27 (d, 1H, J ) 8 Hz), 6.15 (dd, 1H, J ) 2.8, 5.6
Hz), 5.87 (dd, 1H, J ) 2.8, 5.6 Hz), 3.91 (s, 3H), 3.62 (br s, 1H),
.92 (d, 1H, J ) 4 Hz), 2.87 (br s, 1H), 1.77 (ABd, 1H, J ) 8.8
Hz), 1.71 (ABd, 1H, J ) 8.8 Hz), 1.38 (s, 3H); C NMR (100
MHz, CDCl ) δ 202.7, 189.9, 186.0, 159.2, 136.4, 134.9, 134.1,
33.8, 121.1, 119.3, 118.4, 71.7, 62.9, 57.1, 56.4, 52.6, 49.8, 47.9,
4.9, 23.1; νmax (KBr, cm ) 2973, 1757, 1698, 1649, 1280, 1066,
50, 755; HRMS (ES) calcd for C20
37.1080.
(MH ) 257.0451, found 257.0455.
2
Acknowledgment. This work was supported by the Depart-
ment of Science and Technology, New Delhi. S.R.D. acknowl-
edges the Council of Scientific and Industrial Research for a
research fellowship. The authors acknowledge the help of Mr.
Sourav Bhattacharya for the preparation of a few starting
materials, Dr. Asit Patra for molecular absolute energy calcula-
tion of some compounds, and Dr. Pallab Pahari for some
spectroscopic data. The authors are also thankful to Dr. Snehadri
Narayan Khatua, Mr. Lalit Rajput, and Mr. Mrinal Sarkar for
solving the crystallographic data. The NMR facility was
supported by the Fist program of DST, New Delhi.
1
3
3
1
4
9
3
-
1
+
17 5
H O (MH ) 337.1077, found
9-Methoxy-3-methyl-2H-naphtho[2,3-b]pyran-2,5,10-trione (28).
This compound was prepared as a yellowish solid in 44% yield by
flash vacuum pyrolysis of 24 according to the described procedure.
0.45 (1:5 ethyl acetate/petroleum ether); mp 228-229 °C; H
NMR (200 MHz, CDCl ) δ 7.84-7.71 (m, 3H), 7.37 (dd, 1H, J )
1
R
f
3
13
1
(
1
(
.2, 8.2 Hz), 4.05 (s, 3H), 2.28 (d, 3H, J ) 1.4 Hz); C NMR
100 MHz, CDCl ) δ 180.9, 174.3, 160.7, 159.9, 152.9, 135.9,
33.4, 132.2, 131.8, 119.6, 118.6, 117.7, 116.4, 56.7, 17.6; νmax
Supporting Information Available: General experimental
3
methods; experimental procedures and characterization data of
-
1
1
13
KBr, cm ) 1743, 1676, 1388, 1299, 1197, 974, 722; HRMS (ES)
compounds 9, 16, 17, 20, 21, 22, 26, 27, 29, and 37; H, C,
and DEPT-135 NMR copies of compounds 3, 6, 7, 8, 16, 17,
+
calcd for C15
-Hydroxy-3-methyl-2H-naphtho[2,3-b]pyran-2,5,10-trione (Lam-
bertellin) (3). To a stirred solution of 28 (0.02 g, 0.07 mmol) in
dry dichloromethane at 0 °C under N atmosphere was added
10 5
H O (MH ) 271.0607, found 271.0596.
1
13
9
20, 21, 22, 24, 26, 28, and 29; H and C NMR copies of 9,
27, and 37; HMBC and HSQC for compounds 8, 22, 28, and
29; COSY of compound 8; and an ORTEP diagram of epoxide
2
anhydrous aluminum chloride (0.03 g, 0.22 mmol) and the solution
was stirred at rt for 4 h. The reaction was quenched by addition of
2
4. This material is available free of charge via the Internet at
http://pubs.acs.org.
1
5% HCl (1 mL), extracted with dichloromethane (2 × 30 mL).
The extracts were worked up in the usual manner. Yield 72%; R
f
JO801961W
1
604 J. Org. Chem. Vol. 74, No. 4, 2009