Ring-expansion protocol: Preparation of synthetically versatile dihydrotropones

Article abstract of DOI:10.1021/jo802064c

A ring-expansion protocol that consisted of the 1,2-addition of various enolate nucleophiles to 6-trimethylsiloxy-2- cyclohexene-1-one (1) and the NaIO₄-promoted oxidative ring opening of the resulting diols 2, followed by an intramolecular Kno

Full text of DOI:10.1021/jo802064c

SCHEME 1. Oxidative Ring Opening of
3-Cyclohexene-1,2-diols 2, Which May Lead to the Ring
Contraction or the Ring-Expansion Products
Ring-Expansion Protocol: Preparation of
Synthetically Versatile Dihydrotropones
Young-Sun Do,† Ruiying Sun,‡ Hee Jin Kim,‡
Jung Eun Yeo,‡ Sung-Hee Bae,‡ and Sangho Koo*,†,‡
Department of Nano Science and Engineering and
Department of Chemistry, Myong Ji UniVersity, Yongin,
Kyunggi-Do 449-728, Korea
sangkoo@mju.ac.kr
ReceiVed September 17, 2008
was envisioned that the seven-membered conjugated carbonyl
compounds 6 would be synthesized by the ring-expansion
strategy from the same 3-cyclohexene-1,2-diols 2 utilizing the
intramolecular aldol condensation of the immediate oxidative
ring-opening products 3 with Z-configuration. The control of
E/Z-configuration in the oxidative ring-opening reaction of
3-cyclcohexene-1,2-diols 2 therefore plays a decisive role in
producing either the five-membered ring-contraction products
5 or the seven-membered ring-expansion products 6. We have
studied the conditions to exclusively provide Z-configuration
in the oxidative ring-opening reaction of 3-cyclohexene-1,2-
diols 2 and the subsequent cyclization of the resulting ω-formyl
R,ꢀ-unsaturated carbonyl compounds 3 to produce the seven-
membered unsaturated carbocyclic compounds, dihydrotropones
6. Details of the studies and some representative reactions of
the versatile dihydrotropones 6 are described in this paper.
We reported the exclusive preparation of the 1,6-dicarbonyl
compounds 4 with E-configuration by the Pb(OAc)4-promoted
oxidative ring opening of 3-cyclohexene-1,2-diol 2 in MeCN,
in which the initially formed ring-opening product 3 with
Z-configuration was believed to undergo isomerization to the
more stable 4.6 We reinvestigated this ring-opening reaction of
2c (R ) Me) to check the possibility of fishing 3c out of the
reaction mixture by shortening the reaction time.6,7 An aliquot
was taken from the reaction mixture every minute and quenched
A ring-expansion protocol that consisted of the 1,2-addition
of various enolate nucleophiles to 6-trimethylsiloxy-2-
cyclohexene-1-one (1) and the NaIO4-promoted oxidative
ring opening of the resulting diols 2, followed by an
intramolecular Knoevenagel condensation, furnished versatile
dihydrotropones 6. Maintaining Z-configuration in the oxida-
tive ring-opening products 3 is crucial for the success of the
ring-expansion strategy. Dihydrotropones 6 are ripe for
further elaborations such as oxidation to tropones 8 and
Diels-Alder reaction with the Danishefsky′s diene 10 to
afford polycyclic compounds 12.
Seven-membered unsaturated carbocyclic compounds are not
only useful building blocks in organic synthesis1 but also the
key structural motifs of the biologically important natural
products such as colchicine,2 ingenol,3 tropolone,4 etc. The
synthetic approaches to this unusual ring system have been
mostly based on the ring-expansion strategies from the highly
functionalized six-membered ring homologues.5 We have
demonstrated that the five-membered carbocyclic compounds
5 were efficiently assembled by the ring-contraction protocol
from 3-cyclohexene-1,2-diols 2 utilizing the intramolecular
Baylis-Hillman reaction of the Pb(OAc)4-promoted oxidative
ring-opening products 4 with E-configuration (Scheme 1).6 It
1
with 1 M HCl solution. The H NMR analysis of each sample
indicated that 4c was predominantly obtained from the first
sample and that it was not practical to isolate 3c from the
reaction mixture. We found, after many careful experiments,
that the isomerization did not proceed under the reaction
condition but mostly during the quenching/washing processes
with an aqueous acidic solution (Table 1). When no acid was
(5) (a) Ye, T.; McKervey, A. Chem. ReV. 1994, 94, 1091–1160. (b)
Kantorowski, E. J.; Kurth, M. J. Tetrahedron 2000, 56, 4317–4353. (c) Hasegawa,
E.; Tamura, Y.; Suzuki, K.; Yoneoka, A.; Suzuki, T. J. Org. Chem. 1999, 64,
8780–8785. (d) Nair, V.; Sethumadhavan, D.; Nair, S. M.; Rath, N. P.; Eigendorf,
G. K. J. Org. Chem. 2002, 67, 7533–7536. (e) Clayden, J.; Knowles, F. E.;
Menet, C. J. J. Am. Chem. Soc. 2003, 125, 9278–9279. (f) Carren˜o, M. C.; Sanz-
Cuesta, M. J.; Ribagorda, M. Chem. Commun. 2005, 1007–1009. (g) Brocksom,
T. J.; Brocksom, U.; de Sousa, D. P.; Frederico, D. Tetrahedron: Asymmetry
2005, 16, 3628–3632.
† Department of Nano Science and Engineering.
‡ Department of Chemistry.
(1) (a) Pietra, F. Chem. ReV. 1973, 73, 293–364. (b) Rigby, J. H. Tetrahedron
1999, 55, 4521–4538.
(2) Graening, T.; Schmalz, H.-G. Angew. Chem., Int. Ed. 2004, 43, 3230–
3256.
(3) Kuwajima, I.; Tanino, K. Chem. ReV. 2005, 105, 4661–4670.
(4) Pauson, P. L. Chem. ReV. 1955, 55, 9–103.
(6) Yeo, J. E.; Yang, X.; Kim, H. J.; Koo, S. Chem. Commun. 2004, 236–
237.
(7) Teng, W.-D.; Huang, R.; Kwong, C. K.-W.; Shi, M.; Toy, P. H. J. Org.
Chem. 2006, 71, 368–371.
10.1021/jo802064c CCC: $40.75
Published on Web 11/21/2008
2009 American Chemical Society
J. Org. Chem. 2009, 74, 917–920 917

TABLE 1. Control of the Stereochemistry in the Oxidative Ring
Opening of 3-Cyclohexene-1,2-diols 2
SCHEME 2. Reaction Sequence for Dihydrotropone
Synthesis by the Ring-Expansion Strategya
entry
compd
R
reagent
t (h)
3 (%)a
4 (%)a
b
b
b
c
b
b
c
1
2
3
4
5
6
7
8
2a
2b
2c
2c
2d
2e
2e
2a
2b
2c
2d
2e
H
Pb(OAc)4
Pb(OAc)4
Pb(OAc)4
Pb(OAc)4
Pb(OAc)4
Pb(OAc)4
Pb(OAc)4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
5
0
0
0
63
0
0
53
32
53
70
66
83
68
70
89
0
62
93
2
0
0
0
0
Ph
Me
Me
Et
Bu
Bu
H
Ph
Me
Et
d
NaIO4
d
9
NaIO4
d
10
11
12
NaIO4
2
1.25
5
d
NaIO4
d
a See Table 2 for yields and conditions.
Bu
NaIO4
0
a Isolated yields after purification by SiO2 flash column
chromatography. 1H NMR spectra are included in Supporting
Information. b MeCN was used as a solvent at room temperature, and 1
M HCl was added for quench. c MeCN was used as a solvent at room
temperature, and H2O was added for quench and wash. d A 4:1
TABLE 2. Yields of Diols 2, Dihydrotropones 6/Cycloheptatrienols
7, and Tropones 8 in Scheme 2
entry
compd
E
2 (%)a,b
6/7 (%)a
8 (%)a
1
2
3
4
5
6
7
f
CO2Et
C(O)CH3
CN
C(O)CH2CO2Et
C(O)Ph
C(O)NMe2
SO2Ph
85 (6:1)
62/31
70/ 9
100/0
73/0c
56/8
95
96
76
volumetric mixture of THF/H2O was used as
temperature, and no acid was used for wash.
a solvent at room
g
h
i
j
k
l
63 (2.7:1)
94 (1.3:1)
65 (2.3:1)
60 (10:1)
85 (5:1)
d
50e
64g
86h
added to quench and wash the mixture of Pb(OAc)4-mediated
ring-opening reaction products, the Z-isomer 3 was obtained
predominantly even after 30 min (entries 4 and 7). This was
also confirmed by the complete and instantaneous isomerization
of pure 3c to 4c in a 1:1 (v/v) mixture of MeCN and 1 M HCl.
Since it was unavoidable to form acetic acid under the
condition using Pb(OAc)4, thereby producing 4 even in a small
amount (see entry 7), we selected an acid-free NaIO4 condition
to exclusively produce 3. The NaIO4-promoted oxidative ring
opening of 3-cyclohexene-1,2-diols 2 was slower than that with
Pb(OAc)4. However, retention of Z-configuration was realized
by using NaIO4 without acid treatment to produce fair to good
isolated yields of 3 (53-83%) except for unstable dialdehyde
3a (32%), where the reaction was stopped in 30 min to minimize
the decomposition of 3a (entries 8-12).8
Attempted cyclization of 3c (R ) Me in Scheme 1) to
dihydrotropone 6c (R′ ) H) by intramolecular aldol condensa-
tion failed under the conditions utilizing LDA or t-BuOK as a
base and produced only complicated or polymerization products.
It was necessary to activate the R-methylene unit of the carbonyl
group in 3 by another electron-withdrawing group E for smooth
intramolecular Knoevenagel condensation to produce dihy-
drotropones 6. Preparation of the activated unsaturated carbonyl
compounds 3f-3l with Z-configuration and the subsequent
cyclization process to dihydrotropones 6f-6l are delineated and
summarized in Scheme 2 and Table 2.
Various enolate nucleophiles prepared from ethyl acetate,
acetone, acetonitrile, ethyl acetoacetate, acetophenone, N,N-
dimethyl acetamide, and methyl phenyl sulfone were added to
6-trimethylsiloxy-2-cyclohexen-1-one (1)9 in THF at -78 °C
to produce 3-cyclohexene-1,2-diols 2f-2l in 60-95% yields
after desilylation with n-Bu4NF. Two diastereomeric 1,2-diols
were obtained in 1.3-10:1 ratios in the addition reactions
depending on the enolate nucleophiles, but both isomers
underwent a facile oxidative ring-opening reaction by silica-
supported NaIO410 to produce the same acyclic 1,6-dicarbonyl
compounds 3 with Z configuration. The NaIO4-promoted ring
opening of 2k (E ) CONMe2) was very sluggish, and Pb(OAc)4
63/0f
58/19
95 (2:1)
a Isolated yields after purification by SiO2 flash column
chromatography. b Diastereomeric ratios in parenthesis. c Crude yield.
d Decomposition of 6i presumably due to oligomerization. e Oxidation
was carried out by DDQ in refluxing toluene without Et3N. f Pb(OAc)4
was used instead of NaIO4 to induce oxidative ring-opening reaction.
g DBU
was
used
instead
of
Et3N
for
tautomerization.
h Cyclohepta-2,4,6-trienone (8l) was obtained by dehydrosulfonation.
had to be utilized to afford 3k. The intramolecular Knoevenagel
condensation of crude 3f-3l under the mild condition using
SiO2 in CH2Cl2 at ambient temperature, which was serendipi-
tously found during the purification process of the ring-opening
product 3, provided dihydrotropones 6f-6l in decent yields
together with varying amounts of their enol tautomers 7f-7l
(Table 2). The cyclization of 3k (E ) CONMe2) again required
the somewhat stronger condition of heating at 70 °C under SiO2
in dichloroethane for 5 h to produce dihydrotropone 6k.
Dihydrotropones 6 are in equilibrium with easily separable enol
tautomers 7 under the cyclization condition, but 6h (E ) CN),
6i (E ) COCH2CO2Et), and 6k (E ) CONMe2) were exclu-
sively obtained without their enol tautomers (entries 3, 4, and
6 in Table 2).
The structure of the tautomers 7 was unambiguously decided
1
by analysis of H NMR spectra, the formation of which was
easily deduced from the acidity of the allylic proton conjugated
with the two electron-withdrawing groups in dihydrotropones
6. Symmetrical dispositions (coupling patterns) of the four
vinylic protons (H1-H4) around the two central methylene
protons (HM) indicated the structure 7 [for example, H1 6.16
ppm (d, J ) 10.1 Hz, 1H), H2 6.01 ppm (dt, Jd ) 10.1, Jt ) 7.0
Hz, 1H), HM 2.40 ppm (dd, J ) 7.0, 6.6 Hz, 2H), H3 5.35 ppm
(dt, Jd ) 9.7, Jt ) 6.6 Hz, 1H), H4 6.45 ppm (d, J ) 9.7 Hz,
1H) for 7f].
Functionalized dihydrotropones 6 are versatile compounds
that participate in many synthetically useful transformations.11
Dihydrotropones 6 may undergo oxidation to tropones 8. Several
reaction conditions have been sought in a preliminary study.
The mild bromination/dehydrobromination condition utilizing
NBS together with catalytic TMS ·OTf worked for the oxidation
(8) Lena, J. I. C.; Altinel, E.; Birlirakis, N.; Arseniyadis, S. Tetrahedron
Lett. 2002, 43, 2505–2509.
(9) Pennanen, S. I. Synth. Commun. 1985, 15, 865–871.
(10) Zhong, Y.-L; Shing, T. K. M. J. Org. Chem. 1997, 62, 2622–2624.
918 J. Org. Chem. Vol. 74, No. 2, 2009

SCHEME 3. Ring Contraction of Dihydrotropone 6j
of dihydrotropone 6f to tropone 8f (62% yield).12 It was also
found that the oxidation of 6f to 8f by DDQ required the
condition of reflux in toluene for 2 h (70% yield),13 whereas
the enol tautomers 7f underwent smooth oxidation to 8f even
at room temperature within 15 min (90% yield). We thus
selected the condition of treating dihydrotropones 6 (or a mixture
of 6 and 7) first with a base (Et3N or DBU) to induce
tautomerization to 7 and then with DDQ for the facile oxidation
to 8 (the last column in Table 2).14
Dihydrotropone 6i containing both nucleophilic carbon and
electrophilic carbon in one molecule was not stable, and
attempted purification by silica gel chromatography as well as
intended oxidation of the crude 6i led to decomposition
presumably by oligomerization. It was noted that dihydrotropone
6j gave rise to phenolic compound 915 (72% yield) upon
treatment with Et3N for tautomerization. This novel ring
contraction/aromatization occurred only for dihydrotropone 6j.
The mechanism of this reaction is presumed to be the initial
formation of tautomer A-j, 6π electrocyclization to bicyclo[4.1.0]-
heptadiene B-j, and ring fragmentation followed by aromati-
zation to give 9 (Scheme 3). Oxidation of dihydrotropone 6j
was thus carried out without the base treatment, only by DDQ
at reflux in toluene to produce 8j in 50% yield. It was also noted
that the oxidation (Et3N/DDQ) of 6l with a benzene sulfonyl
substituent produced the dehydrosulfonation product cyclohepta-
2,4,6-trienone (8l) in 86% yield.
Dihydrotropones 6 are perfect substrates for the construction
of the polycyclic compounds containing a seven-membered
carbocycle (Scheme 4). The Diels-Alder reaction of dihy-
drotropone 6f (E ) CO2Et) with Danishefsky′s diene 10 in
refluxing toluene produced bicyclic compound 11f (92%) after
acidic workup. Diene 10 reacted with the more electron-deficient
alkene of 6 following the endo-rule (to the keto group) to
produce 11f with the designated regio- and stereochemistry.
Treatment of 11f with DBU induced further cyclization to
tricyclic compound 12f (75%) by the intramolecular conjugate
addition of the γ-carbanion of the cycloheptenone to the
conjugated cyclohexenone moiety. The Diels-Alder reaction
of dihydrotropone 6h (E ) CN) with Danishefsky′s diene 10
provided bicyclic compound 11h (62%). The ꢀ-methoxy sub-
stituent to the carbonyl group in 11h survived an acidic workup
condition, and treatment of 11h with DBU gave the tricyclic
caged compound 12h (66%) by the intramolecular aldol reaction
of the R-carbanion of the cycloheptenone to the cyclohexanone
moiety. The reactivity of the carbanions generated from the
cycloheptenone moiety of bicyclic compounds 11 by DBU
depends on the soft-hard nature of the electrophilic partners:
conjugate addition for the soft γ-carbanion with the soft
unsaturated carbonyl moiety in 11f versus aldol reaction for
the hard R-carbanion with the hard carbonyl moiety in 11h.
In summary, a condition for exclusive Z-control in the
oxidative ring-opening reaction of 3-cyclohexene-1,2-diols 2 has
been established by utilizing NaIO4 with no acid treatment. The
resulting acyclic conjugated carbonyl compounds with Z-
configuration undergo facile intramolecular Knoevenagel con-
densation to produce the ring-expanded dihydrotropones 6,
which are versatile compounds participating in various useful
transformations. This process complements our ring-contraction
protocol from 3-cyclohexene-1,2-diols 2 via the E-controlled
oxidative ring-opening reaction followed by the intramolecular
Baylis-Hillman reaction to produce cyclopentenols 5.6 Studies
on the preparation of diversely substituted dihydrotropones, their
reactions, and applications to the syntheses of the biologically
important polycyclic natural products are currently underway.
Experimental Section
Ring-Opening Reaction of 3-Cyclohexen-1,2-diols 2 with
NaIO4 To Produce Unsaturated Carbonyl Compounds with
Z-Configuration: 2-(Z)-Hexenedial (3a).16 To a stirred solution
of 3-cyclohexene-1,2-diol (2a) (0.47 g, 4.1 mmol) in THF/H2O (32
mL/8 mL) was added NaIO4 (1.07 g, 4.9 mmol). The mixture was
stirred at room temperature for 30 min. The resulting mixture was
then diluted with ethyl acetate, washed with water, dried over
anhydrous Na2SO4, filtered, and concentrated under reduced pres-
sure. The crude product was purified by SiO2 flash chromatography
to give 3a (0.15 g, 1.3 mmol) in 32% yield. Data for 3a: 1H NMR
δ 1.55-1.80 (m, 2H), 2.40-2.65 (m, 2H), 6.53 (ddd, J ) 11.4,
7.8, 3.4 Hz, 1H), 7.31 (ddt, Jd ) 11.4, 3.1, Jt ) 7.9 Hz, 1H), 9.73
(d, J ) 7.8 Hz, 1H), 9.79 (br s, 1H) ppm; 13C NMR δ 21.4, 43.5,
137.9, 146.5, 192.5, 202.0 ppm.
(11) (a) Kashman, Y.; Cherkez, S. Tetrahedron 1972, 28, 155–165. (b)
Kashman, Y.; Awerbouch, O. Tetrahedron 1970, 26, 4213–4225. (c) Franck-
Neumann, M.; Martina, D. Tetrahedron Lett. 1975, 16, 1755–1758. (d) Uvehara,
T.; Takahashi, M.; Kato, T. Tetrahedron Lett. 1984, 25, 3999–4002.
(12) Guha, S. K.; Wu, B.; Kim, B. S.; Baik, W.; Koo, S. Tetrahedron Lett.
2006, 47, 291–293.
Addition Reaction of the Enolates from Various Carbonyl
Compounds to Cyclohexenone 1: (1,6-Dihydroxy-2-
cyclohexen-1-yl)-acetic Acid, Ethyl Ester (2f). To a stirred solution
of diisopropylamine (4.48 mL, 32 mmol) in THF (30 mL) at 0 °C
was added a 1.6 M hexane solution of n-BuLi (18.75 mL, 30 mmol).
The mixture was stirred for 30 min and then cooled to -78 °C. To
this mixture was added ethyl acetate (2.78 mL, 28 mmol), and the
mixture was stirred at -78 °C for 40 min. To this mixture was
then added cyclohexenone 1 (3.70 g, 20 mmol). The reaction
mixture was stirred at -78 °C for 1.5 h and quenched with H2O.
(13) (a) Mak, C.-P.; Bu¨chi, G. J. Org. Chem. 1981, 46, 1–3. (b) Davies,
H. M. L.; Clark, T. J.; Kimmer, G. F. J. Org. Chem. 1991, 56, 6440–6447.
(14) References for tropones. (a) 8f: Horino, H.; Inoue, N.; Asao, T.
Tetrahedron Lett. 1981, 22, 741–744. (b) 8g: Kawamoto, I.; Sugimura, Y.;
Kishida, Y. Tetrahedron Lett. 1973, 877>880. (c) 8h: Morita, N.; Asao, T.;
Tajiri, A.; Sotokawa, H.; Hatano, M. Chem. Lett. 1985, 1879–1882. (d) 8j:
Horikoshi, H.; Miyano, H.; Takayasu, T.; Nitta, M. Synth. Commun. 1999, 29,
4367–4373.
(15) Lattanzi, A.; Senatore, A.; Massa, A.; Scettri, A. J. Org. Chem. 2003,
68, 3691–3694.
(16) Hudlicky, T.; Luna, H.; Barbieri, G.; Kwart, L. D. J. Am. Chem. Soc.
1988, 110, 4735–4741.
J. Org. Chem. Vol. 74, No. 2, 2009 919

SCHEME 4. Diels-Alder Reaction of Dihydrotropones 6 To Produce Polycyclic Compounds
The mixture was diluted with EtOAc, washed with H2O, dried over
anhydrous K2CO3, filtered, and concentrated under reduced pressure.
The crude product was dissolved in THF (30 mL), and treated with
1 M THF solution of n-Bu4NF (22 mL, 22 mmol) at 0 °C. The
mixture was stirred for 1 h, diluted with ethyl acetate, washed with
H2O, dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. The crude product was purified by SiO2 flash
chromatography to give 2f (3.41 g, 17 mmol, a 6:1 diastereomeric
mixture) in 85% yield. Data for 2f (major stereoisomer): 1H NMR
δ 1.29 (t, J ) 7.1 Hz, 3H), 1.76-1.86 (m, 2H), 1.99-2.13 (m,
1H), 2.17-2.28 (m, 1H), 2.51 (A of ABq, J ) 15.6 Hz, 1H), 2.68
(d, J ) 7.7 Hz, 1H), 2.79 (B of ABq, J ) 15.6 Hz, 1H), 3.60 (ddd,
J ) 8.1, 7.7, 5.7 Hz, 1H), 3.98 (s, 1H), 4.15 (q, J ) 7.1 Hz, 2H),
5.67 (ddd, J ) 10.0, 2.4, 1.5 HZ, 1H), 5.84 (ddd, J ) 10.0, 4.5,
2.8 Hz, 1H) ppm; 13C NMR δ 14.0, 23.9, 26.3, 42.7, 60.9, 69.7,
71.8, 129.1, 130.5, 172.7 ppm; IR (KBr) 3444, 1732, 1372, 1182
cm-1; HRMS (FAB+) calcd for C10H17O4 201.1127, found 201.1124.
1H) ppm; 13C NMR δ 14.2, 27.1, 61.1, 105.6, 118.2, 123.3, 124.7,
134.3, 170.1, 172.5 ppm; IR (KBr) 2971, 1739, 1652, 1557, 1372,
1227 cm-1
.
Oxidation of Dihydrotropones to Tropones: 7-Oxo-
1,3,5-cycloheptatrienecarboxylic Acid, Ethyl Ester (8f). To a
stirred solution of 6f (0.2 g, 1.12 mmol) in CH2Cl2 (5 mL) was
added Et3N (0.18 mL, 1.23 mmol) at room temperature. The mixture
was stirred for 15 min, and DDQ (0.26 g, 1.12 mmol) was added.
The reaction mixture was stirred for 15 min, diluted with EtOAc,
washed with 1 M NaHCO3 solution, dried over anhydrous MgSO4,
filtered, and concentrated under reduced pressure. The crude product
was purified by SiO2 flash chromatography to give 8f (0.19 g, 1.06
1
mmol) in 95% yield. Data for 8f: H NMR δ 1.36 (t, J ) 7.1 Hz,
3H), 4.37 (q, J ) 7.1 Hz, 2H), 6.97-7.20 (m, 4H), 7.53 (dd, J )
8.0, 1.1 Hz, 1H) ppm; 13C NMR δ 14.1, 61.9, 132.8, 135.1, 135.8,
136.6, 142.8, 143.4, 167.3, 184.5 ppm; IR (KBr) 1728, 1634, 1590
1235 cm-1; HRMS (CI+) calcd for C10H11O3 179.0708, found
179.0709.
Ring Opening of 3-Cyclohexen-1,2-diols
2
with
SiO2-Supported NaIO4 and Subsequent Cyclization to
Dihydrotropones: 7-Oxo-1,5-cycloheptadienecarboxylic Acid,
Ethyl Ester (6f). To a stirred solution of diol 2f (1.68 g, 8.42 mmol)
in CH2Cl2 (30 mL) was added SiO2-supported NaIO4 (25.9 g, 8.63
mmol, 3 g/mmol). The mixture was stirred at room temperature
for 4 h and filtered under reduced pressure. The filter cake was
rinsed with CHCl3, and the filtrate was concentrated under reduced
pressure. The crude product was then dissolved in CH2Cl2 (30 mL),
and 70-230 mesh silica gel (16.8 g, 2 g/mmol) was added. The
mixture was stirred at room temperature for 2 h and filtered under
reduced pressure. The filtered silica gel was rinsed with CHCl3,
and the filtrate was concentrated under reduced pressure. The crude
product was purified by SiO2 flash chromatography to give
dihydrotropone 6f (1.0 g, 5.2 mmol, 62% yield) and its tautomer
Ring Contraction/Aromatization of Dihydrotropone 6j:
2-(2-Hydroxyphenyl)-1-phenylethanone (9).15 To a stirred solu-
tion of 6j (0.25 g, 1.2 mmol) in CH2Cl2 (10 mL) was added Et3N
(0.5 mL, 3.6 mmol) at 0 °C. The mixture was stirred at 0 °C for
2 h and then diluted with CH2Cl2, washed with water, dried over
anhydrous Na2SO4, filtered, and concentrated under reduced pres-
sure. The crude products was purified by SiO2 flash chromatography
1
to give 9 (0.18 g 0.86 mmol) in 72% yield. Data for 9: H NMR
δ 4.29 (s, 2H), 6.84-6.92 (m, 1H), 6.93-6.99 (m, 1H), 7.13-7.22
(m, 2H), 7.47-7.55 (m, 2H), 7.58-7.66 (m, 1H), 8.06-8.14 (m,
2H) ppm; 13C NMR δ 41.0, 117.6, 120.8, 121.0, 128.8, 129.0, 130.9,
134.0, 135.7, 155.5, 201.1 ppm; IR (KBr) 3412, 1677, 1596, 1456,
1343, 750 cm-1
.
1
7f (0.5 g, 2.6 mmol, 31% yield). Data for 6f: H NMR δ 1.31 (t,
Acknowledgment. This work was supported by a Korea
Research Foundation Grant (KRF-2003-015-C00342).
J ) 7.1 Hz, 3H), 2.43-2.61 (m, 4H), 4.26 (q, J ) 7.1 Hz, 2H),
6.17 (dt, Jd ) 12.1, Jt ) 1.7 Hz, 1H), 6.69 (dt, Jd ) 12.1, Jt ) 5.3
Hz, 1H), 7.35 (t, J ) 6.6 Hz, 1H) ppm; 13C NMR δ 14.1, 26.0,
26.6, 61.2, 132.4, 139.0, 145.5, 145.5, 165.6, 190.8 ppm; IR (KBr)
1732, 1651, 1275 cm-1; HRMS (CI+) calcd for C10H13O3 181.0865,
found 181.0867. Data for 7f: 1H NMR δ 1.37 (t, J ) 7.1 Hz, 3H),
2.40 (dd, J ) 7.0, 6.6 Hz, 2H), 4.32 (q, J ) 7.1 Hz, 2H), 5.35 (dt,
Jd ) 9.7, Jt ) 6.6 Hz, 1H), 6.01 (dt, Jd ) 10.1, Jt ) 7.0 Hz, 1H),
6.16 (d, J ) 10.1 Hz, 1H), 6.45 (d, J ) 9.7 Hz, 1H), 12.72 (br s,
Supporting Information Available: General experimental,
experimental procedures, analytical data, and 1H and 13C NMR
spectra. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO802064C
920 J. Org. Chem. Vol. 74, No. 2, 2009