Novel transformation of 2-substituted alkyl 1-indanone-2-acetates to 6-substituted 3,4-benzotropolones through sequential reduction and oxidation processes using Sm(II) and Ce(IV) salts

Article abstract of DOI:10.1016/j.tetlet.2003.10.083

When 2-substituted alkyl 1-indanone-2-acetates 1 were treated with samarium diiodide, 3-substituted 2-hydroxy-2,3-methano-1-oxo-1,2,3,4- tetrahydronaphthalenes 4 were obtained. The reaction is proposed to proceed through a rearrangement initiated by intramolecular ketone-ester coupling. Oxidation of these products 4 or their silyl ethers 13 by ceric(IV) ammonium nitrate involving regioselective bond cleavage of their bicyclo[4.1.0]-rings produced the corresponding benzotropolone derivatives 10.

Full text of DOI:10.1016/j.tetlet.2003.10.083

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 9317–9320
Novel transformation of 2-substituted alkyl 1-indanone-2-acetates
to 6-substituted 3,4-benzotropolones through sequential reduction
and oxidation processes using Sm(II) and Ce(IV) salts
Kazuki Iwaya, Mutsuko Tamura, Momoe Nakamura and Eietsu Hasegawa*
Department of Chemistry, Faculty of Science, Niigata University, Ikarashi-2 8050, Niigata 950-2181, Japan
Received 15 August 2003; revised 6 October 2003; accepted 10 October 2003
Abstract—When 2-substituted alkyl 1-indanone-2-acetates 1 were treated with samarium diiodide, 3-substituted 2-hydroxy-2,3-
methano-1-oxo-1,2,3,4-tetrahydronaphthalenes 4 were obtained. The reaction is proposed to proceed through a rearrangement
initiated by intramolecular ketone–ester coupling. Oxidation of these products 4 or their silyl ethers 13 by ceric(IV) ammonium
nitrate involving regioselective bond cleavage of their bicyclo[4.1.0]-rings produced the corresponding benzotropolone derivatives
10.
© 2003 Elsevier Ltd. All rights reserved.
Development of effective methods to construct
medium-sized rings is an important target in organic
synthesis.1 Among successful ways to achieve this
objective is an employment of a cyclization and ring
expansion method.2 We have recently discovered that
the reaction of a-ester substituted indanones I (n=1)
with samarium diiodide (SmI2) promoted intramolecu-
lar ketone–ester coupling followed by rearrangement
to finally give one-carbon homologated a-hydroxy
benzocyclohexenones II (n=1) (Eq. (1)).3 Then, we
considered that this method was applicable to the syn-
thesis of benzotropolones4 whose structures are often
found in naturally occurring theaflavins.5 However,
the reaction of a-ester substituted tetralones I (n=2)
with SmI2 did not give the expected a-hydroxy benzo-
cycloheptenones II (n=2) under the same reaction
conditions.6 In this paper, we would like to report the
preliminary results obtained by an exploratory study
on an alternative approach to the synthesis of ben-
zotropolones utilizing
a
two-carbon-homologation
methodology as described in Eq. (2). Although the
direct transformation of III to IV was not successful
by SmI2, we finally discovered that sequential reduc-
tion and oxidation processes using Sm(II) and Ce(IV)
salts, respectively, made such a transformation possi-
ble (see below).
Table 1. Reaction of 2-substituted alkyl 1-indanone-2-acetates 1, 2, 3 with SmI2
Entry
Substrate
R1
R2
Conv. (%)
Yield of 4 (%)
1a
2b
3c
4b
5b
6b
7a
8a
1a
1a
1a
1b
1c
1d
2a
3a
Me
Me
Me
Me
Me
Me
Et
Me
Me
Me
n-Pr
Allyl
PhCH2
Me
99
98
100
98
99
84
48
59
29
66
67
42
47
54
>95
93
Ph
Me
a 1a, 2a or 3a was added to 0.10 M SmI2 solution.
b 1 was added to 0.06 M SmI2 solution.
c 0.10 M SmI2 solution was added to 1a.
Keywords: g-keto ester; ketone–ester coupling; samarium diiodide; cyclopropane ring opening; ceric(IV) ammonium nitrate; benzotropolone.
* Corresponding author. Tel.:/fax: +81-25-262-6159; e-mail: ehase@chem.sc.niigata-u.ac.jp
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.083

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K. Iwaya et al. / Tetrahedron Letters 44 (2003) 9317–9320
(1)
(2)
When methyl 2-methyl-1-indanone-2-acetate 1a7 was
treated with 2.2 equivalents of SmI2, the expected com-
pound 5a (R2=Me) was not obtained. Instead, a rear-
rangement product, 2-hydroxy-2,3-methano-3-methyl-
1-oxo-1,2,3,4-tetrahydronaphthalene 4a was isolated in
48% yield (Eq. (3)) (entry 1 in Table 1).8,9 Modification
of the reaction conditions influenced the yield of 4a to
some extent. For example, the yield of 4a increased
under the diluted conditions (entry 2) while the inverse
addition in which SmI2 was added to the solution of 1a
decreased the yield of 4a (entry 3). Similar rearrange-
ments were also observed for the reaction of other
derivatives 1, 2 and 3 with SmI2 while the yields of the
corresponding products 4 were modest (Table 1).8 It
was then found that the effect of the alkoxy substituent
of the ester group (OR1) on the yield of 4 was rather
small (entries 1, 7 and 8).
Scheme 1.
Table 2. Reaction of 3-substituted 1-hydroxy-2,3-methano-
1-oxo-1,2,3,4-tetrahydronaphthalenes 4 with CAN
Entry
4
R2
Conv. of 4 (%)
Yield of 10 (%)
1
2
3
4
4a
4b
4c
4d
Me
n-Pr
Allyl
PhCH2
100
100
100
100
47
41
39
38
for the related transformations.10a,c,e Some consumption
of 4a was observed in MeCN; however, the expected
ring opening products were not isolated from the com-
plicated product mixture. On the other hand, 4a was
quantitatively recovered in DMF. Then, we conducted
the reaction of 4a with ceric ammonium nitrate
(CAN)10b in MeCN to find the formation of 6-methy-
3,4-benzotropolone 10a (Eq. (4)) (entry 1 in Table 2).11
The same reaction also proceeded in THF to give 10a
(54%). Although 1H HMR analysis of the reaction
mixture of 4a with CAN suggested the presence of
11a,12 10a was isolated by silica gel column chromato-
graphy (Eq. (4)). As one may expect, when the reaction
was conducted in MeOH, the methoxy substituted
product 12a13 that was stable during column chro-
matography was isolated. Reactions of other 4 with
CAN gave the corresponding 10 in moderate yields
(Table 2).11 It should be noted that the acetate of 4a
prepared by the reaction of 9a with acetic anhydride
was not reactive with CAN. As has been seen in related
chemistry,10a–d silyloxy cyclopropanes are known to be
reactive substrates with metal oxidants. Thus, the reac-
tion mixture of 1a with SmI2 was quenched with
Me3SiCl followed by extraction and concentration to
give a reaction mixture which was then treated with
CAN without further purification (Scheme 2).14 The
overall yield of 10a (52%) from 1a in this reaction was
better than that (ca. 25%) obtained under the corre
sponding stepwise conditions (1a“4a“10a). Again,
FeCl3 was found to be ineffective.
(3)
On the basis of the above results and those of a related
study,3 a plausible reaction mechanism, represented by
1 and SmI2, is proposed as shown in Scheme 1. Single
electron transfer from SmI2 to the ketone carbonyl of 1
gives the samarium ketyl radical 6. Subsequent ketyl
radical cyclization onto the ester carbonyl, which might
be reversible, gives the cyclobutoxy radical 7. Then, 7
undergoes ring-opening and re-cyclization liberating
methoxy anion and samarium ion (MeOSmI2) to give 8.
The reaction of 8 with another equivalent of SmI2
giving 9 is followed by hydrolysis to yield 4. Higher
concentration of SmI2 surrounding 8 should further
accelerate the conversion of 8 to 9, which seems to be
consistent with the results presented in Table 1; the
yield of 4a in entry 1 is greater than that in entry 3.
We noticed that the products 4 possess a cyclopropoxy
structure which could be opened with certain metal
oxidants.10 Thus, we first attempted to react 4a with
FeCl3 since Fe(III) salts are known as effective reagents
(4)

K. Iwaya et al. / Tetrahedron Letters 44 (2003) 9317–9320
9319
Scheme 2.
Scheme 3.
References
In Scheme 3, a plausible reaction mechanism is pre-
sented. Single electron transfer from 4 or 13 to CAN
gives their radical cations. The intermediate 14 possess-
ing tertiary carbon radical is formed through subse-
quent deprotonation or desilylation and ring-opening
while the order of each step could not be easily spe-
cified. The reaction of 14 with another equivalent of
CAN followed by attack of certain nucleophiles (Nu−)
to the formed carbocation yields the benzocycloheptan-
dione 11 or 12, depending on the solvents used. If
elimination of HNu from these adducts occurs, the
following keto–enol tautomerization yields 6-substi-
tuted 3,4-benzotropolone 10.
1. Yet, L. Chem. Rev. 2000, 100, 2963–3007 and the references
cited therein.
2. (a) Dowd, P.; Choi, S.-C. Tetrahedron 1989, 45, 77–90; (b)
Roxburg, C. J. Tetrahedron 1993, 49, 10749–10784; (c)
Rousseau, G. Tetrahedron 1995, 51, 2777–2849; (d) Yet, L.
Tetrahedron 1999, 55, 9349–9403.
3. Iwaya, K.; Nakamura, M.; Hasegawa, E. Tetrahedron Lett.
2002, 43, 5067–5070.
4. Representative papers for synthesis of benzotropolones. (a)
Sato, M.; Tsunetsugu, J.; Ebine, S. Bull. Chem. Soc. Jpn.
1972, 45, 638–639; (b) Read, G.; Ruiz, V. M. J. Chem. Soc.,
Perkin Trans. 1 1973, 1223–1224; (c) Friedrichsen, W.;
Plug, C. Tetrahedron Lett. 1992, 33, 7509–7510.
In conclusion, although the conditions are not fully
optimized yet, the results presented above demonstrate
that a novel set of reduction and oxidation processes
using Sm(II) and Ce(IV) salts, respectively, is effective
for the transformation of 2-substituted alkyl 1-
indanone-2-acetates to the benzotropolone derivatives
via 3-substituted 2-hydroxy-2,3-methano-1-oxo-1,2,3,4-
tetrahydronaphthalenes. Studies probing the potential
applicability of this methodology to reductive forma-
tion and oxidative ring-opening of other cyclo-
propanols are continuing.15
5. (a) Sanderson, G. W. In Recent Advances in Phytochem-
istry; Runeckles, V. C.; Tso, T. C., Eds.; Academic Press:
New York, 1972; Vol. 5, pp. 247–316; (b) Lewis, J. R.;
Davis, A. L.; Cai, Y.; Davies, A. P.; Wilking, J. P. G.;
Pennington, M. Phytochemistry 1998, 49, 2511–2519.
6. Iriyama, T.; Iwaya, K.; Hasegawa, E. unpublished results.
7. Indanone 1a was synthesized by the following procedures.
Reaction of 1-indanoe (120 mmol) with diethyl carbonate
(92.7 ml) and NaH (144 mmol) at reflux temperature
provided ethyl 1-indanone-2-carboxylate (85 mmol, 71%).
a-Methylation of ethyl 1-indanone-2-carboxylate (20.0
mmol) by CH3I (80.0 mmol) and NaH (24.0 mmol) gave
ethyl 2-methyl-1-indaone-2-carboxylate (20.0 mmol,
100%). Then, decarboxylation of ethyl 2-methyl-1-
indaone-2-carboxylate (20.0 mmol) was performed with
hydrobromic acid (177.0 mmol) to give 2-methyl-1-
indanone (18.6 mmol, 93%). Resulting 2-methyl-1-
indanone (18.6 mmol) was treated with methyl
bromoacetate (55.8 mmol) and NaH (22.3 mmol) to give
1a (14.1 mmol, 76%). Physical and spectral data of 1a:
colorless solid, mp 59–60°C; IR (KBr) 1729, 1707 cm−1; 1H
NMR (200 MHz, CDCl3) l 7.79 (d, J=7.6 Hz, 1H), 7.60
(dd, J=7.6, 7.6 Hz, 1H), 7.46–7.35 (m, 2H), 3.55 (s, 3H),
3.31 (d, J=17.2 Hz, 1H), 2.96 (d, J=17.2 Hz, 1H), 2.84
(d, J=16.2 Hz, 1H), 2.68 (d, J=16.2 Hz, 1H), 1.23 (s, 3H);
13C NMR (50 MHz, CDCl3) l 209.1, 171.6, 152.1, 135.1,
134.8, 127.4, 126.5, 124.3, 51.6, 46.6, 41.3, 40.2, 24.7. Other
indanones 1, 2a and 3a were similarly synthesized.
Acknowledgements
This work was supported by Grants-in-Aid for Scien-
tific Research on Priority Areas ‘Exploitation of Multi-
element Cyclic Molecules’ (No. 14044030) as well as
Scientific Research C (No. 15550028) from the Ministry
of Education, Culture, Sports, Science and Technology,
Japan. We thank Professor Toshio Suzuki (Faculty of
Engineering, Niigata University) and Professor Masaki
Kamata (Faculty of Education of Human Science,
Niigata University) for their valuable comments. We
also thank Professor Takaaki Horaguchi (Faculty of
Science, Niigata University) for his generous assistance.

9320
K. Iwaya et al. / Tetrahedron Letters 44 (2003) 9317–9320
8. A typical experiment (entry 2 in Table 1): a THF solution
mixture was stirred for 1 h, and was then quenched with
saturated aqueous NaHCO3 (10 mL), and the solution
was stirred under air for 10 min. The following extraction
procedure was the same as that for SmI2 reaction (see
Ref. 8). The crude mixture was separated by thin-layer
chromatography on silica gel (EtOAc:benzene=1:10) to
give 10a (0.23 mmol, 47%). Physical and spectral data of
10a: yellow solid, mp 85–98°C (decomp); IR (KBr) 3266,
(5.0 mL) of indanone 1a (0.50 mmol) was added dropwise
under N2 during 0.1 min to the THF solution (17.0 mL)
of SmI2 (1.10 mmol) at room temperature. The reaction
mixture was stirred for 30 min followed by quenching
with 0.1 M HCl (10 mL), and was stirred under air for 10
min. The resulting mixture was extracted with Et2O (30
mL×3), and then the organic layer was washed with
saturated aqueous NaHCO3, Na2S2O3 and NaCl (30
mL), and dried over MgSO4. The residue obtained by the
concentration of the extract was separated by column
chromatography on silica gel (EtOAc:benzene=1:10) to
give 4a (0.29 mmol, 59%). Physical and spectral data of
4a: colorless solid, mp 40–41°C; IR (KBr) 3440, 1658
1
1638, 1586 cm−1; H NMR (200 MHz, CDCl3) l 8.84 (d,
J=8.2 Hz, 1H), 8.65 (br, 1H), 7.73–7.58 (m, 3H), 7.26 (s,
1H), 7.15 (s, 1H), 2.46 (s, 1H); 13C NMR (50 MHz,
CDCl3) l 180.1, 155.3, 138.2, 136.5, 133.7, 132.7, 132.0,
131.9, 130.6, 128.4, 117.9, 27.2. Reactions of other 4 with
CAN and characterizations of the products 10 were
performed in a similar manner.
1
cm−1; H NMR (200 MHz, CDCl3) l 7.90 (d, J=7.6 Hz,
1H), 7.48 (dd, J=7.6, 7.6 Hz, 1H), 7.34 (dd, J=7.6, 7.6
Hz, 1H), 7.18 (d, J=7.6 Hz, 1H), 3.15 (s, 2H), 1.52 (s,
12. Physical and spectral data of 11a: yellow oil; IR (neat)
1
1729, 1689, 1628 (-ONO2), 861 (-ONO2) cm−1; H NMR
3H), 1.27 (d, J=5.4 Hz, 1H), 1.15 (d, J=5.4 Hz, 1H); 13
C
(200M Hz, CDCl3) l 7.98 (d, J=7.5 Hz, 1H), 7.65 (dd,
J=7.5, 7.5 Hz, 1H), 7.50 (dd, J=7.5, 7.5 Hz, 1H), 7.32
(d, J=7.5 Hz, 1H), 3.42 (d, J=15.5 Hz, 1H), 3.36 (d,
J=12.3 Hz, 1H), 3.25 (d, J=12.3 Hz, 1H), 3.16 (d,
J=15.5 Hz, 1H), 1.87 (s, 1H); 13C NMR (50M Hz,
CDCl3) l 194.6, 190.4, 135.7, 135.0, 133.7, 131.8, 130.1,
128.9, 87.0, 48.6, 42.6, 24.2.
NMR (50 MHz, CDCl3) l 198.2, 139.4, 133.2, 130.2,
128.5, 127.1, 127.0, 67.7, 36.1, 27.4, 25.1, 18.7. Reactions
of other indanones 1, 2a and 3a with SmI2 and character-
izations of the products 4 were performed in the similar
manner.
9. Interestingly, in the related aliphatic systems, 1-methyl-5-
hydroxybicyclo[3.2.0]heptan-7-one
and
1-methyl-6-
13. Physical and spectral data of 12a: yellow oil; IR (neat)
hydroxybicyclo[4.1.0]heptan-5-one were found to exist as
the equilibrium mixture in solution, where the former
isomer is more favorable than the latter one: Jung, M.E.;
Davidov, P. Org. Lett. 2001, 3, 627–629. On the contrary,
the existence of 1-methyl-5-hydroxy-2,3-benzobicyclo-
[3.2.0]heptan-7-one was not confirmed in our benzo-fused
system.
1
1723, 1686 cm−1; H NMR (200 MHz, CDCl3) l 7.93 (d,
J=7.3 Hz, 1H), 7.58 (dd, J=7.3, 7.3 Hz, 1H), 7.43 (dd,
J=7.3, 7.3 Hz, 1H), 7.28 (d, J=7.3 Hz, 1H), 3.26 (s, 1H),
3.17 (d, J=15.0 Hz, 1H), 3.06 (d, J=11.9 Hz, 1H), 2.94
(d, J=15.0 Hz, 1H), 2.80 (d, J=11.9 Hz, 1H), 1.42 (s,
1H); 13C NMR (50 MHz, CDCl3) l 197.3, 191.7, 138.3,
134.3, 134.0, 1315, 129.8, 127.8, 74.9, 49.9, 49.3, 44.0,
23.7.
10. (a) Ito, Y.; Fujii, S.; Saegusa, T. J. Org. Chem. 1976, 41,
2073–2074; (b) Paolobelli, A. B.; Gioacchini, F.; Ruzzi-
coni, R. Tetrahedron Lett. 1993, 34, 6333–6336; (c)
Booker-Milburn, K. I.; Thompson, D. F. J. Chem. Soc.,
Perkin Trans. 1 1995, 2315–2321; (d) Iwasawa, N.; Funa-
hashi, M.; Hayakawa, S.; Ikeno, T.; Narasaka, K. Bull.
Chem. Soc. Jpn. 1999, 72, 85–97; (e) Booker-Milburn, K.
I.; Jones, J. L.; Sibley, G. E. M.; Cox, R.; Meadows, J.
Org. Lett. 2003, 5, 1107–1109.
11. A typical experiment (entry 1 in Table 2): an MeCN
solution (7.0 mL) of 4a (0.50 mmol) was added dropwise
under N2 during 0.1 min to the MeCN solution (3.0 mL)
of CAN (1.10 mmol) at room temperature. The reaction
14. To the reaction mixture obtained from 1a (0.50 mmol)
and SmI2 was added Me3SiCl (5.0 mmol), and the result-
ing solution was stirred under air for 20 min followed by
ethereal extraction. An MeCN solution (7.0 mL) of the
mixture obtained by concentration of the extract was
added to a MeCN solution (3.0 mL) of CAN (1.10 mmol)
at room temperature. Following procedure was the same
as that described in Ref. 11.
15. Latest review of synthesis and reactions of cyclo-
propanols: Kulinkovich, O. G. Chem. Rev. 2003, 103,
2597–2632.