Synthesis of substituted α-tetralones and substituted 1-naphthols via regioselective ring expansion of 1-acyl-1-indanol skeleton

Article abstract of DOI:10.1016/j.tetlet.2011.11.103

Substituted 1-acyl-1-indanols were prepared using the corresponding readily commercially available substituted indanones as starting materials. Treatment of each 1-acyl-1-indanol derivative with sodium methoxide in hot methanol furnished a regiospecific 2-hydroxy-α-tetralone derivative, which was an α-keto rearrangement product. Each substituted 2-hydroxy-α-tetralone then underwent dehydration to afford the corresponding 1-naphthol derivative.

Full text of DOI:10.1016/j.tetlet.2011.11.103

Tetrahedron Letters 53 (2012) 585–588
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of substituted
a-tetralones and substituted 1-naphthols
via regioselective ring expansion of 1-acyl-1-indanol skeleton
⇑
Te-Fang Yang , Kuan-Yu Wang, Hsuan-Wei Li, Yang-Chan Tseng, Tai-Chen Lien
Department of Applied Chemistry, National Chi Nan University, Puli, 545 Nantou, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Substituted 1-acyl-1-indanols were prepared using the corresponding readily commercially available
substituted indanones as starting materials. Treatment of each 1-acyl-1-indanol derivative with sodium
methoxide in hot methanol furnished a regiospecific 2-hydroxy-a-tetralone derivative, which was an a-
Received 8 November 2011
Accepted 21 November 2011
Available online 26 November 2011
keto rearrangement product. Each substituted 2-hydroxy-
a-tetralone then underwent dehydration to
afford the corresponding 1-naphthol derivative.
Keywords:
Ó 2011 Elsevier Ltd. All rights reserved.
Indanone
a
a
-Keto rearrangement
-Tetralone
1-Naphthol
Disubstituted 1-naphthols could be regioselectively synthesized
readily available, would give alkene 2. Dihydroxylation of 2 to a diol
followed by oxidation of the secondary hydroxyl group with a suit-
able agent would then provide 1-acyl-1-indanol 3. The crucial step
in five steps, via dienone-phenol type rearrangement, using 1,4-
naphthoquinone as the precursor.1 Coupling reaction of alkyne with
1,2-aryldialdehyde in the presenceof low valent metal halides, as re-
ported by Pedersen, Utimoto and co-workers, also provided substi-
tuted 1-naphthols.2–4 They found that a metal (Ta or Nb)–alkyne
complex was generated at the beginning of the reaction and imme-
diately used as a dianion synthon for the attack on formyl groups.
Another method for the synthesis of substituted 1-naphthols in-
volved palladium-catalyzed ring opening of an oxabenzonorborna-
diene with aryl halide in the presence of 10 equiv of activated zinc,
and oxidation of the intermediate with IBX.5,6 Furthermore, ruthe-
nium catalyzed aromatization of alkyl enediynes could afford 2-al-
kyl 1-naphthols as well.7 Although the procedures mentioned
above afforded the target product(s) in good to excellentyields, most
of those starting materials were not readily commercial available.
Moreover, some of the target products were found to be unstable
in the presence of certain excess amounts of the oxidant.
of this methodology would be keto rearrangement of 3 to a-tetra-
lone 4. Subsequent dehydration of 4 would cause an automatic tau-
tomerization and furnish 1-naphthol 5. It is noted that Brunner
et al.12 had reported their study on the ring expansion of 9-benzoyl-
fluorene-9-ol, to which 1-benzoyl-1-indanol (vide infra), one of our
substrates, is analogous. However, they found that complete conver-
sion of molten 9-benzoylfluorene-9-ol to a corresponding phenan-
threne-9-one had taken 10 days, even using NiCl2 and suitable
ligand as the catalyst. Herein, we report a general efficient method-
ology for the synthesis of the title compounds under mild and tran-
sition metal-free conditions, starting from commercially available
indanones (1).
Parent 1-acetyl-1-indanol (6c, Table 1, entry 1) was selected as
the first target molecule for the first half part of our work. It was
found that the reaction of 6a with (ethyl)triphenyl-phosphonium
iodide in the presence of potassium t-butoxide gave 6b in moder-
ate yield (60%). Nevertheless, 6b could not be efficiently converted
to 6c after two oxidation reactions were carried out. Therefore, var-
ious 1-benzoyl substituted 1-indanols then became the target mol-
ecules. Thus, the combination of PPh3BnCl or PPh3BnBr, n-BuLi in
THF was employed for the Wittig reaction of 7a–17a, as shown
in Table 1 (entries 2–12).13–15 Among all the experiments for the
reaction, the transformation of 17a to 17b, in which R4 was a phe-
nyl group, turned out to be the most efficient one (17b: a 91% yield,
entry 12). For the conversion of 6b–17b to their corresponding hy-
droxyl ketones (6c–17c), it should be noted that each single
dihydroxylation reaction (step1) gave a mixture of some stereo-
specific diols. Then, treatment of each individual mixture of the
On the other hand, recently, we had reported that [2.2.1]bicyclic
carbinols could undergo ring expansion,8 which was related to the
rearrangement of a
-hydroxy ketones.9–12 In order to further under-
stand the general behavior of keto rearrangement of acyl hydroxyl
cyclic compounds, and to solve or avoid the above problems
described in the literature, we then applied the rearrangement of
-hydroxy ketones to the synthesis of substituted a-tetralones
and substituted 1-naphthols, based on the reactions outlined in
a
Scheme 1. A Wittig reaction of indanone 1, which is commercially
⇑
Corresponding author. Tel.: +886 49 2910960; fax: +886 49 2917956.
E-mail address: tfyang@ncnu.edu.tw (T.-F. Yang).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.11.103

586
T.-F. Yang et al. / Tetrahedron Letters 53 (2012) 585–588
O
O
Ph
Ph
HO
1. TMO, OsO4
2. [O]
Wittig
R
R
R
1
3
2
O
OH
OH
Ph
Ph
- H2O
Keto rearr.
R
R
4
5
Scheme 1. Conversion of substituted indanones to
a
-tetralones and 1-naphthols.
Table 1
Synthesis of various substituted 1-acyl-1-indanols
O
1. TMO, OsO4,
R6
R5
O
H2O, t-BuOH,
R6
R5
HO
PPh3BnCl,
R1
R2
R1
R5
R2
THF, r. t. 4h.
R1
R2
n-BuLi
2. TEMPO, KBr,
NaHCO3, H2O,
CH2Cl2, NaOCl,
THF, reflux,
24 h.
R4
R4
R3
R4
R3
R3
0
oC, 45 min.
6c ~ 17c
6a ~ 17a
6b ~ 17b
Entry
Indanone
Atom or group
Corresponding producta (% yield)
R1
R2
R3
R4
R5
R6
1
2
3
4
5
6
7
8
9
6a
7a
8a
9a
10a
11a
12a
13a
14a
15a
16a
17a
H
H
Br
H
H
Me
H
H
MeO
H
H
H
H
H
Br
H
H
H
H
H
H
H
H
H
Br
H
H
H
H
H
Ph
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
6b (60)b
7b (56)c
8b (77)
6c (28)
7c (61)
8c (48)
9c (64)
10c (45)
11c (47)
12c (77)
13c (53)
14c (53)
15c (32)
16c (57)
17c (64)
9b (59)
10b (59)
11b (63)c
12b (69)
13b (67)
14b (63)c
15b (68)
16b (55)
17b (91)
10
11
12
MeO
H
H
H
H
Ph
H
a
b
c
The % yields of 6c–17c were correspondingly based on 6b–17b (two steps).
Conditions for the conversion of 6a to 6b: PPh3CH2CH3I, t-BuOK, ether, rt, 14 h.
Instead of PPh3BnCl, PPh3BnBr was employed for the Wittig reaction.
stereoisomers (diols), which were not separated, with NaOCl in the
presence of TEMPO furnished a mixture of stereo-specific hydroxyl
ketones. Among all the hydroxyl ketones obtained after the two
oxidation reactions starting from 6b–17b, 12c turned out to be
the one with highest yield (77%, entry 7).
was obtained, but in a low yield (19%). On the other hand, 17d
was obtained in a low yield (29%, entry 11) from the reaction of
17c, in which the phenyl group (R4) might cause a significant steric
effect.
A plausible mechanism for the regioselective ring expansion of
various substituted 1-acyl-1-indanols 6c–17c (except 13c) is illus-
trated in Figure 1. In order to demonstrate how hydroxyl tetralones
6d–17d (except 13d) were exclusively produced in the presence of
sodium methoxide, structures 6c–17c (except 13c) were partially
numbered. Presumably, the carbonyl group on 6c–17c (except
13c) was further polarized by methanol, which is a strong polar
protic solvent. Thus, the oxygen atom on C1 was further partially
negative, and C1 itself further partially positive. Then, the methox-
ide ion obtained the proton from hydroxyl group on C2 of structure
A, such that the oxygen atom possessed a negative charge and che-
lated with sodium to form structure B. Finally, C3 was forced to at-
tack C1 via route a as shown in structure C, which was analogous to
The second half part of our methodology for the synthesis of the
title compounds involved
a-keto rearrangement, which was the
crucial reaction of the entire work. As shown in Table 2,15–17 indi-
vidual treatments of 6c–12c (entries 1–7) and 14c–17c (entries 9–
12) with sodium methoxide in hot methanol resulted in a regiose-
lective ring expansion, which furnished
a-tetralones 6d–12d and
14d–17d, correspondingly, in moderate to good yields. However,
due to some unknown reasons, 13c could not be converted to
13d (entry 8) at all under the same reaction conditions as those
for the other experiments. Therefore, instead of methanol, toluene
was used as the solvent for the treatment of 13c with NaOMe.
Unfortunately, 13d still had not been observed at all. Instead, 13e

T.-F. Yang et al. / Tetrahedron Letters 53 (2012) 585–588
587
Table 2
Ring expansion of substituted 1-acyl-1-indanols and the follow-on dehydration
O
O
OH
R6
R5
HO
OH
R6
R5
R6
R5
R1
R2
R1
R2
R1
R2
MeONa
MeOH,
reflux, t1
TsOH
Toluene,
reflux, t2
R4
R3 R4
R3 R4
R3
6e 17e
~
6d 17d
6c 17c
~
~
Entry
Acyl indanol
Atom or group
t1 (h)
Product (% yield)
t2 (h)
Product (% yield)
R1
R2
R3
R4
R5
R6
1
2
3
4
5
6
7
8
9
6c
7c
8c
9c
10c
11c
12c
13c
14c
15c
16c
17c
H
H
Br
H
H
Me
H
H
MeO
H
H
H
H
H
Br
H
H
H
H
H
H
H
H
H
Br
H
H
H
H
H
Ph
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
12
20
12
12
12
7
12
—
12
20
20
20
6d (91)
7d (95)
8d (88)
9d (84)
10d (71)
11d (95)
12d (91)
13d (—)
14d (79)
15d (86)
16d (70)
17d (29)
1a
12
12
12
14
9
6e (36)
7e (85)
8e (81)
9e (74)
10e (71)
11e (74)
12e (77)
13e (19)
14e (90)
15e (89)
16e (76)
17e (72)
6
12b
6
10
11
12
MeO
H
H
H
H
Ph
12
10
6
H
a
Conditions for the conversion of 6d to 6e: SOCl2, pyridine, À10 °C, 1 h.
Conditions for the conversion of 13c to 13e: MeONa, toluene, reflux, 12 h.
b
Na
Na
MeO
H
O
O
O
O
HO
R6
1
O
R6
R5
R6
R5
MeONa
MeOH
R1
R2
1
1
2
R1
R2
6
R1
R2
2
6
R5
2
6
3
3
3
5
4
5
5
4
2
4
R4
2
R3
2
R4
R4
R3
R3
A
6c ~ 17c
B
O
OH
R6
R5
R1
2
6
1
route a
route b
MeO
Na
H
R2
5
3
4
R4
R3
O
O
b
1
α-tetralones d
R6
R5
(thermodynamically
R1
R2
2
a
3
6
favorable)
5
4
R6
HO
2
R4
R3
O
R1
R2
1
6
2
3
C
5
R5
4
R3 R4
β-tetralones d
(thermodynamically
unfavorable)
Figure 1. Mechanism of the regioselective ring expansion of various substituted 1-acyl-1-indanols (6c–12c and 14c–17c).
that proposed by Turnar and Schor et al.,18 resulting in the release of
ring-strain and the formation of a-tetralones d. On the other hand,
behavior of keto rearrangement of 1-acyl-1-indanol, one of the acyl
hydroxyl cyclic compounds, is further understood.
the attack of C6 to C1 would not occur and b-tetralones d not ob-
served due to the steric hindrance and the rigidity of benzene ring.
The rationale that migration occurred to C3 instead of C6 might in-
clude: (1) The sp3–sp3 hybridized C2–C3 bond is less strong than
the sp2–sp3 hybridized C2–C6 bond, such that the former is subject
to breakage. (2) The migration of C3 can result in the formation of
In conclusion, we have successfully synthesized substituted
2-hydroxy-a-tetralones by means of regioselective ring expansion
of substituted 1-acyl-1-indanols, which were prepared from readily
commercially available substituted indanones. The substituted
1-acyl-1-indanols could undergo consecutive dehydration and tau-
tomerization to give substituted 1-naphthols. Conversion of some of
these substituted 1-naphthols, for example 8e–10e, 16e and 17e, to
some potential useful electronic materials is under investigation.
a-tetralones d, which is thermodynamically stable due to the for-
mation of the conjugated double bond system.19 Thus, the general

588
T.-F. Yang et al. / Tetrahedron Letters 53 (2012) 585–588
mixture was stirred at reflux for 24 h, then, cooled to room temperature,
Acknowledgments
quenched with water (20 mL), and extracted with n-hexane (3 Â 30 mL). The
organic layers were combined, washed with water, dried (Na2SO4) and filtered.
The filtrate was concentrated under reduced pressure. The residue was purified
with silica gel column chromatography (n-hexane) to give the corresponding
products (7b–17b).
This work was supported by National Science Council of
Taiwan, which is gratefully acknowledged. The authors thank the
Regional Instruments Center at National Chung-Hsing University
for high resolution mass spectra.
14. General procedures for the conversion of 6b–17b to 6c–17c. To a mixture of
individual alkene (6b–17b, 4.85 mmol), trimethylamine N-oxide (0.8 g,
7.19 mmol), t-BuOH (20 mL), and water (6 mL) in THF (20 mL) was added
osmium tetroxide (1.2 mL, 2.5 wt% in t-BuOH, 0.097 mmol). The reaction
mixture was stirred at room temperature for 4 h, then cooled to room
temperature and quenched with sodium bicarbonate (20%, 20 mL). The
mixture was extracted with ethyl acetate (3 Â 20 mL). The organic layers
were combined, washed with water, dried (Na2SO4) and concentrated under
reduced pressure. The residue was purified with flash column chromatography
(n-hexane) to give a corresponding diol product. To a mixture of this diol
product, TEMPO (0.03 g, 0.19 mmol), KBr (0.13 g, 1.10 mmol), NaHCO3 (0.13 g,
1.55 mmol) in dichloromethane (20 mL) at 0 °C and water (5 mL) was added
dropwise NaOCl (5.2 mL, 10.76 mmol). After the reaction mixture was stirred
at 0 °C for 45 min, NaHSO3 (5%, 10 mL) was added. Then, the mixture was
extracted with CH2Cl2 (3 Â 20 mL). The organic layers were combined, washed
with water, dried (Na2SO4) and concentrated under reduced pressure. The
residue was then purified with flash column chromatography (6:1, n-hexane/
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.11.103.
References and notes
1. Dodge, J. A.; Chamberlin, A. R. Tetrahedron Lett. 1988, 29, 4827–4830.
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3. Hartung, J. B., Jr.; Pedersen, S. F. J. Am. Chem. Soc. 1989, 111, 4368–5469.
4. Kataoka, Y.; Miyai, J.; Tezuka, M.; Takai, K.; Oshima, K.; Utimoto, K. Tetrahedron
Lett. 1990, 31, 369–372.
EtOAc) to give a corresponding a-tetralone (6c–17c).
15. For the characterizations of the intermediates and final products, please see the
Supplementary data.
5. Chen, C.-L.; Martin, S. F. Org. Lett. 2004, 6, 3581–3584.
6. Chen, C.-L.; Martin, S. F. J. Org. Chem. 2006, 71, 4810–4817.
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Chem. Soc. 2005, 74, 3406–3412.
16. General procedures for the keto rearrangement of 7c–12c and 14c–17c. To a
solution of each 1-acyl-1-indanol derivative (0.50 mmol) in methanol (15 mL)
was added sodium methoxide (0.14 g, 2.5 mmol). The reaction mixture was
heated at reflux for 12 h, then quenched with water (10 mL) and extracted with
dichloromethane (3 Â 20 ml). The organic layers were combined, washed with
water, dried (Na2SO4) and filtered. The filtrate was concentrated under reduced
pressure. The residue was purified with flash column chromatography (6:1, n-
hexane/EtOAc) to give the corresponding hydroxyl tetralone derivatives (7d–
12d and 14d–17d).
8. (a) Yang, T.-F.; Shen, C.-H.; Hsu, C.-T.; Chen, L.-H.; Chuang, C.-H. Tetrahedron
2010, 66, 8734–8738; (b) Yang, T.-F.; Tseng, C.-H.; Shen, C.-H.; Chen, L.-H.; Kao,
L.-T. Tetrahedron 2009, 65, 9854–9861; (c) Yang, T.-F.; Tseng, C.-H. T.; Wu, K.-I.;
Chang, C.-N. J. Org. Chem. 2007, 72, 7034–7037; (d) Yang, T.-F.; Zhang, Z.-N.;
Tseng, C.-H.; Chen, L.-H. Tetrahedron Lett. 2005, 46, 1917–1920.
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Leskowitz, S. J. Am. Chem. Soc. 1951, 73, 2633–2636; (c) Turner, R. B. J. Am.
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1952, 74, 5643–5646.
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17. Data of representative hydroxyl tetralone derivative. Compound 11d (Table 2,
entry 6): a solid; Rf = 0.39 (5:1, n-hexane/EtOAc); mp 72–73 °C; IR (KBr): 3716,
3059, 2925, 1959, 1932, 1872, 1811, 1679, 1611, 1448, 1279, 1087 cmÀ1 1H
;
NMR (300 MHz, CDCl3): d 7.98 (s, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.29–7.24 (m,
5H), 7.07 (d, J = 7.8 Hz, 1H), 4.19 (s, OH), 2.89–2.82 (m, 1H), 2.71–2.60 (m, 2H),
2.47–2.36 (m, 1H), 2.40 (s, 3H); 13C NMR (75 MHz, CDCl3): d 201.01, 141.59,
141.22, 136.85, 135.44, 131.57, 129.08, 128.57, 128.13, 127.78, 126.19, 77.89,
36.79, 26.26, 21.05. HRMS calcd for C17H16O2: 252.1144; found: 252.1150.
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13. General procedures for the preparation of 7b–17b. To
a suspension of
benzyltriphenylphosphonium bromide (1.63 g, 3.76 mmol) in THF (40 mL)
was dropwise added n-BuLi (2.35 mL, 1.6 M in hexanes). After the system was
stirred at room temperature for 2 h, indanone (7a, 0.25 g, 1.89 mmol) or its
derivative (8a–17a, 1.89 mmol) in THF (10 mL) was added. The reaction