Strontium triflate catalyzed one-pot condensation of β-naphthol, aldehydes and cyclic 1,3-dicarbonyl compounds

Article abstract of DOI:10.1016/j.tetlet.2008.09.129

An efficient one-pot condensation of β-naphthol, aldehydes, and cyclic 1,3-dicarbonyl compounds has been achieved with strontium triflate as a catalyst, thus a variety of 8,9,10,12-tetrahydrobenzo[a]xanthen-11-one or 8,9-dihydrobenzo-[f]cyclopenta[b]chrom

Full text of DOI:10.1016/j.tetlet.2008.09.129

Tetrahedron Letters 49 (2008) 7117–7120
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Tetrahedron Letters
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Strontium triflate catalyzed one-pot condensation of b-naphthol,
aldehydes and cyclic 1,3-dicarbonyl compounds
*
Jianjun Li, Wenyuan Tang, Linmei Lu, Weike Su
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient one-pot condensation of b-naphthol, aldehydes, and cyclic 1,3-dicarbonyl compounds has
been achieved with strontium triflate as a catalyst, thus a variety of 8,9,10,12-tetrahydrobenzo[a]xan-
then-11-one or 8,9-dihydrobenzo-[f]cyclopenta[b]chromen-10(11H)-one derivatives were prepared in
good yields.
Received 8 August 2008
Revised 17 September 2008
Accepted 23 September 2008
Available online 26 September 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Strontium triflate
One-pot reaction
Tetrahydrobenzo[a]xanthen-11-one
Dihydrobenzo[f]cyclopenta[b]chromen-
10(11H)-one
Xanthenes and benzoxanthenes have attracted considerable
interest because they possess various biological activities such as
anti-inflammatory,1 antiviral,2 and antibacterial.3 Some of them
have been used as antagonists for paralyzing the action of zoxazo-
lamine4 and in photodynamic therapy.5 Moreover, these com-
pounds can be used as dyes,6 pH-sensitive fluorescent materials
for the visualization of biomolecular assemblies7 and in laser tech-
nologies.8 Therefore, the synthesis of xanthene derivatives (Fig. 1)
is of great importance.
Recently, rare earth metal triflates, a new type of Lewis acid,
were widely used in organic synthesis due to their low toxicity,
high stability, ease of handling, water tolerance, and recoverability
from water.9 In our previous studies, we have successfully applied
metal triflates into several reactions.10 Very recently, we reported
the reaction of b-naphthol, aldehydes, and amides forming amid-
oalkyl naphthols11 and condensation of b-naphthol and aromatic
aldehydes affording dibenzoxanthenes.12 In continuation with
the investigation, we found that one-pot condensation of b-naph-
thol, aldehydes, and cyclic 1,3-dicarbonyl compounds could be
achieved in the presence of strontium triflate, thus tetrahydro-
benzo[a]xanthen-11-one derivatives 5 and dihydrobenzo[f]cyclo-
penta[b] chromen-10-one derivatives 6 were obtained in good
yields. To the best of our knowledge, only a few methods were
reported on the synthesis of tetrahydrobenzo[a]xanthen-11-one
derivatives,13 and no reports are available at all on the synthesis
of dihydrobenzo[f]cyclopenta[b]chromen-10-one derivatives.
Initially, we investigated the condensation reaction of b-naph-
thol, benzaldehyde, and 5,5-dimethylcyclohexane-1,3-dione using
different catalysts at reflux temperature, and the results are listed
in Table 1 (Scheme 1). It was found that metal triflates showed bet-
ter catalytic activity among these catalysts. Most excitingly, when
Sr(OTf)2 was used, the reaction proceeded very smoothly and gave
the product 5a in 85% yield (Table 1, entry 9). Moreover, we found
that the yields were obviously affected by the amount of Sr(OTf)2
loaded. When 1 mol %, 5 mol %, 10 mol %, and 15 mol % of Sr(OTf)2
were used, the yields were 25%, 75%, 85%, and 86%, respectively
(Table 1, entries 9–12). Therefore, 10 mol % of Sr(OTf)2 was suffi-
cient and excessive amount of catalyst did not increase the yields
significantly (Table 1, entries 9). The catalytic activity of the recy-
cled Sr(OTf)2 was also examined. Sr(OTf)2 could be reused five
times for the reaction without noticeable loss of activity (Table 1,
entry 9). In addition, no product was detected in the absence of
the catalyst. The above results showed that Sr(OTf)2 was essential
in the reaction, and the best results were obtained when the reac-
tion was carried out with 10 mol % of Sr(OTf)2 in 1,2-dichloroeth-
ane at 80 °C (Table 1, entry 9).
O
R
O
Figure 1. Xanthenes.
Then, we examined the above reaction in various solvents
(Table 2). The results indicate that different solvents affected the
* Corresponding author. Tel./fax: +86 571 88320752.
E-mail address: suweike@zjut.edu.cn (W. Su).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.09.129

7118
J. Li et al. / Tetrahedron Letters 49 (2008) 7117–7120
Table 1
85% (Table 2, entry 11) better than any other solvents examined
here.
Lewis acids catalyzed one-pot condensation of b-naphthol, benzaldehyde, and 5,5-
dimethylcyclohexane-1,3-dionea
In addition, two by-products were characterized. One was aryl-
14H-dibenzo[a,j]xanthene 7a, the other was trace adduct of
dinaphthalenol, both of which were formed from the condensation
of 2 equiv of b-naphthol and 1 equiv of benzaldehyde (Scheme 2).
The side reactions were also observed in our previous work.12
However, the corresponding of 5a and 7a were the major products
when Sr(OTf)2 was employed as the catalyst, hence, showing good
chemoselectivity (Scheme 2).
Entry
Catayst
Catalyst (mol %)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
La(OTf)3
Y(OTf)3
ZnCl2
10
10
10
10
10
10
10
10
10
1
5
5
5
5
5
5
5
5
5
5
5
5
31
35
35
49
51
73
75
80
AlCl3
Yb(OTf)3
Zn(OTf)2
Mg(OTf)2
Cu(OTf)2
Sr(OTf)2
Sr(OTf)2
Sr(OTf)2
Sr(OTf)2
In order to study the generality of this procedure, a series of
aldehydes and cyclic 1,3-dicarbonyl compounds were applied.
The results are shown in Table 3.
9c
10
11
12
85, 87, 85, 85, 84
25
75
86
5
15
In all cases, aromatic aldehydes substituted with either elec-
tron-donating or electron-withdrawing groups underwent the
reaction smoothly and gave the products in good yields. It could
also be concluded that the aldehydes bearing electron-withdraw-
ing groups required shorter time and gave higher yields (Table 3).
With the successful condensation of aromatic aldehydes, b-
naphthol, and 5,5-dimethylcyclohexane-1,3-dione 3, we further
studied the reaction of aromatic aldehydes, b-naphthol, and cyclo-
pentane-1,3-dione 4 under similar conditions. It was found that
the corresponding tetrahydrobenzo[a]xanthen-11-one 5 and di-
a
Reaction conditions: b-naphthol (1.0 mmol), benzaldehyde(1.0 mmol), and 5,5-
dimethylcyclohexane-1,3-dione (1.1 mmol), 1,2-dichloroethane as solvent, 80 °C.
b
Isolated yield.
Catalyst was reused five times.
c
PhCHO
1a
+
O
O
O
+
OH
Sr(OTf)2
hydrobenzo[f]cyclopenta-[b]chromen-10-one
6 could also be
Ph
O
obtained in good yields (Scheme 3 and Table 3).
3
5a
On the basis of the above results, this process was then
extended to heterocyclic and aliphatic aldehydes. Thiophene-2-
carbaldehyde, propionaldehyde, and pivalaldehyde afforded the
corresponding products (5f, 5g, 5h) in 70%, 75%, and 73% yields,
respectively (Table 3, entries 6–8). Compared with aromatic alde-
hydes, heterocyclic or aliphatic aldehydes afforded relatively lower
yields of the corresponding 5 (Table 3).
A tentative mechanism for the formation of derivatives 5 is pro-
posed in Scheme 4. By referring to the literature,14 we supposed
that the reaction may proceed via the ortho-quinone methides
intermediate 8, which was formed by the nucleophilic addition
of b-naphthol to aldehyde catalyzed with Sr(OTf)2. Subsequent
2
Scheme 1. Reaction of b-naphthol, benzaldehyde, and 5,5-dimethylcyclohexane-
1,3-dione.
efficiency of the reaction. Acetonitrile, ethanol, nitromethane, and
chloroform afforded low yields (Table 2, entries 3–6), while when
water and tetrahydrofuran were used as solvents, no products
were detected (Table 2, entries 1 and 2). The use of solvents such
as [bpy]BF4, DMF, and toluene could improve the yields (Table 2,
entries 8–10). Especially, the reaction could be carried out under
solvent-free condition and gave moderate yield (Table 2, entry 7).
Finally, when 1,2-dichloroethane was used, the yield increased to
Table 3
15
Synthesis of xanthenes in the presence of Sr(OTf)2
Table 2
Entry
R1
R2
Product
Time (h)
Yielda (%)
Solvent effect on the reaction of b-naphthol, benzaldehyde, and 5,5-dimethylcyclo-
hexane-1,3-dione catalyzed by Sr(OTf)2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
C6H5
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
H
H
—
—
5a
5b
5c
5d
5e
5f
5g
5h
5i
5
6
6
5
5
7
7
7
6
5
5
6
5
5
85
82
78
88
86
70
75
73
81
85
86
82
86
89
Entry
Solvent
Temperature
Time (h)
Yielda (%)
3-CH3-4-CH3–C6H3
p-(OCH3)C6H4
p-(Cl)C6H4
m-(NO2)C6H4
CH3CH2
CH3C(CH3)2
2-Thiophene
3-CH3-4-CH3–C6H3
C6H5
1
2
3
4
5
6
7
8
9
Water
THF
CH3CN
CH3CH2OH
CH3NO2
CHCl3
None
[bpy]BF4
DMF
Toluene
ClCH2CH2Cl
80 °C
Reflux
Reflux
Reflux
80 °C
Reflux
80 °C
80 °C
80 °C
80 °C
80 °C
5
5
5
5
5
5
5
5
5
5
5
—
—
<5
<10
30
42
56
60
69
55
85
5j
p-(Cl)C6H4
3-CH3-4-CH3–C6H3
C6H5
5k
6a
6b
6c
10
11
p-(Cl)C6H4
—
a
a
Isolated yield.
Isolated yield.
OH OH
PhCHO
1a
+
O
O
O
O
Catalyst
+
+
+
OH
Ph
5a
O
Ph
Ph
3
7a
Trace
2
Catalyst Sr(OTf)2 yields: 5a, 85%; 7a, 5%
Catalyst Yb(OTf)3 yields: 5a, 51%; 7a, 32%
Scheme 2. The condensation reaction catalyzed with different catalyst.

J. Li et al. / Tetrahedron Letters 49 (2008) 7117–7120
7119
R2
R2
O
O
O
R1
5
O
R2 R2
OH
Sr(OTf)2 (10 mol%)
ClCH2CH2Cl, 80 oC
R1CHO
or
+
3
or
+
O
1
2
O
O
R1
O
4
6
Scheme 3. Sr(OTf)2 catalyzed condensation of b-naphthol, aldehydes, and cyclic 1,3-dicarbonyl compounds.
R1
O
Sr(OTf)2
Sr(OTf)2
H
O
R1
R1
H
Sr(OTf)2
OH
OH
H
OH
OH
H
O
-H+
O
S
r
2
8
(
O
-Sr(OTf)2
T
f
R2 R2
)
2
9
R1
R1
O
O
H
R1
O
R2
R2
R2
R2
-H2O
R2
R2
HO
OH
OH
HO
(TfO)2Sr
O
Sr
(OTf)2
5
11
10
Scheme 4. Proposed mechanism for the condensation reaction of aldehydes, b-naphthol and 1,3-dicarbonyl compounds.
3. Hideo, T.; Teruomi, J. Jpn. Patent 56,005,480, 1981.
substitution of the oxygen atom, which was coordinated by stron-
tium triflate, with cyclic 1,3-dicarbonyl compounds 9 afforded 11.
Then compounds 11 eliminated one molecule of H2O and afforded
title products 5.
In summary, we have described an efficient and mild method
for the preparation of 8,9,10,12-tetrahydrobenzo[a]xanthen-
11-ones and 8,9-dihydrobenzo-[f]cyclopenta[b]chromen-10(11H)-
ones. This process is efficiently promoted by the strontium triflate.
Unlike other existing methods, the advantages of this method in-
clude the use of recyclable catalyst, good chemoselectivity, high
yields, simple workup procedure, and easy isolation. Further appli-
cations of strontium triflate on the extension of this protocol are
ongoing in our group.
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Acknowledgments
We are grateful to the National Key Technology R&D Program
(No. 2007BAI34B00) and National Natural Science Foundation of
China (No. 20676123) for financial support.
15. General procedure for the preparation of 8,9,10,12-tetrahydrobenzo[a]xanthen-11-
one derivatives and 8,9-dihydrobenzo[f]cyclopenta[b]chromen-10(11H)-one
derivatives: To a mixture of b-naphthol (1.0 mmol), aldehyde (1.0 mmol), and
cyclic 1,3-dicarbonyl compounds (1.1 mmol) was added strontium triflate
(0.1 mmol) in 1,2-dichloroethane (2 mL). The mixture was stirred at 80 °C for
the given time (Table 3). The progress of the reaction was monitored by TLC.
After completion of the reaction, water was added and the product was
extracted with ethyl acetate (3 Â 10 mL). The organic layer was dried (MgSO4)
and evaporated, and the crude product was purified by flash chromatography
(ethyl acetate/petroleum ether, 1:20) to provide the pure product.Spectral data
for selected products:
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.09.129.
References and notes
1. Poupelin, J. P.; Saint-Ruf, G.; Foussard-Blanpin, O.; Narcisse, G.; Uchida-Ernouf,
G.; Lacroix, R. Eur. J. Med. Chem. 1978, 13, 67.
2. Lambert, R. W.; Martin, J. A.; Merrett, J. H.; Parkes, K. E. B.; Thomas, G.J. PCT Int.
Appl. WO 9,706,178, 1997.
12-(3,4-dimethylphenyl)-9,9-dimethyl-9,10-dihydro-8H-benzo[a]xanthen-11(12H)-
one (5b). White crystals; mp 181–182 °C; yield: 82%. 1H NMR (500 MHz,

7120
J. Li et al. / Tetrahedron Letters 49 (2008) 7117–7120
CDCl3): d 8.04 (1H, d, J = 8.5 Hz, Ar-H), 7.77–7.72 (2H, m, Ar-H), 7.43–7.25 (3H,
11-(3,4-dimethylphenyl)-8,9-dihydrobenzo[f]cyclopenta [b]chromen-10(11H)-one
(6a). White crystals; mp 223–224 °C; yield: 82%. 1H NMR (500 MHz, CDCl3): d
7.83–7.79 (3H, m, Ar-H), 7.40–7.36 (3H, m, Ar-H), 7.03–6.93 (3H, m, Ar-H), 5.50
(1H, s, CH), 2.79–2.75 (2H, m, CH2), 2.50–2.47 (2H, m, CH2), 2.13 (3H, s, CH3),
2.12 (3H, s, CH3). 13C NMR (125 MHz, CDCl3): 202.5, 177.1, 149.2, 141.2, 136.6,
134.8, 131.9, 131.8, 129.7, 129.4, 129.3, 128.4, 127.1, 125.5, 125.1, 124.2, 119.2,
m, Ar-H), 7.10–7.03 (2H, m, Ar-H), 6.91 (1H, d, J = 8.0 Hz, Ar-H), 5.63 (1H, s, CH),
2.56 (2H, dd, J1 = 2.5 Hz, J2 = 17.5 Hz, CH2), 2.27 (2H, dd, J1 = 4.0 Hz, J2 = 16.0 Hz,
CH2), 2.13 (3H, s, CH3), 2.09 (3H, s, CH3), 1.11 (3H, s, CH3), 0.99 (3H, s, CH3). 13
C
NMR (125 MHz, CDCl3): 196.2, 163.8, 147.7, 142.3, 136.2, 134.4, 131.5, 129.7,
129.5, 128.7, 128.4 (CH Â 2), 127.0, 125.9, 124.9, 123.8, 118.1, 117.1, 114.5,
51.0, 41.4, 34.3, 32.4, 29.2, 27.4, 20.0, 19.4. IR mmax (KBr): 3125, 2958, 1650,
1593, 1398, 1371, 1237, 1226, 1172, cmÀ1. MS (EI) m/z 382 (M+, 40), 277 (100).
117.4, 116.5, 35.5, 33.8, 25.3, 19.9, 19.4. IR
mmax (KBr): 3407, 3131, 1709, 1670,
1591, 1396, 1237, cmÀ1. MS (EI) m/z 340 (M+, 10), 178 (22), 235 (100).