ReCl(CO)5-catalyzed cyclocondensation of phenols with 2-methyl-3-butyn-2-ol to afford 2,2-dimethyl-2H-chromenes

Article abstract of DOI:10.1016/j.tetlet.2011.05.093

A direct one-pot route for the synthesis of 2,2-dimethyl-2H-chromenes by Re(CO)₅Cl-catalyzed cyclocondensation of phenols with 2-methyl-3-butyn-2-ol has been developed. The easy availability of starting materials, mild reaction conditions, high

Full text of DOI:10.1016/j.tetlet.2011.05.093

Tetrahedron Letters 52 (2011) 3926–3928
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Tetrahedron Letters
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ReCl(CO) -catalyzed cyclocondensation of phenols with
5
2-methyl-3-butyn-2-ol to afford 2,2-dimethyl-2H-chromenes
a
a
a,b,
⇑
Hanxiang Zeng , Jia Ju , Ruimao Hua
a
Department of Chemistry, Tsinghua University, Key Laboratory of Organic Optoelectronics & Molecular Engineering of Ministry of Education, Beijing 100084, China
State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A direct one-pot route for the synthesis of 2,2-dimethyl-2H-chromenes by Re(CO) Cl-catalyzed cyclocon-
5
Received 31 March 2011
Revised 16 May 2011
Accepted 20 May 2011
Available online 27 May 2011
densation of phenols with 2-methyl-3-butyn-2-ol has been developed. The easy availability of starting
materials, mild reaction conditions, high atom-efficiency, and the use of a recoverable catalyst are advan-
tages of this procedure.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Condensation
2
2
,2-Dimethyl-2H-chromenes
-Methyl-3-butyn-2-ol
Phenol
Rhenium
2
,2-Dimethyl-2H-chromenes (2,2-dimethyl-2H-1-benzopyran)
reaction of phenols with 2-methyl-3-butyn-2-ol in the presence
of rhenium compounds to give 2,2-dimethyl-2H-chromenes.13
The reaction of 4-methoxyphenol (1a) with 2-methyl-3-butyn-
2-ol (2a) was first studied to optimize the cyclocondensation con-
ditions (Table 1). When a mixture of 1a (1.0 mmol), 2a (3.0 mmol)
structures can be found as parent molecules in a wide variety of
important natural products.1 2,2-Dimethyl-2H-chromenes have
also been well applied as important intermediates to synthesize
2
numerous pharmaceutical and biologically active compounds.
Therefore, a number of synthetic methods have been developed
5
and ReBr(CO) (0.1–0.03 mmol) in toluene (1.5 mL) was heated in a
for the construction of 2,2-dimethyl-2H-chromenes, most notably
sealed tube in air atmosphere with stirring at 130 °C for 24 h, the
GC and GC–MS analyses of the reaction mixtures showed that 2a
was consumed completely, and the desired cycloadduct 6-meth-
oxy-2,2-dimethyl-2H-chromene (3a) was formed in moderate GC
yields (67–56%, entries 1–4). Decreasing the reaction temperature
to 110 °C resulted in a higher yield of 75% (entry 5 vs entry 1), indi-
cating that a lower reaction temperature could significantly im-
prove the formation of 3a, likely due to decreasing the rate of
side reactions of 2a. Indeed, when the reaction was repeated at
90 and 60 °C, 3a was obtained in 78% (entry 6) and 85% GC yields
(entry 7), respectively. However, when the reaction temperature
was further decreased to room temperature, no reaction occurred
(entry 8).
the condensation of metal phenoxides with
a,b-unsaturated car-
3
bonyl compounds, dehydration of chromanols in the presence of
4
acidic compounds, condensation of l,l-diethoxy-3-methyl-2-
5
butene with phenols catalyzed by pyridine, condensation of phe-
nols with 3-methyl-2-butenal either mediated by phenylboronic
6
7
acid, catalyzed by ethylenediamine diacetate, or catalyzed by
8
base under microwave irradiation, ytterbium triflate-catalyzed
reaction of salicylaldehydes, trimethylorthoformate and 2-methyl-
9
propene, and photocyclization of 3-aryl-l,l-dimethylprop-2-en-l-
1
0
ol.
Despite extensive studies into synthetic preparations of
2
,2-dimethyl-2H-chromenes as described above, developing a gen-
eral strategy with high atom-efficiency which uses easily accessi-
ble starting materials under mild conditions is still of interest.
Therefore, in continuation of our interest in the synthesis of O-het-
erocyclic compounds using alkynes as a reaction partner,11 and the
application of low-valence rhenium compounds as catalysts in
In addition, the achieved yield of 3a also exhibited a noticeable
solvent effect. In CH Cl , 3a was obtained in only 63% yield (entry
2 2
9), whereas in p-xylene, cyclohexane, octane and hexane, the reac-
tion afforded 3a in high yields (entries 10–13).
1
2
organic transformations in this work we have investigated the
We also examined the catalytic activity of other rhenium com-
plexes (entries 14–17). Although NH
4
ReO
4
and Re
2
(CO)10 did not
display catalytic activity, ReCl(CO) and CpRe(CO)
5
5
(Cp = cyclopen-
tadienyl) showed high activity, and the highest yield of 3a (95% GC
⇑
Corresponding author. Fax: +86 10 62771149.
E-mail address: ruimao@mail.tsinghua.edu.cn (R. Hua).
yield, 90% isolated yield) was obtained by using 7.0 mol % of
ReCl(CO) .
5
0
040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.05.093

H. Zeng et al. / Tetrahedron Letters 52 (2011) 3926–3928
3927
Table 1
Table 2
a
ReCl(CO)
5
-catalyzed reaction of phenols with 2-methyl-3-butyn-2-ol (2a)a
Reaction of 4-methoxyphenol (1a) with 2-methyl-3-butyn-2-ol (2a)
OH
OH
O
O
cat
Solvent
.
Re(CO) Cl (7 mol%)
Hexane, 60 C, 24 h
5
R
+
OH
+
2a
R
o
O
O
1
3
1
a
2a
3a
Yieldb (%)
Yieldb (%)
Entry
Phenol
Product
Entry
Catalyst (mol %)
Solvent
Temp (°C)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
ReBr(CO)
ReBr(CO)
ReBr(CO)
ReBr(CO)
ReBr(CO)
ReBr(CO)
ReBr(CO)
ReBr(CO)
ReBr(CO)
ReBr(CO)
ReBr(CO)
ReBr(CO)
ReBr(CO)
5
5
5
5
5
5
5
5
5
5
5
5
5
(10)
(7)
(5)
(3)
(7)
(7)
(7)
(7)
(7)
(7)
(7)
(7)
(7)
(7)
(7)
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
130
130
130
130
110
90
60
rt
60
60
60
60
60
60
60
60
60
60
67
64
59
56
75
78
85
<5
63
86
80
90
92
95(90)
90
<5
OH
O
1
2
73
62
1
b
3b
3d
OH
O
O
1
1
c
d
3c
3e
OH
OH
2
CH Cl
2
1
1
1
1
1
1
1
1
1
p-Xylene
Cyclohexane
Octane
Hexane
Hexane
Hexane
Hexane
Hexane
Hexane
3
68
O
ReCl(CO)
ReCp(CO)
NH ReO
Re (CO)10 (7)
[ReCl(CO) (3)
5
4
5
55
68
5
1
e
4
4
(7)
OH
O
2
<5
96
]
4 2
1
f
3f
a
Unless otherwise noted, reactions were carried out using 1.0 mmol of 1a with
.0 mmol of 2-methyl-3-butyn-2-ol and catalyst in 1.5 mL solvent for 24 h in a
sealed tube.
O
O
3
3
f'
13
b
GC yield based on the amount of 1a used. Number in parenthesis is isolated
yield.
OH
6
7
30
53
It is important to note that a white crystal of [ReCl(CO)
4 2
] (67%
3
g
1
g
relative to ReCl(CO) employed) was obtained from the reaction
5
mixture of entry 14, when the reaction mixture was cooled to
ambient temperature, indicating that the homogeneous rhenium(I)
catalyst could be partly recovered after the reaction. The structure
OH
O
Cl
1h
Cl
3h
of the observed [ReCl(CO)
4
]
2
was confirmed by X-ray structure
analysis. Furthermore, [ReCl(CO) might be considered to be
the intermediate of the catalytic procedure, since it showed similar
catalytic activity to ReCl(CO) (entry 18 vs entry 14).
a
1
4
Unless otherwise noted, reactions were carried out using 1.0 mmol of phenols,
.0 mmol of 2a and 0.07 mmol of ReCl(CO) in 1.5 mL hexane.
Isolated yield based on the phenols used.
4 2
]
3
5
b
5
To assess the generality of the given catalytic process, the reac-
tions of a variety of phenols with 2a under the reaction conditions
as indicated in entry 14 of Table 1 were examined. As shown in Ta-
ble 2, the reaction of p-(1b), o-(1c) and m-cresol (1d) afforded the
corresponding 2,2-dimethyl-2H-chromenes 3b, 3c and 3d in good
isolated yields (entries 1–3). It should be noted that the reaction
of 1d with 2a produced two regioisomers, from which 3d was iso-
lated in analytical purity in 68% yield (entry 3). The use of phenol
expected cycloadducts 3i and 3j in 28% and 65% isolated yields,
respectively.
Early transition-metal complexes have found widespread use as
transition metal Lewis acid catalysts in diverse organic transforma-
1
7
tions. In our previous report and other group works, low-valence
rhenium complexes were found to be efficient catalysts to catalyze
1
8
19
dehydration of alcohols and hydroarylation of alkynes to con-
struct C–O and C–C bonds, respectively. Therefore, two possible
routes including a dehydration and hydroarylation are proposed
for the condensation, as shown in Scheme 1. However, since the
current condensation proceeded with high chemoselectivity and
regioselectivity with hydroarylation at the ortho-position of the
phenols only, route A is considered to be more favorable.
(1e) gave a somewhat low yield (55%, entry 4).
Naphthopyrans are an important class of O-heterocyclic com-
1
5
pounds, which are not only found widely in natural products,
1
6
but have also been well-studied as photochromic agents. The gi-
ven catalytic procedure can also be applied to the synthesis of
naphthopyrans by the reaction of naphthol with 2a. For example,
the reaction of b-naphthol (1f) gave two naphthopyran isomers
0
3
f and 3f which were isolated in 68% and 13% yields, respectively
Ph
OH
O
Re(CO) Cl (10 mol%)
Hexane, 60 C, 24 h
5
1
a +
Ph
ð1Þ
(
entry 5).
a-Naphthol (1g) showed low reactivity under similar
o
reaction conditions to give the expected cycloadduct 3g in 30% iso-
2b
MeO
lated yield (entry 6).
1.5 equiv.
3i 28%
Under the same reaction conditions, phenols bearing an elec-
tron-withdrawing group also underwent cycloaddition. For exam-
ple, 4-chlorophenol (1h) reacted with 2a to afford 3h in 53%
isolated yield (entry 7).
HO
O
Re(CO) Cl (10 mol%)
Hexane, 60 C, 24 h
5
1
a +
o
ð2Þ
2
c
MeO
3
.0 equiv.
In addition, the reactions of 1a with 2-phenyl-3-butyn-2-ol (2b)
3j 65%
(
Eq. 1), and with 1-ethynylcyclohexanol (2c) (Eq. 2) afforded the

3
928
H. Zeng et al. / Tetrahedron Letters 52 (2011) 3926–3928
R
O
route A
intramolecular
hydroarylation
dehydration
R
OH
+
cat. Re
2
3
OH
intermolecular
hydroarylation
route B
R
OH
dehydration
1
Scheme 1. Proposed mechanism for rhenium-catalyzed condensation of phenols with propargyl alcohols.
In summary, we have developed rhenium(I)-catalyzed conden-
4 2
data for [Re(CO) Cl] ) associated with this article can be found, in
sation of phenols with 2-methyl-3-butyn-2-ol to afford 2,2-
dimethyl-2H-chromenes in mild to high yields. This procedure
provides a highly atom-efficient route to 2,2-dimethyl-2H-chrom-
enes having various substituents on the benzene ring. Mild
reaction conditions without a requirement for an inert atmosphere
and partial recovery of the rhenium catalyst are notable advanta-
ges of the given catalytic procedure.
the online version, at doi:10.1016/j.tetlet.2011.05.093.
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(
(
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1
1
1
4 2
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(
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Acknowledgment
This project was supported by the National Natural Science
Foundation of China (20972084 and 21032004).
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13
charts of H, C NMR for all products and the full X-ray diffraction