Selective tetrahydropyranylation of alcohols and phenols using titanium(IV) salophen trifluoromethanesulfonate as an efficient catalyst

Article abstract of DOI:10.1002/aoc.3515

Titanium(IV) salophen trifluoromethanesulfonate, [Ti^IV(salophen)(OSO₂CF₃)₂], as a catalyst enables selective tetrahydropyranylation of alcohols and phenols with 3,4-dihydro-2H-pyran. Using this catalytic system, primary, secondary and tertiary alcohols, as well as phenols, were converted to their corresponding tetrahydropyranyl ethers in high yields and short reaction times at room temperature. Investigation of the chemoselectivity of this method showed discrimination between the activity of primary alcohols in the presence of secondary and tertiary alcohols and phenols. This heterogenized catalyst could be reused several times without loss of its catalytic activity. Copyright

Full text of DOI:10.1002/aoc.3515

Full paper
Received: 19 January 2016
Revised: 10 April 2016
Accepted: 20 April 2016
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.3515
Selective tetrahydropyranylation of alcohols
and phenols using titanium(IV) salophen
trifluoromethanesulfonate as an
efficient catalyst
Maryam Yadegari* and Majid Moghadam
IV
Titanium(IV) salophen trifluoromethanesulfonate, [Ti (salophen)(OSO
2
CF
3
)
2
], as a catalyst enables selective tetrahydropyranylation
of alcohols and phenols with 3,4-dihydro-2H-pyran. Using this catalytic system, primary, secondary and tertiary alcohols, as well as
phenols, were converted to their corresponding tetrahydropyranyl ethers in high yields and short reaction times at room
temperature. Investigation of the chemoselectivity of this method showed discrimination between the activity of primary alcohols
in the presence of secondary and tertiary alcohols and phenols. This heterogenized catalyst could be reused several times without
loss of its catalytic activity. Copyright © 2016 John Wiley & Sons, Ltd.
Keywords: titanium Schiff base; alcohol; phenol; 3,4-dihydro-2H-pyran; tetrahydropyranyl ether
[
12]
[13]
In(OTf)3,
[14]
[15]
K CoW O Á3H O,
LiOTf,
PdCl (CH CN) ,
2 3 2
Introduction
5
12 40
2
[16]
[17]
[18,19]
AlCl @polystyrene, H P W O , silica-based sulfonic acid,
3
6 2 18 62
IV
[20,21]
The ability to recover a catalyst and reducing the amount of toxic
waste must be considered as two important features when design-
ing a catalytic synthesis system. Various heterogeneous solid sup-
port systems as catalysts are not environmentally suitable and use
of large amounts of them, in the long run, results in a high quantity
of toxic waste output. Metal Schiff base complexes, especially
heterogeneous instances, with simple recovery capability can pro-
vide efficient catalysts. Salophen and salen tetradentate ligands
and homogeneous and heterogeneous [Sn (TPP)(OTf) ]
[V (TPP)(OTf) ] have been developed for tetrahydropyranylation
of alcohols and phenols.
In the course of our studies on titanium salophen-catalysed reac-
tions, we found them to be effective in catalysing acetylation and
trimethylsilylation of alcohols and phenols and conversion of alde-
hydes to 1,1-diacetates.
of titanium salophen-catalysed reactions to tetrahydropyranylation
of alcohols and phenols.
and
2
IV
[22]
2
[
23–25]
Now we have extended the application
2 2
with N O arrangement and electron-deficient complexes have also
been used to catalyse a wide variety of important chemical trans-
formations, including oxidation of alcohols, sulfides, amines,
alkanes and alkenes by complexes of chromium, iron, magnesium,
[1]
Experimental
ruthenium, cobalt and vanadium, and titanium Schiff base com-
plexes have also been used in developing reactions. For example,
titanium binaphthyl-bridged Schiff base complex in regio and
All chemicals were purchased from Merck or Fluka. Fourier
transform infrared spectra were obtained with potassium bromide
pellets in the range 400–4000 cm with a Nicolet Impact 400D
spectrometer. GC experiments were performed with a Shimadzu
GC-16 A instrument using a 2 m column packed with silicon DC-
[
2]
stereoselective epoxidation of allylic alcohols and in oxidation
À1
[3]
of sulphides, Ti(salen) complex in asymmetric ring opening of
[
4]
[5]
epoxides and pinacol coupling reaction and heterobimetallic
[
6]
Ti–Ga–salen system in enantioselective ring-opening reaction
could be mentioned.
200 or Carbowax 20 m. In the GC experiments, n-decane was used
1
as an internal standard. H NMR spectra were recorded with a
Bruker Avance AQS 400 MHz spectrometer.
Many protective groups have been developed for temporary
blocking of reactive sites in multi-step reactions. For proposing a
synthetic scheme, many factors must be considered like reaction
conditions, reactants and their functional groups and compatibility
of protective groups with reaction conditions. Hence, there is
always a need for selective reagents. Tetrahydropyranylation of
hydroxyl groups can be a good choice especially for most nonacidic
reagents. Facile deprotection under mild acidic conditions is
* Correspondence to: Maryam Yadegari, Department of Environmental Chemistry,
Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran. E-mail:
mym_yadegari@yahoo.com
[
7]
another advantage for this protecting route.
Lewis acid and protonic catalysts such as Bu N Br ,
+
À [8]
[11]
4
3
Department of Environmental Chemistry, Isfahan (Khorasgan) Branch, Islamic
Azad University, Isfahan, Iran
[9]
[10]
AlCl Á6H O,
bis(trimethylsilyl)sulfate,
vanadyl(IV) acetate,
3
2
Appl. Organometal. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.

Yadegari M. and Moghadam M.
Preparation of catalyst
After synthesis of salophen,
(1 mol%) gave the highest yield. The amount of DHP was also opti-
mized and the best result was obtained with a 2:1 molar ratio of
DHP to alcohol as summarized in Table 2. Another factor investi-
[
26]
IV
2 3 2
[Ti (salophen)(OSO CF ) ] as a
[
27]
catalyst was prepared according to the literature.
gated in this work is the effect of OSO
2
CF
CF
3
groups (OTf) on the
]. For this purpose,
IV
catalytic activity of [Ti (salophen)(OSO
2
3 2
)
General procedure for tetrahydropyranylation of alcohols and
the effect of introducing different groups such as Cl and OPh to
the Ti(salophen) was compared with OTf groups in the
tetrahydropyranylation of 4-chlorobenzyl alcohol with DHP. The
phenols with 3,4-Dihydro-2H-pyran (DHP) catalysed by
IV
[
Ti (salophen)(OSO CF ) ]
2
3 2
In a typical procedure, a solution of alcohol or phenol (1 mmol),
IV
[
Ti (salophen)(OSO CF ) ] (0.01 mmol) and DHP (2 mmol per OH
2 3 2
Table 3. Tetrahydropyranylation of alcohols catalysed by
[Ti (salophen)(OSO CF ) ] at room temperature
2 3 2
IV
a
group) in CH Cl (1 ml) was prepared and stirred at room tempera-
2
2
ture for an appropriate time. The progress of the reaction was
monitored by GC and TLC. After completion of the reaction, the sol-
vent was evaporated, n-hexane (10 ml) was added and the catalyst
2 4
was filtered. The filtrates were washed with brine, dried over Na SO
and concentrated under reduced pressure to afford the crude
product, which was confirmed using H NMR and IR spectral data.
Entry
b
1
R
Time (min)
Yield (%)
1
C
6
H
5
CH
CH CH
CH CH CH
2-CH CH
2-CH CH
4-NO CH
3-NO CH
4-ClC CH
2-BrC CH
2-NO CH
4-HOC CH
4-CH OC CH
4-FC CH
n-Octyl
CH C(CH
2
4
4
90
98
95
100
99
100
95
90
95
80
80
70
50
96
98
90
90
90
90
2
C
6
H
5
2
2
Results and discussion
3
C
6
H
5
2
2
2
4
4
3
C
6
H
4
2
1
Tetrahydropyranylation of alcohols and phenols with DHP
IV
5
3
OC
6
H
4
2
2
catalysed by [Ti (salophen)(OSO
2
CF
3
)
2
]
6
2
C
6
H
4
2
2
First, for optimization of the reaction parameters,
tetrahydropyranylation of 4-chlorobenzyl alcohol with DHP was
performed with various solvents and catalyst amounts. Among
7
2
C
6
H
4
2
1
8
6
H
4
2
6
9
6
H
4
2
7
CH
was obtained in CH
neous nature in CH
and CH Cl
.01 mol of [Ti (salophen)(OSO
2
Cl
2
, CH
3
CN, EtOAc, chloroform and n-hexane, a higher yield
10
11
12
13
14
2
C
6
H
4
2
16
1
H
4
2
2
Cl
Cl
2
(Table 1). Since the catalyst has a heteroge-
, catalyst recovery in this solvent is simpler,
6
6
H
4
2
10
1
2
2
3
2
2
was used subsequently as a solvent. The presence of
6
H
4
2
IV
0
2
CF
3
)
2
] for each mole of substrate
6
1
5
6
C
6
H
5
2
3
)
2
4
1
Diphenylmethyl
Cyclohexyl
t-Butyl
20
3
Table 1. Effect of solvent on the tetrahydropyranylation of 4-
IV
a
chlorobenzyl alcohol with DHP catalysed by [Ti (salophen)(OSO
2
CF
3
)
2
]
17
18
b
9
Entry
Solvent
Time (min)
Yield (%)
19
1-Adamantyl
11
1
2
3
4
5
CH
CH
EtOAc
CHCl
n-Hexane
2
Cl
2
6
6
6
6
6
90
79
38
28
16
a
Reaction conditions: alcohol (1 mmol), DHP (2 mmol), catalyst (1 mol%),
Cl (1 ml).
Isolated yield.
3
CN
CH
b
2
2
3
a
Reaction conditions: 4-chlorobenzyl alcohol (1 mmol), catalyst (1 mol
%
), DHP (2 mmol), solvent (0.5 ml).
Table 4. Comparison of results obtained for tetrahydropyranylation of
IV
b
4-nitrobenzyl alcohol catalysed by [Ti (salophen)(OSO CF ) ] with those
Isolated yield.
2
3 2
obtained using recently reported catalysts
Entry
1
Catalyst
Catalyst
T
Time Yield
Ref.
(
mol%)
(°C) (min) (%)
IV
2 3 2
Table 2. Effect of amount of DHP and [Ti (salophen)(OSO CF ) ] on
IV
a
a
[Ti (salophen)
OSO CF
PdCl (CH CN)
[Sn (TPP)(OTf)
1
RT
2
100 This work
the tetrahydropyranylation of 4-chlorobenzyl alcohol
(
2
3 2
) ]
Entry
Solvent
Catalyst
mol%)
DHP/substrate
(mmol)
Time
(min)
Yield
(%)
a
a
a
[15]
[20]
[21]
b
2
3
4
2
3
2
10
1
RT
RT
RT
390 81
(
IV
2
]
6
6
60
62
IV
[Sn (TNH
CMP
Ps–AlCl
2
PP)(OTf)
2
]
1
1
2
3
4
5
CH
CH
CH
CH
CH
2
Cl
Cl
Cl
Cl
Cl
2
2
2:1
2:1
2:1
3:1
1:1
6
6
6
6
6
90
90
75
90
78
@
2
2
1
a
a
[16]
[28]
[14]
[12]
5
6
7
8
3
15
RT
90 91
15 92
2
2
0.5
1
Silica chloride
LiOTf
10 mg RT
2
2
a
60
1
Reflux 180 92
2
2
1
b
K
5
CoW12O40Á3H
2
O
RT
10 80
a
Reaction conditions: 4-chlorobenzyl alcohol, catalyst, DHP, solvent
0.5 ml).
a
(
Isolated yield.
b
b
Isolated yield.
GC yield.
wileyonlinelibrary.com/journal/aoc
Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2016)

Efficient and selective tetrahydropyranylation of alcohols and phenols
results of reactions are, respectively, 90, 51 and 29% for
2
(OPh) ]. The order of activity of these catalysts clearly shows that
by increasing the electron deficiency of the catalyst, catalytic
activity increases.
IV
IV
IV
[
Ti (salophen)(OSO
2
CF
3
)
2
2
], [Ti (salophen)Cl ] and [Ti (salophen)
Under the optimized conditions, numerous types of primary,
secondary and tertiary alcohols were transformed to their corre-
Table 5. Tetrahydropyranylation of phenols with DHP catalysed by
IV
a
2 3 2
[Ti (salophen)(OSO CF ) ] at room temperature
sponding tetrahydropyranyl ethers in the presence of catalytic
IV
amounts of [Ti (salophen)(OSO
2
CF
3
)
2
] at room temperature. The
results, which are summarized in Table 3, showed that all primary,
secondary and tertiary alcohols including aromatic, aliphatic and
cyclic ones were converted efficiently to their corresponding
tetrahydropyranyl ethers.
Entry
b
Ar
Time (min)
Yield (%)
In the case of aromatic alcohols, the nature of substituents has no
significant effect on the tetrahydropyranylation yield. But some
derivatives of benzyl alcohol lead to very large yields. For example,
4-nitrobenzyl alcohol, 2-methoxybenzyl alcohol and 2-methylbenzyl
alcohol give excellent yields in short reaction times. In order to show
the advantage of this method, the tetrahydropyranylation of 4-
1
2
3
4
5
6
7
6
C H
5
5
5
97
92
67
93
90
90
90
4-ClC
4-NO
4-CH
1-Naphthyl
3-CH
2-ClC
6 4
H
2
C
6
H
4
20
4
3
C
6
H
4
7
IV
3
C
6
H
4
4
nitrobenzyl alcohol with DHP catalysed by [Ti (salophen)(OSO CF ) ]
2
3 2
6
H
4
7
is compared with some other available catalysts (Table 4). The results
show that the present catalyst is superior in terms of catalyst amount,
reaction time and product yield and also reusability. Therefore, this
method can beneficial for alcohols that have been less perused or
there are no eligible reports about them.
a
Reaction conditions: phenol (1 mmol), DHP (2 mmol), catalyst (1 mol%),
Cl (1 ml).
Isolated yield.
CH
2 2
b
The tetrahydropyranylation of various phenols was also exam-
ined under the same reaction conditions as those applied for
alcohols. The corresponding tetrahydropyranyl ethers were pro-
duced in high yields and short reaction times (Table 5).
As shown in Scheme 1, a possible mechanism for these reactions
IV
is that DHP is first activated by [Ti (Salophen)(OTf)
2
] to afford reac-
tive agent 1. Nucleophilic attack of alcohol on 1 affords 2 and final
product 3 is formed after proton transfer, simultaneously releasing
the catalyst for the next cycle.
It is noteworthy that this catalyst can be used for chemoselective
tetrahydropyranylation of primary alcohols in the presence of sec-
ondary and tertiary alcohols and phenols (Table 6). The results indi-
cated that primary alcohols are more reactive in the presence of
secondary and tertiary alcohols and phenols.
Catalyst reusability
IV
The reusability of [Ti (salophen)(OSO CF ) ] was also investigated
2
3 2
in the multiple pyranylation of 4-chlorobenzyl alcohol with DHP
under the optimized conditions. Then, the solvent was evaporated,
and the catalyst was washed with Et O, filtered, dried and reused. It
2
was observed that the activity of the catalyst did not decrease after
four consecutive runs.
Scheme 1. Proposed mechanism for tetrahydropyranylation of alcohols
and phenols with DHP catalysed by [Ti (Salophen)(OSO CF ) ].
2 3 2
IV
IV
a
2 3 2 2 2
Table 6. Selective pyranylation of alcohols and phenols catalysed by [Ti (salophen)(OSO CF ) ] in CH Cl
b
b
Entry
R
1
R
2
Time (min)
Yield 1 (%)
Yield 2 (%)
1
2
3
4
C
6
H
5
CH
CH
CH
CH
2
(Ph)
CH
n-Octyl
2
CH
4
4
4
4
90
90
90
90
10
0
C
6
H
5
2
C H
6 5
2
C(CH
3 2
)
C
6
H
5
2
30
15
C
6
H
5
2
6 5
C H
a
2 2
Reaction conditions for a binary mixture: 1 mmol of each alcohol or phenol, DHP (2 mmol), catalyst (1 mol%), CH Cl (1 ml).
b
Isolated yield.
Appl. Organometal. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

Yadegari M. and Moghadam M.
[
[
[
10] Y. Morizawa, I. Mori, T. Hiyama, H. Nozaki, Synthesis 1981, 899.
11] B. M. Choudary, V. Neeraja, M. L. Kantam, J. Mol. Catal. A 2001, 175, 169.
12] M. H. Habibi, S. Tangestaninejad, I. Mohammadpoor-Baltork,
V. Mirkhani, B. Yadollahi, Tetrahedron Lett. 2001, 42, 2851.
Conclusions
In this work, an efficient approach for tetrahydropyranylation of
alcohols and phenols is presented. This catalytic system showed a
good catalytic activity in these reactions.
[
13] T. Mineno, Tetrahedron Lett. 2002, 43, 7975.
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[
[
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Excellent yields, selectivity, easy work-up, extremely mild reac-
tion conditions, applicability for alcohols and phenols, low amount
required for reactions and reusability without significant decrease
in initial activity are unique features and noteworthy advantages
of this heterogeneous catalyst.
2
002, 43, 7589.
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Appl. Organometal. Chem. (2016)