LiBF4: A mild and efficient catalyst for the tetrahydropyranylation of alcohols and their detetrahydropyranylation

Article abstract of DOI:10.1081/SCC-120003397

Catalytic amount of lithium tetrafluoroborate in dry acetonitrile catalyzes an efficient tetrahydropyranylation of different types of alcohols to afford the corresponding tetrahydropyranyl ethers in high yields. Deprotection of tetrahydropyranyl ethers can also be achieved efficiently in the presence of lithium tetrafluoroborate in methanol. The chemoselectivity was observed in the protection of alcoholic function in the presence of phenolic function.

Full text of DOI:10.1081/SCC-120003397

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
LiBF : A MILD AND EFFICIENT CATALYST FOR THE
4
TETRAHYDROPYRANYLATION OF ALCOHOLS AND
THEIR DETETRAHYDROPYRANYLATION
F. Kazemi , A. R. Kiasat & S. Ebrahimi
To cite this article: F. Kazemi , A. R. Kiasat & S. Ebrahimi (2002) LiBF : A MILD AND
4
EFFICIENT CATALYST FOR THE TETRAHYDROPYRANYLATION OF ALCOHOLS AND THEIR
DETETRAHYDROPYRANYLATION, Synthetic Communications, 32:16, 2483-2487, DOI: 10.1081/
SCC-120003397
To link to this article: http://dx.doi.org/10.1081/SCC-120003397
Published online: 16 Aug 2006.
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 16, pp. 2483–2487, 2002
LiBF : A MILD AND EFFICIENT
4
CATALYST FOR THE
TETRAHYDROPYRANYLATION OF
ALCOHOLS AND THEIR
DETETRAHYDROPYRANYLATION
F. Kazemi,* A. R. Kiasat,* and S. Ebrahimi
Chemistry Department, College of Sciences, Shahid
Chamran University, Ahvaz, Iran
ABSTRACT
Catalytic amount of lithium tetrafluoroborate in dry acetoni-
trile catalyzes an efficient tetrahydropyranylation of different
types of alcohols to afford the corresponding tetrahydropy-
ranyl ethers in high yields. Deprotection of tetrahydropyranyl
ethers can also be achieved efficiently in the presence of
lithium tetrafluoroborate in methanol. The chemoselectivity
was observed in the protection of alcoholic function in the
presence of phenolic function.
*
Corresponding authors. E-mail: fkazemi_2000@yahoo.com or akiasat@yahoo.com
483
2
DOI: 10.1081/SCC-120003397
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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2
484
KAZEMI, KIASAT, AND EBRAHIMI
Tetrahydropyranylation of hydroxyl groups has been recognized as
the useful and representative method for the protection of a great number
[1]
of alcohols and phenols. Due to its low cost, its general stability in a
variety of reactions under neutral and basic conditions, and the ease
þ
with which it can be removed under mild H conditions, THP ether is
often the protective group of choice in the synthesis of peptides, nucleotides,
[
2]
carbohydrates, and steroids. Numerous methods have been reported
[
3–5]
for the tetrahydropyranylation of alcohol functionality.
However,
some of them have limitations such as, expensive reagents, use in strongly
acidic media, tedious and time consuming work up procedures, high
temperatures, and long reaction times.
Similar to protection, deprotection of the tetrahydropyranyl ethers
constitutes important processes in the synthetic chemistry of polyfunctional
molecules including the total synthesis of natural products. Although,
[
4–6]
many catalysts
cleavage, but there are few examples which make use of non-aqueous
have been proposed for this carbon–oxygen bond
[
7]
neutral reaction conditions. Therefore, it is still of considerable interest
to develop new efficient catalysts which can be easily prepared, handled, and
used under neutral conditions for the protection as well as deprotection.
The successful applications of LiBF , as a slow BF releasing source,
4
3
[8–11]
in organic synthesis,
prompted us to explore the potential of this lithium
salt as catalyst for tetrahydropyranylation of hydroxyl groups and the
cleavage of tetrahydropyranyl ethers to the parent alcohols.
The catalyst, LiBF , can be easily prepared from tetrafluoroboric
4
acid and LiOH and in comparison with BF ꢀOEt is solid and stable. We
3
2
examined the catalytic ability of LiBF for tetrahydropyranylation of
4
alcohols with 3,4-dihydro-2H-pyran, DHP, in CH CN at room tempera-
3
ture. This catalyst acted very efficiently and it was observed that only 0.2
molar equivalent of the catalyst is enough to protect alcoholic functions
in high to excellent yields within 10–150 min. It is worthy to mention that
lower quantities of LiBF (i.e. 0.1 mol%) also gave satisfactory results at
4
longer reaction time.
The effects of other solvents such as CCl , CHCl , petroleum ether,
4
3
acetone, CH Cl , and n-hexane were also studied, but in comparison
2
2
with CH CN the reactions times were longer and the yields were found to
3
be considerably lower.
The procedure turned out to be general for range of structurally
diverse alcohols. Primary, secondary, tertiary, allylic and benzylic alcohols
as well as phenol were easily and efficiently protected and afforded the
corresponding THP ethers as the exclusive products in high to excellent
1
yield. They were of high purity as determined by TLC and H NMR
spectroscopy. Table 1 includes representative examples.

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LiBF FOR TETRAHYDROPYRANYLATION OF ALCOHOLS
4
2485
Scheme 1.
[
12]
Tetrahydropyranylation of tertiary alcohols
are difficult and only
a few reports are available in the literature for this transformation. Contrary
to the previous reports, as shown in Table 1, our procedure provides excel-
lent yield of tetrahydropyranyl ether of these classes of compounds.
The removal of the protective tetrahydropyranyl group can be carried
out in methanol under similar mild reaction conditions and with the same
ease the protection process. The results collected in Table 1, indicate that
the efficiency of the LiBF catalyzed deprotection is also high satisfactory.
4
The chemoselectivity in the protection of alcoholic function in the
presence of phenolic function was definitely confirmed by the reaction of
p-hydroxy benzyl alcohol with DHP (Scheme 1).
In conclusion, this catalytic method provides a convenient procedure
for mild and efficient protection of different classes of alcohols and also
for deprotection of THP ethers with excellent yields and could serve as a
useful addition to available methods.
EXPERIMENTAL
General
Products were isolated and their physical properties, i.e., n.m.r and
mass spectral data were compared with those of known samples which
are prepared according to literature procedures.
General Procedure for the Protection of Alcohols
LiBF (2 mmol) was added to a solution of alcohol (10 mmol) and
4
DHP (20 mmol) in dry acetonitrile (15 mL). The mixture was stirred at
room temperature for the specified period of time (Table 1). The progress
of reaction was monitored by TLC or GC. After the disappearance of
starting material, solvent was evaporated, NaHCO3 10%(80 mL) was
added and extracted with diethyl ether (3 ꢁ 50 mL). The organic layer was

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2
486
KAZEMI, KIASAT, AND EBRAHIMI
Table 1. Protection and Deprotection of Alcohols Catalyzed with LiBF at Room
4
Temperature
Protection with DHP
Deprotection
Alcohol
Time (min)
Yield (%)
82
a,b
88
Time (min)
Yield (%)
Cyclohexanol
Cyclooctanol
45
150
60
60
45
20
20
25
10
10
90
50
30
60
180
20
90
45
45
60
20
25
25
25
330
75
25
60
25
60
85
85
93
91
88
94
95
97
96
79
84
96
77
1
2
1
2
3
-octanol
-octanol
-phenylethanol
-phenylethanol
-phenylpropanol
92
90
92
96
96
98
95
95
benzyl alcohol
p-chlorobenzyl alcohol
p-nitrobenzyl alcohol
Menthol
Cinnamyl alcohol
Allyl alcohol
t-butanol
b
92
96
c
93
95
91
d
98
80
Phenol
a
molar ratio of DHP to alcohol was 4 : 1.
b
0
reflux conditions were used.
.4 molar equivalent LiBF was used.
4
c
d
GC yield.
washed with water, brine and dried over CaCl successively. Evaporation
2
of solvent, followed by chromatography (ethyl acetate/petroleum ether)
furnished the desired THP ether in 82–96% yields.
General Procedure for the Deprotection of Alcohols
THP ether (10 mmol) was stirred at room temperature in methanol
15 mL) in the presence of 2 mmol of LiBF . After completion of the reac-
4
(
tion, methanol was evaporated in vacuum and the crude product was taken
in ether. The organic layer was washed with water, brine, and dried (anhy-
drous CaCl ). Solvent removal and purification over silica gel gave pure
2
alcohol in 77–97% yields.

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LiBF FOR TETRAHYDROPYRANYLATION OF ALCOHOLS
4
2487
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Received in Japan May 23, 2001

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