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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.