Tetrahydropyranyl ethers
THP-OR, THP ether
T. W. Green, P. G. M. Wuts, Protective Groups in Organic
Synthesis,
Wiley-Interscience, New York, 1999, 49-54, 708-711.
Stability
| H2O: | pH < 1, 100°C | pH = 1, RT | pH = 4, RT | pH = 9, RT | pH = 12, RT | pH > 12, 100°C |
| Bases: | LDA | NEt3, Py | t-BuOK | Others: | DCC | SOCl2 |
| Nucleophiles: | RLi | RMgX | RCuLi | Enolates | NH3, RNH2 | NaOCH3 |
| Electrophiles: | RCOCl | RCHO | CH3I | Others: | :CCl2 | Bu3SnH |
| Reduction: | H2 / Ni | H2 / Rh | Zn / HCl | Na / NH3 | LiAlH4 | NaBH4 |
| Oxidation: | KMnO4 | OsO4 | CrO3 / Py | RCOOOH | I2, Br2, Cl2 | MnO2 / CH2Cl2 |
General
The tetrahydropyranyl ether is a useful protecting group for the protection of alcohols and phenols, offering stability towards strongly basic reaction conditions, organometallics, hydrides, acylating reagents and alkylation reagents. A drawback is the formation of an additional stereocenter that may lead to diastereomeric mixtures if the alcohol already possesses a stereogenic center.
THP ethers are formed under acidic conditions from alcohols and dihydropyran.
The deprotection is usually performed as an acidic hydrolysis or alcoholysis.
Some new methods also allow the protection and deprotection of acid-sensitive molecules by using mild Lewis acids.
Protection of Hydroxyl Compounds
A N,N′-bis[3,5-bis(trifluoromethyl)phenyl]thiourea-catalyzed tetrahydropyran and
2-methoxypropene protection of hydroxyl groups is broadly applicable to
sterically hindered and acid-sensitive substrates.
A mechanistic interpretation of the high catalytic efficiency is given.
M. Kotke, P. R. Schreiner, Synthesis, 2007,
779-790.
A simple and convenient synthetic protocol for the protection of hydroxyl groups
as tetrahydropyranyl ethers as well as carbonyl functionalities as
oxathioacetals and thioacetals has been achieved using a catalytic amount of
silica-supported perchloric acid under solvent-free conditions.
A. T. Khan, T. Parvin, L. H. Choudhury,
Synthesis, 2006, 2497-2502.
The tetrahydropyranylation of a variety of alcohols and phenols under
solvent-free conditions is efficiently catalyzed by bismuth triflate. This
relatively nontoxic catalyst is insensitive to air and small amounts of
moisture. Bismuth triflate also catalyzes the deprotection of THP ethers.
J. R. Stephens, P. L. Butler, C. H. Clow, M. C. Oswald, R. C. Smith, R. S.
Mohan, Eur. J. Org. Chem., 2003, 3827-3831.
The use of zeolite H-beta as an acid catalyst provides a useful alternative to
the known methods for protection of alcohols as THP ethers and the deprotection
of THP ethers. Short reaction time, mild conditions, high yield, the amount of
catalyst, and the recyclability of used catalyst are notable advantages.
J.-E. Choi, K.-Y. Ko, Bull. Korean. Chem. Soc., 2001, 1177-1178.
A mild, environmentally benign, efficient, and highly chemoselective
tetrahydropyranylation of alcohols and phenols is reported, which is catalysed by the CeCl3·7 H2O/NaI
system under solvent-free conditions.
R. Sanz, A. Martinez, J. M. Alvarez-Gutierrez, F. Rodriquez, Eur. J. Org. Chem., 2006,
1383-1386.
Deprotection
The combination of lithium chloride and water in DMSO enables a mild, simple and
convenient method for the selective removal of the THP protecting group at 90°C.
G. Maiti, S. C. Roy, J. Org. Chem., 1996,
61, 6038-6039.
A new and efficient method for the cleavage of the PMP, THP and 1,3-dithiane
protecting groups with Selectfluor™ has been developed.
J. Liu, C.-H. Wong, Tetrahedron Lett., 2002, 43, 4037-4039.
The tetrahydropyranylation of a variety of alcohols and phenols under
solvent-free conditions is efficiently catalyzed by bismuth triflate. This
relatively nontoxic catalyst is insensitive to air and small amounts of
moisture. Bismuth triflate also catalyzes the deprotection of THP ethers.
J. R. Stephens, P. L. Butler, C. H. Clow, M. C. Oswald, R. C. Smith, R. S.
Mohan, Eur. J. Org. Chem., 2003, 3827-3831.
The use of zeolite H-beta as an acid catalyst provides a useful alternative to
the known methods for protection of alcohols as THP ethers and the deprotection
of THP ethers. Short reaction time, mild conditions, high yield, the amount of
catalyst, and the recyclability of used catalyst are notable advantages.
J.-E. Choi, K.-Y. Ko, Bull. Korean. Chem. Soc., 2001, 1177-1178.
Conversion of THP Ethers
The use of 0.2 eq. of TiCl4 and 1.2 eq. of Ac2O
enables a mild direct conversion of THP ethers to acetates.
S. Chandrasekhar, T. Ramachandar, M. V. Reddy, M. Takhi, J. Org. Chem., 2000,
65, 4729-4731.
An efficient and user-friendly procedure has been developed for the oxidative
deprotection of tetrahydropyranyl (THP) ethers with
N-bromosuccinimide (NBS) using β-cyclodextrin (β-CD) in water. A series
of tetrahydropyranyl ethers were oxidatively deprotected at room temperature in
impressive yields.
M. Narender, M. S. Reddy, K. R. Rao, Synthesis, 2004, 1741-1743.
