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Reactions >> Protecting Groups >> Stability

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, 100C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100C
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 CeCl37 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


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


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.