Tetrahydropyranylation of alcohols

Next to iodine there is also another class of neutral Lewis acids known. Tetracyanoethylene, dicyanoketene acetals and derivatives can catalyse reaction due to their tt-Lewis acid properties. They promoted the alcoholysis of epoxides [238], tetrahydropyranylation of alcohols [239], monothioacetahzation of acetals [240], and carbon-carbon bond formation of acetals [241,242] and imines [243] with silylated carbon nucleophiles. 

Several authors reported the use of ionic liquids containing protonic acid in catalysis (118-120). For example, strong Bronsted acidity in ionic liquids has been reported to successfully catalyze tetrahydropyranylation of alcohols (120). Tetra-hydropyranylation is one of the most widely used processes for the protection of alcohols and phenols in multi-step syntheses. Although the control experiments with the ionic liquids showed negligible activity in the absence of the added acids, high yields of product were obtained with the ionic liquid catalysts TPPTS or TPP.HBr-[BMIM]PF6. By rapid extraction of the product from the acidic ionic liquid phase by diethyl ether, the reaction medium was successfully reused for 22 cycles without an appreciable activity loss. A gradual loss of the catalyst and a reduced volume of the ionic liquid were noted, however, as a consequence of transfer to the extraction solvent. 

The search for new catalysts that would be effective for acetalations still stimulates interest. Better yields, and increased rates, have been claimed for the reaction of monosaccharides with acetone in the presence of ferric chloride.48 (Ferric chloride was already known to catalyze acetalation in other series.47) Not yet applied in the carbohydrate field, but potentially useful for sugars, is the separate use of two different catalysts. The first one recommended is pyridinium p-toluenesul-fonate as a mild and efficient catalyst for the tetrahydropyranylation of alcohols.48 The main interest in this catalyst lies in the excellent yields... 

The starting material for the present synthesis was Wieland-Miescher ketone (24), which was converted to the known alcohol (25) by the published procedure [10], Tetrahydropyranylation of alcohol (25) followed by hydroboration-oxidation afforded the alcohol (26), which on oxidation produced ketone (27). Reduction of (27) with metal hydride gave the alcohol (28) (56%). This in cyclohexane solution on irradiation with lead tetraacetate and iodine produced the cyclic ether that was oxidized to obtain the keto-ether (29). Subjection of the keto-ether (29) to three sequential reactions (formylation, Michael addition with methyl vinyl ketone and intramolecular aldol condensation) provided tricyclic ether (30) whose NMR spectrum showed it to be a mixture of C-10 epimers. The completion of the synthesis of pisiferic acid (1) did not require the separation of epimers and thus the tricyclic ether (30) was used for the next step. The conversion of (30) to tricyclic phenol (31) was... 

Hajipour, A.R., Kargosha, M., and Ruoho, A.E. 2009. Tetrahydropyranylation of alcohols under solvent-free conditions. Synthetic Communications, 39 1084-91. 

The tetrahydropyranylation of alcohols under solvent-free conditions is efficiently catalyzed by bismuth triflate (0.1 mol%). The experimental procedure is simple and works well with a variety of alcohols and phenols. The catalyst is insensitive to air and small amounts of moisture, easy to handle and relatively non-toxic. The deprotection of THE ethers is also catalyzed by bismuth triflate (1.0 mol%). 

Armengol et al. [227] used protonated Al-MCM-41 molecular sieve for alkylation of bulky aromatic compounds such as 2,4-di-rerr-butylphenol with a bulky alcohol (cinnamyl alcohol). This reaction did not occur in the presence of large pore HY zeolite indicating the importance of the mesoporous structure of the H-MCM-41 catalyst and the accessibility of active sites. Kloetstra et aL [228] obtained excellent results during the tetrahydropyranylation of alcohols and phenols over Al-MCM-41 (Scheme 3). Bulky alcohols including cholesterol, adamantan-l-ol and 2-naphthol were converted into the corresponding tetrahydropyranyl ethers in relatively short periods of time. 

Pachamuthu, K, Vankar, Y D, Ceric ammonium nitrate-catalyzed tetrahydropyranylation of alcohols and synthesis of 2-deoxy-O-glycosides, J. Org. Chem., 66, 7511-7513, 2001. 

Zr phosphates and phosphites have played a variety of roles in organic transformations, acting as a catalyst support media,550 as heterogeneous catalysts for tetrahydropyranylation of alcohols and phenols,551 and as catalysts for the hydrolysis of phosphodiester compounds.552-556... 

Kloetstra, R van Bekkum, H Catalysis of the tetrahydropyranylation of alcohols and phenols by the H-MCM-41 mesoporous molecular sieve. J. Chem. Research (S) 1995, 26-27. 

Protection and deprotection. CuClj catalyzes tetrahydropyranylation of alcohols," as well as cleavage of phenacyl esters." In the latter process, oxygen is introduced into the refluxing medium (aqueous DMF). 

MW has also accelerated the tetrahydropyranylation of alcohols, phenols 13, and thiols 14 in the presence of hydrated zirconia to give 15 in 80-98% yields within 3-15 min. This method has distinct advantages over the other existing methods, characterized by mild reaction conditions, absence of solvent, shorter reaction time, and easy as well as quick isolation of the products in excellent yields. The hydrated... 

Miscellaneous Reactions. In addition to the key reactions above, DDQ has been used for the oxidative removal of chromium, iron, and manganese from their complexes with arenes and for the oxidative formation of imidazoles and thiadia-zoles from acyclic precursors. Catal)ftic amounts of DDQ also offer a mild method for the oxidative regeneration of carbonyl compounds from acetals, which contrasts with their formation from diazo compounds on treatment with DDQ and methanol in nonpolar solvents. DDQ also provides effective catalysis for the tetrahydropyranylation of alcohols. Furthermore, the oxidation of chiral esters or amides of arylacetic acid by DDQ in acetic acid provides a mild procedure for the synthesis of chiral a-acetoxy derivatives, although the diastereoselectivity achieved so far is only 65-67%. ... 

Karimi, B. and Khalkhali, M. 2005. Solid silica-based sulfonic acid as an efficient and recoverable interphase catalyst for selective tetrahydropyranylation of alcohols and phenols. J. Mol. Catal. A Ghent. 232(1-2) 113-117. 

Kim YJ, Varma RS (2005) Microwave-assisted preparation of imidazolium-based Etrachloroindate(III) and their application in the tetrahydropyranylation of alcohols. Tetrahedron Lett 46 1467-1469... 

Mineno has demonstrated that mdium(III) triflate is an efficient catalyst for the tetrahydropyranylation of alcohols (eq 2). In addition, indium(ni) triflate catalyzes the deprotection of such products to the parent alcohol or their conversion to the corresponding... 

Tetrahydropyranylation of Alcohols. Protection of alcohol functionality as the THP ether is an often-utilized tool in organic synthesis. It must be noted that the reaction of a chiral alcohol with dihydropyran introduces an additional asymmetric center and hence a diastereomeric mixture is obtained (eq 1). This can lead to difficulties with purification, assignment of spectral features, etc., but does not prevent successful implementation. ... 

Tetrahydropyranylation of alcohols can be carried out under very mild conditions in the presence of bis(trimethylsilyl) sulfate (0°C, 1 h, 89-100%). No rearrangement is observed even with tertiary allylic alcohols. ... 

Protective Tetrahydropyranylation of Alcohols and Phenols. With an excess of 3,4-Dihydro-2H-pyran, in the presence of KIO at room temperature, alcohols are transformed quantitatively into their tetrahydropyranyl derivatives. Run in dichloromethane at room temperature, the reaction is complete within 5-30 min (eq 9). The procedure is applicable to primary, secondary, tertiary, and polyfunctional alcohols as well as to phenols. ... 

---