Phenol tetrahydropyranylation

The tetrahydropyranyl ether, prepared from a phenol and dihydropyran (HCl/ EtOAc, 25°, 24 h), is cleaved by aqueous oxalic acid (MeOH, 50-90°, 1-2 h). ... 

The tetrahydropyranyl ether, prepared from a phenol and dihydropyran (HCl/EtOAc, 25°, 24 h) is cleaved by aqueous oxalic acid (MeOH, 50-90°, 1-2 h). Tonsil, Mexican Bentonite earth, HSZ Zeolite, and H3[PW,204o] have also been used for the tetrahydropyranylation of phenols. The use of [Ru(ACN)3(triphos)](OTf)2 in acetone selectively removes the THP group from a phenol in the presence of an alkyl THP group. Ketals of acetophenones are also cleaved. ... 

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. 

Tetrahydropyranyl (TUP) and tetrahydrofuranyl ethers are important protecting groups for alcohols and phenols in organic synthesis, but they can also be converted to other useful functional groups [8, 118]. For example, allylation of a TUP ether should yield a highly functionalized molecule (Scheme 15). 

In 2007, another departure from carbonyl-type activation was marked by Kotke and Schreiner in the organocatalytic tetrahydropyran and 2-methoxypropene protection of alcohols, phenols, and other ROH substrates [118, 145], These derivatives offered a further synthetically useful acid-free contribution to protective group chemistry [146]. The 9-catalyzed tetrahydropyranylation with 3,4-dihydro-2H-pyran (DHP) as reactant and solvent was described to be applicable to a broad spectrum of hydroxy functionalities and furnished the corresponding tetrahydro-pyranyl-substituted ethers, that is, mixed acetals, at mild conditions and with good to excellent yields. Primary and secondary alcohols can be THP-protected to afford 1-8 at room temperature and at loadings ranging from 0.001 to 1.0mol% thiourea... 

Scheme 6.17 Product range of the 9-catalyzed tetrahydropyranylation of sterically hindered and phenolic substrates.

Dihydropyran is of value as a protecting group for alcohols and phenols, and to a lesser extent amines, carboxylic acids and thiols (B-67MI22403, B-81MI22404). The resulting tetrahydropyranyl ethers (736) are stable to base, but are readily cleaved under acidic conditions (Scheme 284). 

Nafion-H has been shown to be effective in a variety of protection-deprotection reactions including (9-trialkylsilylation of alcohols, phenols, and carboxylic acids, as well as the preparation and methanolysis of tetrahydropyranyl (THP) ethers.672 However, when compared, for example, with HBF4-silica or Nafion nanocomposites,... 

A catalytic amount of ruthenium(III) acetylacetonate (2 mol%) [Ru(acac)3] permits solvent-free tetrahydropyranylation of various types of alcohols and phenols at ambient temperature in moderate to excellent yields.94... 

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... 

Hydrogenolysis of the phosphate phenol ether 311.1 [Scheme 4.311] released a phosphoric diester whose inherent acidity was sufficient to cleave the 4-methoxy-tetrahydropyranyl ether function in situ. The desired product 31L2 was recovered as the sodium salt generated with the aid of an ion exchange resin. 

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. 

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... 

S-, N-Protective derivatives. The reagent reacts under mild acid catalysis with primary and secondary alcohols, and with phenols, to form tetrahydropyranyl ethers, which are stable to bases, to RMgX, to L1AIH4, to acetic anhydride in pyridine, and to oxidation. When synthetic operations at another site in the molecule have... 

Chloromethyl methyl ether, used for the preparation of methoxymethyl ether is a carcinogen. It is desirable to convert the phenol into a tetrahydropyranyl ether using dihydropyran. 

The no-bond resonance model of the anomeric effect predicts that, in a series of axial aryloxytetrahydropyran derivatives, the intracyclic bond should shorten and the extracyclic bond should lengthen as the parent phenol becomes more acidic and the ion-paired canonical form any effect should be much smaller in the equatorial case. Careful X-ray crystallographic studies of a series of tetrahydropyranyl ethers (structures in Figure 2.15) indeed showed that for seven such axial compounds, with the p a of ROH spanning 8 units, the lengths (A) of the extracyclic bond (x) and the intracyclic bond n) were given by eqns (2.2) and (2.3), respectively ... 

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. 

A totally different synthesis of the diterpene alkaloids has been reported by Masamune (102-104). The carboxylic acid CCXCII was converted via the bromo ketone CCXCIII to the tetrahydropyranyl ethers CCXCIV. Hydrogenolysis of the latter gave the corresponding phenols CCXCV. Base treatment of CCXCV effected cyclization of only one isomer to furnish a dienone ether (CCXCVI). Catalytic hydrogenation of the benzoate (CCXCVII) gave the tetrahydro cis-fused derivative... 

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... 

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