Tetrahydropyranyl alcohol

Six protective groups for alcohols, which may be removed successively and selectively, have been listed by E.J. Corey (1972B). A hypothetical hexahydroxy compound with hydroxy groups 1 to 6 protected as (1) acetate, (2) 2,2,2-trichloroethyl carbonate, (3) benzyl ether, (4) dimethyl-t-butylsilyl ether, (5) 2-tetrahydropyranyl ether, and (6) methyl ether may be unmasked in that order by the reagents (1) KjCO, or NH, in CHjOH, (2) Zn in CHjOH or AcOH, (3) over Pd, (4) F", (5) wet acetic acid, and (6) BBrj. The groups may also be exposed to the same reagents in the order A 5, 2, 1, 3, 6. The (4-methoxyphenyl)methyl group (=MPM = p-methoxybenzyl, PMB) can be oxidized to a benzaldehyde derivative and thereby be removed at room temperature under neutral conditions (Y- Oikawa, 1982 R. Johansson, 1984 T. Fukuyama, 1985). 

When 16-dehydropregnenolone itself is reduced, less than 3 % of the starting material remains unreduced and reduction of the tetrahydropyranyl ether of 16-dehydropregnenolone (70) in the presence of one mole of t-butyl alcohol is also virtually complete. In both cases, however, crystallization of the crude products gives only modest yields of pure products. 

Enol ethers (15) and mixed acetals (16) are readily obtained from secondary but not from tertiary alcohols, whereas tetrahydropyranyl ethers can be formed even from tertiary alcohols. This is a result of the greater steric requirements of the reagents (17) and (18) as compared to (19). 

Beta- and 3a-alcohols of the 5)5- and 5a-series respectively also form tetrahydropyranyl ethers, cycloalkenyl ethers and mixed acetals. ... 

The 21-hydroxyl group in the corticosteroid series can be protected as the base stable triphenylmethyl ether and tetrahydropyranyl ether. " " Mixed acetals from 21-alcohols are extremely acid sensitive compounds. ... 

Tetrahydropyranyl (THP)-protected nitroethanol can be doubly deprotonated to lithium a-lithionitronate, which is stable to react with various electrophiles. Higher P-nitro alcohols,... 

In 1975, van der Baan and Bickelhaupt reported the synthesis of imide 37 from pyridone 34 as an approach to the hetisine alkaloids, using an intramolecular alkylation as the key step (Scheme 1.3) [23]. Beginning with pyridone 34, alkylation with sodium hydride/allyl bromide followed by a thermal [3,3] Claisen rearrangement gave alkene 35. Next, formation of the bromohydrin with A -bi omosuccinimide and subsequent protection of the resulting alcohol as the tetrahydropyranyl (THP) ether produced bromide 36, which was then cyclized in an intramolecular fashion to give tricylic 37. 

Silica gel successfully catalyzed the stereoselective synthesis of several glucoside terpenoids. Treatment of 49a with propan-2-ol, geraniol, the tetrahydropyranyl (THP) ether of coniferyl alcohol, and (—)-perillyl alcohol gave glucosides 52a-d in good yields (Scheme 12). The acid-labile THP group was retained under these reaction... 

Although alcohols are oxidized by tetra-n-butylammonium persulphate when the reaction is conducted in dichloromethane, tetrahydropyranyl ethers have been produced (>90%) when attempts to oxidize the alcohol are conducted in tetrahydro-pyran (see Chapter 10) [ 19], Tetrahydrofuranyl ethers have been prepared by an analogous method [20,21 ]. Base-mediated elimination of halo acids from P-halo alcohols under phase-transfer catalysed conditions produce oxiranes in high yield (70-85%). The reaction has particular use in the synthesis of epihalohydrins from p,y-dihalo alcohols [22],... 

The alcohol (l mmol) and (TBA)2-S20, (0.98 g, 1.4 mmol) in THF or THP (10 ml) are stirred under reflux for 3 h. The solvent is evaporated under reduced pressure and H20 (25 ml) is added to the residue, which is then extracted with Et20 (2 x 15 ml). The extracts are dried (MgS04) and evaporated to yield the tetrahydrofuranyl or tetrahydropyranyl ether. 

A number of efforts have been devoted to the simplified, acid catalyzed reaction between dihydropyran and alcohols to form THP-ethers. Thus, employing the hydrochloride salt of Reillex 425 (34) [a cross-linked macroreticular poly(4-vinylpyri-dine) resin] the tetrahydropyranylation even of hindered alcohols proceeds under mild conditions in high yields without side-reactions (Scheme 4.20) [107]. 

The involvement of transition-metal allenylidene complexes in homogeneous catalysis was reported for the first time by B. M. Trost and co-workers in 1992 (Scheme 35) [293-295]. The catalytic reactions allowed the preparation of a wide variety of tetrahydropyranyl and furanyl p,y-unsaturated ketones starting from hydroxy-functionalized alkynols and allylic alcohols, the key step in the catalytic... 

Carbohydrates have been included in the wide range of molecules used in the parameterization of MM2 and of MM3. Alcohol and ether parameters have usually been determined from simple alcohols and ethers themselves. However, carbohydrates contain some unusual features in the acetal linkages, and in the many vicinal hydrogen-bonded hydroxyl groups. The "anomeric effect", first discovered by Edward (15) and popularized by Lemieux (16.), is best known in carbohydrates, although, of course, it occurs in other classes of compounds as well. One apparent result of this effect is that an axial alkoxy substituent is often more stable than the corresponding equatorial substituent when attached at the Cl position of a tetrahydropyranyl ring. This effect can be... 

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. 

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