THP group

The THP ether can be converted directly to an acetate by refluxing in AcOH/AcCl (91 % yield). These conditions would probably convert other related acetals to acetates as well. The THP group can also be converted through the 0-SnBu3 to benzyl, MEM, benzoate, and tosylate groups. ... 

N HCl, EtOH, reflux, 90% yield for cholesterol. Although a direct stability comparison was not made, this group should be more stable than the THP group for the same reasons that the anomeric ethers of carbohydrates are more stable than their 2-deoxy counterparts. 

THF, Et3NHCe(ni) (N03)6, 50-100°, 8 h, 30-98% yield. Hindered alcohols give the lower yields. The method was also used to introduce the THP group with tetrahydropyran. 

The advantage of this ketal is that unlike the THP group, only a single isomer is produced in the derivatization. Conditions used to hydrolyze the THP group can be used to hydrolyze this acetal. This group may also find applications in the resolution of racemic alcohols. 

The pixyl ether is prepared from the xanthenyl chloride in 68-87% yield. This group has been used extensively in the protection of the 5 -OH of nucleosides it is readily cleaved by acidic hydrolysis (80% AcOH, 20°, 8-15 min, 100% yield, or 3% trichloroacetic acid). It can be cleaved under neutral conditions with ZnBrj, thus reducing the extent of the often troublesome depurination of A -6-benzyloxy-adenine residues during deprotection. Conditions which remove the pixyl group also partially cleave the THP group (t,/2 for THP at 2 -OH of ribonucleoside = 560 s in 3% Cl2CHC02H/CH2Cl2). ... 

Bu2SnNCS>20, diglyme, H2O, 100°, 82% yield.The THP group,is also cleaved by this reagent. 

Dihydropyran, H3[PW,204o], CH2CI2, rt, 64-96% yield. The same acid can be used to cleave the THP group if methanol is used as solvent.""... 

TBDMSOTf, CH2CI2 Me2S, 95% yield. The THP group is converted directly into a TBDMS ether." ... 

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. ... 

Ru(CH3CN)3(triphos)(OTf)2, acetone, it, 99% yield. Nonphenolic THP groups and dioxolane ketals are stable. 

Pe(phen)3(PF6), CH3CN, H2O, 43-75% yield. Hydroxyl and THP groups are not compatible with these conditions. ... 

The THP derivative of the imidazole nitrogen in purines has been prepared by treatment with dihydropyran (TsOH, 55°, 1.5 h, 50-85% yield). It is cleaved by acid hydrolysis. The THP group is useful for the protection of 1,2,4-triazoles. ... 

The chemoselectivity of converting one OH in (16) into a leaving group will be easier if the other OH Is protected, so it is best to Introduce protection at the start. The easily removed THP group is ideal (Table T 9,1 ). The required Grlgnard reagent is from available halide (17) (p T 1). 

The acetate group in (22) is Inadequate protection for the terminal OH group and a THP group was used instead (Table T 68),... 

The THP group can be removed by dilute aqueous acid. The chemistry involved in both the introduction and deprotection stages is the reversible acid-catalyzed formation and hydrolysis of an acetal (see Part A, Section 7.1). 

A disadvantage of the THP group is the fact that a new stereogenic center is produced at C(2) of the tetrahydropyran ring. This presents no difficulties if the alcohol is achiral, since a racemic mixture results. However, if the alcohol is chiral, the reaction gives a mixture of diastereomers, which may complicate purification and/or characterization. One way of avoiding this problem is to use methyl 2-propenyl ether in place of dihydropyran (abbreviated MOP, for methoxypropyl). No new chiral center... 

Ethyl vinyl ether is also useful for hydroxy group protection. The resulting derivative (1-ethoxyethyl ether) is abbreviated as the EE group.156 As with the THP group, the EE group introduces an additional stereogenic center. 

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... 

Merrifield resin (1 % crosslinked) was employed as the solid support. The problem of oligomerization was prevented by protection of the hydroxyl of 38 as a THP ether by treatment with 3,4-dihydro-2H-pyran (DHP) in the presence of pyridinium /7-toluenesulfonate (PPTS) to give 46. Immobilized 46 was successfully coupled with 24 to give disaccharide 47. The THP group of 47 was easily removed by treatment with acetic acid/water to yield 45. 

This protective group is introduced by an acid-catalyzed addition of the alcohol to the vinyl ether moiety in dihydropyran. />-Toluenesulfonic acid or its pyridinium salt is used most frequently as the catalyst,3 although other catalysts are advantageous in special cases. The THP group can be removed by dilute aqueous acid. The chemistry involved in both the introduction and deprotection stages is the reversible acid-catalyzed formation and hydrolysis of an acetal (see Part A, Section 8.1). 

The THP group, like other acetals and ketals, is inert to nucleophilic reagents and is unchanged under such conditions as hydride reduction, organometallic reactions, or base-catalyzed reactions in aqueous solution. It also protects the hydroxyl group against oxidation. 

Unsaturated tetrahydropyran derivatives have received only cursory attention in the literature as heterocyclic monomers. 2,3-Dihydropyran and several of its substituted derivatives apparently undergo cationic polymerization in a manner typical of vinyl ethers (72MI11103), while tetrahydropyranyl esters of methacrylic acid (123) are fairly typical free radically polymerizable monomers (Scheme 35) (74MI11105). The THP group was used in this study as a protecting group for the acid functionality, and it was found that deprotection of polymers (124) could be accomplished under extremely mild conditions. 

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