Tetrahydropyranyl ethers stable

The cyclohexylidene ketal, prepared from a catechol and cyclohexanone (AI2O3/ TsOH, CH2CI2, reflux, 36 h), is stable to metalation conditions (RX/BuLi) that cleave aiyl methyl ethers. The ketal is cleaved by acidic hydrolysis (coned. HCl/ EtOH, reflux, 1.5 h, 20°, 12 h) it is stable to milder acidic hydrolysis that cleaves tetrahydropyranyl ethers (1 AHCl/EtOH, reflux, 5 h, 91% yield). ... 

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. ... 

Many functional groups are stable to alkaline hydrogen peroxide. Acetate esters are usually hydrolyzed under the reaction conditions although methods have been developed to prevent hydrolysis.For the preparation of the 4,5-oxiranes of desoxycorticosterone, hydrocortisone, and cortisone, the alkali-sensitive ketol side chains must be protected with a base-resistant group, e.g., the tetrahydropyranyl ether or the ethylene ketal derivative. Sodium carbonate has been used successfully as a base with unprotected ketol side chains, but it should be noted that some ketols are sensitive to sodium carbonate in the absence of hydrogen peroxide. The spiroketal side chain of the sapogenins is stable to the basic reaction conditions. 

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). 

Tetrahydropyranyl ethers are stable to bases and the protection is removed by acid-catalyzed hydrolysis. For example, geraniol (1.60) is protected as geraniol tetrahydropyranyl ether (1.80) in the presence of pyridinium p-toluenesulfonate (PPTS) reagent. These ethers are cleaved with PPTS in warm ethanoP (Scheme 1.19). 

The combination of triphenylphosphine with esters of trihaloacetic acids provides a reagent system for the stereo- and regio-selective conversion of alcohols into alkyl halides.The bromine-triphenylphosphine adduct has been used at low temperatures (-50 C in dichloromethane) for the removal of the tetrahydropyranyl protecting group from tetrahydropyranyl ethers derived from secondary and tertiary alcohols.The reactions of tertiary phosphines (and other trivalent phosphorus compounds) with iodine in aprotic solvents have received further study, a range of species being identified.The first reported study of the reactions of trivalent phosphorus compounds with monopositive astatine has led to the identification of stable complexes with triphenylphosphine, trioctylphosphine, and triethylphosphite. 

Epoxidation of tetrahydropyranyl ethers e.g. isopentenyl tetrahydropyranyl ether) produces readily detonatable peroxides which are stable to many commonly used methods of destruction. ... 

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... 

Ether cleavage. The polymer-bound reagent catalyzes hydrolysis of TBS ether and acetals in aqueous acetonitrile. Methoxymethyl and tetrahydropyranyl ethers are stable under such conditions. 

Protecting-group manipulations. Tetrahydropyranyl ethers are switched to t-butyldimethylsilyl ethers on reaetion of RjSiOTf and EtjN in dichloromethane at room temperature. f-Butyl esters also undergo group exchange in the presence of t-butyl ethers. IV-r-Butoxycarbonyl derivatives of primary amines are further silylated with M SiOTf to give the base stable produets. Rapid acetylation of alcohols is promoted by the same catalyst. ... 

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