Hydrolysis tetrahydropyranyl ether

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). ... 

In the latter case, one end of the glycol is protected as its tetrahydropyranyl ether. Upon hydrolysis, a two-armed crown is revealed which may then be treated with the bis-crown precursor identified above. The result will be a tris-crown system and the approach is illustrated below in Eq. (3.35). 

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. 

Schaub ° introduced methyl groups at both the 16a- and 17a-positions by 1,4-addition of methylmagnesium iodide to the A -20-ketone (8) followed by methylation of the intermediate 16a-methyl-17-enolate anion (9) with methyl iodide. After hydrolysis of the tetrahydropyranyl ether group a 40% yield of the 16,17-dimethyl derivative (10) was obtained. With the corresponding 3j -acetoxy derivative, the yield of (10) is only 20%. 

Hydrolysis of cyclic orthoesters Ozonolysis of tetrahydropyranyl ethers Cleavage of vinyl orthoesters... 

In a different sequence of reactions, N-acetylation of 274 and exposure of the intermediate imide 275 to ethanolic KOH gave a mixture (about 2 1) of the desired carboxylic acid 276 together with the starting lactam 274 via the non-selective hydrolysis of the imide moiety of 275 (148a,c). When 276 was treated with /V-bromosuccinimide (NBS), an intermediate bromolactone was produced which was heated at reflux in pyridine in the presence of DBU to give 277. The conversion of the lactone 277 to the lactam 278 was effected by heating 277 in aqueous NaOH followed by protection of the resulting allylic alcohol function as a tetrahydropyranyl ether. 

Show the steps in the mechanism for the hydrolysis of this tetrahydropyranyl ether ... 

The azanorcholesterol (343) has been synthesized184 by condensation of 2-methylpropionaldehyde with 20a-aminopregn-5-en-3/3-ol and subsequent reduction of the intermediate by borohydride. The azahomocholesterol (344) was derived from reaction between the tetrahydropyranyl ether of 20a-aminopregn-5-en-3/3-ol and 4-methylpentanoyl chloride followed by hydride reduction and hydrolysis of the protecting group. 

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). 

Metalatlon of 2-alkynyl and 1,2-alkadienyl tetrahydropyranyl ethers furane synthesis. /-Butyllithium metalates the lithium alkoxide 1 to afford the allenyllithium compound a quantitatively. This anion reacts with alkyl halides or CH3OH to afford 2. Another metalation-alkylation protonation sequence proceeds via b to afford 3. Hydrolysis of the latter intermediate affords furanes directly. The overall sequence can be performed in one pot from a propargyl tetrahydropyranyl ether, r-butyl-lithium, and an aldehyde. ... 

The hydrolysis of p-nitrophenyl tetrahydropyranyl ether does indeed exhibit general acid catalysis with a Bronsted a of 0.5. ... 

Valerianine (13) was synthesized in racemic form by Franck and coworkers (75) in 1970. Diene condensation of 5-methyl-l-cyclopentene carboxaldehyde (175) with 1,3-dimethoxy propene (176) afforded the tetrahydropyranyl ether 177, which, on acid hydrolysis, afforded 9-methoxy-iridodial (178). This compound was not isolated, but was converted directly to ( )-valerianine 13) with either Fe(NH4)2S04 or NH2OH (Scheme 8)... 

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. 

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