Tetrahydropyranyl ether oxidative cleavage

Cleavage of acid-labile protective groups.1 The reaction of H202 (70%, FMC) and CI3CCOOH in CH2C12/(-butyl alcohol converts a dimethyl acetal (1) into a hydroperoxy methyl acetal (a), which can be isolated but which for convenience (and safety) is reduced to the aldehyde 2 in 80% overall yield. The same conditions can effect oxidative cleavage of tetrahydropyranyl and trityl ethers. 

This procedure consists of the synthesis of a precursor, methoxymethyl vinyl ether, an a-hydroxy enol ether, and the intramolecular hydrosilylatlon of the latter followed by oxidative cleavage of the silicon-carbon bonds. The first step, methoxymethylation of 2-bromoethanol, is based on Fujita s method.7 The second and third steps are modifications of results reported by McDougal and his co-workers. Dehydrobromination of 2-bromoethyl methoxymethyl ether to methoxymethyl vinyl ether was achieved most efficiently with potassium hydroxide pellets -9 rather than with potassium tert-butoxide as originally reported for dehydrobromination of the tetrahydropyranyl analog.10 Potassium tert-butoxide was effective for the dehydrobromination, but formed an adduct of tert-butyl alcohol with the vinyl ether as a by-product in substantial amounts. Methoxymethyl vinyl ether is lithiated efficiently with sec-butyllithium in THF and, somewhat less efficiently, with n-butyllithium in tetrahydrofuran. Since lithiation of simple vinyl ethers such as ethyl vinyl ether requires tert-butyllithium,11 metalation may be assisted by the methoxymethoxy group in the present case. 

Oxidative cleavage of t-butyldimethylsilyl ethersThese ethers are usually cleaved with tetra-n-butylammonium fluoride in aprotic solvents. The cleavage is also possible with NCS (1.1 equivalent) in DMSO (75-90% yield). A tetrahydropyranyl group is unaffected by NCS under these conditions. 

Tetrahydropyranyl ethers (I, unsymmetrical acetals) are oxidized exclusively to the hydroxy ester (2) on heating, this is converted into 6-valerolactone (3) with liberation of the alcohol. The reaction thus constitutes a useful method for cleavage of tetrahydropyranyl ethers under neutral conditions. 

---