Ethers, 4-methoxytetrahydropyranyl

The acid lability of 4-methoxytetrahydropyranyl ethers was a key design feature... 

An inherent disadvantage of the TPIP and acetaldehyde acetals is that they contain a new chiral center, giving rise to mixtures of diastereomers if chiral alcohols are involved. This can be overcome by the use of 4-methoxytetrahydropyranyl ethers (Scheme 29). They are extensively applied in oligonucleotide synthesis. The analogous thiopyranyl compounds are hydrolyzed five times more quickly, but their S -dioxides 2(XX) times more slowly, than the corresponding oxygen compounds. 

Methoxytetrahydropyranyl derivatives (31) may be readily prepared by the acid-catalyzed addition of 4-methoxy-5,6-dihydro-2i/-pyran (32) [64] to alcohols. In the case of nucleosides, good yields of pure crystalline monoketals [such as 2 -0-methoxytetrahydropyranyluridine (33)] and bisketals [such as 34 (B = pyrimidine or purine base)] have been obtained [64]. The methoxytetrahydropyranyl group has satisfactory hydrolysis properties in that (33) is approximately three times as labile to aqueous acid as the corresponding tetrahydro-pyranyl derivative (19) [52b]. Since a simple procedure has recently been developed [66] for the preparation of tetrahydro-4ff-pyran-4-one, the enol ether (32) has become a readily accessible reagent. 

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