Enantiomerically pure acetals in organic synthesis: Resolutions and diastereoselective alkylations of alpha-hydroxy esters.

Abstract

The diastereomeric tetrahydropyranyl (THP) and tetrahydrofuranyl (THF) ethers of a variety of α-hydroxyesters were synthesized and separated by column chromatography. The separability of the diastereomers was found to be a general phenomenon which allowed for wide variations in both the THP/THF ring and the α-hydroxyester. The resolved compounds could be deprotonated and alkylated diastereoselectively with a variety of electrophiles. The diastereoselectivity ranged from 1:1 to 12:1 depending on the α-hydroxyester, the alkylating agent, and the reaction conditions. In most cases the diastereomeric products of the alkylation were also separated by column chromatography. This alkylation method was used in the synthesis of the natural product (S)-frontalin and its enantiomer with optical purity. Modifications to the THP and THF rings were synthesized in an attempt to develop a "chiral THP". The (S)-methyl lactyl, (S)-methyl mandelyl, and (R)-pantolactyl 3-benzyloxytetrahydrofuranosides were synthesized and separated. Transacetalization to the methyl furanosides gave "chiral THF's" which were used in the resolution of other racemic α-hydroxyesters.