Synthesis of 4,6-dideoxyfuranoses through the regioselective and diastereoselective oxyfunctionalization of a dimethylphenylsilyl-substituted chiral homoallylic alcohol.

The 4,6-dideoxyfuranoses 10a and 10b have been synthesized by starting from the readily available E-5-dimethylphenylsilyl-2-hexene-4-ol (1) and employing successively three versatile oxyfunctionalization methods, namely photooxygenation, metal-catalyzed epoxidation, and oxidative desilylation. Photooxygenation of the hydroxy vinylsilane 1 and subsequent triphenylphosphine reduction of the hydroperoxides 3 afford the like-4a and unlike-4b diols, which have been converted separately to the tetrahydrofurans (2S*,3R*,5R*)-7a and (2S*,3R*,5S*)-7b by a combination of diastereoselective epoxidation and regioselective intramolecular epoxide-ring opening. In the epoxidation reaction, catalyzed by Ti(OiPr)(4) or VO(acac)(2), only one diastereomer (dr >95:5) of the epoxide 5 is obtained. Further intramolecular opening of the epoxide ring in erythro-5 occurs regioselectively at the C-alpha position and diastereoselectively under inversion of the configuration of the silyl-substituted stereogenic center to generate only one diastereomer of the tetrasubstituted tetrahydrofurans 7. Oxidative desilylation of the latter gave the hitherto unknown 4,6-dideoxyfuranoses 10a and 10b. The use of the optically active E-5-dimethylphenylsilyl-2-hexene-4-ol (1) as starting material, which is readily available through lipase-catalyzed kinetic resolution, leads to the D- and L-4,6-dideoxysorbofuranoses 10a and D- and L-4,6-dideoxyfructofuranoses 10b in up to 98% enantiomeric excess.

Preparation of optically active allylic hydroperoxy alcohols and 1, 3-diols by enzyme-catalyzed kinetic resolution and photooxygenation of chiral homoallylic alcohols.

All four possible enantiomers of the 3-hydroperoxy-4-penten-1-ols 2a, b and their corresponding 4-pentene-1,3-diols 4a,b have been prepared for the first time in high enantiomeric purity (up to 98% ee) and in preparative amounts according to two distinct ways: First the photooxygenation of the racemic homoallylic alcohols 1 gave the racemic hydroperoxy alcohols 2, which have subsequently been kinetically resolved by horseradish peroxidase (HRP); alternatively, first the lipase-catalyzed resolution afforded the optically active homoallylic alcohols 1 and subsequent photooxygenation led to the enantiomerically enriched hydroperoxy alcohols 2.