AQUEOUS ALDOL REACTION OF ALDOSE AND ITS APPLICATION TO THE ENANTIOSPECIFIC SYNTHESIS OF SPIROACERALS

Water compatible prolinamide catalyst 1 derived from carbohydrate¹ are capable of catalyzing the aldol reaction of aldoses in aqueous media (Scheme 1). For example, treatment of D-glyceraldehyde acetonide 3 with acetone in the presence of 1 gave protected deoxyulose 4 in high yield and selectivity. The aqueous aldol reaction is also effective for unprotected aldose. Dideoxy-hexulose 6 was obtained as hemiketal in high efficiency from free D-glyceraldehyde 5. When the reaction was carried out using 2 equiv. of 3, a tandem aldol reaction was occurred and C₂ symmetrical nonulose 7 was isolated in 76% yield as a single diastereomer. Acid catalyzed hydrolysis of this compound afforded enantiomerically pure (R)-spiroacetal 8, whose stereochemistry was determined by X-ray crystallography. ² Asymmetric higher-ulose 10 and the spiroacetal 11 are also prepared from 3 and L-arabinose acetonide 9 using these procedures.

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