1,3-Dioxanone Derivatives from β-Hydroxy-carboxylic Acids and Pivalaldehyde. Versatile Building Blocks for Syntheses of Enantiomerically Pure Compounds. A Chiral Acetoacetic Acid Derivative Preliminary Communication

✍ Scribed by Dieter Seebach; Jürg Zimmermann

• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: German
• Weight: 346 KB
• Volume: 69
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19860690523

✦ Synopsis

9.VI. 86) (R)-3-Hydroxybutyric acid (from the biopolymer PHB) and pivalaldehyde give the crystalline cis-or (R, R)-2-(tert-butyl)-6-methy1-1,3-dioxan-4-one (la), the enolate of which is stable at low temperature in THF solution and can be alkylated diastereoselectively (-3, 4, 5, and 7). Phenylselenation and subsequent elimination give an enantiomerically pure enol acetal 10 of aceto-acetic acid. Some reactions of 10 have been carried out, such as Michael addition (-ll), alkylation on the CH, substituent (+13), hydrogenation of the C=C bond (+la) and photochemical cycloaddition (-16). The overall reactions are substitutions on the one stereogenic center of the starting B-hydroxy acid without racemization and without using a chiral auxiliary.

Our continuing interest in chiral building blocks derived from the readily available enantiomerically pure (3s)-[l-31 and (3R)-3-hydroxybutyrate') [4] [5] has led to the investigation of 1,3-dioxanones 1. These were, for instance, shown [6] to be versatile reagents for nucleophilic ring opening, to give, after removal of the chiral auxiliary, secondary alcohols of high enantiomeric purity.

Here, we report overall enantioselective reactions at the 2-, 3-, and 4-positions of 3-hydroxybutyric acid, i.e. at the 5and 6-position and on the CH, group of a 1,3-dioxanone 1. For this purpose, the 2-(tert-butyl)-l,3-dioxanone l a was chosen'), because all its derivatives readily crystallize and react with high stereoselectivity.

The 1,3-dioxanone l a [6] [7] is prepared from pivalaldehyde and (R)-3-hydroxybutyric acid under acid catalysis.