(E,R,R)-5-Alkylidene-2-tert-butyl-6-methyl-1,3-dioxan-4-ones: preparation from (R)-3-hydroxybutyric acid, cuprate additions, and hydrolyses to 3-hydroxycarboxylic acids with chiral secondary alkyl substituents in the 2-position

Abstract

The Li enolates of (R,R)-2-tert-butyl-6-methyl-1,3-dioxan-4-one adds to aliph. or arom. aldehydes with relative topicity Re, Re. The title compds. are obtained from these aldol adducts by dehydration via their mesylates. Cuprate addn. to these alkylidenedioxanones and quenching with acid produces 5,6-trans-substituted dioxanones in an overall anti addn. of R and H to the exocyclic double bond from the Re and the Si face, resp. The configurations of the products were assigned by NMR spectroscopy and by chem. correlation. Some dioxanone products were hydrolyzed to the free b-hydroxy carboxylic acids. It is also demonstrated that transacetalization of the aldol adducts leads to 1,3-dioxane-5-carboxylic acids (acetal-protected derivs. of double aldols, formally derived from acetic acid). Redn. of these acids with LiAlH4, in turn, produces acetal-protected tris(hydroxyalkyl)methanes. All chiral products are enantiomerically pure. [on SciFinder (R)]