(E,R,R)-5-ALKYLIDENE-2-TERT-BUTYL-6-METHYL-1,3-DIOXAN-4-ONES - PREPARATION FROM (R)-3-HYDROXYBUTYRIC ACID, CUPRATE ADDITIONS, AND HYDROLYZES TO 3-HYDROXYCARBOXYLIC ACIDS WITH CHIRAL SECONDARY ALKYL SUBSTITUENTS IN THE 2-POSITION

Li enolates of (R,R)-2-tert-Butyl-6-methyl-1,3-dioxan-4-one add to aliphatic or aromatic aldehydes with relative topicity Re,Re (2:1 to 10:1, 9 examples). The title compounds are obtained from these aldol adducts by dehydration through mesylates (5 examples, total yields from the dioxanone 35-55%). Cuprate additions (R2CuLi/F3B-OEt2) to these alkylidene dioxanones and quenching with acid produce 5,6-trans-substituted dioxanones in an overall anti addition of R and H to the exocyclic double bond from the Re and the Si face, respectively (5:1 to 40:1, 13 examples, 50-80%). The configurations of the products were assigned by NMR spectroscopy and by chemical correlation. In 8 cases, the dioxanone products were hydrolysed to the corresponding free beta-hydroxycarboxylic acids. It is also demonstrated that transacetalisation of the aldol adducts leads to 1,3-dioxane-5-carboxylic acids (acetal-protected derivatives of ''double aldols'', formally derived from acetic acid, 4 examples). Reduction of these acids with LAH, in turn, produces tris(hydroxyalkyl)methanes (acetal-protected, 3 examples). All chiral products described herein are enantiomercially pure.