α‐Alkylierung von β‐Hydroxycarbonsäuren über 1,3‐Dioxan‐4‐on‐Enolate

Abstract

Highly Diastereoselective α‐Alkylation of β‐Hydroxycarboxylic Acids Through Lithium Enolates of 1,3‐Dioxan‐4‐onesFrom serine, β‐hydroxyisobutyric acid (‘Roche’ acid) and β‐hydroxybutyric acid, the dioxanones 1–6 were prepared. The generation of the enolates of type I with LDA at −75° and alkylation gave products with trans‐configuration whereas protonation of the 5‐methyl‐substituted enolate allowed access to the cis‐configurated β‐hydroxybutyric‐acid derivative 12. Hydrolysis gave the free β‐hydroxy acids of ‘syn’‐and ‘anti’‐configuration. Alkylation of the 6‐unsubstituted dioxanones 1 and 3 yielded predominantly products resulting from attack in the cis‐position of the t‐Bu group. The ‘reactive’ conformation of the enolates involved is tentatively derived from the product configuration. The selectivity of the alkylation is also discussed in terms of the results of an ab‐initio calculation on the enolates M–P.