(2R)‐5‐Alkyl‐2‐tert‐butyl‐6‐methyl‐4H ‐1,3‐dioxin‐4‐one als Zwischenprodukte zur Herstellung von α,β,β‐trisubstituierten β‐Hydroxycarbonsäuren unter Selbstregeneration des stereogenen Zentrums von (R)‐3‐Hydroxybuttersäure

Abstract

(2R)‐5‐Alkyl‐2‐tert‐butyl‐6‐methyl‐4H‐1,3‐dioxin‐4‐ones as Intermediates for the Preparation of α,β,β‐Trisubstituted β‐Hydroxycarboxylic Acids from (R)‐3‐Hydroxybutyric Acid under Self‐Regeneration of the Stereogenic CenterThe exocyclic double bonds of the readily available (2R,6R)‐5‐alkylidene‐2‐tert ‐butyl‐6‐methyl‐1,3‐dioxan‐4‐ones (preceding paper) are shifted to the endocyclic position by treatment with Pd‐C/H2 to give the dioxins 2 ‐ 6 in overall yields of 40‐ 60% (calcd. from the parent tert‐butyl‐methyl‐dioxanone, 4 steps). F3B ‐ OEt2‐mediated Me‐, Bu‐ and Ph‐cuprate additions to the tetrasubstituted double bonds of these dioxinones can be used to prepare the 2‐tert‐butyl‐5,6,6‐trialkyl‐1,3‐dioxanones 7 ‐ 15 (40‐65% yield, 5: 1 to 16: 1 diastereoselectivity) as single isomers. Hydrolysis leads to 5,6,6‐trialkyl hydroxy acids (for instance 16‐18) specified in the title; formally, these compounds are aldol‐type adducts of carboxylic acids to unsymmetrical ketones. — The configurational assignment rests upon NOE measurements and, in one case, upon a chemical correlation. The stereochemical course of the conjugate addition and of the Li enolate protonations, which are responsible for the selective formation of the two new stereogenic centers, is discussed.