(E,R,R)‐5‐Alkyliden‐2‐tert‐butyl‐6‐methyl‐1,3‐dioxan‐4‐one: Herstellung aus (R)‐3‐Hydroxybuttersäure, Cuprat‐Additionen und Hydrolysen zu 3‐Hydroxycarbonsäuren mit chiralen sekundären Alkylgruppen in 2‐Stellung

Abstract

(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‐PositionLi 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 β‐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 enantiomerically pure.