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( 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
Author(s) -
Amberg Willi,
Seebach Dieter
Publication year - 1990
Publication title -
chemische berichte
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 0009-2940
DOI - 10.1002/cber.19901231225
Subject(s) - chemistry , aldol reaction , adduct , acetal , hydrolysis , double bond , medicinal chemistry , nuclear magnetic resonance spectroscopy , stereochemistry , organic chemistry , catalysis
( 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 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 (R 2 CuLi/F 3 BOEt 2 ) 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.