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(2 R )‐5‐Alkyl‐2‐ tert ‐butyl‐6‐methyl‐4 H ‐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
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.19901231226
Subject(s) - chemistry , stereocenter , adduct , stereochemistry , alkyl , aldol reaction , hydrolysis , double bond , yield (engineering) , medicinal chemistry , enantioselective synthesis , organic chemistry , catalysis , materials science , metallurgy
(2 R )‐5‐Alkyl‐2‐ tert ‐butyl‐6‐methyl‐4 H ‐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 Center The exocyclic double bonds of the readily available (2 R ,6 R )‐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/H 2 to give the dioxins 2 ‐ 6 in overall yields of 40‐ 60% (calcd. from the parent tert‐butyl‐methyl‐dioxanone, 4 steps). F 3 B ‐ OEt 2 ‐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.