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Generation of Quaternary Stereocenters by Asymmetric Michael Reactions: Enamine Regiochemistry as Configuration Switch
Author(s) -
Kreidler Burkard,
Baro Angelika,
Frey Wolfgang,
Christoffers Jens
Publication year - 2005
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200401223
Subject(s) - stereocenter , regioselectivity , enamine , chemistry , enantiomer , stereochemistry , michael reaction , absolute configuration , lewis acids and bases , structural isomer , enantioselective synthesis , catalysis , organic chemistry
Regioselective enamine formation from cyclic β‐diketones 1 is obtained by the appropriate choice of activating agent: Brønsted acid catalyzed condensation gives endocyclic enamines 3 as the thermodynamically favored products. Activation with Lewis acid BF 3 ⋅ OEt 2 affords betaines 8 as intermediate products, which can be reacted with L ‐valine diethylamide ( 2 ) to preferentially furnish exocyclic enamines 4 as kinetic products. Derivatives with quaternary stereocenters were accessible from both isomeric enamines by using asymmetric, copper( II )‐catalyzed Michael reactions at ambient temperature. Both regioisomers afford the triketones 7 with the same constitution but bearing the opposite absolute configuration at the quaternary stereocenter. Thus, both enantiomers of the product are prepared by using the same chiral auxiliary derived from L ‐valine.