Generation of quaternary stereocenters by asymmetric Michael reactions: enamine regiochemistry as configuration switch.
Regioselective enamine formation from cyclic beta-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.
Kreidler
Burkard
B
Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
Baro
Angelika
A
Frey
Wolfgang
W
Christoffers
Jens
J