Generation of Quaternary Stereocenters by Asymmetric Michael Reactions: Enamine Regiochemistry as Configuration Switch

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.