Copper-Catalyzed Asymmetric Conjugate Addition of Dimethylzinc to Acyl-N-methylimidazole Michael Acceptors: a Powerful Synthetic Platform

An efficient copper‐catalyzed enantioselective conjugate addition of dimethylzinc to α,β‐ and α,β,γ,δ‐unsaturated 2‐acyl‐N‐methylimidazoles has been achieved using a chiral bidentate hydroxyalkyl‐NHC ligand. The reactions proceeded with both excellent regio‐ and enantioselectivity (14 examples, 87–95 % ee) to afford the desired 1,4‐adducts, which were easily transformed to the corresponding aldehydes, esters, and ketones. Subsequently, this powerful methodology was therefore successfully applied in the synthesis of natural products. Furthermore, an iterative process was also disclosed leading to highly desirable 1,3‐desoxypropionate skeletons (up to 94 % d.e.). Die enantioselektive konjugierte Addition von Dimethylzink an (mehrfach) ungesättigte 2‐Acyl‐N‐methylimidazole erfolgt unter Cu‐Katalyse mit sehr guter Regio‐ und Enantioselektivität (bis zu 95 % ee). Die erhaltenen 1,4‐Addukte können leicht zu den entsprechenden Aldehyden, Estern, Ketonen und Aminen umgesetzt werden. Die Methode wurde in der Synthese von 1,3‐Desoxypropionat‐Untereinheiten und Naturstoffen eingesetzt.