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.). The enantioselective conjugate addition of dimethylzinc to (poly)unsaturated 2‐acyl‐N‐methylimidazoles proceeds under Cu catalysis with excellent regio‐ and enantioselectivities (up to 95 % ee). The resulting 1,4‐adducts can be easily transformed to the corresponding aldehydes, esters, ketones, and amines. This methodology was successfully applied in the synthesis of 1,3‐desoxypropionate subunits and natural products.