An efficient copper-catalyzede nantioselective conjugate addition of dimethylzinc to unsaturated 2-acyl-N-methylimidazoles has been achieved using ac hiral bidentateh ydroxyalkyl-NHC ligand. Ther eactions proceed with excellent regioselectivity (1,4 vs. 1,6 and 1,8) in extended conjugateds ystems to affordt he 1,4-adducts in high enantioselectivities. This regioselectivity could be ascertained by DFT studies highlightingt he crucial role of the imidazole ring. Thanks to the development of efficient protocols to regenerate the unsaturated 2-acyl-N-methylimidazole moiety,a ni terative process has been developed ultimately leading to 3,5,7 all-syn or anti-anti polydeoxypropionate stereodiads.Scheme 5. Applicationo ft he ACA/post-functionalizations equence involving a,b-unsaturated 2-acyl-N-methylimidazole 1h to the synthesis of (+ +)-(S)-Florhydral .Scheme 6. Synthesis of unsaturated di-andt rienic2 -acyl-Nmethylimidazole subtrates 1i-n. Scheme 7. Substrate scope for the 1,4-regioselective ACAo f dimethylzinc to poly-unsaturated 2-acyl-N-methylimidazoles 1i-n catalyzed by L1/Cu(OTf) 2 .Scheme 12. Synthesis of anti,anti 3-(S),5-(R),7-(S)a cyl-N-methylimidazole 2p.

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.).