Design and synthesis of new bidentate alkoxy-NHC ligands for enantioselective copper-catalyzed conjugate addition

A new family of chiral alkoxy-N-heterocyclic carbene (NHC) ligands has been designed for the enantioselective copper-catalyzed conjugate addition of dialkylzincs to enones. These new bidentate NHC ligands were synthesized in high overall yields using a five-step procedure starting from commercially available β-aminoalcohols. Influence of the temperature, base, solvent and copper source were studied in order to optimize the stereoselectivity of the addition. High reactivity and excellent enantioselectivity were obtained at ambient temperature with a range of cyclic enones and dialkylzinc. Addition to acyclic enones has also been studied.

Graphical abstractA new class of chiral alkoxy-NHC ligands readily accessible in a five-step procedure from β-aminoalcohols is described. A small library of these chelating NHCs has been achieved by a modular synthesis allowing the design of the structure backbone. High reactivity and enantioselectivity were obtained at room temperature in the copper-conjugate addition of dialkylzinc to cyclic enones.Figure optionsDownload full-size imageDownload as PowerPoint slide