Enantio‐ and Diastereoselective Synthesis of Chiral Tetrasubstituted α‐Amino Allenoates Bearing a Vicinal All‐Carbon Quaternary Stereocenter with Dual‐Copper‐Catalysis

Abstract

AbstractThe skeletons of chiral tetrasubstituted allenes bearing a vicinal all‐carbon quaternary stereocenter are of importance but still challenging to synthesize. Herein, we report enantio‐ and diastereoselective γ‐additions of 1‐alkynyl ketimines with dual‐copper‐catalysis under mild conditions, affording chiral tetrasubstituted α‐amino allenoates bearing a vicinal all‐carbon quaternary stereocenter in high yields (up to 99 % yield) with excellent enantioselectivities (up to 99 % ee) and diastereoselectivities (up to >20 : 1 dr). Importantly, the stereodivergent synthesis of the products was realized by the asymmetric γ‐addition reaction and the Grignard reagent promoted epimerization. Moreover, the dual‐copper‐catalyzed γ‐addition reactions were smoothly applied to a gram‐scale reaction and adopted to introduce chiral tetrasubstituted allenyl moieties into bioactive molecules. Mechanistic experiments and density functional theory (DFT) calculations demonstrated that the asymmetric γ‐addition reactions were catalyzed by double chiral copper catalysts.