Cu-Catalyzed Diastereo- and Enantioselective Synthesis of Homopropargyl Amines Bearing All-Carbon Quaternary Stereocenters via Chirality Transfer of Hindered Allenylcopper Species

Abstract

The construction of congested acyclic stereocenters with high stereoselectivity is a significant challenge in synthetic chemistry. Herein, we report an efficient method for diastereo- and enantioselective C–C coupling of 1,3-disubstituted enynes with imines for the asymmetric construction of vicinal stereogenic centers, including an all-carbon quaternary center. This coupling was accomplished by chirality transfer from axial-to-central of fully substituted axially chiral allenylcopper intermediates formed in situ from branched enynes with concomitant diastereoselective formation of an additional stereocenter in imine addition enabled by a chiral C₁-symmetric N-heterocyclic carbene (NHC) copper catalyst. DFT calculations provided an enhanced understanding of the silyl effect of allenylcopper nucleophiles on reactivity and the origin of stereoselectivity. Synthetic versatility of the resulting products bearing densely functionalized groups could amplify the significance of the current method.