Ligand-Exchange-Enabled Axially Chiral Recognition in Asymmetric Aminopalladation/Olefination of 2-Alkynylanilides

Chiral recognition for the synthesis of axially chiral biaryl units is a fundamental and challenging topic in organic synthesis. Herein, we documented that an efficient O-ligand exchange between the catalyst and substrate enabled axial chiral recognition in asymmetric aminopalladation/olefination of 2-alkynylanilides and vinyl trifluoromethanesulfonates, providing the axially chiral 3-alkenylindoles with up to 97% ee and 98% yield. This protocol features mild conditions, broad functional group tolerance, scalability, and late-stage modification of bioactive molecules. Experimental and computational studies hinted that O-ligand exchange between the (R)-BIDIME/Pd complex and the alkoxy group of 2-alkynylanilides was crucial to the success of stereoselectivity control.