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.