Central-to-Axial Chirality Conversion Approach Designed on Organocatalytic Enantioselective Povarov Cycloadditions: First Access to Configurationally Stable Indole-Quinoline Atropisomers.

The first stereoselective synthesis of enantioenriched axially chiral indole-quinoline systems is presented. The strategy takes advantage of an organocatalytic enantioselective Povarov cycloaddition of 3-alkenylindoles and N-arylimines, followed by an oxidative central-to-axial chirality conversion process, allowing for access to previously unreported axially chiral indole-quinoline biaryls. The methodology is also implemented for the design and the preparation of challenging compounds exhibiting two stereogenic axes. DFT calculations shed light on the stereoselectivity of the central-to-axial chirality conversion, showing unconventional behavior.