Chiral phosphoric acid-catalyzed atroposelective iodination of N-arylindoles

Axially chiral indoles have garnered significant attention due to their synthetic and biological importance. However, atroposelective halogenation of this scaffold has been rarely explored. This study presents a catalytic and enantioselective iodination of N-arylindoles, achieving precise control over the C−N stereogenic axis. The reaction is facilitated by a chiral phosphoric acid, which promotes iodination at the C-3 position of N-arylindole, followed by iodine migration and deprotonation. A hydrogen-bonding donor on the aromatic ring plays a key role in achieving high enantioselectivities. Under optimized reaction conditions, a wide range of substrates are well-tolerated, and subsequent reactions with various carbonyl electrophiles maintain enantioselectivity. Computational studies provide insights into the origin of enantioselectivity at the plausible enantiodetermining step. (Figure presented.)