Synthesis of Indoline-Fused Macrocycles via Photocatalytic Dearomatization of Indoles

A visible-light-mediated intramolecular dearomative macrocyclization of indoles is described. Utilizing tertiary amines as radical precursors and 4CzIPN as an organic photocatalyst, this protocol facilitates the construction of 11- to 20-membered indoline-fused macrocycles. The reaction scope encompasses various linkers, including those derived from amino acids, and extends to benzothiophene and benzofuran derivatives. X-ray crystallographic analysis confirmed a trans -diastereoselective outcome for the 2,3-disubstituted indoline core. Mechanistic studies suggest a radical-mediated pathway initiated by single-electron transfer (SET). Preliminary biological evaluation identified representative macrocycles with antiproliferative activity against human cancer cell lines, with IC 50 values ranging from 5.3 to 6.6 μM.