Rapid Synthesis of Chiral Figure‐Eight Macrocycles Using a Preorganized Natural Product‐Based Scaffold

Abstract

Chiral D2‐symmetric figure‐eight shaped macrocycles are promising scaffolds for amplifying the chiroptical properties of π‐conjugated systems. By harnessing the inherent and adaptable conformational dynamics of a chiral C2‐symmetric bispyrrolidinoindoline (BPI) manifold, we developed an enantio‐divergent modular synthetic platform to rapidly generate a diverse range of chiral macrocycles, spanning from 14‐ to 66‐membered rings, eliminating the need for optical resolution. Notably, a 32‐membered figure‐eight macrocycle showed excellent circularly polarized luminescence (CPL: |glum| = 1.1×10−2) complemented by a robust emission quantum yield (Φfl = 0.74), to achieve outstanding CPL brightness (BCPL: ε×Φfl×|glum|/2 = 480). Using quadruple Sonogashira couplings, this versatile synthetic platform enables precise adjustments of the angle, distance, and length among intersecting π‐conjugated chromophores. Our synthetic strategy offers a streamlined and systematic approach to significantly enhance BCPL values for a variety of chiral D2‐symmetric figure‐eight macrocycles.