Modular, Scalable Total Synthesis of Lapparbin with a Noncanonical Biaryl Linkage

We report the development of a novel synthetic approach for the highly strained atrop‐Tyr C‐6‐to‐Trp N‐1′ linkage, which can be executed on a decagram scale using a modular strategy involving palladium‐catalyzed C−H arylation followed by Larock macrocyclization. The first total synthesis of lapparbin ( 1 ) was achieved by applying this synthetic strategy. Furthermore, the modular synthesis utilizing C−H arylation and Larock macrocyclization, discovered in the total synthesis of lapparbin ( 1 ), was demonstrated to be applicable to various arbitrary biaryl linkages, including non‐natural types.