Pd-Catalyzed meta -C–H Arylation Using a Convertible Directing Group: Streamlined Construction of Biaryl Cores of Peptide Natural Products

C-H activation has emerged as a prominent frontier in natural product synthesis; however, the use of directing groups (DGs) to functionalize inert C-H bonds for the rapid assembly of complex natural products remains limited. Here, we combine the dual directing/transformable capability of the 2-methoxyiminoacetyl (MIA) group with a norbornene (NBE)-mediated regioselective meta-C-H arylation strategy to develop a concise three-step route to biaryl-based cyclic peptide scaffolds. This protocol sequentially comprises meta-C-H arylation, traceless DG conversion, and macrocyclization. Using this approach, core skeletons of meta-biaryl peptide natural products, including biphenomycin, RP-66453, and arylomycin, were efficiently constructed. This work demonstrates the first practical application of a convertible directing group (MIA) in complex natural product synthesis and provides a powerful "skeleton-editing" strategy for accessing biaryl cyclic peptide architectures.