Formation of substituted aromatic rings in amino acid systems via ruthenium activated SNAr reactions

Abstract

Numerous natural products contain biaryl ether linkages, a functionality that restricts conformational freedom. While there are many methods available to form biaryl ethers, the ruthenium activated reaction offers access to these systems under mild conditions. Previously we showed that cyclic biaryl ether-containing tripeptides K-13 and OF-4949III could be synthesized using a ruthenium activated intramolecular reaction for the macrocyclization step [1]. Here we report the expansion of the ruthenium activated methodology to intermolecular reactions of protected chloro-phenylalanines with heteroatom and carbon nucleophiles as well as intramolecular reactions utilizing the amino acids histidine, cystine, and lysine.