Intramolecular nucleophilic aromatic substitution (S(N)Ar) of preformed ruthenium cyclopentadienyl cationic peptidyl π-complexes forms cyclic biphenyl ethers in convenient, high-yielding reactions. The utility of the method was demonstrated by the efficient convergent total synthesis of two natural products, K-13 and OF4949-III. Several analogs of K-13 and OF4949-I-IV were synthesized in high yields, and one ring system that could not be prepared by a macrolactamization method was formed in high yield by biaryl ether formation from peptidyl ruthenium complexes. Direct comparisons between these two approaches are provided. Transition metal π-complexes of either N-protected or carboxyl-protected amino acids can be used as coupling partners in peptide coupling reactions. Preformed peptidyl ruthenium complexes can be used to synthesize cyclic biphenyl ethers in a combinatorial fashion.