Metal-Catalyzed Derivatization of C-alpha-Tetrasubstituted Amino Acids and Their Use in the Synthesis of Cyclic Peptides

C-alpha-tetrasubstituted amino acids are important building blocks in the design and preparation of novel peptidomimetics. We report on the functionalization of the C-alpha-tetrasubstituted THF amino acid rac-5 by copper(I) catalyzed N-arylation reactions. The aryl bromide substituent of rac-5 is replaced by a variety of aliphatic and aromatic amines. Intramolecular N-arylation yielded only small amounts of a cyclic tripeptide 2, whereas cyclic tripeptide ethers 4 and 50 were obtained in an enantiomerically pure form from a palladium(0)-catalyzed intramolecular O-arylation.