Mild and Nonracemizing Conditions for Ullmann-type Diaryl Ether Formation between Aryl Iodides and Tyrosine Derivatives

Abstract

CuI/N,N-dimethylglycine-catalyzed coupling reaction of L-tyrosine derivatives and L-phenylalanine-derived iodides in the presence of Cs2CO3 works at 90 degrees C to provide the corresponding diaryl ether. Partial racemization occurs when N-Boc- and N-Cbz-protected aromatic amino esters are used, while N-trityl- and N,N-dibenzyl-protected aromatic amino esters give rise to coupling products without loss of optical purity. Little racemization is also observed in cases of N-Boc- and N-Cbz-protected aromatic amino acids as substrates. But their reaction yields are moderate. On the basis of these studies, shorter protocols for assembling (S,S)-isodityrosine and K-13 are developed.