Incorporation of Phosphole Moieties into the Side Chain of Tyrosine and Phenylalanine

A tyrosine derivative with a phosphole moiety covalently attached to the phenolic hydroxy group was successfully prepared through P-O bond-forming reaction, via a nucleophilic substitution reaction at the phosphorus, by slow addition of N-CBz-protected tyrosine methyl ester to a chlorophosphole adduct in the presence of triethylamine, albeit with a low yield. Furthermore, a phenylalanine derivative with a phosphole-containing side chain was conveniently synthesized by Stille cross-coupling reaction of a stannylphosphole reagent with N-Boc-protected 4-iodophenylalanine methyl ester, using Pd(dba)(2) as catalyst, in the absence of any additional ligand. These molecules must be seen as valuable building blocks for the preparation of metalloproteins of interest for chemical, biological, and medical applications.