Negishi cross-coupling reactions of α-amino acid-derived organozinc reagents and aromatic bromides

The Negishi cross-coupling reaction of organozinc iodides derived from α-amino acids with aromatic bromides to give substituted phenylalanine derivatives is described, using either Pd(OAc)2 or Pd2(dba)3 in combination with P(o-Tol)3 as catalyst in DMF at 50 °C. Similar results are obtained using Pd[PtBu3]2 as catalyst. The difference in reactivity displayed between aryl iodides and bromides (ArI>ArBr) has been utilised in a short synthesis of an unsymmetrical, orthogonally protected para-phenylene bis-alanine derivative.