Synthesis of β2-homophenylalanine derivatives by Negishi cross-coupling reactions

Three approaches to the synthesis of β2-homophenylalanine derivatives using Negishi cross-coupling reaction are reported. In the first two approaches, two protected α-iodomethyl-β-amino esters are each converted into the corresponding organozinc iodides, which then undergo Pd-catalysed cross-coupling with aromatic halides to give β2-homophenylalanine derivatives, and the X-ray crystal structure of one product is reported. Alternatively, Negishi cross-coupling of the zinc reagent derived from N-benzyl 3-iodomethyl azetidin-2-one and aryl halides gave 3-benzylazetidin-2-ones, masked β2-homophenylalanine derivatives. The X-ray crystal structure of 1-benzyl-3-[(p-toluenesulfonyloxy)-methyl]-azetidin-2-one confirms the structural assignment.