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

Three approaches to the synthesis of beta(2)-homophenylalanine derivatives using Negishi cross-coupling reaction are reported. In the first two approaches, two protected alpha-iodoniethyl-beta-amino esters are each converted into the corresponding organozinc iodides, which then undergo Pd-catalysed cross-coupling with aromatic halides to give beta(2)-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 beta(2)-homophenylalanine derivatives. The X-ray crystal structure of 1-benzyl-3-[(p-tolunesulfonyloxy)methyl]-azetidin-2-one confirms the Structural assignment. (c) 2008 Elsevier Ltd. All rights reserved.