Catalytic asymmetric synthesis of bis-armed aromatic amino acid derivatives. Problems related to the synthesis of enantiomerically pure bis-methyl ester of the (S,S)-pyridine-2,6-diyl bis-alanine

Abstract

(S,S)-Pyridine-2,6-diyl bis-alanines 8 and 9 carrying protecting groups suitable for peptidc synthesis have been syntnesised from 2.6-pyridinedicarbaldenyde by the phosphonoglycine condensation route followed by catalytic hydrogenation with Rh{(COD)[(R,R)-DIPAMP]}BF4. The alternative route via double Heck coupling of 2,6-dibromopyndmc and benzyl Boc-amidoacry late was unsuccessful although mono-coupling could be achieved. The reasons for this failure are discussed as well as the failure of two mono-armed didehydroamino acid derivatives to undergo hydrogenation with Rh bisphosphme catalysts. The CuCl2 and RhCl3 complexes of the bis-amino derivative 9 were prepared: a 20% e.e. was achieved in the cyclopropanation of styrene with ethyl diazoacetate using the Cu(II)-complex as a catalyst. © Acta Chemica Scandinavica 1996.