ASPECTS OF THE PALLADIUM-CATALYZED COUPLING BETWEEN ARYL HALIDES AND 2-AMIDOACRYLATES

The effect of using different salts, bases, catalysts and solvents as well as protecting groups in 2-amidoacrylate derivatives (olefin component) in the Heck coupling with iodobenzene has been studied. Salt effects, resulting in increased yields, were observed in combination with either NaHCO3 or triethylamine as the base. Pd(OAc)2, PdCl2, Pd/C and hydrogen-activated Pd black could all be used as catalyst with similar results. The best solvents were DMF or acetonitrile. Olefins 1a and 1c, both carrying orthogonal protecting groups, show the most potential for further applications in peptide synthesis. 1,2-Diiodobenzene and 1,8-diiodonaphthalene did not give any coupling products and 1-bromo-2-iodobenzene gave only mono-coupling in mosest yield. In fact, small amounts of either 1,2-diiodobenzene or 1,8-diiodonaphthalene inhibited the coupling in other, normally reactive, cases. In experiments stoichiometric in Pd(OAc)2, it was found that an indolecarboxylic acid derivative was formed from iodobenzene, 2-bromoiodobenzene and 1,2-diiodobenzene, suggesting that ortho-palladation of a phenyl didehydroalanine derivative is involved.