Sonogashira Cross‐Couplings of Dehydroamino Acid Derivatives and Phenylacetylenes

Several phenylacetylenes were coupled under Sonogashira cross‐coupling conditions with the methyl esters of N ‐( tert ‐butoxycarbonyl)‐( E )‐β‐bromo‐ or ‐β,β‐dibromodehydroalanine, to give β‐substituted or β,β‐disubstituted dehydroalanines, respectively. The β‐substituted dehydroalanines were obtained in good to high yields (60−90%) under the usual Sonogashira conditions (1 equiv. of the phenylacetylene, 1 mol % of [Pd(PPh 3 ) 4 ], 2 mol % of CuI, 18 equiv. of NEt 3 in acetonitrile, 24 h at room temp.), with retention of stereochemistry. The β,β‐disubstituted dehydroalanines were, in turn, obtained in moderate to good yields (44−63%) under modified Sonogashira conditions (4 equiv. of the phenylacetylene,10 mol % of [PdCl 2 (PPh 3 ) 2 ], 20 mol % of CuI, 1.4 equiv. of Cs 2 CO 3 in acetonitrile, 2 h at reflux). In the latter reactions, some phenylacetylene dimer and the ( E ) isomer of the monosubstituted coupled products were also isolated to some extent. The Sonogashira products obtained from the 4‐bromophenylacetylene were allowed to react with functionalized benzo[ b ]thiophenes under C−C or C−N palladium‐catalyzed cross‐coupling conditions. Preliminary fluorescence studies were performed for mono‐ and disubstituted (4‐aminophenyl)acetylenic dehydroamino acids and for the benzo[ b ]thiophene derivatives. The results showed that some of the dehydroalanines prepared can be used as fluorescent probes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)