Synthesis of novel amino acids and dehydroamino acids containing the benzo[b]thiophene moiety

Several novel amino acids and dehydroamino acids containing the benzo[b]thiophene moiety were prepared by Michael addition or sequential Michael addition and palladium-catalyzed C-C or C-N cross couplings. The substrates for Michael addition were the methyl esters of N,N-bis(tert-butyloxycarbonyl)dehydroalanine [Boc(2)-DeltaAla-OMe] and N(4-toluenesulfonyl)-N-(tert-butyloxycarbonyl)dehydroala-nine [Tos-DeltaAla(N-Boc)-OMe], and the nucleophiles were aromatic thiols and 3-iodobenzylamine. The addition of mercaptobenzo[b]thiophenes directly to Tos-DeltaAla(N-Boc)-OMe gave stereoselectively, in good yields, the E-isomer of the corresponding dehydrocysteine. When thiophenols and 3-iodobenzylamine were used as nucleophiles the presence of an additional function (halogen or amine) allowed a subsequent palladium-catalyzed cross-coupling reaction with functionalized benzo[b]thiophenes (boronic acids, a halogen or an amine). Using this strategy, several racemic amino acid and dehydroamino acid derivatives, which are linked to the benzo[b]thiophene moiety by an aromatic spacer, were obtained in good yields. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).