Palladium-Catalysed Syntheses of 3-Substituted Indoles and Hetero Analogues

Sammanfattning: 3-Substituted indoles and their analogues - hetero condensed pyrroles (hetero-indoles) - have been synthesised by two different palladium-catalysed reactions: a) A series of 2-silylated 3-substituted (hetero-)indoles have been prepared by palladium-catalysed coupling between o-iodo(het)arylamines and silyl substituted internal acetylenes. The outcome of the reaction was found to depend on the type of silyl substituent (tert-butyl dimethylsilyl or trimethylsilyl) employed. Tryptophan derivatives were obtained by desilylation of the corresponding 2-silylated indoles. Attempted desilylation of 2-silylated 3-hydroxymethyl-hetero-indoles resulted in a ring opening reaction of the pyrrole moiety. b) A series of 3-substituted (hetero-)indoles have been prepared by N-allylation of N-(tert-butoxycarbonyl)-o-iodo(het)arylamines, followed by palladium-catalysed ring closure in a one pot reaction. (Hetero-)indole-3-acetic acid derivatives and (thia-)indole-3-pyruvic acid oxime ethers were thus obtained by employment of ethyl 4-bromocrotonate and the oxime ethers of ethyl (E)-2-oxo-5-bromo-3-pentenoate as N-allylating agents, respectively. Racemic thia-tryptophans were obtained by reduction of the oxime ether function in the corresponding thia-indole-3-pyruvic acid oxime ethers. A novel method, involving treatment of the substrate with silica gel at low pressure, was discovered for the selective removal of N-BOC substituents (BOC=tert-butoxycarbonyl).