A flexible synthesis of indoline, indolizidine, and pyrrolizidine derivatives

New and flexible procedures for the synthesis of indoline, indolizidine, and pyrrolizidine derivatives are described. By these new procedures, the target compounds can be synthesized with high diversity from three building blocks (orthobromo- or ortho-chloro-iodobenzenes, terminal alkynes, and primary amines). The synthetic strategies presented include Sonogashira couplings, Cp2TiMe2-catalyzed hydroaminations of alkynes, and Pd-catalyzed aminations of aryl halides as key steps. Since many of the employed starting materials are commercially available or easily accessible, a huge number of indoline, indolizidine, and pyrrolizidine derivatives is theoretically obtainable by the standard reaction sequences developed. Since the experimental procedures are simple and mostly catalytic, applications of the described methods for automated synthesis are also imaginable. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).