Indole radicals in organic synthesis
The generation and subsequent reactions of radicals formed from aryl halides is now well documented and several natural product syntheses based on aryl radical cyclisation have been reported. However, little work has been published on the generation of radicals in heteroaromatic systems such as indole. Radical reactions, particularly those involving aryl and indole radicals are reviewed. The generation of 2-indolyl radicals and their addition to a variety of radical acceptors to prepare 2-substituted indoles is presented. The addition to aromatic solvent is also reported as an alternative route to the palladium catalysed cross-coupling method for the synthesis of 2-arylindoles. Annulation of indole via indole radicals is also explored. A short synthesis of fused [1,2-a]indoles via radical addition to the benzene ring followed by rearomatisation is described. One example undergoes an unusual radical translocation/addition reaction. The mitomycin skeleton and the mode of biological action of mitomycin are briefly discussed. A new synthetic strategy is described involving a translocation/cyclisation of N-substituted 2-indolyl radicals. An attempted asymmetric synthesis of aziridinomitosenes is described. An investigation of indole C2-C3 radical cyclisation as a route to cyc1opentano[b ]indole alkaloids is described. The effects of substituents on the radical acceptor are explored. Full experimental and spectroscopy data is given for all new and key intermediary compounds.