The development of a method for rhodium-catalyzed olefin aziridination and its application to synthesis of the welwitindolinones

The development of a method for the aziridination of alkenes with Rh(II) dimer catalysts is described. Olefin aziridination is a powerful means of introducing amine functionality into organic substrates, but has only recently found use in organic synthesis. The method described enables the efficient catalytic synthesis of a variety of aziridine products using a novel nitrogen source, 2,2,2-trichloroethylsulfamate (TcesNH2). The utility of these products is displayed through ring-opening reactions of bicyclic aziridines and trichloroethoxysulfonyl (Tces)-protected aziridines. A new application of oxidative aziridine ring opening with Me2SO generates protected alpha-amino ketone products from Tces-aziridines.; The welwitindolinone family of natural products is a recently discovered class of oxindole-derived structures that shows activity against multi-drug resistant cancer cell lines. The successful syntheses of welwitindolinones C and D have evaded the efforts of synthetic chemists to date. The Rh(II)-catalyzed olefin aziridination and subsequent oxidative ring-opening reactions are methods central to an original approach to the preparation of these two compounds. The assembly of advanced intermediates toward welwitindolinones C and D is described, guided by a macrocyclization strategy to assemble their core structures. Alternative strategies to these natural productsare also discussed, along with a new method for the reductive ring opening of acylated oxathiazinane heterocycles to generate protected amine derivatives.