Copper(II)-Mediated Oxidative Coupling Routes to Nitrogen- Heterocycles

Nitrogen-containing heterocycles have attracted considerable attention owing to their prevalence in numerous natural substances as well as their extensive applications in biology and pharmacology. In recent years, great efforts have been devoted to the elaboration of novel synthetic methodologies for the construction of N-heterocycles such as oxindoles and indoles. Reported in 2009 by the Taylor group, access to oxindole scaffolds has been successfully demonstrated via a copper(II)-mediated oxidative coupling approach. Following the same principle, the extension of this method to the formation of the more intricate bis-oxindole skeleton is demonstrated via the double cyclisation of bis-anilides using Cu(OAc)2·H2O as oxidant. The scope of the copper(II)-mediated cyclisation to the formation of 3H-indoles and 1H-indoles from N-aryl enamines is also described.Progress towards the total synthesis of the highly complex spirooxindole alkaloid natural product rankinidine is presented. Towards this end, the application of the copper(II)-mediated cyclisation for the formation of the oxindole core of rankinidine is presented.