Carla Obradors, PhD student under the supervision of Prof. Antonio M. Echavarren, has defended her PhD Thesis entitled “Dissecting Intermolecular Gold Catalysis: Application to the Total Synthesis of Rumphellaone A” (assigned to the Organic and Analytical Chemistry Department of the Universitat Rovira i Virgili) publicly on December 18th at the ICIQ auditorium.
The members of her evaluation committee were: Dr. Paul W. Davies (University of Birmingham), Prof. Ruben Martin (ICIQ) and Prof. Stefan F. Kirsch (Bergische Universität Wuppertal).
Gold-catalyzed intermolecular cycloadditions have proven to be challenging due to the selective activation in the presence of different functionalities. Moreover, the mechanistic proposals for such transformations were based on vage studies and analogies. We have recently developed the macrocyclization of large enynes via [2+2] cycloaddition as well as a cascade [2+2+2] reaction of an alkyne, an alkene and a carbonyl group. Furthermore, we performed a detailed mechanistic study of the [2+2+2] cycloaddition, which led to the discovery of digold structures outside the catalytic cycle. Thus, we designed a set of new catalysts bearing non-coordinating counterions in order to avoid the formation of such species. Improvements from 10 to 30% yield were achieved in most of the gold-catalyzed transformations performed. This effect was rationalized by studing the [2+2] cycloaddition of alkynes and alkenes. Finally, we started the total synthesis of Rumphellaone A using a retrosynthetic analysis based on the studies already mentioned. Attempts towards the enantioselective gold-catalyzed [2+2] cycloaddition have also been performed.