Au(I)- and Pd(II)-NHC catalysis : novel approaches towards the synthesis of fluoroarenes/alkenes and ketone derivatives

Abstract

The preparation of organic molecules utilising synthetically simple and economical strategies is nowadays a big field of study in chemistry. As part of this exciting area of study, this thesis presents a group of new methodologies involving the transformation of simple organic compounds into valuable fluorinated molecules (fluoroarenes and fluoroalkenes) or ketone derivatives. These competitive alternatives to traditional methods exploit the use of transition metal-NHC catalysts (NHC = Nheterocyclic carbene), with particular interest in Au(I) complexes. The exploration of the use of arylsulfonic acids as substrates for the preparation of fluoroarenes was investigated for the first time. Our studies have obtained the first experimental proof of the fluorination of such substrates through either C-S or C-H activation. Preliminary optimisation and mechanistic studies for these reactions have been conducted, obtaining important information that is currenly being used by our research group to further unravel the synthetic value of arylsulfonic acids for aromatic C(sp2)-F bond formation. The use of terminal alkynes as substrates for the synthesis of complex organic molecules has also been exploited. Five new reactions and six sequential methods have been optimised. First, a new Au-catalysed protocol for the iodination of terminal alkynes was reported. This was followed by the individual study on two addition reactions (hydrofluorination and hydration), leading to new synthetic approaches to iodinated fluoroalkenes and ketones, respectively. Finally, these derivatives were further functionalised using coupling chemistry promoted by Pd(II)-NHC catalysts, accessing trisubstituted fluoroalkenes and functionalised ketones. All these reactions were compatible with sequential applications after minor changes, providing fast and easy functionalisation techniques that avoid the isolation of any intermediate, and maintain high performance and selectivity. These methods emphasise the highly convenient use of TM-NHC catalysts as versatile tools for organic synthesis.