A rhodium-catalysed Sonogashira-type coupling exploiting C–S functionalisation: orthogonality with palladium-catalysed variants

This report concerns the development of an efficient Sonogashira-type coupling of arylmethylsulfides and terminal alkynes to generate aryl alkyne motifs. Orthogonal reactivity between traditional Pd catalysts, and the Rh catalysts employed, results in the ability to selectively activate either the C–S bond or C–X bond through catalyst choice. The Rh–bisphosphine catalyst has further been shown to be able to effect a hydroacylation-Sonogashira tandem sequence, and in combination with further onward reactions has been used in the synthesis of heterocycles and polycyclic systems

Carbon-carbon bond formation via rhodium-catalysed C-S activation processes

In the following thesis, new methodologies towards harnessing C-S activation processes are documented. These methods utilise rhodium catalysis and are focused on the activation of aryl methyl sulfides. Chapter 1 provides an overview of the development of metal-catalysed C-S activation chemistry, with a focus on the catalytic systems, reagents and starting materials used to facilitate various C-C bond forming transformations. Chapter 2 describes a novel rhodium-catalysed cross-coupling reaction of aryl and alkyl terminal alkynes with simple aryl sulfides. This resulted in a Sonogashira-type transformation which exhibited orthogonality with traditional palladium catalysed Sonogashira chemistry. Chapter 3 documents a new catalytic system which allowed for the practical and efficient alkyne carbothiolation reactions of ketone-baring methyl sulfides. The carbothiolation products can be conveniently utilised in a one-pot three-component reaction to form highly substituted isoquinolines. Chapter 4 discusses the potential for future work. Chapter 5 presents the experimental data

Activating Group Recycling in Action: A Rhodium-Catalyzed Carbothiolation Route to Substituted Isoquinolines

A new rhodium(I) catalyst allows practical and efficient alkyne carbothiolation reactions to be achieved on synthetically useful ketone-bearing aryl methyl sulfides. The carbothiolation adducts, featuring a ‘recycled methyl sulfide’ activating group, are convenient precursors to highly substituted isoquinolines