Research led by Dr Christopher Jones, Senior Lecturer at the School of Biological and Chemical Sciences has led to the first reporting of transition metal-free intramolecular hydride transfer onto arynes.
The research has been reported in the journal Chemical Science and features alongside artwork created by MSci student Lilla Gombos and postdoctoral research associate Piera Trinchera.
Nitrogen-containing ring systems (‘heterocycles’) are vital to drug discovery and agrochemical development but are often difficult to make. In order to synthesize more advanced heterocycles for these industries, it is highly desirable to attach chemical groups with different properties to the ring (i.e. ‘functionalise’), ideally by selectively substituting at a carbon-hydrogen (C-H) bond on the heterocycle. Breaking a particular C-H bond and substituting that hydrogen with another atom means valuable compounds can be made directly from cheap and more environmentally benign starting materials, offering direct benefits (reduced cost, waste, time) relative to traditional multi-step synthetic methods.
However, this process is challenging (the C-H bond is strong) and most progress has been made using metal catalysts that can be expensive and sometimes toxic. Dr Jones’ work exploits the high level of reactivity of organic molecules called arynes, for the first time, to selectively manipulate C-H bonds in nitrogen heterocycles without having to use metals. The reaction operates via a novel mechanism that enables a range of carbon-based molecules – rarely seen in C-H functionalisation chemistry due to their relative lack of reactivity – to be joined to the heterocycle in a single and operationally simple step.
To learn more about the research, you can read the full publication here.