THIODIV brings together the complementary expertise of Dr Nagnath More (NM, expertise in oxidative reactions and arylation processes) with Dr Paul Davies (Host, expertise in gold catalysis and sulfur-based reaction development).
Gold catalysis attract significant international interest due to its ability to generate metal carbene character from alkynes delivering more sustainable synthesis. Current strategies to address the major challenge of site-selective carbene formation use terminal alkynes, or those with strongly electron-donating- or electron-withdrawing groups. Limitations derive from the gold carbenes environment and its impact on reactivity, or the incorporation of undesired directing groups. THIODIV will study the potential of sulfur-substitution to deliver complementary directing effects while introducing a desirable functional group into the resulting molecule. Preliminary studies show that sulfur can enable gold-catalysed reactivity, yet propose different directing-modes which lead to different regiocontrol. The overall aim of THIODIV is to examine the role of sulfur substitution on alkynes in gold catalysis and clarify its influence on reactivity, and hence allow wider application of sulfur-directing groups in gold catalysis and synthesis more widely.
A diversity-generating dynamic reaction manifold will be used to elucidate key control parameters by studying two approaches, an oxidative rearrangement, and an arylative rearrangement. Alongside insight into reaction control and directing effects, THIODIV will provide new and efficient access to motifs that are featured in numerous bioactive compounds and are highly desirable in industry and academia as synthetic intermediates. While addressing fundamental questions of reactivity and control, THIODIV will also equip NM with the skills to incorporate hit- and lead-like properties into structure-reactivity studies to deliver new molecular entities that are applicable in pharmaceutical discovery.
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