THIODIV · Exploring thioalkynes potential in gold catalysis with a divergent reactivity manifold
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-10-21 → 2022-10-20
- EU contribution
- €224,934
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Exploring thioalkynes potential in gold catalysis with a divergent reactivity manifold
Gold catalyzed activation of alkynes has been used to rapidly establish a diverse portfolio of powerful new transformations. It can allow the rapid and efficient preparation of complex molecules from simple precursors in a way that can reduce the energy and raw material burden for the preparing of necessary organic molecules, such as those needed for the discovery of new and more effective pharmaceuticals to help address growing health needs of our increasing population. A challenge in gold catalyzed reaction of alkynes is controlling the side of the alkyne that reacts first, as this dictates the ultimate reaction outcome and what can be achieved. A powerful way to address this, especially for intermolecular reactions between two or more distinct molecules, is to use a heteroatom substituent. While the potential of oxygen and nitrogen groups here are well established, sulfur is much less well explored despite the well established value of sulfur containing molecules, whether in final targets or for further manipulation. Furthermore, the few examples of sulfur-based reactivity in the field indicate that the role of sulfur is much less inflexible than other heteroatoms, potentially giving rise to different outcomes form the same starting materials, but in a controllable manner. THIODIV aimed to explore the role of sulfur in activation of π-electron of alkynes through coordination with gold-catalyst and implement this idea in the development of unique synthetic transformations. THIODIV was aimed at using a unifying method that could be studied in different types of transformations t provide structural diversity from common starting materials. THIODIV would combine to provide insight into the role of sulfenyl groups in controlling gold mediated reaction outcomes and also illustrate their potential for developing enabling new synthetic methods by making effective new tools and understanding their applicability. .
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- THE UNIVERSITY OF BIRMINGHAM · BirminghamCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union