Exploring thioalkynes potential in gold catalysis with a divergent reactivity manifold

Project Information

THIODIV

Grant agreement ID: 898186

DOI

10.3030/898186

Project closed

EC signature date 28 February 2020

Start date 21 October 2020

End date 20 October 2022

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 224 933,76

EU contribution

€ 224 933,76

Coordinated by

THE UNIVERSITY OF BIRMINGHAM
United Kingdom

Periodic Reporting for period 1 - THIODIV (Exploring thioalkynes potential in gold catalysis with a divergent reactivity manifold)

Reporting period: 2020-10-21 to 2022-10-20

Summary of the context and overall objectives of the project

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. .

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

THIODIV sought to explore how sulfenyl groups can be used to exert control over catalytic processes based on alkynes and gold catalysis. The approach was planned to provide access into new chemical motifs as well as understanding of reactivity. In doing so it would underpin further advances in the field while delivering new methodology to enable synthetic chemistry of complex molecules.

THIODIV has developed effective new synthetic methods. Effective preparation of the desired reaction substrates, that had not previously been used, has been achieved in a way that allows for modification at different positions. Four new catalysis based methods have been developed in THIODIV and each has been studied in terms of reaction optimisation, substrate scope and applications of the catalysis products. As a result we understand which factors that affect reaction pathways, from structure to reaction conditions, and the ways in which we might use those methods via as a detailed exploration of the underpinning chemistry. Extensive optimization studies were run along with structure-reactivity and structure-scope studies. Mechanistic studies support the reactivity hypothesis. A particular advance is the ability take the same type of substrates and using different conditions access two different product outcomes which gives synthetic chemists significant control.

The project was impacted by the limitations associated with the overlapping period of lockdown and social distancing affecting the in-lab time and efficiency that could be achieved, but overall THIODIV has achieved its goals using the planned approach to deliver effective new methods, and to understand scope and limitations and impact of sulfenyl groups on gold catalysis.

Dissemination of the results is underway with two manuscripts in preparation that in due course will be advertised via social media and web-pages as well as in presentations by the host group. The fellow has given presentations at academic and industrial locations over the course of the project advertising the fellowship. Furthermore an outreach activity that the fellow was integral to a key part of, and which involves a secondary education institute, an international company and the host university is planned for separate publication.

Conclusions: The support from the MSC Fellowship has allowed the development of several new synthetic methodology's that provide tools and understanding to advance synthetic organic chemistry enabling those areas that depend on it. By enabling greater understanding, and more sustainable methods this work contributes to society's need for sustainable use of limited natural resources. Furthermore it has provided the fellow with the training needed to expand his skills and knowledge, in new areas of science to him as well as the allied transferable areas vital to being a future research leader. The postdoctoral fellow has secured a scientific position at a leading international company on the basis of his achievements and training in THOIDIV.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

THIODIV has led to the discovery and development of new synthetic methodology, with new chemical transformations that allow the preparation of densely functionalised and novel chemical structures in an efficient manner using gold catalysis. This approach has advanced the tools available to study alkynyl thioether chemistry, the understanding of how sulfenyl groups can be used to affect reactivity under gold catalysis, and tools to access desirable chemical motifs commonly encountered in pharmaceutical development and other areas that depend on organic synthesis. The efficiency of these new catalysis methods feeds into the wider societal need for sustainable chemical synthesis that continue to reduce the environmental impact of required synthesis. Along with the specific new methodologies developed in THIODIV, the study provides the underpinning knowledge to encourage further advanced, particularly in the fields of gold-catalysis utilising sulfenyl groups for controlling interactions.

summary scheme