Multicomponent Photocatalytic a-Tertiary Amine Synthesis
Lead Research Organisation:
University of Cambridge
Department Name: Chemistry
Abstract
Year 1: Generic training activities for all first-year student members of the CDT.
Year 2-4: This project investigates the development of a multicomponent protocol to access a-tertiary amines in protected form from abundant chemical feedstocks, using visible light mediated photoredox catalysis. The optimised reaction conditions consistently form the model product in 91% assay yield, and the desired N-primary a-tertiary amines are easily accessed from the a-tertiary imine reaction products by hydrolysis or hydrogenation. The scope in both ketone and alkene components will be studied, in addition to the reaction mechanism. Towards elucidation of the reaction mechanism, key reaction intermediates will be isolated, enabling investigation of their reactivity, photochemical and photophysical properties. Discussion of the reaction mechanism will be backed up by computational analysis. Although the mechanistic data collected to date are inconclusive, a number of hypotheses have been ruled out, providing a good starting point for future mechanistic studies.
Year 2-4: This project investigates the development of a multicomponent protocol to access a-tertiary amines in protected form from abundant chemical feedstocks, using visible light mediated photoredox catalysis. The optimised reaction conditions consistently form the model product in 91% assay yield, and the desired N-primary a-tertiary amines are easily accessed from the a-tertiary imine reaction products by hydrolysis or hydrogenation. The scope in both ketone and alkene components will be studied, in addition to the reaction mechanism. Towards elucidation of the reaction mechanism, key reaction intermediates will be isolated, enabling investigation of their reactivity, photochemical and photophysical properties. Discussion of the reaction mechanism will be backed up by computational analysis. Although the mechanistic data collected to date are inconclusive, a number of hypotheses have been ruled out, providing a good starting point for future mechanistic studies.
Planned Impact
Who might benefit from this research? How might they benefit from this research?
Students
(a) The major beneficiaries of the CDT will, of course, be the students that train on the program. They will be equipped with a set of skills that will be highly desirable in the organic molecule making industries. Although the proposal is directing towards a need in the pharmaceutical industry, the training and research skills are totally transferable to industries like the argochemical sector (this is an almost seamless transition as the nature of the needs are near identical to that of pharma) but also the fine chemicals industries, CRO's who serve all of these industries. With some adaptation of the skills accrued then the students will also be able to apply their knowledge to problems in the materials industries, like polymers, organic electronics and chemical biology.
(b) Synthesis will also be evolving in academia and students equipped with skills in digital molecular technologies will be at a significant advantage in being apply to implement the skills acquired while training on the CDT. These students could be the rising stars of academia in 10 years time.
(c) The non-research based training will benefit the students by providing a set of transferable skills that will see them thrive in any chosen career.
(d) The industry contacts that will be generated from the variety of interactions planned in the CDT will give students both experience and insight into the machinations of the industrial sector, helping them to gain a different training experience (form industry taught courses) and hands on experience in industrial laboratories.
(e) All student in UCAM will be able to benefit in some way form the CDT. Training courses will not be restricted to CDT students (only courses that require payment will be CDT only, and even then, we will endeavour to make additional places available for non-CDT students). The overall standard of training for all students wil be raised by a CDT, meaning that benefit will be realised across the students of the associated departments. In additional, non CDT students can also be inspired by the research of the CDT and can immerse new techniques into their own groups.
Academic researchers in related fields (PIs)
(a) new research knowledge that results from this program will benefit PIs in UCAM and across the academic community. All research will be pre-competitive, with any commercial interests managed by Cambridge Enterprise
(b) a change in mnidset of how synthetic research is carried out
(c) new collaborations will be generated withing UCAM, but also externally on a national and international level.
(d) better, more closely aligned, interactions with industry as a result of knowledge transfer
(e) access to outstanding students
Broader public
(a) in principle, more potential medicines could be made available by the research of this CDT.
Economy
(a) a new highly skilled workforce literate in disciplines essential to industry needs will be available
(b) higher productivity in industry, faster access to new medicines
(c) spin out opportunities will create jobs and will stimulate the economy
(d) automation will not remove the need for skilled people, it will allow the researchers to think of solutions to the problems we dont yet understand leading to us being able to discover solutions faster
Students
(a) The major beneficiaries of the CDT will, of course, be the students that train on the program. They will be equipped with a set of skills that will be highly desirable in the organic molecule making industries. Although the proposal is directing towards a need in the pharmaceutical industry, the training and research skills are totally transferable to industries like the argochemical sector (this is an almost seamless transition as the nature of the needs are near identical to that of pharma) but also the fine chemicals industries, CRO's who serve all of these industries. With some adaptation of the skills accrued then the students will also be able to apply their knowledge to problems in the materials industries, like polymers, organic electronics and chemical biology.
(b) Synthesis will also be evolving in academia and students equipped with skills in digital molecular technologies will be at a significant advantage in being apply to implement the skills acquired while training on the CDT. These students could be the rising stars of academia in 10 years time.
(c) The non-research based training will benefit the students by providing a set of transferable skills that will see them thrive in any chosen career.
(d) The industry contacts that will be generated from the variety of interactions planned in the CDT will give students both experience and insight into the machinations of the industrial sector, helping them to gain a different training experience (form industry taught courses) and hands on experience in industrial laboratories.
(e) All student in UCAM will be able to benefit in some way form the CDT. Training courses will not be restricted to CDT students (only courses that require payment will be CDT only, and even then, we will endeavour to make additional places available for non-CDT students). The overall standard of training for all students wil be raised by a CDT, meaning that benefit will be realised across the students of the associated departments. In additional, non CDT students can also be inspired by the research of the CDT and can immerse new techniques into their own groups.
Academic researchers in related fields (PIs)
(a) new research knowledge that results from this program will benefit PIs in UCAM and across the academic community. All research will be pre-competitive, with any commercial interests managed by Cambridge Enterprise
(b) a change in mnidset of how synthetic research is carried out
(c) new collaborations will be generated withing UCAM, but also externally on a national and international level.
(d) better, more closely aligned, interactions with industry as a result of knowledge transfer
(e) access to outstanding students
Broader public
(a) in principle, more potential medicines could be made available by the research of this CDT.
Economy
(a) a new highly skilled workforce literate in disciplines essential to industry needs will be available
(b) higher productivity in industry, faster access to new medicines
(c) spin out opportunities will create jobs and will stimulate the economy
(d) automation will not remove the need for skilled people, it will allow the researchers to think of solutions to the problems we dont yet understand leading to us being able to discover solutions faster
Organisations
People |
ORCID iD |
| Matthew Gaunt (Primary Supervisor) | |
| Milo Smith (Student) |
Publications
Henry Blackwell J
(2021)
Modular Photocatalytic Synthesis of a-Trialkyl-a-Tertiary Amines.
in Journal of the American Chemical Society
Kohara K
(2021)
Thiol-Mediated a-Amino Radical Formation via Visible-Light-Activated Ion-Pair Charge-Transfer Complexes
in Journal of the American Chemical Society
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/S024220/1 | 01/06/2019 | 30/11/2027 | |||
| 2276993 | Studentship | EP/S024220/1 | 01/10/2019 | 30/09/2023 | Milo Smith |
| Description | This award has resulted in two publications to date. The first (https://pubs.acs.org/doi/abs/10.1021/jacs.1c07402) describes a new method to prepare a type of biologically-relevant molecule which is challenging to synthesise by other methods. The strategy employs a modern form of catalysis which harnesses the power of visible light ('photoredox catalysis'). The report discloses a distinct advancement on the previous work of both the Gaunt group and the work of others the field. The second (https://pubs.acs.org/doi/abs/10.1021/jacs.1c09445) discloses a fundamental advance in our understanding of the interaction between two types of charged molecule (iminium cations and thiophenolate anions). Specifically, we show that thiophenolate anions undergo single electron transfer to iminium ions when irradiated with visible light. In the publication this new mechanism is applied to a new chemical reaction which enables the controlled union of three starting materials. This work forms the basis of further studies using the same mechanism to make other molecules of interest. Subsequent studies in this vein are underway. Other unpublished work associated to this award has contributed to the development of the Gaunt group's high-throughput experimentation platform. Specifically, studies were conducted in the use of palladium catalysis in the presence of visible light irradiation in 384-well plate format. New methods were developed for the set-up and analysis of reactions of this type, which have informed further studies in the Gaunt laboratory. |
| Exploitation Route | The results disclosed in the publications may form the basis for future studies both within the Gaunt group and by other groups. The results relating to high-throughput experimentation have contributed internally to the development of the Gaunt group's high-throughput experimentation platform, the results of which will be published in peer-reviewed journals in due course. |
| Sectors | Chemicals,Pharmaceuticals and Medical Biotechnology |
| URL | https://pubs.acs.org/doi/abs/10.1021/jacs.1c07402 |