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.

Publications

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Henry Blackwell J (2021) Modular Photocatalytic Synthesis of a-Trialkyl-a-Tertiary Amines. in Journal of the American Chemical Society

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S024220/1 31/05/2019 30/11/2027
2276993 Studentship EP/S024220/1 30/09/2019 29/09/2023 Milo Alexander 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