Synthetic Photochemistry of Carbanion Equivalents

Lead Research Organisation: University of Bristol
Department Name: Chemistry

Abstract

The synthetic photochemistry of many lithiated species is unresearched and undiscovered. Previously in the Clayden group, it was realised that lithiated benzamides may undergo an electrocyclic ring-closing to dearomatize an aromatic ring, giving a conjugated lithium enolate. This enolate then underwent a series of photochemical transformations which gave an overall formation of a cycloheptatriene substrate from a chiral or achiral benzyl benzamide, which is a rather striking transformation considering the use of the simplistic reagents. However, this work was halted since the inefficient tungsten lamps irradiated much unwanted heat, which degraded the sensitive lithiated enolate intermediates. Modern LEDs are much more efficient and affordable and do not produce this unwanted heat radiation. As a result, the group has shown this chemistry can be carried out in good yields and high enantioselectivity (where a chiral centre is present).

Now, we want to interrogate this process, the reactivity of intermediates and the mechanistic pathway for the final product formation. Initially this will involve attempting to measure the UV-spectra of the reactive lithium enolates to identify where they absorb in the electromagnetic spectrum. We then will aim to maximise the light intensity reaching the intermediates as well as optimising the light wavelength emitted onto the mixture. We then have the ability to investigate why our benzamide starting materials are potentially unique in their photochemical transformations, by measuring UV-spectra of related (perhaps achiral or with limited conjugation) amides and observing what wavelength they absorb before attempting to force photochemical transformations of these species by using lamps of specific wavelengths. We hope this can vastly widen the scope for these transformations by allowing the photochemical reaction of a multitude of conjugated systems that differ widely from benzamides.

If similar chemistry cannot be initiated from related starting amides, a possible study on molecular orbitals could be carried out using computational methods or visualisation (such as using virtual reality, VR). Since the photochemical transformations are thought to be pericyclic in nature, the related amides could be examined to identify how their molecular orbitals differ for the required overlap when compared to our known reactions. This computational view could provide interesting data about which photochemical excitations are occurring within the lithiated enolates which allows the photochemical transformations.

We would aim to also investigate the possible mechanisms for these transformations by attempting to trap possible intermediates (such as through a radical-trapping pathway) and attempt to rule out possible pericyclic pathways where possible by isolating key intermediates in the photochemical pathway. This would eventually lead us to utilise our chemistry in application to synthetically challenging pharmaceutical molecules, giving potential (and synthetically simple) application in industry. Considering the wide interest currently forming around photochemistry, this process has the potential to simplify many pathways to larger synthetic rings from simple starting materials in one or two steps.

The novelty of this project arises from the lack of current research on the photochemistry of lithiated benzamides and the potential for facile synthesis of complex structures using just commercial LEDs as the initiator.

This project aims to be a collective mix of synthetic lab-based chemistry with technology incorporations (such as photochemistry, flow and VR). Flow chemistry in particular may provide an efficient approach to obtaining a large amount of final product in a short space of time, assuming temperature control on the flow apparatus can be achieved.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S024107/1 30/09/2019 30/03/2028
2645226 Studentship EP/S024107/1 20/09/2020 29/09/2024 James Edward Mortimer