Mechanistic Understanding leading to Informed Mitigation of Troublesome Dehalogenation in Catalysed Couplings

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Chemistry

Abstract

The aims and objectives of the project are to: i) identify the mechanistic origins of troublesome side reactions that are frequently found to accompany cross-coupling and other metal-catalysed reactions; ii) in particular to identify the source of "H" - the formal reductant in aryldehalogenation, and the source of the formal oxidised species in reductive homocoupling coupling; iii) to distinguish protodeboronation from protodehalogenation in some systems, and to study protodeboronation of boronate esters; iv) on the basis of this mechanistic insight, to design means by which to mitigate or bypass such processes.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509644/1 01/10/2016 30/09/2021
1941152 Studentship EP/N509644/1 01/10/2017 30/09/2021 Hannah Hayes
 
Description Boronic acids and boronic esters are indispensable building blocks in modern synthetic chemistry. Given their widespread use, research focused on their properties is of great importance. Whilst the protodeboronation of a diverse range of boronic acids has been extensively studied in the Lloyd-Jones group, the pathway by which the more stable boronic esters undergo protodeboronation is relatively unknown. Base-catalysed protodeboronation reactions of boronic esters were monitored and the insight gained from kinetics experiments, isotope-labelling studies and reaction simulations has allowed for a possible mechanistic pathway to be postulated.
Exploitation Route The Suzuki-Miyaura cross-coupling is an example of a reaction which uses boronic acids and boronic esters as key reagents and is universally recognised as one of the most important reactions in modern synthetic chemistry. Despite its frequent incorporation as a key step towards the production of active ingredients for drugs and herbicides, the industrial application of this reaction is hindered substantially by the susceptibility of boronic acids and boronic esters to undergo decomposition by a process known as protodeboronation. In different circumstances, the ability to effectively remove remaining boronic acid and boronic ester starting material post process is highly desirable. The potential for taking advantage of protodeboronation as a means to eliminate these reagents is also of great interest. A richer mechanistic understanding of the pathway by which these reagents decompose by protodeboronation has been gained through this research effort. This knowledge may be applied to assist in both the mitigation of this undesirable side reaction and efficient removal of remaining starting material when needed.
Sectors Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description Informed industrial application of boronate esters / stability
First Year Of Impact 2018
Sector Chemicals,Pharmaceuticals and Medical Biotechnology
Impact Types Economic