Catalytic Reactions of Arenes via transient arene Ru Complexes
Lead Research Organisation:
Durham University
Department Name: Chemistry
Abstract
The reactivity of aromatic compounds is significantly altered when bound to transition metals through coordination. Upon coordination, aromatic and benzylic C H bonds become more acidic and the ring itself becomes more electrophilic. As a result, coordinated arenes show improved reactivity in selected reactions. Nucleophilic aromatic substitution of arene metal complexes was particularly well exploited in the 1990s, in which the coordinated metal fragment takes the place of a covalently-bound electron withdrawing group. Recently, there has been somewhat of a renaissance in this field with several research groups (including the Walton group) reporting contemporary reactions of arene complexes, including C H C C and C H C CF3 transformations.
In this PhD project, part-funded by Syngenta, we will explore several new industrially-relevant catalytic reactions of arenes, which are atom efficient and would allow for late-stage functionalisation of aromatic compounds.
The first aim will be nucleophilic fluorination. Fluorinated arenes are important motifs in the agrochemical and pharmaceutical industries. Current methods of fluorination are generally electrophilic or use HF, which requires specialist equipment. An attractive option would be to use a source of fluoride which could undergo a nucleophilic addition to aromatics. We will investigate a nucleophilic fluorination of aromatics, proceeding via a Ru arene complex. The final target is to produce a reaction that is catalytic in Ru. However, the project can be broken down into first looking at fluorination stoichiometric in Ru, before developing the full catalytic process. For the stoichiometric reaction, the activating [CpRu]+ can be recovered by photolysis. We will explore various conditions, including solvent effects and the choice of nucleophilic fluoride to optimise the reaction.
The second aim will be to develop an atom-efficient isoquinoline synthesis. Heterocycles, such as isoquinoline, are important pharmaceutical targets. Generally, current methods of synthesis are atom inefficient. Using our catalytic arene activation methodology we will attempt to synthesise isoquinolines with 100% atom efficiency using catalytic Ru. As with the fluorination reaction above, initially we will develop the reaction stoichiometric in Ru and use photolysis to liberate the bound isoquinoline. Then we will develop the full catalytic cycle.
This PhD project will develop skills in the following areas: (i) Catalytic reaction development; (ii) Synthesis and purification of transition metal complexes using inert atmosphere techniques (Schlenk line processes, degassing solvents, HPLC purification); (iii) characterisation of organic compounds and metal complexes (1D an 2D NMR, Mass Spectrometry; (iv) optimisation of reaction conditions using parallel synthesis equipment (v) mechanism determination using ReactIR and kinetic analyses; (vi) data analysis using computer software (e.g. Excel Solver function to determine reaction kinetics) and (vii) written and oral presentation skills through regular group meetings and update reports.
In this PhD project, part-funded by Syngenta, we will explore several new industrially-relevant catalytic reactions of arenes, which are atom efficient and would allow for late-stage functionalisation of aromatic compounds.
The first aim will be nucleophilic fluorination. Fluorinated arenes are important motifs in the agrochemical and pharmaceutical industries. Current methods of fluorination are generally electrophilic or use HF, which requires specialist equipment. An attractive option would be to use a source of fluoride which could undergo a nucleophilic addition to aromatics. We will investigate a nucleophilic fluorination of aromatics, proceeding via a Ru arene complex. The final target is to produce a reaction that is catalytic in Ru. However, the project can be broken down into first looking at fluorination stoichiometric in Ru, before developing the full catalytic process. For the stoichiometric reaction, the activating [CpRu]+ can be recovered by photolysis. We will explore various conditions, including solvent effects and the choice of nucleophilic fluoride to optimise the reaction.
The second aim will be to develop an atom-efficient isoquinoline synthesis. Heterocycles, such as isoquinoline, are important pharmaceutical targets. Generally, current methods of synthesis are atom inefficient. Using our catalytic arene activation methodology we will attempt to synthesise isoquinolines with 100% atom efficiency using catalytic Ru. As with the fluorination reaction above, initially we will develop the reaction stoichiometric in Ru and use photolysis to liberate the bound isoquinoline. Then we will develop the full catalytic cycle.
This PhD project will develop skills in the following areas: (i) Catalytic reaction development; (ii) Synthesis and purification of transition metal complexes using inert atmosphere techniques (Schlenk line processes, degassing solvents, HPLC purification); (iii) characterisation of organic compounds and metal complexes (1D an 2D NMR, Mass Spectrometry; (iv) optimisation of reaction conditions using parallel synthesis equipment (v) mechanism determination using ReactIR and kinetic analyses; (vi) data analysis using computer software (e.g. Excel Solver function to determine reaction kinetics) and (vii) written and oral presentation skills through regular group meetings and update reports.
People |
ORCID iD |
| James Walton (Primary Supervisor) | |
| Luke Williams (Student) |