General Overview: Dendralenes are a class of molecule whose reactivity is only now started to be investigated. Exploring the reactivity of these novel structures may open up new modes of reactivity for the synthesis of complex polycyclic systems.1 The dendralene’s ability to undergo transmissive, and hence, consecutive pericyclic reactions provides the opportunity to develop new reaction cascades, in which the first reaction sets the scene and activates the dendralene towards the second reaction. Combining multiple reactions into a single pot and increasing functionality and complexity at the same time is one of the goals of more sustainable synthetic chemistry.
Outline: The discovery that dendralenes are both easy to synthesise2 and relatively stable provides the possibility to develop new strategies for the concise synthesis of polycyclic systems present in many biologically active molecules. It has been showed that dendralenes participate in transmissive Diels-Alder reactions (Scheme 1, A) and can generate a range of structurally diverse complex polycyclic systems. We wish to expand the scope of this transmissive reactivity and develop the transmissive 6-electrocyclisation/Diels-Alder reaction of dendralenes.
Initially we will seek to determine the scope and limitations of the transmissive 6-electrocyclisation/Diels-Alder reaction, by constructing differently substituted dendralenes (R = alkyl, aryl, etc) and subjecting them to electrocyclisation conditions and Diels-Alder reactions with a range of dieneophiles. Once this study is complete the reactivity will be reversed and the transmissive Diels-Alder/6-electrocyclisation reaction will be studied. This will provide access to a range of differently substituted polycyclic ring systems.
Once we have an appreciation of the scope of the transmissive pericyclic reactions of dendralenes we will apply the concept to the synthesis of biologically active natural products including the antimicrobial angucylines, cholesterol lowering lovastatins, antimicrobial carneic acids and the anticancer phomopsidins.
All research students follow our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills. All research students take the core training package which provides both a grounding in the skills required for their research, and transferable skills to enhance employability opportunities following graduation. Core training is progressive and takes place at appropriate points throughout a student’s higher degree programme, with the majority of training taking place in Year 1. In conjunction with the Core training, students, in consultation with their supervisor(s), select training related to the area of their research.
The Clarke group trains all members in contemporary synthetic organic chemistry techniques including the handling of air sensitive reagents, toxic chemicals, and reaction safety analysis and structure determination by advanced spectroscopic methods. The student will attend weekly group meetings focusing on the development of literature awareness, presentation of results, problem solving and mechanistic skills. Guidance will also be given on project management and project specific scientific issues. As part of the Organic Chemistry section the student will be exposed to a wide range of visiting speakers through a vibrant external seminar program. The student will also be encouraged to present their work as a poster and as oral presentations at least two different national or international meetings.
The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. The Department strives to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel: https://www.york.ac.uk/chemistry/ed/
. This PhD project is available to study full-time or part-time (50%).
This PhD will formally start on 1 October 2019. Induction activities will start on 30 September.
1. a) H. Hopf and M. S. Sherburn, Angew. Chem. Int. Ed., 2012, 51, 2298. b) M. S. Sherburn, Acc. Chem. Res., 2015, 48, 1961.
2. a) A. D. Payne, A. C. Willis and M. S. Sherburn, J. Am. Chem. Soc., 2005, 127, 12188. b) G. Bojase, A. D. Payne, A. C. Willis and M. S. Sherburn, Angew. Chem., Int. Ed., 2008, 47, 910. c) A. D. Payne, G. Bojase, M. N. Paddon-Row and M. S. Sherburn, Angew. Chem., Int. Ed., 2009, 48, 4836.