Gold-Catalysed Cycloisomerisations

Lead Research Organisation: University of Birmingham
Department Name: School of Chemistry

Abstract

Cyclic structures are are ubiquitous in pharmaceuticals, agrochemicals, natural products and fine chemicals. Thus the preparation of ring systems and being able to control cyclisation reactions is very important and presents a major challenge to organic synthesis. New methods to access these type of species more readily are therefore highly desirable. Shorter, more flexible, easy and efficient routes into useful molecules can have several significant benefits to the wider community. This includes the use of fewer reagents, less hazardous chemicals, and less energy to make important molecules. All of these factors have subsequent benefits in terms of using less of our limited natural resources (chemical and energy) and producing less of the dangerous waste materials that must be disposed off. Potentially, more efficient strategies and transformations can also have economic benefits, making overall processes and the resulting products less costly. The importance of developing more effective approaches cannot therefore be understated and in this research we look at using new highly efficient catalytic methods to access a wide variety of carbo and heterocyclic structures that have clear application throughout synthetic chemistry.

Publications

10 25 50
 
Description This project involved the development and study of a range of cycloisomerisation reactions catalysed by gold species. These allow quite simple, readily assembled chemical precursors to be transformed into more complex structures under mild conditions with high chemical efficiency. Key findings include: the scope of the direct keto-alkyne cycloisomerisation reaction; the importance of adventitious water in these reactions; the discovery of unexpected reaction pathways to provide new transformations; how structural modifications and changes in reaction conditions can be used to influence the varied reaction pathways. A significant advance was establishing that the geometric bias in cyclisation reactions could be overridden through the use of a particular-type of alkyne. This discovery has since been used int eh group to realise new reactivity patterns in the development of novel synthetic methodology and to access complex 3D molecular architectures in an efficient fashion.
Exploitation Route Novel synthetic methodology can be applied in an industrial context for the preparation of organic compounds for various ends (for instance, pharmaceutical and agrochemical) depending on the target structures. The research developed here includes novel transformations and strategies for facile molecular assembly and evaluation of the scope of these reactions to inform potential users. Specifically we discovered here a method to rapidly assemble complex 3D core structures in a single step - providing entry into new natural product-like 3D fragments and highly functionalised heterocycles. It is increasingly recognised that 3D spatially complex systems are valuable starting points for effective pharmaceutical discovery programme.
The discovery of the regiocontrolling effect can be used across a wider variety of new transformations, and has been used to effect new transformations by achieving greater chemical control over complex processes.
Sectors Chemicals,Pharmaceuticals and Medical Biotechnology

URL http://www.birmingham.ac.uk/research/activity/chemistry/Davies/index.aspx
 
Description Convergent and efficient synthesis of novel heteroaromatics
Amount € 209,033 (EUR)
Funding ID 301008 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2013 
End 01/2015
 
Description Efficient Synthesis of N-Heterocycles using Ynamides as Diazo Equivalents
Amount € 200,371 (EUR)
Funding ID 300819 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 03/2012 
End 03/2014
 
Description Company Visit (AstraZeneca) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Industry/Business
Results and Impact Research presentation which sparked discussion and questions.
Year(s) Of Engagement Activity 2010
 
Description Company Visit (Vernalis, Cambridge) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Industry/Business
Results and Impact Research presentation which sparked discussion and questions.
Year(s) Of Engagement Activity 2011
 
Description Company visit (Pfizer, Kent) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Research presentation which sparked discussion and questions.
Year(s) Of Engagement Activity 2010
 
Description Institute visit (ICIQ, Spain) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Research presentation which sparked discussion and questions.
Year(s) Of Engagement Activity 2009
 
Description Institute visit (ICR, London) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Research presentation which sparked discussion and questions.
Year(s) Of Engagement Activity 2009
 
Description SCI 2010 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Talks sparked questions and answers

As a result of my talk on general use of gold catalysis I was invited to give a number of talks at research centres and companies in the UK about my own research
Year(s) Of Engagement Activity 2010
 
Description University Visit (Dublin) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Research presentation which sparked discussion and questions.
Year(s) Of Engagement Activity 2010
 
Description University Visit (Liverpool) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Research presentation which sparked discussion and questions.
Year(s) Of Engagement Activity 2010
 
Description University Visit (Manchester) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Research presentation which sparked discussion and questions.
Year(s) Of Engagement Activity 2010
 
Description University visit (Heriot-Watt) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Research presentation which sparked discussion and questions.
Year(s) Of Engagement Activity 2010
 
Description University visit (Oxford) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Research presentation which sparked discussion and questions.
Year(s) Of Engagement Activity 2010
 
Description University visit (York) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Research presentation which sparked discussion and questions.
Year(s) Of Engagement Activity 2009