Alkynes as Masked Ylides. A Concept for New Reactions and Reactivity

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

Abstract

Ylides are very useful reagents with a diverse range of reactivity, employed in the synthesis of small and large, simple and complex molecules. However, as ylides are sensitive species they can be introduced into a molecule only immediately prior to their use. Their synthetic precursors are also highly reactive species which cannot be carried through other manipulations.So whilst the ylide reactions themselves can be very effective, the long, inefficient, inflexible and intolerant strategies required to introduce them into a molecule, reduces their potential applicability. Similarly, the economy and efficiency of any synthesis that employs them is adversely affected.In this proposed research, a novel catalytic process will allow ylides to be prepared in situ, from robust functionality which can be carried through a variety of transformations unscathed. The flexible strategy to access a range of different ylides, coupled with their subsequent reactions will lead to a diverse array of new transformations. This new approach will result in more economical synthesis by utilising the power of ylide chemistry, whilst bypassing lengthy and inefficent starting material preparations. The resulting synthetic strategies will be shorter and more efficient than at present, with less chemical and time resource consumed and less waste produced.

Publications

10 25 50
 
Description The main discovery and development from this work was that a type of reactivity, that previously was only accessed through the use of highly inefficient, high waste producing and potentially dangerous means, could instead be accessed directly from simpler alkynes through a novel application of gold catalysis which bypasses the indicated problems. We found that sulfur ylides can be prepared directly from alkynes using two different activation approaches under gold and platinum catalysis and developed new highly efficient synthetic methodology as a result. This work established that (1) pi-acid catalysis is productive in the presence of sulfides; (2) gold carbenoids can react with sulfides in a manner analogous to other metal carbenes generated from atom-transfer processes; (3) internal redox processes do give a-oxo-gold carbene reactivity patterns; (4) the synthetic issues such as handling, toxicity and waste associated with diazo-based atom-transfer strategies can be avoided using the alkyne activation approach
Exploitation Route This work can be, and is being, put to use in the further development of more efficient synthetic methodologies for the faster, easier and less wasteful preparation of complex organic molecules and to advance understanding in a fast moving field of gold catalysis. The principles established in the project can and are being more widely applied in reaction design leading to new structures and molecular frameworks of potential interest to in areas such as target identification in high throughput screening assays for therapeutic areas.
Sectors Chemicals,Pharmaceuticals and Medical Biotechnology

URL http://www.birmingham.ac.uk/research/activity/chemistry/Davies/research-topics/index.aspx
 
Description Metal carbenes are highly useful reactive species for synthetic chemistry. Their utility is however tempered by limitations associated with access to them (which include the use of explosive groups which can also be difficult to insert where required in a molecule. The findings from this grant established an alternative route to access the same types of outcomes which has established my research group in the field of gold carbenoid chemistry and sulfur ylide chemistry and has led to global competitiveness for my research group/the UK in this field of fundamental research.
 
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 Efficient Synthesis using Alkynes as Masked Ylides
Amount € 172,241 (EUR)
Funding ID ESAMY 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 07/2010 
End 07/2012
 
Description Novel transformations for the synthesis of nitrogen heterocycles
Amount £76,774 (GBP)
Funding ID 970746 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2010 
End 09/2014
 
Description Novel transformations for the synthesis of nitrogen heterocycles
Amount £24,000 (GBP)
Funding ID 970746 
Organisation AstraZeneca 
Sector Private
Country United Kingdom
Start 09/2010 
End 09/2014
 
Description Euchems 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Talks sparked questions and discussion afterwards

After my talk, my profile was raised within the European network of researchers.
Year(s) Of Engagement Activity 2010
 
Description Metals in Synthesis 
Form Of Engagement Activity Scientific meeting (conference/symposium etc.)
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Talks sparked discussions.

A report on this meeting, including my presentation was published in Johnson Matthey technical review
Year(s) Of Engagement Activity 2008
URL http://www.technology.matthey.com/article/53/2/86-90/http://;http://www.jsps.org/event/pdf/symposium...
 
Description OMCOS 
Form Of Engagement Activity Scientific meeting (conference/symposium etc.)
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk sparked questions and discussion

Led to an invitation to write it up as a paper in Pure and Applied Chemistry.
Year(s) Of Engagement Activity 2009
 
Description RSC GDCH ACS Transatlantic Frontiers of Chemistry Meeting 
Form Of Engagement Activity Scientific meeting (conference/symposium etc.)
Part Of Official Scheme? No
Type Of Presentation poster presentation
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Talks sparked questions and discussion afterwards

Increased visibility for our research
Year(s) Of Engagement Activity 2008
 
Description gregynog 07 
Form Of Engagement Activity Scientific meeting (conference/symposium etc.)
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Talk led to questions and discussions

On the basis of this presentation, I was invited to give a number of talks at Unviersities
Year(s) Of Engagement Activity 2007