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.
Organisations
People |
ORCID iD |
Paul Davies (Principal Investigator) |
Publications
Davies PW
(2008)
Alkynes as masked ylides: gold-catalysed intermolecular reactions of propargylic carboxylates with sulfides.
in Chemical communications (Cambridge, England)
Davies PW
(2009)
Silver-catalysed Doyle-Kirmse reaction of allyl and propargyl sulfides.
in Organic & biomolecular chemistry
Davies PW
(2009)
Gold- or platinum-catalyzed synthesis of sulfur heterocycles: access to sulfur ylides without using sacrificial functionality.
in Angewandte Chemie (International ed. in English)
Davies P
(2010)
Alkynes as "masked" ylides under noble-metal catalysis
in Pure and Applied Chemistry
Davies P
(2011)
A Reactivity Switch in the Gold-Catalysed Coupling of Allyl Sulfides with Propargylic Carboxylates
in Synlett
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 | 06/2010 |
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 | 08/2010 |
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 | 08/2010 |
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 |