Copy of Development of New Catalytic Protocols for Alkene Difunctionalisation

Lead Research Organisation: University of Bristol
Department Name: Chemistry

Abstract

One of the cornerstones of synthetic methodology is the conversion of readily available alkenes into more complex molecules that have both form and function. When the elements of X-X or X-Y are added across a double bond then this process can be termed 'alkene difunctionalisation'. Simple halogenation, protonation and hydroxylation are easily carried out using halogens or mineral acids. Reactions such oxidation, reduction, dihydroxylation generally require more sophisticated reagents and/or catalysts but are broad in scope and ubiquitous in synthetic chemistry. Use of metal catalysis to achieve these goal is highly desirable due to the small amounts of catalyst required and the fact that many of these key processes are rendered asymmetric in the presence of appropriate chiral ligands (eg Sharpless epoxidation/dihydroxylation; Nyori hydrogenation). On the other hand reactions such as diamination, hydroxyamination and carboamination are much less common and although there exists both direct and indirect methods for achieving this they are few in number, substrate specific and often give variable results with respect to regioselectivity. General solutions to these three longstanding problems are highly desirable and would be used widely by the synthetic community. For example, a general catalytic method for the asymmetric synthesis of enantiopure beta amino alcohols from alkenes is a 'Holy Grail' reaction - especially for the pharmaceutical industry, where this structural motif is key to many drug substances (eg beta-blockers).In this proposal we hope to build on our recent discovery that dienes can be selectively diaminated with urea derivatives using Pd(II) catalysts in the presence of a re-oxidant. In particular we hope to expand our findings to include hydroxyamination and carboamination. Our key goal is to enable the these difunctionalisation reactions to be carried out on simple alkenes without the attendant beta-hydride elimination problems we observe at the moment. To achieve this we aim to explore the use of Pt(II)(PPP) catalysts in collaboration with Prof. Mike Gagne (North Carolina, USA). In diene cyclisation studies these catalysts have been shown by the Gagne group to be exceptionally electrophillic and produce C-Pt(II) intermediates that are extremely resistant to beta-hydride elimination. We believe that application of these Pt(II) catalysts will open up new horizons for alkene difunctionalisation.

Publications

10 25 50
 
Description This grant enabled the discovery and development of a number Pd catalysed C-H activation and cascade reactions for the formation of complex heterocyclic ring systems.
Exploitation Route The published results have been cited in a number of papers by other groups.
Sectors Agriculture, Food and Drink,Chemicals,Education,Pharmaceuticals and Medical Biotechnology

 
Description Novartis
Amount £33,000 (GBP)
Funding ID UoB-Novartis CASE 
Organisation Novartis 
Sector Private
Country Global
Start 09/2011 
End 10/2015