DEVELOPING METAL CATION STABILISATION AS A GENERAL PARADIGM FOR O-C REARRANGEMENT PROCESSES

Lead Research Organisation: University of Sheffield
Department Name: Chemistry

Abstract

The overall objective of this work is to develop new and efficient processes for the synthesis of organic molecules that bear useful functional groups. This is an important objective in organic chemistry because it provides the tools for the preparation of new molecular entities and consequently novel fine chemicals. The specific process proposed involves a skeletal rearrangement of a readily available substrate to a cyclic ketone - a common motif in bioactive compounds and natural products. A key element of this rearrangement is the presence of a cation stabilising group. Traditionally, this has been achieved by the incorporation of a proximal oxygen atom. The proposed work aims to use metal-hydrocarbon complexes to significantly expand the range of products available from this general strategy. We wish to study this process, establish its scope and limitations and explore the opportunity to generate new compounds with control of their three-dimensional shape.

Publications

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Zirimwabagabo JO (2014) Pd-Catalyzed kinetic resolution of cyclic enol ethers. An enantioselective route to functionalised pyrans. in Chemical communications (Cambridge, England)

 
Description The stereoselective synthesis of small molecule intermediates bearing useful functional handles is a fundamentally important endeavour in organic chemistry. This project uncovered a transition metal catalysed reaction that promoted the formation of cyclic ketones (a common and important organic fragment) via a novel skeletal rearrangement process. Importantly, through the use of chiral ligands, this process was able convert stereoisomeric mixtures of starting materials into enantiomerically enriched products via a kinetic resolution mechanism. These developments allowed us to advance our initial method that employed stoichiometric cobalt carbonyl complexes into an enantioselective metal catalysed variant, significantly improving its atom economy and utility.
Exploitation Route Our work highlights the potential of a kinetic resolution process for the synthesis of enantiomerically enriched functionalised ketones. This basic science can inform the development of related Pd pi-allyl mediated reactions, in particular with respect to the types of chiral ligand that offer the best levels of enantiocontrol. The products themselves are easily transformed into a range of distinct end products that can form the basis of feedstocks for sp3-rich end prodicts.
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology