Investigation of catalyst effects in enantioselective copper- and rhodium-mediated transformations of α-diazocarbonyl compounds

Slattery, Catherine N.

Investigation of catalyst effects in enantioselective copper- and rhodium-mediated transformations of α-diazocarbonyl compounds

dc.contributor.advisor	Maguire, Anita R.
dc.contributor.author	Slattery, Catherine N.
dc.contributor.funder	Irish Research Council for Science Engineering and Technology	en
dc.contributor.funder	Eli Lilly and Company, United States	en
dc.date.accessioned	2012-07-03T12:31:15Z
dc.date.available	2012-07-03T12:31:15Z
dc.date.issued	2012-04
dc.date.submitted	2012-06
dc.description.abstract	This thesis describes the synthesis and reactivity of a series of α-diazocarbonyl compounds with particular emphasis on the use of copper-bis(oxazoline)-mediated enantioselective C–H insertion reactions leading to enantioenriched cyclopentanone derivatives. Through the use of additives, the enantioselectivity achieved with the copper catalysts for the first time reaches synthetically useful levels (up to 91% ee). Chapter one provides a comprehensive overview of enantioselective C–H insertions with α-diazocarbonyl compounds from the literature. The majority of reports in this section involve rhodium-catalysed systems with limited reports to date of asymmetric C–H insertion reactions in the presence of copper catalysts. Chapter two focuses on the synthesis and C–H insertion reactions of α-diazo-β-keto sulfones leading to α-sulfonyl cyclopentanones as the major product. Detailed investigation of the impact of substrate structure (both the sulfonyl substitutent and the substituent at the site of insertion), the copper source, ligand, counterion, additive and solvent was undertaken to provide an insight into the mechanistic basis for enantiocontrol in the synthetically powerful C–H insertion process and to enable optimisation of enantiocontrol and ligand design. Perhaps the most significant outcome of this work is the enhanced enantioselection achieved through use of additives, substantially improving the synthetic utility of the asymmetric C–H insertion process. In addition to the C–H insertion reaction, mechanistically interesting competing reaction pathways involving hydride transfer are observed. Chapter three reports the extension of the catalyst-additive systems, developed for C–H insertions with α-diazo-β-keto sulfones in chapter two, to C–H insertion in analogous α-diazo-β-keto phosphonate and α-diazo-β-keto ester systems. While similar patterns were seen in terms of ligand effects, the enantiopurities achieved for these reactions were lower than those in the cyclisations with analogous α-diazo-β-keto sulfones. Extension of this methodology to cyclopropanation and oxium ylide formation/[2,3]-sigmatropic rearrangement was also explored. Chapter four contains the full experimental details and spectral characterisation of all novel compounds synthesised in this project, while details of chiral stationary phase HPLC analysis and X-ray crystallography are included in the appendix.	en
dc.description.status	Not peer reviewed	en
dc.description.version	Accepted Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Slattery, C. N. 2012. Investigation of catalyst effects in enantioselective copper- and rhodium-mediated transformations of α-diazocarbonyl compounds. PhD Thesis, University College Cork.	en
dc.identifier.uri	https://hdl.handle.net/10468/619
dc.language.iso	en	en
dc.publisher	University College Cork	en
dc.rights	© 2012, Catherine N. Slattery	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/	en
dc.subject	C-H insertion	en
dc.subject	Diazo	en
dc.subject	Asymmetric catalysis	en
dc.subject	Copper catalysis	en
dc.subject.lcsh	Copper catalysts	en
dc.subject.lcsh	Organic compounds--Synthesis	en
dc.title	Investigation of catalyst effects in enantioselective copper- and rhodium-mediated transformations of α-diazocarbonyl compounds	en
dc.type	Doctoral thesis	en
dc.type.qualificationlevel	Doctoral	en
dc.type.qualificationname	PhD (Chemistry)	en