Greener methodology for the synthesis of alpha-diazocarbonyl compounds and a novel approach to dioxinone derivatives

O'Brien, Claire

Greener methodology for the synthesis of alpha-diazocarbonyl compounds and a novel approach to dioxinone derivatives

dc.check.date	2021-10-25T11:19:24Z
dc.check.embargoformat	Both hard copy thesis and e-thesis	en
dc.check.entireThesis	Entire Thesis Restricted
dc.check.info	Restricted to everyone for five years	en
dc.check.opt-out	No	en
dc.check.reason	This thesis is due for publication or the author is actively seeking to publish this material	en
dc.contributor.advisor	Collins, Stuart G.	en
dc.contributor.author	O'Brien, Claire
dc.contributor.funder	Irish Research Council for Science, Engineering and Technology	en
dc.contributor.funder	GlaxoSmithKline	en
dc.date.accessioned	2016-10-26T11:19:24Z
dc.date.issued	2016
dc.date.submitted	2016
dc.description.abstract	This thesis outlines a more environmentally benign approach to diazo transfer, and the investigation of the reactivity of -diazocarbonyl compounds when subjected to transition metal and lanthanide catalysis. Extensive studies were carried out to find the optimum conditions for a greener diazo transfer methodology, and this was also applied to a continuous process for the synthesis of -diazo--ketoesters. The first chapter includes a literature review of the synthesis and subsequent reactivity of -diazocarbonyl compounds. An overview of the applications of flow chemistry for the synthesis of hazardous intermediates is also included. The applications of lanthanide catalysts in organic synthesis is also discussed. The second chapter outlines the extensive studies undertaken to determine the optimum conditions for a greener diazo transfer methodology, including base and solvent studies. Use of water as a viable solvent for diazo transfer was successfully investigated. Diazo transfer to a range of -diazo--ketoesters was achieved using 5 mol% triethylamine or DMAP in water with high conversions. Polystyrene-supported benzenesulfonyl azide as an alternative diazo transfer reagent was also explored, as well as investigations into cheaper generation of this safer reagent. This polymer-supported benzenesulfonyl azide was used with 25 mol% of base in water to achieve successful diazo transfer to a range of -diazo--ketoesters. The third chapter describes the application of the new methodology developed in Chapter 2 to a continuous processing approach. Various excellent conditions were identified for both batch and flow reactions. A series of -diazo--ketoesters were synthesised with excellent conversions using 25 mol% triethylamine in 90:10 acetone water using flow chemistry. Successful diazo transfer was also achieved using a polymer-supported benzenesulfonyl azide in water under flow conditions. The fourth chapter discusses the reactivity of -diazo--ketoesters under transition metal and lanthanide catalysis. This chapter describes the synthesis of a range of -ketoesters via transesterification, which were used to synthesise a range of novel -diazo--ketoesters that were used in subsequent decomposition reactions. A novel route to dioxinones via rhodium(II) catalysis is reported. Attempted OH and SH insertion reactions in the presence of various lanthanide(II) catalysts are outlined, leading to some unexpected and interesting rearrangement products. The experimental details, including spectroscopic and analytical data for all compounds prepared, are reported at the end of each chapter.	en
dc.description.status	Not peer reviewed	en
dc.description.version	Accepted Version
dc.format.mimetype	application/pdf	en
dc.identifier.citation	O'Brien, C. 2016. Greener methodology for the synthesis of alpha-diazocarbonyl compounds and a novel approach to dioxinone derivatives. PhD Thesis, University College Cork.	en
dc.identifier.endpage	372	en
dc.identifier.uri	https://hdl.handle.net/10468/3216
dc.language	English	en
dc.language.iso	en	en
dc.publisher	University College Cork	en
dc.rights	© 2016, Claire O'Brien.	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/	en
dc.subject	Diazo	en
dc.subject	Green chemistry	en
dc.subject	Flow chemistry	en
dc.thesis.opt-out	false
dc.title	Greener methodology for the synthesis of alpha-diazocarbonyl compounds and a novel approach to dioxinone derivatives	en
dc.type	Doctoral thesis	en
dc.type.qualificationlevel	Doctoral	en
dc.type.qualificationname	PhD (Science)	en
ucc.workflow.supervisor	stuart.collins@ucc.ie