Nickel-Catalysed Arylative Cyclisations of Alkynones & Molecular Editing of Cyclic Ketones

PART I: NICKEL-CATALYSED ANTI-ARYLMETALLATIVE CYCLISATIONS ONTO KETONES A highly enantioselective and regioselective nickel-catalysed domino reaction of the addition of boronic acids across an alkyne, followed by subsequent cyclisation onto a ketone is reported. The reversible E/Z isomerization of...

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Main Author: Green, Harley
Format: Thesis (University of Nottingham only)
Language:English
Published: 2023
Subjects:
Online Access:https://eprints.nottingham.ac.uk/72269/
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author Green, Harley
author_facet Green, Harley
author_sort Green, Harley
building Nottingham Research Data Repository
collection Online Access
description PART I: NICKEL-CATALYSED ANTI-ARYLMETALLATIVE CYCLISATIONS ONTO KETONES A highly enantioselective and regioselective nickel-catalysed domino reaction of the addition of boronic acids across an alkyne, followed by subsequent cyclisation onto a ketone is reported. The reversible E/Z isomerization of the alkenylnickel intermediate is key to enable the overall anti-arylmetallative cyclisation. The process affords enantioenriched tertiary-alcohol-containing products of which the ring system is featured in several diarylindolizidine alkaloids. PART II: MOLECULAR EDITING OF CYCLIC KETONES: C-TO-N ATOM EXCHANGE A process for the molecular editing of α-substituted cyclic ketones by performing a formal C-to-N atom exchange is reported. The key first step involves ring-opening the ketone, with the ketoacid product being leveraged through a Curtius rearrangement to introduce the nitrogen atom. Finally, a ring closing step forms the C-to-N atom exchanged product. This process involves simple air-tolerant chemistry, and the products themselves can be purified without the need for column chromatography with a preliminary scope of five compounds being reported.
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spelling nottingham-722692025-07-31T04:30:10Z https://eprints.nottingham.ac.uk/72269/ Nickel-Catalysed Arylative Cyclisations of Alkynones & Molecular Editing of Cyclic Ketones Green, Harley PART I: NICKEL-CATALYSED ANTI-ARYLMETALLATIVE CYCLISATIONS ONTO KETONES A highly enantioselective and regioselective nickel-catalysed domino reaction of the addition of boronic acids across an alkyne, followed by subsequent cyclisation onto a ketone is reported. The reversible E/Z isomerization of the alkenylnickel intermediate is key to enable the overall anti-arylmetallative cyclisation. The process affords enantioenriched tertiary-alcohol-containing products of which the ring system is featured in several diarylindolizidine alkaloids. PART II: MOLECULAR EDITING OF CYCLIC KETONES: C-TO-N ATOM EXCHANGE A process for the molecular editing of α-substituted cyclic ketones by performing a formal C-to-N atom exchange is reported. The key first step involves ring-opening the ketone, with the ketoacid product being leveraged through a Curtius rearrangement to introduce the nitrogen atom. Finally, a ring closing step forms the C-to-N atom exchanged product. This process involves simple air-tolerant chemistry, and the products themselves can be purified without the need for column chromatography with a preliminary scope of five compounds being reported. 2023-07-31 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/72269/1/Harley%20Green%20Thesis%20%28Corrected%29.pdf Green, Harley (2023) Nickel-Catalysed Arylative Cyclisations of Alkynones & Molecular Editing of Cyclic Ketones. PhD thesis, University of Nottingham. alkynes ketones alkenes heterocyclic chemistry
spellingShingle alkynes
ketones
alkenes
heterocyclic chemistry
Green, Harley
Nickel-Catalysed Arylative Cyclisations of Alkynones & Molecular Editing of Cyclic Ketones
title Nickel-Catalysed Arylative Cyclisations of Alkynones & Molecular Editing of Cyclic Ketones
title_full Nickel-Catalysed Arylative Cyclisations of Alkynones & Molecular Editing of Cyclic Ketones
title_fullStr Nickel-Catalysed Arylative Cyclisations of Alkynones & Molecular Editing of Cyclic Ketones
title_full_unstemmed Nickel-Catalysed Arylative Cyclisations of Alkynones & Molecular Editing of Cyclic Ketones
title_short Nickel-Catalysed Arylative Cyclisations of Alkynones & Molecular Editing of Cyclic Ketones
title_sort nickel-catalysed arylative cyclisations of alkynones & molecular editing of cyclic ketones
topic alkynes
ketones
alkenes
heterocyclic chemistry
url https://eprints.nottingham.ac.uk/72269/