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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Bibliographic Details
Main Author: Green, Harley
Format: Thesis (University of Nottingham only)
Language:English
Published: 2023
Subjects:
Online Access:https://eprints.nottingham.ac.uk/72269/
Description
Summary: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.