Enantioselective Nickel-Catalysed Arylative and Alkenylative Cyclisations onto Electron-Deficient Alkenes via E/Z Isomerisation

Herein is presented a highly enantioselective nickel-catalysed anti-carbometallative-cyclisation reaction of substrates containing an alkyne tethered to an electron-deficient alkene. Enantioenriched cyclopentene products, that are otherwise difficult to synthesise, are obtained in up to 99% yield an...

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Main Author: Gillbard, Simone Marie
Format: Thesis (University of Nottingham only)
Language:English
Published: 2023
Subjects:
Online Access:https://eprints.nottingham.ac.uk/73697/
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author Gillbard, Simone Marie
author_facet Gillbard, Simone Marie
author_sort Gillbard, Simone Marie
building Nottingham Research Data Repository
collection Online Access
description Herein is presented a highly enantioselective nickel-catalysed anti-carbometallative-cyclisation reaction of substrates containing an alkyne tethered to an electron-deficient alkene. Enantioenriched cyclopentene products, that are otherwise difficult to synthesise, are obtained in up to 99% yield and >99% ee. The overall anti-carbometalation of the alkyne is enabled by the critical reversible E/Z isomerisation of alkenylnickel intermediates. Investigation of the substrate scope revealed that alkyne substituents such as (hetero)aryl and alkenyl groups were compatible with the reaction and substrates containing electron-deficient alkenes such as α,β-unsaturated alkyl or (hetero)aryl ketones, nitroalkenes, α,β-unsaturated esters and alkenyl nitriles successfully participated in the reaction. Also, (hetero)arylboronic acid as well as alkenylboronic acids were tolerated in the reaction. Efforts were made towards the synthesis of enantioenriched 6-membered carbo- and heterocyclic products by extending the tether between the alkyne and the electron-deficient alkene in the substrate.
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spelling nottingham-736972023-07-26T04:40:36Z https://eprints.nottingham.ac.uk/73697/ Enantioselective Nickel-Catalysed Arylative and Alkenylative Cyclisations onto Electron-Deficient Alkenes via E/Z Isomerisation Gillbard, Simone Marie Herein is presented a highly enantioselective nickel-catalysed anti-carbometallative-cyclisation reaction of substrates containing an alkyne tethered to an electron-deficient alkene. Enantioenriched cyclopentene products, that are otherwise difficult to synthesise, are obtained in up to 99% yield and >99% ee. The overall anti-carbometalation of the alkyne is enabled by the critical reversible E/Z isomerisation of alkenylnickel intermediates. Investigation of the substrate scope revealed that alkyne substituents such as (hetero)aryl and alkenyl groups were compatible with the reaction and substrates containing electron-deficient alkenes such as α,β-unsaturated alkyl or (hetero)aryl ketones, nitroalkenes, α,β-unsaturated esters and alkenyl nitriles successfully participated in the reaction. Also, (hetero)arylboronic acid as well as alkenylboronic acids were tolerated in the reaction. Efforts were made towards the synthesis of enantioenriched 6-membered carbo- and heterocyclic products by extending the tether between the alkyne and the electron-deficient alkene in the substrate. 2023-07-26 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/73697/1/PhD%20Thesis%20-%20Simone%20Gillbard%20Corrected.pdf Gillbard, Simone Marie (2023) Enantioselective Nickel-Catalysed Arylative and Alkenylative Cyclisations onto Electron-Deficient Alkenes via E/Z Isomerisation. PhD thesis, University of Nottingham. heterocycles electrophiles catalysis domino reactions
spellingShingle heterocycles
electrophiles
catalysis
domino reactions
Gillbard, Simone Marie
Enantioselective Nickel-Catalysed Arylative and Alkenylative Cyclisations onto Electron-Deficient Alkenes via E/Z Isomerisation
title Enantioselective Nickel-Catalysed Arylative and Alkenylative Cyclisations onto Electron-Deficient Alkenes via E/Z Isomerisation
title_full Enantioselective Nickel-Catalysed Arylative and Alkenylative Cyclisations onto Electron-Deficient Alkenes via E/Z Isomerisation
title_fullStr Enantioselective Nickel-Catalysed Arylative and Alkenylative Cyclisations onto Electron-Deficient Alkenes via E/Z Isomerisation
title_full_unstemmed Enantioselective Nickel-Catalysed Arylative and Alkenylative Cyclisations onto Electron-Deficient Alkenes via E/Z Isomerisation
title_short Enantioselective Nickel-Catalysed Arylative and Alkenylative Cyclisations onto Electron-Deficient Alkenes via E/Z Isomerisation
title_sort enantioselective nickel-catalysed arylative and alkenylative cyclisations onto electron-deficient alkenes via e/z isomerisation
topic heterocycles
electrophiles
catalysis
domino reactions
url https://eprints.nottingham.ac.uk/73697/