Aryne-Mediated Arylation of Hantzsch Esters: Access to Highly Substituted Aryl-dihydropyridines, Aryl-tetrahydropyridines and Spiro[benzocyclobutene-1,1′-(3′,4′-dihydropyridines)]

Weitao Sun; Piera Trinchera; Nada Kurdi; David Palomas; Rachel Crespo-Otero; Saeed Afshinjavid; Farideh Javid; Christopher R. Jones

doi:10.1055/s-0037-1611065

Synthesis, Inhaltsverzeichnis

Synthesis 2018; 50(23): 4591-4605
DOI: 10.1055/s-0037-1611065

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Aryne-Mediated Arylation of Hantzsch Esters: Access to Highly Substituted Aryl-dihydropyridines, Aryl-tetrahydropyridines and Spiro[benzocyclobutene-1,1′-(3′,4′-dihydropyridines)]

Weitao Sun

^aSchool of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK eMail: c.jones@qmul.ac.uk

,

Piera Trinchera

^aSchool of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK eMail: c.jones@qmul.ac.uk

,

Nada Kurdi

^aSchool of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK eMail: c.jones@qmul.ac.uk

,

David Palomas

^aSchool of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK eMail: c.jones@qmul.ac.uk

,

Rachel Crespo-Otero

^aSchool of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK eMail: c.jones@qmul.ac.uk

,

Saeed Afshinjavid

^bDepartment of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK

,

Farideh Javid

^bDepartment of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK

,

Christopher R. Jones *

^aSchool of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK eMail: c.jones@qmul.ac.uk

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Abstract

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Abstract

This is a full account of our studies into the generation of highly functionalised 2-aryl-1,2-dihydropyridines and 2-methylene-3-aryl-1,2,3,4-tetrahydropyridines via intermolecular aryne ene reactions of Hantzsch esters. Furthermore, exposure to excess aryne revealed unusual 3′-aryl-spiro[benzocyclobutene-1,1′-(3′,4′-dihydropyridines)]. Mechanistic insights are provided by deuterium-labelling studies and DFT calculations, whilst preliminary cytotoxicity investigations reveal that the spirocycles are selective against colon carcinomas over ovarian cancer cell lines and that all the compounds have high selectivity indices with regards to non-cancer cells.

Key words

arynes - ene reaction - spiro compounds - benzyne - Hantzsch esters - dihydropyridines

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Referenzen

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Zusatzmaterial

Supporting Information