Synthesis 2018; 50(23): 4591-4605
DOI: 10.1055/s-0037-1611065
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© Georg Thieme Verlag Stuttgart · New York

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

Weitao Sun
a  School 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
a  School 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
a  School 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
a  School 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
a  School 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
b  Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK
,
Farideh Javid
b  Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK
,
a  School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK   Email: c.jones@qmul.ac.uk
› Author Affiliations
We are grateful to the EPSRC (EP/M02622/1, C.R.J. and P.T.; EP/K000128/1, R.C.-O.), the Ramsay Memorial Trust (C.R.J.), the China Scholarship Council (W.S.) and the RSC Research Fund for financial support.
Further Information

Publication History

Received: 29 August 2018

Accepted after revision: 27 September 2018

Publication Date:
25 October 2018 (eFirst)

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.

Supporting Information

 
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