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DOI: 10.1055/s-0037-1611065
Aryne-Mediated Arylation of Hantzsch Esters: Access to Highly Substituted Aryl-dihydropyridines, Aryl-tetrahydropyridines and Spiro[benzocyclobutene-1,1′-(3′,4′-dihydropyridines)]
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.Publication History
Received: 29 August 2018
Accepted after revision: 27 September 2018
Publication Date:
25 October 2018 (online)
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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.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1611065.
- Supporting Information
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See selected reviews on DHPs and references therein:
Selected reviews:
Hydride transfer:
Single electron transfer:
Selected synthetic examples using:
In situ adduct detection:
Recent reviews:
Hetero-ene:
Alkene ene:
Intramolecular cyclisation:
Intermolecular alkylation:
For synthetic approaches to spirocyclic compounds, see selected reviews and references therein:
Selected examples of adverse effects: