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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

LanguageEnglish
Pages4591-4605
Number of pages15
JournalSynthesis
Volume50
Issue number23
Early online date25 Oct 2018
DOIs
Publication statusPublished - 2018

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Dihydropyridines
Esters
Cells
Deuterium
Cytotoxicity
Discrete Fourier transforms
Labeling
benzocyclobutene

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Sun, Weitao ; Trinchera, Piera ; Kurdi, Nada ; Palomas, David ; Crespo-Otero, Rachel ; Afshinjavid, Saeed ; Javid, Farideh ; Jones, Christopher R. / Aryne-mediated arylation of Hantzsch esters : access to highly substituted aryl-dihydropyridines, aryl-tetrahydropyridines and spiro[benzocyclobutene-1,1’-(3’,4’-dihydropyridines)]. In: Synthesis. 2018 ; Vol. 50, No. 23. pp. 4591-4605.
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title = "Aryne-mediated arylation of Hantzsch esters: access to highly substituted aryl-dihydropyridines, aryl-tetrahydropyridines and spiro[benzocyclobutene-1,1’-(3’,4’-dihydropyridines)]",
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.",
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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)]. / Sun, Weitao; Trinchera, Piera; Kurdi, Nada; Palomas, David; Crespo-Otero, Rachel; Afshinjavid, Saeed; Javid, Farideh; Jones, Christopher R.

In: Synthesis, Vol. 50, No. 23, 2018, p. 4591-4605.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Aryne-mediated arylation of Hantzsch esters

T2 - Synthesis

AU - Sun, Weitao

AU - Trinchera, Piera

AU - Kurdi, Nada

AU - Palomas, David

AU - Crespo-Otero, Rachel

AU - Afshinjavid, Saeed

AU - Javid, Farideh

AU - Jones, Christopher R.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Benzyne

KW - Arynes

KW - Hantzsch ester

KW - Ene reaction

KW - Didydropyridines

KW - Spirocyclobutenes

U2 - 10.1055/s-0037-1611065

DO - 10.1055/s-0037-1611065

M3 - Article

VL - 50

SP - 4591

EP - 4605

JO - Synthesis

JF - Synthesis

SN - 0039-7881

IS - 23

ER -