Category Archives: Research@QMUL

Aryne-Mediated Arylation of Hantzsch Esters: Access to Highly Substituted Aryl-hydropyridines

Dr David Palomas

https://www.thieme-connect.de/media/synthesis/EFirst/i_z0578_ga_10-1055_s-0037-1611065.gif

Synthesis, 2018, Accepted DOI: 10.1055/s-0037-1611065

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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Intermolecular Aryne Ene Reaction of Hantzsch Esters: Stable Covalent Ene Adducts from a 1,4-Dihydropyridine Reaction

Dr David Palomas

Abstract Image

Org. Lett. 2017, 19174644-4647

The reaction of arynes with 1,4-dihydropyridines affords 2-aryl-1,2-dihydropyridines or 2-methylene-3-aryl-1,2,3,4-tetrahydropyridines via a regioselective C-2 or C-3 arylation. These compounds are the first series of isolable and bench-stable covalent ene adducts formed between dihydropyridines and unsaturated substrates. Experimental studies and DFT calculations provide mechanistic support for a concerted intermolecular aryne ene process, which may have implications for NAD(P)H model reactions.

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