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 (Figure 1a). 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. A selection of these compounds was tested and were found active against ovarian and colon carcinoma. When the C-4 substituted is not hydrogen, excess aryne was found to react with the C-3 product to generate spirocyclic 2-benzocyclobutene-hydropyridines, complex 3D heterocycles which have been synthesized in a single step from simple Hantzsch Esters (HE) starting materials (Figure 1b). These products have also been tested and are selective for colon carcinoma. This scope of the aryne ene reaction will be extended beyond 1,4-dihydropyridines, investigations will begin with more unsaturated N-heterocyclic products like acridines, imidazolidines etc.

Intermolecular aryne ene reaction of Hantzsch esters: Stable covalent ene adducts from a 1,4-dihydropyridine reaction

256th National Meeting (2018)

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