Georges J. Hoornaert

Synthesis of α-carbolines and β-carbolinones via intramolecular Diels-Alder reactions of 2(1H)-pyrazinones

Abstract 2(1 H )-Pyrazinones bearing a X-( o -C 6 H 4 )CC-R moiety (X=NH, NAc) are shown to undergo an intramolecular cycloaddition-elimination reaction on thermolysis in refluxing bromobenzene yielding α-carbolines or β-carbolinones. The product distribution depends strongly on the substitution pattern of the pyrazinone precursors and the solvent used for thermolysis. A high yield and selective formation of β-carbolinones is possible when heating in tetrahydronaphthalene at reflux. Use of acetic anhydride as solvent facilitated the reaction and made it possible to realise a carbolin(on)e unaccessible by thermolysis in the previously mentioned solvents.

Synthesis of cis-fused hexahydro-4aH-indeno[1,2-b]pyridines via intramolecular Ritter reaction and their conversion into tricyclic analogues of NK-1 and dopamine receptor ligands

Abstract Indanol intermediates prepared via Michael addition of 1-indanone β-ketoester and acrylonitrile, followed by Grignard reaction of the ketone group, were submitted to an intramolecular Ritter reaction to produce cis-fused methyl 2-oxo-9b-phenyl-1,2,3,4,5,9b-hexahydro-4aH-indeno[1,2-b]pyridine-4a-carboxylates with 4a,9b-diangular substitution pattern. Further transformation of the bridgehead ester group and the lactam function afforded constrained tricyclic analogues of some monocyclic piperidine NK-1 antagonists and of a bicyclic dopamine receptor ligand.

Stereochemistry and mechanism of acylation of acetylenes

Abstract The addition of acid chloride-AlCl 3 complexes and of acyl triflates to several acetylenes has been performed. Evidence is given that these additions occur at least partly through a vinyl cation intermediate. In the case of aroyl chlorides or aroyl triflates the intermediate vinyl cation can be attacked by the aromatic nucleus of the aroyl group, leading to the formation of indenones. The difference in behaviour between aroyl chloride-AlCl 3 complexes and aroyl triflates is explained by the hardness of the triflate anion as a nucleophile, compared to the tetrachloraluminate anion. Further evidence for the intermediate vinyl cation is found in the formation of rearranged products in the addition of 3,5 dimethoxybenzoyl chloride-AlCl 3 complex and benzoyl triflate to 4,4-dimethyl-2-pentyne.

Synthesis, extraction ability and application in asymmetric synthesis of azacrown ethers derived from D-glucose

New chiral monoaza-15-crown-5 ethers have been synthesised from 1,2:5,6-di-O-isopropylidene-D-mannitol. The substituent at the nitrogen atom has a major influence on the cation extraction ability of the azacrown. These sugar-based crown ethers show asymmetric induction as chiral phase transfer catalysts in the Michael addition of 2-nitropropane to chalcone (67% ee).

Generation of specifically substituted pyridines and pyridones from 2(1h) pyrazinones and acetylenes : A FMO description

Abstract The title compounds were obtained from reaction of variously substituted 2(1H)pyrazinones with acetylenic derivatives. Experimental evidence points out to a two step mechanism : a Diels Alder cycloaddition followed by immediate decomposition of the adducts into the title products via two competitive retro Diels Alder reactions. The product distribution, which is shown to be highly dependent on the substitution pattern of the reactants, is accounted for by a simple FMO model.

Diels-Alder reactions of pyridine o-quinodimethane analogues generated from functionalised o-bis(chloromethyl)pyridines☆

Abstract The polyfunctional 2,3- and 3,4-o-bis(chloromethyl)pyridines 3, produced via cycloaddition of the oxazinones 2 with propargyl chloride and 1,4-dichloro-2-butyne, were used as precursors of various pyridine o-quinodimethane analogues. The 2,3- and 3,4-dimethylenepyridine systems were generated via reductive 1,4-elimination with iodide and trapped in situ with various dienophiles to form the tetrahydroquinoline and -isoquinoline type adducts. A regiospecific cycloaddition was observed for the 3,4-dimethylenepyridine system with electron-rich dienophiles, i.e. dihydrofuran and ethyl vinyl ether, in contrast to the reaction with methyl acrylate.

Synthesis of new pyrrolo[3,4-b]- and [3,4-c]pyridin(on)es and related 1,7-naphthyridinones and 2,7-naphthyridines via intramolecular Diels-Alder reactions of 2(1H)-pyrazinones

Abstract 2(1H)-pyrazinones 7, 10 or 12 with in 6-position a 2-propynylaminomethyl or 3-butynylaminomethyl side chain undergo intramolecular Diels-Alder reactions providing cycloadducts which can be isolated or functionalised in some cases. By further thermolysis of these compounds either pyrrolo-[3,4-b]pyridinones 15 16 and/or pyrrolo[3,4-c]pyridines 17 18 or 1,7-naphthyridinones 25 and/or 2,7-naphthyridines 26 can be generated. Loss of either cyanide or isocyanate from the respective adducts is shown to be dependent on their substitution pattern.

Synthesis of a conformationally restricted dipeptide analogue and its evaluation as a β-turn mimic

Abstract Dichloropyrazinone 3 was converted into a conformationally restricted dipeptide analogue 8 by means of a Diels–Alder strategy. The β-turn characteristics of molecule 8 were examined by molecular modeling and NMR spectroscopy.

Intramolecular Diels-Alder reactions of 2(1H)-pyrazinones: Synthesis of new Furo/Pyrano-pyridinones and -pyridines

Abstract 2(1 H )-Pyrazinones 2–5 with in 3-position either a 3- or 4-alkynyloxy side chain and 2(1 H )-pyrazinones 9–10 carrying the corresponding 2- or 3-alkynyloxy(m)ethyl substituent are shown to undergo intramolecular Diels-Alder reaction. The formation of either fused pyridinones 13 , 16 , 20 , 22 or 24 and/or pyridines 14 , 17 , 19 or 25 depends on the substitution pattern of the anchored pyrazinone and runs via the loss of either nitrile or isocyanate from the intermediate cycloadduct. The influence of the position of the oxygen atom and the length of the side chain on the reaction conditions is also discussed.

Cycloadducts of ethene with 2(1H)-pyrazinones and their conversion into 2,5-diazabicyclo[2.2.2]octane-3,6-diones.

Abstract Cycloaddition of variously substituted 2(1H)-pyrazinones with ethene and subsequent hydrolysis of the adducts 2 provides a general and efficient route to the title compounds 3. Compound 3m was used as a building block for a structural analogue of gliotoxin.