biostudies-literatureBock CMDeutsche ForschungsgemeinschaftEmerging Fields Initiative (EFI) "Chemistry in Live Cells"Wilhelm Sander-StiftungBayerische Forschungsstiftung364-374https://www.ebi.ac.uk/biostudies/studies/S-EPMC5474667biostudies-literatureUnknown6(3)The straightforward and efficient synthesis of complex aza- and carbobicyclic compounds, which are of importance for medicinal chemistry, is a challenge for modern chemical methodology. An unprecedented metal-free six-step domino reaction of aldehydes with malononitrile was presented in our previous study to provide, in a single operation, these bicyclic nitrogen-containing molecules. Presented here is a deeper investigation of this atom-economical domino process by extending the scope of aldehydes, performing post-modifications of domino products, applying bifunctional organocatalysts and comprehensive NMR studies of selected domino products. The thermodynamic aspects of the overall reaction are also demonstrated using DFT methods in conjunction with a semi-empirical treatment of van der ChemistryOpenDeeper Insight into the Six-Step Domino Reaction of Aldehydes with Malononitrile and Evaluation of Antiviral and Antimalarial Activities of the Obtained Bicyclic Products.PMC5474667TS 87/15-1GO 523/16-1TS 87/16-3TS 87/17-12014.019.1ForBIMed-Biomarker in der Infektionsmedizin, grant I1Tsogoeva SBHutterer CFriedrich OLeidenberger MBonisch SParameshwarappa GBauer WKappes BGorling ABock CMMarschall MfalseDeeper Insight into the Six-Step Domino Reaction of Aldehydes with Malononitrile and Evaluation of Antiviral and Antimalarial Activities of the Obtained Bicyclic Products.The straightforward and efficient synthesis of complex aza- and carbobicyclic compounds, which are of importance for medicinal chemistry, is a challenge for modern chemical methodology. An unprecedented metal-free six-step domino reaction of aldehydes with malononitrile was presented in our previous study to provide, in a single operation, these bicyclic nitrogen-containing molecules. Presented here is a deeper investigation of this atom-economical domino process by extending the scope of aldehydes, performing post-modifications of domino products, applying bifunctional organocatalysts and comprehensive NMR studies of selected domino products. The thermodynamic aspects of the overall reaction are also demonstrated using DFT methods in conjunction with a semi-empirical treatment of van der 2017-01-01T00:00:00Z2017 Jun2025-04-04T08:13:06.641Z2019-03-27T02:47:54ZS-EPMC54746672863876910.1002/open.201700005