<div class="csl-bib-body">
<div class="csl-entry">Scharinger, F., Weil, M., Schnürch, M., Schroeder, K., & TU Wien. (2024, July 10). <i>ORGANOCATALYTIC DOMINO REACTION AS POTENT TOOL FOR CHIRAL DIAZABICYCLOALKANE SYNTHESIS</i> [Poster Presentation]. 9th EuChemS Chemistry Congress, Dublin, Ireland. http://hdl.handle.net/20.500.12708/207051</div>
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dc.identifier.uri
http://hdl.handle.net/20.500.12708/207051
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dc.description.abstract
Diazabicycloalkanes and pyridazines hold significant importance as diverse nitrogen-containing heterocycles renowned for their broad spectrum of biological activities. These compounds exhibit versatility, finding utility in approved and experimental drugs as well as agrochemicals.1,2 Symmetric diazabicycloalkanes possess a distinctive structure with a condensed bicyclic ring system bridged by two nitrogen atoms. Despite established methods for synthesizing chiral pyridazines,3,4 the one-step synthesis of the more complex condensed diazabicycloalkane remains a persistent challenge. Conventional methods involve a multi-step indirect approach, starting with the preparation of the chiral precursor IM1, followed by annulation to yield the final product P1 (Scheme 1). However, the multi-step synthesis necessitates protecting-group removal and subsequent modifications to enable cyclization.
Our introduced strategy achieves the one-step synthesis of chiral diazabicycloalkanes by delivering the annulated ring system in a single reaction step. This method involves a direct aza-Michael/aldol reaction of enals alongside modified oxopropanamides, establishing the chiral center via iminium-enamine tandem catalysis. Employing simple diphenylethylendiamine frameworks as dual activation organocatalysts effectively engages both substrate and reagent, providing moderate to high yields and high enantioselectivities (ranging from 80-98%). Notably, our approach showcases high functional group tolerance across various enals and allows in situ modification of the product aldehyde motif without compromising enantioselectivity. Furthermore, by adjusting the quantity of acid cocatalyst, we demonstrate the tunability of enantioselectivity and yield, providing multiple optimization avenues for this synthesis method.5
(1) Szucs, T. Cilazapril. Drugs 1991, 41 (Supplement 1), 18–24. https://doi.org/10.2165/00003495-199100411-00005.
(2) Chalem, F.; Farias, P.; Lizarazo, H.; Peña, P. Diftalone: A New Non-Steroidal Anti-Inflammatory Agent: Comparative Study with Phenylbutazone in the Treatment of Rheumatoid Arthritis. J. Int. Med. Res. 1977, 5 (1), 18–25. https://doi.org/10.1177/030006057700500103.
(3) Kiledal, S. A.; Jourdain, R.; Vellalath, S.; Romo, D. Multicomponent Enantioselective Synthesis of Tetrahydropyridazinones Employing Chiral α,β-Unsaturated Acylammonium Salts. Org. Lett. 2021, 23 (17), 6622–6627. https://doi.org/10.1021/acs.orglett.1c02044.
(4) Dey, R.; Kumar, P.; Banerjee, P. Lewis Acid Catalyzed Annulation of Cyclopropane Carbaldehydes and Aryl Hydrazines: Construction of Tetrahydropyridazines and Application Toward a One-Pot Synthesis of Hexahydropyrrolo[1,2- b]Pyridazines. J. Org. Chem. 2018, 83 (10), 5438–5449. https://doi.org/10.1021/acs.joc.8b00332.
(5) Scharinger, F.; Weil, M.; Schnürch, M.; Schröder, K. Synthesis of Chiral Diazabicycloalkanes via Organocatalytic Aza‐Michael/Aldol Reaction. Adv. Synth. Catal. 2023. https://doi.org/10.1002/adsc.202301125.
en
dc.description.sponsorship
European Commission
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dc.language.iso
en
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dc.subject
diazabicycloalkane
en
dc.subject
organocatalysis
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dc.subject
pyridazine
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dc.title
ORGANOCATALYTIC DOMINO REACTION AS POTENT TOOL FOR CHIRAL DIAZABICYCLOALKANE SYNTHESIS
en
dc.type
Presentation
en
dc.type
Vortrag
de
dc.relation.grantno
7465546 - 04/12/2019
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dc.type.category
Poster Presentation
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tuw.project.title
Kontinourliche Umsetzung von CO2 in ionischen Flüssigkeiten
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tuw.researchinfrastructure
Röntgenzentrum
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tuw.researchTopic.id
M6
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tuw.researchTopic.name
Biological and Bioactive Materials
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tuw.researchTopic.value
100
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tuw.publication.orgunit
E163 - Institut für Angewandte Synthesechemie
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tuw.publication.orgunit
E163-03-5 - Forschungsgruppe Nachhaltige organische Synthese und Katalyse
