Scharinger, Fabian

2023-10-30T13:41:02Z

2023-10-30T13:41:02Z

2023-07-10

<div class="csl-bib-body"> <div class="csl-entry">Scharinger, F. (2023, July 10). <i>Synthesis of novel heterocycles through unconventional organocatalytic frameworks</i> [Poster Presentation]. 22nd European Symposium on Organic Chemistry (ESOC Ghent 2023), Ghent, Belgium.</div> </div>

http://hdl.handle.net/20.500.12708/189303

Many biologically active molecules and natural products contain nitrogen-containing heterocycles, which are recognized as an important class of compounds with significant biological activity.1,2 Using organocatalysis is a highly effective approach to achieve excellent enantioselectivity in their synthesis.3 We intentionally developed an unconventional organocatalyst derived from amino acids and an achiral phosphoric acid counterpart which resulted in exceptional performance for a range of asymmetric transformations, including epoxidation and aziridination of cyclohexenones. This counteranion enhanced organocatalytic approach was then applied to the synthesis of chiral, N-unprotected octahydroacridines. The tandem mechanism, which involves a Michael addition followed by aldol reaction, proved to be an efficient method for synthesizing these compounds in excellent yields and high enantioselectivity. Due to the sensitive nature of the target structure, we observed that privileged organocatalysts like the cinchona-primary amine with TFA (trifluoracetic acid) or diphenylethylendiamine (DPEN) with TFA exhibited significantly lower performance.4 After discovering the octahydroacridine moiety, we proceeded to develop another aza-Michael aldol tandem reaction to produce novel, highly chiral pyridazine structures. We found that double nitrogen-containing heterocycles can be readily formed from enals and a highly reactive keto-pyridazine amide reagent. Similar to the previous reaction, catalyst screening revealed that privileged catalysts for the asymmetric conversion of enals or ketones were inadequate for this application as well. The only catalyst structure capable of achieving enantioselectivities above 90% with excellent yields was the straightforward one-pot preparation of a mono-substituted DPEN in combination with TFA.

Many biologically active molecules and natural products contain nitrogen-containing heterocycles, which are recognized as an important class of compounds with significant biological activity.1,2 Using organocatalysis is a highly effective approach to achieve excellent enantioselectivity in their synthesis.3 We intentionally developed an unconventional organocatalyst derived from amino acids and an achiral phosphoric acid counterpart which resulted in exceptional performance for a range of asymmetric transformations, including epoxidation and aziridination of cyclohexenones. This counteranion enhanced organocatalytic approach was then applied to the synthesis of chiral, N-unprotected octahydroacridines. The tandem mechanism, which involves a Michael addition followed by aldol reaction, proved to be an efficient method for synthesizing these compounds in excellent yields and high enantioselectivity. Due to the sensitive nature of the target structure, we observed that privileged organocatalysts like the cinchona-primary amine with TFA (trifluoracetic acid) or diphenylethylendiamine (DPEN) with TFA exhibited significantly lower performance.4 After discovering the octahydroacridine moiety, we proceeded to develop another aza-Michael aldol tandem reaction to produce novel, highly chiral pyridazine structures. We found that double nitrogen-containing heterocycles can be readily formed from enals and a highly reactive keto-pyridazine amide reagent. Similar to the previous reaction, catalyst screening revealed that privileged catalysts for the asymmetric conversion of enals or ketones were inadequate for this application as well. The only catalyst structure capable of achieving enantioselectivities above 90% with excellent yields was the straightforward one-pot preparation of a mono-substituted DPEN in combination with TFA.

en

organocatalysis

asymmetric synthesis

phosphoric acids

Synthesis of novel heterocycles through unconventional organocatalytic frameworks

Presentation

Vortrag

Poster Presentation

M6

Biological and Bioactive Materials

100

E163 - Institut für Angewandte Synthesechemie

0000-0001-8690-3785

22nd European Symposium on Organic Chemistry (ESOC Ghent 2023)

Union’s Horizon 2020 research

864991

09-07-2023

13-07-2023

On Site

Event for scientific audience

Ghent

BE

esoc2023.org

Scharinger, Fabian

Single Track

Chemie

Pharmazie, Pharmakologie, Toxikologie

1040

3012

80

20

en

conference poster not in proceedings

none

no Fulltext

Publications

http://purl.org/coar/resource_type/c_18co

E163-03-5 - Forschungsgruppe Nachhaltige organische Synthese und Katalyse

0000-0001-8690-3785

E163-03 - Forschungsbereich Organische und Biologische Chemie