BENCH-STABLE AND SOLUBLE FORMALDEHYDE SURROGATES IN ASYMMETRIC
HYDROXYMETHYLATION OF ISOINDOLINONES

k 2022

BENCH-STABLE AND SOLUBLE FORMALDEHYDE SURROGATES IN ASYMMETRIC HYDROXYMETHYLATION OF ISOINDOLINONES

ŠVESTKA, David and Jan OTEVŘEL

Basic information

Original name

BENCH-STABLE AND SOLUBLE FORMALDEHYDE SURROGATES IN ASYMMETRIC HYDROXYMETHYLATION OF ISOINDOLINONES

Authors

ŠVESTKA, David (203 Czech Republic, belonging to the institution) and Jan OTEVŘEL (203 Czech Republic, belonging to the institution)

Edition

Student Scientific Conference MUNI Pharm, Doctoral Students 2022, 2022

Other information

Language

English

Type of outcome

Prezentace na konferencích

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14160/22:00126688

Organization unit

Faculty of Pharmacy

ISBN

978-80-280-0105-6

Keywords in English

Enantioselective organocatalysis; isoindolinone; Takemoto catalyst

Změněno: 16/9/2022 15:19, Mgr. David Švestka

Abstract

V originále

The asymmetric cross-aldol reaction with formaldehyde is one of the most efficient carbon chain extension methods. However, performing this type of reaction is not straightforward. Gaseous formaldehyde is a highly reactive and toxic compound. On the other hand, a formalin solution may cause incompatibility issues with many catalytic systems due to the water presence. Finally, the polymeric precursors thereof (para- or metaformaldehyde) are poorly soluble in many organic solvents causing the slow release of the reactive monomer and overall reaction slowdown. For these reasons, research on bench-stable, soluble, and reactive formaldehyde surrogates (“H2C=O cans”) for catalytic reactions is highly desired. The application of formaldehyde releasers in enantioselective hydroxymethylations has not been sufficiently investigated. Therefore, about 20 formaldehyde surrogates were synthesized and evaluated in the asymmetric reaction with model isoindolinone substrate and chiral non-racemic organocatalyst. Screening of our catalyst library revealed that bifunctional molecules containing a basic moiety (particularly the Takemoto-type catalysts) exhibited the best enantioselectivity outcomes. When combined with formaldehyde releasers based on benzotriazole or parabanic acid derivatives, the reactions achieved almost complete conversion (> 96%) and a very good enantiomeric ratio (87:13) in 24 h. This is in sharp contrast with paraformaldehyde, which provided the enantioenriched product in 10% only.

Links

MUNI/IGA/0916/2021, interní kód MU

Name: Asymmetric organocatalyzed hydroxymethylation of isoindolinones

Investor: Masaryk University

Citovat

ŠVESTKA, David and Jan OTEVŘEL. BENCH-STABLE AND SOLUBLE FORMALDEHYDE SURROGATES IN ASYMMETRIC HYDROXYMETHYLATION OF ISOINDOLINONES. In Student Scientific Conference MUNI Pharm, Doctoral Students 2022. 2022. ISBN 978-80-280-0105-6.

@proceedings{2218064,
   author = {Švestka, David and Otevřel, Jan},
   booktitle = {Student Scientific Conference MUNI Pharm, Doctoral Students 2022},
   keywords = {Enantioselective organocatalysis; isoindolinone; Takemoto catalyst},
   language = {eng},
   isbn = {978-80-280-0105-6},
   title = {BENCH-STABLE AND SOLUBLE FORMALDEHYDE SURROGATES IN ASYMMETRIC HYDROXYMETHYLATION OF ISOINDOLINONES},
   year = {2022}
}

TY  - CONF
ID  - 2218064
AU  - Švestka, David - Otevřel, Jan
PY  - 2022
TI  - BENCH-STABLE AND SOLUBLE FORMALDEHYDE SURROGATES IN ASYMMETRIC HYDROXYMETHYLATION OF ISOINDOLINONES
SN  - 9788028001056
KW  - Enantioselective organocatalysis
KW  - isoindolinone
KW  - Takemoto catalyst
N2  - The asymmetric cross-aldol reaction with formaldehyde is one of the most efficient carbon chain extension methods. However, performing this type of reaction is not straightforward. Gaseous formaldehyde is a highly reactive and toxic compound. On the other hand, a formalin solution may cause incompatibility issues with many catalytic systems due to the water presence. Finally, the polymeric precursors thereof (para- or metaformaldehyde) are poorly soluble in many organic solvents causing the slow release of the reactive monomer and overall reaction slowdown. For these reasons, research on bench-stable, soluble, and reactive formaldehyde surrogates (“H2C=O cans”) for catalytic reactions is highly desired. The application of formaldehyde releasers in enantioselective hydroxymethylations has not been sufficiently investigated. Therefore, about 20 formaldehyde surrogates were synthesized and evaluated in the asymmetric reaction with model isoindolinone substrate and chiral non-racemic organocatalyst. Screening of our catalyst library revealed that bifunctional molecules containing a basic moiety (particularly the Takemoto-type catalysts) exhibited the best enantioselectivity outcomes. When combined with formaldehyde releasers based on benzotriazole or parabanic acid derivatives, the reactions achieved almost complete conversion (> 96%) and a very good enantiomeric ratio (87:13) in 24 h. This is in sharp contrast with paraformaldehyde, which provided the enantioenriched product in 10% only.
ER  -

ŠVESTKA, David and Jan OTEVŘEL. BENCH-STABLE AND SOLUBLE FORMALDEHYDE SURROGATES IN ASYMMETRIC HYDROXYMETHYLATION OF ISOINDOLINONES. In \textit{Student Scientific Conference MUNI Pharm, Doctoral Students 2022}. 2022. ISBN~978-80-280-0105-6.

Detailed Information on Publication Record