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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14160%2F22%3A00126688" target="_blank" >RIV/00216224:14160/22:00126688 - isvavai.cz</a>

Výsledek na webu

—

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 (&gt; 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 (&gt; 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.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů