PERHALOACETALDEHYDES IN THE ENANTIOSELECTIVE ORGANOCATALYZED FRIDEL-CRAFTS ALKYLATION: REACTION CONDITIONS DEVELOPMENT

Kód výsledku v IS VaVaI

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Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

PERHALOACETALDEHYDES IN THE ENANTIOSELECTIVE ORGANOCATALYZED FRIDEL-CRAFTS ALKYLATION: REACTION CONDITIONS DEVELOPMENT

Popis výsledku v původním jazyce

Trihaloacetaldehydes represent useful electrophiles in asymmetric processes that can grant access to many biologically active compounds containing CX3 groups. One of the possibilities for obtaining aromatic trihaloethanols is the asymmetric organocatalyzed Friedel-Crafts reaction between phenol and trihaloacetaldehyde, which represents the subject of our current research. As such, we started with the extensive three-phase catalyst screening. Cinchona alkaloid-based amide derivatives showed the best enantioselectivity in the initial stage of catalyst testing. Improvement of the catalyst structure revealed 3,5-dinitrobenzamide of 9- aminoepicinchonidine as the lead catalytic molecule. Next, a series of optimizations were performed to establish the most suitable reaction conditions. Having the optimal parameters in hand, the reaction between electron-rich phenols and trihaloacetaldehydes or their hemiacetals conveniently provided enantioenriched adducts with good to excellent enantiomeric ratios (up to 99:1) within 12–24 h at 25 °C. The substrate scope included 29 derivatives containing –CF3, –CCl3, –CF2Cl, and –CF2Br groups. Additionally, several stereoretentive downstream transformations of products were identified. This work constitutes the first organocatalyzed method for the synthesis of chiral non-racemic 2,2,2-trihalo-1- hydroxyalkylphenols.

Název v anglickém jazyce

PERHALOACETALDEHYDES IN THE ENANTIOSELECTIVE ORGANOCATALYZED FRIDEL-CRAFTS ALKYLATION: REACTION CONDITIONS DEVELOPMENT

Popis výsledku anglicky

Trihaloacetaldehydes represent useful electrophiles in asymmetric processes that can grant access to many biologically active compounds containing CX3 groups. One of the possibilities for obtaining aromatic trihaloethanols is the asymmetric organocatalyzed Friedel-Crafts reaction between phenol and trihaloacetaldehyde, which represents the subject of our current research. As such, we started with the extensive three-phase catalyst screening. Cinchona alkaloid-based amide derivatives showed the best enantioselectivity in the initial stage of catalyst testing. Improvement of the catalyst structure revealed 3,5-dinitrobenzamide of 9- aminoepicinchonidine as the lead catalytic molecule. Next, a series of optimizations were performed to establish the most suitable reaction conditions. Having the optimal parameters in hand, the reaction between electron-rich phenols and trihaloacetaldehydes or their hemiacetals conveniently provided enantioenriched adducts with good to excellent enantiomeric ratios (up to 99:1) within 12–24 h at 25 °C. The substrate scope included 29 derivatives containing –CF3, –CCl3, –CF2Cl, and –CF2Br groups. Additionally, several stereoretentive downstream transformations of products were identified. This work constitutes the first organocatalyzed method for the synthesis of chiral non-racemic 2,2,2-trihalo-1- hydroxyalkylphenols.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

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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