Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral and Phenols

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

Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral and Phenols

Popis výsledku v původním jazyce

Optically pure trihalogenmethylalcohols are direct precursors for the synthesis of biologically active compounds (e.g., efavirenz, ondacatinib, acetofenate). They could also be transformed by stereospecific reactions to α-amino-, α-hydroxy-, α-fluoroacids, or epoxides, which are important building blocks for the preparation of new chiral nonracemic molecules. One of the possibilities to obtain these aromatic trihalo-genethanols is the asymmetric organocatalyzed Friedel–Crafts reaction of phenol and trihalogenacetal-dehyde, investigated in this project. Accordingly, we prepared 40 organocatalysts that were tested in the model reaction of sesamol and chloral. Cinchona-based amide derivatives showed the best enantioselec-tivity in the preliminary catalyst screening. Additional improvements of the catalyst structure resulted in discovering 3,5-dinitrobenzamide of 9-aminoepicinchonidine as the most convenient molecule. After that, a series of optimization reactions were performed in order to establish the most suitable reaction conditions (catalyst load, solvent type, amount of chloral, temperature, and reaction time). Further, the above catalyst was utilized for the asymmetric Friedel–Crafts reaction of chloral and various electron-rich phenols. High yields and enantiomeric ratios (up to 95:5) of adducts were accomplished within 12–18 h at 25 °C. Our current work represents the first organocatalyzed method for the enantioselective synthesis of this type compounds.

Název v anglickém jazyce

Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral and Phenols

Popis výsledku anglicky

Optically pure trihalogenmethylalcohols are direct precursors for the synthesis of biologically active compounds (e.g., efavirenz, ondacatinib, acetofenate). They could also be transformed by stereospecific reactions to α-amino-, α-hydroxy-, α-fluoroacids, or epoxides, which are important building blocks for the preparation of new chiral nonracemic molecules. One of the possibilities to obtain these aromatic trihalo-genethanols is the asymmetric organocatalyzed Friedel–Crafts reaction of phenol and trihalogenacetal-dehyde, investigated in this project. Accordingly, we prepared 40 organocatalysts that were tested in the model reaction of sesamol and chloral. Cinchona-based amide derivatives showed the best enantioselec-tivity in the preliminary catalyst screening. Additional improvements of the catalyst structure resulted in discovering 3,5-dinitrobenzamide of 9-aminoepicinchonidine as the most convenient molecule. After that, a series of optimization reactions were performed in order to establish the most suitable reaction conditions (catalyst load, solvent type, amount of chloral, temperature, and reaction time). Further, the above catalyst was utilized for the asymmetric Friedel–Crafts reaction of chloral and various electron-rich phenols. High yields and enantiomeric ratios (up to 95:5) of adducts were accomplished within 12–18 h at 25 °C. Our current work represents the first organocatalyzed method for the enantioselective synthesis of this type compounds.

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

2021

Kód důvěrnosti údajů

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