Asymmetric Organocatalyzed Friedel-Crafts Reaction of Trihaloacetaldehydes 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 Trihaloacetaldehydes and Phenols

Popis výsledku v původním jazyce

The trihalogenmethylalcohol moiety is constituent of many nonracemic biologically active compounds (e.g., efavirenz, acetofenate, muironolide A, sigillin A). Optically pure trihalogenmethyl carbinols could be also important building blocks for the preparation of new chiral molecules. One of the possibilities to obtain these aromatic trihalogenethanols is Friedel-Crafts reaction of phenol and trihalogenacetaldehyde. We started with three phase-screening of 40 organocatalysts, that were tested in model reaction of sesamol and chloral. Cinchona alkaloid-based amide derivatives showed the best enantioselectivity. Improvement of the catalyst structure resulted in the discovery of 3,5-dinitrobenzamide of 9-amino-epi-cinchonidine as the most convenient molecule. After that, the series of optimization reactions were performed to establish the most suitable conditions (catalyst load, solvent type, amount of chloral, temperature, and reaction time). The catalyst was utilized for the asymmetric Friedel-Crafts reaction of electron-rich phenols and trihalogenacetaldehydes or their hemiacetals. The substrate scope included more than 20 derivatives containing –CF3, –CCl3, –CF2Cl or –CF2Br groups. A high enantiomeric ratio (up to 97.5:2.5) of adducts was accomplished at 25 °C in 12–24 h. Several transformations of resulting molecules were provided without loss of enantiomeric excess. Our current work represents the first organocatalyzed method for the enantioselective synthesis of this type.

Název v anglickém jazyce

Asymmetric Organocatalyzed Friedel-Crafts Reaction of Trihaloacetaldehydes and Phenols

Popis výsledku anglicky

The trihalogenmethylalcohol moiety is constituent of many nonracemic biologically active compounds (e.g., efavirenz, acetofenate, muironolide A, sigillin A). Optically pure trihalogenmethyl carbinols could be also important building blocks for the preparation of new chiral molecules. One of the possibilities to obtain these aromatic trihalogenethanols is Friedel-Crafts reaction of phenol and trihalogenacetaldehyde. We started with three phase-screening of 40 organocatalysts, that were tested in model reaction of sesamol and chloral. Cinchona alkaloid-based amide derivatives showed the best enantioselectivity. Improvement of the catalyst structure resulted in the discovery of 3,5-dinitrobenzamide of 9-amino-epi-cinchonidine as the most convenient molecule. After that, the series of optimization reactions were performed to establish the most suitable conditions (catalyst load, solvent type, amount of chloral, temperature, and reaction time). The catalyst was utilized for the asymmetric Friedel-Crafts reaction of electron-rich phenols and trihalogenacetaldehydes or their hemiacetals. The substrate scope included more than 20 derivatives containing –CF3, –CCl3, –CF2Cl or –CF2Br groups. A high enantiomeric ratio (up to 97.5:2.5) of adducts was accomplished at 25 °C in 12–24 h. Several transformations of resulting molecules were provided without loss of enantiomeric excess. Our current work represents the first organocatalyzed method for the enantioselective synthesis of this type.

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