Enantioselective organocatalyzed trihaloalkylation of activated 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

Enantioselective organocatalyzed trihaloalkylation of activated phenols

Popis výsledku v původním jazyce

Trihaloacetaldehydes represent useful electrophiles in many asymmetric processes that can grant access to a large number of biologically active compounds containing CX3 groups. One of the possibilities to obtain aromatic trihaloethanols is the asymmetric organocatalyzed Friedel-Crafts reaction between phenol and trihaloacetaldehyde, which represented the subject of our current research. As such, we started with the extensive three-phase catalyst screening. Sesamol and chloral were used as substrates in the model reaction. 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 (catalyst load, solvent type, amount of chloral, temperature, and reaction time). 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 27 derivatives containing –CF3, –CCl3, –CF2Cl, and –CF2Br groups, which suggests a reasonable generality of the developed process. 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

Enantioselective organocatalyzed trihaloalkylation of activated phenols

Popis výsledku anglicky

Trihaloacetaldehydes represent useful electrophiles in many asymmetric processes that can grant access to a large number of biologically active compounds containing CX3 groups. One of the possibilities to obtain aromatic trihaloethanols is the asymmetric organocatalyzed Friedel-Crafts reaction between phenol and trihaloacetaldehyde, which represented the subject of our current research. As such, we started with the extensive three-phase catalyst screening. Sesamol and chloral were used as substrates in the model reaction. 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 (catalyst load, solvent type, amount of chloral, temperature, and reaction time). 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 27 derivatives containing –CF3, –CCl3, –CF2Cl, and –CF2Br groups, which suggests a reasonable generality of the developed process. 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

10401 - Organic chemistry

Projekt

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Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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