Organocatalyzed Asymmetric Henry reaction of Fluoroketones.

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

Organocatalyzed Asymmetric Henry reaction of Fluoroketones.

Popis výsledku v původním jazyce

The enantioenriched nitroaldol adducts can serve as the versatile building blocks for syntheses of bioactive compounds, which is the reason for our continuous interest in the area of the asymmetric Henry reaction. In the current work, we have focused on the organocatalyzed asymmetric Henry reaction of nitroalkanes and fluorinated ketones bearing ?-CF3 and ?-CHF2 moieties. The fluorine content of these molecules can improve many of their pharmacodynamic and pharmacokinetic properties, such as electrostatic interactions, steric volume, lipophilicity, metabolic stability, etc. Accordingly, we have prepared and tested a library of 24 chiral auxiliaries and 31 chiral non-racemic organocatalysts. The primary catalyst screening was performed with ?,?,?-trifluoro-acetophenone and nitromethane as the model substrates. The catalyst based on C2-symmetric bianthrylbis(thiourea), which resulted from this screening, was subjected to the series of further optimization reactions to suggest the remaining reaction parameters. Then the catalyst was applied to the asymmetric synthesis of 15 enantioenriched nitroaldols, which provided the good to excellent enantiomeric excesses (67?97 %). The observed results were, in terms of stereoselectivity, comparable with the previously published most enantioselective organocatalysts, however, the complete conversion was reached in up to 6 times shorter reaction time. The robustness of the developed catalytic process has been checked in the four-step asymmetric synthesis of CF3 tethered (S- halostachine analog

Název v anglickém jazyce

Organocatalyzed Asymmetric Henry reaction of Fluoroketones.

Popis výsledku anglicky

The enantioenriched nitroaldol adducts can serve as the versatile building blocks for syntheses of bioactive compounds, which is the reason for our continuous interest in the area of the asymmetric Henry reaction. In the current work, we have focused on the organocatalyzed asymmetric Henry reaction of nitroalkanes and fluorinated ketones bearing ?-CF3 and ?-CHF2 moieties. The fluorine content of these molecules can improve many of their pharmacodynamic and pharmacokinetic properties, such as electrostatic interactions, steric volume, lipophilicity, metabolic stability, etc. Accordingly, we have prepared and tested a library of 24 chiral auxiliaries and 31 chiral non-racemic organocatalysts. The primary catalyst screening was performed with ?,?,?-trifluoro-acetophenone and nitromethane as the model substrates. The catalyst based on C2-symmetric bianthrylbis(thiourea), which resulted from this screening, was subjected to the series of further optimization reactions to suggest the remaining reaction parameters. Then the catalyst was applied to the asymmetric synthesis of 15 enantioenriched nitroaldols, which provided the good to excellent enantiomeric excesses (67?97 %). The observed results were, in terms of stereoselectivity, comparable with the previously published most enantioselective organocatalysts, however, the complete conversion was reached in up to 6 times shorter reaction time. The robustness of the developed catalytic process has been checked in the four-step asymmetric synthesis of CF3 tethered (S- halostachine analog

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30107 - Medicinal chemistry

Projekt

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Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2019

Kód důvěrnosti údajů

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