Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral
and Phenols

k 2021

Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral and Phenols

ŠVESTKA, David, Jan OTEVŘEL a Pavel BOBÁĽ

Základní údaje

Originální název

Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral and Phenols

Název česky

Asymetrická organokatalyzovaná Friedelova-Craftsova reakce chloralu a fenolů

Autoři

ŠVESTKA, David (203 Česká republika, domácí), Jan OTEVŘEL (203 Česká republika, domácí) a Pavel BOBÁĽ (703 Slovensko, domácí)

Vydání

Student scientific conference MUNI PHARM 2021, 2021

Další údaje

Jazyk

angličtina

Typ výsledku

Prezentace na konferencích

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Kód RIV

RIV/00216224:14160/21:00123233

Organizační jednotka

Farmaceutická fakulta

ISBN

978-80-210-9870-1

Klíčová slova česky

enantioselektivní organokatalýza; chinovníkové alkaloidy; trichlormethylkarbinoly

Klíčová slova anglicky

enantioselective organocatalysis; Cinchona alkaloids; trichloromethyl carbinols

Štítky

ÚChL

Změněno: 20. 4. 2022 17:34, Mgr. David Švestka

Anotace

V originále

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.

Návaznosti

MUNI/A/1510/2020, interní kód MU

Název: Vývoj asymetrické organokatalytické syntézy trihalogenmethylkarbinolů

Investor: Masarykova univerzita, Vývoj asymetrické organokatalytické syntézy trihalogenmethylkarbinolů

Citovat

ŠVESTKA, David, Jan OTEVŘEL a Pavel BOBÁĽ. Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral and Phenols. In Student scientific conference MUNI PHARM 2021. 2021. ISBN 978-80-210-9870-1.

@proceedings{1809477,
   author = {Švestka, David and Otevřel, Jan and Bobáľ, Pavel},
   booktitle = {Student scientific conference MUNI PHARM 2021},
   keywords = {enantioselective organocatalysis; Cinchona alkaloids; trichloromethyl carbinols},
   language = {eng},
   isbn = {978-80-210-9870-1},
   title = {Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral and Phenols},
   url = {https://www.pharm.muni.cz/veda-a-vyzkum/svk/2021/sbornik-abstrakt},
   year = {2021}
}

TY  - CONF
ID  - 1809477
AU  - Švestka, David - Otevřel, Jan - Bobáľ, Pavel
PY  - 2021
TI  - Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral and Phenols
SN  - 9788021098701
KW  - enantioselective organocatalysis
KW  - Cinchona alkaloids
KW  - trichloromethyl carbinols
UR  - https://www.pharm.muni.cz/veda-a-vyzkum/svk/2021/sbornik-abstrakt
N2  - 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.
ER  -

ŠVESTKA, David, Jan OTEVŘEL a Pavel BOBÁĽ. Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral and Phenols. In \textit{Student scientific conference MUNI PHARM 2021}. 2021. ISBN~978-80-210-9870-1.

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