Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral
and Phenols

k 2021

Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral and Phenols

ŠVESTKA, David, Jan OTEVŘEL and Pavel BOBÁĽ

Basic information

Original name

Asymmetric Organocatalyzed Friedel-Crafts Reaction of Chloral and Phenols

Name in Czech

Asymetrická organokatalyzovaná Friedelova-Craftsova reakce chloralu a fenolů

Authors

ŠVESTKA, David (203 Czech Republic, belonging to the institution), Jan OTEVŘEL (203 Czech Republic, belonging to the institution) and Pavel BOBÁĽ (703 Slovakia, belonging to the institution)

Edition

Student scientific conference MUNI PHARM 2021, 2021

Other information

Language

English

Type of outcome

Prezentace na konferencích

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

RIV identification code

RIV/00216224:14160/21:00123233

Organization unit

Faculty of Pharmacy

ISBN

978-80-210-9870-1

Keywords (in Czech)

enantioselektivní organokatalýza; chinovníkové alkaloidy; trichlormethylkarbinoly

Keywords in English

enantioselective organocatalysis; Cinchona alkaloids; trichloromethyl carbinols

Abstract

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.

Links

MUNI/A/1510/2020, interní kód MU

Name: Vývoj asymetrické organokatalytické syntézy trihalogenmethylkarbinolů

Investor: Masaryk University

Citovat

ŠVESTKA, David, Jan OTEVŘEL and 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 and 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.

Detailed Information on Publication Record