Asymmetric Organocatalyzed Friedel-Crafts Reaction of
Trihaloacetaldehydes and Phenols

k 2021

Asymmetric Organocatalyzed Friedel-Crafts Reaction of Trihaloacetaldehydes and Phenols

ŠVESTKA, David, Jan OTEVŘEL a Pavel BOBÁĽ

Základní údaje

Originální název

Asymmetric Organocatalyzed Friedel-Crafts Reaction of Trihaloacetaldehydes and Phenols

Autoři

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

Vydání

55th Advances in Organic, Bioorganic and Pharmaceutical Chemistry Liblice 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

Kód RIV

RIV/00216224:14160/21:00123483

Organizační jednotka

Farmaceutická fakulta

Klíčová slova česky

enantioselektivní organokatalýza; chinovníkové alkaloidy; trihalogenmethylkarbinoly

Klíčová slova anglicky

enantioselective organocatalysis; Cinchona alkaloids; trihalomethyl carbinols

Štítky

ÚChL

Změněno: 21. 4. 2022 14:49, Mgr. David Švestka

Anotace

V originále

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.

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 Trihaloacetaldehydes and Phenols. In 55th Advances in Organic, Bioorganic and Pharmaceutical Chemistry Liblice 2021. 2021.

@proceedings{1816422,
   author = {Švestka, David and Otevřel, Jan and Bobáľ, Pavel},
   booktitle = {55th Advances in Organic, Bioorganic and Pharmaceutical Chemistry Liblice 2021},
   keywords = {enantioselective organocatalysis; Cinchona alkaloids; trihalomethyl carbinols},
   language = {eng},
   title = {Asymmetric Organocatalyzed Friedel-Crafts Reaction of Trihaloacetaldehydes and Phenols},
   year = {2021}
}

TY  - CONF
ID  - 1816422
AU  - Švestka, David - Otevřel, Jan - Bobáľ, Pavel
PY  - 2021
TI  - Asymmetric Organocatalyzed Friedel-Crafts Reaction of Trihaloacetaldehydes and Phenols
KW  - enantioselective organocatalysis
KW  - Cinchona alkaloids
KW  - trihalomethyl carbinols
N2  - 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.
ER  -

ŠVESTKA, David, Jan OTEVŘEL a Pavel BOBÁĽ. Asymmetric Organocatalyzed Friedel-Crafts Reaction of Trihaloacetaldehydes and Phenols. In \textit{55th Advances in Organic, Bioorganic and Pharmaceutical Chemistry Liblice 2021}. 2021.

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