Enantioselective organocatalyzed trihaloalkylation of activated
phenols

k 2022

Enantioselective organocatalyzed trihaloalkylation of activated phenols

ŠVESTKA, David; Jan OTEVŘEL a Pavel BOBÁĽ

Základní údaje

Originální název

Enantioselective organocatalyzed trihaloalkylation of activated phenols

Autoři

ŠVESTKA, David; Jan OTEVŘEL a Pavel BOBÁĽ

Vydání

22nd Tetrahedron Symposium: Catalysis for a Sustainable World, 2022

Další údaje

Jazyk

angličtina

Typ výsledku

Prezentace na konferencích

Obor

10401 Organic chemistry

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14160/22:00126276

Organizační jednotka

Farmaceutická fakulta

Klíčová slova anglicky

Friedel-Crafts; Cinchona; phenol; trihaloacetaldehyde

Změněno: 10. 5. 2023 16:16, JUDr. Sabina Gajdzioková

Anotace

V originále

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.

Návaznosti

MUNI/IGA/0916/2021, interní kód MU

Název: Asymmetric organocatalyzed hydroxymethylation of isoindolinones

Investor: Masarykova univerzita, Asymmetric organocatalyzed hydroxymethylation of isoindolinones

Citovat

ŠVESTKA, David; Jan OTEVŘEL a Pavel BOBÁĽ. Enantioselective organocatalyzed trihaloalkylation of activated phenols. In 22nd Tetrahedron Symposium: Catalysis for a Sustainable World. 2022.

@proceedings{1875166,
   author = {Švestka, David and Otevřel, Jan and Bobáľ, Pavel},
   booktitle = {22nd Tetrahedron Symposium: Catalysis for a Sustainable World},
   keywords = {Friedel-Crafts; Cinchona; phenol; trihaloacetaldehyde},
   language = {eng},
   title = {Enantioselective organocatalyzed trihaloalkylation of activated phenols},
   year = {2022}
}

TY  - CONF
ID  - 1875166
AU  - Švestka, David - Otevřel, Jan - Bobáľ, Pavel
PY  - 2022
TI  - Enantioselective organocatalyzed trihaloalkylation of activated phenols
KW  - Friedel-Crafts
KW  - Cinchona
KW  - phenol
KW  - trihaloacetaldehyde
N2  - 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.
ER  -

ŠVESTKA, David; Jan OTEVŘEL a Pavel BOBÁĽ. Enantioselective organocatalyzed trihaloalkylation of activated phenols. In \textit{22nd Tetrahedron Symposium: Catalysis for a Sustainable World}. 2022.

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