PERHALOACETALDEHYDES IN THE ENANTIOSELECTIVE ORGANOCATALYZED
FRIDEL-CRAFTS ALKYLATION: REACTION CONDITIONS DEVELOPMENT

k 2022

PERHALOACETALDEHYDES IN THE ENANTIOSELECTIVE ORGANOCATALYZED FRIDEL-CRAFTS ALKYLATION: REACTION CONDITIONS DEVELOPMENT

ŠVESTKA, David, Jan OTEVŘEL a Pavel BOBÁĽ

Základní údaje

Originální název

PERHALOACETALDEHYDES IN THE ENANTIOSELECTIVE ORGANOCATALYZED FRIDEL-CRAFTS ALKYLATION: REACTION CONDITIONS DEVELOPMENT

Autoři

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

Vydání

50th Conference SYNTHESIS AND ANALYSIS OF DRUGS, 2022

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/00216224:14160/22:00126749

Organizační jednotka

Farmaceutická fakulta

ISBN

978-80-280-0110-0

Klíčová slova anglicky

Friedel-Crafts; Cinchona; phenol; trihaloacetaldehyde

Štítky

rivok, ÚChL

Změněno: 26. 9. 2022 08:16, Mgr. David Švestka

Anotace

V originále

Trihaloacetaldehydes represent useful electrophiles in asymmetric processes that can grant access to many biologically active compounds containing CX3 groups. One of the possibilities for obtaining aromatic trihaloethanols is the asymmetric organocatalyzed Friedel-Crafts reaction between phenol and trihaloacetaldehyde, which represents the subject of our current research. As such, we started with the extensive three-phase catalyst screening. 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. 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 29 derivatives containing –CF3, –CCl3, –CF2Cl, and –CF2Br groups. 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/A/1510/2020, interní kód MU

Název: Vývoj asymetrické organokatalytické syntézy trihalogenmethylkarbinolů

Investor: Masarykova univerzita, Vývoj asymetrické organokatalytické syntézy trihalogenmethylkarbinolů

MUNI/A/1682/2020, interní kód MU

Název: Návrh, syntéza a hodnocení derivátů skupin léčiv s inhibiční enzymatickou aktivitou

Investor: Masarykova univerzita, Návrh, syntéza a hodnocení derivátů skupin léčiv s inhibiční enzymatickou aktivitou

Citovat

ŠVESTKA, David, Jan OTEVŘEL a Pavel BOBÁĽ. PERHALOACETALDEHYDES IN THE ENANTIOSELECTIVE ORGANOCATALYZED FRIDEL-CRAFTS ALKYLATION: REACTION CONDITIONS DEVELOPMENT. In 50th Conference SYNTHESIS AND ANALYSIS OF DRUGS. 2022. ISBN 978-80-280-0110-0.

@proceedings{2220037,
   author = {Švestka, David and Otevřel, Jan and Bobáľ, Pavel},
   booktitle = {50th Conference SYNTHESIS AND ANALYSIS OF DRUGS},
   keywords = {Friedel-Crafts; Cinchona; phenol; trihaloacetaldehyde},
   language = {eng},
   isbn = {978-80-280-0110-0},
   title = {PERHALOACETALDEHYDES IN THE ENANTIOSELECTIVE ORGANOCATALYZED FRIDEL-CRAFTS ALKYLATION: REACTION CONDITIONS DEVELOPMENT},
   year = {2022}
}

TY  - CONF
ID  - 2220037
AU  - Švestka, David - Otevřel, Jan - Bobáľ, Pavel
PY  - 2022
TI  - PERHALOACETALDEHYDES IN THE ENANTIOSELECTIVE ORGANOCATALYZED FRIDEL-CRAFTS ALKYLATION: REACTION CONDITIONS DEVELOPMENT
SN  - 9788028001100
KW  - Friedel-Crafts
KW  - Cinchona
KW  - phenol
KW  - trihaloacetaldehyde
N2  - Trihaloacetaldehydes represent useful electrophiles in asymmetric processes that can grant access to many biologically active compounds containing CX3 groups. One of the possibilities for obtaining aromatic trihaloethanols is the asymmetric organocatalyzed Friedel-Crafts reaction between phenol and trihaloacetaldehyde, which represents the subject of our current research. As such, we started with the extensive three-phase catalyst screening. 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. 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 29 derivatives containing –CF3, –CCl3, –CF2Cl, and –CF2Br groups. 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. PERHALOACETALDEHYDES IN THE ENANTIOSELECTIVE ORGANOCATALYZED FRIDEL-CRAFTS ALKYLATION: REACTION CONDITIONS DEVELOPMENT. In \textit{50th Conference SYNTHESIS AND ANALYSIS OF DRUGS}. 2022. ISBN~978-80-280-0110-0.

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