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 and Pavel BOBÁĽ

Basic information

Original name

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

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

50th Conference SYNTHESIS AND ANALYSIS OF DRUGS, 2022

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

RIV identification code

RIV/00216224:14160/22:00126749

Organization unit

Faculty of Pharmacy

ISBN

978-80-280-0110-0

Keywords in English

Friedel-Crafts; Cinchona; phenol; trihaloacetaldehyde

Abstract

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.

Links

MUNI/A/1510/2020, interní kód MU

Name: Vývoj asymetrické organokatalytické syntézy trihalogenmethylkarbinolů

Investor: Masaryk University

MUNI/A/1682/2020, interní kód MU

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

Investor: Masaryk University

Citovat

ŠVESTKA, David, Jan OTEVŘEL and 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 and 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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