k 2022

Enantioselective organocatalyzed trihaloalkylation of activated phenols

ŠVESTKA, David, Jan OTEVŘEL and Pavel BOBÁĽ

Basic information

Original name

Enantioselective organocatalyzed trihaloalkylation of activated phenols

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

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

Other information

Language

English

Type of outcome

Prezentace na konferencích

Field of Study

10401 Organic chemistry

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14160/22:00126276

Organization unit

Faculty of Pharmacy

Keywords in English

Friedel-Crafts; Cinchona; phenol; trihaloacetaldehyde
Změněno: 10/5/2023 16:16, JUDr. Sabina Krejčiříková

Abstract

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.

Links

MUNI/IGA/0916/2021, interní kód MU
Name: Asymmetric organocatalyzed hydroxymethylation of isoindolinones
Investor: Masaryk University