Enantioselective organocatalyzed trihaloalkylation of activated phenols

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14160%2F22%3A00126276" target="_blank" >RIV/00216224:14160/22:00126276 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Enantioselective organocatalyzed trihaloalkylation of activated phenols

Original language description

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.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10401 - Organic chemistry

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů