Organocatalyzed Asymmetric Henry reaction of Fluoroketones.

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62157124%3A16370%2F19%3A43878189" target="_blank" >RIV/62157124:16370/19:43878189 - isvavai.cz</a>

Result on the web

—

DOI - Digital Object Identifier

—

Result language

angličtina

Original language name

Organocatalyzed Asymmetric Henry reaction of Fluoroketones.

Original language description

The enantioenriched nitroaldol adducts can serve as the versatile building blocks for syntheses of bioactive compounds, which is the reason for our continuous interest in the area of the asymmetric Henry reaction. In the current work, we have focused on the organocatalyzed asymmetric Henry reaction of nitroalkanes and fluorinated ketones bearing ?-CF3 and ?-CHF2 moieties. The fluorine content of these molecules can improve many of their pharmacodynamic and pharmacokinetic properties, such as electrostatic interactions, steric volume, lipophilicity, metabolic stability, etc. Accordingly, we have prepared and tested a library of 24 chiral auxiliaries and 31 chiral non-racemic organocatalysts. The primary catalyst screening was performed with ?,?,?-trifluoro-acetophenone and nitromethane as the model substrates. The catalyst based on C2-symmetric bianthrylbis(thiourea), which resulted from this screening, was subjected to the series of further optimization reactions to suggest the remaining reaction parameters. Then the catalyst was applied to the asymmetric synthesis of 15 enantioenriched nitroaldols, which provided the good to excellent enantiomeric excesses (67?97 %). The observed results were, in terms of stereoselectivity, comparable with the previously published most enantioselective organocatalysts, however, the complete conversion was reached in up to 6 times shorter reaction time. The robustness of the developed catalytic process has been checked in the four-step asymmetric synthesis of CF3 tethered (S- halostachine analog

Czech name

—

Czech description

—

Type

O - Miscellaneous

CEP classification

—

OECD FORD branch

30107 - Medicinal chemistry

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2019

Confidentiality

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