ENANTIOSELECTIVE CATALYSIS FOR THE SYNTHESIS OF 1-SUBSTITUTED-2,2,2-TRIFLUOROETHYLAMINES

1-Substituted-2,2,2-trifluoroethylamines have emerged as structurally distinct and pharmacologically potent motifs in modern drug design, contributing to enhanced metabolic stability, target selectivity, and bioactivity across various therapeutic classes. This review provides a comprehensive account...

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Дата:2026
Автори: Wzorek, Alicja, Ono, Taizo, Baecker, Daniel, Zhang, Wei, Soloshonok, Vadim
Формат: Стаття
Мова:Англійська
Опубліковано: V.I.Vernadsky Institute of General and Inorganic Chemistry 2026
Онлайн доступ:https://ucj.org.ua/index.php/journal/article/view/761
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Назва журналу:Ukrainian Chemistry Journal

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Ukrainian Chemistry Journal
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author Wzorek, Alicja
Ono, Taizo
Baecker, Daniel
Zhang, Wei
Soloshonok, Vadim
author_facet Wzorek, Alicja
Ono, Taizo
Baecker, Daniel
Zhang, Wei
Soloshonok, Vadim
author_sort Wzorek, Alicja
baseUrl_str
collection OJS
datestamp_date 2026-03-18T15:28:22Z
description 1-Substituted-2,2,2-trifluoroethylamines have emerged as structurally distinct and pharmacologically potent motifs in modern drug design, contributing to enhanced metabolic stability, target selectivity, and bioactivity across various therapeutic classes. This review provides a comprehensive account of their catalytic enantioselective synthesis, encompassing chiral auxiliary-based methods and a wide array of asymmetric catalytic strategies — including hydrogenation, [1,3]-proton shift reactions, nucleophilic additions, and cycloadditions. Emphasis is placed on the stereochemical outcomes achieved with ruthenium, palladium, phosphoric acid, borane, and squaramide-based catalysts, many of which routinely deliver an enantiomeric excess (ee) exceeding 90–99%. Despite these advances, the phenomenon of self-disproportionation of enantiomers (SDE) remains critically underreported, casting doubt on the veracity of ee values in the literature. This review highlights the pronounced SDE behavior of fluorinated amines and underscores the need for rigorous stereochemical validation. By integrating synthetic innovation with epistemic scrutiny, this work aims to guide future research toward more reliable, efficient, and stereochemically sound methodologies for the synthesis of fluorinated amine derivatives.
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spelling oai:ojs2.1444248.nisspano.web.hosting-test.net:article-7612026-03-18T15:28:22Z ENANTIOSELECTIVE CATALYSIS FOR THE SYNTHESIS OF 1-SUBSTITUTED-2,2,2-TRIFLUOROETHYLAMINES Wzorek, Alicja Ono, Taizo Baecker, Daniel Zhang, Wei Soloshonok, Vadim fluorinated amines, catalytic enantioselective synthesis, medicinal chemistry, self-disproportionation of enantiomers, epistemic scrutiny. 1-Substituted-2,2,2-trifluoroethylamines have emerged as structurally distinct and pharmacologically potent motifs in modern drug design, contributing to enhanced metabolic stability, target selectivity, and bioactivity across various therapeutic classes. This review provides a comprehensive account of their catalytic enantioselective synthesis, encompassing chiral auxiliary-based methods and a wide array of asymmetric catalytic strategies — including hydrogenation, [1,3]-proton shift reactions, nucleophilic additions, and cycloadditions. Emphasis is placed on the stereochemical outcomes achieved with ruthenium, palladium, phosphoric acid, borane, and squaramide-based catalysts, many of which routinely deliver an enantiomeric excess (ee) exceeding 90–99%. Despite these advances, the phenomenon of self-disproportionation of enantiomers (SDE) remains critically underreported, casting doubt on the veracity of ee values in the literature. This review highlights the pronounced SDE behavior of fluorinated amines and underscores the need for rigorous stereochemical validation. By integrating synthetic innovation with epistemic scrutiny, this work aims to guide future research toward more reliable, efficient, and stereochemically sound methodologies for the synthesis of fluorinated amine derivatives. V.I.Vernadsky Institute of General and Inorganic Chemistry 2026-01-25 Article Article Organic chemistry Органическая xимия Органічна xімія application/pdf https://ucj.org.ua/index.php/journal/article/view/761 10.33609/2708-129X.91.12.2025.33-72 Ukrainian Chemistry Journal; Vol. 91 No. 12 (2025): Ukrainian Chemistry Journal; 33-72 Украинский химический журнал; Том 91 № 12 (2025): Ukrainian Chemistry Journal; 33-72 Український хімічний журнал; Том 91 № 12 (2025): Ukrainian Chemistry Journal; 33-72 2708-129X 2708-1281 en https://ucj.org.ua/index.php/journal/article/view/761/396
spellingShingle Wzorek, Alicja
Ono, Taizo
Baecker, Daniel
Zhang, Wei
Soloshonok, Vadim
ENANTIOSELECTIVE CATALYSIS FOR THE SYNTHESIS OF 1-SUBSTITUTED-2,2,2-TRIFLUOROETHYLAMINES
title ENANTIOSELECTIVE CATALYSIS FOR THE SYNTHESIS OF 1-SUBSTITUTED-2,2,2-TRIFLUOROETHYLAMINES
title_full ENANTIOSELECTIVE CATALYSIS FOR THE SYNTHESIS OF 1-SUBSTITUTED-2,2,2-TRIFLUOROETHYLAMINES
title_fullStr ENANTIOSELECTIVE CATALYSIS FOR THE SYNTHESIS OF 1-SUBSTITUTED-2,2,2-TRIFLUOROETHYLAMINES
title_full_unstemmed ENANTIOSELECTIVE CATALYSIS FOR THE SYNTHESIS OF 1-SUBSTITUTED-2,2,2-TRIFLUOROETHYLAMINES
title_short ENANTIOSELECTIVE CATALYSIS FOR THE SYNTHESIS OF 1-SUBSTITUTED-2,2,2-TRIFLUOROETHYLAMINES
title_sort enantioselective catalysis for the synthesis of 1-substituted-2,2,2-trifluoroethylamines
topic_facet fluorinated amines
catalytic enantioselective synthesis
medicinal chemistry
self-disproportionation of enantiomers
epistemic scrutiny.
url https://ucj.org.ua/index.php/journal/article/view/761
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