General Synthesis of N-Trifluoromethyl Compounds with N-Trifluoromethyl Hydroxylamine Reagents.
J Am Chem Soc
; 144(4): 1962-1970, 2022 02 02.
Article
en En
| MEDLINE
| ID: mdl-35045700
ABSTRACT
N-CF3 compounds constitute valuable targets in medicinal chemistry. Extensive studies have been reported for the preparation of N-CF3 compounds through fluorination and trifluoromethylation of N-containing compounds. The development of new synthetic methods from abundant and easily available substrates is highly desirable but still challenging. Herein, we report the design and synthesis of novel N-Cbz- and N-Boc-N-trifluoromethyl hydroxylamine reagents by silver-mediated oxidative trifluoromethylation. These reagents have been successfully applied to the direct incorporation of a NCF3 moiety into the commonly used unsaturated substrates under photoredox catalysis. This protocol enables the efficient and regioselective C-H trifluoromethylamination of various (hetero)arenes, including complex bioactive molecules. Furthermore, a variety of alkenes, dienes, and isonitriles undergo tandem trifluoromethylamination/functionalization delivering structurally diverse N-trifluoromethyl aliphatic and heteroaromatic amines. Notably, previously unknown cyclic N-CF3 compounds including N-CF3 oxazolidinones and oxazolones were conveniently prepared with N-Boc-N-trifluoromethyl hydroxylamine reagents. Furthermore, diversification of the resulting α-trifluoromethylamino ketones afforded the largely underexplored N-alkenyl- and N-alkynyl-N-CF3 compounds.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
J Am Chem Soc
Año:
2022
Tipo del documento:
Article
País de afiliación:
China