Efficient Copper‐Catalyzed Direct Intramolecular Aminotrifluoromethylation of Unactivated Alkenes with Diverse Nitrogen‐Based Nucleophiles

Abstract

A mild, convenient, and step-economical intramolecular aminotrifluoromethylation of unactivated alkenes with a variety of electronically distinct, nitrogen-based nucleophiles in the presence of a simple copper salt catalyst, in the absence of extra ligands, is described. Many different nitrogen-based nucleophiles (e.g., basic primary aliphatic and aromatic amines, sulfonamides, carbamates, and ureas) can be employed in this new aminotrifluoromethylation reaction. The aminotrifluoromethylation process allows straightforward access to diversely substituted CF3-containing pyrrolidines or indolines, in good to excellent yields, through a direct difunctionalization strategy from the respective acyclic starting materials. Mechanistic studies were conducted and a plausible mechanism was proposed.

Cascade Multicomponent Synthesis of Indoles, Pyrazoles, and Pyridazinones by Functionalization of Alkenes

“…The remarkable properties of the fluorine group has resulted in the trifluoromethylation of alkenes recently becoming an important tool to incorporate fluorine into organic compounds. [9,10] However, the application of alkene trifluoromethylation in the synthesis of heterocycles has only been seldom explored and not reported for indoles to date. [10] Herein, we describe alkene trifluoromethylation as an entry point for a regioselective multicomponent cascade synthesis of indole derivatives by Fischer indole synthesis.…”

“…[9,10] However, the application of alkene trifluoromethylation in the synthesis of heterocycles has only been seldom explored and not reported for indoles to date. [10] Herein, we describe alkene trifluoromethylation as an entry point for a regioselective multicomponent cascade synthesis of indole derivatives by Fischer indole synthesis. Furthermore, the developed process was applied to the regioselective synthesis of other nitrogen-containing heterocycles such as pyrazole and dihydropyridazinone derivatives.…”

“…Various oxidants were also screened to improve the yield (entries [10][11][12]. The use of PhI(OAc) 2 and K 2 S 2 O 8 as the oxidant led to traces of the product.…”

Mehrkomponentenkaskade zur Synthese von Indolen, Pyrazolen und Pyridazinonen durch Funktionalisierung von Alkenen

“…[9,10] Allerdings ist die Anwendung der Alken-Trifluormethylierung in der Synthese von Heterocyclen nur sehr wenig erforscht und für Indole bis heute nicht berichtet worden. [9,10] Allerdings ist die Anwendung der Alken-Trifluormethylierung in der Synthese von Heterocyclen nur sehr wenig erforscht und für Indole bis heute nicht berichtet worden.…”

“…Es sollte angemerkt werden, dass Arendiazoniumsalze weithin als Quelle für Arenradikale durch Bruch der C-N-Bindung und Eliminierung von Stickstoff verwendet werden. [10][11][12]. [4e, 14] Nach diesem Ergebnis fuhren wir mit der Optimierung der Reaktionsbedingungen fort (siehe Tabelle 1 und die Hintergrundinformationen).…”