Divergent synthesis from reactions of 2-trifluoromethyl-1,3-conjugated enynes with N-acetylated 2-aminomalonates

Abstract

A simple base mediated reaction of 2-trifluoromethyl-1,3-conjugated enynes with N-acetylated 2-aminomalonates was developed, which could deliver two distinct types of products depending on substrates, i.e. 4-trifluoromethyl pyrrolidine derivatives, or gem-difluoro-1,3-conjugated enyne derivatives. Various functionalized 4-(difluoromethylene)-1,2,3,4-tetrahydropyridines could be obtained in good yields via the gold(i)-catalysed 6-endo-dig cyclization of the corresponding gem-difluoro-1,3-conjugated enynes under mild conditions.

A One-Pot Construction of Halogenated Trifluoromethylated Pyrroles through NXS (X = Br, I) Triggered Cascade

“…Very recently, we reported a silver-catalyzed tandem intermolecular and intramolecular hydroamination reaction of 2-trifluoromethyl-1,3-enynes with primary amines, delivering various ring-trifluoromethylated 3-pyrrolines in good yields (Scheme ). During our mechanistic insight into this tandem reaction, we found that treatment of enyne 1a with benzylamine 2a (2.0 equiv) in chlorobenzene at room temperature in the absence of AgNO 3 catalyst for 45 h, both allenyl amine 3aa and homopropargylic amine 4aa were obtained in 41% and 26% isolated yield, respectively, along with recovery 28% of enyne 1a (eq ).…”

Base-Controlled Divergent Synthesis of Fluorine-Containing Benzo[4,5]imidazo[2,1-b][1,3]thiazines from 2-Mercaptobenzimidazoles and β-CF3-1,3-Enynes

“…Based on the obtained results and previous studies, − plausible mechanisms for this reaction are proposed in Scheme . When DBU is used as the base, deprotonation of the 2-mercaptobenzimidazole 1 gives the nucleophilic bis -anion species Int I .…”

“…For example, Xiao and coworkers demonstrated that β-CF 3 -1,3-enynes with a strong electron-deficient aromatic ring are less prone to undergo the defluorinative reaction pathway in the reaction with Nacetylated 2-aminomalonates. 15 With our continuing interest in trifluoromethyl alkenes, herein we disclose a base-controlled divergent cyclization of 2-mercaptobenzimidazoles and β-CF 3 -1,3-enynes, which could deliver trifluoromethylated and fluorinated benzo [4,5]imidazo [2,1-b][1,3]thiazines selectively by simply varying the base from DBU to KOH (Scheme 1B).…”

“…14 Moreover, the defluorinative cyclizations could also deliver cyclic compounds featuring a gem-difluoromethylene terminus through stepwise S N 2′-type reaction and 6-endo-dig cyclization (Scheme 1A, d). 15 Despite those impressive advances, controlling the reaction pathways by simply changing the reaction conditions to allow access to divergent cyclization products from the same starting materials remains a big challenge, since the reaction path is largely governed by the nature of substrates. For example, Xiao and coworkers demonstrated that β-CF 3 -1,3-enynes with a strong electron-deficient aromatic ring are less prone to undergo the defluorinative reaction pathway in the reaction with Nacetylated 2-aminomalonates.…”

Photoinduced allylic defluorinative alkylation of trifluoromethyl alkenes with Katritzky salts under catalyst- and metal-free conditions

“…On the other hand, a gem -difluoroalkene is a versatile synthetic platform, which can be easily and efficiently transformed into other fluorinated skeletons, such as monofluoroalkenyl, 5 difluoromethylene 6 and trifluoromethyl. 7 Therefore, many useful methods including SN2′ reactions, 8 gem -difluoroolefinations 9 and allylic defluorinative cross-coupling reactions 10 have been established for the construction of gem -difluoroalkenes. Among them, the allylic defluorinative cross-coupling reaction has received considerable attention because of its easily available starting materials, mild conditions, high efficiency, and good functionality tolerance.…”