Visible Light Promotes Cascade Trifluoromethylation/Cyclization, Leading to Trifluoromethylated Polycyclic Quinazolinones, Benzimidazoles and Indoles

Abstract

Efficient visible-light-induced radical cascade trifluoromethylation/cyclization of inactivated alkenes with CF3Br, which is a nonhygroscopic, noncorrosive, cheap and industrially abundant chemical, was developed in this work, producing trifluoromethyl polycyclic quinazolinones, benzimidazoles and indoles under mild reaction conditions. The method features wide functional group compatibility and a broad substrate scope, offering a facile strategy to pharmaceutically produce valuable CF3-containing polycyclic aza-heterocycles.

Photocatalytic Cyclization Cascades by Radical Relay toward Pyrrolo[1,2-a]indoles: Synthesis, Mechanism, and Application

“…The merger of radical addition with oxidative radical relay (ORR) has opened a new door to the rapid construction of high-value and complex molecular architectures in the field of organic synthetic chemistry. − In this regard, the radical addition-based ORR process usually employs metal catalysis to relocate radical characters in relay. − Among them, various metals, including copper, nickel, iron, iridium, etc., served as efficient catalysts. Considering the prevalence of pyrrolo­[1,2- a ]­indoles in biologically active compounds and pharmaceutical agents (Scheme ), − the radical addition-based ORR process is of high efficiency for enabling the cyclization cascade of unactivated N -alkene-linked indoles to provide pyrrolo­[1,2- a ]­indoles. − Of note, Zhang and co-workers have developed a Cu-catalyzed trifluoromethyl radical relay for the oxidative cyclization cascade of N -(1-butenyl)­indoles with Togni’s reagent . In these reactions, by following the metal-catalyzed ORR process, a SET oxidation via radical-polar-crossover (RPC) happened to the resulting radical species A, − which was generally ascribed to the formation of the final product pyrrolo­[1,2- a ]­indoles (Scheme ).…”

Electrochemically mediated fluoroalkylation/cyclization of unactivated alkenes: synthesis of polycyclic benzimidazoles containing a CF3 group

“…In this regard, the introduction of trifluoromethyl into drug candidates is a common research strategy in the field of pharmaceutical chemistry. Overall, the common reagents used to introduce trifluoromethyl are Ruppert's reagent, 2 Togni's reagent, 3 Langlois' reagent, 4 Umemoto's reagent, 5 and so on, the traditional process of which inevitably uses oxidizing or reducing reagents and generates waste that is harmful to the environment. 6 Therefore, the development of sustainable and efficient methods for the practical introduction of a CF 3 group into various molecular structures has received increasing attention.…”

Visible light-enabled synthesis of phosphorylated indolizine and pyridoindole derivatives via HAT-mediated radical cascade cyclization

“…In general, these radicals are mainly generated via a single electron transfer (SET) process by releasing halogen anions. [28][29][30][31][32][33] In addition, sulfinates are suitable radical precursors to produce difluorosubstituted carbon-centered radicals through the oxidation of an excited photocatalyst by releasing sulfur dioxide. 34 Similarly, in order to construct the valuable phosphonates bearing the tetrahydroindolizine skeleton, the phosphinoyl radical should be generated from H-phosphonates through an oxidation process.…”