Solvent-Dependent Selective Synthesis of CF₃-Tethered Indazole Derivatives Based on Multiple Bond Activations

Abstract

Presented herein is a solvent-dependent selective synthesis of CF3-tethered indazole derivatives via the cascade reactions of 1-arylpyrazolidinones with trifluoromethyl ynones. Mechanistically, the formation of the title products involves cascade N–H/C–H/C–N/C–C bond cleavage along with pyrazole ring formation and pyrazolidinone ring opening. For the formation of a pyrazole scaffold, 1-phenylpyrazolidinone acts as a C2N2 synthon, while trifluoromethyl ynone serves as a C1 synthon. Meanwhile, trifluoromethyl ynone also acts as an enol unit to facilitate the ring opening of the pyrazolidinone ring and provide a trifluoropropenoxy fragment via cleavage of the alkynyl triple bond and migration of the cleaved moiety. When the reaction was run in trifluoroethanol instead of DCE, it selectively afforded indazole derivatives tethered with a trifluoroethoxy moiety through in situ transesterification. To our knowledge, this is the first synthesis of CF3-tethered indazole derivatives via concurrent alkynyl activation, pyrazole formation, and CF3 migration.

Synthesis of 1,7-Fused Indolines Tethered with Spiroindolinone Based on C–H Activation Strategy with Air as a Sustainable Oxidant

“…In the past several years, our group has committed to developing more robust synthetic methods based on CHA-initiated cascade reactions. As a continuation of our interest in this regard , and in view of the rich reactivity shown by indolin-1-yl­(aryl)­methanimine and diazo oxindole, we sought to explore the CHA reaction between them. It was initially conceived that they might first undergo a C­(sp 2 )–H bond alkylation to give intermediate A , which then would take part in an intramolecular condensation to give polycyclic indoline derivative B (Scheme h).…”

Origin of Ligand and Acid Effects on the Pd-Catalyzed Regiodivergent Coupling Reaction of Indazoles and Isoprene: A DFT Study

“…Previous findings have shown that both rhodium and palladium could promote the coupling of Nsubstituted indazole with allenes for the synthesis of medicinally important targets. 10,11 However, due to the competitive nucleophilic sites between the N 1 and N 2 of indazoles, a mixture of N 1 -or N 2 -isomers is delivered normally under basic conditions. 12,13 Despite the fact that significant advances have been achieved in these pioneering works, the discovery of efficient catalysis for the selective N-allylation of indazoles is very limited.…”

“…Indazoles are important building blocks found in various pharmaceuticals and biologically important molecules due to their biological and chemical activities. − Given their importance as privileged scaffolds in medicinal chemistry, diversely substituted indazole derivatives with different functional groups have received significant attention in recent years, and a large number of synthetic methodologies available in the literature for the functionalization of indazoles have been extensively studied. − The alkylation of indazoles represents one of the most efficient methods in terms of atom- and step-economy. , The transition metal catalyst has been designed as an effective tool for controllable selective functionalization in the alkylation of indazoles. Previous findings have shown that both rhodium and palladium could promote the coupling of N-substituted indazole with allenes for the synthesis of medicinally important targets. , However, due to the competitive nucleophilic sites between the N 1 and N 2 of indazoles, a mixture of N 1 - or N 2 -isomers is delivered normally under basic conditions. , Despite the fact that significant advances have been achieved in these pioneering works, the discovery of efficient catalysis for the selective N-allylation of indazoles is very limited. , Therefore, understanding how to obtain the desired product by regulating the competition for nucleophilic sites between the N 1 and N 2 positions of indazole is crucial for its development in this field. ,, …”

Synthesis of O-Heterocycle Spiro-Fused Cyclopentaquinolinones and Cyclopentaindenes through Visible Light-Induced Radical Cyclization Reactions

“…Among a wide variety of reactions developed in this regard, visible light-induced cascade reactions leading to the formation of polycyclic skeletons starting from simple acyclic substrates are particularly attractive. As a continuation of our own interest in the development of novel methods for the synthesis of spiro/fused heterocyclic compounds, , we recently initiated a study on the reaction of N -( o -ethynylaryl)­acrylamides with O -heterocycles under photo-redox catalysis. Based on this reaction, we were able to establish an efficient and sustainable method for the preparation of O -heterocycle spiro-fused cyclopentaquinolinone derivatives.…”