Cobalt-Catalyzed C–H Activation/Annulation of Benzamides with Fluorine-Containing Alkynes: A Route to 3- and 4-Fluoroalkylated Isoquinolinones

Abstract

The C–H activation/annulation reaction of various benzamides with fluoroalkylated alkynes in the presence of a Co­(acac)2·2H2O catalyst proceeded very smoothly to give the corresponding 3- and 4-fluoroalkylated isoquinolinones in excellent yields with approximately 70% regioselectivities. These regioisomers could be successfully separated and obtained in pure form. Major or minor regioisomers were determined as 4- or 3-fluoroalkylated isoquinolinones, respectively, based on X-ray crystallographic analyses.

Cobalt-Catalyzed Cyclization of 2-Bromobenzamides with Carbodiimides: A New Route for the Synthesis of 3-(Imino)isoindolin-1-ones

“…This result was probably caused by the formation of intermediate 1s-A , which was supposed to be formed by the chelation of two nitrogen atoms on substrate 1s . According to the reports, the formation of 1s-A is favorable than that of 1s-A′ [ 11 , 12 , 13 , 19 ], and complex 1s-A will further convert to 1s-B via activation of a C-Br bond. Therefore, the different intermediates resulted in different reaction behavior.…”

“…This five-membered intermediate can easily combine with subsequent steps to create diverse N -heterocycles ( Scheme 1 ). A variety of late-transition-metals have been shown to possess the ability to form this intermediate for further transformations [ 5 , 7 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ], which have been commonly indicated to construct six- or five-membered N -heterocyclic structures via the 1,2- or 1,1-insertion of molecules containing multiple bonds. For those revealed catalysts, the first-row transition-metal complexes exhibit comparably higher economic efficiency, and our continuing studies on cobalt-catalyzed coupling reactions [ 25 ], as well as the experiences in cyclization reactions [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ], encouraged us to attempt the synthesis of diverse N -heterocyclic scaffolds by using the five-membered cobalacycle intermediate and switching different cyclization partners ( Scheme 2 ).…”

Recent advances in transition-metal catalyzed directed C–H functionalization with fluorinated building blocks

“…Very recently, Konno et al reported the preparation of trifluoromethyl substituted isoquinolinones 235 and 236 by coupling of various benzamide 234 and trifluoromethylated alkyne substrates (Scheme 44). 178 Co(acac) 2 ·2H 2 O (10 mol%) as a catalyst, KOAc (2 equiv.) as a base and AgNO 3 (2 equiv.)…”

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

“…Due to its accessibility, it is well explored in catalysis for many fields, such as cycloaddition reactions [175], polymerization [176], and C-C cross-coupling methods [177]. Several biologically active compounds have been obtained through cobalt catalysis [178][179][180] including its application in C-H activation reactions [181][182][183][184][185]. The synthesis of biologically important compounds using C-H activation techniques has been described by Ackermann and co-workers in 2019 [186].…”