Coupling of Heteroaryl Halides with Chlorodifluoroacetamides and Chlorodifluoroacetate by Nickel Catalysis

Abstract

A nickel‐catalyzed cross‐coupling of heteroaryl halides with chlorodifluoroacetamides and chlorodifluoroacetate has been developed. The combination of NiCl2 ⋅ DME with 4,4′‐diNon‐bpy, co‐ligand PPh3, and additive LiCl renders the catalytic system efficient for the synthesis of medicinal interest heteroaryldifluoroacetamides. The application of the method leads to short and highly efficient synthesis of biologically active molecules, providing a facile route for applications in medicinal chemistry and agrochemistry.

Nickel-Catalyzed Reductive Dicarbofunctionalizations of Alkenes for the Synthesis of Difluorocarbonyl Oxindoles and Isoquinoline-1,3-diones

“…Subsequently, the attempt of increasing or decreasing the reaction temperature would reduce the reaction yield significantly (entries 2 and 17–19). Since the ligand-combination strategy could enhance the efficiency of this kind of reaction, further attempts on screening the various phosphine ligands were tried (see section 1.1 in the Supporting Information), and the experimental results showed that the mixture of DPPE and L1 as co-ligands would improve the reaction yield to 72% (entry 20). The absence of either N -ligands or P -ligands would decrease the reaction yield (entries 3 and 20 in Table and entry 9 in Supporting Information, section 1.1).…”

“…Afterward, with the assistance of Mn-mediated reduction, a more nucleophilic σ-alkyl-Ni(I) complex C is furnished, followed by a second oxidative addition with 2-chloro-2,2-difluorocompounds 2 to form Ni(III) species D via a single-electron-transfer (SET) pathway . In this process, MgCl 2 plays a key role in activating 2-chloro-2,2-difluoro compounds 2 , thereby promoting the oxidative addition process. Reductive elimination of complex D furnishes the desired product 3 , together with a Ni(I) species, followed by the reduction reaction involving Mn(0) to regenerate catalytically active Ni(0), regenerating the catalytic cycle (Scheme a).…”

A Sustainable Access Route to Carbazoles via C–H/C–H Oxidative Functionalization/Cyclization of Arylamines

“…Within N -heterocyclic compounds, the carbazole scaffold emerged prominently, serving as a pivotal motif in various biologically relevant natural products and approved pharmaceuticals. The presence of the carbazole unit frequently correlates with diverse biological activities, leading to its extensive utilization across multiple applications, such as anticancer, antibacterial, antimicrobial, anti-inflammatory, and antiviral functions (see Figure A). − Beyond its biological significance, carbazole derivatives exhibit remarkable properties, including effective photoconductivity, photoreactivity, low ionization potentials, and luminescence, rendering them indispensable as building blocks for materials capable of carrying charges and emitting light (see Figure B). − Considering the numerous applications of carbazole, it is also obvious that considerable efforts have been devoted to developing effective synthetic methodologies to access this privileged scaffold. Traditional methods include the Fisher–Borsche synthesis, − the Graebe–Ullmann synthesis, , or the Cadogan cyclization. , …”