Aminoquinoline-Based Tridentate (NNN)-Copper Catalyst for C-N Bond-Forming Reactions from Aniline and Diazo Compounds.

A new tridentate Cu2+ complex based on (E)-1-(pyridin-2-yl)-N-(quinolin-8-yl)methanimine (PQM) was generated and characterized to support the activation of diazo compounds for the formation of new C-N bonds. This neutral Schiff base ligand was structurally characterized to coordinate with copper(II) in an equatorial fashion, yielding a distorted octahedral complex. Upon characterization, this copper(II) complex was used to catalyze an efficient and cost-effective protocol for C-N bond formation between N-nucleophiles and copper carbene complexes arising from the activation of diazo carbonyl compounds. A substrate scope of approximately 15 different amine-based substrates was screened, yielding 2° or 3° amine products with acceptable to good yields under mild reaction conditions. Reactivity towards phenol and thiophenol were also screened, showing relatively weak C-O or C-S bond formation under optimized conditions.

Three water-soluble copper(II) N-heterocyclic carbene complexes: toward copper-catalyzed ketone reduction under sustainable conditions.

A series of tridentate copper(II) N-heterocyclic carbene (NHC) complexes with imidazole, benzimidazole, and 5,6-dimethylbenzimidazole azole rings were synthesized and comprehensively characterized via X-ray crystallography, ESI-MS, cyclic voltammetry, and UV-Vis and EPR spectroscopic studies. These complexes were then utilized for the optimization of ketone reduction under sustainable conditions using 2-acetylpyridine and phenylsilane. The relationships between product formation, temperature, reaction time, and catalyst loading for the hydrogenation reactions are covered in detail. Reduction of eighteen different aliphatic, cyclic, and aromatic ketones were demonstrated, which were compatible to produce the corresponding products in moderate to good yields. These systems were used to develop related DNA-hybrid catalytic systems, but only supported weak enantioselectivity. Further thermodynamic experiments showed Cu-NHC complexes did not demonstrate specific binding to DNA, which is consistent with their limited selectivity.

Copper complexes for the chemoselective N-arylation of arylamines and sulfanilamides via Chan-Evans-Lam cross-coupling.

Copper(II) complexes with tridentate NNN-ligands were utilized for Chan-Evans-Lam (CEL) cross-coupling reactions to enable the N-arylation of multifarious N-nucleophiles through the activation of aryl boronic acids. A condition-specific methodology was developed to chemoselectively target the amine versus sulfonamide N-arylation of 4-aminobenzenesulfonamide using new catalysts. Two different pyridine-based ligands and corresponding copper(II) complexes were characterized using 1H and 13C-NMR, FTIR, and UV-vis spectroscopy, HRMS, single-crystal X-ray diffraction, and cyclic voltammetry. Solvent and base-controlled cross-coupling reactions were observed, which led to the optimization of selective conditions for targeted C-N bond formation of sulfanilamides. Beyond the chemoselective processes reported here, a breadth of N-nucleophiles including sulfanilamides and arylamines were screened for arylation by this CEL catalyst.

Sodium Trifluoroacetate mediated Copper-Catalyzed aza-Michael addition of α,ß-unsaturated olefins with aromatic amines.

We present a sodium trifluoroacetate (CF3CO2Na) mediated copper-catalyzed aza-Michael addition of aromatic amines with activated olefins under mild, aqueous reaction conditions. This simplistic protocol employs a copper catalyst (10 mol%) and water as solvent. This transformation occurs precisely with aromatic substituted amines containing both electron-donating (EDG) and electron-withdrawing (EWG) groups. A broad range of substrates were tested under the optimized conditions, which are producing good to moderate yields.

Cu-Catalyzed Chan-Evans-Lam Coupling Reactions of 2-Nitroimidazole with Aryl Boronic Acids: An Effort toward New Bioactive Agents against S.†pneumoniae.

The coupling of phenylboronic acids with poorly-activated imidazoles is studied as a model system to explore the use of copper-catalyzed Chan-Evans-Lam (CEL) coupling for targeted C-N bond forming reactions. Optimized CEL reaction conditions are reported for four phenanthroline-based ligand systems, where the ligand 4,5-diazafluoren-9-one (dafo, L2) with 1 molar equivalent of potassium carbonate yielded the highest reactivity. The substrate 2-nitroimidazole (also known as azomycin) has documented antimicrobial activity against a range of microbes. Here N-arylation of 2-nitroimidazole with a range of aryl boronic acids has been successfully developed by copper(II)-catalyzed CEL reactions. Azomycin and a range of newly arylated azomycin derivatives were screened against S. pneumoniae, where 1-(4-(benzyloxy)phenyl)-2-nitro-1H-imidazole (3d) was demonstrated to have a minimal inhibition concentration value of 3.3 µg/mL.

TfOH-promoted Classical Nazarov-type Cyclization of Benzofulvenes: Synthesis of Polycyclic 5H,10'H-spiro[benzo[k]phenanthridine-5,6'-dibenzopentalenes].

The reaction of o-benzofulvene with TfOH leads to intramolecular cyclization through novel C-C and C-N bond formation, resulting in the formation of 5H,10'H-spiro[benzo[k]phenanthridine-5,6'-dibenzopentalene]. This protocol provides a new molecular framework with reasonable to excellent yields and tolerates various electron-withdrawing/donating substituents. This method yields diastereoselectivity of up to >20:1. Furthermore, it is free of bases, oxidants, and metals and proceeds under mild reaction conditions, which are favorable for synthetic organic chemistry.

Pd-Catalyzed Redox-Neutral C-N Coupling Reaction of Iminoquinones with Electron-Deficient Alkenes without External Oxidants: Access of Tertiary (E)-Enamines and Application to the Synthesis of Indoles and Quinolin-4-ones.

A novel and efficient reductive N-alkenylation of iminoquinones with electron-deficient olefins has been successfully developed by Pd(II)-catalyzed redox-neutral reactions, which provides a synthesis of tertiary (E)-enamines. We further demonstrate that the tertiary enamines can be converted to multifarious N-heterocyclic compounds, indoles, and quinolones in good yields.

Synthesis, Isolation, and Characterization of Mono- and Bis-norbornene-Annulated Biarylamines through Pseudo-Catellani Intermediates.

A palladium-catalyzed C-H functionalization of an external ring of N-acyl 2-aminobiaryl with bicyclo[2.2.1]hept-2-ene (norbornene) via multiple C-H bond activations was developed. This study is the first report of the formation of bis-norbornene annulated biarylamines isomers ( syn-3a'/ anti-3a' = 36:64) from multiple C-H bond functionalizations. Additionally, nondirected C-H bond functionalization at the C-4' position with alkenes rendered complete C-H functionalization of five C-H bonds that formed a stable hexasubstituted benzene ring.

Palladium(II)-Catalyzed Mono- and Bis-alkenylation of N-Acetyl-2-aminobiaryls through Regioselective C-H Bond Activation.

We developed palladium-catalyzed oxidative coupling of olefins with N-acyl 2-aminobiaryls through a sequence of ortho C-H bond activation/alkene insertion/reductive elimination. Furthermore, we controlled the selectivity of mono- and bis-alkenylation products with the solvent effect. The developed protocol was promising for a broad substrate scope ranging from activated olefins with a wide variety of functional groups to unactivated olefins.

Palladium-Catalyzed C-H Bond Activation by Using Iminoquinone as a Directing Group and an Internal Oxidant or a Co-oxidant: Production of Dihydrophenanthridines, Phenanthridines, and Carbazoles.

A palladium-catalyzed C-H bond activation reaction, via a redox-neutral pathway, for the preparation of dihydrophenanthridine, phenanthridine, and carbazole derivatives from biaryl 2-iminoquinones is developed. The preinstalled iminoquinone was designed to act as a directing group for ortho C-H activation and an internal oxidant or a co-oxidant. This catalysis proceeded through the following sequence: C-H bond activation, coordination and insertion of activated olefins, ß-hydride elimination, H-shift, insertion, and protonation or ß-hydride elimination. In addition, carbazoles can be prepared efficiently by using this method without the addition of external oxidants.

Iptycenes with an acridinone motif developed through [4+2] cycloaddition of tethered naphthalene and iminoquinone via a radical reaction.

A new class of iptycenes was developed by combining 2-(naphthalen-1-yl)anilines and p-benzoquinones through copper(ii)-mediated radical cyclisation. This unusual cyclisation reaction resulted in the robust and efficient syntheses of iptycenes with an acridinone motif. These iptycenes can be further transformed into planar acridinone heterocyclics through the Diels-Alder reaction.