Morpholine catalyzed direct C3 alkenylation of indoles with α,β-unsaturated aldehydes

Organocatalytic direct C3 alkenylation of indoles has been developed. Simple and readily available morpholine trifluoroacetic acid salt is employed as an efficient catalyst in this oxidative dehydrogenative reaction. Simplicity and practicality constitute the most attractive advantages of this reaction.     

Triphyrin catalyzed direct C–H arylation of benzene with aryl halides

Transition-metal free direct C–H arylation of benzene with aryl halides was achieved by meso-aryl-substituted [14]triphyrins(2.1.1) catalysts in an air atmosphere. Various aryl halides underwent successful direct C–H arylation of benzene to give moderate to high yields of biaryls. A radical mechanism is proposed for this triphyrin catalyzed C–H arylation reaction.     

Silver mediated direct C–H arylation of 3-bromoisothiazole-5-carbonitrile

Palladium catalyzed direct C–H arylation of 3-bromoisothiazole-5-carbonitrile with aryl/hetaryl iodides in the presence of AgF gave 13 4-aryl/hetaryl-3-bromoisothiazole-5-carbonitriles. The scope of this arylation was investigated and explanations for the limitations proposed. 3-Bromoisothiazole-5-carboxamide was isolated as a side-product, and its formation was attributed to Ag⁺-catalyzed hydration of the C-5 nitrile. The analogous phenylation of 3-chloroisothiazole-5-carbonitrile and 3-bromoisothiazole-4-carboxamide gave 3-chloro-4-phenylisothiazole-5-carbonitrile and 3-bromo-5-phenylisothiazole-4-carboxamide in 83 and 64% yields, respectively.     

Copper(II)-catalyzed direct thiolation of C–H bonds in aromatic amides with aryl and aliphatic thiols

An efficient approach for Cu-catalyzed thiolation of C_sp2–H bonds of directing-group-containing aromatic amides with 1°, 2°, and 3° aliphatic thiols and thiophenols has been developed. This method shows excellent functional group tolerance and provides a straightforward way for the preparation of aryl thioethers.     

Palladium-catalyzed C–H alkenylation of quinoxaline N-oxide enabled by a mono-N-protected amino acid

The efficient alkenylation of quinoxaline N-oxide was achieved via Pd-catalyzed C–H activation, using the assistance of a mono-N-protected amino acid. Further deoxygenation of the 2-styrylquinoxaline-N-oxides yielded the corresponding styrylquinoxaline derivatives.     

Oxygen as an oxidant in rhodium(III) catalyzed oxidative C–H/C–H cross-coupling between indoles and oxazoles

A Rh(III)-catalyzed oxidative C–H/C–H cross-coupling between indoles and oxazoles with molecular oxygen as an oxidant has been developed to construct a variety of 2-(indol-2-yl)oxazoles. The chelation-assisted strategy endows this catalytic system with an excellent C2-site selectivity by introducing a pyrimidyl directing group. In addition, polycyclic pyridinium salts are also obtained via Rh(III)-catalyzed C–H activation/cyclization of 2-(indol-2-yl)oxazoles with alkynes.     

Copper nitrate–catalyzed α-bromination of aryl ketones with hydrobromic acid

An efficient method for α-bromination of aryl ketones, using the combination of molecular oxygen and aqueous hydrobromic acid as a brominating agent in the presence of the copper nitrate, has been developed. This catalytic system, which uses cheap and readily available reactants, shows good atom economy with water as the only by-product.     

Copper–Schiff base complex catalyzed oxidation of sulfides with hydrogen peroxide

A straightforward, efficient, and selective oxidation of sulfide to sulfoxide with 30% H₂O₂ catalyzed by copper(II)–Schiff base complex is described. The reactions proceed under mild conditions in acetonitrile at room temperature to provide a variety of aryl and alkyl sulfoxides in excellent yield.     

Rapid access to diverse α-carbolines through sequential transition metal catalyzed amination and direct C–H arylation

An efficient sequence of Pd catalyzed amination and direct C–H arylation for a synthesis of pharmacologically important α-carbolines is described. The outstanding feature in the synthetic sequence is that a combination of DBU and 2-(dicyclohexylphosphino)biphenyl (DCHPB) plays a critical role to not only enhance the reactivity but also suppress hydrodehalogenation in the direct C–H arylation step. The reaction protocol provides α-carbolines with various substituents including base-sensitive ester and ketone moieties in moderate to excellent yields. Moreover, combination with Cu catalyzed amination further enhanced the versatility of the α-carboline synthesis.     

Benzimidazole bearing Pd–PEPPSI complexes catalyzed direct C2-arylation/heteroarylation of N-substituted benzimidazoles

A convenient and highly efficient palladium-catalyzed direct C2-arylation/heteroarylation of N-substituted benzimidazole derivatives such as N-benzyl/3-chlorobenzyl/2,4,6-trimethylbenzyl/2,4,6-triisopropylbenzyl/aryl benzimidazoles with various aryl/heteroaryl bromides in the presence of Pd–PEPPSI (palladium-pyridine enhanced pre-catalyst preparation stabilization and initiation) complexes is reported. In order to that we have prepared a series of different symmetrical and unsymmetrical N,N′-diaralkyl benzimidazole-bearing Pd–PEPPSI complexes. Among all of the the prepared complexes, Pd–PEPPSI- 3 effectively tuned the reaction at a relatively higher rate under mild reaction conditions in an ethanol–water system. In addition, the catalytic process avoids the use of external ligand and additives. Further the reactivity was compared with commercially available copper-N-heterocyclic carbene catalyst, but the reaction was less successful. With the optimized reaction conditions, a wide range of 2-aryl/heteroaryl-N-substituted benzimidazoles were synthesized in good to excellent yields via Csp²-H/Csp²-X biaryl cross-coupling.     

The direct C–H halogenations of indoles

A novel and efficient transition metal-free C–H bond halogenation of indole derivatives has been developed. 3-Halogenated (3-Br, 3-I) indoles are highly regioselectively produced by this protocol. Simple and readily available halide salts (TBAB, KI) are employed as the halogen source. The transition metal-free and the mild conditions make this protocol very easy to handle and practical.     

Palladium-catalyzed oxidative alkynylation of arene C–H bond using the chelation-assisted strategy

Palladium-catalyzed alkynylation of arene C–H bonds with (triisopropylsilyl)acetylene was developed for the first time under oxidative conditions in the present study. Among various type of directing groups examined, the N-phenyl-2-aminopyridine skeleton was shown to be most effective and selective for the Pd-catalyzed direct alkynylation reaction, and the desired alkynylated products were obtained in moderate to good yields.     

Highly stereoselective direct aldol reaction of 4-formylcoumarins with acetone catalyzed by L-proline in water–acetone mixtures

Organocatalyzed direct intermolecular aldol reactions have been developed for substituted 4-formylcoumarins with acetone in water using L-proline and phthalimido-prolinamide catalysts without use of additives. Stereoselective products obtained were in excellent yields (up to 97%) with high purity (up to 99%) and enatioselectivities (up to 95%). The isolated compounds were confirmed by infrared, NMR, high-performance liquid chromatography, and mass spectrometry and some of them by single-crystal x-ray crystallography.     

Base mediated direct C–H amination for pyrimidines synthesis from amidines and cinnamaldehydes using oxygen as green oxidants

A direct metal-free C–H amination reaction of cinnamaldehydes and amidines to realize the synthesis of polysubstituted pyrimidines was developed in the presence of base. This greener synthetic methodology provides a straightforward approach to the synthesis of a variety of pyrimidine derivatives under mild reaction condition using oxygen as sole oxidants.     

Synthesis of tetrahydroindolones and tetrahydrocarbazolones via palladium catalyzed C–H activation

The treatment of bromo homoallyl pyrrolyl/indolyl ketone derivatives with Pd(OAc)₂ in the presence of PPh₃ and Cs₂CO₃ in DMF resulted in the formation of tetrahydroindolones and tetrahydrocarbazolones in moderate to good isolated yields.     

Copper–Oxygen Dynamics in the Tyrosinase Mechanism

The dinuclear copper enzyme, tyrosinase, activates O₂ to form a (μ-η²:η²-peroxido)dicopper(II) species, which hydroxylates phenols to catechols. However, the exact mechanism of phenolase reaction in the catalytic site of tyrosinase is still under debate. We herein report the near atomic resolution X-ray crystal structures of the active tyrosinases with substrate l -tyrosine. At their catalytic sites, CuA moved toward l -tyrosine (CuA1 → CuA2), whose phenol oxygen directly coordinates to CuA2, involving the movement of CuB (CuB1 → CuB2). The crystal structures and spectroscopic analyses of the dioxygen-bound tyrosinases demonstrated that the peroxide ligand rotated, spontaneously weakening its O−O bond. Thus, the copper migration induced by the substrate-binding is accompanied by rearrangement of the bound peroxide species so as to provide one of the peroxide oxygen atoms with access to the phenol substrate's ϵ carbon atom.     

The B–H–B bridging interaction in B-substituted oxazaborolidine–borane complexes: a theoretical study

Ten oxazaborolidine–borane complexes, nine among them boron-substituted (B–R, R=CH₃, CF₃, and OCH₃), are carefully analysed using quantum-chemistry methods to determine their equilibrium geometries and the corresponding oxazaborolidine–borane interaction energies. It is observed that in all B-trifluoromethyl substituted oxazaborolidine–borane complexes and in one B-methyl substituted complex the B–H–B bond is formed and the interaction energies are 1.5–2.5 times as large as in other investigated complexes. We believe that the presented results may be helpful in experimental recognition of oxazaborolidine–borane complexes which may appear, inter alia, as reaction intermediates.     

Copper(I) iodide–catalyzed amidation of phenylboronic acids/aryl bromides using 4-dimethylaminopyridine as ligand

An efficient one-pot synthesis of N-arylbenzamide is described via reaction of phenylboronic acid/aryl bromide with benzamide in the presence of CuI (5 mol%) as catalyst, 4-dimethylaminopyridine (20 mol%) as the ligand, and Cs₂CO₃ (2 mmol) as the base. This protocol was applied to synthesize a small library of N-arylbenzamide in high yields.     

Copper(II) mediated C–H methylthiolation of 2-phenyl pyridines with dimethyl sulfoxide using an amino acid ligand

A novel protocol for the C–H methylthiolation of 2-phenyl pyridines using DMSO as the methylthio source and an amino acid ligand is described. This simple procedure requires neither an oxidant nor additional solvent. The developed protocol tolerates a wide range of functional groups including methyl, methoxy, fluoro, chloro, and in particular the formyl group. This new strategy is highly regioselective and provides aryl methyl sulfides from 2-phenyl pyridines in moderate to good yields.     

Iridium-catalyzed direct ortho-C–H amidation of benzoic acids with sulfonylazides

A mild and efficient iridium-catalyzed ortho-C–H amidation with sulfonyl azides by weakly coordinating carboxylic acid was demonstrated, which provided a novel approach to anthranilic acid derivatives.