4280-36-8

Upstream product

• 110-89-4 piperidine 
• 352-33-0 1-Chloro-4-fluorobenzene 
• 1765-93-1 4-fluoroboronic acid 
• 352-34-1 4-fluoro-1-iodobenzene 
• 2156-71-0 N-chloropiperidine 
• 462-06-6 fluorobenzene 
• 540-36-3 para-difluorobenzene 
• 111-29-5 1 ,5-pentanediol 
• 371-40-4 4-fluoroaniline 
• 142-68-7 TETRAHYDROPYRANE 
• 181705-93-1 4-fluorophenylzinc bromide 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 111-24-0 1,5-dibromo-pentane 
• 176913-70-5 bis(4-fluorophenyl)(hydroxy)borane 

Downstream Products

• 96372-83-7 1-([1,1′-biphenyl]-4-yl)piperidine 
• 1415461-00-5 1-(5-fluoro-2-(piperidin-1-yl)phenyl)naphthalen-2-ol 
• 54660-08-1 1-(4-fluoro-phenyl)-pyrrolidin-2-one 
• 852227-96-4 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl)piperidine 

Relevant academic research and scientific papers

Iodine-Mediated Coupling of Cyclic Amines with Sulfonyl Hydrazides: an Efficient Synthesis of Vinyl Sulfone Derivatives

An efficient iodine-mediated coupling of cyclic amines with sulfonyl hydrazides is reported. This transformation opens a new route to the synthesis of vinyl sulfones derivatives, which is a common structural motif in natural products and pharmaceuticals. Tentative mechanistic studies suggest that this reaction is likely to involve a radical process.

Electron Donor-Acceptor Complex-Initiated Photochemical Cyanation for the Preparation of α-Amino Nitriles

An electron donor-acceptor complex-initiated α-cyanation of tertiary amines has been described. The reaction protocol provides a novel method to synthesize various α-amino nitriles under mild conditions. The reaction can proceed smoothly without the presence of photocatalysts and transition metal catalysts, and either oxidants are unnecessary or O2 is the only oxidant. The practicality of this method is showcased not only by the late-stage functionalization of natural alkaloid derivatives and pharmaceutical intermediate, but also by the applicability of a stop-flow microtubing reactor.

Redox-Neutral β-C(sp3)-H Functionalization of Cyclic Amines via Intermolecular Hydride Transfer

Herein, we report the first redox-neutral and transition-metal-free β-C(sp3)-H functionalization of cyclic amines via a consecutive intermolecular hydride transfer process. A series of N-aryl pyrrolidines and N-aryl 1,2,3,4-tetrahydropyridines decorated with CF3 and carboxylic ester functionalities are directly accessed in good yields from pyrrolidines and piperidines. This work pushes forward the application of the intermolecular hydride transfer strategy in one-step assembly of molecular complexity.

Practical and regioselective amination of arenes using alkyl amines

The formation of carbon–nitrogen bonds for the preparation of aromatic amines is among the top five reactions carried out globally for the production of high-value materials, ranging from from bulk chemicals to pharmaceuticals and polymers. As a result of this ubiquity and diversity, methods for their preparation impact the full spectrum of chemical syntheses in academia and industry. In general, these molecules are assembled through the stepwise introduction of a reactivity handle in place of an aromatic C–H bond (that is, a nitro group, halogen or boronic acid) and a subsequent functionalization or cross-coupling. Here we show that aromatic amines can be constructed by direct reaction of arenes and alkyl amines using photocatalysis, without the need for pre-functionalization. The process enables the easy preparation of advanced building blocks, tolerates a broad range of functionalities, and multigram scale can be achieved via a batch-to-flow protocol. The merit of this strategy as a late-stage functionalization platform has been demonstrated by the modification of several drugs, agrochemicals, peptides, chiral catalysts, polymers and organometallic complexes.

“On Water” promoted N-arylation reactions using Cu (0)/myo-inositol catalytic system

Myo-inositol is originally applied as a cardiovascular medicine in clinic, which can be multi-ton manufactured via extraction from the byproducts in agricultural product processing such as defatted rice bran and corn-soaking water. Herein, the application of myo-inositol (MI) as a novel versatile tridentate O-donor ligand has been first described for promoting Cu-catalyzed amination reaction in aqueous medium.

PIFA-Promoted, Solvent-Controlled Selective Functionalization of C(sp2)-H or C(sp3)-H: Nitration via C-N Bond Cleavage of CH3NO2, Cyanation, or Oxygenation in Water

A novel nitration (via C(sp3)-N breaking/C(sp2)-N formation with CH3NO2) mediated by [bis(trifluoroacetoxy)iodo]benzene (PIFA) is described. The NO2 transfer from CH3NO2 to the aromatic group of the substrate is possible with careful selection of the solvent, NaX, and oxidant. In addition, the solvent-controlled C(sp2)-H functionalization can shift to an α-C(sp3)-H functionalization (cyanation or oxygenation) of the α-C(sp3)-H of cyclic amines.

N-Heterocyclic carbene-palladacyclic complexes: synthesis, characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01 mol%).

Base-assisted, copper-catalyzed N-arylation of (benz)imidazoles and amines with diarylborinic acids

N-Arylation of (benz)imidazoles and amines with diarylborinic acids as cost-effective aryl source has been efficiently effected via Cu(OAc)2-catalyzed Chan-Lam coupling in assistance of tetramethylethylenediamine (TMEDA) in methanol and pyridine (Py) in dichloromethane, respectively, in air at room temperature. The diarylborinic acids could be well accommodated by the Chan-Lam coupling oxidative conditions containing a proper combination of bases and solvents. The steric hindrance appeared to affect the copper-catalyzed N-arylation using the high-order arylboron reagent more significantly than the electronic factors, especially for low reactive anilines and aliphatic amines.

Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands

Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18F-fluorination of aryl boron reagents with 18F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.

Synthetic method for five-component and six-component N-substituted nitrogenous heterocyclic compounds

The invention provides a synthetic method for preparing five-component and six-component N-substituted nitrogenous heterocyclic compounds from aromatic amine and five-component and six-component oxygen heterocyclic compounds via mediation by an aminotitanium intermediate. The five-component and six-component N-substituted nitrogenous heterocyclic compounds provided by the invention specifically refer to N-aryltetrahydropyrrole, N-aryl-2-methyltetrahydropyrrole, N-aryltetrahydropyrane, N-aryl-3,4-dihydro-1H-2-pyrane with a general chemical formula as defined in the specification. In the formula, Ar is a phenyl group, a 4-methylphenyl group, a 2-halophenyl group, a 3-halophenyl group or a 4-halophenyl group. The invention discloses the chemical structures and synthetic method of the compounds.