288588-24-9

Upstream product

• 1569-69-3 Cyclohexanethiol 
• 126747-14-6 4-cyanophenylboronic acid 
• 623-03-0 4-Cyanochlorobenzene 
• 623-00-7 4-bromobenzenecarbonitrile 
• 17796-82-6 N-(cyclohexylthio)-phthalimide 
• 21382-98-9 p-cyanophenyl methyl sulfide 
• 3058-39-7 4-iodobenzonitrile 
• 619-72-7 4-nitrobenzonitrile 
• 1194-02-1 4-fluorobenzonitrile 

Downstream Products

• 928649-50-7 (4-(cyclohexylsulfonyl)phenyl)methanamine 
• 928649-49-4 4-cyclohexanesulfonyl-benzonitrile 

Relevant academic research and scientific papers

Photoactive electron donor-acceptor complex platform for Ni-mediated C(sp3)-C(sp2) bond formation

A dual photochemical/nickel-mediated decarboxylative strategy for the assembly of C(sp3)-C(sp2) linkages is disclosed. Under light irradiation at 390 nm, commercially available and inexpensive Hantzsch ester (HE) functions as a potent organic photoreductant to deliver catalytically active Ni(0) species through single-electron transfer (SET) manifolds. As part of its dual role, the Hantzsch ester effects a decarboxylative-based radical generation through electron donor-acceptor (EDA) complex activation. This homogeneous, net-reductive platform bypasses the need for exogenous photocatalysts, stoichiometric metal reductants, and additives. Under this cross-electrophile paradigm, the coupling of diverse C(sp3)-centered radical architectures (including primary, secondary, stabilized benzylic, α-oxy, and α-amino systems) with (hetero)aryl bromides has been accomplished. The protocol proceeds under mild reaction conditions in the presence of sensitive functional groups and pharmaceutically relevant cores.

Nickel-Catalyzed Inter- and Intramolecular Aryl Thioether Metathesis by Reversible Arylation

A nickel-catalyzed aryl thioether metathesis has been developed to access high-value thioethers. 1,2-Bis(dicyclohexylphosphino)ethane (dcype) is essential to promote this highly functional-group-tolerant reaction. Furthermore, synthetically challenging macrocycles could be obtained in good yield in an unusual example of ring-closing metathesis that does not involve alkene bonds. In-depth organometallic studies support a reversible Ni0/NiII pathway to product formation. Overall, this work not only provides a more sustainable alternative to previous catalytic systems based on Pd, but also presents new applications and mechanistic information that are highly relevant to the further development and application of unusual single-bond metathesis reactions.

Electrochemically Promoted Nickel-Catalyzed Carbon-Sulfur Bond Formation

This work describes a nickel-catalyzed Ullmann-type thiolation of aryl iodidesunder mild electrochemical conditions. The simple undivided cell with graphene/nickel foam electrode setups offers excellent substrate tolerance, affording aryl and alkyl sulfides in good chemical yields. Furthermore, the mechanism for this electrochemical cross-coupling reaction has been investigated by cyclic voltammetry.

Merging Photoredox and Organometallic Catalysts in a Metal–Organic Framework Significantly Boosts Photocatalytic Activities

Metal–organic frameworks (MOFs) have been extensively used for single-site catalysis and light harvesting, but their application in multicomponent photocatalysis is unexplored. We report here the successful incorporation of an IrIII photoredox catalyst and a NiII cross-coupling catalyst into a stable Zr12 MOF, Zr12-Ir-Ni, to efficiently catalyze C?S bond formation between various aryl iodides and thiols. The proximity of the IrIII and NiII catalytic components to each other (ca. 0.6 nm) in Zr12-Ir-Ni greatly facilitates electron and thiol radical transfers from Ir to Ni centers to reach a turnover number of 38 500, an order of magnitude higher than that of its homogeneous counterpart. This work highlights the opportunity in merging photoredox and organometallic catalysts in MOFs to effect challenging organic transformations.

CATALYTIC C-X-BOND METATHESIS THROUGH ARYLATION

The present invention refers to a process for a catalytic aryl transfer to rearrange the backbone of aromatic C-X bonds.

Formation of C-C, C-S and C-N bonds catalysed by supported copper nanoparticles

Transition-metal catalysed cross-coupling reactions are still dominated by palladium chemistry. Within the recent past, copper has gained ground against palladium by virtue of its cheaper price and equivalent function in certain reactions. Four catalysts consisting of copper nanoparticles on zeolite, titania, montmorillonite and activated carbon have been tested in three palladium- and ligand-free cross-coupling reactions to form carbon-carbon, carbon-sulfur and carbon-nitrogen bonds. CuNPs/zeolite has been found to be the best one in the Sonogashira reaction of aryl iodides and arylacetylenes, as well as in the coupling of aryl halides with aryl and alkyl thiols, being reusable in both cases. However, the arylation of nitrogen-containing heterocycles (imidazole, pyrazole, benzimidazole and indole) has been better accomplished with CuNPs/titania, albeit CuNPs/activated carbon showed better recycling properties. The catalytic activity of the nanostructured catalysts has been compared with that of twelve commercial copper catalysts, with the former outperforming the latter in the three types of reactions studied.

Thioetherification via Photoredox/Nickel Dual Catalysis

Hypervalent alkylsilicates represent new and readily accessible precursors for the generation of alkyl radicals under photoredox conditions. Alkyl radicals generated from such silicates serve as effective hydrogen atom abstractors from thiols, furnishing thiyl radicals. The reactive sulfur species generated in this manner can be funneled into a nickel-mediated cross-coupling cycle employing aromatic bromides to furnish thioethers. The serendipitous discovery of this reaction and its utilization for the thioetherification of various aryl and heteroaryl bromides with a diverse array of thiols is described. The S-H selective H atom abstraction event enables a wide range of functional groups, including those bearing protic moieties, to be tolerated. (Chemical Equation Presented).

Discovery of potent and efficacious cyanoguanidine-containing nicotinamide phosphoribosyltransferase (Nampt) inhibitors

A co-crystal structure of amide-containing compound (4) in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein and molecular modeling were utilized to design and discover a potent novel cyanoguanidine-containing inhibitor bearing a sulfone moiety (5, Nampt Biochemical IC50 = 2.5 nM, A2780 cell proliferation IC50 = 9.7 nM). Further SAR exploration identified several additional cyanoguanidine-containing compounds with high potency and good microsomal stability. Among these, compound 15 was selected for in vivo profiling and demonstrated good oral exposure in mice. It also exhibited excellent in vivo antitumor efficacy when dosed orally in an A2780 ovarian tumor xenograft model. The co-crystal structure of this compound in complex with the NAMPT protein was also determined.

Discovery of potent and efficacious cyanoguanidine-containing nicotinamide phosphoribosyltransferase (Nampt) inhibitors

A co-crystal structure of amide-containing compound (4) in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein and molecular modeling were utilized to design and discover a potent novel cyanoguanidine-containing inhibitor bearing a sulfone moiety (5, Nampt Biochemical IC50 = 2.5 nM, A2780 cell proliferation IC50 = 9.7 nM). Further SAR exploration identified several additional cyanoguanidine-containing compounds with high potency and good microsomal stability. Among these, compound 15 was selected for in vivo profiling and demonstrated good oral exposure in mice. It also exhibited excellent in vivo antitumor efficacy when dosed orally in an A2780 ovarian tumor xenograft model. The co-crystal structure of this compound in complex with the NAMPT protein was also determined.

Sulfanylphthalonitrile analogues as selective and potent inhibitors of monoamine oxidase B

It has recently been reported that nitrile containing compounds frequently act as potent monoamine oxidase B (MAO-B) inhibitors. Modelling studies suggest that this high potency inhibition may rely, at least in part, on polar interactions between nitrile functional groups and polar moieties within the MAO-B substrate cavity. In an attempt to identify potent and selective inhibitors of MAO-B and to contribute to the known structure-activity relationships of MAO inhibition by nitrile containing compounds, the present study examined the MAO inhibitory properties of series of novel sulfanylphthalonitriles and sulfanylbenzonitriles. The results document that the evaluated compounds are potent and selective MAO-B inhibitors with most homologues possessing IC50 values in the nanomolar range. In general, the sulfanylphthalonitriles exhibited higher binding affinities for MAO-B than the corresponding sulfanylbenzonitrile homologues. Among the compounds evaluated, 4-[(4-bromobenzyl)sulfanyl]phthalonitrile is a particularly promising inhibitor since it displayed a high degree of selectivity (8720-fold) for MAO-B over MAO-A, and potent MAO-B inhibition (IC50 = 0.025 μM). Based on these observations, this structure may serve as a lead for the development of therapies for neurodegenerative disorders such as Parkinson's disease.