138970-28-2

Upstream product

• 872-85-5 pyridine-4-carbaldehyde 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 696-62-8 para-iodoanisole 
• 100-48-1 pyridine-4-carbonitrile 
• 123-11-5 4-methoxy-benzaldehyde 
• 100-66-3 methoxybenzene 
• 1120-87-2 4-bromopyridin 
• 13139-86-1 4-methoxyphenyl magnesium bromide 

Downstream Products

• 37581-27-4 4-[(4-methoxyphenyl)methyl]piperidine hydrochloride 
• 130407-11-3 4-(1-Methyl-1,2,3,6-tetrahydro-pyridin-4-ylmethyl)-phenol 
• 66414-18-4 4-(pyridin-4-ylmethyl)phenol 
• 35854-35-4 4-[(4-methoxyphenyl)methyl]pyridine 

Relevant academic research and scientific papers

Catalytic Aldehyde and Alcohol Arylation Reactions Facilitated by a 1,5-Diaza-3,7-diphosphacyclooctane Ligand

We report a catalytic method to access secondary alcohols by the coupling of aryl iodides. Either aldehydes or alcohols can be used as reaction partners, making the transformation reductive or redox-neutral, respectively. The reaction is mediated by a Ni catalyst and a 1,5-diaza-3,7-diphosphacyclooctane. This P2N2ligand, which has previously been unrecognized in cross-coupling and related reactions, was found to avoid deleterious aryl halide reduction pathways that dominate with more traditional phosphines and NHCs. An interrupted carbonyl-Heck type mechanism is proposed to be operative, with a key 1,2-insertion step forging the new C-C bond and forming a nickel alkoxide that may be turned over by an alcohol reductant. The same catalyst was also found to enable synthesis of ketone products from either aldehydes or alcohols, demonstrating control over the oxidation state of both the starting materials and products.

Reductive arylation of aliphatic and aromatic aldehydes with cyanoarenes by electrolysis for the synthesis of alcohols

An electroreductive arylation reaction of aliphatic and aromatic aldehydes as well as ketones with electro-deficient (hetero)arenes is described. A variety of cyano(hetero)arenes and carbonyl compounds, especially aliphatic aldehydes, have been examined, providing secondary and tertiary alcohols in moderate to good yields. Mechanistic studies, including cyclic voltammetry (CV), electron paramagnetic resonance (EPR), and divided-cell experiments, support the generation of aliphatic ketyl radicals and persistent heteroaryl radical anions via cathodic reduction followed by radical-radical cross-coupling.

INHIBITORS OF ANTIGEN PRESENTATION BY HLA-DR

Chromanone compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with the inhibition of antigen presentation by HLA-DR.

Visible-Light-Triggered Directly Reductive Arylation of Carbonyl/Iminyl Derivatives through Photocatalytic PCET

The first visible-light-mediated radical-radical cross-coupling strategy that enables the direct arylation of carbonyl/iminyl derivatives in the presence of Et3N has been realized. Such an atom-economical protocol furnishes a broad scope of arylation products such as secondary/tertiary alcohols and amines via a PCET process that facilitates the challenging reduction of C-X (X = O, N). Mechanistic investigation indicates two photocatalytic redox cycles were involved in the process, and Et3N was proved to serve as a dual reductant and proton donor. Moreover, the isolated byproducts and controlled experiments could be considered as powerful supporting evidence for our hypothesis.

Metal-Free Synthesis of C-4 Substituted Pyridine Derivatives Using Pyridine-boryl Radicals via a Radical Addition/Coupling Mechanism: A Combined Computational and Experimental Study

Density functional theory investigations revealed that the pyridine-boryl radical generated in situ using 4-cyanopyridine and bis(pinacolato)diboron could be used as a bifunctional “reagent”, which serves as not only a pyridine precursor but also a boryl radical. With the unique reactivity of such radicals, 4-substituted pyridine derivatives could be synthesized using α,β-unsaturated ketones and 4-cyanopyridine via a novel radical addition/C-C coupling mechanism. Several controlled experiments were conducted to provide supportive evidence for the proposed mechanism. In addition to enones, the scope could be extended to a wide range of boryl radical acceptors, including various aldehydes and ketones, aryl imines and alkynones. Lastly, this transformation was applied in the late-stage modification of a complicated pharmaceutical molecule.

The cooperative effect of Lewis pairs in the Friedel-Crafts hydroxyalkylation reaction: A simple and effective route for the synthesis of (±)-carbinoxamine

An efficient C-C bond formation strategy between aromatic/heteroaromatic π-nucleophiles and Lewis acid activated aldehydes is described. This aromatic electrophilic substitution reaction of arenes or heteroarenes is facilitated by Lewis acid AlBr3. Aromatic rings with electron donating substituents are excellent nucleophilic counterparts in this reaction, generating carbinols in excellent yields (61-94%). The formation of triarylmethanes is also witnessed in the case of certain reactive aldehydes and aromatic π-nucleophiles through reactive carbocation formation. The formation of triarylmethane is reduced to a greater extent via retardation of the second π-nucleophile addition through a Lewis base, for example, pyridine, coordination with an aluminium alkoxide intermediate. Various aliphatic aldehydes also underwent Friedel-Crafts type hydroxyalkylation and generated the expected carbinols in moderate yields (41-53%) in the presence of AlBr3. This protocol has been successfully applied to the synthesize of the (±)-carbinoxamine, a therapeutically important histamine H1 antagonist, in a one-pot manner.

Pyridylmagnesiates: Generation by bromine-metal exchange and enantioselective addition to aldehydes

Butyl and dibutylmagnesiates incorporating chiral ligands have been prepared and their reactivity studied. The reagents were efficient to promote the clean bromine-magnesium exchange of azinyl bromides at room temperature and subsequent reaction with aldehydes affording pyridylcarbinols. (R,R)-TADDOL-based dibutylmagnesiate was the best reagent leading to acceptable to good enantioselectivities, depending on the substrate and on the aldehyde substitution. This is the first example of enantioselective addition of in situ generated pyridylmagnesiate to carbonyl electrophiles.

Convenient, benign and scalable synthesis of 2- and 4-substituted benzylpiperidines

A short, scalable and environmentally benign synthesis of 2- and 4-substituted benzylpiperidines has been developed. The method is based on the temperature-programmed consecutive deoxygenation and heteroaromatic ring saturation of aryl(pyridin-2-yl)- and aryl(pyridin-4-yl)methanols and aryl(pyridin-4-yl)methanones in the presence of Pd/C catalyst. The crucial roles of the temperature, the acidity and the substrate structure in the change of selectivity have been demonstrated by isolation of several substituted aryl(piperidine)methanols. The carbinols and ketones were prepared from commercially available pyridinecarbaldehydes or 4-cyanopyridine and substituted bromobenzenes via organometallic intermediates. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogues: Synthesis and monoamine oxidase catalyzed bioactivation

Eighteen analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and evaluated as substrates of monoamine oxidase. In general, the flexible analogues, characterized by the presence of a methylene (or ethylene) bridge between the aryl/heteroaryl and tetrahydropyridyl moieties, were better substrates of the enzyme than the conformationally restricted MPTP. It is suggested that the increased oxidative activity of these flexible analogues reflects enhanced binding due to the ability of the C-4-aryl/heteroaryl substituent to gain access to a hydrophobic pocket within the substrate binding site.