42362-47-0

Upstream product

• 1122-54-9 methyl (4-pyridyl) ketone 
• 108-86-1 bromobenzene 
• 585-71-7 (1-bromoethyl)benzne 
• 181219-01-2 4-pyridineboronic acid pinacol ester 
• 54813-56-8 1-phenyl-1-(4-pyridyl)ethylene 
• 100-48-1 pyridine-4-carbonitrile 
• 47276-97-1 6,7-dimethoxy-2-methyl-1-(1-phenylethyl)-1,2,3,4-tetrahydroisoquinoline 
• 98-85-1 1-Phenylethanol 
• 110-86-1 pyridine 
• 100-42-5 styrene 
• 19490-94-9 1-phenyl-1-(pyridin-4-yl)ethan-1-ol 
• 2116-65-6 4-benzyl pyridine 
• 74-88-4 methyl iodide 

Downstream Products

• 34361-25-6 1-methyl-4-(1-phenyl-ethyl)-1,2,3,6-tetrahydro-pyridine 
• 19490-94-9 1-phenyl-1-(pyridin-4-yl)ethan-1-ol 
• 14548-46-0 4-Benzoylpyridine 
• 100-41-4 ethylbenzene 

Relevant academic research and scientific papers

A general copper-catalyzed radical C(sp3)?C(sp2) cross-coupling to access 1,1-diarylalkanes under ambient conditions

A general copper-catalyzed C(sp3)?C(sp2) cross-coupling of (hetero)benzyl bromides with the air- and moisture-stable aryl nucleophiles has been developed, providing a facile access to pharmaceutically useful 1,1-di(hetero)arylalkane and 1-aryl-1-heteroarylalkane scaffolds. Critical to the success is the utilization of a proline-based N,N,P-ligand to enhance the reducing capability of copper, thus easily converting benzyl bromides to the corresponding radical species via a single-electron transfer process under ambient conditions. The reaction features a broad substrate scope, covering (hetero)arylboronate esters, oxadiazoles, and benzo[d]oxazoles, as well as primary and secondary (hetero)benzyl bromides with excellent functional group tolerance.

Photoenzymatic Hydrogenation of Heteroaromatic Olefins Using ‘Ene’-Reductases with Photoredox Catalysts

Flavin-dependent ‘ene’-reductases (EREDs) are highly selective catalysts for the asymmetric reduction of activated alkenes. This function is, however, limited to enones, enoates, and nitroalkenes using the native hydride transfer mechanism. Here we demonstrate that EREDs can reduce vinyl pyridines when irradiated with visible light in the presence of a photoredox catalyst. Experimental evidence suggests the reaction proceeds via a radical mechanism where the vinyl pyridine is reduced to the corresponding neutral benzylic radical in solution. DFT calculations reveal this radical to be “dynamically stable”, suggesting it is sufficiently long-lived to diffuse into the enzyme active site for stereoselective hydrogen atom transfer. This reduction mechanism is distinct from the native one, highlighting the opportunity to expand the synthetic capabilities of existing enzyme platforms by exploiting new mechanistic models.

Organoborohydride-catalyzed Chichibabin-type C4-position alkylation of pyridines with alkenes assisted by organoboranes

The first NaBEt3H-catalyzed intermolecular Chichibabin-type alkylation of pyridine and its derivatives with alkenes as the latent nucleophiles is presented with the assistance of BEt3, and a series of branched C4-alkylation pyridines, even highly congested all-carbon quaternary center-containing triarylmethanes can be obtained in a regiospecific manner. Therefore, the conventional reliance on high cost and low availability transition metal catalysts, prior formation of N-activated pyridines, organometallic reagents, and extra oxidation operation for the construction of a C-C bond at the C4-position of the pyridines in previous methods are not required. The corresponding mechanism and the key roles of the organoborane were elaborated by the combination of H/D scrambling experiments, 11B NMR studies, intermediate trapping experiments and computational studies. This straightforward and mechanistically distinct organocatalytic technology not only opens a new door for the classical but still far less well-developed Chichibabin-type reaction, but also sets up a new platform for the development of novel C-C bond-forming methods.

Lewis Acid-Catalyzed Selective Reductive Decarboxylative Pyridylation of N-Hydroxyphthalimide Esters: Synthesis of Congested Pyridine-Substituted Quaternary Carbons

A practical and efficient Lewis acid-catalyzed radical-radical coupling reaction of N-hydroxyphthalimide esters and 4-cyanopyridines with inexpensive bis(pinacolato)diboron as reductant has been developed. With ZnCl2 as the catalyst, a wide range of quaternary 4-substituted pyridines, including highly congested diarylmethyl and triarylmethyl substituents, could be selectively obtained in moderate to good yields with broad functional group tolerance. Combined theoretical calculations and experimental studies indicate that the Lewis acid could coordinate with the cyano group of the pyridine-boryl radical to lower the activation barrier of the C-C coupling pathway, leading to the formation of 4-substituted pyridines. Moreover, it could also facilitate the decyanation/aromatization of the radical-radical coupling intermediate.

Iron-Catalyzed Aerobic Oxidation of (Alkyl)(aryl)azinylmethanes

An iron-catalyzed aerobic oxidation of (alkyl)(aryl)azinylmethanes has been developed leading to tertiary alcohols in moderate to good yields. Hock rearrangement was identified as a major side reaction leading to a complex mixture of undesired products. Addition of thiourea sometimes allows inhibiting this side reaction and steers the reaction towards the desired products.

Light-Induced Alkylation of (Hetero)aromatic Nitriles in a Transition-Metal-Free C-C-Bond Metathesis

A light-induced C-C-σ-bond metathesis was achieved through transition-metal-free activation of an unstrained C(sp3)-C(sp3)-σ-bond in 1-benzyl-1,2,3,4-tetrahydroisoquinolines. A photoredox-mediated single-electron oxidation of these precursor amines yield radical cations which undergo a homolytic cleavage of a C(sp3)-C(sp3)-σ-bond rather than the well-known α-C-H-scission. The resulting carbon-centered radicals are used in the ipso-substitution of (hetero)aromatic nitriles proceeding through another single-electron transfer-mediated C-C-bond cleavage and formation.

Transition-Metal-Free Decarboxylative Photoredox Coupling of Carboxylic Acids and Alcohols with Aromatic Nitriles

A transition-metal-free protocol for the redox-neutral light-induced decarboxylative coupling of carboxylic acids with (hetero)aromatic nitriles at ambient temperature is presented. A broad scope of acids and nitriles is accepted, and alcohols can be coupled in a similar fashion through their oxalate half esters. Various inexpensive sources of UV light and even sunlight can be used to achieve this C-C bond formation proceeding through a free radical mechanism.

Chromium-Catalyzed Regioselective Hydropyridination of Styrenes

The first chromium-catalyzed regioselective addition of para-C-H bonds of pyridines across styrenes is disclosed. The hydrofunctionalization reaction was promoted by a low-cost chromium(III) chloride combining with a cyclohexyl Grignard reagent and 2,2′-bipyridine, which allows for the highly selective formation of branched products via the cleavage of inert C-H bonds of pyridines.

Nickel-catalysed para-CH activation of pyridine with switchable regioselective hydroheteroarylation of allylarenes

para-CH activation of pyridine with allylbenzene is described by Ni/Al cooperative catalysis in combination with a bulkier NHC ligand and a Lewis acid, leading to linear hydroheteroarylation products. Interestingly, the branch selectivity can be achieved by using the combination of a less sterically hindered amino-NHC ligand and AlMe3 through tandem reaction of facile alkene isomerization followed by a slow CH bond activation process.

Cobalt-catalyzed C4-selective direct alkylation of pyridines

How pyridine got its tail: A new catalyst for the atom-economical C4-selective direct alkylation of pyridines is described. A combination of CoBr2 and LiBEt3H catalyzes the reaction of pyridines with 1-alkenes at 70 °C to give alkylation products with C4/C2 ratios of >20:1. Substrate/catalyst ratios of up to 4000, and a turnover number of 3440 were achieved.