Polysubstituted Pyridines Research Articles

ChemInform Abstract: Trimethylsilyl Trifluoromethanesulfonate‐Promoted Cyclocondensation of β‐Ketoenamides and Subsequent Nonaflation to Pyrid‐2‐yl and Pyrid‐4‐yl Nonaflates as Flexible Precursors for Polysubstituted Pyridines.

The intramolecular condensation of β-ketoenamides to 2- and/or 4-pyridone derivatives using either KOt-Bu or trimethylsilyl trifluoromethanesulfonate/Hunig’s base was investigated. Subsequent nonaflation of the cyclization products allowed a facile purification and further functionalization through Suzuki–Miyaura couplings leading to new highly substituted pyridine derivatives. The dependence of the regioselectivity of cyclocondensation on the structure of the β-ketoenamides is discussed.

Thin film microfluidic synthesis of fluorescent highly substituted pyridines

Fluorescent polysubstituted pyridines are readily accessible as a single process using a thin film vortex fluidic device, with the compounds obtained in good yield following simple purification procedures.

Novel 2,4,5‐Trisubstituted Pyridines as Key Intermediates for the Preparation of the TSPO Ligand 6‐F‐PBR28: Synthesis and Full 1H and 13C NMR Characterization

As part of our ongoing research for molecular structures binding to the translocator protein (TSPO 18 kDa), we investigated the preparation of a number of new 2,4,5‐trisubstituted pyridines as novel building blocks. In particular, 5‐amino‐2‐halo‐4‐phenoxypyridines (11, 12, 13) were designed as key intermediates for the synthesis of the recently developed TSPO ligand 6‐F‐PBR28 and its fluorine‐18‐labeled version for positron emission tomography, 6‐[18F]F‐PBR28. We hereby report the chemical preparation as well as the 1H and 13C NMR spectroscopic data of polysubstituted pyridines 2, 3, 4, 5, 6, 7, 7b, 8, 9, 10, 11, 12, 13, 14. The latter demonstrates dramatic changes in electron density repartition of the aromatic ring upon substitution.

An Efficient Synthesis of Poly-Substituted Phenols and Pyridines from Morita-Baylis-Hillman Acetates and Diethyl Oxalacetate

E-mail: kimjn@chonnam.ac.krReceived June 27, 2013, Accepted July 22, 2013Various phenol derivatives were synthesized in a one-pot reaction from MBH acetates and sodium diethyloxalacetate via a [4C+2C] cyclization protocol. In addition, some pyridine derivatives could also besynthesized using the same starting materials, by isolating the S

One-pot synthesis of pyridines from 3-aza-1,5-enynes

Efficient one-pot transformation of 3-aza-1,5-enynes to poly-substituted pyridines in good to excellent yields has been developed. This reaction involved cyclization of 3-aza-enynes and elimination of sulfinyl acids steps.

Trimethylsilyl Trifluoromethanesulfonate-Promoted Cyclocondensation of β-Ketoenamides and Subsequent Nonaflation to Pyrid-2-yl and Pyrid-4-yl Nonaflates as Flexible Precursors for Polysubstituted Pyridines

The intramolecular condensation of β-ketoenamides to 2- and/or 4-pyridone derivatives using either KOt-Bu or trimethylsilyl trifluoromethanesulfonate/Hunig’s base was investigated. Subsequent nonaflation of the cyclization products allowed a facile purification and further functionalization through Suzuki–Miyaura couplings leading to new highly substituted pyridine derivatives. The dependence of the regioselectivity of cyclocondensation on the structure of the β-ketoenamides is discussed.

ChemInform Abstract: Modular Pyridine Synthesis from Oximes and Enals Through Synergistic Copper/Iminium Catalysis.

AbstractRedox activity of copper is combined with the iminium activation strategy to construct various pyridine derivatives, including polysubstituted pyridines.

Synthesis of polysubstituted pyridines via reactions of chalcones and malononitrile in alcohols using Amberlite IRA-400 (OH−)

Polysubstituted pyridine derivatives were synthesized through economical one-pot multicomponent reactions of different α,β-unsaturated ketones, malononitrile, and ethanol or methanol in the presence of Amberlite IRA-400 (OH−) at room temperature. The catalyst is recyclable several times without substantial loss of activity. Other valuable features include the wide range of functional group tolerance, easy and clean synthesis with a simple work-up procedure, and excellent yields under mild conditions.

Dichlorido{2-[(3,5-diphenyl-1H-pyrazol-1-yl-κN2)methyl]pyridine-κN}palladium(II)

The title compound, [PdCl(2)(C(21)H(17)N(3))], is a member of a sequence of Pd, Pt and Co dichloride complexes bearing polysubstituted (pyrazol-1-ylmethyl)pyridine ligands. It is shown that there is a correlation between the steric bulkiness of the bidentate (pyrazol-1-ylmethyl)pyridine ligands and the Pd-N(pyrazole) distances, i.e. the larger the ligand, the longer the bond. In contrast, no trend is observed between the steric properties of the ligand and the Pd-N(pyridine) bond lengths.

Pyridines and pyridine derivatives from vinyl allenes and imines

The Lewis acid mediated reaction of acyclic vinyl allenes and imines, yielding tetrahydropyridines has been carried out. Only one cycloadduct was observed in each case, and thus, the reaction progressed in all cases with total regio-, face- and endo/exo selectivities. The cycloadducts were transformed into polysubstituted pyridines, including bipyridines, by catalytic transfer hydrogenation using cyclohexene as hydrogen donor in good yield. The reaction was extended to the aromatization of the bicyclic cycloadducts prepared in previous works from the reaction of semicyclic vinyl allenes and imines, yielding tetrahydropyridines.

ChemInform Abstract: DPTA‐Catalyzed One‐Pot Regioselective Synthesis of Polysubstituted Pyridines and 1,4‐Dihydropyridines.

AbstractAdvantages of the protocol include excellent yields, environmentally benign source of nitrogen, and mild conditions.

Dual Heterogeneous Catalysis for a Regioselective Three‐ Component Synthesis of Bi‐ and Tri(hetero)arylpyridines

AbstractWe have designed a new, user‐friendly oxidative dual heterogeneous catalytic system capable of promoting polysubstituted pyridines as unique products from simple activated Michael acceptors, 1,3‐dicarbonyls and ammonium acetate. This metal‐free environmentally‐respectful and totally regioselective domino reaction proved to be a great strategy to access bi‐ and triaryl‐type pyridines as well as challenging bi‐ and triheteroaryl‐type pyridines in a single operation.

Synthesis of 2,4-Bis(aryloxy)-1,5-diarylpentane-1,5-diones by Base-Mediated Tandem Reaction

A new, practical, base-mediated method has been developed for the synthesis of 2,4-bis(aryloxy)-1,5-diarylpentane-1,5-diones by a tandem α-methylenation–Michael reaction through activation of two C–Cl bonds. This method permits the use of dichloromethane instead of dibromomethane as a source of one carbon atom for the α-methylenation reaction. The products are useful in syntheses of polysubstituted pyridines and methylenebisbenzofurans.

ChemInform Abstract: Chemo‐ and Regioselective Assembly of Polysubstituted Pyridines and Isoquinolines from Isocyanides, Arynes, and Terminal Alkynes.

We have disclosed a general and efficient synthetic strategy for polysubstituted pyridines and isoquinolines with high chemo- and regioselectivity. In this methodology, 1-alkynyl imines act as the key compound to undergo a sequential alkynyl imine–allenyl imine isomerization/aza-Diels–Alder reaction/aromatization. In the first place, 1-alkynyl imines were formed in situ by a highly selective multicomponent reaction of isocyanides, arynes, and terminal alkynes and reacted with another molecule of arynes or terminal alkynes to furnish target heterocyclic products in a highly efficient and atom-economic manner. On the other hand, we attempted to prepare 1-alkynyl imines by other approaches to undergo a similar reaction sequence to afford polysubstituted pyridines and isoquinolines with a wider range. Different from the first approach, the second approach utilized the preprepared 1-alkynyl imines to introduce the related different substitutents into the final products: arynes or terminal alkynes bearing subst...

ChemInform Abstract: Synthesis of Polysubstituted Pyridines under Combined Microwave and Ultrasound Irradiation: K2CO3‐Promoted Tandem Addition/Cyclization/Hydrogen Shift Process.

AbstractThe multicomponent reaction, efficiently achieved under optimized conditions A), allows an interesting access to pyridine structures of type (IV).

Chemo- and Regioselective Assembly of Polysubstituted Pyridines and Isoquinolines from Isocyanides, Arynes, and Terminal Alkynes

We have disclosed a general and efficient synthetic strategy for polysubstituted pyridines and isoquinolines with high chemo- and regioselectivity. In this methodology, 1-alkynyl imines act as the key compound to undergo a sequential alkynyl imine-allenyl imine isomerization/aza-Diels-Alder reaction/aromatization. In the first place, 1-alkynyl imines were formed in situ by a highly selective multicomponent reaction of isocyanides, arynes, and terminal alkynes and reacted with another molecule of arynes or terminal alkynes to furnish target heterocyclic products in a highly efficient and atom-economic manner. On the other hand, we attempted to prepare 1-alkynyl imines by other approaches to undergo a similar reaction sequence to afford polysubstituted pyridines and isoquinolines with a wider range. Different from the first approach, the second approach utilized the preprepared 1-alkynyl imines to introduce the related different substitutents into the final products: arynes or terminal alkynes bearing substituents different from those of 1-alkynyl imines have been successfully applied for the synthesis a wide variety of pyridines and isoquinolines with diversity.

DPTA-catalyzed one-pot regioselective synthesis of polysubstituted pyridines and 1,4-dihydropyridines

With diphenylammonium triflate (DPAT) as a catalyst, the highly substituted pyridines and dihydropyridines were prepared under solvent-free conditions from aldehydes, ketones, and amines via a one-pot multi-component reaction. The advantages of this protocol include excellent yields, environmentally benign source of nitrogen, mild reaction conditions, and simple manipulation. Different source of nitrogen like urea, thiourea, inorganic ammonium salts, and organic amines were studied. In addition, a novel way was developed for the conversion of primary aliphatic amines into alcohols.

ChemInform Abstract: Tandem One‐Pot Synthesis of Polysubstituted Pyridines Using the Blaise Reaction Intermediate and 1,3‐Enynes.

AbstractSequential reaction of nitriles, Reformatsky reagents and 1,3‐enynes proceeds with complete regio‐ and chemoselectivity to provide the polysubstituted pyridines.

ChemInform Abstract: Synthesis of Unsymmetrical Polysubstituted Pyridines from β‐Sulfonylvinylamines via 1‐Aza‐Allyl Anion Intermediates.

AbstractA modular synthesis of 2,4,6‐trisubstituted pyridines is developed using the base‐promoted cyclocondensation of (Z)‐β‐sulfonylvinylamines with chalcone‐type α,β‐unsaturated ketones.

Regiospecific Synthesis of Polysubstituted Pyridines

Regiospecific Synthesis of Polysubstituted Pyridines