A Facile One‐pot Synthesis of Highly Functionalized Isoxazolyl Imidazo[1,2‐a] Pyridines Through CuI‐Promoted Cyclization

A copper iodide‐promoted cyclization for the synthesis of isoxazolyl imidazo[1,2‐a] pyridines 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j in a one‐pot procedure has been investigated by interaction of 2‐aminopyridines 1a , 1b , 1c , 1d , 1e with nitrostyrylisoxazoles 2a , 2b , 2c , 2d , 2e , 2f under aerial oxidation condition. Similarly, the one‐pot reaction of 2‐amino pyridines 1a , 1b , 1c , 1d , 1e with 4‐bromonitrostyrylisoxazole 2d in the presence of copper iodide under aerial oxidation condition, followed by reaction with phenyl acetylenes in situ afforded highly functionalized imidazo[1,2‐a]pyridines 10a , 10b , 10c , 10d , 10e , 10f , 10g , 10h , 10i , 10j by the Sonogashira coupling.     

Manganese(I)‐Catalyzed C−H Activation/Diels–Alder/retro‐Diels–Alder Domino Alkyne Annulation featuring Transformable Pyridines

Complexity‐increasing Domino reactions comprising C?H allenylation, a Diels–Alder reaction, and a retro‐Diels–Alder reaction were realized by a versatile catalyst derived from earth‐abundant, non‐toxic manganese. The C?H activation/Diels–Alder/retro‐Diels–Alder alkyne annulation sequence provided step‐economical access to valuable indolone alkaloid derivatives through a facile organometallic C?H activation manifold with transformable pyridines.     

Rh/Lewis Acid Catalyzed Regio‐, Diastereo‐ and Enantioselective Addition of 2‐Acyl Imidazoles with Allenes

A highly regio‐, diastereo‐ and enantioselective addition of 2‐acyl imidazoles or 2‐acyl pyridines with allenes promoted by Rh/Lewis acid synergistically catalytic system is described. This atom economic approach leads to the formation of the branched allylic alkylated products including acyclic quaternary all‐carbon stereogenic centres in good yields with good to excellent diastereo‐ and enantioselectivities. Kinetic studies reveal that the rate‐determining step in this process is the oxidative addition of Rh(I) with C—H bond.     

Synthesis of Novel Pyrano[2,3‐b]pyridines from α,α′‐Bis(substituted‐benzylidene)cycloalkanones

In this paper, we describe a two‐step synthesis of a series of tacrine analogues. In the first step, α,α'‐bis(substituted‐benzylidene)cycloalkanones are reacted with malononitrile to afford 2‐amino‐3‐cyano‐4H‐pyrans. The second step involves the conversion of pyrans to pyrano[2,3‐b]pyridines with the use of AlCl₃ as catalyst.     

Synthesis and Herbicidal Activity of 2‐Alkyl(aryl)‐4‐amino‐3‐[alkyl(alkoxy)carbonyl]‐5‐cyano‐6‐[(3‐trifluoromethyl)phenoxy]‐pyridines

To find novel bleaching herbicide lead compounds, a series of novel 2‐alkyl(aryl)‐4‐amino‐3‐[alkyl(alkoxy)carbonyl]‐5‐cyano‐6‐[(3‐trifluoromethyl)phenoxy]‐pyridines was designed and synthesized by the multistep reactions. N,S‐acetal 1 reacted with 2 to obtain multisubstituted pyridines 3 in the presence of zinc nitrate as the catalyst. The target compounds 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k , 5l were formed by the oxidation of 3 , followed by the substitution with 3‐(trifluoromethyl)phenol in the presence of potassium carbonate. Their structures were confirmed by IR, ¹H NMR, EI‐MS, and elemental analyses. The preliminary bioassays indicated that some of them displayed moderate herbicidal activity against dicotyledonous weed Brassica campestris L at the concentration of 100 mg/L.     

Chiroptical Probing of Lanthanide‐Directed Self‐Assembly Formation Using btp Ligands Formed in One‐Pot Diazo‐Transfer/Deprotection Click Reaction from Chiral Amines

A series of enantiomeric 2,6‐bis(1,2,3‐triazol‐4‐yl)pyridines (btp)‐containing ligands was synthesized by a one‐pot two‐step copper‐catalyzed amine/alkyne click reaction. The Eu^III‐ and Tb^III‐directed self‐assembly formation of these ligands was studied in CH₃CN by monitoring their various photophysical properties, including their emerging circular dichroism and circularly polarized luminescence. The global analysis of the former enabled the determination of both the stoichiometry and the stability constants of the various chiral supramolecular species in solution.     

Microwave‐Assisted One‐Pot Synthesis of Substituted 3‐Bromoimidazo[1,2‐a]pyridines and Imidazoheterocycles

Herein, an efficient, one‐pot microwave‐assisted synthesis of a diverse set of 3‐bromoimidazo[1,2‐a]pyridines is being reported with good yields (40–85%). The method involves electrophilic aromatic bromination using bromodimethylsulfonium ion generated in situ via oxidation of HBr salt by DMSO. This methodology was also applied to the synthesis of related imidazoheterocycles. Copyright © 2014 HeteroCorporation     

Transition‐Metal‐Free BF3‐Mediated Oxidative and Non‐Oxidative Cross‐Coupling of Pyridines

We report a BF₃‐mediated direct alkynylation of pyridines at C(2) by using a variety of alkynyllithium reagents (oxidative cross‐coupling). Moreover, we have developed a novel transition‐metal‐free cross‐coupling method between alkylmagnesium reagents and 4‐substituted pyridines, such as isonicotinonitrile and 4‐chloropyridine, by employing BF₃?OEt₂ as a promoter. The combination of these methods enabled us to efficiently prepare a range of di‐, tri‐, and tetrasubstituted pyridines.     

A Cascade Synthesis of Hetero‐arylated Triarylmethanes Through a Double 5‐endo‐dig Cyclization Sequence

A sequential two‐step method for the synthesis of hetero‐arylated triarylmethanes through a Ag‐catalyzed sequential double cyclization–nucleophilic addition cascade is described. This methodology basically involves an initial 5‐endo‐dig cyclization of o‐alkynyl anilines to provide 2‐substituted indole derivatives, which then react with 2‐(2‐enynyl)‐pyridines to afford indolizine‐containing unsymmetrical triarylmethanes through another 5‐endo‐dig cyclization.     

Importance of a Fluorine Substituent for the Preparation of meta‐ and para‐Pentafluoro‐λ6‐sulfanyl‐Substituted Pyridines

Although there are ways to synthesize ortho‐pentafluoro‐λ⁶‐sulfanyl (SF₅) pyridines, meta‐ and para‐SF₅‐substituted pyridines are rare. We disclose herein a general route for their synthesis. The fundamental synthetic approach is the same as reported methods for ortho‐SF₅‐substituted pyridines and SF₅‐substituted arenes, that is, oxidative chlorotetrafluorination of the corresponding disulfides to give pyridylsulfur chlorotetrafluorides (SF₄Cl‐pyridines), followed by chloride/fluoride exchange with fluorides. However, the trick in this case is the presence on the pyridine ring of at least one fluorine atom, which is essential for the successful transformation of the disulfides into m‐and p‐SF₅‐pyridines. After enabling the synthesis of an SF₅‐substituted pyridine, ortho‐F groups can be efficiently substituted by C, N, S, and O nucleophiles through an S_NAr pathway. This methodology provides access to a variety of previously unavailable SF₅‐substituted pyridine building blocks.     

Benzyltrimethylammoniumfluoride Hydrate: An Efficient Catalyst for One‐Pot Synthesis of Hantzsch 1,4‐Dihydropyridines and Their Aromatization

An efficient, cost‐effective and simple protocol has been developed for the synthesis of Hantzsch 1,4‐dihydropyridines and their oxidation into pyridines using benzyltrimethylammonium fluoride hydrate as an excellent catalyst under solvent‐free condition. All of the products synthesized by this method are characterized by various spectroscopic methods (IR, ¹H NMR, ¹³C NMR, and DEPT).     

Chains,Necklaces and Weaving Chain‐link Grids from Self‐Assembly Reactions

Assembly of two ditopic units, a phenanthroline substituted by 4‐ethynyl pyridines at the 2‐and 9‐positions and a dimetallic paddlewheel, gives a linear chain polymer rather than a closed cyclic species, which would appear equally possible. The chain may be decorated by binding a copper‐containing macrocycle around the phenanthroline units to form a polypseudorotaxane. When two phenanthroline ligands are assembled in a first step around copper(I), the paddlewheel acceptor can link them in a second step to form a two‐dimensional interwoven grid that resembles the form of a chain‐link fence. Each copper(I) centre in this structure is chiral, and the crystal shows complete homochirality, implying selection during the assembly process.     

Regio‐ and Stereoselective Synthesis of Functionalized Dihydropyridines,Pyridines, and 2H‐Pyrans: Heck Coupling of Monocyclopropanated Heterocycles

A palladium‐catalyzed coupling between aryl halides and monocyclopropanated pyrroles or furans has been developed, leading to valuable six‐membered N‐ and O‐heterocycles. As the key step, a selective cleavage of the non‐activated endocyclic C?C bond of the 2‐heterobicyclo‐[3.1.0]hexane framework is achieved. The developed method offers access to highly functionalized piperidines, pyridines, and pyrans that are challenging to access by traditional methods.     

NIS/PhI(OAc)2‐Mediated Diamination/Oxidation of N‐Alkenyl Formamidines: Facile Synthesis of Fused Tricyclic Ureas

Facile synthesis of bicyclic ureas by NIS/PhI(OAc)₂‐mediated diamination/oxidation of N‐alkenyl formamidines is reported. Bulky aromatic groups such as 2,6‐diisopropylphenyl and mesityl and alkyl groups were tolerated towards the process. Several control experiments have been performed, and the reaction outcomes indicate that the oxidation process is probably concerted with the diamination cyclization, and succinimide generated from NIS‐mediated aminoamidiniumation step promoted the PhI(OAc)₂‐mediated oxidation step. The new methodology provides an efficient method for the synthesis of fused tricyclic ureas.     

Catalytic [2 + 2 + 2] cycloaddition polymerization of diyne–nitrile monomers in the presence of CoCl2‐6H2O/diphosphine/Zn

Cobalt‐catalyzed [2 + 2 + 2] cocycloaddition reaction of 1,6‐diynes and nitriles to generate substituted pyridines has been applied to the polymerization of diyne–nitrile monomers, the reaction of which proceeded smoothly in a step‐growth fashion to provide linear polymers comprising pyridine structures in the main chain. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 345–351     

Synthesis of dihydrofuro[2,3‐b]pyridines by the reaction of 2‐amino‐4,5‐dihydro‐3‐furancarbonitriles with α,β‐unsaturated carbonyl compounds

The reactions of 2‐amino‐4,5‐dihydro‐3‐furancarbonitriles 1a‐d with α,β‐unsaturated carbonyl compounds in the presence of sodium ethoxide (0.1 equivalent) gave the corresponding Michael adducts 2a‐d , 3a‐d and 4a‐d. Compounds 2a‐d and 3a‐c reacted with sodium alkoxide (1 equivalent) to yield the corresponding 7a‐alkoxyhexahydrofuro[2,3‐b]pyridines 5a‐d, 6a‐d, 7a‐c and 8a‐c . Treatment of 5a‐d, 6a‐d, 7a‐c and 8a‐c with potassium tert‐butoxide produced the corresponding dihydrofuro[2,3‐b]pyridines 9a‐d and 10a‐c . The reaction of 4a‐c with sodium ethoxide (1 equivalent) afforded the corresponding dihydro‐furo[2,3‐b]pyridines 11a‐c .     

One‐Pot,Three‐Component Sulfonimidamide Synthesis Exploiting the Sulfinylamine Reagent N‐Sulfinyltritylamine,TrNSO

Sulfonimidamides are increasingly important molecules in medicinal chemistry and agrochemistry, but their preparation requires lengthy synthetic sequences, which has likely limited their use. We describe a one‐pot de novo synthesis of sulfonimidamides from widely available organometallic reagents and amines. This convenient and efficient process uses a stable sulfinylamine reagent, N‐sulfinyltritylamine (TrNSO), available in one step on 10 gram scale, as a linchpin. In contrast to classical approaches starting from thiols or their derivatives, our TrNSO‐based approach facilitates the rapid assembly of the three reaction components into a variety of differentially substituted sulfonimidamides containing medicinally relevant moieties, including pyridines and indoles. Analogues of the sulfonamide‐containing COX‐2 inhibitor Celecoxib were prepared and evaluated.     

One‐Pot,Three‐Component Sulfonimidamide Synthesis Exploiting the Sulfinylamine Reagent N‐Sulfinyltritylamine,TrNSO

Sulfonimidamides are increasingly important molecules in medicinal chemistry and agrochemistry, but their preparation requires lengthy synthetic sequences, which has likely limited their use. We describe a one‐pot de novo synthesis of sulfonimidamides from widely available organometallic reagents and amines. This convenient and efficient process uses a stable sulfinylamine reagent, N‐sulfinyltritylamine (TrNSO), available in one step on 10 gram scale, as a linchpin. In contrast to classical approaches starting from thiols or their derivatives, our TrNSO‐based approach facilitates the rapid assembly of the three reaction components into a variety of differentially substituted sulfonimidamides containing medicinally relevant moieties, including pyridines and indoles. Analogues of the sulfonamide‐containing COX‐2 inhibitor Celecoxib were prepared and evaluated.     

Overcoming the Limitations of C−H Activation with Strongly Coordinating N‐Heterocycles by Cobalt Catalysis

Strongly coordinating nitrogen heterocycles, including pyrimidines, oxazolines, pyrazoles, and pyridines, were fully tolerated in cobalt‐catalyzed C?H amidations by imidate assistance. Structurally complex quinazolines are thus accessible in a step‐economic manner. Our findings also establish the relative powers of directing groups in cobalt(III)‐catalyzed C?H functionalization for the first time.     

Library‐directed Solution‐ and Solid‐phase Synthesis of 2,4‐Disubstituted Pyridines: One‐pot Approach through 6 π‐Azaelectrocyclization

An efficient one‐pot synthetic procedure for the synthesis of 2,4‐disubstituted pyridines has been successfully established. The method proceeds through a 6π‐azaelectrocyclization‐aromatization sequence. Using this method, a wide variety of pyridine structures substituted at the 2‐position have been rapidly constructed from vinyl stannanes, vinyl iodide, sulfonamide, and a palladium catalyst. The method was further applied to the solid‐phase synthesis wherein the use of a “traceless” sulfonamide linker enabled the rapid preparation of a small library of pyridines with high purity, without any chromatographic separation.