Synthesis of Planar Chiral [2.2]Paracyclophanyl Imidazo[1,5-a]pyridinium Salts for the Rhodium-Catalyzed Asymmetric Arylation

Abstract

Several novel flexibility-restricted imidazo[1,5-a]pyridinium triflates (abbreviated as imidazolium salts) were synthesized from (4S _p,13R _p)-(?)-4-amino-13-bromo[2.2]paracyclophane and pyridylaldehyde. These imidazolium salts can be used as nitrogen-containing heterocyclic carbene precursors in asymmetric catalysis and here they are applied in the Rh-catalyzed asymmetric 1,2-addition of arylboronic acids to aldehydes. After optimizing the catalytic situations and testing a series of substrates, moderate enantioselectivity and good yield were obtained.     

Synthesis of novel fluorescent 3-aryl- and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines by Suzuki cross-coupling reactions

Two series of compounds, 3-aryl- (series A, compounds 2a-j) and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines (series B, compounds 3a-j) have been synthesized by Suzuki cross-coupling reactions, with a triazolopyridine halide and an aryl or heteroaryl boronic acid in moderate to good yields. All compounds obtained are fluorescents, the quantum yields, particularly those of compounds 3f-j, are very high.     

Imidazo[1,5-a]pyridine: a versatile architecture for stable N-heterocyclic carbenes

The imidazo[1,5-a]pyridine skeleton provides a versatile platform for the generation of new types of stable N-heterocyclic carbenes. Rh(I) mono- (6) and biscarbenes (7) from imidazo[1,5-a]pyridin-3-ylidenes (ImPy) and derivatives such as 13 from a mesoionic carbene were synthesized and characterized.     

Pd-catalyzed oxidative cross-coupling of imidazo[1,2-a]pyridine with arenes

A facile method for direct Pd(OAc)₂-catalyzed oxidative cross-coupling of unactivated imidazo[1,2-a]pyridine with simple arenes has been developed. The reaction shows good reaction efficiency, high regioselectivity, and good functional-group compatibility. This approach provides a useful protocol for the preparation of imidazo[1,2-a]pyridine–arene structure of interest in biological and pharmaceutical materials.     

Stable N-heterocyclic carbene derivatives of copper(i) and silver(i) containing radical anion redox active ligands

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Antiparasitic activities of bimetallic N-heterocyclic carbene gold(I) complexes with ferrocene ligands: Relevance of chlorido and phosphino ligands

Gold(I) complexes carrying imidazole-2-ylidene ligands and ferrocene substituents were prepared. Their activities against protozoal Leishmania major and Toxoplasma gondii parasites were analyzed. Certain gold(I) complexes with chlorido and 1,1′-bis(triphenylphosphino)ferrocene ligands revealed promising antiparasitic effects. The new chlorido complexes 5b and 5c showed high activities against T. gondii tachyzoites and L. major promastigotes while the new ferrocene-bridged bis-gold(I) complexes 8a and 8b were particularly active against L. major amastigotes and considerably selective as to toxicity results from Vero cells and macrophages.     

A convenient synthesis of linear pyridinoimidazo[1,2-a]pyridine and pyrroloimidazo[1,2-a]pyridine cores

Two new imidazo[1,2-a]pyridine derivatives, pyridinoimidazo[1,2-a]pyridine (10) and pyrroloimidazo[1,2-a]pyridine (16), were synthesised from 2-amino-4-methyl-5-nitropyridine (1) by linear cyclisation, making use of dimethylformamide dimethylacetal (DMFDMA) as an agent of vinylamine functionalisation. This report describes first the formation of pyridine and pyrroloimidazopyridine from (1), and then the formation of pyridine-fused and pyrrolo-fused pyridine by the Friedländer method and reductive cyclisation followed by treatment of the resulting adduct with chloroacetaldehyde.     

氮杂环卡宾银碘化物[Ag(MEIm)2]+[AgI2]-的合成、结构与催化性能(MEIm=1-methyl-3-ethyl-imidazolyl)

常温下(MEIm)+I-(MEIm=1-methyl-3-ethyl-imidazolyl)与Ag2O按照物质的量比为1∶2在DMSO中反应成功的合成了线型氮杂环卡宾银碘化物[Ag(MEIm)2]+[AgI2]-,化合物通过了元素分析,1H NMR,X-ray衍射表征。配合物属于单斜晶系,空间群为C2/m,a=1.592 5(4)nm,b=0.679 07(14)nm,c=0.927 1(2)nm,β=110.247(5)°,V=0.940 7(4)nm3,Mr=689.86,Z=8,Dc=2.436 g.cm-3,μ(Mo Kα)=5.36 mm-1,F(000)=640,R=0.036,wR=0.105。配合物由阴阳离子对构成,配阳离子中2个卡宾碳原子与银原子呈线型结构。目标化合物对L-lactide的聚合具有高的催化活性。     

Selective,C-3 Friedel-Crafts acylation to generate functionally diverse,acetylated Imidazo[1,2-a]pyridine derivatives

Carbon-carbon bonds are integral for pharmaceutical discovery and development. Frequently, CC bond reactions utilize expensive catalyst/ligand combinations and/or are low yielding, which can increase time and expenditures in pharmaceutical development. To enhance CC bond formation protocols, we developed a highly efficient, selective, and combinatorially applicable Friedel-Crafts acylation to acetylate the C-3 position of imidazo[1,2-a]pyridines. The reaction, catalyzed by aluminum chloride, is both cost effective and more combinatorial friendly compared to acetylation reactions requiring multiple, stoichiometric equivalents of AlCl₃. The protocol has broad application in the construction of acetylated imidazo[1,2-a]pyridines with an extensive substrate scope. All starting materials are common and the reaction requires inexpensive, conventional heating methods for adaptation in any laboratory. Further, the synthesized compounds are predicted to possess GABA activity through a validated, GABA binding model. The developed method serves as a superior route to generate C-3 acetylated imidazo[1,2-a]pyridine building-blocks for combinatorial synthetic efforts.     

Microwave-assisted organic synthesis of 3-substituted-imidazo[1,5-a]pyridines

3-Substituted-imidazo[1,5-a]pyridines were conveniently synthesized in two steps from commercially available picolinic esters under microwave irradiation conditions.     

Regioselective formylation of pyrazolo[3,4-b]pyridine and pyrazolo[1,5-a]pyrimidine systems using Vilsmeier-Haack conditions

Regioselective formylation behavior has been found in the reaction of pyrazolo[3,4-b]pyridines and pyrazolo[1,5-a]pyrimidines via Vilsmeier-Haack conditions. While the 4,5- and 6,7-dihydro derivatives afforded pyrazolo[3,4-b]pyridine-5-carbaldehydes and 4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarbaldehydes, respectively, the aromatic analogs rendered the pyrazolo[1,5-a]pyrimidine-3-carbaldehyde only, and no reaction took place at the pyrazolopyridine derivatives.     

Chemical reactivity of [1,2,3]triazolo[1,5-a]- and [1,5-c]-pyrimidinium salts

The chemical reactivity of the [1,2,3]triazolo[1,5-a]- and [1,5-c]-pyrimidinium salts towards morpholine, water and sodium methoxide have been studied. Among others, new 1-aza and 2-azabutadienes substituted by a [1,2,3]-triazole ring were obtained in the course of the opening of the positively charged pyrimidine ring.     

Novel synthesis of C-3-(hetero)aryl [1,2,3]triazolo[1,5-a]pyridines using the Stille reaction

Herein, we report a novel and high yielding approach for the preparation of the first C-3-organometallic substituted [1,2,3]triazolo[1,5-a]pyridine and its application to the Stille reaction using MAOS.     

Triazolopyridines. Part 26: The preparation of novel [1,2,3]triazolo[1,5-a]pyridine sulfoxides

The regioselective synthesis of new triazolopyridine halides and sulfoxides with the substituent in all different ring positions of [1,2,3]triazolo[1,5-a]pyridines is presented. The triazolo ring opening reaction of some representative sulfoxides to obtain disubstituted pyridines is also studied.     

Novel one pot synthesis of polysubstituted pyrazolo[1,5-a]- and imidazo[1,2-a]pyrimidines

We have described a convenient regioselective one-pot approach to pyrazolo[1,5-a]- and imidazo[1,2-a]pyrimidine derivatives from α,β-unsaturated imines generated in situ and amino heterocycles. Reaction is general with respect to all three components, namely (i) nitrile, (ii) aldehyde, and (iii) amino heterocycle reagents. Good yields (52-77%), convenient isolation of the targeted molecules are the distinct characteristics of the developed protocol.     

Novel synthesis of 2,4-bis(2-pyridyl)-5-(pyridyl)imidazoles and formation of N-(3-(pyridyl)imidazo[1,5-a]pyridine)picolinamidines: nitrogen-rich ligands

Heating a neat 1:2 mixture of 2-picolylamine and 2-cyanopyridine followed by treatment of the resultant red gummy substance with aqueous KOH resulted in the isolation of 2,4,5-tris(2-pyridyl)imidazole (1a) as the major product and N-(3-(2-pyridyl)imidazo[1,5-a]pyridine)picolinamidine (2a) in small amounts. Similarly, by using 3-picolylamine, 2,4,-bis(2-pyridyl)-5-(3-pyridyl)imidazole (1b) and N-(3-(3-pyridyl)imidazo[1,5-a]pyridine)picolinamidine (2b) were isolated, and by using 4-picolylamine, 2,4,-bis(2-pyridyl)-5-(4-pyridyl)imidazole (1c) and N-(3-(4-pyridyl)imidazo[1,5-a]pyridine)picolinamidine (2c) were isolated. The plausible mechanism of the formation of 1a-c and 2a-c is delineated.     

Combinatorial synthesis of 4-oxo-4H-imidazo[1,5-a]quinoxalines and 4-oxo-4H-pyrazolo[1,5-a]quinoxalines

A combinatorial synthetic route yielding imidazo[1,5-a]quinoxalines and pyrazolo[1,5-a]quinoxalines is described. The use of 2-fluoroaniline and 1H-imidazole-4-carboxylic acid, respectively, 1H-pyrazole-3-carboxylic acid in the Ugi-reaction (U-4CR) followed by a nucleophilic aromatic substitution (S_NAr) affords the imidazo- as well as the pyrazolo-[1,5-a]quinoxaline moiety in good yield and high diversity.     

A one-pot synthesis of imidazo[1,5-a]pyridines

A one-pot synthesis of imidazo[1,5-a]pyridines starting from a carboxylic acid and 2-methylaminopyridines allowing introduction of various substituents at the 1- and 3-positions is achieved using propane phosphoric acid anhydride in ethyl or n-butyl acetate at reflux.     

Half-sandwich rhodium complexes containing both N-heterocyclic carbene and ortho-carborane-1,2-dithiolate ligands

A new route was used to synthesize half-sandwich rhodium complexes containing both N-heterocyclic carbenes (NHC) and carborane ligands. The rhodium carbene complexes Cp^∗Rh(L)[S₂C₂(B₁₀H₁₀)] (Cp^∗ = pentamethylcyclopentadienyl, L = 1,3-dimethylimidazolin-2-ylidene; 4) can be obtained from the reaction of Cp^∗Rh(L)Cl₂ (2) with Li₂S₂C₂(B₁₀H₁₀) or from the reaction of Cp^∗Rh[S₂C₂(B₁₀H₁₀)] (3) with silver-NHC complex prepared by direct reaction of an imidazolium precursor and Ag₂O. Complexes 2 and 4 were characterized by IR, NMR spectroscopy, element analysis and X-ray structure analyses.     

Triazolopyridines. Part 25: Synthesis of new chiral ligands from [1,2,3]triazolo[1,5-a]pyridines

The synthesis of new chiral triazolopyridine ligands possessing fluorescent properties is described. The triazolo ring opening was studied in order to obtain new chiral 2,6-disubstituted pyridines. A preliminary coordination assay with Zn(II) is also presented.