Unprecedented regiochemical control in the formation of aryl[1,2-a]imidazopyridines from alkynyliodonium salts: mechanistic insights

Dixon, Luke I.; Carroll, Michael A.; Gregson, Thomas J.; Ellames, George J.; Harrington, Ross W.; Clegg, William

doi:10.1039/c3ob41112e

Cited by 30 publications

(14 citation statements)

References 66 publications

(60 reference statements)

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“…The crystals were prepared by layering a solution of 6 a in DMSO with diethyl ether and submitted to single crystal X‐ray analysis (Figure ). The molecular conformation has a distorted T‐shape with an O9‐I1‐C10 angle of 165.8°, which is similar to the reported arylbenziodoxolones and alkynylbenziodoxolones . The bond angle O9‐I1‐C6 is 72.9° and the C6‐I1‐C10 angle of 93.7° are also similar to previous reports, as are the bond lengths I1−C6 of 2.121 (Å) and I1−C10 of 2.100 (Å).…”

Section: Methodssupporting

confidence: 87%

“…The bond angle O9‐I1‐C6 is 72.9° and the C6‐I1‐C10 angle of 93.7° are also similar to previous reports, as are the bond lengths I1−C6 of 2.121 (Å) and I1−C10 of 2.100 (Å). The I1−O9 bond length of 2.51 Å is significantly larger than in alkynylbenziodoxolones, but in similar length as arylbenziodoxolones . This bond length trend is in agreement with the larger trans influence exerted by vinyl and aryl groups compared to alkynyl and trifluoromethyl groups …”

Section: Methodssupporting

confidence: 76%

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Synthesis, Characterization and Unusual Reactivity of Vinylbenziodoxolones—Novel Hypervalent Iodine Reagents

Stridfeldt

Seemann

Bouma

et al. 2016

Chemistry A European J

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A novel type of hypervalent iodine(III) reagents, vinylbenziodoxolones (VBX), has been synthesized in a one-pot reaction from 2-iodobenzoic acid. VBX is bench stable, has been thoroughly characterized and the cyclic structure is supported by X-ray analysis. The reactivity of VBX was investigated in vinylation of nitrocyclohexane, and delivered vinylated products with opposite regioselectivity compared to acyclic vinyl(aryl)iodonium salts. The reagents could become a powerful tool in vinylation reactions under both metal-free and metal-catalyzed conditions.

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Section: Methodssupporting

confidence: 87%

Section: Methodssupporting

confidence: 76%

Synthesis, Characterization and Unusual Reactivity of Vinylbenziodoxolones—Novel Hypervalent Iodine Reagents

Stridfeldt

Seemann

Bouma

et al. 2016

Chemistry A European J

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“…An understanding of the role of ion‐pairing dynamics, aggregation, and structure–activity relationships is required for effective synthetic reagents to be developed. This is a very understudied field, with only a few examples explicitly exploring the mechanistic role of counterions in complex reactions, [27] especially when changing the ion changes the product outcome; but none focusing on the comparably subtle effects observed here. The former are highly exciting, but the latter class, where changing the counterion simply accelerates or retards a reaction are far more common, and very industrially and biologically relevant.…”

Section: Introductionmentioning

confidence: 99%

Not‐So‐Innocent Anions Determine the Mechanism of Cationic Alkylators

Taimoory

Cataldo

Schäfer

et al. 2021

Chemistry A European J

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Alkylating reagents based on thioimidazolium ionic liquids were synthesized and the influence of the anion on the alkylation reaction mechanism explored in detail using both experimental and computational methods. Thioimidazolium cations transfer alkyl substituents to nucleophiles, however the reaction rate was highly dependent on anion identity, demonstrating that the anion is not innocent in the mechanism. Detailed analysis of the computationally‐derived potential energy surfaces associated with possible mechanisms indicated that this dependence arises from a combination of anion induced electronic, steric and coordinating effects, with highly nucleophilic anions catalyzing a 2‐step process while highly non‐nucleophilic, delocalized anions favor a 1‐step reaction. This work also confirms the presence of ion‐pairs and aggregates in solution thus supporting anion‐induced control over the reaction rate and mechanism. These findings provide new insight into an old reaction allowing for better design of cationic alkylators in synthesis, gene expression, polymer science, and protein chemistry applications.

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“…44 65.07 2g 63.17HURZOL 45 65.16RELQUW 46 64.98 2h 64.74KABMIM 47 66.21RUJNEQ. 48 64.61 2i 63.81MIXZOJ 49 65.44TIDVIN 50 66.07 2j 64.63MIXZUP 51 67.52TUZYEU 52 65.44 2k 65.36MONREO 53 66.12UTITEX 54 62.07 2l 67.34NAGGEH 55 65.27VEGKAU 56 64.34 2m 60.69NAGGEH01 57 64.84WUHKER 58 62.24 2n 62.87NOGRIM 59 65.44YEDHIY 60 63.06 2o 66.69NONFOM 61 64.30ZUNVOV 62 68.57AHOMIV 63 63.75NONFOM01 61 65.95ZUPCOE 62 66.04BEGTUE 64 62.92NUBVUD 65 63.87ZUSSAJ 66 63.31CAJTIQ 67 67.82NUBWAK 65 64.00…”

Section: Resultsmentioning

confidence: 99%

Crystal Correlation Of Heterocyclic Imidazo[1,2-a]pyridine Analogues and Their Anticholinesterase Potential Evaluation

Kwong

Kumar

Mah

et al. 2019

Sci Rep

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Imidazo[1,2-a]pyridine-based compounds are clinically important to the treatments of heart and circulatory failures, while many are under development for pharmaceutical uses. In this study, a series of imidazo[1,2-a]pyridine-based derivatives 2(a–o) were synthesized by reacting a-haloketones with 2-aminopyridines in a basic media at ambient temperature. Single crystal X-ray diffraction studies suggest that with low degree-of-freedom, the introduction of bulky adamantyl or electron-rich biphenyl moiety into the imidazopyridine derivatives will not affect its structural occupancy. Imidazo[1,2-a]pyridine-based derivatives with biphenyl side chain are potential AChE inhibitors. Compound 2h which bears a biphenyl side chain and methyl substituent at the position R4 of the imidazo[1,2-a]pyridine ring showed the strongest AChE inhibition with an IC50 value of 79 µM. However, imidazo[1,2-a]pyridine derivatives with phenyl side chain exhibit better BChE inhibition effect among the series. Compound 2j with 3,4-dichlorophenyl side chain and unsubstituted imidazo[1,2-a]pyridine ring appears to be the strongest BChE inhibitor with an IC50 value of 65 µM and good selectivity. The inhibitory effects of active compounds were further confirmed by computational molecular docking studies. The results unveiled that peripheral anionic sites of AChE and acyl pocket of BChE were the predominated binding sites for the subjected inhibitors.

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Unprecedented regiochemical control in the formation of aryl[1,2-a]imidazopyridines from alkynyliodonium salts: mechanistic insights

Cited by 30 publications

References 66 publications

Synthesis, Characterization and Unusual Reactivity of Vinylbenziodoxolones—Novel Hypervalent Iodine Reagents

Synthesis, Characterization and Unusual Reactivity of Vinylbenziodoxolones—Novel Hypervalent Iodine Reagents

Not‐So‐Innocent Anions Determine the Mechanism of Cationic Alkylators

Crystal Correlation Of Heterocyclic Imidazo[1,2-a]pyridine Analogues and Their Anticholinesterase Potential Evaluation

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