Alkynes and Nitrogen Compounds: Useful Substrates for the Synthesis of Pyrazoles

Neto, José S. S.; Zeni, Gilson

doi:10.1002/chem.201905276

Cited by 49 publications

(22 citation statements)

References 119 publications

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“…Even 100 years after the first reports on the synthesis of pyrazoles, this heterocyclic structure is still used as a model for designing selective protocols in cyclocondensation reactions, and also for biological/pharmacological assays [24–29] . Scheme 3 shows the general synthetic pathway for the regioselective synthesis of pyrazolines 5 and pyrazoles 6 (obtained from dehydration of 5 ), using enones 4 and substituted hydrazines or hydrazides.…”

Section: Synthesis Of Pyrazolines and Pyrazoles Using Nn‐dinucleophilesmentioning

confidence: 99%

Haloacetylated Enol Ethers: a Way Out for the Regioselective Synthesis of Biologically Active Heterocycles

2021

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This review describes advances in the synthesis of heterocyclic scaffolds (associated with their biological activity), using haloacetylated enol ethers as precursors. The wide variety of heterocycles that can be prepared using these precursors, together with the high regioselectivity they usually provide, in [3+2] and [3+3] cyclocondensation reactions, make these starting materials powerful tools. The biological evaluation is also highlighted, given that several analogues of commercially available drugs can be easily accessed.

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Section: Synthesis Of Pyrazolines and Pyrazoles Using Nn‐dinucleophilesmentioning

confidence: 99%

Haloacetylated Enol Ethers: a Way Out for the Regioselective Synthesis of Biologically Active Heterocycles

2021

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“…However, the synthesis of pyrazoles by the reaction of 1,3‐dicarbonyl compounds with hydrazines is not the only method available [1,2] . In particular, the 1,3‐dipolar cycloaddition of diazo compounds to alkynes, [2,4] first discovered by Buchner in 1889, [5] is a highly effective route to pyrazoles, since no σ‐bonds are broken in the process. Recently, such efficient cycloadditions have come to the fore in bioorthogonal chemistry, [6,7] a term first introduced by Bertozzi in 2003 to cover chemical reactions that can be conducted in living systems without disrupting natural processes [8,9] .…”

Section: Figurementioning

confidence: 99%

Diazophosphonates: Effective Surrogates for Diazoalkanes in Pyrazole Synthesis

Ruffell

Smith

Green

et al. 2021

Chemistry A European J

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Diazophosphonates, readily prepared from α‐ketophosphonates by oxidation of the corresponding hydrazones in batch or in flow, are useful partners in 1,3‐dipolar cycloaddition reactions to alkynes to give N‐H pyrazoles, including the first intramolecular examples of such a process. The phosphoryl group imbues a number of desirable properties into the diazo 1,3‐dipole. The electron‐withdrawing nature of the phosphoryl stabilizes the diazo compound making it easier to handle, whilst the ability of the phosphoryl group to migrate readily in a [1,5]‐sigmatropic rearrangement enables its transfer from C to N to aromatize the initial cycloadduct, and hence its facile removal from the final pyrazole product. Overall, the diazophosphonate acts as a surrogate for the much less stable diazoalkane in cycloadditions, with the phosphoryl group playing a vital, but traceless, role. The cycloaddition proceeds more readily with alkynes bearing electron‐withdrawing groups, and is regiospecific with asymmetrical alkynes. The potential of diazophosphonates for use in bioorthogonal cycloadditions is demonstrated by their facile addition to strained alkynes.

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“…Copper catalyzed azide‐alkyne cycloaddition (CuAAC) reaction satisfies all the stringent criteria of the Sharpless click chemistry concept, [2–3] as it is simple and highly efficient, modular and broad in scope, high yielding, and regiospecific, inoffensive byproducts that can be removed by nonchromatographic methods. CuAAC reaction can be conducted in easily removable (e. g., CH 2 Cl 2 ) or benign solvents (e. g., H 2 O) [4–5] …”

Section: Introductionmentioning

confidence: 99%

“…CuAAC reaction can be conducted in easily removable (e. g., CH 2 Cl 2 ) or benign solvents (e. g., H 2 O). [4][5] Substituted 1,2,3-triazoles from CuAAC reaction has been carried out a comprehensive investigation due to the application in natural products synthesis, [4][5][6] designed materials, [7][8][9] bioconjugation, [10,11] and pharmaceuticals. [12][13][14] Furthermore, the experimental and theoretical studies on catalytic mechanism was fundamentally crucial for the effective synthesis and application.…”

Section: Introductionmentioning

confidence: 99%

A DFT Study on the Binuclear Copper(I)‐Catalyzed Synthesis Mechanism of 1,2,3‐Triazolo[1,5‐c]Pyrimidine via Interrupted Click and Ketenimine Rearrangement

2021

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In this paper, the mechanism of the full catalytic cycle for binuclear Cu(I)‐catalyzed sulfonyl azide‐alkyne cycloaddition reaction for the synthesis of triazolopyrimidines was rationalized by density functional theoretical (DFT) calculations. The computed reaction route consists of: (a) formation of dicopper intermediates, including C−H activation of terminal alkyne, 3+2 ring cycloaddition and ring‐reducing reaction and transmetalation, (b) interrupted CuAAC reaction, including di‐copper catalyzed ring‐opening of 2H‐azirines and C−C bond formation to generate the copper‐triazoles and ‐ketenimines, (c) two‐step C−N cross‐coupling and following (d) multi‐step hydrogen transfer by the hydrogen bonding chain of water to promote the C−N formation and another C−N cleavage through the removal of p‐tolyl sulfonamides. Our DFT results indicate that the multi‐step hydrogen transfer process is the rate‐determining step along the potential energy surface profile. The explicit water model was used for systematic determination of barrier for C−C cross‐coupling, C−N bond formation and cleavage, and p‐tolylsulfonamide removal. A critical insight in the interrupted CuAAC reaction was proposed. Further prediction interprets H2O hydrogen bond chain plays an important role in C−N bond formation and cleavage, and the removal of p‐tolylsulfonamide. This may have fundamental guidance on the design of 1, 5‐herterocyclic functionalized triazolopyrimidines via interrupted CuAAC rearrangement reaction, as well as hydrogen bond chain of water.

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Alkynes and Nitrogen Compounds: Useful Substrates for the Synthesis of Pyrazoles

Cited by 49 publications

References 119 publications

Haloacetylated Enol Ethers: a Way Out for the Regioselective Synthesis of Biologically Active Heterocycles

Haloacetylated Enol Ethers: a Way Out for the Regioselective Synthesis of Biologically Active Heterocycles

Diazophosphonates: Effective Surrogates for Diazoalkanes in Pyrazole Synthesis

A DFT Study on the Binuclear Copper(I)‐Catalyzed Synthesis Mechanism of 1,2,3‐Triazolo[1,5‐c]Pyrimidine via Interrupted Click and Ketenimine Rearrangement

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