Intramolecular Cycloaddition Approach to Fused Pyrazoles: Access to 4,5-Dihydro-2H-pyrazolo[4,3-c]quinolines, 2,8-Dihydroindeno[2,1-c]pyrazoles, and 4,5-Dihydro-2H-benzo[e]indazoles

A straightforward and efficient method for the synthesis of pyrazoles fused with 1,2,3,4-tetrahydroquinoline, 2,3-dihydro-1H-indene, or 1,2,3,4-tetrahydronaphthalene involves the formation of the tosylhydrazone from an aromatic substrate carrying aldehyde and acetylenic functionalities at appropriate positions, followed by base-promoted generation of the diazo compound and subsequent intramolecular 1,3-dipolar cycloaddition. A number of functional groups were found to be compatible for this reaction sequence and yields were moderate to very good (44–95%). A plausible reaction mechanism supported by DFT calculations has been provided to explain the formation of products.

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Synthesis of Pyrroles Through the CuH-Catalyzed Coupling of Enynes and Nitriles

10.26434/chemrxiv.12118230.v1 ◽

2020 ◽

Author(s):

Yujing Zhou ◽

Lin Zhou ◽

Luke T. Jesikiewicz ◽

Peng Liu ◽

Stephen L. Buchwald

Keyword(s):

Density Functional Theory ◽

Reaction Mechanism ◽

Dft Calculations ◽

Efficient Method ◽

Density Functional ◽

Coupling Reaction ◽

Copper Hydride ◽

Reductive Coupling ◽

Functional Theory ◽

Subsequent Cyclization

Herein, we describe an efficient method to prepare polysubstituted pyrroles via a copper-hydride (CuH)-catalyzed enyne-nitrile coupling reaction. This protocol accommodates both aromatic and aliphatic substituents and a broad range of functional groups, providing a variety of N-H pyrroles in good yields and with high regioselectivity. We propose that the Cu-based catalyst promotes both the initial reductive coupling and subsequent cyclization steps. Density functional theory (DFT) calculations were performed to elucidate the reaction mechanism.

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Computational study on gold-catalyzed (4 + 3) intramolecular cycloaddition of trienyne: mechanism, reactivity and selectivity

RSC Advances ◽

10.1039/c6ra17436a ◽

2016 ◽

Vol 6 (77) ◽

pp. 73454-73468 ◽

Cited By ~ 5

Author(s):

Meng-Ru Li ◽

Gui-Chang Wang

Keyword(s):

Density Functional Theory ◽

Reaction Mechanism ◽

Dft Calculations ◽

Density Functional ◽

Computational Study ◽

Functional Theory ◽

Intramolecular Cycloaddition

The reaction mechanism, reactivity and selectivity of the Au(i)-catalyzed intramolecular (4 + 3) cycloaddition of trienyne have been studied by density functional theory (DFT) calculations.

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Mild, General, and Regioselective Synthesis of 2-Aminopyridines from Pyridine N-Oxides via N-(2-Pyridyl)pyridinium Salts

Synlett ◽

10.1055/s-0040-1719865 ◽

2022 ◽

Author(s):

Hui Xiong ◽

Adam T. Hoye

Keyword(s):

Reaction Mechanism ◽

Functional Groups ◽

Pyridinium Salt ◽

Regioselective Synthesis ◽

Pyridinium Salts ◽

Reaction Sequence ◽

Sequence Features ◽

Hydrolytic Decomposition ◽

Wide Range ◽

15N Labeling

AbstractA synthesis of 2-aminopyridines from pyridine N-oxides via their corresponding N-(2-pyridyl)pyridinium salts has been demonstrated and investigated. The reaction sequence features a highly regioselective conversion of the N-oxide into its pyridinium salt followed by hydrolytic decomposition of the pyridinium moiety to furnish the 2-aminopyridine product. The method is compatible with a wide range of functional groups, is scalable, and features inexpensive reagents. 15N-labeling results gave products consistent with a Zincke reaction mechanism.

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Derivatives of tetrahydro-2H-pyridine from photorearranged cycloadducts of nitrile oxides

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19900512 ◽

1990 ◽

Vol 55 (2) ◽

pp. 512-523 ◽

Cited By ~ 7

Author(s):

Lubor Fišera ◽

Vladimír Ondruš ◽

Hans-Joachim Timpe

Keyword(s):

Reaction Mechanism ◽

Double Bond ◽

Quantum Yields ◽

Dipolar Cycloaddition ◽

Mercury Lamp ◽

Reaction Sequence ◽

Nitrile Oxides ◽

Photochemical Rearrangement ◽

Benzene Rings ◽

Derivatives Of

1,3-Dipolar cycloaddition of methoxycarbonylnitrile, furannitrile and substituted benzene nitrile oxides (X = 4-CH3, 4-OCH3, 3-OCH3, 4-Cl, 3-Cl, 2,4-diCl, 4-F) to dimethyl 7-(diphenylmethylene)bicyclo[2.2.1]hept-2-ene-5,6-dicarboxylate (XII) led exclusively to exo cycloadducts IV, on irradiation with a low-pressure mercury lamp afforded the required 4-substituted derivatives of dimethyl 2,2-diphenyl-5-formyl-3-azabicyclo[4.3.0]nona-4,9-diene-7,8-dicarboxylate (XI) as sole products. Selectivity of the photorearrangement of isoxazolines IV to enaminoaldehydes XI is due to a stabilization of the biradical VII by the overlap of the radical-electron with π-electrons of the C=C double bond and by two benzene rings. Quantum yields of the photorearrangement, established from the deficit of the starting IV, were found to be greater than those for the analogous oxabicyclic derivatives XVI. The reaction mechanism is proposed and the dependence on various solvents is pointed out; this reaction sequence, viz. the 1,3-dipolar cycloaddition followed by a photochemical rearrangement provides a new method for obtaining derivatives of tetrahydro-2H-pyridine from the well available cyclopentadiene.

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Selective Manganese-Catalyzed Semihydrogenation of Alkynes with in-situ Generated H2 from KBH4 and Methanol

10.33774/chemrxiv-2021-bk2t8 ◽

2021 ◽

Author(s):

Ronald Farrar-Tobar ◽

Stefan Weber ◽

Zita Csendes ◽

Antonio Ammaturo ◽

Sarah Fleissner ◽

...

Keyword(s):

Reaction Mechanism ◽

Dft Calculations ◽

Functional Groups ◽

Hydrogen Gas ◽

Terminal Alkynes ◽

Deuterium Labelling ◽

Reaction Proceeds ◽

Mechanistic Investigations

The selective semihydrogenation of alkynes with the Mn(I) alkyl catalyst fac-[Mn(dippe)(CO)3(CH2CH2CH3)] (dippe = 1,2-bis(di-iso-propylphosphino)ethane) as pre-catalyst is described. Hydrogen gas required for the hydrogenation is generated in situ upon alcoholysis of KBH4 with methanol. A series of aryl-aryl, aryl-alkyl, alkyl-alkyl and terminal alkynes were readily hydrogenated to yield E-alkenes in good to excellent isolated yields. The reaction proceeds at 90°C with catalyst loadings of 0.5 -2 mol%. The implemented protocol tolerates a variety of electron donating and electron withdrawing functional groups including halides, phenols, nitriles, unprotected amines and heterocycles. The reaction can be upscaled to the gram scale. Mechanistic investigations including deuterium labelling studies and DFT calculations were undertaken to provide a reasonable reaction mechanism showing that initially formed Z-isomer undergoes fast isomerization to afford the thermodynamically more stable E-isomer.

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Synthesis of Pyrroles Through the CuH-Catalyzed Coupling of Enynes and Nitriles

10.26434/chemrxiv.12118230 ◽

2020 ◽

Author(s):

Yujing Zhou ◽

Lin Zhou ◽

Luke T. Jesikiewicz ◽

Peng Liu ◽

Stephen L. Buchwald

Keyword(s):

Density Functional Theory ◽

Reaction Mechanism ◽

Dft Calculations ◽

Efficient Method ◽

Density Functional ◽

Coupling Reaction ◽

Copper Hydride ◽

Reductive Coupling ◽

Functional Theory ◽

Subsequent Cyclization

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Reactions of an Aluminium(I) Reagent with 1,2-, 1,3- and 1,5-Dienes: Dearomatisation, Reversibility, and a Pericyclic Mechanism

10.26434/chemrxiv.11400171.v1 ◽

2019 ◽

Author(s):

Clare Bakewell ◽

Martí Garçon ◽

Richard Y Kong ◽

Louisa O'Hare ◽

Andrew J. P. White ◽

...

Keyword(s):

Reaction Mechanism ◽

Dft Calculations ◽

Transition State ◽

Reaction Pathways ◽

Aromatic Rings ◽

Aromatic Character ◽

Pericyclic Reaction

The reactions of an aluminium(I) reagent with a series of 1,2-, 1,3- and 1,5-dienes are reported. In the case of 1,3-dienes the reaction occurs by a pericyclic reaction mechanism, specifically a cheletropic cycloaddition, to form aluminocyclopentene containing products. This mechanism has been interrogated by stereochemical experiments and DFT calculations. The stereochemical experiments show that the (4+1) cycloaddition follows a suprafacial topology, while calculations support a concerted albeit asynchronous pathway in which the transition state demonstrates aromatic character. Remarkably, the substrate scope of the (4+1) cycloaddition includes dienes that are either in part, or entirely, contained within aromatic rings. In these cases, reactions occur with dearomatisation of the substrate and can be reversible. In the case of 1,2- or 1,5-dienes complementary reactivity is observed; the orthogonal nature of the C=C π-bonds (1,2-diene) and the homoconjugated system (1,5-diene) both disfavour a (4+1) cycloaddition. Rather, reaction pathways are determined by an initial (2+1) cycloaddition to form an aluminocyclopropane intermediate which can in turn undergo insertion of a further C=C π-bond leading to complex organometallic products that incorporate fused hydrocarbon rings.

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Catalytic mechanism of the colistin resistance protein MCR-1

Organic & Biomolecular Chemistry ◽

10.1039/d0ob02566f ◽

2021 ◽

Author(s):

Reynier Suardíaz ◽

Emily Lythell ◽

Philip Hinchliffe ◽

Marc van der Kamp ◽

James Spencer ◽

...

Keyword(s):

Reaction Mechanism ◽

Antimicrobial Resistance ◽

Dft Calculations ◽

Catalytic Reaction ◽

Catalytic Mechanism ◽

Cluster Models ◽

Colistin Resistance ◽

Resistance Protein ◽

Catalytic Reaction Mechanism

Elucidation of the catalytic reaction mechanism of MCR-1 enzyme, responsible for the antimicrobial resistance to colistin, using DFT calculations on cluster models.

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1,1,4,4-Tetracyanobutadiene-Functionalized Anthracenes: Regioselectivity of Cycloadditions in the Synthesis of Small Near-IR Dyes

10.26434/chemrxiv.13491135 ◽

2020 ◽

Author(s):

Clotilde Philippe ◽

Anh Thy Bui ◽

Sabrinah Batsongo-Boulingui ◽

ziemowit Pokladek ◽

Katarzyna Matczyszyn ◽

...

Keyword(s):

Solid State ◽

Dft Calculations ◽

Cycloaddition Reaction ◽

Diels Alder ◽

Reaction Sequence ◽

Near Ir

Two small 1,1,4,4-tetracyanobutadiene-functionalized chromophores were obtained by careful leverage of the regioselectivity of the cycloaddition reaction of tetracyanoethylene with anthracene-ynamide derivatives, inducing either a [2+2] or a [4+2] Diels–Alder process. DFT calculations unraveled the mechanism of the [2+2] cycloaddition-retroelectrocyclization reaction sequence with ynamides and elucidated the differing mechanisms in the two substrates. The synthesized dyes presented panchromatic absorption extending into the near-IR, and far-red/near-IR photoluminescence in the solid-state up to 1550 nm.

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C-H Functionalization Reactions of Unprotected N-Heterocycles by Gold Catalyzed Carbene Transfer

10.26434/chemrxiv.12044061 ◽

2020 ◽

Author(s):

Sripati Jana ◽

Claire Empel ◽

Chao Pei ◽

Polina Aseeva ◽

Thanh Vinh Nguyen ◽

...

Keyword(s):

Dft Calculations ◽

Functional Groups ◽

Gold Catalyst ◽

Protecting Groups ◽

Transfer Reactions ◽

Mechanistic Studies ◽

Economic Strategies ◽

Carbene Transfer ◽

Functionalization Reaction

The C-H functionalization reaction of N-heterocycles with unprotected N-H group is one of the most step-economic strategies to introduce functional groups without the need of installation and removal of protecting groups. Despite recent significant advances in C-H functionalization chemistry, this strategy remains unsatisfactorily developed. In this report, we disclose a simple and straightforward protocol to allow for the selective C-H functionalization of unprotected double benzannellated N-heterocycles via gold catalyzed carbene transfer reactions (29 examples, up to 86% yield). The scope of the reaction can also be expanded to the corresponding protected heterocycles (37 examples, up to 98% yield), further demonstrating the generality of this method. Mechanistic studies by DFT calculations underpin the importance of the gold catalyst and reveal that the selectivity of this reaction is driven by trace amounts of water present in the reaction mixture.

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