A Review of Ruthenium-catalyzed C-N Bond Formation Reactions for the Synthesis of Five-membered N-heterocycles

The field of heterocyclic chemistry has been revolutionized using transition metal catalysts in recent years. Various research groups have focused on the development of general protocols to achieve better functional group compatibilities and greater levels of molecular complexity under mild reaction conditions, using easily available starting substrates. The methodologies used earlier for their synthesis were less approachable to organic chemists because of their high cost, highly specified instrumentation and inconvenient methods. For both stereoselective and regioselective synthesis of five-membered nitrogen- containing heterocycles, cyclic reactions that are Ru-catalyzed have known to be very efficient. These methods have many advantages as compared to alternative pathways involved in the synthesis of heterocyclic compounds. In this review article, we concentrated on the synthesis of nitrogen-containing five-membered heterocycles in the presence of a ruthenium catalyst. This review mostly covers the literature published during the period from 1977-2019.

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Modern Organic Synthesis in the Laboratory

10.1093/oso/9780195187984.001.0001 ◽

2008 ◽

Cited By ~ 1

Author(s):

Jie Jack Li ◽

Chris Limberakis ◽

Derek A. Pflum

Keyword(s):

Organic Chemistry ◽

Graduate Students ◽

Organic Synthesis ◽

Functional Group ◽

Bond Formation ◽

Reaction Conditions ◽

Carbon Bond ◽

Oxidation Reduction ◽

Carbon Carbon Bond ◽

Daunting Task

Searching for reaction in organic synthesis has been made much easier in the current age of computer databases. However, the dilemma now is which procedure one selects among the ocean of choices. Especially for novices in the laboratory, it becomes a daunting task to decide what reaction conditions to experiment with first in order to have the best chance of success. This collection intends to serve as an "older and wiser lab-mate" one could have by compiling many of the most commonly used experimental procedures in organic synthesis. With chapters that cover such topics as functional group manipulations, oxidation, reduction, and carbon-carbon bond formation, Modern Organic Synthesis in the Laboratory will be useful for both graduate students and professors in organic chemistry and medicinal chemists in the pharmaceutical and agrochemical industries.

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Visible light induced alkene aminopyridylation using N-aminopyridinium salts as bifunctional reagents

Nature Communications ◽

10.1038/s41467-019-12216-3 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 31

Author(s):

Yonghoon Moon ◽

Bohyun Park ◽

Inwon Kim ◽

Gyumin Kang ◽

Sanghoon Shin ◽

...

Keyword(s):

Dft Calculations ◽

Electrostatic Interaction ◽

Functional Group ◽

Eosin Y ◽

Pyridine Derivatives ◽

Reaction Conditions ◽

Radical Trapping ◽

Molecular Complexity ◽

Pyridinium Nitrogen ◽

Mechanism Of The Reaction

Abstract The development of intermolecular alkene aminopyridylation has great potential for quickly increasing molecular complexity with two valuable groups. Here we report a strategy for the photocatalytic aminopyridylation of alkenes using a variety of N-aminopyridinium salts as both aminating and pyridylating reagents. Using Eosin Y as a photocatalyst, amino and pyridyl groups are simultaneously incorporated into alkenes, affording synthetically useful aminoethyl pyridine derivatives under mild reaction conditions. Remarkably, the C4-regioselectivity in radical trapping with N-aminopyridinium salt can be controlled by electrostatic interaction between the pyridinium nitrogen and sulfonyl group of β-amino radical. This transformation is characterized by a broad substrate scope, good functional group compatibility, and the utility of this transformation was further demonstrated by late-stage functionalization of complex biorelevant molecules. Combining experiments and DFT calculations on the mechanism of the reaction is investigated to propose a complete mechanism and regioselectivity.

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From Alkynes to Heterocycles through Metal-Promoted Silylformylation and Silylcarbocyclization Reactions

Catalysts ◽

10.3390/catal10091012 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1012 ◽

Cited By ~ 1

Author(s):

Gianluigi Albano ◽

Laura Antonella Aronica

Keyword(s):

Detailed Analysis ◽

Heterocyclic Compounds ◽

Functional Group ◽

Biologically Active ◽

Reaction Conditions ◽

Synthetic Compounds ◽

Heterocyclic Derivatives ◽

Nitrogen Heterocyclic ◽

Natural And Synthetic

Oxygen and nitrogen heterocyclic systems are present in a large number of natural and synthetic compounds. In particular, oxa- and aza-silacyclane, tetrahydrofuran, benzofuran, cycloheptadifuranone, cycloheptadipyrrolone, pyrrolidine, lactone, lactam, phthalan, isochromanone, tetrahydroisoquinolinone, benzoindolizidinone, indoline and indolizidine scaffolds are present in many classes of biologically active molecules. Most of these contain a C=O moiety which can be easily introduced using carbonylative reaction conditions. In this field, intramolecular silylformylation and silylcarbocyclization reactions may afford heterocyclic compounds containing a carbonyl functional group together with a vinylsilane moiety which can be further transformed. Considering these two aspects, in this review a detailed analysis of the literature data regarding the application of silylformylation and silylcarbocyclization reactions to the synthesis of several heterocyclic derivatives is reported.

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Pd Catalyzed N1/N4 Arylation of Piperazine for Synthesis of Drugs, Biological and Pharmaceutical Targets: An Overview of Buchwald Hartwig Amination Reaction of Piperazine in Drug Synthesis

Current Organic Synthesis ◽

10.2174/1570179415666171206151603 ◽

2018 ◽

Vol 15 (2) ◽

pp. 208-220 ◽

Cited By ~ 3

Author(s):

Vaibhav Mishra ◽

Tejpal Singh Chundawat

Keyword(s):

Bond Formation ◽

Catalyst Design ◽

Biologically Active ◽

Reaction Conditions ◽

Biological Targets ◽

Amination Reaction ◽

Drug Synthesis ◽

Substituted Piperazine ◽

Approved Drugs ◽

Fda Approved Drugs

Background: Substituted piperazine heterocycles are among the most significant structural components of pharmaceuticals. N1/N4 substituted piperazine containing drugs and biological targets are ranked 3rd in the top most frequent nitrogen heterocycles in U.S. FDA approved drugs. The high demand of N1/N4 substituted piperazine containing biologically active compounds and U.S. FDA approved drugs, has prompted the development of Pd catalyzed C-N bond formation reactions for their synthesis. Buchwald-Hartwig reaction is the key tool for the synthesis of these compounds. Objective: This review provides strategies for Pd catalyzed C-N bond formation at N1/N4 of piperazine in the synthesis of drugs and biological targets with diverse use of catalyst-ligand system and reaction parameters. Conclusion: It is clear from the review that a vast amount of work has been done in the synthesis of N1/N4 substituted piperazine containing targets under the Pd catalyzed Buchwald-Hartwig amination of aryl halides by using different catalyst-ligand systems. These methods have become increasingly versatile as a result of innovation in catalyst design and improvements in reaction conditions. This review gives an overview of recent utilization of Buchwald-Hartwig amination reaction in drug/target synthesis.

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The chemistry of 4-(dicyanomethylene)-3-methyl-l-phenyl-2-pyrazoline-5- ones as a privileged scaffold in synthesis of heterocycles

Current Organic Synthesis ◽

10.2174/1570179417666200924150340 ◽

2020 ◽

Vol 17 ◽

Author(s):

Mohsen A.-M. Gomaa ◽

Huda A. Ali

Keyword(s):

Building Block ◽

Heterocyclic Compounds ◽

Recent Progress ◽

Reaction Conditions ◽

Azacrown Ethers ◽

Wide Range ◽

Privileged Scaffold ◽

Number Of Publications ◽

Near Future

Background : The reactivity of 4-(dicyanomethylene)-3-methyl-l-phenyl-2-pyrazoline-5-one DCNP 1 and its derivatives makes it valuable as a building block for the synthesis of heterocyclic compounds like pyrazolo-imidazoles, - thiazoles, spiropyridines, spiropyrroles, spiropyrans and others. As a number of publications have reported on the reactivity of DCNP and its derivatives, we compiled some features of this interesting molecule. Objective: This article aims to review the preparation of DCNP, its reactivity and application in heterocyclic and dyes synthesis. Conclusion: In this review we have provided an overview of recent progress in the chemistry of DCNP and its significance in synthesis of various classes of heterocyclic compounds and dyes. The unique reactivity of DCNP offers unprecedentedly mild reaction conditions for the generation of versatile cynomethylene dyes from a wide range of precursors including amines, α-aminocarboxylic acids, their esters, phenols, malononitriles and azacrown ethers. We anticipate that more innovative transformations involving DCNP will continue to emerge in the near future.

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Formation of Carbon-Oxygen Bond Mediated by Hypervalent Iodine Reagents Under Metal-free Conditions

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x17999200807140943 ◽

2020 ◽

Vol 17 ◽

Author(s):

Ayesha Jalil ◽

Yaxin O Yang ◽

Zhendong Chen ◽

Rongxuan Jia ◽

Tianhao Bi ◽

...

Keyword(s):

Natural Products ◽

Bond Formation ◽

Building Blocks ◽

Review Article ◽

Hypervalent Iodine ◽

Metal Free ◽

Bioactive Natural Products ◽

The Past ◽

Oxygen Bond ◽

Privileged Scaffolds

: Hypervalent iodine reagents are a class of non-metallic oxidants have been widely used in the construction of several sorts of bond formations. This surging interest in hypervalent iodine reagents is essentially due to their very useful oxidizing properties, combined with their benign environmental character and commercial availability from the past few decades ago. Furthermore, these hypervalent iodine reagents have been used in the construction of many significant building blocks and privileged scaffolds of bioactive natural products. The purpose of writing this review article is to explore all the transformations in which carbon-oxygen bond formation occurred by using hypervalent iodine reagents under metal-free conditions

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Nickel-Catalyzed Multicomponent Coupling Reaction of Alkyl Halides, Isocyanides and H2O: An Expedient Way to Access Alkyl Amides

Synthesis ◽

10.1055/s-0040-1707229 ◽

2020 ◽

Vol 52 (22) ◽

pp. 3466-3472

Author(s):

Yunkui Liu ◽

Bingwei Zhou ◽

Qiao Li ◽

Hongwei Jin

Keyword(s):

Functional Group ◽

Coupling Reaction ◽

Alkyl Halides ◽

Previous Literature ◽

Catalytic Cycle ◽

Reaction Conditions ◽

Multicomponent Coupling ◽

Easy Operation

We herein describe a Ni-catalyzed multicomponent coupling reaction of alkyl halides, isocyanides, and H2O to access alkyl amides. Bench-stable NiCl2(dppp) is competent to initiate this transformation under mild reaction conditions, thus allowing easy operation and adding practical value. Substrate scope studies revealed a broad functional group tolerance and generality of primary and secondary alkyl halides in this protocol. A plausible catalytic cycle via a SET process is proposed based on preliminary experiments and previous literature.

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Rh(III)-Catalyzed Olefination and Alkylation of Arenes with Maleimides: A Tunable Strategy for C(sp2)–H Functionalization

Synthesis ◽

10.1055/s-0037-1610765 ◽

2021 ◽

Author(s):

Hongji Li ◽

Wenjie Zhang ◽

Xueyan Liu ◽

Zhenfeng Tian

Keyword(s):

Room Temperature ◽

Functional Group ◽

Reaction Conditions ◽

Bond Functionalization ◽

Alkylation Process ◽

Coupling Partner

AbstractWe herein report a new nitrogen-directed Rh(III)-catalyzed C(sp2)–H bond functionalization of N-nitrosoanilines and azoxybenzenes with maleimides as a coupling partner, in which the olefination/alkylation process can be finely controlled at room temperature by variation of the reaction conditions. This method shows excellent functional group tolerance, and presents a mild access to the resulting olefination/alkylation products in moderate to good yields.

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Synthesis of Pyrrolo[1,2-a][1,6]- and [1,8]naphthyridines by Alkyne-Carbonyl Metathesis

Synthesis ◽

10.1055/s-0040-1706105 ◽

2020 ◽

Author(s):

Peter Ehlers ◽

Peter Langer ◽

Marian Blanco Ponce ◽

Silvio Parpart ◽

Alexander Villinger ◽

...

Keyword(s):

Heterocyclic Compounds ◽

Metathesis Reaction ◽

Synthetic Methodology ◽

Facile Synthesis ◽

Reaction Conditions ◽

One Pot ◽

Metal Free ◽

Modular Synthesis

AbstractA concise and modular synthesis of pyrrolo[1,2-a][1,6]- and [1,8]naphthyridines by a one-pot two-step reaction consisting of electrophilic acylation followed by an alkyne-carbonyl-metathesis reaction as the final cyclization step is reported. This developed synthetic methodology allows the facile synthesis of these heterocyclic core structures in mainly high overall yields under metal-free conditions. Reaction conditions are carefully optimized and display a novel supplement to access these tricyclic heterocyclic compounds.

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Sulfonyl Radical Triggered Selective Iodosulfonylation and Bicycli-zations of 1,6-Dienes

Chemical Communications ◽

10.1039/d1cc03252f ◽

2021 ◽

Author(s):

Shi-Ping Wu ◽

Dong-Kai Wang ◽

Qing-Qing Kang ◽

Guo-Ping Ge ◽

Hongxing Zheng ◽

...

Keyword(s):

Functional Group ◽

High Selectivity ◽

Reaction Conditions ◽

First Time

A novel sulfonyl radical triggered selective iodosulfonylation and bicyclizations of 1,6-dienes has been described for the first time. High selectivity and efficiency, mild reaction conditions, excellent functional group compatibility, and...

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