Regiocontrolled Gold‐Catalyzed [2+2+2] Cycloadditions of Ynamides with Two Discrete Nitriles to Construct 4‐Aminopyrimidine Cores

Karad, Somnath Narayan; Liu, Rai‐Shung

doi:10.1002/ange.201405312

Cited by 32 publications

(3 citation statements)

References 89 publications

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“…A plausible mechanism is depicted in Scheme on the basis of our control experiments and previous literature reports 9f,g,23,24. Substrate 1 reacts with propargyl alcohol or N‐tosylated 2‐propynylamine in the presence of rhodium(I) complex to generate rhodacyclopentadiene A through cyclometallation.…”

Section: Methodsmentioning

confidence: 73%

A One‐Pot Approach to Phenanthridine Derivatives through Two‐Step Rhodium(I) and Gold(I) Catalysis

Zhu

Chen

et al. 2015

Adv Synth Catal

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An effectiveo ne-pot procedure for the synthesis of phenanthridine derivatives containing N-or O-heterocycles has been developed through at wo-stepr hodium-catalyzed[ 2 + +2+ +2] cycloaddition and gold-catalyzedh eterocyclization under mild conditions.T he substrate scope has been investigated and ap lausible reactionm echanism has been proposed on the basis of control experiments and previousl iterature reports.Keywords: [2+ +2+ +2] cycloaddition;g old catalysis; heterocyclization;o ne-pot procedure;r hodium catalysis Polycyclicc ompounds containingN -a nd O-heterocycles are the core structures in av ariety of pharmacologicala gents and natural alkaloids.[1] Thus far, the development of new synthetic methodso rs trategies for heterocyclic compounds hasbeenavery important area in organic synthesis.[2] Recently,t he synthesiso f substituted or functionalized phenanthridines hasa ttracted much attention sincet hey are the core structural motifsi nm anyb iologically active molecules as shown in Figure 1, andn ew synthetic protocols for these compounds are stillh ighly desirable. [3] Over the past decades,s ynthesis of polycyclic compounds has made significant progress and al arge number of useful andpractical methodshavebeen explored, in which transition metal catalysish as been playing av ery important role.W ith the aid of transition metal catalysis, one can rapidly generate complex molecular structures from easily accessible starting materials under mild reaction conditions.F or example,t he transitionm etal-catalyzed [2+ +2+ +2] cycloaddition reactions of unsaturated compounds are very useful and straightforward methods for constructing polycyclic compounds.[4] Various highly regioselective [2+ +2+ +2] cycloadditions of diynes under Co,N i, Ir, Ru, Au or Rh catalysis have been reported by several groups.[5-10] Furthermore,heterocyclizations of alkynes under transitionm etal catalysis are also practical and straightforward methodst oc onstruct heterocyclic compounds. [11][12][13][14][15][16][17][18] Nowadays,o ne-pot synthesis is becoming an importants trategys incei tc an improve the efficiency of ac hemical reaction. Theo ne-pot reactions combiningt ransitionm etal catalysis ando rganocatalysis leadt om anye legant and effective synthetic protocols. [19,20] On the basis of this strategy,m ultistep chemical transformationsc an be performed sequentially to givec omplexm olecules in as ingle reaction vessel,s ubsequently reducing work-up and purification steps.Recently,t he reactions catalyzed by gold complexes have been exploreds ignificantly.M oreover, some examples about gold-catalyzed cascade reactions and dual-metal catalysisw ith gold ands econd metals have

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Section: Methodsmentioning

confidence: 73%

A One‐Pot Approach to Phenanthridine Derivatives through Two‐Step Rhodium(I) and Gold(I) Catalysis

Zhu

Chen

et al. 2015

Adv Synth Catal

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“…Generally, the nucleophilic reactivity of lone electron pairs on the N‐atom, the π‐coordination reactivity of the C≡N triple bond, and the electrophilic reactivity of the carbon center of the cyano group contribute to the varied transformations of benzonitriles with alkynes. For instance, transition metal (Co, Ru, Rh, Fe, Ni, Ir, Ti, and Au) catalyzed [2+2+2] cyclizations involving either two alkynes and one nitrile or two nitriles and one alkyne provide efficient approaches to the synthesis of multisubstituted pyridines and pyrimidines (Scheme a) –. Meanwhile, the [2+2+1] annulations of one nitrile, one alkyne, and the third external component give rise to oxazole and imidazole derivatives –.…”

Section: Methodsmentioning

confidence: 99%

Manganese‐Catalyzed ortho‐C−H Alkenylation of Aromatic N−H Imidates with Alkynes: Versatile Access to Mono‐Alkenylated Aromatic Nitriles

2016

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So far, the direct C À H alkenylation of aromatic nitriles with alkynes has not been achieved. Herein, we discribe the first manganese-catalyzed C À H alkenylation of aromatic N À H imidates to access mono-alkenylated aromatic nitriles. The reaction is accelerated by the presence of a catalytic amount of sodium pivalate. This protocol is also highlighted by the simple catalytic system, good compatibility of functional groups, and excellent mono-/dialkenylation selectivity as well as E/Z stereoselectivity.

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“…However, corrosive and toxic reagents like ammonium gas and phosphoryl chloride were utilized to get satisfactory yields [ 49 ]. Karad et al developed a metal-catalyzed or strong acid-mediated intermolecular cycloaddition of ynamides with nitriles for the synthesis of 4-aminopyrimidines using Scheme 8 [ 50 ]. Baxendale et al described the microwave synthesis of 4-aminopyrimidines using single nitriles in the presence of a catalyst such as potassium tert -butoxide ( Scheme 9 ).…”

Section: Synthetic Strategies Of Pyrimidinesmentioning

confidence: 99%

Synthetic Strategies of Pyrimidine-Based Scaffolds as Aurora Kinase and Polo-like Kinase Inhibitors

et al. 2021

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The past few decades have witnessed significant progress in anticancer drug discovery. Small molecules containing heterocyclic moieties have attracted considerable interest for designing new antitumor agents. Of these, the pyrimidine ring system is found in multitude of drug structures, and being the building unit of DNA and RNA makes it an attractive scaffold for the design and development of anticancer drugs. Currently, 22 pyrimidine-containing entities are approved for clinical use as anticancer drugs by the FDA. An exhaustive literature search indicates several publications and more than 59 patents from the year 2009 onwards on pyrimidine derivatives exhibiting potent antiproliferative activity. These pyrimidine derivatives exert their activity via diverse mechanisms, one of them being inhibition of protein kinases. Aurora kinase (AURK) and polo-like kinase (PLK) are protein kinases involved in the regulation of the cell cycle. Within the numerous pyrimidine-based small molecules developed as anticancer agents, this review focuses on the pyrimidine fused heterocyclic compounds modulating the AURK and PLK proteins in different phases of clinical trials as anticancer agents. This article aims to provide a comprehensive overview of synthetic strategies for the preparation of pyrimidine derivatives and their associated biological activity on AURK/PLK. It will also present an overview of the synthesis of the heterocyclic-2-aminopyrimidine, 4-aminopyrimidine and 2,4-diaminopyrimidine scaffolds, and one of the pharmacophores in AURK/PLK inhibitors is described systematically.

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Regiocontrolled Gold‐Catalyzed [2+2+2] Cycloadditions of Ynamides with Two Discrete Nitriles to Construct 4‐Aminopyrimidine Cores

Cited by 32 publications

References 89 publications

A One‐Pot Approach to Phenanthridine Derivatives through Two‐Step Rhodium(I) and Gold(I) Catalysis

A One‐Pot Approach to Phenanthridine Derivatives through Two‐Step Rhodium(I) and Gold(I) Catalysis

Manganese‐Catalyzed ortho‐C−H Alkenylation of Aromatic N−H Imidates with Alkynes: Versatile Access to Mono‐Alkenylated Aromatic Nitriles

Synthetic Strategies of Pyrimidine-Based Scaffolds as Aurora Kinase and Polo-like Kinase Inhibitors

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