Organocatalytic azomethine imine-olefin click reaction: high-yielding stereoselective synthesis of spiroindane-1,3-dione-pyrazolidinones

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 In search of developing new useful “click reactions”, herein we report the organocatalytic azomethine imine-olefin [3 + 2]-cycloaddition as a new click reaction for the synthesis of drug-like spiroindane-1,3-dione-pyrazolidinones from indane-1,3-diones, aldehydes and N,N-cyclic azomethine imines through amino acid-catalysis. The scope of this new click reaction is demonstrated using many examples with high reactivity, selectivity and yields.




 




 

Ramachary Dhevalapally

Happy to share with you our recent work on the development of Tomita zipper-cyclization (TZC) reaction…I am sure that this reaction may become useful tool for organic chemists in near future…

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  • Catalysis Laboratory, School of Chemistry, University of Hyderabad
  • Hyderabad, India 500 046
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  Website

  http://chemistry.uohyd.ac.in/~dbr/

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  Professor at University of Hyderabad

  January 31, 2005 to present
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  Studied Development of new catalytic asymmetric reactions at The Scripps Research Institute

  Past: Indian Institute of Science and University of Hyderabad
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  Lives in Hyderabad, India

  From Hyderabad, India · Lived in La Jolla, California

Paper

Organocatalytic azomethine imine-olefin click reaction: high-yielding stereoselective synthesis of spiroindane-1,3-dione-pyrazolidinones

Dhevalapally B. Ramachary,*^a   T. Prabhakar Reddy^a and   A. Suresh Kumar^a  

*Corresponding authors

^a

School of Chemistry, University of Hyderabad, Hyderabad-500 046, India
E-mail: ramsc@uohyd.ac.in
Fax: +91-40-23012460

Org. Biomol. Chem., 2016, Advance Article

DOI: 10.1039/C6OB01009A http://pubs.rsc.org/en/content/articlelanding/2016/ob/c6ob01009a#!divAbstract

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Scheme 1

Ultrasound-assisted synthesis of 2-aryl-4-phenyl-1 H -imidazoles.

A rapid and simple synthetic procedure to synthesize diversely substituted 2-aryl-4-phenyl-1H-imidazoles has been reported. Other salient features of this protocol include milder conditions, atom-economy, easy extraction, and minimum wastes. The present procedure may find application in the synthesis of biologically active molecules.

 

An expeditious green route toward 2-aryl-4-phenyl-1H-imidazoles

• Debasish BandyopadhyayEmail author,
• Lauren C Smith,
• Daniel R Garcia,
• Ram N Yadav and
• Bimal K BanikEmail author

Organic and Medicinal Chemistry Letters20144:9

DOI: 10.1186/s13588-014-0009-7

 

General procedure for the synthesis of 2-aryl-4-phenyl-1H-imidazoles

A solution of the aldehyde (1 mmol) and threefold excess of ammonium acetate (3 mmol) in methanol (2 mL) was placed in a B5510-DTH (Branson ultrasonic cleaner; Model-5510, frequency 42 KHz with an output power 135 Watts; Branson Ultrasonics, Danbury, CT, USA) sonicator at room temperature. The ultrasonic irradiation was started and a solution of phenylglyoxal monohydrate (1 mmol) in methanol (1 mL) was slowly added dropwise (by a syringe) to the above solution during a period of 15 min. The resulting mixture was continued to irradiate as specified in Table 1. After completion of the reaction (monitored by TLC with an interval of 5 min), the methanol was evaporated under reduced pressure and the crude mass was extracted with ethyl acetate (2 × 5 mL). The combined organic layer was washed with brine (10 mL) and water (10 mL) successively and dried over anhydrous sodium sulfate. The extract was then concentrated, and the crude product was purified using flash chromatography (neutral alumina, 1% triethylamine in methanol) to afford pure compounds.

 http://orgmedchemlett.springeropen.com/articles/10.1186/s13588-014-0009-7

////////////Imidazole,  Green chemistry ,  Ultrasound,  Heterocycles ,  Medicinal chemistry , Azaheterocycles

Nickel-Catalyzed Cross-Coupling of Organolithium Reagents

During the past years, Feringa and co-workers have developed very efficient palladium-catalyzed methodologies for the cross-coupling of organolithium reagents. 

They have now described that nickel-based catalytic systems are also able to successfully cross-couple these organometallic reagents to a variety of (hetero)aryl electrophiles ( Chem. Eur. J. 2016, 22, 3991). 

The reactions take place in toluene at room temperature with a 50% molar excess of the organolithium reagent and are usually finished within an hour. 

In order to limit the formation of reduced (hetero)aryl electrophile, a different catalyst has to be used for the efficient coupling of aryl- or alkyl-lithium reagents, a N-heterocyclic carbene ligated one (C3 above) for the former and bis(diethyldiphosphino)ethane ligated one (C1 above) for the latter. 

While the substrate scope appears to be limited by the high reactivity of the organometallic partner, these nickel-catalyzed protocols allow a number of less usual electrophiles, such as methyl ethers or fluorides, to engage in the cross-coupling reaction.

 See original article

Homogeous Catalysis

Nickel-Catalyzed Cross-Coupling of Organolithium Reagents with (Hetero)Aryl Electrophiles (pages 3991–3995)Dorus Heijnen, Dr. Jean-Baptiste Gualtierotti, Dr. Valentín Hornillos and Prof. Dr. Ben L. Feringa
Version of Record online: 4 FEB 2016 | DOI: 10.1002/chem.201505106

Nickel-catalyzed cross-coupling of aromatic electrophiles with organolithium reagents is presented. The use of a commercially available nickel N-heterocyclic carbene complex allows reaction with a variety of (hetero)aryllithium compounds, whereas a commercially available electron-rich nickel bisphosphine complex smoothly converts alkyllithium species into the corresponding coupled product.

 http://onlinelibrary.wiley.com/doi/10.1002/chem.201505106/full

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1H NMR

 Compounds containing a sulfur–fluoride bond are receiving escalating attention in both the chemical and the biological literature. The need to activate the S–F bond through formation of a hydrogen bond in the presence of a proximal nucleophile forms the basis for sulfonyl fluorides to be utilized as privileged biocompatible orthogonal electrophiles in biological systems. Arvidsson at the Karolinska Institute and his co-workers at the University of KwaZulu-Natal reported an efficient, ligand-free, and additive free Suzuki–Miyaura coupling that is compatible with an aromatic sulfonyl fluoride moiety ( J. Org. Chem. 2016, 81, 2618). After extensive optimization studies, mild reaction conditions were identified that minimized hydrolysis of the aromatic sulfonyl fluoride. Palladium acetate was the most effective catalyst, and utilization of triethylamine as the base afforded the highest yield. The reaction was conducted in water as solvent, at room temperature. These mild reaction conditions were compatible with a variety of functional groups on the boronic acid, including: nitro, chloro, fluoro, nitrile, and ethers. The desired biaryl sulfonyl fluorides were obtained in good-to-excellent yields.

19 F NMR

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On-Water Synthesis of Biaryl Sulfonyl Fluorides

Praveen K. Chinthakindi^†, Hendrik G. Kruger^†, Thavendran Govender^†, Tricia Naicker^†, and Per I. Arvidsson^*‡

^† Catalysis and Peptide Research Unit, University of KwaZulu-Natal, Durban, 4041, South Africa

^‡ Science for Life Laboratory, Drug Discovery & Development Platform & Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 21 Stockholm, Sweden

J. Org. Chem., 2016, 81 (6), pp 2618–2623

DOI: 10.1021/acs.joc.5b02770

*E-mail: per.arvidsson@scilifelab.se.

 http://pubs.acs.org/doi/abs/10.1021/acs.joc.5b02770




 GC MS

 HR MS

 

 

 

 

 
 Praveen Kumar

PhD

PostDoc Position

University of KwaZulu-Natal, Durban · School of Pharmacy and Pharmacology

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  University of KwaZulu-Natal

  School of Pharmacy and Pharmacology

  Durban, KwaZulu-Natal, South Africa

Research experience

• May 2014–
  present

  PostDoc Position

  University of KwaZulu-Natal · School of Pharmacy and Pharmacology · Catalysis and Peptide Research Unit
  South Africa · Durabn
• Jan 2009–
  Jan 2014

  SRF

  Indian Institute of Integrative Medicine · Bio-Organic Chemistry Division (IIIM) · Dr. S. Koul
  India · Jammu

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• Supporting Info

An efficient Passerini tetrazole reaction (PT-3CR)

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC00910G, Communication

Ajay L. Chandgude, Alexander Domling
A sonication accelerated, catalyst free, simple, high yielding and efficient method for the Passerini-type three-component reaction (PT-3CR) has been developed.

An efficient Passerini tetrazole reaction (PT-3CR)

see
http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C6GC00910G?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

An efficient Passerini tetrazole reaction (PT-3CR)

Ajay L. Chandgude^a and   Alexander Dömling*^a  

*

Corresponding authors

^a

Department of Drug Design, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands 
E-mail: a.s.s.domling@rug.nl
Web: http://www.drugdesign.nl/

Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC00910G

 A sonication accelerated, catalyst free, simple, high yielding and efficient method for the Passerini-type three-component reaction (PT-3CR) has been developed. It comprises the reaction of an aldehyde/ketone, an isocyanide and a TMS-azide in methanol:water (1:1) as the solvent system. The use of sonication not only accelerated the rate of the reaction but also provided good to excellent quantitative yields. This reaction is applicable to a broad scope of aldehydes/ketones and isocyanides.

  
Ajay L. Chandgude

• 
  University of Groningen

  Groningen Research Institute of Pharmacy (GRIP)

  Groningen, Netherlands

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Self-optimisation of the final stage in the synthesis of EGFR kinase inhibitor AZD9291 using an automated flow reactor

React. Chem. Eng., 2016, Advance Article
DOI: 10.1039/C6RE00059B, Paper

Open Access

  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

Nicholas Holmes, Geoffrey R. Akien, A. John Blacker, Robert L. Woodward, Rebecca E. Meadows, Richard A. Bourne
Self-optimising flow reactors combine online analysis with evolutionary feedback algorithms to rapidly achieve optimum conditions.

Self-optimisation of the final stage in the synthesis of EGFR kinase inhibitor AZD9291 using an automated flow reactor

Self-optimising flow reactors combine online analysis with evolutionary feedback algorithms to rapidly achieve optimum conditions. This technique has been applied to the final bond-forming step in the synthesis of AZD9291, an irreversible epidermal growth factor receptor kinase inhibitor developed by AstraZeneca. A four parameter optimisation of a telescoped amide coupling followed by an elimination reaction was achieved using at-line high performance liquid chromatography. Optimisations were initially carried out on a model compound (2,4-dimethoxyaniline) and the data used to track the formation of various impurities and ultimately propose a mechanism for their formation. Our protocol could then be applied to the optimisation of the 2-step telescoped reaction to synthesise AZD9291 in 89% yield.

Paper

Self-optimisation of the final stage in the synthesis of EGFR kinase inhibitor AZD9291 using an automated flow reactor

Nicholas Holmes,^a   Geoffrey R. Akien,^ab   A. John Blacker,^ac  Robert L. Woodward,^d   Rebecca E. Meadows^d and  Richard A. Bourne*^acd  

*Corresponding authors

^aInstitute of Process Research and Development, School of Chemistry, University of Leeds, Leeds, UK
E-mail: r.a.bourne@leeds.ac.uk

^bDepartment of Chemistry, Faraday Building, Lancaster University, Lancaster, UK

^cSchool of Chemical and Process Engineering, University of Leeds, Leeds, UK

^dAstraZeneca Pharmaceutical Development, Silk Road Business Park, Macclesfield, UK

React. Chem. Eng., 2016, Advance Article

DOI: 10.1039/C6RE00059B

http://pubs.rsc.org/en/Content/ArticleLanding/2016/RE/C6RE00059B#!divAbstract

Scheme 1 Synthesis of the model acrylamide 6 via the β-chloroamide 5 intermediate.

Scheme 2 Proposed mechanisms to dimers 8a and 8b. The observation of a peak corresponding to 7suggested a Rauhut–Currier mechanism to 8b but subsequent LC-MS-MS analysis showed the major dimer to most likely be 8a. All observed peaks from offline LC-MS are displayed.

///////Self-optimisation, synthesis, EGFR kinase inhibitor, AZD9291,  automated flow reactor