Visible-light photoredox catalysis: direct synthesis of fused β-carbolines through an oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade in batch and flow microreactors

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Fused β-carbolines were synthesized via a visible light photoredox catalyzed oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade in batch and flow microreactors. Several structurally diverse heterocyclic scaffolds were obtained in good yields by coupling of tetrahydro-β-carbolines with a variety of dipolarophiles under photoredox multiple C–C bond forming events. The photoredox coupling of tetrahydro-β-carboline with 1,4-benzoquinone was significantly faster in continuous flow microreactors and the desired products were obtained in higher yields compared to batch reactors.

Visible-light photoredox catalysis: direct synthesis of fused β-carbolines through an oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade in batch and flow microreactors

D. Chandrasekhar,^a   Satheesh Borra,^a  Jeevak Sopanrao Kapure,^b   Ghule Shailendra Shivaji,^b  Gannoju Srinivasulu^b and   Ram Awatar Maurya*^ac  

*

Corresponding authors

^a

Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India 
E-mail: ramaurya@iict.res.in

^b

National Institute of Pharmaceutical Education and Research, Balanagar, Hyderabad-500035, India

^c

Academy of Scientific and Innovative Research, New Delhi 110025, India

Org. Chem. Front., 2015,2, 1308-1312

DOI: 10.1039/C5QO00207A 

 http://pubs.rsc.org/en/content/articlelanding/2015/qo/c5qo00207a#!divAbstract
 Jeevak Kapure

 http://pubs.rsc.org/en/content/articlelanding/2015/qo/c5qo00207a#!divAbstract





 


 

 

 

Ram Awatar Maurya

Fused β-carbolines were synthesized via a visible light photoredox catalyzed oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade in batch and flow microreactors.

Several structurally diverse heterocyclic scaffolds were obtained in good yields by coupling of tetrahydro-β-carbolines with a variety of dipolarophiles under photoredox multiple C–C bond forming events.

The photoredox coupling of tetrahydro-β-carboline with 1,4-benzoquinone was significantly faster in continuous flow microreactors and the desired products were obtained in higher yields compared to batch reactors.

Synthetic procedures General experimental procedures for the synthesis of N-alkylated of tetrahydro-β-carbolines 1a-f: In a 25 mL round bottom flask, tryptoline (86 mg, 0.5 mmol), α-halo carbonyls (0.5 mmol), Et3N (50 mg, 0.5 mmol) and CH2Cl2 (5 mL) was taken and the reaction mixture was stirred at ambient temperature for 2 h. Next the reaction mixture was diluted with CH2Cl2 (15 mL) and washed with water. The organic layer was dried over anhydrous Na2SO4 and evaporated to yield a crude product which was purified by silica-gel column chromatography using ethyl acetate/hexane in increasing polarity to yield compounds 1a-f.

General experimental procedures for the visible light photoredox catalyzed coupling of Nalkylated of tetrahydro-β-carbolines 1a-f with dipolarophiles 2a-g under batch conditions: In a 25 mL round bottom flask, tetrahydro-β-carbolines 1a-f (0.1 mmol), dipolarophiles 2a-g (0.1 mmol), [Ru(bpy)3Cl2]·6H2O (0.5 mol%) and MeCN (5 mL) was taken. The reaction vessel was kept at a distance of 10 cm (approx.) from a visible light source (11W white LED bulb) and the reaction mixture was stirred in open air condition until the reaction was complete (TLC). Next the reaction mixture was concentrated to give a crude product which was purified Electronic Supplementary Material (ESI) for Organic Chemistry Frontiers. This journal is © the Partner Organisations 2015 by silica-gel column chromatography using ethyl acetate/hexane in increasing polarity to yield compounds 3a-n

General experimental procedures for the visible light photoredox catalyzed coupling of Nalkylated of tetrahydro-β-carbolines 1a with dipolarophiles 2a in flow microreactors: A solution of tetrahydro-β-carboline 1a (0.2 mmol) and dipolarophile 2a (0.2 mmol) in MeCN (5 mL) was kept in one syringe and the solutions of photocatalyst [Ru(bpy)3Cl2]·6H2O (0.001 mmol in 5 mL MeCN) and t-BuOOH (2 mmol in 2 mL MeCN) were taken in two separate syringes. All the three solutions were pumped via two syringe pumps and mixed on an Xjunction and flown through the capillary microreactor wrapped over a visible light source (11W white LED bulb). Under stable conditions, exactly 6 mL of the reaction mixture was collected, concentrated to yield a crude product which was purified by silica-gel column chromatography using ethyl acetate/hexane in increasing polarity to yield compounds 3a

     

Ram Awatar Maurya

PhD

INSPIRE FACULTY

Indian Institute of Chemical T..., Hyderabad · Medicinal Chemistry and Pharmacology Division (IICT)

RESEARCH EXPERIENCE

 Mar 2012–Jun 2012, PostDoc Position

• Pohang University of Science and Technology · Department of Chemical Engineering · Prof Dong Pyo Kim
  South Korea · Andong
• Sep 2009–Feb 2012, Post Doctoral Fellow
  Chungnam National University
  South Korea · Daejeon

 

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The Lewis acid MgCl₂ allows control of the metalation regioselectivity of uracils and uridines. In the absence of the Lewis acid, metalation of uracil and uridine derivatives with TMPMgCl·LiCl occurs at the position C(5). In the presence of MgCl₂, zincation using TMP₂Zn·2LiCl·2MgCl₂ occurs at the position C(6). This metalation method provides easy access to functionalized uracils and uridines. Using TMP₂Zn·2LiCl·2MgCl₂ also allows to functionalize cytidine derivatives at the position C(6).

The selective functionalization of uridines is an important synthetic goal because of the biological relevance of many substituted uridines. They are known to display antibiotic, antifungal, anticancer, and antiviral activity. Knochel and co-workers at Ludwig-Maximilians-Universität extended their investigation of metalation of heterocyclic systems to uridines. They reported the regioselective metalation of uridines at the C(5) or C(6) position and the subsequent functionalization of these metalated nucleoside derivatives with electrophiles ( Org. Lett. 2016, 18, 1068). Metalation of a protected uridine (A) with a slight excess of TMPMgCl·LiCl afforded the C(5) magnesiated uridine (C(5):C(6) = 98:2) in quantitative yield. The presence of MgCl₂ inversed the regioselectivity of the metalation. Zincation of a protected uridine (A) with 1.2 equiv of TMP₂Zn·2LiCl·2MgCl₂ produced the C(6) bis-zincated uridine (C(5):C(6) = 3:97) also in quantitative yield. The C(5) or C(6) metalated uridines were then functionalized with a variety of electrophiles. This chemistry was successfully extended to the regioselective C6 metalation and functionalization of cytidines. The deprotection of the substituted uridines and cytidines afforded the corresponding functionalized nucleosides.

      

Lewis Acid Triggered Regioselective Magnesiation and Zincation of Uracils, Uridines, and Cytidines

Lydia Klier, Eider Aranzamendi, Dorothée Ziegler, Johannes Nickel, Konstantin Karaghiosoff, Thomas Carell, and Paul Knochel^*

Department Chemie, Ludwig-Maximilians-Universität, Butenandtstrasse 5-13, 81377 München, Germany

Org. Lett., 2016, 18 (5), pp 1068–1071

DOI: 10.1021/acs.orglett.6b00190

*E-mail: paul.knochel@cup.uni-muenchen.de.

 

 http://pubs.acs.org/doi/abs/10.1021/acs.orglett.6b00190

 

 

 

 

 

 

 

 

 

////////////////Lewis Acid,  Regioselective Magnesiation, Zincation, Uracils, Uridines, Cytidines

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

• 
  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