A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines

A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC02517J, Communication

Xihong Liu, Dongxu Yang, Kezhou Wang, Jinlong Zhang, Rui Wang
A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles has been reported under mild conditions.

A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines

Xihong Liu,^a   Dongxu Yang,^a   Kezhou Wang,^a  Jinlong Zhang^a and   Rui Wang*^ab  

http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C6GC02517J?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

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Corresponding authors

^a

School of Life Sciences, Institute of Biochemistry and Molecular Biology, Lanzhou University, Lanzhou 730000, P. R. China
E-mail: wangrui@lzu.edu.cn

^b

State Key Laboratory of Chiroscience, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, P. R. China
E-mail: bcrwang@polyu.edu.hk

Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC02517J

We have reported herein a catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles by which a series of five-ring-fused tetrahydroisoquinolines featuring an indoline scaffold were obtained as single diastereomers in moderate to high yields without any additives under mild conditions. Moreover, the current method provides a novel and convenient approach for the efficient incorporation of two biologically important scaffolds (tetrahydroisoquinoline and indoline).


ethyl 13b-nitro-8-tosyl-8,8a,13b,13c-tetrahydro-5H-indolo[2',3':3,4]pyrazolo[5,1- a]isoquinoline-9(6H)-carboxylate

ethyl 13b-nitro-8-tosyl-8,8a,13b,13c-tetrahydro-5H-indolo[2',3':3,4]pyrazolo[5,1- a]isoquinoline-9(6H)-carboxylate:
White solid, m.p. 153 – 154 oC; 94% yield; 1H NMR (300 MHz, CDCl3) δ 7.86 (d, J = 8.2 Hz, 2H), 7.78 (d, J = 7.9 Hz, 1H), 7.30 – 7.13 (m, 5H), 7.1 (s, 1H), 7.05 – 6.94 (m, 1H), 6.94 – 6.87 (m, 1H), 6.59 (t, J = 7.6 Hz, 3H), 6.28 (d, J = 7.6 Hz, 1H), 4.78 (s, 1H), 4.37 (q, J = 7.1 Hz, 2H), 2.80 – 2.58 (m, 2H), 2.33 (s, 3H), 2.31 – 2.11 (m, 2H), 1.41 (t, J = 7.1 Hz, 3H) ppm;

13C NMR (75 MHz, CDCl3) δ 152.1, 144.6, 142.6, 134.0, 132.1, 129.3, 129.0, 128.7, 128.3, 127.5, 127.3, 126.2, 122.8, 121.1, 115.5, 104.5, 84.9, 70.7, 62.8, 48.5, 29.1, 21. 6, 14.3 ppm;

HRMS (ESI): C27H26N4NaO6S [M + Na]+ calcd: 557.1465, found: 557.1476.


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Register Today for the ACS Symposium in India on Recent Advances in Drug Development, 11-12 November 2016 in Hyderabad, India

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A Brønsted Acid–Primary Amine as a Synergistic Catalyst for Stereoselective Asymmetric Diels–Alder Reactions

Ramachary Dhevalapally

September 14 · 

 on facebook wrote, quote

I am happy to share with you our laboratory recent publication on asymmetric catalysis.

This communication deals with the understanding and development of Brønsted Acid-Primary Amine as a Synergistic-catalyst for Stereoselective Asymmetric Barbas [4+2]-cycloaddition reaction by using 2-aminobuta-1,3-diene-catalysis under ambient conditions.

I believe this reaction can become good tool for chemists.

I congratulate my co-workers for their hard work to make this work more successful.

For more information, please click below link:
http://onlinelibrary.wiley.com/doi/10.1002/ejoc.201601011/full          ..........unquote

http://onlinelibrary.wiley.com/store/10.1002/ejoc.201601011/asset/supinfo/ejoc201601011-sup-0001-SupMat.pdf?v=1&s=df97504ed59dfa57793737f8f4186106bcbac24c

(1R,3S,5S)-5-hydroxy-3-methyl-2'-oxospiro[cyclohexane-1,3'-indoline]-2,2-dicarbonitrile (7ag): Prepared by following the procedure E and purified by column chromatography using EtOAc/hexane and isolated as solid.

[]D 25 = –119.2 (c = 0.1 g/100 mL, CHCl3, 99% ee);

IR (Neat): max 3313, 2977, 2930, 1701, 1618, 1479, 1350, 1272, 1246, 1200, 1148, 1066, 1014 and 750 cm-1 ; 

1H NMR (CDCl3)  8.58 (1H, br s, NH), 7.64 (1H, d, J = 8.0 Hz), 7.41 (1H, t, J = 7.5 Hz), 7.23 (1H, t, J = 7.5 Hz), 6.99 (1H, d, J = 7.5 Hz), 5.32 (1H, dd, J = 11.0, 4.0 Hz), 4.22-4.18 (1H, m), 3.44-3.89 (1H, m), 2.33 (1H, dd, J = 16.0, 4.0 Hz), 2.20-2.13 (2H, m), 1.89 (1H, dt, J = 13.0, 3.5 Hz), 1.40 (3H, d, J = 6.5 Hz); 

13C NMR S-15 (CDCl3, DEPT-135)  178.2 (C, N_C=O), 139.8 (C), 130.9 (CH), 127.6 (C), 124.9 (CH), 124.2 (CH), 112.9 (C, CN), 111.8 (C, CN), 110.8 (CH), 64.7 (CH), 52.3 (C), 47.2 (C), 36.9 (CH2), 34.0 (CH2), 28.8 (CH), 18.4 (CH3); 

HRMS m/z 304.1060 (M + Na), calcd for C16H15N3O2Na 304.1062.

Ramachary D B

Details

• 

   

Dr. D. B. Ramchary, Ph.D. Associate Professor 
   School of Chemistry
   University of Hyderabad
   Prof. C. R. Rao Road, Gachibowli
   Hyderabad, 500046, India
   Tel: 0091-40-23134816
   Email: ramsc@uohyd.ernet.in

Ramachary obtained his Masters degree (General Chemistry) at the University of Hyderabad in 1996. There as part of curricula he studied and actively involved in the project, entitled Synthesis and Utilization of Aromatic Radical Anions for Reduction of Carbon Monoxide (with Prof. M. Periasamy).

Ramachary obtained his Doctoral degree (Organic Synthesis) at the Indian Institute of Science, Bangalore for his research work on Total Synthesis of Sesquiterpenes Containing Three Contiguous Quaternary Carbon Atoms (with Prof. A. Srikrishna).

In January 2002, he moved to Prof. Carlos F. Barabas III research group as Skaggs Post Doctoral fellow at The Scripps Research Institute, San Diego. After three year post doctoral studies at TSRI, he then joined as Faculty member in School of Chemistry, University of Hyderabad in Jan 2005, where at present he is a Reader.

Dr Ramachary has been awarded the INSA Medal for Young Scientists in Chemical Sciences for the year 2006 for his outstanding contributions to the emerging area of asymmetric organocatalysis.

The main focus of his research group is to engineer the novel and green asymmetric cascade and multi-component reactions (MCRs) to generate the biologically important molecules and natural products in a single step via emerging chiral amines or amino acid-catalysis.

His research group is actively engaged in the design and synthesis of novel enzyme mimetic small organic amines and amino acids to catalyze the fundamental organic reactions in enantioselective manner.

His interest about inquisitive questions like how small can be highly active and stereo-selective catalysts and what are the minimal functional and structural features required in a chiral catalyst had made him to venture in the most advanced versions of synthetic chemistry. 

For the more information about his research group please Click here for Home Page

Significant Publications:
D. B. Ramachary, M. Kishor and Y. Vijayendar Reddy, Development of Pharmaceutical Drugs, Drug Intermediates and Ingredients by Using Direct Organo-Click Reactions, Eur. J. Org. Chem., 2007, xxxx-xxxx (DOI: 10.1002/ejoc.200701014).

D. B. Ramachary, G. Babul Reddy and Rumpa Mondal, New Organocatalyst for Friedel-Crafts Alkylation of 2-Naphthols with Isatins: Application of an Organo-Click Strategy for the Cascade Synthesis of Highly Functionalized Molecules, Tetrahedron Lett., 2007, 48, 7618-7623.

D. B. Ramachary and M. Kishor, Organocatalytic Sequential One-Pot Double Cascade Asymmetric Synthesis of Wieland-Miescher Ketone Analogs from a Knoevenagel/Hydrogenation/Robinson Annulation Sequence: Scope and Applications of Organocatalytic Bio-Mimetic Reductions, J. Org. Chem., 2007, 72, 5056-5068.

D. B. Ramachary, K. Ramakumar and V. V. Narayana, Organocatalytic Cascade Reactions Based on Push-Pull Dienamine Platform: Synthesis of Highly Substituted Anilines, J. Org. Chem., 2007, 72, 1458-1463.

D. B. Ramachary and G. Babul Reddy, Towards Organo-Click Reactions: Development of Pharmaceutical Ingredients by Using Direct Organocatalytic Bio-Mimetic Reductions, Org. Biomol. Chem., 2006, 4, 4463-4468.

D. B. Ramachary and Rumpa Mondal, Direct Organocatalytic Hydroalkoxylation of a,b-Unsaturated Ketones, Tetrahedron Lett., 2006, 47, 7689-7693.

Jorly Joseph, D. B. Ramachary, Eluvathingal D. Jemmis, Electrostatic Repulsion as an additional Selectivity Factor in Asymmetric Proline Catalysis, Org. Biomol. Chem., 2006, 4, 2685-2689.

D. B. Ramachary, M. Kishor and G. Babul Reddy, Development of Drug Intermediates by Using Direct Organocatalytic Multi-Component Reactions, Org. Biomol. Chem., 2006, 4, 1641-1646.

D. B. Ramachary, M. Kishor and K. Ramakumar, A Novel and Green Protocol for Two-Carbon Homologation: A Direct Amino Acid/K2CO3-Catalyzed Four-Component Reaction of Aldehydes, Active Methylenes, Hantzsch Esters and Alkyl Halides, Tetrahedron Lett., 2006, 47, 651-656.

D. B. Ramachary, K. Ramakumar and M. Kishor, Direct Organocatalytic in situ Generation of Novel Push-Pull Dienamines: Application in Tandem Claisen-Schmidt/Iso-Aromatization Reactions, Tetrahedron Lett., 2005, 46, 7037-7042.

D. B. Ramachary and Carlos F. Barbas III, Direct Amino Acid-Catalyzed Asymmetric Desymmetrization of meso-Compounds: Tandem Aminoxylation/O-N Bond Heterolysis Reactions, Org. Lett., 2005, 7, 1577-1580.

D. B. Ramachary, Naidu S. Chowdari and Carlos F. Barbas III, Organocatalytic Asymmetric Domino Knoevenagel/Diels-Alder Reactions: A Bioorganic Approach to the Diastereospecific and Enantioselective Construction of Highly Substituted Spiro[5,5]undecane-1,5,9-triones, Angew. Chem. Int. Ed., 2003, 42, 4233-4237. 

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Molybdenum- and tungsten-based olefin metathesis catalysts have demonstrated excellent results in the control of cis (Z-) selectivity as well as enantioselectivity. However, their air and moisture sensitivity, which requires the use of a glovebox, has prevented their more widespread use by organic chemists. Now we report on developed, preweighed Mo catalysts formulated in paraffin tablets. 

The significantly improved air stability, high homogeneity, and uniformity of the pellets allow researchers to carry out reactions on the bench avoiding the need of a glovebox.

The two different Mo-based complexes which were packed into tablets are XiMoPac-Mo001 (1) that can be used to achieve endo-selective enyne ring-closing metathesis (RCM) reactions, interalia; and XiMoPac-Mo003 (2) which was reported among the best catalysts to promote Z-selective cross-metathesis. 

For the evaluation of the wax-protected catalysts commonly used, highly reproducible robust model reactions were chosen: homo cross-metathesis (HCM) of functionalized (e.g., methyl 9-decenoate) and unfunctionalized (allylbenzene) terminal olefins, and ring closing metathesis (RCM) of diethyl diallylmalonate. The yields and conversions were comparable with those which can be achieved in glovebox with nonformulated catalysts. 

Exposure to air did not cause any significant reduction in conversion while the product selectivity (targeted product vs homologues derived from double bond isomerization) remained high. In contrast, exposure to air caused a measurable drop in the conversion with the nonprotected catalyst. Furthermore, the formulated catalysts remained unaffected even after 4 h of exposure to air, showing its enhanced air stability. 

In conclusion, these commercially available air-stable Mo-catalyst tablets allow the reactions to be accomplished using ordinary Schlenk techniques, and hence simplify catalyst handling in pilot laboratories and plants.

From Box to Bench: Air-Stable Molybdenum Catalyst Tablets for Everyday Use in Olefin Metathesis

Levente Ondi*†, Gergely M. Nagy†, Janos B. Czirok†, Agota Bucsai†, and Georg E. Frater‡

† XiMo Hungary Ltd., 7. Zahony Str., Budapest HU-1031, Hungary

‡ XiMo AG, 3. Altsagenstrasse, Horw/Luzern CH-6048, Switzerland

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.6b00161

*Telephone: (36) 1 580 2202; Fax: (36) 1-580 2201; E-mail: levente.ondi@ximo-inc.com.

http://pubs.acs.org/doi/abs/10.1021/acs.oprd.6b00161

Levente Ondi

Director of R. & D. at XiMo Hungary Ltd.

https://hu.linkedin.com/in/levente-ondi-2005931a

Experience

Director of R&D

XiMo Hungary Ltd.

December 2012 – Present (3 years 11 months)

Head of Chemistry Lab.

XiMo Hungary Ltd.

December 2010 – December 2012 (2 years 1 month)

Senior Research Scientist

Servier Research Institute of Medicinal Chemistry

January 2008 – December 2010 (3 years)

Head of R&D Laboratory II.

Chemical Future Pharma Ltd.

June 2005 – December 2007 (2 years 7 months)

Research Scientist

Chemical Future Pharma Ltd.

March 1999 – August 2001 (2 years 6 months)

Education

Swiss Federal Institute of Technology Lausanne

Ph.D., Organometallic Chemistry

2001 – 2005

Budapesti Mûszaki és Gazdaságtudományi Egyetem / Technical University of Budapest

Master of Science (M.Sc.), Chemical Engineering

1993 – 1999

Ximo Hungary Kft.  

Website

Directions

Chemical Plant

Address: Budapest, Záhony utca 7. D épület, 1031 Hungary

Prof. Dr. Georg Fráter

Chief Operating Officer

 

• Over 30 years experience in the Swiss chemical industry
• Over 20 years in the fragrance and flavor industry, five as Research Director for Givaudan
• Former President Swiss Chemical Society (SCS)
• Former Professor at the University of Zürich
• Current member of the board of Thales Nano

 

Education: Ph.D. University of Zurich; M.Sc. University of Zurich

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