Asian Journal of Research in Chemistry

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Synthesis of Piperidine Bound 3,4,5-Trisubstituted Isoxazolines Via 1,3- Dipolar Cycloaddition Reactions Catalyzed By N-Heterocyclic Carbene


Affiliations
1 Centre for Pharmaceutical Science, Institute of Science and Technology, JNTU, Hyderabad
2 Department of Chemistry, Kakatiya University, Warangal, 506 009, India
3 Department of Chemistry, Satavahana University, Karimnagar, 505 001, India
     

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A first example of organo-N-heterocyclic carbene (NHC) catalyzed click-type fast 1,3-dipolar cycloaddition of nitrile oxides with piperidine alkene alkaloids was developed for the regioselective synthesis of 3,4,5-trisubstituted isoxazolines. Triethylamine (Et3N) was employed as an effective base to generate both nitrile oxide and the organo- NHC catalyst in situ. This catalytic approach was used to attach a variety of substituents, including other biologically active fragments, onto the isoxazoline ring to selectively design multinucleus structures. A catalytic cycle is proposed and the remarkable regiocontrol in the formation of isoxazolines was ascribed to a beneficial zwitterion intermediate developed by the interaction of the strongly nucleophilic organo-NHC catalyst with alkene followed by nitrile oxide.

Keywords

1,3-dipolar Cycloaddition, N-heterocyclic Carbene, Isoxazolines, Piperidine Alkene Alkaloids
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  • Huisgen R. 1,3-Dipolar Cycloadditions. Past and Future. Angew. Chem., Int. Ed.Engl., 1963; 2: 565-598.

  • Hein J E, Fokin V V. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(I) acetylides. Chem. Soc. Rev. 2010; 39: 1302-1315.

  • Back T G, Clary K N, Gao D. Cycloadditions and Cyclizations of Acetylenic, Allenic, and Conjugated Dienyl Sulfones. Chem. Rev. 2010; 110: 4498-4553.

  • Sanders B C, Friscourt F, Ledin P A, Mbua N E, Arumugam S, Guo J, Boltje T J,Popik V V, Boons G-J. Metal-free sequential [3 + 2]-dipolar cycloadditions using cyclooctynes and 1,3-dipoles of different reactivity. J. Am. Chem. Soc. 2011; 133: 949-957.

  • Kissane M, Maguire A R. Asymmetric 1,3-dipolar cycloadditions of acrylamides. Chem. Soc. Rev. 2010; 39: 845- 883.

  • Rück-Braun K, Freysoldt T H E, Wierschem F. 1,3-Dipolar cycloaddition on solid supports: nitrone approach towards isoxazolidines and isoxazolines and subsequent transformations. Chem. Soc. Rev. 2005; 34: 507-516.

  • Scott G, Fokin V V. Ruthenium-Catalyzed Cycloaddition of Nitrile Oxides and Alkynes: Practical Synthesis of Isoxazoles. Angew. Chem. 2008; 120: 8409-8411.

  • Himo F, Lovell T, Hilgraf R, Rostovtsev V V, Noodleman L, Sharpless K B,Fokin V V. Copper(I)-Catalyzed Synthesis of Azoles. DFT Study Predicts Unprecedented Reactivity and Intermediates. J. Am. Chem. Soc. 2005; 127: 210-216.

  • Hansen T V, Wu P, Fokin V V. One-Pot Copper(I)-Catalyzed Synthesis of 3,5- Disubstituted Isoxazoles. J. Org. Chem. 2005; 70: 7761-7764.

  • Vieira A A, Bryk F R, Conte G, Bortoluzzi A J, Gallardo H. 1,3- Dipolar cycloaddition reaction applied to synthesis of new unsymmetric liquid crystal compounds-based isoxazole. Tetrahedron Lett. 2009; 50: 905-908.

  • List B. Introduction: Organocatalysis. Chem. Rev. 2007; 107: 5413.

  • Bertelsen S, Jorgensen K A. Organocatalysis-after the gold rush. Chem. Soc. Rev. 2009; 38: 2178.

  • Yoshida K, Furuta T, Kawabata T. Organocatalytic Chemoselective Monocylation of 1,n-Linear Diols. Angew. Chem., Int. Ed. 2011; 50: 4888-4892.

  • Nair V, Pillai A N, Beneesh, P B, Suresh E. Engaging the Pyridine-DMAD Zwitterion in a Novel Strategy for the Selective Synthesis of Highly Substituted Benzene and Cyclopentenedione Derivatives. Org. Lett. 2005; 7: 4625-4628.

  • Zhu X-F, Henry C E, Kwon O. Stable Tetravalent Phosphonium Enolate Zwitterions.J. Am. Chem. Soc. 2007; 129: 6722.

  • Siebert M R, Yudin A K, Tantillo D J. Cycloaddition/Ring Opening Reaction Sequences of N-Alkenyl Aziridines: Influence of the Aziridine Nitrogen on Stereoselectivity. Org. Lett. 2008; 10: 57-60.

  • Kankala S, Edulla R, Modem S, Vadde R, Vasam C S. NHeterocyclic carbene catalyzed intramolecular crossed aldehyde– ketone benzoin condensation in the chalcone of ophthalaldehyde: a facile synthesis of naphthalenones. Tetrahedron Lett. 2011; 52: 3828-3831.

  • Breslow R. On the Mechanism of Thiamine Action. IV.1 Evidence from Studies on Model Systems. J. Am. Chem. Soc. 1958; 80: 3719-3726.

  • Enders D, Niemeier O, Henseler A. Organocatalysis by NHeterocyclic Carbenes. Chem. Rev. 2007; 107: 5606-5655.

  • Phillips E M, Chan A, Scheid K A. Discovering New Reactions with N-Heterocyclic Carbene Catalysis. Aldrichim. Acta. 2009; 42: 55-66.

  • Bugaut X, Liu F, Glorius F. N-Heterocyclic Carbene (NHC)- Catalyzed Intermolecular Hydroacylation of Cyclopropenes. J. Am. Chem. Soc. 2011; 133: 8130.

  • Kankala, S.; Vadde, R.; Vasam, C. S. N-Heterocyclic carbenecatalyzed 1,3-dipolar cycloaddition reactions: a facile synthesis of 3,5-di- and 3,4,5-trisubstituted isoxazoles. Org. Biomol. Chem. 2011; 9: 7869-7876.rhythm and reduces the force of the heart's pumping (14).


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  • Synthesis of Piperidine Bound 3,4,5-Trisubstituted Isoxazolines Via 1,3- Dipolar Cycloaddition Reactions Catalyzed By N-Heterocyclic Carbene

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Authors

Prasad Gundepaka
Centre for Pharmaceutical Science, Institute of Science and Technology, JNTU, Hyderabad
Shravankumar Kankala
Department of Chemistry, Kakatiya University, Warangal, 506 009, India
Hanmanthu Guguloth
Department of Chemistry, Kakatiya University, Warangal, 506 009, India
Shylaja Kotte
Department of Chemistry, Kakatiya University, Warangal, 506 009, India
Vinutha Chakilam
Department of Chemistry, Kakatiya University, Warangal, 506 009, India
Mukkanti Kagga
Centre for Pharmaceutical Science, Institute of Science and Technology, JNTU, Hyderabad
Ravinder Vadde
Department of Chemistry, Kakatiya University, Warangal, 506 009, India
Chandra Sekhar Vasam
Department of Chemistry, Satavahana University, Karimnagar, 505 001, India

Abstract


A first example of organo-N-heterocyclic carbene (NHC) catalyzed click-type fast 1,3-dipolar cycloaddition of nitrile oxides with piperidine alkene alkaloids was developed for the regioselective synthesis of 3,4,5-trisubstituted isoxazolines. Triethylamine (Et3N) was employed as an effective base to generate both nitrile oxide and the organo- NHC catalyst in situ. This catalytic approach was used to attach a variety of substituents, including other biologically active fragments, onto the isoxazoline ring to selectively design multinucleus structures. A catalytic cycle is proposed and the remarkable regiocontrol in the formation of isoxazolines was ascribed to a beneficial zwitterion intermediate developed by the interaction of the strongly nucleophilic organo-NHC catalyst with alkene followed by nitrile oxide.

Keywords


1,3-dipolar Cycloaddition, N-heterocyclic Carbene, Isoxazolines, Piperidine Alkene Alkaloids

References