3-Aryl-5-vinyl-2-isoxazolines and 3-Aryl-5-vinylisoxazoles from Aryl Nitrile Oxides and Methyl Vinyl Ketone Lithium Enolate: 
Reaction Limits and Synthetic Utility Exploitation

Antonio Salomone; Antonio Scilimati; Paola Vitale

doi:10.1055/s-0034-1379640

Synthesis, Table of Contents

Synthesis 2015; 47(06): 807-816
DOI: 10.1055/s-0034-1379640

paper

3-Aryl-5-vinyl-2-isoxazolines and 3-Aryl-5-vinylisoxazoles from Aryl Nitrile Oxides and Methyl Vinyl Ketone Lithium Enolate: Reaction Limits and Synthetic Utility Exploitation

Antonio Salomone

^aDipartimento di Farmacia-Scienze del Farmaco Università degli Studi di Bari ‘A. Moro’, Via E. Orabona 4, 70125 Bari, Italy Email: paola.vitale@uniba.it

^bConsorzio Interuniversitario Nazionale Metodologie e Processi Innovativi di Sintesi (CINMPIS) Università degli Studi di Bari ‘A. Moro’, Via E. Orabona 4, 70125 Bari, Italy

,

Antonio Scilimati

^aDipartimento di Farmacia-Scienze del Farmaco Università degli Studi di Bari ‘A. Moro’, Via E. Orabona 4, 70125 Bari, Italy Email: paola.vitale@uniba.it

,

Paola Vitale*

^aDipartimento di Farmacia-Scienze del Farmaco Università degli Studi di Bari ‘A. Moro’, Via E. Orabona 4, 70125 Bari, Italy Email: paola.vitale@uniba.it

› Author Affiliations

Abstract

All articles of this category

Dedicated to Claudio Salomone, born November 24, 2014

Abstract

3-Aryl-5-hydroxy-5-vinyl-2-isoxazolines were synthesized by reacting aryl nitrile oxides with the lithium enolate of methyl vinyl ketone (MVK) at –78 °C. Fair to good yields are obtained in the case of aryl nitrile oxides bearing electron-withdrawing groups on the aryl moiety or less bulky groups. Conversely, lower yields or no reaction was observed in the presence of hindered aryl nitrile oxides. Such a behavior was confirmed by ab initio calculations of the activation energies for three reactions. A number of 3-aryl-5-vinylisoxazoles were quantitatively obtained by dehydration/aromatization of the corresponding 5-hydroxy-2-isoxazolines under acidic conditions. The side-chain elaboration is reported as a synthetic utility of some vinylisoxazoles and vinylisoxazolines.

Key words

5-vinylisoxazolines - 5-vinylisoxazoles - aryl nitrile oxides - ketone lithium enolates - DFT/B3LYP ab initio calculations

Full Text

References

References

1a Pinho e Melo TM. V. D. Curr. Org. Chem. 2005; 9: 925
1b Gandolfig R, Grünanger P In Chemistry of Heterocyclic Compounds: Isoxazoles . Vol. 49, Part 2. Grünanger P, Vita-Finzi P, Dowling JE. Wiley; Hoboken: 1999
1c Cicchi S, Cordero FM, Giomi D. Prog. Heterocycl. Chem. 2012; 24: 317
1d Silva AM. S, Tomé AC, Pinho e Melo TM. V. D, Elguero J. Five-Membered Heterocycles: 1,2-Azoles. Part 2. Isoxazoles and Isothiazoles . In Modern Heterocyclic Chemistry . Vol. 1. Alvarez-Builla J, Vaquero JJ, Barluenga J. Wiley-VCH; Weinheim: 2011. Chap. 9, 727-808
1e Nishiwaki N, Kobiro K, Kiyoto H, Hirao S, Sawayama J, Saigo K, Okajima Y, Uehara T, Maki A, Ariga M. Org. Biomol. Chem. 2011; 9: 2832
1f Cecchi L, De Sarlo F, Machetti F. Eur. J. Org. Chem. 2006; 4852
1g Grecian S, Fokin VV. Angew. Chem. Int. Ed. 2008; 47: 8285

2a Pevarello P, Amici R, Brasca MG, Villa M, Varasi M. Targets Heterocycl. Syst. 1999; 3: 301
2b Perrone MG, Malerba P, Uddin MdJ, Vitale P, Panella A, Crews BC, Daniel CK, Ghebreselasie K, Nickels M, Tantawy MN, Manning HC, Marnett LJ, Scilimati A. Eur. J. Med. Chem. 2014; 80: 562
2c Vitale P, Tacconelli S, Perrone MG, Malerba P, Simone L, Scilimati A, Lavecchia A, Dovizio M, Marcantoni E, Bruno A, Patrignani P. J. Med. Chem. 2013; 56: 4277
2d Calvello R, Panaro MA, Carbone ML, Cianciulli A, Perrone MG, Vitale P, Malerba P, Scilimati A. Pharmacol. Res. 2011; 65: 137
2e Vitale P, Perrone MG, Malerba P, Lavecchia A, Scilimati A. Eur. J. Med. Chem. 2014; 74: 606
2f Di Nunno L, Vitale P, Scilimati A, Tacconelli S, Patrignani P. J. Med. Chem. 2004; 47: 4881

3 Tavares A, Livotto PR, Gonçalves PF. B, Merlo AA. J. Braz. Chem. Soc. 2009; 20: 1742
4 Gilchrist TL. J. Chem. Soc., Perkin Trans. 1 1999; 2849

5a Akiba K, Kashiwagi K, Ohyama Y, Yamamoto Y, Ohkata K. J. Am. Chem. Soc. 1985; 107: 2721
5b Kijma M, Nambu Y, Endo T. J. Org. Chem. 1985; 50: 1140

6 Di Nunno L, Scilimati A, Vitale P. Tetrahedron 2005; 61: 2623
7 Kashima C. J. Org. Chem. 1975; 40: 526

8a Di Nunno L, Vitale P, Scilimati A, Simone L, Capitelli F. Tetrahedron 2007; 63: 12388
8b Di Nunno L, Vitale P, Scilimati A. Tetrahedron 2008; 64: 11198

9a Vitale P, Scilimati A. Curr. Org. Chem. 2013; 17: 1986
9b Vitale P, Scilimati A. Synthesis 2013; 45: 2940
9c Trogu E, Cecchi L, De Sarlo F, Guideri L, Ponticelli F, Machetti F. Eur. J. Org. Chem. 2009; 5971
9d Takikawa H, Hikita K, Suzuki K. Synlett 2007; 2252

10a Di Nunno L, Scilimati A, Vitale P. Tetrahedron 2005; 61: 11270
10b Di Nunno L, Scilimati A, Vitale P. Tetrahedron 2006; 62: 1610

11a Baranski A. Pol. J. Chem. 1981; 55: 1189
11b Qazi NA, Singh PP, Jan S, Kumar H, Sampath M. Synlett 2007; 1449
11c Ambler PW, Paton RM, Tout JM. J. Chem. Soc., Chem. Commun. 1994; 2661
11d Ambler PW, Paton RM, Tout JM. J. Chem. Soc., Chem. Commun. 1995; 911
11e Ponticello IS. J. Polym. Sci. Polym. Chem. Ed. 1975; 13: 415

12a Kano H, Adachi I. Japanese Patent 40023172, 1965 ; Chem. Abstr. 1966, 64, 84595.
12b Bertini V, De Munno A, Pelosi P, Pino P. J. Heterocycl. Chem. 1968; 5: 621
12c Batra S, Rastogi SK, Patra A, Bhaduri AP. Tetrahedron Lett. 2000; 41: 5971
12d Sokolov SD, Azarevich OG, Vinogradova SM. Khim. Geterotsikl. Soedin. 1988; 5: 710 ; Chem. Abstr. 1989, 110, 231555
12e Vagina LK, Chistokletov VN, Petrov AA. Zh. Obshch. Khim. 1966; 2: 417 ; Chem. Abstr. 1966, 65, 38487

13a Jarrar AA, Hussein AQ, Madi AS. J. Heterocycl. Chem. 1990; 27: 275
13b Kheruze YI, Galishev VA, Petrov AA. Zh. Org. Khim. 1988; 24: 944 ; Chem. Abstr. 1989, 110, 95065
13c Annunziata R, Cinquini M, Cozzi F, Raimondi L, Restelli A. Helv. Chim. Acta 1985; 68: 1217
13d Annunziata R, Cinquini M, Cozzi F, Raimondi L. J. Chem. Soc., Chem. Commun. 1985; 403
13e Sumimoto S, Ueda N, Imoto M. Kogyo Kagaku Zasshi 1963; 66: 1505 ; Chem. Abstr. 1964, 61, 55130

14a Brubaker JD, Myers AG. Org. Lett. 2007; 9: 3523
14b Brandi A, De Sarlo F, Guarna A, Goti A. Heterocycles 1985; 23: 2019
14c DalPiaz V, Ciciani G, Costanzo A, Auzzi G, Chimichi S. Heterocycles 1984; 22: 1741
14d Novozhilov YV, Karabanov MV, Korsakov MK, Semenychev EV, Yasinskii OA. Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol. 2009; 52: 1 ; Chem. Abstr. 2010, 152, 591904

15 Bertini V, Pocci M, Provenzano F, De Munno A. Macromolecules 1981; 14: 1833
16 Perrone MG, Vitale P, Malerba P, Altomare A, Rizzi R, Lavecchia A, Di Giovanni C, Novellino E, Scilimati A. Chem. Med. Chem. 2012; 7: 629
17 Di Nunno L, Scilimati A. Tetrahedron 1987; 43: 2181

18a Hine J. Physical Organic Chemistry . McGraw-Hill Book Co. Inc; New York: 1962. Chap. 4
18b Smith MB, March J. March’s Advanced Organic Chemistry. Reaction, Mechanism, and Structure . 6th ed. Wiley; Hoboken: 2007: Chap. 9, 404
18c Hansch C, Leo A, Taft RW. Chem. Rev. 1991; 91: 165

For computational studies about nucleophilic additions of lithium enolates, see:

19a Li Y, Paddon-Row MN, Houk KN. J. Org. Chem. 1990; 55: 481
19b Pratt LM, Van Nguyen N, Ramachandran B. J. Org. Chem. 2005; 70: 4279

20 Unpublished results.
21 Suffert J. J. Org. Chem. 1989; 54: 509
22 For references concerning the chemistry of aryl niltrile oxides: Torssell KB. G. In Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis . Feuer H. VCH; Weinheim: 1988. Chap. 2, 55-74
23 Vitale P, Di Nunno L, Scilimati A. Synthesis 2010; 3195
24 Granovsky A. A.; Firefly version 8.0; www http://classic.chem.msu.su/gran/firefly/index.html.
25 Schmidt MW, Baldridge KK, Boatz JA, Elbert ST, Gordon MS, Jensen JH, Koseki S, Matsunaga N, Nguyen KA, Su S, Windus TL, Dupuis V, Montgomery V. J. Comput. Chem. 1993; 14: 1347

Supplementary Material

Supporting Information