1,3-Dipolar Cycloaddition of Nitrile Imines with Functionalized Acetylenes: Regiocontrolled Sc(OTf)₃-Catalyzed Synthesis of 4- and 5-Substituted Pyrazoles

Abstract

1,3-Dipolar cycloaddition of C-aryl-N-aryl- and C-carboxymethyl-N-aryl-nitrile imines with functionalized acetylenes have been studied. Regioisomeric mixtures have been obtained with the 5-substituted pyrazole as the major cycloadduct. Under scandium triflate catalysis a reversal in the regiochemistry was observed, especially in the case of C-carboxymethyl-N-aryl-nitrile imines.

Keywords

dipolar cycloadditions - regiochemistry - nitrile imines - pyrazoles - scandium triflate

References and Notes

• 1 Padwa A. 1,3-Dipolar Cycloaddition Chemistry   J. Wiley and Sons; New York: 1984. 
• 2 Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry toward Heterocycles and Natural Products   Padwa A. Pearson WH. John Wiley; Hoboken: 2003. 
• 3 Elguero J. Goya P. Jagerovic N. Silva AMS. Targets Heterocycl. Syst.  2002,  6:  52 
• 4a Elguero J. In Comprehensive Heterocyclic Chemistry II   Katritzky RA. Rees CW. Scriven EF. Pergamon; Oxford: 1996. 
• 4b Behr LC. Fusco R. Jarboe CH. In Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles and Condensed Rings   Wiley RH. Interscience Publishers; New York: 1967. 
• 5a Katritzky AR. Handbook of Heterocyclic Chemistry   Pergamon; New York: 1985.  p.416 
• 5b Qi X. Ready JM. Angew. Chem. Int. Ed.  2007,  46:  3242 
• 5c Jiang N. Li C.-J. Chem. Commun.  2004,  394 
• 5d Vuluga D. Legros J. Crousse B. Bonnet-Delpon D. Green Chem.  2009,  11:  156 
• 6 Huisgen R. Seidel M. Wallbillich G. Knupfer H. Tetrahedron  1962,  17:  3 
• 7 Caramelle P. Grunanger P. 1,3-Dipolar Cycloaddition Chemistry   J. Wiley and Sons ; New York: 1984.  Chap. 3. p.338 
• 8 Huisgen R. Sustmann R. Wallbillich G. Chem. Ber.  1967,  100:  1786 
• 9a Conti P. Pinto A. Tamburini L. Rizzo V. De Micheli C. Tetrahedron  2007,  63:  5554 
• 9b Ponti A. Molteni G. J. Org. Chem.  2001,  66:  5252 
• 10a Bernardi L. Bonini BF. Comes Franchini M. Fochi M. Folegatti M. Grilli S. Mazzanti A. Ricci A. Tetrahedron: Asymmetry  2004,  15:  245 
• 10b Bonini BF. Boschi F. Comes Franchini M. Fochi M. Fini F. Mazzanti A. Ricci A. Synlett  2006,  543 
• 11a Kanemasa S. Nishiuchi M. Kamimura A. Hori K.
  J. Am. Chem. Soc.  1994,  116:  2324 
• 11b Murahashi S. Imada Y. Kohno M. Kawakami T. Synlett  1993,  395 
• 11c Tamura O. Yamaguchi T. Noe K. Sakamoto M. Tetrahedron Lett.  1993,  34:  4009 
• 11d Tokunaga Y. Ihara M. Fukumoto K. Tetrahedron Lett.  1996,  37:  6157 
• 11e Sanchez-Blanco AI. Gothelf KA. Jorgensen KA. Tetrahedron Lett.  1997,  38:  7923 
• 12 Wang CJ. Liang G. Xue ZY. Gao F. J. Am. Chem. Soc.  2008,  130:  17250 ; and references therein
• 13 Suge H. Ebiura Y. Fukushima K. Kakehi A. Baba T. J. Org. Chem.  2005,  70:  10782 
• 14 Sibi MP. Stanley LM. Soeta T. Adv. Synth. Catal.  2006,  348:  2371 
• 15 Balas L. Jousseaume B. Langwost B. Tetrahedron Lett.  1989,  30:  4525 
• 16 Sommer WJ. Weck M. Langmuir  2007,  23:  11991 
• 17 Pfefferkorn JA. Choi C. Larsen SD. Auerbach B. Hutchings R. Park W. Askew V. Dillon L. Hanselman JC. Lin Z. Lu GH. Robertson A. Sekerke C. Harris MS. Pavlovsky A. Bainbridge G. Caspers N. Kowala M. Tait BD. J. Med. Chem.  2008,  51:  31 
• 18 Stieber F. Grether U. Waldmann H. Chem. Eur. J.  2003,  9:  3270 
• 19 El-Abadelah MM. Hussein AQ. Kamal MR. Al-Adhami KH. Heterocycles  1988,  27:  917 
• 20 Sakamoto T. Kikugawa Y. Chem. Pharm. Bull.  1988,  36:  800 
• 21 Diaz A. J. Org. Chem.  1977,  42:  3949 
• 22a Caramella P. Grunanger P. 1,3-Dipolar Cycloaddition Chemistry   J. Wiley and Sons; New York: 1984.  Chap. 3. p.296 
• 22b Hegarty AF. Cashman MP. Scott FL.
  J. Chem. Soc., Perkin Trans. 2  1972,  44 
• 23a Garanti L. Molteni G. Zecchi G. Heterocycles  1995,  40:  777 
• 23b Broggini G. Garanti L. Molteni G. Zecchi G. Heterocycles  1997,  45:  1945 
• 24a Perez P. Domingo LR. Aurell MJ. Contreras R. Tetrahedron  2003,  59:  3117 
• 24b Perez P. Domingo LR. Aurell MJ. Contreras R. Tetrahedron  2002,  58:  4417 
• 25 Parr RG. Pearson RG. J. Am. Chem. Soc.  1983,  105:  7512 
• 26 Kanemasa S. Ueno N. Shiranase M. Tetrahedron Lett.  2002,  43:  657 

27

General Procedure for the 1,3-DC of 1 and 2 with with 3a-c and 5a-c To a solution of 1 or 2 (1 mmol) and the precursor of the 1,3-dipoles (1 mmol) in 1,4-dioxane (4.4 mL) was added Ag₂CO₃ (0.69 g, 2.5 mmol) and catalytic Sc(OTf)₃ (0.1 mmol) as specified in Tables  [¹] and  [²] . The reaction mixture was stirred at 80 ˚C for 18 h. The reaction was then filtered on Celite and the solvent was removed under vacuum. Purification was carried out as reported in the Supporting Information. Characterization for all the compounds is available as Supporting Information.