Highly Efficient Copper- and Palladium-Free One-Pot Coupling of Alkynes with Sodium Carboxylate Salts Using Cyanuric and Magnesium Chlorides

Abstract

A facile and highly efficient copper- and palladium-free procedure for the one-pot synthesis of ynones via coupling of sodium carboxylate salts with alkynes is described. In this method, cross-coupling of terminal alkynes with a mixture of structurally diverse sodium carboxylate salts, cyanuric chloride and triethylamine in the presence of magnesium chloride furnishes the corresponding ynones in good to excellent yields at room temperature.

Key words

one-pot synthesis - alkyne - cyanuric chloride - sodium carboxylate salt - ynone

References and Notes

• 1a Mead D. Asato AE. Denny M. Liu RSH. Hanzawa Y. Taguchi T. Yamada A. Kobayashi N. Hosoda A. Kobayashi Y. Tetrahedron Lett.  1987,  28:  259 
• 1b Chowdhury C. Kundu NG. Tetrahedron  1999,  55:  7011 
• 1c Quesnelle CA. Gill P. Dodier M. St. Laurent D. Serrano-Wu M. Marinier A. Martel A. Mazzucco CE. Stickle TM. Barrett JF. Vyas DM. Balasubramanian BN. Bioorg. Med. Chem. Lett.  2003,  13:  519 
• 2a Hojo M. Omita K. Hosomi A. Tetrahedron Lett.  1993,  34:  485 
• 2b Arcadi A. Marenelli F. Rossi E. Tetrahedron  1999,  55:  13233 
• 2c Kelin AV. Sromek AW. Gevorgyan V. J. Am. Chem. Soc.  2001,  123:  2074 
• 2d Jeevnandan A. Narkunan K. Ling Y. J. Org. Chem.  2001,  66:  6014 
• 2e Grotjahn DB. Van S. Combs D. Lev DA. Schneider C. Rideout M. Meyer C. Hernandez G. Mejorado L. J. Org. Chem.  2002,  67:  9200 
• 2f Karpov AS. Muller TJ. Org. Lett.  2003,  5:  3451 
• 3a Muzart J. Piva O. Tetrahedron Lett.  1988,  29:  2321 
• 3b Shaw JE. Sherry JJ. Tetrahedron Lett.  1971,  4379 
• 3c Sheats WB. Olli LK. Stout R. Lundeen JT. Justus R. Nigh WG. J. Org. Chem.  1979,  44:  4075 
• 4a Maeda Y. Kakiuchi N. Matsumura S. Nishimura T. Kawamura T. Uemura S. J. Org. Chem.  2002,  67:  6718 ; and references therein
• 4b Augé J. Lubin-Germain N. Seghrouchni L. Tetrahedron Lett.  2003,  44:  819 
• 5a Corey EJ. Kyler K. Raju N. Tetrahedron Lett.  1984,  25:  5115 
• 5b Campestrini S. Furia FD. Modena G. J. Org. Chem.  1990,  55:  3658 
• 5c Hirao T. Misu D. Agawa T. Tetrahedron Lett.  1986,  27:  933 
• 6a Mohamed Ahmed MS. Mori A. Org. Lett.  2003,  5:  3057 ; and all references therein
• 6b Liang B. Huang M. You Z. Xiong Z. Lu K. Fathi R. Chen J. Yang Z.
  J. Org. Chem.  2005,  70:  6097 
• 7a Goure WF. Wright ME. Davis PD. Labadie SS. Stille JK. J. Am. Chem. Soc.  1984,  106:  6417 
• 7b Grisp GT. Scott WJ. Stille JK. J. Am. Chem. Soc.  1984,  106:  7500 
• 7c Arcadi A. Cacchi S. Marinelli F. Ace P. Sanzi G. Synlett  1995,  823 
• 8a Palimkar SS. Harish Kumar P. Jogdand NR. Daniel T. Lahoti RJ. Srinivasan KV. Tetrahedron Lett.  2006,  47:  5527 
• 8b Alonso DA. Nájera C. Pacheco MC. J. Org. Chem.  2004,  69:  1615 
• 8c Chen L. Li C.-J. Org. Lett.  2004,  6:  3151 
• 8d Cox RJ. Ritson DJ. Dane TA. Berge J. Charmant JPH. Kantacha A. Chem. Commun.  2005,  1037 
• 8e Likhar PR. Subhas MS. Roy M. Roy S. Kantam ML. Helv. Chim. Acta  2008,  91:  259 
• 8f Chen J.-Y. Lin T.-C. Chen S.-C. Chen A.-J. Mou C.-Y. Tsai F.-Y. Tetrahedron  2009,  65:  10134 
• 8g Bakherad M. Keivanloo A. Bahramian B. Rajaie M. Tetrahedron Lett.  2010,  51:  33 
• 9a Tohda Y. Sonogashira K. Hagihara N. Synthesis  1977,  777 
• 9b Verkruijsse HD. Heus-Kloos YA. Brandsma L. J. Organomet. Chem.  1988,  338:  289 
• 9c Logue MW. Teng K. J. Org. Chem.  1982,  47:  2549 
• 9d Wakamatsu T. Okuda Y. Oshima K. Nozaki H. Bull. Chem. Soc. Jpn.  1985,  58:  2425 
• 9e Pérez I. Sestelo JP. Sarandeses LA. J. Am. Chem. Soc.  2001,  123:  4155 
• 9f Kakusawa N. Yamaguchi K. Kurita J. Tsuchiya T. Tetrahedron Lett.  2000,  41:  4143 
• 10 Davis RB. Scheiber DH. J. Am. Chem. Soc.  1956,  78:  1675 
• 11a Normant JF. Synthesis  1972,  63 
• 11b Logue MW. Moore GL. J. Org. Chem.  1975,  40:  131 
• 12 Fontaine M. Chauvelier J. Barchewitz P. Bull. Soc. Chim. Fr.  1962,  2145 
• 13 Compagnon PL. Grosjean B. Lacour M. Bull. Soc. Chim. Fr.  1975,  779 
• 14 Yashina OG. Zarva TV. Vereshchagin LI. Zh. Org. Khim.  1967,  3:  219 ; Chem. Abstr. 1967, 66, 94664
• 15 Vereshchagin LI. Yashina OG. Zarva TV. Zh. Org. Khim.  1966,  2:  1895 ; Chem. Abstr. 1967, 66, 46070p
• 16a Utimoto K. Tanaka M. Kitai M. Nozaki H. Tetrahedron Lett.  1978,  2301 
• 16b Birkofer L. Ritter A. Uhlenbrauck H. Chem. Ber.  1963,  96:  3280 
• 16c Walton DRM. Waugh F. J. Organomet. Chem.  1972,  37:  45 
• 16d Gallagher WP. Maleczka RE. J. Org. Chem.  2003,  68:  6775 
• 17 Markó IE. Southern JM. J. Org. Chem.  1990,  55:  3368 
• 18 Himbert G. Angew. Chem., Int. Ed. Engl.  1979,  18:  405 
• 19 Chowdhury C. Kundu NG. Tetrahedron Lett.  1996,  37:  7323 
• 20a Lee KY. Lee MJ. Kim JN. Tetrahedron  2005,  61:  8705 
• 20b Keivanloo A. Bakherad M. Bahramian B. Baratnia S. Tetrahedron Lett.  2011,  52:  1498 
• 21 Dishart KT. Levine R. J. Am. Chem. Soc.  1956,  78:  2268 
• 22 Blotny G. Tetrahedron  2006,  62:  9507 ; and all references cited therein
• 23a Soltani Rad MN. Khalafi-Nezhad A. Asrari Z. Behrouz S. Amini Z. Behrouz M. Synthesis  2009,  3983 
• 23b Soltani Rad MN. Khalafi-Nezhad A. Asrari Z. Behrouz S. Synthesis  2010,  2599 
• 25a Venkataraman K. Wagle DR. Tetrahedron Lett.  1979,  3037 
• 25b Bandgar BP. Pandit SS. Tetrahedron Lett.  2002,  43:  3413 
• 25c Kaminski ZJ. Paneth P. Rudzinski J. J. Org. Chem.  1998,  63:  4248 
• 25d Rayle HL. Fellmeth L. Org. Process Res. Dev.  1999,  3:  172 

24

Similar reaction conditions were employed for carboxylic acid, except that Et₃N (6.6 equiv) was employed

26

General procedure for coupling of alkynes with sodium carboxylate salts using cyanuric chloride: To a solution of sodium carboxylate salt (3.3 mmol) in anhydrous MeCN (5 mL), was added TCT (1 mmol) and the reaction mixture was stirred at r.t. for 10 min. A solution of the appropriate alkyne (3 mmol), Et₃N (3.3 mmol) and MgCl₂ (3.3 mmol) in anhydrous MeCN (5 mL) was added and the solution was stirred for a further 50-110 min (until TLC indicated completion of the reaction, see Table  [5] ). The solution was filtered and the solvent was evaporated under vacuum. The remaining foam was then diluted in CHCl₃ (50 mL) and subsequently washed with H₂O (2 × 50 mL). The organic layer was dried (Na₂SO₄) and evaporated. The crude product was purified by short column chromatography on silica gel (n-hexane-EtOAc, 20:1).