Copper-Nanoparticle-Catalyzed A³ Coupling via C-H Activation

Abstract

Recyclable metal nanoparticles provide an efficient, economic, and novel route for the synthesis of propargylamines via three-component A³ coupling reaction of aromatic aldehyde, amine and alkyne. This method provides a wide range of substrate applicability. This protocol avoids the use of heavy metal, co-catalyst and gives propargylamines in quantitative yield.

Key words

metal nanoparticles - propargylamines - heterogeneous catalysis - cyclic secondary amines - one-pot multicomponent reaction

References and Notes

• 1a Li CJ. Acc. Chem. Res.  2002,  35:  533 
• 1b Sonogashira K. In Handbook of Organopalladium Chemistry for Organic Synthesis   Negishi E. John Wiley and Sons; New York: 2002.  p.493 
• 1c Dyker G. Angew. Chem. Int. Ed.  1999,  38:  1698 
• 2a Yan W. Wang R. Xu Z. Xu J. Lin L. Shen Z. Zhou Y. J. Mol. Catal. A: Chem.  2006,  25:  81 
• 2b Kidwai M. Bansal V. Saxena A. Aerry S. Mozumdar S. Tetrahedron Lett.  2006,  47:  8049 
• 2c Wang Z. Xiao P. Shen B. He N. Coll. Surf. A  2006,  276:  116 
• 3 Catalysis: An Integrated Approach, In Studies in Surface Science and Catalysis, Vol. 123   2nd ed.:  Vansanten RA. VanLeeuwen PWNM. Moulijn JA. Averill BA. Elsevier; Amsterdam: 1999. 
• 4 Klabunde JK. Nanoscale Materials in Chemistry   John Wiley and Sons; New York: 2001.  p.226 
• 5a Boulton AA. Davis BA. Durden DA. Dyck LE. Juorio AV. Li XM. Paterson IA. Yu PH. Drug Dev. Res.  1997,  42:  150 
• 5b Huffman MA. Yasuda N. DeCamp AE. Grabowski EJJ. J. Org. Chem.  1995,  60:  1590 
• 5c Konishi M. Ohkuma H. Tsuno T. Oki T. VanDuyne GD. Clardy J. J. Am. Chem. Soc.  1990,  112:  3715 
• 6a Miura M. Enna M. Okuro K. Nomura M. J. Org. Chem.  1995,  60:  4999 
• 6b Jenmalm A. Berts W. Li YL. Luthman K. Csoregh I. Hacksell U. J. Org. Chem.  1994,  59:  1139 
• 6c Nilsson B. Vargas HM. Ringdahl B. Hacksell U. J. Med. Chem. Soc.  1992,  35:  285 
• 7a Dyker G. Angew. Chem.  1999,  38:  1698 
• 7b Naota I. Takaya H. Murahashi SI. Chem. Rev.  1998,  98:  2599 
• 8a Yan W. Wang R. Xu Z. Xu J. Lin L. Shen Z. Zhou Y. J. Mol. Catal. A: Chem.  2006,  255:  81 
• 8b Zhang Y. Santos AM. Herdtweck E. Mink J. Kuhn FE. New J. Chem.  2005,  29:  366 
• 8c Wei C. Li Z. Li CJ. Org. Lett.  2003,  5:  4473 
• 9a Kantam ML. Prakash BV. Reddy C. Reddy V. Sreedhar B. Synlett  2005,  2329 
• 9b Wei C. Li CJ. J. Am. Chem. Soc.  2003,  125:  9584 
• 10 Lo VKY. Liu Y. Wong MK. Che CM. Org. Lett.  2006,  8:  1529 
• 11a Shi L. Tu YQ. Wang M. Zhang FM. Fan CA. Org. Lett.  2004,  6:  1001 
• 11b Syeda HZS. Halder R. Karla SS. Das J. Iqbal J. Tetrahedron Lett.  2002,  43:  6485 
• 11c Kabalka GW. Wang L. Pagni RM. Synlett  2001,  676 
• 11d Ju Y. Li CJ. Varma RS. QSAR Comb. Sci.  2004,  23 
• 11e Orlandi S. Colombo F. Benaglia M. Synthesis  2005,  1689 
• 11f Gommermann N. Knochel P. Chem. Eur. J.  2006,  12:  4380 
• 11g Bieber LW. da Silva MF. Tetrahedron Lett.  2004,  45:  8281 
• 12 Fischer C. Carreira EM. Org. Lett.  2001,  3:  4319 
• 13 Hua LP. Lei W. Chin. J. Chem.  2005,  23:  1076 
• 14 Li CJ. Wei C. Chem. Commun.  2002,  268 
• 15 Zhang L. Wei C. Varma RS. Li CJ. Tetrahedron Lett.  2004,  45:  2443 
• 16 Choudary BM. Sridhar C. Kantam ML. Sridhar B. Tetrahedron Lett.  2004,  45:  7319 
• 17 Leadbeater NE. Torenius HM. Tye H. Mol. Diversity  2003,  7:  135 
• 18 Sreedhar B. Reddy PS. Prakash BV. Ravindra A. Tetrahedron Lett.  2005,  46:  7019 
• 19 Park SB. Alper H. Chem. Commun.  2005,  1315 
• 20a Kidwai M. Venkataramanan R. Dave B. Green Chem.  2001,  3:  278 
• 20b Kidwai M. Bansal V. Mothsra P. J. Mol. Catal. A: Chem.  2007,  268:  76 
• 20c Kidwai M. Mothsra P. Bansal V. Somvanshi RK. Ethayathulla AS. Dey S. Singh TP. J. Mol. Catal. A: Chem.  2006,  265:  177 
• 20d Kidwai M. Mothsra P. Tetrahedron Lett.  2006,  47:  5029 
• 20e Kidwai M. Mothsra P. Bansal V. Goyal R. Monatsh. Chem.  2006,  137:  1189 
• 21a Kidwai M. Bansal V. Saxena A. Shankar R. Mozumdar S. Tetrahedron Lett.  2006,  47:  4161 
• 21b Saxena A. Kumar A. Mozumdar S. Appl. Catal. A: Gen.  2007,  317:  210 
• 23 Mallick M. Witcomp M. Scurrell M. Mater. Chem. Phys.  2006,  97:  283 

22

Preparation of Cu Nanoparticles: A chemical method involving the reduction of Cu²⁺ ions to Cu(0) in a reverse micellar system was employed to prepare the Cu nanoparticles. Poly(oxyethylene)(tetramethyl)phenyl ether, commercially known as Triton X-100 (TX-100) was used as surfactant in the process. To a reverse micellar solution of CuSO_{4 (aq)}, another reverse micellar solution of N₂H_{2 (aq)} was added with constant stirring. In the presence of N₂ atmosphere the resulting solution was further stirred for 3 h to allow the complete Oswald ripening (particle growth). The Cu nanoparticles were extracted using anhyd EtOH followed by centrifugation. By varying the H₂O content parameter W_o (defined as the molar ratio of water to surfactant concentration, W_o = [H₂O]/[surfactant]) the size of nanoparticles could be controlled. The nanoparticles prepared were spherical in shape, with an average size of 18 ± 2 nm as confirmed by TEM photograph and QELS data. The metallic nature of the Cu(0) nanoparticles was confirmed by a characteristic UV absorption of the particles dispersed in cyclohexane (580 nm).
Typical Procedure A 50-mL round-bottomed flask was charged with aromatic or heterocylic aldehydes 1a-h (1 mmol), secondary amine (1 mmol) and phenylacetylene (1.5 mmol) in MeCN (5 mL) and the contents of the flask were stirred under a nitrogen atmosphere followed by the addition of Cu nanoparticles (15 mol%, 18 ± 2 nm). The resulting solution was refluxed at 100-110 °C for the appropriate time mentioned in Table [4] . The extent of reaction was monitored by TLC. After completion of the reaction, the reaction mixture was centrifuged at 2000-3000 rpm, at 10 °C for 5 min. The organic layer was decanted and the remaining Cu nanoparticles were reused for further reactions. The organic layer was dried over anhyd Na₂SO₄ and the solvent was removed in vacuo. The crude product was subjected to purification by silica gel column chromatography using a mixture of 15% EtOAc, 5% MeOH and 80% PE as eluent to yield the propargylamine 3a-h. The structures of all the products were unambiguously established on the basis of their spectral analysis (IR, ¹H NMR, ¹³C NMR and GC-MS data). All the products are known compounds.