Copper(I)-Catalysed Deacetylenative Cross-Coupling Reaction of Terminal Alkynes with Propargylic Amines via C(sp)–C(sp³) Bond Cleavage

Abstract

The catalytic deacetylenative coupling reaction of terminal alkynes with various N-substituted propargylic amines proceeded in the presence of CuCl (10 mol%) and Na₂HPO₄ (4 equiv) in THF at 130 °C to give the corresponding substituted propargylic amines in good to high yields.

Key words

alkynes - amines - copper - cleavage - catalysis

• References and Notes

• 1a Dyker G. Angew. Chem. Int. Ed. 1999; 38: 1698
• 1b Ritleng V, Sirlin C, Pfeffer M. Chem. Rev. 2002; 102: 1731
• 1c Kakiuchi F, Kochi T. Synthesis 2008; 3013
• 1d Kulkarni AA, Daugulis O. Synthesis 2009; 4087
• 1e McGlacken GP, Bateman LM. Chem. Soc. Rev. 2009; 38: 2447
• 1f Chen X, Engle KM, Wang D.-H, Yu J.-Q. Angew. Chem. Int. Ed. 2009; 48: 5094
• 1g Ackermann L, Vicente R, Kapdi AR. Angew. Chem. Int. Ed. 2009; 48: 9792
• 2a Li CJ. Acc. Chem. Res. 2009; 42: 335
• 2b Scheuermann CJ. Chem. Asian. J. 2010; 5: 436
• 3 Murahashi S, Hirano T, Yano T. J. Am. Chem. Soc. 1978; 100: 348
• 4a Murahashi SI, Komiya N, Terai H, Nakae T. J. Am. Chem. Soc. 2003; 125: 15312
• 4b Murahashi SI, Komiya N, Terai H. Angew. Chem. Int. Ed. 2005; 44: 6931
• 5 Li Z, Li CJ. J. Am. Chem. Soc. 2004; 126: 11810
• 6 Li Z, Bohle DS, Li CJ. Proc. Natl. Acad. Sci. U.S.A. 2006; 103: 8928
• 7a Zhang Y, Li CJ. Angew. Chem. Int. Ed. 2006; 45: 1949
• 7b Zhang Y, Li CJ. J. Am. Chem. Soc. 2006; 128: 4242
• 8 Li Z, Cao L, Li CJ. Angew. Chem. Int. Ed. 2007; 46: 6505
• 9 Zhang Y, Feng J, Li CJ. J. Am. Chem. Soc. 2008; 130: 2900
• 10 Sugiishi T, Kimura A, Nakamura H. J. Am. Chem. Soc. 2010; 132: 5332
• 11 Sugiishi T, Nakamura H. J. Am. Chem. Soc. 2012; 134: 2504
• 12 Kim Y, Nakamura H. Chem. Eur. J. 2011; 17: 12561
• 13 Typical Procedure for the Preparation of N,N-Dihexyl-5-methylhex-1-yn-3-amine (1c, Table 2, Entry 2) To a solution of CuBr(I) (0.036 g, 0.25 mmol) in toluene (100 mL) were added ethynyltrimethylsilane (0.69 mL, 5 mmol), isobutylaldehyde (0.54 mL, 5 mmol), and N,N-dihexylamine (1.17 mL, 5 mmol) under nitrogen atmosphere, and the mixture was stirred for 2 d at r.t. The mixture was filtered on a Celite bed and concentrated. The residue was dissolved in THF (10 mL) and TBAF (1 M in THF, 1.6 mL) was added at 0 °C. The mixture was stirred at 0 °C for 30min, diluted with H₂O, and extracted with Et₂O. The organic layer was washed with brine, dried over anhyd MgSO₄, and concentrated. Purification by column chromatography on silica gel with hexane as eluent gave the amine 1c (1.15 g, 82% yield) as a colorless liquid. ¹H NMR (400 MHz, CDCl₃): δ = 3.53 (td, J = 7.6, 2.4 Hz, 1 H), 2.51–2.44 (m, 2 H), 2.33–2.26 (m, 2 H), 2.15 (d, J = 2.4 Hz, 1 H), 1.88 (nonet, J = 6.8 Hz, 1 H), 1.48–1.23 (m, 18 H), 0.92–0.86 (m, 12 H). ¹³C NMR (100 MHz, CDCl₃): δ = 83.5, 71.7, 51.7, 51.5, 43.3, 32.0, 28.8, 27.4, 25.0, 22.9, 22.8, 22.6, 14.3. IR (neat): 3309, 2929, 2858, 1467, 1379, 1166, 1093 cm^–1. ESI-HRMS: m/z calcd for C₁₉H₃₈N [M + H]⁺: 280.3004; found: 280.3002
• 14 N,N-Dihexyl-5-methyl-1-phenylhex-1-yn-3-amine (2c, Table 2, Entry 2) Yield 101 mg (94%); colorless liquid. ¹H NMR (400 MHz, CDCl₃): δ = 7.41–7.37 (m, 2 H), 7.30–7.23 (m, 3 H), 3.74 (t, J = 7.6 Hz, 1 H), 2.59–2.52 (m, 2 H), 2.44–2.37 (m, 2 H), 1.95 (sept, J = 6.8 Hz, 1 H), 1.57 (t, J = 7.2 Hz, 2 H), 1.52–1.22 (m, 16 H), 0.96 (t, J = 6.4 Hz, 6 H), 0.90–0.87 (m, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 131.8, 128.3, 127.7, 123.9, 89.5, 84.4, 52.2, 51.8, 43.3, 32.0, 28.7, 27.4, 25.1, 22.8, 22.7, 14.2. IR (neat): 2955, 2928, 2857, 1597, 1488, 1466, 1378, 1366, 1312, 1166, 1092, 1026, 911, 754, 690, 584, 527 cm^–1. ESI-HRMS: m/z calcd for C₂₅H₄₂N [M + H]⁺: 356.3317; found: 356.3312