Copper-Catalyzed One-Pot Synthesis of Functionalized 1,4-Dihydroazete Derivatives from Sulfonyl Azides, Terminal Alkynes, and Tetramethylguanidine

Abstract

Ketenimine intermediates generated by the addition of copper acetylides to sulfonyl azides are trapped by tetramethyl­guanidine to afford 1,4-dihydro-N,N-dimethyl-3-aryl(alkyl)-4-­aryl(alkyl)sulfoniminoazet-2-amine derivatives in moderate to good yields.

Key words

1,4-dihydroazete - copper iodide - tetramethyl­guanidine - sulfonyl azide - terminal alkyne - ketenimine

• References and Notes

• 1 Alcaide B, Almendros P In Progress in Heterocyclic Chemistry . Vol. 17. Gribble GW, Joule JA. Elsevier; Oxford: 2005: 64-83
• 2 Parrick J, Mehta LK In Comprehensive Heterocyclic Chemistry II . Padwa A. Elsevier; Oxford: 1996: 659-720
• 3 Pinder AR. Nat. Prod. Rep. 1992; 9: 491
• 4 Furin GG, Lopyrev VA, Zhuzhgov EI, Protsuk NI. Russ. J. Org. Chem. 2000; 36: 99
• 5 Zanatta N, Barichello R, Bonacorso HG, Martins MA. P. Synthesis 1999; 765
• 6 Yoakim C, Ogilvie WW, Cameron DR, Chabot C, Guse I, Hache B, Naud J, O’Meara JA, Plante R, Deziel R. J. Med. Chem. 1998; 41: 2882
• 7 Kvaerno L, Werder M, Hauser H, Carreira EM. J. Med. Chem. 2005; 48: 6035
• 8 Bisacchi GS, Slusarchyk WA, Bolton SA, Hartl KS, Jacobs G, Mathur A, Meng W, Ogletree ML, Pi Z, Sutton JC, Treuner U, Zahler R, Zhao G, Seiler SM. Bioorg. Med. Chem. Lett. 2004; 14: 2227
• 9 Ma Y, Qian CT. Tetrahedron Lett. 2000; 41: 945
• 10 Burtosolo AC. B, Correa CR. D. Tetrahedron Lett. 2006; 47: 6377
• 11 George L, Bernhardt PV, Netsch KP, Wentrup C. Org. Biomol. Chem. 2004; 2: 3518
• 12 Finnerty JJ, Wentrup C. J. Org. Chem. 2004; 69: 1909
• 13 Wang J, Wang J, Zhu Y, Lu P, Wang Y. Chem. Commun. 2011; 47: 3275
• 14 Whiting M, Fokin VV. Angew. Chem. Int. Ed. 2006; 45: 3157
• 15 Xu X, Cheng D, Li J, Guo H, Yan J. Org. Lett. 2007; 9: 1585
• 16 Cui SL, Lin XF, Wang YG. Org. Lett. 2006; 8: 4517
• 17 Cui SL, Wang J, Wang YG. Tetrahedron 2008; 64: 487
• 18 Yao W, Pan L, Zhang Y, Wang G, Wang X, Ma C. Angew. Chem. Int. Ed. 2010; 49: 9210
• 19 Yavari I, Nematpour M, Yavari S, Sadeghizadeh F. Tetrahedron Lett. 2012; 53: 1889
• 20 Yavari I, Nematpour M, Ghazanfarpour-Darjani M. Tetrahedron Lett. 2012; 53: 942
• 21 General Procedure for the Synthesis of Compounds 4
  To a mixture of sulfonyl azide 2, (1.2 mmol), alkyne 1 (1 mmol), and CuI (0.1 mmol), Et₃N (1 mmol) in THF (2 mL) was slowly added tetramethylguanidine (1 mmol). The mixture was stirred at r.t. After completion of the reaction [about 12 h; TLC (EtOAc–hexane = 1:5) monitoring], the mixture was diluted with CH₂Cl₂ (2 mL) and aq NH₄Cl solution (3 mL), stirred for 30 min, and the layers were separated. The aqueous layer was extracted with CH₂Cl₂ (3 × 3 mL), and the combined organic fractions were dried (Na₂SO₄) and concentrated under reduced pressure. The residue was purified by flash column chromatography [silica gel (230–400 mesh; Merck), hexane–EtOAc = 5:1] to give the product. 1,4-Dihydro-N,N-dimethyl-3-phenyl-4-tosyliminoazet-2-amine (4a) Yellow oil; yield 0.27 g (80%). IR (KBr): ν_max = 3438, 2923, 1511, 1396, 1270, 1139, 1083 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 2.38 (3 H, s, Me), 2.80 (6 H, s, NMe₂), 3.94 (1 H, s, NH), 7.18 (2 H, t, ³ J = 7.5 Hz, Ar), 7.24 (1 H, t, ³ J = 7.5 Hz, Ar), 7.25–7.28 (4 H, m, Ph), 7.76 (2 H, d, ³ J = 7.9 Hz, Ar). ¹³C NMR (125.7 MHz, CDCl₃): δ = 29.7 (Me), 40.5 (NMe₂), 88.3 (C), 125.7 (CH), 126.4 (2 CH), 128.1 (2 CH), 128.7 (2 CH), 129.6 (2 CH), 137.5 (C), 141.1 (C), 142.3 (C), 166.1 (C), 169.2 (C). MS (EI): m/z (%) = 341 (2) [M⁺], 297 (8), 271 (12), 155 (100), 145 (22), 91 (70), 77 (54). Anal. Calcd (%) for C₁₈H₁₉N₃O₂S (341.00): C, 63.32; H, 5.61; N, 12.31. Found: C, 63.79; H, 5.54; N, 12.38. 1,4-Dihydro-N,N-dimethyl-3-phenyl-4-benzenesulfoniminoazet-2-amine (4b) Yellow oil; yield 0.27 g (82%). IR (KBr): ν_max = 3437, 2929, 1520, 1400, 1273, 1142, 1087 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 2.85 (6 H, s, NMe₂), 3.98 (1 H, s, NH), 7.15 (2 H, t, ³ J = 7.5 Hz, Ar), 7.20 (1 H, t, ³ J = 7.5 Hz, Ar), 7.23 (2 H, d, ³ J = 7.5 Hz, Ar), 7.25–7.29 (3 H, m, Ph), 7.78 (2 H, d, ³ J = 7.9 Hz, Ar). ¹³C NMR (125.7 MHz, CDCl₃): δ = 40.6 (NMe₂), 88.5 (C), 125.6 (CH), 126.5 (2 CH), 128.3 (2 CH), 128.8 (2 CH), 129.7 (2 CH), 137.5 (CH), 140.2 (C), 142.5 (C), 165.7 (C), 170.8 (C). MS (EI): m/z (%) = 327 (3) [M⁺], 283 (12), 257 (17), 145 (31), 141 (100), 77 (54). Anal. Calcd (%) for C₁₇H₁₇N₃O₂S (327.05): C, 62.36; H, 5.23; N, 12.83. Found: C, 62.06; H, 5.18; N, 12.75. 1,4-Dihydro-N,N-dimethyl-3-phenyl-4-methanesulfoniminoazet-2-amine (4c) Yellow oil; yield 0.20 g (74%). IR (KBr): ν_max = 3435, 2925, 1531, 1401, 1271, 1120 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 2.81 (3 H, s, Me), 2.93 (6 H, s, NMe₂), 4.01 (1 H, s, NH), 7.26 (2 H, t, ³ J = 7.4 Hz, Ar), 7.30 (1 H, t, ³ J = 7.4 Hz, Ar), 7.42 (2 H, d, ³ J = 7.4 Hz, Ar). ¹³C NMR (125.7 MHz, CDCl₃): δ = 29.2 (Me), 40.4 (NMe₂), 87.2 (C), 124.4 (CH), 125.7 (2 CH), 126.4 (2 CH), 140.9 (C), 162.3 (C), 172.5 (C). MS (EI): m/z (%) = 265 (2) [M⁺], 221 (10), 195 (14), 145 (30), 79 (100), 77 (44). Anal. Calcd (%) for C₁₂H₁₅N₃O₂S (265.00): C, 54.32; H, 5.70; N, 15.06. Found: C, 54.66; H, 5.64; N, 15.16. 1,4-Dihydro-N,N-dimethyl-3-propyl-4-tosyliminoazet-2-amine (4d) Yellow oil; yield 0.20 g (67%). IR (KBr): ν_max = 3436, 2924, 1510, 1397, 1271, 1138, 1084 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.87 (3 H, t, ³ J = 6.9 Hz, Me), 1.57–1.62 (2 H, m, CH₂), 2.38 (3 H, s, Me), 2.52 (2 H, t, ³ J = 7.0 Hz, CH₂), 2.91 (6 H, s, NMe₂), 3.94 (1 H, s, NH), 7.24 (2 H, d, ³ J = 8.0 Hz, Ar), 7.81 (2 H, d, ³ J = 8.0 Hz, Ar). ¹³C NMR (125.7 MHz, CDCl₃): δ = 13.8 (Me), 21.4 (CH₂), 22.7 (CH₂), 29.7 (Me), 40.5 (NMe₂), 86.1 (C), 126.5 (2 CH), 128.4 (2 CH), 139.0 (C), 142.0 (C), 166.6 (C), 172.5 (C). MS (EI): m/z (%) = 307 (2) [M⁺], 263 (14), 197 (14), 155 (100), 111 (28), 91 (55), 77 (44), 43 (22). Anal. Calcd (%) for C₁₅H₂₁N₃O₂S (307.01): C, 58.61; H, 6.89; N, 13.67. Found: C, 58.89; H, 6.94; N, 13.54. 1,4-Dihydro-N,N-dimethyl-3-propyl-4-benzenesulfoniminoazet-2-amine (4e) Yellow oil; yield 0.17 g (60%). IR (KBr): ν_max = 3455, 2925, 1513, 1269, 1142, 1087 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.87 (3 H, t, ³ J = 7.0 Hz, Me), 1.57–1.60 (2 H, m, CH₂), 2.51 (2 H, t, ³ J = 7.0 Hz, CH₂), 2.89 (6 H, s, NMe₂), 3.93 (1 H, s, NH), 7.39 (1 H, t, ³ J = 8.0 Hz, Ar), 7.43 (2 H, t, ³ J = 8.0 Hz, Ar), 7.91 (2 H, d, ³ J = 8.0 Hz, Ar). ¹³C NMR (125.7 MHz, CDCl₃): δ = 13.9 (Me), 21.1 (CH₂), 22.8 (CH₂), 40.5 (NMe₂), 86.1 (C), 124.3 (CH), 125.6 (2 CH), 128.2 (2 CH), 135.7 (C), 162.9 (C), 172.4 (C). MS (EI): m/z (%) = 293 (3) [M⁺], 249 (13), 223 (8), 141 (100), 111 (18), 77 (34), 43 (35). Anal. Calcd (%) for C₁₄H₁₉N₃O₂S (293.00): C, 57.31; H, 6.53; N, 14.32. C, 57.16; H, 6.48; N, 14.21. 1,4-Dihydro-N,N-dimethyl-3-propyl-4-methanesulfoniminoazet-2-amine (4f) Yellow oil; yield 0.13 g (57%). IR (KBr): ν_max = 3436, 1518, 1269, 1142, 1086 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.86 (3 H, t, ³ J = 6.9 Hz, Me), 1.57–1.61 (2 H, m, CH₂), 2.50 (2 H, t, ³ J = 6.9 Hz, CH₂), 2.76 (3 H, s, Me), 2.90 (6 H, s, NMe₂) 3.92 (1 H, s, NH). ¹³C NMR (125.7 MHz, CDCl₃): δ = 13.8 (Me), 19.1 (CH₂), 22.6 (CH₂), 29.6 (Me), 40.5 (NMe₂), 86.7 (C), 162.9 (C), 172.5 (C). MS (EI): m/z (%) = 231 (2) [M⁺], 187 (11), 161 (18), 119 (41), 79 (100), 43 (25). Anal. Calcd (%) for C₉H₁₇N₃O₂S (231.02): C, 46.73; H, 7.41; N, 18.17. Found: C, 47.02; H, 7.34; N, 18.08. 1,4-Dihydro-N,N-dimethyl-3-butyl-4-tosyliminoazet-2-amine (4g) Yellow oil; yield 0.20 g (62%). IR (KBr): ν_max = 3452, 2933, 1520, 1401, 1270, 1118 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.85 (3 H, t, ³ J = 6.9 Hz, Me), 1.23–1.27 (2 H, m, CH₂), 1.59–1.62 (2 H, m, CH₂), 2.40 (3 H, s, Me), 2.50 (2 H, t, ³ J = 7.0 Hz, CH₂), 2.85 (6 H, s, NMe₂), 3.97 (1 H, s, NH), 7.38 (2 H, d, ³ J = 8.0 Hz, Ar), 7.92 (2 H, d, ³ J = 8.0 Hz, Ar). ¹³C NMR (125.7 MHz, CDCl₃): δ = 13.9 (Me), 19.4 (CH₂), 22.4 (CH₂), 27.3 (CH₂), 30.4 (Me), 40.3 (NMe₂), 86.6 (C), 125.6 (2 CH), 128.2 (2 CH), 137.7 (C), 141.2 (C), 166.0 (C), 172.5 (C). MS (EI): m/z (%) = 321 (3) [M⁺], 277 (16), 251 (13), 155 (100), 125 (20), 91 (51), 77 (41), 57 (52). Anal. Calcd (%) for C₁₆H₂₃N₃O₂S (321.00): C, 59.78; H, 7.21; N, 13.07. Found: C, 59.51; H, 7.27; N, 13.18. 1,4-Dihydro-N,N-dimethyl-3-butyl-4-benzenesulfoniminoazet-2-amine (4h) Yellow oil; yield 0.17 g (57%). IR (KBr): ν_max = 3413, 2926, 1517, 1401, 1268, 1141, 1086 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.84 (3 H, t, ³ J = 6.9 Hz, Me), 1.24–1.28 (2 H, m, CH₂), 1.59–1.62 (2 H, m, CH₂), 2.49 (2 H, t, ³ J = 7.0 Hz, CH₂), 2.92 (6 H, s, NMe₂), 3.98 (1 H, s, NH), 7.26 (1 H, t, ³ J = 7.9 Hz, Ar), 7.39 (2 H, t, ³ J = 7.9 Hz, Ar), 7.80 (2 H, d, ³ J = 7.9 Hz, Ar). ¹³C NMR (125.7 MHz, CDCl₃): δ = 14.1 (Me), 20.0 (CH₂), 22.5 (CH₂), 27.3 (CH₂), 40.5 (NMe₂), 86.4 (C), 125.6 (CH), 128.7 (2 CH), 129.6 (2 CH), 138.6 (C), 167.3 (C), 172.5 (C). MS (EI): m/z (%) = 307 (3) [M⁺], 263 (12), 237 (10), 141 (100), 125 (29), 77 (35), 57 (50). Anal. Calcd (%) for C₁₅H₂₁N₃O₂S (307.00): C, 58.61; H, 6.89; N, 13.67. Found: C, 58.86; H, 6.74; N, 13.55. 1,4-Dihydro-N,N-dimethyl-3-butyl-4-methanesulfoniminoazet-2-amine (4i) Yellow oil; yield 0.13 g (53%). IR (KBr): ν_max = 3513, 2934, 1521, 1403, 1270, 1118, 1042 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.85 (3 H, t, ³ J = 6.9 Hz, Me), 1.21–1.29 (2 H, m, CH₂), 1.62–1.66 (2 H, m, CH₂), 2.47 (2 H, t, ³ J = 7.0 Hz, CH₂), 2.82 (3 H, s, Me), 2.90 (6 H, s, NMe₂), 3.96 (1 H, s, NH). ¹³C NMR (125.7 MHz, CDCl₃): δ = 14.0 (Me), 19.8 (CH₂), 22.4 (CH₂), 27.3 (CH₂), 30.7 (Me), 40.4 (NMe₂), 86.2 (C), 166.2 (C), 172.6 (C). MS (EI): m/z (%) = 245 (2) [M⁺], 201 (12), 175 (10), 125 (39), 79 (100), 57 (46). Anal. Calcd (%) for C₁₀H₁₉N₃O₂S (245.00): C, 48.95; H, 7.81; N, 17.13. Found: C, 48.76; H, 7.75; N, 17.04
• 22 Recently, Sharpless and co-workers established anhydrous conditions with CuI in CHCl₃/2,6-lutidine at 0 °C to prevent intermediate 6 from decomposing and provide selective formation of the desired 1-sulfonyltriazoles: Yoo EJ, Ahlquist M, Kim SH, Bae I, Fokin VV, Sharpless KB, Chang S. Angew. Chem. Int. Ed. 2007; 46: 1730
• 23 Cassidy MP, Raushel J, Fokin VV. Angew. Chem. Int. Ed. 2006; 45: 3154
• 24 Lu P, Wang Y. Synlett 2010; 165
• 25 Yoo EJ, Ahlquist M, Bae I, Sharpless KB, Fokin VV, Chang S. J. Org. Chem. 2008; 73: 5520