A Novel Synthesis of Spiro(imidazolidine-2,3′-benzo[b]thiophene) by One-Pot Reaction of Arynes, Aryl Isothiocyanates and N-Heterocyclic Carbenes

Abstract

A novel synthesis of spiro(imidazolidine-2,3′-­benzo[b]thiophene) by one-pot reaction of aryl isothiocyanates, N-heterocyclic carbenes and arynes using (phenyl)[2-(trimethyl­silyl)phenyl]iodonium triflate as precursor is reported.

Key words

one-pot reaction - arynes - N-heterocyclic carbenes - aryl isothiocyanates - spiro heterocyclic compounds

References and Notes

• For reviews see:
• 1a Kessar SV. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Pergamon; Oxford: 1991.  p.483 
• 1b Pellissier H. Santelli M. Tetrahedron  2003,  59:  701 
• 1c Hart H. In Supplement C2: The Chemistry of Triple-Bonded Functional Groups   Patai S. Wiley; Chichester, U.K.: 1994.  Chap. 18. p.1017-1134  
• 2 Himeshima Y. Sonoda T. Kobayashi H. Chem. Lett.  1983,  1211 
• 3a Liu Z. Larock RC. Org. Lett.  2003,  5:  4673 
• 3b Liu Z. Larock RC. Org. Lett.  2004,  6:  99 
• 3c Yoshida H. Minabe T. Ohshita J. Chem. Commun.  2005,  3454 
• 3d Tambar UK. Stoltz BM. J. Am. Chem. Soc.  2005,  127:  5340 
• 3e Yoshida H. Watanabe M. Ohshita J. Tetrahedron Lett.  2005,  46:  6729 
• 3f Yoshida H. Watanabe M. Ohshita J. Chem. Commun.  2005,  3292 
• 3g Yoshida H. Watanabe M. Ohshita J. Chem. Lett.  2005,  34:  1538 
• 3h Yoshida H. Shirakawa E. Honda Y. Angew. Chem. Int. Ed.  2002,  41:  3247 
• 3i Liu Z. Larock RC. J. Am. Chem. Soc.  2005,  127:  13112 
• 3j Yoshida H. Minabe T. Ohshita J. Chem. Commun.  2004,  1980 
• 4 Yoshida H. Fukushima H. Ohshita J. Kunai A. Angew. Chem. Int. Ed.  2004,  43:  3935 
• 5a Yoshida H. Ikadai J. Shudo M. J. Am. Chem. Soc.  2003,  125:  6638 
• 5b Yoshida H. Tanino K. Ohshita J. Angew. Chem. Int. Ed.  2004,  43:  5052 
• 5c Yoshida H. Tanino K. Ohshita J. Chem. Commun.  2005,  5678 
• 5d Yoshida H. Honda Y. Shirakawa E. Chem. Commun.  2001,  1880 
• 6 Gothelf KV. Jørgensen KA. Chem. Rev.  1998,  98:  863 
• 7a Winberg HE. Coffman DD. J. Am. Chem. Soc.  1965,  87:  2776 
• 7b Regitz M. Hocker J. Schössler W. Weber B. Liedhegener A. Justus Liebigs Ann. Chem.  1971,  748:  1 
• 7c Liu MF. Wang B. Cheng Y. Chem. Commun.  2006,  1215 
• For the reaction of 1,3-dipolar compounds containing a central heteroatom with arynes, see:
• 8a Taylor EC. Sobieray DM. Tetrahedron  1991,  47:  9599 
• 8b Matsumoto T. Sohma T. Hatazaki S. Suzuki K. Synlett  1993,  843 
• 8c Hussain H. Kianmehr E. Durst T. Tetrahedron Lett.  2001,  42:  2245 
• 8d Kitamura T. Fukatsu N. Fujiwara Y. J. Org. Chem.  1998,  63:  8579 
• 8e Kurita J. Kakusawa N. Yasuike S. Tsuchiya T. Heterocycles  1990,  31:  1937 
• 9a Kitamura T. Yamane M. J. Chem. Soc., Chem. Commun.  1995,  983 
• 9b Kitamura T. Todaka M. Fujiwar Y. Org. Synth.  2002,  78:  104 
• 9c Kitamura T. Yamane M. Inoue K. J. Am. Chem. Soc.  1999,  121:  11674 
• 9d Kitamura T. Aoki Y. Isshiki S. Wasai K. Fujiwara Y. Tetrahedron Lett.  2006,  47:  1709 
• 12 Frisch MJ. Gaussian 03, Revision B.01, Gaussian Inc., Pittsburgh Pa: 2003. 
• 13a Friedman L. Logullo FM. J. Org. Chem.  1969,  34:  3089 
• 13b Logullo FM. Seitz AH. Friedman L. Org. Synth.  1968,  48:  12 
• 13c Okuma K. Yamamoto T. Shirokawa T. Kitamura T. Fujiwara Y. Tetrahedron Lett.  1996,  37:  8883 

10

Procedure for the Preparation of Compound 4aa: At ambient temperature, 1,3-bis(2,4,6-trimethylphenyl)imid-azolinium chloride (2a; 1 mmol) was mixed with phenyl isothiocyanate 3a (1 mmol) in anhyd THF (20 mL), and then NaH (1.2 mmol, 65% in mineral oil) was added. After 12 h H₂O (5 mL) was added to the mixture. The mixture was then diluted with CH₂Cl₂ (15 mL) and washed. The organic layer was dried over MgSO₄, and concentrated to give inner salt 4aa as yellow crystal. Compound 4aa was further purified by recrystallization from CH₂Cl₂ and PE, through which the pure inner salt 4aa was obtained. Data of 4aa: yellow solid; mp 252-253 °C. IR (KBr): 1548, 1511, 1480, 1280 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.25 (s, 4 H), 6.82-6.92 (m, 2 H), 6.67-6.71 (t, J = 8 Hz, 1 H), 5.96-5.98 (d, J = 8 Hz, 1 H), 4.16 (s, 4 H), 2.56 (s, 12 H), 2.27 (s, 6 H), 1.33 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 165.3, 150.5, 139.6, 136.8, 130.9, 129.7, 129.5, 128.4, 125.8, 122.1, 119.7, 49.1, 21.0, 18.6, 16.9. MS (EI): m/z (%) = 455 (72.41) [M⁺], 441 (100). Anal. Calcd for C₂₉H₃₃N₃S: C, 76.44; H, 7.30; N, 9.22. Found: C, 76.38; H, 7.37; N, 9.19.

11

Procedure for the Preparation of Compound 7aa: The mixture of 5aa (0.5 mmol) and silica gel (100 mg) in EtOH-H₂O (10 mL, 1:1) was stirred at ambient temperature. When the reaction was complete (monitored by TLC), the mixture was diluted with EtOAc (15 mL) and filtered. The organic layer was dried over MgSO₄. Removal of the solvent in vacuum, and purification of the residue by silica gel chromatography with n-hexane-EtOAc (10:1) as eluent gave the product 7aa. Data of 7aa: yellow solid; mp 134-136 °C. IR (KBr): 1706, 1591, 1309 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.96-7.98 (d, J = 8 Hz, 1 H), 7.60-7.64 (t, J = 8 Hz, 1 H), 7.33-7.39 (m, 2 H), 7.23-7.29 (m, 2 H), 7.17-7.20 (m, 1 H), 6.96-6.98 (d, J = 8 Hz, 1 H), 2.23 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 185.0, 157.1, 149.2, 144.5, 143.30, 136.90, 130.8, 130.2, 128.1, 127.7, 126.8, 126.6, 126.5, 124.5, 117.3, 17.7. MS (EI): m/z (%) = 253 (9.80) [M⁺], 149 (100). Anal. Calcd for C₁₅H₁₁NOS: C, 71.12; H, 4.38; N, 5.53. Found: C, 71.04; H, 4.43; N, 5.55. Crystal data for 7aa: C₁₅H₁₁NOS, M = 253.31, T = 293 K, monoclinic, space group: P-1/c, a = 4.1713 (12), b = 18.949 (5), c = 15.561 (4) Å, α = 90 (4)°, β = 85.469 (4)°, γ = 89.231 (4)°, V = 1223.5 (6) ų, Z = 4, ρ_calcd = 1.375 g cm^-3, absorption coefficient: 0.250 mm^-1, reflections collected/unique: 6951/2651 [R(int) = 0.1071], final R indices [I >2σ(I)] R1 = 0.0484, R2 = 0.0989. For the crystallographic data in CIF, see CCDC: 641755.

14

Procedure for the Preparation of Compound 5: At ambient temperature, imidazolinium salt 2 (0.5 mmol) was mixed with aryl isothiocyanate 3 (0.5 mmol) in anhyd THF (10 mL), and then NaH (0.6 mmol, 65% in mineral oil) was added. After 12 h when the reaction was complete (monitored by TLC), phenyl[2-(trimethylsilyl)phenyl]io-donium triflate (1b; 1 mmol) and 18-crown-6 (1.5 mmol) in THF (10 mL) were added to the mixture and then KF (1.5 mmol) was added. After completion of the reaction, the mixture was diluted with EtOAc (10 mL) and washed with H₂O and brine. The organic layer was dried over MgSO₄. Removal of the solvent in vacuum, and purification of the residue by silica gel chromatography with n-hexane-EtOAc (10:1) as eluent gave the product 5. Selected data of 5aa: low melting point solid. IR (neat): 1706, 1623, 1483, 1448 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.96-7.98 (d, J = 8 Hz, 1 H), 7.59-7.63 (t, J = 8 Hz, 1 H), 7.34-7.38 (m, 2 H), 7.25-7.27 (m, 2 H), 7.18-7.20 (m, 1 H), 6.96-6.98 (d, J = 8 Hz, 1 H), 6.82 (s, 4 H), 3.15 (s, 4 H), 2.28 (s, 12 H), 2.27 (s, 3 H), 2.23 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 185.1, 157.1, 149.2, 144.5, 143.3, 136.9, 131.5, 130.8, 130.2, 129.7, 129.5, 128.1, 127.7, 126.8, 126.6, 126.5, 125.0, 117.3, 49.1, 20.5, 18.4, 17.8. MS (EI): m/z (%) = 531 (3.24) [M⁺], 148 (100). Anal. Calcd for C₃₅H₃₇N₃S: C, 79.05; H, 7.01; N, 7.90. Found: C, 78.96; H, 7.09; N, 7.93.