Improved Synthetic Method for 5-[(Phenylthio)methyl]oxazoline Derivatives: Electrophilic Cyclization of Allylic Amide Using a Brønsted Acid and Tetrabutylammonium Chloride under Mild Conditions

Abstract

The synthesis of oxazolines using electrophilic cyclization of allylic amide is a simple and powerful method. However, cyclization involving arylsulfenylation requires harsh reaction conditions. We found that the reaction proceeds under mild heating conditions with the combination of a Brønsted acid and tetrabutylammonium chloride. This method enabled the synthesis of 5-[(arylsulfenyl)methyl]oxazoline derivatives under mild conditions and demonstrated high tolerance for various functional groups.

Key words

oxazoline - oxazine - thioether - sulfide - electrophilic cyclization

• References and Notes


For selected reviews, see:
• 1a Tilvi S, Singh KS. Curr. Org. Chem. 2016; 20: 898
• 1b Jin Z. Nat. Prod. Rep. 2006; 23: 464
• 1c Yeh VS. C. Tetrahedron 2004; 60: 11995
• 1d Lewis JR. Nat. Prod. Rep. 2002; 19: 223
• 1e Roy RS, Gehring AM, Milne JC, Belshaw PJ, Walsh CT. Nat. Prod. Rep. 1999; 16: 249
• 1f Wipf P. Chem. Rev. 1995; 95: 2115

For selected reviews, see:
• 2a Kakkar S, Narasimhan B. BMC Chem. 2019; 13: 16
• 2b Bansal S, Halve AK. Int. J. Pharm. Sci. Res. 2014; 5: 4601

For selected reviews, see:
• 3a Hargaden GC, Guiry PJ. Chem. Rev. 2009; 109: 2505
• 3b McManus HA, Guiry PJ. Chem. Rev. 2004; 104: 4151
• 3c Kaldor SW, Kalish VJ, Davies JF, Shetty BV, Fritz JE, Appelt K, Burgess JA, Campanale KM, Chirgadze NY, Clawson DK, Dressman BA, Hatch SD, Khalil DA, Kosa MB, Lubbehusen PP, Muesing MA, Patick AK, Reich SH, Su KS, Tatlock JH. J. Med. Chem. 1997; 40: 3979

For selected reviews, see:
• 4a Sambiagio C, Schönbauer D, Blieck R, Dao-Huy T, Pototschnig G, Schaaf P, Wiesinger T, Zia MF, Wencel-Delord J, Besset T, Maesa BU. W, Schnürch M. Chem. Soc. Rev. 2018; 47: 6603
• 4b Sammakia T, Latham HA. J. Org. Chem. 1996; 61: 1629

For selected reviews, see:
• 5a Gant TG, Meyers AI. Tetrahedron 1994; 50: 2297
• 5b Frump JA. Chem. Rev. 1971; 71: 483
• 5c Wiley RH, Bennett LL. Chem. Rev. 1949; 44: 447

For selected papers of electrophilic cyclization of allylic amide except C–S bond formation, see:
• 6a Minakata S, Morino Y, Oderaotoshi Y, Komatsu M. Org. Lett. 2006; 8: 3335
• 6b Bongini A, Cardillo G, Orena M, Sandri S, Tomasin C. J. Chem. Soc., Perkin Trans. 1 1986; 1345
• 6c Goodman L, Winstein S. J. Am. Chem. Soc. 1957; 79: 4788
• 6d Goodman L, Winstein S, Boschan R. J. Am. Chem. Soc. 1958; 80: 4312
• 6e Jaganathan A, Garzan A, Whitehead DC, Staples RJ, Borhan B. Angew. Chem. Int. Ed. 2011; 50: 2593
• 6f Yin Q, You S.-L. Org. Lett. 2013; 15: 4266
• 6g Toste FD. Science 2011; 334: 1681
• 6h Scheidt F, Thiehoff C, Yilmaz G, Meyer S, Daniliuc CG, Kehr G, Gilmour R. Beilstein J. Org. Chem. 2018; 14: 1021
• 6i Chretien F, Chapleur Y. J. Org. Chem. 1988; 53: 3615
• 6j Berkowitz DB, McFadden JM, Chisowa E, Semerad CL. J. Am. Chem. Soc. 2000; 122: 11031
• 6k Godfrey JD, Gordon EM, Langen DJ. V. Tetrahedron Lett. 1987; 28: 1603
• 6l Roush WR, Straub JA, Brown RJ. J. Org. Chem. 1987; 52: 5127
• 6m Kawamura S, Sekine D, Sodeoka M. J. Fluorine Chem. 2017; 203: 115
• 6n Alhalib A, Kamouka S, Moran WJ. Org. Lett. 2015; 17: 1453
• 6o Moon NG, Harned AM. Tetrahedron Lett. 2013; 54: 2960
• 7a Abd El SamiiZ. K. M, Al AshmawyM. I, Mellor JM. Tetrahedron Lett. 1987; 28: 1949
• 7b Abd El SamiZ. K. M, Al AshmawyM. I, Mellor JM. J. Chem. Soc., Perkin Trans. 1 1988; 2509
• 7c Tiecco M, Tingoli M, Testaferri L, Balducci R. J. Org. Chem. 1992; 57: 4025
• 7d Yu J, Tian H, Gao C, Yang H, Jiang Y, Fu H. Synlett 2015; 26: 676
• 7e Senadi GC, Guo B.-C, Hub W.-P, Wang J.-J. Chem. Commun. 2016; 52: 11410
• 7f Miyamoto Y, Mitani N, Yanagi R, Kashimura S, Suga S, Yoshida J, Matsumoto K. Heterocycles 2018; 96: 1373
• 8 Hostier T, Ferey V, Ricci G, Pardo DG, Cossy J. Chem. Commun. 2015; 51: 13898
• 9 When TBAB was used, small amount of the 5-(bromomethyl)oxazoline derivative was produced as a byproduct (Scheme 6).
• 10a Behforouz M, Kerwood JE. J. Org. Chem. 1969; 34: 51
• 10b Levchenko ES, Markovskii LN, Shermolovich YG. Zh. Org. Khim. 1982; 18: 1191
• 11a Kozel VN, Rozhenko AB, Pashinnik VE, Shermolovich YG. Phosphorus, Sulfur Silicon Relat. Elem. 2009; 184: 1149
• 11b Ferry A, Billard T, Langlois BR, Bacqué E. Angew. Chem. Int. Ed. 2009; 48: 8551
• 11c Fanghänel E, Kühnemund K.-H, Richter AM. Synthesis 1983; 50
• 12 Zelčans G, Hutton TK, Rios R, Shibata N. Benzenesulfenyl Chloride . In e-EROS Encyclopedia of Reagents for Organic Synthesis . John Wiley & Sons; New York: 2013. doi DOI: 10.1002/047084289X.rb019.pub3
• 13a Epstein WW, Sweat FW. Chem. Rev. 1967; 67: 247
• 13b Fernández I, Khiar N. Chem. Rev. 2003; 103: 3651
• 13c Colomer I, Velado M, de la Pradilla RF, Viso A. Chem. Rev. 2017; 117: 14201
• 13d Han J, Soloshonok VA, Klika KD, Drabowicz J, Wzorek A. Chem. Soc. Rev. 2018; 47: 1307
• 13e Kupwade RV. J. Chem. Rev. 2019; 1: 99
• 14 Experimental Procedure for Substrate Scopes (Scheme 2)A 15 mL test tube equipped with a three-way cock was charged with a magnetic stirrer, N-(2-phenylprop-2-en-1-yl)benzamide (1a, 47.5 mg, 0.20 mmol), N-(phenylthio)pyrrolidine-2,5-dione (2, 49.7 mg, 0.24 mmol, 1.2 equiv), and tetrabutylammonium chloride (11.1 mg, 0.04 mmol, 20 mol%). The test tube was evacuated and refilled with dry argon gas three times. Dry DMF (2.0 mL) was added to give a clear solution. (+)-10-Camphorsulfonic acid (9.2 mg, 0.40 mmol, 20 mol%) was added under a slow stream of argon gas. The reaction mixture was heated to 40 °C for 24 h. After being cooled to room temperature, the reaction mixture was quenched by adding of saturated aqueous Na₂S₂O₃ (1.0 mL) and saturated aqueous NaHCO₃ (1.0 mL). The separated aqueous layer was extracted with EtOAc three times, and the combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The residue was purified by flash column chromatography (hexane/EtOAc, 7:3) as eluent to give to 3a (66.4 mg, 0.192 mmol, 96%) as a colorless oil.¹H NMR (500 MHz, CDCl₃): δ = 7.85 (d, J = 8.0 Hz, 2 H), 7.48 (t, J = 7.4 Hz, 1 H), 7.39 (t, J = 7.7 Hz, 2 H), 7.33 (s, 4 H), 7.31–7.27 (m, 2 H), 7.20–7.11 (m, 3 H), 4.45 (d, J = 14.6 Hz, 1 H), 4.17 (d, J = 14.6 Hz, 1 H), 3.57 (d, J = 14.0 Hz, 1 H), 3.49 (d, J = 14.0 Hz, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 162.8, 141.8, 135.9, 133.7, 131.4, 130.4, 128.8, 128.7, 128.3, 128.2, 127.3, 126.5, 126.3, 88.2, 66.5, 45.9.
• 15 Experimental Procedure for the Synthesis of Compound 5To a solution of 5-(4-chlorophenyl)-2-phenyl-5-[(phenylthio)-methyl]-4,5-dihydrooxazole (3n, 51.3 mg, 0.135 mmol) in THF (1.3 mL), dilute hydrochloric acid (1.0 mol/L, 1.3 mL) was added. The reaction mixture stirred at room temperature. After being stirred for 24 h, the reaction mixture was quenched by saturated aqueous NaHCO₃. The organic phase was separated, and the aqueous phase was extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The residue was purified by flash column chromatography (hexane/EtOAc, 6:4) as eluent to give to 5 (44.8 mg, 0.113 mmol, 83%) as a white solid.¹H NMR (500 MHz, CDCl₃): δ = 7.64 (d, J = 7.4 Hz, 2 H), 7.48 (t, J = 7.4 Hz, 1 H), 7.43–7.36 (m, 4 H), 7.29–7.23 (m, 4 H), 7.22–7.14 (m, 3 H), 6.48 (br s, 1 H), 4.02 (dd, J = 13.9, 6.3 Hz, 1 H), 4.03 (br s, 1 H), 3.68 (dd, J = 13.9, 6.3 Hz, 1 H), 3.58 (d, J = 13.5 Hz, 1 H), 3.39 (d, J = 13.5 Hz, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 168.4, 141.1, 135.5, 133.8, 133.5, 131.8, 130.5, 129.0, 128.6, 128.5, 127.0, 126.9, 126.8, 76.4, 49.0, 45.9.
• 16 Experimental Procedure for the Synthesis of Compound 6To a solution of 5-(4-chlorophenyl)-2-phenyl-5-[(phenylthio)methyl]-4,5-dihydrooxazole (3n, 50.4 mg, 0.127 mmol) in MeCN (2.7 mL), sodium hypochloride solution (10.5%, 0.21 mL, 1.1 equiv) was added. The reaction mixture stirred at room temperature. After completion of the reaction, the reaction mixture was quenched by saturated aqueous Na₂S₂O₃. The organic phase was separated, and the aqueous phase was extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The residue was purified by flash column chromatography (hexane/EtOAc 4:6) as eluent to give an inseparable mixture of diastereoisomers 6a and 6b (46.7 mg, 0.113 mmol, 89%) as a colorless oil.¹H NMR (500 MHz, CDCl₃): δ = 8.08 (d, J = 8.0 Hz, 2 H, diastereomer A), δ = 7.92 (d, J = 8.0 Hz, 2 H, diastereomer B), 7.68–7.40 (m, 8 H, A), 7.68–7.40 (m, 12 H, B), 7.38–7.30 (m, 4 H, A), 4.80 (d, J = 14.9 Hz, 1 H, A), 4.55 (d, J = 14.9 Hz, 1 H, B), 4.28 (d, J = 14.9 Hz, 1 H, B), 4.22 (d, J = 14.9 Hz, 1 H, A), 3.60 (d, J = 13.7 Hz, 1 H, B), 3.51 (d, J = 14.3 Hz, 1 H, A), 3.40 (d, J = 14.3 Hz, 1 H, A), 3.33 (d, J = 13.7 Hz, 1 H, B). ¹³C NMR (125 MHz, CDCl₃): δ = 162.8, 162.6, 144.5, 144.3, 141.6, 140.1, 134.4, 134.1, 131.8, 131.8, 131.3, 131.2, 129.4, 129.4, 129.2, 129.1, 128.5, 128.5, 128.4, 128.2, 127.0, 127.0, 126.5, 125.9, 124.1, 123.9, 86.1, 85.9, 70.1, 69.1, 67.6, 66.8.