Synlett 2012; 23(8): 1187-1190
DOI: 10.1055/s-0031-1290917
letter
© Georg Thieme Verlag Stuttgart · New York

Application of PhSCF2CF2SiMe3 as a Tandem Anion and Radical Tetra­fluoroethylene Equivalent: Fluoride-Catalyzed Addition to N-Substituted Cyclic Imides Followed by Radical Cyclization

Yana Chernykh
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague, Czech Republic, Fax: +420(220)183578   eMail: beier@uochb.cas.cz
,
Stanislav Opekar
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague, Czech Republic, Fax: +420(220)183578   eMail: beier@uochb.cas.cz
,
Blanka Klepetářová
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague, Czech Republic, Fax: +420(220)183578   eMail: beier@uochb.cas.cz
,
Petr Beier*
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague, Czech Republic, Fax: +420(220)183578   eMail: beier@uochb.cas.cz
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Publikationsverlauf

Received: 19. Januar 2012

Accepted after revision: 02. März 2012

Publikationsdatum:
17. April 2012 (online)


Abstract

PhSCF2CF2SiMe3 undergoes a fluoride-catalyzed nucleophilic addition to N-substituted cyclic amides affording adducts in moderate to good yields. Reductive cleavage of the phenylsulfanyl group of N-methylated adducts under radical conditions yields the corresponding tetrafluoroethyl-containing adducts in excellent yields. Under the same reduction conditions, N-allylated adducts undergo 6-exo radical cyclization to afford the corresponding tetrafluorinated 1-azabicyclic compounds in moderate to good yields and cis selectivities.

Supporting Information

 
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    • 13a 5-Hydroxy-1-methyl-5-[1,1,2,2-tetrafluoro-2-(phenylthio)ethyl]pyrrolidin-2-one (2a′)A solution of TBAT (108 mg, 10 mol%) in dry THF (2 mL) was added dropwise to a solution of PhSCF2CF2SiMe3 (1.13 g, 4 mmol) and 1a (226 mg, 2 mmol) in dry THF (10 mL). The mixture was stirred at r.t. under argon for 1 h, followed by the addition of aq HF (4 mL, 1 M), and stirred at 35 °C for another hour. The reaction product was extracted in Et2O (3 × 25 mL), the combined organic phase was washed with brine (15 mL), dried (MgSO4), and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography (SiO2, PE–EtOAc) to give the desired product 2a (349 mg, 54% yield); white solid; mp 116–118 °C; Rf = 0.26 (PE–EtOAc, 50:50). 1H NMR (400 MHz, CDCl3): δ = 2.10–2.18 (m, 1 H), 2.39–2.45 (m, 2 H), 2.67–2.74 (m, 1 H), 2.87 (s, 3 H), 5.34 (br s, 1 H), 7.38–7.43 (m, 2 H), 7.46–7.50 (m, 1 H), 7.62–7.65 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 26.3, 28.8, 29.5, 90.7–91.2 (m), 116.0 (tt, 1 J CF = 262.2 Hz, 2 J CF = 30.9 Hz), 123.8, 124.8 (tt, 1 J CF = 289.0 Hz, 2 J CF = 35.1 Hz), 129.2, 130.6, 137.2, 175.7. 19F NMR (376 MHz, CDCl3): δ = –118.7 (dd, 1 F, 2 J FF = 273.2 Hz, 3 J FF = 8.0 Hz), –117.5 (dd, 1 F, 2 J FF = 273.2 Hz, 3 J FF = 3.4 Hz), –85.4 (dd, 1 F, 2 J FF = 224.5 Hz, 3 J FF = 8.0 Hz), –83.6 (d, 1 F, 2 J FF = 224.5 Hz, 3 J FF = 3.4 Hz). IR (film): νmax = 3191, 1680, 1578, 1105, 753, 691 cm–1. MS (EI): m/z (%) = 190 (5), 114 (100), 109 (11), 86 (9), 58 (13). HRMS (ESI+): m/z calcd for C13H14F4NO2S [MH]+: 324.06759; found: 324.06760
    • 14a 5-Hydroxy-1-methyl-5-(1,1,2,2-tetrafluoroethyl)- pyrrolidin-2-one (3a)A solution of n-Bu3SnH (470 μL, 1.75 mmol) and AIBN (25 mg, 0.15 mmol) in dry toluene (3 mL) was added over 1 h using a syringe pump to a refluxing solution of 2a (323 mg, 1 mmol) in dry toluene (5 mL). The resulting mixture was refluxed under argon for 3 h, followed by concentration under reduced pressure and purification by flash column chromatography (SiO2, PE–EtOAc) to give product 3a (202 mg, 94% yield); colorless oil; Rf = 0.23 (PE–EtOAc, 60:40). 1H NMR (400 MHz, CDCl3): δ = 1.90–2.00 (m, 1 H), 2.26–2.38 (m, 2 H), 2.41–2.50 (m, 1 H), 2.73 (d, 3 H, J = 2.5 Hz), 6.59 (tdd, 1 H, 2 J HF = 51.5 Hz, 3 J HF = 9.6, 3.5 Hz), 7.36 (br d, 1 H, J = 2.8 Hz). 13C NMR (100 MHz, CDCl3): δ = 25.8, 28.4, 28.8, 88.7–90.2 (m), 173.8. 19F NMR (376 MHz, CDCl3): δ = –138.3 (ddd, 1 F, 2 J FF = 301.0 Hz, 3 J FF = 10.7, 7.1 Hz), –134.3 (ddd, 1 F, 2 J FF = 301.0 Hz, 3 J FF = 12.5, 1.3 Hz), –130.6 (ddd, 1 F, 2 J FF = 265.8 Hz, 3 J FF = 12.5, 7.1 Hz), –126.8 (ddd, 1 F, 2 J FF = 265.8 Hz, 3 J FF = 10.7, 1.3 Hz). IR (film): νmax = 3204, 1687, 1110 cm–1. MS (EI): m/z (%) = 198 (6), 114 (100), 101 (8), 86 (20), 58 (45). HRMS (ESI+): m/z calcd for C7H10F4NO2 [MH]+: 216.06422; found: 216.06417
    • 15a 7,7,8,8-Tetrafluoro-8a-hydroxy-6-methylhexa-hydroindolizin-3(2H)-one (3b)A solution of n-Bu3SnH (470 μL, 1.75 mmol) and AIBN (25 mg, 0.15 mmol) in dry toluene (3 mL) was added over 3 h using a syringe pump to a refluxing solution of 2b (349 mg, 1 mmol) in dry toluene (5 mL). The resulting mixture was refluxed under argon overnight, followed by concentration under reduced pressure and purification by flash column chromatography (SiO2, PE–EtOAc) to give product 3b (188 mg, 78% yield); white solid; cis/trans = 76:24; mp (cis) 160–162 °C; Rf = 0.42 (PE–EtOAc, 25:75). 1H NMR (400 MHz, CDCl3): δ = 0.91 (dd, 3 H, 3 J HH = 7.3 Hz, 4 J HH = 3.8 Hz, trans), 1.02 (d, 3 H, 3 J HH = 6.7 Hz, cis), 1.88–1.97 (m, 2 H, cis + trans), 2.10–2.25 (m, 2 H, cis + trans), 2.28–2.35 (m, 1 H, cis), 2.37–2.40 (m, 1 H, trans), 2.42–2.53 (m, 2 H, cis + trans), 2.69–2.79 (m, 1 H, cis), 3.16–3.23 (m, 1 H, trans), 3.61–3.69 (m, 1 H, trans), 3.77–3.88 (m, 1 H, cis), 7.08 (s, 1 H, trans), 7.11 (s, 1 H, cis). 13C NMR (100 MHz, CDCl3): δ (cis) = 8.0 (d, J = 5.6 Hz), 25.9, 28.6, 35.3 (t, 2 J CF = 21.4 Hz), 36.1 (d, J = 8.3 Hz), 88.1–88.7 (m), 171.8. 19F NMR (376 MHz, CDCl3): δ = –140.9 (ddd, 1 F, 2 J FF = 252.4 Hz, 3 J FF = 16.1, 10.4 Hz, cis), –135.8 (ddd, 1 F, 2 J FF = 257.8 Hz, 3 J FF = 16.3, 12.1 Hz, trans), –124.7 (ddd, 1 F, 2 J FF = 255.1 Hz, 3 J FF = 16.1, 14.6 Hz, cis), –121.2 (ddd, 1 F, 2 J FF = 255.1 Hz, 3 J FF = 18.1, 10.4 Hz, cis), –121.1 (ddd, 1 F, 2 J FF = 252.4 Hz, 3 J FF = 18.1, 14.6 Hz, cis), –120.4 (ddd, 1 F, 2 J FF = 257.4 Hz, 3 J FF = 17.9, 12.1 Hz, trans), –117.2 (ddd, 1 F, 2 J FF = 257.8 Hz, 3 J FF = 17.9, 12.4 Hz, trans), –106.1 (ddd, 1 F, 2 J FF = 257.4 Hz, 3 J FF = 16.3, 12.4 Hz, trans). IR (film): νmax = 3252, 1699, 116 cm–1. MS (EI): m/z (%) = 241 (2) [M]+, 221 (58), 201 (22), 173 (12), 112 (100), 84 (77), 55 (35). HRMS (EI+): m/z calcd for C9H11F4NO2 [M]+: 241.0726; found: 241.0731
  • 16 CCDC-860878 (for cis-3b) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif
  • 17 Bootwicha T, Panichakul D, Kuhakarn C, Prabpai S, Kongsaeree P, Tuchinda P, Reutrakul V, Pohmakotr M. J. Org. Chem. 2009; 74: 3798
    • 18a 1-Methyl-5-[1,1,2,2-tetrafluoro-2-(phenylthio)-ethyl]pyrrolidin-2-one (4a)To a solution of 2a (323 mg, 1 mmol) in CH2Cl2 (5 mL) was added dropwise triethylsilane (0.8 mL, 5 mmol) and BF3 ·OEt2 (377 μL, 3 mmol) under argon atmosphere. The mixture was refluxed for 2.5 h, followed by the addition of sat. NaHCO3 solution (10 mL), and extracted with CH2Cl2 (3 × 25 mL). The combined extracts were washed with brine and dried over anhyd MgSO4. Filtration followed by evaporation gave a crude product, which was purified by flash column chromatography (SiO2, PE–EtOAc) to give the desired product 4a (282 mg, 92% yield); colorless oil; Rf = 0.26 (PE–EtOAc, 80:20). 1H NMR (400 MHz, CDCl3): δ = 2.15–2.34 (m, 3 H), 2.44–2.59 (m, 1 H), 2.95 (d, 3 H, J = 2.0 Hz), 4.04–4.13 (m, 1 H), 7.37–7.43 (m, 2 H), 7.44–7.51 (m, 1 H), 7.56–7.68 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 19.6–19.8 (m), 29.0, 30.9–31.0 (m), 60.8–61.4 (m), 129.3, 130.7, 137.2. 19F NMR (376 MHz, CDCl3): δ = –120.7 (dd, 1 F, 2 J FF = 270.9 Hz, 3 J FF = 20.1 Hz), –111.0 (d, 1 F, 2 J FF = 270.9 Hz), –86.3 (s, 2 F). IR (film): νmax = 3063, 1707, 1577, 1108 cm–1. MS (EI): m/z (%) = 109 (6), 98 (100), 42 (5). HRMS (ESI+): m/z calcd for C13H13F4NNaOS [MNa]+: 330.05453; found: 330.05462