LETTER
Pentafluorosulfanyl-Containing Indoles and Oxindoles
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(8) Beier, P.; Pastýříková, T. Tetrahedron Lett. 2011, 52, 4392.
(9) Pastýříková, T.; Iakobson, G.; Vida, N.; Pohl, R.; Beier, P.
Eur. J. Org. Chem. 2012, 2123.
(10) Vida, N.; Beier, P. J. Fluorine Chem. 2012, 143, 130.
(11) Beier, P.; Pastýříková, T. Beilstein J. Org. Chem. 2013, 9,
411.
(12) Frischmuth, A.; Unsinn, A.; Groll, K.; Stadtmüller, H.;
Knochel, P. Chem. Eur. J. 2012, 18, 10234.
(13) Makosza, M.; Danikiewicz, W.; Wojciechowski, K. Liebigs
Ann. Chem. 1988, 203.
mg, 0.27 mmol), p-chlorobenzaldehyde (41 mg, 0.30 mmol,
1.1 equiv), TsOH (cat.) and benzene (15 mL) was heated to
reflux for 4 h using a Dean–Stark apparatus, followed by
removal of the solvent under reduced pressure. The residue
was dissolved in cold CH2Cl2 (10 mL), saturated Na2CO3
was added, and the mixture was vigorously stirred. The
aqueous layer was extracted with CH2Cl2 (2 × 5 mL), the
combined organic phase was dried, and the solvent was
removed under reduced pressure followed by the
purification by column chromatography (silica gel, hexane–
CH2Cl2–EtOAc, 65:32.5:2.5) to give 9a (110 mg, 83%) as a
white solid; mp 194.5–195.5 °C (EtOH); Rf = 0.26 (hexane–
acetone, 80:20). IR (film): 3070, 1635, 1591, 1305, 1146,
1115, 1015, 857, 848, 840, 829, 818 cm–1. 1H NMR (400
MHz, CDCl3): δ = 4.68 (s, 2 H), 7.19–7.24 (m, 3 H), 7.40–
7.51 (m, 5 H), 7.59–7.68 (m, 4 H), 7.77 (s, 1 H). 13C (100
MHz, CDCl3): δ = 57.5, 115.5 (quint, J = 4.8 Hz), 123.4
(quint, J = 4.8 Hz), 126.7, 128.5, 128.8, 129.2, 130.3, 132.3,
133.7, 138.3, 138.5, 150.6, 154.9 (quint, J = 17.6 Hz), 160.3.
19F NMR (376 MHz, CDCl3): δ = 62.4 (d, J = 150.3 Hz, 4 F),
82.2–83.9 (m, 1 F). MS (EI): m/z (%) = 495 (4) [M]+, 356
(38), 355 (17), 354 (100), 229 (9), 227 (26), 109 (12), 89
(15), 77 (8). HRMS (EI): m/z [M]+ calcd. for
(14) 6-(Pentafluorosulfanyl)-1H-indole (3):12 10% Pd/C (360
mg) was added to a solution of 5a7a (466 mg, 1.62 mmol) and
acetic acid (277 μL, 4.85 mmol, 3 equiv) in EtOAc (5 mL)
and the mixture was hydrogenated in an autoclave (10 bar)
at room temperature for 24 h. The catalyst was filtered off,
the filter was washed with EtOAc (3 × 10 mL), and the
solvent was removed under reduced pressure. The resulting
residue was purified by column chromatography (silica gel,
hexane–EtOAc) to give 3 as a white solid (194 mg, 50%);
mp 97.1–98.4 °C; Rf = 0.46 (hexane–EtOAc, 85:15). 1H
NMR (600 MHz, CDCl3): δ = 6.62 (ddd, J = 3.2, 2.0, 1.0 Hz,
1 H), 7.40 (dd, J = 3.2, 2.5 Hz, 1 H), 7.53 (dd, J = 8.8,
2.0 Hz, 1 H), 7.66 (dquint., J = 8.8, 0.6 Hz, 1 H), 7.86 (ddd,
J = 2.0, 1.0, 0.5 Hz, 1 H), 8.43 (br s, 1 H). 13C (150 MHz,
CDCl3): δ = 102.9, 109.8 (quint, J = 4.9 Hz), 117.3 (quint,
J = 4.5 Hz), 120.1, 127.9, 129.7, 133.8, 148.8 (quint,
J = 16.6 Hz). 19F NMR (376 MHz, CDCl3): δ = 65.1 (d,
J = 149.9 Hz, 4 F), 85.8–87.4 (m, 1 F). MS (EI): m/z
(%) = 243 (100) [M]+, 135 (42), 116 (40), 108 (21), 89 (28).
HRMS (EI): m/z [M]+ calcd for C8H6F5NS: 243.0141; found:
243.0135.
(15) 5-(Pentafluorosulfanyl)-1H-indole (4): Prepared as
described for 3 from 10% Pd/C (600 mg), 67a (623 mg, 2.16
mmol) and acetic acid (370 μL, 6.49 mmol, 3 equiv) in EtOH
(6 mL) in 20 h, giving 4 as a white solid (362 mg, 69%) after
purification by column chromatography (silica gel, hexane–
EtOAc); mp 85.2–87.0 °C; Rf = 0.22 (hexane–EtOAc,
85:15). IR (film): 3493, 3122, 1615, 1512, 1419, 1331,
1257, 1096, 1072, 897, 835, 819, 808 cm–1. 1H NMR (500
MHz, CDCl3): δ = 6.64 (ddd, J = 3.2, 2.1, 0.9 Hz, 1 H), 7.30
(dd, J = 3.2, 2.3 Hz, 1 H), 7.35 (dquint., J = 9.0, 0.9 Hz,
1 H), 7.58 (dd, J = 9.0, 2.2 Hz, 1 H), 8.09 (dt, J = 2.2,
0.9 Hz, 1 H), 8.33 (br s, 1 H). 13C (125.7 MHz, CDCl3):
δ = 104.1, 110.4, 119.3 (quint, J = 4.7 Hz), 119.4 (quint,
J = 4.7 Hz), 126.5, 126.7, 136.2, 147.1 (quint, J = 16.1 Hz).
19F NMR (470 MHz, CDCl3): δ = 65.4 (d, J = 149.7 Hz, 4 F),
86.7–87.8 (m, 1 F). MS (EI): m/z (%) = 243 (100) [M]+, 135
(38), 116 (44), 108 (19), 89 (24). HRMS (EI): m/z [M]+ calcd
for C8H6F5NS: 243.0141; found: 243.0150.
C20H15ClF5NO2S2: 495.0153; found: 495.0166.
(19) 2-(4-Chlorophenyl)-6-(pentafluorosulfanyl)-1H-indole
(10a): To a stirred suspension KOH (113 mg, 2.02 mmol, 10
equiv) in DMSO (3 mL), a suspension of 9a (100 mg, 0.202
mmol) in DMSO (3 mL) was added and the mixture was
stirred at r.t. for 30 min. Aqueous NH4Cl (10 mL) was added
and the product was extracted into Et2O (3 × 5 mL). The
organic phase was washed with water (2 × 5 mL), dried, and
solvent was removed under reduced pressure. Purification
by column chromatography (silica gel, hexane–EtOAc) gave
10a (49 mg, 68%) as a white solid; mp 161–164 °C;
Rf = 0.45 (hexane–CH2Cl2, 60:40). IR (film): 3474, 1483,
1073, 1010, 935, 837, 828, 815, 812 cm–1. 1H NMR (400
MHz, acetone-d6): δ = 7.03 (dd, J = 2.1, 0.9 Hz, 1 H), 7.49–
7.54 (m, 3 H), 7.69–7.73 (m, 1 H), 7.86–7.90 (m, 2 H), 7.94–
7.95 (m, 1 H), 11.14–11.30 (m, 1 H). 13C (100 MHz,
acetone-d6): δ = 100.5, 100.6, 110.7 (quint, J = 5.1 Hz),
117.9 (quint, J = 4.6 Hz), 120.9, 128.0, 130.0, 131.3, 132.1,
134.6, 136.4, 142.0, 149.3 (quint, J = 16.1 Hz). 19F NMR
(376 MHz, acetone-d6): δ = 66.1 (d, J = 148.0 Hz, 4 F),
87.8–89.5 (m, 1 F). MS (EI): m/z (%) = 355 (37) [M]+, 354
(17) [M]+, 353 (100) [M]+, 247 (10), 245 (29), 226 (10), 191
(15), 190 (15), 123 (10), 105 (7). HRMS (EI): m/z [M]+ calcd
for C14H9ClF5NS: 353.0064; found: 353.0074.
(20) Brown, G. D.; Wong, H. Tetrahedron 2004, 60, 5439.
(21) (a) Lu, S.; Wang, R.; Yang, Y.; Li, Y.; Shi, Z.; Zhang, W.;
Tu, Z. J. Org. Chem. 2011, 76, 5661. (b) Lu, S.; Wei, S.;
Wang, W.; Zhang, W.; Tu, Z. Eur. J. Org. Chem. 2011,
5905.
(22) Kenda, B.; Quesnel, Y.; Ates, A.; Michel, P.; Turet, L.;
Mercier, J. WO 128692 A2, 2006, (compound x160) Chem.
Abstr. 2006, 146, 45393.
(16) Wojciechowski, K.; Makosza, M. Bull. Soc. Chim. Belg.
1986, 95, 671.
(17) Kraus, G. A.; Guo, H.; Kumar, G.; Pollock, G. III.;
Carruthers, H.; Chaudhary, D.; Beasley, J. Synthesis 2010,
1386.
(18) [2-Benzenesulfonylmethyl-5-(pentafluorosulfanyl)phenyl]-
(4-chlorobenzylinene)amine (9a): A mixture of 87a (100
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 855–859