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PRACTICAL SYNTHETIC PROCEDURES
13C NMR (67.8 MHz, CDCl3): d = 12.8, 18.0, 22.0, 32.0, 71.5, 84.7,
114.0, 116.6, 118.9, 121.2, 124.1, 125.4, 125.5, 125.6, 125.8, 127.4,
127.8, 128.7, 130.0, 131.1, 131.2, 134.0, 135.9, 142.2.
tion of indoles by using propargylic alcohols as a new type
of electrophile.
1H NMR (270 MHz) and 13C NMR (67.8 MHz) spectra were mea-
sured on a Jeol Excalibur 270 spectrometer using CDCl3 as solvent.
HPLC analyses were performed on a Hitachi L-7100 apparatus
equipped with a UV detector using 25 cm × 4.6 mm Daicel Chiral-
cel OD and Chiralpak IA columns. Mass spectra were measured on
a Jeol JMS-700 mass spectrometer.
HRMS (EI): m/z [M] calcd for C31H37NSi: 451.2695; found:
451.2688.
5-Fluoro-3-[1-(1-naphthyl)prop-2-ynyl]-1-(triisopropylsilyl)-
1H-indole (3m)
Brown oil; yield: 51%; 80% ee [HPLC (Daicel Chiralpak OD,
hexane–i-PrOH, 49:1, flow rate = 0.5 mL/min, l = 254 nm): tR =
12.4 (minor), 16.9 min (major)].
1H NMR (270 MHz, CDCl3): d = 1.06 (dd, J = 4.9, 7.5 Hz, 18 H),
1.52–1.63 (m, 3 H), 2.47 (d, J = 2.4 Hz, 1 H), 5.85 (d, J = 2.4 Hz, 1
H), 6.85 (dt, J = 2.6, 9.1 Hz, 1 H), 7.07–7.12 (m, 2 H), 7.34–7.47
(m, 4 H), 7.59 (d, J = 6.9 Hz, 1 H), 7.78 (d, J = 8.2 Hz, 1 H), 7.84–
7.87 (m, 1 H), 8.18–8.22 (m, 1 H).
All reactions were carried out under a dry N2 atmosphere. Chiral
disulfide 2 was prepared according to our previous procedure.3 1-
Phenylprop-2-yn-1-ol (1a) is commercially available. Preparation
of other propargylic alcohols was carried out according to literature
methods.6 1-(Triisopropylsilyl)-1H-indole was prepared according
to the literature method.7 DCE and THF were distilled under N2
over P2O5 and Na benzophenone ketyl, respectively, and degassed.
All products were fully characterized.5
13C NMR (67.8 MHz, CDCl3): d = 12.7, 17.9, 32.1, 71.8, 84.3, 104.4
(d, JC-F = 24 Hz), 109.8 (d, JC-F = 26 Hz), 114.5 (d, JC-F = 10 Hz),
116.9 (d, JC-F = 5 Hz), 124.0, 125.4, 125.5, 125.8, 125.9, 128.1,
128.8, 130.1 (d, JC-F = 10 Hz), 131.1, 132.3, 134.1, 135.4, 138.1,
157.6 (d, JC-F = 235 Hz).
3-[1-(1-Naphthyl)prop-2-ynyl]-1-(triisopropylsilyl)-1H-indole
(3g); Typical Procedure
In a 200-mL round-bottomed flask were placed [Cp*RuCl]4 (55.3
mg, 0.05 mmol) and bis[(R)-1-(6¢-phenyl-1,1¢:4¢,1¢¢-terphenyl-2¢-
yl)propyl] disulfide (2, 76.4 mg, 0.10 mmol) under N2. Anhyd THF
(10 mL) was added and the mixture was magnetically stirred at r.t.
for 12 h. The solvent was evaporated in vacuo. Then, NH4BF4 (21.8
mg, 0.20 mmol) and anhyd DCE (50 mL) were added under N2, and
the mixture was magnetically stirred at r.t. After the addition of 1g
(365 mg, 2.0 mmol) and 1-(triisopropylsilyl)-1H-indole (1.64 g, 6.0
mmol), the reaction flask was kept at 40 °C for 23 h. The solvent
was concentrated under reduced pressure by an aspirator, and then
the residue was purified by flash column chromatography (silica
gel, hexane–EtOAc; hexane only to 100:1) to give 3g (634 mg,
72%) as a pale yellow oil; 93% ee [HPLC (Daicel Chiralpak IA,
hexane–i-PrOH, 99:1, flow rate = 0.5 mL/min, l = 254 nm): tR =
11.6 (major), 14.0 min (minor)].
HRMS (EI): m/z [M] calcd for C30H34FNSi: 455.2445; found:
455.2460.
6-Fluoro-3-[1-(1-naphthyl)prop-2-ynyl]-1-(triisopropylsilyl)-
1H-indole (3n)
Yellow oil; yield: 78%; 81% ee [HPLC (Daicel Chiralpak OD,
hexane–i-PrOH, 49:1, flow rate = 0.5 mL/min, l = 254 nm): tR =
12.9 (minor), 18.6 min (major)].
1H NMR (270 MHz, CDCl3): d = 1.07 (dd, J = 5.1, 7.6 Hz, 18 H),
1.52–1.64 (m, 3 H), 2.45 (d, J = 2.5 Hz, 1 H), 5.88 (d, J = 2.5 Hz, 1
H), 6.78 (dt, J = 2.2, 9.1 Hz, 1 H), 7.03 (s, 1 H), 7.15 (dd, J = 2.2,
11.0 Hz, 1 H), 7.29–7.46 (m, 4 H), 7.56 (d, J = 7.1 Hz, 1 H), 7.77
(d, J = 8.2 Hz, 1 H), 7.84–7.87 (m, 1 H), 8.20–8.23 (m, 1 H).
13C NMR (67.8 MHz, CDCl3): d = 12.6, 18.0, 32.0, 71.7, 84.4, 100.4
(d, JC-F = 26 Hz), 108.2 (d, JC-F = 24 Hz), 116.9, 119.8 (d, JC-F = 10
Hz), 124.0, 125.4, 125.5, 125.8, 125.9, 126.1, 128.0, 128.8, 130.8
(d, JC-F = 4 Hz), 131.1, 134.0, 135.6, 141.7 (d, JC-F = 12 Hz), 159.7
(d, JC-F = 237 Hz).
3-[1-(1-Naphthyl)prop-2-ynyl]-1H-indole (4)
In a 20-mL round-bottomed flask was placed 3g (634 mg, 1.45
mmol) under N2. Anhyd THF (7.5 mL) was added and the mixture
was cooled to 0 °C. Then, 1 M TBAF in THF (2.9 mL, 2.9 mmol)
was added dropwise to the mixture and the mixture was magnetical-
ly stirred at 0 °C for 1 h. CH2Cl2 (20 mL) was added and the organic
layer was washed with H2O (3 × 20 mL). The aqueous layer was ex-
tracted with CH2Cl2 (3 × 10 mL) and the combined organic layers
were dried (anhyd MgSO4). The solvent was concentrated under re-
duced pressure by an aspirator, and the residue was purified by flash
column chromatography (silica gel, hexane–EtOAc, 10:1) to give 45
(360 mg, 88%) as a white solid; 93% ee. The product was further
purified by recrystallization (hexane–EtOAc) to give enantiomeri-
cally pure 4 (223 mg, 55%); >99% ee [HPLC (Daicel Chiralpak IA,
hexane–i-PrOH, 9:1, flow rate = 1.0 mL/min, l = 254 nm): tR = 15.1
(major), 16.5 min (minor)].
HRMS (EI): m/z [M] calcd for C30H34FNSi: 455.2445; found:
455.2451.
Acknowledgment
This work was supported by Grants-in-Aid for Scientific Research
for Young Scientist (S) (No. 19675002) and for Scientific Research
on Priority Areas (No. 18066003) from the Ministry of Education,
Culture, Sports, Science and Technology, Japan. K.K. acknowled-
ges the Global COE Program for Chemistry Innovation.
[a]D27 –6.3 (c 1.10, CHCl3).
References
6-Methyl-3-[1-(1-naphthyl)prop-2-ynyl]-1-(triisopropylsilyl)-
1H-indole (3j)
(1) For recent reviews, see: (a) Jørgensen, K. A. Synthesis 2003,
1117. (b) Bandini, M.; Melloni, A.; Umani-Ronchi, A.
Angew. Chem. Int. Ed. 2004, 43, 550. (c) Bandini, M.;
Emer, E.; Tommasi, S.; Umani-Ronchi, A. Eur. J. Org.
Chem. 2006, 3527. (d) Poulsen, T. B.; Jørgensen, K. A.
Chem. Rev. 2008, 108, 2903.
(2) For recent examples of asymmetric Friedel–Crafts
alkylation of indole derivatives, see: (a) Li, C.-F.; Liu, H.;
Liao, J.; Cao, Y.-J.; Liu, X.-P.; Xiao, W.-J. Org. Lett. 2007,
9, 1847. (b) Yang, H.; Hong, Y.-T.; Kim, S. Org. Lett. 2007,
9, 2281. (c) Terada, M.; Sorimachi, K. J. Am. Chem. Soc.
2007, 129, 292. (d) Kang, Q.; Zhao, Z.-A.; You, S.-L. J. Am.
Brown oil; yield: 83%; 92% ee [HPLC (Daicel Chiralpak OD, hex-
ane–i-PrOH, 49:1, flow rate = 0.5 mL/min, l = 254 nm): tR = 13.7
(minor), 18.0 min (major)].
1H NMR (270 MHz, CDCl3): d = 1.08 (dd, J = 5.1, 7.6 Hz, 18 H),
1.55–1.66 (m, 3 H), 2.42–2.44 (br, 4 H), 5.89 (s, 1 H), 6.84 (d,
J = 7.9 Hz, 1 H), 7.02 (s, 1 H), 7.19–7.44 (m, 5 H), 7.56 (d, J = 7.1
Hz, 1 H), 7.75 (d, J = 8.2 Hz, 1 H), 7.82–7.86 (m, 1 H), 8.22–8.26
(m, 1 H).
Synthesis 2008, No. 23, 3869–3873 © Thieme Stuttgart · New York