G
N. Zhang et al.
Paper
Synthesis
2-Hydroxy-2-(1H-indol-1-yl)-1-(4-isopropylphenyl)ethan-1-one
(4e)
1H NMR (400 MHz, CDCl3): δ = 7.92–7.80 (m, 2 H), 7.61 (d, J = 7.9 Hz, 1
H), 7.54 (d, J = 8.3 Hz, 1 H), 7.30 (t, J = 7.7 Hz, 1 H), 7.18 (t, J = 7.5 Hz, 1
H), 7.02 (t, J = 8.5 Hz, 2 H), 6.95 (d, J = 3.1 Hz, 1 H), 6.83 (d, J = 7.2 Hz, 1
H), 6.53 (d, J = 3.0 Hz, 1 H), 5.11 (d, J = 7.3 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 192.38, 167.66, 165.09, 135.31,
131.65, 131.55, 129.22, 128.60, 128.58, 124.90, 122.81, 121.31,
120.78, 116.33, 116.11, 109.26, 104.67, 76.76.
Orange oil; yield: 23.4 mg (80%).
1H NMR (400 MHz, CDCl3): δ = 7.74 (d, J = 8.2 Hz, 2 H), 7.56 (dd, J =
13.7, 8.1 Hz, 2 H), 7.26 (t, J = 7.6 Hz, 1 H), 7.15 (d, J = 7.5 Hz, 1 H), 7.11
(d, J = 8.3 Hz, 2 H), 6.94 (d, J = 3.2 Hz, 1 H), 6.82 (d, J = 7.4 Hz, 1 H), 6.47
(d, J = 3.2 Hz, 1 H), 5.26 (d, J = 7.4 Hz, 1 H), 2.80 (hept, J = 6.8 Hz, 1 H),
1.13 (d, J = 2.5 Hz, 3 H), 1.11 (d, J = 2.5 Hz, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C16H12FNNaO2: 292.0744; found:
13C NMR (100 MHz, CDCl3): δ = 193.31, 156.60, 135.44, 129.92,
129.20, 129.09, 127.06, 124.99, 122.65, 121.19, 120.61, 109.36,
104.38, 76.56, 34.18, 23.27.
292.0743.
2-Hydroxy-2-(1H-indol-1-yl)-1-(1-methyl-1H-pyrrol-2-yl)ethan-1-
one (4j)
HRMS (ESI): m/z [M + Na]+ calcd for C19H19NNaO2: 316.1308; found:
White solid; yield: 22.0 mg (87%); mp 112–113 °C.
316.1306.
1H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 7.8 Hz, 1 H), 7.51 (d, J = 8.3
Hz, 1 H), 7.23 (t, J = 7.6 Hz, 1 H), 7.12 (t, J = 7.4 Hz, 1 H), 7.05 (d, J = 3.3
Hz, 1 H), 6.73 (s, 1 H), 6.64 (d, J = 4.1 Hz, 1 H), 6.60 (d, J = 7.1 Hz, 1 H),
6.49 (d, J = 3.2 Hz, 1 H), 5.90 (dd, J = 4.2, 2.4 Hz, 1 H), 5.38 (d, J = 7.1 Hz,
1 H), 3.90 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 182.52, 135.33, 133.40, 129.12,
126.42, 125.18, 122.39, 121.10, 121.06, 120.30, 109.53, 109.48,
103.85, 76.68, 37.64.
2-Hydroxy-2-(1H-indol-1-yl)-1-(3-methoxyphenyl)ethan-1-one
(4f)
Orange oil; yield: 25.0 mg (89%).
1H NMR (400 MHz, CDCl3): δ = 7.58 (dd, J = 16.2, 8.1 Hz, 2 H), 7.37 (d,
J = 7.7 Hz, 1 H), 7.34 (d, J = 2.1 Hz, 1 H), 7.28 (t, J = 7.5 Hz, 1 H), 7.24–
7.12 (m, 2 H), 7.04 (dd, J = 8.2, 2.0 Hz, 1 H), 6.96 (d, J = 3.3 Hz, 1 H),
6.84 (d, J = 7.3 Hz, 1 H), 6.51 (d, J = 3.2 Hz, 1 H), 5.16 (d, J = 7.3 Hz, 1 H),
3.63 (s, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C15H14N2NaO2: 277.0947; found:
13C NMR (100 MHz, CDCl3): δ = 193.77, 159.72, 135.46, 133.33,
129.98, 129.26, 124.88, 122.81, 121.80, 121.33, 120.74, 112.50,
109.26, 104.67, 76.84, 55.25.
277.0946.
Ethyl 2-(tert-Butyldimethylsiloxy)-2-(1H-indol-1-yl)acetate (5)
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NNaO3: 304.0944; found:
304.0943.
A solution of 2a (2 g, 9.12 mmol), tert-butylchlorodimethylsilane
(1.84 g, 12.22 mmol), Et3N (3.2 mL, 23.35 mmol), and DMAP (111.4
mg, 0.91 mmol) in anhyd THF (15 mL) was stirred under a dry N2 at-
mosphere for 12 h, at the end of which time NH4Cl was added. The
mixture was extracted with EtOAc (3 × 25 mL). The combined organ-
ics were washed with brine (40 mL), dried (Na2SO4), and filtered. Re-
moval of solvent by rotary evaporation and purification by flash col-
umn chromatography (silica gel, PE/EtOAc, 40:1) afforded 5 (2.33 g,
77%) as a colorless oil.
1H NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 7.8 Hz, 1 H), 7.51 (d, J = 8.2
Hz, 1 H), 7.34 (d, J = 3.3 Hz, 1 H), 7.24 (t, J = 7.2 Hz, 1 H), 7.16 (t, J = 7.4
Hz, 1 H), 6.58 (d, J = 3.3 Hz, 1 H), 6.17 (s, 1 H), 4.20 (qq, J = 10.8, 7.1 Hz,
2 H), 1.22 (t, J = 7.1 Hz, 3 H), 0.92 (s, 9 H), 0.15 (s, 3 H), –0.07 (s, 3 H).
2-Hydroxy-2-(1H-indol-1-yl)-1-(4-methoxyphenyl)ethan-1-one
(4g)
Pink solid; yield: 24.0 mg (85%); mp 111–112 °C.
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.9 Hz, 2 H), 7.48 (dd, J =
15.7, 8.1 Hz, 2 H), 7.18 (t, J = 7.6 Hz, 1 H), 7.06 (t, J = 7.5 Hz, 1 H), 6.86
(d, J = 3.3 Hz, 1 H), 6.71 (d, J = 7.3 Hz, 1 H), 6.66 (d, J = 8.9 Hz, 2 H), 6.40
(d, J = 3.2 Hz, 1 H), 5.18 (d, J = 7.3 Hz, 1 H), 3.62 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 192.05, 164.74, 135.46, 131.35,
129.20, 125.01, 124.97, 122.66, 121.23, 120.62, 114.23, 109.33,
104.36, 76.45, 55.43.
13C NMR (100 MHz, CDCl3): δ = 168.01, 135.16, 129.10, 125.64,
121.99, 120.94, 120.21, 110.24, 103.21, 78.13, 61.73, 25.44, 18.07,
13.98, –5.32, –5.44.
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NNaO3: 304.0944; found:
304.0943.
HRMS (ESI): m/z [M + Na]+ calcd for C18H27NNaO3Si: 356.1652; found:
356.1651.
2-Hydroxy-2-(1H-indol-1-yl)-1-(naphthalen-2-yl)ethan-1-one
(4h)
White solid; yield: 24.0 mg (80%); mp 99–100 °C.
2-(tert-Butyldimethylsiloxy)-2-(1H-indol-1-yl)ethan-1-ol (6)
1H NMR (400 MHz, CDCl3): δ = 8.32 (s, 1 H), 7.86 (dd, J = 8.7, 1.5 Hz, 1
H), 7.73 (d, J = 8.7 Hz, 2 H), 7.69 (d, J = 8.4 Hz, 1 H), 7.60 (dd, J = 16.5,
8.1 Hz, 2 H), 7.52 (t, J = 7.2 Hz, 1 H), 7.43 (t, J = 7.5 Hz, 1 H), 7.31 (t, J =
7.6 Hz, 1 H), 7.16 (t, J = 7.5 Hz, 1 H), 7.01 (d, J = 3.3 Hz, 1 H), 6.98 (d, J =
7.1 Hz, 1 H), 6.49 (d, J = 3.2 Hz, 1 H), 5.25 (d, J = 7.1 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 193.85, 136.12, 135.50, 132.05,
131.32, 129.86, 129.44, 129.38, 129.30, 128.91, 127.67, 127.04,
124.98, 123.55, 122.81, 121.35, 120.74, 109.37, 104.67, 76.89.
To a cooled suspension of LiAlH4 (114 mg, 3.0 mmol) in dry Et2O (13
mL) was added dropwise a solution of 5 (1.0 g, 3.0 mmol) in dry Et2O
(2 mL) slowly under an argon atmosphere. The mixture was stirred
for 30 min at this temperature. Sat. aq potassium sodium tartrate (10
mL) was added to the mixture and it was extracted with Et2O (3 × 10
mL). The combined organic layer was washed with water and brine,
dried (Na2SO4), and concentrated in vacuo. The residual oil was puri-
fied by column chromatography (silica gel, PE/EtOAc, 20:1) to afford 6
(813 mg, 93%) as a colorless oil.
1H NMR (400 MHz, CDCl3): δ = 7.66 (d, J = 7.8 Hz, 1 H), 7.51 (d, J = 8.2
Hz, 1 H), 7.28–7.23 (m, 2 H), 7.17 (t, J = 7.4 Hz, 1 H), 6.57 (d, J = 3.2 Hz,
1 H), 5.88 (t, J = 6.0 Hz, 1 H), 3.85 (ddt, J = 17.2, 11.4, 6.3 Hz, 2 H), 1.99
(s, 1 H), 0.93 (s, 9 H), 0.11 (s, 3 H), –0.17 (s, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C20H15NNaO2: 324.0995; found:
324.0993.
1-(4-Fluorophenyl)-2-hydroxy-2-(1H-indol-1-yl)ethan-1-one (4i)
Red oil; yield: 22.3 mg (83%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H