Denmark et al.
ice/2-propanol bath for 15 min, and 12.96 mL (1.55 M in hexane,
0.1 mmol, 1.25 equiv) of an n-BuLi solution was slowly added.
The resulting mixture was stirred for 5 min before being allowed
to warm to 0 °C (ice bath) slowly. The solution was stirred for 20
min at 0 °C before being added to the solution prepared above.
The reaction mixture was stirred at 0 °C for 18 h, whereupon satd
solvent was removed under reduced pressure by rotary evaporation
(23 °C, 20 mmHg) to give a dark-red residue. A solution of the
residue in toluene (0.5 mL) was loaded onto a silica gel column
(22 g, 20 × 100 mm), which was eluted with toluene (20 × 10 mL
fractions). Recrystallization of the material from the pure fractions
(hexane, 50 mL) afforded 234 mg (84%) of 28a as yellow needles.
2
1
aq NaHCO
3
(15.0 mL) solution was added and the contents were
Data for 28a: mp 129-132 °C (hexane); H NMR (500 MHz,
transferred to a 250-mL separatory funnel. The aqueous layer was
3
CDCl ) 8.28 (d, J ) 8.3, 2 H), 8.19 (d, J ) 8.3, 1 H), 7.50 (m, 3
separated and extracted with EtOAc (4 × 35 mL). The combined
H), 7.38 (dd, J ) 7.8, 7.1, 1 H), 7.29 (dd, J ) 7.5, 7.3, 1 H), 6.69
organic layers were dried over Na
SO
2 4
and filtered through #4
(s, 1 H), 1.4 (s, 9H); 13C NMR (125.6 MHz, CDCl
3
) 149.8, 146.9,
Whatman filter paper. The solvent was removed under reduced
pressure using rotary evaporation (23 °C, 20 mmHg) to give a
yellow oil which was immediately purified by silica gel chroma-
tography (350 g, 60 × 100 mm) by first eluting with hexane (300
mL) followed by hexane/EtOAc, 9/1 (30 × 50 mL fractions) to
afford 3.34 g (71%) of 11 as a clear, colorless semisolid. Data for
141.4, 137.9, 137.8, 129.3, 128.9, 125.4, 123.4, 123.1, 121.0, 115.5,
112.1, 84.4, 27.7 IR 2980, 1736, 1601, 1558, 1517, 1451, 1394,
1325, 1225, 1213, 1160, 1133, 1107, 1026, 911, 858; MS: (EI,
70 eV) 338, 324, 323, 268, 267, 223, 208, 180, 178, 57; R
0.32 (hexane/EtOAc, 9/1) [silica gel, UV]. Anal. Calcd for
: C, 67.44; H, 5.36; N, 8.28. Found: C, 67.39; H, 5.27;
f
19 18 2 4
C H N O
-
5
1
1
1: bp 125 °C (7 × 10 mmHg, ABT); H NMR (500 MHz,
CDCl ) 7.96 (dd, J ) 8.53, 0.733, 1 H), 7.56 (d, J ) 7.81, 1 H),
.30 (dt, J ) 8.53, 1.22, 1 H), 7.21 (dt, J ) 7.81, 0.733, 1 H), 6.89
s, 1 H), 2.80 (s, 1 H), 1.73 (s, 9H), 0.45 (s, 6H); 13C NMR (125.6
MHz, CDCl ) 152.4, 140.8, 137.2, 131.1, 124.9, 122.7, 121.2, 119.5,
15.5, 84.8, 28.1, 0.13; IR 3405, 2977, 2248, 1903, 1720, 1517,
471, 1444, 1376, 1336, 1251, 1213; MS (EI, 70 eV) 291, 235,
20, 218, 192, 191, 176, 173, 130, 75, 57; R 0.36 (hexane/EtOAc,
/1) [silica gel, UV]. Anal. Calcd for C15 Si: C, 61.82; H,
.26 N, 4.81. Found: C, 61.54; H, 7.26; N, 4.80.
Preparation of Sodium N-Boc-dimethyl(2-indolyl)silanolate
N, 8.23.
3
Representative Procedure for the Cross-Coupling of Pre-
+
-
7
(
formed Sodium N-Boc-dimethyl(2-indoyl)silanolates (Na 11 )
with Aryl Iodides: Preparation of N-Boc-2-[4′-(ethoxycarbon-
yl)phenyl]indole (28j) (Table 4, Entry 2). To a flame-dried, 5-mL,
round-bottomed flask equipped with a magnetic stir bar was added
washed 98% NaH (29 mg, 1.2 mmol, 1.2 equiv) inside a drybox,
followed by toluene (0.1 mL). Then a solution of N-Boc-dimethyl-
(2-indolyl)silanol (11) (349 mg, 1.2 mol, 1.2 equiv) in toluene (0.9
mL) was added dropwise using a Pasture pipet to the NaH
suspension. Once effervescence ceased, ethyl 4-iodobenzoate (168
3
1
1
2
4
7
f
H
21NO
3
+
-
(Na 11 ). To a flame-dried, 25-mL, conical flask with stir bar was
µL, 1.0 mmol, 1.0) was added along with Pd
2
(dba)
3 3
‚CHCl (52
added 93 mg (3.86 mmol, 1.0 equiv) of NaH and toluene (2.0 mL)
inside a drybox. In a separate flame-dried, 5-mL, conical flask was
prepared a solution of 11 (1.20 g, 4.1 mmol, 1.06 equiv) in toluene
mg, 0.05 mmol, 0.05 equiv). The flask was sealed with a rubber
septum and removed from the drybox. After being stirred at rt for
3 h, the reaction mixture was transferred to a 125 mL separatory
(
2 mL). The silanol solution was added dropwise to the stirred
2
funnel and diluted with H O (25 mL) and EtOAc (20 mL). The
suspension of NaH at room temperature. After effervescence had
ceased, the resulting suspension was stirred for an additional 30
min. The supernatant was removed carefully by Pasteur pipet, the
precipitate was washed with toluene (1.0 mL), and the supernatant
was removed once again. Residual solvent was removed under high
organic layer was separated, and the aqueous layer was washed
with EtOAc (5 × 25 mL). The combined organic layers were dried
4
over MgSO and filtered through #4 Whatman filter paper. The
solvent was removed under reduced pressure using rotary evapora-
tion (23 °C, 20 mmHg) to give a dark-red residue. A solution of
the residue in toluene (0.5 mL) was loaded onto a silica gel column
(175 g, 20 × 100 mm) and was eluted with toluene (20 × 10 mL
fractions). Recrystallization of the material from the pure fractions
from boiling (hexane/toluene, 20/1) afforded 28j (298 mg, 82%)
as white needles. The physical and spectroscopic data matched those
+
-
vacuum (0.1 mmHg) to afford 1.04 g (86%) of Na 11 as a white
+
-
1
powder that was stored in a drybox. Data for Na 11 : H NMR
500 MHz, C ) 7.98 (d, J ) 8.3, 1 H), 7.47 (d, J ) 7.6, 1 H),
(
6 6
D
7
9
3
.26 (t, J ) 7.7, 1 H), 7.17 (t, J ) 7.6, 1 H), 6.86 (s, 1 H), 1.31 (s,
+
1
H), 0.49 (s, 6H); HRMS calcd for C15
3
H20NNaO Si (M )
24
14.1188, found 314.1183.
from the literature. Data for 28j: mp 104-105 °C (hexane/toluene
1
Representative Procedure for Equilibrative Deprotonation
3
(20/1)); H NMR (500 MHz, CHCl ) 8.21 (d, J ) 8.3, 1 H), 8.09
of N-Boc-dimethyl(2-indolyl)silanol (11) in the Cross-Coupling
Reaction with Aryl Iodides: Preparation of N-Boc-2(4′-nitro-
phenyl)indole (28a) (Table 3, Entry 1). To a flame-dried, 5-mL,
round-bottomed flask equipped with a magnetic stir bar was added
(d, J ) 8.5, 2 H), 7.57 (d, J ) 7.3, 1 H), 7.50 (d, J ) 8.5, 2 H),
7.35 (t, J ) 8.4, 1 H), 7.26 (t, J ) 8.1, 1 H), 6.63 (s, 1 H), 4.41 (q,
13
J ) 7.1, 2 H), 1.42 (t, J ) 7.2, 3 H), 1.34 (s, 9H); C NMR (125
3
MHz, CHCl ) 65.5, 150.0, 139.5, 138.9, 137.6, 130.9, 129.1, 128.9,
192 mg (2.0 mmol, 2.0 equiv) of NaOt-Bu and CuI (190 mg, 1.0
128.35, 124.7, 123.1, 120.7, 115.3, 110.9, 83.9, 81.1, 28.2, 27.6;
mmol, 1.0 equiv) inside a dry box. The flask was removed from
the drybox, and 4-iodonitrobenzene (249 mg, 1.0 mmol) and 52
R
f
) 0.12 (hexane/EtOAc, 9/1) [silica gel, UV].
Representative Procedure for the Cross-Coupling of Pre-
+
-
mg (0.05 mmol, 0.05 equiv) of Pd
2
(dba)
3
‚CHCl
3
were added. The
formed Sodium Dimethyl(2-furyl)silanolate (Na 26 ) with Aryl
Bromides: Preparation of 2-(2-Methylphenyl)furan (42f) (Table
11, Entry 11). To a flame-dried, 5-mL, round-bottomed flask
equipped with a magnetic stir bar was added washed 98% NaH
(29 mg, 1.2 mmol, 1.2 equiv) inside a drybox, followed by toluene
(0.2 mL). Then a solution of dimethyl(2-furyl)silanol (26) (170 mg,
1.2 mol, 1.2 equiv) in toluene (0.8 mL) was added dropwise using
a Pasteur pipet to the NaH suspension. Once effervescence ceased,
2-bromotoluene (120 µL, 1.0 mmol) was added along with 37 (18
mg, 0.025 mmol, 0.025 equiv). The flask was sealed with a rubber
septum and removed from the drybox. After being stirred at 50 °C
for 3 h, the reaction mixture was transferred to a 125 mL separatory
flask was sealed with a rubber septum and evacuated (0.1 mmHg)
for a period of 5 min. The flask was then back-filled with dry argon,
and this cycle was repeated twice. Finally, the solids were dissolved
in toluene (600 µL), and the mixture was stirred for 10 min before
addition of the silanol solution prepared below. In a separate flame-
dried, 5-mL, conical flask was added of 11 (349 mg, 1.2 mmol,
1
5
.2 equiv), which was placed under high vacuum (0.1 mmHg) for
min before being back-filled with argon. The silanol was dissolved
in toluene (300 µL), and this solution was added to the above
mixture by syringe. The round-bottomed flask containing silanol
was washed with toluene (100 µL), and that rinse was added to
the reaction mixture. After being stirred at 50 °C for 24 h, the dark-
red, crude reaction mixture was transferred to a 125-mL separatory
2
funnel and diluted with H O (25 mL) and EtOAc (20 mL). The
organic layer was separated, and the aqueous layer was washed
funnel containing deionized H
The organic layer was separated, and the aqueous layer was washed
2
O (60 mL) and EtOAc (20 mL).
with EtOAc (5 × 25 mL). The combined organic layers were dried
4
over MgSO , filtered, and concentrated using rotary evaporation
with EtOAc (5 × 20 mL). The combined organic layers were dried
(23 °C, 20 mmHg). The crude product was purified by column
chromatography (SiO
(20 × 100 mm), hexane/EtOAc 9/1), and
over MgSO
4
and filtered through #4 Whatman filter paper. The
2
1454 J. Org. Chem., Vol. 73, No. 4, 2008
Denmark, Scott E.
