Preparation and reactions of 4-, 5-, and 6-methoxy substituted 3-lithioindoles and 3-indolylzinc derivatives

Article abstract of DOI:10.1055/s-2001-10812

The preparation of 4-, 5-, and 6-methoxy substituted 3-lithio-1-(trialkylsilyl)indoles 4b-d by metalation of the corresponding 3-bromoindoles, and their reactions with iodomethane, DMF, ethylene oxide and aziridines are reported. Transmetalation of 3-lithioindoles 4b-d with ZnCl₂ afforded 3-indolylzinc chlorides 11b-d, which underwent Pd(0)-catalyzed cross-coupling reactions with 2-halopyridines to give 4-, 5-, and 6-methoxy substituted 3-(2-pyridyl)indoles.

Full text of DOI:10.1055/s-2001-10812

PAPER
267
Preparation and Reactions of 4-, 5-, and 6-Methoxy Substituted
3-Lithioindoles and 3-Indolylzinc Derivatives
Mercedes Amat,* Fátima Seffar, Núria Llor, Joan Bosch
Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028-Barcelona, Spain
Fax +34(93)4024539; E-mail: amat@farmacia.far.ub.es
Received 3 July 2000;revised 18 September 2000
intermediates in the synthesis of biologically active indole
alkaloids, such as physostigmine and harmaline, and the
more complex monoterpenoid indole alkaloids reserpine,
sarpagine, mitragynine, ibogaine and vindoline.9
Abstract: The preparation of 4-, 5-, and 6-methoxy substituted
3-lithio-1-(trialkylsilyl)indoles 4b-d by metalation of the corre-
sponding 3-bromoindoles, and their reactions with iodomethane,
DMF, ethylene oxide and aziridines are reported. Transmetalation
of 3-lithioindoles 4b-d with ZnCl2 afforded 3-indolylzinc chlorides
11b-d, which underwent Pd(0)-catalyzed cross-coupling reactions
with 2-halopyridines to give 4-, 5-, and 6-methoxy substituted 3-(2-
pyridyl)indoles.
OR
NR1R2
RO
N(CH3)2
Key words: indoles, lithium, zinc, cross-coupling, pyridylindoles,
silyl protecting groups
N
H
N
H
R = H, R1 = R2 = H Serotonin
R = H, R1 = R2 = Me Bufotenine
R = Me, R1 = H, R2 = Ac Melatonin
R = H Psilocin
R = PO3H2 Psilocybin
In 1994 we reported that 3-lithio-1-(trialkylsilyl)indoles,
prepared by halogen-metal exchange from the corre-
sponding 3-bromo derivatives, are stable species that effi-
Me
MeHN
O
ciently react with
regioselectively give 3-substituted indoles.1 Due to its
steric requirements and non-coordinating abilities,2
a variety of electrophiles to
O
N
N
N
MeO
N
H
H
a
Me
Me
Me
bulky trialkylsilyl group prevents the undesired migration
of the lithium atom from the 3 to the 2 position of the in-
dole ring, which occurs in 3-lithioindoles bearing the
more usual N-benzenesulfonyl protecting group.3
3-Lithio-1-(trialkylsilyl)indoles have proven to be versa-
tile synthetic intermediates with a variety of applications,4
including the preparation of valuable 3-indolylboronic
acids5 and 3-indolylzinc derivatives,6 which can undergo
Pd(0)-catalyzed cross coupling reactions. In particular,
3-indolylzinc halides react in excellent yields with di-
versely substituted 2-halopyridines to give 3-(2-py-
ridyl)indoles, from which we have accomplished the
formal total synthesis of several alkaloids of the Strychnos
and uleine groups.6b
Physostigmine
Harmaline
Figure Structures of some naturally occurring indoles
The required 3-bromo-1-(trialkylsilyl)methoxyindoles
were prepared in excellent yield by silylation of the lithi-
um salt of the corresponding 4-, 5-, and 6-methoxyindoles
1, followed by addition of NBS at -78 °C in a one-pot re-
action. The use of t-BuMe2SiCl gave satisfactory results
in the preparation of bromoindoles 3c and 3d (5- and
6-methoxy series), but the bromo derivative 3a proved to
be unstable and decomposed during column chromatogra-
phy (Scheme 1). For this reason, we prepared the 1-triiso-
propylsilyl derivative 3b, since in a previous work4b we
had observed that N-(triisopropylsilyl)indoles are more
stable towards hydrolysis than the N-(tert-butyldimethyl-
silyl) analogs. In contrast, all attempts to prepare 7-meth-
oxy-1-(trialkylsilyl)indoles 2e by treatment of the lithium
or the sodium salt of 7-methoxyindole with tert-butyldi-
methyl-silyl chloride or the less bulky trimethylsilyl chlo-
ride were unsuccessful, due to the steric hindrance of
the 7-methoxy substituent which lies in the space near to
the nitrogen atom.
In this paper we describe the preparation of 4-, 5-, and
6-methoxy substituted 3-lithio-1-(trialkylsilyl)indoles,
their reactions with electrophiles, and their conversion to
the corresponding 4-, 5-, and 6-methoxy-3-indolylzinc
halides. To our knowledge, 1-(benzenesulfonyl)-5-meth-
oxy-3-lithioindole was the only methoxy substituted
3-lithioindole reported at the begining of our studies,7,8
and their generation and manipulation require tempera-
tures as low as -100 °C to avoid the rearrangement to the
more stable 2-lithio isomer.7 Hydroxyindoles and their
methyl or benzyl ethers have acquired great importance as
synthetic precursors of physiologically active hydroxy-
tryptamines, such as serotonin and the pineal hormone
melatonin, as well as of the naturally occurring hallucino-
gens psilocin, bufotenine, and psilocybin (Figure). Hy-
droxy- and methoxyindoles are also important
Treatment of a THF solution of 3-bromoindoles 3b-d
with 2.2 equivalents of t-BuLi at -78 °C for 10 minutes,
followed by addition of a THF solution of iodomethane at
-78 °C afforded the respective 3-methylindoles 5a, 7a,
and 9a, which were desilylated by treatment with Bu4NF
to give the unprotected 3-methylindoles 6a (Scheme 2),
Synthesis 2001, No. 2, 267–275 ISSN 0039-7881 © Thieme Stuttgart · New York

268
M. Amat et al.
PAPER
R1
SiR3
Br
R1
R1
R1
Sit-BuMe2
Sii-Pr3
a 4-MeO
b 4-MeO
c 5-MeO
d 6-MeO
e 7-MeO
f 4-NO2
NBS/THF
Base/ClSiR3/THF
Sit-BuMe2
Sit-BuMe2
SiR3
N
H
N
3b-d,f,g:
45-92%
N
2a,g: 98%; 2f: 91%
SiR3
SiR3
3
1
2
Sii-Pr
Sii-Pr33
Base: n-BuLi or NaH
g 5-NO2
Scheme 1
8a (Scheme 3), and 10a (Scheme 4) in 50%, 87%, and
89% overall yields, respectively, from the corresponding
3-bromoindoles 3. Minor amounts of the respective 3-un-
substituted indoles 2b-d were also isolated, but not the
starting 3-bromoindoles 3b-d, thus indicating that the
lithio derivatives 4b-d are generated in an essentially
quantitative manner. 4-, 5-, and 6-methoxy substituted
1-(trialkylsilyl)-3-lithioindoles 4b-d proved to be stable
species, which do not undergo rearrangement of the lithi-
um atom to the indole 2-position or the ortho-position10
with respect to the methoxy substituent, even upon warm-
ing to room temperature. Thus, when a solution of
3-lithio-5-methoxyindole 4c was allowed to reach 25 °C,
before the addition of iodomethane, the yield of the pro-
tected 3-methylindole 7a was similar to that obtained at
-78 °C.
MeO
R
MeO
Li
a
b
3c
N
N
Sit-BuMe2
Sit-BuMe2
7
4c
yield: see
experimental
a R = Me
b R = CHO
c R = CH2CH2OH
d R = CH2CH2NHSO2C6H4p-MeO
e R = CH2CH2NHTs
R = CO2t-Bu
g R = CON(CH2)2
c
MeO
R
f
N
H
8
h R = CH2CH2NH2
i R = CH2CH2NHAc Melatonin
Reagents and conditions: a) t-BuLi/THF, -78 °C; b) 7a-i: see expe-
rimental; c) Desilylation: Bu4NF/THF, r.t., 10 min, Conversion of 8e
to 8i: i. NH3(liq)/Na/THF, -78 °C, ii. Ac2O/Et3N/THF, r.t., 3 h
Scheme 3
OMe
OMe
R
Li
a
b
R
Li
3d
a
b
3b
MeO
N
MeO
N
5a: 72%
5b: 54%
N
N
4d
Sit-BuMe2
Sit-BuMe2
9
Sii-Pr3
Sii-Pr3
5
4b
10a: 89%
10b: 74%
c
6a: 69%
6b: 85%
c
a R = Me
b R = CHO
OMe
R
a R = Me
b R = CHO
R
MeO
N
H
N
10
H
6
Reagents and conditions: a) t-BuLi/THF, -78 °C; b) Methylation:
MeI/THF, -78 °C to r.t., Formylation: DMF/THF, -78 °C (reverse
addition), 15 min; c) Bu4NF/THF, r.t., 10 min
Reagents and conditions: a) t-BuLi/THF, -78 °C; b) Methylation:
MeI/THF, -78 °C to r.t., Formylation: DMF/THF, -78 °C (reverse
addition), 15 min; c) Bu4NF/THF, r.t., 10 min
Scheme 4
Scheme 2
ucts, we decided to study the reaction of the 3-lithioindole
4c with ethylene oxide and aziridines. Ring opening of
aziridines with indoles requires the presence of an elec-
tron-withdrawing group on the aziridine nitrogen. Thus,
N-acylaziridines undergo ring opening upon treatment
with indoles in the presence of Lewis acids.11 On the other
hand, the reaction of indolyllithium with N-sulfonyl (tosyl
or mesyl) or N-acylaziridines affords tryptamines along
with the corresponding N-substituted indoles,12 whereas
indolylmagnesium bromide derivatives in the presence of
CuBr•SMe2 afford regioselectively 3-substituted in-
doles.13 As expected, the addition of a saturated THF so-
lution of ethylene oxide to 4c afforded the silylated
5-methoxytryptophol 7c in 56% yield, which was desilyl-
ated to the known14 tryptophol 8c (Scheme 3). Similarly,
When a THF solution of 3-lithioindoles 4b-d was added
to a solution of DMF at -78 °C (reverse addition),
3-formyl-1-(trisopropylsilyl)indole 5b and the desilylated
3-formylindoles 8b and 10b were isolated in 54%, 80%,
and 74% yields, respectively (Schemes 3 and 4). This re-
sult corroborates that the triisopropylsilyl group is more
stable towards hydrolysis than the tert-butyldimethylsilyl
group, thus allowing the isolation of the N-silylated deriv-
atives in 3-acylindoles.4b In these reactions, small
amounts of the corresponding 3-unsubstituted indoles
2b-d were also formed. A subsequent treatment of 5b
with Bu4NF afforded the deprotected 3-formylindole 6b.
Since 5-methoxytryptamine and 5-methoxytryptophol are
important intermediates in the synthesis of natural prod-
Synthesis 2001, No. 2, 267–275 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Preparation and Reactions of 3-Lithioindoles
269
Li
3-lithioindole 4c satisfactorily reacted with N-sulfonyl
ZnCl
MeO
MeO
a
b
(p-methoxybenzenesulfonyl or tosyl) aziridines in the
15
58-73%
N
presence of CuBr•SMe2 and BF3•OEt2
to give
N
SiR3
4b-d
11b-d
tryptamines 7d (61%) and 7e (50%). However, in the ab-
sence of the Lewis acid the reaction failed from both the
3-lithioindole 4c and the corresponding cuprate. Also un-
successful were the attempts to prepare tryptamine deriv-
atives bearing a N-substituent easier to remove than
sulfonyl. Thus, treatment of N-(tert-butoxycarbon-
yl)aziridine16 or N-(benzyloxycarbonyl)aziridine17 with 3-
lithioindole 4c under the above conditions gave a complex
mixture, whereas in the absence of Cu salt and Lewis acid
the 3-acylindoles 8f (43%) or 8g (38%), respectively,
were obtained.18 Desilylation of 7e with Bu4NF, followed
by removal of the tosyl group from the resulting known19
Nb-sulfonyltryptamine 8e with sodium in liquid ammonia,
afforded 5-methoxytryptamine 8h (58% overall yield),
which was then acetylated to give the pineal hormone me-
latonin (8i).
SiR3
N
N
MeO
MeO
c
N
N
H
87-96%
R
CH3
CH3
12b-d
13b-d
b 4-MeO, R = Sii-Pr3
c 5-MeO, R = Sit-BuMe2
d 6-MeO, R = Sit-BuMe2
Reagents and conditions: a) ZnCl2/THF, r.t., 30 min; b) 2-bromo-4-
methylpyridine/(Ph3P)4Pd/THF, reflux, 4 h, c) Bu4NF/THF, r.t., 10
min
Scheme 5
Mps were determined on a Gallenkamp melting point apparatus and
are uncorrected. NMR spectra were recorded on either a Varian
Gemini 200 operating at 200 MHz for 1H and 50.3 MHz for 13C, or
In order to explore the viability of our method for the syn-
thesis of indole derivatives bearing an amino group on the
benzene ring, we also prepared the N-silylated 4- and 5-ni-
tro-3-bromoindoles 3f and 3g, by treatment of 4- and 5-ni-
troindole (1f and 1g, respectively) with NaH, followed by
silylation with triisopropylsilyl chloride and subsequent
halogenation of the resulting silylnitroindoles 2f and 2g
with NBS (Scheme 1). The use of BuLi, instead of NaH,
to generate the indolyl anion of 4-nitroindole 1f was not
satisfactory as a consequence of the concomitant addition
of the organometallic reagent to the benzene ring of in-
dole.20 Unfortunately, treatment of 4-, and 5-nitro substi-
tuted 3-bromoindoles 3f and 3g with t-BuLi, followed by
addition of iodomethane afforded complex mixtures from
which the corresponding 3-methylindoles could not be
isolated.21
1
a Varian Gemini 300 operating at 300 MHz for H and 75.5 MHz
for 13C. Chemical shifts are reported in values ppm relative to TMS
as internal reference. Abbreviations used in NMR analyses are as
follows: s = singlet, d = doublet, t = triplet, dd = doublet of dou-
blets, dt = doublet of triplets, td = triplet of doublets, m = multiplet,
br = broad. IR spectra were recorded on a FTIR Perkin-Elmer 1600
spectrometer with samples prepared as either KBr pellets or thin
films on NaCl salt plates and only noteworthy absorptions are listed.
TLC was done on SiO2 (silica gel 60 F254, Merck), and the spots
were located with aq KMnO4 solution. Column chromatography
was carried out on SiO2 (silica gel 60, SDS, 70-200 microns). Flash
chromatography was carried out on SiO2 (silica gel 60, SDS, 35-70
microns). All reagents were purchased from Aldrich or Fluka and
were used without further purification. Solvents for chromatogra-
phy were distilled at atmospheric pressure prior to use and dried us-
ing standard procedures. Drying of the organic extracts during the
workup of reactions was performed over Na2SO4. Evaporation of
solvents was accomplished with a rotatory evaporator. Microanaly-
ses and HRMS were performed by Centre d’Investigació i Desen-
volupament (CSIC), Barcelona.
As has been mentioned before, 3-(2-pyridyl)indoles can
be prepared by Pd(0)-catalyzed heteroarylation of 3-in-
dolylzinc derivatives with 2-halopyridines. In order to ex-
tend the scope of the method to the synthesis of methoxy
substituted 3-(2-pyridyl)indoles, we generated the 3-in-
dolylzinc chlorides 11b-d by transmetalation of the cor-
responding methoxy-3-lithioindoles 4b-d,22 and then
allowed them to react with 2-bromo-4-methylpyridine in
the presence of Pd(0) in refluxing THF (Scheme 5). The
best conditions were found to be the use of 0.1 equivalent
of Pd(PPh3)4 with respect to the 2-halopyridine. In this
manner, methoxy-3-(2-pyridyl)indoles 12b-d were ob-
tained in 73%, 58%, and 61% yield, respectively. The cor-
responding 3-unsubstituted indoles 2b-d were isolated as
1-(tert-Butyldimethylsilyl)-4-methoxyindole (2a)
A solution of BuLi (0.7 mL of a 1.6 M solution in hexane,
1.1 mmol) was added dropwise to a solution of 4-methoxyindole23
(1a; 100 mg, 0.68 mmol) in anhyd THF (3 mL) cooled to -78 °C,
and the temperature was raised to -10 °C. After 15 min the reaction
mixture was cooled to -50 °C, and TBDMSCl (164 mg, 1.1 mmol)
was added. The solution was warmed to 0 °C, stirred for 3 h, and
poured into H2O (10 mL). The mixture was extracted with CH2Cl2
(3 î 10 mL), and the combined organic extracts were dried, fil-
tered, and concentrated in vacuo. The crude residue was purified by
flash chromatography (SiO2, CH2Cl2) affording pure 2a as a white
solid. Mp 40 – 41 °C; yield: 176 mg (98%).
byproducts, but the formation of 3,3’-biindoles was not IR (film): u = 1260, 1136 cm–1.
1H NMR (CDCl3, 300 MHz): d = 0.63 (s, 6 H, SiCH3), 0.96 [s, 9 H,
C(CH3)3], 3.98 (s, 3 H, OCH3), 6.58 (d, J = 8.0 Hz, 1 H, H-7), 6.77
(m, 1 H, H-3), 7.00-7.21 (m, 3 H, H-2, H-5, and H-6).
13C NMR (CDCl3, 75.5 MHz): d = -4.1 (SiCH3), 19.4 [C(CH3)3],
26.2 [C(CH3)3], 55.1 (OCH3), 99.6 (C-3), 101.8 (C-5), 107.4 (C-7),
121.8 (C-3a), 121.9 (C-6), 129.4 (C-2), 142.4 (C-7a), 153.2 (C-4).
observed. Finally, the deprotected methoxy-3-(2-py-
ridyl)indoles 13b-d were obtained in good yields by
treatment of 12b-d with Bu4NF.
The new organometal methoxyindoles reported here,
namely 3-lithioindoles 4b-d and 3-indolylzinc chlorides
11b-d, are useful and versatile intermediates for the syn-
thesis of indole derivatives.
HRMS: m/z calcd for C15H23NOSi (M+) 261.1549. Found:
261.1539.
Synthesis 2001, No. 2, 267–275 ISSN 0039-7881 © Thieme Stuttgart · New York

270
M. Amat et al.
PAPER
4-, 5-, and 6-Methoxy Substituted 3-Bromo-1-(trialkylsilyl)in-
doles 3b-d; General Procedure
persion in mineral oil, 8.4 mmol) was added and the temperature
was raised to 25 °C. After stirring for 1 h, the mixture was cooled to
-50 °C, and TIPSCl (1.5 g, 11.7 mmol) was added. The stirring was
continued for 3 h at 0 °C and the reaction mixture was poured into
H2O (15 mL). The aqueous phase was extracted with CH2Cl2
(3 î 15 mL) and the combined organic layers were dried (Na2SO4)
and concentrated in vacuo to give crude silylindoles 2f or 2g, which
were purified by flash chromatography (CH2Cl2) on silica gel.
Freshly crystallized N-bromosuccinimide (290 mg, 1.60 mmol) was
added to a cooled (-78 °C) solution of 2f or 2g (400 mg,
1.26 mmol) in anhyd THF (5 mL), and the resulting mixture was
stirred at this temperature for 2 h and warmed to r.t. Hexane (4 mL)
and pyridine (0.05 mL) were added, the resulting suspension was
filtered through a Celite pad, and the filtrate was concentrated in
vacuo. The crude residue was immediately purified by flash chro-
matography on alumina (CH2Cl2/hexane, 7:3).
A 250 mL three-necked round bottom flask equipped with a mag-
netic stirrer was charged with a solution of methoxyindole 1b,23 1c24
or 1d25 (3.0 g, 20.4 mmol) in anhyd THF (84 mL) and flushed with
argon. The flask was submerged in a dry ice/acetone bath, and a so-
lution of BuLi (16.6 mL of a 1.6 M solution in hexane, 26.5 mmol)
was added dropwise. The mixture was warmed to -10 °C, stirred
for 15 min, and cooled to -50 °C. Then, a solution of the trialkyl-
silyl chloride (t-BuMe2SiCl or i-Pr3SiCl, 26.5 mmol) in anhyd THF
(20 mL) was added dropwise, and the mixture was stirred at 0 °C for
3 h. The solution was cooled to -78 °C, and freshly crystallized
N-bromosuccinimide (4.7 g, 26.5 mmol) was added. After stirring
for 2 h, the mixture was warmed to 25 °C, and hexane (60 mL) and
pyridine (0.6 mL) were added. The resulting suspension was filtered
through a Celite pad, the filtrate was concentrated in vacuo, and the
crude residue was immediately purified by flash chromatography
on alumina (CH2Cl2/hexane, 1:1).
4-Nitro-1-(triisopropylsilyl)indole (2f)
Yield: 1.8 g (91%). Yellow solid, mp 58 – 59 °C.
3-Bromo-4-methoxy-1-(triisopropylsilyl)indole (3b)
Yield: 6.8g (87%). White solid, mp 64 – 65 °C.
IR (film): u = 1259, 1133, 736 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.13 (d, J = 7.5 Hz, 18 H, CH3),
1.65 (m, 3 H, SiCH), 3.94 (s, 3 H, OCH3), 6.56 (dd, J = 6.2, 2.3 Hz,
1 H, H-5), 7.05-7.13 (m, 3 H, H-2, H-6, and H-7).
13C NMR (CDCl3, 75.5 MHz): d = 12.7 (SiCH), 18.0 (CH3), 55.4
(OCH3), 90.3 (C-3), 100.8 (C-5), 107.4 (C-7), 118.9 (C-3a), 122.9
(C-6), 129.3 (C-2), 141.9 (C-7a), 153.6 (C-4).
IR (film): u = 1513, 1322, 1281 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.15 (d, J = 7.5 Hz, 18 H, CH3),
1.69 (m, 3 H, SiCH), 7.28 (t, J = 8.0 Hz, 1 H, H-6), 7.41 (dd,
J = 3.2, 0.8 Hz, 1 H, H-3), 7.51 (d, J = 3.2 Hz, 1 H, H-2), 7,81 (d,
J = 8.0 Hz, 1 H, H-7), 8.14 (d, J = 8.1 Hz, 1 H, H-5).
13C NMR (CDCl3, 75.5 MHz): d = 12.8 (SiCH), 17.9 (CH3), 105.2
(C-3), 117.7 (C-5), 120.2 (C-6 and C-7), 125.8 (C-3a), 135.9 (C-2),
140.4 (C-7a), 143.0 (C-4).
3-Bromo-4-nitro-1-(triisopropylsilyl)indole (3f)
Anal. calcd for C18H28BrNOSi (382.4): C, 56.53; H, 7.38; N, 3.66.
Found: C, 56.67; H, 7.61; N, 3.62.
Yield: 225 mg (45%). Yellow solid, mp 69 – 70 °C.
IR (film): u = 1517, 1351, 884, 733 cm–1.
3-Bromo-1-(tert-butyldimethylsilyl)-5-methoxyindole (3c)
Yield: 5.4 g (78%). White solid, mp 65 – 67 °C.
IR (film): u = 1261, 1211, 1167, 1028, 791 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.15 (d, J = 7.5 Hz, 18 H, CH3),
1.69 (m, 3 H, SiCH), 7.24 (t, J = 8.0 Hz, 1 H, H-6), 7.45 (br s, 1 H,
H-2), 7.71 (d, J = 8.0 Hz, 1H , H-7), 7.72 (d, J = 8.0 Hz, 1 H, H-5).
1H NMR (CDCl3, 300 MHz): d = 0.58 (s, 6 H, SiCH3), 0.92 [s, 9 H,
C(CH3)3], 3.89 (s, 3 H, OCH3), 6.85 (dd, J = 9.0, 2.5 Hz, 1 H, H-6),
6.98 (d, J = 2.5 Hz, 1 H, H-4), 7.14 (s, 1 H, H-2), 7,35 (d, J = 9.0
Hz, 1 H, H-7).
13C NMR (CDCl3, 75.5 MHz): d = -4.1 (SiCH3), 19.3 [C(CH3)3],
29.2 [C(CH3)3], 55.7 (OCH3), 93.2 (C-3), 100.2 (C-4), 113.0 (C-6),
114.9 (C-7), 130.2 (C-2 and C-3a), 135.0 (C-7a), 154.7 (C-5).
13C NMR (CDCl3, 75.5 MHz): d = 12.7 (SiCH), 17.9 (CH3), 117.3
(C-6), 118.7 (C-7), 121.0 (C-5), 121.1 (C-3a), 135.3 (C-2), 142.4
(C-7a), 142.5 (C-4).
Anal. calcd for C17H25BrN2O2Si (397.4): C, 51.38; H, 6.34; N, 7.05.
Found: C, 51.54; H, 6.63; N, 6.93.
5-Nitro-1-(triisopropylsilyl)indole (2g)
Yield: 1.9 g (98%). Yellow solid, mp 50 – 51 °C.
Anal. calcd for C15H22BrNOSi (340.3): C, 52.90; H, 6.52; N, 4.12.
Found: C, 52.60; H, 6.44; N, 4.28.
IR (film): u = 1508, 1343, 1285 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.15 (d, J = 7.5 Hz, 18 H, CH3),
1.71 (m, 3 H, SiCH), 6.79 (d, J = 3.2 Hz, 1 H, H-3), 7.40 (d, J = 3.2
Hz, 1 H, H-2), 7.52 (d, J = 9.3 Hz, 1 H, H-7), 8.06 (dd, J = 9.3, 2.5
Hz, 1 H, H-6), 8.57 (d, J = 2.5 Hz, 1 H, H-4).
3-Bromo-1-(tert-butyldimethylsilyl)-6-methoxyindole (3d)
Yield: 6.4 g (92%). White solid, mp 50 – 52 °C.
IR (film): u = 1300, 1210, 1171, 1130, 1025, 798 cm–1.
1H NMR (CDCl3, 300 MHz): d = 0.58 (s, 6 H, SiCH3), 0.94 [s, 9 H,
C(CH3)3], 3.84 (s, 3 H, OCH3), 6.86 (dd, J = 8.6, 2.0 Hz, 1 H, H-5),
6.97 (d, J = 2.0 Hz, 1 H, H-7), 7.05 (s, 1 H, H-2), 7.43 (d, J = 8.6
Hz, 1 H, H-4).
13C NMR (CDCl3, 75.5 MHz): d = -4.1 (SiCH3), 19.4 [C(CH3)3],
26.2 [C(CH3)3], 55.6 (OCH3), 93.4 (C-3), 98.3 (C-7), 109.9 (C-5),
119.5 (C-4), 124.3 (C-3a), 128.3 (C-2), 141.0 (C-7a), 156.6 (C-6).
13C NMR (CDCl3, 75.5 MHz): d = 12.7 (SiCH), 17.9 (CH3), 106.8
(C-3), 113.4 (C-7), 116.8 (C-6), 117.3 (C-4), 130.8 (C-3a), 134.3
(C-2), 141.6 (C-7a), 144.1 (C-5).
3-Bromo-5-nitro-1-(triisopropylsilyl)indole (3g)
Yield: 364 mg (73%). Yellow solid, mp 65 – 66 °C.
IR (film): u = 1510, 1344, 732 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.15 (d, J = 7.5 Hz, 18 H, CH3),
1.70 (m, 3 H, SiCH), 7.38 (s, 1 H, H-2), 7.52 (d, J = 9.3 Hz, 1 H, H-
7), 8.10 (dd, J = 9.3, 2.5 Hz, 1 H, H-6), 8.53 (d, J = 2.5 Hz, 1 H, H-
4).
13C NMR (CDCl3, 75.5 MHz): d = 12.7 (SiCH), 17.8 (CH3), 95.5
(C-3), 114.1 (C-7), 116.3 (C-6), 117.8 (C-4), 129.7 (C-3a), 132.9
(C-2), 142.3 (C-7a), 143.4 (C-5).
Anal. calcd for C15H22BrNOSi (340.3): C, 52.94; H, 6.52; N, 4.12.
Found: C, 52.94; H, 6.65; N, 4.03.
4- and 5-Nitro Substituted 3-Bromo-1-(triisopropylsilyl)indoles
3f and 3g; General Procedure
A 100 mL three-necked round bottom flask equipped with a mag-
netic stirrer was charged with a solution of nitroindole 1f26 or 1g
(1.0 g, 6.2 mmol) in anhyd THF (16 mL), flushed with N2, and the
solution was cooled to -78 °C. Then, NaH (368 mg of a 55% dis-
Anal. calcd for C17H25BrN2O2Si (397.4): C, 51.38; H, 6.34; N, 7.05.
Found: C, 51.33; H, 6.43; N, 6.98.
Synthesis 2001, No. 2, 267–275 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Preparation and Reactions of 3-Lithioindoles
5-Methoxy Series
271
3-Lithioindoles 4b-d; General Procedure
A solution of t-BuLi (2.2 equiv of a 1.7 M solution in pentane) was
added to a 0.33 M solution of the bromoindole 3b, 3c or 3d in anhyd
THF cooled to -78 °C, and the mixture was stirred under argon for
10 min.
A mixture (9:1, 390 mg) of indoles 7a and 2c, which could not be
completely separated, was obtained after flash chromatography
(SiO2, CH2Cl2/hexane). Compound 8a (206 mg, 87% overall yield
from bromoindole 3c) was obtained from the above mixture of 7a
and 2c (390 mg) following the general procedure for desilylation.
Eluent for chromatography: CH2Cl2/hexane (7:3).
Methylation of 3-Lithioindoles 4b-d; General Procedure
A 3.5 M solution of MeI (2.7 equiv) in anhyd THF was added to a
solution of the 3-lithioindole 4b-d, prepared from the correspond-
ing 3-bromoindole 3b-d (500 mg) as described above, and the mix-
ture was stirred at -78 °C for 15 min. The mixture was allowed to
warm up to r.t. and poured into sat aq Na2CO3 (10 mL). The aqueous
layer was extracted with Et2O (3 î 10 mL), and the combined or-
ganic extracts were dried (Na2SO4) and concentrated in vacuo to
give a mixture of the 3-methylindole and the respective 3-unsubsti-
tuted indole.
1-(tert-Butyldimethylsilyl)-5-methoxy-3-methylindole (7a)
Yellow oil.
IR (film): u = 1258, 1230, 1190 cm–1.
1H NMR (CDCl3, 300 MHz): d = 0.59 (s, 6 H, SiCH3), 0.96 [s, 9 H,
C(CH3)3], 2.34 (s, 3 H, CH3), 3.92 (s, 3 H, OCH3), 6.86 (dd, J = 8.9,
2.2 Hz, 1 H, H-6), 6.96 (br s, 1 H, H-2), 7.03 (d, J = 2.2 Hz, 1 H, H-
4), 7.40 (d, J = 8.9 Hz, 1 H, H-7).
13C NMR (CDCl3, 75.5 MHz): d = -4.2 (SiCH3), 9.6 (CH3), 19.3
[C(CH3)3], 26.1 [C(CH3)3], 55.4 (OCH3), 100.4 (C-4), 111.0 (C-6),
113.0 (C-3), 114.2 (C-7), 128.8 (C-2), 132.1 (C-3a), 136.2 (C-7a),
153.7 (C-5).
Deprotection of Silylindoles; General Procedure
A 1.0 M solution of Bu4NF(1.1 equiv) in THF was added to a 0.2 M
solution of the silylindole in anhyd THF, and the mixture was
stirred at r.t. for 10 min. After quenching with sat aq Na2CO3, the
mixture was extracted with CH2Cl2, the combined organic layers
were dried (Na2SO4) and concentrated in vacuo, and the residue was
chromatographed (flash, SiO2).
3-Methyl-5-methoxyindole (8a)27
1H NMR (CDCl3, 300 MHz): d = 2.30 (s, 3 H, CH3), 3.87 (s, 3 H,
OCH3), 6.85 (dd, J = 8.7, 2.5 Hz, 1 H, H-6), 6.95 (m, 1 H, H-2),
7.01 (d, J = 2.5 Hz, 1 H, H-4), 7.23 (d, J = 8.7 Hz, 1 H, H-7), 7.8
(br s, 1 H, NH).
4-Methoxy Series
13C NMR (CDCl3-CD3OD, 75.5 MHz): d = 9.5 (CH3), 55.8 (OCH3),
100.5 (C-4), 111.0 (C-3), 111.6 (C-6 and C-7), 122.6 (C-2), 128.3
(C-3a), 131.4 (C-7a), 153.4 (C-5).
Indoles 5a (oil, 300 mg, 72% yield) and 2b (white solid, 100 mg)
were obtained after flash chromatography (SiO2, CH2Cl2/hexane,
1:1). Compound 6a (140 mg, 69% yield) was obtained from pure 5a
(400 mg) following the general procedure for desilylation. Eluent
for chromatography: CH2Cl2/hexane (1:1).
6-Methoxy Series
A mixture (93:7, 402 mg) of indoles 9a and 2d, which could not be
completely separated, was obtained after flash chromatography
(SiO2, CH2Cl2/hexane). Compound 10a (211 mg, 89% overall yield
from bromoindole 3d) was obtained from the above mixture of 9a
and 2d (402 mg) following the general procedure for desilylation.
Eluent for chromatography: CH2Cl2/hexane (9:1).
4-Methoxy-3-methyl-1-(triisopropylsilyl)indole (5a)
IR (film): u = 1259, 1150 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.12 (d, J = 7.5 Hz, 18 H, CH3),
1.65 (m, 3 H, SiCH), 2.46 (s, 3 H, CH3), 3.89 (s, 3 H, OCH3), 6.47
(d, J = 7.5 Hz, 1 H, H-5), 6.82 (br s, 1 H, H-2), 6.99 (t, J = 7.5 Hz,
1 H, H-6), 7.05 (d, J = 7.5 Hz, 1 H, H-7).
13C NMR (CDCl3, 75.5 MHz): d = 12.5 (CH3), 12.7 (SiCH), 18.2
(CH3), 55.0 (OCH3), 99.4 (C-5), 107.4 (C-7), 113.7 (C-3), 120.9 (C-
3a), 121.8 (C-6), 127.1 (C-2), 143.0 (C-7a), 154.9 (C-4).
1-(tert-Butyldimethylsilyl)-6-methoxy-3-methylindole (9a)
Yellow oil.
IR (film): u = 1619, 1484, 1202, 1130 cm–1.
1H NMR (CDCl3, 300 MHz): d = 0.56 (s, 6 H, SiCH3), 0.94 [s, 9 H,
C(CH3)3], 2.28 (s, 3 H, CH3), 3.84 (s, 3 H, OCH3), 6.80 (dd, J = 8.7,
2.2 Hz, 1 H, H-5), 6.82 (s, 1 H, H-2), 6.98 (d, J = 2.2 Hz, 1 H, H-7),
7.41 (d, J = 8.7 Hz, 1 H, H-4).
4-Methoxy-1-(triisopropylsilyl)indole (2b)
IR (film): u = 1488, 1259, 1133 cm–1.
13C NMR (CDCl3, 75.5 MHz): d = -4.1 (SiCH3), 19.5 [C(CH3)3],
26.3 [C(CH3)3], 55.6 (OCH3), 98.3 (C-7), 108.2 (C-5), 113.3 (C-3),
118.9 (C-4), 125.7 (C-3a), 126.9 (C-2), 125.7 (C-3a), 142.0 (C-7a),
155.8 (C-6).
1H NMR (CDCl3, 300 MHz): d = 1.12 (d, J = 7.5 Hz, 18 H, CH3),
1.68 (m, 3 H, SiCH), 3.94 (s, 3 H, OCH3), 6.52 (d, J = 7.8 Hz, 1 H,
H-5), 6.72 (d, J = 3.2 Hz, 1 H, H-3), 7.05 (t, J = 7.8 Hz, 1 H, H-6),
7.13 (d, J = 7.8 Hz, 1 H, H-7), 7.14 (d, J = 3.2 Hz, 1 H, H-2).
6-Methoxy-3-methylindole (10a)28
13C NMR (CDCl3, 75.5 MHz):d = 12.8 (SiCH), 18.0 (CH3), 55.1
(OCH3), 99.5 (C-3), 101.7 (C-5), 107.0 (C-3a), 107.3 (C-7), 121.9
(C-6), 129.5 (C-2), 142.1 (C-7a), 153.1 (C-4).
HRMS: m/z calcd for C18H29NOSi (M+) 303.2018. Found:
303.2007.
1H NMR (CDCl3, 300 MHz): d = 2.30 (s, 3 H, CH3), 3.84 (s, 3 H,
OCH3), 6.79 (dd, J = 8.5, 2.3 Hz, 1 H, H-5), 6.83 (d, J = 2.3 Hz, 1
H, H-7), 6.85 (m, 1 H, H-2), 7.45 (d, J = 8.5 Hz, 1 H, H-4), 7.73 (br
s, 1 H, NH).
13C NMR (CDCl3, 75.5 MHz): d = 9.7 (CH3), 55.6 (OCH3), 94.5 (C-
7), 108.9 (C-5), 111.5 (C-3), 119.4 (C-4), 120.3 (C-2), 122.7 (C-3a),
136.9 (C-7a), 156.3 (C-6).
4-Methoxy-3-methylindole (6a)
White solid, mp 50 °C.
IR (film): u = 3389, 1506, 1259 cm–1.
1H NMR (CDCl3, 300 MHz): d = 2.47 (s, 3 H, CH3), 3.89 (s, 3 H,
OCH3), 6.45 (d, J = 8.0 Hz, 1 H, H-5), 6.76 (m, 1 H, H-2), 6.89 (dd,
J = 8.0, 0.7 Hz, 1 H, H-7), 7.05 (t, J = 8.0 Hz, 1 H, H-6), 7.70 (br s,
1 H, NH).
13C NMR (CDCl3, 75.5 MHz): d = 12.2 (CH3), 55.1 (OCH3), 99.2
(C-5), 104.4 (C-7), 112.1 (C-3), 117.9 (C-3a), 120.2 (C-6), 122.6
(C-2), 138.0 (C-7a), 155.2 (C-4).
Formylation of 3-Lithioindoles 4b-d; General Procedure
A solution of 3-lithioindole 4b-d, prepared from 500 mg of the cor-
responding 3-bromoindole 3b-d as described above, was added via
canula to a 3.5 M solution of DMF (3.0 equiv) in anhyd THF, and
the mixture was stirred at -78 °C for 15 min. Aqueous workup was
carried out as described in the above general procedure for methyl-
ation to give a mixture of the 3-formylindole and the respective
3-unsubstituted indole, which were separated by flash chromatogra-
phy (SiO2).
HRMS: m/z calcd for C10H11NO (M+) 161.0841. Found: 161.0823.
Synthesis 2001, No. 2, 267–275 ISSN 0039-7881 © Thieme Stuttgart · New York

272
M. Amat et al.
PAPER
4-Methoxy Series
Indoles 5b (235 mg, 54% yield) and 2b (155 mg) were obtained.
Eluent for chromatography: CH2Cl2/hexane (8:2).
13C NMR (CDCl3, 75.5 MHz): d = -4.1 (SiCH3), 19.6 [C(CH3)3],
26.3 [C(CH3)3], 55.6 (OCH3), 98.3 (C-7), 104.5 (C-3), 108.9 (C-5),
120.8 (C-4), 125.6 (C-3a), 129.8 (C-2), 141.7 (C-7a), 155.7 (C-6).
3-Formyl-4-methoxy-1-(triisopropylsilyl)indole (5b)
1-(tert-Butyldimethylsilyl)-3-(2-hydroxyethyl)-5-methoxyin-
dole (7c)
White solid, mp 130 – 131 °C.
IR (film) 1650, 1508 cm–1.
A saturated solution of ethylene oxide in anhyd THF (2 mL) was
added via canula to a solution of 3-lithioindole 4c, prepared from
3-bromoindole 3c (500 mg) as described above, and the mixture
was stirred at -78 °C for 15 min. The resulting mixture was poured
into aq sat Na2CO3 (10 mL), and the aqueous layer was extracted
with CH2Cl2. The combined organic extracts were dried (Na2SO4)
and concentrated in vacuo. The residue was chromatographed
(flash, SiO2, CH2Cl2/AcOEt, 9:1) to give 7c (250 mg, 56% yield) as
a colorless oil and 2c (150 mg).
1H NMR (CDCl3, 300 MHz): d = 1.14 (d, J = 7.5 Hz, 18 H, CH3),
1.71 (m, 3 H, SiCH), 3.98 (s, 3 H, OCH3), 6.72 (dd, J = 5.2, 3.5 Hz,
1 H, H-5), 7.15 (m, 2 H, H-6 and H-7), 7.97 (s, 1 H, H-2), 10.11 (s,
1 H, CHO).
13C NMR (CDCl3, 75.5 MHz): d = 12.6 (SiCH), 17.9 (CH3), 55.3
(OCH3), 102.4 (C-5), 107.8 (C-7), 111.4 (C-3a), 121.4 (C-7a),
123.4 (C-6), 135.5 (C-2), 143.0 (C-3), 154.5 (C-4), 188.6 (s, 1H,
CHO).
3-Formyl-4-methoxyindole (6b)29
Compound 6b (190 mg, 85% yield) was obtained as a white solid
from pure 5b (424 mg) following the general procedure for desilyl-
ation. Eluent for chromatography: CH2Cl2.
1H NMR (CDCl3, 300 MHz): d = 4.06 (s, 3 H, OCH3), 6.73 (d,
J = 8.0 Hz, 1 H, H-5), 7.09 (d, J = 8.0 Hz, 1 H, H-7), 7.22 (t, J = 8.0
Hz, 1 H, H-6), 7.93 (d, J = 3.2 Hz, 1 H, H-2), 9.2 (br s, 1 H, NH),
10.5 (s, 1 H, CHO).
13C NMR (CDCl3, 75.5 MHz): d = 55.3 (OCH3), 102.5 (C-5), 105.4
(C-7), 119.3 (C-3), 124.2 (C-6), 128.9 (C-2), 137.8 (C-7a), 154.4
(C-4), 188.8 (CHO).
IR (film): u = 3425, 1478, 1220, 1036 cm–1.
1H NMR (CDCl3, 300 MHz): d = 0.60 (s, 6 H, SiCH3), 0.92 [s, 9 H,
C(CH3)3], 3.0 (t, J = 6.6 Hz, 2 H, CH2), 3.87 (s, 3 H, OCH3), 3.89
(t, J = 6.6 Hz, 2 H, CH2OH), 6.82 (dd, J = 8.9, 2.5 Hz, 1 H, H-6),
7.01 (s, 1 H, H-2), 7.03 (d, J = 2.5 Hz, 1 H, H-4), 7.37 (d, J = 8.9
Hz, 1 H, H-7).
13C NMR (CDCl3, 75.5 MHz): d = -4.1 (SiCH3), 19.4 (SiC), 26.2
(CH3), 28.7 (CH2), 55.7 (OCH3), 62.4 (CH2OH), 100.5 (C-4), 111.4
(C-6), 113.7 (C-3), 114.6 (C-7), 129.9 (C-2), 131.2 (C-3a), 136.5
(C-7a), 153.8 (C-5).
3-(2-Hydroxyethyl)-5-methoxyindole (8c)14
Compound 8c (142 mg, 84%) was obtained from 7c (270 mg) fol-
lowing the general procedure for desilylation. Eluent for chroma-
tography (flash, SiO2): CH2Cl2/EtOAc (8:2).
1H NMR (CDCl3, 300 MHz): d = 2.96 (t, J = 6.6 Hz, 2 H, H-1’),
3.83 (s, 3 H, OCH3), 3.86 (t, J = 6.6 Hz, 2 H, H-2’), 6.84 (dd,
J = 8.7, 2.4 Hz, 1 H, H-6), 6.95 (d, J = 2.4 Hz, 1 H, H-2), 7.03 (d,
J = 2.4 Hz, 1 H, H-4), 7.18 (d, J = 8.7 Hz, 1 H, H-7), 8.15 (br s, 1
H, NH).
5-Methoxy Series
Indoles 8b (205 mg, 80% yield) and 2c (20 mg), were obtained. Elu-
ent for chromatography: CH2Cl2.
3-Formyl-5-methoxyindole (8b)30
1H NMR (CDCl3, 300 MHz): d = 3.89 (s, 3 H, OCH3), 6.33 (dd,
J = 9.0, 2.5 Hz, 1 H, H-6), 7.33 (d, J = 9.0 Hz, 1 H, H-7), 7.81 (m,
2 H, H-2 and H-4), 8.75 (br s, 1 H, N-H), 10.0 (s, 1 H, CHO).
13C NMR (CDCl3, 75.5 MHz): d = 55.8 (OCH3), 103.1 (C-4), 112.4
(C-6), 115.0 (C-7), 119.6 (C-3), 125.2 (C-3a), 131.4 (C-7a), 135.6
(C-2), 156.6 (C-5), 185.2 (CHO).
13C NMR (CDCl3, 75.5 MHz): d = 28.5 (C-1’), 55.8 (OCH3), 62.4
(C-2’), 100.4 (C-4), 111.4 (C-6), 111.9 (C-3), 123.3 (C-2), 127.5 (C-
3a), 131.4 (C-7a), 153.5 (C-5).
1-(tert-Butyldimethylsilyl)-5-methoxyindole (2c)4a
1H NMR (CDCl3, 300 MHz): d = 0.57 (s, 6 H, SiCH3), 0.91 [s, 9 H,
C(CH3)3], 3.84 (s, 3 H, OCH3), 6.53 (dd, J = 3.3, 0.7 Hz, 1 H, H-3),
6.80 (dd, J = 9.0, 2.5 Hz, 1 H, H-6), 7.08 (d, J = 2.5 Hz, 1 H, H-4),
7.14 (d, J = 3.3 Hz, 1 H, H-2), 7.38 (d, J = 9.0 Hz, 1 H, H-7).
1-(tert-Butyldimethylsilyl)-5-methoxy-N-(4-methoxybenzene-
sulfonyl)tryptamine (7d)
A solution of t-BuLi (1.14 mL of a 1.7 M solution in pentane,
1.94 mmol) was added dropwise to a solution of 3-bromoindole 3c
(300 mg, 0.88 mmol) in anhyd Et2O (3.0 mL) cooled to -78 °C, and
the mixture was stirred under argon for 10 min. CuBr•SMe2 (96 mg,
0.46 mmol) was added, and the stirring was continued for 15 min at
the same temperature. Then, a solution of 1-(4-methoxybenzene-
sulfonyl)aziridine32 (375 mg, 1.76 mmol) and BF3•OEt2 (265 mL,
2.1 mmol) in anhyd Et2O (6 mL) was added via canula to the above
mixture. After stirring at -78 °C for 4 h, the reaction was quenched
with sat aq Na2CO3 (10 mL). The mixture was extracted with
CH2Cl2 (3 î 15 mL), and the combined organic extracts were dried
(Na2SO4) and concentrated in vacuo to give a residue. Flash chro-
matography (SiO2, hexane/EtOAc, 8:2) afforded pure 7d (257 mg,
61% yield) as a white solid, mp 85 – 86 °C.
13C NMR (CDCl3, 75.5 MHz): d = -4.05 (SiCH3), 19.4 [C(CH3)3],
26.3 [C(CH3)3], 55.7 (OCH3), 112.2 (C-3), 104.5 (C-4), 11.3 (C-6),
114.4 (C-7), 131.7 (C-2), 131.8 (C-3a), 135.9 (C-7a), 154.0 (C-5).
6-Methoxy Series
Indoles 10b (190 mg, 74% yield) and 2d (40 mg) were obtained.
Eluent for chromatography: CH2Cl2/hexane (8:2).
3-Formyl-6-methoxyindole (10b)31
1H NMR (CDCl3, 300 MHz): d = 3.86 (s, 3 H, OCH3), 6.91 (d,
J = 2.0 Hz, 1 H, H-7), 6.97 (dd, J = 8.6, 2.0 Hz, 1 H, H-5), 7.75 (d,
J = 3.0 Hz, 1 H, H-2), 8.19 (d, J = 8.6 Hz, 1 H, H-4), 8.7 (br s, 1 H,
NH), 10.0 (s, 1 H, CHO).
13C NMR (CDCl3/CD3OD, 75.5 MHz): d = 55.5 (OCH3), 95.4 (C-
7), 112.0 (C-5), 118.4 (C-3), 118.9 (C-3a), 122.1 (C-4), 136.3 (C-
2), 138.0 (C-7a), 157.4 (C-6), 185.5 (CHO).
IR (KBr): u = 3480, 1550, 1317, 1162 cm–1.
1H NMR (CDCl3, 300 MHz): d = 0.56 (s, 6 H, SiCH3), 0.90 [s, 9 H,
C(CH3)3], 2.89 (t, J = 6.6 Hz, 2 H, CH2), 3.25 (m, 2 H, CH2N), 3.80
(s, 3 H, OCH3), 3.85 (s, 3 H, OCH3), 4.30 (t, J = 6.3 Hz, 1 H, NH),
6.80 (m, 2 H, H-4 and H-6), 6.87 (dm, J = 9.0 Hz, 2 H, m-H), 6.90
(s, 1 H, H-2), 7.35 (d, J = 9.6 Hz, 1 H, H-7), 7.66 (dm, J = 9.0 Hz,
2 H, o-H).
13C NMR (CDCl3, 75.5 MHz): d = -4.1 (SiCH3), 19.4 [C(CH3)3],
25.5 (CH2), 26.3 [C(CH3)3], 42.7 (NCH2), 55.5 (OCH3), 55.7
(OCH3), 100.3 (C-4), 111.6 (C-6), 113.1 (C-3), 114.1 (2 m-C),
1-(tert-Butyldimethylsilyl)-6-methoxyindole (2d)5b
1H NMR (CDCl3, 300 MHz): d = 0.62 (s, 6 H, SiCH3), 0.97 [s, 9 H,
C(CH3)3], 3.87 (s, 3 H, OCH3), 6.56 (dd, J = 3.2, 0.8 Hz, 1 H, H-3),
6.83 (dd, J = 8.7, 2.2 Hz, 1 H, H-5), 7.05 (d, J = 2.2 Hz, 1 H, H-7),
7.09 (d, J = 3.2 Hz, 1 H, H-2), 7.52 (d, J = 8.7 Hz, 1 H, H-4).
Synthesis 2001, No. 2, 267–275 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Preparation and Reactions of 3-Lithioindoles
273
114.7 (C-7), 129.1 (2 o-C), 130.0 (C-2), 130.7 (i-C), 131.3 (C-3a),
136.5 (C-7a), 153.9 (C-5), 162.7 (p-C).
3-lithioindoles 4b-d in THF prepared as described above, and the
mixture was stirred at r.t. for 30 min. A 0.1 M solution of Pd(PPh3)4
(0.1 equiv) in anhyd THF was added to a 0.5 M solution of 2-bro-
mo-4-methylpyridine34 (1 equiv) in anhyd THF. The mixture was
stirred at r.t. for 10 min and then transferred via canula to a solution
of indolylzinc chloride 11b-d (1.5 equiv) prepared as described
above. The resulting mixture was heated at reflux for 4 h, cooled,
and poured into sat aq Na2CO3. The combined aqueous layers were
extracted with Et2O, and the organic extracts were dried (Na2SO4)
and concentrated to give a mixture of the 3-(2-pyridyl)indole 12b-
d and the corresponding 3-unsubstituted indoles 2b-d, which were
separated by flash chromatography (SiO2).
Anal. calcd for C24H34N2O4SSi (474.7): C, 60.73; H, 7.22; N, 5.90.
Found: C, 60.85; H, 7.31; N, 5.94.
1-(tert-Butyldimethylsilyl)-5-methoxy-N-(4-methylbenzene-
sulfonyl)tryptamine (7e)
Operating as described for 7d, from 3-bromoindole 3c (250 mg,
0.74 mmol) and 1-(4-methylbenzenesulfonyl)aziridine33 (292 mg,
1.48 mmol), pure compound 7e (169 mg, 50% yield) was obtained
as a white solid, (mp 92 – 93 °C) after flash chromatography (SiO2,
hexane/EtOAc, 7:3).
IR (film): u = 3450, 1699, 1479, 1216, 1148 cm–1.
4-Methoxy Series
1H NMR (CDCl3, 300 MHz): d = 0.56 (s, 6 H, SiCH3), 0.90 [s, 9 H,
C(CH3)3], 2.39 (s, 3H, ArCH3), 2.89 (t, J = 6.6 Hz, 2 H, CH2), 3.25
(m, 2 H, CH2N), 3.80 (s, 3 H, OCH3), 4.42 (t, J = 6.0 Hz, 1 H, NH),
6.80 (m, 2 H, H-4 and H-6), 6.90 (s, 1 H, H-2), 7.20 (d, J = 8.0 Hz,
2 H, m-H), 7.34 (d, J = 9.6 Hz, 1 H, H-7), 7.62 (d, J = 8.0 Hz, 2 H,
o-H).
From 2-bromo-4-methylpyridine (180 mg, 1.05 mmol) and 3-bro-
moindole 3b (600 mg, 1.57 mmol) were obtained pyridylindole 12b
(300 mg, 73% yield) and 4-methoxyindole 2b (224 mg). Eluent for
chromatography: CH2Cl2/EtOH (98:2).
4-Methoxy-3-(4-methyl-2-pyridyl)-1-(triisopropylsilyl)indole
(12b)
13C NMR (CDCl3, 75.5 MHz): d = -4.1 (SiCH3), 19.4 [C(CH3)3],
21.4 (ArCH3), 25.5 (CH2), 26.3 [C(CH3)3], 42.8 (CH2N), 55.6
(OCH3), 100.2 (C-4), 111.6 (C-6), 113.1 (C-3), 114.7 (C-7), 126.9
(2 m-C), 129.5 (2 o-C), 130.0 (C-2), 130.7 (C-3a), 136.5 (C-7a),
136.7 (i-C), 143.2 (p-C), 153.9 (C-5).
Solid, mp 57 – 58 °C.
IR (film): u = 1603, 1226, 1269, 1105 cm–1.
1H NMR (CDCl3, 300 MHz, assignments aided by H-13C HET-
1
COR): d = 1.18 (d, J = 7.4 Hz, 18 H, CH3), 1.75 (m, 3 H, CH), 2.40
(s, 3 H, CH3), 3.87 (s, 3 H, OCH3), 6.62 (dd, J = 7.8, 1.0 Hz, 1 H,
H-5), 6.95 (dm, J = 5.0 Hz, 1 H, H-5’), 7.11 (t, J = 7.8 Hz, 1 H, H-
6), 7.18 (dd, J = 7.8, 1.0 Hz, 1 H, H-7), 7.60 (s, 1 H, H-2), 7.66 (m,
1 H, H-3’), 8.46 (d, J = 5.0 Hz, 1 H, H-6’).
13C NMR (CDCl3, 75.5 MHz): d = 12.8 (SiCH), 18.2 [SiCH(CH3)2],
21.2 (CH3), 55.1 (OCH3), 101.2 (C-5), 107.7 (C-7), 118.5 (C-3a),
120.3 (C-3), 121.3 (C-5’), 122.1 (C-6), 125.9 (C-3’), 131.7 (C-2),
143.4 (C-7a), 145.8 (C-4’), 148.3 (C-6’), 154.0 (C-4), 154.8 (C-2’).
N-[2-(5-Methoxyindol-3-yl)ethyl]4-methylbenzenesulfonamide
(8e)19
Compound 8e (113 mg, 89%) was obtained from 7e (168 mg,
0.36 mmol) following the general procedure for desilylation. Eluent
for chromatography (flash, SiO2): CH2Cl2/EtOAc (7:3).
1H NMR (CDCl3, 300 MHz): d = 2.39 (s, 3 H, ArCH3), 2.74 (s, 1 H,
NH), 2.89 (t, J = 6.6 Hz, 2 H, CH2), 3.21 (t, J = 6.6 Hz, 2 H, CH2N),
3.80 (s, 3 H, OCH3), 6.82 (m, 2 H, H-4 and H-6), 6.95 (s, 1 H, H-2),
7.22 (m, 3 H, H-7 and m-H), 7.61 (dm, J = 8.0 Hz, 2 H, o-H).
13C NMR (CDCl3, 75.5 MHz): d = 21.2 (ArCH3), 25.3 (CH2), 42.7
(CH2N), 55.7 (OCH3), 100.0 (C-4), 110.8 (C-3), 111.9 (C-6*),
112.0 (C-7*), 123.2 (C-2), 126.7 (2 m-C), 127.0 (C-3a), 129.4 (2 o-
C), 131.4 (C-7a), 136.4 (i-C), 143.2 (p-C), 153.6 (C-5) (*assign-
ments excahngeable).
4-Methoxy-3-(4-methyl-2-pyridyl)indole (13b)
Compound 13b (117 mg, 91% yield) was obtained from pyridylin-
dole 12b (213 mg, 0.54 mmol) following the general procedure for
desilylation. Eluent for chromatography: CH2Cl2/EtOH (99:1).
Mp 93 – 94 °C.
IR (film): u = 3500, 1610, 1541, 1339, 1246, 1093 cm–1.
1H NMR (CDCl3, 300MHz): d = 2.40 (s, 3 H, CH3), 3.90 (s, 3 H,
OCH3), 6.61 (dd, J = 8.0, 1.0 Hz, 1 H, H-5), 6.97 (dm, J = 5.0 Hz,
1 H, H-5’), 7.04 (dd, J = 8.0, 1.0 Hz, 1 H, H-7), 7.16 (t, J = 8.0 Hz,
1 H, H-6), 7.60 (d, J = 2.7 Hz, 1 H, H-2), 7.77 (m, 1 H, H-3’), 8.45
(d, J = 5.0 Hz, 1 H, H-6’), 8.90 (br s, 1 H, N-H).
13C NMR (CDCl3, 75.5 MHz): d = 21.3 (CH3), 55.2 (OCH3), 101.0
(C-5), 105.0 (C-7), 115.2 (C-3), 118.5 (C-3a), 121.5 (C-5’), 123.0
(C-6), 124.8 (C-2), 125.8 (C-3’), 138.5 (C-7a), 146.2 (C-4’), 148.3
(C-6’), 154.2 (C-4), 154.5 (C-2’).
Melatonin (8i)
Liquid ammonia (100 mL) was distilled into a solution of sulfon-
amide 8e (100 mg, 0.29 mmol) in anhyd THF (8 mL) kept at -78 °C
under argon. Then, Na was added in small pieces, resulting in a deep
blue solution which was stirred for 15 min and quenched with solid
NH4Cl. The ammonia was allowed to evaporate, the mixture was di-
luted with H2O and extracted with Et2O (3 î 15 mL), and the com-
bined organic extracts were dried (Na2SO4) and concentrated in
vacuo. The residue was chromatographed (flash, CH2Cl2/Et3N, 9:1)
to give pure 3-(2-aminoethyl)-5-methoxyindole (8h) (36 mg, 65%).
The identity of 8h was established by comparison of its spectro-
scopic data with those of a commercial sample. A solution of 8h
(40 mg, 0.21 mmol), Ac2O (30 mL, 0.32 mmol), and Et3N (47 mL,
0.34 mmol) in THF (2 mL) was stirred at r.t. for 3 h. The resulting
mixture was concentrated under reduced pressure and the residue
was dissolved in EtOAc. The organic solution was washed with sat
aq Na2CO3 (2 î 10 mL), dried (Na2SO4), and concentrated in vac-
uo. The residue was chromatographed (CH2Cl2/EtOH, 99:1) to give
melatonin 8i (27 mg, 55%). The identity of melatonin was estab-
lished by comparison of its spectroscopic data with those of a com-
mercial sample.
Anal. calcd for C15H14N2O (238.3): C, 75.61; H, 5.92; N, 11.76.
Found: C, 75.67; H, 5.92; N, 11.75.
5-Methoxy Series
From 2-bromo-4-methylpyridine (336 mg, 1.95 mmol) and 3-bro-
moindole 3c (1.0 g, 2.94 mmol) were obtained pyridylindole 12c
(oil, 396 mg, 58% yield) and 5-methoxyindole 2c (465 mg). Eluent
for chromatography: CH2Cl2.
1-(tert-Butyldimethylsilyl)-5-methoxy-3-(4-methyl-2-py-
ridyl)indole (12c)
IR (film): u = 1603, 1465, 1209, 1171, 1035 cm–1.
1H NMR (CDCl3, 300 MHz, assignments aided by H-13C HET-
1
COR): d = 0.64 (s, 6 H, SiCH3), 0.95 [s, 9 H, C(CH3)3], 2.40 (s, 3 H,
CH3), 3.91 (s, 3 H, OCH3), 6.86 (dd, J = 9.0, 2.5 Hz, 1 H, H-6), 6.94
(dm, J = 5.0 Hz, 1 H, H-5’), 7.42 (d, J = 9.0 Hz, 1 H, H-7), 7.48 (m,
1 H, H-3’), 7.67 (s, 1 H, H-2), 7.84 (d, J = 2.5 Hz, 1 H, H-4), 8.52
(d, J = 5.0 Hz, 1 H, H-6’).
3-Indolylzinc Chlorides 11b-d and Pd(0)-Catalyzed Cross-
Coupling Reactions; General Procedure
A 0.35 M solution of anhyd ZnCl2 (1.1 equiv, fused by flame-drying
under reduced pressure) in anhyd THF was added to a solution of
Synthesis 2001, No. 2, 267–275 ISSN 0039-7881 © Thieme Stuttgart · New York

274
M. Amat et al.
PAPER
13C NMR (CDCl3, 75.5 MHz): d = -3.96 (SiCH3), 19.3 [C(CH3)3],
21.2 (CH3), 26.3 [C(CH3)3], 55.8 (OCH3), 103.2 (C-4), 111.5 (C-6),
114.6 (C-7), 119.1 (C-3), 121.1 (C-3’), 121.2 (C-5’), 129.4 (C-3a),
131.6 (C-2), 137.1 (C-7a), 146.9 (C-4’), 149.3 (C-6’), 154.7 (C-5),
154.9 (C-2’).
(project 2FD97-1086). Thanks are also due to the Comissionat per
Universitats i Recerca (Generalitat de Catalunya) for Grant
1999SGR-00079.
References
5-Methoxy-3-(4-methyl-2-pyridyl)indole (13c)
Compound 13c (237 mg, 96% yield) was obtained from pyridylin-
dole 12c (363 mg, 1.03 mmol) following the general procedure for
desilylation. Eluent for chromatography: CH2Cl2/EtOH (99:1); mp
135 °C.
(1) (a) Amat, M.; Hadida, S.; Sathyanarayana, S.; Bosch, J. J.
Org. Chem. 1994, 59, 10.
(b) Amat, M.; Hadida, S.; Sathyanarayana, S.; Bosch, J. Org.
Synth. 1997, 74, 248.
(2) (a) Beswick, P. J.; Greenwood, C. S.; Mowlem, T. J.;
Nechvatal, G.; Widdowson, D. A. Tetrahedron 1988, 44,
7325.
IR (film): u = 3450, 1606, 1469, 1216, 800 cm–1.
1H NMR (CDCl3, 300MHz): d = 2.40 (s, 3 H, CH3), 3.92 (s, 3 H,
OCH3), 6.90 (dd, J = 8.8, 2.7 Hz, 1 H, H-6), 6.94 (dm, J = 5.2 Hz,
1 H, H-5’), 7.31 (d, J = 8.8 Hz, 1 H, H-7), 7.48 (m, 1 H, H-3’), 7.72
(d, J = 2.8 Hz, 1 H, H-2), 7.87 (d, J = 2.5 Hz, 1 H, H-4), 8.36 (br s,
1 H, N-H), 8.52 (d, J = 5.2 Hz, 1 H, H-6’).
(b) Bray, B. L.; Mathies, P. H.; Naef, R.; Solas, D. R.; Tidwell,
T. T.; Artis, D. R.; Muchowski, J. M. J. Org. Chem. 1990, 55,
6317.
(c) Iwao, M. Heterocycles 1993, 36, 29.
13C NMR (CDCl3, 75.5 MHz): d = 21.2 (CH3), 56.0 (OCH3), 103.1
(C-4), 112.1 (C-7), 112.4 (C-6), 116.5 (C-3), 121.1 (C-3’), 121.3
(C-5’), 125.0 (C-2), 126.0 (C-3a), 132.0 (C-7a), 147.2 (C-4’), 149.1
(C-6’), 154.9 (C-5), 155.0 (C-2’).
(3) (a) Saulnier, M. G.; Gribble, G. W. J. Org. Chem. 1982, 47,
757.
(b) Gribble, G. W.; Barden, T. C. J. Org. Chem. 1985, 50,
5900.
(c) Conway, S. C.; Gribble, G. W. Heterocycles 1990, 30, 627.
(4) (a) Griffen, E. J.; Roe, D. G.; Snieckus, V. J. Org. Chem.
1995, 60, 1484.
Anal. calcd for C15H14N2O (238.3): C, 75.61; H, 5.92; N, 11.76.
Found: C, 75.26; H, 5.83; N, 11.43.
6-Methoxy Series
(b) Amat, M.; Sathyanarayana, S.; Hadida, S.; Bosch, J.
Heterocycles 1996, 43, 1713.
(c) Amat, M.; Pshenichnyi, G.; Bosch, J.; Molins, E.;
Miravitlles, C. Tetrahedron: Asymmetry 1996, 7, 3091.
(d) Ma, C.; Yu, S.; He, X.; Liu, X.; Cook, J. M. Tetrahedron
Lett. 2000, 41, 2781.
From 2-bromo-4-methylpyridine (336 mg, 1.95 mmol) and 3-bro-
moindole 3d (1.0 g, 2.94 mmol) were obtained pyridylindole 12d
(oil, 420 mg, 61% yield) and 6-methoxyindole 2d (453 mg). Eluent
for chromatography: CH2Cl2.
1-(tert-Butyldimethylsilyl-)-6-methoxy-3-(4-methyl-2-py-
(5) (a) Kawasaki, I.; Yamashita, M.; Ohta, S. Chem. Pharm. Bull.
ridyl)indole (12d)
1
1996, 44, 1831.
(b) Kawasaki, I.; Katsuma, H.; Nakayama, Y.; Yamashita, M.;
Ohta, S. Heterocycles 1998, 48, 1887.
(c) Hoerrner, R. S.; Askin, D.; Volante, R. P.; Reider, P. J.
Tetrahedron Lett. 1998, 39, 3455.
1H NMR (CDCl3, 300 MHz, assignments aided by H-13C HET-
COR): d = 0.65 (s, 3 H, SiCH3), 0.97 [s, 9 H, C(CH3)3], 2.40 (s, 3 H,
CH3), 3.87 (s, 3 H, OCH3), 6.90 (dd, J = 8.8, 2.3 Hz, 1 H, H-5), 6.93
(dm, J = 5.0 Hz, 1 H, H-5’), 7.05 (d, J = 2.3 Hz, 1 H, H-7), 7.50 (m,
1 H, H-3’), 7.62 (s, 1 H, H-2), 8.17 (d, J = 8.8 Hz, 1 H, H-4), 8.51
(d, J = 5.0 Hz, 1 H, H-6’).
13C NMR (CDCl3, 75.5 MHz): d = -3.9 (SiCH3), 19.5 [C(CH3)3],
21.2 (CH3), 26.4 [C(CH3)3], 55.6 (OCH3), 98.5 (C-7), 109.6 (C-5),
119.2 (C-3), 121.2 (C-4), 121.3 (C-3’), 121.4 (C-5’), 123.2 (C-3a),
129.9 (C-2), 142.9 (C-7a), 146.9 (C-4’), 149.3 (C-6’), 154.7 (C-2’),
155.8 (C-6).
(6) (a) Amat, M.; Hadida, S.; Bosch, J. Tetrahedron Lett. 1994,
35, 793.
(b) Amat, M.; Hadida, S.; Pshenichnyi, G.; Bosch, J. J. Org.
Chem. 1997, 62, 3158.
(7) Saulnier, M. G.; Gribble, G. W. J. Org. Chem. 1983, 48, 2690.
(8) (a) More recently the preparation of 3-lithioindole 4d has been
reported: see reference 5b.
(b) For the generation of 4-(benzyloxy)-1-(triisopropylsilyl)-
3-lithioindole, see: Vedejs, E.; Barda, D. A. Org. Lett. 2000,
2, 1033.
(c) See also, Gerasimov, M.; Marona-Lewicka, D.; Kurrasch-
Orbaugh, D. M.; Qandil, A. M.; Nichols, D. E. J. Med. Chem.
1999, 42, 4257.
6-Methoxy-3-(4-methyl-2-pyridyl)indole (13d)
Compound 13d (134 mg, 87% yield) was obtained from pyridylin-
dole 12d (227 mg, 0.65 mmol) following the general procedure for
desilylation. Eluent for chromatography: CH2Cl2/EtOH (98:2); mp
120 °C.
IR (film): u = 3400, 1625, 1549, 1460, 1199, 1164, 803 cm–1.
(9) Neuss, N. In Indole and Biogenetically Related Alkaloids;
Phillipson, J. D., Zenk, M. H., Eds.; Academic Press: London,
1980; Chapter 17.
(10) For the ortho litiation of a 5-methoxyindole, see: Sundberg, R.
J.; Parton, R. L. J. Org. Chem. 1976, 41, 163.
(11) (a) Sato, K.; Kozikowski, A. P. Tetrahedron Lett. 1989, 30,
4073.
1H NMR (CDCl3, 300 MHz): d = 2.40 (s, 3 H, CH3), 3.83 (s, 3 H,
OCH3), 6.88 (d, J = 2.0 Hz, 1 H, H-7), 6.90 (dd, J = 8.5, 2.0 Hz, 1
H, H-5), 6.94 (dm, J = 5.0 Hz, 1 H, H-5’), 7.51 (m, 1 H, H-3’), 7.64
(d, J = 2.6 Hz, 1 H, H-2), 8.20 (d, J = 8.5 Hz, 1 H, H-4), 8.38 (br s,
1 H, NH), 8.51 (d, J = 5.0 Hz, 1 H, H-6’).
13C NMR (CDCl3, 75.5 MHz): d = 21.0 (CH3), 55.3 (OCH3), 94.8
(C-7), 110.2 (C-5), 115.9 (C-3), 119.4 (C-3a), 120.5 (C-4), 121.2
(C-3’), 121.7 (C-5’), 123.8 (C-2), 137.6 (C-7a), 147.9 (C-4’), 148.4
(C-6’), 154.5 (C-2’), 156.0 (C-6).
(b) Shima, I.; Shimazaki, N.; Imai, K.; Hemmi, K.;
Hashimoto, M. Chem. Pharm. Bull. 1990, 38, 564.
(c) Dauban, P.; Dubois, L.; Tran Huu Dau, M. E.; Dodd, R. H.
J. Org. Chem. 1995, 60, 2035.
(d) Bennani, Y. L.; Zhu, G.-D.; Freeman, J. C. Synlett 1998,
754.
Anal. calcd for C15H14N2O (238.3): C, 75.61; H, 5.92; N, 11.76.
Found: C, 75.87; H, 5.85; N, 11.62.
(12) Onistschenko, A.; Stamm, H. Chem. Ber. 1989, 122, 2397.
(13) Ezquerra, J.; Pedregal, C.; Lamas, C.; Pastor, A.; Alvarez, P.;
Vaquero, J. J. Tetrahedron Lett. 1996, 37, 683.
(14) Beck, A. L.; Mascal, M.; Moody, C. J.; Coates, W. J. J. Chem.
Soc., Perkin Trans. 1 1992, 813.
Acknowledgement
This work was supported by the DGICYT, Spain (project PB94-
0214) and, in part, by the CICYT (Spain)-European Commision
Synthesis 2001, No. 2, 267–275 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Preparation and Reactions of 3-Lithioindoles
275
(15) (a) Kozikowski, A. P.; Ishida, H.; Isobe, K. J. Org. Chem.
1979, 44, 2788.
(b) Eis, M. J.; Ganem, B. Tetrahedron Lett. 1985, 26, 1153.
(16) Cheng, C.-C.; Lu, Y.-L. Chem. Commun. 1998, 253.
(17) Zinic, M.; Alihodzic, S.; Skaric, V. J. Chem. Soc., Perkin
Trans. 1 1993, 21.
(24) Kralt, T.; Asma, W. J.; Haeck, H. H.; Moed, H. D. Recl. Trav.
Chim. Pays-Bas 1961, 80, 313.
(25) Feldman, P. L.; Rapoport, H. Synthesis 1986, 735.
(26) Bergman, J.; Sand, P. Org. Synth. 1987, 65, 146.
(27) Gan, T.; Liu, R.; Yu, P.; Zhao, S.; Cook, J. M. J. Org. Chem.
1997, 62, 9298.
(18) For the competitive attack of organolithium reagents at the
carbonyl atom of N-acylaziridines, see:
(28) Fleming, I.; Woolias, M. J. Chem. Soc., Perkin Trans. 1 1979,
827.
(a) Hassner, A.; Kascheres, A. Tetrahedron Lett. 1970, 4623.
(b) Wattanasin, S.; Kathawala, F. G. Tetrahedron Lett. 1984,
25, 811.
(29) Somei, M.; Yamada, F.; Kunimoto, M.; Kaneko, C.
Heterocycles 1984, 22, 797.
(30) Moody, C. J.; Swann, E. J. Chem. Soc., Perkin Trans. 1 1993,
(19) Wilkinson, S. J. Chem. Soc. 1958, 2079.
(20) (a) Bartoli, G.; Leardini, R.; Medici, A.; Rosini, G. J. Chem.
Soc., Perkin Trans 1 1978, 692.
2561.
(31) Allen, M. S.; Hamaker, L. K.; La Loggia, A. J.; Cook, J. M.
Synth. Commun. 1992, 22, 2077.
(32) Scott, F. L.; Flynn, E. Tetrahedron Lett. 1964, 1675.
(33) Martin, A. E.; Ford, T. M.; Bulkowski, J. E. J. Org. Chem.
1982, 47, 412.
(b) Bartoli, G.; Bosco, M.; Baccolini, G. J. Org. Chem. 1980,
45, 522.
(c) Quick, J.; Saha, B. Tetrahedron Lett. 1994, 35, 8553.
(21) In fact, incorporation of the t-Bu group at the indole 4-position
was observed after treatment of 5-nitroindole 1g with t-BuLi.
(22) For an alternative method for the preparation of 3-indolylzinc
halides, see: Sakamoto, T.; Kondo, Y.; Takazawa, N.;
Yamanaka, H. J. Chem. Soc., Perkin Trans. 1 1996, 1927.
(23) Batcho, A. D.; Leimgruber, W. Org. Synth. 1985, 63, 214.
(34) Case, F. H. J. Am. Chem. Soc. 1946, 68, 2574.
Article Identifier:
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Synthesis 2001, No. 2, 267–275 ISSN 0039-7881 © Thieme Stuttgart · New York