Convenient synthesis of tryptophols and tryptophol homologues by hydroamination of alkynes

Article abstract of DOI:10.1016/j.tet.2005.05.093

A novel method is presented for the one-pot synthesis of substituted 3-(2-hydroxyethyl)- and 3-(3-hydroxypropyl)indoles (tryptophols and homotryptophols) from aryl hydrazines and silyl-protected ω- (hydroxyoalkyl)alkynes. Various tryptophol derivatives were prepared directly in good yield with excellent regioselectivity via a domino reaction sequence consisting of a titanium-catalyzed hydroamination of the alkyne, [3+3]-rearrangement of the resulting aryl hydrazone, and subsequent deprotection of the hydroxy group.

Full text of DOI:10.1016/j.tet.2005.05.093

Tetrahedron 61 (2005) 7622–7631
Convenient synthesis of tryptophols and tryptophol homologues
by hydroamination of alkynes
*
Vivek Khedkar, Annegret Tillack, Manfred Michalik and Matthias Beller
¨ ¨
Leibniz-Institut fur Organische Katalyse (IfOK) an der Universitat Rostock e.V., Albert-Einstein-Str. 29a, D-18055 Rostock, Germany
Received 15 April 2005; revised 30 May 2005; accepted 31 May 2005
Available online 17 June 2005
Abstract—A novel method is presented for the one-pot synthesis of substituted 3-(2-hydroxyethyl)- and 3-(3-hydroxypropyl)indoles
(tryptophols and homotryptophols) from aryl hydrazines and silyl-protected u-(hydroxyoalkyl)alkynes. Various tryptophol derivatives were
prepared directly in good yield with excellent regioselectivity via a domino reaction sequence consisting of a titanium-catalyzed
hydroamination of the alkyne, [3C3]-rearrangement of the resulting aryl hydrazone, and subsequent deprotection of the hydroxy group.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
been used to prepare Pemedolac, a compound that has been
found to be one of the most potent analgesics known and
that displays anti-inflammatory activity similar to that of
Etodolac (Scheme 1).10
There is a continuing interest in the development of new
methods for the synthesis of indole derivatives due to their
importance as building blocks for pharmaceuticals and
natural products.1 For some time, we have been involved in
this area focusing on the application of catalytic method-
ologies such as hydrohydrazinomethylation of olefins,2
carbonylations,3 and hydroamination of alkynes4 for the
synthesis and refinement of indoles. Most notably, a new,
one-pot method for the synthesis of functionalized
tryptamines and tryptamine homologues starting from
commercially available aryl hydrazines and chloroalkyl-
alkynes has been developed by us.5 Based on this work, we
became interested in the preparation of tryptophol deriva-
tives. Among the numerous naturally-occuring indoles,
tryptophols6 are characterized by a C-3 hydroxyethyl side
chain that may or may not be a- and or b-substituted.
Scheme 1. Examples of biologically active tryptophols.
Although different creative approaches have been
developed for the synthesis of tryptophols,11 the Fischer
indole reaction remains the most important method to create
substituted indoles.12 In this benchmark reaction, aldehydes
or ketones react with aryl hydrazines to give the
corresponding hydrazones, which subsequently undergo a
[3,3]-sigmatropic rearrangement to yield the respective
indole in the presence of a Brønstedt or Lewis acid. Despite
its versatility, the Fischer indole reaction with aldehydes
constitutes a two-step procedure, which sometimes proceeds
in low yield. More specifically the synthesis of tryptophol-
like compounds via Fischer indole synthesis can be
troublesome due to side-reactions of the free or protected
hydroxyaldehyde. An elegant solution to this problem has
been described very recently by Campos et al., who used
substituted enol ethers or enol lactones as a substitute for the
hydroxyaldehyde.13
The production of tryptophol, by tryptophan metabolism,
has been implicated as one of the pathophysiological
mechanisms that provoke sleeping sickness upon infection
by trypanosomes.7 Therefore, it is not surprising that a number
of derivatives are known to posses interesting biological
activity, for example, esters of 5-methoxytryptophol show
anti-cholinergic activity.8 Of pharmaceutical importance is
also 7-ethyltryptophol as this compound is used for the
synthesis of Etodolac, a non-steroidal anti-inflammatory drug
(NSAID).9 In addition, 2-phenyl-2-(3-indolyl)-1-ethanol has
Keywords: Amination; Indoles; Catalysis.
*
Corresponding author. Tel.: C49 381 1281113; fax: C49 381 12815000;
e-mail: matthias.beller@ifok.uni-rostock.de
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.05.093

V. Khedkar et al. / Tetrahedron 61 (2005) 7622–7631
7623
Table 1. Reaction of 1-tert-butyldimethylsilyloxy-4-pentyne with
N-methyl-N-phenylhydrazinea
2. Results and discussion
Here, we describe for the first time a convenient synthesis of
tryptophols from alkynes and aryl hydrazines. As shown in
Scheme 2, our strategy involved as a key step, the titanium-
catalyzed hydroamination of a suitably protected hydroxy-
alkylalkyne to give the N-aryl-N-hydroxy-alkylhydrazone 4.
Then a [3,3]-sigmatropic rearrangement to the correspond-
ing indole 5 should take place and finally deprotection will
lead to the free tryptophol.
Entry
Ligand
Ti(NEt2)4
(mol%)
Ligand
(mol%)
Yieldb 6a
(%)
7
1
5
5
10
10
!5
8
2
3
70
9
5
10
40
Scheme 2. Synthesis of tryptophols.
4
5
6
7
1
2.5
5
2
5
10
20
58
62
75
90
Indeed, when we reacted 1-tert-butyldimethylsilyloxy-4-
pentyne 2 with N-methyl-N-phenylhydrazine 3 in the
presence of 5 mol% bis(2,6-di-tert-butyl-4-methyl-
phenoxo)-bis(diethylamido)titanium 1 (complex 1 is
formed in situ from commercially available Ti(NEt2)4 and
2,6-di-tert-butyl-4-methylphenol)14–16 the corresponding
hydrazone 4 was the major product. Subsequent treatment
of the reaction mixture with an excess of ZnCl2 gave the
corresponding silyl-protected tryptophol 6a in 75% isolated
yield!
10
10
a Reaction conditions: for hydroamination: 2.0 mmol 1-tert-butyldimethyl-
silyloxy-4-pentyne, 2.4 mmol N-methyl-N-phenylhydrazine, 4 ml tolu-
ene, 100 8C, 24 h. For Fischer indole cyclization: 6.0 mmol ZnCl2,
100 8C, 24 h.
b Isolated yield based on 1-tert-butyldimethylsilyloxy-4-pentyne.
general, the sterically hindered monodentate ligand 10 gave
higher yield compared to the less sterically hindered
monodentate ligands 7 and 8 (Table 1, entries 1, 2, and 6).
By employing ligand 7 the catalytic activity decreased to
give only !5% yield.
It is noteworthy that the initial hydrohydrazination reaction
of the alkyne proceeds selectively to give exclusively the
2,3-disubstituted indole 6a (Markovnikov isomer).17 Selec-
tive formation of the 2-methyl-indole derivative 6a instead
of the corresponding homotryptophol is explained by the
relative stability of the corresponding imidotitanium alkyne
p-complexes,4 which undergo a formal [2C2]-cyclo-
addition to give the titanaazacyclobutene derivative.
Subsequent protonation by excess hydrazine and tautomeri-
zation leads to the hydrazone product 4 and the active
catalyst is recovered.
The reaction using bidentate ligand 9 gave 40% yield of the
corresponding indole 6a (Table 1, entry 3). Therefore,
further optimization of reaction conditions was carried out
by using ligand 10. Next, we turned our interest to improve
the yield of product 6a by loading different concentration of
catalyst.
The model reaction of 1-tert-butyldimethylsilyloxy-4-
pentyne with N-methyl-N-phenylhydrazine proceeds in the
presence of Ti(NEt2)4 and different aryloxo ligands.
Subsequent addition of 3 equiv of ZnCl2 allowed for the
cyclization of the initially generated hydrazone into the
corresponding indole.
As shown in Table 1, an excellent yield (90%) of indole was
achieved applying 10 mol% Ti(NEt2)4 and 20 mol% of
ligand 10 (Table 1, entry 7). Nevertheless, also at lower
catalyst loading (1 mol% Ti(NEt2)4 and 2 mol% 10) a good
yield (58%) of the corresponding indole 6a was obtained
(Table 1, entry 4).
The reactions using different aryloxo ligands were
performed at 100 8C for 24 h in toluene in the presence of
5 mol% Ti(NEt2)4. As shown in Table 1, all tested ligands
gave selectively the Markovnikov addition product. In
Next, we were interested to test the in situ catalyst system
for the one-pot synthesis of various functionalized trypto-
phols (Scheme 3; Tables 2 and 3). For this purpose, we used
two silyl-protected 2- and 3-hydroxyalkylalkynes and

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V. Khedkar et al. / Tetrahedron 61 (2005) 7622–7631
various N,N-disubstituted aryl hydrazines. All formed
indoles were deprotected by using tetra-n-butylammonium
fluoride (TBAF) at room temperature for 4–8 h in THF.
Regioselective hydroamination/cyclization to the corre-
sponding indole products 6a–m was possible for a range
of aryl hydrazines with different substituents such as Me, Cl,
F, MeO, and Bn (40–97% yield). Interestingly, it is not
necessary to purify or isolate the silyl-protected tryptophol.
Hence, the reaction of N-benzyl-4-fluoro-phenylhydrazine
and N-methyl-4-methylphenylhydrazine with 1-tert-butyl-
dimethylsilyloxy-4-pentyne, and 1-tert-butyldimethylsilyl-
oxy-5-hexyne gave in a one-pot reaction the tryptophols 11d
and 11j in good isolated yields (Table 2, entry 4 and Table 3,
entry 3).
Scheme 3. Synthesis of different tryptophols.
Table 2. Reaction of 1-tert-butyldimethylsilyloxy-4-pentyne with various substituted hydrazinesa
Entry
Alkyne
Hydrazine
Product 6
Yieldb (%)
6
11 (a–g)
1
6a
6b
6c
6d
6e
6f
90
75
84
81
2
80
90
76
85
83
89
3
4
Not
isolated
5
80
95
84
6c
7d
6g
a Reaction conditions: for hydroamination: 2–3 mmol 1-tert-butyldimethylsilyloxy-4-pentyne, 2.5–4.5 mmol arylhydrazine, 4 ml toluene, 100 8C, 24 h. For
Fischer indole cyclization: 6.0 mmol ZnCl2, 100 8C, 24 h. For deprotection of alcohol: 2 equiv TBAF, rt, 4–8 h, 10 ml THF.
b Isolated yield based on 1-tert-butyldimethylsilyloxy-4-pentyne.
c Markovnikov:anti-Markovnikov selectivityZ97:3; 4-Cl:6-Cl regioselectivityZw2:1.
d Markovnikov:anti-Markovnikov selectivityZ84:16; 4-Cl:6-Cl regioselectivityZw2:1.

V. Khedkar et al. / Tetrahedron 61 (2005) 7622–7631
Table 3. Reaction of different alkynes with various substituted hydrazinesa
7625
Entry
Alkyne
Hydrazine
Product 6
Yieldb (%)
6
11 (h–m)
1
6h
6i
85
90
2
97
84
75
75
88
84
3
6j
Not
isolated
4c
5d
6
6k
6l
71
84
40
6m
a Reaction conditions: for hydroamination: 2–3 mmol silyl-protected alkyne, 2.5–4.5 mmol arylhydrazine, 4 ml toluene, 100 8C, 24 h. For Fischer indole
cyclization: 6.0 mmol ZnCl2, 100 8C, 24 h. For deprotection of alcohol: 2 equiv TBAF, room temperature, 4–8 h, 10 ml THF.
b Isolated yield based on alkyne.
c Markovnikov:anti-Markovnikov selectivityZ93:7; 4-Cl:6-Cl regioselectivityZw2:1.
d Markovnikov:anti-Markovnikov selectivityZ83:17; 4-Cl:6-Cl regioselectivityZw2:1.
Apart from terminal alkynes, an internal alkyne also reacted
with N-methyl-N-phenylhydrazine to give the correspond-
ing homotryptophol 6m in 40% isolated yield (Table 3,
entry 6).
been developed. Starting from commercially available aryl
hydrazines and alkynes, a variety of potentially active
indoles are obtained selectively in the presence of a catalytic
amount of Ti(NEt2)4 and 2,6-tert-butyl-4-methyl-phenol
(10). The presented approach constitutes the most efficient
access for the here shown substituted tryptophols and
tryptophol homologues.
In general, the hydrohydrazination step proceeds preferen-
tially to the Markovnikov addition product. However, in
case of disubstituted aryl hydrazines (Table 2, entries 6, 7
and Table 3, entries 4, 5) and N-benzyl-N-(3-chloro-
phenyl)hydrazine a small amount of the anti-Markovnikov
addition product was also observed (M:anti-MZ84:16 to
97:3). In the second step subsequent cyclization of the
hydrazones using an excess ZnCl2 afforded the correspond-
ing indoles in good yields (71–97%). The mixture of the
Markovnikov and the anti-Markovnikov products (11g and
11l) can be easily separated by column chromatography.
However, it was not possible to separate the mixture
of regioisomers (6-Cl:4-Cl) of the Markovnikov and the
anti-Markovnikov products.
4. Experimental
4.1. General reagents
All reactions were carried out under an argon atmosphere.
Starting materials were used as received from Aldrich,
Fluka, Acros, and Strem and unless otherwise noted were
used without further purification. Alkynes were degassed,
˚
flushed with argon and stored over molecular sieves (4 A).
Absolute solvents were purchased from Flukaw. The 2- and
3-hydroxyalkylalkynes were protected according to
literature.18
3. Conclusion
Silica gel column chromatography was performed with
230–400 mesh ASTM silica gel from Merck,w which was
used as received.
In conclusion, a new efficient method for the synthesis of
functionalized tryptophols and tryptophol homologues has

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V. Khedkar et al. / Tetrahedron 61 (2005) 7622–7631
4.2. General spectroscopic methods
127.8, 120.4, 118.7, 117.8, 108.5, 107.4, 63.8, 29.4, 28.4,
25.9, 22.7, 10.2, K5.2. MS (EI, 70 eV) m/z (relative
intensity): 303 (19) [MC], 246 (30), 231 (2), 205 (3), 189 (1),
172 (16), 158 (100), 143 (6), 128 (3), 115 (6), 91 (2), 73 (8),
41 (4), 28 (3). HRMS Calcd for C18H29NOSi: 303.20184.
Found: 303.20170.
1H and 13C NMR data were recorded on a Brukerw ARX
400 with QNP probe head (1H, 400.13 MHz), (13C, 100.61,
125.75 MHz) at 25 8C. Resonances are reported in d (ppm)
relative to CDCl3. Coupling constants J are reported in Hz.
1H and 13C NMR assignments, where given, were based on
2D experiments or comparison with related structures.
The following abbreviations were used to specify multi-
plicity, shape, and other properties: s, singlet; d, doublet; t,
triplet; q, quartet; quint, quintet; sept, septet; m, multiplet;
br, broad.
4.3.2. N-Benzyl-3-(2-{tert-butyldimethylsilyloxy}ethyl)-
2-methyl-1H-indole (6b). According to GP (step 1),
1-tert-butyldimethylsilyloxy-4-pentyne (0.25 ml, 1.1 mmol)
and N-benzyl-N-phenylhydrazine (0.19 ml, 1.4 mmol) were
employed. Isolated yield: 75%, light brown oil.
MS data were obtained on AMD 402/3 of AMD Intectraw.
Electron impact spectra (EI) were recorded at 70 eV,
chemical ionization (CI) was with iso-butane.
1H NMR (CDCl3, 400 MHz): dZ7.55–7.53 (m, 1H), 7.24–
7.18 (m, 4H), 7.10–7.07 (m, 2H), 6.97–6.95 (dd, JZ1.6,
8.3 Hz, 2H), 5.29 (s, 2H), 3.78 (t, JZ7.5 Hz, 2H), 2.98 (t,
JZ7.6 Hz, 2H), 2.30 (s, 3H), 0.88 (s, 9H), 0.01 (s, 6H). 13C
NMR (CDCl3, 100 MHz): dZ138.0, 136.4, 133.5, 128.6,
128.1, 127.1, 125.9, 120.7, 118.9, 117.9, 108.9, 108.3, 63.7,
46.5, 28.4, 25.9, 18.4, 10.3, K5.2. MS (EI, 70 eV) m/z
(relative intensity): 379 (27) [MC], 322 (24), 248 (10), 234
(88), 216 (5), 195 (11), 183 (13), 142 (7), 128 (1), 115 (3),
91 (100), 73 (10), 41 (4), 29 (3). HRMS Calcd for
C24H33NOSi: 379.23315. Found: 379.23231.
Melting points (mp) of the solid compounds were recorded
on a Leica Galen III on the glass slide and are uncorrected.
IR spectra of solid compounds were recorded as KBr pellets
(nujol) on a Nicoletw Magna 550. Liquid compounds were
analyzed capillarily. Absorption bands are given as
wavenumbers n~ in cmK1
.
4.3. General procedure for synthesis of tryptophols (GP)
4.3.3. 3-(2-{tert-Butyldimethylsilyloxy}ethyl)-5-chloro-
1,2-dimethyl-1H-indole (6c). According to GP (step 1),
1-tert-butyldimethylsilyloxy-4-pentyne (0.25 ml, 1.1 mmol)
and N-(4-chlorophenyl)-N-methylhydrazine (0.22 ml,
1.65 mmol) were employed. Isolated yield: 84%, brown oil.
Step 1 (hydroamination/cyclization). In an Ace-pressure
tube under an argon atmosphere the ligand 2,6-tert-butyl-4-
methylphenol (20 mol%) was dissolved in 4 ml toluene.
To this solution hydrazine, alkyne, and Ti(NEt2)4
(10 mol%) were added. The reaction mixture was heated
at 100 8C for 24 h, which resulted in the formation of the
corresponding hydrazone. The pressure tube was opened
under argon and 3 equiv ZnCl2 was added. The reaction
mixture was again heated at 100 8C for 24 h. After filtration
and removal of the solvents in vacuo, the desired indole
product was isolated by column chromatography in ethyl
acetate/hexane.
1H NMR (CDCl3, 400 MHz): dZ7.49 (d, JZ1.7 Hz, 1H),
7.14 (d, JZ8.7 Hz, 1H), 7.09 (dd, JZ1.7,8.5 Hz, 1H), 3.75
(t, JZ7.4 Hz, 2H), 3.64 (s, 3H), 2.92 (t, JZ7.4 Hz, 2H),
2.37 (s, 3H), 0.91 (s, 9H), 0.03 (s, 6H). 13C NMR (CDCl3,
100 MHz): dZ135.1, 134.8, 128.9, 124.4, 120.4, 117.4,
109.3, 107.6, 63.7, 29.6, 28.2, 25.9, 18.3, 10.3, K5.3. MS
(EI, 70 eV) m/z (relative intensity): 337 (18) [MC], 322 (4),
280 (52), 265 (2), 245 (1), 206 (29), 192 (100), 171 (10), 154
(12), 140 (7), 128 (2), 115 (4), 105 (3), 91 (1), 88 (9), 73 (9),
57 (4), 41 (4), 28 (3). HRMS Calcd for C18H28ClNOSi:
337.16287. Found: 337.16330.
Step 2 (deprotection of alcohol). The indole isolated after
step 1 was dissolved in 10 ml THF and cooled to 0 8C. Then
2 equiv of TBAF was added slowly. The reaction mixture
was stirred at room temperature for 4–8 h. After removal of
the solvent in vacuo, the mixture was diluted with water and
5 ml of dichloromethane. The product was extracted with
dichloromethane (3!25 ml). The combined organic
extracts were dried over anhydrous MgSO4 and concen-
trated in vacuo. The crude product was purified by column
chromatography in ethyl acetate/hexane to yield the
corresponding tryptophols.
4.3.4. N-Benzyl-3-(2-{tert-butyldimethylsilyloxy}ethyl)-
5-methoxy-2-methyl-1H-indole (6e). According to GP
(step 1), 1-tert-butyldimethylsilyloxy-4-pentyne (0.47 ml,
2.0 mmol) and N-(4-methoxyphenyl)-N-methylhydrazine
(228 mg, 2.4 mmol) were employed. Isolated yield: 80%,
brown oil.
1H NMR (CDCl3, 400 MHz): dZ7.22–7.17 (m, 3H), 7.12
(d, JZ8.4 Hz, 1H), 7.08–6.99 (m, 2H), 6.80–6.69 (m, 2H),
5.26 (s, 2H), 3.82 (s, 3H), 3.69 (t, JZ6.5 Hz, 2H), 2.70 (t,
JZ6.5 Hz, 2H), 2.01 (s, 3H), 0.87 (s, 9H), 0.03 (s, 6H). 13C
NMR (CDCl3, 100 MHz): dZ154.9, 141.5, 137.9, 132.3,
128.6, 128.5, 127.1, 125.8, 110.5, 109.9, 107.9, 100.2, 62.1,
55.8, 46.4, 28.5, 25.9, 18.2, 10.3, K5.3. MS (EI, 70 eV) m/z
(relative intensity): 409 (32) [MC], 352 (16), 303 (12), 278
(3), 264 (46), 251 (100), 212 (12), 186 (4), 160 (22), 144 (3),
129 (1), 115 (2), 91 (74), 73 (9), 59 (5), 41 (5), 28 (19).
HRMS Calcd for C25H35NO2Si: 409.24371. Found:
409.24235.
4.3.1. 3-(2-{tert-Butyldimethylsilyloxy}ethyl)-1,2-di-
methyl-1H-indole (6a). According to GP (step 1), 1-tert-
butyldimethylsilyloxy-4-pentyne (0.25 ml, 1.1 mmol) and
N-methyl-N-phenylhydrazine (0.16 ml, 1.4 mmol) were
employed. Isolated yield: 90%, light brown oil.
1H NMR (CDCl3, 400 MHz): dZ7.50 (d, JZ7.7 Hz, 1H),
7.22 (d, JZ7.9 Hz, 1H), 7.13 (td, JZ1.1, 7.5 Hz, 1H), 7.06
(td, JZ1.0, 7.4 Hz, 1H), 3.75 (t, JZ7.8 Hz, 2H), 3.62 (s,
3H), 2.96 (t, JZ7.8 Hz, 2H), 2.35 (s, 3H), 0.89 (s, 9H), 0.03
(s, 6H). 13C NMR (CDCl3, 100 MHz): dZ136.4, 133.6,

V. Khedkar et al. / Tetrahedron 61 (2005) 7622–7631
7627
4.3.5. N-Benzyl-3-(2-{tert-butyldimethylsilyloxy}ethyl)-
4-chloro-5-fluoro-2-methyl-1H-indole/N-benzyl-3-(2-
{tert-butyldimethylsilyloxy}ethyl)-6-chloro-5-fluoro-2-
methyl-1H-indole (2:1) (6f). According to GP (step 1),
1-tert-butyldimethylsilyloxy-4-pentyne (0.47 ml, 2.0 mmol)
3H), 2.77 (t, JZ6.1 Hz, 2H), 2.34 (s, 3H), 1.80 (quint, JZ
6.8 Hz, 2H), 0.92 (s, 9H), 0.05 (s, 6H). 13C NMR (CDCl3,
100 MHz): dZ136.5, 132.7, 127.7, 120.3, 118.4, 118.0,
110.9, 108.3, 62.4, 34.0, 29.4, 25.9, 20.4, 18.2, 10.1, K5.2.
MS (EI, 70 eV) m/z (relative intensity): 317 (44) [MC], 302
(4), 260 (70), 245 (6), 232 (5), 202 (4), 184 (13), 170 (7),
158 (100), 144 (8), 130 (4), 115 (3), 89 (11), 75 (6), 59 (8),
41 (1), 29 (1). HRMS Calcd for C19H31NOSi: 317.21750.
Found: 317.21704.
and
N-(3-chloro-4-fluorophenyl)-N-benzylhydrazine
(413 mg, 1.65 mmol) were employed. Isolated yield: 95%,
brown oil.
1H NMR (CDCl3, 400 MHz): dZ7.32–7.17 (m, 3H), 7.00
(dd, JH,HZ3.9 Hz, JF,HZ8.7 Hz, 1H), 6.95–6.91 (m, 2H),
6.85 (t, JH,HZJF,HZ8.9 Hz, 1H), 5.25 (s, 2H), 3.87 (t, JZ
7.1 Hz, 2H), 3.22 (t, JZ7.1 Hz, 2H), 2.34 (s, 3H), 0.89 (s,
9H), 0.03 (s, 6H)/7.36 (d, JF,HZ9.0 Hz, 1H), 7.34–7.17 (m,
3H), 7.18 (d, JF,HZ6.1 Hz, 1H), 6.95–6.91 (m, 2H), 5.23 (s,
2H), 3.78 (t, JZ7.0 Hz, 2H), 2.92 (t, JZ7.0 Hz, 2H), 2.31
(s, 3H), 0.88 (s, 9H), 0.01 (s, 6H). 13C NMR (CDCl3,
100 MHz): dZ154.1, 137.2, 137.1, 133.6, 128.6, 127.4,
125.7, 125.0, 109.9, 109.2, 109.1, 107.7, 64.8, 46.7, 28.5,
25.9, 18.3, 10.5, K5.3/153.9, 137.0, 135.9, 133.7, 128.6,
127.4, 127.0, 125.7, 114.3, 109.2, 108.9, 104.2, 64.4, 46.7,
28.2, 25.9, 18.3, 10.4, K5.2. MS (EI, 70 eV) m/z (relative
intensity): 432 (10) [MC], 397 (15), 340 (7), 316 (19), 286
(42), 262 (2), 235 (32), 205 (5), 195 (4), 185 (2), 159 (6),
142 (4), 129 (6), 115 (8), 99 (3), 91 (100), 77 (7), 65 (19),
57 (7), 49 (21), 41 (7), 28 (5). HRMS Calcd for
C24H3135ClFNOSi: 431.18475. Found: 431.18489.
4.3.8. N-Benzyl-3-(3-{tert-butyldimethylsilyloxy}pro-
pyl)-2-dimethyl-1H-indole (6i). According to GP
(step 1), 1-tert-butyldimethylsilyloxy-5-hexyne (0.49 ml,
2.0 mmol) and N-benzyl-N-phenylhydrazine (0.43 ml,
3.0 mmol) were employed. Isolated yield: 97%, light
brown oil.
1H NMR (CDCl3, 400 MHz): dZ7.57–7.55 (m, 1H), 7.24–
7.17 (m, 4H, H-21), 7.10–7.05 (m, 2H), 6.94 (d, JZ6.9 Hz,
2H), 5.28 (s, 2H), 3.63 (t, JZ7.4 Hz, 2H), 2.81 (t, JZ
7.4 Hz, 2H), 2.28 (s, 3H), 1.84 (quint, JZ7.3 Hz, 2H), 0.91
(s, 9H), 0.05 (s, 6H). 13C NMR (CDCl3, 100 MHz): dZ
138.2, 136.4, 132.6, 128.9, 128.6, 127.1, 125.9, 120.6,
118.7, 118.1, 111.6, 108.8, 62.4, 46.4, 33.8, 25.9, 20.4, 18.2,
10.1, K5.2. MS (EI, 70 eV) m/z (relative intensity): 393
(51) [MC], 378 (2), 336 (32), 308 (1), 286 (11), 245 (8), 234
(23), 195 (12), 167 (2), 143 (6), 115 (2), 91 (100), 76 (6), 57
(8), 41 (3). HRMS Calcd for C25H36NOSi: [MC CH]:
394.25662. Found: 394.25622.
4.3.6. N-Benzyl-3-(2-{tert-butyldimethylsilyloxy}ethyl)-
4,5-dichloro-2-methyl-1H-indole/N-benzyl-3-(2-(tert-
butyldimethylsilyloxy(ethyl)-5,6-dichloro-2-methyl-1H-
indole (2:1) (6g). According to GP (step 1), 1-tert-
butyldimethylsilyloxy-4-pentyne (0.47 ml, 2.0 mmol)
and N-(3,4-dichlorophenyl)-N-benzylhydrazine (440 mg,
1.65 mmol) were employed. Isolated yield: 84%, brown oil.
4.3.9. N-Benzyl-3-(3-{tert-butyldimethylsilyloxy}pro-
pyl)-3-chloro-2-methyl-1H-indole/N-benzyl-3-(3-{tert-
butyldimethylsilyloxy}propyl)-3-dichloro-2-methyl-1H-
indole (2:1) (6k). According to GP (step 1), 1-tert-
butyldimethylsilyloxy-5-hexyne (0.49 ml, 2.0 mmol) and
N-(3-chlorophenyl)-N-benzylhydrazine (696 mg, 3.0 mmol)
were employed. Isolated yield: 71%, brown oil.
1H NMR (CDCl3, 400 MHz): dZ7.29–7.24 (m, 3H), 7.14
(d, JZ8.7 Hz, 1H), 7.01 (d, JZ8.7 Hz, 1H), 6.93–6.91 (m,
2H), 5.29 (s, 2H), 3.85 (t, JZ6.4 Hz, 2H), 3.79 (t, JZ
6.4 Hz, 2H), 2.31 (s, 3H), 0.90 (s, 9H), 0.03 (s, 6H)/7.63 (s,
1H), 7.29–7.24 (m, 3H), 7.25 (s, 1H), 6.93–6.91 (m, 2H),
5.25 (s, 2H), 3.70 (t, JZ6.5 Hz, 2H), 3.94 (t, JZ6.5 Hz, 2H),
2.28 (s, 3H), 0.89 (s, 9H), 0.02 (s, 6H). 13C NMR (CDCl3,
100 MHz): dZ136.8, 136.5, 136.2, 128.1, 127.5, 125.4,
125.7, 123.5, 122.1, 120.6, 110.4, 108.4, 63.5, 46.7, 28.1,
25.9, 18.2, 10.4, K5.3/136.9, 135.8, 135.2, 128.1, 128.0,
127.5, 125.7, 124.3, 121.9, 119.2, 112.5, 108.7, 64.8, 46.7,
28.5, 25.9, 18.3, 10.4, K5.3. MS (EI, 70 eV) m/z (relative
intensity): 447 (5) [MC KH], 390 (15), 356 (1), 316 (5), 302
(14), 291 (5), 265 (49), 251 (3), 215 (2), 181 (1), 145 (1),
115 (1), 91 (100), 75 (4), 65 (6), 57 (4), 41 (3), 28 (2).
HRMS Calcd for C24H3135Cl2NOSi: 447.15521. Found:
447.15576.
1H NMR (CDCl3, 400 MHz): dZ7.34–7.30 (m, 3H), 7.26–
7.24 (m, 2H), 7.04 (t, JZ8.2 Hz, 1H), 6.59–6.56 (m, 2H),
4.61 (s, 2H), 3.62 (t, JZ6.0 Hz, 2H), 2.21 (t, JZ6.0 Hz, 2H),
1.93 (s, 3H), 1.64–1.58 (m, 2H), 0.88 (s, 9H), 0.03 (s, 6H)/
7.34–7.30 (m, 3H), 7.21–7.19 (m, 3H), 6.59–6.56 (m, 2H),
4.61 (s, 2H), 3.62 (t, JZ6.8 Hz, 2H), 2.21 (t, JZ6.8 Hz, 2H),
1.93 (s, 3H), 1.64–1.58 (m, 2H), 0.89 (s, 9H), 0.04 (s, 6H).
13C NMR (CDCl3, 100 MHz): dZ137.7, 135.5, 130.1,
128.7, 127.0, 126.5, 125.7, 123.4, 116.6, 112.1, 110.5, 62.5,
54.0, 31.7, 25.9, 24.9, 18.1, 10.2, K5.3/137.7, 135.5, 130.1,
128.7, 127.0, 126.5, 125.7, 123.4, 116.6, 112.1, 110.5, 62.5,
54.0, 31.7, 25.9, 24.9, 18.1, 10.2, K5.3. MS (EI, 70 eV) m/z
(relative intensity): 427 (39) [MC KH], 412 (2), 370 (45),
342 (6), 320 (1), 295 (3), 279 (14), 268 (17), 234 (10), 204
(2), 177 (2), 143 (2), 115 (2), 101 (2), 91 (100), 73 (6), 65 (5),
58 (4), 41 (3), 29 (1). HRMS Calcd for C25H3435ClNOSi:
427.20981. Found: 427.20884.
4.3.7. 3-(3-{tert-Butyldimethyl)silyloxy}propyl)-1,2-
dimethyl-1H-indole (6h). According to GP (step 1),
1-tert-butyldimethylsilyloxy-5-hexyne (0.49 ml, 2.0 mmol)
and N-methyl-N-phenylhydrazine (0.28 ml, 2.4 mmol) were
employed. Isolated yield: 85%, light brown oil.
4.3.10. N-Benzyl-3-(3-{tert-butyldimethylsilyloxy}pro-
pyl)-4,5-dichloro-2-methyl-1H-indole/N-benzyl-3-(3-
(tert-butyldimethylsilyloxy(propyl)-5,6-dichloro-2-
methyl-1H-indole (2:1) (6l). According to GP (step 1),
1-tert-butyldimethylsilyloxy-5-hexyne (0.49 ml, 2.0 mmol)
and N-(3,4-dichlorophenyl)-N-benzylhydrazine (801 mg,
3.0 mmol) were employed. Isolated yield: 84%, brown oil.
1H NMR (CDCl3, 400 MHz): dZ7.51 (d, JZ7.9 Hz, 1H),
7.22 (d, JZ7.9 Hz, 1H), 7.12 (t, JZ1.0, 7.5 Hz, 1H), 7.04
(td, JZ0.8, 7.4 Hz, 1H), 3.64 (t, JZ6.1 Hz, 2H), 3.62 (s,

7628
V. Khedkar et al. / Tetrahedron 61 (2005) 7622–7631
1H NMR (CDCl3, 400 MHz): dZ7.28–7.20 (m, 3H), 7.10
(d, JZ8.7 Hz, 1H), 7.00 (d, JZ8.7 Hz, 1H), 6.90–6.87 (m,
2H), 5.28 (s, 2H), 3.66 (t, JZ6.4 Hz, 2H), 3.00 (t, JZ
6.4 Hz, 2H), 2.28 (s, 3H), 1.64–1.60 (m, 2H), 0.91 (s, 9H, H),
0.05 (s, 6H)/7.65 (s, 1H), 7.28–7.20 (m, 3H), 7.25 (s, 1H),
6.90–6.87 (m, 2H), 5.26 (s, 2H), 3.60 (t, JZ6.2 Hz, 2H),
2.75 (t, JZ6.2 Hz, 2H), 2.27 (s, 3H), 1.58–1.50 (m, 2H),
0.89 (s, 9H), 0.04 (s, 6H). 13C NMR (CDCl3, 100 MHz): dZ
137.1, 135.6, 130.5, 128.8, 128.4, 127.8, 127.5, 127.1,
125.7, 121.9, 110.3, 108.3, 62.5, 46.6, 35.6, 25.9, 22.9, 18.4,
10.4, K5.3/137.0, 130.5, 130.2, 128.7, 128.3, 127.8, 125.5,
123.5, 122.1, 119.1, 114.9, 108.7, 61.9, 46.7, 33.6, 25.9,
21.6, 18.3, 10.4, K5.3. MS (EI, 70 eV) m/z (relative
intensity): 462 (75) [MC], 448 (8), 406 (100), 387 (18), 313
(28), 268 (25), 235 (6), 211 (7), 171 (8), 115 (8), 92 (20), 77
(15), 65 (4), 57 (11), 41 (9), 28 (5). HRMS Calcd for
C23H3335Cl2NOSi: 461.17084. Found: 461.17087.
1H NMR (CDCl3, 400 MHz): dZ7.46 (d, JZ2.0 Hz, 1H),
7.13 (d, JZ8.7 Hz, 1H), 7.09 (dd, JZ2.0, 8.7 Hz, 1H), 3.78
(t, JZ6.5 Hz, 2H), 3.62 (s, 3H), 2.93 (t, JZ6.5 Hz, 2H),
2.36 (s, 3H), 1.49 (br, 1H, OH). 13C NMR (CDCl3,
100 MHz): dZ135.7, 135.0, 128.7, 124.6, 120.8, 117.3,
109.5, 106.6, 62.8, 29.6, 27.8, 10.3. MS (EI, 70 eV) m/z
(relative intensity): 223 (34) [MC], 192 (100), 177 (9), 157
(16), 142 (6), 128 (4), 115 (10), 101 (3), 87 (1), 75 (3), 63 (1),
56 (1), 42 (2), 31 (5). FT IR (nujol, cmK1): 3288, 2930,
2870, 1611, 1569, 1477, 1433, 1409, 1371, 1331, 1283,
1261, 1245, 1200, 1174, 1134, 1072, 1048, 985, 935, 897,
862, 809, 787, 747, 636, 585, 533, 476, 428. HRMS Calcd
for C12H1435ClNO: 223.07639. Found: 223.07672.
4.3.14. 2-(N-Benzyl-5-fluoro-2-methyl-1H-indole-3-yl)
ethanol (11d). According to GP (step 2), crude product
6d (964 mg, 3.0 mmol) and TBAF (1 M in THF, 6.0 ml,
6.0 mmol) were employed. Isolated yield: 76%, colorless
oil.
4.3.11. 2-(1,2-Dimethyl-1H-indole-3-yl)ethanol (11a).19
According to GP (step 2), product 6a (300 mg, 1.0 mmol)
and TBAF-trihydrate (630 mg, 2.0 mmol) were employed.
Isolated yield: 81%, colorless oil.
1H NMR (CDCl3, 400 MHz): dZ7.28–7.24 (m, 3H), 7.19
(dd, JH,HZ2.3 Hz, JF,HZ9.5 Hz, 1H), 7.19 (dd, JF,H
Z
4.0 Hz, JH,HZ8.5 Hz, 1H), 6.93 (d, JZ6.5 Hz, 2H), 6.83
(td, JH,HZ2.3 Hz, JH,HZJF,HZ9.1 Hz, 1H), 5.27 (s, 2H),
3.82 (t, JZ6.5 Hz, 2H), 2.97 (t, JZ6.5 Hz, 2H), 2.31 (s, 3H),
1.57 (br, 1H, OH). 13C NMR (CDCl3, 100 MHz): dZ159.0,
137.5, 135.8, 133.0, 128.8, 127.3, 125.8, 124.9, 109.6,
190.5, 109.1, 107.6, 62.8, 46.7, 28.0, 10.4. MS (EI, 70 eV)
m/z (relative intensity): 283 (5) [MC], 266 (6), 252 (33), 239
(4), 213 (17), 199 (7), 162 (2), 122 (7), 115 (1), 91 (100), 75
(5), 65 (13), 39 (3), 28 (2). FT IR (neat, cmK1): 3357, 3063,
3030, 2935, 2877, 1706, 1622, 1604, 1583, 1506, 1482,
1453, 1419, 1359, 1300, 1250, 1204, 1139, 1140, 969, 851,
791, 728, 694, 629, 589, 433. HRMS Calcd for C18H18FNO:
283.13724. Found: 283.13764.
1H NMR (CDCl3, 400 MHz): dZ7.52 (d, JZ7.9 Hz, 1H),
7.25 (d, JZ7.8 Hz, 1H), 7.16 (td, JZ1.1, 8.1 Hz, 1H), 7.07
(td, JZ1.0, 7.9 Hz, 1H), 3.81 (t, JZ6.4 Hz, 2H), 3.65 (s,
3H), 2.98 (t, JZ6.4 Hz, 2H), 2.37 (s, 3H), 1.52 (br, 1H, OH).
13C NMR (CDCl3, 100 MHz): dZ136.6, 134.2, 127.7,
120.7, 118.9, 117.8, 108.6, 106.6, 62.9, 29.5, 27.9, 10.2. MS
(EI, 70 eV) m/z (relative intensity): 189 (49) [MC], 170 (1),
158 (100), 143 (18), 128 (7), 115 (15), 102 (6), 91 (4), 84
(69), 77 (5), 57 (4), 47 (20), 41 (5), 29 (7). FT IR (neat, cmK1):
3366, 3052, 2934, 1614, 1566, 1473, 1432, 1411, 1370,
1331, 1245, 1193, 1149, 1129, 1041, 1021, 909, 886, 738,
647, 609, 560, 433. HRMS Calcd for C12H15NO:
189.11537. Found: 189.11525.
4.3.15. 2-(N-Benzyl-5-methoxy-2-methyl-1H-indole-3-yl)
ethanol (11e). According to GP (step 2), product 6e
(328 mg, 0.8 mmol) and TBAF (1 M in THF, 1.6 ml,
1.6 mmol) were employed. Isolated yield: 85%, light
green solid, mp: 78–80 8C.
4.3.12. 2-(N-Benzyl-2-methyl-1H-indole-3-yl)ethanol
(11b).19 According to GP (step 2), product 6b (296 mg,
0.78 mmol) and TBAF-trihydrate (492 mg, 1.6 mmol) were
employed. Isolated yield: 80%, colorless oil.
1H NMR (CDCl3, 400 MHz): dZ7.57 (d, JZ8.3 Hz, 1H),
7.27–7.19 (m, 4H), 7.14–7.07 (m, 2H), 6.96 (dd, JZ1.6,
6.5 Hz, 2H), 5.30 (s, 2H), 3.84 (t, JZ6.5 Hz, 2H), 3.02 (t,
JZ6.5 Hz, 2H), 2.31 (s, 3H), 1.49 (br, 1H, OH). 13C NMR
(CDCl3, 100 MHz): dZ137.8, 136.5, 134.0, 128.7, 127.9,
127.2, 125.9, 121.0, 119.2, 117.9, 109.0, 107.4, 62.9, 46.5,
28.0, 10.3. MS (EI, 70 eV) m/z (relative intensity): 265
(100) [MC], 234 (66), 218 (49), 189 (2), 143 (24), 128 (6),
115 (13), 102 (14), 91 (89), 77 (14), 65 (33), 51 (10), 39 (11),
31 (22). FT IR (neat, cmK1): 3311, 3054, 2923, 2863, 1614,
1604, 1567, 1494, 1471, 1452, 1435, 1369, 1339, 1297,
1262, 1219, 1191, 1176, 1125, 1083, 1035, 1014, 922, 903,
873, 817, 749, 724, 694, 652, 554, 454, 432. HRMS Calcd
for C18H19NO: 265.14667. Found: 265.14531.
1H NMR (CDCl3, 400 MHz): dZ7.26–7.20 (m, 3H), 7.12
(m, 1H), 7.10–7.02 (m, 2H), 6.75 (dd, JZ2.1 Hz, JZ
8.6 Hz, 2H), 5.28 (s, 2H), 3.80 (s, 3H), 3.68 (t, JZ7.5 Hz,
2H), 2.75 (t, JZ7.5 Hz, 2H), 2.04 (s, 3H), 1.47 (br, 1H, OH).
13C NMR (CDCl3, 100 MHz): dZ154.0, 141.0, 137.9,
135.6, 134.7, 132.4, 128.7, 125.8, 110.7, 109.9, 101.9, 99.1,
62.0, 55.8, 46.4, 28.1, 10.4. MS (EI, 70 eV) m/z (relative
intensity): 295 (66) [MC], 264 (31), 251 (75), 236 (6), 218
(2), 174 (7), 160 (57), 147 (4), 130 (5), 116 (4), 91 (100), 77
(3), 65 (10), 39 (2), 29 (1). FT IR (nujol, cmK1): 3368, 3052,
2931, 2852, 1610, 1596, 1460, 1445, 1372, 1321, 1249,
1186, 1128, 1085, 969, 877, 739, 692, 540, 432. HRMS
Calcd for C19H21NO2: 295.15723. Found: 295.15768.
4.3.16. 2-(N-Benzyl-4-chloro-5-fluoro-2-methyl-1H-
indole-3-yl)ethanol/2-(N-benzyl-6-chloro-5-fluoro-2-
methyl-1H-indole-3-yl)ethanol (2:1) (11f). According to
GP (step 2), product 6f (518 mg, 1.2 mmol) and TBAF (1 M
in THF, 2.4 ml, 2.4 mmol) were employed. Isolated yield:
83%, white solid, mp: 74–77 8C.
4.3.13. 2-(5-Chloro-2-methyl-1H-indole-3-yl)ethanol
(11c). According to GP (step 2), product 6c (539 mg,
1.6 mmol) and TBAF (1 M in THF, 3.14 ml, 3.14 mmol)
were employed. Isolated yield: 90%, white solid, mp:
64–67 8C.

V. Khedkar et al. / Tetrahedron 61 (2005) 7622–7631
7629
1H NMR (CDCl3, 400 MHz): dZ7.27–7.18 (m, 3H), 6.99
(dd, JH,HZ3.9 Hz, JF,HZ8.9 Hz, 1H), 6.92–6.88 (m, 3H),
5.26 (m, 2H), 3.88 (t, JZ6.8 Hz, 2H), 3.24 (t, JZ6.8 Hz,
2H), 2.32 (s, 3H), 1.56 (br, 1H, OH)/7.29 (d, JF,HZ9.9 Hz,
1H), 7.27–7.18 (m, 3H), 7.16 (d, JF,HZ6.0 Hz, 1H), 6.92–
6.88 (m, 2H), 5.23 (s, 2H), 3.80 (t, JZ6.6 Hz, 2H), 2.94 (t,
JZ6.6 Hz, 2H), 2.30 (s, 3H), 1.56 (br, 1H, OH). 13C NMR
(CDCl3, 100 MHz): dZ152.4, 136.9, 137.1, 133.7, 128.8,
127.5, 125.7, 124.8, 110.1, 109.5, 109.3, 107.8, 64.1, 46.8,
28.2, 10.5/152.2, 137.3, 136.3, 132.8, 128.8, 127.5, 126.7,
125.6, 114.0, 109.5, 107.9, 104.1, 62.7, 46.7, 27.9, 10.4. MS
(EI, 70 eV) m/z (relative intensity): 317 (13) [MC], 286 (64),
262 (2), 235 (42), 205 (5), 195 (5), 185 (1), 159 (6), 145 (4),
129 (6), 117 (3), 109 (4), 99 (2), 91 (100), 77 (4), 65 (14), 57
(5), 49 (20), 41 (4), 28 (7). FT IR (nujol, cmK1): 3355, 3029,
2929, 2856, 1604, 1568, 1486, 1467, 1445, 1414, 1371,
1356, 1299, 1263, 1242, 1217, 1177, 1147, 1062, 1025, 986,
935, 856, 796, 766, 691, 605, 532, 465, 432. HRMS Calcd
for C18H1735ClFNO: 317.12207. Found: 317.12568.
136.8, 136.1, 130.8, 128.9, 127.5, 125.8, 125.6, 123.8,
122.3, 119.1, 110.8, 108.8, 61.8, 46.7, 31.0, 22.9/136.9,
135.4, 130.2, 128.5, 128.0, 127.5, 125.6, 124.7, 123.0,
119.2, 108.5, 107.5, 61.8, 46.5, 31.0, 22.9. MS (EI, 70 eV)
m/z (relative intensity): 333 (16) [MC KH], 302 (100), 289
(34), 254 (5), 215 (4), 199 (2), 176 (7), 141 (5), 115 (3), 101
(2), 91 (85), 85 (21), 77 (4), 65 (8), 57 (2), 43 (13), 29 (5).
FT IR (nujol, cmK1): 3357, 3028, 2928, 2856, 1602, 1587,
1498, 1479, 1445, 1419, 1392, 1350, 1291, 1266, 1245,
1227, 1186, 1137, 1088, 1047, 996, 942, 875, 756, 716, 699,
623, 582, 475, 432. HRMS Calcd for C18H1735Cl2NO:
333.06873. Found: 333.06876.
4.3.19. 3-(1,2-Dimethyl-1H-indole-3-yl)propanol (11h).
According to GP (step 2), product 6h (507 mg, 1.6 mmol)
and TBAF (1 M in THF, 3.2 ml, 3.2 mmol) were employed.
Isolated yield: 90%, colorless oil.
1H NMR (CDCl3, 400 MHz): dZ7.51 (d, JZ7.7 Hz, 1H),
7.23 (d, JZ8.1 Hz, 1H), 7.14 (td, JZ1.3, 8.2 Hz, 1H), 7.06
(td, JZ1.2, 8.0 Hz, 1H), 3.67 (t, JZ6.5 Hz, 2H), 3.64 (s,
3H, H), 2.81 (t, JZ6.5 Hz, 2H), 2.35 (s, 3H), 1.87 (quint,
JZ6.5 Hz, 2H), 1.32 (br, 1H, OH). 13C NMR (CDCl3,
100 MHz): dZ136.5, 132.8, 127.6, 120.4, 118.6, 117.8,
110.4, 108.5, 62.5, 33.6, 29.4, 20.4, 10.1. MS (EI, 70 eV)
m/z (relative intensity): 203 (13) [MC], 172 (1), 158 (87),
143 (7), 128 (6), 115 (100), 102 (1), 91 (1), 75 (1), 65 (1), 55
(1), 42 (2), 28 (1). FT IR (neat, cmK1): 3355, 3051, 2935,
2855, 1613, 1566, 1472, 1440, 1410, 1370, 1331, 1247,
1191, 1148, 1128, 1060, 1013, 983, 919, 856, 738, 654, 559,
433. HRMS Calcd for C13H17NO: 203.13101. Found:
203.13123.
4.3.17. 2-(N-Benzyl-4,5-dichloro-2-methyl-1H-indole-3-
yl)ethanol/2-(N-Benzyl-5,6-dichloro-2-methyl-1H-
indole-3-yl)ethanol (2:1) (11g, M). According to GP (step
2), product 6g (897 mg, 2.0 mmol) and TBAF (1 M in THF,
4.0 ml, 4.0 mmol) were employed. Isolated yield: 60%, off
white solid, mp: 95–97 8C.
1H NMR (CDCl3, 400 MHz): dZ7.27–7.22 (m, 3H), 7.12
(d, JZ8.5 Hz, 1H), 7.02 (d, JZ8.7 Hz, 1H), 6.92–6.88 (dd,
JZ1.0, 7.0 Hz, 2H), 5.27 (s, 2H), 3.88 (t, JZ6.7 Hz, 2H),
3.25 (t, JZ6.7 Hz, 2H), 2.33 (s, 3H,), 1.55 (br, 1H, OH)/
7.64 (s, 1H), 7.27–7.22 (m, 3H), 7.25 (s, 1H), 6.92–6.88 (dd,
JZ1.0, JZ7.0 Hz, 2H), 5.23 (s, 2H), 3.81 (t, JZ6.5 Hz,
2H), 2.95 (t, JZ6.5 Hz, 2H), 2.30 (s, 3H), 1.55 (br, 1H, OH)
4.3.20. 3-(N-Benzyl-2-methyl-1H-indole-3-yl)propanol
(11i).20 According to GP (step 2), product 6i (707 mg,
1.8 mmol) and TBAF (1 M in THF, 3.6 ml, 3.6 mmol) were
employed. Isolated yield: 84%, colorless oil.
.
13C NMR (CDCl3, 100 MHz): dZ136.8, 136.2, 136.0,
128.2, 127.5, 125.8, 125.7, 123.8, 122.2, 119.0, 110.5,
108.5, 64.1, 46.8, 28.4, 10.5/136.9, 135.4, 135.2, 128.2,
128.0, 127.5, 125.8, 124.7, 123.0, 119.2, 108.2, 107.6, 62.8,
46.8, 27.8, 10.4. MS (EI, 70 eV) m/z (relative intensity): 333
(16) [MC KH], 302 (23), 289 (13), 254 (2), 215 (2), 198 (2),
175 (3), 142 (4), 111 (1), 99 (2), 91 (100), 85 (26), 77 (2), 65
(10), 57 (2), 43 (11), 29 (4). FT IR (nujol, cmK1): 3356,
3029, 2928, 2856, 1678, 1603, 1537, 1499, 1457, 1426,
1411, 1370, 1345, 1290, 1243, 1222, 1207, 1176, 1147,
1062, 1027, 996, 933, 865, 776, 716, 696, 613, 525, 435,
439. HRMS Calcd for C18H1735Cl2NO: 333.06873. Found:
333.06876.
1H NMR (CDCl3, 400 MHz): dZ7.57–7.54 (m, 1H), 7.25–
7.16 (m, 4H), 7.07–7.05 (m, 2H), 6.93 (d, JZ6.5 Hz, 2H),
5.27 (s, 2H), 3.64 (t, JZ6.3 Hz), 2.83 (t, JZ6.3 Hz, 2H),
2.27 (s, 3H), 1.89 (quint, JZ6.3 Hz, 2H), 1.49 (br, 1H, OH).
13C NMR (CDCl3, 100 MHz): dZ138.0, 136.4, 132.6,
128.6, 127.8, 127.1, 125.8, 120.7, 118.9, 118.9, 111.1,
108.9, 62.4, 46.4, 33.4, 20.4, 10.1. MS (EI, 70 eV) m/z
(relative intensity): 279 (31) [MC], 234 (68), 218 (41), 189
(4), 142 (23), 129 (8), 115 (18), 102 (11), 91 (100), 77 (14),
65 (23), 51 (13), 39 (11), 31 (17). FT IR (neat, cmK1): 3361,
3053, 3029, 2933, 2858, 1605, 1584, 1567, 1495, 1468,
1453, 1415, 1367, 1336, 1300, 1260, 1180, 1147, 1062,
1028, 974, 919, 850, 738, 696, 634, 558, 455, 434. HRMS
Calcd for C19H20NO: 279.16231. Found: 279.16249.
4.3.18. 3-(N-Benzyl-4,5-dichloro-1H-indole-3-yl)propa-
nol/3-(N-Benzyl-5,6-dichloro-1H-indole-3-yl)propanol
(2:1) (11g, anti-M). According to GP (step 2), product 6g
(1155.0 mg, 2.5 mmol) and TBAF (1 M in THF, 5.0 ml,
5.0 mmol) were employed. Isolated yield: 29%, off white
solid, mp: 97–99 8C.
4.3.21. 3-(1,2,3-Trimethyl-1H-indole-3-yl)propanol
(11j). According to GP (step 2), crude product 6j and
TBAF (1 M in THF, 6.0 ml, 6.0 mmol) were employed.
Isolated yield: 75%, white solid, mp: 49–51 8C.
1H NMR (CDCl3, 400 MHz): dZ7.38–7.25 (m, 3H), 7.13
(d, JZ8.7 Hz, 1H), 7.03 (d, JZ8.7 Hz, 1H), 6.91–6.89 (dd,
JZ1.0, 6.3 Hz, 2H), 6.5 (s, 1H), 5.31 (s, 2H), 3.73–3.68 (m,
2H), 2.79 (t, JZ6.5 Hz, 2H), 2.02–1.91 (m, 2H), 1.57 (br,
1H, OH)/7.62 (s, 1H), 7.38–7.25 (m, 3H), 7.24 (s, 1H),
6.91–6.89 (dd, JZ1.0, 6.3 Hz, 2H), 6.3 (s, 1H), 5.27 (s, 2H),
3.73–3.68 (m, 2H), 2.76 (t, JZ6.5 Hz, 2H), 2.02–1.91 (m,
2H), 1.57 (br, 1H, OH). 13C NMR (CDCl3, 100 MHz): dZ
1H NMR (CDCl3, 400 MHz): dZ7.28 (s, 1H), 7.11 (d, JZ
8.1 Hz, 1H), 6.95 (dd, JZ1.6, 8.3 Hz, 1H), 3.65 (t, JZ
6.4 Hz, 2H), 3.60 (s, 3H), 2.77 (t, JZ6.4 Hz, 2H, H), 2.44 (s,
3H), 2.32 (s, 3H), 1.87 (quint, JZ6.4 Hz, 2H), 1.45 (br, 1H,
OH). 13C NMR (CDCl3, 100 MHz): dZ135.6, 134.9, 132.8,

7630
V. Khedkar et al. / Tetrahedron 61 (2005) 7622–7631
127.7, 121.9, 117.6, 109.8, 108.1, 62.6, 33.6, 29.4, 21.4,
20.4, 10.1. MS (EI, 70 eV) m/z (relative intensity): 217 (27)
[MC], 198 (1), 186 (2), 172 (100), 157 (5), 142 (2), 128 (2),
115 (4), 91 (2), 77 (1), 57 (2), 39 (1), 28 (1). FT IR (nujol,
cmK1): 3295, 3014, 2917, 2850, 1619, 1581, 1565, 1489,
1443, 1410, 1370, 1321, 1299, 1246, 1208, 1181, 1156,
1135, 1072, 1028, 912, 896, 862, 781, 751, 694, 661, 586,
505, 430. HRMS Calcd for C14H19NO: 217.14667. Found:
217.14671.
732, 698, 632, 595, 456, 429. HRMS Calcd for C19H1935Cl2-
NOSi: 347.08438. Found: 347.08328.
4.3.24. 3-(N-Benzyl-4,5-dichloro-1H-indole-3-yl)butanol/
3-(N-Benzyl-5,6-dichloro-1H-indole-3-yl) butanol (2:1)
(11l, anti-M). According to GP (step 2), product 6l
(1155.0 mg, 2.5 mmol) and TBAF (1 M in THF, 5.0 ml,
5.0 mmol) were employed. Isolated yield: 26%, white solid,
mp: 71–74 8C.
1H NMR (CDCl3, 400 MHz): dZ7.27–7.21 (m, 3H), 7.09
(d, JZ8.7 Hz, 1H), 6.96 (d, JZ8.5 Hz, 1H), 6.87 (dd, JZ
1.8, 7.3 Hz, 2H), 5.25 (s, 2H), 3.62–3.58 (m, 2H), 2.69–2.62
(m, 2H), 1.80–1.72 (m, 2H), 1.70–1.60 (m, 2H), 1.47 (br,
1H, OH)/7.61 (s, 1H), 7.27–7.21 (m, 3H), 7.25 (s, 1H), 6.87
(dd, JZ1.8, 7.3 Hz, 2H), 5.21 (s, 2H), 3.62–3.58 (m, 2H),
2.69–2.62 (m, 2H), 1.80–1.72 (m, 2H), 1.70–1.60 (m, 2H),
1.47 (br, 1H, OH). 13C NMR (CDCl3, 100 MHz): dZ136.0,
136.61, 135.8, 128.9, 127.6, 127.5, 125.7, 125.6, 124.3,
122.1, 110.6, 108.7, 62.3, 46.6, 32.1, 26.4, 24.3/136.9,
135.5, 130.2, 128.9, 128.8, 127.6, 125.7, 122.9, 122.1,
120.6, 112.1, 110.4, 62.3, 46.4, 32.1, 26.3, 24.2. MS (EI,
70 eV) m/z (relative intensity): 347 (45) [MC], 302 (21),
289 (58), 276 (7), 253 (8), 238 (3), 214 (5), 198 (4), 175 (9),
149 (6), 149 (5), 127 (4), 111 (6), 99 (32), 91 (100), 71 (14),
65 (38), 57 (15), 43 (25), 31 (23). FT IR (nujol, cmK1):
3351, 3087, 3064, 3030, 2936, 2867, 1604, 1588, 1563,
1539, 1496, 1452, 1406, 1355, 1330, 1259, 1209, 1155,
1141, 1121, 1101, 1069, 1029, 983, 946, 906, 868, 837, 776,
732, 698, 654, 575, 468, 456. HRMS Calcd for
C19H1935Cl2NO: 347.08438. Found: 347.08555.
4.3.22. 3-(N-Benzyl-4-chloro-1H-indole-3-yl)propanol/
3-(N-Benzyl-6-chloro-1H-indole-3-yl) propanol (2:1)
(11k). According to GP (step 2), product 6k (728 mg,
1.7 mmol) and TBAF (1 M in THF, 3.4 ml, 3.4 mmol) were
employed. Isolated yield: 75%, colorless oil.
1H NMR (CDCl3, 400 MHz): dZ7.45 (d, JZ8.3 Hz, 1H),
7.30–7.21 (m, 4H), 6.92 (t, JZ8.2 Hz, 1H), 6.91–6.89 (m,
2H), 5.27 (s, 2H), 3.70 (t, JZ6.3 Hz, 2H), 3.05 (t, JZ
6.3 Hz, 2H), 2.29 (s, 3H), 1.91–1.80 (m, 2H), 1.40, (br, 1H,
OH)/7.30–7.21 (m, 3H), 7.17 (d, JZ1.8 Hz, 1H), 6.98–6.94
(m, 2H), 6.91–6.89 (m, 2H), 5.23 (s, 2H), 3.64 (t, JZ6.2 Hz,
2H), 2.81 (t, JZ6.2 Hz, 2H), 2.27 (s, 3H), 1.91–1.80 (m,
2H), 1.40, (br, 1H, OH). 13C NMR (CDCl3, 100 MHz): dZ
137.4, 136.8, 135.6, 128.7, 127.3, 126.5, 125.3, 124.3,
120.6, 119.5, 108.9, 107.7, 62.4, 46.6, 33.4, 21.5, 10.2/
137.9, 134.3, 133.5, 128.7, 127.3, 126.6, 125.7, 125.3,
118.8, 111.6, 107.9, 62.2, 46.6, 32.2, 21.0, 10.1. MS (EI,
70 eV) m/z (relative intensity): 313 (70) [MC], 268 (94),
254 (17), 246 (3), 204 (3), 178 (4), 164 (3), 142 (6), 115 (5),
100 (2), 91 (100), 77 (4), 65 (17), 55 (5), 43 (12), 29 (7). FT
IR (neat, cmK1): 3354, 3028, 2928, 2855, 1605, 1598, 1567,
1496, 1477, 1445, 1419, 1373, 1356, 1298, 1263, 1243,
1219, 1176, 1137, 1068, 1027, 996, 932, 835, 766, 726, 696,
609, 532, 445, 433. HRMS Calcd for C19H2035ClNO:
313.12335. Found: 313.12378.
4.3.25. 3-(1-Methyl-2-phenyl-1H-indole-3-yl)propanol
(11m). According to GP (step 2), crude product 6m and
TBAF (1 M in THF, 0.6 ml, 0.6 mmol) were employed.
Isolated yield: 84%, colorless oil.
1H NMR (CDCl3, 400 MHz): dZ7.59 (d, JZ7.9 Hz, 1H),
7.48–7.41 (m, 4H), 7.31–7.27 (m, 2H), 7.21 (td, JZ1.2,
7.6 Hz, 1H), 7.09 (td, JZ1.0, 6.9 Hz, 1H), 3.73 (s, 3H), 3.52
(t, JZ6.6 Hz, 2H), 2.94 (t, JZ6.6 Hz, 2H), 1.80 (quint, JZ
6.6 Hz, 2H), 1.52 (br, 1H, OH). 13C NMR (CDCl3,
100 MHz): dZ136.7, 136.6, 135.5, 129.7, 128.5, 127.0,
125.9, 121.3, 119.6, 114.4, 108.8, 61.6, 32.6, 29.4, 20.7. MS
(EI, 70 eV) m/z (relative intensity): 265 (67) [MC], 247 (1),
232 (4), 220 (100), 204 (25), 179 (10), 165 (4), 152 (2), 144
(14), 115 (10), 102 (4), 91 (2), 77 (4), 57 (5), 42 (10), 28 (3).
FT IR (neat, cmK1): 3373, 3053, 2933, 2871, 1601, 1553,
1493, 1440, 1402, 1371, 1328, 1255, 1209, 1177, 1152,
1131, 1091, 1058, 940, 924, 844, 771, 743, 703, 675, 639,
610, 565, 501. HRMS Calcd for C18H19NO: 265.14667.
Found: 265.14601.
4.3.23. 3-(N-Benzyl-4,5-dichloro-2-methyl-1H-indole-3-
yl)propanol/3-(N-Benzyl-5,6-dichloro-2-methyl-1H-
indole-3-yl)propanol (2:1) (11l, M). According to GP (step
2), product 6l (1155.0 mg, 2.5 mmol) and TBAF (1 M in
THF, 5.0 ml, 5.0 mmol) were employed. Isolated yield:
62%, white solid, mp: 70–73 8C.
1H NMR (CDCl3, 400 MHz): dZ7.25–7.21 (m, 3H), 7.10
(d, JZ8.5 Hz, 1H), 6.99 (d, JZ8.5 Hz, 1H), 6.89–6.87 (m,
2H), 5.25 (s, 2H), 3.69 (t, JZ6.4 Hz, 2H), 3.04 (t, JZ
6.4 Hz, 2H), 2.29 (s, 3H), 1.95–1.82 (m, 2H), 1.54 (br, 1H,
OH)/7.60 (s, 1H), 7.25–7.21 (m, 3H), 7.24 (s, 1H), 6.89–
6.87 (m, 2H), 5.21 (s, 2H), 3.64 (t, JZ6.3 Hz, 2H), 2.77 (t,
JZ6.3 Hz, 2H), 2.27 (s, 3H), 1.95–1.82 (m, 2H), 1.54 (br,
1H, OH). 13C NMR (CDCl3, 100 MHz): dZ137.0, 135.9,
135.0, 128.8, 127.4, 127.1, 125.7, 125.6, 124.4, 122.0,
111.1, 108.4, 62.2, 46.6, 35.3, 21.0, 10.2/137.0, 135.5,
130.1, 128.8, 127.6, 127.4, 125.7, 123.6, 122.1, 119.0,
112.1, 110.4, 61.9, 46.6, 33.3, 20.20, 10.1. MS (EI, 70 eV)
m/z (relative intensity): 347 (14) [MC KH], 302 (100), 286
(54), 267 (7), 238 (11), 205 (6), 185 (3), 158 (4), 149 (7),
128 (3), 115 (4), 99 (5), 91 (90), 77 (8), 65 (27), 57 (4), 41
(2), 31 (6). FT IR (nujol, cmK1): 3425, 3064, 3030, 2936,
2864, 1604, 1591, 1496, 1473, 1448, 1411, 1355, 1299,
1219, 1162, 1133, 1102, 1060, 1028, 889, 867, 837, 787,
Acknowledgements
This work has been supported by the State of Mecklenburg–
Vorpommern. In addition, financial support from the BMBF
(Bundesministerium fu¨r Bildung und Forschung), the VCI,
and Gru¨nenthal AG are gratefully acknowledged. We thank
Mrs. C. Mewes, Mrs. H. Baudisch, Mrs. A. Lehmann, and
Mrs. S. Buchholz (all IfOK) for their excellent technical and
analytical support.

V. Khedkar et al. / Tetrahedron 61 (2005) 7622–7631
7631
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