Preparation of 3,4-enynoindoles via directed lithiation and application to the synthesis of 3,4-carbocycloindoles

Article abstract of DOI:10.1016/S0040-4020(02)00525-2

Lithiation at C4 of the indole nucleus is readily directed by several functional groups. The 4-substituted indoles thus obtained are transformed into suitable substrates for metathesis reactions. Ring-closing metathesis effected on these compounds lead to skeletons related to several indole alkaloids.

Full text of DOI:10.1016/S0040-4020(02)00525-2

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 5407±5415
Preparation of 3,4-enynoindoles via directed lithiation
and application to the synthesis of 3,4-carbocycloindoles
 Â
Leticia Perez-Serrano, Luis Casarrubios, Gema Domõnguez, Guillermo Freire
p
Â
and Javier Perez-Castells
 Â
Departamento de Quõmica, Facultad de Ciencias Experimentales y de la Salud, Universidad San Pablo-CEU, Urb. Monteprõncipe,
Boadilla del Monte, 28668 Madrid, Spain
Received 8 March 2002; revised 2 May 2002; accepted 21 May 2002
AbstractÐLithiation at C4 of the indole nucleus is readily directed by several functional groups. The 4-substituted indoles thus obtained are
transformed into suitable substrates for metathesis reactions. Ring-closing metathesis effected on these compounds lead to skeletons related
to several indole alkaloids. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
Several electrophiles were introduced successfully using
dimethylaminomethyl and methoxymethyl as directing
groups. Aldehydes reacted smoothly in good yields, and
bromine and iodine were readily introduced. Reactive
halides such as allyl bromide gave poor results in agreement
with those reported in the literature for other halides.10
Propylene oxide reacted with the gramine derivative 1 in
excellent yield but with ether 3 it gave a mixture of the
desired 4-substituted compound 15, and compound 17
(Scheme 2). The formation of 17 can be explained if the
lithiation of 3 occurs partially at C2. Then the silyl group
migrates to that position as described recently for other
indoles lithiated with BuLi.11 Methoxide is then lost to
The synthesis of 3,4-disubstituted indoles is an important
step to obtain several biologically active alkaloids, such as
ergot alkaloids, hapalindoles and others. The formation of
these compounds usually implies to construct the pyrrole
ring from a suitable benzenoid precursor.1 The direct
functionalization of the 4 position in the indole has been
scarcely done and normally goes via thallation2 or mercu-
ration3 reactions. Directed lithiation4 of the 4 position has
only been reported in few substrates derived from gramine.5
Functionalization at the 7 position of the indole has been
reported using this methodology.6 Additionally, the directed
lithiation has been applied for the synthesis of claviciptic
acid,7 and other related alkaloids.8 In this paper, we have
extended the directed lithiation of indole at the 4 position of
other substrates and we have transformed the resulting
compounds into tricyclic indoles related to natural products,
by means of metathesis reactions catalyzed by ruthenium
complexes.9
t
give intermediate C which reacts with BuLi to give D.
Finally, the electrophile reacts with the anionic nitrogen to
yield 17. Selecting suitable reaction conditions, the forma-
tion of 17 can be minimized to only 10% (Scheme 2). We
have not observed compounds analog to 17 in the reaction
with DMF.
On the other hand, compounds 2 and 4, with an extra methyl-
ene in the directing group, did not react, showing that in
these cases the directing group is too far to effect its func-
tion. We also tried to use an amide to direct lithiation in the
indole. Thus, compound 18a was reacted under the same
conditions using propylene oxide as electrophile. The major
2. Results and discussion
A modi®cation of the methodology reported by Iwao5 was
applied to several substrates, bearing several directing
groups (Scheme 1). Thus, lithiation at C4 of indoles 1±4
was accomplished with tBuLi in ether and after addition of
different electrophiles the corresponding 3,4-disubstituted
indoles 5±16 were obtained. The results are summarized
in Table 1.
Keywords: indoles; lithiation; enynes; metathesis; cyclizations.
Corresponding author. Tel.: 134-91372-4700; fax: 134-91351-0475;
e-mail: jpercas@ceu.es
p
Scheme 1.
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00525-2

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L. Perez-Serrano et al. / Tetrahedron 58 (2002) 5407±5415
5408
Table 1. Funtionalization at C4 in indoles by directed lithiation
Subs.
R1
Electrophile
R2
Prod.
Yielda (%)
1
1
1
CH2NMe2
CH2NMe2
CH2NMe2
I2
CH3CHO
CH2vCHCHO
I
CHOHCH3
CHOHCHvCH2
5
6
7
80
70
80
1
1
CH2NMe2
CH2NMe2
8
9
90
98
1
1
1
2
3
3
CH2NMe2
CH2NMe2
CH2NMe2
(CH2)2NMe2
CH2OMe
CH2vCHCH2Br
CH2CHvCH2
CH2CHOHCH3
Br
10
11
12
13
14
15
16
20
90
CBr4
DMF
I2
60
CH2CHOHCH3
CHO
,5b
55
CH2OMe
CH2CHOHCH3
I
50c
,5
4
(CH2)2OMe
a
Of pure material with correct spectroscopic data (1H, 13C NMR, IR).
Another 60% of 2-substituted compound was obtained.
See Scheme 2.
b
c
product in this reaction was the 2-silylated indole 19a
(50%), and also 30% of compound 20a was formed. This
implies a C2 lithiation, followed by migration of the triiso-
propylsilyl group, and partial reaction at the indole nitrogen.
We tried to favor lithiation at C4 by increasing the steric
demand of the substituents in the starting material, and thus
prepared compound 18b. The reaction of 18b afforded 40%
of the 2-silylated compound 19b, 15% of compound 20b
Scheme 2. The reaction of compound 3 with tBuLi and propylene oxide.
Scheme 3. The reaction of amides 18 with tBuLi and propylene oxide.

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L. Perez-Serrano et al. / Tetrahedron 58 (2002) 5407±5415
5409
Scheme 4. Metathesis reactions of compounds 23 and 24.
and only 10% of the desired 4-substituted compound 21b
(Scheme 3). From these results, we conclude that the amide
is not a good directing group for the 4 position in the indole
nucleus.
salt by reaction with benzyl bromide. The parent salt
obtained from 22 and methyl iodide was insoluble in
ethereal solvents and was practically unreactive against
Grignard reagents. Thus the benzyldimethylammonium
salt was used and it was reacted with convenient Grignard
reagents to yield 23 and 24 in good yields. These
compounds were reacted with 7% second generation
Grubbs' catalyst 28. Ring-closing metathesis (RCM) of
compound 23 yielded compound 25 readily, which however
Some of the 3,4-disubstituted indoles described above were
transformed into suitable precursors for metathesis reac-
tions. Thus, a Stille coupling of compound 5 gave the
4-vinylindole 22 which was transformed into its ammonium
Scheme 5. Metathesis reactions of compounds 29±31.

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L. Perez-Serrano et al. / Tetrahedron 58 (2002) 5407±5415
5410
decomposed partially after 15 min at room temperature.
Enyne metathesis of 24 proceeded with total conversion in
crude (1H NMR), and led to a mixture of 26a,b and 27.
Unfortunately, products 26 were unstable and decomposed
even in a Florisilw column, so they could not be isolated.
Attempts to effect a Diels±Alder reaction by adding maleic
anhydride to the metathesis reaction mixture were also
unsuccessful. After 3 days, no adduct was formed and
when heating, or on addition of other Lewis acid type
catalysts the result was decomposition. On the other hand,
compound 27 could be isolated in 35% yield. It may be
formed by cross-metathesis of compound 26a. This
compound is air-stable and can be chromatographed over
silica gel. We have found these type of dimeric compounds
in other enyne metathesis of indoles (Scheme 4).12
with water (25 mL) and extracted with ether (3£25 mL).
The combined organic phases were dried (MgSO4) and
concentrated. The crude was puri®ed by ¯ash chroma-
tography (CHCl3/MeOH 3:1) to obtain 1.2 g (65%) of 2 as
a colorless oil. 1H NMR (CDCl3) d 1.13 (d, 18H, Jˆ7.7 Hz),
1.62±1.74 (m, 3H), 2.36 (s, 6H), 2.61±2.66 (m, 2H), 2.91±
2.97 (m, 2H), 7.03 (s, 1H), 7.10±7.14 (m, 2H), 7.45±7.48
(m, 1H), 7.57±7.60 (m, 1H); 13C NMR (CDCl3) d 141.2,
130.8, 128.1, 121.2, 119.1, 118.4, 115.8, 113.8, 60.1, 45.3,
23.7, 18.0, 12.7; IR (neat) n 1610, 1465, 1450 cm21; Anal.
calcd for C21H36N2Si: C, 73.19; H, 10.53; N, 8.13. Found: C,
73.38; H, 10.74; N, 7.96.
4.1.2. 3-Methoxymethyl-1-triisopropylsilyl-1H-indole (3).
A solution of 3.0 g (18.60 mmol) of indole-3-carboxylic
acid in MeOH (150 mL) was saturated with HCl (g). The
mixture was heated under re¯ux for 24 h. The solvent was
evaporated under vacuum and the crude puri®ed by ¯ash
chromatography (hexane/EtOAc 1:1) to obtain 3.1 g
(quantitative) of the corresponding methyl ester. 1.5 g
(8.56 mmol) of this compound were added to a suspension
of 0.31 g (10.27 mmol) of NaH (80% in paraf®n) in THF
(17 mL) at 08C. After stirring for 3 h, 1.34 mL
(10.27 mmol) of triisopropylsilyl chloride was added drop-
wise and the mixture was allowed to warm at room tempera-
ture overnight. The solution was quenched with water
(15 mL), and extracted with ether (3£15 mL). The com-
bined organic phases were dried (MgSO4) and concentrated.
The crude was puri®ed by ¯ash chromatography (hexane/
EtOAc 9:1) to obtain 3.7 g (60%) of 3-carboxymethyl-1-
triisopropylsilylindole as a colorless oil. To 2.8 g (8.50
mmol) of this compound in dry THF (40 mL) and under
argon, a solution of 14.1 mL (21.2 mmol) of DIBAL-H
(1.5 M/Toluene) in dry THF (60 mL) was added dropwise
at 2788C. The reaction mixture was stirred for 24 h. The
reaction was then quenched by addition of saturated
aqueous sodium tartrate (70 mL) and extracted with
EtOAc (3£50 mL). The combined extracts were dried
(MgSO4) and evaporated under vacuum. Without further
puri®cation, a solution of this crude in 10 mL of dry THF
was added to 0.3 g (10.15 mmol) of NaH (80% in paraf®n)
in 20 mL of dry THF at 08C under argon. After vigorous
stirring for 15 min, a solution of 0.17 mL (12.70 mmol) of
iodomethane in 5 mL of dry THF was added dropwise and
kept at 08C for 1 h. The resulting mixture was then stirred at
room temperature overnight. Then, water (15 mL) was
added and the mixture was extracted with ether
(3£15 mL). The organic layers were dried (MgSO4) and
the solvent was removed under vacuo. The crude was puri-
®ed by ¯ash chromatography (hexane/EtOAc 99:1) to
In the same way, compounds 7±9 were transformed into the
enyne 29 and the dienes 30 and 31 via protection of the
hydroxy group and displacement of the trimethylammonium
salt with a Grignard reagent. Metathesis reactions using 7%
of catalyst 28 afforded the diene 32 and compounds 33 and
34 in good yields. These compounds are stable and could be
isolated and characterized (Scheme 5).
3. Conclusion
In conclusion, the functionalization at the position 4 of the
indole nucleus has been investigated. This can be a good
entry to 3,4-disubstituted indoles which can be readily
transformed into adequate substrates for RCMand enyne
metathesis reactions. The resulting products are related to
ergot alkaloids like claviciptic acid.
4. Experimental
4.1. General methods
Melting points were determined on a BuÈchi 530 apparatus
and are uncorrected. Thin layer chromatography (TLC) was
accomplished using Merck TLC aluminum sheets (silica gel
60 F254). Flash column chromatography was carried out on
Merck silica gel (230±400 mesh) and Florisilw. All 1H NM R
and 13C NMR spectra were recorded on a Bruker AM-300
instrument. Chemical shifts are given in ppm relative to
TMS (1H, 0.00 ppm) or to the corresponding 13C solvent
signal. IR spectra were recorded on a Perkin±Elmer 1330
spectrophotometer and are given in cm21. Elemental
analyses were performed in the UCMMicroanalysis Service
(Facultad de Farmacia, Universidad Complutense de
Madrid, Spain). Ruthenium benzylidene complex 28 was
obtained following literature methods.13
1
obtain 1.6 g (60%, two steps) of 3 as a colorless oil. H
NMR (CDCl3) d 1.13 (d, 18H, Jˆ7.7 Hz), 1.62±1.77 (m,
3H), 3.39 (s, 3H), 4.67 (s, 2H), 7.14±7.17 (m, 2H), 7.22 (s,
1H), 7.47±7.50 (m, 1H), 7.67±7.70 (m, 1H); 13C NM R
(CDCl3) d 141.4, 130.6, 130.5, 121.6, 119.8, 119.0, 114.9,
113.9, 66.6, 57.4, 18.1, 12.7; IR (neat) n 1615, 1470,
1450 cm21; Anal. calcd for C19H31NOSi: C, 71.87; H,
9.84; N, 4.41. Found: C, 72.03; H, 9.99; N, 4.24.
4.1.1.
Dimethyl[2-(1-triisopropylsilyl-1H-indol-3-yl)-
ethyl]-amine (2). Indole was transformed into N,N-di-
methyltryptamine following the method described by
Glennon.14 1.0 g (5.32 mmol) of this compound was added
to a suspension of 0.19 g (6.38 mmol) of NaH (80% in
paraf®n) in THF (25 mL) at 08C. After stirring for 3 h,
0.85 mL (6.38 mmol) of triisopropylsilyl chloride were
added dropwise and the mixture was allowed to warm at
room temperature overnight. The solution was quenched
4.1.3. 3-(2-Methoxyethyl)-1-triisopropylsilyl-1H-indole
(4). Following the same procedure employed for the syn-
thesis of 3, from 5.0 g (28.50 mmol) of 1H-indole-3-acetic
acid, and after puri®cation by ¯ash chromatography

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5411
(hexane/EtOAc 1:1), 4.7 g (85%) of the corresponding
methylester was obtained. From 4.3 g (23.70 mmol) of
this ester, 0.78 g (26.7 mmol) of NaH and 3.42 mL (25.00
mmol) of tiisopropylsilyl chloride, and after puri®cation by
¯ash chromatography (hexane/EtOAc 10:1), 4.9 g (60%)
of 3-carboxyethyl-1-triisopropylsilylindole was obtained.
From 2.4 g (7.03 mmol) of this compound, 11.7 mL
(17.60 mmol) of DIBAL-H and then by treatment with
0.25 g (8.44 mmol) of NaH and 1.6 mL (10.54 mmol) of
MeI, and after puri®cation by ¯ash chromatography
(hexane/EtOAc 99:1), 1.4 g (60%, two steps) of 4 was
Jˆ7.1 Hz), 7.44±7.48 (m, 3H), 7.59 (dd, 4H, J1ˆ8.2 Hz,
J2ˆ1.6 Hz), 7.77 (d, 1H, Jˆ7.7 Hz); 13C NMR (CDCl3) d
166.6, 140.5, 135.7, 131.5, 130.8, 130.3, 129.7, 128.1,
121.8, 120.7, 120.2, 116.7, 115.4, 48.2, 28.2, 21.2, 19.8;
IR (neat) n 1610, 1540, 1450, 1430 cm21; Anal. calcd for
C31H38N2OSi: C, 77.13; H, 7.93; N, 5.80. Found: C, 77.34;
H, 8.10; N, 5.63.
4.2. General procedure for the synthesis of compounds
5±17
1
tBuLi (1.60 mmol) was added dropwise to a stirred solution
of the corresponding indole (1.00 mmol) in dry ether (5 mL)
at 2788C and under argon. After 15 min, the mixture was
allowed to warm to 08C (ca. 20 min), and stirred at 08C for
an additional 1.5 h. After cooling to 2788C, the electrophile
(Table 1) (2.50 mmol) was added in small portions. The
resulting mixture was stirred for 15 min at 2788C and
then allowed to warm to room temperature for 1 h. 10 mL
of water were added and the crude extracted with ether
(3£10 mL). Evaporation of the solvent and puri®cation by
¯ash chromatography (hexane/EtOAc and CHCl3/MeOH
mixtures) yielded pure 5±17 compounds.
obtained as a colorless oil. H NMR (CDCl3) d 1.13 (d,
18H, Jˆ7.7 Hz), 1.61±1.76 (m, 3H), 3.04 (t, 2H, Jˆ
7.7 Hz), 3.40 (s, 3H), 3.67 (t, 2H, Jˆ7.7 Hz), 7.07±7.16
(m, 3H), 7.46±7.49 (m, 1H), 7.58±7.61 (m, 1H); 13C
NMR (CDCl3) d 141.1, 131.0, 128.7, 121.2, 119.2, 118.5,
114.5, 113.8, 73.0, 58.5, 25.7, 18.1, 12.8; IR (neat) n 1610,
1465, 1450 cm21; Anal. calcd for C20H33NOSi: C, 72.45; H,
10.03; N, 4.22. Found: C, 72.65; H, 10.21; N, 4.05.
4.1.4. N,N-Diethyl-1-triisopropylsilyl-1H-indole-3-carb-
oxamide (18a). Following the method described by
Knight,15 N-(p-toluenesulfonyl)indole was treated with
oxalyl chloride and diethylamine to obtain the N,N-di-
ethyl-1-phenylsulfonylindole-3-carboxamide. After hydroly-
sis of this tosylamide with 1.00 equiv. of KOH in MeOH
and puri®cation by ¯ash chromatography (hexane/
EtOAc 2:1), N,N-diethylindole-3-carboxamide (85%) was
obtained. 0.18 g (0.83 mmol) of this compound was added
to a suspension of 0.03 g (0.99 mmol) of NaH (80% in
paraf®n) in THF (5 mL) at 08C. After stirring for 3 h,
0.81 mL (0.99 mmol) of triisopropylsilyl chloride was
added dropwise and the mixture was allowed to warm to
room temperature overnight. The solution was quenched
with water (5 mL). The aqueous layers were extracted
with ether (3£5 mL) and the combined organic phases
dried (MgSO4) and concentrated. The crude was puri®ed
by ¯ash chromatography (hexane/EtOAc 4:1) to obtain
4.2.1. (4-Iodo-1-triisopropylsilyl-1H-indol-3-ylmethyl)-
dimethylamine (5). Following the general procedure,
from 0.50 g (1.50 mmol) of 1, 1.40 mL (2.40 mmol) of
tBuLi and 0.96 g (3.80 mmol) of iodine, and after puri®-
cation by ¯ash chromatography (hexane/EtOAc 1:1),
1
0.54 g (80%) of pure 5 was obtained as a yellow oil. H
NMR (CDCl3) d 1.15 (d, 18H, Jˆ7.7 Hz), 1.69±1.82 (m,
3H), 2.99 (s, 6H), 4.98 (s, 2H), 6.94 (t, 1H, Jˆ7.7 Hz), 7.58
(d, 1H, Jˆ8.2 Hz), 7.66 (d, 1H, Jˆ8.2 Hz), 8.08 (s, 1H); 13C
NMR (CDCl3) d 141.7, 138.5, 132.6, 129.7, 123.9, 114.9,
106.4, 84.4, 52.2, 42.7, 18.1, 12.6; IR (neat) n 1540, 1470,
1410 cm21; Anal. calcd for C20H33IN2Si: C, 52.62; H, 7.29;
N, 6.14. Found: C, 52.82; H, 7.50; N, 6.00.
1
0.3 g (95%) of 18a as a colorless oil. H NMR (CDCl3) d
4.2.2. 3-Dimethylaminomethyl-4-(1-hydroxyethyl)-1-tri-
isopropylsilyl-1H-indole (6). Following the general pro-
cedure, from 0.50 g (1.50 mmol) of 1, 1.40 mL (2.40
mmol) of tBuLi and 0.47 mL (3.80 mmol) of acetaldehyde,
and after puri®cation by ¯ash chromatography (hexane/
EtOAc 1:1), 0.39 g (70%) of pure 6 was obtained as a color-
less oil. 1H NMR (CDCl3) d 1.13 (d, 18H, Jˆ7.7 Hz), 1.64±
1.74 (m, 3H), 1.72 (d, 3H, Jˆ6.6 Hz), 2.25 (s, 6H), 3.27 (d,
1H, Jˆ13.0 Hz), 4.34 (d, 1H, Jˆ13.0 Hz), 5.49 (q, 1H, Jˆ
6.6 Hz), 7.09 (s, 1H), 7.11±7.19 (m, 2H), 7.41 (d, 1H, Jˆ
8.2 Hz); 13C NMR (CDCl3) d 142.9, 138.5, 132.3, 127.5,
121.8, 116.2, 114.2, 113.7, 65.1, 57.9, 44.3, 20.6, 18.1, 12.7;
IR (neat) n 3180, 1460, 1420 cm21; Anal. calcd for
C22H38N2OSi: C, 70.53; H, 10.22; N, 7.48. Found: C,
70.75; H, 10.44; N, 7.25.
1.15 (d, 18H, Jˆ7.7 Hz), 1.23 (t, 6H, Jˆ7.1 Hz), 1.63±1.78
(m, 3H), 3.55 (q, 4H, Jˆ7.1 Hz), 7.17±7.20 (m, 2H), 7.44
(s, 1H), 7.48±7.51 (m, 1H), 7.78±7.81 (m, 1H); 13C NM R
(CDCl3) d 166.6, 140.2, 130.8, 129.3, 121.9, 120.5, 120.4,
114.1, 113.6, 41.1, 17.7, 13.6, 12.4; IR (neat) n 1620, 1540,
1450, 1430 cm21; Anal. calcd for C22H36N2OSi: C, 70.91;
H, 9.74; N, 7.52. Found: C, 71.15; H, 9.95; N, 7.36.
4.1.5.
N,N-Diisopropyl-1-(tert-butyldiphenylsilyl)-1H-
indole-3-carboxamide (18b). Following same procedure
described for 18a, from 7.0 g (25.80 mmol) of 1-tosyl-
indole, 1.25 mL (129.00 mmol) of oxalyl chloride, 17.2 g
(129.00 mmol) of AlCl3, 13.7 mL (98.00 mmol) of triiso-
propylamine and treatment of the corresponding carboxa-
mide with KOH/MeOH, yielded after puri®cation by ¯ash
chromatography (hexane/EtOAc 2:1), 1.4 g (32%, two
steps) of N,N-diisopropylindole-3-carboxamide. The pro-
tection of this compound by treatment with 0.26 g
(9.90 mmol) of NaH and 2.30 mL (9.90 mmol) of tert-butyl-
diphenylsilyl chloride, and after puri®cation by ¯ash
chromatography (hexane/EtOAc 4:1), gave 2.0 g (56%) of
18b as a colorless oil. 1H NMR (CDCl3) d 1.24 (s, 9H), 1.37
(d, 12H, Jˆ6.1 Hz), 3.96 (bs, 2H), 6.79 (d, 1H, Jˆ8.2 Hz),
6.88 (t, 1H, Jˆ7.1 Hz), 7.10 (t, 1H, Jˆ8.2 Hz), 7.37 (t, 4H,
4.2.3. 1-(3-Dimethylaminomethyl-4-(1-hydroxy-2-pro-
penyl)-1-triisopropylsilyl-1H-indole (7). Following the
general procedure, from 0.50 g (1.50 mmol) of 1, 1.40 mL
(2.40 mmol) of tBuLi and 0.26 mL (3.80 mmol) of acrolein,
and after puri®cation by ¯ash chromatography (hexane/
EtOAc 4:1), 0.46 g (80%) of pure 7 was obtained as a color-
less oil. 1H NMR (CDCl3) d 1.12 (d, 18H, Jˆ7.7 Hz), 1.63±
1.74 (m, 3H), 2.23 (s, 6H), 3.56 (d, 1H, Jˆ12.7 Hz), 3.97 (d,
1H, Jˆ12.7 Hz), 5.33 (d, 1H, Jˆ10.4 Hz), 5.45 (d, 1H,

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5412
Jˆ17.0 Hz), 5.68±5.70 (m, 1H), 6.31±6.42 (m, 1H), 7.07±
7.09 (m, 3H), 7.40±7.43 (m, 1H); 13C NMR (CDCl3) d
136.8, 140.9, 143.1, 132.4, 127.1, 121.6, 119.6, 114.4,
114.1, 114.0, 72.1, 57.4, 44.1, 18.0, 12.7; IR (neat) n
3320, 1470, 1420 cm21; Anal. calcd for C23H38N2OSi: C,
71.45; H, 9.91; N, 7.25. Found: C, 71.65; H, 10.21; N, 7.00.
as a colorless oil. 1H NMR (CDCl3) d 1.12 (d, 18H,
Jˆ7.7 Hz), 1.35 (d, 3H, Jˆ6.0 Hz), 1.63±1.73 (m, 3H),
2.25 (s, 6H), 3.10 (d, 2H, Jˆ6.6 Hz), 3.33 (d, 1H, Jˆ
12.9 Hz), 3.97 (d, 1H, Jˆ12.9 Hz), 4.01 (q, 1H, Jˆ
6.0 Hz), 6.94 (d, 1H, Jˆ7.1 Hz), 7.05 (s, 1H), 7.09 (t, 1H,
Jˆ7.1 Hz), 7.33 (d, 1H, Jˆ8.2 Hz); 13C NMR (CDCl3) d
142.4, 132.5, 132.2, 129.3, 121.8, 121.5, 114.2, 111.9, 69.6,
56.5, 43.9, 41.6, 25.1, 18.0, 12.7; IR (neat) n 3270, 1470,
1420 cm21; Anal. calcd for C23H40N2OSi: C, 71.08; H,
10.37; N, 7.21. Found: C, 71.29; H, 10.56; N, 7.05.
4.2.4. 3-Dimethylaminomethyl-4-(1-hydroxy-2-methyl-
2-propenyl)-1-triisopropylsilyl-1H-indole (8). Following
the general procedure, from 2.50 g (7.57 mmol) of 1,
7.12 mL (12.11 mmol) of tBuLi and 1.65 mL (18.92
mmol) of methacrolein, and after puri®cation by ¯ash
chromatography (CHCl3/MeOH 19:1), 3.25 g (90%) of
4.2.8. (4-Bromo-1-triisopropylsilyl-1H-indol-3-ylmethyl)-
dimethylamine (12). Following the general procedure,
from 0.30 g (0.91 mmol) of 1, 0.85 mL (1.45 mmol) of
tBuLi and 0.75 g (2.27 mmol) of carbon tetrabromide, and
after puri®cation by ¯ash chromatography (CHCl3/MeOH
1:1), 0.22 g (60%) of pure 12 was obtained as a yellow oil.
1H NMR (CDCl3) d 1.13 (d, 18H, Jˆ7.7 Hz), 1.63±1.75 (m,
3H), 2.42 (s, 6H), 4.03 (s, 2H), 6.96 (t, 1H, Jˆ7.7 Hz), 7.29
(d, 1H, Jˆ7.7 Hz), 7.39 (s, 1H), 7.44 (d, 1H, Jˆ8.8 Hz); 13C
NMR (DMSO-d6) d 137.9, 127.9, 125.0, 123.3, 122.4,
113.0, 111.5, 110.4, 53.7, 44.1, 17.9, 12.2; IR (neat) n
1540, 1470, 1420 cm21; Anal. calcd for C20H33BrN2OSi:
C, 71.08; H, 10.37; N, 7.21. Found: C, 71.29; H, 10.55;
N, 7.03.
1
pure 8 was obtained as a colorless oil. H NMR (CDCl3)
d 1.12 (d, 18H, Jˆ7.7 Hz), 1.57 (bs, 1H), 1.63±1.73 (m,
3H), 1.80 (s, 3H), 2.22 (s, 6H), 3.55 (d, 1H, Jˆ12.3 Hz),
3.96 (d, 1H, Jˆ12.3 Hz), 5.13 (bs, 1H), 5.27 (bs, 1H), 5.52
(bs, 1H), 7.02 (t, 1H, Jˆ7.1 Hz), 7.07±7.10 (m, 2H), 7.40
(d, 1H, Jˆ8.2 Hz); 13C NMR (CDCl3) d 147.2, 143.2, 136.0,
132.3, 127.4, 121.7, 119.7, 114.2, 113.8, 111.1, 75.0, 57.5,
44.2, 21.3, 18.0, 12.7; IR (neat) n 3310, 1550, 1470,
1420 cm21; Anal. calcd for C24H40N2OSi: C, 71.94; H,
10.06; N, 6.99. Found: C, 72.16; H, 10.28; N, 6.80.
4.2.5. (E)-3-Dimethylaminomethyl-4-(1-hydroxy-2-methyl-
2-butenyl)-1-triisopropylsilyl-1H-indole (9). Following
the general procedure, from 2.57 g (7.79 mmol) of 1,
4.2.9. 3-Methoxymethyl-1-triisopropylsilyl-1H-indole-4-
carbaldehyde (14). Following the general procedure,
from 0.20 g (0.63 mmol) of 3, 0.56 mL (1.01 mmol) of
tBuLi and 0.12 mL (1.57 mmol) of N,N-dimethylforma-
mide, and after puri®cation by ¯ash chromatography
(hexane/EtOAc 24:1), 1.17 g (55%) of pure 14 was obtained
t
7.3 mL (12.46 mmol) of BuLi and 1.96 mL (19.47 mmol)
of (E)-2-methyl-2-butenal, and after puri®cation by ¯ash
chromatography (CHCl3/MeOH 99:1), 3.1 g (98%) of pure
9 was obtained as a pale yellow oil. 1H NMR (CDCl3) d 1.13
(d, 18H, Jˆ7.7 Hz), 1.63±1.73 (m, 3H), 1.69 (s, 3H), 1.75
(d, 3H, Jˆ6.6 Hz), 2.21 (s, 6H), 3.44 (d, 1H, Jˆ13.0 Hz),
4.03 (d, 1H, Jˆ13.0 Hz), 5.52 (s, 1H), 5.78 (q, 1H, Jˆ
6.6 Hz), 6.95 (d, 1H, Jˆ7.1 Hz), 7.04±7.08 (m, 2H), 7.39
(d, 1H, Jˆ8.2 Hz); 13C NMR (CDCl3) d 143.1, 137.0, 136.7,
132.2, 127.6, 121.6, 119.7, 119.2, 114.1, 113.6, 75.5, 57.5,
44.2, 18.0, 15.0, 13.1, 12.7; IR (neat) n 3360, 1470,
1420 cm21; Anal. calcd for C25H42N2OSi: C, 72.41; H,
10.21; N, 6.76. Found: C, 72.62; H, 10.40; N, 6.57.
1
as a colorless oil. H NMR (CDCl3) d 1.14 (d, 18H, Jˆ
7.7 Hz), 1.63±1.76 (m, 3H), 3.44 (s, 3H), 4.78 (s, 2H),
7.27 (t, 1H, Jˆ7.7 Hz), 7.42 (s, 1H), 7.73 (d, 1H, Jˆ
8.2 Hz), 7.79 (d, 1H, Jˆ7.7 Hz), 10.52 (s, 1H); 13C NM R
(CDCl3) d 194.5, 143.2, 134.6, 130.4, 130.1, 121.1, 119.4,
117.4, 115.8, 57.1, 44.8, 18.0, 12.7; IR (neat) n 1680, 1600,
1460 cm21; Anal. calcd for C20H31NO2Si: C, 69.52; H, 9.04;
N, 4.05. Found: C, 69.70; H, 9.23; N, 3.91.
4.2.6. (4-Allyl-1-triisopropylsilyl-1H-indol-3-ylmethyl)-
dimethylamine (10). Following the general procedure,
from 0.25 g (0.76 mmol) of 1, 0.72 mL (1.22 mmol) of
tBuLi and 0.23 mL (1.90 mmol) of 3-bromo-1-propene,
and after puri®cation by ¯ash chromatography (hexane/
EtOAc 9:1), 0.54 g (20%) of pure 10 was obtained as a
colorless oil. 1H NMR (CDCl3) d 1.13 (d, 18H, Jˆ
7.7 Hz), 1.64±1.74 (m, 3H), 2.23 (s, 6H), 3.51 (s, 2H),
3.96 (d, 2H, Jˆ6.0 Hz), 4.96±5.06 (m, 2H), 6.09±6.22
(m, 1H), 6.11 (d, 1H, Jˆ7.1 Hz), 7.03±7.08 (m, 2H), 7.33
(d, 1H, Jˆ8.2 Hz); 13C NMR (CDCl3) d 142.3, 138.9, 132.9,
131.6, 130.1, 129.0, 121.4, 120.6, 114.9, 112.0, 56.5, 45.0,
37.3, 18.1, 12.8; IR (neat) n 1470, 1420 cm21; Anal. calcd
for C23H38N2Si: C, 74.53; H, 10.33; N, 7.56. Found: C,
74.71; H, 10.54; N, 7.38.
4.2.10. 4-(2-Hydroxypropyl)-1-(3-Methoxymethyl-1-tri-
isopropylsilyl-1H-indole (15). Following the general
procedure but at 2308C, from 0.20 g (0.63 mmol) of 3,
0.56 mL (1.01 mmol) of BuLi and 0.11 mL (1.57 mmol)
of propylene oxide, and after puri®cation (hexane/EtOAc
t
19:1 and then 3:1), 0.12 g (50%) of pure 15 and 0.021 g
(10%) of pure 17 as colorless oil was obtained. H NM R
1
(CDCl3) d 1.13 (d, 18H, Jˆ7.7 Hz), 1.35 (3H, d, Jˆ6.0 Hz),
1.64±1.74 (m, 3H), 2.64 (bs, 1H), 3.04 (dd, 1H, J1ˆ13.7 Hz,
J2ˆ8.8 Hz), 3.23 (dd, 1H, J1ˆ13.7 Hz, J2ˆ3.9 Hz), 3.39 (s,
3H), 3.99±4.10 (m, 1H), 4.67 (dd, 2H, J1ˆ30.2 Hz, J2ˆ
11.5 Hz), 6.96 (d, 1H, Jˆ7.1 Hz), 7.10 (t, 1H, Jˆ8.2 Hz),
7.21 (s, 1H), 7.37 (d, 1H, Jˆ8.2 Hz); 13C NMR (CDCl3) d
142.6, 132.7, 131.7, 129.0, 121.8, 121.6, 114.3, 112.4, 69.4,
68.0, 56.8, 42.7, 23.4, 18.1, 12.8; IR (neat) n 3420, 1460,
1420 cm21; Anal. calcd for C22H37NO2Si: C, 70.35; H, 9.93;
N, 3.73. Found: C, 70.56; H, 10.15; N, 3.56.
4.2.7. 1-(3-Dimethylaminomethyl-1-triisopropylsilyl-1H-
indol-4-yl)-propan-2-ol (11). Following the general pro-
cedure, from 0.30 g (0.91 mmol) of 1, 0.85 mL (1.45
4.2.11. 1-(2-Hydroxypropyl)-3-(2,2-dimethylpropyl)-2-tri-
isopropylsilyl-1H-indole (17). Following the general
procedure, from 0.20 g (0.63 mmol) of 3, 0.56 mL (1.01
t
mmol) of BuLi and 0.16 mL (2.27 mmol) of propylene
oxide, and after puri®cation by ¯ash chromatography
(CHCl3/MeOH 24:1), 0.32 g (90%) of pure 11 was obtained
t
mmol) of BuLi and 0.11 mL (1.57 mmol) of propylene

Â
L. Perez-Serrano et al. / Tetrahedron 58 (2002) 5407±5415
5413
oxide, and after puri®cation, 0.097 g (45%) of pure 17 and
0.047 g (20%) of pure 15 was obtained. 1H NMR (CDCl3) d
0.96 (s, 9H), 1.09 (d, 6H, Jˆ7.7 Hz), 1.16 (d, 12H, Jˆ
7.1 Hz), 1.22 (d, 3H, Jˆ6.0 Hz), 1.60±1.71 (m, 3H), 2.83
(d, 1H, Jˆ14.3 Hz), 2.90 (d, 1H, Jˆ14.3 Hz), 4.11±4.30 (m,
3H), 7.04 (t, 1H, Jˆ7.1 Hz), 7.16 (t, 1H, Jˆ7.1 Hz), 7.32 (d,
1H, Jˆ8.2 Hz), 7.64 (d, 1H, Jˆ8.2 Hz); 13C NMR (CDCl3)
d 139.4, 135.4, 131.0, 127.5, 121.8, 121.3, 118.3, 110.0,
66.7, 53.9, 38.3, 33.0, 31.0, 19.8, 19.4, 14.1; IR (neat) n
3300, 1600, 1460, 1430 cm21; Anal. calcd for C25H43NOSi:
C, 74.75; H, 10.79; N, 3.49. Found: C, 74.96; H, 10.92; N,
3.33.
C31H38N2OSi: C, 77.13; H, 7.93; N, 5.80. Found: C,
77.32; H, 8.19; N, 5.62.
4.3.4. N,N-Diisopropyl 2-(tert-butyldiphenylsilyl)-1-(2-
hydroxypropyl)-1H-indole-3-carboxamide (20b). 1H
NMR (CDCl3) d 1.02 (s, 12H), 1.30±1.40 (bs, 12H),
3.90±4.00 (m, 3H), 4.09 (dd, 1H, J1ˆ13.7 Hz, J2ˆ
6.1 Hz), 4.20 (q, 1H, Jˆ6.0 Hz), 6.81 (dd, 1H, J1ˆ6.0 Hz,
J2ˆ1.6 Hz), 7.06±7.16 (m, 3H), 7.28 (t, 2H, Jˆ7.7 Hz),
7.34±7.44 (m, 3H), 7.49 (d, 2H, Jˆ7.1 Hz), 7.65 (d, 2H,
Jˆ6.0 Hz), 7.72 (dd, 1H, J1ˆ6.0 Hz, J2ˆ1.6 Hz); 13C NM R
(DMSO-d6) d 165.0, 135.5, 134.8, 134.6, 133.4, 132.8,
129.2, 127.4, 127.1, 126.3, 121.2, 119.6, 119.2, 112.2,
109.6, 68.1, 52.6, 46.8, 26.3, 20.5, 20.2, 18.0; IR (neat) n
3400, 1610, 1470 cm21; Anal. calcd for C34H44N2O2Si: C,
75.51; H, 8.20; N, 5.18. Found: C, 75.73; H, 8.38; N, 5.01.
4.3. Synthesis of compounds 19±21
Following the general procedure of funtionalization at C4,
from 0.15 g (0.40 mmol) of 18a, 0.38 mL (0.64 mmol) of
tBuLi and 0.07 mL (1.00 mmol) of propylene oxide, and
after puri®cation by ¯ash chromatography (hexane/EtOAc
4:1), 0.07 g (50%) of pure 19a and 0.05 g (30%) of pure 20a
as colorless oils was obtained. From 0.2 g (0.43 mmol)
of 18b, 0.40 mL (0.68 mmol) of tBuLi and 0.07 mL
(1.10 mmol) of propylene oxide, and after puri®cation by
¯ash chromatography (hexane/EtOAc 4:1), 0.08 g (40%) of
pure 19b, 0.03 g (15%) of pure 20b and 0.02 g (10%) of
pure 21b as colorless oil were obtained.
4.3.5. N,N-Diisopropyl 1-(tert-butyldiphenylsilyl)-4-(2-
hydroxypropyl)-1H-indole-3-carboxamide (21b). 1H
NMR d 1.25 (s, 12H), 1.25±1.30 (bs, 6H), 1.34 (d, 6H,
Jˆ6.6 Hz), 2.90 (dd, 1H, J1ˆ13.7 Hz, J2ˆ8.8 Hz), 3.01±
3.09 (m, 1H), 3.47 (q, 1H, Jˆ7.1 Hz), 4.00±4.29 (m, 2H),
6.74 (d, 1H, Jˆ7.7 Hz), 6.87 (t, 1H, Jˆ7.7 Hz), 6.94 (d, 1H,
Jˆ7.1 Hz), 7.25 (d, 1H, Jˆ6.0 Hz), 7.34±7.49 (m, 6H),
7.55±7.61 (m, 4H); 13C NMR (DMSO-d6) d 167.3, 140.7,
135.3, 134.5, 132.6, 131.5, 130.5, 129.0, 128.3, 127.9,
127.3, 121.8, 117.2, 112.7, 66.7, 47.8, 41.9, 28.0, 20.6,
20.5, 19.2; IR (neat) n 3400, 1610, 1470 cm21; Anal.
calcd for C34H44N2O2Si: C, 75.51; H, 8.20; N, 5.18.
Found: C, 75.71; H, 8.39; N, 5.00.
4.3.1. N,N-Diethyl 2-triisopropylsilyl-1H-indole-3-carb-
1
oxamide (19a). H NMR (CDCl3) d 1.14 (d, 18H, Jˆ
7.7 Hz), 1.16±1.30 (bs, 6H), 1.46±1.60 (m, 3H), 3.20±
3.40 (bs, 2H), 3.40±3.70 (bs, 2H), 7.11 (t, 1H, Jˆ7.7 Hz),
4.4. Synthesis of compound 22
7.19 (t, 1H, Jˆ7.7 Hz), 7.39 (d, 1H, Jˆ8.2 Hz), 7.49 (d, 1H,
1
4.4.1. Dimethyl-(1-triisopropylsilyl-4-vinyl-1H-indol-3-yl-
methyl)amine (22). Stille coupling16 of 5 with vinyltri-
butyltin yielded, after puri®cation by ¯ash chromatography
(hexane/EtOAc 4:1 and then 1:1), pure 22 (71%) as a color-
less oil. 1H NMR (CDCl3) d 1.13 (d, 18H, Jˆ7.7 Hz), 1.64±
1.74 (m, 3H), 2.27 (s, 6H), 3.54 (s, 2H), 5.28 (dd, 1H,
J1ˆ11.0 Hz, J2ˆ1.6 Hz), 5.70 (dd, 1H, J1ˆ17.6 Hz, J2ˆ
1.6 Hz), 7.09 (s, 1H), 7.10 (t, 1H, Jˆ7.7 Hz), 7.27 (d, 1H,
Jˆ8.2 Hz), 7.39 (d, 1H, Jˆ8.2 Hz), 7.75 (dd, 1H, J1ˆ
17.6 Hz, J2ˆ11.0 Hz) 13C NMR (CDCl3) d 142.2, 136.8,
132.1, 131.8, 128.3, 121.5, 117.1, 116.1, 114.1, 113.2,
56.6, 45.0, 18.0, 12.7; IR (neat) n 1460, 1410 cm21; Anal.
calcd for C22H36N2Si: C, 74.09; H, 10.17; N, 7.86. Found: C,
74.27; H, 10.38; N, 7.69.
Jˆ8.2 Hz), 8.25 (bs, 1H); H NM R (CD6) d 0.99 (t, 6H,
6
Jˆ7.1 Hz), 1.16 (dd, 18H, J1ˆ7.7 Hz, J2ˆ1.6 Hz), 1.44±
1.56 (m, 3H), 3.35 (q, 4H, Jˆ7.1 Hz), 7.13±7.39 (m, 3H),
7.59 (d, 1H, Jˆ7.1 Hz), 7.82 (bs, 1H); 13C NM R (CD6) d
6
167.8, 138.1, 134.6, 127.1, 124.2, 122.9, 122.9, 120.5,
120.2, 111.4, 30.2, 19.2, 13.5, 12.0; IR (neat) n 3300,
1600, 1460, 1430 cm21; Anal. calcd for C22H36N2OSi: C,
70.91; H, 9.74; N, 7.52. Found: C, 71.09; H, 9.98; N, 7.34.
4.3.2. N,N-Diethyl 1-(2-hydroxypropyl)-2-triisopropyl-
silyl-1H-indole-3-carboxamide (20a). H NMR (CDCl3)
1
d 1.16 (d, 12H, Jˆ7.7 Hz), 1.18 (d, 6H, Jˆ7.7 Hz), 1.26±
1.36 (m, 6H), 1.56±1.73 (m, 6H), 3.11±3.28 (m, 1H), 3.36±
3.51 (m, 1H), 3.54±3.72 (m, 2H), 4.10±4.47 (m, 5H), 7.09
(t, 1H, Jˆ7.1 Hz), 7.20 (td, 1H, J1ˆ8.2 Hz, J2ˆ1.6 Hz),
7.42 (d, 1H, Jˆ8.2 Hz), 7.48 (d, 1H, Jˆ8.1 Hz); 13C NM R
(DMSO-d6) d 165.2, 135.7, 129.0, 126.5, 121.1, 120.0,
119.3, 109.8, 109.7, 65.1, 52.7, 40.3, 20.3, 17.2, 13.2,
11.7; IR (neat) n 3400, 1600, 1460 cm21; Anal. calcd for
C25H42N2O2Si: C, 69.72; H, 9.83; N, 6.50. Found: C, 69.91;
H, 9.99; N, 6.30.
4.5. Synthesis of compounds of 23 and 24
General procedure. The benzyldimethylammonium salt of
22 was prepared by reaction of this product with 2.0 equiv.
of benzylbromide in dry benzene at room temperature. After
18 h of reaction, 4 equiv. of ethynylmagnesium chloride
0.5 Mor vinylmagnesium bromide 1.0 Mwere slowly
added to an ice-cooled solution of the ammonium salt in
10 mL of dry THF. The mixture was re¯uxed under argon
overnight, and then was treated with 10 mL of a saturated
aqueous NH4Cl solution and extracted with EtOAc
(3£10 mL). The organic phase was washed with brine,
dried (MgSO4) and concentrated. The crude thus obtained,
was puri®ed by ¯ash chromatography (hexane) to obtain the
corresponding diene 23 and enyne 24.
4.3.3. N,N-Diisopropyl 2-(tert-butyldiphenylsilyl)-1H-
indole-3-carboxamide (19b). H NMR (CDCl3) d 0.97
1
(d, 12H, Jˆ4.9 Hz), 1.15 (s, 9H), 1.50±1.60 (m, 2H), 7.01
(t, 1H, Jˆ6.7 Hz), 7.13 (t, 1H, Jˆ6.7 Hz), 7.30±7.38 (m,
6H), 7.50±7.53 (m, 4H), 10.26 (bs, 1H); 13C NMR (DMSO-
d6) d 166.5, 138.0, 135.7, 133.0, 128.7, 127.9, 127.0, 125.8,
125.5, 121.9, 118.6, 118.2, 111.7, 47.1, 28.2, 20.1, 17.3;
IR (neat) n 3440, 1610, 1450 cm21; Anal. calcd for

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L. Perez-Serrano et al. / Tetrahedron 58 (2002) 5407±5415
5414
4.5.1. 3-Allyl-1-triisopropylsilyl-4-vinyl-1H-indole (23).
Following the general procedure, from 1.50 g (4.21 mmol)
of 22, 1.01 mL (8.42 mmol) of BnBr and 16.84 mL
(16.84 mmol) of vinylmagnesium bromide, and after puri-
®cation by ¯ash chromatography, 0.86 g (60%) of pure 23
was obtained as a colorless oil. 1H NMR (CDCl3) d 1.13 (d,
18H, Jˆ7.1 Hz), 1.60±1.75 (m, 3H), 3.65 (d, 2H, Jˆ
5.5 Hz), 5.02 (dd, 1H, J1ˆ17.0 Hz, J2ˆ1.6 Hz), 5.09 (dd,
1H, J1ˆ9.9 Hz, J2ˆ1.6 Hz), 5.26 (dd, 1H, J1ˆ11.0 Hz,
J2ˆ1.6 Hz), 5.67 (dd, 1H, J1ˆ17.0 Hz, J2ˆ1.6 Hz), 6.07±
6.20 (m, 1H), 7.00 (s, 1H), 7.09 (t, 1H, Jˆ7.7 Hz), 7.23 (d,
1H, Jˆ8.8 Hz), 7.40 (d, 1H, Jˆ7.7 Hz), 7.44 (dd, 1H, J1ˆ
17.0 Hz, J2ˆ11.0 Hz); 13C NMR (CDCl3) d 142.1, 137.9,
136.0, 131.8, 130.0, 128.1, 121.4, 117.1, 116.3, 115.6,
114.5, 113.4, 31.9, 18.1, 12.8; IR (neat) n 1460,
1410 cm21; Anal. calcd for C22H33NSi: C, 77.81; H, 9.79;
N, 4.12. Found: C, 77.99; H, 9.98; N, 4.00.
4.6.2. 3-Allyl-4-[1-(tert-butyldimethylsilanyloxy)allyl]-1-
triisopropylsilanyl-1H-indole (30). H NMR (CDCl3) d
1
20.09 (s, 3H), 0.01 (s, 3H), 0.91 (s, 9H), 1.12 (d, 18H,
Jˆ7.7 Hz), 1.62±1.72 (m, 3H), 3.60±3.64 (m, 2H), 4.94±
5.21 (m, 4H), 5.83±5.85 (m, 1H), 6.05±6.18 (m, 2H), 6.97
(s, 1H), 7.09 (t, 1H, Jˆ7.7 Hz), 7.24 (d, 1H, Jˆ8.2 Hz), 7.35
(d, 1H, Jˆ7.7 Hz); 13C NMR (CDCl3) d 142.2, 142.1, 138.2,
136.3, 130.1, 127.1, 121.2, 117.4, 115.6, 115.1, 112.7, 71.9,
31.9, 26.0, 18.4, 18.2, 12.9, 24.5, 24.7; IR (neat) n 1470,
1430 cm21; Anal. calcd for C29H49NOSi2: C, 71.98; H,
10.21; N, 2.89. Found: C, 72.20; H, 10.38; N, 2.71.
4.6.3. 3-Allyl-4-[1-(tert-butyldimethylsilyloxy)-2-methyl-
allyl]-1-triisopropylsilyl-1H-indole (31). 1H NM
(CDCl3) d 20.22 (s, 3H), 20.01 (s, 3H), 0.88 (s, 9H),
1.12 (d, 18H, Jˆ7.7 Hz), 1.64±1.72 (m, 3H), 1.76 (s, 3H),
3.50±3.66 (m, 2H), 4.70 (s, 1H), 4.84 (s, 1H), 5.00 (dd, 1H,
J1ˆ19.2 Hz, J2ˆ1.6 Hz), 5.10 (dd, 1H, J1ˆ11.5 Hz, J2ˆ
1.6 Hz), 5.67 (s, 1H), 6.04±6.18 (m, 1H), 6.94 (s, 1H),
7.08 (t, 1H, Jˆ7.7 Hz), 7.24 (d, 1H, Jˆ7.7 Hz), 7.35 (d,
1H, Jˆ8.2 Hz); 13C NMR (CDCl3) d 148.6, 142.0, 138.3,
135.6, 130.0, 128.0, 120.7, 118.9, 115.6, 115.5, 112.8, 112.1,
75.1, 32.0, 25.9, 20.0, 18.3, 18.2, 12.9, 24.6, 24.9; IR (neat)
n 1460, 1420 cm21; Anal. calcd for C30H51NOSi2: C, 72.37;
H, 10.32; N, 2.81. Found: C, 72.55; H, 10.14; N, 2.63.
R
4.5.2. 3-(2-Propynyl)-1-triisopropylsilyl-4-vinyl-1H-indole
(24). Following the general procedure, from 1.50 g
(4.21 mmol) of 22, 1.01 mL (8.42 mmol) of BnBr and
33.68 mL (16.84 mmol) of ethynylmagnesium chloride,
and after puri®cation by ¯ash chromatography, 0.88 g
1
(62%) of pure 24 was obtained as a colorless oil. H NM R
(CD3OD) d 1.02 (d, 18H, Jˆ7.3 Hz), 1.54±1.64 (m, 3H),
2.35 (t, 1H, Jˆ2.1 Hz), 3.67 (d, 2H, Jˆ2.1 Hz), 5.16 (dd,
1H, J1ˆ11.0 Hz, J2ˆ1.6 Hz), 5.53 (dd, 1H, J1ˆ17.0 Hz,
J2ˆ1.6 Hz), 6.95 (t, 1H, Jˆ7.3 Hz), 7.08 (d, 1H, Jˆ
7.3 Hz), 7.19 (s, 1H), 7.29 (d, 1H, Jˆ8.5 Hz), 7.41 (dd,
1H, J1ˆ17.0 Hz, J2ˆ11.0 Hz) 13C NMR (CDCl3) d 142.2,
135.6, 131.7, 130.4, 127.3, 121.6, 117.3, 115.3, 113.6,
112.9, 82.9, 69.6, 18.2, 18.1, 12.8; IR (neat) n 3320,
2120, 1470, 1420 cm21; Anal. calcd for C22H31NSi: C,
78.27; H, 9.26; N, 4.15. Found: C, 78.50; H, 9.47; N, 4.01.
4.7. General procedure for the ring-closing metathesis
The corresponding diene or enyne (1.00 mmol) was
dissolved in 20 mL of dry toluene under argon. To this
solution, ruthenium catalyst 28 (0.05 mmol) was added
and the reaction was re¯uxed for 4±6 h (TLC). The mixture
was ®ltered through celite and the solvent evaporated under
vacuum. The crude thus obtained was puri®ed by ¯ash
chromatography (hexane) to obtain the corresponding
3,4-carbocycloindoles.
4.6. Synthesis of compounds 29±31
4.7.1. 1-Triisopropylsilyl-1,3-dihydrobenzo[cd]indole (25).
Following the general procedure, from 0.10 g (0.29 mmol)
of 23, 17 mg (0.02 mmol) of 28, and after a short Florisilw
column, 0.07 g (78%) of 25 was obtained as a colorless oil
General procedure. Compounds 7±9 were protected as their
TBDMS derivatives.17 Using the same procedure employed
in the synthesis of 23 and 24, these compounds were trans-
formated into their trimethylammonium salts by reaction
with CH3I. Conversion to 29±31 was achieved by treatment
of these salts with ethynylmagnesium chloride or vinylmag-
nesium bromide. Usual work-up and puri®cation by ¯ash
chromatography (hexane) yielded pure enyne 29 (70%,
three steps) and dienes 30 (75%, three steps) and 31
(75%, three steps).
1
which turned dark in ca. 15 min. H NMR (CDCl3) d 1.12
(d, 18H, Jˆ7.7 Hz), 1.57±1.70 (m, 3H), 3.85 (bs, 2H), 5.93
(dt, 1H, J1ˆ9.9 Hz, J2ˆ3.8 Hz), 6.54 (dt, 1H, J1ˆ9.9 Hz,
J2ˆ2.2 Hz), 6.65 (d, 1H, Jˆ6.6 Hz), 6.85 (s, 1H), 6.95 (t,
1H, Jˆ8.2 Hz), 7.15 (d, 1H, Jˆ8.2 Hz).
4.7.2. Bis-1,2-[1-triisopropylsilyl-1,3-dihydrobenzo[cd]-
indol-4-yl]ethylene (27). Following the general procedure,
from 0.10 g (0.30 mmol) of 24, 18 mg (0.020 mmol) of 28
and after puri®cation, 35 mg (35%) of pure 27 was obtained
4.6.1. 4-[1-(tert-Butyldimethylsilyloxy)-2-methylbut-2-
enyl]-3-prop-2-ynyl-1-triisopropylsilyl-1H-indole (29).
1H NMR (CDCl3) d 20.25 (s, 3H), 0.02 (s, 3H), 0.86 (s,
9H), 1.14 (dd, 18H, J1ˆ7.7 Hz, J2ˆ1.1 Hz), 1.57 (d, 3H,
Jˆ6.6 Hz), 1.63±1.73 (m, 3H), 1.66 (s, 1H), 2.20 (t, 1H,
Jˆ2.2 Hz), 3.69 (d, 1H, Jˆ19.2 Hz), 3.88 (dd, 1H, J1ˆ
19.2 Hz, J2ˆ2.2 Hz), 5.23 (q, 1H, Jˆ6.6 Hz), 5.58 (bs,
1H), 7.07 (t, 1H, Jˆ7.7 Hz), 7.17 (d, 1H, Jˆ7.7 Hz), 7.28
(s, 1H), 7.37 (d, 1H, Jˆ8.2 Hz); 13C NMR (CDCl3) d 142.4,
139.2, 135.4, 130.1, 127.3, 121.1, 120.6, 119.8, 113.1,
112.7, 83.8, 78.1, 69.3, 25.9, 18.3, 18.2, 18.1, 13.6, 13.4,
12.9, 24.8, 24.9; IR (neat) n 1460, 1420 cm21; Anal. calcd
for C31H51NOSi2: C, 73.02; H, 10.08; N, 2.75. Found: C,
73.20; H, 10.26; N, 2.60.
1
as a pale yellow oil. H NMR (CDCl3) d 1.15 (d, 18H, Jˆ
7.7 Hz), 1.62±1.72 (m, 3H), 4.05 (bs, 2H), 6.64 (s, 1H), 6.67
(s, 1H), 6.76 (d, 1H, Jˆ7.1 Hz), 6.95±7.02 (m, 2H), 7.17 (d,
1H, Jˆ8.2 Hz);13C NMR (CDCl3) d 137.9, 137.1, 130.2,
129.5, 128.1, 127.1, 125.2, 122.9, 115.2, 114.0, 113.4,
29.7, 18.1, 12.7; IR (neat) n 1460, 1440 cm21; Anal. calcd
for C42H58N2Si2: C, 77.96; H, 9.03; N, 4.33. Found: C,
78.17; H, 9.19; N, 4.06.
4.7.3. 6-(tert-Butyldimethylsilyloxy)-7-methyl-8-propenyl-
2-triisopropylsilyl-6,9-dihydro-2H-2-aza-benzo[cd]-
azulene (32). Following the general procedure, from 0.07 g

Â
L. Perez-Serrano et al. / Tetrahedron 58 (2002) 5407±5415
5415
(0.15 mmol) of 29, 9 mg (0.010 mmol) 28, and after puri®-
References
cation, 0.05 g (65%) of pure 32 was obtained as a colorless
oil. 1H NMR (CDCl3) d 0.11 (s, 6H), 1.02 (s, 9H), 1.12 (dd,
18H, J1ˆ7.7 Hz, J2ˆ3.8 Hz), 1.58±1.70 (m, 3H), 1.81 (s,
3H), 1.84 (s, 3H), 3.64 (d, 1H, Jˆ15.4 Hz), 3.89 (d, 1H,
Jˆ15.4 Hz), 5.78±5.89 (m, 1H), 6.39±6.43 (m, 2H), 6.87
(s, 1H), 7.00 (t, 1H, Jˆ8.2 Hz), 7.08 (d, 1H, Jˆ7.1 Hz), 7.21
(d, 1H, Jˆ8.2 Hz); 13C NMR (CDCl3) d 140.7, 138.3, 135.7,
130.0, 129.2, 128.6, 124.9, 123.4, 121.2, 115.7, 112.8,
112.3, 71.9, 26.1, 26.0, 18.7, 18.6, 18.2, 12.8, 12.1, 25.0,
25.1; IR (neat) n 1460, 1430 cm21; Anal. calcd for
C31H51NOSi2: C, 73.02; H, 10.08; N, 2.75. Found: C,
73.23; H, 10.25; N, 2.59.
Â
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6,9-dihydro-2H-2-azabenzo[cd]azulene (33). Following
the general procedure, from 0.10 g (0.21 mmol) of 30,
12.5 mg (0.015 mmol) of 28, and after puri®cation, 0.07 g
(75%) of pure 33 was obtained as a colorless oil. 1H NM Rd
(CDCl3) 0.14 (s, 3H), 0.15 (s, 3H), 1.00 (s, 9H), 1.12 (dd,
18H, J1ˆ7.7 Hz, J2ˆ1.1 Hz), 1.61±1.71 (m, 3H), 3.27±3.35
(m, 1H), 3.70 (d, 1H, Jˆ14.8 Hz), 5.97 (t, 1H, Jˆ2.7 Hz),
6.11 (s, 1H), 6.90 (s, 1H), 7.08 (t, 1H, Jˆ7.1 Hz), 7.16 (d,
1H, Jˆ7.1 Hz), 7.29 (d, 1H, Jˆ8.2 Hz); 13C NMR (CDCl3)
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113.9, 112.7, 70.5, 31.7, 25.9, 18.4, 18.2, 12.8, 24.6,
24.9; IR (neat) n 1460, 1430 cm21; Anal. calcd for
C27H45NOSi2: C, 71.14; H, 9.95; N, 3.07. Found: C,
71.32; H, 10.16; N, 2.91.
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4.7.5. 6-(tert-Butyldimethylsilyloxy)-7-methyl-2-triiso-
propylsilyl-6,9-dihydro-2H-2-aza-benzo[cd]azulene (34).
Following the general procedure, from 0.10 g (0.20 mmol)
of 31, 12 mg (0.014 mmol) of 28 and after puri®cation,
0.08 g (85%) of pure 34 was obtained as a colorless oil.
1H NMR (CDCl3) d 0.26 (s, 3H), 0.33 (s, 3H), 1.20 (s,
9H), 1.34 (d, 18H, Jˆ7.1 Hz), 1.79±1.94 (m, 3H), 2.00 (s,
3H), 3.50±3.57 (m, 1H), 3.84 (dd, 1H, J1ˆ14.8 Hz,
J2ˆ4.4 Hz), 5.91±5.96 (m, 1H), 6.26 (bs, 1H), 7.09 (s,
1H), 7.21±7.30 (m, 2H), 7.48 (d, 1H, Jˆ7.7 Hz); 13C
NMR (CDCl3) d 148.7, 143.4, 141.2, 134.8, 128.6, 125.3,
121.1, 120.9, 115.6, 112.7, 72.5, 31.6, 26.0, 24.7, 18.5, 18.2,
12.9, 24.9, 25.0; IR (neat) n 1460, 1430 cm21; Anal. calcd
for C28H47NOSi2: C, 71.58; H, 10.08; N, 2.98. Found: C,
71.79; H, 10.26; N, 2.80.
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Acknowledgements
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The authors are grateful to the DGCYT (MEC Spain,
PB98-0053) and the Universidad San Pablo-CEU (2/01)
for ®nancial support. Pre-doctoral fellowship from the
Universidad San Pablo-CEU is gratefully acknowledged
by L. P.-S.
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