A new procedure for the preparation of 2-vinylindoles and their [4+2] cycloaddition reaction

Article abstract of DOI:10.1016/j.tet.2011.05.064

A new approach for the synthesis of 2-vinylindole derivatives by 5-exo mode cyclization of 2-(3-silyloxymethylallenyl)anilines was developed. The starting allenylanilines were easily prepared by the Stille coupling of o-iodoaniline and allenylstannanes. T

Full text of DOI:10.1016/j.tet.2011.05.064

Tetrahedron 67 (2011) 5133e5141
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A new procedure for the preparation of 2-vinylindoles and their [4þ2]
cycloaddition reaction
*
Yaseen Ali Mosa Mohamed, Fuyuhiko Inagaki, Ryohei Takahashi, Chisato Mukai
Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 April 2011
Received in revised form 16 May 2011
Accepted 17 May 2011
Available online 25 May 2011
A new approach for the synthesis of 2-vinylindole derivatives by 5-exo mode cyclization of 2-(3-
silyloxymethylallenyl)anilines was developed. The starting allenylanilines were easily prepared by the
Stille coupling of o-iodoaniline and allenylstannanes. The formed 2-vinylindole derivatives were trans-
formed into several carbazole derivatives via the [4þ2] cycloaddition reaction with suitable dienophiles.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Allenes
SN2’ reaction
2-Vinylindoles
DielseAlder reaction
1. Introduction
In our previous studies, we developed a new procedure for the
generation of the reactive indole-2,3-quinodimethane intermediates
2 from the allenylanilines 1 via the SN20-type reaction in the 5-endo-
type manner (Fig. 1).1 This method was entirely different from the
well-known ones2 that took advantage of the 1,4-elimination-type or
related reactions of the 2,3-disubstituted indole derivatives. The
indole-2,3-quinodimethane intermediates 2 were successively cap-
tured by several dienophiles in the same reaction vessel to afford the
tetrahydro- and dihydrocarbazole derivatives 3.
We envisaged that the similar SN20-type reaction of allenylani-
lines 4 via the 5-exo mode ring-closing reaction would furnish the
2-vinylindole derivatives 5,3 which are known to be a useful com-
ponent for the syntheses of some drugs4 and natural products.5 We
now describe a new entry for the preparation of 2-vinylindole
frameworks and their [4þ2] cycloaddition leading to an alterna-
tive method for the construction of the carbazole derivatives 6.
Fig. 1. Formation of carbazole derivatives based on SN20 cyclization and DielseAlder
reaction.
(tert-butyldimethylsilyloxymethyl)allenyl} aniline derivatives 9.
According to a previous procedure,1,7 7 was treated with allenyl-
stannane 8a8 in DMF in the presence of 3 mol % of Pd2(dba)3,
tri-2-furylphosphine (TFP, 24 mol %), and CuI (10 mol %) at room
temperature for 2 h to produce the allenylaniline derivative 9a in
79% yield (Table 1, entry 1). Other allenylstannanes 8bed (R1¼Me,
Et, CH2OBn: R2¼H) gave the corresponding allenylanilines 9bed in
good yields (entries 2e4). The tetrasubstituted derivatives 9e,f
(R1¼CH2OBn: R2¼Bu, (CH2)4OPMB) were produced in moderate
yields from 7 and the tetrasubstituted allenylstannanes 8e,f (en-
tries 5 and 6).
2. Results and discussion
At the beginning of this project, the Stille coupling reaction6 of
the N-(tert-butoxycarbonyl)-2-iodoaniline (7) and 3-(tert-butyldi-
methylsilyloxymethyl)-1-(tributylstannyl)allene derivatives 8 was
conducted for the preparation of the N-(tert-butoxycarbonyl)-2-{3-
* Corresponding author. Tel.: þ81 76 234 4411; fax: þ81 76 234 4410; e-mail
address: cmukai@kenroku.kanazawa-u.ac.jp (C. Mukai).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.064

5134
Y.A.M. Mohamed et al. / Tetrahedron 67 (2011) 5133e5141
Table 2
SN20 cyclization of 2-(4-silyloxybuta-1,2-dienyl)anilines 9
Table 1
Stille coupling of o-iodoaniline 7 and allenylstannanes 8
Entry Substrate R1
R2
Base
Solvent Temp Time Product
(ꢀC) (h)
(%)
1
2
3
4
5
6
7
9a
9b
9c
9e
9f
H
Me
Et
H
H
H
TBAF THF
TBAF THF
TBAF THF
TBAF THF
rt
0.2
5
5
0.5
0.5
4
11a (83)
12b (50)
12c (45)
11e (62)
11f (73)
11b (66)
11b (80)
45
45
0
0
110
85
Entry
Allene
R1
R2
Time (h)
Product
Yield (%)
CH2OBn Bu
CH2OBn (CH)2OPMB TBAF THF
Me
Me
1
2
3
4
8a
8b
8c
8d
8e
8f
H
Me
Et
CH2OBn
CH2OBn
CH2OBn
H
H
H
H
2
3
5
4
12
6
9a
9b
9c
9d
9e
9f
79
90
78
88
49
50
9b
9b
H
H
K2CO3 DMF
K2CO3/ DMF
Et2CO3
K2CO3/ DMF
Et2CO3
4
5
Bu
6a
(CH2)4OPMB
8
9c
Et
H
95
5
11c (85)
a
The reaction was heated at 70 ꢀC.
By taking the [4þ2] cycloaddition reaction of the 2-vinylindoles,
in particular the compounds having a substituent on the vinyl posi-
tion (RsH), into account, we tried to remove a Boc group on the
nitrogen atom of the indole nucleus, which should be predicted to
disturb the planarity due to the nonbonding interaction with an R
With the required allenylanilines 9 in hand, the ring-closing
reaction for the construction of 2-vinylindole derivatives 11 was
examined (Scheme 1). After removing the TBS group of the 1,3-
disubstituted allene derivative 9a with TBAF in THF at 0 ꢀC, the
resulting 10a (83%) was successfully converted into N-(tert-butox-
ycarbonyl)-2-vinylindole (11a) in 73% yield by ethoxycarbonylation
followed by TBAF treatment. The 1,1,3-trisubstituted allene de-
rivatives 9b and 9c having a methyl or ethyl group on the vinyl
position also provided the corresponding 2-vinylindole derivatives
11b and 11c in good yields. TBAF treatment of the 1,1,3-
trisubstituted allene derivative 9d directly and unexpectedly pro-
duced the 2-vinylindole derivative 11d in 79% yield. This was in
sharp contrast to the cases in which the desilylated products 10aec
were obtained upon exposure of 9aec to TBAF.
11
group. Treatment of 2-vinylindole 11b (R¼Me) with TFA in CH2Cl2
at room temperature afforded 1,1-dimethyloxazolo[3,4-a]indol-
3(1H)-one (14b) in 76% yield (Table 3, entry 1). Similar results were
observed under other acidic conditions (HCl in AcOEt,11,12 and TMSCl,
NaI in CH3CN,13 entries 2 and 3). In contrast to these acidic conditions,
exposure to KOH in MeOH at 70 ꢀC gave the desired 2-vinylindole
derivatives 13bed in moderate to high yields (entries 4e6).
Table 3
Deprotection of A/-Boc group of 2-vinylindoles 11
Entry Substrate
R
Additive
Solv.
Temp Time (h) Product (%)
1
2
3
4
5
6
11b
11b
11b
11b
11c
11d
Me
Me
Me
Me
Et
TFA
HCI
CH2CI2 rt
AcOEt rt
1
6
0.5
5
5
14b (76)
14b (45)
14b (85)
13b (92)
13c (56)
13d (83)
TMSCI, Nal CH3CN rt
KOH
KOH
MeOH 70 ꢀC
MeOH 70 ꢀC
MeOH 70 ꢀC
CH2OBn KOH
5
The experimental results summarized in Tables 2 and 3 revealed
Scheme 1. Formation of 2-vinylindoles 11.
that the one-step conversion of 9 into 11 required basic conditions,
and a Boc group of 11 could also be removed by the base treatment.
Thus, the direct one-step transformation of 9 into 13 would be at-
tainable under proper basic conditions. After screening several
basic conditions, we finally established the following conditions
that treatment of 9aed with KOH in DMSO at room temperature
producing the desired 13aed in satisfactory yields as expected
(Table 4, entries 1e4).
Based on the direct conversion of the allenylaniline 9d to 2-
vinylindole 11d, we reinvestigated the one-step conversion of
allenylanilines 9 into 11 (Table 2). Treatment of the allenylaniline
9a with TBAF in THF at room temperature (not at 0 ꢀC) afforded
the desired 2-vinylindole derivative 11a in 83% yield (entry 1).9 At
a
higher temperature (45 ꢀC), N-(tert-butoxycarbonyl)-2-
Table 4
(2-hydroxy-1-alkylethyl)indole derivatives 12b,c were obtained
instead of 11b,c (entries 2 and 3). On the other hand, the tetra-
substituted allene derivatives 9e,f were converted to the desired
2-vinyl-3-substituted indole derivatives 11e (62%) and 11f (73%)
at 0 ꢀC (entries 4 and 5). K2CO3 was used as a base for the for-
mation of the indole derivatives from the allenylanilines in pre-
vious papers.1,7 Thus, K2CO3 was again found to be a suitable base
for the transformation of the allenylanilines 9b,c to 2-vinylindoles
11b,c. In fact, 11b,c were obtained in satisfactory yields when 9b,c
were reacted with K2CO3 in DMF at rather higher reaction tem-
peratures (85e110 ꢀC)(entries 6e8).10
Formation of 2-vinylindoles 13
Entry
Substrate
R
Time (h)
Product (%)
1
2
3
4
9a
9b
9c
9d
H
Me
Et
CH2OBn
0.25
6
6
13a (76)
13b (73)
13c (75)
13d (90)
10

Y.A.M. Mohamed et al. / Tetrahedron 67 (2011) 5133e5141
5135
In addition, the successive Stille coupling reaction and KOH
derivative 15a (R¼H) in 60% yield (entry 1). The methyl congener
15b (R¼Me) was also obtained from 13b17b,18 in 65% yield as
a mixture of two isomers (1:2) (entry 2). Dimethyl fumarate, N-
phenylmaleimide, and 1,4-naphthoquinone were found to be
proper dienophiles for the formation of the corresponding tetra-
hydrocarbazole derivatives 15ceh (entries 3e8). In the case of
the dimethyl acetylenedicarboxylate, the initially formed dihy-
drocarbazoles were oxidized resulting in the production of 15i,j in
moderate yields (entries 9 and 10).
treatment offered
a more efficient synthesis of 3-methyl-2-
vinylindole (13g) (42%) as shown in Scheme 2.14,15
3. Conclusions
Scheme 2. Formation of 3-metyl-2-vinylindoles (13g).
In summary, we have developed a novel and efficient procedure
for the formation of the 2-vinylindole derivatives19 from N-(tert-
butoxycarbonyl)-2-{3-(tert-butyldimethylsilyloxymethyl)allenyl}
aniline derivatives, which were easily prepared from the Stille
coupling of the N-(tert-butoxycarbonyl)-o-iodoaniline and allenyl-
stannanes, via a 5-exo mode cyclization under basic conditions. In
addition, these 2-vinylindole derivatives could be applied to the
syntheses of the carbazole derivatives.
Finally, the application of 2-vinylindoles 13 for the synthesis of
the carbazole derivatives was invesitagted (Table 5).3f,16 A sus-
pension of 2-vinylindole (13a)17 and fumaronitrile in toluene was
heated under reflux to afford the desired tetrahydrocarbazole
Table 5
4. Experimental
4.1. General
DielseAlder reaction of 2-vinylindole derivatives 13
Melting points are uncorrected. IR spectra were measured in
CHCl3. 1H NMR spectra were taken in CDCl3 unless otherwise in-
dicated. CHCl3 (7.26 ppm) for silyl compounds and tetramethylsi-
lane (0.00 ppm) for compounds without a silyl group were used as
internal standards. 13C NMR spectra were recorded in CDCl3 with
CDCl3 (77.00 ppm) as an internal standard. All reactions were car-
ried out under a nitrogen atmosphere. Silica gel (silica gel 60,
230e400 mesh) was used for chromatography. Organic extracts
were dried over anhydrous Na2SO4.
Entry
Dienophile
Product and yield
1
2
4.2. Preparation of propargyl alcohol derivative
4.2.1. 1-Benzyloxy-2-(tert-butyldimethylsilyloxy)methyl-3-butyn-2-
ol. To a solution of 1-benzyloxy-3-(tert-butyldimethylsilyloxy)
propan-2-one20 (60 mg, 0.20 mmol) in Et2O (1 mL) was added
3
4
ethynyl magnesium bromide (0.50
M in THF, 0.60 mL,
0.30 mmol) at 0 ꢀC. After stirring for 1.5 h at the same temper-
ature, the reaction mixture was quenched by saturated aqueous
NH4Cl, extracted with Et2O. The extract was washed with water
and brine, dried and concentrated to dryness. The residue was
chromatographed with hexane/AcOEt (9:1) to give 1-benzyloxy-
2-(tert-butyldimethylsilyloxy)methyl-3-butyn-2-ol (49 mg, 76%)
5
as a colorless oil. IR 3547, 3308 cmꢁ1 1H NMR
; d 7.35e7.25 (m,
5H), 4.64 (s, 2H), 3.78, 3.71 (ABq, JAB¼9.7 Hz, 2H), 3.61, 3.57 (ABq,
6
7
JAB¼9.6 Hz, 2H), 3.01 (s, 1H), 2.43 (s, 1H), 0.90 (s, 9H), 0.085 (s,
3H), 0.081 (s, 3H); 13C NMR
d 137.8, 128.4, 127.70, 127.68, 83.8,
73.7, 72.8, 72.7, 70.4, 66.7, 25.8, 18.3, ꢁ5.40, ꢁ5.44; EIMS m/z 320
(Mþ, 18); EI HRMS calcd for C18H28O3Si 320.1808, found
320.1799.
8
4.3. General procedure for the preparation of propargyl
alcohols
nBuLi (1.3 M in hexane, 0.25 mL, 0.34 mmol) was added to
a solution of 1-hexyne derivative (0.41 mmol) in THF (0.7 mL)
at ꢁ78 ꢀC and the mixture was stirred for 1 h at ꢁ40 ꢀC.1-Benzyloxy-
3-(tert-butyldimethylsilyloxy)propan-2-one (100 mg, 0.34 mmol)
was added to the mixture and then the reaction mixture was
warmed to room temperature. After stirring until the complete
disappearance of the starting material (monitored by TLC), the
mixture was quenched by water, extracted Et2O. The extract was
9
10
aDiastereomeric ratios were determined by isolated yields.

5136
Y.A.M. Mohamed et al. / Tetrahedron 67 (2011) 5133e5141
washed with water and brine, dried and concentrated to dryness.
The residue was chromatographed with hexane/AcOEt (15:1) to
give the corresponding propargyl alcohols.
J¼6.4, 2.7 Hz, 1H), 4.78e4.73 (m, 1H), 4.22e4.12 (m, 2H), 1.62e1.26
(m, 12H), 1.00e0.85 (m, 24H), 0.08 (s, 6H).
4.4.2. 4-(tert-Butyldimethylsilyloxy)-3-methyl-1-(tributylstannyl)-
4.3.1. 1-Benzyloxy-2-(tert-butyldimethylsilyloxy)methyl-3-octyn-2-
1,2-butadiene (8b). Colorless oil; IR 1936 cmꢁ1 1H NMR
;
ol. Colorless oil; IR 3545, 2245 cmꢁ1; 1H NMR
d
7.36e7.27 (m, 5H),
d
5.05e5.00 (m, 1H), 4.11e4.10 (m, 2H), 1.66 (td, J¼10.7, 3.7 Hz, 3H),
4.65, 4.62 (ABq, JAB¼9.3 Hz, 2H), 3.75 (d, J¼9.6 Hz, 1H), 3.66 (d,
J¼9.6 Hz, 1H), 3.56, 3.54 (ABq, JAB¼9.3 Hz, 2H), 2.91 (br s, 1H), 2.21
(t, J¼6.9 Hz, 2H), 1.51e1.46 (m, 2H), 1.43e1.37 (m, 2H), 0.95e0.90
1.57e0.88 (m, 36H), 0.07 (s, 6H); 13C NMR
d
206.2, 88.4, 75.8, 66.2,
28.9, 27.2, 25.9,18.4,15.2,13.7,10.5, ꢁ5.3; EIMS m/z 488 (Mþ, 8.2); EI
HRMS calcd for C23H48OSiSn 488.2496, found 488.2494.
(m, 12H), 0.08 (s, 3H), 0.07 (s, 3H); 13C NMR
d 138.1, 128.3, 127.61,
127.58, 85.7, 79.8, 73.5, 73.0, 70.5, 66.8, 30.6, 25.8, 21.9, 18.4, 18.3,
13.6, ꢁ5.41, ꢁ5.43; EIMS m/z 376 (Mþ, 3.4); EI HRMS calcd for
C22H36O3Si 376.2434, found 376.2428.
4.4.3. 4-(tert-Butyldimethylsilyloxy)-3-ethyl-1-(tributylstannyl)-1,2-
butadiene (8c). Colorless oil; IR 1933 cmꢁ1; 1H NMR
d
5.11 (tt, J¼4.1,
2.3 Hz, 1H), 4.15 (td, J¼6.9, 2.3 Hz, 2H), 2.06e1.90 (m, 2H), 1.59e1.47
(m, 6H), 1.35e1.26 (m, 6H), 1.02 (t, J¼7.3 Hz, 3H), 0.94e0.87 (m,
4.3.2. 1-Benzyloxy-2-(tert-butyldimethylsilyloxy)methyl-8-(p-me-
24H), 0.06 (s, 6H); 13C NMR
d 205.6, 95.1, 76.7, 65.3, 29.0, 27.2, 26.0,
thoxybenzyloxy)-3-octyne-2-ol. Colorless oil; IR 3545, 2243 cmꢁ1
;
21.5, 18.4, 13.7, 12.4, 10.4, ꢁ5.2, ꢁ5.3; EIMS m/z 502 (Mþ, 6.5); EI
1H NMR
d
7.34e7.24 (m, 7H), 6.87 (d, J¼9.2 Hz, 2H), 4.63 (s, 2H), 4.41
HRMS calcd for C24H50OSiSn 502.2653, found 502.2648.
(s, 2H), 3.80 (s, 3H), 3.74 (d, J¼9.8 Hz, 1H), 3.66 (d, J¼9.8 Hz, 1H),
3.56, 3.53 (ABq, JAB¼9.6 Hz, 2H), 3.44 (t, J¼6.6 Hz, 2H), 2.23 (t,
J¼7.5 Hz, 2H), 1.71e1.66 (m, 2H), 1.63e1.57 (m, 2H), 0.89 (s, 9H),
4.4.4. 3-Benzyloxymethyl-4-(tert-butyldimethylsilyloxy)-1-(tributyl-
stannyl)-1,2-butadiene (8d). Colorless oil; IR 1934 cmꢁ1 1H NMR
;
0.08 (s, 3H), 0.07 (s, 3H); 13C NMR
d
159.0, 138.1, 130.6, 129.2, 128.3,
d 7.25e7.17 (m, 5H), 5.10e5.09 (m, 1H), 4.42 (s, 2H), 4.15e4.14 (m,
127.59,127.56,113.7, 85.3, 80.1, 73.5, 73.0, 72.5, 70.4, 69.4, 66.8, 55.2,
28.8, 25.8, 25.2, 18.5, 18.3, ꢁ5.41, ꢁ5.44; DART MS m/z 513 (Mþþ1,
69); DART HRMS calcd for C30H45O5Si 513.3036, found 513.3041.
2H), 4.05e4.02 (m, 2H), 1.45e1.39 (m, 6H), 1.26e1.17 (m, 6H),
0.97e0.78 (m, 24H), ꢁ0.02 (s, 6H); 13C NMR
d 205.6, 138.7, 128.2,
127.7, 127.3, 90.3, 76.9, 71.4, 69.0, 62.3, 29.0, 27.2, 25.9, 18.4, 13.7,
10.5, ꢁ5.3; DART MS m/z 595 (Mþþ1, 34); DART HRMS calcd for
C30H55O2SiSn 595.2993, found 595.2987.
4.3.3. 1-(tert-Butyldimethylsilyloxy)-3-pentyn-2-ol. To a solution of
2-(tert-butyldimethylsilyloxy)acetaldehyde21 (800 mg, 4.6 mmol)
in Et2O (9 mL) was added propynyl magnesium bromide (0.50 M
in THF, 10 mL, 5.0 mmol) at 0 ꢀC. After stirring for 2.5 h at the same
temperature, the reaction mixture was quenched by saturated
aqueous NH4Cl, extracted with Et2O. The extract was washed with
water and brine, dried and concentrated to dryness. The residue
was chromatographed with hexane/AcOEt (9:1) to give 1-(tert-
butyldimethylsilyloxy)-3-pentyn-2-ol (690 mg, 70%) as a colorless
4.4.5. 1-Benzyloxy-2-(tert-butyldimethylsilyloxymethyl)-4-(tributyl-
stannyl)-2,3-octadiene (8e). Colorless oil; IR 1936 cmꢁ1 1H NMR
;
d
7.27e7.17 (m, 5H), 4.45 (d, J¼11.6 Hz, 1H), 4.39 (d, J¼11.6 Hz, 2H),
4.14e3.97 (m, 4H), 2.06e2.02 (m, 2H), 1.54e0.81 (m, 43H), ꢁ0.02 (s,
6H); 13C NMR
199.7, 138.9, 128.2, 127.6, 127.2, 94.2, 92.1, 71.2, 69.8,
d
62.6, 32.6, 32.5, 29.0, 27.5, 27.3, 25.9, 22.3, 18.4, 13.7, 10.3, ꢁ5.3;
EIMS m/z 650 (Mþ, 1.4); EI HRMS calcd for C34H62O2SiSn 650.3541,
found 650.3533.
oil. IR 3545, 2359 cmꢁ1
;
1H NMR
d
4.35 (s, 1H), 3.71 (dd, J¼10.0,
3.7 Hz, 1H), 3.57 (dd, J¼10.0, 7.8 Hz, 1H), 2.61e2.60 (m, 1H), 1.83 (d,
J¼1.8 Hz, 3H), 0.90 (s, 9H), 0.09 (s, 3H), 0.08 (s, 3H); 13C NMR
4.4.6. 1-Benzyloxy-2-(tert-butyldimethylsilyloxymethyl)-8-(p-me-
thoxybenzyloxy)-4-(tributylstannyl)-2,3-octadiene (8f). Colorless oil;
d
81.8, 67.2, 63.2, 30.3, 25.8, 18.3, 3.5, ꢁ5.4; DART MS m/z 215
(Mþþ1, 39); DART HRMS calcd for C11H23O2Si 215.1467, found
IR 1936 cmꢁ1; 1H NMR
d
7.28e7.16 (m, 7H), 6.78 (d, J¼8.7 Hz, 2H),
215.1470.
4.45, 4.40 (ABq, JAB¼11.4 Hz, 2H), 4.34 (s, 2H), 4.16e3.97 (m, 4H),
3.71 (s, 3H), 3.36 (t, J¼6.4 Hz, 2H), 2.11e2.01 (m, 2H), 1.61e1.55 (m,
2H), 1.49e0.80 (m, 38H), ꢁ0.01 (s, 6H); 13C NMR
d 199.6, 159.0,
4.4. General procedure for preparation of allenylstannanes
138.8, 130.7, 129.1, 128.2, 127.5, 127.2, 113.6, 94.0, 92.3, 72.4, 71.2,
69.9, 69.5, 62.5, 55.1, 32.6, 32.4, 29.0, 27.5, 27.0, 25.9, 18.3, 13.7, 10.3,
ꢁ5.3; FABMS m/z 787 (Mþþ1, 0.1); FAB HRMS calcd for
C42H71O4SiSn 787.4144, found 787.4148.
To a solution of propargyl alcohol derivative (1.0 mmol) in
CH2Cl2 (10 mL) were added Et3N (0.28 mL, 2.0 mmol) and MsCl
(0.10 mL, 1.3 mmol) at 0 ꢀC. The reaction mixture was stirred for 1 h,
quenched by addition of saturated aqueous NaHCO3 and extracted
with CH2Cl2. The extract was washed with water and brine, dried,
4.5. Palladium(0)-catalyzed coupling reaction of iodoaniline
7 with allenylstannane 8
i
and concentrated to dryness. To a solution of Pr2NH (0.24 mL,
1.6 mmol) in THF (10 mL) was added nBuLi (1.5 M hexane solution,
0.93 mL, 1.4 mmol) at ꢁ30 ꢀC. After 30 min, Bu3SnH (0.40 mL,
1.5 mmol) was added. The reaction mixture was stirred for 30 min
at the same temperature and then cooled to ꢁ78 ꢀC. CuBr$SMe2
(310 mg, 1.5 mmol) was then added to the reaction mixture and
stirring for 30 min at ꢁ78 ꢀC. The crude mesylate in THF (3.0 mL)
was added to the reaction mixture and the mixture was stirred for
20 min at the same temperature. The reaction mixture was
quenched by addition of saturated aqueous NH4Cl and extracted
with Et2O. The extract was washed with water and brine, dried, and
concentrated to dryness. The residue was chromatographed with
hexane and then hexane/AcOEt (50:1) to give the corresponding
allenylstannane 8.
To a solution of iodoaniline 7 (320 mg, 1.0 mmol) and allenyl-
stannane 8 (1.1 mmol) in DMF (10 mL) were added TFP (56 mg,
0.24 mmol), CuI (19 mg, 0.10 mmol), and Pd2(dba)3 (27 mg,
0.030 mmol) at room temperature. After stirring until the complete
disappearance of the starting material (monitored by TLC), the
mixture was quenched by addition of 10% aqueous NH3 solution,
and extracted with Et2O. The extract was washed with water and
brine, dried, and concentrated to dryness. The residue was chro-
matographed with hexane/Et2O to give the corresponding 2-
allenylaniline 9. The chemical yields were summarized in Table 1.
4.5.1. N-(tert-Butoxycarbonyl)-2-[4-(tert-butyldimethylsilyloxy)-1,2-
butadienyl]aniline (9a). Yellow oil; IR 3392, 1950, 1724 cmꢁ1 1H
;
NMR
d
7.89 (d, J¼7.8 Hz, 1H), 7.39 (br s, 1H), 7.23e7.19 (m, 1H),
4.4.1. 4-(tert-Butyldimethylsilyloxy)-1-(tributylstannyl)-1,2-
7.18e7.16 (m, 1H), 7.03e6.99 (m, 1H), 6.36 (td, J¼6.4, 3.2 Hz, 1H),
5.69e5.65 (m, 1H), 4.34e4.31 (m, 2H), 1.51 (s, 9H), 0.89 (s, 9H), 0.08
butadiene (8a)8. Colorless oil; IR 1929 cmꢁ1 1H NMR
; d 5.12 (dt,

Y.A.M. Mohamed et al. / Tetrahedron 67 (2011) 5133e5141
5137
(s, 6H); 13C NMR
d
204.5, 153.1, 136.1, 129.1, 127.9, 123.4, 122.5, 121.4,
at 0e40 ꢀC until the complete disappearance of the starting material
(monitored by TLC), the mixture was quenched by saturated aque-
ous NH4Cl, extracted with Et2O. The extract was washed with water
and brine, dried and concentrated to dryness. The residue was
chromatographed with hexane/AcOEt (9:1) to give indole products.
The chemical yields were summarized in Scheme 1 and Table 2.
95.5, 93.7, 80.1, 60.6, 28.3, 25.8, 18.3, ꢁ5.2, ꢁ5.3; DART MS m/z 376
(Mþþ1, 100); DART HRMS calcd for C21H34NO3Si 376.2308, found
376.2305.
4.5.2. N-(tert-Butoxycarbonyl)-2-[4-(tert-butyldimethylsilyloxy)-3-
methyl-1,2-butadienyl]aniline (9b). Colorless oil; IR 3393, 1948,
1726 cmꢁ1; 1H NMR
d
7.95 (d, J¼8.2 Hz, 1H), 7.61 (br s,1H), 7.22e7.17
4.6.1. N-(tert-Butoxycarbonyl)-2-(4-hydroxy-1,2-butadien-2-yl)ani-
(m, 1H), 7.12 (dd, J¼7.8, 1.8 Hz, 1H), 7.01e6.97 (m, 1H), 6.28e6.26 (m,
1H), 4.22 (dd, J¼12.4, 3.2 Hz,1H), 4.18 (dd, J¼12.4, 3.2 Hz,1H),1.83 (d,
line (10a). Yellow oil; IR 3396, 1944, 1728 cmꢁ1; 1H NMR
d 7.85 (br
s,1H), 7.32 (br s,1H), 7.23 (t, J¼7.2 Hz,1H), 7.17 (d, J¼7.2 Hz,1H), 7.05
J¼3.2 Hz, 3H), 1.51 (s, 9H), 0.88 (s, 9H), 0.06 (s, 6H); 13C NMR
d 201.8,
(t, J¼7.2 Hz,1H), 6.40 (br s,1H), 5.78 (q, J¼5.8 Hz,1H), 4.30 (br s, 2H),
153.0, 136.5, 129.4, 127.6, 122.9, 122.5, 120.6, 103.8, 93.4, 80.0, 64.3,
28.4, 25.8, 18.3, 15.5, ꢁ5.36, ꢁ5.38; EIMS m/z 389 (Mþ, 4.7); EI HRMS
calcd for C22H35NO3Si 389.2386, found 389.2384.
1.52 (s, 9H); 13C NMR
d 204.7, 153.0, 136.2, 129.3, 128.1, 123.79,
123.77, 121.7, 95.3, 94.3, 81.1, 60.3, 28.4; DART MS m/z 262 (Mþþ1,
100); DART HRMS calcd for C15H20NO3 262.1443, found 262.1443.
4.5.3. N-(tert-Butoxycarbonyl)-2-[3-(tert-butyldimethylsilylox-
4.6.2. N-(tert-Butoxycarbonyl)-2-(4-hydroxy-3-methyl-1,2-
ymethyl)-1,2-pentadienyl]aniline (9c). Yellow oil; IR 3396, 1960,
butadienyl)aniline (10b). Colorless oil; IR 3377, 1948, 1728 cmꢁ1; 1H
1728 cmꢁ1
;
1H NMR
d
7.97 (d, J¼7.8 Hz, 1H), 7.66 (s, 1H), 7.21e7.17
NMR
d
7.91 (br s, 1H), 7.59 (br s, 1H), 7.21 (t, J¼7.6 Hz, 1H), 7.13 (d,
(m, 1H), 7.13e7.11 (m, 1H), 7.00e6.97 (m, 1H), 6.38e6.37 (m, 1H),
4.25e4.24 (m, 2H), 2.17e2.11 (m, 2H), 1.51 (s, 9H), 1.11 (t, J¼7.3 Hz,
J¼7.6 Hz, 1H), 7.01 (t, J¼7.6 Hz, 1H) 6.34 (br s, 1H), 4.19 (dd, J¼13.4,
2.7 Hz, 1H), 4.14 (dd, J¼13.4, 2.7 Hz, 1H), 1.86 (d, J¼3.1 Hz, 3H), 1.52
3H), 0.88 (s, 9H), 0.06 (s, 6H); 13C NMR
d
201.1, 152.9, 136.6, 129.3,
(s, 9H); 13C NMR
d 201.2, 153.0, 136.5, 129.4, 128.0, 123.3, 122.4,
127.6,122.9,122.3,120.4,110.6, 95.3, 80.0, 63.5, 28.3, 25.8, 22.4,18.3,
12.0, ꢁ5.36, ꢁ5.40; FABMS m/z 404 (Mþþ1, 9.5); FAB HRMS calcd
for C23H38NO3Si 404.2621, found 404.2625.
120.8, 104.3, 94.3, 80.7, 63.9, 28.3, 15.8; EIMS m/z 275 (Mþ, 4.0); EI
HRMS calcd for C16H21NO3 275.1521, found 275.1516.
4.6.3. N-(tert-Butoxycarbonyl)-2-(3-hydroxymethyl-1,2-pentadienyl)
4.5.4. N-(tert-Butoxycarbonyl)-2-[3-benzyloxymethyl-4-(tert-bu-
aniline (10c). Yellow oil; IR 3373, 1944, 1728 cmꢁ1 1H NMR
; d 7.94
tyldimethylsilyloxy)-1,2-butadienyl]aniline (9d). Colorless oil; IR
(br s, 1H), 7.62 (br s, 1H), 7.23e7.20 (m, 1H), 7.14 (dd, J¼7.6, 1.4 Hz,
1H), 7.01 (t, J¼7.6 Hz, 1H), 6.45 (s, 1H), 4.23 (dd, J¼13.4, 2.7 Hz, 1H),
4.20 (dd, J¼13.4, 2.7 Hz, 1H), 2.22e2.10 (m, 2H), 1.52 (s, 9H), 1.12 (t,
3398, 1952, 1724 cmꢁ1; 1H NMR
d
7.88 (d, J¼8.2 Hz, 1H), 7.42 (br s,
1H), 7.27e7.15 (m, 6H), 7.11 (dd, J¼7.8, 1.4 Hz, 1H), 6.97 (td, J¼7.8,
1.4 Hz, 1H), 6.36 (tt, J¼3.2, 1.8 Hz, 1H), 4.51 (s, 2H), 4.30 (d, J¼3.2 Hz,
2H), 4.13 (d, J¼1.8 Hz, 2H), 1.43 (s, 9H), 0.82 (s, 9H), 0.03 (s, 3H), 0.02
J¼7.8 Hz, 3H); 13C NMR
d 200.6, 152.8, 136.4, 129.4, 127.9, 123.2,
123.1, 120.6, 111.3, 96.1, 80.7, 62.9, 28.2, 22.8, 12.0; DART MS m/z 290
(Mþþ1, 30); DART HRMS calcd for C17H24NO3 290.1756, found
290.1737.
(s, 3H); 13C NMR
d 202.4, 153.1, 137.8, 136.4, 129.3, 128.3, 127.9, 127.7,
127.6, 123.2, 122.4, 121.3, 105.6, 94.5, 80.0, 72.1, 67.9, 61.3, 28.3, 25.8,
18.3, ꢁ5.37, ꢁ5.39; FABMS m/z 518 (Mþþ23, 2.4); FAB HRMS calcd
for C29H41NNaO4Si 518.2703, found 518.2710.
4.6.4. 1-(tert-Butoxylcarbonyl)-2-vinyl-1H-indole (11a). Colorless oil;
IR 1724 cmꢁ1; 1H NMR
d
8.07 (d, J¼8.2 Hz,1H), 7.50 (d, J¼7.8 Hz,1H),
4.5.5. N-(tert-Butoxycarbonyl)-2-[1-benzyloxy-2-(tert-butyldime-
thylsilyloxymethyl)-2,3-octadien-4-yl]aniline (9e). Colorless oil; IR
7.28e7.21 (m, 3H), 6.72 (s,1H), 5.69 (dd, J¼17.4,1.4 Hz,1H), 5.28 (dd,
J¼11.0, 1.8 Hz, 1H), 1.69 (s, 9H); 13C NMR
d 150.5, 139.8, 136.6, 129.4,
3421, 1960, 1718 cmꢁ1
;
1H NMR
d
7.92 (d, J¼7.3 Hz, 1H), 7.63e7.62
129.2, 124.1, 122.9, 120.4, 115.8, 115.6, 106.9, 84.2, 28.2; EIMS m/z
243 (Mþ, 8.6); EI HRMS calcd for C15H17NO2 243.1259, found
243.1552.
(m, 1H), 7.27e7.14 (m, 7H), 7.00e6.98 (m, 1H), 4.57, 4.53 (ABq,
JAB¼12.4, 2H), 4.20, 4.16 (ABq, JAB¼12.4 Hz, 2H), 4.08e4.04 (ABq,
JAB¼11.9 Hz, 2H), 2.31 (t, J¼7.8 Hz, 2H), 1.53e1.27 (m, 13H), 0.85 (t,
J¼7.3 Hz, 2H), 0.81 (s, 9H), ꢁ0.02 (s, 3H), ꢁ0.04 (s, 3H); 13C NMR
4.6.5. 2-(3-Benzyloxyprop-1-en-2-yl)-1-(tert-butoxylcarbonyl)-1H-
d
198.7, 153.4, 138.1, 135.9, 128.3, 127.7, 127.64, 127.56, 127.5, 127.2,
indole (11d). Colorless oil; IR 1728 cmꢁ1 1H NMR
; d 8.08 (d,
122.8, 121.1, 104.8, 103.4, 80.0, 72.0, 67.7, 61.8, 33.8, 30.1, 28.4, 25.8,
22.4, 18.2, 14.0, ꢁ5.35, ꢁ5.42; FABMS m/z 552 (Mþþ1, 0.5); FAB
HRMS calcd for C33H50NO4Si 552.3509, found 552.3507.
J¼8.1 Hz, 1H), 7.50 (d, J¼7.3 Hz, 1H), 7.31e7.18 (m, 7H), 6.54 (s, 1H),
5.48 (d, J¼1.3 Hz, 1H), 5.40 (d, J¼1.3 Hz, 1H), 4.53 (s, 2H), 4.29 (s,
2H), 1.58 (s, 9H); 13C NMR
d 150.2, 140.4, 139.3, 138.2, 136.7, 129.2,
128.3, 127.7, 127.5, 124.2, 122.8, 120.4, 116.3, 115.4, 110.3, 84.0, 72.3,
72.1, 28.0; EIMS m/z 363 (Mþ, 9.7); EI HRMS calcd for C23H25NO3
363.1834, found 363.1838.
4.5.6. N-(tert-Butoxycarbonyl)-2-[1-benzyloxy-2-(tert-butyldime-
thylsilyloxymethyl)-8-(p-methoxybenzyloxy)-2,3-octadien-4-yl]ani-
line (9f). Colorless oil; IR 3420, 1954, 1718 cmꢁ1; 1H NMR
d 7.97 (d,
J¼8.2 Hz,1H), 7.67 (br s, 1H), 7.28e7.17 (m, 9H), 7.01 (t, J¼7.8 Hz,1H),
6.85 (d, J¼8.7 Hz, 2H), 4.58 (s, 2H), 4.40 (s, 2H), 4.24, 4.19 (ABq,
JAB¼12.4 Hz, 2H), 4.12, 4.07 (ABq, JAB¼12.4 Hz, 2H), 3.79 (s, 3H), 3.41
(t, J¼6.4 Hz, 2H), 2.40e2.35 (m, 2H), 1.68e1.51 (m, 4H), 1.47 (s, 9H),
4.6.6. 2-(3-Benzyloxyprop-1-en-2-yl)-1-(tert-butoxylcarbonyl)-3-
butyl-1H-indole (11e). Colorless oil; IR 1724 cmꢁ1 1H NMR
; d 8.02
(d, J¼8.2 Hz, 1H), 7.45 (d, J¼7.6 Hz, 1H), 7.21e7.16 (m, 7H), 5.60 (s,
1H), 5.19 (s, 1H), 4.49 (s, 2H), 4.11 (s, 2H), 2.60e2.58 (m, 2H),
1.52e1.48 (m, 11H), 1.34e1.28 (m, 2H), 0.86e0.81 (m, 3H); 13C NMR
0.84 (s, 9H), 0.01 (s, 3H), ꢁ0.01 (s, 3H); 13C NMR
d 198.6, 159.0, 153.4,
138.0,135.9,130.6,129.2,129.0,128.4,128.3,127.7,127.6,126.9,122.8,
121.1, 113.7, 104.6, 103.7, 80.1, 72.5, 72.0, 69.8, 67.6, 61.7, 55.2, 33.8,
29.4, 28.4, 25.8, 24.6, 18.2, ꢁ5.36, ꢁ5.42; FABMS m/z 710 (Mþþ23,
0.5); FAB HRMS calcd for C41H57NNaO6Si 710.3853, found 710.3845.
d 159.1, 139.1, 138.3, 135.9, 134.1, 130.0, 128.3, 127.6, 127.5, 124.2,
122.4, 121.9, 119.1, 116.5, 115.6, 83.7, 72.6, 72.4, 33.1, 28.1, 24.3, 23.1,
14.0; EIMS m/z 419 (Mþ, 4.4); EI HRMS calcd for C27H33NO3
419.2460, found 419.2459.
4.6. General procedure for the treatment of allenylanilines 9
with TBAF in THF
4.6.7. 1-(tert-Butoxylcarbonyl)-2-(3-benzyloxyprop-1-en-2-yl)-3-[4-
(p-methoxybenzyloxy)methyl]-1H-indole (11f). Colorless oil; IR
1722 cmꢁ1; 1H NMR
7.31e7.19 (m, 9H), 6.87e6.85 (m, 2H), 5.664e5.660 (m, 1H),
5.261e5.257 (m,1H), 4.54 (s, 2H), 4.41 (s, 2H), 4.18 (s, 2H), 3.79 (s, 3H),
d
8.09 (d, J¼8.2 Hz, 1H), 7.51 (d, J¼6.9 Hz, 1H),
To a solution of allenylaniline 9 (0.10 mmol) in THF (1 mL) was
added TBAF (0.50 M in THF, 1.0 mL, 0.50 mmol) at 0 ꢀC. After stirring

5138
Y.A.M. Mohamed et al. / Tetrahedron 67 (2011) 5133e5141
3.45e3.41 (m, 2H), 2.69e2.66 (m, 2H),1.70e1.67 (m, 4H),1.58 (s, 9H);
13C NMR
159.0, 150.1, 139.0, 138.2, 135.9, 134.2, 130.6, 129.9, 129.2,
128.3, 127.6, 127.5, 124.2, 122.4, 121.5, 119.1, 116.6, 115.5, 113.7, 83.7,
72.6, 72.5, 72.4, 69.8, 55.2, 29.9, 28.0, 27.4, 24.3; EIMS m/z 555 (Mþ,
57); EI HRMS calcd for C35H41NO5 555.2985, found 555.2988.
starting material (monitored by TLC), the mixture was quenched by
saturated aqueous NH4Cl, extracted with Et2O. The extract was
washedwith waterand brine, dried and concentrated to dryness. The
residue was chromatographed with hexane/AcOEt (9:1) to afford
vinylindole 11. The chemical yields were summarized in Table 2.
d
4.6.8. 1-(tert-Butoxycarbonyl)-2-(1-hydroxypropan-2-yl)-1H-indole
4.7.5. 3-Methyl-2-vinyl-1H-indole (13g). To a solution of 1-(tert-
butyldimethylsilyloxy)-3-pentyn-2-ol (64 mg, 0.30 mmol) in CH2Cl2
(3 mL) were added Et3N (0.084 mL, 0.60 mmol) and MsCl (0.030 mL,
0.39 mmol) at 0 ꢀC. The reaction mixture was stirred for 1 h,
quenched by addition of saturated aqueous NaHCO3 and extracted
with CH2Cl2. The extract was washed with water and brine, dried,
(12b). Colorless oil; IR 3468, 1740 cmꢁ1 1H NMR
; d 8.26 (br s, 1H),
7.55 (d, J¼7.8 Hz, 1H), 7.33 (d, J¼8.2 Hz, 1H), 7.16e7.12 (m, 1H),
7.09e7.05 (m, 1H), 6.31 (s, 1H), 4.25 (dd, J¼10.5, 6.9 Hz, 1H), 4.19
(dd, J¼10.5, 6.9 Hz, 1H), 3.30 (sex, J¼6.9 Hz, 1H), 1.48 (s, 9H), 1.42 (d,
J¼6.9 Hz, 3H); 13C NMR
d 153.4, 140.7, 135.9, 128.2, 121.4, 120.1,
119.6, 110.6, 99.0, 82.5, 71.2, 32.8, 27.7, 16.4; EIMS m/z 275 (Mþ, 93);
and concentrated to dryness. To a solution of Pr2NH (0.072 mL,
i
EI HRMS calcd for C16H21NO3 275.1521, found 275.1525.
0.48 mmol) in THF (3 mL) was added nBuLi (1.5 M hexane solution,
0.28 mL, 0.42 mmol) at ꢁ30 ꢀC. After 30 min, Bu3SnH (0.12 mL,
0.45 mmol) was added. The reaction mixture was stirred for 30 min
at the same temperature and then cooled to ꢁ78 ꢀC. CuBr$SMe2
(93 mg, 0.45 mmol) was then added to the reaction mixture and
stirring for 30 min at ꢁ78 ꢀC. The crude mesylate in THF (1.0 mL) was
added to the reaction mixture and the mixture was stirred for
20 min at the same temperature. The reaction mixture was
quenched by addition of saturated aqueous NH4Cl and extracted
with Et2O. The extract was washed with water and brine, dried, and
concentrated to dryness. The residue was a short pad of silica gel
with hexane/AcOEt (50:1) to give the crude 1-(tert-butyldime-
thylsilyloxy)-3-(tributylstannyl)-2,3-pentadiene. To a solution of
iodoaniline 7 (25 mg, 0.078 mmol) and the crude 1-(tert-butyldi-
methylsilyloxy)-3-(tributylstannyl)-2,3-pentadiene in DMF (1 mL)
were added TFP (4.3 mg, 0.018 mmol), CuI (1.5 mg, 7.8ꢂ10ꢁ3 mmol)
and Pd2(dba)3 (2.2 mg, 2.3ꢂ10ꢁ3 mmol) at room temperature. After
stirring for 12 h at the same temperature, the mixture was quenched
by addition of 10% aqueous NH3 solution, and extracted with Et2O.
The extract was washed with water, brine, dried, and concentrated
to dryness. To a solution of the crude allenylanilines in DMSO (1 mL)
was added KOH (22 mg, 0.39 mmol) at room temperature. After
stirring for 20 min, the reaction mixture was quenched by water and
extracted with Et2O. The extract was washed with water and brine,
dried and concentrated to dryness. The residue was chromato-
graphed with hexane/AcOEt (20:1) to afford 13g (13 mg, 42% from 7)
4.6.9. 1-(tert-Butoxycarbonyl)-2-(1-hydroxybutan-2-yl)-1H-indole
(12c). Yellowoil; IR3468,1740cmꢁ1; 1H NMR
d 8.19 (br s,1H), 7.55 (d,
J¼7.8 Hz, 1H), 7.34 (d, J¼8.2 Hz,1H), 7.16e7.12 (m, 1H), 7.09e7.06 (m,
1H), 6.31 (s,1H), 4.31 (dd, J¼10.5, 6.4 Hz,1H), 4.24 (dd, J¼10.5, 5.5 Hz,
1H), 3.07e3.01 (m, 1H), 1.86e1.72 (m, 2H), 1.46 (s, 9H), 0.95 (t,
J¼7.3 Hz, 3H); 13C NMR
d 153.4, 139.3, 135.9, 128.3, 121.3, 120.0, 119.6,
110.6,100.0, 82.4, 69.8, 40.3, 27.7, 24.4,11.8; DART MS m/z 290 (Mþþ1,
99); DART HRMS calcd for C17H24NO3 290.1756, found 290.1760.
4.7. General procedure for the cyclization of allenylanilines 10
To a solution of alcohol 10 (0.10 mmol) in pyridine (0.3 mL), was
added ethyl chloroformate (0.018 mL, 0.20 mmol) at 0 ꢀC. The re-
action mixture was stirred for 30 min at the same temperature and
concentrated to dryness. The residuewas a short pad of silica gel with
hexane/AcOEt (15:1) to give the crude carbonate. To a solution of the
crude carbonate in THF (1 mL) was added TBAF (0.10 mL, 0.30 mmol)
at 0 ꢀC. After stirring for 1 h, the mixture was quenched by saturated
aqueous NH4Cl and extracted with Et2O. The extract was washed
with water and brine, dried and concentrated to dryness. The residue
was chromatographed with hexane/AcOEt (20:1) to give 2-
vinylindole 11. The chemical yields were summarized in Scheme 1.
4. 7.1. 1-(tert-Butoxylcarbonyl)-2-(propen-2-yl)indole
(11b). Colorless oil; IR 1728 cmꢁ1; 1H NMR
d
8.08 (d, J¼7.9 Hz, 1H),
7.49 (d, J¼7.6 Hz, 1H), 7.28e7.25 (m, 1H), 7.22e7.19 (m, 1H), 6.44 (s,
1H), 5.17 (br s, 2H), 2.09 (s, 3H), 1.65 (s, 9H); 13C NMR
150.1, 142.9,
as colorless needles. Mp 81.5e82 ꢀC (hexane); IR 3474 cmꢁ1
;
1H
NMR
d
7.96 (br s, 1H), 7.53 (d, J¼8.2 Hz, 1H), 7.29 (d, J¼8.2 Hz, 1H),
d
7.20e7.07 (m, 2H), 6.86 (dd, J¼17.9, 11.0 Hz, 1H), 5.43 (d, J¼17.9 Hz,
139.2, 136.8, 129.2, 124.0, 122.8, 120.4, 115.3, 115.1, 108.3, 83.9, 28.0,
23.2; EIMS m/z 257 (Mþ, 74); EI HRMS calcd for C16H19NO2 257.1416,
found 257.1414.
1H), 5.24 (d, J¼11.0 Hz,1H), 2.33 (s, 3H); 13C NMR
d 136.1, 132.1, 129.4,
129.0, 125.6, 123.0, 119.4, 119.0, 110.6, 110.4, 8.6; EIMS m/z 157 (Mþ,
92); EI HRMS calcd for C11H11N 157.0891, found 157.0893.
4.7.2. 2-(1-Buten-2-yl)-1-(tert-butoxylcarbonyl)-1H-indole
4.7.6. 1,1-Dimethyloxazolo[3,4-a]indol-3(1H)-one
(14b). TMSCl
(11c). Yellow oil; IR 1728 cmꢁ1
;
1H NMR
d
8.10 (d, J¼8.2 Hz, 1H),
(0.015 mL, 0.12 mmol) was added to a solution of NaI (18 mg,
0.12 mmol) in acetonitrile (0.2 mL). After stirring for 20 min, a so-
lution of compound 11b (10 mg, 0.039 mmol) in acetonitrile (0.2 mL)
was added to the reaction mixture and further stirred for 30 min.
The reaction mixture was quenched by addition of methanol and
water, extracted with CH2Cl2. The extract was washed with water,
brine, dried, and concentrated to dryness. The residue was chro-
matographed with hexane/AcOEt (19:1) to afford compound 14b
(6.7 mg, 85%) as colorless crystals mp 64.5e65 ꢀC (CH2Cl2); IR
7.49 (d, J¼7.8 Hz, 1H), 7.29e7.25 (m, 1H), 7.22e7.19 (m, 1H), 6.42 (s,
1H), 5.16e5.14 (m, 2H), 2.40 (q, J¼7.3 Hz, 2H), 1.63 (s, 9H), 1.04 (t,
J¼7.3 Hz, 3H); 13C NMR
d 150.1, 145.5, 141.8, 136.8, 129.2, 123.9,
122.7, 120.3, 115.3, 113.3, 109.1, 83.8, 29.6, 28.0, 12.9; EIMS m/z 271
(Mþ, 10); EI HRMS calcd for C17H21NO2 271.1572, found 271.1570.
4.7.3. Treatment of 9b with K2CO3 in DMF. To a solution of 9b
(46 mg, 0.12 mmol) in DMF (1 mL) was added K2CO3 (26 mg,
0.18 mmol) at room temperature. After stirring at 110 ꢀC for 4 h, the
mixture was quenched by water, extracted with Et2O. The extract
was washed with water and brine, dried and concentrated to dry-
ness. The residue was chromatographed with hexane/AcOEt (9:1)
to afford 11b (20 mg, 66%).
1782 cmꢁ1
;
1H NMR
d
7.95 (d, J¼8.1 Hz, 1H), 7.57 (d, J¼8.1 Hz, 1H),
7.37e7.29 (m, 2H), 6.30 (s, 1H), 1.78 (s, 6H); 13C NMR
d
149.3, 145.4,
134.5, 129.9, 124.0, 123.8, 121.4, 112.9, 96.2, 83.6, 27.6; EIMS m/z 201
(Mþ, 90); EI HRMS calcd for C12H11NO2 201.0790, found 201.0793.
4.7.7. Treatment of 11b with TFA in CH2Cl2. To a solution of 11b
(20 mg, 0.10 mmol) in CH2Cl2 (1 mL) was added TFA (0.6ꢂ10ꢁ2 mL,
0.11 mmol) at room temperature. After stirring for 1 h, the mixture
was quenched by saturated aqueous NaHCO3, extracted with
CH2Cl2. The extract was washed with water and brine, dried and
4.7.4. Treatment of 9 with K2CO3 and Et2CO3 in DMF. To a solution of
allenylaniline 9 (0.12 mmol) inDMF (1 mL) were addedK2CO3 (20 mg,
0.14 mmol) and Et2CO3 (0.14 mL, 1.2 mmol) at room temperature.
After stirring at 85e95 ꢀC until the complete disappearance of the

Y.A.M. Mohamed et al. / Tetrahedron 67 (2011) 5133e5141
5139
concentrated to dryness. The residue was chromatographed with
hexane/AcOEt (19:1) to afford 14b (15 mg, 76%).
3470 cmꢁ1; 1H NMR
d
11.72 (br s, 1H), 7.51 (d, J¼7.8 Hz, 1H), 7.35 (d,
J¼8.2 Hz,1H), 7.13e7.08 (m,1H), 7.07e7.03 (m,1H), 4.83 (d, J¼6.0 Hz,
1H), 3.87 (dt, J¼6.0, 4.1 Hz, 1H), 2.94e2,81 (m, 2H), 2.25e2.22 (m,
4.7.8. Treatment of 11b with HCl in AcOEt. To a solution of HCl
(4 mmol) in AcOEt (1 mL) was added 11b (20 mg, 0.10 mmol) at
room temperature. After stirring for 6 h, the mixture was quenched
by saturated aqueous NaHCO3, extracted with AcOEt. The extract
was washed with water and brine, dried and concentrated to dry-
ness. The residue was chromatographed with hexane/AcOEt (19:1)
to afford 14b (9.0 mg, 45%).
2H); 13C NMR
d 135.7, 134.5, 125.1, 121.5, 120.0, 119.23, 119.20, 117.2,
111.3, 99.6, 28.7, 27.2, 23.6, 20.0; DART MS m/z 222 (Mþþ1, 54); DART
HRMS calcd for C14H12N3 222.1031, found 222.1028.
4.9.2. (1R*,3R*,4S*)- and (1R*,3S*,4R*)-1,2,3,4-Tetrahydro-1-methyl-
1H-carbazole-3,4-dicarbonitrile (15b). Major diastereomer; Color-
less needles; mp 204e205 ꢀC (AcOEt); IR 3468, 2247 cmꢁ1; 1H NMR
(DMSO-d6)
d
11.3 (br s, 1H), 7.53 (d, J¼7.9 Hz, 1H), 7.36 (d, J¼7.9 Hz,
4.8. General procedure for the deprotection of Boc group of
2-vinylindole 11
1H), 7.13 (t, J¼7.9 Hz, 1H), 7.06 (t, J¼7.9 Hz, 1H), 4.82 (d, J¼4.5 Hz,
1H), 3.98e3.96 (m, 1H), 3.15e3.11 (m, 1H), 2.37 (dt, J¼13.7, 6.9 Hz,
1H), 1.88e1.83 (m, 1H), 1.37 (d, J¼6.9 Hz, 3H); 13C NMR
d 138.9,
KOH (22 mg, 0.40 mmol) was added to a solution of 11
(0.10 mmol) in methanol (1 mL). After stirring for5 h at 70 ꢀC, the
reaction mixture was cooled and concentrated. The residue was
chromotographed with hexane/AcOEt (9:1) to afford compound 13.
The chemical yields were summarized in Table 3.
135.9,125.1,121.6,120.1,119.3,119.2,117.4,111.4, 99.4, 31.3, 27.7, 27.1,
25.8, 19.1; DART MS m/z 236 (Mþþ1, 20); DART HRMS calcd for
C15H14N3 236.1188, found 236.1199.
Minor diastereomer; Colorless needles; mp 257.5e259 ꢀC
(AcOEt); IR 3470, 2361 cmꢁ1 1H NMR (DMSO-d6)
; d 11.2 (br s, 1H),
7.51 (d, J¼7.3 Hz, 1H), 7.31 (d, J¼7.3 Hz, 1H), 7.07 (t, J¼7.3 Hz, 1H),
7.01 (t, J¼7.3 Hz, 1H), 4.76 (dd, J¼10.5, 2.3 Hz, 1H), 3.75e3.69 (m,
1H), 3.10e3.01 (m, 1H), 2.34 (ddd, J¼13.2, 5.5, 2.7 Hz, 1H), 1.79e1.70
4.8.1. 2-(Propen-2-yl)-1H-indole (13b)17b,18. Colorless crystals; IR
3448 cmꢁ1
;
1H NMR
d
8.17 (s, 1H), 7.57 (d, J¼7.8 Hz, 1H), 7.33 (t,
J¼8.1 Hz, 1H), 7.20e7.16 (m, 1H), 7.09e7.06 (m, 1H), 6.55 (d,
(m, 1H), 1.25 (d, J¼6.9 Hz, 3H); 13C NMR
d 138.6, 135.9, 124.8, 121.4,
J¼1.2 Hz, 1H), 5.30 (br s, 1H), 5.08 (d, J¼1.2 Hz, 1H), 2.19 (s, 3H).
120.5, 119.3, 119.2, 117.2, 111.4, 99.0, 33.4, 29.3, 28.4, 27.4, 18.7; DART
MS m/z 236 (Mþþ1, 81); DART HRMS calcd for C15H14N3 236.1188,
found 236.1200.
4.8.2. 2-(Buten-2-yl)-1H-indole (13c). Colorless needles, mp
85.5e86 ꢀC (hexane); IR 3475, 3427 cmꢁ1; 1H NMR
d 8.14 (br s, 1H),
7.57 (d, J¼7.8 Hz, 1H), 7.33 (d, J¼8.2 Hz, 1H), 7.19e7.15 (m, 1H), 7.08
4.9.3. (1R*,3R*,4S*)- and (1R*,3S*,4R*)-Dimethyl 1,2,3,4-tetrahydro-1-
methyl-9H-carbazole-3,4-dicarboxylate (15c). Major diastereomer;
Colorless needles; mp 148e149 ꢀC (AcOEt); IR 3472, 1728 cmꢁ1; 1H
(t, J¼8.2 Hz, 1H), 6.56 (s, 1H), 5.31 (s, 1H), 5.09 (s, 1H), 2.55 (q,
J¼7.3 Hz, 2H), 1.22 (t, J¼7.3 Hz, 3H); 13C NMR
d 141.5, 138.1, 136.3,
128.8, 122.5, 120.7, 119.9, 110.6, 108.0, 100.7, 27.0, 13.3; EIMS m/z 171
NMR
d
7.86 (br s, 1H), 7.61 (d, J¼7.8 Hz, 1H), 7.30e7.28 (m, 1H),
(Mþ, 22); EI HRMS calcd for C12H13N 171.1048, found 171.1046.
7.16e7.13 (m, 1H), 7.12e7.08 (m, 1H), 4.37 (d, J¼4.2 Hz, 1H), 3.74 (s,
3H), 3.67 (s, 3H), 3.46 (dt, J¼6.8, 4.2 Hz, 1H), 3.10 (sex, J¼6.8 Hz, 1H),
2,36 (dt, J¼13.4, 6.8 Hz, 1H), 2.05 (ddd, J¼13.4, 6.8, 4.2 Hz, 1H), 1.37
4.8.3. 2-[3-(Benzyloxy)propen-2-yl]-1H-indole (13d). Colorless crys-
tals, mp 93e94 ꢀC (CH2Cl2); IR 3475, 3427 cmꢁ1
;
1H NMR
d
8.69
(d, J¼6.8 Hz, 3H); 13C NMR
d 174.1, 174.0, 138.7, 135.8, 126.9, 121.5,
(br s, 1H), 7.59e7.55 (m, 1H), 7.38e7.28 (m, 6H), 7.19e7.13 (m, 1H),
7.10e7.04 (m, 1H), 6.65 (dd, J¼2.0, 0.8 Hz, 1H), 5.64 (s, 1H),
119.6, 119.0, 110.6, 104.8, 52.10, 52.08, 40.8, 40.5, 31.2, 26.0, 20.0;
DART MS m/z 302 (Mþþ1, 88); DART HRMS calcd for C17H20NO4
302.1392, found 302.1392.
5.32e5.31 (m, 1H), 4.60 (br s, 2H), 4.43 (br s, 2H); 13C NMR
d 137.7,
136.6, 136.2, 135.8, 128.5, 128.4, 128.0, 127.9, 122.4, 120.6, 120.0,
113.5, 110.8, 100.3, 72.2, 71.8; EIMS m/z 263 (Mþ, 86); EI HRMS calcd
for C18H17NO 263.1310, found 263.1312.
Minor diastereomer; Colorless needles; mp 129.5e130 ꢀC
(AcOEt); IR 3472, 1734 cmꢁ1 1H NMR
; d 7.92 (br s, 1H), 7.51 (d,
J¼7.8 Hz,1H), 7.30 (d, J¼7.8 Hz,1H), 7.16e7.12 (m,1H), 7.09e7.06 (m,
1H), 4.19 (dd, J¼10.3, 2.4 Hz,1H), 3.81 (s, 3H), 3.75 (s, 3H), 3.32 (ddd,
J¼12.9, 10.3, 2.4 Hz, 1H), 3.20e3.14 (m, 1H), 2.44 (ddd, J¼10.3, 5.1,
2.4 Hz, 1H), 1.76e1.60 (m, 1H), 1.35 (d, J¼7.1 Hz, 3H); 13C NMR
4.8.4. Treatment of 9 with KOH in DMSO. KOH (22 mg, 0.40 mmol)
was added to a solution of 9 (0.10 mmol) in DMSO (1 mL). After
stirring for 0.25e10 h at room temperature, the reaction mixture
was concentrated. The residue was chromotographed with hexane/
AcOEt (9:1) to afford compound 13. The chemical yields were
summarized in Table 4.
d
174.2, 174.1, 138.8, 135.9, 126.8, 121.5, 119.7, 118.9, 110.7, 104.6,
52.10, 52.06, 44.0, 40.5, 34.1, 26.0, 20.0; EIMS m/z 301 (Mþ, 55); EI
HRMS calcd for C17H19NO4 301.1314, found 301.1316.
4.9.4. (1R*,3R*,4S*)- and (1R*,3S*,4R*)-Dimethyl 1,2,3,4-tetrahydro-1-
4.8.5. 2-Vinyl-1H-indole (13a)17b,c. Colorless crystals; IR 3475 cmꢁ1
1H NMR
7.20e7.16 (m, 1H), 7.10e7.06 (m, 1H), 6.74 (dd, J¼17.9, 11.0 Hz, 1H),
6.50 (s, 1H), 5.53 (d, J¼17.9 Hz, 1H), 5.26 (d, J¼11.0 Hz, 1H).
;
ethyl-9H-carbazole-3,4-dicarboxylate (15d). Major diastereomer;
d
8.16 (br s, 1H), 7.56 (d, J¼7.8 Hz, 1H), 7.33 (d, J¼8.2 Hz, 1H),
Yellow oil; IR 3472, 1728 cmꢁ1 1H NMR
; d 7.87 (br s, 1H), 7.61 (d,
J¼7.8 Hz, 1H), 7.28 (d, J¼7.8 Hz, 1H), 7.14 (t, J¼7.8 Hz, 1H), 7.10 (t,
J¼7.8 Hz, 1H) 4.36 (d, J¼5.0 Hz, 1H), 3.74 (s, 3H), 3.67 (s, 3H),
3.48e3.44 (m, 1H), 2.96e2.89 (m, 1H), 2.29 (ddd, J¼13.3, 7.8, 6.0 Hz,
1H), 2.14 (ddd, J¼13.3, 5.3, 3.7 Hz, 1H), 1.92e1.83 (m, 1H), 1.71e1.62
4.9. General procedure for synthesis of carbazole derivatives
(m, 1H), 1.06 (t, J¼7.3 Hz, 3H); 13C NMR
d 174.14, 174.12, 137.9, 135.8,
To a solution of 2-vinylindole 13 (0.058 mmol) in toluene
(0.6 mL) was added dienophiles (0.29 mmol). After the reaction
mixture was heated under reflux until the complete disappearance
of the starting material (monitored by TLC), the mixture was cooled
and concentrated. The residue was chromatographed with hexane/
AcOEt to give the corresponding carbazole derivatives 15. The
chemical yields were summarized in Table 5.
126.9, 121.6, 119.7, 119.0, 110.5, 105.5, 52.12, 52.10, 41.0, 40.5, 32.7,
27.9, 27.3,11.5; EIMS m/z 315 (Mþ, 44); EI HRMS calcd for C18H21NO4
315.1471, found 315.1465.
Minor diastereomer; Colorless needles; mp 131e132 ꢀC (hex-
ane/AcOEt); IR 3472, 1732 cmꢁ1 1H NMR
; d 7.94 (br s, 1H), 7.49 (d,
J¼7.9 Hz, 1H), 7.30 (d, J¼7.9 Hz, 1H), 7.14 (t, J¼7.9 Hz, 1H), 7.08 (t,
J¼8.2 Hz, 1H), 4.17 (dd, J¼10.7, 2.7 Hz, 1H), 3.81 (s, 3H), 3.76 (s, 3H),
3.27 (ddd, J¼12.9, 10.7, 2.7 Hz, 1H), 3.04e2.99 (m, 1H), 2.48 (ddd,
J¼10.7, 4.1, 2.7 Hz, 1H), 1.98e1.93 (m, 1H), 1.67e1.61 (m, 1H),
4.9.1. (3R*,4S*)-1,2,3,4-Tetrahydro-1H-carbazole-3,4-dicarbonitrile
(15a). Colorless needles; mp 168.5e169 ꢀC (hexane/AcOEt); IR
1.56e1.53 (m, 1H), 1.02 (t, J¼7.2 Hz, 3H); 13C NMR
d 174.14, 174.12,

5140
Y.A.M. Mohamed et al. / Tetrahedron 67 (2011) 5133e5141
137.9, 135.8, 126.9, 121.6, 119.7, 119.0, 110.5, 105.5, 52.11, 52.10, 41.0,
40.5, 32.7, 27.9, 27.3, 11.5; DART MS m/z 316 (Mþþ1, 82); DART
HRMS calcd for C18H22NO4 316.1549, found 316.1544.
2.98e2.90 (m, 2H), 1.02 (t, J¼7.2 Hz, 3H); 13C NMR
d 170.2, 166.9,
140.82, 139.86, 127.9, 127.0, 126.5, 125.9, 121.9, 121.6, 120.8, 119.5,
118.5, 111.0, 52.9, 52.3, 24.0, 13.5; EIMS m/z 311 (Mþ, 40); EI HRMS
calcd for C18H17NO4 311.1158, found 311.1153.
4.9.5. (3aR*,10cR*)-1,3,3a,4,5,10c-Hexahydro-1,3-dioxo-2-phenyl-6H-
pyrrolo[3,4-c]carbazole (15e)16b. Yellow crystals; IR 3470,
Acknowledgements
1715 cmꢁ1 1H NMR
; d 7.99e7.97 (m, 1H), 7.95 (br s, 1H), 7.41e7.37
(m, 2H), 7.34e7.29 (m, 2H), 7.24e7.20 (m, 2H), 7.19e7.14 (m, 2H),
4.47 (d, J¼7.8 Hz, 1H), 3.60e3.55 (m, 1H), 2.82e2.78 (m, 2H),
2.70e2.62 (m, 1H), 2.11e2.02 (m, 1H).
This work was supported in part by a Grant-in Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science
and Technology, Japan, for which we are thankful. Y. A. M. M. thanks
the Ministry of Higher Education and Scientific Research, Egypt, for
the fellowship.
4.9.6. (3aR*,10cR*)-1,3,3a,4,5,10c-Hexahydro-1,3-dioxo-5-methyl-2-
phenyl-6H-pyrrolo[3,4-c]carbazole (15f)16f. Major diastereomer;
Yellow crystals; IR 3474, 1713 cmꢁ1 1H NMR
; d 8.04 (br s, 1H),
References and notes
8.01e7.98 (m, 1H), 7.39e7.16 (m, 8H), 4.48 (dd, J¼8.1, 1.5 Hz, 1H),
3.64e3.57 (m, 1H), 3.07e2.96 (m, 1H), 2.76e2.68 (m, 1H), 1.77e1.66
(m, 1H), 1.41 (d, J¼7.0 Hz, 3H).
1. (a) Kuroda, N.; Takahashi, Y.; Yoshinaga, K.; Mukai, C. Org. Lett. 2006, 8,
1843e1845; (b) Inagaki, F.; Mizutani, M.; Kuroda, N.; Mukai, C. J. Org. Chem.
2009, 74, 6402e6405.
Minor diastereomer; Yellow crystals; IR 3470, 1715 cmꢁ1 1H
;
2. For selected references, see: (a) Magnus, P.; Gallagher, T.; Brown, P.; Pappalardo,
P. Acc. Chem. Res. 1984, 17, 35e41; (b) Pindur, U.; Erfanian-Abdoust, H. Chem.
Rev. 1989, 89, 1681e1689; (c) Vice, S. F.; Nandin de Carvalho, H.; Taylor, N. G.;
Dmitrienko, G. I. Tetrahedron Lett. 1989, 30, 7289e7292; (d) Fray, E. B.; Moody,
C. J.; Shah, P. Tetrahedron 1992, 49, 439e450; (e) Rao, M. V. B.; Satyanarayana, J.;
Ila, H.; Junjappa, H. Tetrahedron Lett. 1995, 36, 3385e3388; (f) Ciganek, E.;
Schubert, E. M. J. Org. Chem. 1995, 60, 4629e4634; (g) Jakiwczyk, O. M.; Nielsen,
K. E.; Nandin de Carvalho, H.; Dmitrienko, G. I. Tetrahedron Lett. 1997, 38,
6541e6544; (h) Laronze, M.; Sapi, J. Tetrahedron Lett. 2002, 43, 7925e7928.
3. For selected references of the 2-vinylindole synthesis, see: (a) Amat, M.; Llor,
N.; Checa, B.; Molins, E.; Bosch, J. J. Org. Chem. 2010, 75, 178e189; (b) Barluenga,
NMR
d
8.03e8.00 (m, 2H), 7.48e7.14 (m, 8H), 4.42 (dd, J¼8.0, 1.0 Hz,
1H), 3.46 (td, J¼8.0, 5.8 Hz, 1H), 3.16e3.09 (m, 1H), 2.44 (dt, J¼12.1,
5.8 Hz, 1H), 2.12e2.01 (m, 1H), 1.37 (d, J¼6.8 Hz, 3H).
4.9.7. (3aR*,5R*,10cR*)- and (3aR*,5S*,10cR*)-1,3,3a,4,5,10c-Hexahy-
dro-1,3-dioxo-5-ethyl-2-phenyl-6H-pyrrolo[3,4-c]carbazole
(15g). Major diastereomer; Colorless needles; mp 189e190 ꢀC
(AcOEt); IR 3474,1713 cmꢁ1; 1H NMR
d 8.05 (br s,1H), 8.01e8.00 (m,
ꢀ
ꢀ
1H), 7.40e7.38 (m, 2H), 7.33e7.32 (m, 2H), 7.23e7.15 (m, 4H), 4.46
(dd, J¼8.2,1.7 Hz,1H), 3.62 (dt, J¼8.2, 4.8 Hz,1H), 2.91e2.86 (m,1H),
2.69 (dt, J¼13.4, 4.8 Hz, 1H), 2.01e1.97 (m, 1H), 1.78 (ddd, J¼13.4,
7.8, 4.8 Hz, 1H), 1.68e1.61 (m, 1H), 1.10 (d, J¼7.8 Hz, 3H); 13C NMR
J.; Jimenez-Aquino, A.; Azner, F.; Valdes, C. J. Am. Chem. Soc. 2009, 131,
4031e4041; (c) Ambrogio, I.; Cacchi, S.; Fabrizi, G.; Prastaro, A. Tetrahedron
ꢀ
2009, 65, 8916e8929; (d) Bennasar, M.-L.; Zulaica, E.; Sole, D.; Roca, T.; García-
Díaz, D.; Alonso, S. J. Org. Chem. 2009, 74, 8359e8368; (e) Kraus, G. A.; Guo, H.
Org. Lett. 2008, 10, 3061e3063; (f) Fayol, A.; Fang, Y.-Q.; Lautens, M. Org. Lett.
2006, 8, 4203e4206; (g) Shen, M.; Li, G.; Lu, B. Z.; Hossain, A.; Roschangar, F.;
d
178.1, 175.9, 137.9, 135.7, 131.9, 128.9, 128.3, 126.8, 126.3, 122.1,
ꢀ
Farina, V.; Senanayake, C. H. Org. Lett. 2004, 6, 4129e4132; (h) Perez-Serrano, L.;
120.3, 120.2, 110.6, 103.5, 40.0, 39.9, 31.6, 26.7, 25.6, 11.1; DART MS
m/z 345 (Mþþ1, 64); DART HRMS calcd for C22H21N2O2 345.1603,
found 345.1586.
ꢀ
ꢀ
ꢀ
Casarrubios, L.; Domínguez, G.; Gonzalez-Perez, P.; Perez-Catells, J. Synthesis
2002, 1810e1812; (i) Hudkins, R. L.; Diebold, J. L.; Marsh, F. D. J. Org. Chem. 1995,
60, 6218e6220; (j) Macor, J. E.; Newman, M. E.; Ryan, K. Tetrahedron Lett. 1989,
30, 2509e2512; (k) Sundberg, R. J.; Bloom, J. D. J. Org. Chem. 1980, 45,
3382e3387; (l) For review; Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105,
2873e2920.
Minor diastereomer; Colorless needles; mp 183.5e185 ꢀC
(AcOEt); IR 3470,1713 cmꢁ1; 1H NMR
d 8.03e8.01 (m,1H), 7.99 (br s,
4. (a) Conde, J. J.; McGuire, M.; Wallace, M. Tetrahedron Lett. 2003, 44, 3081e3084;
(b) Repic, O.; Prasad, K.; Lee, G. T. Org. Process Res. Dev. 2001, 5, 519e527.
1H), 7.45e7.42 (m, 2H), 7.39e7.26 (m, 4H), 7.23e7.15 (m, 2H), 4.45
(dd, J¼8.7,1.4 Hz,1H), 3.46 (dt, J¼8.7, 6.4 Hz,1H), 2.93e2.87 (m,1H),
2.35e2.32 (m, 2H), 1.82e1.74 (m, 1H), 1.61e1.53 (m, 1H), 1.09 (d,
ꢁ
5. Macabeo, A. P. G.; Krohn, K.; Gehle, D.; Read, R. W.; Brophy, J. J.; Cordell, G. A.;
Franzblau, S. G.; Aguinaldo, A. M. Phytochemistry 2005, 66, 1158e1162.
6. For leading references, see: (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25,
508e524; (b) Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React.1997, 50,1e652.
7. Mukai, C.; Takahashi, Y. Org. Lett. 2005, 7, 5793e5796.
J¼7.3 Hz, 3H); 13C NMR
d 178.7, 175.9, 138.3, 135.8, 132.0, 129.1,
128.4, 127.0, 126.3, 122.2, 120.3, 120.29, 120.27, 110.6, 102.7, 39.55,
39.46, 34.4, 28.1, 27.8, 12.1; EIMS m/z 344 (Mþ,100); EI HRMS calcd
for C22H20N2O2 344.1525, found 344.1533.
8. Shaykoon, M. S. A.; Inagaki, F.; Mukai, C. Heterocycles 2010, 80, 133e139.
9. We previously reported only one example for the formation of the 7-aza-2-
vinylindole derivative from the corresponding 3-(3-silyloxymethyl)allenyl-2-
aminopyridine with TBAF at room temperature, see: Ref. 7.
4.9.8. (7aR*,13aR*)-6,7,7a,8,13,13a-Hexahydro-8,13-dioxo-5H-naph-
10. When the 12c was treated with K2CO3 and Et2CO3 in THF at 95 ꢀC for 5 h, 11c
was not obtained. In addition, no intermediate was detected during the cycli-
zation of 9c under the K2CO3 condition. Therefore, 11c should directly be
formed from 9 by an SN2’ reaction.
tho[2,3-c]carbazole (15h). Red needles; mp 75e78 ꢀC (CH2Cl2); IR
3468, 1688 cmꢁ1
;
1H NMR
d
8.08 (dd, J¼7.2, 1.4 Hz, 1H), 8.02 (dd,
J¼7.2, 1.4 Hz, 1H), 7.88 (br s, 1H), 7.70e7.64 (m, 2H), 7.49 (d,
J¼7.6 Hz, 1H), 7.22 (d, J¼7.9 Hz, 1H), 7.10e7.08 (m, 1H), 7.06e7.04
(m, 1H), 4.56e4.55 (m, 1H), 3.53e3.50 (m, 1H), 3.03e2.98 (m, 1H),
2.84e2.80 (m, 1H), 2.65e2.60 (m, 1H), 2.07e2.02 (m, 1H); 13C NMR
11. Cavelier, F.; Enjalbal, C. Tetrahedron Lett. 1996, 37, 5131e5134.
12. Gibson, F. S.; Bergmeier, S. C.; Rapoport, H. J. Org. Chem. 1994, 59, 3216e3218.
13. Olar, G. A.; Narang, S. C. Tetrahedron 1982, 38, 2225e2277.
14. The treatment of 7 with 8b in DMSO in the presence of Pd2(dba)3, TFP, and CuI
at room temperature for 3 h, followed by heating with KOH at 120 ꢀC for 4 h
afforded 11b (69%) and 13b (23%).
d
197.7, 197.4, 135.8, 134.7, 134.5, 134.09, 134.06, 134.0, 127.1, 126.9,
15. The treatment of 7 with 8c in DMF in the presence of Pd2(dba)3, TFP, and CuI at
room temperature for 3 h, followed by heating with K2CO3 at 100 ꢀC for 5 h
afforded 11c (45%) and 13c (8%).
126.6, 121.6, 120.0, 118.8, 110.5, 105.9, 48.3, 47.3, 23.9, 20.6; DART
MS m/z 302 (Mþþ1, 33); DART HRMS calcd for C20H16NO2 302.1181,
found 302.1183.
16. For selected references of the DielseAlder reaction of vinylindoles, see: (a) Tan,
F.; Li, F.; Zhang, X.-X.; Wang, X.-F.; Cheng, H.-G.; Chen, J.-R.; Xiao, W.-J. Tetra-
hedron 2011, 67, 446e451; (b) Gioia, C.; Bernardi, L.; Ricci, A. Synthesis 2010,
161e170; (c) Jones, S. B.; Simmons, B.; MacMillan, D. W. C. J. Am. Chem. Soc.
2009, 131, 13606e13607; (d) Abbiati, G.; Canevari, V.; Facoetti, D.; Rossi, E. Eur. J.
4.9.9. Dimethyl 1-methyl-9H-carbazole-3,4-dicarboxylate
(15i)22. Yellow crystals; IR 3468, 1717 cmꢁ1 1H NMR
; d 8.36 (br s,
ꢂ
1H), 7.90e7.86 (m, 2H), 7.45e7.43 (m, 2H), 7.27e7.21 (m, 1H), 4.14
Org. Chem. 2007, 517e525; (e) C¸ avdar, H.; Sarac¸ oglu, N. J. Org. Chem. 2006, 71,
7793e7799; (f) Eitel, M.; Pindur, U. J. Org. Chem. 1990, 55, 5368e5374.
17. (a) Cheng, H.-G.; Chen, C.-B.; Tan, F.; Chang, N.-J.; Chen, J.-R.; Xiao, W.-J. Eur. J.
Org. Chem. 2010, 4976e4980; (b) Pindur, U.; Eitel, M. J. Heterocycl. Chem. 1991,
28, 951e954; (c) Pindur, U.; Pfeuffer, L.; Kim, M.-H. Helv. Chim. Acta 1989, 72,
65e72.
18. Mahanty, J. S.; De, M.; Das, P.; Kundu, N. G. Tetrahedron 1997, 53, 13397e13418.
19. More recently, we reported the total synthesis of goniomitine using the 2-
vinylindole derivative, which was directly prepared by successive Stille
(s, 3H), 3.93 (s, 3H), 2.56 (s, 3H).
4.9.10. Dimethyl 1-ethyl-9H-carbazole-3,4-dicarboxylate
(15j). Yellow needles; mp 170e171 ꢀC (hexane); IR 3460,
1734 cmꢁ1; 1H NMR
d
8.41 (br s, 1H), 7.42e7.40 (m, 1H), 7.34e7.20
(m, 1H), 7.26 (s, 1H), 7.19e7.12 (m, 2H), 4.03 (s, 3H), 3.80 (s, 3H),

Y.A.M. Mohamed et al. / Tetrahedron 67 (2011) 5133e5141
5141
coupling and cyclization of 3-(benzyloxymethyl)-1-substituted-1-(tributyl-
20. Steiner, O.; Tamm, C. Tetrahedron Lett. 1993, 34, 6729e6732.
stannyl)allene with N-(tert-butoxycarbonyl)-2-iodoaniline in one step, see:
Mizutani, M.; Inagaki, F.; Nakanishi, T.; Yanagihara, C.; Tamai, I.; Mukai, C. Org.
Lett. 2011, 13, 1796e1799.
21. Imashiro, R.; Uehara, H.; Barbas, C. F., III. Org. Lett. 2010, 12, 5250e5253.
22. Laronze, M.; Boisbrun, M.; Leonce, S.; Pfeiffer, B.; Renard, P.; Lozach, O.; Meijer, L.;
ꢀ
Lansiaux, A.; Bailly, C.;Sapi, J.; Laronze, J.-Y. Bioorg. Med. Chem. 2005,13, 2263e2283.