CAN and iodine-catalyzed reaction of indole or 1-methylindole with α,β-unsaturated ketone or aldehyde

Article abstract of DOI:10.1016/j.tetlet.2005.11.058

CAN (cerium ammonium nitrate) and iodine can catalyze the reactions of indole or 1-methylindole with α,β-unsaturated ketone or aldehyde in DMSO/H₂O (5:1) or ether solution at room temperature to obtain moderate to high yields of different produ

Full text of DOI:10.1016/j.tetlet.2005.11.058

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 487–492
CAN and iodine-catalyzed reaction of indole or 1-methylindole
with a,b-unsaturated ketone or aldehyde
Shengkai Ko, Chunchi Lin, Zhijay Tu, Yi-Fu Wang, Chieh-Chieh Wang and
Ching-Fa Yao*
Department of Chemistry, National Taiwan Normal University 88, Sec. 4, Tingchow Road, Taipei 116, Taiwan, ROC
Received 13 October 2005; revised 9 November 2005; accepted 11 November 2005
Available online 6 December 2005
Abstract—CAN (cerium ammonium nitrate) and iodine can catalyze the reactions of indole or 1-methylindole with a,b-unsaturated
ketone or aldehyde in DMSO/H2O (5:1) or ether solution at room temperature to obtain moderate to high yields of different
products.
ꢀ 2005 Published by Elsevier Ltd.
Indole and their derivatives are well known as biolo-
gically active substances.1 Organic chemists are pay-
ing attention to synthesize different kinds of indole
compounds, including bis(indolyl)methanes,2 b-indolyl-
nitro,3 b-indolylketone,4 and b-indolylalcohol5 com-
pounds, etc. It has been reported in the literature
that 1 equiv of trans-cinnamaldehyde can react with
2 equiv of indole to yield bis(indolyl)methane in high
yield2g,i,j,o,p or 1 equiv of 2-cyclohexen-1-one can react
with 1 equiv of indole to obtain high yields of b-indolyl-
cyclohexanone.4g However, our recent study about the
same reactions found that different results were observed
and trisindolylalkane was also isolated when trans-cinna-
maldehyde or 2-cyclohexen-1-one reacted with the same
amount of indole, which was reported in the literature
under the same conditions. Until now, only two litera-
tures have been reported about the preparation of the
above compounds.6 For example, it has also been
reported by Harrington and Keer that trisindolylcyclo-
hexane was given in 6% yield under ultra high pressure
condition6a and Shi et al. have also reported that these
compounds can be prepared by using metal triflate as
catalyst.6b However, both methods have some disadvan-
tages, such as harsh reaction condition (13 kbar), long
reaction time (1–3 days), and the use of expensive metal
catalysts.6
Based on these observations and reports, we wish to
improve the same reactions to obtain high yields of
different products as described above using other proper
reagents under simple conditions. It has been reported
that cerium ammonium nitrate (CAN) is well known
and has been used as a oxidation reagent or catalyst in
many organic reactions recently.4b,7 The advantages of
this catalyst are cheap, environmentally benign, and
commercially available. To observe the catalytic effect
of CAN, 1 equiv of 2-cyclohexen-1-one 1a was used to
react with 4 equiv of indole 2a in the presence of differ-
ent amounts of CAN in DMSO/H2O (5:1) solution at
room temperature (Eq. 1 and Table 1). First, neither
1,4-addition product 4aa nor 1,4- and then 1,2-addition
product 5aa was observed when the reaction was per-
formed in the absence of any reagent for 20 h (entry
1). However, the reaction was improved dramatically
and 14% of 4aa and 85% of 5aa were generated when
the same reaction was carried out in the presence of
0.1 equiv of CAN for 12 h (entry 2). Surprisingly, only
93% of 5aa was obtained when the same reaction was
carried out for 20 h (entry 3).
To improve the optimized yield of 5aa, the amount of
CAN was increased to 0.3 equiv and, as expected, the
yield of 4aa was decreased to 8% only but 5aa was
increased to 92% for 6 h (entry 4). Fortunately, only
99% of the single product 5aa was generated when the
same reaction was carried out for 13 h (entry 5).9
Although the increase of CAN to 0.5 equiv can acceler-
ate the reaction dramatically, however, the yields of 4aa
and 5aa were decreased to 11% and 77% for 2 h and
Keywords: Catalyzed; CAN; Indole; Iodine; Trisindolylalkane.
*
Corresponding author. Tel./fax: +886
cheyaocf@scc.ntnu.edu.tw
2
29309092; e-mail:
0040-4039/$ - see front matter ꢀ 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2005.11.058

488
S. Ko et al. / Tetrahedron Letters 47 (2006) 487–492
Table 1. Reaction of a,b-unsaturated ketone 1 and indole 2a in the presence of cerium ammonium nitrate
H
H
N
N
O
O
DMSO/H2O
+
+
CAN
+
N
H
N
H
N
H
ð1Þ
1a
2a
3
4aa
5aa
O
O
O
O
N
MeO
1b
1c
1d
1e
2b
Entry
1 (1 equiv)
2 (4 equiv)
3 (equiv)
Time (h)
4a (%)
5a (%)
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
—
20
12
20
6
13
2
4
1
1/6
72
4
4aa (—)
4aa (14)
4aa (—)
4aa (8)
4aa (—)
4aa (11)
4aa (—)
4ba (99)
4ca (90)
4da (62)
4ea (60)
5aa (—)
5aa (85)
5aa (93)
5aa (92)
5aa (99)
5aa (77)
5aa (85)
5ba (—)
5ca (—)
5da (—)
5ea (—)
0.1
0.1
0.3
0.3
0.5
0.5
0.3
0.3
0.3
0.3
10
11
a NMR yields.
only 85% of 5aa was observed for 4 h (entries 6 and 7).
Possible explanation is that the starting material or
product may be destroyed during reaction if the exother-
mic reactions occur too fast when excess amount of
CAN was added. According to the above results we
can conclude that CAN actually can catalyze the reac-
tion efficiently to obtain high yields of 5aa and the best
amount of CAN to be used in this reaction is 0.3 equiv.
In addition to 1a, similar reactions were also conducted
by using 1b–e, respectively, under similar conditions and
the results were shown as entries of 8–11.
number of eclipsing interaction which was generated
from the further reaction product of 5ba.11
Next, reactions of a,b-unsaturated aldehyde 6 and 2a
were investigated and interesting results were shown as
Eq. 2 and Table 2. For example, when crotonaldehyde
6a was used to react with 2a in the presence of 0.1 equiv
of CAN at room temperature for 1 h, only 99% of 7aa
was generated but no bis(indolyl)methane 8aa was
observed when the mixture was checked by NMR or
GCMS (entry 1). However, not only 64% of 7ba but also
29% of 8ba was also generated when b-methylcrotonal-
dehyde 6b was used (entry 2). Compared to 6a or 6b, the
results of the use of 6c or 6d were slightly different and
only 32% of 7ca and 66% of 8ca or 20% of 7da and
80% of 8da were generated (entries 3 and 4). We were
surprised to find that only 99% of 8ea was generated
when 6e was used (entry 5).
Based on the data of Table 1, we found different and
interesting results were observed between 1a and 1b–e.
Only 1a can undergo the 1,4-addition to yield 4aa first
and then the intermediate 4aa can react with indole 2a
to undergo 1,2-addition to obtain 5aa finally. However,
1b–e only can undergo 1,4-addition to yield medium to
high yields of 4ba–ea, respectively. About the generation
of the different products from 1a and 1b, we proposed
that the torsional strain effect plays an important and
major role to the product or intermediate during reac-
tion. The addition of the first equivalent of 2a to 1a or
to 1b forms 3-indolylcyclohexanone 4aa or 3-indolyl-
cyclopentanone 4ba. When further reaction occurs, the
conversion of the sp2 carbon atom of the carbonyl func-
tional group of 4aa to a sp3 of six-membered ring of 5aa
leads to a completely staggered (chair) arrangement and
reduces the torsional strain. On the contrary, the tor-
sional strain is increased because of the increase in the
Based on Tables 1 and 2, we can conclude that the use of
a,b-unsaturated ketone 1 can generate 4 and/or 5 and
the use of a,b-unsaturated aldehyde 6 yield 7 and/or 8.
The reaction mechanisms for the generation of 7 and 5
are all proposed to proceed through the 1,4-addition
first and then to undergo the 1,2-addition but 8 is pro-
posed to proceed through the 1,2-addition only which
is different from the generation of 4 by proceeding
through the 1,4-addition only. These different results
possibly could be explained by the different steric
hindrances between aldehyde and ketone. Aldehyde is

S. Ko et al. / Tetrahedron Letters 47 (2006) 487–492
Table 2. CAN-catalyzed reaction of a,b-unsaturated aldehyde 6 with indole 2a
489
H
H
N
N
H
3
1
HN
R
R
CHO
N
DMSO/H O
2
+
+
+
CAN
3
1
3
N
2
R
R
R
R
H
1
2
R
R
2
R
N
H
ð2Þ
6
2a
3
7
8
O
CHO
CHO
Ph
CHO
CH
CHO
H
Ph
Ph
H C
3
H C
3
3
6a
6b
6c
6d
6e
Entry
1
3 (equiv)
Time (h or min)
7a (%)
8a (%)
1
2
3
4
5
6a
0.1
0.1
0.1
0.1
0.1
1 h
10 min
1 h
5 min
15 min
7aa (99)
7ba (64)
7ca (32)
7da (20)
7ea (—)
8aa (—)
8ba (29)
8ca (66)
8da (80)
8ea (99)
6b
6c
6d
6e
a NMR yields.
always more reactive than ketone because the formyl
group is much smaller than the acyl group. This
assumption could also be proved by the fact that only
0.1 equiv of CAN is required for the aldehyde but at
least 0.3 equiv of CAN is required for ketone under
similar condition. In addition to the above description,
the generation of the different products 7 and 8 from
aldehydes such as 7aa from 6a and 8ea from 6e could
also be explained by the presence of the different steric
effects which were generated from the presence of the
different groups at a and/or b carbon in these two
substrates.
Because indole derivatives are important biologically ac-
tive compounds which have profound medical applica-
tions, development of a reaction that uses catalytic
amount of mild toxic and readily available iodine should
greatly contribute to the creation of environmentally be-
nign processes. It has been reported by Banik et al. that
iodine can catalyze the Michael reaction of indole with
a,b-unsaturated ketone to undergo conjugate addition
to offer high yields of 4 under solvent-free condition effi-
ciently4g and by Shi et al. that both 4 and 5 were or only
5 was generated when similar reactions were carried out
by using Yb(OTf)3 or Zr(OTf)4 as catalyst.6b
H
H
N
N
O
Et2O, rt
I2
+
+
ð4Þ
N
H
N
H
N
H
4aa
2a
9
5aa
Recently, the use of molecular iodine has received
considerable attention as an inexpensive, nontoxic, and
readily available catalyst for various organic transfor-
mations to afford the corresponding products in excel-
lent yields with high selectivity. The mild Lewis acidity
associated with iodine enhanced its usage in organic
synthesis to realize several organic transformations
using stoichiometric levels to catalytic amounts. Owing
to numerous advantages associated with this eco-
friendly element, iodine has been explored as a powerful
catalyst for various organic transformations.2i,4c,g,8
Based on the above study and those viewpoints of
iodine, we then changed CAN to iodine as a catalyst.
Similar to the results of Table 1, both 4aa and 5aa or
only 5aa were observed when 1 equiv of 1a reacted with
4 equiv of 2a in the presence of different amounts of I2 in
1 mL of diethyl ether (Et2O) solution (Eq. 3 and Table
3). When only 0.15 equiv of I2 was used, not only 4aa
but also 5aa was isolated (entry 1). The most significant
and interesting results were that only 93% or 99% of 5aa
was obtained when 0.3 or 0.5 equiv of 9 I2 (iodine) was
used for 2 or 1 h under similar conditions (entries 3 and

490
S. Ko et al. / Tetrahedron Letters 47 (2006) 487–492
Table 3. Reaction of a,b-unsaturated ketone 1 and indole 2a/2b in the presence of molecular iodine
R4
R4
N
O
N
O
Et2O
I2
+
+
+
N
ð3Þ
R4
N
R4
N
R4
2a: R4 = H
2b: R4 = CH3
1a
9
4aa
5aa
Entry
1 (1 equiv)
2 (4 equiv)
I2 (equiv)
Time (h)
4a (%)
5a (%)
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
2a
2a
2a
2a
2a
2b
2a
2a
2a
2a
0.15
0.3
0.3
0.5
1
0.3
0.3
0.3
0.3
0.3
1.5
1
2
1
1
5/12
2/3
1/6
72
5
4aa (28)
4aa (5)
5aa (49)
5aa (68)
5aa (93)
5aa (99)
5aa (62)
5ab (99)
5ba (—)
5ca (—)
5da (—)
5ea (—)
4aa (—)
4aa (—)
4aa (—)
4ab (—)
4ba (92)
4ca (91)
4da (43)
4ea (79)
10
a NMR yields.
4).10 Unfortunately, only 62% of 5aa was observed when
I2 was increased to 1 equiv (entry 5). These results indi-
cate that the use of 0.3 equiv of I2 is good enough for
this reaction. Based on the above condition, similar
reactions were conducted by using 1a–d and 2a or 2b
to obtain different yields of 4 and the results were shown
as entries of 6–10. Compared to the results of Table 1 by
using CAN, most of the substrates except 1d could pro-
duce moderate to high yields of 4 when the reaction was
conducted in the presence of I2. To substrate 1d, only
49% of 4da was generated compared to the use of
CAN whose yield was 62%. The only difference is that
all reactions were conducted in DMSO–H2O solution
by using CAN and in ether solution by using I2.
Table 4. Reaction of a,b-unsaturated aldehyde 6 and indole 2 in the presence of molecular iodine
R4
N
R4
N
R3
R1
CHO
R2
Et2O, rt
R3
I2
+
+
N
R4
ð5Þ
R1
R2
N
R4
2a: R4 = H
2b: R4 = CH3
6
9
7
Entry
6
2
I2 (equiv)
Time
7a (%)
1
2
3
4
5
6
7
8
9
6a
6a
6b
6b
6c
6c
6d
6e
2a
2b
2a
2b
2a
2b
2a
2a
2a
2b
2a
2b
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
15 min
10 min
10 min
10 min
3 h
7aa (95)
7ab (86)
7ba (99)
7bb (76)
7ca (93)
7cb (95)
7da (28)b
7ea (—)c
7fa (79)
7fb (82)
7ga (87)
7gb (95)
30 min
5 min
10 min
10 min
10 min
10 min
10 min
R1 = p-MeOC6H4, R2 = H, R3 = H 6f
10
11
12
R1 = o-MeOC6H4, R2 = H, R3 = H 6g
a NMR yield.
b 46% of bis(indolyl)methane 8da was also generated.
c 99% of bis(indolyl)methane 8ea was generated.

S. Ko et al. / Tetrahedron Letters 47 (2006) 487–492
491
J.; Mauger, H.; Vallee, Y. Tetrahedron Lett. 1997, 38,
8518; (e) Babu, G.; Sridhar, N.; Perumal, P. T. Synth.
Commun. 2000, 30, 1609; (f) Chalaye-Mauger, H.; Denis,
J.; Averbuch-Pouchot, M.; Vallee, Y. Tetrahedron 2000,
56, 791; (g) Yadav, J. S.; Readdy, B. V. S.; Murthy, Ch. V.
S. R.; Kumar, M.; Madan, Ch. Synthesis 2001, 783; (h)
Chakrabarty, M.; Ghosh, N.; Basak, R.; Harigaya, Y.
Tetrahedron Lett. 2002, 43, 4075; (i) Bandgar, B. P.;
Shaikh, K. A. Tetrahedron Lett. 2003, 44, 1959; (j) Yadav,
J. S.; Reddy, B. V. S.; Sunitha, S. Adv. Synth. Catal. 2003,
349; (k) Ji, S.-J.; Zhou, M.-F.; Gu, D.-G.; Wang, S.-Y.;
Loh, T.-P. Synlett. 2003, 2077; (l) Ji, S.-J.; Zhou, M.-F.;
Gu, D.-G.; Wang, S.-Y.; Loh, T.-P. Eur. J. Org. Chem.
2004, 1584; (m) Bartoli, G.; Bosco, M.; Foglia, G.;
Giuliani, A.; Marcantoni, E.; Sambri, L. Synthesis 2004,
6, 895; (n) Mi, X.; Luo, S.; He, J.; Cheng, J.-P.
Tetrahedron Lett. 2004, 45, 4567; (o) Sharma, G. V. M.;
Reddy, J. J.; Lakshmi, P. S.; Krishna, P. R. Tetrahedron
Lett. 2004, 45, 7729; (p) Wang, L.; Han, J.; Tian, H.;
Sheng, J.; Fan, Z.; Tang, X. Synlett 2005, 337.
About the generation of 4aa and 5aa, the mechanism
was proposed to proceed through the 1,4-addition first
to obtain 4aa and then 4aa can react with 2a continu-
ously to undergo the 1,2-addition to generate 5aa. In or-
der to prove this assumption, 1 equiv of 4aa was used to
react with 3 equiv of 2a in the presence of 0.3 equiv of
iodine in 1 mL of ether for 1 h and 87% 5aa was isolated
(Eq. 4). This result is good enough to explain why both 4
and 5 were generated when the same reaction was
quenched or workup for shorter reaction time and only
5 was generated for longer reaction time.
Based on Tables 1–3, similar reactions of 6 and 2 in the
presence 0.1 equiv of I2 were also studied and the results
were shown as Eq. 5 and Table 4. Compared to the
results of Table 2, slight results were observed. To sub-
strates 6a–c and 6f–g, only products 7aa–ca and 7fa–ga
were generated but no products 8 were observed. Possi-
ble explanation for the different results may be assumed
due to that CAN belongs to hard acid but I2 belongs to
soft acid under similar reactions, so that most of the
starting material 6a–c and 6f–g can undergo the 1,4-
addition and then 1,2-addition predominately in the
presence of I2. However, to 6d, 8da is the major products
and to 6e, 8ea is the only product and both products
were all proposed to be generated from the 1,2-addition
only and these results were also similar to the results of
the use of CAN. These special results can also be
explained by the steric hinderance which was generated
from the presence of different groups at b-carbon of
aldehyde. This is the reason why these two substrates
prefer to proceed thorough 1,2-addition to undergo
the 1,4-addition and then 1,2-addition.
3. (a) Noland, W. E.; Hartman, P. J. J. Chem. Soc. 1954, 76,
3227; (b) Noland, W. E.; Christensen, G. M.; Sauer, G. L.;
Dutton, G. G. S. J. Chem. Soc. 1955, 77, 456; (c) Lloyd, D.
H.; Nichols, D. E. J. Org. Chem. 1986, 51, 4294; (d)
Chakrabarty, M.; Basak, R.; Ghosh, N. Tetrahedron Lett.
2001, 41, 3913; (e) Komoto, I.; Kobayashi, S. Org. Lett.
2002, 4, 1115; (f) Chakrabarty, M.; Basak, R.; Ghosh, N.;
Harigaya, Y. Tetrahedron 2004, 60, 1941.
4. (a) Yadav, J. S.; Abraham, S.; Reddy, B. V. S.; Sabitha, G.
Synthesis 2001, 2165; (b) Ji, S.-J. Synlett. 2003, 2074; (c)
Wang, S.-Y.; Ji, S.-J.; Loh, T.-P. Synlett 2003, 2377; (d)
Alam, M. M.; Varala, R.; Adapa, S. R. Tetrahedron Lett.
2003, 44, 5115; (e) Srivastava, N.; Banik, B. K. J. Org.
Chem. 2003, 68, 2109; (f) Arcadi, A.; Bianchi, G.; Chiarini,
M.; DÕ Anniballe, G.; Marinelli, F. Synlett 2004, 944; (g)
Banik, B. K.; Fernandez, M.; Alvarez, C. Tetrahedron
Lett. 2005, 46, 2479.
5. (a) Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-
Ronchi, A. J. Org. Chem. 2002, 67, 5386; (b) Bandini, M.;
Fagioli, M.; Melloni, A.; Umani-Ronchi, A. Adv. Synth.
Catal. 2004, 573; (c) Bandini, M.; Cozzi, P. G.; Melchi-
orre, P.; Umani-Ronchi, A. Angew. Chem., Int. Ed. 2004,
43, 84.
6. (a) Harrington, P.; Keer, M. A. Can. J. Chem. 1998, 76,
1256; (b) Shi, M.; Cui, S.-C.; Li, Q.-J. Tetrahedron 2004,
60, 6679.
7. (a) Hwu, J. R.; King, K. Y. Curr. Sci. 2001, 81, 1043; (b)
Nair, V.; Panicker, S. B.; Nair, L. G.; George, T. G.;
Augustine, A. Synlett. 2003, 156; (c) Sommermann, T.
Synlett 2003, 834.
In conclusion, we have observed different results com-
pared to the literature report by using CAN or iodine
as catalyst when 1 or 6 with excess amount of indole
or 1-methylindole. The generation of the different prod-
ucts can be explained by the presence of the different ste-
ric hindrances of starting material and the different
Lewis acidities of the catalyst. The advantages of the
use of CAN and iodine as catalysts for the reactions
are efficiency, easy to handle, and under mild condition
and these catalyst are also cheap and commercially
available.
8. (a) Kim, K. M.; Ryu, E. K. Tetrahedron Lett. 1996, 37,
1441; (b) Firouzabadi, H.; Iranpoor, N.; Hazarkhani, H.
J. Org. Chem. 2001, 66, 7527; (c) Ramalinga, K.;
Vijayalakshmi, P.; Kaimal, T. N. B. Tetrahedron Lett.
2002, 43, 879; (d) Firouzabadi, H.; Iranpoor, N.; Sobhani,
S. Tetrahedron Lett. 2002, 43, 3653; (e) Yadav, J. S.;
Reddy, B. V. S.; Reddy, M. S.; Prasad, A. R. Tetrahedron
Lett. 2002, 43, 9703; (f) Das, B.; Banerjee, J.; Ramu, R.;
Pal, R.; Ravindranath, N.; Ramesh, C. Tetrahedron Lett.
2003, 44, 5465; (g) Saeeng, R.; Sirion, U.; Sahakitpichan,
P.; Isobe, M. Tetrahedron Lett. 2003, 44, 6211; (h) Ji, S.-J.;
Wang, S.-Y.; Zhang, Y.; Loh, T.-P. Tetrahedron 2004, 60,
2051; (i) Yadav, J. S.; Reddy, B. V. S.; Shubashree, S.;
Sadashiv, K. Tetrahedron Lett. 2004, 45, 2951; (j) Phukan,
P. J. Org. Chem. 2004, 69, 4005; (k) Phukan, P. Tetra-
hedron Lett. 2004, 45, 4785; (l) Sun, J.; Dong, Y.; Wang,
X.; Wang, S.; Hu, Y. J. Org. Chem. 2004, 69, 8932; (m)
Bhosale, R. S.; Bhosale, S. V.; Bhosale, S. V.; Wang, T.;
Zubaidha, P. K. Tetrahedron Lett. 2004, 45, 9111; (n) Ke,
Acknowledgements
Financial support of this work by the National Science
Council of the Republic of China and National Taiwan
Normal University (ORD93-C) is gratefully acknow-
ledged.
References and notes
1. Sundberg, R. J. The Chemistry of Indoles; Academic Press:
New York, 1970.
2. (a) Bergman, J.; Hoegberg, S.; Lindstroem, J. Tetrahedron
1970, 26, 3347; (b) Banerjee, A.; Mukhopadhyay, A. K.
Indian J. Chem. 1982, 21B, 239; (c) Chen, D.; Yu, L.;
Wang, P. G. Tetrahedron Lett. 1996, 37, 4467; (d) Denis,

492
S. Ko et al. / Tetrahedron Letters 47 (2006) 487–492
B.; Qin, Y.; He, Q.; Huang, Z.; Wang, F. Tetrahedron
6.46 (d, 1H, J = 2.4 Hz), 6.59 (d, 1H, J = 2.0 Hz), 6.80–
7.62 (m, 16H); 13C NMR (100 MHz, CDCl3): d 23.2, 31.0,
34.0, 36.5, 40.3, 43.8, 111.1, 111.2, 118.5, 118.6, 118.8,
119.3, 119.6, 120.8, 121.0, 121.1, 121.3, 121.7, 121.8, 122.5,
123.3, 126.5, 126.6, 136.2, 137.0; HRMS calculated for
C30H27N3 429.2205 (M+), found 429.2196.
Lett. 2005, 46, 1751; (o) Chu, C.-M.; Gao, S.; Sastry, M.
N. V.; Yao, C.-F. Tetrahedron Lett. 2005, 46, 4971; (p)
Ko, S.; Sastry, M. N. V.; Lin, C.; Yao, C.-F. Tetrahedron
Lett. 2005, 46, 5771; (q) More, S. V.; Sastry, M. N. V.;
Wang, C.-C.; Yao, C.-F. Tetrahedron Lett. 2005, 46, 6345.
9. A typical experimental procedure for the preparation of
5aa: A 10 mL of round-bottomed flask was charged with
2-cyclohexen-1-one 1a (0.096 g, 1.0 mmol), indole 2a
(0.468 g, 4.0 mmol), and CAN (0.164 g, 0.3 mmol) in
1 mL of the polar solvent DMSO/H2O (5:1). The mixture
was then stirred at room temperature until the reaction
was completed (6 h, monitored by TLC). The reaction
mixture was treated with dilute HCl solution, extracted
with ethyl acetate (2 · 5 mL). The solvent was removed
under reduced pressure and the residue was purified by
column chromatography by using hexane/EA (5:1) to give
4aa and 5aa. Compound 4aa: 1H NMR (400 MHz,
CDCl3): d 1.75–2.04 (m, 3H), 2.20 (m, 1H), 2.35–2.55
(m, 2H), 2.61 (m, 1H), 2.77 (m, 1H), 3.42 (m, 1H), 6.92 (d,
1H, J = 2.0 Hz), 7.08–7.61 (m, 4H), 8.17 (br s, 1H, NH);
13C NMR (100 MHz, CDCl3): d 24.9, 31.8, 36.0, 41.6,
48.1, 111.4, 119.1, 119.4, 119.6, 120.5, 122.2, 126.2,
136.5, 212.2; HRMS calculated for C14H15NO 213.1154
(M+), found 213.1148. Compound 5aa: 1H NMR
(400 MHz, CDCl3): d 1.50–1.58 (m, 1H), 1.70–1.90 (m,
2H), 2.10–2.34 (m, 3H), 2.90 (m, 1H), 3.10–3.19 (m, 2H),
10. A typical experimental procedure for the preparation of
5aa: A 10 mL of round-bottomed flask was charged with
2-cyclohexen-1-one 1a (0.096 g, 1.0 mmol), indole 2a
(0.468 g, 4.0 mmol), and iodine 9 (0.076 g, 0.3 mmol) in
1 mL of diethyl ether. The mixture was then stirred at
room temperature for 2 h until the reaction was com-
pleted, which can be checked by TLC. The reaction
mixture was treated with ice cold saturated Na2S2O3
solution, extracted with ethyl acetate (2 · 5 mL). The
solvent was removed under reduced pressure and the
residue was checked by NMR to indicate the mixture
contained 93% of 5aa and then the mixture was purified by
column chromatography by using hexane/EA = 5:1 to
give pure 5aa.
11. (a) Brown, H. C.; Ham, G. J. Am. Chem. Soc. 1956, 78,
2735; (b) Brown, H. C.; Ichikawa, K. Tetrahedron 1957,
221; (c) Schneider, H.-J.; Thomas, F. J. Am. Chem. Soc.
1980, 102, 1424; (d) Carey, F. A.; Sundberg, R. J.
Advanced Organic Chemistry. Part A: Structure and
Mechanisms, 4th ed.; Kluwer Academic/Plenum Publish-
ers: New York, 2000, p 171.