Manganese chloride as an efficient catalyst for selective transformations of indoles in the presence of a keto carbonyl group

Article abstract of DOI:10.1002/adsc.201100211

Catalysis by manganese chloride tetrahydrate was found to be effective for the selective transformation of indoles, with which the desired acid-catalyzed reaction could be promoted and, at the same time, a side reaction that also needs assistance of acid, the electrophilic reaction of indole with the co-existing keto carbonyl group, does not occur. Some acid-catalyzed reactions, such as the ring-opening reaction of 2-alkoxy-3,4-dihydropyran with indole, and transesterification of β-keto ester with an alcohol that contains a C-3 unsubstituted indole fragment, could be performed smoothly by using manganese chloride as catalyst. A new multicomponent reaction of indole, 3,4-dihydropyran and β-keto ester was also developed with catalysis by manganese chloride. Copyright

Full text of DOI:10.1002/adsc.201100211

FULL PAPERS
DOI: 10.1002/adsc.201100211
Manganese Chloride as an Efficient Catalyst for Selective
Transformations of Indoles in the Presence of a Keto Carbonyl
Group
Minghao Li,a,c Jie Yang,a,c and Yanlong Gua,b,*
a
Institute of Physical Chemistry and Industrial Catalysis, Hubei Key Laboratory of Material Chemistry and Service Failure,
School of Chemistry and Chemical Engineering, Huazhong University of Sciences and Technology, 1037 Luoyu Road,
Hongshan Division, Wuhan, Hubei Province 430074, Peopleꢀs Republic of China
Fax : (+86)-(0)27-8754-4532; e-mail: klgyl@hust.edu.cn
b
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Lanzhou
730000, Peopleꢀs Republic of China
M. Li and J. Yang contributed equally to this work.
c
Received: March 24, 2011; Published online: June 16, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100211.
Abstract: Catalysis by manganese chloride tetrahy- with an alcohol that contains a C-3 unsubstituted
drate was found to be effective for the selective indole fragment, could be performed smoothly by
transformation of indoles, with which the desired using manganese chloride as catalyst. A new multi-
acid-catalyzed reaction could be promoted and, at component reaction of indole, 3,4-dihydropyran and
the same time, a side reaction that also needs assis- b-keto ester was also developed with catalysis by
tance of acid, the electrophilic reaction of indole manganese chloride.
with the co-existing keto carbonyl group, does not
occur. Some acid-catalyzed reactions, such as the
ring-opening reaction of 2-alkoxy-3,4-dihydropyran Keywords: acid catalysis; indoles; manganese chlo-
with indole, and transesterification of b-keto ester ride; selective transformations; tandem reactions
Introduction
plored in search of improved efficiencies and cost-ef-
fectiveness.
In the context of green chemistry, the implementation
The indole ring system exists ubiquitously in natu-
of methodologies giving selective access to elaborate rally occurring products, and many indole-containing
scaffolds, while combining molecular diversity with compounds exhibit important biological and pharma-
eco-compatibility, is a great challenge for organic ceutical activities.[4] The synthesis and derivatization
chemists.[1] Many research projects have, therefore, of indoles has, therefore, been a major area of focus
been driven forward by one particular motivation: for organic chemists over the years.[5] As an electron-
easy access of complex molecules in combination with rich heteroaromatic system, indole has often been
the potential to site-selectively introduce chemical used as a model substrate in electrophilic aromatic
functionalities.[2] The importance of this area has been substitutions. Generally, the most reactive position of
well documented by one of the twelve principles of indole in these reactions is the C-3 site. Although the
green chemistry, reduce derivatives. Although many high reactivity can render indoles readily applicable
methodologies for chemoselective control in various in many reactions, when an electrophile that contains
reactions have been well established by means of cat- two or more reactive sites was used, how to control
alysis with enzymes or organic and organometallic the reaction selectivity has become a great challenge.
compounds, the reported methods often involve prac-
In this paper, we report an efficient catalyst for cat-
tical difficulties due to high costs of catalyst, limited alytic selective transformations of indoles in the pres-
substrate scope or lack of green properties.[3] There- ence of a keto carbonyl group. It is well known that,
fore, new catalytic systems are being continuously ex- in the presence of acid catalyst, the keto carbonyl
group will undergo an electrophilic reaction with
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Table 1. Electrophilic ring-opening reaction of dihydropyran
1a with indole 2a.[a]
indole to form diindolylmethane derivatives. This re-
action is particularly favorable to C-3 unsubstituted
indoles that contain an electron-donating group. As a
result, derivatization of C-3 unsubstituted indole in
the presence of a keto carbonyl group is not easy, and
generally cannot be performed in the presence of
acid. However, we found unexpectedly that MnCl2
can be used, in the presence of a keto carbonyl group,
as a highly selective catalyst for transformations of in-
doles by means of three acid-catalyzed reactions: (i)
ring-opening reaction of 2-alkoxy-3,4-dihydropyran
with indole; (ii) transesterification of b-keto ester
with an alcohol that contains a C-3 unsubstituted
indole fragment; and (iii) an “ABCC”-type four-com-
ponent reaction of b-keto ester, 3,4-dihydropyran and
indole. While the desired reactions proceed well, the
keto carbonyl groups involved in the structure of sub-
strates or products remain unaltered although a
highly reactive C-3 unsubstituted indole was also in-
volved in the reaction system.
Entry Catalyst
Solvent
Yield [%][b]
1
2
3
4
5
6
7
–
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
0
TsOH
ScACTHNGURETNNU(G OTf)3
InCl3
FeCl3
H3BO3
28 (23)
31 (22)
25 (26)
10
21 (17)
20
montmorillonite K10 CH3NO2
8
9
Amberlyst-15
MnCl2
MnACTHNGUETR(UNNG OAc)2·4H2O
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
toluene
1,4-dioxane
CH3CN
ClCH2CH2Cl 39
16
40 (81)
trace
30 (34)
82
trace
trace
31
10
11
12
13
14
15
16
17
18
MnBr2
Results and Discussion
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
Initially, the reaction of 2-alkoxy-3,4-dihydropyran 1a
and indole 2a was investigated. This type of electro-
philic ring-opening reaction of 2-alkoxy-3,4-dohydro-
pyran has just been reported by us by using thiols or
thiophenols as nucleophiles.[6] Although the reactions
of thiol or thiophenol proceeded very well in the pres-
ence of many Lewis acid catalysts, when indole was
used as nucleophile, control of the reaction selectivity
is not easy. For example, the ring-opening reaction of
2-aryl-3,4-dihydropyran with indole can only be per-
water
–
trace
59
[a]
[b]
Solvent: 1.0 mL, 1a: 0.25 mmol, 2a: 0.63 mmol.
Yield in brackets was obtained in the presence of
0.8 equiv. water.
formed by using manganese chloride tetrahydrate as such as p-toluenesulfonic acid (TsOH), ScACHTUNGTRENNUNG(OTf)3,
catalyst, and other acids were proved to be inappro- InCl3 and FeCl3 were used as catalysts, 1a was almost
priate for this reaction.[7] Inspired by this specific ob- completely consumed at the end of the reaction, and
servation, we thus decided to explore the application a diACTHUNTGRNEUNG(indolyl)methane derivative 3a was obtained from
of this catalyst in organic synthesis. In fact, manga- a messy mixture in poor yields (entries 2 to 5). In
nese chloride has been rarely used before as a catalyst order to control the reaction selectivity, a weak acid,
in organic synthesis.[8] For this reason, we wanted to boric acid, was then examined. And it was found that
know what this catalyst can contribute for improving the starting materials, 1a and 2a, remained unaltered
current organic synthesis.
in these cases, as a result, only small amount of 3a
Although the reaction of indole with 2-aryl-3,4-di- was detected (entry 6). Solid acids, such as montmoril-
hydropyran has been reported by us,[7] the ring-open- lonite K10 and Amberlyst 15, were also used in this
ing reaction of 2-alkoxy-3,4-dihydropyran with indole reaction and no selectivity was observed (entries 7
has not been reported yet. Importantly, the latter re- and 8). Many other acid catalysts were also examined
action might be able to generate a double substituted and no positive results were obtained (see Supporting
product that is inaccessible with our previous reac- Information). In a later study, anhydrous MnCl2 was
tion. As indole is a very reactive nucleophile, and also used, and the yield of 3a reached to 40% (entry 9).
considering the fact that reactivity of 2-alkoxy-3,4-di- Owing to the fact that 1a was completely consumed
hydropyran is quite high, it may not easy to control in this case, efforts to further improve the reaction
the selectivity of this ring-opening reaction. There- yield were in vain. Other manganese salts, such as
fore, our investigation was started from the reaction MnACTHNUTRGEN(UNG OAc)2 and MnBr2, were also examined and the
of 2-butoxy-3,4-dihydropyran 1a and an indole 2a. As yields are rather poor (entries 10 and 11). Encouraged
shown in Table 1, no reaction occurs in the absence of by the promising result obtained with anhydrous
catalyst (entry 1). When some conventional acids, MnCl2, manganese chloride tetrahydrate was then ex-
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Manganese Chloride as an Efficient Catalyst for Selective Transformations of Indoles
Table 2. Electrophilic ring-opening reaction of the dihydropyrans with indoles catalyzed by
MnCl2 tetrahydrate.
amined. And to our great delight, an 82% of yield and dihydropyrans are applicable in this system, and
was obtained in this case (entry 12). This result im- the desired products were obtained in good to excel-
plies that a small amount of water is helpful for the lent yields. It should be noted that the skeleton of the
progress of the model reaction. We therefore re-ex- obtained product contains not only a fragment of di-
amined some of the other catalysts by adding small
ACHTUNGTREN(NGNU indolyl)methane, which is, sometimes, biologically
amount of waters into the reaction system, and as active and pharmaceutically interesting,[9] but also a
shown in Table 1, nearly the same performances were moiety of a b-dicarbonyl compound that has been
observed with the exception of anhydrous MnCl2, widely used in organic synthesis. Although the prod-
which gives an 81% yield with the aid of water uct could be theoretically synthesized by (i) enolate
(entry 9). Therefore, at this stage, the best catalyst for alkylation or (ii) Michael addition of b-dicarbonyl
the model reaction is MnCl2 tetrahydrate. The solvent compound to acrolein and the following selective
also plays a crucial role for the occurrence of the electrophilic reaction of the formyl group of the prod-
model reaction, and nitromethane was found to be uct with indole (see Supporting Information), our
the best one among all the examined solvents in present method exhibits some advantages including
Table 1 (entries 13 to 18).
Having these results in hand, we then examined the dure and easy control of reaction selectivity.
substrate generality of the MnCl2·4H2O-catalyzed To probe the mechanism of the model reaction, we
minimization of wastes, simplified operation proce-
electrophilic ring-opening of 1a-type dihydropyrans treated an analogous dihydropyran, 1b, in nitrome-
with indoles. And as shown in Table 2, many indoles thane with 30 mol% of MnCl2 tetrahydrate in the ab-
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Scheme 1. Subdivisions of the model reaction and the by-products identified in the reaction systems.
sence of indole. As shown in Scheme 1, an aldehyde, the reaction. Out of these considerations, we thus pro-
4a, was obtained in 56% of yield after 11 h of reaction posed a possible mechanism for the model reaction in
at 808C. It should be noted that 4a is the only product Scheme 2. In the beginning of the reaction, the dihy-
in this reaction, and the moderate yield mainly result- dropyran substrate 1a was activated with the aid of
ed from incomplete conversion of 1b. Following treat- MnCl2 catalyst to form a cyclic oxocarbenium ion in-
ment of 4a with 2a in the presence of 30 mol% of termediate (I). This step was generally catalyzed by a
MnCl2 tetrahydrate resulted in the quantitative for- Lewis acid.[11] Although formation of a linear oxocar-
mation of 3i. Two other acids, TsOH and ScACTHNUTRGNE(NUG OTf)3, benium ion might be also possible through a cleavage
À
were also examined in this procedure in the presence of the C O bond in the ring, but compared with the
of 1.2 equivalents of water. It was found that 1b was cyclic one, it should be much less stable because of
completely consumed in the first step, but, however, the lack of a conjugation effect. Once (I) was formed,
4a was obtained only in a small amount (yield it tended to react with water to form an aldehyde
<20%). Two by-products, 4b and 4c were isolated (IV) that can further interact with indole to generate
with nearly 30% overall yield from the obtained 3a. In view of the fact that 40% of the yield was ob-
messy mixture. There are some other by-products that tained under anhydrous conditions, we thus suspect
are difficult to isolate in the reaction mixture. Fur- that the other way to 3a is also possible, in which
thermore, TsOH and ScACHTNUGTRENUNG(OTf)3 were proved to be water was not involved. Out of this consideration, an-
non-selective for the formation of 3i in the second other reaction pathway was also proposed in
step because a messy mixture was formed in these Scheme 2. Interaction of (I) with indole might form
cases.
an intermediate (II).[12] In the presence of MnCl2, (II)
À
On the basis of these results, we can conclude that underwent cleavage of the C-2 O bond to form a
the model reaction is susceptible to both catalyst and ring-opening intermediate (III) that tended to react
water. Kobayashi and his co-workers have accom- with the next indole to generate the final product
plished a classification of many Lewis acids according 3a.[13]
to their activities in organic reactions.[10] In the rank-
It should be noted that mechanism of the present
ing of Kobayashi, anhydrous MnCl2 was considered as ring-opening reaction is different from that of our
an inactive one. Therefore, we believe that the acid previous report in which a monotransthioacetalization
strength of MnCl2 might be responsible for the high occurs and the aldehyde intermediate might not be
selectivity. When water was added into the reaction formed.[6] No matter what kind of mechanism the re-
system, it might play two functions involving (i) facili- action follows, we can confirm at this stage that man-
tating the formation of reaction intermediate, and (ii) ganese chloride tetrahydrate has indeed a specific
tuning the Lewis acidity of MnCl2 to be suitable for ability for distinguishing the reactivity difference be-
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Manganese Chloride as an Efficient Catalyst for Selective Transformations of Indoles
Scheme 2. Plausible mechanism for the model reaction.
tween three kinds of carbonyl groups including alde- Particularly, in the case of 1,3-cyclohexanedione, the
hyde-carbonyl, ketone-carbonyl and ester-carbonyl, generated products underwent a dehydration step to
and thus is capable of controlling the reaction selec- form a cyclized skeleton.
tivity. Inspired by this fact, we suspect that other nu-
The above-mentioned ring-opening reactions have
cleophiles that are able to react with an aldehyde demonstrated that manganese chloride tetrahydrate
could also be used in this type of reaction. As shown has a specific ability for selectively promoting the
in Scheme 3, in the presence of catalytic amount of transformation of indole. In order to further extend
MnBr2 or MnCl2, 1,3-cyclohexanedione and 2-methyl- the use of this specific ability of manganese chloride
furan could react readily with a 1a-type dihydropyran. tetrahydrate, we then investigated other organic reac-
Scheme 3. Ring-opening of the dihydropyran with other nucleophiles.
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tions. The transesterification of b-keto esters with an poor efficiencies of these catalysts mainly resulted
alcohol has been extensively investigated by using from a lack of selectivity to 10a. Solid catalysts, such
acids or bases as catalysts.[14] When acid catalysts were as montmorillonite K10 and Amberlyst 15, were also
used, extra efforts have to be made for inhibiting used, and no clear selectivity was obtained (entries 10
some side reactions because the keto carbonyl groups and 11).
in b-keto esters are normally reactive under acidic
In the later study, MnCl2·4H2O was used as cata-
conditions toward some nucleophiles.[15] Particularly, lyst, and in this case, the yield of 10a reached 90%
when N-(2-hydroxy)ethylindole 9a was used as an al- (entry 12). This result implies that MnCl2·4H2O has a
cohol, as the generated product 10a contains both a unique ability to catalyze the reaction of 9a and 2b
keto carbonyl group and a reactive C-3 unsubstituted without affecting the chemical stability of the keto
indole fragment, controlling of the reaction selectivity carbonyl group of 10a or 2b. Other manganese salts,
could be a hard task for us. As we expected, various such as Mn
conventional acids, such as H2SO4, TsOH, Sc(OTf)3, and only moderate yields were obtained (entries 13
Bi(OTf)3, Y(OTf)3, SnCl4, FeCl3, InCl3 and ZnCl2, and 14). Anhydrous MnCl2 also worked well, but the
ACHTUGNRTEN(NUGN OAc)2 and MnBr2, were also examined,
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
were found to be ineffective for this transesterifica- yield of 10a was slightly inferior to that of
tion although substrate 2b was almost completely con- MnCl2·4H2O (entry 15). Interestingly, by adding
sumed in the most cases (Table 3, entries 1 to 9). The 0.4 equivalents of water into the anhydrous MnCl2
system, the reaction yield could be improved to the
level of that with MnCl2·4H2O. Further investigations
revealed that, like in the case of the first model reac-
tion, the solvent also plays a key role in controlling
the reaction selectivity, and the best result was ob-
tained by using toluene as medium (entries 16 to 20).
It should be noted that, during the reaction, both an-
hydrous MnCl2 and MnCl2·4H2O are soluble in tolu-
ene at the reaction temperature. Therefore, the role
of water here is not facilitating formation of a crystal
of the catalyst. Although the acid strength of manga-
nese chloride tetrahydrate is not strong, a small
amount of water here might play a role in tuning the
acid strength of the manganese catalyst to be suitable
for the reaction. This point deserves further investiga-
tion.
Other b-keto esters were also examined in the
transesterification of 2b, and the results are listed in
Table 4. All the examined b-keto esters can selective-
ly react with 9a to afford the corresponding products
in good to excellent yields. It should be noted that the
same reactions under the identical conditionws over
Table 3. Transesterification of 9a with 2b in different condi-
tions.[a]
Entry Catalyst
Solvent Recovery
rate of 2b
Yield of
10a [%]
[%]
1
2
3
4
5
6
7
8
9
H2SO4
TsOH
toluene 12
toluene 11
toluene <5
toluene <5
toluene 13
toluene <5
toluene 16
toluene 10
toluene 18
<5
<5
<5
<5
25
<5
8
6
Sc
Bi
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
YACHTUNGTRENNUNG(OTf)3
SnCl4
FeCl3
InCl3
ZnCl2
two conventional acids, TsOH and ScACTHNUTRGENUG(N OTf)3, afforded
<5
20
only small amount of products. In these cases, most of
the substrates were consumed at the end of the reac-
tion, and many spots were observed on TLC detec-
tion. These results indicated that (i) controlling of the
selectivity is the key to render the reaction possible;
(ii) the high selectivity of MnCl2·4H2O for catalyzing
the model reaction is not an individual phenomenon,
and is efficient for the synthesis of many 10a-type
indole derivatives.
In view of the unique ability of MnCl2·4H2O for
both acting as a mild acid catalyst and preventing the
electrophilic reaction of the keto carbonyl group with
indoles, this catalyst might be capable of promoting
the reactions of many keto carbonyl-containing com-
pounds and C-3 unsubstituted indoles. We then inves-
tigated a novel multicomponent reaction of 9a, 3,4-di-
10[b] montmorillonite toluene 22
K10
11[c]
12
Amberlyst 15
MnCl2·4H2O
toluene 17
toluene
13
90
6
13
14
15
Mn
MnBr2
MnCl2
(OAc)2
toluene 20
toluene 22
toluene 10
55
40
80 (89)[e]
16
MnCl2·4H2O
–
31
41
34
30
20
15
17[d] MnCl2·4H2O
CH3NO2 40
dioxane 51
DMF
18[d] MnCl2·4H2O
19
20
MnCl2·4H2O
MnCl2·4H2O
<5
DMSO <5
[a]
[b]
[c]
[d]
[e]
Solvent: 2.5 mL, 9a: 1.2 mmol, 2b: 1.0 mmol.
20.0 mg solid catalyst were used.
Proton exchange ability is 4.7 mmolgÀ1.
1008C.
Yield in brackets was obtained by adding 0.4 equiv. hydropyran (11a) and indoles using MnCl2·4H2O as
water.
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Manganese Chloride as an Efficient Catalyst for Selective Transformations of Indoles
Table 4. Reaction of 2b with different b-keto esters catalyzed
In order to shed light on the reaction mechanism, a
ring-opening reaction of 11a with indole was also ex-
amined, and it was found that the reaction proceeded
very well in the presence of catalytic amount of
MnCl2·4H2O. Importantly, subsequeent treatment of
the obtained ring-opening product with 9a afforded
12a in an excellent yield (see Supporting Informa-
tion). These results imply that the reaction might pro-
ceed indeed through a cascade ring-opening and
transesterification pathway. It should also be noted
that this multicomponent reaction has never been re-
ported before. This demonstrated that MnCl2·4H2O
can really be used as an effective catalyst for selective
organic synthesis.
by MnCl2·4H2O.[a]
Entry b-Keto ester
Time Product Catalyst[d] Yield
[h]
(%)
MnCl2
Sc
TsOH
82
1[b]
9b
10b
Having these promising results in hand, our interest
is naturally moved to how to use the product that was
obtained with the manganese chloride tetrahydrate
catalyst. In the first model reaction, we are able to
synthesize a 1,3-dicarbonyl compound with a frag-
(OTf)3 <5
6
MnCl2
86
ScACTHNUTRGEN(UNG OTf)3 15
2
9c
10c
10d
TsOH
38
ment of a diACTHNUGRTNEUNG(indolyl)methane moiety. It is known that
MnCl2
87
3[c]
9d
ScACTHNGUTRENU(NG OTf)3 10
2-(3-arylpropyl)-b-diketones can undergo a radical
cyclization to form the skeleton of tetrahydronaphtha-
lene.[17] This type of cyclization reaction has been uti-
lized by us for converting the ring-opening product of
2-aryl-3,4-dihydropyran with indole to a valuable
product.[6] Inspired by our previous result, we suspect-
ed that this oxidative cyclization reaction should also
be effective for converting the 3a-type product. In
order to confirm our hypothesis and to verify both of
the usefulness of 3a-type products and the effective-
ness of manganese chloride tetrahydrate as a catalyst,
we thus started a three-step synthesis involving: (i) a
domino Knoevenagel/oxo-Diels–Alder reaction of
butyl vinyl ether (13a), acetylacetone (14a) and aque-
ous formaldehyde that generated a dihydropyran 1c
TsOH
MnCl2
ScACTHNUTRGENUG(N OTf)3
16
81
8
4
9e
9f
10e
10f
TsOH
<5
MnCl2
88
Sc
ACHTUNGTRENNUNG
5
TsOH
[a]
Toluene: 2.5 mL, b-keto ester: 1.2 mmol, 2b: 1.0 mmol.
b-Keto ester/2b=1/3.
Reaction time: 14 h.
[b]
[c]
[d]
The catalyst was used with hydrate.
catalyst (Table 5). The reaction proceeded in a cas- in 87% yield; (ii) MnCl2·4H2O-catalyzed electrophilic
cade pathway involving (i) electrophilic ring-opening ring-opening of 1c with indole that generated the cor-
reaction of 11a with indole, and (ii) transesterification responding product, 3b, in 98% yield, and (iii) Mn-
of the generated hydroxy-functionalized diindolylme-
ACHTUNGRTEN(NUNG OAc)3-promoted radical cyclization of 3b in acetic
thane with 9a. The first step has been investigated by acid to afford a novel 2,3,4,9-tetrahydro-1H-carbazole
Yadav and his co-workers by using InCl3 as catalyst.[16] derivative 15a in 48% yield. The molecular skeleton
However, for the model multicomponent reaction, of 15a was known to possess antiangiogenic activity.[18]
InCl3 was proved to be ineffective due to extensive Although the method of accessing this skeleton is
formation of many by-products (entry 1). Other acids, available, it only works for the synthesis of the unsub-
(OTf)3, Amberlyst-15, stituted one,[19] but how to modify the skeleton with
such as TsOH, ScACHTUNTRGENNUG(OTf)3, BiACHTUGNTRENNUGN
montmorillonite K10 and H3BO3 were also examined, substituent groups is still a big challenge. The method
and no yield >40% was obtained (entries 2 to 7). To in Scheme 4 not only offers an alterative route for the
our delight, the same reaction over MnCl2·4H2O cata- synthesis of this skeleton, but is also capable of modi-
lyst proceeded well and the desired product 12a was fying the structure, and thus is valuable for organic
obtained in 82% yield (entry 8). Anhydrous MnCl2 synthesis.
was also examined, and the result is the same as that
observed in the first reaction, the yield obtained was
slightly inferior (entry 9). Investigation of the sub- Conclusions
strate scope revealed that many indoles could be used
in this reaction, and the corresponding products were In conclusion, MnCl2 tetrahydrate was proved to be
obtained in moderate to good yields (entries 10 to an effective catalyst for selective transformations of
14).
indoles in the presence of a keto carbonyl group. Al-
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Table 5. Multicomponent reactions of indoles 2c–h, 9a and 11a.[a]
Entry
Indole
Catalyst
InCl3
Product
Yield [%]
1
2
3
4
5
6
7
8
2c
2c
2c
2c
2c
2c
2c
2c
2c
2d
2e
2f
2g
2h
12a
12a
12a
12a
12a
12a
12a
12a
12a
12b
12c
12d
12e
12f
<5
<5
<5
<5
32
29
38
82
74
58
68
73
72
Sc
Bi
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
TsOH
Amberlyst 15
montmorillonite K10
H3BO3
MnCl2·4H2O
MnCl2
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
9
10
11[b]
12
13
14
63
[a]
Nitromethane, 1.5 mL, 9a: 2.0 mmol, indole: 2.5 mmol, 11a: 1.0 mmol.
Reaction time: 17 h.
[b]
Scheme 4. Synthesis of 2,3,4,9-tetrahydro-1H-carbazole 15a.
1558
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Adv. Synth. Catal. 2011, 353, 1551 – 1564

Manganese Chloride as an Efficient Catalyst for Selective Transformations of Indoles
Tests for the other catalyst were all performed according
to an analogous procedure with above mentioned.
though the side reaction between the keto carbonyl
and C-3 unsubstituted indole is normally catalyzed by
acid, some acid-catalyzed reactions, such as the ring-
opening reaction of 2-butoxy-3,4-dihydropyran with
indole and transesterification of a b-keto ester with
an alcohol that contains a C-3 unsubstituted indole
fragment, could be performed smoothly by using
MnCl2·4H2O as catalyst. A new multicomponent reac-
Procedure for Transesterification of 2b
In a typical reaction, toluene (2.5 mL) was mixed with tert-
butyl acetylacetate (189.6 mg, 1.2 mmol), MnCl2·4H2O
(19.8 mg, 0.1 mmol) and N-(2-hydroxyethyl)indole 2b
(161.0 mg, 1.0 mmol) under air. The mixture was stirred for
tion of indole, 3,4-dihydropyran and 9a was also de- 11 h at 1108C. After reaction, the mixture was mixed with
ethyl acetate (6.0 mL), petroleum ether (6.0 mL) and brine
(12 mL). After 15 min of stirring at room temperature, the
organic phases were combined together and dried with
Na2SO4. Then, through preparative TLC, the product 3a was
obtained in 90% yield.
veloped with catalysis of MnCl2·4H2O. This work also
indicated to us that MnCl2 might be able to play a
more important role in homogeneous catalysis than
we have expected before. In spite of these promising
results, the reasons for the obtained high selectivity
by using MnCl2 as catalyst are still unknown at this
stage, this should be the next topic of our study.
The other reactions were performed as an analogous pro-
cedure.
Procedure for Three-Component Reaction of 2c, 9a
and 11a
Experimental Section
In a typical reaction, nitromethane (1.5 mL) was mixed with
9a (316.4 mg, 2.0 mmol), 11a (84.1 mg, 1.0 mmol), 2c
(293.0 mg, 2.5 mmol) and MnCl2·4H2O (19.8 mg, 0.1 mmol)
under air. The mixture was stirred for 10 h at 1008C. After
reaction, the mixture was mixed with ethyl acetate (6.0 mL),
petroluem ethers (6.0 mL) and brine (12 mL). After 15 min
of stirring at room temperature, the organic phases were
combined together and dried with Na2SO4. Then, through
preparative TLC, the product 5a was obtained in 82% yield.
The other reactions were performed as an analogous pro-
cedure.
All the chemicals were used as it was received. 2-butoxy-
3,4-dihydropyrans were prepared in water according to our
reported method starting from olefins, 1,3-dicarbonyl com-
pounds and formaldehyde aqueous solution.[20] N-(2-Hy-
droxyethyl)indole was prepared in DMSO from indole and
2-chloroethanol according to a literature method.[21] All re-
actions were conducted in a 10-mL V-type flask equipped
with triangle magnetic stirring.
Typical Procedure for Electrophilic Ring-Opening
Reaction of Dihydropyran 1a with Indole
Procedure for Synthesis of 15a
In a typical reaction, nitromethane (1.0 mL) was mixed with
1a (60.5 mg, 0.25 mmol), 2a (73.0 mg, 0.63 mmol) and
MnCl2·4H2O (5.0 mg, 10 mol%) under air. The mixture was
stirred for 11 h at 908C. After reaction, the mixture was
cooled to room temperature and the desired product, 3a,
was obtained by preparative TLC using a mixed solution of
ethyl acetate and petroleum ether as eluting solvent (the
ratio of ethyl acetate/petroleum ether is 1/2); yield: 82.2 mg
(82%).
The synthesis was started from the preparation of dihydro-
pyran 1c. In a U-type reaction flask equipped with magnetic
stirring, vinyl n-butyl ether, 9a (100.0 mg, 1.0 mmol), was
mixed with acetylacetone (10a, 200.1 mg, 2.0 mmol) and
formaldehyde aqueous solution (37 wt%, 202.8 mg,
2.5 mmol) under air. The mixture was stirred at 808C for
7 h. After reaction, the reaction mixture was cooled to room
temperature. After addition of brine (5.0 mL), the aqueous
phase was extracted with a mixture of ethyl acetate and hep-
tane (v/v=1/1, 5.0 mLꢂ3). The obtained organic phases
were then combined together and dried with anhydrous
Na2SO4. After evaporation under reduced pressure, the de-
sired product 1c was obtained by silica gel column chroma-
tography using a mixed solution of ethyl acetate and petro-
leum ether as eluting solvent (the ratio of ethyl acetate/pe-
troleum ether is 1/20); yield: 184.6 mg (87%).
Tests for substrate scope and the reactions with other nu-
cleophiles were all performed according to an analogous
procedure with above mentioned.
Procedure for Mechanism Study
In a typical reaction, nitromethane (1.0 mL) was mixed with
1b (152.2 mg, 0.5 mmol) and MnCl2·4H2O (15.0 mg,
30 mol%) under air. The mixture was stirred for 11 h at
808C. After reaction, the mixture was cooled to room tem-
perature and the desired product, 4a, was obtained by prep-
arative TLC using a mixed solution of ethyl acetate and pe-
troleum ether as eluting solvent (the ratio of ethyl acetate/
petroleum ether is 1/4); yield: 69.5 mg (56%).
Then, the obtained 4a was mixed with nitromethane
(1.0 mL), indole (81.9 mg, 0.7 mmol) and MnCl2·4H2O
(18.5 mg, 30 mol%). The mixture was then heated at 808C
for 11 h. After reaction, the mixture was cooled to room
temperature and the desired product, 3h, was formed in
quantitative yield.
The synthesis of 3b was performed according to the pro-
cedure described in the part of ring-opening reaction. Final-
ly, 3b was obtained in 98% yield (317.3 mg).
Radical cyclization of 3b was performed in acetic acid
using a V-type flask as reactor. Thus, acetic acid (2.5 mL)
was added into the flask that contain the obtained 3b
(0.85 mmol), and then, manganese triacetate dihydrate
(559.6 mg, 2.1 mmol) was added. The mixture was then
stirred at 608C for 4 h. After reaction, aqueous Na2CO3 so-
lution (2N, 15 mL) was added and then the mixture was ex-
tracted with a mixture of ethyl acetate and heptane (v/v=1/
1, 20 mLꢂ3). The obtained organic phases were combined
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1559

Minghao Li et al.
FULL PAPERS
together and dried with anhydrous Na2SO4. After evapora-
tion under reduced pressure, 11a was obtained through a
preparative TLC isolation using a mixed solution of ethyl
acetate and petroleum ether as eluting solvent (the ratio of
ethyl acetate/petroether is 1/5); yield: 151.5 mg (0.41 mmol,
48%).
Ja =6.8 Hz, Jb =9.6 Hz, 1H), 3.71 (td, Ja =6.8 Hz, Jb =9.6 Hz,
1H), 4.91 (dd, Ja =2.4 Hz, Jb =4.0 Hz, 1H); 13C NMR: d=
13.7, 18.1, 19.1, 19.8, 26.2, 28.2, 31.6, 68.3, 79.2, 97.8, 103.4,
160.3, 167.7; IR: n=2962, 2934, 2873, 1703, 1630, 1456, 1366,
1339, 1299, 1283, 1247, 1175, 1119, 1076, 1011, 865, 771 cmÀ1
;
HR-MS (ESI): m/z=270.1822, calcd. for C15H26O4 [M]+:
270.1831.
2-Methoxyethyl
2-butoxy-6-methyl-3,4-dihydro-2H-
Characterization Data of Newly Synthesized Products
pyran-5-carboxylate (1f): Colorless liquid; 1H NMR
(CDCl3): d=0.91 (t, J=7.2 Hz, 3H), 1.35 (sext, J=7.2 Hz,
2H), 1.56 (quint, J=6.8 Hz, 2H), 1.69–1.79 (m, 1H), 1.81–
1.89 (m, 1H), 2.24 (s, 3H), 2.28–2.39 (m, 2H), 3.37 (s, 3H),
3.52 (td, Ja =6.8 Hz, Jb =9.6 Hz, 1H), 3.61 (t, J=4.8 Hz,
2H), 3.79 (td, Ja =6.4 Hz, Jb =9.2 Hz, 1H), 4.23 (dt, Ja =
0.8 Hz, Jb =4.0 Hz, 2H), 5.03 (dd, Ja =2.8 Hz, Jb =3.6 Hz,
1H); 13C NMR: d=13.7, 17.7, 19.1, 19.9, 25.9, 31.6, 58.8,
62.7, 68.3, 70.6, 97.9, 101.7, 162.0, 168.0; IR: n=2958, 2935,
2874, 2819, 1707, 1628, 1454, 1403, 1379, 1338, 1289, 1272,
Ethyl 2-butoxy-6-methyl-3,4-dihydro-2H-pyran-5-carbox-
ylate (1a): Colorless liquid; 1H NMR (CDCl3): d=0.91 (t,
J=7.6 Hz, 3H), 1.28 (t, J=7.2 Hz, 3H), 1.36 (sext, J=
7.6 Hz, 2H), 1.53–1.61 (m, 2H), 1.70–1.80 (m, 1H), 1.81–
1.90 (m, 1H), 2.24 (t, J=1.6 Hz, 3H), 2.26–2.43 (m, 2H),
3.53 (td, Ja =6.8 Hz, Jb =9.6 Hz, 1H), 3.80 (td, Ja =6.4 Hz,
Jb =9.6 Hz, 1H), 4.15 (q, J=6.8 Hz, 2H), 5.02 (dd, Ja =
2.8 Hz, Jb =4.0 Hz, 1H); 13C NMR: d=13.6, 14.3, 17.7, 19.1,
19.8, 26.0, 31.6, 59.5, 68.3, 97.8, 101.9, 161.4, 168.1; IR: n=
2929, 2935, 2872, 1706, 1629, 1456, 1378, 1456, 1378, 1337,
1272, 1237, 1192, 1170, 1119, 1075, 1011, 984, 863, 769,
600 cmÀ1; HR-MS (ESI): m/z=242.1529, calcd. for C13H22O4
[M]+: 242.1518.
1237, 1196, 1119, 1077, 1011, 984, 863, 768, 539, 496 cmÀ1
;
HR-MS (ESI): m/z=295.1525, calcd. for C14H24NaO5 [M+
Na]+: 295.1521.
Ethyl 2-acetyl-5,5-di(1H-indol-3-yl)pentanoate (3a):
Yellow solid; mp 44–468C; 1H NMR (CDCl3): d=1.17 (t,
J=6.8 Hz, 3H), 1.84–2.00 (m, 2H), 2.06 (s, 3H), 2.09–2.22
(m, 2H), 3.41 (t, J=7.2 Hz, 1H), 4.10 (q, J=6.8 Hz, 2H),
4.43 (t, J=7.2 Hz, 1H), 6.75 (dd, Ja =2.0 Hz, Jb =5.2 Hz,
2H), 6.99 (t, J=7.2 Hz, 2H), 7.09 (t, J=7.2 Hz, 2H), 7.18
(d, J=8.4 Hz, 2H), 7.54 (d, J=8.0 Hz, 2H), 7.88 (s, 2H);
13C NMR: d=14.1, 14.3, 27.1, 28.9, 33.3, 34.0, 60.0, 61.5,
111.4, 119.1, 119.1, 119.3, 119.5, 121.7, 122.0, 126.9, 127.0,
136.7, 170.1, 204.0; IR: n=3412, 3118, 3055, 2977, 2932,
2868, 1731, 1707, 1617, 1484, 1455, 1420, 1358, 1339, 1272,
1219, 1150, 1094, 1013, 734, 587 cmÀ1; HR-MS (ESI): m/z=
425.1822, calcd. for C25H26N2O3 [M+Na]+: 425.1841.
3-[3,3-Di(1H-indol-3-yl)propyl]pentane-2,4-dione and
(E)-3-(1-hydroxyethylidene)-6,6-di(1H-indol-3-yl)hexan-
Ethyl
2-butoxy-6-phenyl-3,4-dihydro-2H-pyran-5-car-
1
boxylate (1b): Colorless liquid; H NMR (CDCl3): d=0.91
(q, J=7.2 Hz, 6H), 1.39 (sext, J=7.6 Hz, 2H), 1.56–1.64 (m,
2H), 1.81–1.90 (m, 1H), 1.93–2.00 (m, 1H), 2.52 (Ja =6.0 Hz,
Jb =8.8 Hz, 2H), 3.59 (dt, Ja =6.4 Hz, Jb =9.2 Hz, 1H), 3.87–
3.95 (m, 3H), 5.18 (dd, Ja =2.4 Hz, Jb =3.6 Hz, 1H), 7.32 (s,
5H); 13C NMR: d=13.7, 13.9, 18.4, 19.3, 26.0, 31.7, 59.7,
68.5, 98.3, 104.5, 127.6, 128.5, 128.7, 137.2, 159.7, 168.2; IR:
n=3082, 3026, 2935, 2872, 1692, 1634, 1446, 1371, 1339,
1292, 1246, 1153, 1125, 1057, 952, 761, 697 cmÀ1; HR-MS
(ESI): m/z=327.1567, calcd. for C18H24NaO4 [M+Na]+:
327.1572.
1-(2-Butoxy-6-methyl-3,4-dihydro-2H-pyran-5-yl)etha-
none (1c): Colorless liquid; 1H NMR (CDCl3): d=0.90 (t,
J=7.6 Hz, 3H), 1.35 (sext, J=7.6 Hz, 2H), 1.55 (quint, J=
6.8 Hz, 2H), 1.71–1.84 (m, 1H), 1.85–1.97 (m, 1H), 2.17 (s,
3H), 2.18 (s, 3H), 2.25–2.35 (m, 1H), 2.41–2.52 (m, 1H),
3.53 (td, Ja =6.4 Hz, Jb =9.6 Hz, 1H), 3.78 (td, Ja =6.8 Hz,
Jb =9.6 Hz, 1H), 5.04 (t, J=3.2 Hz, 1H); 13C NMR: d=13.3,
18.5, 18.8, 20.0, 25.8, 28.8, 31.3, 67.8, 97.0, 109.9, 160.3, 197.7;
IR: n=2959 ,2935, 2872, 1676, 1586, 1454, 1428, 1378, 1355,
1278, 1235, 1218, 1171, 1118, 1063, 1009, 963, 932, 863, 659,
1
2-one (3b): Yellow solid; mp 76–788C; H NMR (CDCl3):
d=1.85 (s, 2H), 1.93 (s, 4H), 1.94–2.10 (m, 2.6H), 2.14–2.24
(m, 1.4H), 3.50 (t, J=6.8 Hz, 0.7H), 4.37 (t, J=7.2 Hz, 1H),
6.68 (d, J=1.4 Hz, 2H), 6.78 (d, J=1.6 Hz, 0.6H), 6.94–7.03
(m, 2H), 7.06 (t, J=7.2 Hz, 2H), 7.10–7.19 (m, 2H), 7.49 (d,
J=8.0 Hz, 1.4H), 7.55 (d, J=8.0 Hz, 0.6H), 7.84 (s, 1.4H),
7.96 (s, 0.6H); 13C NMR: d=22.8, 26.5, 27.2, 29.4, 33.4, 34.2,
36.8, 68.6, 110.7, 111.5, 111.6, 119.1, 119.2, 119.2, 119.2,
119.5, 119.6, 121.8, 121.9, 122.0, 122.0, 126.9, 127.0, 136.7,
136.7, 191.5, 205.4; IR: n=3411, 2922, 1721, 1693, 1618,
1549, 1513, 1487, 1455, 1419, 1357, 1339, 1275, 1244, 1223,
1125, 1095, 1010, 743, 600, 586, 508 cmÀ1; HR-MS (ESI):
m/z=395.1722, calcd. for C24H24N2NaO2 [M+Na]+:
395.1735.
581 cmÀ1
;
HR-MS (ESI): m/z=212.1309, calcd. for
C12H20NaO3 [M+Na]+: 212.1310.
Methyl 2-butoxy-6-methyl-3,4-dihydro-2H-pyran-5-car-
1
boxylate (1d): Colorless liquid; H NMR (CDCl3): d=0.91
(t, J=7.6 Hz, 3H), 1.35 (sext, J=7.6 Hz, 2H), 1.51–1.60 (m,
2H), 1.69–1.79 (m, 1H), 1.81–1.90 (m, 1H), 2.24 (t, J=
1.6 Hz, 3H), 2.26–2.41 (m, 2H), 3.53 (td, Ja =6.4 Hz, Jb =
9.6 Hz, 1H), 3.68 (s, 3H), 3.78 (dt, Ja =6.8 Hz, Jb =9.6 Hz,
1H), 5.03 (dd, Ja =2.4 Hz, Jb =3.6 Hz, 1H); 13C NMR: d=
13.6, 17.5, 19.1, 19.6, 25.9, 31.5, 50.6, 68.1, 97.7, 101.6, 161.6,
168.3; IR: n=2957, 2872, 1710, 1630, 1435, 1380, 1339, 1276,
1119, 1079, 1011, 860, 769 cmÀ1; HR-MS (ESI): m/z=
251.1243, calcd. for C12H20NaO4 [M+Na]+: 251.1259.
tert-Butyl 2-butoxy-6-methyl-3,4-dihydro-2H-pyran-5-
carboxylate (1e): Colorless liquid; 1H NMR (CDCl3): d=
0.83 (t, J=7.2 Hz, 3H), 1.28 (sext, J=8.0 Hz, J=2H), 1.40
(s, 9H), 1.49 (quint, J=8.0 Hz, 2H), 1.60–1.70 (m, 1H),
1.71–1.80 (m, 1H), 2.12 (s, 3H), 2.15–2.30 (m, 2H), 3.44 (td,
2-Methoxyethyl
2-acetyl-5,5-di(1H-indol-3-yl)penta-
noate (3c): Yellow solid; mp 71–738C; 1H NMR (CDCl3):
d=1.80–1.99 (m, 2H), 2.01 (s, 3H), 2.05–2.20 (m, 2H), 3.23
(s, 3H), 3.40 (d, J=7.6 Hz, 1H), 3.42–3.46 (m, 2H), 4.15–
4.21 (m, 2H), 4.40 (t, J=6.8 Hz, 1H), 6.72 (dd, Ja =2.0 Hz,
Jb =9.6 Hz, 2H), 6.97 (t, J=7.2 Hz, 2H), 7.07 (t, J=7.6 Hz,
2H), 7.16 (d, J=8.0 Hz, 2H), 7.50 (d, J=8.0 Hz, 2H), 7.95
(bs, 2H); 13C NMR: d=27.1, 28.9, 33.3, 34.0, 58.9, 59.7, 64.2,
70.2, 111.4, 119.0, 119.1, 119.2, 119.5, 121.7, 122.0, 126.9,
127.0, 136.7, 170.1, 203.9; IR: n=3411, 3115, 3055, 2931,
2871, 1735, 1711, 1642, 1618, 1548, 1487, 1456, 1421, 1370,
1357, 1339, 1245, 1222, 1201, 1151, 1126, 1096, 1042, 1030,
1560
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ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 1551 – 1564

Manganese Chloride as an Efficient Catalyst for Selective Transformations of Indoles
1012, 744, 597, 425 cmÀ1; HR-MS (ESI): m/z=455.1944,
calcd. for C26H28N2NaO4 [M+Na]+: 455.1947.
1340, 1279, 1224, 1187, 1154, 1094, 1012, 743, 691, 588, 489,
420 cmÀ1
HR-MS (ESI): m/z=487.2000, calcd. for
C30H28N2NaO3 [M+Na]+: 487.1998.
;
Methyl 2-acetyl-5,5-bis(5-bromo-1H-indol-3-yl)penta-
noate (3d): Yellow solid; mp 60–628C; 1H NMR (CDCl3):
d=1.81–1.99 (m, 2H), 2.05–2.13 (m, 2H), 2.14 (s, 3H), 3.49
(t, J=6.8 Hz, 1H), 3.68 (s, 3H), 4.28 (t, J=7.2 Hz, 1H), 6.88
(d, J=12.0 Hz, 2H), 7.10 (d, J=8.8 Hz, 2H), 7.16 (d, J=
8.4 Hz, 2H), 7.59 (d, J=4.8 Hz, 2H), 8.23 (bs, 2H);
13C NMR: d=26.9, 29.2, 32.7, 33.9, 52.7, 59.5, 112.3, 113.0,
118.1, 118.3, 121.7, 121.8, 123.1, 124.7, 128.4, 128.4, 135.3,
170.5, 203.8; IR: n=3421, 3401, 3125, 2938, 2869, 1733, 1713,
1566, 1460, 1374, 1360, 1340, 1274, 1219, 1152, 1100, 1049,
885, 797, 648, 586 cmÀ1; HR-MS: (ESI): m/z=566.9867,
calcd. for C24H22Br2N2NaO3 [M+Na]+: 566.9895.
Methyl
2-acetyl-5,5-bis(6-fluoro-1H-indol-3-yl)penta-
noate (3i): Yellow solid; mp 80–828C; 1H NMR (CDCl3):
d=1.86–2.23 (m, 2H), 2.08–2.20 (m, 5H), 3.49 (t, J=7.2 Hz,
1H), 3.66 (s, 3H), 4.36 (t, J=7.6 Hz, 1H), 6.75 (dt, Ja =
0.8 Hz, Jb =9.6 Hz, 2H), 6.86 (d, J=2.0 Hz, 1H), 6.88 (d, J=
2.0 Hz, 1H), 6.90 (d, J=2.0 Hz, 1H), 6.93 (d, J=2.4 Hz,
1H), 7.35–7.41 (m, 2H), 8.17 (bs, 2H); 13C NMR: 13C NMR:
d=27.0, 29.1, 33.0, 34.0, 52.6, 59.6, 97.5, 97.7, 107.7, 107.9,
119.0, 119.1, 120.0, 120.1, 122.0, 122.1, 123.4, 123.4, 136.5,
136.6, 158.6, 161.0, 170.5, 204.1; IR: 3417, 3126, 3068, 2954,
2934, 2865, 1733, 1711, 1625, 1550, 1497, 1455, 1343, 1303,
1251, 1216, 1140, 1121, 1092, 1045, 951, 837, 805, 606,
tert-Butyl 2-acetyl-5,5-di(1H-indol-3-yl)pentanoate (3e):
Yellow solid; mp 64–668C; 1H NMR (CDCl3): d=1.40 (s,
9H), 1.72–2.00 (m, 2H), 2.06 (s, 3H), 2.09–2.26 (m, 2H),
3.33 (t, J=7.2 Hz, 1H), 4.42 (t, J=7.2 Hz, 1H), 6.73 (s, 2H),
6.99 (t, J=7.2 Hz, 2H), 7.09 (t, J=6.8 Hz, 2H), 7.18 (d, J=
8.0 Hz, 2H), 7.53 (d, J=8.0 Hz, 2H), 7.86 (bs, 2H);
13C NMR: d=27.0, 28.0, 28.9, 33.2, 34.1, 61.1, 82.1, 111.4,
119.0, 119.2, 119.2, 119.5, 121.7, 122.0, 127.0, 136.7, 169.4,
204.4; IR: n=3413, 3055, 2976, 2932, 2866, 1729, 1705, 1620,
1549, 1484, 1456, 1420, 1393, 1376, 1339, 1281, 1248, 1142,
1096, 1011, 929, 814, 743, 597 cmÀ1; HR-MS (ESI): m/z=
453.2137, calcd. for C27H30N2NaO3 [M+Na]+: 453.2154.
Methyl 2-acetyl-5,5-di(1H-indol-3-yl)pentanoate (3f):
478 cmÀ1
;
HR-MS (ESI): m/z=447.1512, calcd. for
C24H22F2N2NaO3 [M+Na]+: 447.1496.
Methyl 2-acetyl-5,5-bis(1-methyl-1H-indol-3-yl)penta-
1
noate (3j): Red liquid; H NMR (CDCl3): d=1.86–2.06 (m,
2H), 2.08 (t, J=1.6 Hz, 3H), 2.12–2.30 (m, 2H), 3.40–3.48
(m, 1H), 3.60 (s, 3H), 3.61 (s, 3H), 3.64 (t, J=1.6 Hz, 3H),
4.43–4.53 (m, 1H), 6.83 (td, Ja =1.6 Hz, Jb =7.6 Hz, 2H),
6.98–7.08 (m, 2H), 7.12–7.19 (m, 2H), 7.21 (d, J=8.0 Hz,
2H), 7.58 (q, J=2.8 Hz, 2H); 13C NMR: d=27.3, 29.0, 32.8,
33.8, 34.0, 52.5, 59.8, 109.4, 118.1, 118.3, 118.7, 119.7, 121.5,
126.5, 127.4, 127.5, 137.4, 170.5, 203.5; IR: n=3051, 2948,
2877, 2824, 1739, 1714, 1613, 1547, 1483, 1471, 1425, 1371,
1358, 1328, 1242, 1208, 1153, 1077, 1012, 986, 909, 738, 800,
738, 647, 630, 585, 557, 512 cmÀ1; HR-MS (ESI): m/z=
439.1975, calcd. for C26H28N2NaO3 [M+Na]+: 439.1998.
Ethyl b-oxo-a-(3-oxopropyl)benzenepropanoate (4a):
Colorless liquid; 1H NMR (CDCl3): d=1.06 (t, J=7.2 Hz,
3H), 2.12–2.28 (m, 2H), 2.45–2.62 (m, 2H), 4.04 (dq, Ja =
1.2 Hz, Jb =7.2 Hz, 2H), 4.35 (t, J=7.2 Hz, 1H), 7.39 (t, J=
7.6 Hz, 2H), 7.50 (t, J=7.6 Hz, 1H), 7.20 (dd, Ja =1.2 Hz,
Jb =7.2 Hz, 2H), 9.67 (s, 1H); 13C NMR: d=13.9, 21.2, 41.1,
52.6, 61.5, 128.6, 128.8, 133.7, 135.8, 169.6, 194.9, 201.3; IR:
n=3063, 2981, 2938, 2872, 2831, 2728, 1731, 1685, 1594,
1447, 1369, 1247, 1192, 1164, 1096, 1074, 1024, 1004, 910,
851, 781, 736, 692, 597, 518, 495 cmÀ1.
1
Yellow solid; mp 98–1008C; H NMR (CDCl3): d=1.80–1.95
(m, 2H), 1.98 (s, 3H), 2.02–2.16 (m, 2H), 3.39 (t, J=7.2 Hz,
1H), 3.55 (s, 3H), 4.39 (t, J=7.2 Hz, 1H), 6.66 (dd, Ja =
2.0 Hz, Jb =9.2 Hz, 2H), 6.96 (t, J=7.6 Hz, 2H), 7.05 (t, J=
7.2 Hz, 2H), 7.10 (d, J=8.0 Hz, 2H), 7.50 (dd, Ja =2.4 Hz,
Jb =7.6 Hz, 2H), 7.84 (s, 2H); 13C NMR: d=27.2, 29.1, 33.3,
34.1, 52.6, 59.7, 111.6, 119.0, 119.1, 119.2, 119.5, 121.8, 122.1,
126.9, 127.0, 136.7, 170.7, 204.3; IR: n=3410, 3055, 3008,
2953, 2929, 2864, 1735, 1708, 1618, 1487, 1455, 1430, 1357,
1340. 1278, 1243, 1220, 1151, 1095, 1011, 744, 585 cmÀ1; HR-
MS (ESI): m/z=411.1661, calcd. for C24H24N2NaO3 [M+
Na]+: 411.1685.
Methyl 2-acetyl-5,5-bis(5-methoxy-1H-indol-3-yl)penta-
1
1
noate (3g): Red liquid; H NMR
N
5-Oxo-5-phenylpentanal (4b): Colorless liquid; H NMR
2H), 2.07 (d, J=2.4 Hz, 3H), 2.10–2.22 (m, 2H), 3.46 (q, J=
6.4 Hz, 1H), 3.62 (d, J=1.6 Hz, 3H), 3.74 (d, J=2.8 Hz,
6H), 4.35 (q, J=6.4 Hz, 1H), 6.74–6.79 (m, 2H), 6.79–6.84
(m, 2H), 6.99–7.05 (m, 2H), 7.08 (d, J=8.8 Hz, 2H), 8.04
(bs, 1H), 8.09 (bs, 1H); 13C NMR (CDCl3): d=27.1, 28.9,
33.0, 34.1, 52.5, 56.0, 59.6, 101.7, 101.7, 111.6, 111.7, 112.1,
118.7, 118.8, 122.8, 122.8, 127.3, 132.0, 153.6, 170.6, 203.9,
(CDCl3): d=2.08 (t, J=7.2 Hz, 2H), 2.60 (dt, Ja =1.2 Hz,
Jb =6.8 Hz, 2H), 3.06 (t, J=6.8 Hz, 2H), 7.46 (t, J=8.0 Hz,
2H), 7.56 (tt, Ja =2.0 Hz, Jb =7.2 Hz, 1H), 7.95 (dd, Ja =
1.6 Hz, Jb =8.8 Hz, 2H); 13C NMR: d=16.5, 37.3, 43.1,
128.0, 128.7, 133.2, 136.7, 199.4, 202.0; IR: n=3058, 2963,
2940, 2725, 1726, 1689, 1595, 1448, 1410, 1372, 1292, 1257,
1231, 1197, 1182, 1098, 1072, 1054, 1029, 999, 938, 917, 735,
691, 567 cmÀ1.
204.0; HR-MS (ESI): m/z=471.1892, calcd.
for
C26H28N2NaO5 [M+Na]+: 471.1896.
5-n-Butyl 1-ethyl 2-benzoylpentanedioate (4c): Colorless
1
Ethyl 2-benzoyl-5,5-di(1H-indol-3-yl)pentanoate (3h):
Yellow solid; mp 74–768C; 1H NMR (CDCl3): d=1.05 (t,
J=7.2 Hz, 3H), 2.05–2.18 (m, 2H), 2.18–2.29 (m, 2H), 4.05
(q, J=7.2 Hz, 2H), 4.31 (t, J=6.8 Hz, 1H), 4.46 (t, J=
7.2 Hz, 1H), 6.71 (d, J=2,0 Hz, 2H), 6.97 (q, J=7.2 Hz,
2H), 7.06 (t, J=7.2 Hz, 2H), 7.15 (d, J=8.0 Hz, 2H), 7.29
(t, J=7.6 Hz, 2H), 7.44 (t, J=7.2 Hz, 1H), 7.51 (t, J=
8.4 Hz, 2H), 7.81 (d, J=7.6 Hz, 2H), 7.86 (s, 2H);
13C NMR: d=14.1, 28.0, 33.4, 34.0, 54.4, 61.6, 111.5, 119.1,
119.3, 119.5, 119.5, 121.8, 122.2, 127.0, 127.0, 128.7, 128.8,
133.7, 136.2, 136.7, 136.7, 170.4, 196.0; IR: n=3408, 3055,
2977, 2962, 2932, 2863, 1728, 1678, 1595, 1453, 1453, 1420,
liquid; H NMR (CDCl3): d=0.92 (t, J=7.2 Hz, 3H), 1.18
(t, J=7.2 Hz, 3H), 1.35 (sext, J=7.6 Hz, 2H), 1.59 (quint,
J=7.2 Hz, 2H), 2.30 (dq, Ja =2.0 Hz, Jb =6.4 Hz, 2H), 2.45
(dt, Ja =3.2 Hz, Jb =6.4 Hz, 2H), 4.08 (t, J=6.8 Hz, 2H),
4.14 (dt, Ja =1.2 Hz, Jb =7.2 Hz, 2H), 4.50 (t, J=7.6 Hz,
1H), 7.49 (t, J=7.6 Hz, 2H), 7.60 (tt, Ja =1.2 Hz, Jb =7.6 Hz,
1H), 8.03 (dd, Ja =1.2 Hz, Jb =8.4 Hz, 2H); 13C NMR: d=
13.7, 14.0, 19.1, 24.0, 30.6, 31.5, 52.8, 61.5, 64.5, 128.7, 128.8,
133.6, 136.0, 169.6, 172.9, 195.0; IR: n=3063, 2961, 2935,
2873, 1734, 1686, 1638, 1594, 1449, 1370, 1251, 1184, 1156,
1069, 1025, 980, 876, 854, 781, 740, 693, 597 cmÀ1; HR-MS
(ESI): m/z=320.1629, calcd. for C18H24O5 [M]+: 320.1624.
Adv. Synth. Catal. 2011, 353, 1551 – 1564
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1561

Minghao Li et al.
FULL PAPERS
Methyl 2-acetyl-5,5-bis(5-methylfuran-2-yl)pentanoate
(6a): Colorless liquid; H NMR (CDCl3): d=1.70–1.95 (m,
7.6 Hz, 2H), 2.17 (t, J=7.2 Hz, 2H), 3.16 (s, 2H), 4.14 (t,
J=5.6 Hz, 2H), 4.25 (t, J=5.2 Hz, 2H), 6.43 (d, J=3.2 Hz,
1H), 6.97 (d, J=3.2 Hz, 1H), 7.05 (t, J=7.6 Hz, 1H), 7.14
(t, J=7.2 Hz, 1H), 7.21 (d, J=4.4 Hz, 1H), 7.56 (d, J=
7.6 Hz, 1H); 13C NMR (CDCl3): d=13.6, 17.0, 44.8, 48.8,
63.8, 101.9, 109.4, 119.7, 121.2, 121.8, 128.3, 128.8, 136.2,
167.1, 202.8; IR: n=3103, 3030, 2964, 2953, 2876, 1747, 1714,
1649, 1618, 1513, 1463, 1403, 1364, 1334, 1316, 1260, 1226,
1205, 1154, 1126, 1073, 1047,764, 743, 720, 583, 570,
1
4H), 2.13 (s, 3H), 2.18 (s, 6H), 3.36 (t, J=7.2 Hz, 1H), 3.66
(s, 3H), 3.88 (t, J=7.2 Hz, 1H), 5.80 (s, 2H), 5.87 (d, J=
2.8 Hz, 2H); 13C NMR: d=13.5, 26.0, 28.7, 30.5, 38.7, 52.3,
59.3, 106.0, 106.5, 150.8, 153.0, 170.0, 202.8; IR: n=3105,
2952, 2923, 2872, 1743, 1716, 1613, 1564, 1450, 1436, 1358,
1245, 1217, 1148, 1021, 949, 783 cmÀ1; HR-MS (ESI): m/z=
341.1357, calcd. for C18H22NaO5 [M]+: 341.1365.
Ethyl
2-acetyl-4-(1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-
423 cmÀ1
;
HR-MS (ESI): m/z=296.1247, calcd. for
1H-xanthen-9-yl)butanoate (8a): Yellow liquid; 1H NMR
(CDCl3): d=1.27 (t, J=7.2 Hz, 3H), 1.64–1.75 (m, 2H),
1.77–2.02 (m, 6H), 2.21 (s, 3H), 2.25–2.37 (m, 4H), 2.45–
2.56 (m, 4H), 3.36 (t, J=7.2 Hz, 1H), 3.87 (t, J=8.0 Hz,
1H), 4.19 (q, J=7.2 Hz, 2H); 13C NMR: d=14.1, 19.9, 27.0,
27.2, 28.9, 29.9, 32.8, 33.5, 59.5, 61.5, 117.1, 117.2, 169.6,
191.1, 192.0, 203.0; IR: n=3071, 2957, 2873, 1722, 1650,
1610, 1460, 1426, 1401, 1371, 1328, 1275, 1221, 1183, 1136,
C16H19NNaO3 [M+Na]+: 296.1263.
2-(1H-1-Indolyl)ethyl 2-benzoylacetate ACHTNUTRGNE(NUG 10e): Brown
liquid; 1H NMR (CDCl3): d=3.83 (s, 2H), 4.26 (t, J=
5.2 Hz, 2H), 4.38 (t, J=5.6 Hz, 2H), 6.44 (q, J=1.2 Hz,
1H), 6.99 (d, J=3.2 Hz, 1H), 7.08 (dt, Ja =1.2 Hz, Jb =
6.8 Hz, 1H), 7.16 (t, J=8.0 Hz, 1H), 7.27 (d, J=8.4 Hz,
1H), 7.31–7.42 (m, 2H), 7.51 (t, J=6.8 Hz, 1H), 7.59 (d, J=
8.0 Hz, 1H), 7.77 (dd, Ja =1.6 Hz, Jb =8.8 Hz, 2H);
13C NMR (CDCl3): d=44.9, 45.6, 64.0, 102.0, 109.3, 119.7,
121.2, 121.8, 128.2, 128.6, 128.9, 134.0, 135.8, 136.1, 167.4,
192.4; IR: n=3056, 2954, 1745, 1685, 1617, 1600, 1462, 1451,
1411, 1362, 1333, 1316, 1266, 1208, 1188, 1146, 1102, 1082,
1048, 1012, 1001, 744, 723, 689, 427 cmÀ1; HR-MS (ESI):
m/z=330.1095, calcd. for C19H17NNaO3 [M+Na]+: 330.1106.
1075, 1017, 955, 914, 863, 826, 759, 744, 607, 523, 502 cmÀ1
;
HR-MS (ESI): m/z=374.1723, calcd. for C21H26O6 [M]+:
374.1729.
2-(1H-1-Indolyl)ethyl acetoacetate ACTHNUTRGNEUNG(10a): Brown liquid;
1H NMR (CDCl3): d=2.05 (s, 3H), 3.29 (s, 2H), 4.30 (t, J=
5.2 Hz, 2H), 4.38 (t, J=4.8 Hz, 2H), 6.48 (dd, Ja =0.8 Hz,
Jb =3.2 Hz, 1H), 7.05 (d, J=4.8 Hz, 1H), 7.09 (dt, Ja =
1.2 Hz, Jb =8.0 Hz, 1H), 7.19 (dt, Ja =0.8 Hz, Jb =6.8 Hz,
1H), 7.29 (dd, Ja =0.4 Hz, Jb =8.0 Hz, 1H), 7.60 (d, J=
8.0 Hz, 1H); 13C NMR (CDCl3): d=30.2, 44.8, 49.7, 63.9,
102.0, 109.2, 119.7, 121.2, 121.9, 128.1, 128.7, 136.1, 166.8,
200.4; IR: n=3102, 3054, 2957, 1745, 1716, 1656, 1614, 1513,
1464, 1444, 1403, 1362, 1334, 1315, 1262, 1249, 1203, 1174,
1150, 1051, 1012, 764, 745, 694, 596, 541, 428 cmÀ1; HR-MS
(ESI): m/z=268.0938, calcd. for C14H15NNaO3 [M+Na]+:
268.0950.
2-(1H-1-Indolyl)ethyl
AHCTUNGRTEGNUN(N 10f): Brown liquid; H NMR (CDCl3): d=3.79 (s, 3H), 3.81
2-(4-methoxybenzoyl)acetate
1
(s, 2H), 4.30 (t, J=5.6 Hz, 2H), 4.40 (t, J=5.6 Hz, 2H), 6.44
(d, J=2.8 Hz, 1H), 6.83 (td, Ja =2.0 Hz, Jb =9.2 Hz, 2H),
7.02 (d, J=3.2 Hz, 1H), 7.09 (t, J=8.0 Hz, 1H), 7.17 (t, J=
8.4 Hz, 1H), 7.30 (d, J=8.4 Hz, 1H), 7.60 (d, J=7.6 Hz,
1H), 7.75 (td, Ja =2.0 Hz, Jb =8.8 Hz, 1H); 13C NMR
(CDCl3): d=44.9, 45.4, 55.6, 63.9, 101.9, 109.2, 114.1, 119.7,
121.1, 121.8, 128.2, 128.7, 128.9, 130.9, 136.1, 164.1, 167.6,
190.8; IR: n=3102, 3055, 3009, 2958, 2937, 2841, 1744, 1676,
1601, 1577, 1512, 1463, 1421, 1362, 1318, 1263, 1217, 1174,
1148, 1117, 1083, 1026, 994, 838, 810, 765, 745, 639, 609, 569,
445, 425 cmÀ1; HR-MS (ESI): m/z=360.1206, calcd. for
C20H19NNaO4 [M+Na]+: 360.1212.
2-(1H-1-Indolyl)ethyl isobutyrylacetate ACHTNUTRGNE(NUG 10b): Brown
1
liquid; H NMR (CDCl3): d=1.03 (s, 3H), 1.04 (s, 3H), 2.53
(sept, 6.8 Hz, 1H), 3.37 (s, 2H), 4.30 (t, J=7.6 Hz, 2H), 4.39
(dt, Ja =0.8 Hz, Jb =6.0 Hz, 2H), 6.48 (Ja =0.4 Hz, Jb =
3.2 Hz, 1H), 7.06 (d, J=3.2 Hz, 1H), 7.08 (dt, Ja =0.8 Hz,
Jb =8.0 Hz, 1H), 7.19 (dt, Ja =1.2 Hz, Jb =7.2 Hz, 1H), 7.30
(d, J=8.0 Hz, 1H), 7.60 (d, J=8.0 Hz, 1H); 13C NMR
(CDCl3): d=17.9, 41.3, 44.9, 46.7, 63.8, 101.9, 109.2, 119.7,
121.1, 121.8, 128.1, 128.7, 136.1, 167.2, 206.4; IR: n=3103,
3055, 2972, 2935, 2876, 1748, 1712, 1651, 1618, 1514, 1464,
1363, 1335, 1315, 1102, 1083, 1046, 1011, 969, 764, 744, 720,
695, 421 cmÀ1; HR-MS (ESI): m/z=296.1250, calcd. for
C16H19NNaO3 [M+Na]+: 296.1263.
e-(1H-Indol-3-yl)-1H-indole-3-pentyl acetoacetate ACHTUNGTRENNUNG(12a):
1
Brown liquid; H NMR (CDCl3): d=1.34–1.43 (m, 2H), 1.63
(quint, J=6.8 Hz, 2H), 2.09 (s, 3H), 2.16 (dd, Ja =7.6 Hz,
Jb =15.6 Hz, 2H), 3.30 (s, 2H), 4.03 (t, J=6.8 Hz, 2H), 4.40
(t, J=7.6 Hz, 1H), 6.79 (d, J=2.4 Hz, 2H), 7.00 (dt, Ja =
0.8 Hz, Jb =7.6 Hz, 2H), 7.10 (dt, Ja =0.8 Hz, Jb =7.6 Hz,
2H), 7.20 (d, J=8.4 Hz, 2H), 7.54 (d, J=8.0 Hz, 2H), 7.88
(s, 2H); 13C NMR (CDCl3): d=24.4, 28.4, 30.1, 33.8, 35.2,
49.9, 65.4, 111.2, 118.9, 119.4, 119.8, 121.6, 121.6, 126.9,
136.5, 167.3, 201.2; IR: n=3417, 3056, 2934, 1713, 1618,
1454, 1421, 1338, 1294, 1244, 1221, 1151, 1125, 1094, 1046,
930, 909, 739, 596, 585, 420 cmÀ1; HR-MS (ESI): m/z=
425.1827, calcd. for C25H26N2NaO3 [M+Na]+: 425.1841.
2-(1H-1-Indolyl)ethyl pivaloylacetate
ACHTUNGTRENUN(NG 10c): Brown
1
liquid; H NMR (CDCl3): d=1.09 (s, 7.3H), 1.13 (s, 1.7H),
3.43 (s, 2H), 4.31 (t, J=5.2 Hz, 2H), 4.39 (t, J=5.6 Hz, 2H),
6.47 (d, J=3.2 Hz, 1H), 7.07 (d, J=2.8 Hz, 1H), 7.10 (d, J=
7.6 Hz, 1H), 7.18 (t, J=8.4 Hz, 1H), 7.31 (d, J=8.4 Hz,
1H), 7.60 (d, J=7.6 Hz, 1H); 13C NMR (CDCl3): d=26.0,
43.7, 44.8, 44.9, 63.7, 101.9, 109.3, 119.6, 121.1, 121.8, 128.2,
128.7, 136.1, 167.6, 208.0; IR: n=3102, 3055, 2969, 2937,
2909, 2872, 1748, 1706, 1646, 1614, 1513, 1479, 1464, 1400,
1366, 1334, 1316, 1269, 1240, 1203, 1146, 1101, 1082, 1065,
1049, 1009, 932, 909, 765, 743, 720, 566, 553, 424 cmÀ1; HR-
MS (ESI): m/z=310.1406, calcd. for C17H21NNaO3 [M+
Na]+: 310.1419.
e-[1H-(4-Chloro)indol-3-yl]-1H-(4-chloro)indole-3-
1
pentyl acetoacetate
N
d=1.50–1.60 (m, 2H), 1.66 (quint, J=6.8 Hz, 2H), 1.99 (q,
J=7.6 Hz, 2H), 2.15 (s, 3H), 3.37 (s, 2H), 4.08 (t, J=6.4 Hz,
2H), 5.64 (t, 6.4 Hz, 1H), 6.58 (d, J=2.4 Hz, 2H), 6.97 (dd,
Ja =5.6 Hz, Jb =7.6 Hz, 4H), 7.10 (dd, Ja =2.6 Hz, Jb =
6.8 Hz, 2H), 8.21 (d, J=2.0 Hz, 2H); 13C NMR (CDCl3):
d=24.3, 28.4, 30.2, 33.3, 37.8, 50.0, 65.5, 110.0, 120.3, 121.1,
122.1, 123.1, 123.6, 126.3, 138.1, 167.4, 201.6; IR: n=3420,
3176, 3127, 3065, 2939, 2865, 1740, 1715, 1618, 1558, 1477,
1427, 1362, 1338, 1188, 1149, 1040, 982, 938, 911, 819, 779,
2-(1H-1-Indolyl)ethyl butyroacetate
ACHTUNGTREN(NUNG 10d): Brown liquid;
1H NMR (CDCl3): d=0.79 (t, J=7.6 Hz, 3H), 1.44 (sext, J=
1562
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Adv. Synth. Catal. 2011, 353, 1551 – 1564

Manganese Chloride as an Efficient Catalyst for Selective Transformations of Indoles
746, 555, 547, 492, 475, 411 cmÀ1; HR-MS (ESI): m/z=
493.1053, calcd. for C25H24Cl2N2NaO3 [M+Na]+: 493.1062.
8.4 Hz,1H), 7.41 (d, J=8.0 Hz, 1H), 7.68 (d, J=7.6 Hz,
1H), 7.87 (bs, 1H), 8.95 (bs, 1H); 13C NMR: d=27.6, 27.9,
28.4, 28.6, 29.3, 67.9, 111.2, 111.3, 115.4, 118.9, 119.2, 119.4,
119.4, 119.9, 122.0, 122.5, 123.0, 126.5, 126.6, 130.1, 136.6,
136.7, 206.4, 207.3;IR: n=3416, 3053, 2936, 2856, 1715, 1688,
1617, 1489, 1456, 1419, 1356, 1291, 1223, 1179, 1142, 1090,
1010, 973, 750. 694, 592 cmÀ1; HR-MS (ESI): m/z=393.1588,
calcd. for C24H22N2NaO2 [M+Na]+: 393.1579.
e-[1H-(5-Bromo)indol-3-yl]-1H-(5-bromo)indole-3-
1
pentyl acetoacetate
N
d=1.27–1.38 (m, 2H), 1.60 (quint, J=6.8 Hz, 2H), 2.04–2.12
(m, 2H), 2.15 (s, 3H), 3.38 (s, 2H), 4.03 (t, J=6.8 Hz, 2H),
4.22 (t, J=7.6 Hz, 1H), 6.88 (d, J=2.0 Hz, 2H), 7.10 (d, J=
8.4 Hz, 2H), 7.16 (dd, Ja =1.6 Hz, Jb =8.4 Hz, 2H), 7.61 (d,
J=1.6 Hz, 2H), 8.20 (d, J=2.0 Hz, 2H); 13C NMR (CDCl3):
d=24.3, 28.2, 30.2, 33.8, 34.6, 50.0, 65.4, 112.2, 112.8, 118.9,
121.8, 122.9, 124.5, 128.5, 135.2, 167.3, 201.4; IR: n=3418,
3123, 3075, 2936, 2862, 1732, 1716, 1642, 1622, 1566, 1455,
1415, 1359, 1317, 1277, 1268, 1175, 1151, 1097, 1037, 883,
866, 795, 766, 755, 584, 421 cmÀ1; HR-MS (ESI): m/z=
581.0025, calcd. for C25H24Br2N2NaO3 [M+Na]+: 581.0051.
Acknowledgements
The authors thank the National Natural Science Fundation of
China for the financial support (20903042). This work was
also supported by Specialized Research Fund for the Doctor-
al Program of Higher Education (20090142120081). The
Program for new Century Excellent Talents in the University
of China (NCET-10-0383) and Chutian Scholar Program of
the Hubei provincial government are also acknowledged. YG
thanks also Ms. Ping Liang and all the other stuff members
in the Analytical and Testing Center of HUST, for her sup-
portive and constant contributions to our work.
e-[1H-(1-Methyl)indol-3-yl]-1H-(1-methyl)indole-3-
1
pentyl acetoacetate
N
d=1.38–1.50 (m, 2H), 1.68 (quint, J=6.8 Hz, 2H), 2.11 (s,
3H), 2.20 (dd, Ja=7.6 Hz, Jb=15.6 Hz, 2H), 3.29 (s, 2H),
3.63 (s, 6H), 4.07 (t, J=6.8 Hz, 2H), 4.44 (t, J=7.6 Hz, 1H),
6.82 (s, 2H), 7.01 (dt, Ja =0.8 Hz, Jb =8.0 Hz, 2H), 7.15 (dt,
Ja =0.8 Hz, Jb =8.0 Hz, 2H), 7.22 (d, J=8.0 Hz, 2H), 7.58
(d, J=8.0 Hz, 2H); 13C NMR (CDCl3): d=24.7, 28.7, 30.2,
32.7, 33.9, 36.0, 50.1, 65.5, 109.3, 118.6, 118.9, 119.7, 121.4,
126.3, 127.6, 137.4, 167.3, 200.9; IR: n=3054, 3026, 2935,
2865, 2825, 1740, 1716, 1622, 1548, 1471, 1421, 1372, 1327,
1242, 1151, 1098, 1039, 1013, 972, 911, 945, 798, 737, 549,
539, 418, 410 cmÀ1; HR-MS (ESI): m/z=453.2159, calcd. for
C27H30N2NaO3 [M+Na]+: 453.2154.
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e-[1H-(5-Methoxy)indol-3-yl]-1H-(5-methoxy)indole-3-
1
pentyl acetoacetate
N
d=1.36–1.47 (m, 2H), 1.61–1.71 (m, 2H), 2.13 (s, 3H), 2.14–
2.20 (m, 2H), 3.33 (s, 2H), 3.74 (s, 6H), 4.06 (t, J=6.8 Hz,
2H), 4.32 (t, J=7.6 Hz, 1H), 6.77 (dd, Ja =2.4 Hz, Jb =
8.4 Hz, 2H), 6.87 (d, J=2.0 Hz, 2H), 7.01 (d, J=2.4 Hz,
2H), 7.13 (d, J=8.8 Hz, 2H), 8.04 (s, 2H); 13C NMR
(CDCl3): d=24.4, 28.4, 30.1, 33.8, 34.9, 50.0, 55.9, 65.4,
101.8, 111.3, 111.8, 119.4, 122.5, 127.4, 131.8, 153.4, 167.3,
201.2; IR: n=3417, 2937, 2860, 2831, 1736, 1716, 1622, 1585,
1477, 1452, 1415, 1359, 1210, 1171, 1104, 1038, 921, 835, 799,
773, 750, 733, 628, 543, 415 cmÀ1; HR-MS (ESI): m/z=
485.2043, calcd. for C27H30N2NaO5 [M+Na]+: 485.2052.
e-[1H-(6-Fluoro)indol-3-yl]-1H-(6-fluoro)indole-3-
1
pentyl acetoacetate
N
d=1.32–1.43 (m, 2H), 1.58–1.70 (m, 2H), 2.08–2.18 (m,
5H), 3.36 (s, 2H), 4.05 (t, J=6.8 Hz, 2H), 4.32 (t, J=7.6 Hz,
1H), 6.74 (dt, Ja =2.4 Hz, Jb =9.6 Hz, 2H), 6.88 (d, J=
2.4 Hz, 2H), 6.92 (dd, Ja =2.4 Hz, Jb =9.6 Hz, 2H), 7.38 (dd,
Ja =5.2 Hz, Jb =8.8 Hz, 2H), 8.12 (d, J=1.6 Hz, 2H);
13C NMR (CDCl3): d=24.3, 28.4, 30.1, 33.8, 34.9, 50.0, 65.4,
97.3, 97.6, 107.5, 107.8, 119.7, 120.0, 120.1, 121.7, 121.8,
123.5, 136.4, 136.5, 158.6, 160.9, 167.3, 201.4; IR: n=3417,
3217, 3125, 3066, 2938, 2862, 1735, 1715, 1622, 1552, 1495,
1454, 1410, 1140, 1092, 1036, 952, 910, 837, 801, 732, 605,
486, 477, 420 cmÀ1; HR-MS (ESI): m/z=461.1658, calcd. for
C25H24F2N2NaO3 [M+Na]+: 461.1653.
1,1’-(4-(1H-indol-3-yl)-2,3,4,9-tetrahydro-1H-carba-
zole-1,1-diyl)diethanone ACTHNUTRGNEUGN(15a): Yellow solid, mp 100–
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