Base-mediated chemo- and stereoselective addition of 5-aminoindole/ tryptamine and histamines onto alkynes

Article abstract of DOI:10.1021/jo402352v

Transition-metal-free chemo- and stereoselective addition of 5-aminoindole (1a), tryptamine (1b), and histamine (1c) to alkynes 2a-s to synthesize the indolyl/imidazolyl enamines 3a-p, 5a-o, and 6a-e using superbasic solutions of alkali-metal hydroxides in DMSO is described. The addition of N-heterocycles onto alkynes takes places chemoselectively without affecting the 1 amino groups (aromatic and aliphatic) of 5-aminoindole, tryptamine, and histamine. The stereochemistry of the products was found to be dependent upon reaction time; an increase in reaction time leads to the formation of a mixture of E/Z isomers and the thermodynamically stable E addition product. The chemoselective addition of N-heterocycle 1a onto alkyne over thiophenol 7 and phenol 8 is supported by control experiments. Competitive experiments showed that 5-aminoindole was more reactive than tryptamine, and histamine was found to be the least reactive. The present methodology provides an efficient chemoselective method to synthesize a variety of (Z)-enamines of 5-aminoindole, tryptamine, and histamine without affecting the 1 amino group. The presence of the free amino group in enamines could be further used for synthetic elaboration, which proved to be highly advantageous for structural and biological activity assessments.

Full text of DOI:10.1021/jo402352v

Article
pubs.acs.org/joc
Base-Mediated Chemo- and Stereoselective Addition of
5‑Aminoindole/Tryptamine and Histamines onto Alkynes
Akhilesh K. Verma,*,† Monika Patel,† Megha Joshi,† Pravin R. Likhar,‡ Rakesh K. Tiwari,§
and Keykavous Parang§
†Synthetic Organic Chemistry Research Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India
‡Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500607, India
§College of Pharmacy, Chapman University, Orange, California 92866, United States
S
* Supporting Information
ABSTRACT: Transition-metal-free chemo- and stereoselec-
tive addition of 5-aminoindole (1a), tryptamine (1b), and
histamine (1c) to alkynes 2a−s to synthesize the indolyl/
imidazolyl enamines 3a−p, 5a−o, and 6a−e using superbasic
solutions of alkali-metal hydroxides in DMSO is described.
The addition of N-heterocycles onto alkynes takes places
chemoselectively without affecting the 1° amino groups
(aromatic and aliphatic) of 5-aminoindole, tryptamine, and
histamine. The stereochemistry of the products was found to
be dependent upon reaction time; an increase in reaction time
leads to the formation of a mixture of E/Z isomers and the
thermodynamically stable E addition product. The chemo-
selective addition of N-heterocycle 1a onto alkyne over
thiophenol 7 and phenol 8 is supported by control experiments. Competitive experiments showed that 5-aminoindole was more
reactive than tryptamine, and histamine was found to be the least reactive. The present methodology provides an efficient
chemoselective method to synthesize a variety of (Z)-enamines of 5-aminoindole, tryptamine, and histamine without affecting
the 1° amino group. The presence of the free amino group in enamines could be further used for synthetic elaboration, which
proved to be highly advantageous for structural and biological activity assessments.
Several methodologies have been developed for the synthesis
of functionalized tryptamines. For example, the substrates
obtained by the Japp−Klingemann reaction are well-known for
obtaining a diverse class of tryptamines.9 In 1997, Dong and
Busacca provided an easily accessible route for the synthesis of
tryptamines and tryptophols by using sequential transition-
metal-catalyzed reactions via a regioselective hydroformylation
of functionalized anilines.10 Beller and co-workers reported a
titanium-catalyzed one -pot synthesis of tryptamines and their
derivatives using chloroalkylalkynes and arylhydrazines.11 Nicolau
and co-workers have developed an elegant cascade approach for
the synthesis of substituted tryptamines from anilines.12
INTRODUCTION
■
Indole and its derivatives are widespread components of a variety of
natural products and drug molecules.1 Tryptamines and the other
members of this class such as serotonin, melatonin, and histamine
represent important examples, due to their potent neurological
activities.2,3 Other drugs belonging to the tryptan class such as
sumatriptan, rizatriptan, and zolmitriptan (Figure 1) have proven to
be significant advances in the acute treatment of migraine
headaches.4 Glennon and co-workers reported substituted trypt-
amines as efficient agents with high selectivity for the 5-HT6
serotonin receptor.5 Thus, due to the medicinal and pharmaceutical
importance of indoles and tryptamines, functionalization of these
heterocycles using cost-effective and easily accessible starting
materials is an important area of current research.6
The stereo- and chemoselective synthesis of alkenes and
biologically important compounds is an important protocol for
the synthesis of natural products and industrially relevant
compounds.7 Very recently Feringa and co-workers found a
significant improvement in antibacterial activity of the aza
analogue of the quinolones by optical control of the
stereochemistry of the product. The Z isomer of the aza-
quinolone was found to be 4- and 8-fold active on E. coli
(Gram-negative) and M. luteus (Gram-positive)8 (Figure 2).
The formation of N−C bonds by the addition of amines and
N-heterocycles to alkenes and alkynes represents an attractive
process for the synthesis of nitrogen heterocycles, enamines,
substituted amines, imines, and natural products.13 The inter-
and intramolecular additions of primary amines to alkynes have
been well recognized. A wide variety of catalysts such as
titanium,14 zirconium,15 tantalum,16a rhodium,16b cesium,17a
17b
and K3PO4
have been used for the addition of primary
Received: October 25, 2013
© XXXX American Chemical Society
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Figure 1. Common antimigraine drugs to tryptan family.
Scheme 1. N-Alkenylation of Indoles using a Palladium
Catalyst
involved (i) base-mediated regio- and stereoselective inter-
molecular addition of alkynes to N-heterocycles22a and (ii)
regioselective preferential nucleophilic addition of N-hetero-
cycles to haloarylalkynes over N-arylation of aryl halides,
confirming the mechanism proposed for the synthesis of
indolo- and pyrrolo[2,1-a]isoquinolines.22b In a continuation of
our ongoing work on the hydroamination of alkynes, herein we
wish to report the chemo- and stereoselective addition of 5-
aminoindole, tryptamine, and histamine without affecting the 1°
amino group (Scheme 2). The presence of a free amino group in
enamines could be further used for synthetic elaboration, which
increases the synthetic utility of this developed procedure for
structural and biological activity assessments.
Figure 2. Antibacterial activity of E and Z isomers of aza-quinolone.
amines onto alkynes (Figure 3A). Yamamoto and Marks have
explored the intramolecular catalytic hydroamination strategy
RESULTS AND DISCUSSION
■
To identify the optimal reaction conditions for the reaction, we
examined the reaction of 5-aminoindole (1a) with 3-ethynyl-
toluene (2a) using our previously optimized reaction
conditions, i.e. 0.2 equiv of KOH in DMSO at 120 °C for
30 min,; the product (Z)-1-(3-methylstyryl)-1H-indol-5-amine
(3a) was obtained in 45% yield (Table 1, entry 1).22 The
product 3a was obtained in 74% yield upon increasing the
loading of KOH from 0.2 to 0.5 equiv (entry 2); however, the
use of 1.0 equiv of base gave no improvement in the yield of the
product 3a (entry 3). An increase in the reaction time from 0.5
to 1 h provided the product 3a in 72% yield in a 40:60
stereoisomeric ratio (entry 4). However, a further increase in
reaction time from 1 to 2 h provided the thermodynamically
stable trans isomer in a 95:5 ratio in 70% yield (entry 5). When
the reaction was carried out at 100 °C for 2 h, product 3a was
obtained in 43% yield in a 10:90 stereoisomeric ratio (entry 6).
An increase in reaction temperature afforded the product 3a in
comparatively lower yield (entry 7). Other bases such as
NaOH, CsOH·H2O, and KOtBu afforded the product 3a in 69,
62, and 60% yields respectively (entries 8−10); however, Et3N
was found to be ineffective (entry 11). When the reaction was
carried out in the absence of base, the reactants remained
almost unchanged during the course of the reaction (entry 12).
Applying Ruimao conditions, no hydroamination product was
observed (entries 13 and 14).23,24 The use of zirconium,
palladium, and copper catalysts reported in the literature for
Figure 3. Selected examples of the hydroamination of alkynes using
primary and secondary amines.
for the construction of pyrrolidine heterocycles (Figure 3B).18
An elegant approach for the synthesis of indoles and pyrroles
was reported by Knochel19a,b and Ackermann19c−g by using
hydroamination chemistry. However, in contrast to the addition
of primary and secondary amines, addition of N-heterocycles to
alkynes has not been much explored.
In 1999 Knochel reported the first example of the addition of
heterocyclic amines to alkynes17 using CsOH·H2O, and later
Kondo20a reported the addition of pyrrole to diphenylacetylene
using the phosphazene superbase P4-t-Bu. Very recently Wu20b
and co-workers reported the regio- and stereoselective N-alkenyl-
ation of indoles20c using a palladium catalyst (Scheme 1).
In 2009 we reported the copper-catalyzed tandem synthesis
of indolo- and pyrrolo[2,1-a]isoquinolines via hydroamination
followed by intramolecular C-2 arylation.21 Our recent study
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Scheme 2. Chemo- and Stereoselective Addition of 5-Aminoindole, Tryptamine, and Histamine to Alkynes
a
Table 1. Optimization of the Reaction Conditions
b
c
entry
alkyne
base (amt (equiv))
catalyst
solvent
time (h)/T (°C)
yield (%) of 3a/3p (E:Z)
d
1
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2p
2p
2p
2p
2p
KOH (0.2)
KOH (0.5)
KOH (1.0)
KOH (0.5)
KOH (0.5)
KOH (0.5)
KOH (0.5)
NaOH (0.5)
CsOH·H2O (0.5)
KOtBu (0.5)
Et3N (0.5)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
toluene
DMF
0.5/120
0.5/120
0.5/120
1.0/120
2.0/120
2.0/100
0.5/140
0.5/120
1.0/120
1.0/120
24/120
6.0/120
24/100
24/120
24/100
4/80
45 (0:100)
d
2
74 (0:100)
d
3
74 (00:100)
d
4
72 (40:60)
d
5
70 (95:05)
d
6
43 (10:90)
d
7
64 (00:100)
d
8
69 (00:100)
d
9
62 (00:100)
d
10
11
12
1323
1424
1515
1625
1726
60 (20:80)
NR
NR
CuCl
NR
AgOTf
NR
Cp2ZrCl2
toluene
MeCN
NMP
e
e
e
e
e
e
f
PA-Pd
g
g
K2CO3
Cu/Al-HT
Cp2ZrCl2
24/120
1.0/100
1.0/80
h
18
toluene
MeCN
NMP
h
f
19
PA-Pd
h
20
K2CO3
Cu/Al-HT
1.0/120
20/120
20/120
20/120
20/120
20/120
i
21
22
23
24
25
KOH (0.5)
KOH (1.0)
KOH (2.0)
KOH (2.5)
KOH (2.0)
DMSO
DMSO
DMSO
DMSO
toluene
30 (00:100)
i
42 (00:100)
i
62 (00:100)
i
62 (00:100)
NR
a
b
Reactions were performed using N-heterocycle 1a (1.0 mmol), alkyne 2a/2p (1.0 mmol), and 1.5 mL of solvent. Total yield of two isomers.
c
d
e
f
g
h
Stereoisomeric ratio. Product 3a is formed. Inseparable complex mixtures. PA denotes polymer assisted. HT is the hydrotalcite of Cu/Al. Using
i
microware irradiation at 100 W. Product 3p is formed.
the hydroamination of primary amines failed to provide the
hydroaminated product 3a/4a (entries 15−17).15,25,26 The
reaction was also performed under microwave conditions using
the above catalysts; however, we failed to obtain the
hydroaminated product (entries 18−20). The reaction of the
internal alkyne 1,2-di-m-tolylethyne (2p) with 1a using 0.5
equiv of KOH at 120 °C for 20 h afforded the product 3p in
30% yield (entry 21). An increase of KOH loading from 0.5 equiv
to 1.0 and then to 2.0 equiv afforded the product 3p in 42 and 62%
yields, respectively, with Z stereoselectivity (entries 22 and 23). A
further increase of the loading of base from 2.0 to 2.5 equiv gave no
improvement in the yield of the product 3p (entry 24). Toluene
was found to be ineffective for the reaction (entry 25).
Chemoselective Addition of 5-Aminoindole to Alkynes.
After optimizing the reaction conditions for the chemoselective
addition of alkynes onto amines, we examined the scope and
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a
Table 2. Chemo- and Stereoselective Addition of 5-Aminoindole to Alkynes
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Table 2. continued
a
Reactions were performed using 1a (1.0 mmol), alkyne 2 (1.0 mmol), and 0.5 equiv of KOH in 1.5 mL of DMSO at 120 °C for 0.5 h unless
b
c
d
otherwise noted. Reaction was run for 2.0 h. Reaction was run for 1.0 h. Reaction was carried out using 2.0 equiv of KOH for 20 h.
generality of the reaction by utilizing a variety of alkynes (Table 2,
entries 1−16). Addition of 5-aminoindole (1a) on terminal
alkynes 2a−n provided the corresponding Z-addition products
3a−n chemoselectively in good yields without affecting the 1°
amino group (entries 1−14). The substituents attached on the
alkynes have no significant effect on the yields of the products
(entries 1−8). The reaction of 1,3-diethynylbenzene (2i) with 1a
provided the monohydroaminated product 3i in 46% yield along
with an inseparable complex mixture of other possible byproducts
(entry 9). Reaction of alkyne 2j with 1a for 2 h provided the E-
addition product 3j in 72% yield (entry 10); however, reaction of
alkynes 2k−n with 5-aminoindole for 1 h provided mixtures of
E/Z isomers 3k−n in 69−75% yields (entries 11−14). Reactions
of internal alkynes 2o,p afforded the hydroaminated products 3o,p
in moderate yield using 2.0 equiv of KOH at 120 °C for 20 h
(entries 15 and 16).
agents having wide applications in pharmaceutical and
medicinal chemistry.2,3 Tryptamine-based drugs such as
sumatriptan, rizatriptan, and zolmitriptan have attracted
considerable attention due to their prominent biological
activities. The success of the chemoselective addition of the
5-aminoindole onto alkynes encouraged us in the addition of
tryptamine (bearing a 1° aliphatic amino group) to alkynes.
Under the optimized reaction conditions (Table 1, entry 2),
reaction of tryptamine (1b) with alkynes 2a−r afforded the
desired (Z)-styryl enamines 5a−l,n,o chemoselectively in
moderate to good yields (Table 3, entries 1−12, 14, and 15).
It is interesting to note that no hydroamination was observed
on the 1° amino group of the tryptamine. Dialkyne 2i on
reaction with 1b provided the monohydroaminated product 5f
with Z stereoselectivity in 42% yield (entry 6). However, when
the reaction of 1b with dialkyne 2s was allowed to run for 3 h,
the product 5m was obtained in 40% yield with E stereo-
selectivity (entry 13). Internal alkynes 2o,p provided the Z
isomers in 60 and 62% yields, respectively (entries 14 and 15).
Chemo- and Stereoselective Addition of Tryptamine
to Alkynes. The tryptamine skeleton is an important
substructure occurring in both natural products and therapeutic
E
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a
Table 3. Chemo- and Stereoselective Addition of Tryptamine to Alkynes
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Table 3. continued
a
The reactions were performed using amines 1 (1.0 mmol), alkynes 2 (1.0 mmol), and 0.5 equiv of KOH in 1.5 mL of DMSO at 120 °C for 1 h
b
c
unless otherwise noted. The reaction was run for 3 h. The reaction was performed using 2.0 equiv of KOH for 24 h.
Chemo- and Stereoselective Addition of Histamine to
role in many immunological and natural processes.27 The
Alkynes. Histamine and its derivatives play a very significant
success of the chemoselective addition of 5-aminoindole 1a
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a
Table 4. Chemo- and Stereoselective Addition of Histamine to Alkynes
a
The reactions were performed using N-heterocycle 1 (0.5 mmol), 1.0 mmol of the alkyne 2, and 0.5 equiv of KOH in 1.5 mL of DMSO at 120 °C
b
c
d
e
for 2 h. Reaction was run for 4 h. Reaction was run for 3 h. Reaction was run for 24 h. Triethylamine (2.0 equiv) was added.
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Scheme 3. Competitive Study: Hydroamination vs Thiolation and Hydroxylation
Scheme 4. Reactivity Behavior of 5-Aminoindole, Tryptamine, and Histamine with Alkynes
and, tryptamine 1b onto various terminal and internal alkynes
further encouraged us for the reaction of commercially available
histamine 1c onto alkynes (Table 4).
Further reaction of histidine methyl ester hydrochloride 1d
with alkyne 2q (using triethylamine for neutralization) under
the optimized reaction conditions did not provide the desired
product 6g (entry 7).
Comparative Study: Hydroamination vs Thiolation
and Hydroxylation. Base-catalyzed nuleophilic addition
reactions of alkynes were first reported in 1957,28 and later
on the pioneering work of Trofimov et al. further demonstrated
that a KOH−DMSO suspension played an important role in
the activation of a variety of nucleophilic substrates.29 In a
recent report by his group,30 they also explained that the
Reaction of histamine 1c with alkyne 2q provided the Z-
addition product 6a selectively in 50% yield after running the
reaction for 2 h (Table 4, entry 1). However, to obtain the
stereoselective E-addition product 6b, it required 4 h to
complete the reaction (entry 2). When the reaction was
allowed to run for 3 h, a mixture of E/Z isomers was obtained
(entries 3−5). However, addition of histamine onto internal
alkyne 2o failed to give the desired product 6f (entry 6).
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addition of N-heterocyclic amines to alkynes is an exception to
the trans-nucleophilic addition rule.31 In our reaction system,
we also observed that other nucleophiles such as phenols and
thiols react with alkynes at a snail’s pace in contrast to the case for
N-heterocycles, to provide the corresponding addition products in
the superbasic KOH−-DMSO suspension (Scheme 3).32
in 52% yield (Scheme 4iii). Finally, we performed a combined
reaction using heterocycles 1a−c with 3 equiv of alkyne 2b for 0.5
h and found that Z-stereoselective products 3a and 5a were
obtained in 70 and 44% yields, respectively; however, product 6c
was obtained in only 15% yield (Scheme 4iv).
These observations can be explained on the basis of the
reactivity behavior of 1a−c (Figure 4). In the case of 1a, the
In order to observe the comparative studies between 5-
aminoindole (1a), 4-methoxythiophenol (7), and 4-methyl-
phenol (8) with alkyne 2a, we carried out a control experiment
(Scheme 3i). First we reacted 1a, 7, and 8 (1.0 mmol each)
with 1.0 mmol of alkyne 2a using 0.5 equiv of KOH in 1.5 mL
of DMSO at 120 °C for 30 min. We observed that product 3a
was obtained in 73% yield; however, the formation of
compounds 9 and 10 was not observed. In another set of
reactions we carried out the reaction of 1a, 7, and 8 with
3.0 mmol of alkyne 2a using 1.5 equiv of KOH at 120 °C for
8 h. It was noted that product 3a (E isomer) was obtained in
68% yield along with a trace amount of thiolation product 9,
and no hydroxylation product 10 was observed (Scheme 3ii).
The possible reason could be due to the low nucleophilicity of
the thiophenol and phenol in comparison to that of indole.
Another control experiment was performed using 5-amino-
indole and carbazole 11 as N-nucleophile. We carried out the
reaction of 1a (1.0 mmol) and 11 (1.0 mmol) with 1.0 mmol of
alkyne 2a using 0.5 equiv of KOH at 120 °C for 0.5 h. It was
observed that product 3a (Z isomer) was found in 72% yield;
however, formation of product 12 was not observed. The
possible reason for this could be the tricyclic structure of the
carbazole, which alters its nucleophilicity (Scheme 3iii).
The nucleophilicity of the heterocyclic amine plays an
important role in the product formation. The enamines 3a−p
synthesized from 5-aminoindole (1a) and alkynes 2a−p were
obtained in good yields and required less reaction time;
however, products 5a−o synthesized by using tryptamine 1b
were obtained in moderate yields and required longer reaction
time in comparison to heterocycle 1a. The products 6a−e
obtained by the reaction of histamine 1c with alkynes
2a,g,j,k,o,q were obtained in lower yields and required longer
reaction times in comparison to the case for 1a,b (compare the
yields and reaction times of the products of Tables 1 and 2 vs
Table 3).
To validate the reactivity behavior of 5-aminoindole,
tryptamine, and histamine with alkynes, we performed four
sets of reactions and monitored the formation of products at
different time intervals (Scheme 4). In the first set of reactions
we reacted 1a with alkyne 2a using 0.5 equiv of KOH and
monitored the reaction products after 25, 45, and 120 min
intervals. We observed that after 25 min product 3a (only Z
isomer) was obtained in 74% yield; however, after 45 min a
40:60 E:Z mixture was obtained in 72% yield and after 2 h the
thermodynamically stable E isomer was observed in 70% yield
(Scheme 4i). Similarly, in another set of reaction we performed
the reaction of tryptamine 1b with alkyne 2a using reaction
conditions similar to those used for the first set of reactions; we
noticed that after 25 min product 5a (only Z isomer) was
formed in only 36% yield and after 45 min the stereoselective
Z-addition product was obtained in 62% yield. Running the
reaction for 2 h, we observed that mixture of E and Z isomers
were obtained in a 30:70 sterioisomeric ratio (Scheme 4ii). The
reaction of histamine 1c with 2a was found to be sluggish, as the
hydroaminated product 6c (only Z isomer) was obtained in only
10 and 30% yields after running the reaction for 25 and 45 min;
however, after 2 h the Z-stereoselective product 6c was obtained
Figure 4. pKa values and reactivity behavior of the N-heterocycles 1a−c.
presence of the electron-rich indole ring system (+R effect of
−NH2) increases the reactivity of the N-heterocyclic amine,
which facilitates the formation of the addition products,
whereas in the case of histamine 1c, the nucleophilicity of
−NH decreases due to the −I effect of another nitrogen
present in the ring. The pKa values of 5-aminoindole (1a;
17.38), tryptamine (1b; 10.02), and histamine (1c; 6.04) also
support the reactivity behavior of the N-heterocycles.33
CONCLUSION
■
In conclusion, we have demonstrated a general and efficient
approach for the chemo- and stereoselective addition of 5-
aminoindole, tryptamine, and histamine to a broad range of
alkynes to synthesize a variety of indolyl/imidazolyl enamines.
This developed chemistry involves base-mediated and tran-
sition-metal-free chemoselective addition of benchtop and
inexpensive N-heterocycles to commercially available alkynes
without affecting the 1° amino groups (aromatic and aliphatic)
present in the substrates and provides a synthetically useful
handle in the products for further elaboration. The stereo-
chemistry of the products can be controlled by tuning the
reaction time. Competition experiments demonstrated the
chemoselective addition of 5-aminoindole onto alkyne over
thiophenol and phenol. We observed that 5-aminoindole was
more reactive than tryptamine, and histamine was found to be
the least reactive, as validated by the control experiments. It is
likely that the operational simplicity of the developed protocol
will make it attractive for the synthesis of a variety of
stereoselective enamines of biological importance. Further
investigations of the scope of this attractive chemistry are
underway and will be reported in due course.
EXPERIMENTAL SECTION
■
General Information and Method. All of the reactions were
performed in an oven-dried Schlenk flask under an argon atmosphere.
Column chromatography was performed using neutral and basic
alumina. TLC analysis was performed on commercially prepared 60
F254 silica gel plates. Visualization of spots on TLC plates was
accomplished with UV light (254 nm) and staining over an I2
1
chamber. H NMR (400 MHz) and 13C NMR (100 MHz) spectra
were recorded in CDCl3 and (CD3)2SO. Chemical shifts for carbons
are reported in ppm from tetramethylsilane and are referenced to the
carbon resonance of the solvent. Data are reported as follows:
chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet, dd = doublet of doublets, br s = broad singlet),
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coupling constants in hertz, and integration. High-resolution mass
spectra were recorded with a q-TOF electrospray mass spectrometer,
and Iinfrared spectra were recorded on a FT-IR spectrophotometer.
All purchased chemicals were used as received. All melting points are
uncorrected.
General Procedure for the Synthesis of Internal Alkyne 2p.
The 1,2-diarylalkyne 2p was prepared by the Sonogashira coupling
reaction of the corresponding aryl iodide with terminal alkynes using
the reported procedure and confirmed by comparison of its physical
and spectral data (1H NMR, 13C NMR, and HRMS) with those
reported in the literature.34
General Procedure for the Addition of N-Heterocycles to
Alkynes. The compounds were synthesized as per the previously
reported procedure.22 To a solution of the N-heterocycle (1.0 mmol)
in 1.5 mL of DMSO were added finely crushed KOH (0.5 equiv) and
alkyne (1.0 mmol). The resulting mixture was heated at 120 °C. The
progress of the reaction was monitored by TLC. After the complete
consumption of alkynes, the reaction mixture was warmed to room
temperature. The reaction mixture was diluted with water (8 mL) and
extracted with ethyl acetate (5 mL × 3); further, the organic layer was
washed with brine solution (5 mL × 3) and dried over Na2SO4. The
crude reaction mixture was purified by column chromatography, using
basic/neutral aluminum oxide.
2.7 Hz, 1H), 6.25 (d, J = 2.9 Hz, 1H), 6.18 (d, J = 8.8 Hz, 1H), 4.64
(br s, 2H), 2.52−2.48 (m, 2H), 1.53−1.46 (m, 2H), 1.32−1.21 (m,
2H), 0.86 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, (CD3)2SO) δ
142.7, 141.5, 132.4, 129.0, 128.9, 128.3, 126.4, 123.3, 117.8, 112.3,
110.6, 103.8, 102.8, 34.6, 32.9, 21.8, 13.8; IR spectrum in film (νmax
,
cm−1) 3394, 2923, 2854, 1655, 1460, 806, 766, 734; HRMS (ESI)
calcd for C20H22N2 (M + H+) 291.1861, found 291.1861.
(Z)-1-(4-tert-Butylstyryl)-1H-indol-5-amine (3f). The product was
obtained as a brown oil (217.5 mg, 75%): 1H NMR (400 MHz,
(CD3)2SO) δ 7.22 (d, J = 8.7 Hz, 2H), 7.04 (t, J = 7.8 Hz, 3H), 6.93−
6.89 (m, 2H), 6.65 (d, J = 1.8 Hz, 1H), 6.49 (dd, J = 8.7 and 2.3 Hz,
1H), 6.22 (d, J = 3.2 Hz, 1H), 6.14 (d, J = 9.1 Hz, 1H), 4.62 (br s,
2H), 1.18 (s, 9H); 13C NMR (100 MHz, (CD3)2SO) δ 149.9, 142.8,
132.2, 129.1, 129.0, 128.2, 126.4, 125.2, 123.4, 117.8, 112.4, 110.6,
103.9, 102.9, 34.4, 31.1; IR spectrum in film (νmax, cm−1) 3326, 2961,
1648, 1478, 800, 756, 717; HRMS (ESI) calcd for C20H22N2 (M + H+)
291.1861, found 291.1860.
(Z)-1-(3-Methoxystyryl)-1H-indol-5-amine (3g). The product was
obtained as a brown semisolid (200.6 mg, 76%): 1H NMR (400 MHz,
(CD3)2SO) δ 7.16 (t, J = 8.0 Hz, 1H), 7.07−7.01 (m, 2H), 6.91(d, J =
2.9 Hz, 1H), 6.77−6.71 (m, 2H), 6.67−6.64 (m, 2H), 6.51 (dd, J = 8.8
and 2.2 Hz, 1H), 6.25 (d, J = 2.9 Hz, 1H), 6.19 (d, J = 8.8 Hz, 1H),
4.64 (br s, 2H), 3.57 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.4,
140.4, 136.4, 130.6, 129.4, 129.3, 127.4, 123.6, 121.3, 118.3, 113.6,
Some data were recorded in CDCl3, which does not show the
−NH2 proton; to confirm the −NH2 proton, we have reported the IR
data.
113.3, 112.8, 110.7, 105.8, 103.0, 55.0; IR spectrum in film (νmax
,
cm−1) 3357, 2958, 1648, 1479, 794, 756, 693; HRMS (ESI) calcd for
C17H16N2O (M + H+) 265.1341 found 265.1341.
(Z)-1-(3-Methylstyryl)-1H-indol-5-amine (3a). The product was
obtained as a brown semisolid (183.5 mg, 74%): 1H NMR (400 MHz,
CDCl3) δ 7.09−7.02 (m, 2H), 6.95−6.90 (m, 3H), 6.88 (d, J = 3.2 Hz,
1H), 6.82 (d, J = 1.8 Hz, 1H), 6.78 (d, J = 9.1 Hz, 1H), 6.60 (dd, J =
8.2 and 2.3 Hz, 1H), 6.22 (d, J = 3.2 Hz, 1H), 6.07 (d, J = 9.1 Hz, 1H),
2.18 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 140.3, 137.9, 135.0,
130.7, 129.4, 128.2, 128.1, 127.4, 125.6, 123.2, 118.2, 112.8, 110.6,
105.9, 102.9, 21.3; IR spectrum in film (νmax, cm−1) 3375, 2925, 1626,
1477, 772, 723, 696; HRMS (ESI) calcd for C17H16N2 (M + H+)
249.1391, found 249.1391.
(Z)-1-(4-Methylstyryl)-1H-indol-5-amine (3b). The product was
obtained as a brown semisolid (188.4 mg, 76%): 1H NMR (400 MHz,
(CD3)2SO) δ 7.07−7.00 (m, 5H), 6.96 (d, J = 9.1 Hz, 1H), 6.90 (d,
J = 3.2 Hz, 1H), 6.70 (s,1H), 6.53 (d, J = 8.7 Hz, 1H), 6.24 (d, J = 3.2
Hz, 1H), 6.17 (d, J = 9.1 Hz, 1H), 4.63 (br s, 2H), 2.23 (s, 3H); 13C
NMR (100 MHz, (CD3)2SO) δ 142.8, 136.6, 132.2, 129.0, 128.9,
128.2, 126.3, 123.3, 117.6, 112.3, 110.6, 103.7, 102.8, 20.8; IR
spectrum in film (νmax, cm−1) 3394, 2922, 1653, 1477, 819, 726, 710;
HRMS (ESI) calcd for C17H16N2 (M + H+) 249.1391, found
249.1391.
(Z)-1-(2-(Thiophen-3-yl)vinyl)-1H-indol-5-amine (3c). The prod-
uct was obtained as a brown oil (177.6 mg, 74%): 1H NMR
(400 MHz, CDCl3) δ 7.07−7.03 (m, 3H), 6.96 (d, J = 2.9 Hz, 1H),
6.84 (d, J = 2.2 Hz, 1H), 6.73−6.68 (m, 2H), 6.59 (dd, J = 8.0 and 2.2
Hz, 1H), 6.30 (d, J = 2.9 Hz, 1H), 6.21 (d, J = 8.8 Hz, 1H), 13C NMR
(100 MHz, CDCl3) δ 140.2, 135.6, 130.6, 129.5, 127.8, 127.6, 125.2,
124.3, 122.9, 115.5, 112.9, 110.8, 105.8, 102.8; IR spectrum in film
(νmax, cm−1) 3403, 2921, 1646, 1476, 797, 757, 711; HRMS (ESI)
calcd for C14H12N2S (M + H+) 241.0799, found 241.0799.
(Z)-1-(4-Ethylstyryl)-1H-indol-5-amine (3d). The product was
obtained as a brown semisolid (196.5 mg, 75% yield); 1H NMR
(400 MHz, (CD3)2SO) δ 7.01−6.95 (m, 5H), 6.89 (d, J = 9.1 Hz,
1H), 6.83 (d, J = 3.2 Hz, 1H), 6.61 (d, J = 2.3 Hz, 1H), 6.45 (dd, J =
8.7 and 1.8 Hz, 1H), 6.17 (d, J = 2.7 Hz, 1H), 6.10 (d, J = 9.1 Hz, 1H),
4.56 (br s, 2H), 2.46 (q, J = 7.3 Hz, 2H), 1.05 (t, J = 7.7 Hz, 3H); 13C
NMR (100 MHz, (CD3)2SO) δ 143.4, 143.3, 133.0, 129.6, 129.4,
128.9, 128.3, 126.8, 123.8, 118.2, 112.8, 111.1, 104.2, 103.3, 28.4, 15.9;
IR spectrum in film (νmax, cm−1): 3421, 2964, 1649, 1458, 799, 755,
716; HRMS (ESI) calcd for C18H18N2 (M + H+) 263.1548, found
263.1548.
(Z)-1-(2-(6-Methoxynaphthalen-2-yl)vinyl)-1H-indol-5-amine
(3h). The product was obtained as a brown solid (194.6 mg, 62%): mp
1
125−130 °C; H NMR (400 MHz, (CD3)2SO) δ 7.67 (t, J = 4.4 Hz,
2H), 7.61(d, J = 8.8 Hz, 1H), 7.23 (d, J = 2.2 Hz, 1H), 7.12−7.05 (m,
4H), 6.92 (d, J = 2.9 Hz, 1H), 6.70 (d, J = 2.2 Hz, 1H), 6.52 (dd, J =
8.8 and 2.2 Hz, 1H), 6.34 (d, J = 8.8 Hz, 1H), 6.25 (d, J = 2.9 Hz, 1H),
4.65 (br s, 2H), 3.83 (s, 3H); 13C NMR (100 MHz, (CD3)2SO) δ
157.5, 142.9, 133.4, 130.4, 129.3, 129.1, 129.0, 128.3, 127.4, 126.59,
126.55, 126.4, 123.7, 118.9, 117.6, 112.3, 110.7, 105.9, 103.7, 102.9,
55.2; IR spectrum in film (νmax, cm−1) 3356, 2925, 1625, 1482, 758,
721, 669; HRMS (ESI) calcd for C21H18N2O (M + H+) 315.1497,
found 315.1496.
(Z)-1-(3-Ethynylstyryl)-1H-indol-5-amine (3i). The product was
obtained as a brown oil (118.6 mg, 46%): 1H NMR (400 MHz,
CDCl3) δ 7.31 (s, 1H), 7.25 (d, J = 7.3 Hz, 1H), 7.12−7.06 (m, 3H),
6.84−6.82 (m, 3H), 6.60 (d, J = 8.8 Hz, 1H), 6.25−6.24 (m, 1H), 6.03
(dd, J = 9.5 and 3.7 Hz, 1H), 2.95 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 140.6, 135.5, 132.3, 130.9, 130.6, 129.5, 128.9, 128.4, 127.2,
124.2, 122.2, 116.5, 112.9, 110.6, 105.9, 103.5, 83.3, 77.6; IR spectrum
in film (νmax, cm−1) 3422, 3351, 2924, 1648, 1479, 798, 718, 692;
HRMS (ESI) calcd for C18H14N2 [M]+ 258.1157, found 258.1157.
(E)-1-(4-(Trifluoromethyl)styryl)-1H-indol-5-amine (3j). The prod-
1
uct was obtained as a brown oil (217.4 mg, 72%): H NMR (400
MHz, CDCl3) δ 7.57 (d, J = 14.6 Hz, 1H), 7.51−7.49 (m, 2H), 7.42−
7.40 (m, 2H), 7.32 (d, J = 2.9 Hz, 1H), 7.29 (d, J = 8.8 Hz, 1H), 6.83
(d, J = 2.2 Hz, 1H), 6.66 (dd, J = 8.8 and 2.2 Hz, 1H), 6.51 (d, J = 14.7
Hz, 1H), 6.43 (d, J = 3.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
141.0, 140.1, 130.4, 130.3, 128.8, 128.3, 128.0, 125.7 (q, J = 4.7 Hz,
1C), 125.4, 124.0, 113.3, 110.8, 110.2, 106.2, 105.3; IR spectrum in
film (νmax, cm−1) 3431, 2926, 1653, 1458, 850, 714, 609; HRMS (ESI)
calcd for C17H13F3N2 [M]+ 302.1031, found 302.1030.
1-(4-(Trifluoromethoxy)styryl)-1H-indol-5-amine (3k). The prod-
uct was obtained as a brown oil (219.4 mg, 69%) as a mixture of Z and
1
E isomers (77:23): H NMR (400 MHz, CDCl3) δ 7.47 [d, J = 14.6
Hz, 0.3H (for minor)], 7.35−7.31 [m, 1H (for major)], 7.27 [d, J =
6.5 Hz, 0.4 H (for minor)], 7.13−7.10 [m, 2.3H (major + minor)],
7.04 [d, J = 8.6 Hz, 1H (for major)], 6.99 [d, J = 8.2 Hz, 2H (for
major)], 6.84−6.81 [m, 3.2H (major + minor)], 6.66 [dd, J = 8.6 and
2.2 Hz, 0.3H (for minor)], 6.60 [dd, J = 8.7 and 2.2 Hz, 1.0 H (for
major)], 6.51 [d, J = 14.6 Hz, 0.3H (23% for minor regioisomer)],
6.42 [d, J = 3.2 Hz, 0.2 H (for minor)], 6.26 [d, J = 3.2 Hz, 1H (77%
for major regioisomer)], 6.07 [d, J = 9.1 Hz, 1H (for major)]; 13C
NMR (100 MHz, CDCl3), (major + minor) δ 148.0, 140.8, 140.6,
(Z)-1-(4-Butylstyryl)-1H-indol-5-amine (3e). The product was
obtained as a brown semisolid (208.8 mg, 72%): 1H NMR (400
MHz, (CD3)2SO) δ 7.07−7.02 (m, 5H), 6.97 (d, J = 9.5 Hz, 1H), 6.90
(d, J = 3.5 Hz, 1H), 6.68 (d, J = 2.2 Hz, 1H), 6.52 (dd, J = 8.7 and
K
dx.doi.org/10.1021/jo402352v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
135.2, 133.8, 130.5, 130.0, 129.6, 127.1, 126.6, 124.7, 124.2, 124.1,
121.4, 120.8, 116.9, 113.2, 113.0, 111.2, 110.7, 110.2, 106.2, 105.9,
104.8, 103.5; IR spectrum in film (νmax, cm−1) 3423, 2926, 1649, 1479,
849, 716, 671; HRMS (ESI) calcd for C17H13F3N2O (M + H+)
319.1058, found 319.1058.
(d, J = 8.7 Hz, 1H), 6.47 (d, J = 7.3 Hz, 1H), 6.42 (d, J = 2.9 Hz, 1H),
6.36 (dd, J = 8.8 and 2.2 Hz, 1H), 4.59 (br s, 2H), 2.25 (s, 3H), 2.08
(s, 3H); 13C NMR (100 MHz, (CD3)2SO) δ 142.2, 138.3, 137.8,
137.1, 135.5, 134.6, 129.8, 129.43, 129.41, 128.7, 128.6, 128.4, 128.1,
126.1, 125.3, 124.7, 123.0, 112.5, 111.1, 103.7, 102.3, 21.1, 21.0; IR
spectrum in film (νmax, cm−1) 3429, 2922, 1626, 1478, 825, 763, 698;
HRMS (ESI) calcd for C24H22N2 (M + H+) 339.1861, found 339.1860.
(Z)-2-(1-(3-Methylstyryl)-1H-indol-3-yl)ethanamine (5a). The
product was obtained as a brown oil (176.6 mg, 64%): 1H NMR
(400 MHz, (CD3)2SO) δ 7.55 (d, J = 7.3 Hz, 1H), 7.40 (d, J = 8.7 Hz,
1H), 7.18−7.07 (m, 4H), 7.05−6.99 (m, 2H), 6.96−6.89 (m, 2H), 6.24
(d, J = 9.5 Hz, 1H), 3.25 [br s, 7H; 2H (for NH2) + 5H (for moisture)],
2.73−2.69 (m, 4H), 2.18 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 137.9,
136.3, 135.0, 129.3, 128.21, 128.18, 125.7, 124.9, 122.9, 122.6, 120.3,
118.9, 118.3, 114.8, 114.0, 110.1, 41.9, 29.7, 21.3; IR spectrum in film
(νmax, cm−1) 3359, 2924, 1645, 1462, 798, 740, 696; HRMS (ESI) calcd
for C19H20N2 (M + H+) 277.1704, found 277.1705.
(Z)-2-(1-(4-Methylstyryl)-1H-indol-3-yl)ethanamine (5b). The
product was obtained as a yellow oil (179.4 mg, 65%): 1H NMR
(400 MHz, CDCl3) δ 7.59 (d, J = 7.3 Hz, 1H), 7.36 (d, J = 8.0 Hz,
1H), 7.25 (t, J = 7.3 Hz, 1H), 7.18 (t, J = 8.0 Hz, 1H), 7.07 (m, 4H),
6.88 (m, 2H), 6.20 (d, J = 8.8 Hz, 1H), 2.94 (t, J = 6.6 Hz, 2H), 2.81
(m, 2H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 137.2, 136.2,
132.0, 128.9, 128.4, 128.0, 124.8, 122.4, 120.1, 118.8, 118.7, 114.8,
110.0, 41.9, 29.1, 21.1; IR spectrum in film (νmax, cm−1) 3360, 2921,
1651, 1462, 822, 742, 711; HRMS (ESI) calcd for C19H20N2 (M + H+)
277.1704, found 277.1705.
1-(2-Methylstyryl)-1H-indol-5-amine (3l). The product was
obtained as a brown semisolid (186.0 mg, 75%) as a mixture of Z
and E isomers (75:25): 1H NMR (400 MHz, (CD3)2SO) δ 7.77 [d, J =
2.9 Hz, 0.5H (for minor)], 7.74 [s, 0.2H (for minor)], 7.68 [d, J = 8.0
Hz, 0.3H (for minor)], 7.57 [d, J = 8.7 Hz, 0.4H (for minor)], 7.23−
7.15 [m, 4.3H (major + minor)], 7.13−7.03 [m, 2H (major + minor)],
6.88 [d, J = 14.6 Hz, 0.4 H (for minor)], 6.75 [d, J = 1.4 Hz, 0.3H (for
minor)], 6.67 [d, J = 2.2 Hz, 0.9H (for major)], 6.63 [dd, J = 8.8 and
2.2 Hz, 0.3H (for minor)], 6.59−6.56 [m, 2H (for major)], 6.42 [d,
J = 3.6 Hz, 0.3H;(for minor)], 6.14 [d, J = 3.6 Hz, 0.9H (for major)],
6.10 [d, J = 9.5 Hz, 1H (for major)], 4.66 [br s, 2.7 H (major +
minor)], 2.36 [s, 1H (25% for minor regioisomer)], 2.13 [s, 3H (75%
for major regioisomer)]; 13C NMR (100 MHz, (CD3)2SO), (major +
minor) δ 143.0, 142.9, 135.9, 135.2, 135.18, 134.6, 130.2, 130.1, 129.8,
129.2, 128.9, 128.8, 128.6, 127.3, 126.3, 126.1, 125.9, 125.4, 125.1,
124.6, 124.4, 124.0, 112.8, 112.5, 112.4, 110.7, 110.3, 109.3, 104.2,
103.9, 103.7, 103.2, 19.8, 19.5; IR spectrum in film (νmax, cm−1) 3420,
3345, 2923, 2859, 1651, 1622, 1479, 1456, 755, 717, 619; HRMS
(ESI) calcd for C17H16N2 (M + H+) 249.1391, found 249.1391.
1-(3,5-Dimethoxystyryl)-1H-indol-5-amine (3m). The product was
obtained as brown oil (205.8 mg, 70%) as a mixture of Z and E
isomers (75:25): 1H NMR (400 MHz, (CD3)2SO) δ 7.93 [d, J = 14.6
Hz, 0.4H (for minor)], 7.65−7.62 [m, 0.8H (for major)], 7.05−6.94
[m, 3H (major + minor)], 6.74−6.67 [m, 2.5H (major + minor)], 6.60
[dd, J = 8.8 and 2.2 Hz, 0.3H (for minor)], 6.52 [dd, J = 8.0 and 1.4
Hz, 1H (for major)], 6.39 [d, J = 3.6 Hz, 0.3H (for minor)], 6.33−6.30
[m, 1.3H (major + minor)], 6.27−6.25 [m, 2.9H (major + minor)], 6.12
[d, J = 9.5 Hz, 1H;(for major)], 4.62 [ br s, 2.3H (major + minor)], 3.74
[s, 2H (25% for minor regioisomer)], 3.55 [s, 6H (75% for major
regioisomer)]; 13C NMR (100 MHz, (CD3)2SO), (major + minor) δ
160.7, 160.2, 143.0, 142.8, 138.6, 136.9, 129.8, 129.1, 128.9, 126.5, 124.9,
124.2, 124.0, 117.5, 112.4, 112.3, 111.4, 111.0, 110.7, 106.3, 104.4, 103.9,
103.8, 103.6, 102.9, 99.5, 98.5, 55.2, 54.9; IR spectrum in film (νmax, cm−1)
3430, 3358, 2936, 2837,1651, 1622, 1480, 1456, 855, 829, 756, 689, 617;
HRMS (ESI) calcd for C18H18N2O2 (M + H+) 295.1446, found 295.1446.
1-(2-([1,1′-Biphenyl]-4-yl)vinyl)-1H-indol-5-amine (3n). The prod-
uct was obtained as a brown solid (223.2 mg, 72%) as a mixture of Z
and E isomers (1:1): mp 95−100 °C; 1H NMR (400 MHz,
(CD3)2SO) δ 7.96 (d, J = 14.6 Hz, 1.3H), 7.69 (d, J = 3.6 Hz, 1H),
7.65−7.59 (m, 10H), 7.53 (d, J = 8.0 Hz, 1.9H), 7.43−7.36 (m, 4.4H),
7.31−7.27 (m, 2H), 7.19 (d, J = 8.0 Hz, 1.3H), 7.06 (d, J = 9.5 Hz,
1H), 7.02 (d, J = 10.2 Hz, 1H), 6.94 (d, J = 2.9 Hz, 1H), 6.79 (d, J =
15.3 Hz, 1H), 6.68−6.66 (m, 2H), 6.59 (dd, J = 8.0 and 2.2 Hz, 1H),
6.50 (dd, J = 7.3 and 0.7 Hz, 1H), 6.39 (d, J = 3.6 Hz, 1H), 6.26−6.20
(m, 2H), 4.66 (br s, 4H); 13C NMR (100 MHz, (CD3)2SO) δ 143.1,
143.0, 139.9, 139.5, 138.8, 137.7, 136.0, 134.4, 129.9, 129.2, 129.0,
127.6, 127.3, 126.9, 126.6, 126.5, 126.4, 126.1, 124.6, 124.1, 117.2,
112.6, 112.5, 110.9, 110.9, 110.8, 104.6, 104.0, 103.97, 103.2; IR
spectrum in film (νmax, cm−1) 3406, 3327, 1648, 1478, 1458, 759, 723,
696; HRMS (ESI) calcd for C22H18N2 (M + H+) 311.1548, found
311.1549.
(Z)-2-(1-(2-(Thiophen-3-yl)vinyl)-1H-indol-3-yl)ethanamine (5c).
1
The product was obtained as a brown oil (174.2 mg, 65%): H NMR
(400 MHz, CDCl3) δ 7.52 (d, J = 8.0 Hz, 1H), 7.24−7.22 (m, 1H),
7.17−7.13 (m, 1H), 7.10−7.04 (m, 3H), 6.86 (s, 1H), 6.75 (d , J = 8.7
Hz, 1H), 6.67 (d , J = 5.8 Hz, 1H), 6.23 (d, J = 8.8 Hz, 1H), 2.91 (t , J =
7.3 Hz, 2H), 2.79 (t , J = 6.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
139.2, 136.4, 135.6, 128.2, 127.7, 125.3, 125.0, 124.3, 122.65, 122.56,
120.2, 119.0, 115.3, 114.9, 114.0, 110.3, 42.0, 28.9; IR spectrum in film
(νmax, cm−1) 3414, 2925, 1648, 1462, 798, 744, 645; HRMS (ESI) calcd
for C16H16N2S (M + H+) 269.1112, found 269.1111.
(Z)-2-(1-(4-tert-Butylstyryl)-1H-indol-3-yl)ethanamine (5d). The
1
product was obtained as an orange oil (200.3 mg, 63%): H NMR
(400 MHz, (CD3)2SO) δ 7.52 (d, J = 7.8 Hz, 1H), 7.32 (d , J = 7.8 Hz,
1H), 7.21 (d , J = 8.7 Hz, 2H), 7.13−7.05 (m, 2H), 7.02−7.00 (m,
3H), 6.87 (s, 1H), 6.25 (d , J = 9.1 Hz, 1H), 3.29 [br s, 10H, 2H (for
NH2) and 8H (for moisture)], 2.71−2.67 (m, 4H), 2.49 (s, 9H); 13C
NMR (100 MHz, (CD3)2SO) δ 150.0, 135.7, 132.0, 128.2, 127.9, 125.1,
124.4, 123.1, 122.3, 120.0, 118.9, 118.8, 115.0, 110.4, 41.7, 34.3, 31.0,
28.2; IR spectrum in film (νmax, cm−1) 3425, 2961, 1649, 1462 832, 744;
HRMS (ESI) calcd for C22H26N2 (M + H+) 319.2174, found 319.2173.
(Z)-2-(1-(3-Methoxystyryl)-1H-indol-3-yl)ethanamine (5e). The
product was obtained as a brown oil (181.0 mg, 62%): 1H NMR
(400 MHz, CDCl3) δ 7.57 (d, J = 7.3 Hz, 1H), 7.35 (d, J = 8.0 Hz,
1H), 7.24 (d, J = 8.0 Hz, 1H), 7.18−7.14 (m, 2H), 6.94 (d , J = 10.3
Hz, 1H), 6.87 (s, 1H), 6.79 (d, J = 7.3 Hz, 1H), 6.78−6.75 (m, 1H),
6.71 (s, 1H), 6.20 (d , J = 9.5 Hz, 1H), 3.65 (s, 3H), 2.92 (t, J = 6.6
Hz, 2H), 2.79 (t, J = 6.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
159.4, 136.4, 129.3, 128.2, 124.9, 123.2, 122.5, 121.3, 120.3, 119.0,
118.2, 115.0, 114.0, 113.1, 110.2, 55.1, 41.0, 29.2; IR spectrum in KBr
(νmax, cm−1) 3432, 2926, 1630, 1466, 740, 615; HRMS (ESI) calcd for
C19H20N2O (M + H+) 293.1654, found 293.1654.
(Z)-2-(1-(3-Ethynylstyryl)-1H-indol-3-yl)ethanamine (5f). The
product was obtained as a brown oil (120.1 mg, 42%): 1H NMR
(400 MHz, (CD3)2SO) δ 7.56 (d, J = 7.3 Hz, 1H), 7.36−7.30 (m,
3H), 7.24 (t, J = 8.0 Hz, 2H), 7.17−7.14 (m, 2H), 6.94 (d, J = 9.5 Hz,
1H), 6.79 (s, 1H), 6.13 (d, J = 9.5 Hz, 1H), 3.02 (s, 1H), 2.95 (t, J =
5.8 Hz, 2H), 2.81 (t, J = 5.8 Hz, 2H), 2.52 (br s, 2H); 13C NMR (100
MHz, CDCl3) δ 136.3, 135.3, 132.2, 131.0, 129.0, 128.4, 124.7, 123.8,
122.8, 122.2, 120.6, 119.1, 116.8, 115.0, 114.0, 110.1, 83.2, 77.5, 41.6,
28.3; IR spectrum in film (νmax, cm−1) 3291, 2923, 2852, 1651, 1461,
801, 744, 692; HRMS (ESI) calcd for C20H18N2 (M + H+) 287.1548,
found 287.1548.
(Z)-1-(1,2-Diphenylvinyl)-1H-indol-5-amine (3o). The product was
obtained as a brown oil (186.0 mg, 60%): 1H NMR (400 MHz,
(CD3)2SO) δ 7.34−7.32 (m, 3H), 7.28 (s, 1H), 7.20−7.17 (m, 2H),
7.12−7.11 (m, 3H), 6.96 (d, J = 2.9 Hz, 1H), 6.82−6.80 (m, 2H), 6.76
(d, J = 2.2 Hz, 1H), 6.53 (d, J = 8.8 Hz, 1H), 6.42 (d, J = 3.6 Hz, 1H),
6.36 (dd, J = 8.8 and 2.2 Hz, 1H), 4.58 (br s, 2H); 13C NMR (100 MHz,
(CD3)2SO) δ 142.3, 138.2, 135.6, 134.7, 129.5, 128.8, 128.6, 128.4,
128.2, 127.9, 125.7, 124.8, 112.6, 111.2, 103.8, 102.6; IR spectrum in film
(νmax, cm−1) 3423, 2927, 1626, 1458, 762, 695; HRMS (ESI) calcd for
C22H18N2 (M + H+) 311.1548, found 311.1547.
(Z)-1-(1,2-Di-m-tolylvinyl)-1H-indol-5-amine (3p). The product
1
was obtained as a brown oil (226.9 mg, 62%): H NMR (400 MHz,
(CD3)2SO) δ 7.23−7.19 (m, 2H), 7.14 (d, J = 7.3 Hz, 1H), 7.10 (s,
1H), 6.98−6.92 (m, 4H), 6.76 (d, J = 2.2 Hz, 1H), 6.69 (s, 1H), 6.53
L
dx.doi.org/10.1021/jo402352v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(Z)-2-(1-(4-(Trifluoromethyl)styryl)-1H-indol-3-yl)ethanamine
(5g). The product was obtained as a brown solid (198.0 mg, 60%): mp
85−90 °C; H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 8.0 Hz, 1H),
120.8, 119.4, 117.3, 117.2, 111.9, 110.2, 109.6, 83.7, 77.6, 41.8, 28.9; IR
spectrum in film (νmax, cm−1) 3368, 3280, 2924, 2853, 1648, 1460,
804, 739, 617; HRMS (ESI) calcd for C20H18N2 (M + H+) 287.1548,
found 287.1548.
(Z)-2-(1-(1,2-Diphenylvinyl)-1H-indol-3-yl)ethanamine (5n). The
product was obtained as a brown oil (202.8 mg, 60%): 1H NMR (400
MHz, CDCl3) δ 7.55 (d, J = 8.0 Hz, 1H), 7.24−7.15 (m, 6H), 7.04−
6.98 (m,3H), 6.96−6.92 (m, 2H), 6.79 (d, J = 8.0 Hz, 1H), 6.70−6.68
(m, 3H), 2.92 (t, J = 6.6 Hz, 2H), 2.83 (t, J = 6.6 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 138.2, 136.3, 135.8, 134.8, 128.8, 128.6, 128.4,
128.2, 127.7, 126.4, 126.2, 124.4, 122.2, 119.8, 118.8, 114.8, 112.0,
42.0, 29.0; IR spectrum in film (νmax, cm−1) 3369, 2926, 1626, 1459,
743, 695, 668; HRMS (ESI) calcd for C24H22N2 (M + H+) 339.1861,
found 339.1861.
(Z)-2-(1-(1,2-Di-m-tolylvinyl)-1H-indol-3-yl)ethanamine (5o). The
product was obtained as a yellow oil (226.9 mg, 62%): 1H NMR (400
MHz, CDCl3) δ 7.55 (d, J = 7.3 Hz, 1H), 7.15−7.09 (m, 1H), 7.06−
6.99 (m, 3H), 6.96−6.92 (m, 2H), 6.89−6.79 (m, 4H), 6.70 (s, 1H),
6.52 (s, 1H), 6.38 (d, J = 7.3 Hz, 1H), 2.93 (t, J = 6.4 Hz, 2H), 2.85 (t,
J = 5.9 Hz, 2H), 2.23 (s, 3H), 2.04 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 138.5, 138.4, 137.8, 136.4, 136.1, 134.9, 129.8, 129.7, 128.7,
128.6, 128.5, 128.2, 126.9, 126.6, 125.6, 124.6, 123.6, 122.4, 119.8,
1
7.41 (d, J = 8.0 Hz, 2H), 7.25−7.15 (m, 4H), 7.10 (t, J = 7.3 Hz, 1H),
6.94 (d, J = 9.5 Hz, 1H), 6.73 (s, 1H), 6.13 (d, J = 8.7 Hz, 1H), 2.91 (t,
J = 7.3 Hz, 2H), 2.81 (t, J = 6.6 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 138.7, 136.2, 128.8, 128.2, 125.3, 125.2 (q, J = 3.8 Hz, 1C),
124.9, 124.6, 123.0, 120.8, 119.1, 116.8, 115.0, 110.3, 41.4, 27.4; IR
spectrum in film (νmax, cm−1) 3364, 2925, 2854, 1652, 1462, 800, 744,
668; HRMS (ESI) calcd for C19H17F3N2 (M + H+) 331.1422, found
331.1422.
(Z)-2-(1-(4-(Trifluoromethoxy)styryl)-1H-indol-3-yl)ethanamine
1
(5h). The product was obtained as a yellow oil (204.1 mg, 59%): H
NMR (400 MHz, (CD3)2SO) δ 7.55 (d, J = 7.3 Hz, 1H), 7.36 (d, J =
8.0 Hz, 1H), 7.24 (s, 3H), 7.19−7.16 (m, 2H), 7.13−7.07 (m, 2H),
6.85 (s, 1H), 6.31 (d, J = 9.5 Hz, 1H), 3.16 [br s, 9H; 2H (for NH2) +
7H (for moisture)], 2.71−2.66 (m, 4H); 13C NMR (100 MHz,
(CD3)2SO) δ 147.2, 135.6, 134.5, 130.2, 128.0, 124.5, 124.1, 122.5,
121.3, 120.9, 120.2, 119.0, 118.8, 116.4, 115.9, 110.5, 42.0, 28.8; IR
spectrum in film (νmax, cm−1) 3404, 2924, 1648, 1461, 814, 744, 670;
HRMS (ESI) calcd for C19H17F3N2O (M + H+) 347.1371, found
347.1371.
(Z)-2-(1-(2-Methylstyryl)-1H-indol-3-yl)ethanamine (5i). The
product was obtained as a yellow oil (168.3 mg, 61%): 1H NMR
(400 MHz, (CD3)2SO) δ 7.39 (dd, J = 8.0 and 2.9 Hz, 2H), 7.16 (d,
J = 9.5 Hz, 1H), 7.11−7.03 (m, 3H), 6.99−6.90 (m, 3H), 6.46 (s, 1H),
6.08 (d, J = 9.5 Hz, 1H), 2.71 (br s, 2H), 2.50−2.45 (m, 4H), 2.03 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 139.0, 136.2, 134.8, 130.0,
128.8, 127.9, 127.4, 125.6, 124.2, 123.1, 122.4, 120.2, 118.8, 115.0,
114.3, 109.6, 41.7, 28.9, 19.8; IR spectrum in film (νmax, cm−1) 3418,
2924, 1652, 1462, 743; HRMS (ESI) calcd for C19H20N2 (M + H+)
277.1704, found 277.1704.
118.9, 114.6, 112.1, 42.2, 29.0, 21.6, 21.4; IR spectrum in film (νmax
,
cm−1) 3369, 2924, 2854, 1628, 1458, 768, 698, 668; HRMS (ESI)
calcd for C26H26N2 (M + H+) 367.2174, found 367.2173.
(Z)-2-(1-Styryl-1H-imidazol-4-yl)ethanamine (6a). The product
1
was obtained as a yellow-brown oil (106.5 mg, 50%): H NMR (400
MHz, CDCl3) δ 7.34 (m, 2H), 7.23 (t, J = 1.8 Hz, 1H), 7.21 (t, J = 1.8
Hz, 1H), 7.06 (dd, J = 7.8 and 1.8 Hz, 2H), 6.62 (d, J = 9.1 Hz, 1H),
6.55 (s, 1H), 6.23 (d, J = 9.6 Hz, 1H), 2.87 (t, J = 6.4 Hz, 2H), 2.57 (t,
J = 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 140.8, 136.6, 133.8,
128.8, 128.7, 128.5, 128.2, 127.2, 126.0, 122.4, 115.3, 41.6, 32.1; IR
spectrum in film (νmax, cm−1) 3363, 2925, 1656, 1494, 753, 698, 628;
HRMS (ESI) calcd for C13H15N3 [M]+ 213.1266, found 213.1266.
(E)-2-(1-(4-(Trifluoromethyl)styryl)-1H-imidazol-4-yl)ethanamine
(Z)-2-(1-(2,4-Dimethoxystyryl)-1H-indol-3-yl)ethanamine (5j).
The product was obtained as a brown oil (186.7 mg, 58%): 1H
NMR (400 MHz, (CD3)2SO) δ 8.26 (s, 1H), 7.51 (d, J = 7.3 Hz, 1H),
7.31 (d, J = 8.0 Hz, 1H), 7.11 (t , J = 7.3 Hz, 1H), 7.07−7.03 (m, 1H),
6.93 (s, 1H), 6.32 (t, J = 2.2 Hz, 1H), 6.25 (d, J = 2.2 Hz, 2H), 6.19 (d,
J = 9.5 Hz, 1H), 3.52 (s, 6H), 2.90 (br s, 2H), 2.68 (m, 4H), 13C NMR
(100 MHz, (CD3)2SO) δ 160.2, 136.6, 135.7, 127.9, 124.3, 123.8,
122.3, 120.1, 118.9, 118.3, 115.4, 110.5, 109.4, 106.3, 101.8, 99.7, 54.9, 42.1,
28.8; IR spectrum in film (νmax, cm−1) 3368, 2935, 1648, 744, 688; HRMS
(ESI) calcd for C20H22N2O2 (M + H+) 323.1759, found 323.1761.
(Z)-2-(1-Styryl-1H-indol-3-yl)ethanamine (5k). The product was
1
(6b). The product was obtained as a brown oil (146.1 mg, 52%): H
NMR (400 MHz, (CD3)2SO) δ 8.31 (s, 1H), 7.97−7.91 (m, 1H),
7.70−7.65 (m, 4H), 7.48 (s, 1H), 7.01 (d, J = 14.6 Hz, 1H), 2.99 (br s,
2H), 2.79 (t, J = 6.4 Hz, 2H), 2.57 (t, J = 6.8 Hz, 2H); 13C NMR (100
MHz, (CD3)2SO) δ 142.3, 140.2, 137.5, 127.9, 127.5, 127.4, 126.8,
126.6, 126.1 (q, J = 4.7 Hz, 1C), 123.5, 114.8, 113.0, 41.9, 32.5; IR
spectrum in film (νmax, cm−1) 3420, 2254, 1661, 824, 763; HRMS
+
(ESI) calcd for C14H14F3N3 [M] 281.1140, found 281.1140.
1
obtained as an orange oil (157.2 mg, 60%): H NMR (400 MHz,
2-(1-(3-Methylstyryl)-1H-imidazol-4-yl)ethanamine (6c). The
product was obtained as a yellow -brown oil (122.5 mg, 54%) as a
mixture of Z and E isomers (1:1): 1H NMR (400 MHz, (CD3)2SO) δ
7.50 (s, 1H), 7.29 (s, 1H), 7.18 (t, J = 7.3 Hz, 1H), 7.13−7.09 (m,
2H), 7.07 (t, J = 5.1 Hz, 2H), 6.91−6.88 (m, 3H), 6.81−6.75 (m, 3H),
6.67−6.59 (m, 2H), 6.32 (d, J = 9.5 Hz, 1H), 3.25 [br s, 10H; 2H
(NH2 for Z isomer) + 2H (NH2 for E isomer) + 6H (for moisture)],
2.78 (t, J = 7.3 Hz, 2H), 2.73 (t, J = 7.3 Hz, 2H), 2.58−2.52
(m, 4H), 2.22 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz,
(CD3)2SO), (major + minor) δ 140.2, 139.4, 138.8, 137.8, 136.7,
135.8, 134.0, 133.4, 129.2, 129.0, 128.6, 128.5, 128.3, 126.4, 125.4,
125.1, 123.2, 123.0, 122.7, 121.9, 121.3, 115.5, 115.0, 40.1, 31.5, 27.1,
20.9; IR spectrum in film (νmax, cm−1) 3364, 2924, 1642, 1466, 760,
697; HRMS (ESI) calcd C14H17N3 [M]+ 227.1422, found 227.1421.
2-(1-(3-Methoxystyryl)-1H-imidazol-4-yl)ethanamine (6d). The
product was obtained as a brown oil (121.5 mg, 50%) as a mixture
(CD3)2SO) δ 7.49 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 8.0 Hz, 1H), 7.17−
7.08 (m, 7H), 6.84 (d , J = 8.7 Hz, 1H), 6.74 (s, 1H), 6.15 (d, J = 8.7
Hz, 1H), 2.85 (t, J = 6.6 Hz, 2H), 2.73 (t , J = 6.6 Hz, 2H), 2.21 (br s,
2H); 13C NMR (100 MHz, CDCl3) δ 139.3, 136.3, 135.1, 128.6,
128.3, 128.1, 127.5, 124.9, 123.1, 122.6, 120.4, 119.0, 118.6, 114.7,
114.0, 110.2, 41.7, 28.5; IR spectrum in film (νmax, cm−1) 3370, 2924,
1651, 1462, 744, 694; HRMS (ESI) calcd for C18H18N2 (M + H+)
263.1548, found 263.1548.
(Z)-2-(1-(4-Methoxystyryl)-1H-indol-3-yl)ethanamine (5l). The
product was obtained as a brown oil (192.7 mg, 66%): 1H NMR
(400 MHz, CDCl3) δ 7.50 (d, J = 8.0 Hz, 1H), 7.25 (d, J = 8.0 Hz,
1H), 7.17−7.13 (m, 2H), 7.07 (t, J = 7.3 Hz, 1H), 7.00 (d, J = 8.0 Hz,
1H), 6.80 (s, 1H), 6.74 (d , J = 9.5 Hz, 1H), 6.67 (d, J = 8.8 Hz, 2H),
6.12 (d, J = 8.8 Hz, 1H), 3.69 (s, 3H), 2.90 (t, J = 5.8 Hz, 2H), 2.78 (t ,
J = 6.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 158.9, 139.2, 136.3,
130.0, 128.0, 127.3, 125.0, 122.6, 121.8, 120.2, 119.5, 118.9, 114.3,
114.0, 113.7, 110.3, 55.2, 41.8, 28.4; IR spectrum in film (νmax, cm−1)
3386, 2921, 1640, 1460, 833, 743; HRMS (ESI) calcd for C19H20N2O
(M + H+) 293.1654, found 293.1654.
1
of Z and E isomers (66:34): H NMR (400 MHz, (CD3)2SO) δ 7.46
[s, 0.9H (for major)], 7.28 [s, 0.6H (for minor)], 7.20−7.11 [m, 1.4H
(major + minor)], 6.88 [d, J = 7.5 Hz, 1H (for major)], 6.81−6.77 [m,
2.7H (major + minor)], 6.70 [s, 0.7H (for minor)]; 6.66 [d, J = 5.1
Hz, 0.9H (for major)], 6.61−6.58 [m, 1.4H (major + minor)], 6.49 [d,
J = 10.2 Hz, 0.6H (for minor)], 6.30 [d, J = 10.2 Hz, 1.6H (for
minor)], 3.61 [s, 3H (66% for major regioisomer)], 3.54 [s, 1.6H
(34% for minor regioisomer)], 2.97 [br s, 3H, (major + minor)],
2.68−2.65 [m, 3H (major + minor)], 2.45−2.42 [m, 2H (major +
minor)]; 13C NMR (100 MHz, (CD3)2SO), (major + minor) δ
159.23, 159.19, 140.5, 136.6, 135.8, 135.4, 134.7, 129.7, 129.4, 128.3,
(E)-2-(1-(4-Ethynylstyryl)-1H-indol-3-yl)ethanamine (5m). The
product was obtained as a brown oil (114.1 mg, 40%): 1H NMR
(400 MHz, CDCl3) δ 7.57 (d, J = 14.7 Hz, 1H), 7.51 (d, J = 8.0 Hz,
1H), 7.44 (d, J = 8.8 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.30−7.18 (m,
4H), 7.12−7.07 (m, 2H), 6.50 (d, J = 14.7 Hz, 1H), 3.05 (s, 1H), 3.01
(t, J = 4.4 Hz, 2H), 2.86 (t, J = 5.8 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 136.9, 132.6, 132.0, 128.9, 128.6, 125.3, 124.0, 123.2, 121.2,
M
dx.doi.org/10.1021/jo402352v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
126.4, 123.4, 123.4, 122.3, 121.3, 120.9, 120.8, 114.8, 114.3, 113.8,
113.4, 113.0, 54.9, 54.8, 40.4, 40.1, 31.7, 28.0 ; IR spectrum in film
(νmax, cm−1) 3414, 1652, 765, 695, 632; HRMS (ESI) calcd for
C14H17N3O [M]+ 243.1372, found 243.1372.
(7) (a) Siau, W. Y.; Zhang, Y.; Zhao, Y. Top. Curr. Chem. 2012, 327,
33. (b) Jain, S. C. J. Org. Chem. 1983, 48, 2266. (c) Furstner, A.; Guth,
O.; Rumbo, A.; Seidel, G. J. Am. Chem. Soc. 1999, 121, 11108.
(d) Ghosh, A. K.; Wang, Y.; Kim, J. T. J. Org. Chem. 2001, 66, 8973.
(e) Furstner, A.; Davies, P. W. Chem. Commun. 2005, 2307.
(f) Chermichenko, K.; Madarasz, A.; Papai, I.; Nieger, M.; Leskela,
M.; Repo, T. Nat. Chem. 2013, 5, 718.
(8) Velena, W. A.; Berg, J. P. V.; Hansen, M. J.; Szymanski, W.;
Driessen, A. J. M.; Feringa, B. L. Nat. Chem. 2013, 5, 1.
(9) Jhanwar, A.; Tyagi, R.; Vashistha, B.; Srivastava, V.; Singh, B.;
Kishore, D. Int. J. Chem. Sci. 2009, 7, 2222 and references cited therein.
(10) Dong, Y.; Busacca, C. A. J. Org. Chem. 1997, 62, 6464.
(11) Khedkar, V.; Tillack, A.; Michalik, M.; Beller, M. Tetrahedron
Lett. 2004, 45, 3123.
2-(1-(4-(Trifluoromethoxy)styryl)-1H-imidazol-4-yl)ethanamine
(6e). The product was obtained as a brown oil (151.4 mg, 51%) as a
mixture of Z and E isomers (1:1): 1H NMR (400 MHz, (CD3)2SO) δ
7.80−7.72 (m, 1.3H), 7.51 (d, J = 8.7 Hz, 2H), 7.44 (s, 1H), 7.37 (s,
1H), 7.28−7.22 (m, 4H), 7.16−7.14 (m, 2H), 6.96−6.87 (m, 3H),
6.63−6.60 (m, 1H), 6.31(d, J = 9.6 Hz, 1H), 3.03 (br s, 4H), 2.72
(t, J = 6.4 Hz, 2H), 2.65−2.62 (m, 4H), 2.48 (t, J = 7.3 Hz, 2H); 13C
NMR (100 MHz, (CD3)2SO) δ 147.7, 147.2, 140.7, 136.7, 136.6,
135.0, 133.5, 130.3, 130.1, 127.5, 124.9, 124.1, 123.0, 121.4, 121.1,
119.6, 114.6, 114.4, 112.6, 41.4, 41.2, 32.0, 31.7; IR spectrum in film
(νmax, cm−1) 3412, 2918, 2850, 1658, 1506, 953, 808, 754, 670, 626;
(12) Nicolaou, K. C.; Krasovskiy, A.; Trapanier, V. E.; Chen, D. Y. K.
Angew. Chem., Int. Ed. 2008, 47, 4217.
+
HRMS (ESI) calcd for C14H14F3N3O [M]
297.1090.
297.1089, found
(13) (a) Muller, T. E.; Beller, M. Chem. Rev. 1998, 98, 675.
(b) Deiters, A.; Martin, S. F. Chem. Rev. 2004, 104, 2199. (c) Muller,
T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Chem. Rev.
2008, 108, 3795. (d) Pohlki, F.; Doye, S. Chem. Soc. Rev. 2003, 32,
104. (e) Severin, R.; Doye, S. Chem. Soc. Rev. 2007, 36, 1407. and
references cited therein (f) Chinchilla, R.; Najera, C. Chem. Rev. 2013,
DOI: 10.1021/cr400133p. (g) Li, H.; Wen, M.; Lu, G.; Wang, Z. X.
Dalton Trans. 2012, 41, 9091. (h) Bariwalab, J.; Eycken, E. V. Chem.
Soc. Rev. 2013, DOI: 10.1039/c3cs60228a.
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2923. (b) Ackermann, L.; Sandmann, R.; Kaspar, L. T. Org. Lett. 2009,
11, 2031. (c) Ackermann, L. Organometallics 2003, 22, 4367.
(d) Ackermann, L.; Sandmann, R.; Villar, A.; Kaspar, L. T. Tetrahedron
2008, 64, 769. (e) Bytschkov, I.; Doye, S. Eur. J. Org. Chem. 2001,
4411. (f) Pohlki, F.; Doye, S. Angew. Chem., Int. Ed. 2001, 40, 2305.
(15) (a) Walsh, P. J.; Baranger, A. M.; Bergman, R. G. J. Am. Chem.
Soc. 1992, 114, 1708. (b) Leitch, D. C.; Payne, P. R.; Dunbar, C. R.;
Schafer, L. L. J. Am. Chem. Soc. 2009, 131, 18246. (c) Leitch, D. C.;
Turner, C. S.; Schafer, L. L. Angew. Chem., Int. Ed. 2010, 49, 6382.
(16) (a) Anderson, L. L.; Arnold, J.; Bergman, R. G. Org. Lett. 2004,
6, 2519. (b) Fukumoto, Y.; Asai, H.; Shimizu, M.; Chatani, N. J. Am.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Figures giving 1H and 13C NMR and HRMS spectra for
selected compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail for A.K.V.: averma@acbr.du.ac.in.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the Council of Scientific and
Industrial Research (01(2466)/11/EMR-II) and DU-DST-
PURSE Grant for financial support and the USIC, University
of Delhi, for providing instrumentation facilities. M.P. is
thankful to the DST for a JRF and M.J. to the CSIR for SRF
fellowship.
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