Copper-Catalyzed Three-Component Reaction for Regioselective Aryl- and Heteroarylselenation of Indoles using Selenium Powder

Article abstract of DOI:10.1021/acs.joc.6b00229

A new and efficient copper-catalyzed C₃ aryl- and heteroarylselenation of indoles employing selenium powder has been developed. The advantages of this chemistry involve the use of cheap selenating reagents, tolerance of a variety of functional groups, and practicality. In addition, this protocol has been further elaborated in an intramolecular phenylselenation of a (hetero) aryl C-H bond to construct an important motif of benzoselenopheno[3,2-b]indole. A preliminary mechanism study suggests that the reaction starts with a Ullman-type selenation between aryl iodides and selenium, followed by an oxidative cross-coupling with indole. The utility of this method has been demonstrated in an efficient gram-scale synthesis and an application to the synthesis of tubulin polymerization inhibitor.

Full text of DOI:10.1021/acs.joc.6b00229

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Article
Copper-Catalyzed Three-Component Reaction for Regioselective
Aryl- and Heteroarylselenation of Indoles Using Selenium Powder
Dongping Luo, Ge Wu, Hang Yang, Miaochang Liu, Wenxia Gao, Xiaobo Huang, Jiuxi Chen, and Huayue Wu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00229 • Publication Date (Web): 18 May 2016
Downloaded from http://pubs.acs.org on May 19, 2016
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Copper-Catalyzed Three-Component Reaction for Regioselective Aryl- and
Heteroarylselenation of Indoles Using Selenium Powder
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Dongping Luo,† Ge Wu,*,‡ Hang Yang,† Miaochang Liu,† Wenxia Gao,† Xiaobo Huang,† Jiuxi
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Chen† and Huayue Wu*, †
†College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, China
‡School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, China
ABSTRACT: A new and efficient copperꢀcatalyzed C3ꢀarylꢀ and heteroarylselenation of indoles
employing selenium powder is developed. The advantages of this chemistry involve the use of
cheap selenating reagents, the tolerance of a variety of functional groups and the practicality. In
addition, this protocol has been further elaborated in an intramolecular phenylselenation of (hetero)
aryl CꢀH bond to construct an important motif of benzoselenopheno [3,2ꢀb]indole.The preliminary
mechanism study suggests that the reaction starts with a Ullmanꢀtype selenation between aryl
iodides and selenium, followed by an oxidative crossꢀcoupling with indole. The utility of this
method has been demonstrated in an efficient gramꢀscale synthesis and an application to the
synthesis of tubulin polymerization inhibitor.
INTRODUCTION
Selective CꢀSe bond formation is of great importance in modern organic synthesis, since the
seleniumꢀcontaing architectures are prevalent in a diverse of drug candidates, biologically active
compounds, and functional organic materials.1 Considering the significance of organoselenium
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compounds, especially the 3ꢀselenylindoles2 display the biological activity of antitumor activity3
and as inhibitor of tubulin polymerization.4 Therefore, the development of a new synthetic route
for the introduction of stable, economical selenium reagent into organic skeleton would be
significant synthetic value.
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In recent years, transitionꢀmetal catalyzed crossꢀcoupling reactions have become the most
important methdology for the construction of CꢀSe bonds.5 On the basis of selenium source, there
are two general methods for the construction of CꢀSe bonds to synthesize diaryl selenides. The
first approach is involved the transitionꢀmetal catalyzed crossꢀcoupling reaction between
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prefunctionalized aryl substrates with nucleophilic organoselenium reagents (selenol,6 ArSeSnR3,
diselenides8) under basic condtions. Wheras arylselenols have been used as the original material to
prepare these phenylselenation reagent.6 Most arylselenols suffer from the trouble handling
because of unpleasant odors and instability, which hamper their applications in pharmaceutical
industry. Recently, the direct transformation phenyselenation of inert CꢀH bond with diaryl
selenides has emerged as comprising and complementary routes.9 However, most of these works
are highly problematic due to the loss of one equivalent of PhSeꢀ as waste, requiring external
copper or silver salts as oxidant. The second newborn avenue is transitionꢀmetal catalyzed C–Se
bond formation using the elemental selenium as selenating reagent, which is mainly limit to afford
symmetrical diaryl selenides.10 The use of selenium powder, which is commercial available, stable
and easyꢀtoꢀhandle, as a crossꢀcoupling partner to construct CꢀSe bond is a more straightforward
and attractive alternative. However, the relative reports of the activation selenium element are
scarce.11 This is presumably due to the affinity of selenium to transition metal, and easily form the
stability transitionꢀmetal selenium clusters,12 which attenuate the activity of catalysts. From these
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wonderful advancing achievements, it is thereby envisioned that a single Se atom to bridge two
crossꢀcoupling partners of Csp2ꢀX and Csp2ꢀH strategy under transitionꢀmetal catalyzed might be
more practical and economical. Such a method would receive a considerable attention for
designing counterintuitive synthetic strategies that are unattainable by other means, such as
intramolecular phenylselenation of (hetero)arene CꢀH bond. Herein we report a new and efficient
copperꢀcatalyzed C3ꢀphenylselenation of indoles through double C−Se bonds formation, using
(hetero) aryl iodides, elemental selenium and indoles as reactants.
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To achieve the copperꢀcatalyzed arylselenation of indole with selenium powder and aryl
iodides, the following issues need to be considered: (i) Free (NH) indole has three accessible
reaction positions,13 in order to access the highly regioselectivity, the catalyst system for the
Cꢀarylselenation of indoles should avoid to produce Nꢀarylation of indole under the reaction
conditions;14 (ii) The cleavage of the acidic NꢀH of indole usually requires basic conditions to
enable the nucleophilicity of C3 posiiton; Otherwise, if the CꢀH bond of indole cleavage is
relatively slow, the symmetrical diaryl diselenides would formed from aryl iodides with elemental
selenium by copperꢀcatalyed. Based on these considerations, the strategy to solve these problems
are to develop robust conditions that could match the rate of copperꢀcatalyzed selenation of aryl
iodides with elemental selenium and the rate of transmetalation of indoleꢀmetal intermediate
species,15 to suppress the undesired sideꢀreactions including the homoꢀcoupling of PhSeCu
species.
RESULTS AND DISCUSSION
Table 1. Reaction Optimizationa
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entry
1
[Cu]
base
solvent
Yield (%)b
35
CuI
CuI
Na3PO4. 12H2O
Na3PO4. 12H2O
Na3PO4. 12H2O
Na3PO4. 12H2O
Na3PO4. 12H2O
Na3PO4. 12H2O
Na3PO4. 12H2O
Na3PO4. 12H2O
Na3PO4. 12H2O
Na2CO3
DMF
Toluene
1,4ꢀDioxane
CH3CN
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
2
none
none
none
60
3
CuI
4
CuI
5
CuI
6
CuBr2
CuCl2
Cu(OAc)2
CuO
CuO
CuO
CuO
CuO
CuO
CuO
56
7
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8
64
9
92
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13
14c
15d
16
75
K2CO3
79
NaOAc
42
K3PO4
50
Na3PO4. 12H2O
Na3PO4. 12H2O
Na3PO4. 12H2O
31
54
0
aReaction condition: 0.2 mmol iodobenzene, 0.6 mmol Se, 0.5 mmol indole, 0.02 mmol [Cu], 0.8
mmol base, 2 mL solvent, N2, 110 ℃, 24 h. bIsolated yield. cUnder O2. dUnder air.
The project began with the study on the reaction between iodobenzene (1a) and indole (2a). After
initial optimizations, it was found that 2a was transformed into the desired C3ꢀarylsenelonation
product (3a) in 35% isolated yield (entry 1), along with a small amount of the diphenyl diselenide
byproduct (Table 1, entry 1). Among the several solvents examined, DMSO was the optimal
solvent, afforded the product in 60 % isolated yield (entry 5), and the reaction became sluggish
when solvents like toluene, 1, 4ꢀdioxane and CH3CN were used (entries 2ꢀ4). Among various
copper salts tested, the best result was obtained with CuO, providing the product in 92% yield
(entries 9). And then, we screened an array of bases; the use of Na2CO3 and NaOAc gave slightly
lower yields (entries 10ꢀ13). N2 atmosphere is essential for this reaction, and when the reaction
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was conducted under O2 or air, decreased the yield of the reaction (entries 14, 15). This would be
due to the reasons that O2 could intercept the catalytic intermediate in the process, and indole is
not stable under high O2 concentration. A control experiment showed that the copper catalyst is
essential for this transformation since no coupling product was obtained in the absence of copper
(entry 16). Of particular note, in all cases, the reaction show excellent regioselectivity and no
2ꢀarylselenolation of indoles or Nꢀaryl indoles byproducts were observed from analysis of the
crude reactions mixtures.
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Scheme 1. Aryl iodides Scopea
aReaction conditions: aryl iodides (0.2 mmol), Se8 (0.6 mmol), indole (0.5 mmol), CuO (0.02
.
b
mmol), Na3PO4 12H2O (0.8 mmol), DMSO (2 mL), 110 °C, 24 h, N2, isolated yields. CuO (20
mol %).
With the optimal conditions in hand, the scope of the substrates was explored. A wide range
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of aryl iodides were employed and the reaction generally proceeded smoothly, afforded the
corresponding products in good to excellent yields (Scheme 1). When iodobenzenes bearing a
variety of electronꢀdonating groups, such as methyl (3b), methoxy (3k), and trifluoromethyl (3e),
the reactions reacted smoothly and good yields were obtained. The reaction of iodobenzene
bearing electronꢀwithdrawing groups such as fluoro (3g), chloro (3h), bromo (3i), acetyl (3j),
aldehyde (3m), and nitro(3n) gave the corresponding products in moderate to excellent yields. The
compatibility of these functional groups in this reaction provided an opportunity for further
elaboration to achieve more complex products. It was noteworthy that steric hindrance did not
have great effect on the reaction, for example, when methyl substitute located on the Cꢀ2, Cꢀ3, Cꢀ4
position of benzene iodide, similar yields (3b, 3d, 3f) were observed. It was remarkable that
heterocyclic iodides, such as pyridine, thiophene and quinoline also provided the corresponding
products (3o, 3p, 3q) in good yields.
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Scheme 2. Indoles Scope
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Furthermore, a diverse of substituted indoles were subjected to the optimal reaction
conditions to explore the scope and generality of this reaction (Scheme 2). A variety of functional
groups on the benzene ring of indoles were compatible, such as methyl(4a, 4i, 4o), fluoride(4d, 4j),
chloride(4k), bromide(4e, 4l), methoxy (4b, 4f, 4p) and nitro(4h), which had little effect on the
reactivity and the regioselectivity of reactions. When the introduction of the methyl and phenyl
occupied at the C2 of indole, the corresponding products were obtained (4p, 4q, 4r) in good yields.
The free NH group of indole was found to play a critical role, the more nucleophilic
1ꢀmethylindole (3s) and electronꢀpoor NꢀAc(3m) and NꢀTs (3n) of indole did not undergo the
copperꢀmediated arylselenation reaction. To investigate whether arylselenation for other
heterocyclic compounds such as functionalized pyrroles、 benzofuranes、thianaphthene and
benzimidazole under current reaction condition, however, only slight decomposition of the starting
materials without the expected products. Based on these experiments result, it’s perhaps that the
relative stability of C3 nucleophilicity of indole was critical successful for this reaction.
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Scheme 3. Intramolecular C-Se Bond Formation
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Next, the synthetic method was extended to intramolecular CꢀSe bond formation, providing a
straightforward pathway to synthesize Benzoselenopheno[3,2ꢀb]indole. As shown in Scheme 3,
the cyclization starting substrates could be easily prepared by use of Fischer indole synthesis
approach. Overall, good to excellent yields of 6 were obtained, and various substituents on the
indole ring showed nonbiased to the efficiency of the reactions. A variety of functional groups
such as electronꢀdonating groups methyl(6b, 6k), methoxy (6f), trifluoromethoxy (6g), and
electronꢀwithdrawing groups fluoride(6c), chloride(6d), and bromide(6e) were compatible.
Disubstituted on benzene ring of Benzoselenopheno[3,2ꢀb]indole could also be obtained (6h, 6i,
6j). These results highlight the generality of the new method. The products of intramolecular
reactions also could be potential compounds for electronic materials.16
Scheme 4. Gram-Scale Synthesis and Application
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The utility of this new method was further demonstrated by an efficient gramꢀscale synthesis
and an application to the synthesis of an important inhibitor (Scheme 4). The copperꢀcatalyzed
double CꢀSe bond formation produced the proudct 3a in 79% yield as 2.14 gram under standard
reaction conditions. Inaddition, application of the new method in a twoꢀstep synthesis of 3ꢀ(3, 4,
5ꢀTrimethoxyphenylselenyl)ꢀmethylꢀindole4 was achieved, a reported efficient inhibitor in the
tubulin polymerization and disrupt tubulin microtubule dynamics. Subsequent methylation
treated with CH3I afforded the target product in 68% overall yield.
Scheme 5. Preliminary mechanism investigation
To understand the reaction mechanism, controll experiments were conducted (Scheme 5).
First, a stoichiometric reaction of PhSeCu with simple indole under N2 atmosphere did not
promote the reaction, but the desired product 3a was obtained in 92% isolated yield under O2
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atmosphere. The lack of reactivity with PhSeCu under N2 indicated that the CꢀSe bond formation
of indole probably proceeded through the oxidative crossꢀcoupling pathway. An interesting
phenomenon was observed, however, when adding 3 equivalent of selenium powder under N2
atmosphere, 3ꢀphenyselenation of indole 3a and the byproduct diphenyl selenide were obtained in
a 1:1 ratio and the PhSeCu went to full conversion (eq 2); these experiments could explain the
transformation needs an excess amount of element Se. Secondly, As shown in eq 3, it suggested
that PhSeCu may be a chemical competent intermediate produced in situ during the catalytic cycle.
It could also rationalize why a small amount of diphenyl diselenides were detected in the reaction.
Finally, when the radical inhibitor TEMPO was added to the reaction conditions, product 3a was
still obtained in 91% yield, which in turn suggested that a radicalꢀinvolved mechanism could be
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ruled out.
Scheme 6. Proposed Catalytic Cycle
On the basis of above observations and related literatures,17 a plausible mechanism for the
reaction is proposed (Scheme 6). It is wellꢀknown that selenium readily transformed to selenide
anion and selenite in the presence of a base.18 A proposed catalytic cycle could start with an
oxidative addition of iodobenzene with CuX, followed by ligand exchange with Se2ꢀ to generate
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the intermediate (III). Then, reductive elimination of (III) will generate the arylselenium anion(IV),
which reacts with CuX to form the PhSeCu(V) species. Then, base assisted metalation of indole
with PhSeCu led to (VI) through selenite instantaneous oxidation, followed by immediate
reductive eliminaton to provide the desired product and regenerate the CuX catalyst. At this stage,
the accurate role of elemental selenium is vague, but indeed participates in the oxidation step
according to the above experimental results.
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In summary, we have developed a new and efficient copper catalyzed threeꢀcomponent
reaction for the selective synthesis of unsymmetrical diphenyl selenides. Commercial available,
stable, easyꢀtoꢀhandle elemental selenium was used as selenating reagent. In addition, both
intermolecular and intramolecular reactions were achieved to set linear or cyclic selenating system.
Moreover, good to excellent yields were obtained and the reaction can tolerate a wide scope of
functional groups. Furthermore, early mechanism study suggests that copperꢀcatalyzed direct
double CꢀSe bonds formation proceeds through Ullmanꢀtype selenation of aryl iodides and
selenium and consequential oxidative crossꢀcoupling with indole. Further studies on the reaction
mechanism and the development of new strategies of selective selenation transformations are
underway in our laboratory.
EXPERIMENTAL SECTION
General Remarks. 1H NMR (500 MHz), 13C NMR (125 MHz) and 19F NMR (470 MHz) spectra
were recorded in DMSOꢀd6 solutions using 500 MHz spectrometer. Highꢀresolution mass spectra
were recorded on an ESIꢀQꢀTOF mass spectrometer. All reactions were conducted using standard
Schlenk techniques. Column chromatography was performed using EM silica gel 60 (300−400
mesh). Copies of their 1H NMR and 13C NMR spectra are provided. 2ꢀ(2ꢀiodophenyl)ꢀ1Hꢀindole19,
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2ꢀ(2ꢀiodophenyl)ꢀ5ꢀmethylꢀ1Hꢀindole19, 5ꢀfluoroꢀ2ꢀ(2ꢀiodophenyl)ꢀ1Hꢀindole19, 5ꢀchloroꢀ2ꢀ
(2ꢀiodophenyl)ꢀ1Hꢀindole19, 5ꢀbromoꢀ2ꢀ(2ꢀiodophenyl)ꢀ1Hꢀindole19, 2ꢀ(2ꢀiodophenyl)ꢀ5ꢀmethoxy
ꢀ1Hꢀindole19, 2ꢀ(2ꢀiodophenyl)ꢀ5ꢀ(trifluoromethoxy)ꢀ1Hꢀindole19, 2ꢀ(2ꢀiodophenyl)ꢀ4,6ꢀdimethyl
ꢀ1Hꢀindole19,4,6ꢀdifluoroꢀ2ꢀ(2ꢀiodophenyl)ꢀ1Hꢀindole19, 4,6ꢀdichloroꢀ2ꢀ(2ꢀiodophenyl)
ꢀ1Hꢀindole19, 2ꢀ(2ꢀiodophenyl)ꢀ7ꢀmethylꢀ1Hꢀindole19 and PhSeCu20 were prepared according to
the reported procedures. 1H and 13C spectra of known compounds were in accordance with those
described in the literatures.
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Procedure for Intermolecular Phenylselenation of Indole Reactions: To a 10 mL Schlenk tube
equipped with a stir bar was added aryl iodide 1 (0.2 mmol), indole 2 (0.5 mmol), Se (47.4 mg, 0.6
mmol), CuO (10 mol %), Na3PO4.12H2O (0.8 mmol) in DMSO (2 mL). The tube was evacuated
and refilled with N2 three times. The reaction mixture was stirred at 110 oC for 24 h. After cooling
down, the reaction mixture was diluted with 10 mL of ethyl ether, filtered through a pad of silica
gel, followed by washing the pad of the silica gel with the same solvent (20 mL). The filtrate was
washed with water (3×15 mL). The organic phase was dried over Na2SO4, filtered, concentrated
under reduced pressure. The residue was then purified by flash chromatography on silica gel to
provide the corresponding product.
Procedure for Intramolecular Phenylselenation of Indole Reactions: To a 10 mL Schlenk tube
equipped with a stir bar was added substrate 5 (0.2 mmol), Se (47.4 mg, 0.6 mmol), CuO (10
mol %), Na3PO4.12H2O (0.8 mmol) in DMSO (2 mL). The tube was evacuated and refilled with
o
N2 three times. The reaction mixture was stirred at 110 C for 24 h. After cooling down, the
reaction mixture was diluted with 10 mL of ethyl ether, filtered through a pad of silica gel,
followed by washing the pad of the silica gel with the same solvent (20 mL). The filtrate was
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washed with water (3×15 mL). The organic phase was dried over Na2SO4, filtered, concentrated
under reduced pressure. The residue was then purified by flash chromatography on silica gel to
provide the corresponding product.
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Preliminary Mechanism Investigation: Two 10 mL of Schlenk tubes equipped with a stir bar
.
were added with PhSeCu (0.2 mmol), indole (0.5 mmol), Na3PO4 12H2O (0.8 mmol) in DMSO
(2 mL). In the first tube, The tube was evacuated and refilled N2 three times. In the other tube,
The tube was fitted with a rubber septum, and then it was evacuated and refilled with O2 three
o
times. These reactions mixture were stirred at 110 C for 24 h (see Scheme 5, eq 1). To a 10 mL
Schlenk tube equipped with a stir bar was added PhSeCu (0.2 mmol), Se (31.6 mg, 0.4 mmol),
indole (0.5 mmol), Na3PO4.12H2O (0.8 mmol) in DMSO (2 mL). The tube was evacuated and
refilled with N2 three times. The reaction mixture was stirred at 110 oC for 24 h(see Scheme 5, eq
2). To a 10 mL Schlenk tube equipped with a stir bar was added aryl iodide 1 (0.2 mmol), indole 2
(0.5 mmol), Se (47.4 mg, 0.6 mmol), PhSeCu (10 mol %), Na3PO4.12H2O (0.8 mmol) in DMSO
(2 mL). The tube was evacuated and refilled with N2 three times. The reaction mixture was stirred
at 110 oC for 24 h(see Scheme 5, eq 3). After cooling down, the reaction mixture was diluted with
10 mL of ethyl ether, filtered through a pad of silica gel, followed by washing the pad of the silica
gel with the same solvent (20 mL). The filtrate was washed with water (3×15 mL). The organic
phase was dried over Na2SO4, filtered, concentrated under reduced pressure. The residue was then
purified by flash chromatography on silica gel to provide the corresponding product.
Characterization Data of Compounds 3, 4, 6, 7a:
3ꢀ(phenylseleno)ꢀ1Hꢀindole(3a) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a white solid (50.2 mg, 92 % yield). The 1H, 13C NMR spectra
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3ꢀ(oꢀtolylseleno)ꢀ1Hꢀindole(3b) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a white solid (45.6 mg, 80 % yield). The 1H, 13C NMR spectra
were in accordance with those described in the literature.22
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2ꢀ((1Hꢀindolꢀ3ꢀyl)seleno)benzonitrile (3c) Following the general procedure, 0.04 mmol CuO,
using 7:1 petroleum etherꢀEtOAc as the eluant afforded a brown solid (46.6 mg, 78 % yield), mp
103ꢀ105 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 11.85 (s, 1H), 7.84 (d, J = 2.5 Hz, 1H), 7.80 (d, J =
7.5 Hz, 1H), 7.53 (d, J = 8.5 Hz, 1H), 7.41 – 7.36 (m, 2H), 7.29 (t, J = 7.5 Hz, 1H), 7.21 (t, J = 7.5
Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 6.90 (d, J = 8.0 Hz, 1H). 13C NMR (125 MHz, DMSOꢀd6) δ
139.1, 136.7, 133.6, 133.6, 133.5, 129.1, 128.7, 126.3, 122.2, 120.4, 118.6, 117.3, 112.3, 110.8,
93.0. HRMS (EI, 70 eV) calcd for C15H10N2Se [M+]: 298.0009, found 298.0013.
3ꢀ(mꢀtolylseleno)ꢀ1Hꢀindole (3d) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a brown viscous oil(46.3 mg, 81 % yield). 1H NMR (500 MHz,
DMSOꢀd6) δ 11.67 (s, 1H), 7.73 (d, J = 2.5 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 8.0 Hz,
1H), 7.17 (t, J = 7.5 Hz, 1H), 7.08ꢀ7.02 (m, 3H), 6.91 (d, J = 7.5 Hz, 2H), 2.16 (s, 3H). 13C NMR
(125 MHz, DMSOꢀd6) δ 138.3, 136.6, 133.5, 132.7, 129.5, 128.9, 128.6, 126.4, 125.3, 121.9,
120.0, 119.0, 112.1, 95.1, 20.8. HRMS (EI, 70 eV) calcd for C15H13NSe [M+]: 287.0213, found
287.0214.
3ꢀ((4ꢀ(trifluoromethyl)phenyl)seleno)ꢀ1Hꢀindole (3e) Following the general procedure, using 7:1
petroleum etherꢀEtOAc as the eluant afforded a yellowish solid (59.1 mg, 87 % yield), mp
1
123−124 °C. H NMR (500 MHz, DMSOꢀd6) δ 11.79 (s, 1H), 7.80 (s, 1H), 7.53ꢀ7.49 (m, 3H),
7.38 (d, J = 7.5 Hz, 1H), 7.31 (d, J = 7.5 Hz, 2H), 7.20 (t, J = 7.0 Hz, 1H), 7.08 (t, J = 7.0 Hz, 1H).
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13C NMR (125 MHz, DMSO) δ 140.4, 136.7, 133.3, 129.2, 128.0, 126.0 (d, JF = 31.3 Hz), 125.6
(q, JF = 5.0 Hz), 124.3 (d, JF = 270.0 Hz), 122.2, 120.3, 118.8, 112.3, 93.7. 19F NMR (470 MHz,
DMSOꢀd6): δ ꢀ60.86 (s, 3F). HRMS (ESI) calcd for C15H10F3NSe [M+Na]+: 363.9823, found
363.9827.
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3ꢀ(pꢀtolylseleno)ꢀ1Hꢀindole (3f) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a white solid (44.6 mg, 78 % yield). The 1H, 13C NMR spectra
were in accordance with those described in the literature.21
3ꢀ((4ꢀfluorophenyl)seleno)ꢀ1Hꢀindole (3g) Following the general procedure, 0.04 mmol CuO,
using 7:1 petroleum etherꢀEtOAc as the eluant afforded a brown solid (49.3 mg, 85 % yield), mp
1
135−136 °C. H NMR (500 MHz, DMSOꢀd6) δ 11.68 (s, 1H), 7.74 (s, 1H), 7.48 (d, J = 8.0 Hz,
1H), 7.41 (d, J = 8.0 Hz, 1H), 7.22 – 7.16 (m, 3H), 7.09ꢀ7.02 (m, 3H). 13C NMR (125 MHz,
DMSOꢀd6) δ 160.8 (d, JF = 241.3 Hz), 136.6, 132.7, 130.3 (d, JF = 7.5 Hz), 129.30, 128.4 (d, JF =
3.8 Hz), 122.0, 120.1, 118.9, 116.1 (d, JF = 22.5 Hz), 112.1, 95.4. 19F NMR (470 MHz, DMSOꢀd6):
δ ꢀ117.40 (s, 1F). HRMS (EI, 70 eV) calcd for C14H10FNSe [M+]: 290.9962, found 290.9962.
3ꢀ((4ꢀchlorophenyl)seleno)ꢀ1Hꢀindole (3h) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a white solid (52.4 mg, 85 % yield). The 1H, 13C NMR spectra
were in accordance with those described in the literature.21
3ꢀ((4ꢀbromophenyl)seleno)ꢀ1Hꢀindole (3i) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a brown solid (60.6 mg, 86 % yield), mp 131ꢀ135 °C. 1H NMR
(500 MHz, DMSOꢀd6) δ 11.73 (s, 1H), 7.76 (s, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.39ꢀ7.34 (m, 3H),
7.18 (t, J = 7.5 Hz, 1H), 7.09ꢀ7.06 (m, 3H). 13C NMR (125 MHz, DMSOꢀd6) δ 136.6, 133.3, 132.9,
131.8, 130.0, 129.2, 122.1, 120.1, 118.8, 118.6, 112.2, 94.5. HRMS (EI, 70 eV) calcd for
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C14H10BrNSe [M+]: 350.9162, found 350.9162.
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1ꢀ(4ꢀ((1Hꢀindolꢀ3ꢀyl)seleno)phenyl)ethanꢀ1ꢀone (3j) Following the general procedure, 0.04 mmol
CuO, using 7:1 petroleum etherꢀEtOAc as the eluant afforded a yellow solid (32.1 mg, 51 % yield),
mp 139ꢀ141 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 11.78 (s, 1H), 7.79 (d, J = 2.5 Hz, 1H), 7.73 (d,
J = 8.5 Hz, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.24 – 7.18 (m, 3H), 7.09 –
7.06 (m, 1H), 2.47 (s, 3H). 13C NMR (125 MHz, DMSOꢀd6) δ 197.0, 141.6, 136.7, 134.1, 133.1,
129.2, 128.7, 127.3, 122.1, 120.2, 118.8, 112.2, 93.8, 26.4. HRMS (EI, 70 eV) calcd for
C16H13NOSe [M+]: 315.0162, found 315.0168.
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3ꢀ((4ꢀmethoxyphenyl)seleno)ꢀ1Hꢀindole (3k) Following the general procedure, 0.04 mmol CuO,
using 7:1 petroleum etherꢀEtOAc as the eluant afforded a white solid (45.9 mg, 76 % yield) , mp
113−115 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 11.58 (s, 1H), 7.69 (s, 1H), 7.45 (t, J = 8.0 Hz, 2H),
7.20 – 7.14 (m, 7.4 Hz, 3H), 7.06 (t, J = 7.0 Hz, 1H), 6.78 (d, J = 7.5 Hz, 2H), 3.66 (s, 3H). 13C
NMR (125 MHz, DMSOꢀd6) δ 157.9 , 136.5 , 132.1 , 130.7, 129.4 , 123.0 , 121.8, 119.8 , 119.0 ,
114.8 , 111.9 , 96.5 , 55.0. HRMS (EI, 70 eV) calcd for C15H13NOSe [M+]: 303.0162, found
303.0159.
4ꢀ((1Hꢀindolꢀ3ꢀyl)seleno)benzonitrile (3l) Following the general procedure, 0.04 mmol CuO,
using 7:1 petroleum etherꢀEtOAc as the eluant afforded a brown liquid (52.9 mg, 89 % yield). 1H
NMR (500 MHz, DMSOꢀd6) δ 11.83 (s, 1H), 7.80 (s, 1H), 7.58 (d, J = 7.5 Hz, 2H), 7.53 (d, J =
8.0 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.26 (d, J = 8.0 Hz, 2H), 7.21 (t, J = 7.5 Hz, 1H), 7.09 (t, J
= 7.5 Hz, 1H). 13C NMR (125 MHz, DMSOꢀd6) δ 142.5, 136.7, 133.4, 132.4, 129.1, 128.0, 122.3,
120.4, 118.9, 118.7, 112.3, 107.7, 93.3. HRMS (EI, 70 eV) calcd for C15H10N2Se [M+]: 298.0009,
found 298.0008.
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4ꢀ((1Hꢀindolꢀ3ꢀyl)seleno)benzaldehyde (3m) Following the general procedure, using 7:1
petroleum etherꢀEtOAc as the eluant afforded a yellow solid (43.1 mg, 72 % yield), mp
143−145 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 11.81 (s, 1H), 9.85 (s, 1H), 7.80 (d, J = 2.5 Hz,
1H), 7.67 (d, J = 8.0, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz,
2H), 7.20 (t, J = 7.5 Hz, 1H), 7.08 (t, J = 7.5 Hz, 1H). 13C NMR (125 MHz, DMSOꢀd6) δ 192.1,
143.9, 136.7, 133.7, 133.3, 129.9, 129.2, 127.6, 122.2, 120.3, 118.8, 112.3, 93.5. HRMS (ESI)
calcd for C15H11NOSe [M+H]+: 302.0079, found 302.0080.
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3ꢀ((4ꢀnitrophenyl)seleno)ꢀ1Hꢀindole (3n) Following the general procedure, 0.04 mmol CuO, using
7:1 petroleum etherꢀEtOAc as the eluant afforded a yellow liquid (58.3 mg, 92 % yield). 1H NMR
(500 MHz, DMSOꢀd6) δ 11.86 (s, 1H), 8.00 (d, J = 8.5 Hz, 2H), 7.82 (s, 1H), 7.54 (d, J = 8.0 Hz,
1H), 7.37ꢀ7.33 (m, 3H), 7.21 (t, J = 7.5 Hz, 1H), 7.09 (t, J = 7.0 Hz, 1H). 13C NMR (125 MHz,
DMSOꢀd6) δ 145.5, 145.3, 136.7, 133.4, 129.1, 127.8, 123.8, 122.3, 120.4, 118.7, 112.3, 93.2.
HRMS (EI, 70 eV) calcd for C14H10N2O2Se [M+]: 317.9907, found 317.9912.
3ꢀ(pyridinꢀ2ꢀylseleno)ꢀ1Hꢀindole (3o) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a white solid (44.8 mg, 82 % yield), mp 103−104 °C. 1H NMR
(500 MHz, DMSOꢀd6) δ 11.75 (s, 1H), 8.37 (s, 1H), 7.76 (s, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.44 –
7.40 (m, 2H), 7.20 (t, J = 7.0 Hz, 1H), 7.10 ꢀ 7.08 (m, 2H), 6.70 (d, J = 7.5 Hz, 1H). 13C NMR
(125 MHz, DMSOꢀd6) δ 159.2, 149.5, 136.9, 136.7, 133.1, 129.3, 122.1, 121.9, 120.2 (2C), 118.9,
112.2, 94.5. HRMS (ESI) calcd for C13H10N2Se [M+H]+: 275.0082, found 275.0088.
3ꢀ(thiophenꢀ3ꢀylseleno)ꢀ1Hꢀindole (3p) Following the general procedure, using 7:1 petroleum
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etherꢀEtOAc as the eluant afforded a yellow viscous oil (36.1 mg, 65 % yield). H NMR (500
MHz, DMSOꢀd6) δ 11.58 (s, 1H), 7.70 (t, J = 2.0 Hz, 1H), 7.53 – 7.42 (m, 3H), 7.23 – 7.12 (m,
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2H), 7.08 (t, J = 7.5 Hz, 1H), 6.91 (d, J = 5.0 Hz, 1H). 13C NMR (125 MHz, DMSOꢀd6) δ 136.4,
131.8, 129.7, 129.3, 127.0 , 126.1, 123.0, 121.9, 119.86 , 119.0, 112.0, 96.2. HRMS (ESI) calcd
for C12H9NSSe [M+H]+: 279.9694, found 279.9704.
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4ꢀ((1Hꢀindolꢀ3ꢀyl)seleno)ꢀ7ꢀchloroquinoline (3q) Following the general procedure, using 7:1
petroleum etherꢀEtOAc as the eluant afforded a yellow solid (43.6 mg, 61 % yield), mp
176−177 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 11.94 (s, 1H), 8.45 (d, J = 4.0 Hz, 1H), 8.21 (d, J
= 8.5 Hz, 1H), 8.08 (s, 1H), 7.89 (s, 1H), 7.75 (d, J = 8.5 Hz, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.36 (d,
J = 8.0 Hz, 1H), 7.23 (t, J = 7.5 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 6.79 (d, J = 4.0 Hz, 1H). 13C
NMR (125 MHz, DMSOꢀd6) δ 150.7, 147.6, 146.6, 136.9, 134.4, 133.9, 129.1, 128.2, 127.5, 126.7,
125.7, 122.3, 120.5, 120.2, 118.7, 112.4, 91.3. HRMS (ESI) calcd for C17H11ClN2Se [M+H]+:
358.9849, found 358.9864.
4ꢀmethylꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4a) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a brown solid (52.2 mg, 91 % yield), mp 141ꢀ142 °C. 1H NMR
(500 MHz, DMSOꢀd6) δ 11.66 (s, 1H), 7.66 (d, J = 2.5 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.20 –
7.09 (m, 5H), 7.04 (t, J = 7.5 Hz, 1H), 6.77 (d, J = 7.0 Hz, 1H), 2.57 (s, 3H). 13C NMR (125 MHz,
DMSOꢀd6) δ 137.1, 136.1, 133.8, 130.1, 129.1, 127.5, 126.7, 125.3, 122.0, 121.5, 110.2, 93.8,
18.4. HRMS (EI, 70 eV) calcd for C15H13NSe [M+]: 287.0213, found 287.0215.
4ꢀ(benzyloxy)ꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4b) Following the general procedure, using 7:1
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petroleum etherꢀEtOAc as the eluant afforded a atropurpureus liquid (59.8 mg, 79 % yield). H
NMR (500 MHz, DMSOꢀd6) δ 11.61 (s, 1H), 7.49 (d, J = 2.5 Hz, 1H), 7.29 – 7.27 (m, 2H), 7.25 –
7.21 (m, 3H), 7.20 – 7.15 (m, 4H), 7.11 – 7.04 (m, 3H), 6.61 (d, J = 7.5 Hz, 1H), 5.07 (s, 2H). 13
C
NMR (125 MHz, DMSOꢀd6) δ 152.6, 138.7, 137.3, 135.5, 131.8, 128.8, 128.2, 127.9, 127.1, 126.8,
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125.2, 122.7, 118.6, 105.4, 101.7, 93.0, 68.8. HRMS (EI, 70 eV) calcd for C21H17NOSe [M+]:
379.0475, found 379.0478.
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3ꢀ(phenylseleno)ꢀ1Hꢀindoleꢀ4ꢀcarbonitrile (4c) Following the general procedure, using 7:1
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petroleum etherꢀEtOAc as the eluant afforded a yellow solid (35.7 mg, 60 % yield). The H, 13C
NMR spectra were in accordance with those described in the literature. 22
5ꢀfluoroꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4d) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a brown solid (47.5 mg, 82 % yield), mp 126ꢀ128 °C. 1H NMR
(500 MHz, DMSOꢀd6) δ 11.81 (s, 1H), 7.82 (s, 1H), 7.52 – 7.48 (m, 1H), 7.19 – 7.00 (m, 7H). 13
C
NMR (125 MHz, DMSOꢀd6) δ 157.6 (d, JF = 231.3 Hz), 134.8, 133.3 (d, JF = 11.3 Hz) , 130.2 (d,
JF = 10.0 Hz), 129.1, 128.2, 125.7, 113.4 (d, JF = 8.8 Hz), 110.3 (d, JF = 26.3 Hz), 103.6 (d, JF =
23.8 Hz), 95.1. 19F NMR (470 MHz, DMSOꢀd6): δ ꢀ123.42 (s, 1F). HRMS (EI, 70 eV) calcd for
C14H10FNSe [M+]: 290.9962, found 290.9969.
5ꢀbromoꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4e) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a brown solid (57.6 mg, 82 % yield). The 1H, 13C NMR
spectra were in accordance with those described in the literature.21
5ꢀmethoxyꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4f) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a brown viscous oil (50.7 mg, 84 % yield). The 1H, 13C NMR
spectra were in accordance with those described in the literature.21
3ꢀ(phenylseleno)ꢀ1Hꢀindoleꢀ5ꢀcarbonitrile (4g) Following the general procedure, using 7:1
petroleum etherꢀEtOAc as the eluant afforded a brown solid (42.2 mg, 71 % yield), mp
141ꢀ143 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 12.23 (s, 1H), 7.98 (s, 1H), 7.83 (s, 1H), 7.67 (d, J
= 8.5 Hz, 1H), 7.53 (d, J = 8.5 Hz, 1H), 7.20 – 7.14 (m, 5H). 13C NMR (125 MHz, DMSOꢀd6) δ
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138.6, 135.5, 132.8, 129.4, 129.2, 128.5, 126.0, 124.8, 124.3, 120.2, 113.6, 102.3, 96.5. HRMS
(EI, 70 eV) calcd for C15H10N2Se [M+]: 298.0009, found 298.0014.
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5ꢀnitroꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4h) Following the general procedure,0.04 mmol Cu, using
7:1 petroleum etherꢀEtOAc as the eluant afforded a yellow solid (50.1 mg, 79 % yield), mp
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141ꢀ143 °C. H NMR (500 MHz, DMSOꢀd6) δ 12.39 (s, 1H), 8.29 (s, 1H), 8.08 (d, J = 11.5 Hz,
2H), 7.69 (d, J = 8.5 Hz, 1H), 7.23 – 7.14 (m, 5H). 13C NMR (125 MHz, DMSOꢀd6) δ 141.5,
139.9, 136.7, 132.6, 129.2, 129.1, 128.5, 126.0, 117.3, 115.6, 112.8, 98.1. HRMS (EI, 70 eV)
calcd for C14H10N2O2Se [M+]: 317.9907, found 317.9915.
6ꢀmethylꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4i)
Following the general procedure, using 7:1 petroleum etherꢀEtOAc as the eluant afforded a yellow
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solid (51.0 mg, 89 % yield), mp 140−143 °C. H NMR (500 MHz, DMSOꢀd6) δ 11.52 (s, 1H),
7.63 (s, 1H), 7.27 (d, J = 5.5 Hz, 2H), 7.17 – 7.09 (m, 5H), 6.89 (d, J = 8.0 Hz, 1H), 2.40 (s, 3H).
13C NMR (125 MHz, DMSOꢀd6) δ 137.0, 133.8, 132.0, 131.2, 129.0, 128.0, 127.4, 125.5, 121.8,
118.7, 111.8, 94.7, 21.2. HRMS (EI, 70 eV) calcd for C15H13NSe [M+]: 287.0213, found 287.0216.
6ꢀfluoroꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4j) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a brown solid (53.9 mg, 93 % yield), mp 131ꢀ132 °C. 1H NMR
(500 MHz, DMSOꢀd6) δ 11.75 (s, 1H), 7.74 (s, 1H), 7.36 (dd, J = 8.5, 5.0 Hz, 1H), 7.28 (d, J = 9.5
Hz, 1H), 7.16 – 7.10 (m, 5H), 6.94 – 6.91 (m, 1H). 13C NMR (125 MHz, DMSOꢀd6) δ 159.2 , (d,
JF = 233.8 Hz), 136.4 (d, JF = 13.8 Hz), 133.4 (d, JF = 12.5 Hz), 129.1, 128.2, 126.2, 125.7, 120.1
(d, JF = 10.0 Hz), 108.6 (d, JF = 25 Hz), 98.1 (d, JF = 26.3 Hz), 95.3. 19F NMR (470 MHz,
DMSOꢀd6): δ ꢀ121.07 (s, 1F). HRMS (EI, 70 eV) calcd for C14H10FNSe [M+]: 290.9962, found
290.9969.
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6ꢀchloroꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4k) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a brown solid (51.6 mg, 84 % yield), mp 127ꢀ130 °C. 1H NMR
(500 MHz, DMSOꢀd6) δ 11.82 (s, 1H), 7.79 (s, 1H), 7.55 – 7.54 (m, 1H), 7.40 – 7.38 (m, 1H),
7.18 – 7.07 (m, 6H). 13C NMR (125 MHz, DMSOꢀd6) δ 136.9, 133.8, 133.2, 129.0, 128.3, 128.2,
126.7, 125.7, 120.3, 111.7, 95.5. HRMS (EI, 70 eV) calcd for C14H10ClNSe [M+]: 306.9667, found
306.9672.
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6ꢀbromoꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4l) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a brown solid (64.6 mg, 92 % yield), mp 126ꢀ127 °C. 1H NMR
(500 MHz, DMSOꢀd6) δ 11.80 (s, 1H), 7.77 (s, 1H), 7.68 (s, 1H), 7.34 (d, J = 8.5 Hz, 1H), 7.21 –
7.10 (m, 6H). 13C NMR (125 MHz, DMSOꢀd6) δ 137.5, 133.8, 133.3, 129.1, 128.6, 128.2, 125.7,
123.0, 120.8, 114.8, 114.7, 95.4. HRMS (EI, 70 eV) calcd for C14H10BrNSe [M+]: 350.9162, found
350.9168.
methyl 3ꢀ(phenylseleno)ꢀ1Hꢀindoleꢀ6ꢀcarboxylate (4m) Following the general procedure, using
7:1 petroleum etherꢀEtOAc as the eluant afforded a white solid (53.5 mg, 81 % yield), mp
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144ꢀ146 °C. H NMR (500 MHz, DMSOꢀd6) δ 12.07 (s, 1H), 8.15 (s, 1H), 7.99 (d, J = 2.0 Hz,
1H), 7.70 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.5 Hz, 1H), 7.19 – 7.10 (m, 5H), 3.86 (s, 3H). 13C
NMR (125 MHz, DMSOꢀd6) δ 166.9, 136.4, 135.9, 133.2, 133.2, 129.1, 128.2, 125.7, 123.2, 120.6,
118.9, 114.0, 95.7, 51.7. HRMS (EI, 70 eV) calcd for C16H13NO2Se [M+]: 331.0112, found
331.0115.
3ꢀ(phenylseleno)ꢀ1Hꢀindoleꢀ6ꢀcarbaldehyde (4n) Following the general procedure, using 7:1
petroleum etherꢀEtOAc as the eluant afforded a brown solid (39.1 mg, 65 % yield), mp
144ꢀ147 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 12.24 (s, 1H), 10.03 (s, 1H), 8.06 (d, J = 10.0 Hz,
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2H), 7.61 (d, J = 8.0 Hz, 1H), 7.56 (d, J = 8.5 Hz, 1H), 7.18 – 7.10 (m, 5H). 13C NMR (125 MHz,
DMSOꢀd6) δ 192.6, 137.2, 136.1, 134.3, 133.0, 131.1, 129.1, 128.3, 125.8, 119.9, 119.5, 115.9,
96.2. HRMS (EI, 70 eV) calcd for C15H11NOSe [M+]: 301.0006, found 301.0013.
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7ꢀmethylꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4o) Following the general procedure, using 7:1 petroleum
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etherꢀEtOAc as the eluant afforded a brown liquid (52.1 mg, 91 % yield). H NMR (500 MHz,
DMSOꢀd6) δ 11.71 (s, 1H), 7.75 (d, J = 2.5 Hz, 1H), 7.30 – 7.28 (m, 1H), 7.19 – 7.13 (m, 4H),
7.08 (t, J = 7.0 Hz, 1H), 6.99 (d, J = 6.5 Hz, 2H), 2.54 (s, 3H). 13C NMR (125 MHz, DMSOꢀd6) δ
136.1, 133.8, 132.3, 129.3, 128.9, 128.1, 125.4, 122.5, 121.3, 120.1, 116.6, 95.5, 16.6. HRMS (EI,
70 eV) calcd for C15H13NSe [M+]: 287.0213, found 287.0208.
5ꢀmethoxyꢀ2ꢀmethylꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4p) Following the general procedure, using 7:1
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petroleum etherꢀEtOAc as the eluant afforded a yellow liquid (51.9 mg, 82 % yield). H NMR
(500 MHz, DMSOꢀd6) δ 11.48 (s, 1H), 7.27 (d, J = 9.0 Hz, 1H), 7.18 – 7.15 (m, 2H), 7.11 – 7.08
(m, 3H), 6.80 (d, J = 2.5 Hz, 1H), 6.74 (dd, J = 9.0, 2.5 Hz, 1H), 3.69 (s, 3H), 2.45 (s, 3H). 13C
NMR (125 MHz, DMSOꢀd6) δ 154.1, 142.2, 133.7, 131.4, 130.9, 129.1, 127.8, 125.4, 111.9, 110.8,
100.6, 93.3, 55.3, 12.7. HRMS (EI, 70 eV) calcd for C16H15NOSe [M+]: 317.0319, found
317.0319.
2ꢀmethylꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4q) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a white solid (53.1 mg, 93 % yield). The 1H, 13C NMR spectra
were in accordance with those described in the literature.21
2ꢀphenylꢀ3ꢀ(phenylseleno)ꢀ1Hꢀindole (4r) Following the general procedure, using 7:1 petroleum
etherꢀEtOAc as the eluant afforded a yellow viscous oil (59.9 mg, 86 % yield). The 1H, 13C NMR
spectra were in accordance with those described in the literature.21
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1ꢀHꢀbenzo[4,5]selenopheno[3,2ꢀb]indole (6a)Following the general procedure, using 7:1
petroleum etherꢀEtOAc as the eluant afforded a brown solid (47.0 mg, 87 % yield), mp
232ꢀ234 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 12.15 (s, 1H), 8.09 (t, J = 7.5 Hz, 2H), 7.76 (d, J =
8.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H), 7.30 (t, J = 7.5 Hz, 1H), 7.25 (t, J =
7.0 Hz, 1H), 7.13 (t, J = 7.5 Hz, 1H). 13C NMR (125 MHz, DMSOꢀd6) δ 141.7, 139.8, 139.0,
129.2, 127.6, 124.9, 124.4, 124.3, 122.6, 121.4, 119.3, 119.3, 112.3, 110.9. HRMS (ESI) calcd for
C14H10NSe [M+H]+: 271.9973, found 271.9980.
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3ꢀmethylꢀ10Hꢀbenzo[4,5]selenopheno[3,2ꢀb]indole (6b) Following the general procedure, using
7:1 petroleum etherꢀEtOAc as the eluant afforded a dark brown solid (48.3 mg, 85 % yield), mp
239ꢀ240 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 12.02 (s, 1H), 8.09 ꢀ 8.04 (m, 2H), 7.53 (s, 1H),
7.49 ꢀ 7.45 (m, 2H), 7.29 (t, J = 7.5 Hz, 1H), 7.08 (d, J = 8.0 Hz, 1H), 2.42 (s, 3H). 13C NMR (125
MHz, DMSOꢀd6) δ 141.6, 139.1, 138.2, 129.3, 128.0, 127.6, 125.0, 124.5, 124.3, 124.2, 121.3,
118.9, 112.1, 110.4, 21.2. HRMS (ESI) calcd for C15H12NSe [M+H]+: 286.0129, found 286.0119.
3ꢀfluoroꢀ10Hꢀbenzo[4,5]selenopheno[3,2ꢀb]indole (6c) Following the general procedure, using 7:1
petroleum etherꢀEtOAc as the eluant afforded a light brown solid (50.7 mg, 88 % yield), mp
238ꢀ240 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 12.26 (s, 1H), 8.11 – 8.07 (m, 2H), 7.65 (d, J =
9.5 Hz, 1H), 7.56 (dd, J = 8.5, 4.5 Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H), 7.32 (t, J = 7.5 Hz, 1H), 7.09
(t, J = 9.0 Hz, 1H). 13C NMR (125 MHz, DMSO) δ 156.8 (d, JF = 231.3 Hz), 142.1, 140.9, 136.5,
129.0, 127.7, 125.0, 124.8, 124.5 (d, JF = 11.3 Hz), 121.6, 113.2 (d, JF = 10.0 Hz), 110.7 (t, JF =
5.0 Hz), 110.5, 104.5 (d, JF = 25.0 Hz). 19F NMR (470 MHz, DMSOꢀd6): δ ꢀ123.9 (s, 1F). HRMS
(ESI) calcd for C14H9FNSe [M+H]+: 289.9879, found 289.9893.
3ꢀchloroꢀ10Hꢀbenzo[4,5]selenopheno[3,2ꢀb]indole (6d) Following the general procedure, using
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7:1 petroleum etherꢀEtOAc as the eluant afforded a brown solid (55.4 mg, 91 % yield), mp
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263ꢀ265 °C. H NMR (500 MHz, DMSOꢀd6) δ 12.38 (s, 1H), 8.11 – 8.09 (m, 2H), 7.94 (s, 1H),
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7.59 (d, J = 9.0 Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H), 7.32 (t, J = 7.5 Hz, 1H), 7.24 (d, J = 8.5 Hz, 1H).
13C NMR (125 MHz, DMSOꢀd6) δ 142.3, 140.6, 138.3, 128.9, 127.7, 125.4, 125.1, 124.9, 123.7,
122.4, 121.7, 118.8, 113.7, 110.4. HRMS (ESI) calcd for C14H9ClNSe [M+H]+: 305.9583, found
305.9585.
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3ꢀbromoꢀ10Hꢀbenzo[4,5]selenopheno[3,2ꢀb]indole (6e) Following the general procedure, using
7:1 petroleum etherꢀEtOAc as the eluant afforded a brown solid (55.9 mg, 80 % yield), mp
263ꢀ264 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 12.37 (s, 1H), 8.07 – 8.12 (m, 3H), 7.54 (d, J = 8.5
Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H), 7.36 – 7.31 (m, 2H). 13C NMR (125 MHz, DMSOꢀd6) δ 142.3,
140.4, 138.5, 128.8, 127.7, 126.1, 125.0, 124.9, 124.9, 121.8, 121.6, 114.2, 111.5, 110.2. HRMS
(ESI) calcd for C14H9BrNSe [M+H]+: 349.9078, found 349.9090.
3ꢀmethoxyꢀ10Hꢀbenzo[4,5]selenopheno[3,2ꢀb]indole (6f) Following the general procedure, using
7:1 petroleum etherꢀEtOAc as the eluant afforded a brown solid (52.3 mg, 87 % yield), mp
214ꢀ215 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 11.98 (s, 1H), 8.07 (d, J = 8.0 Hz, 1H), 8.04 (d, J =
8.0 Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), 7.32 (s, 1H), 7.28 (t, J = 7.5 Hz, 1H), 6.89 – 6.87 (m, 1H),
3.81 (s, 3H). 13C NMR (125 MHz, DMSOꢀd6) δ 153.5, 141.6, 139.6, 134.8, 129.4, 127.6, 124.9,
124.6, 124.3, 121.3, 113.0, 112.8, 110.5, 101.2, 55.4. HRMS (ESI) calcd for C15H12NOSe [M+H]+:
302.0079, found 302.0079.
3ꢀ(trifluoromethoxy)ꢀ10Hꢀbenzo[4,5]selenopheno[3,2ꢀb]indole (6g) Following the general
procedure, using 7:1 petroleum etherꢀEtOAc as the eluant afforded a light brown solid (67.3 mg,
95 % yield), mp 222ꢀ223 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 12.45 (s, 1H), 8.11 (t, J = 8.5 Hz,
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2H), 7.93 (s, 1H), 7.66 – 7.63 (m, 1H), 7.50 (t, J = 6.5 Hz, 1H), 7.34 (t, J = 6.5 Hz, 1H), 7.22 (d, J
= 7.5 Hz, 1H). 13C NMR (125 MHz, DMSOꢀd6) δ 142.4, 141.7, 141.1, 138.3, 128.9, 127.7, 125.1,
125.0, 124.5, 121.7, 120.5 (q, JF = 252.5 Hz) , 116.1, 113.2, 112.1, 111.0. 19F NMR (470 MHz,
DMSOꢀd6): δ ꢀ56.9 (s, 3F). HRMS (ESI) calcd for C15H9F3NOSe [M+H]+: 355.9796, found
355.9812.
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2,4ꢀdimethylꢀ10Hꢀbenzo[4,5]selenopheno[3,2ꢀb]indole (6h) Following the general procedure,
using 7:1 petroleum etherꢀEtOAc as the eluant afforded a white solid (57.2 mg, 96 % yield), mp
205ꢀ206 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 11.97 (s, 1H), 8.08 (dd, J = 12.0, 8.0 Hz, 2H), 7.48
(t, J = 7.5 Hz, 1H), 7.27 (t, J = 7.5 Hz, 1H), 7.19 (s, 1H), 6.78 (s, 1H), 2.55 (s, 3H), 2.42 (s, 3H).
13C NMR (125 MHz, DMSOꢀd6) δ 141.8, 140.1, 137.6, 132.3, 129.2, 127.9 , 127.6, 125.0, 123.8,
122.3, 121.3, 121.2, 110.1, 109.9, 21.5, 18.8. HRMS (ESI) calcd for C16H14NSe [M+H]+:
300.0286, found 300.0276.
2,4ꢀdifluoroꢀ10Hꢀbenzo[4,5]selenopheno[3,2ꢀb]indole (6i) Following the general procedure, using
7:1 petroleum etherꢀEtOAc as the eluant afforded a brown solid (59.4 mg, 97 % yield), mp
197ꢀ199 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 12.65 (s, 1H), 8.13 (dd, J = 16.0, 8.0 Hz, 2H), 7.52
(t, J = 7.5 Hz, 1H), 7.36 – 7.30 (m, 2H), 7.02 (t, J = 10.5 Hz, 1H). 13C NMR (125 MHz, DMSOꢀd6)
δ 158.8 (dd, JF = 11.3, 237.5 Hz), 154.2 (dd, JF = 16.3, 245.0 Hz), 141.9, 141.3 (dd, JF = 12.5,
15.0 Hz), 139.5 (d, JF = 2.5 Hz), 128.5, 127.8, 125.3, 124.8, 121.7, 110.3 (d, JF = 21.3 Hz), 106.7,
95.5 (dd, JF = 3.8, 26.3 Hz), 94.8 (dd, JF = 22.5, 28.8 Hz). 19F NMR (470 MHz, DMSOꢀd6): δ
ꢀ116.8 (s, 1F), 120.2 (s, 1F). HRMS (ESI) calcd for C14H8F2NSe [M+H]+: 307.9785, found
307.9788.
2,4ꢀdichloroꢀ10Hꢀbenzo[4,5]selenopheno[3,2ꢀb]indole (6j) Following the general procedure, using
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7:1 petroleum etherꢀEtOAc as the eluant afforded a yellowish solid (65.8 mg, 97 % yield), mp
218ꢀ219 °C. 1H NMR (500 MHz, DMSOꢀd6) δ 12.70 (s, 1H), 8.15 (t, J = 6.5 Hz, 2H), 7.65 (s, 1H),
7.53 (t, J = 7.0 Hz, 1H), 7.37 (t, J = 7.0 Hz, 1H), 7.33 (s, 1H). 13C NMR (125 MHz, DMSOꢀd6) δ
142.5, 140.4, 140.2, 128.3, 127.8, 127.0, 125.3, 125.2, 124.1, 122.0, 121.9, 118.7, 111.3, 109.2.
HRMS (ESI) calcd for C14H8Cl2NSe [M+H]+: 339.9194, found 339.9185.
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1ꢀmethylꢀ10Hꢀbenzo[4,5]selenopheno[3,2ꢀb]indole (6k) Following the general procedure, using
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7:1 petroleum etherꢀEtOAc as the eluant afforded a dark brown solid (34.7 mg, 61 % yield). H
NMR (500 MHz, DMSOꢀd6) δ 11.91 (s, 1H), 8.22 (d, J = 7.5 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H),
7.58 (d, J = 6.5 Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H), 7.29 (t, J = 7.5 Hz, 1H), 7.04 (d, J = 7.0 Hz, 2H),
2.59 (s, 3H). 13C NMR (125 MHz, DMSOꢀd6) δ 141.6, 139.4, 138.9, 129.5, 127.6, 124.9, 124.3,
124.0, 123.2, 121. 7, 121.6, 119.5, 117.0, 111.5, 17.1. HRMS (ESI) calcd for C15H12NSe [M+H]+:
286.0129, found 286.0119.
5ꢀmethoxyꢀ1,2ꢀdimethylꢀ3ꢀ((3,4,5ꢀtrimethoxyphenyl)seleno)ꢀ1Hꢀindole (7a) Following the
general procedure, using 7:1 petroleum etherꢀEtOAc as the eluant afforded a white solid (57.1 mg,
68 % yield). The 1H, 13C NMR spectra were in accordance with those described in the literature.4
ASSOCIATED CONTENT
Supporting Information
1H、13C、19F NMR and HRMS spectral data of all compounds reported. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: huayuewu@wzu.edu.cn
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*Eꢀmail: wuge@wmu.edu.cn
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The authors declare no competing financial interest.
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ACKNOWLEDGMENT
Financial support from National Natural Science Foundation of China (21272176, 21372177 and
21202122), Zhejiang Provincial Natural Science Foundation (LY14B020009, LY15B020001) and
the Innovation Fund Project for Graduate Student of Wenzhou University is greatly appreciated.
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