Highly Chemo- and Regioselective Vinylation of N-Heteroarenes with Vinylsulfonium Salts

Article abstract of DOI:10.1021/acs.joc.8b00682

An efficient chemo- and regioselective N-vinylation of N-heteroarenes has been developed using vinylsulfonium salts. The reaction proceeded under mild and transition-metal-free conditions and consistently provided moderate to high yields of vinylation pro

Full text of DOI:10.1021/acs.joc.8b00682

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Note
Highly Chemo- and Regioselective Vinylation
of N-Heteroarenes with Vinylsulfonium Salts
Mingwei Zhou, Xuefei Tan, Yimin Hu, Hong C Shen, and Xuhong Qian
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00682 • Publication Date (Web): 25 May 2018
Downloaded from http://pubs.acs.org on May 25, 2018
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Page 1 of 10
The Journal of Organic Chemistry
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Highly Chemoꢀ and Regioselective Vinylation of NꢀHeteroarenes
with Vinylsulfonium Salts
Mingwei Zhou,a,b Xuefei Tan,b Yimin Hu,b Hong C. Shen,*b Xuhong Qian*a
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a Shanghai Key Laboratory of Chemical Biology, East China University of Science and Technology, Shanghai 200237, Chiꢀ
na
b Roche Innovation Center Shanghai, Roche Pharmaceutical Research and Early Development, Shanghai 201203, China
Supporting Information Placeholder
R1
Y
R2
X
R1
Ar
Y
N
DBU
N
R2
S+
-
Ar
X
Ar
+
DMSO
H
BPh4
Ar
E-isomer
up to 96%
ABSTRACT: An efficient chemoꢀ and regioselective Nꢀvinylation of Nꢀheteroarenes has been developed using vinylsulfonium
salts. The reaction proceeded under mild and transitionꢀmetalꢀfree conditions and consistently provided moderate to high yields of
vinylation products with 100% Eꢀstereoselectivity. This reaction is also highly chemoselective, and compatible with a variety of
functional groups, such as ꢀNHR, ꢀNH2, ꢀOH, ꢀCOOH, ester, etc.
Nitrogenꢀcontaining heterocyclic compounds are common strucꢀ
O
O
tural motifs of natural products, agrochemicals, and pharmaceutiꢀ
cals, and they are also useful intermediates in a number of indusꢀ
trial processes.1 Diverse vinylation derivatives of Nꢀheteroarenes
are widely incorporated in materials for potentially medicinal use
(Figure 1),2 information recording and storage,3 construction of
molecular muscle fiber mimics,4 and fluorescence labels.5 The E/Z
configuration of the vinyl group can often result in different bioꢀ
logical activity,6 photochromic properties and applications.7 As
such, it is important to develop stereoꢀ and chemoselective syntheꢀ
sis of alkenes which are present in natural products and molecules
of particular biological significance in medicinal chemistry.8
O
HO
HO
NH
N
Cl
Cl
OH
HO
N
N
N
OH
N
N
OH
HO
N
N
O
H
O
N
H
N
O
OH
OH
b
a
c
Serum/Glucocorticoid-Regulated Chemopreventive Agents Lipoprotein Drugs Targeting Beta-Amyloid
Kinase 1 Inhibitors, SI-113
Disorders, Betanin
.CF3CO2H
NH
N
N
N
N
N
In literature several methodologies have been developed for
vinylation of Nꢀheteroarenes (Scheme 1). In 1999, Knochel and
colleagues published the first example of the addition of heterocyꢀ
clic amines to alkynes using CsOH·H2O (eq 1).9 Later the Kondo
group reported the addition of pyrrole to diphenylacetylene emꢀ
ploying the phosphazene superbase P4ꢀtꢀBu.10 Verma et al. disꢀ
closed the regioꢀ and stereoselective addition of Nꢀheteroarenes to
alkynes using KOH, and founded that the ratio of Z/E products
was dependent upon time as well as the choice of base.11 Trofimov
and coꢀworkers found that regioselectivity was also dependent
upon the structures of substrates.12 Recently, Mao reported that a
high selectivity of Zꢀproducts could be obtained by heating the
reaction mixture in DMSO with potassium phosphate.13 Other
approaches include the use of trimethylsilylacetylene derivatives
(eq 2)14 and 3ꢀarylpropiolic acid (eq 3)15 as vinylation reagents.
However, the regioselectivity of reaction is poor. Beside alkynes,
vinyl halides are always used as the vinylation reagent for Nꢀ
heteroarene substrates applying the Cu/Pd catalyst with good
yields and excellent selectivity of the corresponding Eꢀisomer
products (eq 4).16 Since the nucleophilic groups like phenols,
N
O
O
N
N
HN
F
ONa
O
F
OH
F
O
O
N
N
H
e
f
d
Proto-Oncogene tyrosine-Protein
Kinase Src Inhibitors; Abl Kinase
Inhibitors, AP-24226
DNA Topoisomerase II
Inhibitors, Makaluvamine E
PPARgamma Partial Agonists
Figure 1. Nꢀheterocyclic vinyl arene compounds of medicinal interests.
amines, etc., could also react with vinyl halides, apparently this
method may present the functional group compatibility issue.16 On
the other hand, electrophiles such as bromides and iodides may be
incompatible with conditions involving Cu or Pd catalysts. Thereꢀ
fore, the previously described procedures are rather limited in
scope and selectivity, especially for the formation of Eꢀisomers.17
A new method of highly chemoꢀ and regioꢀselectivity transitionꢀ
metalꢀfree vinylation of Nꢀheteroarene to form pure Eꢀisomers
could be an attractive alternative approach to interesting natural
products or compounds of medicinal chemistry interest, as deꢀ
scribed in scheme 1.
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on the reaction yields (Table 1, entries 5ꢀ9). The use of DMSO and
Scheme 1. Vinylation of NꢀHeteroarenes
Previous work:
3 equiv. of DBU provided the best yield (Table 1, entry 5). Similar
to our previous report,18 the byproduct such as Nꢀalkyl sulfonium
(see Scheme 5) was observed if DBU was insufficient (e.g., < 3
equiv.) particularly for indole substrates containing an electronꢀ
donating group. A weaker base such as TEA gave a very poor
yield of the desirable product primarily due to the formation of the
Nꢀalkyl sulfonium species, which failed to undergo further elimiꢀ
1
2
3
4
5
6
7
8
Y
R1
X
Ar
R2 Ar
Y
R1
R2 Ar
X
N
eq 1 (Ref. 9~13)
eq 2 (Ref. 14)
Ar
N
H
Base
Z/E
R1
X
Y
R2 Ar
Ar
Si
R1
Y
R2
Ar
N
X
Ar
N
H
[Cu]
Z/E
1
nation (Table 1, entry 7). The H NMR of the isolated product
O
Y
R1
R2 Ar
Z/E
X
Ar
showed that the coupling constant between the two hydrogen atꢀ
oms on the double bond is 14.5 Hz. By comparing with the literaꢀ
ture data,14 it can be confirmed that the product is solely the Eꢀ
isomer. In addition, no Zꢀisomer product was observed by examinꢀ
ing the crude reaction mixture in DMSOꢀd6 at different reaction
time intervals (i.e. at every 30 min from time zero of the reaction
up to 6 h, when the reaction was complete) via 1H NMR and
LC/MS.
R1
Y
OH
R2
Ar
N
eq 3 (Ref. 15)
eq 4 (Ref. 16)
X
Ar
N
Base
9
H
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R1
Y
X
R2 Ar
X
R1
Y
Ar
R2
Ar
N
X
N
H
[Cu] or [Pd]
E
Ar
This work:
+
Ar
S
R1
Y
N
1. High chemo-selectivity
2. High regio-selectivity
3. Broad group tolerance
BPh4-
Y
R1
R2
Ar
X
Scheme 2. Vinylation of NꢀHeteroarenes Substratesa, c
R2
Ar
X
N
H
DBU
Ar
E
S+
BPh4
R1
Recently, we have developed a cyclopropanation method for oxꢀ
indoles, and found that the vinylation byproduct of unprotected
“N” could be obtained without the addition of zinc triflate under
the reaction condition.18 This finding prompted us to explore the
vinylation of Nꢀheteroarene with various vinylsulfonium salts. In
2003, Mukaiyama and coꢀworkers reported the synthesis of αꢀ
imidostyrenes and 2ꢀarylaziridines with βꢀphenylvinylsulfonium
salts.19 In 2014 and 2015, the Aggarwal group reported the syntheꢀ
sis of 6ꢀ and 7ꢀmembered Nꢀheterocycles, epoxideꢀ and cycloproꢀ
paneꢀfused heterocycles with αꢀphenylvinylsulfonium salts.20
However, the vinylation reaction of Nꢀheteroarenes with αꢀ
phenylvinylsulfonium salts has not been disclosed. Herein, we
explored the chemoꢀ and regioꢀselectivity of the vinylation of Nꢀ
heteroarenes with αꢀvinylsulfonium salts.
R2
-
R1
Ar
R2
N
Ar
N
DBU, DMSO
H
2b~2r
1b~1r
O
O
Cl
HO
O
N
N
N
N
2b, 93%
2d, 61%
2c, 74%
2e, 93%
OH
O
O
O
N
O2N
H
OH
N
N
N
N
N
Table 1. Optimization of the Vinylation of Indole 1aa
2f, 96%
2g, 92%
2i, 92%
S+
2h, 86%
N
BPh4
-
Cl
N
N
N
H
Base
N
N
N
N
N
N
Cl
1a
2a
Entry
Base (equiv.)
DBU (2.0)
DBU (2.0)
DBU (2.0)
DBU (2.0)
DBU (3.0)
Cs2CO3 (2.0)
TEA (3.0)
Solvent
DCM
Yield (%)b
1
2
70
73
76
81
83
76
<5c
38
36
83
2k, 87%
2l, 84%
2m, 85%
2j, 82%
MeCN
DMF
3
O
4
DMSO
DMSO
DMF
N
N
N
HO
5
O
N
N
N
N
N
6
7
DMSO
DMSO
DMSO
DMSO-d6
8
K3PO4(3.0)
NaOH (3.0)
DBU (3.0)
2n, 82%
2o, 89%
2q, 91% b
2p, 95%
9
10
aReaction conditions: 1a (0.2 mmol, 1.0 equiv.), αꢀphenylvinylsulfonium
salt (0.24 mmol, 1.2 equiv.), with indicated amount of base, 1 mL of solꢀ
vent; the reaction mixture was stirred at room temperature (ca. 21oC) for 12
h. bIsolated yields are shown. cLC/MS yield.
O
N
O
2r, 72%
aReaction conditions: Nꢀheteroarene (0.4 mmol, 1.0 equiv.), αꢀ
phenylvinylsulfonium salt (0.48 mmol, 1.2 equiv.), DBU (1.2 mmol, 3.0
equiv.), in 2 mL of DMSO, at room temperature (ca. 21oC), stirring for 12
Initially, we investigated the vinylation of indole with the αꢀ
phenylvinylsulfonium salt. Efforts to optimize vinylation with
indole are summarized in Table 1. To our delight, a 70% isolated
yield of product 2a was obtained with DBU as the base and DCM
as the solvent in our first attempt (Table 1, entry 1). Apparently,
polar solvents such as DMSO and DMF improved the yield (Table
1, entries 2ꢀ4). Different bases appeared to have a profound impact
b
h. Nꢀheteroarene (0.4 mmol, 1.0 equiv.), vinylsulfonium salt (0.96 mmol,
2.4 equiv.), DBU (1.2 mmol, 3.0 equiv.), in 2 mL of DMSO, at room temꢀ
c
perature (ca. 21oC), stirring for 12 h. Isolated yields for all products deꢀ
scribed herein.
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The Journal of Organic Chemistry
With the optimized conditions in hand, we firstly examined the
4d and 4e afforded 1,1ꢀdisubstituted vinylation product 5d and 5e,
respectively, in high yield employing cesium carbonate as the
base. This result is consistent with the previous report19 in which
the reaction of βꢀphenylvinylsulfonium salts with metal salts of
cyclic imides also provided 1,1ꢀdisubstituted vinylation product.
To our surprise, βꢀarylvinylsulfonium salts 4f and 4g led to the Eꢀ
isomer product 5f and 5g, respectively, without any detectable
amount of 1,1ꢀdisubstituted vinylation product. In addition, the
position of the nitro substitution dictates the regionꢀselectivity of
the product (4e to 5e, and 4f to 5f). We speculate that strong elecꢀ
tronꢀwithdrawing pyrimidine and pꢀnitrophenyl groups favored the
nucleophilic addition to occur at the distal carbon of the vinyl
group in a conjugate fashion relative to pyrimidine or nitrophenyl
leading to the 1, 2ꢀdisubstituted vinylation product. The precise
mechanistic rationale for such striking regioselectivity will be
scope of indole substrates. As shown in Scheme 2 (2bꢀ2i), reacꢀ
tions of substrates containing electronꢀrich or electronꢀ
withdrawing substituents afforded high regioselectivity of the Eꢀ
isomer products in good to excellent yields. Remarkably, phenol
1d, acid 1g, ester 1e, and even amino alcohol 1h, underwent vinylꢀ
ation to afford the corresponding products in good yields. All reacꢀ
tions demonstrated high chemoꢀ and regioselectivity. Then we
explored other Nꢀheteroarene substrates such as imidazole, azainꢀ
dole, benzimidazole, 7Hꢀpyrrolo[2,3ꢀd]pyrimidine substrates (1jꢀ
1p). To our delight, all reactions provided pure Eꢀisomers in good
yield. Interestingly, the reaction of oxindole 1q proceeded with
both cyclopropanation at the 3ꢀC position and the vinylation on the
“N” position, affording 2q in 91% yield using 2.4 equiv. of the αꢀ
phenylvinylsulfonium salt. Lastly, benzo[de]isoquinolineꢀ1,3ꢀ
dione 1r afforded the product 2r in 72% yield.
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further
explored.
Interestingly,
the
reaction
of
βꢀ
To explore the vinylation of different vinylsulfonium salts, we
subsequently synthesized several vinylsulfonium salts from aryl or
heteroaryl vinyl compounds according to the procedure developed
by Aggarwal, et al. (Scheme 3). 20
arylvinylsulfonium salt (4dꢀ4g) proceeded with much lower yields
when DBU was used as the base (<30%), but with improved yields
when cesium carbonate was employed.
Scheme 4. NꢀVinylation of Indole with Different Vinylꢀ
Scheme 3. Synthesis of Different Vinylsulfonium Saltsd
sulfonium saltsc
S+
N
Ar
S+
H
Ar
S+
N
Ar
Ar
(a), (b), (c)
or
N
BPh4
S+
-
or
or
BPh4
-
BPh4
II
-
BPh4
-
Ar
DBU, DMSO
Ar
IV
Ar
I
III
I
II
5a~g
3a~g
4a~g
4a~g
Br
N
N
S+
N
S+
BPh4
S+
BPh4
-
BPh4
-
-
4c, 53%
4a, 45%
4b, 39%
Br
5a, 78% a
5b, 70% a
5c, 85% a
S+
S+
S+
BPh4
O
N+
BPh4
-
BPh4
-
N
O
N
-
N
O
O
N+
O
O
N+
O
O
4d, 22%
S+
BPh4
4e, 34%
4f, 25%
O
N+
O
O
O
5e, 81% b
5d, 86% b
5f, 36% b
N
-
N
Br
N
4g, 56%
N
N
a
Reaction Conditions: vinyl substrate (1.0 equiv.), bromine (0.95 equiv.),
tetrahydrothiophene (3.0 equiv.), acetonitrile (2 mL/mmol), 0 °C to room
temperature (ca. 21oC), stirring for 2ꢀ12 h. bsulfonium bromide (1.0
equiv.), sodium tetraphenylboron (0.95 equiv.), acetone/water (4:1, 2
Br
5g, 61% b
aReaction conditions: indole (0.4 mmol, 1.0 equiv.), αꢀ
phenylvinylsulfonium (0.48 mmol, 1.2 equiv.), DBU (1.2 mmol), in 2 mL
of DMSO, at room temperature (ca. 21oC), under air, stirring for 12 h.
bReaction conditions: indole (0.4 mmol, 1.0 equiv.), αꢀ
phenylvinylsulfonium salt (0.48 mmol, 1.2 equiv.), Cs2CO3 (1.2 mmol, 3.0
equiv.), in 2 mL of DMSO, at room temperature (ca. 21oC), under air,
stirring for 12 h. cIsolated yields.
c
mL/mmol), at room temperature (ca. 21oC), 2 h. sulfonium tetraphenylꢀ
borate (1.0 equiv.), K2CO3 (2.0 equiv.), acetone/water (1:1, 8 mL/mmol), 2
h. dIsolated yields for all products described herein.
Interestingly, we found that the electronic properties of the aryl
group resulted in two different sulfonium salts (Scheme 3, I and
II). Substrates containing electronꢀneutral or weak electronꢀ
withdrawing groups, such as 4ꢀmethylphenyl (3a), 3ꢀbromophenyl
(3b) and naphthyl (3c) produced 1,1ꢀdisubstituted vinylsulfonium
salts (4aꢀ4c, αꢀarylvinylsulfonium salts). The electron deficient
vinylaryls such as benzoate (3d), 3ꢀnitrobenzene (3e), 4ꢀ
nitrobenzene (3f) and 5ꢀbromopyrimidine (3g) resulted in the forꢀ
mation of 1,2ꢀdisubstituted Eꢀvinylsulfonium salts (4dꢀ4g, βꢀ
arylvinylsulfonium salts).
Based on the vinylation results of αꢀarylvinylsulfonium salts and
Nꢀheteroarenes, we proposed a reaction mechanism in Scheme 5.
Firstly, the Nꢀheteroarene substrates presumably underwent deproꢀ
tonation in the presence of DBU. Following the addition of the
nitrogen of Nꢀheteroarenes to the vinylsulfonium salt, analogous to
the Michael addition, the resulting anion could be doubly stabiꢀ
lized via the adjacent sulfonium group and aryl group. The subseꢀ
quent protonation could take place by an intramolecular proton
transfer from the βꢀposition of the sulfonium to the αꢀposition
(path b of Scheme 5), or by a protonation of the ammonium salt of
DBU (path a of Scheme 5). The resulting intermediate could then
undergo an elimination of the sulfide to generate the desired prodꢀ
With various vinylsulfonium salts in hand, we explored their
vinylation with indole (Scheme 4). The 1,1ꢀdisubstituted vinylꢀ
sulfonium salts (αꢀarylvinylsulfonium salts) (4aꢀ4c) produced Eꢀ
isomer products (5aꢀ5c) with satisfactory yields under the previꢀ
ously optimized conditions. By contrast, βꢀarylvinylsulfonium salt
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uct. The trans configuration of the olefin is preferred due to the
antiꢀrelationship of the two aryl moieties which are most sterically
bulky during the E2 elimination.
EXPERIMENTAL SECTION
1
2
3
4
5
6
7
8
General information. NMR spectra were obtained on a Bruker
AV IIꢀ400 MHz spectrometer (1H NMR at 400 MHz, 13C NMR at
100 MHz). The 1H NMR chemical shifts were measured relative to
CDCl3, CD3OD or DMSOꢀd6 as the internal reference (CDCl3: δ =
7.26 ppm; CD3OD: δ = 3.31 ppm; DMSOꢀd6: δ = 2.50 ppm). The
13C NMR chemical shifts were given using CDCl3, MeOD or
DMSOꢀd6 as the internal standard (CDCl3: δ = 77.16 ppm;
CD3OD: δ = 49.00 ppm; DMSOꢀd6: δ = 39.52 ppm). Mass specꢀ
troscopy data were collected on an HRMSꢀESI instrument. Reaꢀ
gents, solvents and starting materials were obtained from commerꢀ
cial sources and used without further purification unless otherwise
noted. Starting materials 1aꢀ1r and 3aꢀ3h were purchased from
Aldrich, Acros, Sinopharma, Shaoyuan, or Wuxipharma, and used
without further purification.
Scheme 5. The Proposed Vinylation Reaction Mechanism of
the αꢀArylvinylsulfonium Salts and NꢀHeteroarenes
+
Ar
S
Y
BPh
-
4
Y
N
Ar
X
Y
DBU
- H+
Ar
X
N
+
9
X
Ar
S
H
N -
-
H
H
10
11
12
13
14
15
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19
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46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
Ar
path a
path b
+ H+
proton transfer
Y
Y
N
Y
X
N
X
Ar
Ar
Ar
X
N
DBU
H
+
+
S
S
H
-
H
General Procedure A for arylvinylsulfonium salts. Arylvinylꢀ
sulfonium salts were synthesized from the corresponding vinyl
substrates according to the reported procedures in 3 steps.20
+ H+
H
H
H
H
Ar
Ar
Ar
General Procedure for the synthesis of αꢀaryl substituted broꢀ
moethyl sulfonium bromides (step 1). A flask was charged with
bromine (1.0 equiv.) in MeCN (2 mL/mmol) at 0 °C. To this was
added tetrahydrothiophene (3.5 equiv.) dropwise over 5 min leadꢀ
ing to the formation of a yellow precipitate. The reaction mixture
was stirred for 10 min before the addition of a styrene derivative
(2.0 equiv.) dropwise over 5 min. The reaction mixture was then
warmed to rt to generate a homogeneous solution (the yellow preꢀ
cipitate persisted for a longer time with increasingly electron defiꢀ
cient styrenes), followed by a subsequent precipitation of the sulꢀ
fonium bromide. The reaction mixture was stirred for 30 min beꢀ
fore being diluted with Et2O (5 mL/mmol) to ensure full precipitaꢀ
tion/removal of the excess reagents. The solid precipitate was isoꢀ
lated by removal of the ethereal supernatant by filtration and
washed with a further portion of Et2O (2.5 mL/mmol) before dryꢀ
ing under a vacuum to yield the desired αꢀaryl substituted bromoꢀ
ethyl sulfonium bromide.
To determine the protonation pathway, we performed an experꢀ
iment using deuteriumꢀlabelled material 3h (Scheme 6) to probe
the vinylation mechanism. With the same reaction conditions as
described in Scheme 3, the deuteration sulfonium salt 4h was obꢀ
tained in 35% yield from 2,2ꢀdideuteriovinylbenzene 3h. The reacꢀ
tion of indole 1a and sulfonium salt 4h resulted in the formation of
5h in 70% yield, without the detection of 6 or 7, which supports
path a as the plausible reaction mechanism.
Scheme 6. Experiment Using Deuteriumꢀlabelled Material to
Probe Reaction Mechanisme
N
H
N
1a
H
S+
BPh4
(a), (b), (c)
35%
(d) DBU, DMSO
D
-
70%
D
D
D
D
D
3h
4h
5h
General Procedure for the Synthesis of αꢀAryl Substituted
Bromoethyl Sulfonium Tetraphenylborates (step 2). Freshly
prepared αꢀaryl substituted bromoethyl sulfonium bromide (1
equiv.) was dissolved in acetone:H2O (4:1, 0.5 M). To the resultꢀ
ing solution was added sodium tetraphenylborate (0.95 equiv.).
The reaction mixture was then stirred for 30 min before a second
portion of H2O (10 mL/mmol) was added followed by filtration of
the solid precipitate. The isolated precipitate was washed with H2O
(3 × 10 mL/mmol). The filtrate was then discarded and the residue
was dried under high vacuum for 24 h with gentle heating (warm
water bath) to give the corresponding αꢀaryl substituted bromoethꢀ
yl sulfonium tetraphenylborates.
N
N
D
D
H
6
7
a
Reaction conditions: 2,2ꢀdideuteriovinylbenzene (9.4 mmol, 1.0 equiv.),
bromine (8.9 mmol, 0.95 equiv.), tetrahydrothiophene (28.2 mmol, 3.0
equiv.), acetonitrile (19 mL), 0 °C to room temperature (ca. 21oC), stirring
b
for 5 h. sulfonium bromide (3.9 mmol, 1.0 equiv.), sodium tetraphenylꢀ
boron (3.7 mmol, 0.95 equiv.), acetone/water (4:1, 8.0 mL), at room temꢀ
perature (ca. 21oC), 2 h. csulfonium tetraphenylborate (3.7 mmol, 1.0
equiv.), K2CO3 (7.4 mmol, 2.0 equiv.), acetone/water (1:1, 30 mL), 2 h.
dindole (0.4 mmol, 1.0 equiv.), 4h (0.48 mmol, 1.2 equiv.), DBU (1.2
mmol, 3.0 equiv.), in 2 mL of DMSO, at room temperature (ca. 21oC),
under air, stirring for 12 h. eIsolated yields for all products described hereꢀ
in.
General Procedure for the synthesis of αꢀaryl substituted viꢀ
nylsulfonium tetraphenylborates (step 3). αꢀAryl substituted
bromoethyl sulfonium tetraphenylborate (1 equiv.) was dissolved
in acetone:H2O (1:1, 0.1 M). To the resulting solution was added
potassium carbonate (2.0 equiv.). The reaction mixture was stirred
till the reaction completed (checked by NMR), and then filtered
and washedwith H2O (3 × 10 mL/mmol). The filtrate was then
discarded and the isolated solid was collected and dried over vacuꢀ
um to give the desired αꢀaryl substituted vinylsulfonium tetraꢀ
phenylborates.
In summary, an efficient and convenient chemoꢀ and regioselecꢀ
tive vinylation of Nꢀheteroarenes has been developed using a viꢀ
nylsulfonium salt. The reaction proceeded under mild and transiꢀ
tionꢀmetalꢀfree conditions, and provided modest to excellent yields
of the completely Eꢀstereoselective vinylation products in most
cases. This reaction is highly chemoselective, and compatible with
ꢀNHR, ꢀNH2, ꢀOH, ꢀCOOH, ester, and other functional groups that
could be sensitive towards strong basic conditions. As such we
envision that this methodology will find its applications in mediciꢀ
nal chemistry in the future.
1ꢀ[1ꢀ(pꢀtoyl)vinyl)tetrahydroꢀ1Hꢀthiophenꢀ1ꢀium
tetraphenylꢀ
borate (4a). 4a was prepared (General Procedure A) from 1ꢀ
methylꢀ4ꢀvinylꢀbenzene (4.72 g) and used without further purificaꢀ
tion in the next step; 9.33 g, 45% total yield; white solid; Mp:
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The Journal of Organic Chemistry
154−157 °C; 1H NMR (400 MHz, DMSO): δ 7.45ꢀ7.50 (m, J = 8.2
15.3 Hz, 1H), 7.14ꢀ7.22 (m, 8H), 6.92 (t, J = 7.3 Hz, 8H), 6.74ꢀ
6.83 (m, 4H), 3.71 (m, 2H), 3.57 (m, 2H), 2.29ꢀ2.42 (m, 2H), 2.14ꢀ
2.26 (m, 2H); 13C Dept135 (100 MHz, DMSO): δ 144.3 (CH),
136.0 (CH), 135.2 (CH), 131.2 (CH), 125.8 (CH), 125.7 (CH),
122.8 (CH), 122.0 (CH), 119.3 (CH), 47.9 (CH2), 29.0 (CH2); 13C
NMR (100 MHz, DMSO): δ 164.6, 164.1, 163.6, 163.1, 148.8,
144.3, 136.0, 135.3, 135.2, 131.2, 125.8, 125.7, 122.8, 122.0,
119.3, 47.9, 28.9; HRMS (ESIꢀTOF) m/z: [M – BPh4]+ Calcd for
C12H14NO2S 236.0740; Found 236.0742.
Hz, 2H), 7.28ꢀ7.39 (m, J = 8.1 Hz, 2H), 7.14ꢀ7.22 (m, 8H), 6.92 (t,
J = 7.4 Hz, 8H), 6.75ꢀ6.82 (m, 4H), 6.39 (d, J = 3.6 Hz, 1H), 6.23
(d, J = 3.6 Hz, 1H), 3.64ꢀ3.75 (m, 2H), 3.49ꢀ3.60 (m, 2H), 2.35 (s,
3H), 2.03ꢀ2.20 (m, 4H); 13C Dept135 (100 MHz, DMSO): δ136.0
(CH), 130.3 (CH), 128.1(CH), 125.8 (CH), 125.5(CH2),
122.0(CH), 45.4(CH2), 28.3(CH2), 21.3(CH3); 13C NMR (100
MHz, DMSO): δ 164.6, 164.1, 163.6, 163.1, 140.9, 136.0, 135.7,
130.8, 130.3, 129.6, 128.1, 126.8, 125.8, 125.5, 122.0, 45.4, 28.3,
21.3; HRMS (ESIꢀTOF) m/z: [M – BPh4]+ Calcd for C13H17S
205.1046; Found: 205.1046.
1
2
3
4
5
6
7
8
1ꢀ[(E)ꢀ2ꢀ(4ꢀnitrophenyl)vinyl]tetrahydrothiophenꢀ1ꢀium
tetraꢀ
9
phenylborate (4f). 4f was prepared (General Procedure A) from 1ꢀ
nitroꢀ4ꢀvinylꢀbenzene (3.0 g) and used without further purification
in the next step; 2.8 g, 25% total yield; yellow solid; Mp: 157ꢀ160
°C; 1H NMR (400 MHz, DMSO): δ 8.35 (d, J = 8.8 Hz, 2H), 7.93
(d, J = 8.8 Hz, 2H), 7.79 (d, J = 15.3 Hz, 1H), 7.47 (d, J = 15.4 Hz,
1H), 7.13ꢀ7.25 (m, 8H), 6.92 (t, J = 7.4 Hz, 8H), 6.74ꢀ6.85 (m,
4H), 3.72 (m, 2H), 3.61 (m, 2H), 2.28ꢀ2.47 (m, 2H), 2.22 (m, 2H);
13C Dept135 (100 MHz, DMSO): δ 144.1 (CH), 136.0 (CH), 129.8
(CH), 125.8 (CH), 124.7 (CH), 122.0 (CH), 120.8 (CH), 48.0
(CH2), 29.0 (CH2); 13C NMR (100 MHz, DMSO): δ 164.6, 164.1,
163.6, 163.1, 144.1, 139.7, 136.0, 129.8, 125.8, 124.7, 122.0,
120.8, 48.0, 29.0; HRMS (ESIꢀTOF) m/z: [M – BPh4]+ Calcd for
C12H14NO2S 236.0740; Found 236.0742.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀ[1ꢀ(3ꢀbromophenyl)vinyl]tetrahydrothiophenꢀ1ꢀium tetraphenylꢀ
borate (4b). 4b was prepared (General Procedure A) from 1ꢀ
bromoꢀ3ꢀvinylꢀbenzene (7.32 g) and used without further purificaꢀ
tion in the next step; 9.19 g, 39% total yield; white solid; Mp:
136−139 °C; 1H NMR (400 MHz, DMSO): δ 7.85 (s, 1H), 7.74 (d,
J = 8.2 Hz, 1H), 7.61 (d, J = 7.4 Hz, 1H), 7.48 (t, J = 7.6 Hz, 1H),
7.14ꢀ7.21 (m, 8H), 6.92 (t, J = 7.4 Hz, 8H), 6.75ꢀ6.83 (m, 4H),
6.54 (d, J = 3.8 Hz, 1H), 6.36 (d, J = 3.8 Hz, 1H), 3.66ꢀ3.78 (m,
2H), 3.41ꢀ3.66 (m, 2H), 2.06ꢀ2.24 (m, 4H); 13C Dept135 (100
MHz, DMSO): 136.0 (CH), 133.7(CH), 131.8 (CH), 131.1(CH),
128.0 (CH2), 127.3 (CH), 125.8 (CH), 122.0 (CH), 45.7 (CH2),
28.4 (CH2); 13C NMR (100 MHz, DMSO): δ 164.6, 164.1, 163.6,
163.1, 136.1, 136.0, 134.6, 133.7, 131.8, 131.1, 128.0, 127.3,
125.8, 122.9, 122.0, 45.7, 28.4; HRMS (ESIꢀTOF) m/z: [M–
BPh4]+ Calcd for C12H14BrS 268.9994; Found: 268.9990.
5ꢀbromoꢀ2ꢀ[(E)ꢀ2ꢀtetrahydrothiophenꢀ1ꢀiumꢀ1ꢀylvinyl]pyrimidine
tetraphenylborate (4g). 4g was prepared (General Procedure A)
from 5ꢀbromoꢀ2ꢀvinylꢀpyrimidine (1.0 g) and used without further
purification in the next step; 1.80 g, 56% total yield; white solid;
1ꢀ[1ꢀ(2ꢀnaphthyl)vinyl]tetrahydrothiophenꢀ1ꢀium
tetraphenylꢀ
1
borate (4c). 4c was prepared (General Procedure A) from 2ꢀ
vinylnaphthalene (2.1 g) and used without further purification in
the next step; 4.05 g, 53% total yield; white solid; Mp: 167−170
Mp: 160ꢀ161 °C; H NMR (400 MHz, DMSO): δ 9.13 (s, 2H),
7.72 (d, J = 15.1 Hz, 1H), 7.64 (d, J = 15.1 Hz, 1H), 7.14ꢀ7.22 (m,
8H), 6.92 (t, J = 7.4 Hz, 8H), 6.75ꢀ6.83 (m, 4H), 3.64ꢀ3.78 (m,
4H), 2.13ꢀ2.31 (m, 4H); 13C Dept135 (100 MHz, DMSO): δ 159.0
(CH), 142.9 (CH), 136.0 (CH), 136.0 (CH), 127.2 (CH), 125.8
(CH), 122.0 (CH), 47.8 (CH2), 29.0 (CH2); 13C NMR (100 MHz,
DMSO): δ 164.6, 164.1, 163.6, 163.1, 159.2, 159.0, 142.9, 136.0,
127.2, 125.8, 122.0, 120.9, 47.8, 29.0; HRMS (ESIꢀTOF) m/z: [M
– BPh4]+ Calcd for C10H12BrN2S 270.9899; Found 270.9895.
1
°C; H NMR (400 MHz, DMSO): δ 8.16ꢀ8.22 (m, 1H), 7.98ꢀ8.11
(m, 3H), 7.73 (dd, J = 1.9, 8.6 Hz, 1H), 7.60ꢀ7.67 (m, 2H), 7.18 (br
dd, J = 3.8, 5.1 Hz, 8H), 6.92 (t, J = 7.3 Hz, 8H), 6.75ꢀ6.83 (m,
4H), 6.62 (d, J = 3.7 Hz, 1H), 6.39 (d, J = 3.8 Hz, 1H), 3.71ꢀ3.83
(m, 2H), 3.60ꢀ3.70 (m, 2H), 2.08ꢀ2.25 (m, 4H); 13C Dept135 (100
MHz, DMSO): δ 136.0 (CH), 129.6 (CH), 129.0 (CH), 128.3
(CH), 128.2 (CH), 128.0 (CH), 127.8 (CH), 126.5 (CH2), 125.8
(CH), 125.0 (CH), 122.0 (CH), 45.6 (CH2), 28.4 (CH2); 13C NMR
(100 MHz, DMSO): δ 164.6, 164.1, 163.6, 163.1, 136.0, 135.9,
133.8, 132.9, 131.1, 129.6, 129.0, 128.3, 128.2, 128.0, 127.8,
126.5, 125.8, 125.0, 122.0, 45.6, 28.4; HRMS (ESIꢀTOF) m/z: [M
– BPh4]+ Calcd for C16H17S 241.1046; Found 241.1042.
benzene;1ꢀ(2,2ꢀdideuterioꢀ1ꢀmethylꢀvinyl)tetrahydrothiophenꢀ1ꢀ
ium tetraphenylborate (4h). 4h was prepared (General Procedure
A) from 2,2ꢀdideuteriovinylbenzene (1.0 g) and used without furꢀ
ther purification in the next step; 1.50 g, 35% total yield; white
1
solid; Mp: 165ꢀ167 °C; H NMR (400 MHz, DMSO): δ 7.56ꢀ7.62
(m, 2H), 7.49ꢀ7.56 (m, 3H), 7.15ꢀ7.21 (m, 8H), 6.92 (t, J = 7.4 Hz,
8H), 6.75ꢀ6.82 (m, 4H), 3.66ꢀ3.78 (m, 2H), 3.53ꢀ3.62 (m, 2H),
2.05ꢀ2.21 (m, 4H); 13C Dept135 (100 MHz, DMSO): δ 136.0
(CH), 130.9 (CH), 129.8 (CH), 129.1(CH), 128.2 (CH), 126.9
(CH), 125.8 (CH), 122.0 (CH), 45.4 (CH2), 28.3 (CH2); 13C NMR
(100 MHz, DMSO): δ 164.6, 164.1, 163.6, 163.1, 136.0, 135.6,
133.6, 130.9, 129.8, 129.1, 128.3, 126.9, 125.8, 122.0, 45.4, 28.3;
HRMS (ESIꢀTOF) m/z: [M – BPh4]+ Calcd for C12H13D2S
193.1015; Found 193.1013.
methyl
4ꢀ[(E)ꢀ2ꢀtetrahydrothiophenꢀ1ꢀiumꢀ1ꢀylvinyl]benzoate
tetraphenylborate (4d). 4d was prepared (General Procedure A)
from methyl 4ꢀvinylbenzoate (2.2 g) and used without further puriꢀ
fication in the next step; 1.66 g, 22% total yield; white solid; Mp:
1
158ꢀ160 °C; H NMR (400 MHz, DMSO): δ 8.05 (d, J = 8.2 Hz,
2H), 7.81 (d, J = 8.2 Hz, 2H), 7.73 (d, J = 15.3 Hz, 1H), 7.38 (d, J
= 15.3 Hz, 1H), 7.18 (br s, 8H), 6.92 (br t, J = 7.2 Hz, 8H), 6.72ꢀ
6.85 (m, 4H), 3.87 (s, 3H),3.71 (m, 2H), 3.56 (m, 2H), 2.34 (m,
2H), 2.21 (m, 2H); 13C Dept135 (100 MHz, DMSO): δ 145.4
(CH), 136.0 (CH), 130.2 (CH), 129.0 (CH), 125.8 (CH), 122.0
(CH), 118.9 (CH), 52.9 (CH3), 47.9 (CH2), 28.9 (CH2); 13C NMR
(100 MHz, DMSO): δ 166.1, 164.6, 164.1, 163.6, 163.1, 145.4,
137.9, 136.0, 131.7, 130.2, 129.0, 125.8, 122.0, 118.9, 52.9, 47.9,
28.9; HRMS (ESIꢀTOF) m/z: [M – BPh4]+ Calcd for C14H17O2S
249.0944; Found 249.0939.
General Procedure B for Nꢀheteroarene substrates’ vinylation
with αꢀphenylvinylsulfonium salt. To a 5 mL Schlenk tube were
added Nꢀheteroarene substrates (0.4 mmol, 1.0 equiv.), αꢀ
phenylvinylsulfonium salt (0.48 mmol, 1.2 equiv.) and DMSO (2
mL). The mixture was stirred at room temperature for 2 min and to
the mixture was added DBU (182.4 mg, 1.2 mmol, 3.0 equiv.).
The mixture was stirred for 12 hours at room temperature till the
reaction was complete. To the resulting mixture was added satuꢀ
rated ammonium chloride solution (10 mL), and the mixture was
then extracted with EtOAc (3 x 50 mL). The combined organic
layers were washed with H2O (2 x 10 mL), dried with anhydrous
sodium sulfate. After concentration, the crude product was purified
1ꢀ[(E)ꢀ2ꢀ(3ꢀnitrophenyl)vinyl]tetrahydrothiophenꢀ1ꢀium
tetraꢀ
phenylborate (4e). 4e was prepared (General Procedure A) from 1ꢀ
nitroꢀ3ꢀvinylꢀbenzene (3.0 g) and used without further purification
in the next step; 3.8 g, 34% total yield; yellow solid; Mp: 149ꢀ151
1
°C; H NMR (400 MHz, DMSO): δ 8.60 (s, 1H), 8.31 (d, J = 7.9
Hz, 1H), 8.07 (d, J = 7.8 Hz, 1H), 7.71ꢀ7.86 (m, 2H), 7.49 (d, J =
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The Journal of Organic Chemistry
Page 6 of 10
using column chromatography on silica gel using an appropriate
eluent.
7.29 (m, 1H), 6.94 (d, J = 14.5 Hz, 1H), 6.81 (d, J = 3.6 Hz, 1H),
3.94 (s, 3H); 13C Dept135 (100 MHz, DMSO): δ 129.2 (CH),
127.4 (CH), 126.6 (CH), 126.5 (CH), 124.0 (CH), 123.7 (CH),
123.6 (CH), 115.4 (CH), 111.1 (CH), 106.8 (CH), 52.3 (CH3);
13C NMR (100 MHz, DMSO): δ 167.4, 138.2, 136.3, 129.2, 128.8,
127.4, 126.6, 126.5, 124.0, 123.7, 123.6, 122.6, 115.4, 111.1,
106.8, 52.3; HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for
C18H16NO2 278.1176; Found: 278.1177.
1
2
3
4
5
6
Compounds (2aꢀ2r, 5aꢀ5c, 5h) were prepared according to Genꢀ
eral Procedure B.
1ꢀ[(E)ꢀstyryl]indole (2a). A purification by flash chromatography
(petroleum ether: ethyl acetate = 10:0 to 10:5) gave 2a (72.7 mg)
1
as a white solid in 83% yield. Mp: 119−121 °C; H NMR (400
7
8
9
MHz, MeOD): δ δ 7.92 (d, J = 14.6 Hz, 1H), 7.67ꢀ7.78 (m, 2H),
7.54ꢀ7.62 (m, 3H), 7.30ꢀ7.41 (m, 2H), 7.20ꢀ7.30 (m, 2H), 7.12ꢀ
7.17 (m, 1H), 6.84 (d, J = 14.6 Hz, 1H), 6.68 (d, J = 3.4 Hz, 1H);
13C Dept135 (100 MHz, MeOD): δ 128.4 (CH), 126.3 (CH), 125.4
(CH), 123.4 (CH), 123.3 (CH), 122.3 (CH), 120.5 (CH), 120.4
(CH), 113.5 (CH), 109.4 (CH), 104.8 (CH); 13C NMR (100 MHz,
MeOD): δ 136.4, 135.9, 129.3, 128.4, 126.3, 125.4, 123.4, 123.3,
122.3, 120.6, 120.4, 113.5, 109.4, 104.8; HRMS (ESIꢀTOF) m/z:
[M+H]+ Calcd for C16H14N 220.1121; Found: 220.1127.
1ꢀ[(E)ꢀstyryl]indoleꢀ6ꢀcarbonitrile (2f). A purification by flash
chromatography (petroleum ether: ethyl acetate = 10:0 to 10:5)
gave 2f (93.7 mg) as a white solid in 96% yield. Mp: 128−131 °C.
1H NMR (400 MHz, MeOD): δ 8.25 (s, 1H), 8.03 (d, J = 3.4 Hz,
1H), 7.99 (d, J = 14.5 Hz, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.59ꢀ7.63
(m, 2H), 7.35ꢀ7.44 (m, 3H), 7.24ꢀ7.30 (m, 1H), 6.97 (d, J = 14.5
Hz, 1H), 6.82 (d, J = 3.4 Hz, 1H), 1.22ꢀ1.38 (m, 1H), 0.86ꢀ1.01
(m, 1H); 13C Dept135 (100 MHz, DMSO): δ129.1 (CH), 128.6
(CH), 127.5 (CH), 126.6 (CH), 123.7 (CH), 122.4 (CH), 116.3
(CH), 115.6 (CH), 106.2 (CH); 13C NMR (100 MHz, DMSO): δ
136.2, 134.9, 132.2, 129.1, 128.6, 127.5, 126.6, 123.7, 122.4,
120.8, 116.3, 115.6, 106.2, 104.5; HRMS (ESIꢀTOF) m/z: [M +
H]+ Calcd for C17H13N2 245.1073; Found: 245.1063.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5ꢀchloroꢀ1ꢀ[(E)ꢀstyryl]indole (2b). A purification by flash chromaꢀ
tography (petroleum ether: ethyl acetate = 10:0 to 10:5) gave 2b
(94.1 mg) as a white solid in 93% yield. Mp: 109−110 °C; 1H
NMR (400 MHz, MeOD): δ 7.89 (d, J = 14.5 Hz, 1H), 7.80 (d, J =
3.4 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.55ꢀ7.60 (m, 3H), 7.37 (t, J
= 7.7 Hz, 2H), 7.21ꢀ7.27 (m, 2H), 6.88 (d, J = 14.5 Hz, 1H), 6.66
(d, J = 3.4 Hz, 1H); 13C Dept135 (100 MHz, MeOD): δ128.4
(CH), 126.6 (CH), 125.5 (CH), 125.1 (CH), 123.0 (CH), 122.4
(CH), 119.9 (CH), 114.6 (CH), 110.8 (CH), 104.2 (CH); 13C NMR
(100 MHz, MeOD): δ 136.1, 134.3, 130.3, 128.4, 126.6, 126.1,
125.5, 125.1, 123.0, 122.4, 119.9, 114.6, 110.8, 104.2; HRMS
(ESIꢀTOF) m/z: [M+H]+ Calcd for C16H13ClN 254.0731; Found:
254.0731.
2ꢀoxoꢀ2ꢀ[1ꢀ[(E)ꢀstyryl]indolꢀ3ꢀyl]acetic acid (2g). A purification
by flash chromatography (petroleum ether: ethyl acetate = 10:0 to
0:10) gave 2g (107.1 mg) as a yellow solid in 92% yield. Mp:
164−167 °C; 1H NMR (400 MHz, MeOD): δ 8.77 (s, 1H), 8.36 (d,
J = 7.5 Hz, 1H), 7.97 (d, J = 14.6 Hz, 1H), 7.84 (d, J = 8.2 Hz,
1H), 7.65 (d, J = 7.7 Hz, 2H), 7.29ꢀ7.47 (m, 5H), 7.17 (d, J = 14.6
Hz, 1H); 13C Dept135 (100 MHz, DMSO): δ129.2 (CH), 127.9
(CH), 126.9 (CH), 124.5 (CH), 123.8 (CH), 123.6 (CH), 122.0
(CH), 118.6 (CH), 112.0 (CH); 13C NMR (100 MHz, MeOD): δ
168.6, 136.7, 135.1, 134.7, 128.5, 127.5, 126.8, 126.1, 124.2,
123.3, 122.4, 121.9, 119.6, 114.6, 110.4; HRMS (ESIꢀTOF) m/z:
[M+H]+ Calcd for C18H14NO3 292.0968; Found: 292.0970.
5ꢀmethoxyꢀ1ꢀ[(E)ꢀstyryl]indole (2c). A purification by flash chroꢀ
matography (petroleum ether: ethyl acetate = 10:0 to 10:5) gave 2c
(73.7 mg) as a white solid in 74% yield. Mp: 134−135 °C; 1H
NMR (400 MHz, MeOD): δ 7.85 (d, J = 14.6 Hz, 1H), 7.67ꢀ7.70
(m, 1H), 7.62 (d, J = 8.3 Hz, 1H), 7.55 (d, J = 7.4 Hz, 2H), 7.35 (t,
J = 7.7 Hz, 2H), 7.17ꢀ7.27 (m, 1H), 7.12 (d, J = 2.3 Hz, 1H), 6.92
(dd, J = 2.5, 8.9 Hz, 1H), 6.80 (d, J = 14.6 Hz, 1H),6.60 (d, J = 3.2
Hz, 1H), 3.85 (s, 3H); 13C Dept135 (100 MHz, DMSO): δ 129.1
(CH), 126.9 (CH), 126.2 (CH), 125.3 (CH), 124.6 (CH), 113.1
(CH), 112.5 (CH), 111.8 (CH), 105.5 (CH), 103.2 (CH), 55.8
(CH3); 13C NMR (100 MHz, DMSO): δ 155.0, 136.8, 131.0, 129.7,
129.1, 126.9, 126.2, 125.3, 124.6, 113.2, 112.6, 111.8, 105.5,
103.3, 55.8; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C17H16NO
250.1226; Found: 250.1220.
1ꢀ(isopropylamino)ꢀ3ꢀ[1ꢀ[(E)ꢀstyryl]indolꢀ4ꢀyl]oxyꢀpropanꢀ2ꢀol
(2h). A purification by flash chromatography (petroleum ether:
ethyl acetate = 10:0 to 0:10) gave 2h (120.4 mg) as a colorless
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slurry in 86% yield. H NMR (400 MHz, MeOD): δ 8.57 (br s,
1H), 7.88 (d, J = 14.6 Hz, 1H), 7.66 (d, J = 3.4 Hz, 1H), 7.56 (d, J
= 7.6 Hz, 2H), 7.33ꢀ7.41 (m, 3H), 7.17ꢀ7.28 (m, 2H), 6.85 (d, J =
14.6 Hz, 1H), 6.80 (d, J = 3.4Hz, 1H), 6.70 (d, J = 7.7 Hz, 1H),
4.35 (m, 1H), 4.21 (m, 1H), 4.17 (m, 1H), 3.47 (m, 1H), 3.36 (m,
1H), 3.22 (m, 1H), 1.39 (dd, J = 3.4, 6.48 Hz, 6H); 13C Dept135
(100 MHz, MeOD): δ 128.4 (CH), 126.5 (CH), 125.4 (CH), 123.4
(CH), 123.3 (CH), 122.2 (CH), 114.0 (CH), 103.5 (CH), 101.9
(CH), 101.8 (CH), 69.7 (CH2), 65.7 (CH), 50.6 (CH), 47.3 (CH2),
18.1 (CH3), 17.5 (CH3); 13C NMR (100 MHz, MeOD): δ 151.9,
137.4, 136.2, 128.4, 126.5, 125.4, 123.4, 123.3, 122.2, 119.6,
114.0, 103.5, 101.9, 101.8, 69.7, 65.7, 50.6, 47.3, 18.1, 17.5;
HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C22H27N2O2 351.2067;
Found: 351.2067.
1ꢀ[(E)ꢀstyryl]indolꢀ5ꢀol (2d). A purification by flash chromatogꢀ
raphy (petroleum ether: ethyl acetate = 10:0 to 10:5) gave 2d (57.3
mg) as a white solid in 61% yield. Mp: 163−165 °C; 1H NMR (400
MHz, MeOD): δ 7.83 (d, J = 14.6 Hz, 1H), 7.64 (d, J = 3.4 Hz,
1H), 7.54 (m, 3H), 7.35 (t, J = 7.2 Hz, 2H), 7.18ꢀ7.24 (m, 1H),
6.97 (d, J = 3.4 Hz, 1H), 6.83 (m, 1H), 6.77 (d, J = 14.6 Hz, 1H),
6.52 (d, J = 3.3 Hz, 1H), 4.62 (s, 1H); 13C Dept135 (100 MHz,
MeOD): δ 128.3 (CH), 126.1 (CH), 125.2 (CH), 124.1 (CH), 123.6
(CH), 112.6 (CH), 111.9 (CH), 109.9 (CH), 104.9 (CH), 104.2
(CH); 13C NMR (100 MHz, MeOD): δ 151.6, 136.6, 130.7, 130.2,
128.3, 126.1, 125.2, 124.1, 123.6, 112.6, 111.9, 109.9, 104.9,
104.2; HRMS (ESIꢀTOF) m/z: [M+ H]+ Calcd for C16H14NO
236.1070; Found: 236.1066.
5ꢀnitroꢀ1ꢀ[(E)ꢀstyryl]indole (2i). A purification by flash chromaꢀ
tography (petroleum ether: ethyl acetate = 10:0 to 10:3) gave 2i
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(97.2 mg) as a yellow solid in 92% yield. Mp: 144ꢀ146 °C. H
NMR (400 MHz, DMSO): δ8.62 (s, 1H), 8.23~8.26 (m, 2H), 8.20
(d, J = 5.0 Hz, 1H), 8.13ꢀ8.17 (m, 1H), 7.68 (d, J = 7.1 Hz, 2H),
7.40 (t, J = 7.2 Hz, 2H), 7.24ꢀ7.31 (m, 1H), 7.13 (d, J = 14.6 Hz,
1H), 7.02 (d, J = 3.4 Hz, 1H); 13C Dept135 (100 MHz, DMSO):
δ129.2 (CH), 128.4 (CH), 127.7 (CH), 126.7 (CH), 123.7 (CH),
118.2 (CH), 118.1 (CH), 116.8 (CH), 111.7 (CH), 107.7 (CH); 13C
NMR (100 MHz, DMSO): δ142.2, 138.6, 136.0, 129.2, 128.5,
128.4, 127.7, 126.7, 123.7, 118.2, 118.1, 116.8, 111.7, 107.7;
HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C16H13N2O2 265.0972;
Found:265.0974.
methyl 1ꢀ[(E)ꢀstyryl]indoleꢀ5ꢀcarboxylate (2e). A purification by
flash chromatography (petroleum ether: ethyl acetate = 10:0 to
10:5) gave 2e (103.0 mg) as a white solid in 93% yield. Mp:
129−130 °C; 1H NMR (400 MHz, MeOD): δ 8.35 (s, 1H), 7.97 (s,
1H), 7.93ꢀ7.96 (m, 1H), 7.87 (d, J = 3.7 Hz, 1H), 7.80 (d, J = 8.8
Hz, 1H), 7.59 (d, J = 7.7 Hz, 2H), 7.38 (t, J = 7.3 Hz, 2H), 7.23ꢀ
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The Journal of Organic Chemistry
1ꢀ[(E)ꢀstyryl]imidazole (2j). A purification by flash chromatogꢀ
7ꢀ[(E)ꢀstyryl]pyrrolo[2,3ꢀd]pyrimidine (2o). A purification by
flash chromatography (petroleum ether: ethyl acetate = 10:0 to
0:10) gave 2o (72.5 mg) as a white solid in 82% yield. Mp:
raphy (petroleum ether: ethyl acetate = 10:0 to 10:5) gave 2j (55.8
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mg) as a white solid in 82% yield. Mp: 86−87 °C. H NMR (400
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MHz, MeOD): δ 8.02 (s, 1H), 7.72 (d, J = 14.7 Hz, 1H), 7.62 (s,
1H), 7.53 (d, J = 6.9 Hz, 2H), 7.34ꢀ7.46 (m, 2H), 7.24ꢀ7.34 (m,
1H), 7.10 (s, 1H), 7.02 (d, J = 14.7 Hz, 1H); 13C Dept135 (100
MHz, MeOD): δ 136.6 (CH), 128.7 (CH), 128.5 (CH), 127.5 (CH),
126.0 (CH), 122.7 (CH), 118.8 (CH), 116.5 (CH); 13C NMR (100
MHz, MeOD): δ 136.6, 134.8, 128.7, 128.5, 127.5, 126.0, 122.7,
118.8, 116.5; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C11H11N2
171.0917; Found: 171.0916.
105−107 °C. H NMR (400 MHz, MeOD): δ 9.02 (s, 1H), 8.88 (s,
1H), 8.14 (d, J = 14.9 Hz, 1H), 8.04 (d, J = 3.8 Hz, 1H), 7.58ꢀ7.61
(m, 2H), 7.40 (t, J = 7.5 Hz, 2H), 7.30 (m, 1H), 7.25 (d, J = 14.9
Hz, 1H), 6.87 (d, J = 3.8 Hz, 1H); 13C Dept135 (100 MHz,
DMSO): δ 152.2 (CH) , 150.4 (CH), 129.4 (CH), 127.8 (CH),
127.5 (CH), 126.4 (CH), 121.9 (CH), 117.0 (CH), 102.8 (CH); 13C
NMR (100 MHz, DMSO): δ 152.2, 150.4, 150.0, 135.9, 129.4,
127.8, 127.5, 126.4, 121.9, 119.9, 117.0, 102.8; HRMS (ESIꢀTOF)
m/z: [M+H]+ Calcd for C14H12N3 222.1026; Found: 222.1029.
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1ꢀ[(E)ꢀstyryl]pyrrolo[3,2ꢀb]pyridine (2k). A purification by flash
chromatography (petroleum ether: ethyl acetate = 10:0 to 10:5)
gave 2k (76.6 mg) as a white solid in 87% yield. Mp: 136−139 °C.
1H NMR (400 MHz, MeOD): δ 8.40 (d, J = 4.8 Hz, 1H), 8.25 (d, J
= 8.3 Hz, 1H), 8.11 (d, J = 3.7 Hz, 1H), 7.94 (d, J = 14.6 Hz, 1H),
7.60 (d, J = 7.6 Hz, 2H), 7.24ꢀ7.43 (m, 4H), 6.99 (d, J = 14.6 Hz,
1H), 6.82 (d, J = 3.6 Hz, 1H); 13C Dept135 (100 MHz, DMSO): δ
144.3 (CH), 129.2 (CH), 128.3 (CH), 127.3 (CH), 126.4 (CH),
124.1 (CH), 118.5 (CH), 117.8 (CH), 114.9 (CH), 106.0 (CH); 13C
NMR (100 MHz, DMSO): δ 147.4, 144.3, 136.3, 129.2, 128.9,
128.3, 127.3, 126.4, 124.1, 118.5, 117.8, 114.9, 106.0; HRMS
(ESIꢀTOF) m/z: [M+H]+ Calcd for C15H13N2 221.1073; Found:
221.1071.
1ꢀ[(E)ꢀstyryl]benzimidazole (2p). A purification by flash chromaꢀ
tography (petroleum ether: ethyl acetate = 10:0 to 10:5) gave 2p
(83.6 mg) as a white solid in 95% yield. Mp: 94−96 °C. H NMR
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(400 MHz, MeOD): δ 8.59 (s, 1H), 7.85ꢀ7.90 (m, 2H), 7.74 (d, J =
7.8 Hz, 1H), 7.62 (d, J = 7.6 Hz, 2H), 7.29ꢀ7.45 (m, 5H), 7.21 (d, J
= 14.7 Hz, 1H); 13C Dept135 (100 MHz, MeOD): δ 141.3 (CH),
128.5 (CH), 127.6 (CH), 126.1 (CH), 123.9 (CH), 123.0 (CH),
121.2 (CH), 120.1 (CH), 119.1 (CH), 110.8 (CH); 13C NMR (100
MHz, MeOD): δ 142.9, 141.3, 135.0, 132.5, 128.5, 127.6, 126.1,
123.9, 123.0, 121.2, 120.1, 119.1, 110.8; HRMS (ESIꢀTOF) m/z:
[M+H]+ Calcd for C15H13N2 221.1073; Found: 221.1075.
2ꢀphenylꢀ1'ꢀ[(E)ꢀstyryl]spiro[cyclopropaneꢀ1,3'ꢀindoline]ꢀ2'ꢀone
(2q). The title compound 2q was prepared according to general
procedure B with 2.4 equiv. of αꢀphenylvinylsulfonium salt. A
purification by flash chromatography (petroleum ether: ethyl aceꢀ
tate = 10:0 to 10:5) gave 2q (122.7 mg) as a white solid in 91%
1ꢀ[(E)ꢀstyryl]pyrrolo[2,3ꢀb]pyridine (2l). A purification by flash
chromatography (petroleum ether: ethyl acetate = 10:0 to 10:5)
gave 2l (73.9 mg) as a white solid in 84% yield. Mp: 87−88 °C. 1H
NMR (400 MHz, MeOD): δ 8.33 (m, 1H), 8.20 (d, J = 14.9 Hz,
1H), 8.04 (d, J = 8.0 Hz, 1H), 7.92 (d, J = 4.0 Hz, 1H), 7.56 (d, J =
7.7 Hz, 2H), 7.37 (t, J = 7.2 Hz, 2H), 7.19ꢀ7.27 (m, 2H), 7.03 (d, J
= 14.9 Hz, 1H), 6.71 (d, J = 4.0 Hz, 1H); 13C Dept135 (100 MHz,
DMSO): δ 143.8 (CH), 129.7 (CH), 129.3 (CH), 127.3 (CH),
126.1 (CH), 126.0 (CH), 122.8 (CH), 117.8 (CH), 114.5 (CH),
103.6 (CH); 13C NMR (100 MHz, DMSO): δ 147.0, 143.8, 136.5,
129.7, 129.3, 127.3, 126.1, 126.0, 122.8, 121.6, 117.8, 114.5,
103.6; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C15H13N2
221.1073; Found: 221.1072.
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yield. Mp: 105−108 °C. H NMR (400 MHz, MeOD): δ 7.55 (d, J
= 7.0 Hz, 2H), 7.21ꢀ7.48 (m, 12H), 6.76 (t, J = 7.4 Hz, 1H), 6.08
(d, J = 7.4 Hz, 1H), 3.36ꢀ3.37 (m, 1H), 2.19ꢀ2.28 (m, 2H); 13C
Dept135 (100 MHz, MeOD): δ 129.7 (CH), 128.4 (CH), 128.1
(CH), 127.3 (CH), 127.1 (CH), 126.8 (CH), 126.6 (CH), 125.7
(CH), 122.2 (CH), 120.7 (CH), 120.3 (CH), 120.2 (CH), 109.3
(CH), 37.0 (CH2), 21.8 (CH); 13C NMR (100 MHz, MeOD): δ
176.1, 141.6, 136.2, 134.6, 129.7, 128.4, 128.1, 127.3, 127.1,
126.9, 126.6, 125.7, 122.2, 120.7, 120.3, 120.2, 109.3, 37.0, 33.3,
21.8; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C24H20NO
338.1539; Found: 338.1541.
4,6ꢀdichloroꢀ1ꢀ[(E)ꢀstyryl]pyrrolo[2,3ꢀb]pyridine (2m). A purifiꢀ
cation by flash chromatography (petroleum ether: ethyl acetate =
10:0 to 10:5) gave 2m (97.9 mg) as a white solid in 85% yield.
2ꢀ[(E)ꢀstyryl]benzo[de]isoquinolineꢀ1,3ꢀdione (2r). A purification
by flash chromatography (petroleum ether: ethyl acetate = 10:0 to
10:5) gave 2r (86.1 mg) as a white solid in 72% yield. Mp:
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Mp: 69−70 °C. H NMR (400 MHz, MeOD): δ 8.04 (d, J = 14.9
Hz, 1H), 7.99 (d, J = 3.8 Hz, 1H), 7.56 (d, J = 7.7 Hz, 2H), 7.38 (t,
J = 8.0 Hz, 2H), 7.31 (s, 1H), 7.27 (m, 1H), 7.13 (d, J = 14.9 Hz,
1H), 6.77 (d, J = 3.6 Hz, 1H); 13C Dept135 (100 MHz, DMSO): δ
129.4 (CH), 127.9 (CH), 127.7 (CH), 126.5 (CH), 122.0 (CH),
117.2 (CH), 117.1 (CH), 101.6 (CH); 13C NMR (100 MHz,
DMSO): δ 145.8, 144.5, 137.3, 135.7, 129.4, 127.9, 127.7, 126.5,
122.0, 119.4, 117.2, 117.1, 101.6; HRMS (ESIꢀTOF) m/z: [M+H]+
Calcd for C15H11Cl2N2 289.0294; Found: 289.0300.
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172−173 °C. H NMR (400 MHz, CDCl3): δ 8.68 (d, J = 7.2 Hz,
2H), 8.26 (d, J = 8.0 Hz, 2H), 7.81 (t, J = 7.7 Hz, 2H), 7.62 (d, J =
15.2 Hz, 1H), 7.53ꢀ7.57 (m, 3H), 7.39 (t, J = 7.2 Hz, 2H), 7.30 (m,
1H); 13C Dept135 (100 MHz, CDCl3): δ 134.2 (CH), 131.7 (CH),
128.7 (CH), 128.3 (CH), 127.9 (CH), 127.1 (CH), 126.7 (CH),
120.7 (CH); 13C NMR (100 MHz, DMSO): δ 163.8, 136.0, 134.2,
131.7, 131.6, 128.7,128.3, 128.0, 127.9, 127.1, 126.7, 122.6,
120.7; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C20H14NO2
300.1019; Found: 300.1017..
1ꢀ[(E)ꢀstyryl]pyrrolo[2,3ꢀb]pyridineꢀ5ꢀcarboxylic acid (2n).
A
purification by flash chromatography (petroleum ether: ethyl aceꢀ
tate = 10:0 to 0:10) gave 2n (86.6 mg) as a white solid in 82%
1ꢀ[(E)ꢀ2ꢀ(pꢀtolyl)vinyl]indole (5a). A purification by flash chromaꢀ
tography (petroleum ether: ethyl acetate = 10:0 to 10:5) gave 5a
(72.7 mg) as a white solid in 78% yield. Mp: 115−116 °C. 1H
NMR (400 MHz, DMSO): δ 8.05 (d, J = 14.6 Hz, 1H), 7.92ꢀ7.94
(m, 2H), 7.60 (d, J = 7.7 Hz, 1H), 7.52 (d, J = 8.1 Hz, 2H), 7.23ꢀ
7.27 (m, 1H), 6.91 (d, J = 14.6 Hz, 1H), 6.70 (d, J = 3.30 Hz, 1H),
2.31 (s, 3H); 13C Dept135 (100 MHz, DMSO): δ 129.7 (CH),
126.2 (CH), 124.8 (CH), 123.5 (CH), 122.9 (CH), 121.2 (CH),
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yield. Mp: 238−241 °C. H NMR (400 MHz, MeOD): δ 9.00 (s,
1H), 8.66 (s, 1H), 8.23 (d, J = 14.9 Hz, 1H), 8.04 (d, J = 3.8 Hz,
1H), 7.59 (d, J = 7.3 Hz, 2H), 7.39 (t, J = 7.7 Hz, 2H), 7.25ꢀ7.31
(m, 1H), 7.15 (d, J = 14.9 Hz, 1H), 6.85 (d, J = 4.0 Hz, 1H); 13C
Dept135 (100 MHz, DMSO): δ 145.4 (CH), 131.4 (CH), 129.4
(CH), 127.6 (CH), 126.3 (CH), 122.3 (CH), 116.0 (CH), 104.7
(CH); 13C NMR (100 MHz, DMSO): δ 167.5, 148.5, 145.4, 136.1,
131.4, 129.4, 127.6, 126.3, 122.3, 121.0, 120.8, 116.0, 104.7;
HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C16H13N2O2 265.0972;
Found: 265.0975.
121.1 (CH), 113.8 (CH), 111.0 (CH), 105.5 (CH), 21.3 (CH3); 13
C
NMR (100 MHz, DMSO): δ 136.3, 135.9, 133.8, 129.7, 129.1,
126.2, 124.8, 123.5, 122.9, 121.2, 121.1, 113.8, 111.0, 105.5, 21.3;
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HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C17H16N 234.1277;
Found: 234.1277.
Hz, 1H), 7.35ꢀ7.41 (m, 2H), 7.04ꢀ7.19 (m, 4H), 6.65 (d, J = 3.2
Hz, 1H), 5.69 (s, 1H), 5.48 (s, 1H), 3.93 (s, 3H); 13C Dept135 (100
MHz, CDCl3): δ 129.9 (CH), 128.5 (CH), 126.9 (CH), 122.2 (CH),
121.1 (CH), 120.4 (CH), 111.7 (CH), 110.1 (CH2), 103.5 (CH),
52.3 (CH3); 13C NMR (100 MHz, CDCl3): δ 166.6, 144.2, 141.3,
136.3, 130.7, 129.9, 129.3, 128.5, 126.9, 122.2, 121.1, 120.4,
111.7, 110.1, 103.5, 52.3; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd
for C18H16NO2 278.1176; Found: 278.1175.
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1ꢀ[(E)ꢀ2ꢀ(3ꢀbromophenyl)vinyl]indole (5b). A purification by flash
chromatography (petroleum ether: ethyl acetate = 10:0 to 10:5)
gave 5b (83.2 mg) as a white solid in 70% yield. Mp: 112−113 °C.
1H NMR (400 MHz, DMSO): δ 8.22 (d, J = 14.6 Hz, 1H), 8.02 (d,
J=8.0 Hz, 1H), 7.92ꢀ7.95 (m, 2H), 7.60 (dd, J = 5.8, 7.3 Hz, 2H),
7.36ꢀ7.43 (m, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.22ꢀ7.31 (m, 1H),
7.16 (t, J = 7.3 Hz, 1H), 6.93 (d, J = 14.6 Hz, 1H), 6.74 (d, J = 3.3
Hz, 1H); 13C Dept135 (100 MHz, DMSO): δ 131.2 (CH), 129.4
(CH), 128.3 (CH), 125.7 (CH), 125.5 (CH), 124.6 (CH), 123.1
(CH), 121.4 (CH), 121.3 (CH), 111.9 (CH), 111.3 (CH), 106.2
(CH); 13C NMR (100 MHz, DMSO): δ 139.5, 136.0, 131.2, 129.4,
129.2, 128.3, 125.7, 125.5, 124.6, 123.1, 122.8, 121.4, 121.3,
111.9, 111.3, 106.2; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for
C16H13BrN 298.0226; Found: 298.0212.
1ꢀ[1ꢀ(3ꢀnitrophenyl)vinyl]indole (5e). A purification by flash
chromatography (petroleum ether: ethyl acetate = 10:0 to 10:2)
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MHz, CDCl3): δ 8.21 (td, J = 1.0, 2.38 Hz, 1H), 8.16 (m, 1H), 7.60
(d, J = 7.4 Hz, 1H), 7.40ꢀ7.48 (m, 2H), 6.97ꢀ7.10 (m, 4H), 6.60 (d,
J = 3.5 Hz, 1H), 5.66 (d, J = 1.0 Hz, 1H), 5.47 (d, J = 0.9 Hz, 1H);
13C Dept135 (100 MHz, CDCl3): δ 132.7 (CH), 129.7 (CH), 128.3
(CH), 123.9 (CH), 122.5 (CH), 121.7 (CH), 121.3 (CH), 120.7
(CH), 111.5 (CH), 110.6 (CH2), 104.1(CH). 13C NMR (100 MHz,
CDCl3): δ 148.7, 143.0, 138.9, 136.2, 132.7, 129.7, 129.4, 128.3,
123.9, 122.5, 121.7, 121.3, 120.7, 111.5, 110.6, 104.1;HRMS
(ESIꢀTOF) m/z: [M+H]+ Calcd for C16H13N2O2 265.0972; Found:
265.0974.
1ꢀ[(E)ꢀ2ꢀ(2ꢀnaphthyl)vinyl]indole (5c). A purification by flash
chromatography (petroleum ether: ethyl acetate = 10:0 to 10:5)
gave 5c (91.5 mg) as a white solid in 85% yield. Mp: 192−195 °C.
1H NMR (400 MHz, DMSO): δ 8.27 (d, J = 14.6 Hz, 1H), 8.02ꢀ
8.04 (m, 2H), 7.97ꢀ7.99 (m, 2H), 7.87ꢀ7.93 (m, 3H), 7.62 (d, J =
7.7 Hz, 1H), 7.37ꢀ7.55 (m, 2H), 7.29 (t, J = 7.4 Hz, 1H), 7.17ꢀ7.13
(m, 1H), 7.13 (d, J = 14.6 Hz, 1H), 6.75 (d, J = 3.3 Hz, 1H); 13C
Dept135 (100 MHz, DMSO): δ 128.6 (CH), 128.1 (CH), 128.0
(CH), 126.9 (CH), 126.0 (CH), 125.3 (CH), 124.8 (CH), 124.7
(CH), 124.1 (CH), 123.0 (CH), 121.3 (CH), 113.7 (CH), 111.1
(CH), 105.9 (CH); 13C NMR (100 MHz, DMSO): δ 136.0, 134.4,
133.9, 132.5, 129.2, 128.6, 128.1, 128.0, 126.9, 126.0, 125.3,
124.8, 124.7, 124.1, 123.0, 121.3, 113.7, 111.1, 105.9; HRMS
(ESIꢀTOF) m/z: [M+H]+ Calcd for C20H16N 270.1277; Found:
270.1266.
1ꢀ[(E)ꢀ2ꢀ(4ꢀnitrophenyl)vinyl]indole (5f). A purification by flash
chromatography (petroleum ether: ethyl acetate = 10:0 to 10:2)
gave 5f (38 mg) as a yellow solid in 36% yield. Mp: 199−200 °C.
1H NMR (400 MHz, CDCl3): δ 8.15ꢀ8.17 (d, J = 8.0 Hz, 2H), 7.79
(d, J = 14.4 Hz, 1H), 7.58 (dd, J = 1.0, 7.8 Hz, 1H), 7.44ꢀ7.55 (m,
4H), 7.27 (t, J = 7.4 Hz, 1H), 7.13ꢀ7.18 (m, 1H), 6.67 (d, J = 3.4
Hz, 1H), 6.63 (d, J = 14.4 Hz, 1H); 13C Dept135 (100 MHz,
CDCl3): δ 126.9 (CH), 125.7 (CH), 124.4 (CH), 123.4 (CH), 123.3
(CH), 121.8 (CH), 121.6 (CH), 110.7 (CH), 109.6 (CH), 107.2
(CH). HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C16H13N2O2
265.0972; Found: 265.0967.
1ꢀ[(E)ꢀ1ꢀdeuterioꢀ2ꢀphenylꢀvinyl]indole (5h). A purification by
flash chromatography (petroleum ether: ethyl acetate = 10:0 to
10:5) gave 5h (61.6 mg) as a white solid in 70% yield. Mp:
1ꢀ[(E)ꢀ2ꢀ(5ꢀbromopyrimidinꢀ2ꢀyl)vinyl]indole (5g). A purification
by flash chromatography (petroleum ether: ethyl acetate = 10:0 to
10:5) gave 5e (73.0 mg) as a white solid in 61% yield. Mp:
1
120−121 °C. H NMR (400 MHz, MeOD): δ 7.70ꢀ7.76 (m, 2H),
1
7.55ꢀ7.61 (m, 3H), 7.30ꢀ7.41 (m, 2H), 7.20ꢀ7.30 (m, 2H), 7.12ꢀ
7.17 (m, 1H), 6.84 (s, 1H), 6.68 (d, J = 3.7 Hz, 1H); 13C Dept135
(100 MHz, MeOD): δ 128.4 (CH), 126.3 (CH), 125.4 (CH), 123.4
(CH), 122.3 (CH), 120.5 (CH), 120.4 (CH), 113.3 (CH), 109.4
(CH), 104.8; 13C NMR (100 MHz, MeOD): δ 136.4, 135.9, 129.3,
128.4, 126.3, 125.4, 123.4, 122.3, 120.5, 120.4, 113.3, 109.4,
104.8; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C16H13DN
221.1184; Found: 221.1169.
161−163 °C. H NMR (400 MHz, CDCl3): δ 8.67 (s, 2H), 8.63 (d,
J = 14.0 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.66ꢀ7.72 (m, 1H), 7.63
(d, J = 7.7 Hz, 1H), 7.54 (d, J = 3.6 Hz, 1H), 7.34 (t, J = 7.6 Hz,
1H), 7.23 (t, J = 7.3 Hz, 1H), 6.75 (d, J = 3.9 Hz, 1H), 6.68 (d, J =
14.0 Hz, 1H); 13C Dept135 (100 MHz, CDCl3): δ 157.5 (CH),
132.4 (CH), 123.6 (CH), 122.0 (CH), 121.4 (CH), 110.1 (CH),
109.5 (CH), 108.0 (CH); 13C NMR (100 MHz, CDCl3): δ 163.2,
157.5, 136.1, 132.4, 129.7, 123.6, 122.0, 121.4, 116.0, 110.1,
109.5, 108.0; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for
C14H11BrN3 300.0131; Found: 300.0154.
General Procedure C for Nꢀheteroarene substrates’ vinylation
with βꢀphenylvinylsulfonium salt. To a 5 mL Schlenk tube were
added Nꢀheteroarene substrates (0.4 mmol, 1.0 equiv.) and βꢀ
phenylvinylsulfonium salt (0.48 mmol, 1.2 equiv.) in DMSO (2
mL). The mixture was stirred at room temperature for 2 min and to
the mixture was added Cs2CO3 (391.2 mg, 1.2 mmol, 3.0 equiv.).
The mixture was stirred for 12 hours at room temperature till the
reaction was complete. To the resulting mixture was added satuꢀ
rated ammonium chloride solution (10 mL), and the mixture was
then extracted with EtOAc (3 x 50 mL). The combined organic
layers were washed with H2O (2 x 10 mL), dried with anhydrous
sodium sulfate. After concentration, product 5 was purified using
column chromatography on silica gel using an appropriate eluent.
Compounds (5d, 5e, 5f, 5g) was prepared according to general
procedure C.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: xxxxxxxx
All 1H and 13C NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Authors
* Eꢀmail: hong.shen.hs1@roche.com.
xhqian@ecust.edu.cn
methyl 4ꢀ(1ꢀindolꢀ1ꢀylvinyl)benzoate (5d). A purification by flash
chromatography (petroleum ether: ethyl acetate = 10:0 to 10:5)
gave 5d (95.3 mg) as a white solid in 86% yield. Mp: 105−107 °C.
1H NMR (400 MHz, CDCl3): δ 7.99ꢀ8.04 (m, 2H), 7.66 (d, J = 7.3
ORCID
Hong C. Shen: 0000ꢀ0002ꢀ3477ꢀ8932
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The Journal of Organic Chemistry
Closing Alkyne Metathesis. Comparative Investigation of Two Differꢀ
Notes
ent Catalyst Systems and Application to the Stereoselective Synthesis
of Olfactory Lactones, Azamacrolides, and the Macrocyclic Perimeter
of the Marine Alkaloid Nakadomarin A. J. Am. Chem. Soc. 1999, 121,
11108ꢀ11113. (d) Ghosh, A. K.; Wang, Y.; Kim, J. T. Total Synthesis
of Microtubuleꢀstabilizing Agent (ꢀ)ꢀLaulimalide. J. Org. Chem. 2001,
66, 8973ꢀ8982. (e) Furstner, A.; Davies, P. W. Alkyne Metathesis.
Chem. Commun. 2005, 18, 2307ꢀ2320. (f) Chernichenko, K.;
Madarasz, A.; Papai, I.; Nieger, M.; Leskela, M. A FrustratedꢀLewisꢀ
pair Approach to Catalytic Reduction of Alkynes to cisꢀAlkenes. Nat.
Chem. 2013, 5, 718ꢀ723.
1
2
3
4
5
6
7
8
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank Liqing Chen (Roche Innovation Center Shanghai) for
analytical support in mass spectrometry, Leimin Wang (Roche
Innovation Center Shanghai) and Inken Plitzko (Roche Innovation
Center Basel) for support in NMR.
9
(9) Tzalis, D.; Koradin, C.; Knochel, P. Cesium Hydroxide Cataꢀ
lyzed Addition of Alcohols and Amine Derivatives to Alkynes and
Styrene. Tetrahedron Lett. 1999, 40, 6193ꢀ6195.
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