MnO2 mediated sequential oxidation/olefination of alkyl-substituted heteroarenes with alcohols

Article abstract of DOI:10.1016/j.tet.2020.130968

A practical and efficient ligand-free MnO₂ mediated sequential oxidation and olefination has been developed for the facile synthesis of a broad range of unsaturated N-heteroazaarenes from simple alkyl-substituted heteroarenes and alcohols. The procedure tolerates a series of functional groups, such as methoxyl, chloro, bromo, iodo, vinyl, phenolic and hetero groups, providing the olefination products in moderate to good yields.The protocol could be conducted at mild conditions and used environmentally friendly air as the clear oxidant.

Full text of DOI:10.1016/j.tet.2020.130968

Journal Pre-proof
MnO mediated sequential oxidation/olefination of alkyl-substituted heteroarenes with
2
alcohols
Chunyan Zhang, Zehua Li, Yanchen Fang, Shaohua Jiang, Maorong Wang, Guoying
Zhang
PII:
S0040-4020(20)30060-0
https://doi.org/10.1016/j.tet.2020.130968
TET 130968
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 26 November 2019
Revised Date: 10 January 2020
Accepted Date: 20 January 2020
Please cite this article as: Zhang C, Li Z, Fang Y, Jiang S, Wang M, Zhang G, MnO mediated
2
sequential oxidation/olefination of alkyl-substituted heteroarenes with alcohols, Tetrahedron (2020), doi:
https://doi.org/10.1016/j.tet.2020.130968.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition
of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of
record. This version will undergo additional copyediting, typesetting and review before it is published
in its final form, but we are providing this version to give early visibility of the article. Please note that,
during the production process, errors may be discovered which could affect the content, and all legal
disclaimers that apply to the journal pertain.
© 2020 Published by Elsevier Ltd.

Tetrahedron
1
0.Graphical Abstract
To create your abstract, type over the instructions in the
MnO2 Mediated Sequential Oxidation/
Olefination of Alkyl-Substituted Heteroarenes
with Alcohols
Chunyan Zhang,a Zehua Li,a Yanchen Fang,a Shaohua Jiang,b Maorong Wang,c and Guoying Zhang*a,b
a Key Laboratory of Sensor Analysis of Tumor Marker, Ministry of Education; Shandong Key Laboratory of Biochemical Analysis; Key
Laboratory of Analytical Chemistry for Life Science in Universities of Shandong; College of Chemistry and Molecular Engineering.
Qingdao University of Science and Technology, Qingdao 266042, PR China
b College of Materials Science and Engineering, Nanjing Forestry University, Nanjing 210037, P. R. China
c State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, 308 Ningxia Road, Qingdao 266071, P. R. China

Tetrahedron
1
Pergamon
MnO2 Mediated Sequential Oxidation/Olefination of Alkyl-
Substituted Heteroarenes with Alcohols
Chunyan Zhang,a, Zehua Li,a, Yanchen Fang,a Shaohua Jiang,b Maorong Wang,c and Guoying Zhang*a,b
a Key Laboratory of Sensor Analysis of Tumor Marker, Ministry of Education; Shandong Key Laboratory of Biochemical Analysis; Key
Laboratory of Analytical Chemistry for Life Science in Universities of Shandong; College of Chemistry and Molecular Engineering.
Qingdao University of Science and Technology, Qingdao 266042, PR China
b College of Materials Science and Engineering, Nanjing Forestry University, Nanjing 210037, P. R. China
c State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, 308 Ningxia Road, Qingdao 266071, P. R. China
+These authors contributed equally to this work.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A practical and efficient ligand-free MnO2 mediated sequential oxidation and olefination has
been developed for the facile synthesis of a broad range of unsaturated N-heteroazaarenes from
simple alkyl-substituted heteroarenes and alcohols. The procedure tolerates a series of
functional groups, such as methoxyl, chloro, bromo, iodo, vinyl, phenolic and hetero groups,
providing the olefination products in moderate to good yields.The protocol could be conducted
at mild conditions and used environmentally friendly air as the clear oxidant.
Available online
Keywords:
Manganese dioxide
Olefination
Alcohol
Heteroarenes
1. Introduction
An attractive approach to circumvent these problems is
abundantly available metal catalyzed acceptorless
As one of the most important fundamental structural motifs,
unsaturated N-heteroaromatic compounds has been considered as
a privileged structure in natural products, pharmaceuticals and
functional materials (Figure 1).1 As such, the development of
efficient methods toward these complex molecules is of great
significance to chemical, medicinal and material science and has
attracted a great deal of attention over the past decades.2 Plenty of
powerful synthetic routes, including many named reactions,3
catalytic coupling4 or olefin metathesis,5 have been developed to
access such kinds of molecules. However, multi-step functional
group manipulations and unavoidable generation of stoichiometric
amount of undesired waste are the few shortcomings in these
reactions.
dehydrogenative condensation (ADC),6 which enables the
synthesis of di-substituted alkenes compounds from alcohols
combination of catalytic dehydrogenation and condensation steps.
Moreover, alcohols can be obtained from indigestible and
abundantly available lignocellulose biomass.7 Kempe8 and Maji
group9 pioneered a novel manganese-catalyzed reaction leading to
di-substituted olefins synthesis using alcohols with N-heteroarenes
at the same time, the reaction proceeds via ADC process,
Figure 1. Selected bioactive compounds with unsaturated N-heteroarene
moiety.
Scheme 1. Methods for Mn-catalyzed olefination.

2
Tetrahedron
producing only water and hydrogen as green coproducts (Scheme
1, top). However, metal complexes or addition of capricious
ligands for catalyst activation are generally required to maintain
the catalytic cycle, thereby limiting the potential scope of this
environmentally benign transformation. These results together
with our progress on the use of alcohols as green partners for
metal catalyzed coupling reactions,10 prompted us to envision that
alcohols might be oxidized in MnO2/air catalytic system and
condensed with methylazaarenes for the synthesis of di-
substituted olefins. Moreover, to the best of our knowledge, MnO2
catalyzed oxidation/olefination of alcohols and methylazaarenes
to synthesis unsaturated N-heteroaromatic has not been reported.
Herein, we present on the first protocol for successful
implementation of the MnO2 catalyzed oxidation of alcohols with
a variety of alkyl-substituted azaarenes via olefination process,
which allows for synthesis of various multiple-substituted alkenes
under mild condition.
styrylpyrazine (3a) was obtained in 12% yield, when the reaction
was conducted in the presence of Cs2CO3 under an air atomsphere
(Table 1, entry 1). This result indicated that our proposed sequential
oxidation/olefination reactions of methylazaarene with alcohol was
indeed possible. Base screening indicated that when the reaction
was ran in presence of KOH, the desired product was obtained best
yield and the high regioselective (Table 1, entry 5). The reaction
still worked even under oxygen atmosphere (oxygen balloon) and
3a was obtained in good yield. Other inorganic bases or organic
bases, did not improve the reactivity (Table 1, entries 2-9). Further
investigation of the solvents revealed that the reactivity was affected
by the nature of the solvents, and the best result was achieved with
t-AmOH as the solvent. Meanwhile, reaction in other alcohol
solvents, such as t-BuOH, i-PrOH and EtOH resulted in lower yield
or no reaction (Table 1, entries 10-12). This reactivity trend(t-
AmOH > t-BuOH > i-PrOH > EtOH) is that sterically hindered
alcohols suppress the competing aldol reaction with benzaldehyde
intermediate, revealing that the mechanism may via aldehyde
species. No appreciable increase in yield of olefination product was
obtained in ether solvents or non-polar solvent. Finally, control
reactions demonstrated that the low yield of 3a was obtained under
nitrogen atmosphere or in the absence of catalyst or base (Table 1,
entries 16-18).
2. Results and discussion
As an initial attempt, the reaction between phenylmethanol (1a)
and 2-methylpyrazine (2a) was chosen as the model reaction for
optimization of the reaction conditions (Table 1).
Table 1. Optimization of the reaction conditions a
Table 2. Substrate scope of N-heteroaromatics a
N
N
N
N
N
R
MnO2 (10 mol%)
KOH (1 equiv)
MnO2
R
Ph
N
-hetero
+
N-hetero
+
R'
OH
+
Ph
OH
1a
Ph
R'
n
N
2a
n
t-AmOH
3a
4a
1a-n
2a-2n
3a-n
Entry
1
Base
Solvent
3a (%)
12
3a/4a
N
N
N
N
Cs2CO3
K2CO3
Na2CO3
CsOH
KOH
t-AmOH
t-AmOH
t-AmOH
t-AmOH
t-AmOH
> 20:1
-
N
Ph
N
Ph
Ph
Ph
2
< 5
< 5
83
3a, 93%
3b, 81%
3c, 61%
-
3
19:1
> 20:1
17:1
-
4
N
O
N
5
96 (72)b
N
Ph
6
NaOH
t-BuOLi
t-AmOH
t-AmOH
t-AmOH
t-AmOH
t-BuOH
i-PrOH
EtOH
53
Ph
3d, 53%b
3e, 71%
3f, 52%
7
< 5
63
16:1
18:1
19:1
> 20:1
-
8
t-BuONa
t-BuOK
KOH
KOH
KOH
KOH
KOH
KOH
-
9
89
Ph
N
10
11
12
13
14
15
16
17
18
88
Ph
N
3g
, 23%
3h
, 94%
12
0
N
OMe
Cl
> 20:1
16:1
> 20:1
-
THF
32
Ph
Diglyme
Toluene
t-AmOH
t-AmOH
t-AmOH
90
Ph
N
Ph
N
Ph
3k, 46%c
3i, 82%
3j, 91%
19
0
N
N
N
N
N
11c (10)d
< 5e
KOH
KOH
> 20:1
-
Ph
N
a General conditions: 1a (0.55 mmol), 2a (0.5 mmol), MnO2 (0.05 mmol),
base (0.5 mmol), solvent (1.0 mL), 120 oC, 21 h. Yield of 3a and the ratio
of 3a/4a determined by GC-analysis using n-cetane as an internal
standard. b Under oxygen. c No MnO2. d No MnO2, 48 h. e Under nitrogen.
3l, 38%c
3m, 36%c
3n, 32%c
a
General conditions: 1a (0.55 mmol), 2 (0.5 mmol), MnO2 (10 mol%),
KOH (0.5 mmol), t-AmOH (1.0 mL), air, 120 oC, 21 h. Isolated yield,
b
o
c
unless otherwise noted. 1a (2.0 mmol), 140 C, 36 h. 1a (2.0 mmol),
KOH (1.0 mmol), 140 oC, 48 h.
Because manganese precatalyst has shown to be highly effective
for the dehydragenation/olefination of methylazaarenes with
alcohols,8,9 we initially focused on exploring conditions using MnO2
as readily available catalyst at 120 °C. The desired (E)-2-
Taken together, we can conclude that the oxidation/olefination
was carried out by stirring t-AmOH solution of phenylmethanol, 2-
methylpyrazine, 10 mol% of MnO2, and an equivalent of KOH at

Tetrahedron
3
Table 3. Substrate scope of alcohols a
120oC under an air for 21 hours to give the olefination product 3a in
the best yield.
On the basis of the results described above, a variety of N-
heteroaromatics were submitted to the MnO2-catalyzed
oxidant/olefination reaction to investigate its substrate scope and
generality (Table 2). 2-Methylpyrazine and 3-methylpyridazine
substrates gave the corresponding products in high yields (3a-3b).
The oxidation/olefiantion reaction of 2,6-dimethylpyrazine or 4-
methylpyridine (lower acidity of methyl) reacted with
phenylmethanol resulted in modearate yields of the desired products
3c-3d. When the pyrazine core was replaced with benzo[d]oxazole,
the olefination reaction still took place to give 3e in 71% yield.
Although the reaction of 4-methylquinoline and 1-
methylisoquinoline offered 3f and 3g in moderate yields, the
reaction with 2-methylquinoline proceeded smoothy to produce the
desired adduct 3h in excellent yield. The yield of product is likely
related to the stability of the enamine intermediate, which increases
in the order 3g < 3f < 3h. This result showing that the olefination
mechanism may via enamine intermediate. Methyl-substituted N-
heteroarenes derived from 2-methylquinoline were effective
substrates and smoothly reacted with benzyl alcohol to provide the
corresponding products 3i and 3j in 82 and 91% yield, respectively.
Ethyl or benzyl substituted azaarenes were less reactive, and the
olefination products 3k-3n were isolated in moderate yields when
the reaction temperature and time were increased. These results may
be due to large steric hindrance of the methylenyl of the azaarenes.
Yield (%)
5a, 89
5b, 81
5c, 73
5d, 68
5e, 66
5f, 84
1
Entry
1
R
1d
1k
1l
4-CH3C6H4
4-ClC6H4
4-BrC6H4
2-thienyl
2
3
2a
1p
1b
1c
1d
1e
1f
4
5
2-CH3C6H4
3-CH3C6H4
4-CH3C6H4
2,4,6-(CH3)3C6H2
4-t-BuC6H4
4-PhC6H4
2-CH3OC6H4
4-CH3OC6H4
2-ClC6H4
4-ClC6H4
4-BrC6H4
4-IC6H4
6
5g, 93
5h, 64
5i, 91
7
8
9
5j, 83
1g
1h
1i
10
11
12
13
14
15
16
17
18
19
20
21b
22b
23b
5k, 71
5l, 92
5m, 57
5n, 84
5o, 66
5p, 48
5q, 77
5r, 58
5s, 74
5t, 53b
5u, 61b
5v, 56b
5w, 68b
1j
1k
1l
2l
1m
1n
1o
1p
1q
1r
1s
1t
1-Naphthyl
2-furyl
2-thienyl
Furthermore, the scope of the alcohols was also explored and the
results are shown in Table 3. The procedure tolerated well some
functional groups, such as methyl, phenyl, methoxy, halogen and
heteroarene, with good yields. The electronic effects of substituent
in alcohol had some effect on the reaction. Generally, the alcohols
with electron-withdrawing groups gave slightly lower yields than
those electron-donating analogues (5a vs 5b-c and 5g, 5i, 5l vs 5n-
5p). An obvious steric hindrance effect on the reactivity was
observed, which was demonstrated by the reactivities of 5e vs 5g
and 5m vs 5n. It is worth noting that the tolerance of halogen group
on the aromatic ring in this olefination protocol offers an
opportunity for subsequent transformations, which facilitates
expedient synthesis of complex unsaturate N-heteroarenes (5b-5c,
5m-5p). Naphthyl-substituted alcohol was also compatible with this
process, furnishing the desired product 5q in 87% yield. In addition
to aromatic-substituted alcohols, although the reaction of furan-2-
ylmethanol gave the corresponding product 5r in moderate yield,
the reaction with thiophen-2-ylmethanol proceeded smoothy to give
5s in good yield. Pyridin-2-ylmethanol was also a good reaction
partner, and (E)-2-(2-(pyridin-2-yl)vinyl)quinoline 5x was isolated
in 52% yield. To extend the scope of our catalytic system, we also
tested more challenging aliphatic alcohols under the standard
procedure. 2-Ethylbutan-1-ol was initially surveyed and the reaction
proceeded smoothly to give the desired olefination 5t in moderate
yield. Furthermore, similar results were obtained in the reactions of
aliphatic alcohols with different substituted to deliver the desired
adducts 5u-5w efficiently in good yields. And importantly,
unsaturate alcohol substrates, citronellol, was also good reaction
partner, providing the corresponding product 5y in 66% yield, while
the internal double bond remained intact.
Et2CH
t-Bu
Cyclopropyl
Cyclohexyl
a
General conditions: 1 (0.55 mmol), 2a or 2l (0.5 mmol), MnO2 (10
mol%), KOH (0.5 mmol), t-AmOH (1.0 mL), air, 120 C, 21 h. Isolated
o
yield. b 1 (2.0 mmol), KOH (1.0 mmol), 140 oC, 48 h.
To further demonstrate the robustness of our system, we were
able to run experiments on gram scale in the presence of 10 mol%
of MnO2 to produce the olefination adducts 3a and 3j in 73% (1.33
g) and 75% (1.73 g) yield, respectively.
Scheme 2. Gram scale experiments.
To validate the recyclability of current oxidant/olefination, the
reuse investigation was performed in the model reaction of 1a with
2a in presence of 10 mol% of MnO2. After the completion of
reaction, a small aliquot of the reaction mixture was analyzed by

4
Tetrahedron
unsaturated
available
N-heteroaromatics
alcohols and
from
alkylazaarenes
commercially
via
GC to monitor product 3a formation. Then the reaction mixture was
filtered, washed with ethyl acetate, water and ethanol, dried on
vacuum, the catalyst of MnO2 was recovered and continued to
catalyze for another reaction. It is shown in Figure. 2 that the
olefination could be repeated at least five times with the fifth run
giving a 81% yield of 3a. And the catalytic activity of the recovered
MnO2 dried on the oxygen atmosphere better than argon (see the
Supporting Information for details), these results indicate that the
catalyst MnO2 can can be re-generated by oxygen or air.
100
oxidation/olefination under the aerobic conditions. The
method is compatible with a variety of functional groups
and can be used to prepare a range of 1,2-disubstitued
unsaturated N-heteroaromatics. Further investigations to
gain a detailed mechanistic understanding as well as
application of this aerobic oxidative catalytic system to
other oxidation/olefination reactions are currently in
progress.
90
80
70
60
50
40
4. Experimental section
4.1 General Information
1H and 13C spectra were obtained on a Brüker AVIII300
(300 MHz) or AVII (500 MHz) spectrometer. Proton-
decoupled spectra are denoted as {1H}. Chemical shifts (δ)
were reported in parts per million (ppm) using the residual
solvent signal as an internal standard (CDCl3: δH = 7.26
ppm, δC = 77.16 ppm). All coupling constants (J values)
were reported in Hertz (Hz). Multiplicities were reported as
follows: s, singlet; d, doublet; t, triplet; m, multiplet. High-
resolution mass spectrometry (HRMS) measurements were
1
2
3
4
5
Cycle Number [n]
Figure 2. Reusability of MnO2 Catalyst
The practice and convenience of this proceed to unsaturated N-
heteroaromatics can be di-olefination of substrates containing two
methyl groups as well, the corresponding products 7a and 7b were
isolated in reasonable yields, respectively.
recorded on
a Bruker Daltronics microTOF (ESI)
spectrometer. Flash chromatography was carried out using
matrix 60 silica.
4.2 General procedure for synthesis of products (1)substrates
General procedure for MnO2 catalyzed oxidation/olefination
reaction (3a-3n, 5a-5y, 7a-7a)
Using a nitrogen-filled glove box, an oven-dried Schlenk
tube (100 mL volume) was charged with a magnetic stirring
bar, MnO2 (0.05 mmol), KOH (0.5 mmol), alcohols (1) (0.55
mmol), heteroarenes (2) (0.5 mmol) and t-AmOH (1 mL).
Then the Schlenk tube was closed tightly with a teflon cap,
removed from the glove box. A reflux condenser was
evacuated and refilled with dry air and then attached to the
Schlenk tube maintaining dry air stream. A bubble counter
was attached to the top of the condenser and the whole
system was purged with dry air for 15 seconds. The Schlenk
tube was immersed into a pre-heated oil bath (design
temperature). After design time the reaction was cooled, a
small aliquot of the organic phase was analyzed by GC or
GC-MS to monitor product formation. Purification of the
remainder by column chromatography on silica gel
(petroleum ether/ethyl acetate = 20/1 – 5/1) gave the
corresponding products in the reported yield.
Scheme 3. MnO2 catalyzed di-olefination.
On the basis of the results we obtained here and previous
reports,7,8 a plausible mechanism for the present process can be
proposed. In this scenario, initial alcohol is oxidized by air in the
presence of MnO2 to generate aldehyde. After enamine was formed
under the base condition, nucleophilic attack of the enamine into the
C=O bond of aldehyde gained the intermediate I. Subsequent
elimination releases water in the presence of base and give rise to
the unsaturated N-heteroaromatic product.
4.2.1 (E)-2-styrylpyrazine (3a)
The title compound was prepared according to the
general procedure and purified by column chromatography
1
to give a white solid, 169 mg, 93% yield. H NMR (300
Scheme 4. Possible mechanism of olefination.
MHz, CDCl3): δ 8.59 (s, 1H), 8.49 (s, 1H), 8.35 (d, J = 2.3
Hz, 1H), 7.70 (d, J = 16.1 Hz, 1H), 7.55 (d, J = 8.1 Hz, 2H),
7.38 – 7.28 (m, 3H), 7.11 (d, J = 16.1 Hz, 1H) ppm. 13C
NMR (75 MHz, CDCl3): δ 151.3, 144.4, 143.8, 142.8,
136.0, 135.2, 129.0, 128.9, 127.3, 124.0. HRMS (ESI)
calcd. for C12H11N2 [M+H]: 183.0922, found: 183.0931.
3. Conclusion
In summary, we have developed an efficient MnO2/air
catalytic system that allows the direct formation of

Tetrahedron
5
4.2.2 (E)-3-styrylpyridazine (3b)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 53mg, 23% yield. 1H NMR (300 MHz,
CDCl3): δ 8.57 (d, J = 5.6 Hz, 1H), 8.39 (d, J = 8.4 Hz, 1H),
8.01 (s, 2H), 7.84 (d, J = 8.2 Hz, 1H), 7.67 (ddd, J = 15.3,
14.8, 7.1 Hz, 4H), 7.58 (d, J = 5.6 Hz, 1H), 7.43 (dd, J =
10.9, 4.4 Hz, 2H), 7.38 – 7.29 (m, 1H) ppm; 13C NMR (75
MHz, CDCl3): δ 154.6, 142.5, 136.9, 136.8, 135.8, 129.9,
128.8, 128.6, 127.5, 127.3, 127.2, 124.5, 122.9, 120.0 ppm.
HRMS (ESI) calcd. for C17H14N [M+H]: 232.1126, found:
232.1141.
The title compound was prepared according to the general
procedure and purified by column chromatography to give a
yellow solid, 147 mg, 81% yield. H NMR (300 MHz,
CDCl3): δ 8.98 (d, J = 4.8 Hz, 1H), 7.63 (d, J = 16.4 Hz, 1H),
7.55 (t, J = 4.9 Hz, 2H), 7.52 (s, 1H), 7.40 – 7.36 (m, 1H),
7.31 (dd, J = 8.7, 4.6 Hz, 3H), 7.26 (d, J = 5.2 Hz, 1H) ppm.
13C NMR (75 MHz, CDCl3): δ 158.3, 149.7, 135.9, 135.2,
129.1, 128.9, 127.4, 126.4, 125.2, 123.9 ppm. HRMS (ESI)
calcd. for C12H11N2 [M+H]: 183.0922, found: 183.0928.
1
4.2.3 (E)-2-methyl-6-styrylpyrazine (3c)
4.2.8 (E)-2-styrylquinoline (3h)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
the colorless oil 119 mg, 61% yield.
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 217 mg, 94% yield. H NMR (300 MHz,
CDCl3): δ 8.20 – 8.07 (m, 2H), 7.79 (d, J = 8.0 Hz, 1H),
7.69 (ddd, J = 15.4, 6.3, 4.5 Hz, 5H), 7.50 (t, J = 7.5 Hz,
1H), 7.47 – 7.38 (m, 3H), 7.37 – 7.30 (m, 1H) ppm; 13C
NMR (75 MHz, CDCl3): δ 155.9, 148.1, 136.4, 136.3,
134.4, 129.7, 129.1, 128.9, 128.7, 128.6, 127.4, 127.2,
126.1, 119.2 ppm. HRMS (ESI) calcd. for C17H14N [M+H]:
232.1126, found: 232.1133.
1
1H NMR (300 MHz, CDCl3): δ 8.46 (s, 1H), 8.29 (s, 1H),
7.73 (d, J = 16.1 Hz, 1H), 7.59 (d, J = 7.1 Hz, 2H), 7.37 (dt,
J = 13.9, 6.9 Hz, 3H), 7.14 (d, J = 16.1 Hz, 1H), 2.59 (s, 3H)
ppm. 13C NMR (75 MHz, CDCl3): δ 153.3, 150.1, 142.6,
140.5, 136.2, 134.7, 128.8, 127.3, 124.5, 21.8 ppm. HRMS
(ESI) calcd. for C13H13N2 [M+H]: 197.1079, found:
197.1082.
4.2.4 (E)-4-styrylpyridine (3d)
4.2.9 (E)-6-chloro-2-styrylquinoline (3i)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 95 mg, 53% yield. H NMR (300 MHz,
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 217 mg, 82% yield. H NMR (300 MHz,
1
1
CDCl3): δ 8.59 (d, J = 4.4 Hz, 2H), 7.65 – 7.49 (m, 2H),
7.38 (dt, J = 15.3, 6.3 Hz, 5H), 7.34 – 7.26 (m, 2H), 7.03 (d,
J = 16.3 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): δ 150.0,
144.7, 136.1, 133.2, 128.8, 128.7, 127.0, 125.9, 120.8 ppm.
HRMS (ESI) calcd. for C13H12N [M+H]: 182.0970, found:
182.0978.
CDCl3): δ 8.11 – 7.94 (m, 2H), 7.76 (d, J = 2.1 Hz, 1H),
7.71 (d, J = 11.8 Hz, 1H), 7.68 – 7.58 (m, 4H), 7.42 (d, J =
8.2 Hz, 2H), 7.40 – 7.30 (m, 2H) ppm; 13C NMR (75 MHz,
CDCl3): δ 156.1, 146.5, 136.3, 135.4, 134.9, 131.8, 130.6,
128.8, 128.4, 127.8, 127.3, 126.2, 120.2 ppm. HRMS (ESI)
calcd. for C17H13ClN [M+H]: 266.0736, found: 266.0736.
4.2.5 General (E)-2-styrylbenzo[d]oxazole (3e)
4.2.10 (E)-6-methoxy-2-styrylquinoline (3j)
The title compound was prepared according to the
general procedure and purified by column chromatography
to give a white solid, 156 mg, 71% yield. H NMR (300
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 237 mg, 91% yield. H NMR (300 MHz,
1
1
MHz, CDCl3): δ 8.06 (d, J = 8.5 Hz, 1H), 8.01 (d, J = 8.5
Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.69 – 7.62 (m, 1H), 7.57
– 7.48 (m, 2H), 7.44 (dt, J = 8.0, 4.0 Hz, 2H), 7.22 (d, J =
2.1 Hz, 1H), 6.51 (d, J = 2.8 Hz, 1H), 6.43 (dd, J = 3.3, 1.8
Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): δ 162.8, 150.4,
142.2, 139.4, 135.1, 129.7, 128.9, 127.5, 125.2, 124.5,
119.8, 113.9, 110.3 ppm. HRMS (ESI) calcd. for C15H12NO
[M+H]: 222.0919, found: 222.0908.
CDCl3): δ 8.01 (s, 1H), 7.98 (s, 1H), 7.63 (d, J = 5.9 Hz,
2H), 7.62 – 7.58 (m, 2H), 7.43 – 7.37 (m, 3H), 7.36 – 7.26
(m, 2H), 7.04 (d, J = 2.8 Hz, 1H), 3.91 (s, 3H) ppm; 13C
NMR (75 MHz, CDCl3): δ 157.6, 153.6, 144.0, 136.6,
135.1, 133.3, 130.5, 128.8, 128.7, 128.4, 128.2, 127.1,
122.3, 119.5, 105.2, 55.5 ppm. HRMS (ESI) calcd. for
C18H16NO [M+H]: 262.1232, found: 262.1241.
4.2.11 (E)-4-(1,2-diphenylvinyl)pyridine (3k)
4.2.6 (E)-4-styrylquinoline (3f)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a yellow solid 118mg, 46% yield. H NMR (300 MHz,
1
a white solid, 120 mg, 52% yield. H NMR (300 MHz,
DMSO-d6): δ 8.82 (s, 2H), 7.77 (dd, J = 23.0, 11.7 Hz, 6H),
7.52 – 7.28 (m, 7H) ppm; 13C NMR (75 MHz, DMSO-d6):
δ 148.4, 142.5, 135.8, 133.3, 128.2, 128.0, 126.6, 124.3
ppm. HRMS (ESI) calcd. for C19H16N [M+H]: 258.1283,
found: 258.1291.
CDCl3): δ 8.96 (s, 1H), 8.24 (t, J = 8.2 Hz, 2H), 7.88 – 7.74
(m, 2H), 7.71 – 7.57 (m, 4H), 7.44 (dt, J = 26.5, 11.5 Hz,
4H) ppm; 13C NMR (75 MHz, CDCl3): δ 149.9, 148.4,
143.0, 136.4, 135.1, 129.8, 129.3, 128.8, 128.7, 127.0,
126.5, 126.3, 123.4, 122.7, 116.9 ppm. HRMS (ESI) calcd.
for C17H14N [M+H]: 232.1126, found: 232.1128.
4.2.12 (E)-2-(1-phenylprop-1-en-2-yl)pyrazine (3l)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
4.2.7 (E)-1-styrylisoquinoline (3g)

6
Tetrahedron
1
1
the colorless oil 74 mg, 38% yield. H NMR (300 MHz,
CDCl3): δ 8.86 (s, 1H), 8.56 (s, 1H), 8.45 (d, J = 2.1 Hz,
1H), 7.50 (s, 1H), 7.45 – 7.36 (m, 4H), 7.34 – 7.27 (m, 1H),
2.38 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ 143.4,
142.6, 141.9, 137.1, 1321, 129.4, 128.3, 127.4, 15.4 ppm.
HRMS (ESI) calcd. for C13H13N2 [M+H]: 197.1079, found:
197.1075.
a white solid, 189 mg, 73% yield. H NMR (300 MHz,
CDCl3): δ 8.63 (s, 1H), 8.54 (s, 1H), 8.43 (s, 1H), 7.69 (d, J
= 16.1 Hz, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 8.4
Hz, 2H), 7.14 (d, J = 16.1 Hz, 1H) ppm; 13C NMR (75
MHz, CDCl3): δ 144.4, 143.9, 143.0, 135.0, 133.9, 132.0,
128.7, 124.64, 123.0 ppm. HRMS (ESI) calcd. for
C12H10BrN2 [M+H]: 261.0027, found: 261.0032.
4.2.13 2-(1-(naphthalen-1-yl)prop-1-en-2-yl)pyrazine (3m)
(E:Z= 7:1)
4.2.18 (E)-2-(2-(thiophen-2-yl)vinyl)pyrazine (5d)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a yellow solid, 127 mg, 68% yield. H NMR (300 MHz,
1
a yellow solid 89 mg, 36% yield. H NMR (300 MHz,
CDCl3): δ 8.53 (d, J = 17.7 Hz, 2H), 8.38 (s, 1H), 7.88 (d, J
= 15.8 Hz, 1H), 7.30 (d, J = 5.0 Hz, 1H), 7.21 (d, J = 3.0
Hz, 1H), 7.04 (dt, J = 5.0, 3.4 Hz, 1H), 6.94 (d, J = 15.8 Hz,
1H) ppm; 13C NMR (75 MHz, CDCl3): δ 150.8, 144.2,
143.5, 142.5, 141.5, 128.6, 127.9, 127.8, 126.3, 123.0 ppm.
HRMS (ESI) calcd. for C10H9N2S [M+H]: 189.0486, found:
189.0492.
CDCl3): δ = 8.95 (s, 1H), 8.62 (s, 1H), 8.51 (s, 1H), 8.21 (s,
0.19H), 8.09-8.07 (m, 0.35H), 8.03-8.00 (m, 2H), 7.92-7.86
(m, 1H), 7.86-7.83 (m, 1.27H), 7.72-7.69 (m, 0.25H), 7.55-
7.46 (m, 5.05H), 7.32 (s, 0.18H), 7.22-7.21 (2, 0.22H), 6.97
-6.95 (m, 0.15H), 2.45 (s, 0.48H), 2.25 (s, 3H) ppm; 13C
NMR (75 MHz, CDCl3): δ 154.7, 143.6, 142.8, 141.9,
135.5, 134.4, 133.6, 131.9, 130.3, 128.5, 127.9, 126.8,
126.2, 126.0, 125.3, 125.0, 15.6 ppm. HRMS (ESI) calcd.
for C17H15N2 [M+H]: 247.1235, found: 247.1241.
4.2.19 (E)-2-(2-methylstyryl)quinoline (5e)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
the colorless oil, 162 mg, 66% yield.1H NMR (300 MHz,
CDCl3): δ 8.16 (t, J = 8.5 Hz, 2H), 8.00 (d, J = 16.2 Hz,
1H), 7.85 – 7.71 (m, 4H), 7.54 (dd, J = 8.1, 7.0 Hz, 1H),
7.37 (d, J = 16.2 Hz, 1H), 7.33 – 7.29 (m, 1H), 2.57 (s, 3H)
ppm; 13C NMR (75 MHz, CDCl3): δ 156.1, 148.2, 136.5,
136.2, 135.1, 132.0, 130.5, 130.1, 129.6, 129.2, 128.4,
127.4, 127.2, 126.2, 126.1, 125.7, 119.2, 19.9 ppm.HRMS
(ESI) calcd. for C18H16N [M+H]: 246.1283, found:
246.1289.
4.2.14 (E)-2-(hex-2-en-2-yl)pyrazine (3n)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a yellow solid 53 mg, 32% yield. H NMR (300 MHz,
CDCl3): δ 8.64 (s, 1H), 8.45 (s, 1H), 8.33 (s, 1H), 5.90 (d, J
= 10.0 Hz, 1H), 2.23 (s, 3H), 1.81 – 1.69 (m, 1H), 0.96 –
0.89 (m, 2H), 0.59 (dd, J = 5.6, 3.5 Hz, 2H) ppm. 13C NMR
(75 MHz, CDCl3): δ 143.2, 141.6, 141.1, 138.6, 130.4,
129.8, 13.9, 11.7, 7.9 ppm. HRMS (ESI) calcd. for
C10H15N2 [M+H]: 163.1235, found: 163.1241.
4.2.20 (E)-2-(3-methylstyryl)quinoline (5f)
4.2.15 (E)-2-(4-methylstyryl)pyrazine (5a)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 205 mg, 84% yield. H NMR (300 MHz,
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
CDCl3): δ 8.13 (d, J = 8.6 Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H),
7.79 (d, J = 8.1 Hz, 1H), 7.75 – 7.67 (m, 2H), 7.65 (d, J =
7.8 Hz, 1H), 7.47 (dt, J = 28.9, 11.8 Hz, 4H), 7.29 (d, J =
1
a white solid, 174 mg, 89% yield. H NMR (300 MHz,
CDCl3): δ 8.59 (d, J = 31.0 Hz, 2H), 8.40 (s, 1H), 7.73 (d, J
= 16.1 Hz, 1H), 7.50 (d, J = 7.9 Hz, 2H), 7.21 (d, J = 7.8
Hz, 2H), 7.12 (d, J = 16.1 Hz, 1H), 2.39 (s, 3H) ppm; 13C
NMR (75 MHz, CDCl3): δ 151.5, 144.2, 143.7, 142.5,
139.2, 135.2, 133.3, 129.6, 127.3, 123.0, 21.4 ppm. HRMS
(ESI) calcd. for C13H13N2 [M+H]: 197.1079, found:
197.1082.
7.5 Hz, 1H), 7.15 (d, J = 7.4 Hz, 1H), 2.41 (s, 3H) ppm; 13
C
NMR (75 MHz, CDCl3): δ 156.1, 148.3, 138.4, 136.5,
136.3, 134.5, 129.7, 129.5, 129.2, 128.9, 128.7, 123.0,
127.5, 126.1, 124.5, 119.2, 21.5 ppm. HRMS (ESI) calcd.
for C18H16N [M+H]: 246.1283, found: 246.1291.
4.2.21 (E)-2-(4-methylstyryl)quinolines (5g)
4.2.16 (E)-2-(4-chlorostyryl)pyrazine (5b)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 227 mg, 93% yield.1H NMR (300 MHz,
CDCl3): δ 8.12 (d, J = 8.6 Hz, 1H), 8.07 (d, J = 8.5 Hz, 1H),
7.78 (d, J = 8.1 Hz, 1H), 7.70 (dt, J = 5.3, 4.7 Hz, 2H), 7.65
(d, J = 5.0 Hz, 1H), 7.55 (d, J = 8.0 Hz, 2H), 7.49 (dd, J =
8.0, 7.0 Hz, 1H), 7.37 (d, J = 16.3 Hz, 1H), 7.22 (d, J = 8.0
Hz, 2H), 2.39 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ
156.1, 148.2, 138.7, 136.2, 134.3, 133.7, 129.6, 129.5,
129.1, 128.0, 127.4, 127.2, 127.2, 126.0, 119.1, 21.3 ppm.
HRMS (ESI) calcd. for C18H16N [M+H]: 246.1283, found:
246.1285.
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 174 mg, 81% yield. H NMR (300 MHz,
CDCl3): δ 8.63 (s, 1H), 8.54 (s, 1H), 8.43 (s, 1H), 7.69 (d, J
= 16.1 Hz, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 8.4
Hz, 2H), 7.14 (d, J = 16.1 Hz, 1H) ppm; 13C NMR (75
MHz, CDCl3): δ 150.8, 144.3, 143.7, 142.9, 134.6, 134.4,
133.7, 128.9, 128.4, 124.4 ppm. HRMS (ESI) calcd. for
C12H10ClN2 [M+H]: 217.0532, found: 217.0541.
1
4.2.17 (E)-2-(4-bromostyryl)pyrazine (5c)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
4.2.22 (E)-2-(2,4,6-trimethylstyryl)quinoline(5h)

Tetrahedron
7
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 175mg, 64% yield.
3H) ppm; 13C NMR (75 MHz, CDCl3): δ 160.1, 156.3,
148.3, 136.2, 134.0, 129.7, 129.3, 129.1, 128.7, 127.5,
127.2, 126.9, 125.9, 119.2, 114.3, 55.4 ppm. HRMS (ESI)
calcd. for C18H16NO [M+H]: 262.1232, found: 262.1238.
1H NMR (300 MHz, CDCl3): δ 8.12 (dd, J = 12.2, 8.6 Hz,
2H), 7.83 – 7.66 (m, 4H), 7.50 (dd, J = 8.1, 6.9 Hz, 1H),
6.94 (dd, J = 11.1, 5.5 Hz, 3H), 2.44 (s, 6H), 2.32 (s, 3H)
ppm; 13C NMR (75 MHz, CDCl3): δ 156.3, 148.3, 137.0,
136.5, 136.5, 136.3, 134.1, 133.1, 132.9, 129.7, 129.3,
129.0, 127.5, 127.4, 126.1, 119.0, 21.3, 21.1 ppm. HRMS
(ESI) calcd. for C20H20N [M+H]: 274.1596, found:
274.1599.
4.2.27 (E)-2-(2-chlorostyryl)quinolines (5m)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
the colorless oil, 151 mg, 57% yield. H NMR (300 MHz,
CDCl3): δ 8.13 (dd, J = 25.6, 12.7 Hz, 2H), 7.93 – 7.68 (m,
3H), 7.57 – 7.41 (m, 2H), 7.35 – 7.28 (m, 1H) ppm; 13C
NMR (75 MHz, CDCl3): δ 155.7, 148.1, 136.3, 134.5,
134.0, 131.7, 130.1, 129.9, 129.7, 129.4, 129.2, 127.4,
127.4, 127.0, 126.9, 126.33, 118.9 ppm. HRMS (ESI) calcd.
for C17H13ClN [M+H]: 266.0736, found: 266.0742.
4.2.23 (E)-2-(4-(tert-butyl)styryl)quinoline (5i)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a white solid, 261mg, 91% yield. H NMR (300 MHz,
4.2.28 (E)-2-(4-chlorostyryl)quinolines (5n)
CDCl3): δ 8.12 (d, J = 8.6 Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H),
7.79 (d, J = 8.0 Hz, 1H), 7.69 (dd, J = 17.2, 8.8 Hz, 3H),
7.59 (d, J = 8.3 Hz, 2H), 7.49 (dd, J = 7.9, 7.0 Hz, 1H),
7.46 – 7.34 (m, 3H), 1.35 (s, 9H) ppm; 13C NMR (75 MHz,
CDCl3): δ 156.3, 152.0, 148.3, 136.3, 134.3, 133.8, 129.7,
129.2, 128.3, 127.5, 127.3, 127.1, 126.1, 125.8, 119.2, 34.8,
31.3 ppm. HRMS (ESI) calcd. for C21H22N [M+H]:
288.1752, found: 288.1763.
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a white solid, 222 mg, 84% yield. H NMR (300 MHz,
CDCl3): δ 8.14 (d, J = 8.5 Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H),
7.79 (d, J = 8.1 Hz, 1H), 7.75 – 7.62 (m, 3H), 7.60 – 7.48
(m, 3H), 7.37 (dd, J = 12.1, 3.7 Hz, 3H) ppm; 13C NMR (75
MHz, CDCl3): δ 155.5, 148.2, 136.3, 135.0, 134.2, 132.9,
129.8, 129.4, 129.2, 128.9, 128.3, 127.5, 127.3, 126.2,
119.3 ppm. HRMS (ESI) calcd. for C17H13ClN [M+H]:
266.0736, found: 266.0739.
4.2.24 (E)-2-(2-([1,1'-biphenyl]-4-yl)vinyl)quinoline (5j)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
4.2.29 (E)-2-(4-bromostyryl)quinolines (5o)
1
a white solid, 254 mg, 83% yield. H NMR (300 MHz,
CDCl3): δ 8.15 (d, J = 8.5 Hz, 1H), 8.10 (d, J = 8.5 Hz, 1H),
7.80 (d, J = 8.1 Hz, 1H), 7.78 – 7.71 (m, 4H), 7.70 – 7.59
(m, 5H), 7.54 – 7.48 (m, 2H), 7.45 (d, J = 7.2 Hz, 2H), 7.37
(dd, J = 11.2, 4.6 Hz, 1H) ppm; 13C NMR (75 MHz,
CDCl3): δ 155.9, 148.2, 141.3, 140.4, 136.3, 135.5, 133.9,
129.7, 129.1, 128.9, 128.8, 127.7, 127.5, 127.4, 127.3,
126.9, 126.1, 119.3 ppm. HRMS (ESI) calcd. for C23H18N
[M+H]: 308.1439, found: 308.1442.
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 204 mg, 66% yield. H NMR (300 MHz,
1
CDCl3): δ 8.14 (d, J = 8.6 Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H),
7.79 (d, J = 8.1 Hz, 1H), 7.71 (dd, J = 8.4, 7.0 Hz, 1H),
7.66 (d, J = 1.3 Hz, 1H), 7.62 (d, J = 5.8 Hz, 1H), 7.55 –
7.48 (m, 5H), 7.38 (d, J = 16.3 Hz, 1H) ppm; 13C NMR (75
MHz, CDCl3): δ 155.5, 148.1, 136.5, 135.4, 133.1, 131.9,
129.8, 129.5, 129.1, 128.6, 127.5, 127.4, 126.3, 122.5,
119.3 ppm. HRMS (ESI) calcd. for C17H13BrN [M+H]:
310.0231, found: 310.0242.
4.2.25 (E)-2-(2-methoxystyryl)quinoline (5k)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
the colorless oil, 185 mg, 71% yield. H NMR (300 MHz,
4.2.30 (E)-2-(4-iodostyryl)quinolines (5p)
1
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 171 mg, 48% yield.1H NMR (300 MHz,
CDCl3): δ 8.14 (d, J = 8.5 Hz, 1H), 8.08 (d, J = 8.9 Hz, 1H),
7.79 (d, J = 8.1 Hz, 1H), 7.72 (t, J = 8.4 Hz, 3H), 7.63 (dd,
J = 12.4, 7.3 Hz, 2H), 7.51 (t, J = 7.5 Hz, 1H), 7.43 – 7.35
(m, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ 155.5, 148.2,
137.9, 136.4, 136.0, 133.1, 129.8, 129.7, 129.2, 128.8,
127.5, 127.4, 126.3, 119.4, 94.2 ppm. HRMS (ESI) calcd.
for C17H13IN [M+H]: 358.0093, found: 358.0098.
CDCl3): δ 8.10 (t, J = 8.0 Hz, 2H), 8.03 (d, J = 16.6 Hz,
1H), 7.79 – 7.66 (m, 4H), 7.52 – 7.41 (m, 2H), 7.36 – 7.27
(m, 1H), 7.01 (t, J = 7.5 Hz, 1H), 6.94 (d, J = 8.3 Hz, 1H),
3.93 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ 157.4,
156.7, 148.2, 136.1, 129.7, 129.6, 129.3, 129.2, 127.4,
127.2, 127.2, 126.0, 125.5, 120.8, 119.0, 111.0, 55.5 ppm.
HRMS (ESI) calcd. for C18H16NO [M+H]: 262.1232, found:
262.1241.
4.2.26 (E)-2-(4-methoxystyryl)quinoline (5l)
4.2.31 (E)-2-(2-(naphthalen-1-yl)vinyl)quinolines (5q)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 240 mg, 92% yield. H NMR (300 MHz,
CDCl3): δ 8.14 (d, J = 8.5 Hz, 1H), 8.09 (d, J = 8.5 Hz, 1H),
7.81 (d, J = 8.1 Hz, 1H), 7.77 – 7.69 (m, 2H), 7.64 (dd, J =
11.4, 6.7 Hz, 3H), 7.51 (t, J = 7.4 Hz, 1H), 7.34 (s, 1H),
7.29 (d, J = 1.7 Hz, 2H), 6.97 (d, J = 7.3 Hz, 2H), 3.88 (s,
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
1
a white solid, 217 mg, 77% yield. H NMR (300 MHz,
CDCl3): δ 8.54 (d, J = 16.0 Hz, 1H), 8.36 (d, J = 8.2 Hz,
1H), 8.16 (t, J = 8.8 Hz, 2H), 7.97 – 7.84 (m, 3H), 7.81 (d,
J = 8.1 Hz, 1H), 7.78 – 7.68 (m, 2H), 7.62 – 7.53 (m, 3H),

8
Tetrahedron
7.53 – 7.45 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3): δ
156.0, 148.3, 136.5, 136.4, 134.0, 133.7, 133.7, 131.8,
131.7, 131.5, 131.3, 129.7, 129.3, 128.9, 128.6, 127.6,
127.5, 127.4, 126.4, 126.3, 126.2, 125.9, 125.7, 124.2,
123.7, 119.5, 117.4 ppm. HRMS (ESI) calcd. for C21H16N
[M+H]: 282.1283, found: 282.1283.
procedure and purified by column chromatography to give
the colorless oil, 109 mg, 56% yield. H NMR (300 MHz,
1
CDCl3): δ 7.92 (dd, J = 8.6, 2.7 Hz, 2H), 7.63 (d, J = 8.1
Hz, 1H), 7.56 (ddd, J = 8.3, 7.0, 1.3 Hz, 1H), 7.44 – 7.25
(m, 2H), 6.69 (d, J = 15.7 Hz, 1H), 6.30 (dd, J = 15.7, 9.3
Hz, 1H), 1.76 – 1.48 (m, 1H), 0.88 – 0.80 (m, 2H), 0.61 –
0.48 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3): δ 156.1,
148.1, 142.0, 136.0, 129.4, 128.9, 128.2, 127.3, 126.9,
125.6, 118.8 , 14.9, 8.0 ppm. HRMS (ESI) calcd. for
C14H14N [M+H]: 196.1126, found: 196.1126.
4.2.32 (E)-2-(2-(furan-2-yl)vinyl)quinolines (5r)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a yellow solid, 128 mg, 58% yield. H NMR (300 MHz,
4.2.37 (E)-2-(2-cyclohexylvinyl)quinolines (5w)
CDCl3): δ 7.80 (d, J = 16.4 Hz, 1H), 7.76 – 7.68 (m, 1H),
7.63 – 7.59 (m, 2H), 7.54 (dd, J = 5.0, 4.2 Hz, 1H), 7.48 –
7.37 (m, 3H), 7.34 (dd, J = 6.2, 3.3 Hz, 2H), 7.09 (d, J =
15.7 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3): δ 155.6,
152.8, 148.3, 143.1, 136.3, 129.7, 129.2, 127.5, 127.3,
126.8, 126.0, 121.7, 119.9, 111.9, 111.1 ppm. HRMS (ESI)
calcd. for C15H12NO [M+H]: 222.0919, found: 222.0921.
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
the colorless oil, 161 mg, 68% yield. H NMR (300 MHz,
CDCl3): δ 8.03 (d, J = 8.5 Hz, 2H), 7.73 (d, J = 8.1 Hz, 1H),
7.66 (t, J = 7.7 Hz, 1H), 7.51 (d, J = 8.5 Hz, 1H), 7.45 (dd,
J = 11.4, 4.3 Hz, 1H), 6.78 (dd, J = 16.1, 6.2 Hz, 1H), 6.67
(d, J = 16.1 Hz, 1H), 2.24 (s, 1H), 1.92 – 1.69 (m, 5H), 1.40
– 1.19 (m, 5H) ppm; 13C NMR (75 MHz, CDCl3): δ 156.7,
148.0, 143.3, 136.0, 129.4, 129.0, 128.6, 127.3, 127.0,
125.7, 118.6, 41.1, 32.5, 26.1, 25.9 ppm. HRMS (ESI)
calcd. for C17H20N [M+H]: 238.1596, found: 238.1596.
4.2.33 (E)-2-(2-(thiophen-2-yl)vinyl)quinolines (5s)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a yellow solid, 175 mg, 74% yield. H NMR (300 MHz,
CDCl3): δ 7.92 (dd, J = 14.8, 8.5 Hz, 2H), 7.69 (d, J = 16.1
Hz, 1H), 7.61 – 7.51 (m, 2H), 7.37 (d, J = 8.5 Hz, 1H), 7.33
(dt, J = 8.0, 3.9 Hz, 1H), 7.13 (d, J = 5.1 Hz, 1H), 7.07 (dd,
J = 9.8, 6.2 Hz, 2H), 6.96 – 6.86 (m, 1H) ppm; 13C NMR
(75 MHz, CDCl3): δ 155.4, 148.1, 141.9, 136.1, 129.6,
129.0, 128.1, 128.0, 127.7, 127.4, 127.1, 125.9, 125.9,
119.2 ppm. HRMS (ESI) calcd. for C15H12NS [M+H]:
238.0690, found: 238.0687.
4.2.37 (E)-2-(2-(pyridin-2-yl)vinyl)quinolines (5x)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 121 mg, 52% yield.1H NMR (300 MHz,
CDCl3): δ 8.68 – 8.51 (m, 1H), 8.11 (t, J = 8.5 Hz, 2H),
7.81 (dd, J = 4.0, 2.3 Hz, 2H), 7.74 (d, J = 8.1 Hz, 1H),
7.66 (ddd, J = 13.0, 8.1, 5.0 Hz, 3H), 7.54 (d, J = 6.9 Hz,
1H), 7.47 (t, J = 7.5 Hz, 1H), 7.16 (dd, J = 7.0, 3.8 Hz, 1H)
ppm; 13C NMR (75 MHz, CDCl3): δ 155.1, 154.9, 149.7,
136.8, 136.7, 134.0, 132.1, 130.0, 129.0, 127.5, 126.6,
122.9, 122.8, 120.3, 109.9 ppm. HRMS (ESI) calcd. for
C16H13N2 [M+H]: 233.1079, found: 233.1079.
4.2.34 (E)-2-(3-ethylpent-1-en-1-yl)quinolines (5t)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
the colorless oil, 139 mg, 53% yield.1H NMR (300 MHz,
CDCl3): δ 8.04 (dd, J = 8.5, 5.4 Hz, 2H), 7.74 (d, J = 8.1
Hz, 1H), 7.66 (dd, J = 8.4, 7.0 Hz, 1H), 7.56 (d, J = 8.6 Hz,
1H), 7.45 (dd, J = 8.1, 6.9 Hz, 1H), 6.70 (d, J = 16.0 Hz,
1H), 6.55 (dd, J = 16.0, 8.6 Hz, 1H), 2.09 (ddt, J = 13.4, 8.8,
4.4 Hz, 1H), 1.49 (ddt, J = 21.0, 13.6, 6.8 Hz, 4H), 0.92 (t,
J = 7.4 Hz, 6H) ppm; 13C NMR (75 MHz, CDCl3): δ 156.5,
148.0, 141.8, 136.0, 131.3, 129.4, 129.1, 127.4, 127.1 125.8,
118.5, 46.8, 27.5, 11.9 ppm. HRMS (ESI) calcd. for
C16H20N [M+H]: 263.1310, found: 263.1310.
4.2.38 (E)-2-(4,8-dimethylnona-1,7-dien-1-yl)quinolines
(5y)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
the colorless oil, 184 mg, 66% yield. H NMR (300 MHz,
CDCl3): δ 7.97 (t, J = 8.5 Hz, 2H), 7.67 (d, J = 8.1 Hz, 1H),
7.59 (t, J = 7.7 Hz, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.38 (t, J
= 7.5 Hz, 1H), 6.71 (dt, J = 30.0, 11.4 Hz, 2H), 5.04 (t, J =
6.3 Hz, 1H), 2.39 – 2.19 (m, 1H), 2.10 (dt, J = 14.3, 7.1 Hz,
1H), 1.96 (dt, J = 15.6, 7.6 Hz, 2H), 1.61 (s, 3H), 1.54 (s,
3H), 1.37 (ddd, J = 9.1, 6.4, 3.2 Hz, 1H), 1.23 – 1.13 (m,
1H), 0.90 (d, J = 6.7 Hz, 3H) ppm; 13C NMR (75 MHz,
CDCl3): δ 156.3, 136.2, 132.1, 131.2, 129.5, 129.0, 127.4,
127.1, 125.8, 124.6, 118.6, 40.6, 36.8, 32.7, 25.7, 25.6, 19.6,
17.7 ppm. HRMS (ESI) calcd. for C20H26N [M+H]:
280.2065, found: 280.2071.
4.2.35 (E)-2-(3,3-dimethylbut-1-en-1-yl)quinolines (5u)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
the colorless oil, 128 mg, 61% yield. H NMR (300 MHz,
CDCl3): δ 7.95 (d, J = 8.5 Hz, 2H), 7.64 (d, J = 8.1 Hz, 1H),
7.57 (t, J = 7.7 Hz, 1H), 7.46 (d, J = 8.7 Hz, 1H), 7.36 (t, J
= 7.5 Hz, 1H), 6.74 (d, J = 16.2 Hz, 1H), 6.57 (d, J = 16.3
Hz, 1H), 1.11 (s, 10H) ppm; 13C NMR (75 MHz, CDCl3): δ
156.8, 148.1, 148.0, 136.0, 129.4, 129.0, 127.3, 127.0,
126.4, 125.7, 118.5, 33.8, 29.4 ppm. HRMS (ESI) calcd.
for C15H18N [M+H]: 212.1439, found: 212.1442.
4.2.39 (E)-2,6-di((E)-styryl)pyrazine (7a)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a yellow solid 150 mg, 53% yield.1H NMR (300 MHz,
DMSO-d6): δ 8.76 (s, 2H), 7.79 (s, 1H), 7.73 (s, 1H), 7.69
(d, J = 7.4 Hz, 4H), 7.43 (d, J = 6.4 Hz, 4H), 7.39 (s, 2H),
4.2.36 (E)-2-(2-cyclopropylvinyl)quinolines (5v)
The title compound was prepared according to the general

Tetrahedron
9
7.35 (d, J = 7.3 Hz, 2H) ppm; 13C NMR (75 MHz, DMSO-
S. Kanyiva, T. Hiyama, J. Am. Chem. Soc. 2008, 130, 2448; (
j) M.
Tobisu, I. Hyodo, N. Chatani, J. Am. Chem. Soc. 2009, 131, 12070;
) J. Wu, X. Cui, L. Chen, G. Jiang, Y. Wu, J. Am. Chem. Soc.
2009, 131, 13888; ( ) M. Kim, J. Kwak, S. Chang, Angew. Chem.,
Int. Ed. 2009, 48, 8935; ( ) J. J. Mousseau, J. A. Bull, A. B.
Charette, Angew. Chem., Int. Ed. 2010, 49, 1115; ( ) Fukumoto, M.
Hirano, N. Matsubara, N. Chatani, J. Org. Chem. 2017, 82, 13649;
) T.-Y. Feng, H.-X. Li, D. J. Young, J.-P. Lang, J. Org. Chem.
2017, 82, 4113; ( ) F, Xiao, C. Liu, S. Yuan, H. Huang, G.-J.
Deng, J. Org. Chem. 2018, 83, 10420; ( ) S.-S. Li, L. Zhou, L.
Wang, H. Zhao, L. Yu, J. Xiao, Org. Lett. 2018, 20, 138.
3 For selected examples of Witting reaction, see: ( ) G. Wittig, G.
Geissler, Justus Liebigs Ann. Chem. 1953, 580, 44; ( ) B. E.
Maryanoff, A. B. Reitz, Chem. Rev. 1989, 89, 863; ( ) Q.-Q. Li, Z.
Shah, J.-P. Qu, Y.-B. Kang, J. Org. Chem. 2018, 83. 296; ( ) C.
Schultze, B. Schmidt, J. Org. Chem. 2018, 83, 5210. For selected
examples of Horner–Wadsworth–Emmons reaction, see: ( ) L.
Horner, H. Hoffmann, H. G. Wippel, G. Klahre, Chem. Ber. 1959,
92, 2499; ( ) W. S. Wadsworth, W. D. Emmons, J. Am. Chem. Soc.
1961, 83, 1733; ( ) J. Clayden, S. Warren, Angew. Chem. Int. Ed.
1996, 35, 241. For selected examples of Peterson olefination, see:
) D. J. Peterson, J. Org. Chem. 1968, 33, 780-784; ( ) L. F. v.
Staden, D. Gravestock, D. J. Ager, Chem. Soc. Rev. 2002, 31, 195;
) M. C. Fernández, A. Díaz, J. J. Guillín, O. Blanco, M. Ruiz, V.
Ojea, J. Org. Chem., 2006, 71, 6958; ( ) R. E. Beveridge, R. A.
Batey, Org. Lett., 2013, 15, 3086. For selected examples of Julia
olefination, see: ( ) M. Julia, J.-M. Paris, Tetrahedron Lett. 1973,
14, 4833; ( ) S. Banerjee, S. Sinha, P. Pradhan, A. Caruso, D.
Liebowitz, D. Parrish, M. Rossi, B. Zajc, J. Org. Chem., 2016, 81
d6): δ 149.3, 141.4, 135.5, 133.9, 128.4, 126.8, 124.1, 109.0
ppm. HRMS (ESI) calcd. for C20H17N2 [M+H]: 285.1392,
found: 285.1387.
(
k
l
m
n
4.2.40 (E)-2,5-di((E)-styryl)pyrazine (7b)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a yellow solid 116 mg, 41% yield.1H NMR (300 MHz,
DMSO-d6): δ 8.61 (s, 2H), 7.84 (d, J = 16.2 Hz, 2H), 7.69
(d, J = 7.8 Hz, 4H), 7.40 (t, J = 7.5 Hz, 5H), 7.35 – 7.25 (m,
3H) ppm; 13C NMR (75 MHz, DMSO-d6): δ 147.9, 142.3,
135.4, 133.0, 127.9, 126.3, 123.8 ppm. HRMS (ESI) calcd.
for C20H17N2 [M+H]: 285.1392, found: 285.1390.
(o
p
q
a
b
c
d
e
Notes
The authors declare no competing financial interest.
f
g
Acknowledgments
(h
i
This research was supported by the Shandong Provincial
Natural Science Foundation of China (Nos. ZR2017MB029,
ZR2017BB060), the Qingdao Science and Technology
Foundation (18-2-2-49-jch), the Qingdao University of
Science and Technology Talent Startup Fund Foundation
(QUSTHX201921) for financial support.
(j
k
l
m
,
,
Supplementary Material
3983; (n) A. K. Simlandy, S. Mukherjee, J. Org. Chem., 2017, 82
Supplementary data associated with this article can be found,
in the online version, at
4851.
4
For selected examples of Heck coupling reaction, see: (
Heck, J. P. Nolley, J. Org. Chem. 1972 37, 2320; ( ) M. J. D.
Pires, D. L. Poeira, S. I. Purificação, M. M. B. Marques, Org. Lett.
2016, 18, 3250; ( ) J. A. Carmona, V. Hornillos, P. Ramírez-
a) R. F.
,
b
References
c
1
(
a
) S. Matar, L. F. Hatch, in Chemistry of Petrochemical Processes
Gulf Professional Publishing, Woburn, 2001; ( ) Henry, G. D.
Tetrahedron 2004, 60, 6043; ( ) Michael, J. P. Nat. Prod. Rep.
2005, 22, 627; ( ) T. Laird, Org. Process Res. Dev. 2006, 10, 851;
) L.-C. Campeau, K. Fagnou, Chem. Soc. Rev. 2007, 36, 1058; (
,
López, A. Ros, J. Iglesias-Sigüenza, E. Gómez-Bengoa, R.
Fernández, J. M. Lassaletta, J. Am. Chem. Soc. 2018, 140, 11067.
b
c
For selected examples of Suzuki coupling reaction, see: (
Ferré-Filmon, L. Delaude, A. Demonceau, A. F. Noels, Coord.
Chem. Rev. 2004 248, 2323; ( ) J. P. G. Rygus and C. M.
Crudden, J. Am. Chem. Soc. 2017, 139, 18124; ( ) P. Guo, H.
Zhang, J. Zhou, F. Gallou, M. Parmentier, H. Wang, J. Org. Chem.
2018, 83, 7523; ( ) D. M. Knoll, S. Bräse, ACS Omega, 2018,
12158; ( ) S. H. Nazari, J. E. Bourdeau, M. R. Talley, G. A.
Valdivia-Berroeta, S. J. Smith, D. J. Michaelis, ACS Catalysis
2018, , 86.
) T. M. Trnka, R. H. Grubbs, Acc. Chem. Res. 2001, 34, 18; (
d) K.
d
(
e
f)
,
g
M. C. Bagley, C. Glover, E. A. Merritt, Synlett 2007, 2459; (
Wang, Y.-T. Chang, Chem. Commun. 2008, 1173; (
Lim, Y. Lee, J. M. Kang, H. Kim, S. Jang, S. Oh, M. Jung, Eur. J.
Med. Chem. 2009, 44, 3166; ( ) D. Simoni, M. Roberti, F. P.
g
) S.
h
h
) J. C. Jung, E.
i
3,
i
j
Invidiata, E. Aiello, S. Aiello, P. Marchetti, R. Baruchello, M.
Eleopra, A. Di Cristina, S. Grimaudo, N. Gebbia, L. Crosta, F.
,
8
Dieli, M. Tolomeo, Bioorg. Med. Chem. Lett. 2006, 16, 3245; (
N.-Y. Kang, H.-H. Ha, S.-W. Yun, Y. H. Yu, Y.-T. Chang, Chem.
Soc. Rev. 2011, 40, 3613; ( ) Q. Li, J.-S. Lee, C. Ha, C. B. Park, G.
Yang, W. B. Gan, Y.-T. Chang, Angew. Chem. Int. Ed. 2004, 43
6331; ( ) R. Fanelli, É. Besserer-Offroy, A. René, J. Côté, P.
Tétreault, J. Collerette-Tremblay, J.-M. Longpré, R. Leduc, J.
Martinez, P. Sarret, F. Cavelier, J. Med. Chem. 2015, 58, 7785; (
S. Jiang, G. Duan, U. Kuhn, M. Mörl, V. Altstädt, A. L. Yarin, A.
Greiner, Angew. Chem. Int. Ed. 2017, 56, 3285; ( ) S. Jiang, S.
Agarwal, A. Greiner, Angew. Chem. Int. Ed. 2017, 56, 15520.
For selected examples, see: ( ) M. Murakami, S. Hori, J. Am.
Chem. Soc. 2003, 125, 4720; ( ) R. Dumeunier, I. E. Markó in
Modern Carbonyl Olefination: Methods and Applications (Ed.: T.
Takeda), Wiley-VCH, Weinheim, 2004; ( ) L.-C. Campeau, S.
Rousseaux, K. Fagnou, J. Am. Chem. Soc. 2005, 127, 18020; (
J.-P. Leclerc, K. Fagnou, Angew. Chem., Int. Ed. 2006, 45, 7781;
) K. S. Kanyiva, Y. Nakao, T. Hiyama, Angew. Chem., Int. Ed.
2007, 46, 8872; ( ) L.-C. Campeau, M. Bertrand-Laperle, J.-P.
Leclerc, E. Villemure, S. Gorelsky, K. Fagnou, J. Am. Chem. Soc.
2008, 130, 3266; ( ) L.-C. Campeau, D. J. Shipper, K. Fagnou, J.
Am. Chem. Soc. 2008, 130, 3276; ( ) A. Larivée, J. J. Mousseau,
A. B. Charette, J. Am. Chem. Soc. 2008, 130, 52; ( ) Y. Nakao, K.
j)
5
6
(a
b
)
R. H. Grubbs, Handbook of Metathesis, WileyVCH, Weinheim,
2003
) C. Gunanathan, D. Milstein, Science 2013, 341, 1229712. (
H. Crabtree, Chem. Rev. 2015, 115, 127. ( ) D. Deng, B. Hu, M.
Yang and D. Chen, Organometallics. 2018, 37, 2386; ( ) P. J.
k
.
,
(a
b) R.
l
c
d
m
)
Llabres-Campaner, R. Ballesteros-Garrido, R. Ballesteros and B.
Abarca, J. Org. Chem. 2018, 83, 521.
n
7
(a
) C. O. Tuck, E. Perez, I. T. Horvath, R. A. Sheldon, M. Poliakoff,
Science 2012, 337, 695; ( ) T. P. Vispute, H. Zhang, A. Sanna, R.
Xiao, G. W. Huber, Science 2010, 330, 1222; ( ) S. Michlik, R.
Kempe, Nature Chemistry 2013, , 140; ( ) F. Kallmeier, R.
Kempe, Angew. Chem. Int. Ed. 2018, 57, 46.
b
2
a
b
c
5
d
c
8
9
G. Zhang, T. Irrgang, T. Dietel, F. Kallmeier, R. Kempe, Angew.
Chem. Int. Ed. 2018, 57, 9131.
d
)
M. K. Barman, S. Waiba, B. Maji, Angew. Chem. Int. Ed. 2018, 57
,
(e
9126.
f
10 (a) B. Blank, R. Kempe, J. Am. Chem. Soc. 2010, 132, 924. (b) F.
Kallmeier, T. Irrgang, T. Dietel, R. Kempe, Angew. Chem. Int. Ed.
2016, 55, 11806; (c) F. Kallmeier, B. Dudziec, T. Irrgang, R. Kempe,
Angew. Chem. Int. Ed. 2017, 56, 7261; (d) N. Deibl, R. Kempe,
g
h
i

10
Tetrahedron
Angew. Chem. Int. Ed. 2017, 56, 1663; (e) C. Zhang, G. Zhang, S.
Luo, C. Wang, H. Li, Org. Biomol. Chem., 2018, 16, 8467.

Tetrahedron
1
Pergamon
MnO2 Mediated Sequential Oxidation/Olefination of Alkyl-
Substituted Heteroarenes with Alcohols
+
+
Chunyan Zhang,a, Zehua Li,a, Yanchen Fang,a Shaohua Jiang,b Maorong Wang,c and Guoying Zhang*a,b
a Key Laboratory of Sensor Analysis of Tumor Marker, Ministry of Education; Shandong Key Laboratory of Biochemical Analysis; Key
Laboratory of Analytical Chemistry for Life Science in Universities of Shandong; College of Chemistry and Molecular Engineering.
Qingdao University of Science and Technology, Qingdao 266042, PR China
b College of Materials Science and Engineering, Nanjing Forestry University, Nanjing 210037, P. R. China
c State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, 308 Ningxia Road, Qingdao 266071, P. R. China
+These authors contributed equally to this work.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A practical and efficient ligand-free MnO2 mediated sequential oxidation and olefination has
been developed for the facile synthesis of a broad range of unsaturated N-heteroazaarenes from
simple alkyl-substituted heteroarenes and alcohols. The procedure tolerates a series of
functional groups, such as methoxyl, chloro, bromo, iodo, vinyl, phenolic and hetero groups,
providing the olefination products in moderate to good yields.The protocol could be conducted
at mild conditions and used environmentally friendly air as the clear oxidant.
Available online
Keywords:
Manganese dioxide
Olefination
Alcohol
Heteroarenes
1. Introduction
An attractive approach to circumvent these problems is
abundantly available metal catalyzed acceptorless
As one of the most important fundamental structural motifs,
unsaturated N-heteroaromatic compounds has been considered as
a privileged structure in natural products, pharmaceuticals and
functional materials (Figure 1).1 As such, the development of
efficient methods toward these complex molecules is of great
significance to chemical, medicinal and material science and has
attracted a great deal of attention over the past decades.2 Plenty of
powerful synthetic routes, including many named reactions,3
catalytic coupling4 or olefin metathesis,5 have been developed to
access such kinds of molecules. However, multi-step functional
group manipulations and unavoidable generation of stoichiometric
amount of undesired waste are the few shortcomings in these
reactions.
dehydrogenative condensation (ADC),6 which enables the
synthesis of di-substituted alkenes compounds from alcohols
combination of catalytic dehydrogenation and condensation steps.
Moreover, alcohols can be obtained from indigestible and
abundantly available lignocellulose biomass.7 Kempe8 and Maji
group9 pioneered a novel manganese-catalyzed reaction leading to
di-substituted olefins synthesis using alcohols with N-heteroarenes
at the same time, the reaction proceeds via ADC process,
Figure 1. Selected bioactive compounds with unsaturated N-heteroarene
moiety.
Scheme 1. Methods for Mn-catalyzed olefination.

2
Tetrahedron
producing only water and hydrogen as green coproducts (Scheme
1, top). However, metal complexes or addition of capricious
ligands for catalyst activation are generally required to maintain
the catalytic cycle, thereby limiting the potential scope of this
environmentally benign transformation. These results together
with our progress on the use of alcohols as green partners for
metal catalyzed coupling reactions,10 prompted us to envision that
alcohols might be oxidized in MnO2/air catalytic system and
condensed with methylazaarenes for the synthesis of di-
substituted olefins. Moreover, to the best of our knowledge, MnO2
catalyzed oxidation/olefination of alcohols and methylazaarenes
to synthesis unsaturated N-heteroaromatic has not been reported.
Herein, we present on the first protocol for successful
implementation of the MnO2 catalyzed oxidation of alcohols with
a variety of alkyl-substituted azaarenes via olefination process,
which allows for synthesis of various multiple-substituted alkenes
under mild condition.
styrylpyrazine (3a) was obtained in 12% yield, when the reaction
was conducted in the presence of Cs2CO3 under an air atomsphere
(Table 1, entry 1). This result indicated that our proposed sequential
oxidation/olefination reactions of methylazaarene with alcohol was
indeed possible. Base screening indicated that when the reaction
was ran in presence of KOH, the desired product was obtained best
yield and the high regioselective (Table 1, entry 5). The reaction
still worked even under oxygen atmosphere (oxygen balloon) and
3a was obtained in good yield. Other inorganic bases or organic
bases, did not improve the reactivity (Table 1, entries 2-9). Further
investigation of the solvents revealed that the reactivity was affected
by the nature of the solvents, and the best result was achieved with
t-AmOH as the solvent. Meanwhile, reaction in other alcohol
solvents, such as t-BuOH, i-PrOH and EtOH resulted in lower yield
or no reaction (Table 1, entries 10-12). This reactivity trend(t-
AmOH > t-BuOH > i-PrOH > EtOH) is that sterically hindered
alcohols suppress the competing aldol reaction with benzaldehyde
intermediate, revealing that the mechanism may via aldehyde
species. No appreciable increase in yield of olefination product was
obtained in ether solvents or non-polar solvent. Finally, control
reactions demonstrated that the low yield of 3a was obtained under
nitrogen atmosphere or in the absence of catalyst or base (Table 1,
entries 16-18).
2. Results and discussion
As an initial attempt, the reaction between phenylmethanol (1a)
and 2-methylpyrazine (2a) was chosen as the model reaction for
optimization of the reaction conditions (Table 1).
Table 1. Optimization of the reaction conditions a
Table 2. Substrate scope of N-heteroaromatics a
Entry
1
Base
Solvent
3a (%)
12
3a/4a
> 20:1
-
Cs2CO3
K2CO3
Na2CO3
CsOH
KOH
t-AmOH
t-AmOH
t-AmOH
t-AmOH
t-AmOH
2
< 5
< 5
83
-
3
19:1
> 20:1
17:1
-
4
5
96 (72)b
6
NaOH
t-BuOLi
t-BuONa
t-BuOK
KOH
t-AmOH
t-AmOH
t-AmOH
t-AmOH
t-BuOH
i-PrOH
EtOH
53
7
< 5
63
16:1
18:1
19:1
> 20:1
-
8
9
89
10
11
12
13
14
15
16
17
18
88
KOH
12
KOH
0
KOH
> 20:1
16:1
> 20:1
-
THF
32
KOH
Diglyme
Toluene
t-AmOH
t-AmOH
t-AmOH
90
KOH
19
-
0
11c (10)d
< 5e
KOH
> 20:1
-
KOH
a General conditions: 1a (0.55 mmol), 2a (0.5 mmol), MnO2 (0.05 mmol),
base (0.5 mmol), solvent (1.0 mL), 120 oC, 21 h. Yield of 3a and the ratio
of 3a/4a determined by GC-analysis using n-cetane as an internal standard.
b Under oxygen. c No MnO2. d No MnO2, 48 h. e Under nitrogen.
a
General conditions: 1a (0.55 mmol), 2 (0.5 mmol), MnO2 (10 mol%),
KOH (0.5 mmol), t-AmOH (1.0 mL), air, 120 oC, 21 h. Isolated yield,
b
o
c
unless otherwise noted. 1a (2.0 mmol), 140 C, 36 h. 1a (2.0 mmol),
KOH (1.0 mmol), 140 oC, 48 h.
Because manganese precatalyst has shown to be highly effective
for the dehydragenation/olefination of methylazaarenes with
alcohols,8,9 we initially focused on exploring conditions using MnO2
as readily available catalyst at 120 °C. The desired (E)-2-
Taken together, we can conclude that the oxidation/olefination
was carried out by stirring t-AmOH solution of phenylmethanol, 2-
methylpyrazine, 10 mol% of MnO2, and an equivalent of KOH at

Tetrahedron
3
Table 3. Substrate scope of alcohols a
120oC under an air for 21 hours to give the olefination product 3a in
the best yield.
On the basis of the results described above, a variety of N-
heteroaromatics were submitted to the MnO2-catalyzed
oxidant/olefination reaction to investigate its substrate scope and
generality (Table 2). 2-Methylpyrazine and 3-methylpyridazine
substrates gave the corresponding products in high yields (3a-3b).
The oxidation/olefiantion reaction of 2,6-dimethylpyrazine or 4-
methylpyridine (lower acidity of methyl) reacted with
phenylmethanol resulted in modearate yields of the desired products
3c-3d. When the pyrazine core was replaced with benzo[d]oxazole,
the olefination reaction still took place to give 3e in 71% yield.
Although the reaction of 4-methylquinoline and 1-
methylisoquinoline offered 3f and 3g in moderate yields, the
reaction with 2-methylquinoline proceeded smoothy to produce the
desired adduct 3h in excellent yield. The yield of product is likely
related to the stability of the enamine intermediate, which increases
in the order 3g < 3f < 3h. This result showing that the olefination
mechanism may via enamine intermediate. Methyl-substituted N-
heteroarenes derived from 2-methylquinoline were effective
substrates and smoothly reacted with benzyl alcohol to provide the
corresponding products 3i and 3j in 82 and 91% yield, respectively.
Ethyl or benzyl substituted azaarenes were less reactive, and the
olefination products 3k-3n were isolated in moderate yields when
the reaction temperature and time were increased. These results may
be due to large steric hindrance of the methylenyl of the azaarenes.
Yield (%)
5a, 89
5b, 81
5c, 73
5d, 68
5e, 66
5f, 84
1
Entry
1
R
1d
1k
1l
4-CH3C6H4
4-ClC6H4
4-BrC6H4
2-thienyl
2
3
2a
1p
1b
1c
1d
1e
1f
4
5
2-CH3C6H4
3-CH3C6H4
4-CH3C6H4
2,4,6-(CH3)3C6H2
4-t-BuC6H4
4-PhC6H4
2-CH3OC6H4
4-CH3OC6H4
2-ClC6H4
4-ClC6H4
4-BrC6H4
4-IC6H4
6
5g, 93
5h, 64
5i, 91
7
8
9
5j, 83
1g
1h
1i
10
11
12
13
14
15
16
17
18
19
20
21b
22b
23b
5k, 71
5l, 92
5m, 57
5n, 84
5o, 66
5p, 48
5q, 77
5r, 58
5s, 74
5t, 53b
5u, 61b
5v, 56b
5w, 68b
1j
1k
1l
2l
1m
1n
1o
1p
1q
1r
1s
1t
1-Naphthyl
2-furyl
2-thienyl
Furthermore, the scope of the alcohols was also explored and the
results are shown in Table 3. The procedure tolerated well some
functional groups, such as methyl, phenyl, methoxy, halogen and
heteroarene, with good yields. The electronic effects of substituent
in alcohol had some effect on the reaction. Generally, the alcohols
with electron-withdrawing groups gave slightly lower yields than
those electron-donating analogues (5a vs 5b-c and 5g, 5i, 5l vs 5n-
5p). An obvious steric hindrance effect on the reactivity was
observed, which was demonstrated by the reactivities of 5e vs 5g
and 5m vs 5n. It is worth noting that the tolerance of halogen group
on the aromatic ring in this olefination protocol offers an
opportunity for subsequent transformations, which facilitates
expedient synthesis of complex unsaturate N-heteroarenes (5b-5c,
5m-5p). Naphthyl-substituted alcohol was also compatible with this
process, furnishing the desired product 5q in 87% yield. In addition
to aromatic-substituted alcohols, although the reaction of furan-2-
ylmethanol gave the corresponding product 5r in moderate yield,
the reaction with thiophen-2-ylmethanol proceeded smoothy to give
5s in good yield. Pyridin-2-ylmethanol was also a good reaction
partner, and (E)-2-(2-(pyridin-2-yl)vinyl)quinoline 5x was isolated
in 52% yield. To extend the scope of our catalytic system, we also
tested more challenging aliphatic alcohols under the standard
procedure. 2-Ethylbutan-1-ol was initially surveyed and the reaction
proceeded smoothly to give the desired olefination 5t in moderate
yield. Furthermore, similar results were obtained in the reactions of
aliphatic alcohols with different substituted to deliver the desired
adducts 5u-5w efficiently in good yields. And importantly,
unsaturate alcohol substrates, citronellol, was also good reaction
partner, providing the corresponding product 5y in 66% yield, while
the internal double bond remained intact.
Et2CH
t-Bu
Cyclopropyl
Cyclohexyl
a
General conditions: 1 (0.55 mmol), 2a or 2l (0.5 mmol), MnO2 (10
mol%), KOH (0.5 mmol), t-AmOH (1.0 mL), air, 120 C, 21 h. Isolated
o
yield. b 1 (2.0 mmol), KOH (1.0 mmol), 140 oC, 48 h.
To further demonstrate the robustness of our system, we were
able to run experiments on gram scale in the presence of 10 mol%
of MnO2 to produce the olefination adducts 3a and 3j in 73% (1.33
g) and 75% (1.73 g) yield, respectively.
Scheme 2. Gram scale experiments.
To validate the recyclability of current oxidant/olefination, the
reuse investigation was performed in the model reaction of 1a with
2a in presence of 10 mol% of MnO2. After the completion of
reaction, a small aliquot of the reaction mixture was analyzed by

4
Tetrahedron
unsaturated
available
N-heteroaromatics
alcohols and
from
alkylazaarenes
commercially
via
GC to monitor product 3a formation. Then the reaction mixture was
filtered, washed with ethyl acetate, water and ethanol, dried on
vacuum, the catalyst of MnO2 was recovered and continued to
catalyze for another reaction. It is shown in Figure. 2 that the
olefination could be repeated at least five times with the fifth run
giving a 81% yield of 3a. And the catalytic activity of the recovered
MnO2 dried on the oxygen atmosphere better than argon (see the
Supporting Information for details), these results indicate that the
catalyst MnO2 can can be re-generated by oxygen or air.
oxidation/olefination under the aerobic conditions. The
method is compatible with a variety of functional groups
and can be used to prepare a range of 1,2-disubstitued
unsaturated N-heteroaromatics. Further investigations to
gain a detailed mechanistic understanding as well as
application of this aerobic oxidative catalytic system to
other oxidation/olefination reactions are currently in
progress.
4. Experimental section
4.1 General Information
1H and 13C spectra were obtained on a Brüker AVIII300
(300 MHz) or AVII (500 MHz) spectrometer. Proton-
decoupled spectra are denoted as {1H}. Chemical shifts (δ)
were reported in parts per million (ppm) using the residual
solvent signal as an internal standard (CDCl3: δH = 7.26
ppm, δC = 77.16 ppm). All coupling constants (J values)
were reported in Hertz (Hz). Multiplicities were reported as
follows: s, singlet; d, doublet; t, triplet; m, multiplet. High-
resolution mass spectrometry (HRMS) measurements were
Figure 2. Reusability of MnO2 Catalyst
The practice and convenience of this proceed to unsaturated N-
heteroaromatics can be di-olefination of substrates containing two
methyl groups as well, the corresponding products 7a and 7b were
isolated in reasonable yields, respectively.
recorded on
a Bruker Daltronics microTOF (ESI)
spectrometer. Flash chromatography was carried out using
matrix 60 silica.
4.2 General procedure for synthesis of products (1)substrates
General procedure for MnO2 catalyzed oxidation/olefination
reaction (3a-3n, 5a-5y, 7a-7a)
Using a nitrogen-filled glove box, an oven-dried Schlenk
tube (100 mL volume) was charged with a magnetic stirring
bar, MnO2 (0.05 mmol), KOH (0.5 mmol), alcohols (1) (0.55
mmol), heteroarenes (2) (0.5 mmol) and t-AmOH (1 mL).
Then the Schlenk tube was closed tightly with a teflon cap,
removed from the glove box. A reflux condenser was
evacuated and refilled with dry air and then attached to the
Schlenk tube maintaining dry air stream. A bubble counter
was attached to the top of the condenser and the whole
system was purged with dry air for 15 seconds. The Schlenk
tube was immersed into a pre-heated oil bath (design
temperature). After design time the reaction was cooled, a
small aliquot of the organic phase was analyzed by GC or
GC-MS to monitor product formation. Purification of the
remainder by column chromatography on silica gel
(petroleum ether/ethyl acetate = 20/1 – 5/1) gave the
corresponding products in the reported yield.
Scheme 3. MnO2 catalyzed di-olefination.
On the basis of the results we obtained here and previous
reports,7,8 a plausible mechanism for the present process can be
proposed. In this scenario, initial alcohol is oxidized by air in the
presence of MnO2 to generate aldehyde. After enamine was formed
under the base condition, nucleophilic attack of the enamine into the
C=O bond of aldehyde gained the intermediate I. Subsequent
elimination releases water in the presence of base and give rise to
the unsaturated N-heteroaromatic product.
4.2.1 (E)-2-styrylpyrazine (3a)
The title compound was prepared according to the
general procedure and purified by column chromatography
1
to give a white solid, 169 mg, 93% yield. H NMR (300
Scheme 4. Possible mechanism of olefination.
MHz, CDCl3): δ 8.59 (s, 1H), 8.49 (s, 1H), 8.35 (d, J = 2.3
Hz, 1H), 7.70 (d, J = 16.1 Hz, 1H), 7.55 (d, J = 8.1 Hz, 2H),
7.38 – 7.28 (m, 3H), 7.11 (d, J = 16.1 Hz, 1H) ppm. 13C
NMR (75 MHz, CDCl3): δ 151.3, 144.4, 143.8, 142.8,
136.0, 135.2, 129.0, 128.9, 127.3, 124.0. HRMS (ESI)
calcd. for C12H11N2 [M+H]: 183.0922, found: 183.0931.
3. Conclusion
In summary, we have developed an efficient MnO2/air
catalytic system that allows the direct formation of

Tetrahedron
5
4.2.2 (E)-3-styrylpyridazine (3b)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 53mg, 23% yield. 1H NMR (300 MHz,
CDCl3): δ 8.57 (d, J = 5.6 Hz, 1H), 8.39 (d, J = 8.4 Hz, 1H),
8.01 (s, 2H), 7.84 (d, J = 8.2 Hz, 1H), 7.67 (ddd, J = 15.3,
14.8, 7.1 Hz, 4H), 7.58 (d, J = 5.6 Hz, 1H), 7.43 (dd, J =
10.9, 4.4 Hz, 2H), 7.38 – 7.29 (m, 1H) ppm; 13C NMR (75
MHz, CDCl3): δ 154.6, 142.5, 136.9, 136.8, 135.8, 129.9,
128.8, 128.6, 127.5, 127.3, 127.2, 124.5, 122.9, 120.0 ppm.
HRMS (ESI) calcd. for C17H14N [M+H]: 232.1126, found:
232.1141.
The title compound was prepared according to the general
procedure and purified by column chromatography to give a
yellow solid, 147 mg, 81% yield. H NMR (300 MHz,
CDCl3): δ 8.98 (d, J = 4.8 Hz, 1H), 7.63 (d, J = 16.4 Hz, 1H),
7.55 (t, J = 4.9 Hz, 2H), 7.52 (s, 1H), 7.40 – 7.36 (m, 1H),
7.31 (dd, J = 8.7, 4.6 Hz, 3H), 7.26 (d, J = 5.2 Hz, 1H) ppm.
13C NMR (75 MHz, CDCl3): δ 158.3, 149.7, 135.9, 135.2,
129.1, 128.9, 127.4, 126.4, 125.2, 123.9 ppm. HRMS (ESI)
calcd. for C12H11N2 [M+H]: 183.0922, found: 183.0928.
1
4.2.3 (E)-2-methyl-6-styrylpyrazine (3c)
4.2.8 (E)-2-styrylquinoline (3h)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
the colorless oil 119 mg, 61% yield.
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 217 mg, 94% yield. H NMR (300 MHz,
1
1H NMR (300 MHz, CDCl3): δ 8.46 (s, 1H), 8.29 (s, 1H),
7.73 (d, J = 16.1 Hz, 1H), 7.59 (d, J = 7.1 Hz, 2H), 7.37 (dt,
J = 13.9, 6.9 Hz, 3H), 7.14 (d, J = 16.1 Hz, 1H), 2.59 (s, 3H)
ppm. 13C NMR (75 MHz, CDCl3): δ 153.3, 150.1, 142.6,
140.5, 136.2, 134.7, 128.8, 127.3, 124.5, 21.8 ppm. HRMS
(ESI) calcd. for C13H13N2 [M+H]: 197.1079, found:
197.1082.
CDCl3): δ 8.20 – 8.07 (m, 2H), 7.79 (d, J = 8.0 Hz, 1H),
7.69 (ddd, J = 15.4, 6.3, 4.5 Hz, 5H), 7.50 (t, J = 7.5 Hz,
1H), 7.47 – 7.38 (m, 3H), 7.37 – 7.30 (m, 1H) ppm; 13C
NMR (75 MHz, CDCl3): δ 155.9, 148.1, 136.4, 136.3,
134.4, 129.7, 129.1, 128.9, 128.7, 128.6, 127.4, 127.2,
126.1, 119.2 ppm. HRMS (ESI) calcd. for C17H14N [M+H]:
232.1126, found: 232.1133.
4.2.4 (E)-4-styrylpyridine (3d)
4.2.9 (E)-6-chloro-2-styrylquinoline (3i)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 95 mg, 53% yield. H NMR (300 MHz,
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 217 mg, 82% yield. H NMR (300 MHz,
1
1
CDCl3): δ 8.59 (d, J = 4.4 Hz, 2H), 7.65 – 7.49 (m, 2H),
7.38 (dt, J = 15.3, 6.3 Hz, 5H), 7.34 – 7.26 (m, 2H), 7.03 (d,
J = 16.3 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): δ 150.0,
144.7, 136.1, 133.2, 128.8, 128.7, 127.0, 125.9, 120.8 ppm.
HRMS (ESI) calcd. for C13H12N [M+H]: 182.0970, found:
182.0978.
CDCl3): δ 8.11 – 7.94 (m, 2H), 7.76 (d, J = 2.1 Hz, 1H),
7.71 (d, J = 11.8 Hz, 1H), 7.68 – 7.58 (m, 4H), 7.42 (d, J =
8.2 Hz, 2H), 7.40 – 7.30 (m, 2H) ppm; 13C NMR (75 MHz,
CDCl3): δ 156.1, 146.5, 136.3, 135.4, 134.9, 131.8, 130.6,
128.8, 128.4, 127.8, 127.3, 126.2, 120.2 ppm. HRMS (ESI)
calcd. for C17H13ClN [M+H]: 266.0736, found: 266.0736.
4.2.5 General (E)-2-styrylbenzo[d]oxazole (3e)
4.2.10 (E)-6-methoxy-2-styrylquinoline (3j)
The title compound was prepared according to the
general procedure and purified by column chromatography
to give a white solid, 156 mg, 71% yield. H NMR (300
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 237 mg, 91% yield. H NMR (300 MHz,
1
1
MHz, CDCl3): δ 8.06 (d, J = 8.5 Hz, 1H), 8.01 (d, J = 8.5
Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.69 – 7.62 (m, 1H), 7.57
– 7.48 (m, 2H), 7.44 (dt, J = 8.0, 4.0 Hz, 2H), 7.22 (d, J =
2.1 Hz, 1H), 6.51 (d, J = 2.8 Hz, 1H), 6.43 (dd, J = 3.3, 1.8
Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): δ 162.8, 150.4,
142.2, 139.4, 135.1, 129.7, 128.9, 127.5, 125.2, 124.5,
119.8, 113.9, 110.3 ppm. HRMS (ESI) calcd. for C15H12NO
[M+H]: 222.0919, found: 222.0908.
CDCl3): δ 8.01 (s, 1H), 7.98 (s, 1H), 7.63 (d, J = 5.9 Hz,
2H), 7.62 – 7.58 (m, 2H), 7.43 – 7.37 (m, 3H), 7.36 – 7.26
(m, 2H), 7.04 (d, J = 2.8 Hz, 1H), 3.91 (s, 3H) ppm; 13C
NMR (75 MHz, CDCl3): δ 157.6, 153.6, 144.0, 136.6,
135.1, 133.3, 130.5, 128.8, 128.7, 128.4, 128.2, 127.1,
122.3, 119.5, 105.2, 55.5 ppm. HRMS (ESI) calcd. for
C18H16NO [M+H]: 262.1232, found: 262.1241.
4.2.11 (E)-4-(1,2-diphenylvinyl)pyridine (3k)
4.2.6 (E)-4-styrylquinoline (3f)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a yellow solid 118mg, 46% yield. H NMR (300 MHz,
1
a white solid, 120 mg, 52% yield. H NMR (300 MHz,
DMSO-d6): δ 8.82 (s, 2H), 7.77 (dd, J = 23.0, 11.7 Hz, 6H),
7.52 – 7.28 (m, 7H) ppm; 13C NMR (75 MHz, DMSO-d6):
δ 148.4, 142.5, 135.8, 133.3, 128.2, 128.0, 126.6, 124.3
ppm. HRMS (ESI) calcd. for C19H16N [M+H]: 258.1283,
found: 258.1291.
CDCl3): δ 8.96 (s, 1H), 8.24 (t, J = 8.2 Hz, 2H), 7.88 – 7.74
(m, 2H), 7.71 – 7.57 (m, 4H), 7.44 (dt, J = 26.5, 11.5 Hz,
4H) ppm; 13C NMR (75 MHz, CDCl3): δ 149.9, 148.4,
143.0, 136.4, 135.1, 129.8, 129.3, 128.8, 128.7, 127.0,
126.5, 126.3, 123.4, 122.7, 116.9 ppm. HRMS (ESI) calcd.
for C17H14N [M+H]: 232.1126, found: 232.1128.
4.2.12 (E)-2-(1-phenylprop-1-en-2-yl)pyrazine (3l)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
4.2.7 (E)-1-styrylisoquinoline (3g)

6
Tetrahedron
1
1
the colorless oil 74 mg, 38% yield. H NMR (300 MHz,
CDCl3): δ 8.86 (s, 1H), 8.56 (s, 1H), 8.45 (d, J = 2.1 Hz,
1H), 7.50 (s, 1H), 7.45 – 7.36 (m, 4H), 7.34 – 7.27 (m, 1H),
2.38 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ 143.4,
142.6, 141.9, 137.1, 1321, 129.4, 128.3, 127.4, 15.4 ppm.
HRMS (ESI) calcd. for C13H13N2 [M+H]: 197.1079, found:
197.1075.
a white solid, 189 mg, 73% yield. H NMR (300 MHz,
CDCl3): δ 8.63 (s, 1H), 8.54 (s, 1H), 8.43 (s, 1H), 7.69 (d, J
= 16.1 Hz, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 8.4
Hz, 2H), 7.14 (d, J = 16.1 Hz, 1H) ppm; 13C NMR (75
MHz, CDCl3): δ 144.4, 143.9, 143.0, 135.0, 133.9, 132.0,
128.7, 124.64, 123.0 ppm. HRMS (ESI) calcd. for
C12H10BrN2 [M+H]: 261.0027, found: 261.0032.
4.2.13 2-(1-(naphthalen-1-yl)prop-1-en-2-yl)pyrazine (3m)
(E:Z= 7:1)
4.2.18 (E)-2-(2-(thiophen-2-yl)vinyl)pyrazine (5d)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a yellow solid, 127 mg, 68% yield. H NMR (300 MHz,
1
a yellow solid 89 mg, 36% yield. H NMR (300 MHz,
CDCl3): δ 8.53 (d, J = 17.7 Hz, 2H), 8.38 (s, 1H), 7.88 (d, J
= 15.8 Hz, 1H), 7.30 (d, J = 5.0 Hz, 1H), 7.21 (d, J = 3.0
Hz, 1H), 7.04 (dt, J = 5.0, 3.4 Hz, 1H), 6.94 (d, J = 15.8 Hz,
1H) ppm; 13C NMR (75 MHz, CDCl3): δ 150.8, 144.2,
143.5, 142.5, 141.5, 128.6, 127.9, 127.8, 126.3, 123.0 ppm.
HRMS (ESI) calcd. for C10H9N2S [M+H]: 189.0486, found:
189.0492.
CDCl3): δ = 8.95 (s, 1H), 8.62 (s, 1H), 8.51 (s, 1H), 8.21 (s,
0.19H), 8.09-8.07 (m, 0.35H), 8.03-8.00 (m, 2H), 7.92-7.86
(m, 1H), 7.86-7.83 (m, 1.27H), 7.72-7.69 (m, 0.25H), 7.55-
7.46 (m, 5.05H), 7.32 (s, 0.18H), 7.22-7.21 (2, 0.22H), 6.97
-6.95 (m, 0.15H), 2.45 (s, 0.48H), 2.25 (s, 3H) ppm; 13C
NMR (75 MHz, CDCl3): δ 154.7, 143.6, 142.8, 141.9,
135.5, 134.4, 133.6, 131.9, 130.3, 128.5, 127.9, 126.8,
126.2, 126.0, 125.3, 125.0, 15.6 ppm. HRMS (ESI) calcd.
for C17H15N2 [M+H]: 247.1235, found: 247.1241.
4.2.19 (E)-2-(2-methylstyryl)quinoline (5e)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
the colorless oil, 162 mg, 66% yield.1H NMR (300 MHz,
CDCl3): δ 8.16 (t, J = 8.5 Hz, 2H), 8.00 (d, J = 16.2 Hz,
1H), 7.85 – 7.71 (m, 4H), 7.54 (dd, J = 8.1, 7.0 Hz, 1H),
7.37 (d, J = 16.2 Hz, 1H), 7.33 – 7.29 (m, 1H), 2.57 (s, 3H)
ppm; 13C NMR (75 MHz, CDCl3): δ 156.1, 148.2, 136.5,
136.2, 135.1, 132.0, 130.5, 130.1, 129.6, 129.2, 128.4,
127.4, 127.2, 126.2, 126.1, 125.7, 119.2, 19.9 ppm.HRMS
(ESI) calcd. for C18H16N [M+H]: 246.1283, found:
246.1289.
4.2.14 (E)-2-(hex-2-en-2-yl)pyrazine (3n)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a yellow solid 53 mg, 32% yield. H NMR (300 MHz,
CDCl3): δ 8.64 (s, 1H), 8.45 (s, 1H), 8.33 (s, 1H), 5.90 (d, J
= 10.0 Hz, 1H), 2.23 (s, 3H), 1.81 – 1.69 (m, 1H), 0.96 –
0.89 (m, 2H), 0.59 (dd, J = 5.6, 3.5 Hz, 2H) ppm. 13C NMR
(75 MHz, CDCl3): δ 143.2, 141.6, 141.1, 138.6, 130.4,
129.8, 13.9, 11.7, 7.9 ppm. HRMS (ESI) calcd. for
C10H15N2 [M+H]: 163.1235, found: 163.1241.
4.2.20 (E)-2-(3-methylstyryl)quinoline (5f)
4.2.15 (E)-2-(4-methylstyryl)pyrazine (5a)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 205 mg, 84% yield. H NMR (300 MHz,
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
CDCl3): δ 8.13 (d, J = 8.6 Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H),
7.79 (d, J = 8.1 Hz, 1H), 7.75 – 7.67 (m, 2H), 7.65 (d, J =
7.8 Hz, 1H), 7.47 (dt, J = 28.9, 11.8 Hz, 4H), 7.29 (d, J =
1
a white solid, 174 mg, 89% yield. H NMR (300 MHz,
CDCl3): δ 8.59 (d, J = 31.0 Hz, 2H), 8.40 (s, 1H), 7.73 (d, J
= 16.1 Hz, 1H), 7.50 (d, J = 7.9 Hz, 2H), 7.21 (d, J = 7.8
Hz, 2H), 7.12 (d, J = 16.1 Hz, 1H), 2.39 (s, 3H) ppm; 13C
NMR (75 MHz, CDCl3): δ 151.5, 144.2, 143.7, 142.5,
139.2, 135.2, 133.3, 129.6, 127.3, 123.0, 21.4 ppm. HRMS
(ESI) calcd. for C13H13N2 [M+H]: 197.1079, found:
197.1082.
7.5 Hz, 1H), 7.15 (d, J = 7.4 Hz, 1H), 2.41 (s, 3H) ppm; 13
C
NMR (75 MHz, CDCl3): δ 156.1, 148.3, 138.4, 136.5,
136.3, 134.5, 129.7, 129.5, 129.2, 128.9, 128.7, 123.0,
127.5, 126.1, 124.5, 119.2, 21.5 ppm. HRMS (ESI) calcd.
for C18H16N [M+H]: 246.1283, found: 246.1291.
4.2.21 (E)-2-(4-methylstyryl)quinolines (5g)
4.2.16 (E)-2-(4-chlorostyryl)pyrazine (5b)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 227 mg, 93% yield.1H NMR (300 MHz,
CDCl3): δ 8.12 (d, J = 8.6 Hz, 1H), 8.07 (d, J = 8.5 Hz, 1H),
7.78 (d, J = 8.1 Hz, 1H), 7.70 (dt, J = 5.3, 4.7 Hz, 2H), 7.65
(d, J = 5.0 Hz, 1H), 7.55 (d, J = 8.0 Hz, 2H), 7.49 (dd, J =
8.0, 7.0 Hz, 1H), 7.37 (d, J = 16.3 Hz, 1H), 7.22 (d, J = 8.0
Hz, 2H), 2.39 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ
156.1, 148.2, 138.7, 136.2, 134.3, 133.7, 129.6, 129.5,
129.1, 128.0, 127.4, 127.2, 127.2, 126.0, 119.1, 21.3 ppm.
HRMS (ESI) calcd. for C18H16N [M+H]: 246.1283, found:
246.1285.
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 174 mg, 81% yield. H NMR (300 MHz,
CDCl3): δ 8.63 (s, 1H), 8.54 (s, 1H), 8.43 (s, 1H), 7.69 (d, J
= 16.1 Hz, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 8.4
Hz, 2H), 7.14 (d, J = 16.1 Hz, 1H) ppm; 13C NMR (75
MHz, CDCl3): δ 150.8, 144.3, 143.7, 142.9, 134.6, 134.4,
133.7, 128.9, 128.4, 124.4 ppm. HRMS (ESI) calcd. for
C12H10ClN2 [M+H]: 217.0532, found: 217.0541.
1
4.2.17 (E)-2-(4-bromostyryl)pyrazine (5c)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
4.2.22 (E)-2-(2,4,6-trimethylstyryl)quinoline(5h)

Tetrahedron
7
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 175mg, 64% yield.
3H) ppm; 13C NMR (75 MHz, CDCl3): δ 160.1, 156.3,
148.3, 136.2, 134.0, 129.7, 129.3, 129.1, 128.7, 127.5,
127.2, 126.9, 125.9, 119.2, 114.3, 55.4 ppm. HRMS (ESI)
calcd. for C18H16NO [M+H]: 262.1232, found: 262.1238.
1H NMR (300 MHz, CDCl3): δ 8.12 (dd, J = 12.2, 8.6 Hz,
2H), 7.83 – 7.66 (m, 4H), 7.50 (dd, J = 8.1, 6.9 Hz, 1H),
6.94 (dd, J = 11.1, 5.5 Hz, 3H), 2.44 (s, 6H), 2.32 (s, 3H)
ppm; 13C NMR (75 MHz, CDCl3): δ 156.3, 148.3, 137.0,
136.5, 136.5, 136.3, 134.1, 133.1, 132.9, 129.7, 129.3,
129.0, 127.5, 127.4, 126.1, 119.0, 21.3, 21.1 ppm. HRMS
(ESI) calcd. for C20H20N [M+H]: 274.1596, found:
274.1599.
4.2.27 (E)-2-(2-chlorostyryl)quinolines (5m)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
the colorless oil, 151 mg, 57% yield. H NMR (300 MHz,
CDCl3): δ 8.13 (dd, J = 25.6, 12.7 Hz, 2H), 7.93 – 7.68 (m,
3H), 7.57 – 7.41 (m, 2H), 7.35 – 7.28 (m, 1H) ppm; 13C
NMR (75 MHz, CDCl3): δ 155.7, 148.1, 136.3, 134.5,
134.0, 131.7, 130.1, 129.9, 129.7, 129.4, 129.2, 127.4,
127.4, 127.0, 126.9, 126.33, 118.9 ppm. HRMS (ESI) calcd.
for C17H13ClN [M+H]: 266.0736, found: 266.0742.
4.2.23 (E)-2-(4-(tert-butyl)styryl)quinoline (5i)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a white solid, 261mg, 91% yield. H NMR (300 MHz,
4.2.28 (E)-2-(4-chlorostyryl)quinolines (5n)
CDCl3): δ 8.12 (d, J = 8.6 Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H),
7.79 (d, J = 8.0 Hz, 1H), 7.69 (dd, J = 17.2, 8.8 Hz, 3H),
7.59 (d, J = 8.3 Hz, 2H), 7.49 (dd, J = 7.9, 7.0 Hz, 1H),
7.46 – 7.34 (m, 3H), 1.35 (s, 9H) ppm; 13C NMR (75 MHz,
CDCl3): δ 156.3, 152.0, 148.3, 136.3, 134.3, 133.8, 129.7,
129.2, 128.3, 127.5, 127.3, 127.1, 126.1, 125.8, 119.2, 34.8,
31.3 ppm. HRMS (ESI) calcd. for C21H22N [M+H]:
288.1752, found: 288.1763.
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a white solid, 222 mg, 84% yield. H NMR (300 MHz,
CDCl3): δ 8.14 (d, J = 8.5 Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H),
7.79 (d, J = 8.1 Hz, 1H), 7.75 – 7.62 (m, 3H), 7.60 – 7.48
(m, 3H), 7.37 (dd, J = 12.1, 3.7 Hz, 3H) ppm; 13C NMR (75
MHz, CDCl3): δ 155.5, 148.2, 136.3, 135.0, 134.2, 132.9,
129.8, 129.4, 129.2, 128.9, 128.3, 127.5, 127.3, 126.2,
119.3 ppm. HRMS (ESI) calcd. for C17H13ClN [M+H]:
266.0736, found: 266.0739.
4.2.24 (E)-2-(2-([1,1'-biphenyl]-4-yl)vinyl)quinoline (5j)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
4.2.29 (E)-2-(4-bromostyryl)quinolines (5o)
1
a white solid, 254 mg, 83% yield. H NMR (300 MHz,
CDCl3): δ 8.15 (d, J = 8.5 Hz, 1H), 8.10 (d, J = 8.5 Hz, 1H),
7.80 (d, J = 8.1 Hz, 1H), 7.78 – 7.71 (m, 4H), 7.70 – 7.59
(m, 5H), 7.54 – 7.48 (m, 2H), 7.45 (d, J = 7.2 Hz, 2H), 7.37
(dd, J = 11.2, 4.6 Hz, 1H) ppm; 13C NMR (75 MHz,
CDCl3): δ 155.9, 148.2, 141.3, 140.4, 136.3, 135.5, 133.9,
129.7, 129.1, 128.9, 128.8, 127.7, 127.5, 127.4, 127.3,
126.9, 126.1, 119.3 ppm. HRMS (ESI) calcd. for C23H18N
[M+H]: 308.1439, found: 308.1442.
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 204 mg, 66% yield. H NMR (300 MHz,
1
CDCl3): δ 8.14 (d, J = 8.6 Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H),
7.79 (d, J = 8.1 Hz, 1H), 7.71 (dd, J = 8.4, 7.0 Hz, 1H),
7.66 (d, J = 1.3 Hz, 1H), 7.62 (d, J = 5.8 Hz, 1H), 7.55 –
7.48 (m, 5H), 7.38 (d, J = 16.3 Hz, 1H) ppm; 13C NMR (75
MHz, CDCl3): δ 155.5, 148.1, 136.5, 135.4, 133.1, 131.9,
129.8, 129.5, 129.1, 128.6, 127.5, 127.4, 126.3, 122.5,
119.3 ppm. HRMS (ESI) calcd. for C17H13BrN [M+H]:
310.0231, found: 310.0242.
4.2.25 (E)-2-(2-methoxystyryl)quinoline (5k)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
the colorless oil, 185 mg, 71% yield. H NMR (300 MHz,
4.2.30 (E)-2-(4-iodostyryl)quinolines (5p)
1
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 171 mg, 48% yield.1H NMR (300 MHz,
CDCl3): δ 8.14 (d, J = 8.5 Hz, 1H), 8.08 (d, J = 8.9 Hz, 1H),
7.79 (d, J = 8.1 Hz, 1H), 7.72 (t, J = 8.4 Hz, 3H), 7.63 (dd,
J = 12.4, 7.3 Hz, 2H), 7.51 (t, J = 7.5 Hz, 1H), 7.43 – 7.35
(m, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ 155.5, 148.2,
137.9, 136.4, 136.0, 133.1, 129.8, 129.7, 129.2, 128.8,
127.5, 127.4, 126.3, 119.4, 94.2 ppm. HRMS (ESI) calcd.
for C17H13IN [M+H]: 358.0093, found: 358.0098.
CDCl3): δ 8.10 (t, J = 8.0 Hz, 2H), 8.03 (d, J = 16.6 Hz,
1H), 7.79 – 7.66 (m, 4H), 7.52 – 7.41 (m, 2H), 7.36 – 7.27
(m, 1H), 7.01 (t, J = 7.5 Hz, 1H), 6.94 (d, J = 8.3 Hz, 1H),
3.93 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ 157.4,
156.7, 148.2, 136.1, 129.7, 129.6, 129.3, 129.2, 127.4,
127.2, 127.2, 126.0, 125.5, 120.8, 119.0, 111.0, 55.5 ppm.
HRMS (ESI) calcd. for C18H16NO [M+H]: 262.1232, found:
262.1241.
4.2.26 (E)-2-(4-methoxystyryl)quinoline (5l)
4.2.31 (E)-2-(2-(naphthalen-1-yl)vinyl)quinolines (5q)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 240 mg, 92% yield. H NMR (300 MHz,
CDCl3): δ 8.14 (d, J = 8.5 Hz, 1H), 8.09 (d, J = 8.5 Hz, 1H),
7.81 (d, J = 8.1 Hz, 1H), 7.77 – 7.69 (m, 2H), 7.64 (dd, J =
11.4, 6.7 Hz, 3H), 7.51 (t, J = 7.4 Hz, 1H), 7.34 (s, 1H),
7.29 (d, J = 1.7 Hz, 2H), 6.97 (d, J = 7.3 Hz, 2H), 3.88 (s,
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
1
a white solid, 217 mg, 77% yield. H NMR (300 MHz,
CDCl3): δ 8.54 (d, J = 16.0 Hz, 1H), 8.36 (d, J = 8.2 Hz,
1H), 8.16 (t, J = 8.8 Hz, 2H), 7.97 – 7.84 (m, 3H), 7.81 (d,
J = 8.1 Hz, 1H), 7.78 – 7.68 (m, 2H), 7.62 – 7.53 (m, 3H),

8
Tetrahedron
7.53 – 7.45 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3): δ
156.0, 148.3, 136.5, 136.4, 134.0, 133.7, 133.7, 131.8,
131.7, 131.5, 131.3, 129.7, 129.3, 128.9, 128.6, 127.6,
127.5, 127.4, 126.4, 126.3, 126.2, 125.9, 125.7, 124.2,
123.7, 119.5, 117.4 ppm. HRMS (ESI) calcd. for C21H16N
[M+H]: 282.1283, found: 282.1283.
procedure and purified by column chromatography to give
the colorless oil, 109 mg, 56% yield. H NMR (300 MHz,
1
CDCl3): δ 7.92 (dd, J = 8.6, 2.7 Hz, 2H), 7.63 (d, J = 8.1
Hz, 1H), 7.56 (ddd, J = 8.3, 7.0, 1.3 Hz, 1H), 7.44 – 7.25
(m, 2H), 6.69 (d, J = 15.7 Hz, 1H), 6.30 (dd, J = 15.7, 9.3
Hz, 1H), 1.76 – 1.48 (m, 1H), 0.88 – 0.80 (m, 2H), 0.61 –
0.48 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3): δ 156.1,
148.1, 142.0, 136.0, 129.4, 128.9, 128.2, 127.3, 126.9,
125.6, 118.8 , 14.9, 8.0 ppm. HRMS (ESI) calcd. for
C14H14N [M+H]: 196.1126, found: 196.1126.
4.2.32 (E)-2-(2-(furan-2-yl)vinyl)quinolines (5r)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a yellow solid, 128 mg, 58% yield. H NMR (300 MHz,
4.2.37 (E)-2-(2-cyclohexylvinyl)quinolines (5w)
CDCl3): δ 7.80 (d, J = 16.4 Hz, 1H), 7.76 – 7.68 (m, 1H),
7.63 – 7.59 (m, 2H), 7.54 (dd, J = 5.0, 4.2 Hz, 1H), 7.48 –
7.37 (m, 3H), 7.34 (dd, J = 6.2, 3.3 Hz, 2H), 7.09 (d, J =
15.7 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3): δ 155.6,
152.8, 148.3, 143.1, 136.3, 129.7, 129.2, 127.5, 127.3,
126.8, 126.0, 121.7, 119.9, 111.9, 111.1 ppm. HRMS (ESI)
calcd. for C15H12NO [M+H]: 222.0919, found: 222.0921.
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
the colorless oil, 161 mg, 68% yield. H NMR (300 MHz,
CDCl3): δ 8.03 (d, J = 8.5 Hz, 2H), 7.73 (d, J = 8.1 Hz, 1H),
7.66 (t, J = 7.7 Hz, 1H), 7.51 (d, J = 8.5 Hz, 1H), 7.45 (dd,
J = 11.4, 4.3 Hz, 1H), 6.78 (dd, J = 16.1, 6.2 Hz, 1H), 6.67
(d, J = 16.1 Hz, 1H), 2.24 (s, 1H), 1.92 – 1.69 (m, 5H),
1.40 – 1.19 (m, 5H) ppm; 13C NMR (75 MHz, CDCl3): δ
156.7, 148.0, 143.3, 136.0, 129.4, 129.0, 128.6, 127.3,
127.0, 125.7, 118.6, 41.1, 32.5, 26.1, 25.9 ppm. HRMS
(ESI) calcd. for C17H20N [M+H]: 238.1596, found:
238.1596.
4.2.33 (E)-2-(2-(thiophen-2-yl)vinyl)quinolines (5s)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
a yellow solid, 175 mg, 74% yield. H NMR (300 MHz,
CDCl3): δ 7.92 (dd, J = 14.8, 8.5 Hz, 2H), 7.69 (d, J = 16.1
Hz, 1H), 7.61 – 7.51 (m, 2H), 7.37 (d, J = 8.5 Hz, 1H), 7.33
(dt, J = 8.0, 3.9 Hz, 1H), 7.13 (d, J = 5.1 Hz, 1H), 7.07 (dd,
J = 9.8, 6.2 Hz, 2H), 6.96 – 6.86 (m, 1H) ppm; 13C NMR
(75 MHz, CDCl3): δ 155.4, 148.1, 141.9, 136.1, 129.6,
129.0, 128.1, 128.0, 127.7, 127.4, 127.1, 125.9, 125.9,
119.2 ppm. HRMS (ESI) calcd. for C15H12NS [M+H]:
238.0690, found: 238.0687.
4.2.37 (E)-2-(2-(pyridin-2-yl)vinyl)quinolines (5x)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a white solid, 121 mg, 52% yield.1H NMR (300 MHz,
CDCl3): δ 8.68 – 8.51 (m, 1H), 8.11 (t, J = 8.5 Hz, 2H),
7.81 (dd, J = 4.0, 2.3 Hz, 2H), 7.74 (d, J = 8.1 Hz, 1H),
7.66 (ddd, J = 13.0, 8.1, 5.0 Hz, 3H), 7.54 (d, J = 6.9 Hz,
1H), 7.47 (t, J = 7.5 Hz, 1H), 7.16 (dd, J = 7.0, 3.8 Hz, 1H)
ppm; 13C NMR (75 MHz, CDCl3): δ 155.1, 154.9, 149.7,
136.8, 136.7, 134.0, 132.1, 130.0, 129.0, 127.5, 126.6,
122.9, 122.8, 120.3, 109.9 ppm. HRMS (ESI) calcd. for
C16H13N2 [M+H]: 233.1079, found: 233.1079.
4.2.34 (E)-2-(3-ethylpent-1-en-1-yl)quinolines (5t)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
the colorless oil, 139 mg, 53% yield.1H NMR (300 MHz,
CDCl3): δ 8.04 (dd, J = 8.5, 5.4 Hz, 2H), 7.74 (d, J = 8.1
Hz, 1H), 7.66 (dd, J = 8.4, 7.0 Hz, 1H), 7.56 (d, J = 8.6 Hz,
1H), 7.45 (dd, J = 8.1, 6.9 Hz, 1H), 6.70 (d, J = 16.0 Hz,
1H), 6.55 (dd, J = 16.0, 8.6 Hz, 1H), 2.09 (ddt, J = 13.4, 8.8,
4.4 Hz, 1H), 1.49 (ddt, J = 21.0, 13.6, 6.8 Hz, 4H), 0.92 (t,
J = 7.4 Hz, 6H) ppm; 13C NMR (75 MHz, CDCl3): δ 156.5,
148.0, 141.8, 136.0, 131.3, 129.4, 129.1, 127.4, 127.1 125.8,
118.5, 46.8, 27.5, 11.9 ppm. HRMS (ESI) calcd. for
C16H20N [M+H]: 263.1310, found: 263.1310.
4.2.38 (E)-2-(4,8-dimethylnona-1,7-dien-1-yl)quinolines (5y)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
the colorless oil, 184 mg, 66% yield. H NMR (300 MHz,
CDCl3): δ 7.97 (t, J = 8.5 Hz, 2H), 7.67 (d, J = 8.1 Hz, 1H),
7.59 (t, J = 7.7 Hz, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.38 (t, J
= 7.5 Hz, 1H), 6.71 (dt, J = 30.0, 11.4 Hz, 2H), 5.04 (t, J =
6.3 Hz, 1H), 2.39 – 2.19 (m, 1H), 2.10 (dt, J = 14.3, 7.1 Hz,
1H), 1.96 (dt, J = 15.6, 7.6 Hz, 2H), 1.61 (s, 3H), 1.54 (s,
3H), 1.37 (ddd, J = 9.1, 6.4, 3.2 Hz, 1H), 1.23 – 1.13 (m,
1H), 0.90 (d, J = 6.7 Hz, 3H) ppm; 13C NMR (75 MHz,
CDCl3): δ 156.3, 136.2, 132.1, 131.2, 129.5, 129.0, 127.4,
127.1, 125.8, 124.6, 118.6, 40.6, 36.8, 32.7, 25.7, 25.6, 19.6,
17.7 ppm. HRMS (ESI) calcd. for C20H26N [M+H]:
280.2065, found: 280.2071.
4.2.35 (E)-2-(3,3-dimethylbut-1-en-1-yl)quinolines (5u)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
1
the colorless oil, 128 mg, 61% yield. H NMR (300 MHz,
CDCl3): δ 7.95 (d, J = 8.5 Hz, 2H), 7.64 (d, J = 8.1 Hz, 1H),
7.57 (t, J = 7.7 Hz, 1H), 7.46 (d, J = 8.7 Hz, 1H), 7.36 (t, J
= 7.5 Hz, 1H), 6.74 (d, J = 16.2 Hz, 1H), 6.57 (d, J = 16.3
Hz, 1H), 1.11 (s, 10H) ppm; 13C NMR (75 MHz, CDCl3): δ
156.8, 148.1, 148.0, 136.0, 129.4, 129.0, 127.3, 127.0,
126.4, 125.7, 118.5, 33.8, 29.4 ppm. HRMS (ESI) calcd.
for C15H18N [M+H]: 212.1439, found: 212.1442.
4.2.39 (E)-2,6-di((E)-styryl)pyrazine (7a)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a yellow solid 150 mg, 53% yield.1H NMR (300 MHz,
DMSO-d6): δ 8.76 (s, 2H), 7.79 (s, 1H), 7.73 (s, 1H), 7.69
(d, J = 7.4 Hz, 4H), 7.43 (d, J = 6.4 Hz, 4H), 7.39 (s, 2H),
4.2.36 (E)-2-(2-cyclopropylvinyl)quinolines (5v)
The title compound was prepared according to the general

Tetrahedron
7.35 (d, J = 7.3 Hz, 2H) ppm; 13C NMR (75 MHz, DMSO-
d6): δ 149.3, 141.4, 135.5, 133.9, 128.4, 126.8, 124.1, 109.0
ppm. HRMS (ESI) calcd. for C20H17N2 [M+H]: 285.1392,
found: 285.1387.
9
Kanyiva, T. Hiyama, J. Am. Chem. Soc. 2008, 130, 2448; (j) M.
Tobisu, I. Hyodo, N. Chatani, J. Am. Chem. Soc. 2009, 131, 12070;
(k) J. Wu, X. Cui, L. Chen, G. Jiang, Y. Wu, J. Am. Chem. Soc.
2009, 131, 13888; (l) M. Kim, J. Kwak, S. Chang, Angew. Chem.,
Int. Ed. 2009, 48, 8935; (m) J. J. Mousseau, J. A. Bull, A. B.
Charette, Angew. Chem., Int. Ed. 2010, 49, 1115; (n) Fukumoto, M.
Hirano, N. Matsubara, N. Chatani, J. Org. Chem. 2017, 82, 13649;
(o) T.-Y. Feng, H.-X. Li, D. J. Young, J.-P. Lang, J. Org. Chem.
2017, 82, 4113; (p) F, Xiao, C. Liu, S. Yuan, H. Huang, G.-J.
Deng, J. Org. Chem. 2018, 83, 10420; (q) S.-S. Li, L. Zhou, L.
Wang, H. Zhao, L. Yu, J. Xiao, Org. Lett. 2018, 20, 138.
4.2.40 (E)-2,5-di((E)-styryl)pyrazine (7b)
The title compound was prepared according to the general
procedure and purified by column chromatography to give
a yellow solid 116 mg, 41% yield.1H NMR (300 MHz,
DMSO-d6): δ 8.61 (s, 2H), 7.84 (d, J = 16.2 Hz, 2H), 7.69
(d, J = 7.8 Hz, 4H), 7.40 (t, J = 7.5 Hz, 5H), 7.35 – 7.25 (m,
3H) ppm; 13C NMR (75 MHz, DMSO-d6): δ 147.9, 142.3,
135.4, 133.0, 127.9, 126.3, 123.8 ppm. HRMS (ESI) calcd.
for C20H17N2 [M+H]: 285.1392, found: 285.1390.
3 For selected examples of Witting reaction, see: (a) G. Wittig, G.
Geissler, Justus Liebigs Ann. Chem. 1953, 580, 44; (b) B. E.
Maryanoff, A. B. Reitz, Chem. Rev. 1989, 89, 863; (c) Q.-Q. Li, Z.
Shah, J.-P. Qu, Y.-B. Kang, J. Org. Chem. 2018, 83. 296; (d) C.
Schultze, B. Schmidt, J. Org. Chem. 2018, 83, 5210. For selected
examples of Horner–Wadsworth–Emmons reaction, see: (e) L.
Horner, H. Hoffmann, H. G. Wippel, G. Klahre, Chem. Ber. 1959,
92, 2499; (f) W. S. Wadsworth, W. D. Emmons, J. Am. Chem. Soc.
1961, 83, 1733; (g) J. Clayden, S. Warren, Angew. Chem. Int. Ed.
1996, 35, 241. For selected examples of Peterson olefination, see:
(h) D. J. Peterson, J. Org. Chem. 1968, 33, 780-784; (i) L. F. v.
Staden, D. Gravestock, D. J. Ager, Chem. Soc. Rev. 2002, 31, 195;
(j) M. C. Fernández, A. Díaz, J. J. Guillín, O. Blanco, M. Ruiz, V.
Ojea, J. Org. Chem., 2006, 71, 6958; (k) R. E. Beveridge, R. A.
Batey, Org. Lett., 2013, 15, 3086. For selected examples of Julia
olefination, see: (l) M. Julia, J.-M. Paris, Tetrahedron Lett. 1973,
14, 4833; (m) S. Banerjee, S. Sinha, P. Pradhan, A. Caruso, D.
Notes
The authors declare no competing financial interest.
Acknowledgments
This research was supported by the Shandong Provincial
Natural Science Foundation of China (Nos. ZR2017MB029,
ZR2017BB060), the Qingdao Science and Technology
Foundation (18-2-2-49-jch), the Qingdao University of
Science and Technology Talent Startup Fund Foundation
(QUSTHX201921) for financial support.
Liebowitz, D. Parrish, M. Rossi, B. Zajc, J. Org. Chem., 2016, 81
3983; (n) A. K. Simlandy, S. Mukherjee, J. Org. Chem., 2017, 82
4851.
,
,
Supplementary Material
Supplementary data associated with this article can be found,
in the online version, at
4
For selected examples of Heck coupling reaction, see: (a) R. F.
Heck, J. P. Nolley, J. Org. Chem. 1972, 37, 2320; (b) M. J. D.
Pires, D. L. Poeira, S. I. Purificação, M. M. B. Marques, Org. Lett.
2016, 18, 3250; (c) J. A. Carmona, V. Hornillos, P. Ramírez-
López, A. Ros, J. Iglesias-Sigüenza, E. Gómez-Bengoa, R.
Fernández, J. M. Lassaletta, J. Am. Chem. Soc. 2018, 140, 11067.
For selected examples of Suzuki coupling reaction, see: (d) K.
Ferré-Filmon, L. Delaude, A. Demonceau, A. F. Noels, Coord.
Chem. Rev. 2004, 248, 2323; (g) J. P. G. Rygus and C. M.
Crudden, J. Am. Chem. Soc. 2017, 139, 18124; (h) P. Guo, H.
Zhang, J. Zhou, F. Gallou, M. Parmentier, H. Wang, J. Org. Chem.
References
1
(a) S. Matar, L. F. Hatch, in Chemistry of Petrochemical Processes,
Gulf Professional Publishing, Woburn, 2001; (b) Henry, G. D.
Tetrahedron 2004, 60, 6043; (c) Michael, J. P. Nat. Prod. Rep.
2005, 22, 627; (d) T. Laird, Org. Process Res. Dev. 2006, 10, 851;
(e) L.-C. Campeau, K. Fagnou, Chem. Soc. Rev. 2007, 36, 1058; (f)
M. C. Bagley, C. Glover, E. A. Merritt, Synlett 2007, 2459; (g) S.
Wang, Y.-T. Chang, Chem. Commun. 2008, 1173; (h) J. C. Jung, E.
Lim, Y. Lee, J. M. Kang, H. Kim, S. Jang, S. Oh, M. Jung, Eur. J.
Med. Chem. 2009, 44, 3166; (i) D. Simoni, M. Roberti, F. P.
Invidiata, E. Aiello, S. Aiello, P. Marchetti, R. Baruchello, M.
Eleopra, A. Di Cristina, S. Grimaudo, N. Gebbia, L. Crosta, F.
Dieli, M. Tolomeo, Bioorg. Med. Chem. Lett. 2006, 16, 3245; (j)
N.-Y. Kang, H.-H. Ha, S.-W. Yun, Y. H. Yu, Y.-T. Chang, Chem.
Soc. Rev. 2011, 40, 3613; (k) Q. Li, J.-S. Lee, C. Ha, C. B. Park, G.
2018, 83, 7523; (i) D. M. Knoll, S. Bräse, ACS Omega, 2018, 3,
12158; (j) S. H. Nazari, J. E. Bourdeau, M. R. Talley, G. A.
Valdivia-Berroeta, S. J. Smith, D. J. Michaelis, ACS Catalysis,
2018, 8, 86.
5
6
(a) T. M. Trnka, R. H. Grubbs, Acc. Chem. Res. 2001, 34, 18; (b)
R. H. Grubbs, Handbook of Metathesis, WileyVCH, Weinheim,
2003
.
Yang, W. B. Gan, Y.-T. Chang, Angew. Chem. Int. Ed. 2004, 43
,
(a) C. Gunanathan, D. Milstein, Science 2013, 341, 1229712. (b) R.
H. Crabtree, Chem. Rev. 2015, 115, 127. (c) D. Deng, B. Hu, M.
Yang and D. Chen, Organometallics. 2018, 37, 2386; (d) P. J.
Llabres-Campaner, R. Ballesteros-Garrido, R. Ballesteros and B.
Abarca, J. Org. Chem. 2018, 83, 521.
(a) C. O. Tuck, E. Perez, I. T. Horvath, R. A. Sheldon, M. Poliakoff,
Science 2012, 337, 695; (b) T. P. Vispute, H. Zhang, A. Sanna, R.
Xiao, G. W. Huber, Science 2010, 330, 1222; (c) S. Michlik, R.
6331; (l) R. Fanelli, É. Besserer-Offroy, A. René, J. Côté, P.
Tétreault, J. Collerette-Tremblay, J.-M. Longpré, R. Leduc, J.
Martinez, P. Sarret, F. Cavelier, J. Med. Chem. 2015, 58, 7785; (m)
S. Jiang, G. Duan, U. Kuhn, M. Mörl, V. Altstädt, A. L. Yarin, A.
Greiner, Angew. Chem. Int. Ed. 2017, 56, 3285; (n) S. Jiang, S.
Agarwal, A. Greiner, Angew. Chem. Int. Ed. 2017, 56, 15520.
For selected examples, see: (a) M. Murakami, S. Hori, J. Am. Chem.
Soc. 2003, 125, 4720; (b) R. Dumeunier, I. E. Markó in Modern
Carbonyl Olefination: Methods and Applications (Ed.: T. Takeda),
Wiley-VCH, Weinheim, 2004; (c) L.-C. Campeau, S. Rousseaux,
K. Fagnou, J. Am. Chem. Soc. 2005, 127, 18020; (d) J.-P. Leclerc,
K. Fagnou, Angew. Chem., Int. Ed. 2006, 45, 7781; (e) K. S.
7
2
Kempe, Nature Chemistry 2013,
5, 140; (d) F. Kallmeier, R.
Kempe, Angew. Chem. Int. Ed. 2018, 57, 46.
G. Zhang, T. Irrgang, T. Dietel, F. Kallmeier, R. Kempe, Angew.
Chem. Int. Ed. 2018, 57, 9131.
M. K. Barman, S. Waiba, B. Maji, Angew. Chem. Int. Ed. 2018, 57
9126.
8
9
,
Kanyiva, Y. Nakao, T. Hiyama, Angew. Chem., Int. Ed. 2007, 46
8872; (f) L.-C. Campeau, M. Bertrand-Laperle, J.-P. Leclerc, E.
Villemure, S. Gorelsky, K. Fagnou, J. Am. Chem. Soc. 2008, 130
3266; (g) L.-C. Campeau, D. J. Shipper, K. Fagnou, J. Am. Chem.
Soc. 2008, 130, 3276; (h) A. Larivée, J. J. Mousseau, A. B.
Charette, J. Am. Chem. Soc. 2008, 130, 52; (i) Y. Nakao, K. S.
,
10 (a) B. Blank, R. Kempe, J. Am. Chem. Soc. 2010, 132, 924. (b) F.
Kallmeier, T. Irrgang, T. Dietel, R. Kempe, Angew. Chem. Int. Ed.
2016, 55, 11806; (c) F. Kallmeier, B. Dudziec, T. Irrgang, R. Kempe,
Angew. Chem. Int. Ed. 2017, 56, 7261; (d) N. Deibl, R. Kempe,
,

10
Tetrahedron
Angew. Chem. Int. Ed. 2017, 56, 1663; (e) C. Zhang, G. Zhang, S.
Luo, C. Wang, H. Li, Org. Biomol. Chem., 2018, 16, 8467.

Declaration of interests
☐ The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.
☐The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests:
The authors declare no competing financial interest.