Rh/O2-Catalyzed C8 Olefination of Quinoline N-Oxides with Activated and Unactivated Olefins

Article abstract of DOI:10.1021/acs.joc.8b03176

The rhodium/O₂ system-catalyzed distal C(sp²)-H olefination of quinoline N-oxides is developed. Molecular oxygen has been explored as an economic and clean oxidant, an alternative to inorganic oxidants. A wide substrate scope with respect to quinoline N-oxides and olefins (activated acrylates and styrenes; unactivated aliphatic olefins) demonstrates the robustness of the developed catalytic method. Interestingly, 2-substituted quinoline N-oxides also afforded good yields of the corresponding C8-olefinated products. Kinetic isotope studies and deuterium-labeling experiments have been performed to understand the preliminary mechanistic pathway. The applicability of the developed method is demonstrated by utilizing natural product-derived substrates and by converting the C8-olefinated quinoline N-oxides into various other useful molecules.

Full text of DOI:10.1021/acs.joc.8b03176

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Article
Rh/O2-Catalyzed C8 Olefination of Quinoline N-
oxides with Activated and Unactivated Olefins
Ritika Sharma, Rakesh Kumar, and Upendra Sharma
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03176 • Publication Date (Web): 29 Jan 2019
Downloaded from http://pubs.acs.org on January 29, 2019
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The Journal of Organic Chemistry
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Rh/O2-Catalyzed C8 Olefination of Quinoline N-oxides with
Activated and Unactivated Olefins
Ritika Sharma, Rakesh Kumar, and Upendra Sharma*
Natural Product Chemistry and Process Development Division and AcSIR, CSIR- IHBT, Palampur-176061, India
Supporting Information
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ABSTRACT: The rhodium/O2 system catalyzed distal C(sp2)-H olefination of quinoline N-oxides is developed. Molecular oxygen
has been explored as economic and clean oxidant, alternative to inorganic oxidants. Wide substrate scope with respect to quinoline
N-oxides and olefins (activated: acrylates, styrenes, and un-activated: aliphatic olefins) demonstrates the robustness of the developed
catalytic method. Interestingly, 2-substituted quinoline N-oxides also afforded good yields of the corresponding C8-olefinated prod-
ucts. Kinetic isotope studies and deuterium labeling experiments have been performed to understand the preliminary mechanistic
pathway. The applicability of the developed method is demonstrated by utilizing natural product derived substrates and by converting
the C8-olefinated quinoline N-oxides into various other useful molecules.
KEYWORDS: rhodium catalyst, molecular oxygen, quinoline N-oxides, olefins, olefination.
INTRODUCTION
In modern organic chemistry, transition metal catalyzed direct ox-
idative coupling via C-H bond functionalization has been consid-
ered as a specific step to reduce the waste generation and to achieve
high selectivity.1 Transition metal catalyzed methods involve re-
duction of a metal catalyst from higher oxidation state to lower ox-
idation state often for the completion of the catalytic cycle, a
stoichiometric amount of oxidant is required which leads to the
generation of unavoidable waste.2 For replacing these stoichiomet-
rically used metal and non-metal based oxidants, molecular O2, the
second most abundant gas in nature, is considered an appealing ox-
idant.3 Low cost and H2O as the sole byproduct further provide
strong motivation to use O2 as clean oxidant.3b, 4 In this perspective,
combining C-H activation methodology with molecular O2 as
oxidant, provide an ideal way towards green and sustainable chem-
ical processes.5
Swapping the common oxidants with molecular O2 is challenging
as it can be used as an oxidant in reactions involving β-hydride
elimination step but compatibility with reductive elimination is still
rare.6 The representative examples wherein O2 is utilized as oxidant
include, Rh-catalyzed method for the synthesis of acetic acid,7 Pd-
catalyzed C-H bond oxidation,8 Cu-catalyzed Sonogashira reaction
Scheme 1. Rh(III)/O2 Catalyzed Functionalization and Syn-
for the alkynylation of polyfluoroarenes with terminal alkynes,9
thesis of Nitrogen Containing Heterocyclic
Compounds
Ru‐ catalyzed annulation reaction,10 Pd-catalyzed hydroxylation
of arene,11 and Rh-catalyzed annulation etc.12
RESULTS AND DISCUSSION
Synthesis and functionalization of nitrogen-containing heterocyclic
scaffolds are important due to their use in organic synthesis, mate-
rial science, and drugs.13 In this regard, quinolines play a central
role due to their medicinal benefits and are also an invaluable tem-
plate in asymmetric synthesis.14 Indeed, various methods have been
explored already for regioselective functionalization at C2 position
of quinoline,15 but C8 position still necessitates immediate expedi-
tious efforts.16 Although, catalytic methods have been developed
already for C-C,17 C-N18 and C-X (halogen)18 bond formation at
the C8 position of quinoline, use of a stoichiometric amount of
metal oxidant warrant further improvement. On the other hand,
Rh/O2-catalytic system have also been explored for the functional-
ization and synthesis of different nitrogen-containing heterocy-
cles,12, 19 any such example in case of distal C8 bond functionali-
zation of quinoline is still awaited (Scheme 1). Recently, we have
reported C8 olefination of quinoline by using Rh(III)-catalyst and
Cu(OAc)2.H2O as oxidant (Scheme 1).17f Herein we disclose an op-
erationally simple Rh(III)/O2-catalyzed direct C8 olefination of
quinoline N-oxide with acrylates, styrenes and aliphatic olefins
(Scheme 1).
One of the major synthetic target in organic synthesis is to utilize
molecular oxygen as an oxidant and henceforth we initiated to ex-
amine the reaction between quinoline N-oxide (1a) and ethyl acry-
late (2a) in the presence of [RhCp*Cl2]2/AgSbF6 catalyst, acetic
acid as additive and DCE as solvent, under O2 atmosphere at 100
°C. Unfortunately, the product was not observed due to sluggish
reaction (Table 1, entry 5). Optimization with various solvents gave
inappropriate results at 100 °C whereas at lower temperature com-
paratively better results were observed. Although, good yields were
observed in case of EtOH/H2O at 70 °C, the maximum yield of 77%
was obtained using acetone as solvent (Table 1, entries 6-8). Fur-
ther, lowering the temperature or time of reaction resulted in a
lower yield of the desired product (Table 1, entries 9-10). Increase
or diminution in the catalyst loading lowers the yield of the
expected product (Table 1, entries 11-12). Alteration in the Rh-cat-
alyst or Ag-salt does not prove good for current reaction (Table 1,
entries 13 and 14). To our delight, use of 2 equiv. of acetic acid at
70 °C for 24 h under O2 atmosphere provided 86% of the desired
product (Table 1, entry 1). Furthermore, the control experiments
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(Table 1, entries 2-4) revealed that Rh(III)/ AgSbF6, acetic acid as
an additive and O2 atmosphere are mandatory for current transfor-
mation. Other pivotal reaction conditions addressing the effect of
altered parameters were also monitored for critical optimization.
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Table 2. Scope with Quinoline N-oxidesa
Table 1. Optimization Studya
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entry
variation from standard condition
3a yield (%)[b]
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None
without catalyst
86 (82)[c]
n.d.
without AcOH
N2 atmosphere
n.d.
traces
n.d.
DCE, AcOH (1 equiv.), 100 °C
EtOH, AcOH (1 equiv.)
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H2O, AcOH (1 equiv.)
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(CH3)2CO, AcOH (1 equiv.)
at room temperature
12 h
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[Cp*RhCl2]2 (10 mol%)/ AgSbF6 (40 mol%)
[Cp*RhCl2]2 (2.5 mol%)/ AgSbF6 (10 mol%)
[Rh(acac)(nbd)] instead of [Cp*RhCl2]2
AgBF4 instead of AgSbF6
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areaction conditions: 1 (0.10 mmol), 2 (0.20 mmol), [Cp*RhCl2]2 (5 mol%), AgSbF6
(20 mol%), acetic acid (2 equiv.), acetone (0.22 M), 70 oC, 24 h.
Traces
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10
Under our earlier developed reaction conditions for C8-olefina-
tion17f and alkylation17g either lower yield of C8-olefinated product
(I)/no reaction or 3-hydroxyquinoline 8-yl propanoates derivatives
(II)17i were observed in case of 2-substituted quinolines (Scheme
2). To our delight, 2-methyl quinoline N-oxide (4a) reacted
smoothly with 2a affording the C8 olefinated product (5a) in 76%
yield under current reaction conditions. Various other 2-substituted
quinoline N-oxides were reacted with different acrylates under
developed reaction conditions (Table 3). Use of methyl or n-butyl
acrylate in place of 2a did not affect the output of the reaction and
provided better yields (78-81%) of the corresponding desired prod-
uct (5b-c). Interestingly, 2-phenyl and 2,6-disubstituted quinoline
N-oxides also reacted well with 2a, affording 5d-g in 75-89%
yields.
Without AgSbF6
areaction conditions: 1a (0.10 mmol), 2a (0.20 mmol), [Cp*RhCl ] (5 mol%), AgSbF6
2
2
(20 mol%), acetic acid (2 equiv.), acetone (0.22 M), 70 oC, 24 h. bYield based on
NMR analysis of crude reaction mixture using DMF as an internal standard. cIsolated
yield in parentheses.
With the best optimized condition, scope of reaction was explored
by reacting various substituted quinoline N-oxides with 2a (Table
2). Reaction of 1a with 2a using [RhCp*Cl2]2/ AgSbF6 (5 mol%/
20 mol%) catalyst and acetic acid (2 equiv.) as an additive in the
presence of acetone at 70 °C under O2 atmosphere for 24 h afforded
3a in 82% isolated yield. The catalytic method was found to be
compatible with electron donating methyl group at C3, C4, and C6
positions of quinoline N-oxide affording moderate to good yields
of C8 olefinated product (3b-d, 51-76%). Unfortunately, the 7-me-
thyl and 5-nitro quinoline N-oxide were not found compatible
under developed reaction conditions as in both cases no product
was observed (3e-f). This might be due to steric hindrance in case
of methyl at C7 and strong electron withdrawing effect of 5-nitro
group. The 5-Cl substituted quinoline N-oxide was also found
compatible affording product (3g, 71%) in good yield. Quinoline
N-oxide with substituents such as –tBu, -OMe and –CO2Me at C6
position reacted smoothly affording the olefinated product in 68-
78% yields (3h-j). Notably, the halogen substituents such as –F, -
Cl and –Br were well tolerated giving corresponding C8-substi-
tuted product (3k-m) with 61-70% yields, providing an opportunity
for further functionalization. The current method is also applicable
for the polycyclic quinolines including benzo[f]quinoline and phe-
nanthridine affording the corresponding desired product in good
yields (3n-o).
Scheme 2. Reaction of 2-Substituted Quinoline N-oxide with
an Olefin
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them interesting and challenging substrates.20 Reaction of 1a with
vinyl cyclohexane, allyl cyclohexane, 1-hexene and 1-heptene (7o-
r) provided the desired products (8o-r) in 57-62% yields. These
reactions demonstrate the generality of developed Rh(III)/O2 cata-
lytic system with respect to olefins.
Table 3. Scope with 2-Substituted Quinoline N-oxidesa
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Table 5. Scope with Styrenes and Aliphatic Olefinsa
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areaction conditions: 1 (0.10 mmol), 2 (0.20 mmol), [Cp*RhCl2]2 (5 mol%), AgSbF6
(20 mol%), acetic acid (2 equiv.), acetone (0.22 M), 70 oC, 24 h.
After successfully exploring the substrate scope with various quin-
oline N-oxides, the substrate scope with acrylates was attempted
(Table 4).
Table 4. Scope with Acrylatesa
areaction conditions: 1 (0.10 mmol), 2 (0.20 mmol), [Cp*RhCl2]2 (5 mol%), AgSbF6
(20 mol%), acetic acid (2 equiv.), acetone (0.22 M), 70 oC, 24 h.
To probe the mechanism of Rh(III)/O2 system various preliminary
experiments were performed (Scheme 3). The rhodacycle complex
prepared via earlier reported method,17f was found successful to
catalyze the current reaction, indicating its intermediacy in the cat-
alytic cycle. Deuterium lebeling experiments were performed with
methanol-d4 and acetic acid-d4. In deuterium labeling experi-
ments, deuteration was observed at C8 position of quinoline N-ox-
ide in the presence or absence of acrylate (2a) under standard reac-
tion conditions indicating the reversible nature of initial C-H acti-
vation step (Scheme 3). To get insight into the kinetics of the
reaction, competition and two parallel experiments were carried out
by reacting 1a and 1a-d7 with 2a under standard reaction conditions
for 5 h. The KH/KD ratio was 1.85 and 1.26 in case of competition
and parallel reactions, respectively, suggesting that C-H bond
cleavage may not be the rate-determining step (Scheme 3).21 Com-
petitive control experiment revealed that electron rich quinoline N-
oxides are more favorable than electron poor substrates with ethyl
acrylate for the formation of product (SI).
areaction conditions: 1 (0.10 mmol), 2 (0.20 mmol), [Cp*RhCl2]2 (5 mol%), AgSbF6
(20 mol%), acetic acid (2 equiv.), acetone (0.22 M), 70 oC, 24 h.
A wide range of acrylates including methyl, n-butyl, t-butyl, cyclo-
hexyl, and polyfluorinated acrylates reacted successfully affording
the desired alkenylated product in good yields (6a-f). Sterically
hindered tert-butyl methacrylate and benzyl methacrylate success-
fully underwent this coupling reaction, affording 6g-h in moderate
yields. Acrylate substrate derived from bulky alcohol as well as
from natural products such as 3-hydroxy adamantane, 9-anthranyl
methyl, vitamin E, and estrone also reacted successfully (entries 6i-
l).
In addition to acrylates, styrenes and aliphatic olefins also worked
well under developed reaction condition (Table 5). Various sty-
rene’s substituted with electron-rich as well as electron-deficient
functional groups at -ortho, -meta or -para positions of phenyl ring
were well compatible with the current Rh(III)/O2 catalytic system,
affording the desired products in 67-81% yields (8a-j). Other sub-
stituted olefins such as penta-fluoro styrene, 1-vinyl naphthalene,
and 2-vinylnaphthalene also reacted smoothly to provide 8k-m in
59-73% yields. Moreover, (vinylsulfonyl)benzene also provided
the desired product (8n) in 61% yield under standard conditions.
The abundance and unreactive nature of aliphatic olefins made
Scheme 3. Deuterium Labeling Experiments
On the basis of preliminary experiments and literature, a tentative
mechanistic pathway has been proposed (Scheme 4).17 Initially, the
[RhCp*Cl2]2 precursors in the presence of AgSbF6 and acetic acid
give active Rh (III) species (A) which reacts with 1a to form five-
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membered rhodacycle (B). Intermediate B was able to catalyze the
olefinated quinoline N-oxide was further converted into various
reaction and also detected in ESI-MS analysis of crude reaction
mixture. Olefin interaction with rhodacycle (B), followed by inser-
tion leads to the formation of intermediate D. The subsequent β-
hydride elimination provided species F (detected in ESI-MS). In
the presence of O2 and AcOH, Rh(III) might be regenerated from
species F to continue the catalytic cycle along with the formation
of desired product (3a).
other valuable molecules to demonstrate the synthetic utility of the
developed catalytic method. The current catalytic system found its
utility by avoiding any post-work up as well as organic or inorganic
oxidants.
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EXPERIMENTAL SECTION
General information
All reactions were carried out in screw cap reaction vials under air
atmosphere. All solvents were bought from Aldrich in sure-seal
bottle and used as such. Chemicals were bought from Sigma Al-
drich, Alfa-aesar and TCI. For column chromatography, silica gel
(230-400 mesh) from Merck was used. A gradient elution using n-
hexane and ethyl acetate was performed based on Merck alumin-
ium TLC sheets (silica gel 60F254).
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Analytical information: All isolated compounds are character-
1
ized by H NMR, 13C NMR, IR and LC-MS. Mass spectra were
recorded on Water Q-ToF-Micro Micromass. Nuclear magnetic
resonance spectra were recorded either on a Bruker-Avance 600 or
300 MHz instrument. Copies of 1H and 13C NMR are provided in
1
supporting information. All H NMR experiments are reported in
units, parts per million (ppm) and were measured relative to the
signals for residual chloroform (7.24), Methanol (3.31 and 4.78)
and acetone (2.05) in the deuterated solvents. All 13C NMR spectra
were reported in ppm relative to deuterated chloroform (77.23),
methanol (49.15) and acetone (29.92 and 206.68) and all were ob-
tained with 1H decoupling. The melting points were recorded on a
Bronsted Electrothermal 9100.
Scheme 4. Probable Reaction Pathway
General procedure for the preparation of Quinoline N-Ox-
ides.24
Utility of current method was demonstrated by functionalization of
3a and 8a under various metal-free conditions (Scheme 5). Product
3a and 8a were successfully converted to corresponding 2-aryl-8-
olefinated quinoline N-oxides (3aa and 8aa) by following the liter-
ature procedures.22 Reduction using phenylboronic acid afforded
alkenylated product in good yields (3ab and 8ab).23 C2 chlorina-
tion17a and methoxylation17a, 24 of product 8a afforded correspond-
ing products in 81 and 89% yields, respectively.
All solid reactants, m-CPBA (4 mmol) and quinoline (2 mmol)
were added in schlenk tube and put under vacuum for 2 h, then
CH2Cl2 (4 mL) was added at 0 °C. The reaction was allowed to
stirred at room temperature for 12 h. On completion, the reaction
mixture was extracted with ethyl acetate and organic extract was
dried over Na2SO4, filtered and concentrated under reduced pres-
sure. The crude product was purified by flash chromatography on
silica gel (230-400 mesh size) with n-hexane: EtOAc to afford de-
sired N-Oxide. All synthesized N-oxides are known compounds
[(1b-e, 1g, 1k, 1l and 1m),24c (1f, 1h),24d 1i,24e 1n,24f 1o,24g 4a-c,24h
4d,15f 4e,24i 4f,18 4g24j].
Characterization Data. 5-Nitro quinoline 1-oxide (1f).24d Yellow
precipitates, yield = 304 mg (80%). Isolated from flash chromatog-
1
raphy (85% EtOAc/ n-hexane; silica gel 230-400 mesh size). H
NMR (600 MHz, CDCl3, δ): 9.16 (d, J = 8.4 Hz, 1H), 8.73 (d, J =
6.6 Hz, 1H), 8.60 (d, J = 9.0 Hz, 1H), 8.50 (d, J = 7.8 Hz, 1H), 7.93
– 7.90 (m, 1H), 7.62 – 7.59 (m, 1H). 13C{1H} NMR (150 MHz,
CDCl3, δ): 146.0, 142.1, 136.8, 128.9, 126.9, 126.4, 124.0, 123.9,
122.4.
6-tert-butyl quinoline 1-oxide (1h).24d Pale Yellow liquid, yield
= 290 mg (72%). Isolated from flash chromatography (92%
1
EtOAc/ n-hexane; silica gel 230-400 mesh size). H NMR (600
MHz, CDCl3, δ): 8.66 (d, J = 9.6 Hz, 1H), 8.56 (d, J = 6.6 Hz, 1H),
7.89 – 7.87 (m, 1H), 7.80 – 7.79 (m, 2H), 7.31 (dd, J = 8.4, 6.0 Hz,
1H), 1.43 (s, 9H). 13C{1H} NMR (150 MHz, CDCl3, δ): 152.2,
139.7, 135.5, 130.5, 129.8, 127.3, 123.2, 120.8, 119.3, 35.1, 31.0.
Scheme 5. Functionalization of C8-Olefinated Product
General Procedure for C8 Olefination of Quinoline N-Oxides
with Olefins. To an oven-dried screw cap reaction vial charged
with a spinvane magnetic stir-bar, [Cp*RhCl2]2 (5 mol%) and
AgSbF6 (20 mol%) were added. Depending on the physical state of
the quinoline N-oxide (0.1 mmol) and olefin (0.2 mmol), solid
compounds were weighed along with the other reagents, whereas
In summary, an operationally simple Rh(III)/O2 based catalytic
system for C8 functionalization of quinoline N-oxides with a wide
range of substrates including 2-substituted quinolines and aliphatic
olefins under milder reaction conditions has been developed. More
than fifty quinoline N-oxide derivatives were synthesized. C8
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liquid reagents, AcOH (2 equiv.) were added by micropipette and
122.4, 122.3, 120.0, 60.5, 14.2. IR (ZnSe) νmax (cm-1): 3078, 2981,
1707, 1631, 1313, 1178, 1103, 1024, 939, 835, 752. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C14H13ClNO3, 278.0578; found,
278.0565.
acetone was added by laboratory syringe, respectively. The reac-
tion vial was closed with screw cap and the reaction mixture was
purged with O2 using baloon. Then kept for vigorous stirring on a
preheated heating block at 70 °C for 24 h. After completion, the
reaction mixture was allowed to cool, filtered through celite and
washed with DCM. Collected DCM fraction of crude reaction mix-
ture was evaporated under reduced pressure. The residue was puri-
fied by flash chromatography using silica gel (230-400 mesh size)
or using acidic alumina and n-hexane: EtOAc as eluent.
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(E)-6-(tert-Butyl)-8-(3-ethoxy-3-oxoprop-1-en-1-yl)quinoline 1-
oxide (Table 2, entry 3h). Yellow liquid, yield = 22.3 mg (74%).
Isolated from flash chromatography (79% EtOAc/ n-hexane; silica
gel 230-400 mesh size). 1H NMR (300 MHz, CDCl3, δ): 9.13 (d, J
= 15.6 Hz, 1H), 8.31 (d, J = 6.0 Hz, 1H), 7.66 – 7.57 (m, 3H), 7.17
(dd, J = 8.4, 6.0 Hz, 1H), 5.91 (d, J = 15.6 Hz, 1H), 4.18 (q, J = 7.2
Hz, 2H), 1.30 (s, 9H), 1.27 – 1.23 (m, 3H). 13C{1H} NMR (75
MHz, CDCl3, δ): 166.6, 151.4, 147.3, 138.1, 136.7, 131.9, 131.2,
130.5, 126.5, 125.0, 121.3, 119.0, 60.4, 34.9, 30.9, 14.3. IR (ZnSe)
νmax (cm-1): 2985, 1715, 1628, 1161, 1043, 961, 730, 657. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C18H22NO3, 300.1594; found,
300.1609.
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-6-methoxyquinoline (Ta-
ble 2, entry 3i). Brown liquid, yield = 18.6 mg (68%). Isolated from
flash chromatography (88% EtOAc/ n-hexane; silica gel 230-400
mesh size). 1H NMR (600 MHz, CDCl3, δ): 9.12 (d, J = 15.6 Hz,
1H), 8.31 (d, J = 6.0 Hz, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.26 – 7.20
(m, 2H), 7.09 (d, J = 3.0 Hz, 1H), 5.97 (d, J = 15.6 Hz, 1H), 4.27
(q, J = 7.2 Hz, 2H), 3.93 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H). 13C{1H}
NMR (150 MHz, CDCl3, δ): 166.4, 158.3, 146.3, 135.4, 135.3,
133.3, 133.1, 125.5, 123.3, 121.7, 119.1, 107.1, 60.3, 55.7, 14.2. IR
(ZnSe) νmax (cm-1): 2962, 1898, 1328, 1215, 1164, 840, 751. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C15H16NO4, 274.1074; found,
274.1066.
9
Characterization Data. (E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)
quinoline 1-oxide (Table 2, entry 3a). White transparent precipi-
tates, yield = 20 mg (82%). mp 142-144 °C. Isolated from chroma-
tography (90% EtOAc/ n-hexane; silica gel 230-400 mesh size). 1H
NMR (600 MHz, CD3OD, δ): 9.18 (d, J = 15.6 Hz, 1H), 8.61 (d, J
= 6.0 Hz, 1H), 8.11 (dd, J = 19.8, 8.4 Hz, 2H), 7.83 (d, J = 7.2 Hz,
1H), 7.75 - 7.72 (m, 1H), 7.52 – 7.55 (m, 1H), 6.08 (d, J = 15.6 Hz,
1H), 4.27 (dd, J = 14.4, 7.2 Hz, 2H), 1.34 (t, J = 7.2 Hz, 3H).
13C{1H} NMR (150 MHz, CD3OD, δ): 166.9, 146.7, 138.7, 138.3,
132.2, 132.1, 130.5, 130.3, 129.6, 128.6, 121.7, 118.4, 60.2, 13.2.
IR (ZnSe) νmax (cm-1): 2961, 1716, 1580, 1324, 1093, 1002, 734.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C14H14NO3, 244.0968;
found, 244.0950.
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14
15
16
17
18
19
20
21
22
23
24
25
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27
28
29
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32
33
34
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37
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55
56
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59
60
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-3-methylquinoline
1-
oxide (Table 2, entry 3b). Pale yellow precipitates, yield = 15.2 mg
(59%). mp 190-191 °C. Isolated from column chromatography
(70% EtOAc/ n-hexane; acidic alumina). 1H NMR (300 MHz,
CDCl3, δ): 9.21 (d, J = 15.6 Hz, 1H), 8.37 (s, 1H), 7.78 (dd, J = 6.9,
3.0 Hz, 1H), 7.56 – 7.53 (m, 3H), 6.00 (d, J = 15.6 Hz, 1H), 4.32 –
4.25 (m, 2H), 2.45 (s, 3H), 1.36 (t, J = 7.2 Hz, 3H). 13C{1H} NMR
(150 MHz, CDCl3, δ): 166.6, 146.8, 139.0, 137.6, 131.9, 131.6,
131.2, 130.88, 130.85, 129.3, 128.5, 119.1, 60.5, 18.4, 14.4. IR
(ZnSe) νmax (cm-1): 2954, 1721, 1610, 1338,1078, 935, 780. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C15H16NO3, 258.1125; found,
258.1133.
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-4-methylquinoline 1-ox-
ide (Table 2, entry 3c). Brownish liquid, yield = 13.2 mg (51%).
Isolated from column chromatography (76% EtOAc/ n-hexane;
acidic alumina). 1H NMR (600 MHz, CDCl3, δ): 9.19 (d, J = 15.6
Hz, 1H), 8.37 (d, J = 6.0 Hz, 1H), 7.97 (s, 1H), 7.63 – 7.59 (m, 2H),
7.14 (d, J = 6.0 Hz, 1H), 5.94 (d, J = 15.6 Hz, 1H), 4.28 – 4.25 (m,
2H), 2.64 (s, 3H), 1.33 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (150
MHz, CDCl3, δ): 166.7, 147.4, 139.2, 136.5, 134.8, 132.1, 131.4,
131.0, 128.1, 126.1, 122.1, 118.5, 60.4, 18.9, 14.4. IR (ZnSe) νmax
(cm-1): 2922, 1706, 1623, 1305, 1179, 1096, 963, 795. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C15H16NO3, 258.1125; found,
258.1133.
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-6-(methoxycar-
bonyl)quinoline 1-oxide (Table 2, entry 3j). Brown liquid, yield =
20.8 mg (69%). Isolated from flash chromatography (85% EtOAc/
n-hexane; silica gel 230-400 mesh size). 1H NMR (600 MHz,
CDCl3, δ): 9.14 (d, J = 15.6 Hz, 1H), 8.57 – 8.54 (m, 2H), 8.19 (s,
1H), 7.83 (d, J = 8.4 Hz, 1H), 7.39 – 7.37 (m, 1H), 6.07 (d, J = 15.6
Hz, 1H), 4.29 (q, J = 7.2 Hz, 2H), 4.01 (s, 3H), 1.35 (t, J = 7.2 Hz,
3H). 13C{1H} NMR (150 MHz, CDCl3, δ): 166.7, 165.5, 146.2,
141.6, 139.3, 132.7, 132.4, 131.8, 131.1, 130.3, 127.7, 122.7,
120.4, 60.9, 53.2, 14.7. IR (ZnSe) νmax (cm-1): 3059, 1723, 1712,
1630, 1443, 1377, 1214, 1176, 1137, 1032, 802, 766. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C16H16NO5, 302.1023; found,
302.1005.
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-6-fluoroquinoline 1-ox-
ide (Table 2, entry 3k). Brown liquid, yield = 17.5 mg (67%). Iso-
lated from flash chromatography (82% EtOAc/ n-hexane; silica gel
1
230-400 mesh size). H NMR (600 MHz, CDCl3, δ): 9.10 (d, J =
15.6 Hz, 1H), 8.47 (d, J = 6.0 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H),
7.50 (dd, J = 7.8, 2.4 Hz, 1H), 7.41 (dd, J = 9.0, 2.4 Hz, 1H), 7.36
(dd, J = 8.4, 6.0 Hz, 1H), 6.02 (d, J = 15.6 Hz, 1H), 4.29 (dd, J =
14.4, 7.2 Hz, 2H), 1.36 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (150
MHz, CDCl3, δ): 166.2, 160.65 (JCF = 250.5 Hz), 145.4, 137.1,
136.7, 134.86 (JCF = 9.0 Hz), 133.07 (JCF = 10.5 Hz), 126.5, 122.6,
121.20 (JCF = 27.0 Hz), 120.2, 112.87 (JCF = 22.5 Hz), 60.6, 14.3.
19F NMR (565 MHz, CDCl3, δ): -110.2. IR (ZnSe) νmax (cm-1):
3079, 2981, 1707, 1619, 1573, 1383, 1270, 1175, 880, 658. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C14H13FNO3, 262.0874; found,
262.0870.
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-6-methylquinoline
1-
oxide (Table 2, entry 3d). Brown liquid, yield = 19.6 mg (76%).
Isolated from column chromatography (82% EtOAc/ n-hexane;
acidic alumina). 1H NMR (300 MHz, CDCl3, δ): 9.07 (d, J = 15.6
Hz, 1H), 8.27 (s, 1H), 7.55 – 7.48 (m, 2H), 7.33 (s, 1H), 7.16 – 7.11
(m, 1H), 5.87 (d, J = 15.9 Hz, 1H), 4.19 – 4.12 (m, 2H), 2.38 (s,
3H), 1.22 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (75 MHz, CDCl3, δ):
166.6, 146.8, 138.5, 138.1, 136.8, 133.7, 132.0, 131.1, 128.7,
126.4, 121.4, 119.0, 60.3, 21.1, 14.3. IR (ZnSe) νmax (cm-1): 2981,
1701, 1628, 1160, 1031, 657. HRMS (ESI-TOF) m/z: calcd for
C15H16NO3 [M + H]+ 258.1125; found 258.1128.
(E)-6-Chloro-8-(3-ethoxy-3-oxoprop-1-en-1-yl)quinoline
1-
oxide (Table 2, entry 3l). Brown precipitates, yield = 17 mg (61%).
mp 111-112 °C. Isolated from flash chromatography (80% EtOAc/
n-hexane; silica gel 230-400 mesh size). 1H NMR (600 MHz,
CDCl3, δ): 9.09 (d, J = 15.6 Hz, 1H), 8.46 (d, J = 6.0 Hz, 1H), 7.86
(d, J = 2.4 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 1.2 Hz,
1H), 7.35 - 7.33 (m, 1H), 6.02 (d, J = 15.6 Hz, 1H), 4.30 (q, J = 7.2
Hz, 2H), 1.37 – 1.35 (m, 3H). 13C{1H} NMR (150 MHz, CDCl3,
δ): 166.2, 145.3, 138.4, 137.4, 134.4, 133.7, 132.6, 131.7, 128.0,
125.2, 122.6, 120.1, 60.6, 14.3. IR (ZnSe) νmax (cm-1): 3038, 2984,
2349, 1709, 1627, 1373, 1188, 1029, 827, 757, 688. HRMS (ESI-
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-5-chloroquinoline
1-
oxide (Table 2, entry 3g). Brown liquid, yield = 19.7 mg (71%).
Isolated from flash chromatography (84% EtOAc/ n-hexane; silica
gel 230-400 mesh size). 1H NMR (600 MHz, CDCl3, δ): 9.08 (d, J
= 16.2 Hz, 1H), 8.45 (dd, J = 6.0, 1.2 Hz, 1H), 8.02 (d, J = 2.4 Hz,
1H), 7.69 – 7.71 (m, 1H), 7.63 (dd, J = 8.4, 1.2 Hz, 1H), 7.32 (dd,
J = 8.4, 6.0 Hz, 1H), 6.0 (d, J = 15.6 Hz, 1H), 4.27 – 4.30 (m, 2H),
1.35 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (150 MHz, CDCl3, δ):
166.1, 145.1, 138.6, 137.3, 134.1, 133.6, 132.8, 131.3, 124.8,
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TOF) m/z: [M + H]+ calcd for C14H13ClNO3, 278.0578; found,
278.0591.
(E)-6-Bromo-8-(3-ethoxy-3-oxoprop-1-en-1-yl)quinoline 1-ox-
1H), 7.55 – 7.45 (m, 2H), 7.30 – 7.27 (m, 1H), 5.91 (d, J = 15.6 Hz,
1H), 4.19 – 4.15 (m, 2H), 2.61 (s, 3H), 1.70 – 1.60 (m, 2H), 1.42 –
1.35 (m, 2H), 0.93 – 0.88 (t, J = 7.5, 3H). 13C{1H} NMR (75 MHz,
CDCl3, δ): 166.8, 147.6, 139.7, 131.8, 131.3, 130.5, 129.8, 129.7,
127.4, 125.8, 123.4, 118.6, 64.3, 30.8, 19.2, 19.0, 13.8. IR (ZnSe)
νmax (cm-1): 2957, 1703, 1625, 1328, 1163, 900, 825, 761, 651.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C17H20NO3, 286.1438;
found, 286.1422.
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-2-phenyl 1-oxide (Table
3, entry 5d). Brown liquid, yield = 25.2 mg (79%). Isolated from
column chromatography (25% EtOAc/ n-hexane; acidic alumina).
1H NMR (600 MHz, CDCl3, δ): 9.19 (d, J = 15.6 Hz, 1H), 7.92 –
7.90 (m, 2H), 7.87 (dd, J = 7.8, 1.8 Hz, 1H), 7.75 (d, J = 8.4 Hz,
1H), 7.64 – 7.62 (m, 1H), 7.58 (t, J = 7.8 Hz, 1H), 7.54 – 7.46 (m,
4H), 5.97 (d, J = 15 Hz, 1H), 4.28 – 4.24 (m, 2H), 1.33 (t, J = 7.2
Hz, 3H). 13C{1H} NMR (150 MHz, CDCl3, δ): 166.8, 147.9, 146.5,
140.6, 133.4, 132.2, 132.1, 131.0, 129.7, 129.6, 129.5, 128.4,
128.1, 125.5, 123.9, 118.3, 60.3, 14.4. IR (ZnSe) νmax (cm-1): 3059,
2980, 1703, 1631, 1598, 1365, 1174, 1026, 758, 690. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C20H18NO3, 320.1281; found,
320.1290.
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-2,6-dimethylquinoline 1-
oxide (Table 3, entry 5e). Yellow liquid, yield = 24.1 mg (89%).
Isolated from flash chromatography (72% EtOAc/ n-hexane; silica
gel 230-400 mesh size). 1H NMR (300 MHz, CDCl3, δ): 9.20 (d, J
= 15.6 Hz, 1H), 7.59 – 7.55 (m, 2H), 7.43 (s, 1H), 7.29 (d, J = 8.4
Hz, 1H), 5.95 (d, J = 15.9 Hz, 1H), 4.31 – 4.24 (m, 2H), 2.65 (s,
3H), 2.50 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (75 MHz,
CDCl3, δ): 166.7, 147.6, 146.7, 138.3, 137.5, 133.8, 131.1, 130.7,
128.7, 125.3, 123.4, 118.7, 60.3, 21.0, 18.9, 14.4. IR (ZnSe) νmax
(cm-1): 2983, 1703, 1628, 1573, 1386, 1325, 1100, 1030, 854, 650.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H18NO3, 272.1281;
found, 272.1296.
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-2-methyl-6-bromoquino-
line 1-oxide (Table 3, entry 5f). Light yellow liquid, yield = 25.2
mg (75%). Isolated from column chromatography (50% EtOAc/ n-
hexane; acidic alumina). 1H NMR (600 MHz, CDCl3, δ): 9.10 (d, J
= 15.6 Hz, 1H), 7.97 (d, J = 1.8 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H),
7.55 (d, J = 8.4 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 5.97 (d, J = 15.6
Hz, 1H), 4.30 – 4.26 (m, 2H), 2.64 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H).
13C{1H} NMR (150 MHz, CDCl3, δ): 166.3, 147.7, 146.0, 138.7,
134.3, 133.4, 131.6, 131.3, 124.5, 124.2, 121.2, 119.6, 60.5, 19.0,
14.4. IR (ZnSe) νmax (cm-1): 3064, 2981, 2924, 1705, 1631, 1558,
1307, 1238, 1172, 1033, 862, 767. HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C15H15BrNO3, 336.0230; found, 336.0213.
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-2-methyl-6-nitroquino-
line 1-oxide (Table 3, entry 5g). Brown sticky liquid, yield = 23.3
mg (77%). Isolated from column chromatography (54% EtOAc/ n-
hexane; acidic alumina). 1H NMR (600 MHz, CDCl3 + (CD3)2CO,
δ): 9.11 (d, J = 15.6 Hz, 1H), 8.75 (d, J = 2.4 Hz, 1H), 8.33 (d, J =
2.4 Hz, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 8.4 Hz, 1H), 6.09
(d, J = 15.6 Hz, 1H), 4.31 (q, J = 7.2 Hz, 2H), 2.71 (s, 3H), 1.37 (t,
J = 7.2 Hz, 3H). 13C{1H} NMR (150 MHz, CDCl3 + (CD3)2CO, δ):
166.4, 151.1, 146.0, 145.8, 142.0, 134.5, 130.4, 126.4, 125.9,
125.6, 124.5, 120.9, 61.1, 19.6, 14.7. IR (ZnSe) νmax (cm-1): 2961,
1720, 1626, 1333, 1257, 1082, 1027, 794. HRMS (ESI-TOF) m/z:
calcd for C15H15N2O5 [M + H]+ 303.0975; found 303.0983.
(E)-8-(3-Methoxy-3-oxoprop-1-en-1-yl)quinoline 1-oxide (Ta-
ble 4, entry 6a). Yellow sticky liquid, yield = 17.7 mg (77%). Iso-
lated from flash chromatography (84% EtOAc/ n-hexane; silica gel
230-400 mesh size). 1H NMR (600 MHz, CD3OD, δ): 9.12 (d, J =
15.6 Hz, 1H), 8.54 (d, J = 6.0, 1.2 Hz, 1H), 8.01 (d, J = 8.4, 1.2 Hz,
1H), 7.98 – 7.96 (m, 1H), 7.72 – 7.71 (m, 1H), 7.64 – 7.61 (m, 1H),
7.46 (q, J = 8.4, 6 Hz, 1H), 6.04 (d, J = 15.6 Hz, 1H), 3.80 (s, 3H).
13C{1H} NMR (150 MHz, CD3OD, δ): 167.3, 146.9, 138.4, 138.2,
132.1, 131.9, 130.3, 130.2, 129.4, 128.5, 121.6, 117.9, 50.8. IR
(ZnSe) νmax (cm-1): 2923, 1693, 1434, 1307, 1201, 1185, 819, 787.
1
2
3
4
5
6
7
8
ide (Table 2, entry 3m). Yellow precipitates, yield = 22.6 mg
(70%). mp 126-127 °C. Isolated from flash chromatography (80%
1
EtOAc/ n-hexane; silica gel 230-400 mesh size). H NMR (600
MHz, CDCl3, δ): 9.09 (d, J = 15.6 Hz, 1H), 8.47 (d, J = 6 Hz, 1H),
8.03 (d, J = 1.8 Hz, 1H), 7.71 (d, J = 1.2 Hz, 1H), 7.65 (d, J = 8.4
Hz, 1H), 7.33 (dd, J = 8.4, 6 Hz, 1H), 6.02 (d, J = 15.6 Hz, 1H),
4.30 (dd, J = 13.8, 7.2 Hz, 2H), 1.36 (t, J = 7.2 Hz, 3H). 13C{1H}
NMR (150 MHz, CDCl3 δ): 166.2, 145.2, 138.7, 137.4, 134.2,
133.7, 132.9, 131.4, 125.0, 122.5, 122.4, 120.2, 60.6, 14.3. IR
(ZnSe) νmax (cm-1): 3099, 3035, 2349, 1709, 1622, 1558, 1445,
1388, 1165, 1025, 755, 658. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C14H13BrNO3, 322.0073; found, 322.0065.
(E)-5-(3-Ethoxy-3-oxoprop-1-en-1-yl)benzo[f]quinoline 4-oxide
(Table 2, entry 3n). Yellow liquid, yield = 21.1 mg (72%). Isolated
from flash chromatography (72% EtOAc/ n-hexane; silica gel 230-
400 mesh size). 1H NMR (600 MHz, CDCl3, δ): 9.16 (d, J = 16.8
Hz, 1H), 8.58 – 8.55 (m, 3H), 7.97 (d, J = 7.8 Hz, 1H), 7.93 (s, 1H),
7.79 – 7.74 (m, 2H), 7.52 – 7.49 (m, 1H), 6.09 (d, J = 15 Hz, 1H),
4.33 (dd, J = 13.8, 7.2 Hz, 2H), 1.38 (t, J = 7.2 Hz, 3H). 13C{1H}
NMR (150 MHz, CDCl3, δ): 166.8, 147.5, 139.8, 137.6, 133.0,
131.5, 129.8, 129.24, 129.20, 129.0, 128.6, 123.3, 122.0, 120.9,
117.9, 60.4, 14.4. IR (ZnSe) νmax (cm-1): 2928, 1698, 1375, 1238,
1163, 1030, 748, 715, 658. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C18H16NO3, 294.1125; found, 294.1120.
(E)-4-(3-Ethoxy-3-oxoprop-1-en-1-yl)phenanthridine 5-oxide
(Table 2, entry 3o). Brown liquid, yield = 18.8 mg, (64%). Isolated
from flash chromatography (82% EtOAc/ n-hexane; silica gel 230-
400 mesh size). 1H NMR (600 MHz, CDCl3, δ): 9.11 (d, J = 15.6
Hz, 1H), 8.56 – 8.50 (m, 3H), 7.91 (d, J = 7.8 Hz, 1H), 7.87 (s, 1H),
7.75 – 7.70 (m, 2H), 7.49 – 7.47 (m, 1H) 6.06 (d, J = 15.6 Hz, 1H),
4.30 (q, J = 7.2 Hz, 2H), 1.36 (t, J = 7.2 Hz, 3H). 13C{1H} NMR
(150 MHz, CDCl3, δ): 166.9, 147.5, 139.5, 137.6, 133.0, 131.4,
129.8, 129.2, 129.1, 129.0, 128.9, 128.7, 123.3, 122.0, 121.3,
117.7, 60.4, 14.4. IR (ZnSe) νmax (cm-1): 2990, 2349, 1715, 1693,
1305, 1175, 962, 753, 624. HRMS (ESI-TOF) m/z: [M + H]+calcd
for C18H16NO3, 294.1125; found, 294.1130.
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11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-2-methylquinoline
1-
oxide (Table 3, entry 5a). Brown liquid, yield = 19.6 mg (76%).
Isolated from flash chromatography (80% EtOAc/ n-hexane; silica
gel 230-400 mesh size). 1H NMR (300 MHz, CDCl3, δ): 9.18 (d, J
= 15.9 Hz, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H),
7.60 – 7.50 (m, 2H), 7.35 (d, J = 8.4 Hz, 1H), 5.93 (d, J = 14.1 Hz,
1H), 4.28 - 4.22 (m, 2H), 2.66 (s, 3H), 1.35 – 1.30 (m, 3H). 13C{1H}
NMR (75 MHz, CD3OD, δ): 168.3, 150.1, 148.7, 140.0, 133.3,
131.8, 131.4, 131.2, 129.7, 128.9, 124.8, 119.1, 61.5, 18.9, 14.6. IR
(ZnSe) νmax (cm-1): 2934, 2390, 1715, 1602, 1431,1087, 784, 642.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H16NO3, 258.1125;
found, 258.1130.
(E)-8-(3-Methoxy-3-oxoprop-1-en-1-yl)-2-methylquinoline 1-
oxide (Table 3, entry 5b). Light yellow liquid, yield = 19.0 mg
(78%). Isolated from flash chromatography to (73% EtOAc/ n-hex-
ane; silica gel 230-400 mesh size). 1H NMR (300 MHz, CDCl3, δ):
9.18 (d, J = 15.9 Hz, 1H), 7.86 (dd, J = 7.8, 1.8 Hz, 1H), 7.71 (d, J
= 8.4 Hz, 1H), 7.61 – 7.51 (m, 2H), 7.37 (d, J = 8.7 Hz, 1H), 5.92
(d, J = 15.9 Hz, 1H), 3.79 (s, 3H), 2.67 (s, 3H). 13C{1H} NMR (150
MHz, CDCl3, δ): 167.1, 147.9, 147.7, 139.7, 131.7, 131.0, 130.5,
129.9, 127.5, 126.0, 123.5, 118.1, 51.6, 19.0. IR (ZnSe) νmax (cm-
1): 2951, 2348, 1709, 1615, 1435, 1208, 985, 824, 648. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C14H14NO3, 244.0968; found,
244.0944.
(E)-8-(3-Butoxy-3-oxoprop-1-en-1-yl)-2-methylquinoline 1-ox-
ide (Table 3, entry 5c). Brown liquid, yield = 23.2 mg (81%). Iso-
lated from flash chromatography (70% EtOAc/ n-hexane; silica gel
1
230-400 mesh size). H NMR (300 MHz, CDCl3, δ): 9.17 (d, J =
15.6 Hz, 1H), 7.78 (dd, J = 7.8, 1.8 Hz, 1H), 7.60 (d, J = 8.7 Hz,
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The Journal of Organic Chemistry
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C13H12NO3, 230.0812;
found, 230.0830.
31.1, 25.3, 23.5. IR (ZnSe) νmax (cm-1): 2933, 2857, 1698, 1628,
1383, 1302, 1220, 1166, 1013, 818, 751, 658. HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C18H20NO3, 298.1438; found, 298.1450.
(E)-8-(3-(tert-Butoxy)-2-methyl-3-oxoprop-1-en-1-yl)quinoline
1-oxide (Table 4, entry 6g). Yellow liquid, yield = 19.7 mg (69%).
Isolated from column chromatography (55% EtOAc/ n-hexane;
acidic alumina). 1H NMR (300 MHz, CDCl3, δ): 8.68 (s, 1H), 8.47
(d, J = 6.0 Hz, 1H), 7.84 (d, J = 8.1 Hz, 1H), 7.75 (d, J = 8.4 Hz,
1H), 7.64 – 7.59 (m, 1H), 7.47 (d, J = 6.9 Hz, 1H), 7.32 – 7.27 (m,
1H), 1.86 (s, 3H), 1.58 (s, 9H). 13C{1H} NMR (75 MHz, CDCl3,
δ): 167.9, 140.3, 137.1, 132.7, 131.9, 131.2, 128.5, 128.0, 126.4,
126.1, 125.8, 121.2, 80.3, 28.2, 13.6. IR (ZnSe) νmax (cm-1): 2977,
1695, 1658, 1387, 1223, 1183, 749, 658. HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C17H20NO3, 286.1438; found, 286.1445 .
(E)-8-(3-(Benzyloxy)-2-methyl-3-oxoprop-1-en-1-yl)quinoline
1-oxide (Table 4, entry 6h). Brown liquid, yield = 20.7 mg (65%).
Isolated from column chromatography (62% EtOAc/ n-hexane;
acidic alumina). 1H NMR (300 MHz, CDCl3, δ): 8.83 (s, 1H), 8.48
(dd, J = 6.0, 1.2 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.79 (d, J = 8.4
Hz, 1H), 7.65 – 7.60 (m, 1H), 7.49 – 7.45 (m, 3H), 7.41 – 7.29 (m,
4H), 5.30 (s, 2H), 1.93 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3, δ):
168.4, 145.0, 141.8, 136.9, 136.6, 132.5, 131.9, 130.8, 128.7,
128.5, 128.1, 128.0, 127.9, 126.1, 123.8, 121.3, 66.4, 13.7. IR
(ZnSe) νmax (cm-1): 2966, 2923, 2953, 1702, 1698, 1588, 1453,
1379, 1245, 1108, 745, 688. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C20H18NO3, 320.1281; found, 320.1300.
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4
5
6
7
8
(E)-8-(3-(Butoxy)-3-oxoprop-1-en-1-yl)quinoline 1-oxide (Ta-
ble 4, entry 6b). Yellow sticky liquid, yield = 22.5 mg (83%). Iso-
lated from flash chromatography (80% EtOAc/ n-hexane; silica gel
1
230-400 mesh size). H NMR (600 MHz, CDCl3, δ): 9.22 (d, J =
15.6 Hz, 1H), 8.48 (d, J = 6.0 Hz, 1H), 7.87 (dd, J = 7.8, 1.2 Hz,
1H), 7.73 (d, J = 7.8, 1H), 7.64 (d, J = 6.6, 1H), 7.59 (t, J = 7.8,
1H), 7.31 – 7.29 (m, 1H) 6.0 (d, J = 15.6 Hz, 1H), 4.24 – 4.22 (m,
2H), 1.74 – 1.69 (m, 2H), 1.48 – 1.44 (m, 2H), 0.97 (t, J = 7.2 Hz,
3H). 13C{1H} NMR (150 MHz, CDCl3, δ): 166.7, 146.8, 139.8,
137.2, 131.9, 131.7, 131.5, 129.8, 128.4, 126.2, 121.4, 119.1, 64.4,
30.8, 19.2, 13.8. IR (ZnSe) νmax (cm-1): 3057, 2956, 2872, 1703,
1629, 1568, 1382, 1305, 1220, 1163, 1060, 962, 819, 758. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C16H18NO3, 272.1281; found,
272.1266.
(E)-8-(3-(tert-Butoxy)-3-oxoprop-1-en-1-yl)quinoline 1-oxide
(Table 4, entry 6c). Brown liquid, yield = 21.8 mg (80%). Isolated
from flash chromatography (90% EtOAc/ n-hexane; silica gel 230-
400 mesh size). 1H NMR (600 MHz, CDCl3, δ): 9.08 (d, J = 15.6
Hz, 1H), 8.46 (d, J = 6.0 Hz, 1H), 7.84 – 7.83 (m, 1H), 7.72 (d, J =
8.4 Hz, 1H), 7.61 – 7.60 (m, 1H), 7.57 – 7.54 (m, 1H), 7.29 – 7.26
(m, 1H), 5.89 (d, J = 15.6 Hz, 1H), 1.53 (s, 9H). 13C{1H} NMR (75
MHz, CDCl3, δ): 165.9, 145.7, 139.8, 137.2, 131.95, 131.86, 131.6,
129.6, 128.3, 126.2, 121.4, 121.3, 80.3, 28.2. IR (ZnSe) νmax (cm-
1): 2978, 1694, 1625, 1308, 1220, 1143, 817, 756. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C16H18NO3, 272.1281; found,
272.1281.
(E)-8-(3-Oxo-3-(2,2,3,3,3-pentafluoropropoxy)prop-1-en-1-
yl)quinoline 1-oxide (Table 4, entry 6d). Yellow liquid, yield = 24.2
mg (70%). Isolated from flash chromatography (75% EtOAc/ n-
hexane; silica gel 230-400 mesh size). 1H NMR (300 MHz, CDCl3,
δ): 9.33 (d, J = 15.6 Hz, 1H), 8.55 (d, J = 6.0 Hz, 1H), 7.94 – 7.90
(m, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.69 – 7.63 (m, 2H), 7.37 (dd, J
= 8.4, 6.0 Hz, 1H), 6.05 (d, J = 15.6 Hz, 1H), 4.73 – 4.64 (m, 2H).
13C{1H} NMR (75 MHz, CDCl3, δ): 164.7, 149.5, 139.3, 137.8,
132.0, 131.8, 130.9, 130.3, 128.8, 128.6, 128.1, 127.7, 121.7,
116.6, 59.2. 19F NMR (565 MHz, CDCl3, δ) -83.7, -123.3. IR
(ZnSe) νmax (cm-1): 2967, 2925, 1731, 1628, 1193, 1106, 759, 655.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H11F5NO3,
348.0654; found, 348.0634.
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8-((E)-3-(((1s,5R,7S)-3-hydroxyadamantan-1-yl)oxy)-3-ox-
oprop-1-en-1-yl)quinoline 1-oxide (Table 4, entry 6i). Brown liq-
uid, yield = 28.8 mg (79%). Isolated from flash chromatography
1
(80% EtOAc/ n-hexane; silica gel 230-400 mesh size). H NMR
(300 MHz, CDCl3, δ): 9.09 (d, J = 15.6 Hz, 1H), 8.48 (d, J = 5.4
Hz, 1H), 7.84 (d, J = 7.2 Hz, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.64 –
7.54 (m, 2H), 7.30 (d, J = 6.6 Hz, 1H), 5.89 (d, J = 15.6 Hz, 1H),
2.33 (s, 2H), 2.20 – 2.03 (m, 6H), 1.77 – 1.66 (m, 3H), 1.62 – 1.48
(m, 2H), 1.27 – 1.23 (m, 1H). 13C{1H} NMR (75 MHz, CDCl3, δ):
165.6, 146.2, 139.8, 137.5, 132.0, 131.9, 131.8, 129.8, 128.5,
126.7, 121.5, 121.0, 81.3, 70.4, 49.4, 44.2, 40.1, 34.9, 31.4. IR
(ZnSe) νmax (cm-1): 2913, 2855, 1698, 1285, 1108, 908, 750, 620.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C22H24NO4, 366.1700;
found, 366.1708.
(E)-8-(3-(Anthracen-9-ylmethoxy)-3-oxoprop-1-en-1-yl)quino-
line 1-oxide (Table 4, entry 6j). Brown precipitates, yield = 26.3
mg (65%). mp 194-195 °C. Isolated from flash chromatography
(E)-8-(3-((3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptade-
cafluorodecyl)oxy)-3-oxoprop-1-en-1-yl)quinoline 1-oxide (Table
4, entry 6e). Brown precipitates, yield = 50.2 mg (76%). mp 175-
176 °C. Isolated from flash chromatography (78% EtOAc/ n-hex-
ane; silica gel 230-400 mesh size). 1H NMR (300 MHz, CDCl3, δ):
9.26 (d, J = 15.6 Hz, 1H), 8.50 (d, J = 6.0 Hz, 1H), 7.90 (d, J = 7.5
Hz, 1H), 7.77 (d, J = 8.1 Hz, 1H), 7.63 (d, J = 7.8 Hz, 2H), 7.36 –
7.31 (m, 1H), 6.01 (d, J = 15.6 Hz, 1H), 4.54 (t, J = 6.6 Hz, 2H),
2.60 – 2.53 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3, δ): 166.0,
148.0, 139.6, 137.4, 131.9, 131.6, 131.3, 130.0, 128.4, 126.6,
121.5, 117.9, 56.3, 31.0 – 30.4 (m). 19F NMR (565 MHz, CDCl3,
δ): -80.7 – -80.8 (m), -113.5 – -113.6 (m), -121.6 – -121.7 (m), -
121.8 – -122.0 (m), -122.7 – -122.8 (m), -123.46 – -123.53 (m), -
126.1 – -126.2 (m). IR (ZnSe) νmax (cm-1): 2982, 1715, 1628, 1197,
1144, 963, 819, 654. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C22H13F17NO3, 662.0618; found, 662.0604 .
(E)-8-(3-(Cyclohexyloxy)-3-oxoprop-1-en-1-yl)quinoline 1-ox-
ide (Table 4, entry 6f). Brown liquid, yield = 19.0 mg (64%). Iso-
lated from flash chromatography (75% EtOAc/ n-hexane; silica gel
230-400 mesh size). 1H NMR (300 MHz, Acetone-d6, δ): 9.24 (d,
J = 15.6 Hz, 1H), 8.50 (d, J = 6.0 Hz, 1H), 8.07 – 8.04 (m, 1H),
7.92 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 7.2 Hz, 1H), 7.70 – 7.65 (m,
1H), 7.47 (dd, J = 8.4, 6.0 Hz, 1H), 6.00 (d, J = 15.6 Hz, 1H), 4.86
– 4.79 (m, 1H), 1.92 – 1.87 (m, 2H), 1.79 – 1.72 (m, 2H), 1.57 –
1.51 (m, 2H), 1.47 – 1.142 (m, 2H), 1.39 – 1.31 (m, 2H). 13C{1H}
NMR (75 MHz, Acetone-d6, δ): 165.5, 146.8, 139.4, 137.4, 132.2,
131.3, 130.8, 130.4, 128.4, 126.0, 122.0, 118.5, 78.3, 71.9, 31.5,
1
(85% EtOAc/ n-hexane; silica gel 230-400 mesh size). H NMR
(600 MHz, CDCl3, δ): 9.25 (d, J = 15.6 Hz, 1H), 8.52 (s, 1H), 8.48
– 8.41 (m, 3H), 8.05 (d, J = 8.4 Hz, 2H), 7.80 (dd, J = 7.8, 1.8 Hz,
1H), 7.68 (d, J = 8.4 Hz, 1H), 7.62 – 7.60 (m, 2H), 7.54 – 7.50 (m,
4H), 7.25 (dd, J = 8.4, 6.0, 1H), 6.32 (s, 2H), 6.01 (d, J = 15.6 Hz,
1H). 13C{1H} NMR (150 MHz, CDCl3, δ): 166.8, 147.7, 139.7,
137.2, 134.6, 131.7, 131.6, 131.5, 131.4, 131.2, 129.8, 129.1,
129.0, 128.3, 126.7, 126.5, 125.1, 124.2, 121.4, 118.5, 58.9. IR
(ZnSe) νmax (cm-1): 2982, 2857, 1715, 1628, 1303, 1158, 733, 657.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C27H20NO3, 406.1438;
found, 406.1415
(E)-8-(3-Oxo-3-((5,7,8-trimethyl-2-(5,8,12-trimethyltridecan-2-
yl)chroman-6-yl)oxy)prop-1-en-1-yl)quinoline 1-oxide (Table 4,
entry 6k). Brown liquid, yield = 36.2 mg (59%). Isolated from flash
chromatography (80% EtOAc/ n-hexane; silica gel 230-400 mesh
1
size). H NMR (300 MHz, CDCl3, δ): 9.40 (d, J = 15.6 Hz, 1H),
8.43 (d, J = 6.3 Hz, 1H), 7.82 (d, J = 8.1 Hz, 1H), 7.68 (d, J = 8.1
Hz, 2H), 7.57 (t, J = 7.8 Hz, 1H), 7.27 – 7.22 (m, 1H), 6.16 (d, J =
15.6 Hz, 1H), 2.56 – 2.51 (m, 2H), 2.10 (s, 2H), 2.03 (s, 6H), 1.99
(s, 3H), 1.75 – 1.67 (m, 2H), 1.49 – 1.42 (m, 2H), 1.33 – 1.30 (m,
2H), 1.17 (s, 13H), 1.09 – 1.01 (m, 3H), 0.80 - 0.76 (m, 12H).
13C{1H} NMR (75 MHz, CDCl3, δ): 165.2, 149.3, 148.4, 140.6,
139.8, 137.4, 131.9, 131.8, 131.5, 130.0, 128.4, 127.0, 126.4,
125.3, 122.9, 121.5, 118.0, 117.3, 75.0, 39.4, 37.5, 37.4, 37.3, 32.8,
32.7, 31.2, 30.9, 28.0, 24.8, 24.5, 22.7, 22.6, 21.1, 20.6, 19.8, 19.7,
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 12
19.6, 13.1, 12.3, 11.9. IR (ZnSe) νmax (cm-1): 2945, 1728, 1627,
(E)-8-(3-Nitrostyryl)quinoline 1-oxide (Table 5, entry 8e). Yel-
1481, 1379, 1220, 1140, 981, 757. HRMS (ESI-TOF) m/z: [M +
low precipitates, yield = 19.9 mg (68%). mp 164-166 °C. Isolated
from flash chromatography (79% EtOAc/ n-hexane; silica gel 230-
400 mesh size). 1H NMR (600 MHz, CDCl3, δ): 8.96 (d, J = 15.6
Hz, 1H), 8.53 (d, J = 6.0 Hz, 1H), 8.39 (s, 1H), 8.13 – 8.11 (m, 1H),
7.96 (d, J = 7.8 Hz, 1H), 7.87 – 7.86 (m, 1H), 7.81 – 7.78 (m, 2H),
7.65 (t, J = 7.8 Hz, 1H), 7.56 – 7.54 (m, 1H), 7.32 (dd, J = 8.4, 6.0
Hz, 1H), 6.72 (d, J = 15.6 Hz, 1H). 13C{1H} NMR (150 MHz,
CDCl3, δ): 148.7, 139.8, 139.7, 137.6, 133.9, 133.3, 132.2, 132.1,
131.0, 129.4, 128.8, 128.5, 127.0, 126.9, 121.9, 121.7, 121.2. IR
(ZnSe) νmax (cm-1): 3150, 2341, 1573, 1528, 1345, 1220, 945, 842,
721. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C17H13N2O3,
293.0921; found, 293.0923.
(E)-8-(4-Methylstyryl)quinoline 1-oxide(Table 5, entry 8f). Pale
yellow precipitates, yield = 19.6 mg (75%). mp 94-95 °C. Isolated
from flash chromatography (82% EtOAc/ n-hexane; silica gel 230-
400 mesh size). 1H NMR (600 MHz, CDCl3, δ): 8.83 (d, J = 16.2
Hz, 1H), 8.48 (dd, J = 6.0, 1.2 Hz, 1H), 7.81 (d, J = 7.2 Hz, 1H),
7.77 (d, J = 7.8 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.59 (t, J = 7.8
Hz, 1H), 7.51 (d, J = 7.8 Hz, 2H), 7.26 (dd, J = 8.4, 6.0 Hz, 1H),
7.19 (d, J = 7.8 Hz, 2H), 6.71 (d, J = 15.6 Hz, 1H), 2.38 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3, δ): 139.9, 137.5, 137.3, 135.1,
134.5, 132.2, 130.5, 129.8, 129.6, 129.3, 128.4, 127.9, 126.8,
126.5, 120.9, 21.3. IR (ZnSe) νmax (cm-1): 3152, 2917, 2349, 1584,
1507, 1379, 1214, 987, 815, 753. HRMS (ESI-TOF) m/z: [M + H]+
calcd for C18H16NO, 262.1226; found, 262.1241.
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2
3
4
5
6
7
8
H]+ calcd for C40H56NO4, 614.4204; found, 614.4220.
(E)-8-(3-((13-Methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-deca-
hydro-6H-cyclopenta[a]phenanthren-3-yl)oxy)-3-oxoprop-1-en-
1-yl)quinoline 1-oxide (Table 4, entry 6l). Brown liquid, yield =
21.0 mg (45%). Isolated from column chromatography (75%
1
EtOAc/ n-hexane; silica gel 230-400 mesh size). H NMR (300
MHz, CDCl3, δ): 9.38 (d, J = 15.6 Hz, 1H), 8.60 (d, J = 6.0 Hz,
1H), 7.96 – 7.93 (m, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 7.2
Hz, 1H), 7.70 – 7.65 (m, 1H), 7.40 (dd, J = 8.4, 6.0 Hz, 1H), 7.32
(d, J = 8.7 Hz, 1H), 6.99 – 6.93 (m, 2H), 6.20 (d, J = 15.6 Hz, 1H),
2.97 – 2.92 (m, 2H), 2.58 – 2.43 (m, 2H), 2.09 – 2.04 (m, 2H), 1.61
– 1.54 (m, 3H), 1.27 (s, 6H), 0.94 (s, 3H). 13C{1H} NMR (75 MHz,
CDCl3, δ): 165.2, 148.8, 148.5, 139.3, 137.92, 137.87, 137.2,
132.1, 131.9, 131.1, 130.2, 128.6, 126.3, 121.73, 121.65, 118.9,
118.3, 50.5, 48.0, 44.2, 38.0, 35.9, 31.9, 31.6, 29.7, 26.4, 25.8, 22.7,
21.6, 13.9. IR (ZnSe) νmax (cm-1): 2933, 2924, 1728, 1627, 1492,
1382, 1305, 1219, 1139, 1053, 1008, 819, 746, 665. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C30H30NO4, 468.2169; found,
468.2187.
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(E)-8-Styrylquinoline 1-oxide (Table 5, entry 8a). Orange liquid,
yield = 19.5 mg (79%). Isolated from flash chromatography (75%
1
EtOAc/ n-hexane; silica gel 230-400 mesh size). H NMR (300
MHz, CDCl3, δ): 8.87 (d, J = 16.2 Hz, 1H), 8.48 (dd, J = 6.0, 1.2
Hz, 1H), 7.83 – 7.77 (m, 2H), 7.72 (dd, J = 8.4, 1.2 Hz, 1H), 7.63
– 7.57 (m, 3H), 7.41 – 7.35 (m, 2H), 7.30 – 7.26 (m, 2H), 6.72 (d,
J = 15.9 Hz, 1H). 13C{1H} NMR (75 MHz, CDCl3, δ): 140.0, 137.9,
137.4, 134.4, 132.2, 130.7, 130.6, 129.8, 128.5, 128.4, 128.1,
127.4, 126.9, 126.3, 120.9. IR (ZnSe) νmax (cm-1): 3057, 3023,
1702, 1580, 1219, 951, 813, 741, 691, 550. HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C17H14NO, 248.1070; found, 248.1060.
(E)-8-(2-Methylstyryl)quinoline 1-oxide(Table 5, entry 8b).
Brown sticky, yield = 18.8 mg (72%). Isolated from flash chroma-
tography (72% EtOAc/ n-hexane; silica gel 230-400 mesh size) 1H
NMR (300 MHz, CDCl3, δ): 8.61 (d, J = 15.9 Hz, 1H), 8.48 (d, J =
5.7 Hz, 1H), 7.73 – 7.67 (m, 4H), 7.54 – 7.45 (m, 1H), 7.20 – 7.15
(m, 2H), 7.13 – 7.07 (m, 2H), 6.80 (d, J = 15.9 Hz, 1H), 2.37 (s,
3H). 13C{1H} NMR (75 MHz, CDCl3, δ): 139.7, 137.9, 136.7,
135.6, 134.6, 132.1, 131.9, 131.2, 130.2, 128.5, 128.1, 127.6,
127.4, 126.3, 120.9, 20.0. IR (ZnSe) νmax (cm-1): 3088, 3016, 2973,
1557, 1333, 1219, 1166, 963, 744, 544. HRMS (ESI-TOF) m/z: [M
+ H]+ calcd for C18H16NO, 262.1226; found, 262.1233.
(E)-8-(4-(tert-Butyl)styryl)quinoline 1-oxide (Table 5, entry 8g).
Yellow precipitates, yield = 20.3 mg (67%). mp 178-180 °C. Iso-
lated from flash chromatography (80% EtOAc/ n-hexane; silica gel
1
230-400 mesh size). H NMR (300 MHz, CDCl3, δ): 8.83 (d, J =
15.9 Hz, 1H), 8.48 (d, J = 1.8 Hz, 1H), 7.81 – 7.72 (m, 3H), 7.56
(d, J = 8.1 Hz, 3H), 7.40 (d, J = 8.1, 2H), 7.28 – 7.25 (m, 1H), 6.72
(d, J = 15.9 Hz, 1H), 1.36 (s, 9H). 13C{1H} NMR (75 MHz, CDCl3,
δ): 150.6, 139.9, 137.5, 135.1, 134.5, 132.2, 130.5, 129.9, 129.7,
128.4, 127.9, 126.6, 126.5, 125.4, 120.9, 34.6, 31.3. IR (ZnSe) νmax
(cm-1): 2962, 2888, 2349, 1698, 1379, 1220, 822, 759, 648. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C21H22NO, 304.1696; found,
304.1701.
(E)-8-(4-Bromostyryl)quinoline 1-oxide (Table 5, entry 8h).
Yellow liquid, yield = 24.1 mg (74%). Isolated from flash chroma-
tography (74% EtOAc/ n-hexane; silica gel 230-400 mesh size). 1H
NMR (600 MHz, CDCl3, δ): 8.78 (d, J = 16.2 Hz, 1H), 8.48 (d, J =
6.0 Hz, 1H), 7.79 – 7.74 (m, 3H), 7.57 (t, J = 7.8 Hz, 1H), 7.42 (dd,
J = 18.0, 8.4 Hz, 4H), 7.28 – 7.25 (m, 1H), 6.59 (d, J = 16.2 Hz,
1H). 13C{1H} NMR (150 MHz, CDCl3, δ): 139.5, 137.8, 136.8,
133.7, 132.1, 131.7, 131.3, 130.9, 128.5, 128.42, 128.37, 128.3,
127.5, 121.2, 121.1. IR (ZnSe) νmax (cm-1): 3067, 2344, 1643, 1597,
1488, 1219, 817, 752, 655. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C17H13BrNO, 326.0175; found, 326.0171.
(E)-8-(4-Nitrostyryl)quinoline 1-oxide (Table 5, entry 8i). Yel-
low precipitates, yield = 20.7 mg (71%). mp 205-207 °C. Isolated
from flash chromatography (78% EtOAc/ n-hexane; silica gel 230-
400 mesh size). 1H NMR (300 MHz, CDCl3, δ): 8.92 (d, J = 15.9
Hz, 1H), 8.43 (d, J = 6.0 Hz, 1H), 8.15 – 8.11 (m, 2H), 7.79 – 7.52
(m, 6H), 7.26 – 7.18 (m, 1H), 6.63 (d, J = 15.9 Hz, 1H). 13C{1H}
NMR (75 MHz, CDCl3, δ): 146.7, 144.4, 139.8, 137.6, 135.4,
133.2, 132.1, 130.9, 129.0, 128.5, 127.2, 127.0, 126.8, 124.0,
121.3. IR (ZnSe) νmax (cm-1): 2923, 2851, 1711, 1587, 1503, 1334,
949, 814, 743, 578. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C17H13N2O3, 293.0921; found, 293.0903.
(E)-8-(4-Cyanostyryl)quinoline 1-oxide (Table 5, entry 8j). Yel-
low precipitates, yield = 19.3 mg (71%). mp 265-267 °C. Isolated
from flash chromatography (74% EtOAc/ n-hexane; silica gel 230-
400 mesh size). 1H NMR (600 MHz, CDCl3, δ): 8.97 (d, J = 16.2
Hz, 1H), 8.51 (d, J = 6.0 Hz, 1H), 7.86 (d, J = 7.8 Hz, 1H), 7.80 –
7.78 (m, 2H), 7.68 – 7.64 (m, 5H), 7.34 – 7.29 (m, 1H), 6.68 (d, J
= 16.2 Hz, 1H). 13C{1H} NMR (150 MHz, CDCl3, δ): 142.4, 137.7,
134.5, 133.3, 133.2, 132.9, 132.4, 132.1, 131.0, 128.9, 128.5,
(E)-8-(3-Methylstyryl)quinoline 1-oxide (Table 5, entry 8c). Yel-
low liquid, yield = 21.2 mg (81%). Isolated from flash chromatog-
1
raphy (77% EtOAc/ n-hexane; silica gel 230-400 mesh size). H
NMR (600 MHz, CDCl3, δ): 8.82 (d, J = 16.2 Hz, 1H), 8.51 (dd, J
= 6.0, 1.2 Hz, 1H), 7.81 – 7.75 (m, 3H), 7.59 (t, J = 7.8 Hz, 1H),
7.44 (s, 1H), 7.37 (d, J = 7.8 Hz, 1H), 7.29 – 7.26 (m, 2H), 7.09 (d,
J = 7.8 Hz, 1H), 6.68 (d, J = 16.2 Hz, 1H), 2.39 (s, 3H). 13C{1H}
NMR (150 MHz, CDCl3, δ): 139.7, 138.1, 137.8, 137.7, 134.2,
132.1, 130.8, 130.3, 130.0, 128.5, 128.4, 128.33, 128.30, 128.1,
127.4, 124.3, 120.9, 21.5. IR (ZnSe) νmax (cm-1): 3053, 2917, 1693,
1588, 1379, 1218, 952, 814, 746, 655. HRMS (ESI-TOF) m/z: [M
+ H]+ calcd for C18H16NO, 262.1226; found, 262.1230.
(E)-8-(3-Bromostyryl)quinoline 1-oxide (Table 5, entry 8d).
Brown liquid, yield = 25.1 mg (77%). Isolated from flash chroma-
tography (75% EtOAc/ n-hexane; silica gel 230-400 mesh size). 1H
NMR (300 MHz, CDCl3, δ): 8.63 (d, J = 15.9 Hz, 1H), 8.44 (d, J =
6.3 Hz, 1H), 7.71 – 7.64 (m, 3H), 7.55 – 7.47 (m, 2H), 7.34 (d, J =
7.8 Hz, 1H), 7.26 – 7.18 (m, 2H), 7.12 – 7.06 (m, 1H), 6.44 (d, J =
15.9 Hz, 1H). 13C{1H} NMR (150 MHz, CDCl3, δ): 139.9, 137.9,
133.6, 132.1, 132.0, 131.1, 130.3, 130.1, 129.6, 128.6, 128.5,
128.1, 127.6, 127.7, 125.4, 122.8, 121.1. IR (ZnSe) νmax (cm-1):
3058, 2349, 1693, 1588, 1472, 1303, 1218, 950, 751, 658. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C17H13BrNO, 326.0175; found,
326.0161.
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127.5, 127.2, 126.9, 121.3, 110.4. IR (ZnSe) νmax (cm-1): 2958,
mesh size). H NMR (300 MHz, CDCl3, δ): 8.45 – 8.42 (m, 1H),
8.00 (d, J = 15.6 Hz, 1H), 7.73 – 7.63 (m, 3H), 7.55 – 7.49 (m, 1H),
7.24 – 7.18 (m, 1H), 5.87 – 5.78 (m, 1H), 2.23 – 2.19 (m, 2H), 1.86
– 1.82 (m, 3H), 1.76 – 1.65 (m, 4H), 1.30 – 1.22 (m, 3H), 1.08 –
1.04 (m, 1H). 13C{1H} NMR (75 MHz, CDCl3, δ): 139.8, 137.3,
134.9, 132.4, 132.1, 131.0, 130.6, 128.3, 127.5, 126.2, 120.7, 41.0,
38.3, 33.3, 26.6, 26.4. IR (ZnSe) νmax (cm-1): 2919, 2844, 1692,
1419, 966, 819, 756. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C18H22NO, 268.1696; found, 268.1686.
2923, 2224, 1652, 1593, 1223, 1184, 810, 743. HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C18H13N2O, 273.1022; found, 273.1015.
(E)-8-(2-(Perfluorophenyl)vinyl)quinoline 1-oxide (Table 5, en-
try 8k). Yellow precipitates, yield = 19.9 mg (59%). mp 140-142
°C. Isolated from flash chromatography (70% EtOAc/ n-hexane;
silica gel 230-400 mesh size). 1H NMR (300 MHz, CDCl3, δ): 9.08
(d, J = 16.5 Hz, 1H), 8.45 (d, J = 6.0 Hz, 1H), 7.95 (d, J = 8.1 Hz,
1H), 7.84 (d, J = 8.7 Hz, 1H), 7.78 – 7.75 (m, 1H), 7.67 – 7.62 (m,
1H), 7.42 – 7.36 (m, 1H), 6.49 (d, J = 15.9 Hz, 1H). 13C{1H} NMR
(75 MHz, CDCl3, δ): 146.9 – 143.5 (m), 140.65 – 140.37 (m),
140.0, 137.8, 133.4, 132.62, 132.56, 131.2, 130.0, 128.9, 126.5,
122.2, 112.67 – 112.53 (m). 19F NMR (565 MHz, CDCl3, δ): -
138.57 – -138.64 (m), -153.4 – -153.5 (m), -159.3 – -159.4 (m). IR
(ZnSe) νmax (cm-1): 2924, 1701, 1150, 900, 733, 658. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C17H9F5NO, 338.0599; found,
338.0585.
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4
5
6
7
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(E)-8-(Hex-1-en-1-yl)quinoline 1-oxide (Table 5, entry 8q). Yel-
low liquid, yield = 12.0 mg (53%). Isolated from flash chromatog-
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raphy (65% EtOAc/ n-hexane; silica gel 230-400 mesh size). H
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NMR (300 MHz, CDCl3, δ): 8.45 – 8.43 (m, 1H), 8.03 (d, J = 15.3
Hz, 1H), 7.73 – 7.61 (m, 3H), 7.54 – 7.49 (m, 1H), 7.24 – 7.18 (m,
1H), 5.88 – 5.78 (m, 1H), 2.36 – 2.28 (m, 2H), 1.58 – 1.50 (m, 2H),
1.47 – 1.40 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (75
MHz, CDCl3, δ): 139.8, 137.3, 134.9, 132.09, 132.06, 131.4, 130.9,
128.3, 127.5, 126.3, 120.7, 32.7, 31.5, 22.4, 14.0. IR (ZnSe) νmax
(cm-1): 3102, 2929, 1692, 1225, 854, 793, 622. HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C15H18NO, 228.1383; found, 228.1400.
(E)-8-(Hept-1-en-1-yl)quinoline 1-oxide (Table 5, entry 8r).
Brown liquid, yield = 13.7 mg (57%). Isolated from flash chroma-
tography (60% EtOAc/ n-hexane; silica gel 230-400 mesh size). 1H
NMR (600 MHz, CDCl3, δ): 8.45 (dd, J = 6.0, 1.2 Hz, 1H), 8.03 (d,
J = 15.6 Hz, 1H), 7.73 – 7.71 (m, 1H), 7.69 (dd, J = 8.4, 1.2 Hz,
1H), 7.63 (dt, J = 7.2, 1.2 Hz, 1H), 7.54 – 7.51 (m, 1H), 7.22 (dd, J
= 8.4, 6.0 Hz, 1H), 5.84 (dt, J = 15.6, 6.6 Hz, 1H), 2.33 – 2.29 (m,
2H), 1.59 – 1.54 (m, 2H), 1.41 - 1.37 (m, 4H), 0.94 - 0.92 (m, 3H).
13C{1H} NMR (150 MHz, CDCl3, δ): 139.7, 137.4, 134.9, 132.3,
132.1, 131.3, 131.1, 128.3, 127.5, 126.5, 120.7, 33.0, 31.6, 29.1,
22.6, 14.1. IR (ZnSe) νmax (cm-1): 3075, 2926, 2854, 1692, 1455,
945, 821, 780. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C16H20NO, 242.1539; found, 242.1556.
(E)-8-(2-(Naphthalen-1-yl)vinyl)quinoline 1-oxide (Table 5, en-
try 8l). Brown liquid, yield = 21.7 mg (73%). Isolated from flash
chromatography (75% EtOAc/ n-hexane; silica gel 230-400 mesh
1
size). H NMR (300 MHz, CDCl3, δ): 8.88 (d, J = 15.6 Hz, 1H),
8.51 (dd, J = 6.0, 1.5 Hz, 1H), 8.35 – 8.32 (m, 1H), 7.89 – 7.88 (m,
3H), 7.84 – 7.81 (m, 2H), 7.75 (dd, J = 8.4, 1.5 Hz, 1H), 7.69 – 7.62
(m, 1H), 7.57 – 7.51 (m, 2H), 7.45 (d, J = 15.9 Hz, 1H), 7.31 – 7.26
(m, 2H). 13C{1H} NMR (75 MHz, CDCl3, δ): 140.1, 137.5, 135.2,
134.6, 133.8, 133.6, 132.2, 131.4, 131.0, 128.6, 128.5, 128.2,
127.8, 126.5, 126.4, 125.90, 125.86, 125.6, 124.5, 123.9, 121.0. IR
(ZnSe) νmax (cm-1): 2923, 2851, 1711, 1587, 1334, 949, 814, 743,
578. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H16NO,
298.1226; found, 298.1230 .
(E)-8-(2-(Naphthalen-2-yl)vinyl)quinoline 1-oxide (Table 5, en-
try 8m). Yellow liquid, yield = 19.9 mg (67%). Isolated from flash
chromatography (73% EtOAc/ n-hexane; silica gel 230-400 mesh
1
size). H NMR (300 MHz, CDCl3, δ): 9.02 (d, J = 15.9 Hz, 1H),
(E)-8-(3-Ethoxy-3-oxoprop-1-en-1-yl)-2-(4-methoxy-
8.50 (dd, J = 6.3, 1.2 Hz, 1H), 7.94 (s, 1H), 7.89 – 7.82 (m, 5H),
7.80 – 7.73 (m, 2H), 7.62 (t, J = 7.8 Hz, 1H), 7.49 – 7.45 (m, 2H),
7.30 – 7.26 (m, 1H), 6.90 (d, J = 15.9 Hz, 1H). 13C{1H} NMR (75
MHz, CDCl3, δ): 139.9, 137.5, 135.5, 134.3, 133.7, 133.0, 132.2,
131.0, 130.6, 129.9, 128.4, 128.2, 128.1, 128.0, 127.7, 126.5,
126.1, 125.7, 124.4, 121.0. IR (ZnSe) νmax (cm-1): 2931, 2820,
1702, 1457, 1208, 849, 780, 678, 523. HRMS (ESI-TOF) m/z: [M
+ H]+ calcd for C21H16NO, 298.1226; found, 298.1215.
phenyl)quinoline 1-oxide (Scheme 5, 3aa). To an oven-dried screw
cap reaction vial charged with a spinvane magnetic stir-bar, aryldi-
azonium tetrafluoroborate salt (0.1 mmol), 8-substituted quinoline
N-oxide (3a, 3 equiv.) and sodium acetate (2 equiv.) were added in
MeCN (5 ml) and stir for 6 h at room temperature. After comple-
tion, reaction mixture was diluted with ethyl acetate and washed
with brine solution three time. Organic layer was dried over anhy-
drous Na2SO4 and evaporated under reduced pressure. Brownish
liquid, yield = 29.0 mg (90%). Isolated from flash chromatography
(E)-8-(2-(Phenylsulfonyl)vinyl)quinoline 1-oxide (Table 5, entry
8n). Orange liquid, yield = 18.9 mg (61%). Isolated from column
chromatography (65% EtOAc/ n-hexane; acidic alumina). 1H NMR
(300 MHz, CDCl3, δ): 9.20 (d, J = 15.0 Hz, 1H), 8.49 – 8.45 (m,
1H), 8.10 – 8.07 (m, 2H), 7.91 – 7.88 (m, 1H), 7.76 – 7.73 (m, 1H),
7.61 – 7.56 (m, 5H), 7.33 (dd, J = 8.4, 6.0 Hz, 1H), 6.44 (d, J =
15.0 Hz, 1H). 13C{1H} NMR (75 MHz, CDCl3, δ): 146.1, 140.9,
139.7, 137.2, 133.2, 131.8, 131.6, 130.5, 129.4, 129.3, 128.4,
127.8, 126.4, 126.3, 121.8. IR (ZnSe) νmax (cm-1): 3101, 2925,
1825, 1588, 1445, 1140, 1028, 680, 558. HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C17H14NO3S, 312.0689; found, 312.0672.
(E)-8-(2-Cyclohexylvinyl)quinoline 1-oxide (Table 5, entry 8o).
Brown liquid, yield = 14.4 mg (57%). Isolated from flash chroma-
tography (70% EtOAc/ n-hexane; silica gel 230-400 mesh size). 1H
NMR (300 MHz, CDCl3, δ): 8.44 (dd, J = 6.0, 1.2 Hz, 1H), 8.02 (d,
J = 15.9 Hz, 1H), 7.73 – 7.62 (m, 3H), 7.55 – 7.49 (m, 1H), 7.24 –
7.19 (m, 1H), 5.78 (dd, J = 15.6, 6.6 Hz, 1H), 2.31 – 2.22 (m, 1H),
1.96 – 1.92 (m, 2H), 1.83 – 1.68 (m, 4H), 1.43 – 1.30 (m, 4H).
13C{1H} NMR (75 MHz, CDCl3, δ): 139.9, 137.7, 137.4, 135.1,
132.1, 130.9, 129.3, 128.3, 127.4, 126.3, 120.7, 41.0, 32.9, 26.3,
26.1. IR (ZnSe) νmax (cm-1): 2928, 2852, 1620, 1590, 752. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C17H20NO, 254.1539; found,
254.1530.
1
(35% EtOAc/ n-hexane; silica gel 230-400 mesh size). H NMR
(300 MHz, CDCl3, δ): 9.20 (d, J = 15.6 Hz, 1H), 7.95 (d, J = 8.7
Hz, 2H), 7.85 (dd, J = 7.8, 1.8 Hz, 1H), 7.72 (d, J = 8.7 Hz, 1H),
7.64 – 7.54 (m, 2H), 7.51 (d, J = 8.7 Hz, 1H), 7.04 (d, J = 8.7 Hz,
2H), 5.96 (d, J = 15.6 Hz, 1H), 4.27 (q, J = 7.2 Hz, 2H), 3.89 (s,
3H), 1.34 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (75 MHz, CDCl3, δ):
166.8, 160.6, 148.0, 146.3, 140.6, 132.0, 131.1, 130.6, 129.6,
127.9, 125.5, 123.7, 118.0, 113.8, 60.3, 55.4, 14.4. IR (ZnSe) νmax
(cm-1): 2998, 2845, 1712, 1653, 1595, 1435, 1250, 1136, 834, 768.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H20NO4, 350.1387;
found, 350.1400.
(E)-Ethyl-3-(quinolin-8-yl)acrylate ( Scheme 5, 3ab).17f To an
oven-dried screw cap reaction vial charged with a spinvane mag-
netic stir-bar, 8-substituted quinoline N-oxide (3a, 0.1 mmol), phe-
nylboronic acid (1.5 equiv.) and 0.5 ml DCE were added. The re-
action mixture was allowed to stir at 120 °C for 12 h. After com-
pletion the reaction mixture was diluted with DCM and washed
with water three times. Combined organic layer was dried over an-
hydrous sodium sulfate and evaporated under reduced pressure.
Brown sticky liquid, yield = 20.4 mg (90%). Isolated from flash
chromatography (15% EtOAc/ n-hexane; silica gel 230-400 mesh
1
size). H NMR (300 MHz, CDCl3, δ): 9.01 (dd, J = 4.2, 1.8 Hz,
(E)-8-(3-Cyclohexylprop-1-en-1-yl)quinoline 1-oxide (Table 5,
entry 8p). Yellow liquid, yield = 16.6 mg (62%). Isolated from
flash chromatography (62% EtOAc/ n-hexane; silica gel 230-400
1H), 8.92 (d, J = 16.2 Hz, 1H), 8.19 (dd, J = 8.4, 1.8 Hz, 1H), 8.01
(d, J = 7.2 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.61 – 7.56 (m, 1H),
7.48 (dd, J = 8.4, 4.2 Hz, 1H), 6.85 (d, J = 16.2 Hz, 1H), 4.34 (q, J
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= 7.2 Hz, 2H), 1.42 – 1.37 (m, 3H). 13C{1H} NMR (75 MHz,
DCM. Collected DCM fraction of crude reaction mixture was evap-
CDCl3, δ): 167.1, 150.2, 146.2, 140.9, 136.3, 133.2, 130.0, 128.5,
128.0, 126.3, 121.6, 120.8, 60.5, 14.4. IR (ZnSe) νmax (cm-1) 2922,
2852, 1716, 1651, 1606, 1452, 1259, 1170, 1132, 840, 736.
orated under reduced pressure. Pale yellow sticky liquid, yield =
21.5 mg (81%). Isolated from flash chromatography (15% EtOAc/
n-hexane; silica gel 230-400 mesh size). 1H NMR (300 MHz,
CDCl3, δ): 8.38 (d, J = 16.8 Hz, 1H), 8.13 – 8.09 (m, 2H), 7.77 –
7.67 (m, 3H), 7.62 – 7.57 (m, 1H), 7.45 – 7.32 (m, 5H). 13C{1H}
NMR (75 MHz, CDCl3, δ): 149.9, 145.5, 139.0, 137.6, 135.4,
131.0, 128.6, 127.8, 127.2, 127.1, 126.9, 126.8, 126.1, 124.0,
122.5. IR (ZnSe) νmax (cm-1): 3055, 2924, 2850, 1726, 1587, 1489,
1419, 1315, 1116, 964, 829, 750, 692. HRMS (ESI-TOF) m/z: [M
+ H]+ calcd for C17H13ClN, 266.0731; found, 266.0745.
1
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3
4
5
6
7
8
2-(4-Methoxyphenyl)-8-styrylquinoline 1-oxide (Scheme 5, 8aa).
To an oven-dried screw cap reaction vial charged with a spinvane
magnetic stir-bar, 8-substituted quinoline N-oxide (8a, 0.1 mmol),
phenylboronic acid (1.5 equiv.) and 0.5 ml DCE were added. The
reaction mixture was allowed to stir at 120 °C for 12 h. After com-
pletion the reaction mixture was diluted with DCM and washed
with water three times. Combined organic layer was dried over an-
hydrous sodium sulfate and evaporated under reduced pressure.
Brown liquid, yield = 21.5 mg (85%). Isolated from flash chroma-
tography (40% EtOAc/ n-hexane; silica gel 230-400 mesh size). 1H
NMR (300 MHz, CDCl3, δ): 8.69 (d, J = 15.9 Hz, 1H), 7.91 – 7.79
(m, 4H), 7.63 (d, J = 7.8 Hz, 1H), 7.59 – 7.48 (m, 3H), 7.36 – 7.33
(m, 2H), 7.31 – 7.21 (m, 1H), 7.03 (d, J = 9.0 Hz, 2H), 6.67 (d, J =
15.9 Hz, 1H), 3.87 (s, 1H). 13C{1H} NMR (75 MHz, CDCl3, δ):
160.8, 137.9, 135.3, 134.5, 132.2, 31.4, 131.3, 130.8, 129.6, 128.7,
128.5, 128.2, 128.1, 127.4, 126.9, 123.3, 114.3, 113.9, 55.4. IR
(ZnSe) νmax (cm-1): 3057, 2927, 2837, 1691, 1602, 1500, 1440,
1249, 1178, 1028, 829, 750. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C24H20NO2, 354.1489; found, 354.1490.
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ASSOCIATED CONTENT
Supporting Information
Experimental procedures, details of optimization studies, charac-
terization data for all synthesized compounds including 1H and 13
NMR spectra. This material is available at http://pubs.acs.org.
C
AUTHOR INFORMATION
Corresponding
Author:
*upendra@ihbt.res.in;
upen-
draihbt@gmail.com
(E)-8-Styrylquinoline (Scheme 5, 8ab).17f To an oven-dried
screw cap reaction vial charged with a spinvane magnetic stir-bar,
8-substituted quinoline N-oxide (8a, 0.1 mmol), phenylboronic
acid (1.5 equiv.) and 0.5 ml DCE were added. The reaction mixture
was allowed to stir at 120 °C for 12 h. After completion the reaction
mixture was diluted with DCM and washed with water three times.
Combined organic layer was dried over anhydrous sodium sulfate
and evaporated under reduced pressure. Pale yellow precipitates,
yield = 21.7 mg (94%). mp 96-98 °C. Isolated from flash chroma-
tography (12% EtOAc/ n-hexane; silica gel 230-400 mesh size). 1H
NMR (300 MHz, CDCl3, δ): 8.99 – 8.97 (m, 1H), 8.50 (d, J = 16.5
Hz, 1H), 8.18 – 8.15 (m, 1H), 8.07 (d, J = 7.5 Hz, 1H), 7.77 – 7.74
(m, 1H), 7.71 – 7.69 (m, 2H), 7.61 – 7.54 (m, 1H), 7.45 – 7.34 (m,
4H), 7.31 – 7.25 (m, 1H). 13C{1H} NMR (75 MHz, CDCl3, δ):
149.5, 146.0, 137.8, 136.3, 136.1, 130.6, 129.1, 128.6, 127.7,
127.3, 127.0, 126.5, 125.2, 124.7, 121.2. IR (ZnSe) νmax (cm-1):
3053, 1597, 1496, 1263, 1135, 968, 821, 790, 736, 692.
Web address:
http://www.ihbt.res.in/en/staff/scientific-
staff?chronoform=sctdetail&task=detail&id=41
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
Authors are grateful to the Director, CSIR-IHBT for continuous
encouragement. R.S. and R.K. acknowledge CSIR and UGC, New
Delhi for SRF, respectively. Financial support from CSIR
(MLP0203/HCP010) and SERB-DST (EMR/2014/001023) is also
acknowledged. CSIR-IHBT communication no. for this manuscript
is 4355.
REFERENCES
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Yu, J.-Q.; Shi, Z., Eds. Springer Berlin Heidelberg: Berlin,
Heidelberg, 2010; pp 165-194; (b) Li, B.-J.; Shi, Z.-J., From
C(sp2)–H to C(sp3)–H: Systematic Studies on Transition Metal-
Catalyzed Oxidative C–C Formation. Chem. Soc. Rev. 2012, 41,
5588-5598; (c) Song, G.; Wang, F.; Li, X., C–C, C–O and C–N
Bond Formation via Rhodium(iii)-Catalyzed Oxidative C–H
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2-Methoxy-8-styrylquinoline (Scheme 5, 8ac). To an oven-dried
screw cap reaction vial charged with a spinvane magnetic stir-bar,
8-substituted quinoline N-oxide (8a, 0.1 mmol) and p-toluenesul-
fonic chloride (0.15 mmol) in 2 ml methanol were added. The re-
action mixture was allowed to stir at room temperature for 15 min.,
then triethyl amine (2 equiv.) was added and reaction continued at
room temperature for 12 h. After completion, the reaction mixture
was diluted with 1M HCl and DCM. Collected DCM fraction of
crude reaction mixture washed with saturated sodium bicarbonate
solution three times. Combined organic layer was dried over anhy-
drous sodium sulfate and evaporated under reduced pressure.
Transparent sticky liquid, yield = 23.2 mg (89%). Isolated from
flash chromatography (20% EtOAc/ n-hexane; silica gel 230-400
1
mesh size). H NMR (300 MHz, CDCl3, δ): 8.37 (d, J = 16.5 Hz,
1H), 8.03 – 7.99 (m, 2H), 7.79 – 7.64 (m, 3H), 7.49 – 7.39 (m, 4H),
7.33 – 7.40 (m, 1H), 6.97 (d, J = 8.7 Hz, 1H), 4.16 (s, 3H). 13C{1H}
NMR (75 MHz, CDCl3, δ): 161.6, 144.0, 139.1, 138.2, 133.8,
129.7, 128.76, 127.5, 127.0, 126.7, 125.8, 125.4, 125.2, 123.8,
112.9, 53.4. IR (ZnSe) νmax (cm-1): 3047, 2943, 2845, 1614, 1573,
1483, 1330, 1269, 1128, 1020, 968, 827, 746, 688. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C18H16NO, 262.1226; found,
262.1230.
2-Chloro-8-styrylquinoline (Scheme 5, 8ad). To an oven-dried
screw cap reaction vial charged with a spinvane magnetic stir-bar,
8-substituted quinoline N-oxide (8a, 0.1 mmol) and thionyl chlo-
ride (2 ml) were added. The reaction mixture was allowed to stir at
50 °C for 12 h. After completion, the reaction mixture was col-
lected in round bottom flask and reaction vial was washed with
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