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CuBrZnI2 Combo-Catalysis for Mild CuICuIII Switching and sp2 CH


Activated Rapid Cyclization to Quinolines and Their Sugar-Based
Chiral Analogues: A UVVis and XPS Study
Ramij R. Mondal, Saikat Khamarui, and Dilip K. Maiti*
Department of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata 700009, India
S Supporting Information
*

ABSTRACT: An unprecedented CuBrZnI2 combo-catalyzed mild Cu1


CuIII switching activation of sp2 CH of highly electron-rich arenes is
reported. Anilines, aldehydes, and terminal alkynes were rapidly coupled
together at ambient temperature to construct a ubiquitous quinoline
framework through cyclization of the CC bond. This smart solvent-free
strategy was exploited for the direct synthesis of valuable 4-substituted, 2,4disubstituted, and thermally labile sugar-based chiral quinolines in good
yields. In contrast to the frequently used iminealkyne cyclization reaction,
this uncommonly mild CuICuIII combo-catalysis for a rapid threecomponent cyclization is expected to proceed through the formation of a
exible propargyl amine intermediate, which provides a CuI-procatalyst for
rapid sp2 CH activation with cyclization involving transient CuIII species.
The in situ generation of transient CuIII species was conrmed through
online ultravioletvisible spectroscopy (UVvis), electrospray ionization mass spectrometry (ESI-MS), and X-ray photoelectron
spectroscopy (XPS) analyses.

are used as lead and antimalarial drugs, chiral architecture for


materials, and asymmetric catalysts.3943 Sugar-based chiral
quinolines have recently been used as a new antioxidant
modulator for amyloid aggregation, an Hg2+-sensor, and potent
antimicrobial, antituberculosis, and DNA-intercalating antitumor agents (AE, Figure 1).4448 In light of the diverse
applications of chiral quinolines, a few methods have been
developed for their preparation: Friedlander condensation
using costly precursors consisting of -C-glycosidic ketones and
2-aminobenzaldehyde derivatives to form methylene-bridged
sugar quinolines upon heating in the presence of pyrrolidine
(25 mol %),45 CuI-catalyzed sugar-based alkyneazide quinoline cycloaddition to 1,2,3-triazole-bridged chiral quinolines,46
and PPh3AuCl (10 mol %)AgSbF6 (10 mol %)-catalyzed
propargyl sugar aldehyde and aniline cycloaddition to quinoline-pyrano-fused sugars,47 as well as a few other methods.48
Quinolines directly attached to the chiral centers such as
quinine analogues are used in antimalarial and other medical
applications. In this regard, sugar molecules directly attached to
the quinoline skeleton are potential drug candidates. To the
best of our knowledge, synthesis of 2-substituted sugar-based
chiral quinolines is unknown in the literature. Thus, the
development of a simple and mild strategy toward the direct
synthesis of acidic and thermally sensitive 2-substituted sugar-

INTRODUCTION
Direct sp2 CH metallation18 is an active area of research
because it can be used for ecient functionalization of arenes
without the use of specially designed, halogenated, and/or
hazardous precursors. In general, sp2 CH activation of arenes
requires high temperatures, which greatly hampers achieving
the desired selectivity and obtaining thermally labile compounds such as valuable sugar-based chiral compounds. Thus,
activating an sp2 CH bond, especially in electron-rich arenes
such as anilines,913 under mild conditions is desirable and will
open up new opportunities toward the selective construction of
ubiquitous heterocycles such as quinolines and their valuable
chiral analogues through multicomponent1416 domino cyclization1723 reactions. In this regard, we envisaged the development and exploitation of a new CuICu III switching
catalysis2430 under mild conditions, which would eciently
deliver CH-activated CC/CX bonds to form functional
groups with tandem cyclization toward an unprecedented
general synthesis of quinolones, with an improved reaction rate,
selectivity, and substrate scope. The mechanisms of the widely
used catalysis with CuI-compounds2435 that pass through a
CuICuIII transition have not been thoroughly investigated.
The scope of the reported CH metallation through a CuI
CuIII transition3135 is also limited because of high temperatures and/or stringent reaction conditions.
Chirality plays a pivotal role in the lives of plants and
animals, such as in biochemical transformations and the
functioning of drugs.3638 Naturally occurring chiral cinchona
alkaloids bearing a quinoline motif and other chiral analogues
2016 American Chemical Society

Received: August 11, 2016


Accepted: August 15, 2016
Published: August 25, 2016
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Figure 1. 2-Substituted (AD) and 2,3-fused (E) bioactive sugar-based quinolines.

mol % each) for the three-component reaction among 2bromoaniline (1a, 1 mmol), 4-ethynyltoluene (2a, 1 mmol),
and paraformaldehyde (3a, 1.2 mmol) in dierent solvents
(entries 911, Table 1) to achieve the 4-substituted quinoline
4a at room temperature in 6065% yield. Gratifyingly, the yield
(81%) and the reaction rate (30 min) signicantly improved
under the solvent-free conditions (entry 12). The combocatalysis selectively produced 4a. The possible regioisomer 5a
was not detected. Catalyst loading was optimized [CuBr (7 mol
%)ZnI2 (9 mol %)] under solvent-free conditions. To
understand the role of the counter anion of the combocatalyst, several experiments were performed with dierent
ZnIICuI-combinations (entries 1317) under similar reaction
conditions, but the reactions were not ecient. Interestingly,
when using a higher and more stable oxidation state of copper
in CuBr2, the reaction was unsuccessful (entry 18). We
investigated the reaction with the commonly used sp2 CH
activating PdII and RuII as well as several other prospective
catalysts (entries 1925), and the results were not encouraging.
Interestingly, MoO(acac)2 was found to be the alternative to
ZnI2 (entry 26). However, ZnI2 was our cocatalyst of choice
because of its low cost and easy availability. The reaction with
the nonmetallic Lewis acid cum oxidant PhIO7881 was
unsuccessful because of the complexation and/or oxidation of
the aromatic amine (1a, entry 27). The reaction was completely
blocked in an N2 atmosphere, which conrmed the need for
aerial oxygen in the construction of quinolines (4a, entry 28).
However, the yield did not improve when the reaction was
performed in an oxygen atmosphere (entry 29).
Tolerance of various functionalities was successfully screened
for this new method (Scheme 2) through the synthesis of a
large number of valuable 4-substituted quinolines82 bearing
both unsubstituted and substituted aromatic residues (Table 2),
a heterocycle (4b, entry 2), a biphenyl system (4j, entry 10),
and a naphthalene moiety (4k, entry 11). Essentially, there was
no limitation regarding the substrate choice because the
reactions occurred smoothly to produce their respective
quinolines on using aromatic amines bearing halogen (1ad,
entries 14 and 917), alkyl (1eg and 1i, entries 57 and
18), and alkoxy (1h, entry 8) groups. We initially concentrated
on using formaldehyde to derive less substituted quinolines,
which found novel applications. Unsubstituted aniline was also
eective in the robust cyclization reaction (1j, entry 19). Aryl
alkynes bearing alkyl, aryl, methoxy, and thiophenyl (2ag)
groups were tolerated. An aliphatic alkyne also responded well
under the developed reaction conditions (2h, entry 12). In
general, these simple, mild, and solvent-free products were fully
characterized using spectroscopic analyses (Supporting Information). The structure of 4a was conrmed using single
crystal X-ray diraction analyses (Scheme 2),83 and that of 4h

based chiral quinolines will be a valuable addition to the


existing modern synthetic approaches to quinolines.
The synthesis of achiral quinolines, such as transition metalcatalyzed cyclization4954 and alkyneimine addition reactions,5557 is well-documented in the literature.5863 However,
instead of making unstable imines through cumbersome
approaches, development of an in situ coupling strategy using
amines, aldehydes, and terminal alkynes and easy metallation to
the ortho-sp2 CH through coordination of the triple bond of
the in situ-generated exible propargyl amine (I, Scheme 1)
Scheme 1. Combo-Catalysis for Mild sp2 CH-Activated
Cyclization

moiety will be a valuable addition to the existing methods for


the synthesis of chiral quinolines directly attached to sugars
under mild conditions. In this context, the combination of two
catalysts will be more useful for the direct NC and CC
coupling of an aldehydecarbon (3) with an amine (1) and a
terminal alkyne (2). Combo-catalysis is an emerging area, and
we6466 and others6771 have established it as a powerful tool
in modern organic synthesis. For instance, the diverse
cyclization reactions catalyzed by VO(acac)2CeCl3, Ni(0)
Cu(I), and MoVICeCl3 developed by our group provide easy
access to a wide range of heterocycles.6466 CuBrZnI2mediated NN/CN coupling for oxidative cyclization,67
PdIRuI-mediated Suzuki cross-coupling reactions,68 AuClLn
AgSbF6-tuned CC coupled aromatization,69 TiCr-catalyzed
polymerization reactions,70 and [IrCuCl2]2AgNTf2-guided
amination71 through sp2 CH activation are very useful in
the synthesis of combo-catalysis functionalized and sugar-based
optically pure quinolines (4) under mild reaction conditions,
with a signicantly improved reaction rate, yield, and selectivity
(without 5). Interestingly, Cu(I/II) compounds7277 and
organozinc(II)78 were reported as active catalysts for the
coupling of secondary aliphatic amines with aldehydes and
alkynes with the respective propargyl amines.

RESULTS AND DISCUSSION


After several unsuccessful attempts using potential combocatalysts6471 (entries 18, Table 1), we used ZnI2CuBr (10
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Table 1. Survey and Optimization of Cyclization Reactiona

entry

metal catalystb

solventc

time (h)

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29

AgOTf, TiCl4
V2O5, CeCl3
CeCl3, AgVO3
Yb(OTf)3, MoO(acac)2
RuCl3, Cs2CO3
RuCl3, Ag2CO3
[IrCODCl]2, AgClO4
RhCl3, Cu(OTf)2
ZnI2CuBr
ZnI2CuBr
ZnI2CuBr
ZnI2CuBrf
Zn(OAc)2CuBr
ZnCl2CuBr
ZnI2CuCl
ZnI2CuI
ZnI2CuOTf
ZnI2CuBr2
ZnI2FeSO4
ZnI2AgOTf
ZnI2AuCl
ZnI2PdCl2
ZnI2Ru(dppe)Cl2
ZnI2PtBr2
ZnI2Pd(PPh3)4
MoO(acac)2CuBr
PhIO
ZnI2CuBr
ZnI2CuBr

CH2Cl2, rt, air


CH2Cl2, rt, air
CH2Cl2, rt, air
CH2Cl2, rt, air
CH2Cl2, rt, air
CH2Cl2, rt, air
CH2Cl2, rt, air
CH2Cl2, rt, air
CH2Cl2, rt, air
PhMe, reux, air
THF, reux, air
rt, air
rt, air
rt, air
rt, air
rt, air
rt, air
rt, air
rt, air
rt, air
rt, air
rt, air
rt, air
rt, air
rt, air
rt, air
rt, air
rt, N2
rt, O2

24
24
24
24
24
24
24
24
4.0
4.0
4.0
0.5
1.5
1.0
1.0
1.0
2.5
12
12
12
3.0
3.5
4.0
3.0
5.0
10
4.0
24
0.4

4a, yield (%)d,e

62
60
65
81
55
61
66
68
53
42
31
54
45
41
48
23
60

82

1a (1 mmol), 2a (1 mmol), and 3a (1.2 mmol). b10 mmol %. c10 mL. d4a puried by column chromatography. e5a not detected. fOptimum
catalyst loading: ZnI2 (9 mol %)CuBr (7 mol %).

Scheme 2. Highly Selective Direct Synthesis of Quinolines

74%). Moreover, all of the synthesized products were fully


characterized using relevant spectroscopic analyses (Supporting
Information).
Next, we turned our attention to expanding the scope of the
mild tandem cyclization process to achieve valuable sugar-based
chiral quinolines. Gratifyingly, the use of glyceraldehydes
produced the desired optically pure compound 7a (eq 1,
Scheme 3) under the developed reaction conditions (entry 12,
Table 1). To understand the versatility of the asymmetric
approach, we used dierent pentose sugar aldehydes (6b,c; eqs

was conrmed through a comparison with known spectroscopic


data.
The widespread bioactivity and pharmaceutical application of
the 2,4-disubstituted quinoline derivatives8489 led us to
investigate their synthesis using the simple combo-catalysis
strategy. To our delight, the strategy was equally applicable for
aldehydes bearing aliphatic (3b, entry 1, Table 3) as well as
aromatic (3ce, entries 24) residues to produce 2,4disubstituted quinolines (4tw).90 This mild and solvent-free
approach was quite fast (23 h) and had good yields (63
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Table 2. Synthesized Quinolines and Reaction Data

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Table 2. continued

Table 3. List of 2,4-Disubstituted Quinoline Derivativesa

ZnI2: 9 mol % and CuBr: 7 mol %.

dry methanol appeared at 529 nm (max) in the UVvis


spectrum (Figure 2), which is very close to the literature value
for the [aryl-CuIIIBr]Br complex reported by Ribas, Stahl, and
colleagues.91 The XPS spectrum (Figure 3) of the reaction
mixture showed the presence of two symbolic peaks at 931.9
and 952.08 eV for CuI and 933.9 and 953.8 eV for transient
CuIII.92
To establish the reaction mechanism, we conducted two
separate control experiments (4a, entry 1, Table 2) with CuBr
and ZnI2, and the reaction did not occur. The cyclization
reaction was unsuccessful upon using the imine 2-BrC6H4
NCH2 and the alkyne 2a under the reaction conditions

2 and 3), which produced the desired products 7bd in 1.5


2.0 h in good yield (6370%). The scope of the mild combocatalysis was successfully established for the direct synthesis of
functionalized chiral quinolines bearing triose, pentose, and
hexose sugar moieties (7af, eqs 14) with a rapid reaction
rate (1.52.0 h) and good yield (6372%). The optical purity
of the quinolines was veried on a semipreparative chiral HPLC
column and by measuring the optical rotation.
Ultravioletvisible (UVvis) spectroscopy and X-ray photoelectron spectroscopy (XPS) of the new combo-catalysis
process were performed to understand the reaction. A strong
absorption band of the reaction mixture (entry 1, Table 2) in
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Scheme 3. One-Step Synthesis of Sugar-Based Chiral Quinolinesa

CuBr: 7 mol % and ZnI2: 9 mol %.

Figure 2. UVvis study for the detection of aryl-CuIII-species (529


nm).
Figure 3. XPS study for detection of CuICuIII species.

(entry 12, Table 1), which indicates that the reaction


progressed without the formation of an imine intermediate.
On the basis of the UVvis and XPS data, controlled
experiments, and literature reports, we propose that CuI rst
activates the terminal CH of the alkyne93 to produce RC
CCu (II, Scheme 4). This observation is also supported by
the fact that the reaction was completely blocked upon using

internal alkynes. The CC and CN bond formation between


aldehyde (3), aromatic amine (1), and II with ZnI2 may give
rise to propargyl amine intermediate III.16 The intermediate III
bearing the exible CC bond allows CuI to easily activate the
aromatic CH and -bonds for oxidative CH insertion with
CC coupling94 to aryl-CuIII-based intermediate (IV). The
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(TLC) was performed on 0.25 mm extra-hard silica gel plates


with a UV254 uorescent indicator. The reported melting
points are uncorrected. 1H NMR and 13C NMR spectra were
recorded at ambient temperature using 300 MHz spectrometers
(300 MHz for 1H and 75 MHz for 13C). Chemical shifts were
reported in parts per million from the tetramethylsilane internal
reference, and coupling constants were reported in Hertz.
Proton multiplicities were represented as s (singlet), d
(doublet), dd (double doublet), t (triplet), q (quartet), and
m (multiplet). Infrared spectra were recorded on a Fourier
transform infrared (FT-IR) spectrometer in thin lms. Highresolution mass spectrometry (HR-MS) data were acquired by
electron spray ionization on a Q-ToF-microquadrupole mass
spectrometer. Optical rotation of the chiral compounds was
measured on a polarimeter using a standard 10 cm quartz cell in
a sodium-D lamp at ambient temperature. Electronic
absorption spectra were recorded using a UVvisNIR
spectrophotometer. XPS analyses with the reaction mixture
were performed on an XPS instrument.
General Procedure for the Synthesis of Quinolines. A
mixture of aromatic amine (1, 1 mmol), alkyne (2, 1 mmol),
aldehyde (3, 1.25 mmol), and the metal catalysts ZnI2 (9 mol
%) and CuBr (7 mol %) together with anhydrous MgSO4 was
taken in a mortar and thrashed with a pestle for approximately
25180 min. The progress of the reaction was monitored using
TLC. The reaction mixture was extracted with ethyl acetate (25
mL), and the organic layer was washed successively with a
saturated sodium bicarbonate solution (1 10 mL) and brine
(2 10 mL). The organic layer was then dried over anhydrous
Na2SO4, ltered, and evaporated in a rotary evaporator under
reduced pressure at room temperature. The crude mass was
subjected to column chromatography with 5% ethyl acetate
hexane to obtain the corresponding desired product. Thus, the
reaction with 2-bromoaniline (1a, 1.0 mmol, 177 mg), 4ethynyltoluene (2a, 1.0 mmol, 116 mg), and paraformaldehyde
(3a, 1.25 mmol, 40 mg) produced 8-bromo-4-p-tolylquinoline
(4a) in 81% yield (240 mg, 0.81 mmol) after purication using
column chromatography on silica gel (60120 mesh) with
ethyl acetatepetroleum ether (1:25, v/v) as the eluent. The
structure of the product (4a) was conrmed using single-crystal
X-ray diractometry. The synthesized quinolines (4aw) were
characterized using NMR (1H and 13C), FT-IR, melting point
(solid compounds only), and mass spectral (HR-MS) analyses.
Characterization Data of Substituted Quinolines (4a
w). 8-Bromo-4-p-tolylquinoline (4a). Yield: 81% (240 mg,
0.81 mmol). Characteristic: yellow solid. Melting point: 9798
C. 1H NMR (300 MHz, CDCl3): 8.99 (1H, d, J = 4.5 Hz),
7.99 (1H, d, J = 7.5 Hz), 7.87 (1H, d, J = 8.5 Hz), 7.077.33
(6H, m), 2.38 (3H, s). 13C NMR (75 MHz, CDCl3): 149.9,
149.3, 144.7, 138.3, 134.0, 132.8, 128.9, 128.8, 127.8, 126.3,
125.6, 124.2, 121.6, 20.7. FT-IR (KBr, cm1): 1604, 1589, 1575,
1484, 1453, 1398, 1383, 783, 754, 731, 709. HR-MS (m/z) for
C16H12BrN (M+): calculated 297.0153, found 297.0155 (one of
the major peaks).
Bromo-6-methyl-4-(thiophen-3-yl)quinoline (4b). Yield:
80% (243 mg, 0.80 mmol). Characteristic: greenish black
solid. Melting point: 111112 C. 1H NMR (300 MHz,
CDCl3): 8.868.89 (1H, m), 7.847.85 (1H, m), 7.697.71
(1H, m), 7.427.46 (2H, m), 7.31 (1H, t, J = 4.8 Hz), 7.17
7.24 (1H, m), 2.40 (3H, s). 13C NMR (75 MHz, CDCl3):
149.7, 144.1, 143.3, 138.1, 137.2, 135.2, 128.8, 128.0, 126.4,
125.1, 124.7, 124.6, 122.0, 21.4. FT-IR (KBr, cm1): 1609,
1580, 1556, 1474, 1430, 1360, 1019, 831, 686. HR-MS (m/z)

Scheme 4. Combo-Catalysis Cycle

generation of the transient CuIII-species was conrmed using


UVvis (Figure 2), XPS (Figure 3), and electrospray ionization
mass spectrometry (ESI-MS) (for IV; e/z 441.8867 [M + H],
appearance of multiple peaks due to the presence of the
isotopes of the two Br atoms) analyses of the sample taken
from the ongoing reaction (4a, entry 1, Table 2). The sevenmembered organometallic compound IV immediately transforms into the desired product 4 through the reductive
elimination of CuI and aromatization through the formation of
the transient intermediate V in the presence of molecular
oxygen and CuX.95 The control experiments for the amine
aldehydealkyne coupled cyclization (entries 20 and 21; Table
1) were unsuccessful in the absence of air or oxygen. However,
the active role of oxygen during the transformation of CuI to
reactive CuIII species may not be avoided.

CONCLUSIONS
In conclusion, a ZnII/CuI combo-catalyzed, solvent-free rapid
general synthesis of quinolines was demonstrated through an
uncommonly mild, sp2 CH-activated tandem cyclization of
anilinesaldehydesalkynes. The scope of this mild strategy
was expanded to the direct synthesis of the widely used 2- and
2,4-disubstituted quinolines and also a new class of valuable
chiral quinolines bearing sugar moieties directly attached to the
chiral center at the C2-position. This method includes a proper
example of copper(I)-catalyzed sp2 CH activation and
functionalization with in situ-generated aryl copper(III) species.
UVvis, XPS, ESI-MS, and control experiments were
successfully carried out to establish the reaction mechanism
involving mild CuICuIII switching catalysis. This simple and
mild combo-catalysis strategy with ecient sp2 CH activation
at ambient temperature may create another frontier in the
modern synthesis of valuable heterocycles and their chiral
analogues.

EXPERIMENTAL SECTION
General Information. All reagents were purchased from
commercial suppliers and used without further purication,
unless otherwise specied. Commercially supplied ethyl acetate
and petroleum ether were distilled before use. The petroleum
ether used in our experiments had a boiling range of 6080 C.
Column chromatography was performed on silica gel (60120
mesh, 0.120.25 mm). Analytical thin-layer chromatography
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for C14H10BrNS (M+): calculated 302.9717, found 302.9713


(one of the major peaks).
6-Bromo-8-methyl-4-phenyl-quinoline (4c). Yield: 78%
(233 mg, 0.78 mmol). Characteristic: grey oil. 1H NMR (300
MHz, CDCl3): 8.868.89 (1H, m), 7.807.83 (1H, m),
7.477.52 (1H, m), 7.347.45 (5H, m), 7.217.24 (1H, m),
2.33 (3H, s). 13C NMR (75 MHz, CDCl3): 149.7, 148.4,
144.2, 137.8, 137.1, 135.1, 129.5, 128.6, 128.5, 128.0, 124.8,
122.2, 21.4. FT-IR (neat, cm1): 1612, 1584, 1570, 1481, 1445,
1431, 1366, 1246, 1032, 863, 763, 701, 620. HR-MS (m/z) for
C16H12BrN (M+): calculated 297.0153, found 297.0157 (one of
the major peaks).
5,8-Dichloro-4-phenylquinoline (4d). Yield: 72% (197 mg,
0.72 mmol). Characteristic: yellow oil. 1H NMR (300 MHz,
CDCl3): 8.96 (1H, d, J = 4.2 Hz), 7.70 (1H, d, J = 8.4 Hz),
7.41 (1H, d, J = 8.4 Hz), 7.317.35 (3H, m), 7.207.23 (3H,
m). 13C NMR (75 MHz, CDCl3): 149.8, 149.3, 145.7, 140.1,
133.3, 130.1, 129.9, 129.2, 129.2, 128.8, 128.0, 127.8, 125.7,
118.8. FT-IR (neat, cm1): 1645, 1603, 1591, 1563, 1480, 1381,
1178, 1027, 832, 810, 783. HR-MS (m/z) for C15H9Cl2N (M+):
calculated 273.0112, found 273.0117 (one of the major peaks).
6-Ethyl-4-phenylquinoline (4e). Yield: 67% (156 mg, 0.67
mmol). Characteristic: brown oil. 1H NMR (300 MHz,
CDCl3): 8.78 (1H, d, J = 4.5 Hz), 8.01 (1H, d, J = 8.7
Hz), 7.59 (1H, s), 7.477.52 (1H, m), 7.407.44 (5H, m),
7.197.22 (1H, m), 2.67 (2H, q, J = 7.5 Hz), 1.17 (3H, t, J =
7.5 Hz). 13C NMR (75 MHz, CDCl3): 149.0, 147.9, 147.4,
142.8, 138.2, 131.6, 130.4, 129.6, 129.5, 128.5, 128.4, 128.3,
126.7, 123.3, 121.3, 29.1, 15.5. FT-IR (neat, cm1): 1620, 1588,
1561, 1482, 1432, 1379, 1353, 1045, 867, 834, 741, 710. HRMS (m/z) for C17H15N (M+): calculated 233.1204, found
233.1203.
6-Isopropyl-4-p-tolylquinoline (4f). Yield: 67% (175 mg,
0.67 mmol). Characteristic: yellow oil. 1H NMR (300 MHz,
CDCl3): 8.78 (1H, s), 8.03 (1H, d, J = 8.7 Hz), 7.66 (1H, s),
7.54 (1H, dd, J = 8.7, 1.8 Hz), 7.33 (2H, d, J = 7.8 Hz), 7.25
(2H, d, J = 8.1 Hz), 7.167.19 (1H, m), 2.882.97 (1H, m),
2.38 (3H, s), 1.18 (6H, d, J = 6.6 Hz). 13C NMR (75 MHz,
CDCl3): 143.4, 142.5, 141.8, 141.5, 132.5, 129.6, 124.0, 123.7,
123.6, 123.1, 121.1, 116.4, 115.7, 28.6, 18.2, 15.6. FT-IR (neat,
cm1): 1614, 1584, 1569, 1501, 1456, 1384, 1042, 859, 817,
755, 698. HR-MS (m/z) for C19H19N (M+): calculated
261.1517, found 262.1594 (M+ + H).
4-(4-Methoxyphenyl)-5,7-dimethylquinoline (4g). Yield:
80% (210 mg, 0.80 mmol). Characteristic: brown solid. Melting
point: 8283 C. 1H NMR (300 MHz, CDCl3): 8.70 (1H, d,
J = 4.5 Hz), 7.75 (1H, s), 7.13 (2H, d, J = 8.7 Hz), 7.05 (2H, d,
J = 3.9 Hz), 6.88 (2H, d, J = 8.4 Hz), 3.80 (3H, s), 2.42 (3H, s),
1.94 (3H, s). 13C NMR (75 MHz, CDCl3): 159.3, 149.9,
148.7, 148.4, 138.9, 135.3, 134.7, 132.2, 129.8, 127.4, 124.7,
123.0, 113.3, 55.3, 24.4, 21.4. FT-IR (KBr, cm1): 2970, 1666,
1609, 1571, 1514, 1492, 1457, 1435, 1248, 1032, 832. HR-MS
(m/z) for C18H17NO (M+): calculated 263.1310, found
263.1313.
6-Methoxy-4-phenylquinoline (4h).96 Yield: 67% (157 mg,
0.67 mmol). Characteristic: brown oil. 1H NMR (300 MHz,
CDCl3): 8.80 (1H, d, J = 4.5 Hz), 8.08 (1H, d, J = 9.3 Hz),
7.52 (5H, s), 7.39 (1H, dd, J = 9.3, 2.7 Hz), 7.30 (1H, d, J = 4.2
Hz), 7.19 (1H, d, J = 2.4 Hz), 3.78 (3H, s). 13C NMR (75
MHz, CDCl3): 157.9, 147.3, 147.2, 144.5, 138.2, 131.0, 129.2,
128.6, 128.3, 127.7, 121.8, 121.6, 103.7, 55.4. FT-IR (KBr,
cm1): 2925, 1623, 1584, 1501, 1432, 1248, 1030, 856. HR-MS

(m/z) for C16H13NO (M+): calculated 235.0997, found


235.0996.
8-Bromo-4-m-tolylquinoline (4i). Yield: 77% (230 mg, 0.77
mmol). Characteristic: yellow solid. Melting point: 9798 C.
1
H NMR (300 MHz, CDCl3): 8.90 (1H, d, J = 4.5 Hz), 7.90
(1H, d, J = 7.5 Hz), 7.74 (1H, d, J = 8.4 Hz), 7.227.28 (2H,
m), 7.107.20 (4H, m), 2.30 (3H, s). 13C NMR (75 MHz,
CDCl3): 150.6, 149.4, 145.5, 138.4, 137.4, 133.1, 130.1, 129.4,
128.5, 128.3, 126.8, 126.6, 126.1, 125.1, 122.1, 21.4. HR-MS
(m/z) for C16H12BrN (M+): calculated 297.0153, found
297.0152 (one of the major peaks).
4-(Biphenyl-4-yl)-8-bromoquinoline (4j). Yield: 73% (262
mg, 0.73 mmol). Characteristic: brown solid. Melting point:
130132 C. 1H NMR (300 MHz, CDCl3): 9.01 (1H, d, J =
4.5 Hz), 8.01 (1H, dd, J = 7.5, 0.9 Hz), 7.90 (1H, dd, J = 8.4,
0.9 Hz), 7.67 (2H, dd, J = 8.1, 1.8 Hz), 7.61 (2H, dd, J = 8.7,
1.5 Hz), 7.267.49 (7H, m). 13C NMR (75 MHz, CDCl3):
150.6, 148.9, 145.6, 141.6, 140.2, 136.4, 133.2, 130.0, 128.9,
128.2, 127.8, 127.3, 127.1, 126.9, 126.0, 125.2, 122.2. FT-IR
(KBr, cm1): 1639, 1599, 1579, 1494, 1450, 1405, 839, 763,
734, 714, 698. HR-MS (m/z) for C21H14BrN (M+): calculated
359.0310, found 359.0306 (one of the major peaks).
8-Bromo-4-(6-methoxynaphthalen-2-yl)quinoline (4k).
Yield: 72% (261 mg, 0.72 mmol). Characteristic: brown solid.
Melting point: 148149 C. 1H NMR (300 MHz, CDCl3):
9.00 (1H, d, J = 4.2 Hz), 8.01 (1H, dd, J = 7.5, 0.9 Hz), 7.90
(1H, dd, J = 8.4, 0.9 Hz), 7.817.83 (2H, m), 7.73 (1H, d, J =
9.0 Hz), 7.49 (1H, d, J = 1.5 Hz), 7.397.46 (1H, m), 7.30
(1H, t, J = 7.9 Hz), 7.137.17 (2H, m), 3.89 (3H, s). 13C NMR
(75 MHz, CDCl3): 157.9, 149.9, 149.1, 133.9, 132.7, 131.9,
129.2, 128.0, 127.9, 127.1, 126.6, 126.5, 125.7, 121.9, 119.2,
105.2, 54.9. FT-IR (KBr, cm1): 1625, 1604, 1580, 1492, 1452,
1384, 1252, 1209, 1026, 853, 819, 768, 747. HR-MS (m/z) for
C20H15BrNO (M+ + H): calculated 364.0337, found 364.0334
(M+ + H, one of the major peaks).
8-Bromo-4-(o-tolyloxymethyl)quinoline (4l). Yield: 65%
(212 mg, 0.65 mmol). Characteristic: brown solid. Melting
point: 7879 C. 1H NMR (300 MHz, CDCl3): 8.97 (1H, d,
J = 3.6 Hz), 8.00 (1H, d, J = 7.5 Hz), 7.88 (1H, d, J = 8.4 Hz),
7.59 (1H, d, J = 3.3 Hz), 7.35 (1H, t, J = 7.5 Hz), 7.097.13
(2H, m), 6.85 (2H, t, J = 8.4 Hz), 5.44 (2H, s), 2.23 (3H, s).
13
C NMR (75 MHz, CDCl3): 156.2, 151.1, 145.1, 143.2,
133.2, 131.1, 127.2, 127.1, 126.9, 125.8, 122.7, 121.3, 120.0,
111.3, 66.4, 16.3. FT-IR (KBr, cm1): 1646, 1601, 1587, 1463,
1368, 1306, 1291, 1191, 1020, 754. HR-MS (m/z) for
C17H14BrNO (M+): calculated 327.0259, found 327.0261
(one of the major peaks).
8-Bromo-4-phenylquinoline (4m). Yield: 75% (212 mg,
0.75 mmol). Characteristic: brown oil. 1H NMR (300 MHz,
CDCl3): 8.978.98 (1H, m), 7.98 (1H, dd, J = 7.2, 4.5 Hz),
7.79 (1H, dd, J = 8.1, 1.5 Hz), 7.177.46 (7H, m). 13C NMR
(75 MHz, CDCl3): 150.5, 149.3, 145.5, 137.5, 133.2, 129.5,
128.6, 128.2, 126.9, 126.0, 125.1, 122.2. FT-IR (neat, cm1):
1611, 1581, 1490, 1442, 1391, 1372, 779, 751, 731, 702. HRMS (m/z) for C15H10BrN (M+): calculated 282.9997, found
282.9994 (one of the major peaks).
8-Bromo-4-(4-methoxyphenyl)quinoline (4n). Yield: 70%
(220 mg, 0.70 mmol). Characteristic: brown solid. Melting
point: 7880 C. 1H NMR (300 MHz, CDCl3): 8.94 (1H,
dd, J = 4.3, 1.2 Hz), 7.90 (1H, dd, J = 7.5, 1.2 Hz), 7.84 (1H, d,
J = 8.4 Hz), 7.247.34 (4H, m), 6.96 (2H, dd, J = 9.7, 1.8 Hz),
3.79 (3H, s). 13C NMR (75 MHz, CDCl3): 160.0, 150.5,
149.1, 145.5, 133.1, 130.8, 129.7, 128.4, 126.7, 126.0, 125.0,
258

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122.1, 114.1, 55.4. FT-IR (KBr, cm1): 1666, 1607, 1584, 1513,
1489, 1455, 1386, 1248, 1178, 1037, 837, 766. HR-MS (m/z)
for C16H12BrNO (M+): calculated 313.0102, found 313.0104
(one of the major peaks).
8-Bromo-6-methyl-4-phenylquinoline (4o). Yield: 71%
(212 mg, 0.71 mmol). Characteristic: grey oil. 1H NMR (300
MHz, CDCl3): 8.868.89 (1H, m), 7.807.83 (1H, m),
7.477.52 (1H, m), 7.347.45 (5H, m), 7.217.24 (1H, m),
2.33 (3H, s). 13C NMR (75 MHz, CDCl3): 149.7, 148.4,
144.2, 137.8, 137.1, 135.1, 129.5, 128.6, 128.5, 128.0, 124.8,
122.2, 21.4. FT-IR (neat, cm1): 1612, 1584, 1570, 1481, 1445,
1431, 1366, 1246, 1032, 863, 763, 701, 620. HR-MS (m/z) for
C16H12BrN (M+): calculated 297.0153, found 297.0157 (one of
the major peaks).
8-Bromo-6-methyl-4-m-tolylquinoline (4p). Yield: 70%
(218 mg, 0.70 mmol). Characteristic: yellow solid. Melting
point: 126128 C. 1H NMR (300 MHz, CDCl3): 8.87 (1H,
d, J = 4.2 Hz), 7.80 (1H, s), 7.52 (1H, s), 7.30 (1H, t, J = 7.5
Hz), 7.197.22 (2H, m), 7.137.16 (2H, m), 2.34 (3H, s),
2.32 (3H, s). 13C NMR (75 MHz, CDCl3): 149.1, 148.1,
143.6, 137.8, 137.2, 136.5, 134.6, 129.5, 128.7, 127.9, 127.5,
126.1, 124.3, 124.1, 121.7, 20.9. FT-IR (KBr, cm1): 1610,
1603, 1573, 1482, 1468, 1439, 1376, 1364, 1022, 882, 786, 754,
710. HR-MS (m/z) for C17H15BrN (M+ + H): calculated
312.0388, found 312.0389 (M+ + H, one of the major peaks).
5,8-Dichloro-4-m-tolylquinoline (4q). Yield: 62% (178 mg,
0.62 mmol). Characteristic: yellow solid. Melting point: 80 C.
1
H NMR (300 MHz, CDCl3): 8.93 (1H, dd, J = 3.9, 1.8 Hz),
7.667.70 (1H, m), 7.377.41 (1H, m), 7.287.30 (1H, m),
7.167.21 (2H, m), 6.997.02 (2H, m), 2.30 (3H, s). 13C
NMR (75 MHz, CDCl3): 149.8, 149.4, 145.7, 140.0, 137.4,
133.3, 130.1, 129.9, 129.2, 129.1, 128.7, 127.6, 126.0, 125.8,
118.5, 21.4. FT-IR (KBr, cm1): 1642, 1606, 1589, 1569, 1483,
1383, 1189, 1020, 847, 814, 784. HR-MS (m/z) for
C16H11Cl2N (M+): calculated 287.0269, found 287.0271 (one
of the major peaks).
8-Methyl-4-phenylquinoline (4r). Yield: 67% (147 mg, 0.67
mmol). Characteristic: brown oil. 1H NMR (300 MHz,
CDCl3): 8.858.88 (1H, m), 7.65 (1H, d, J = 8.4 Hz),
7.437.48 (1H, m), 7.377.39 (5H, m), 7.157.30 (2H, m),
2.76 (3H, s). 13C NMR (75 MHz, CDCl3): 148.6, 147.7,
138.5, 137.3, 129.5, 129.5, 128.4, 128.2, 126.7, 126.2, 123.9,
121.1, 18.6. FT-IR (neat, cm1): 1602, 1582, 1571, 1477, 1432,
1383, 1364, 1055, 867, 839, 735, 711. HR-MS (m/z) for
C16H13NNa (M+ + Na): calculated 242.0946, found 242.0948
(M+ + Na).
4-p-Tolylquinoline (4s). Yield: 78% (171 mg, 0.78 mmol).
Characteristic: blackish oil. 1H NMR (300 MHz, CDCl3):
8.87 (1H, d, J = 4.2 Hz), 8.12 (1H, d, J = 8.7 Hz), 7.89 (1H, d, J
= 8.4 Hz), 7.66 (1H, t, J = 7.5 Hz), 7.43 (1H, t, J = 7.5 Hz),
7.197.36 (5H, m), 2.40 (3H, s). 13C NMR (75 MHz, CDCl3):
149.8, 148.7, 148.4, 138.3, 134.9, 129.6, 129.4, 129.3, 129.2,
126.8, 126.5, 125.9, 121.2, 21.2. FT-IR (neat, cm1): 1614,
1586, 1569, 1501, 1460, 1421, 1390, 1276, 1010, 819, 764. HRMS (m/z) for C16H13N (M+): calculated 219.1048, found
219.1052.
8-Bromo-2-isobutyl-4-p-tolylquinoline (4t). Yield: 70%
(247 mg, 0.70 mmol). Characteristic: brown oil. 1H NMR
(300 MHz, CDCl3): 8.05 (1H, d, J = 8.4 Hz), 7.82 (1H, d, J =
8.1 Hz), 7.60 (1H, t, J = 7.5 Hz), 7.307.38 (2H, m), 7.24 (2H,
d, J = 7.8 Hz), 7.16 (1H, s), 2.80 (2H, d, J = 7.2 Hz), 2.37 (3H,
s), 2.072.20 (1H, m), 0.91 (6H, d, J = 6.6 Hz). 13C NMR (75
MHz, CDCl3): 161.6, 148.8, 148.0, 138.3, 135.2, 129.4, 129.3,

129.2, 128.9, 125.7, 125.4, 122.2, 48.1, 29.4, 22.6, 21.2. FT-IR
(neat, cm1): 1624, 1590, 1573, 1499, 1456, 1344, 1127, 1053,
855, 817, 760, 711, 698. HR-MS (m/z) for C20H20BrN (M+):
calculated 353.0779, found 353.0781 (one of the major peaks).
6-Ethyl-2-(4-nitrophenyl)-4-p-tolylquinoline (4u). Yield:
66% (243 mg, 0.66 mmol). Characteristic: grey solid. Melting
point: 130132 C. 1H NMR (300 MHz, CDCl3): 8.29 (4H,
s), 8.09 (1H, d, J = 8.7 Hz), 7.73 (1H, s), 7.66 (1H, s), 7.58
(1H, d, J = 8.7 Hz), 7.40 (2H, d, J = 7.8 Hz), 7.31 (2H, d, J =
8.1 Hz), 2.72 (2H, q, J = 7.5 Hz), 2.43 (3H, s), 1.21 (3H, t, J =
7.5 Hz). 13C NMR (75 MHz, CDCl3): 153.2, 149.2, 148.2,
147.6, 145.6, 143.5, 138.5, 135.2, 131.0, 130.1, 129.3, 128.7,
128.1, 126.2, 123.9, 123.3, 119.0, 21.2, 19.0, 15.4. FT-IR (KBr,
cm1): 2960, 2926, 1725, 1595, 1548, 1516, 1492, 1456, 1343,
1110, 847, 821, 699. HR-MS (m/z) for C24H20N2O2 (M+):
calculated 368.1525, found 368.1529.
8-Bromo-2-(2-bromophenyl)-6-methyl-4-phenylquinoline
(4v). Yield: 63% (273 mg, 0.63 mmol). Characteristic: brown
oil. 1H NMR (300 MHz, CDCl3): 8.85 (1H, s), 8.38 (1H, dd,
J = 7.8 Hz), 7.088.13 (1H, m), 7.95 (1H, dd, J = 7.2 Hz),
7.747.82 (2H, m), 7.607.66 (1H, m), 7.47 (1H, s), 7.14
7.25 (2H, m), 7.04 (1H, d, J = 8.1 Hz), 2.35 (3H, s), 2.16 (3H,
s). 13C NMR (75 MHz, CDCl3): 159.5, 157.5, 147.6, 140.1,
137.9, 137.2, 135.3, 135.2, 133.4, 132.4, 131.3, 130.0, 129.6,
128.6, 128.4, 127.7, 126.8, 125.3, 124.4, 123.9, 122.0, 21.4. FTIR (neat, cm1): 1671, 1587, 1539, 1470, 1433, 1356, 827, 756,
702. HR-MS (m/z) for C22H15Br2N (M+): calculated 450.9571,
found 450.9574 (one of the major peaks).
8-Bromo-6-methyl-2-(2-nitrophenyl)-4-m-tolylquinoline
(4w). Yield: 74% (319 mg, 0.74 mmol). Characteristic:
colorless solid. Melting point: 121122 C. 1H NMR (300
MHz, CDCl3): 8.85 (1H, s), 8.38 (1H, dd, J = 7.8, 1.2 Hz),
8.088.13 (1H, m), 7.95 (1H, dd, J = 7.5, 1.8 Hz), 7.747.82
(2H, m), 7.607.66 (1H, m), 7.47 (1H, s), 7.147.25 (2H, m),
7.04 (1H, d, J = 8.1 Hz), 2.35 (3H, s), 2.16 (3H, s). 13C NMR
(75 MHz, CDCl3): 156.7, 147.0, 137.9, 134.0, 133.7, 133.6,
133.4, 132.6, 131.3, 131.0, 130.2, 129.6, 129.1, 128.9, 127.5,
124.5, 119.3, 118.6, 115.7, 20.6, 20.0. FT-IR (KBr, cm1): 1627,
1607, 1571, 1518, 1487, 1337, 1209, 1077, 807, 738. HR-MS
(m/z) for C23H17BrN2O2 (M+): calculated 432.0473, found
432.0476 (one of the major peaks).
Characterization Data of Chiral Sugar-Based Quinoline Derivatives (7af). Synthesis of compound 7 was
performed according to the procedure for compound 4.
(R)-2-(2,2-Dimethyl-1,3-dioxolan-4-yl)-6-methoxy-4-phenylquinoline (7a). Yield: 65% (218.0 mg, 0.65 mmol).
1
Characteristic: black oil. []25
D 78.40 (c 0.18, CHCl3). H
NMR (300 MHz, CDCl3): 8.27 (1H, d, J = 9.3 Hz), 7.64
(1H, s), 7.56 (4H, s), 7.46 (1H, d, J = 8.4 Hz), 7.26 (1H, d, J =
1.5 Hz), 7.22 (1H, s), 4.11 (1H, dd, J = 16.0, 7.8 Hz), 3.80 (3H,
s), 3.27 (1H, dd, J = 12.0, 3.6 Hz), 3.16 (1H, dd, J = 12.0, 7.2
Hz), 1.58 (3H, s), 1.52 (3H, s). 13C NMR (75 MHz, CDCl3):
158.5, 156.5, 152.6, 141.7, 137.6, 129.1, 128.9, 128.8, 128.4,
127.5, 123.3, 121.3, 121.3, 118.7, 110.8, 104.1, 70.5, 67.2, 55.7,
26.8, 26.4. FT-IR (neat, cm1): 1713, 1627, 1589, 1496, 1378,
1256, 1210, 1163, 1072, 883, 836, 758, 707. HR-MS (m/z) for
C21H21NO3 (M+): calculated 335.1521, found 335.1524.
2-((3aR,5R,6R,6aR)-6-(Benzyloxy)-2,2dimethyltetrahydrofuro[3,2-d][1,3]dioxol-5-yl)-8-bromo-4-ptolylquinoline (7b). Yield: 68% (371.5 mg, 0.68 mmol).
1
Characteristic: yellow oil. []25
D 53.70 (c 0.20, CHCl3). H
NMR (300 MHz, CDCl3): 8.05 (1H, d, J = 7.5 Hz), 7.92
(1H, d, J = 8.7 Hz), 7.76 (1H, s), 7.267.42 (5H, m), 7.06
259

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7.16 (3H, m), 6.83 (2H, d, J = 7.2 Hz), 6.19 (1H, d, J = 3.0
Hz), 5.72 (1H, d, J = 2.7 Hz), 4.75 (1H, d, J = 12.6 Hz), 4.55
4.58 (1H, m), 4.41 (1H, d, J = 11.7 Hz), 4.19 (1H, d, J = 11.7
Hz), 2.64 (3H, s), 1.61 (3H, s), 1.39 (3H, s). 13C NMR (75
MHz, CDCl3): 158.4, 150.0, 149.7, 145.0, 138.8, 134.4, 132.9,
128.9, 128.8, 128.1, 126.4, 125.8, 124.4, 121.4, 117.9, 112.2,
105.6, 84.1, 83.4, 78.5, 72.7, 26.8, 26.4, 21.2. FT-IR (neat,
cm1): 1713, 1631, 1582, 1491, 1451, 1379, 1209, 1084, 1021,
905, 866, 764, 701. HR-MS (m/z) for C30H28BrNO4 (M+):
calculated 545.1201, found 545.1204 (one of the major peaks).
2-((3aR,5R,6S,6aR)-6-(Benzyloxy)-2,2dimethyltetrahydrofuro[3,2-d][1,3]dioxol-5-yl)-8-bromo-4-ptolylquinoline (7c). Yield: 63% (344.0 mg, 0.63 mmol).
1
Characteristic: yellow oil. []25
D 62.43 (c 0.19, CHCl3). H
NMR (300 MHz, CDCl3): 8.03 (1H, d, J = 7.2 Hz), 7.91
(1H, d, J = 8.4 Hz), 7.75 (1H, s), 7.257.40 (5H, m), 7.03
7.14 (3H, m), 6.82 (2H, d, J = 7.2 Hz), 6.17 (1H, d, J = 3.3
Hz), 5.70 (1H, d, J = 3.0 Hz), 4.72 (1H, d, J = 3.0 Hz), 4.55
(1H, d, J = 3.0 Hz), 4.40 (1H, d, J = 11.7 Hz), 4.17 (1H, d, J =
12.0 Hz), 2.45 (3H, s), 1.60 (3H, s), 1.38 (3H, s). 13C NMR
(75 MHz, CDCl3): 158.3, 149.9, 149.3, 144.7, 138.3, 134.0,
132.8, 128.9, 128.8, 127.8, 126.3, 125.6, 124.2, 121.4, 117.8,
112.2, 105.7, 84.1, 83.4, 78.3, 72.7, 26.7, 26.4, 21.2. FT-IR
(neat, cm1): 1712, 1623, 1586, 1489, 1455, 1382, 1217, 1078,
1029, 859, 707. HR-MS (m/z) for C30H28BrNO4 (M+):
calculated 545.1201, found 545.1206 (one of the major peaks).
2-((3aR,5R,6S,6aR)-6-(Benzyloxy)-2,2dimethyltetrahydrofuro[3,2-d][1,3]dioxol-5-yl)-5,7-dimethyl4-phenylquinoline (7d). Yield: 70% (337.0 mg, 0.70 mmol).
1
Characteristic: yellow oil. []25
D 59.00 (c 0.80, CHCl3). H
NMR (300 MHz, CDCl3): 7.78 (1H, s), 7.50 (1H, s), 7.30
7.40 (5H, m), 7.057.15 (4H, m), 6.82 (2H, d, J = 7.2 Hz),
6.13 (1H, d, J = 3.6 Hz), 5.60 (1H, d, J = 3.0 Hz), 4.71 (1H, d, J
= 3.6 Hz), 4.43 (1H, d, J = 3.0 Hz), 4.33 (1H, d, J = 11.7 Hz),
4.06 (1H, d, J = 11.7 Hz), 2.50 (3H, s), 1.98 (3H, s), 1.57 (3H,
s), 1.32 (3H, s). 13C NMR (75 MHz, CDCl3): 155.3, 149.0,
148.7, 142.5, 139.1, 137.3, 135.2, 131.9, 128.8, 128.7, 128.0,
127.2, 126.8, 123.7, 122.0, 112.1, 105.5, 84.0, 83.3, 72.3, 26.9,
26.4, 24.2, 21.3. FT-IR (neat, cm1): 1714, 1621, 1579, 1488,
1453, 1376, 1211, 1082, 1024, 863, 698. HR-MS (m/z) for
C31H31NO4 (M+): calculated 481.2253, found 481.2255.
8-Bromo-4-phenyl-2-((3aR,5R,5aS,8aS,8bR)-2,2,7,7-tetramethyltetrahydro-3aH-bis[1,3]dioxolo[4,5-b:4,5-d]pyran-5yl)quinoline (7e). Yield: 72% (369.5 mg, 0.72 mmol).
1
Characteristic: brown oil. []25
D 80.63 (c 0.95, CHCl3). H
NMR (300 MHz, CDCl3): 8.008.03 (1H, m), 7.837.86
(1H, m), 7.73 (1H, d, J = 2.7 Hz), 7.497.50 (5H, m), 7.41
(1H, d, J = 8.1 Hz), 7.267.27 (1H, m), 5.78 (1H, d, J = 4.8
Hz), 5.28 (1H, s), 5.00 (1H, d, J = 7.8 Hz), 4.814.83 (1H, m),
4.46 (1H, dd, J = 2.7, 2.1 Hz), 1.63 (3H, s), 1.50 (3H, s), 1.40
(3H, s), 1.31 (3H, s). 13C NMR (75 MHz, CDCl3): 159.2,
148.7, 144.9, 144.8, 138.2, 132.7, 132.4, 129.6, 128.4, 128.3,
127.4, 126.2, 125.7, 120.7, 117.9, 109.4, 108.8, 96.7, 73.6, 71.5,
71.0, 70.9, 26.2, 25.9, 24.9, 24.2. FT-IR (neat, cm1): 1712,
1634, 1600, 1508, 1453, 1382, 1255, 1211, 1166, 1068, 1003,
905, 764, 702. HR-MS (m/z) for C26H26BrNO5 (M+):
calculated 511.0994, found 511.0997 (one of the major peaks).
6-Methoxy-4-phenyl-2-((3aR,5R,5aS,8aS,8bR)-2,2,7,7-tetramethyltetrahydro-3aH-bis[1,3]dioxolo[4,5-b:4,5-d]pyran5-yl)quinoline (7f). Yield: 67% (310.5 mg, 0.67 mmol).
1
Characteristic: yellow oil. []25
D 56.70 (c 1.2, CHCl3). H
NMR (300 MHz, CDCl3): 8.00 (1H, dd, J = 7.5, 1.5 Hz),
7.59 (1H, d, J = 1.5 Hz), 7.447.55 (5H, m), 7.317.36 (1H,

m), 7.177.18 (1H, m), 5.745.75 (1H, m), 5.18 (1H, s), 4.84
(1H, dd, J = 6.3, 1.5 Hz), 4.76 (1H, dd, J = 5.7, 2.1 Hz), 4.41
4.44 (1H, m), 3.75 (3H, s), 1.60 (3H, s), 1.41 (3H, s), 1.37
(3H, s), 1.28 (3H, s). 13C NMR (75 MHz, CDCl3): 157.5,
155.7, 146.9, 143.7, 138.8, 130.6, 129.3, 128.4, 128.0, 126.9,
121.4, 120.4, 109.1, 108.8, 103.7, 96.7, 73.6, 71.0, 70.7, 55.3,
26.2, 25.9, 24.9, 24.2. FT-IR (neat, cm1): 1713, 1622, 1593,
1560, 1493, 1381, 1255, 1214, 1166, 1068, 1012, 889, 833, 760.
HR-MS (m/z) for C27H29NO6 (M+): calculated 463.1994,
found 463.1992.

ASSOCIATED CONTENT

S Supporting Information
*

The Supporting Information is available free of charge on the


ACS Publications website at DOI: 10.1021/acsomega.6b00185.
Detailed experimental procedures, XRD, spectroscopic
data, and spectra (PDF)
Crystallographic information (CIF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: dkmchem@caluniv.ac.in.
Notes

The authors declare no competing nancial interest.

ACKNOWLEDGMENTS
Financial support from DST (SR/S1/OC-05/2012 and SR/S5/
GC-04/2012) and UGC (SRF) is gratefully acknowledged.
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ACS Omega 2016, 1, 251263

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