Stereoselective synthesis of tetrahydroquinolines through an imino-ene cyclization reaction

Article abstract of DOI:10.1002/ejoc.201201363

Tetrahydroquinolines have been efficiently synthesized in good yields with excellent stereoselectivity. The reaction between α-allylic anilines and aldehydes proceeds through an imino-ene cyclization that is mediated by boron trifluoride-diethyl ether. Co

Full text of DOI:10.1002/ejoc.201201363

FULL PAPER
DOI: 10.1002/ejoc.201201363
Stereoselective Synthesis of Tetrahydroquinolines Through an Imino-Ene
Cyclization Reaction
Somasekhar Bondalapati,[a] Kiran Indukuri,[a] Priya Ghosh,[a] and Anil K. Saikia*[a]
Keywords: Synthetic methods / Nitrogen heterocycles / Cyclization / Diastereoselectivity / Lewis acids
Tetrahydroquinolines have been efficiently synthesized in
good yields with excellent stereoselectivity. The reaction be-
tween α-allylic anilines and aldehydes proceeds through an
imino-ene cyclization that is mediated by boron trifluoride–
diethyl ether.
(see Scheme 1). To achieve our goal initially, 4-methyl-N-
(5-methylhex-4-en-1-yl)benzenesulfonamide (1) was treated
with m-nitrobenzaldehyde at room temperature. In the pres-
ence of boron trifluoride–diethyl ether and in dichlorometh-
ane, this reaction only furnished self-cyclized product 5 in
82% yield, and the aldehyde coupled product 4 was not
detected (see Scheme 2). We explored the reaction further
with various Lewis acids such as In(OTf)3, Bi(OTf)3,
Sc(OTf)3, TMSOTf, and FeCl3 in different solvents such
as CH2Cl2 and benzene. However, in contradiction to our
hypothesis, the reaction gave only the self-cyclized product
Introduction
The tetrahydroquinoline unit is important in synthetic
chemistry because of its presence in many biologically
active natural products[1] and pharmaceuticals.[2] In organic
synthesis, some tetrahydroquinolines have been used as li-
gands.[3] The preparation of 1,2,3,4-tetrahydroquinolines
has been accomplished by several methods such as an intra-
molecular aza-Michael addition,[4] an imino-Diels–Alder
reaction,[5] an intramolecular hydroamination,[6] the re-
duction of quinolines,[7] and other approaches.[8] The imino-
ene reaction has been used for the synthesis of homoallylic
amines[9] as well as the synthesis of benzimidazole[10] and
thiazolidines.[11] Recently, we prepared oxygen[12] and sul-
fur[13] heterocycles by using the oxonium-ene and thionium-
ene cyclization reaction, respectively. Herein, we report a
methodology for the synthesis of tetrahydroquinolines. The
reaction between an aldehyde and α-allylic aniline proceeds
through an imino-ene cyclization that is mediated by boron
trifluoride–diethyl ether.
1
in all of the cases. These structures were confirmed by H
NMR analysis. In addition, the free amine did not undergo
any cyclization reaction.[14]
Scheme 1. Proposed reaction for piperidine synthesis.
Results and Discussion
In continuation of our interest in the synthesis of hetero-
cyclic compounds through the ene-cyclization reac-
tion,[12,13] we searched for a methodology for the synthesis
of substituted piperidines. We envisioned that the reaction
between 4-methyl-N-(5-methylhex-4-en-1-yl)benzenesulfon-
amide (1) and aldehyde 2 in the presence of a Lewis acid
would provide access to 2,3-disubstituted piperidines 4
through an intramolecular iminium-ene cyclization reaction
Scheme 2. Formation of piperidine from 4-methyl-N-(5-methylhex-
4-en-1-yl)benzenesulfonamide.
[a] Department of Chemistry, Indian Institute of Technology Gu-
wahati,
Guwahati 781039, India
Fax: +91-361-2690762
E-mail: asaikia@iitg.ernet.in
Homepage: http://shilloi.iitg.ernet.in/~chem/faculty/FacultyP/
AKS_WEB/index.html
From these results, we speculated on the utility of free
aromatic amine 6 to react with aldehyde 2 and produce im-
ine 7 as the reaction intermediate. Imine 7 would then be
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201363.
952
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Stereoselective Synthesis of Tetrahydroquinolines
activated by a Lewis acid, which would enable a facile at- Table 1. Synthesis of 2,3-disubstituted tetrahydroquinolines.
tack by the alkene moiety to afford the corresponding
imino-ene product 8 (see Scheme 3).
Scheme 3. Proposed synthesis of tetrahydroquinoline through
imino-ene reaction.
In an initial attempt, arylamine 6 was treated with m-
nitrobenzaldehyde (2f) in the presence of boron trifluoride–
diethyl ether at room temperature. The reaction gave the
desired product as a mixture of isomers 8f and 8fЈ in a ratio
of 93:7. The major and minor isomers were separated by
column chromatography, and the products were charac-
terized by NMR spectroscopy (see Scheme 4). The coupling
constant of the H-2 proton of 8f is 4 Hz, whereas the cou-
pling constant of the same proton in 8fЈ is 9.2 Hz.
Scheme 4. Synthesis of 1,2,3,4-tetrahydroquinoline.
To improve the diastereoselectivity, the reaction was per-
formed at –20 °C. To our delight, only the single dia-
stereomer 8f was detected in the 1H NMR of crude reaction
mixture. It is noteworthy that the temperature had a signifi-
cant influence on the diastereoselectivity of the reaction. It
was also shown that dichloromethane, in comparison to
other solvents such as THF and toluene, was the desired
solvent for the reaction. Having established the optimized
[a] Yields refer to isolated yield. The compounds are characterized
conditions, we then explored the scope of the reaction by
by IR spectroscopy, 1H, 13C, and 19F NMR spectroscopy, and mass
using a wide variety of aromatic and heteroaromatic alde-
spectrometry.
hydes as shown in Table 1. In the case of the aromatic alde-
hydes, the substituent on the ring had a substantial effect on
the yield of the reaction. Aromatic aldehydes with electron- tion. Moreover, in all of the cases studied, 2,3-disubstituted
withdrawing substituents on the ring gave good yields in tetrahydroquinolines 8a–8j were obtained in high purity
comparison to the aromatic aldehydes with electron-donat- without any side product and with a high degree of dia-
1
ing groups on the ring. Among all of the aromatic alde- stereoselectivity, as determined from the H and 13C NMR
hydes listed in Table 1, 2,6-dichlorobenzaldehyde was the spectra of the crude product. Substituted anilines (see
best substrate for this reaction. On the other hand, aliphatic Table 1, Entries d and e) were also studied. Although
aldehydes such as butanal and cyclohexane carboxaldehyde methyl-substituted aniline (see Table 1, Entry d) gave a
failed to yield the desired tetrahydroquinolines. The reason good yield, fluoro-substituted aniline (see Table 1, Entry e)
for this is presumed to be the instability of N-arylaldimine failed to give the desired product, and the starting materials
9 (see Scheme 5), which is formed during the course of reac- were recovered from the reaction mixture. The stereochem-
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953

S. Bondalapati, K. Indukuri, P. Ghosh, A. K. Saikia
FULL PAPER
istry of the 2,3-disubstituted tetrahydroquinolines was es- method is highly diastereoselective. Furthermore, it can be
1
tablished by COSY experiments and the values of the H used for the synthesis of functionalized quinolines.
NMR coupling constants. The coupling constants of the H-
2 and H-3 protons of major isomer are in the range of 2.8–
4.0 Hz, which indicates a cis relationship of the substituents Experimental Section
(see Figure 1). The cis geometry of the substituents was fur-
General Methods: All of the reagents were commercially obtained.
ther confirmed unambiguously by the single-crystal X-ray
BF3·Et2O was distilled from CaH2 prior to use.1H NMR spectro-
structure analysis of compound 8d.[15]
scopic data were recorded with a Varian AS 400 (400 MHz) spec-
trometer, and the samples were dissolved in CDCl3 with TMS as
the internal standard. The 13C NMR spectroscopic data were ob-
tained with a Varian AS 400, which operated at 100 MHz. IR spec-
tra were recorded with a Nicolet Impact 410 FTIR spectrometer.
HRMS spectra were recorded using the APCI mode. Elemental
analyses were performed with a Perkin–Elmer 2400 series II CHNS
analyzer. Melting points were measured in open capillary tubes.
General Procedure for the Synthesis Tetrahydroquinolines
(2R*,3R*)-1,2,3,4-Tetrahydro-2-phenyl-3-(prop-1-en-2-yl)quinoline
(8a): An oven-dried round-bottomed flask was charged with the
aldehyde (53 mg, 0.5 mmol, 1 equiv.) and dichloromethane (2 mL),
and the resulting solution was cooled to –20 °C. To this solution
was added aniline (80 mg, 0.5 mmol, 1 equiv.) in CH2Cl2 (2 mL) all
at once. The mixture was stirred at the same temperature for 5 min.
To this stirring solution was added boron trifluoride–diethyl ether
(90 mg, 0.6 mmol, 1.2 equiv.). After stirring at room temperature
for 1 h, the mixture was poured into a saturated solution of
NaHCO3 (5 mL). The reaction mixture was extracted with dichlo-
romethane (2ϫ10 mL) and then washed with brine and water. The
organic layers were collected, dried with Na2SO4, filtered, and con-
centrated. The resultant crude residue was purified by column
chromatography over silica gel (petroleum ether/EtOAc, 98:2) to
Scheme 5. Mechanism of the reaction.
afford 8a as a colorless solid (93 mg, 75%); m.p. 58–60 °C. 1H
NMR (400 MHz, CDCl3): δ = 1.69 (s, 3 H), 2.69 (dd, J = 16.0 and
5.2 Hz, 1 H), 2.76 (dd, J = 16.0 and 10.8 Hz, 1 H), 2.86 (ddd, J =
10.8, 5.2, and 4.0 Hz, 1 H), 4.42 (br. s, 2 H), 4.68 (br. s, 1 H), 4.77
(t, J = 1.2 Hz, 1 H), 6.58 (d, J = 8.0 Hz, 1 H), 6.67 (t, J = 7.6 Hz,
1 H), 7.00–7.10 (m, 2 H), 7.12–7.15 (m, 2 H), 7.21–7.25 (m, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 22.9, 28.3, 43.8, 57.9,
112.8, 113.4, 117.0, 120.7, 127.2, 127.3, 127.5, 127.9, 129.6, 142.7,
144.1, 144.8 ppm. IR: ν = 2917, 1607, 1492, 1451, 1265, 1156, 746,
˜
700 cm–1. HRMS [APCI (atmospheric pressure chemical ioniza-
tion)]: calcd. for C18H19N [M + H]+ 250.1590; found 250.1586.
C18H19N (249.35): calcd. C 86.70, H 7.68, N 5.62; found C 86.64,
H 7.72, N 5.59.
Figure 1. Confirmation of stereochemistry of 2,3-disubstituted
tetrahydroquinoline 8.
The mechanism of the reaction can be explained. The
aldehyde upon reaction with an amine forms imine 9, which
is activated by the Lewis acid and then undergoes nucleo-
philic attack by the alkene moiety to produce cationic inter-
mediate 11 through the six-membered cyclic transition state
10. In transition state structure 10, the six-membered aro-
matic ring takes a position in such a way that the other aryl
and isopropenyl groups are trans to it. In this configuration,
the protons appear on the same side of the aromatic ring
to make the system more stable. Finally, intermediate 11
eliminates a proton to furnish tetrahydroquinoline 8.
(2R*,3R*)-1,2,3,4-Tetrahydro-3-(prop-1-en-2-yl)-2-p-tolylquinoline
(8b): Colorless solid (96 mg, 73 %); m.p. 65–67 °C. 1H NMR
(400 MHz, CDCl3): δ = 1.70 (s, 3 H), 2.30 (s, 3 H), 2.69 (dd, J =
15.6 and 4.8 Hz, 1 H), 2.75 (dd, J = 15.6 and 10.4 Hz, 1 H), 2.84
(ddd, J = 10.4, 4.8, and 3.6 Hz, 1 H), 4.37 (br. s, 1 H), 4.44 (br. s,
1 H), 4.63 (d, J = 3.6 Hz, 1 H), 4.77 (t, J = 1.2 Hz, 1 H), 6.56 (d,
J = 8.0 Hz, 1 H), 6.66 (t, J = 7.2 Hz, 1 H), 7.00–7.10 (m, 6 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 21.3, 23.0, 28.3, 43.9, 57.7,
112.7, 113.5, 117.0, 120.8, 127.3, 127.4, 128.6, 129.6, 136.8, 139.8,
144.2, 145.0 ppm. IR: ν = 2920, 2854, 1606, 1492, 1438, 1265, 1154,
˜
744 cm–1. HRMS (APCI): calcd. for C19H21N [M + H]+ 264.1747;
found 264.1738. C19H21N (263.38): calcd. C 86.65, H 8.04, N 5.32;
found C 86.75, H 7.97, N 5.41.
(2R*,3R*)-1,2,3,4-Tetrahydro-2-(4-methoxyphenyl)-3-(prop-1-en-2-
yl)quinoline (8c): Gum (89 mg, 64%). 1H NMR (400 MHz, CDCl3):
δ = 1.69 (s, 3 H), 2.68 (dd, J = 16.0 and 4.8 Hz, 1 H), 2.74 (dd, J
= 16.0 and 10.4 Hz, 1 H), 2.82 (ddd, J = 10.4, 4.8, and 2.8 Hz, 1
Conclusions
In conclusion, we have developed a mild and efficient
method for the synthesis of 2,3-disubstituted 1,2,3,4-tetra-
hydroquinolines from aldehydes and 2-allylic anilines. This H), 3.76 (s, 3 H), 4.36 (br. s, 1 H), 4.44 (br. s, 1 H), 4.62 (d, J =
954
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Stereoselective Synthesis of Tetrahydroquinolines
2.8 Hz, 1 H), 4.78 (s, 1 H), 6.56 (d, J = 8.0 Hz, 1 H), 6.65 (t, J = found 268.1501. C18H18FN (267.34): calcd. C 80.87, H 6.79, N
7.2 Hz, 1 H), 6.75–6.77 (m, 2 H), 7.00–7.10 (m, 4 H) ppm. 13C 5.24; found C 80.93, H 6.82, N 6.88.
NMR (100 MHz, CDCl3): δ = 22.9, 28.3, 43.9, 55.3, 57.3, 112.8,
(2R*,3R*)-2-(2,6-Dichlorophenyl)-1,2,3,4-tetrahydro-3-(prop-1-en-
2-yl)quinoline (8i): Colorless gum (155 mg, 95 %). 1H NMR
(400 MHz, CDCl3): δ = 1.62 (s, 3 H), 2.92–3.07 (m, 3 H), 4.33 (br.
s, 1 H), 4.35 (br. s, 1 H), 4.70 (s, 1 H), 5.55 (t, J = 3.6 Hz, 1 H),
6.50 (d, J = 8.0 Hz, 1 H), 6.67 (t, J = 7.2 Hz, 1 H), 7.00–7.05 (m,
2 H), 7.10 (t, J = 8.0 Hz, 1 H), 7.29 (d, J = 8.4 Hz, 2 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 23.0, 32.3, 43.4, 57.2, 114.0, 114.4,
117.4, 121.4, 127.0, 128.5, 129.3, 130.0, 136.1, 136.3, 144.4,
113.2, 113.4, 117.0, 120.7, 127.3, 128.5, 129.6, 134.9, 144.2, 145.0,
158.8 ppm. IR: ν = 2923, 2851, 1607, 1494, 1246, 1073, 1035, 830,
˜
745 cm–1. HRMS (APCI): calcd. for C19H21NO [M + H]+
280.1696; found 280.1686. C19H21NO (279.38): calcd. C 81.68, H
7.58, N 5.01; found C 81.57, H 7.62, N 4.95.
(2R*,3R*)-1,2,3,4-Tetrahydro-6-methyl-2-(4-nitrophenyl)-3-(prop-
1-en-2-yl)quinoline (8d): Red solid (129 mg, 84%); m.p. 96–98 °C.
1H NMR (400 MHz, CDCl3): δ = 1.76 (s, 3 H), 2.26 (s, 3 H), 2.62
(dd, J = 15.6 and 10.8 Hz, 1 H), 2.69 (dd, J = 15.6 and 4.8 Hz, 1
H), 2.86 (ddd, J = 10.8, 4.8, and 3.6 Hz, 1 H), 4.33 (br. s, 1 H),
4.38 (br. s, 1 H), 4.77 (d, J = 3.6 Hz, 1 H), 4.80 (s, 1 H), 6.54 (d, J
= 8.0 Hz, 1 H), 6.85 (s, 1 H), 6.89 (d, J = 8.4 Hz, 1 H), 7.28 (d, J
= 8.4 Hz, 1 H), 6.08 (d, J = 8.4 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 20.6, 23.1, 28.0, 43.8, 57.4, 113.5, 113.7,
123.0, 124.5, 126.9, 128.2, 128.3, 130.2, 140.9, 143.9, 147.2,
145.5 ppm. IR: ν = 2920, 1608, 1588, 1483, 1266, 888, 780,
˜
745 cm–1. HRMS (APCI): calcd. for C18H17Cl2N [M + H]+
318.0811; found 318.0823. C18H17Cl2N (318.25): calcd. C 67.93, H
5.38, N 4.40; found C 67.87, H 5.35, N 4.48.
(2R*,3R*)-1,2,3,4-Tetrahydro-2-(2,4-dinitrophenyl)-3-(prop-1-en-2-
yl)quinoline (8j): Red solid (156 mg, 92%); m.p. 95–97 °C. 1H NMR
(400 MHz, CDCl3): δ = 1.69 (s, 3 H), 2.61 (dd, J = 16.4 and
10.8 Hz, 1 H), 2.76 (dd, J = 16.4 and 4.0 Hz, 1 H), 2.88 (dt, J =
10.8, 4.0, and 3.6 Hz, 1 H), 4.15 (br. s, 1 H), 4.47 (d, J = 3.6 Hz, 1
H), 4.77 (t, J = 1.2 Hz, 1 H), 5.75 (t, J = 4.0 Hz, 1 H), 6.63 (d, J
= 8.0 Hz, 1 H), 6.74 (d, J = 7.6 Hz, 1 H), 7.03 (d, J = 7.2 Hz, 1
H), 7.10 (t, J = 7.6 Hz, 1 H), 7.79 (d, J = 8.8 Hz, 1 H), 8.30 (d, J
= 8.8 Hz, 1 H), 8.61 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 23.6, 28.6, 42.9, 52.6, 113.9, 114.8, 118.2, 119.4, 120.0, 126.3,
150.4 ppm. IR: ν = 2918, 1617, 1509, 1343, 1107, 804 750 cm–1.
˜
HRMS (APCI): calcd. for C19H20N2O2 [M + H]+ 309.1598; found
309.1660. C19H20N2O2 (308.38): calcd. C 74.00, H 6.54, N 9.08;
found C 73.92, H 6.58, N 9.15.
(2R*,3R*)-1,2,3,4-Tetrahydro-2-(3-nitrophenyl)-3-(prop-1-en-2-yl)-
1
quinoline (8f): Red solid (119 mg, 81%); m.p. 73–75 °C. H NMR
(400 MHz, CDCl3): δ = 1.78 (s, 3 H), 2.64 (dd, J = 16.4 and
10.8 Hz, 1 H), 2.74 (dd, J = 16.4 and 4.0 Hz, 1 H), 2.88 (ddd, J =
10.8, 4.4, and 4.0 Hz, 1 H), 4.36 (br. s, 1 H), 4.44 (br. s, 1 H), 4.81
(br. s, 2 H), 6.62 (d, J = 8.0 Hz, 1 H), 6.70 (t, J = 6.8 Hz, 1 H),
7.02 (d, J = 7.2 Hz, 1 H), 7.08 (t, J = 7.6 Hz, 1 H), 7.40 (t, J =
8.0 Hz, 1 H), 7.50 (d, J = 7.6 Hz, 1 H), 7.96 (s, 1 H), 8.07 (d, J =
8.4 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 23.1, 28.0,
43.6, 57.1, 113.6 (2 C), 117.7, 120.2, 122.3, 122.5, 127.6, 128.8,
127.8, 129.8, 131.7, 142.8, 143.8, 144.6, 146.8, 149.3 ppm. IR: ν =
˜
2922, 2850, 1606, 1588, 1530, 1494, 1349, 1265, 747 cm–1. HRMS
(APCI): calcd. for C18H17N3O4 [M + H]+ 340.1292; found
340.1287. C18H17N3O4 (339.35): calcd. C 63.71, H 5.05, N 12.38;
found C 63.65, H 5.14, N 12.50.
Methyl 4-[(2R*,3R*)-3-(Prop-1-en-2-yl)-1,2,3,4-tetrahydroquinolin-
2-yl]benzoate (8k): Colorless solid (133 mg, 87%); m.p. 106–108 °C.
1H NMR (400 MHz, CDCl3): δ = 1.70 (s, 3 H), 2.70 (d, J = 7.6 Hz,
2 H), 2.87 (ddd, J = 7.6, 4.0, and 3.6 Hz, 1 H), 3.89 (s, 3 H), 4.39
(br. s, 1 H), 4.42 (br. s, 1 H), 4.73 (d, J = 3.6 Hz, 1 H), 4.77 (t, J
= 1.2 Hz, 1 H), 6.59 (d, J = 7.6 Hz, 1 H), 6.68 (t, J = 7.6 Hz, 1 H),
7.01 (d, J = 7.6 Hz, 1 H), 7.06 (t, J = 7.2 Hz, 1 H), 7.20 (d, J =
8.4 Hz, 2 H), 7.89 (d, J = 8.4 Hz, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 22.9, 28.1, 43.6, 52.1, 57.6, 113.1, 113.4, 117.2, 120.4,
127.3, 127.4, 128.9, 129.1, 129.5, 143.7, 144.2, 147.9, 167.1 ppm.
129.7, 133.5, 143.3, 143.9, 144.7, 147.8 ppm. IR: ν = 2926, 2853,
˜
1608, 1531, 1493, 1350, 1265, 740, 704 cm–1. HRMS (APCI): calcd.
for C18H18N2O2 [M + H]+ 295.1441; found 295.1435. C18H18N2O2
(294.35): calcd. C 73.45, H 6.16, N 9.52; found C 73.56, H 6.22, N
9.47.
(2R*,3R*)-2-(4-Bromophenyl)-1,2,3,4-tetrahydro-3-(prop-1-en-2-
1
yl)quinoline (8g): Brown gum (122 mg, 77%). H NMR (400 MHz,
IR: ν = 2918, 2854, 1717, 1602, 1494, 1276, 1109, 748 cm–1. HRMS
CDCl3): δ = 1.70 (s, 3 H), 2.67 (d, J = 7.6 Hz, 2 H), 2.82 (ddd, J
= 7.6, 4.5, and 4.0 Hz, 1 H), 4.35 (br. s, 1 H), 4.41 (br. s, 1 H), 4.60
(d, J = 4.0 Hz, 1 H), 4.79 (t, J = 1.2 Hz, 1 H), 6.55 (d, J = 8.0 Hz,
1 H), 6.66 (t, J = 7.6 Hz, 1 H), 6.97–7.06 (m, 4 H), 7.30–7.34 (m,
2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 23.0, 28.1, 43.7, 57.3,
113.2, 113.5, 117.3, 120.5, 121.1, 127.4, 129.2, 129.7, 131.0, 141.7,
˜
(APCI): calcd. for C20H21NO2 [M + H]+ 308.1645; found 308.1652.
C20H21NO2 (307.39): calcd. C 78.15, H 6.89, N 4.56; found C
78.23, H 6.78, N 4.62.
(2R*,3R*)-2-(Furyl-2-yl)-1,2,3,4-tetrahydro-3-(prop-1-en-2-yl)-
quinoline (8l): Colorless solid (84 mg, 70%); m.p. 63–65 °C. 1H
NMR (400 MHz, CDCl3): δ = 1.76 (s, 3 H), 2.76 (dd, J = 15.2 and
4.0 Hz, 1 H), 2.85 (ddd, J = 11.2, 4.0, and 3.6 Hz, 1 H), 2.88 (dd,
J = 15.2 and 11.2 Hz, 1 H), 4.31 (br. s, 1 H), 4.64 (br. s, 1 H), 4.74
(d, J = 3.6 Hz, 1 H), 3.82 (br. s, 1 H), 6.04 (d, J = 2.8 Hz, 1 H),
6.25 (dd, J = 3.2 and 1.6 Hz, 1 H), 6.54 (d, J = 7.2 Hz, 1 H), 6.67
(t, J = 7.2 Hz, 1 H), 6.98–7.00 (m, 2 H), 7.27 (s, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 22.3, 28.3, 42.6, 52.2, 106.6, 110.3,
111.9, 114.7, 120.9, 127.2, 129.5, 141.4, 143.1, 145.0, 156.0 ppm.
143.8, 144.4 ppm. IR: ν = 2919, 1605, 1485, 1265, 896, 825,
˜
746 cm–1. HRMS (APCI): calcd. for C18H18BrN [M + H]+
318.0811; found 318.0823. C18H18BrN (328.25): calcd. C 65.86, H
5.53, N 4.27; found C 65.76, H 5.47, N 4.35.
(2R*,3R*)-2-(4-Fluorophenyl)-1,2,3,4-tetrahydro-3-(prop-1-en-2-
yl)quinoline (8h): Colorless liquid (100 mg, 75 %). 1H NMR
(400 MHz, CDCl3): δ = 1.63 (s, 3 H), 2.63 (d, J = 8.0 Hz, 1 H),
2.76 (ddd, J = 8.0, 4.0, and 3.6 Hz, 1 H), 4.31 (br. s, 1 H), 4.34 (br.
s, 1 H), 4.59 (s, 1 H), 4.72 (s, 1 H), 6.50 (d, J = 7.6 Hz, 1 H), 6.60
(t, J = 7.6 Hz, 1 H), 6.82–6.86 (m, 2 H), 6.93–6.98 (m, 2 H), 7.00–
7.04 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 22.9, 28.1,
43.8, 57.2, 113.0, 113.5, 114.7 (d, J = 21.3 Hz), 117.2, 120.5, 127.4,
128.9 (d, J = 7.5 Hz), 129.6, 138.4, 143.9, 144.6, 162.1 (d, J =
IR: ν = 2966, 2919, 1607, 1493, 1263, 1144, 1011, 894, 743 cm–1.
˜
HRMS (APCI): calcd. for C16H17NO [M + H]+ 240.1383; found
240.1387. C16H17NO (239.32): calcd. C 80.30, H 7.16, N 5.85;
found C 80.36, H 7.21, N 8.79.
244.3 Hz) ppm. 19F NMR (376 MHz, CDCl3/C6F6): δ = 45.82– Supporting Information (see footnote on the first page of this arti-
45.90 (m, F) ppm. IR: ν = 2922, 2853, 1605, 1223, 1157, 839, cle): H, 13C, and 19F NMR spectra of all compounds and X-ray
1
˜
746 cm–1. HRMS (APCI): calcd. for C18H18FN [M + H]+ 268.1496;
structure and crystal parameters of compound 8d.
Eur. J. Org. Chem. 2013, 952–956
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
955

S. Bondalapati, K. Indukuri, P. Ghosh, A. K. Saikia
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Acknowledgments
The authors are grateful to the council of Scientific and Industrial
Research (CSIR), New Delhi for the financial support [grant
number 01(2332)/09/EMR-II].
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Received: October 15, 2012
Published Online: January 3, 2013
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