Photosensitized Diels-Alder reactions of N-arylimines: Synthesis of tetrahydroquinoline derivatives

Article abstract of DOI:10.1016/S0040-4039(02)02328-6

Irradiation (λ>345 nm) of catalytic amounts of 2,4,6-triphenylpyrylium tetrafluoroborate (TPT) in a CH₂Cl₂ solution of N-aryl imines and α-methylstyrene or styrene produced the corresponding [4+2] cycloaddition products, tetrahydroquinoline derivatives, in good yield. The reaction was controlled by the relative oxidation potentials of the dienophile and the diene.

Full text of DOI:10.1016/S0040-4039(02)02328-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 9433–9436
Photosensitized Diels–Alder reactions of N-arylimines:
synthesis of tetrahydroquinoline derivatives
Wei Zhang, Xiaodong Jia, Li Yang and Zhong-Li Liu*
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China
Received 20 June 2002; revised 30 September 2002; accepted 11 October 2002
Abstract—Irradiation (u>345 nm) of catalytic amounts of 2,4,6-triphenylpyrylium tetrafluoroborate (TPT) in a CH2Cl2 solution
of N-aryl imines and a-methylstyrene or styrene produced the corresponding [4+2] cycloaddition products, tetrahydroquinoline
derivatives, in good yield. The reaction was controlled by the relative oxidation potentials of the dienophile and the diene. © 2002
Elsevier Science Ltd. All rights reserved.
The tetrahydroquinoline moiety is involved in many
biologically active alkaloids, hence variety of
using TPT is that it absorbs light in the visible region
(umax=417 and 369 nm in CH2Cl2)8a and is highly
soluble in CH2Cl2. Furthermore, since it is a salt, there
is no net charge separation associated with the electron
transfer step, hence deactivation through back-electron
transfer is effectively circumvented.
a
approaches have been developed for synthesis of the
tetrahydroquinoline skeleton.1 The [4+2] Diels–Alder
reaction between N-arylimines and electron-rich
dienophiles is probably the most powerful synthetic
tool for constructing N-containing six-membered hete-
rocyclic compounds including tetrahydroquinolines.1b,2
This imino Diels–Alder reaction has been reported to
be catalyzed by BF.3Et2O2a,b and other Lewis acids,2c
transition metal carbonyls,2d lanthanide triflates,2e–i
trifluoroacetic acid2j and 2,3-dichloro-5,6-dicyano-p-
benzoquinone (DDQ).2k Recent progress includes the
use of triphenyl phosphonium perchlorate as the
catalyst3 and the one-pot reaction using in situ formed
imines from benzaldehyde and amines.4 To our sur-
prise, however, although photochemically induced
Diels–Alder reactions have been well documented,5 the
photosensitized imino Diels–Alder reaction has not
been reported previously.6 As part of our ongoing
research program on the synthetic potential of photoin-
duced electron transfer (PET) reactions7 we report
herein the first PET-catalyzed Diels–Alder reaction of
N-arylimines with a-methylstyrene and styrene which
produces tetrahydroquinoline derivatives in good
yields. The PET reaction was initiated by 2,4,6-
triphenylpyrylium tetrafluoroborate (TPT) which has
been widely used as an electron transfer photosensitizer
to induce Diels–Alder reactions.8 The advantage of
Irradiation at u]345 nm of a deaerated anhydrous
CH2Cl2 solution (50 ml) of the N-arylimine (1, 1
mmol), a-methylstyrene (2a, 1.5 mmol) and a catalytic
amount of 2,4,6-triphenylpyrylium tetrafluoroborate
(TPT, 0.05 mmol) at ambient temperature for 16–24
Keywords: photoinduced electron transfer; imines; tetra-
hydroquinolines; cycloaddition.
* Corresponding author. Tel.: +86-931-891-1186; fax: +86-931-862-
5657; e-mail: liuzl@lzu.edu.cn
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02328-6

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W. Zhang et al. / Tetrahedron Letters 43 (2002) 9433–9436
hours produced the tetrahydroquinoline derivatives 3
and 4 in good yield as a mixture of two stereoisomers.
On the other hand, when styrene (2b) was used instead
of 2a, the yield of 3 and 4 was significantly diminished,
while the aromatized quinoline 5 and the amine 6 were
produced, even as predominant products in some cases
(Scheme 1). Careful column chromatography by elution
with hexane/acetone (20:1 to 10:1) gave the pure prod-
ucts which were fully identified and the configuration
evaluated by 2D NMR spectroscopy.9 The results are
listed in Table 1.
Alder reaction with 2 acting as the dienophile, similar
to the photosensitized cyclodimerization of 1,1-
diphenylethene10a (Scheme 2). The formation of 5 is
easily understood since cation radicals bearing protons
are extremely easy to deprotonate due to their high
acidity11 and protonated imines may be easily
reduced.12
The free energy change, DG, for the photoinduced
electron transfer between TPT and 2a and 2b is calcu-
lated to be −0.62 and −0.42 eV, respectively, by using
the Rehm–Weller equation,13,8c demonstrating that the
reaction is thermodynamically feasible. On the other
hand, since the oxidation potentials of 1 (1.73, 1.50 and
1.89 V versus SCE for 1a, 1c and 1g respectively14) are
close to those of 2 (1.67 and 1.87 V versus SCE for 2a
and 2b, respectively,8c electron transfer between photo-
excited TPT and 1 should also be possible. However,
irradiation of TPT with 1 in the absence of 2 produced
nothing but small amounts of aldehydes and amines
from the decomposition of 1. It is seen from Table 1
that substitution of the electron withdrawing nitro
group in 1 appreciably shortened the reaction time and
increased the conversion and yield, while the electron
It can be seen from Table 1 that the terminal carbon of
2 added regioselectively to the carbon of the C=N
bond of 1 giving exclusively the 4-substituted tetra-
hydroquinoline derivatives 3 and 4, and/or the corre-
sponding quinoline derivative 5 in the case of 2b. The
ratio of syn/anti isomers was approximately 2:1.
Since no reaction ever took place in the dark even
under refluxing conditions or in the absence of TPT
under the same experimental conditions with prolonged
irradiation, this reaction might be rationalized as a
PET-catalyzed non-synchronous cation radical Diels–
Table 1. PET-induced reactions of N-arylimines (1) with styrenes (2)
1
2
t (h)
Conv. (%)
Products and yieldsa (%)
R1
R2
R3
1a
1b
1c
1d
1e
1f
1g
1h
1a
1b
1f
H
H
H
H
CH3O
H
NO2
NO2
NO2
H
2a CH3
2a CH3
2a CH3
2a CH3
2a CH3
2a CH3
2a CH3
2a CH3
2b H
2b H
2b H
2b H
2b H
24
24
24
24
24
16
16
24
24
24
16
16
24
60
65
50
43
85
80
88
45
65
72
87
90
55
3a 41
3b 45
3c 40
3d 36
3e 50
3f 55
3g 58
3h 42
3a% 8
3b% 18
3f% 32
3g% 30
3h% 25
4a 28
4b 18
4c 15
4d 12
4e 22
4f 24
4g 25
4h 20
4a% Trace
4b% Trace
4f% 15
4g% 9
4h% 5
CH3
CH3O
CH3
Cl
CH3
Cl
CH3O
H
CH3
CH3
Cl
5a 47
5b 45
5f 23
5g 28
5h 25
6a 28
6b 10
6f 18
6g 20
6h 16
H
NO2
NO2
NO2
1g
1h
CH3O
a Yields of isolated products based on conversion of 1.
Scheme 2.

W. Zhang et al. / Tetrahedron Letters 43 (2002) 9433–9436
9435
donating methoxy group decreased the yield. This sug-
gests that preferential photooxidation of 2 as shown in
Scheme 2 is necessary for the reaction to take place
efficiently. Methoxy substitution in 1 makes its oxida-
tion potential lower than 2 (e.g. 1.50 V versus SCE for
1c14) and able to quench the photoexcited TPT prefer-
entially, hence the yield of the cross cycloaddition
products decreases.
5. (a) Lewis, F. D. In Photoinduced Electron Transfer,
Part C; Fox, M. A.; Channon, M., Eds.; Elsevier:
Amsterdam, 1988; p. 1 Chapt. 4.1; (b) Mariano, P. S.
In Photoinduced Electron Transfer Part C; Fox, M. A.;
Channon, M., Eds.; Elsevier: Amsterdam, 1988; p. 372
Chapt. 4.6.
6. PET-induced reaction between N-arylimines and chlo-
ranil has been reported to form CꢀO coupling products
of the imine and chloranil keeping the C=N bond
intact (Chen, C. F.; Zhang, Z. G.; Yan B. Z.; Xu, J.
H. Tetrahedron Lett. 1994, 49, 9221.
7. (a) Jin, M.; Zhang, D.; Yang, L.; Liu, Y.; Liu, Z. L.
Tetrahedron Lett. 2000, 41, 7357; (b) Jin, M. Z.; Yang,
L.; Wu, L. M.; Liu, Y. C.; Liu, Z. L. Chem Commun.
1998, 2451; (c) Zhang, W.; Yang, L.; Wu, L. M.; Liu,
Y. C.; Liu, Z. L. J. Chem. Soc., Perkin Trans. 2 1998,
1189; (d) Guo, X.; Wu, L.; Yang, L.; Liu, Y. C.; Liu,
Z. L. Science in China (B) 1999, 42, 170; (e) Zhang,
W.; Shao, X.; Yang, L.; Liu, Z. L.; Chow, Y. L. J.
Chem. Soc., Perkin Trans. 2 2002, 1029.
8. (a) Miranda, M. A.; Garcia, H. Chem. Rev. 1994, 94,
1063; (b) Peglow, T.; Blechert, S.; Steckhan, E. Chem.
Commun. 1999, 433; (c) Martiny, M.; Steckhan, E.;
Esch, T. Chem. Ber. 1993, 126, 1671; (d) Gieseler, A.;
Steckhan, E.; Wiest, O.; Knoch, F. J. Org. Chem. 1991,
56, 1405; (e) Wiest, O.; Steckhan, E. Angew. Chem.,
Int., Ed. Engl. 1993, 105, 101.
In conclusion this work provides a convenient photo-
chemical approach to construct tetrahydroquinoline
and quinoline skeletons which can presumably be
extended to other systems. Since the reaction might be
modulated by alternating the relative oxidation poten-
tials of the dienophile and the diene, and the reduction
potential of the photosensitizer as well, more general
synthetic utility is expected.
Acknowledgements
This work was supported by the National Natural
Science Foundation of China (29972018 and QT Pro-
gram 29802005).
9. Representative spectral data of the products. Com-
pound 3a: colorless needles, mp: 128–129°C (uncor.).
HR-ESI-MS: 300.1744 (calcd. for C22H21N+H+,
300.1747). 1H NMR (400 MHz, CDCl3): l=1.67 (s,
3H, CH3), 2.0 (dd, J=2.8, 13.2 Hz, 1H, H-3e), 2.34
(dd, J=11.7, 13.2 Hz, 1H, H-3a), 4.64 (dd, J=2.8,11.7
Hz, 1H, H-2), 6.63 (dd, J=7.6, 7.6 Hz, 1H, H-6), 6.65
(d, J=7.2 Hz, 1H, H-8), 6.73 (d, J=8.0 Hz, 1H, H-5),
7.04 (dd, J=8.0, 8.0 Hz, 1H, H-7), 7.19–7.50 (m, 10H,
2×Ph). 13C NMR (100.08 MHz, CDCl3): l=29.7
(CH3), 42.2 (C-4), 49.9 (CH2), 54.1 (CH), 114.6 (C-8),
117.8 (C-6), 125.8 (C-5), 126.7 (2C, Ph), 126.9 (1C, Ph),
127.3 (2C, Ph), 127.7 (C-7), 128.0 (2C, Ph), 128.6 (2C,
Ph), 129.9 (1C, Ph), 139.2 (1C, Ph), 144.1 (1C, Ph),
145.0 (C-10), 150.2 (C-9). Compound 4a: colorless
needles, mp: 109–110°C (uncor.). HR-ESI-MS: 300.1742
(calcd. for C22H21N+H+, 300.1747). 1H NMR (400
MHz, CDCl3): l=1.80 (s, 3H, CH3), 2.21 (dd, J=12.0,
13.1 Hz, 1H, H-3a), 2.31(dd, J=3.2, 13.1, 1H, H-3e),
4.06 (dd, J=3.2, 12.0 Hz, 1H, H-2), 6.65 (d, J=8.2
Hz, 1H, H-8), 6.81 (dd, J=7.0, 7.0 Hz, 1H, H-6), 7.15
(d, J=7.0 Hz, 1H, H-5), 7.24 (dd, J=7.0, 8.2 Hz, 1H,
H-7), 7.12–7.37 (m, 10H, 2×Ph). 13C NMR (100.08
MHz, CDCl3): l=29.6 (CH3), 41.6 (C-4), 47.9 (CH2),
53.2 (CH), 114.3 (C-8), 117.3 (C-6), 125.8 (C-5), 126.7
(2C, Ph), 127.1 (2C, Ph), 127.6 (2C, Ph),128.2 (2C, Ph),
128.3 (C-7), 128.6 (2C, Ph), 140.5 (1C, Ph), 144.2 (1C,
Ph), 144.6 (C-10), 150.4 (C-9). The coupling constants
of H-2 suggests its axial conformation in both 3a and
4a. The significant low-field shift of H-3e and up-field
shift of H-2 of 4a in comparison with those of 3a
suggests an axial 4-phenyl group in 4a while an equato-
rial 4-phenyl group in 3a. The stereochemistry was
confirmed by their NOESY spectra which show a clear
cross peak between the 4-methyl and H-2 in 3a, with
no such correlation in 4a.
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