Reactivity and mechanistic insight into visible-light-induced aerobic cross-dehydrogenative coupling reaction by organophotocatalysts

Article abstract of DOI:10.1002/chem.201102299

With visible-light irradiation, a mild, simple, and efficient metal-free photocatalytic system for the facile construction of sp³-sp ³ C-C bonds between tertiary amines and activated C-H bonds has been achieved. Spectroscopic study a

Full text of DOI:10.1002/chem.201102299

DOI: 10.1002/chem.201102299
Reactivity and Mechanistic Insight into Visible-Light-Induced Aerobic Cross-
Dehydrogenative Coupling Reaction by Organophotocatalysts
Qiang Liu,[a, b] Ya-Nan Li,[a, b] Hui-Hui Zhang,[a] Bin Chen,[a] Chen-Ho Tung,[a] and
Li-Zhu Wu*[a]
Abstract: With visible-light irradiation,
a mild, simple, and efficient metal-free
photocatalytic system for the facile
(tetrabutylammonium salt) (TBA-eosin
Y) takes place to generate TBA-eosin
Y radical anion, which can subsequent-
ly react with nucleophiles and molecu-
lar oxygen. More strikingly, electron
spin resonance (ESR) measurements
provide direct evidence for the forma-
ÀC
tion of superoxide radical anions (O2
)
construction of sp –sp C C bonds be-
rather than singlet oxygen (1O2) during
visible-light irradiation. This active spe-
cies is therefore believed to be respon-
sible for the large rate of acceleration
of the aerobic photocatalytic reactions.
3
3
À
À
tween tertiary amines and activated C
H bonds has been achieved. Spectro-
scopic study and product analysis dem-
onstrate for the first time that photoin-
duced electron transfer from N-aryl
tetrahydroisoquinolines to eosin Y bis-
À
À
Keywords: C C coupling · C H ac-
tivation · electron transfer · molecu-
lar oxygen · photochemistry
Introduction
an operationally simple method for the oxidative coupling
of nitroalkanes by using visible-light photoredox catalysis.
The reaction proceeds in high chemical yields by using IrIII
catalyst without the need for an external oxidant. Rueping
et al.[7] combined photoredox catalysis and Lewis base catal-
ysis to develop a dual catalytic system for the Mannich reac-
tion. The two successful cases of CDC and Mannich reac-
tions indicate that the visible-light-induced catalysis is an in-
teresting subject even though the high cost and potential
toxicity of RuII and IrIII complexes as well as their limited
availability are disadvantages of the metal-based methods.
More importantly, the mechanism of the photocatalytic
CDC and Mannich reactions has never been explored. Mo-
lecular oxygen (O2) was found capable of facilitating the
photoredox catalysis remarkably, but the active species of
O2 involved in the reaction mechanism remains elusive.
Particular interest in visible-light-initiated catalytic reac-
The development of efficient methods for the formation of
C C bonds is one of the fundamental challenges of organic
synthesis. Transition-metal-catalyzed C H bond activations
À
À
À
and subsequent C C bond formations have aroused much
interest and have recently made great progress.[1] The cross-
dehydrogenative coupling (CDC) reaction, a powerful tool
to develop sustainable chemical processes, features the for-
À
À
mation of C C bonds directly from two different C H
bonds under oxidative conditions.[2] This straightforward re-
action provides an alternative to the separate steps of pre-
functionalization and defunctionalization that have tradi-
tionally been part of synthetic design. In 2003, Murahashi
et al.[3] reported the first example of an aerobic catalytic
[4,5]
À
method for C C bond formation. Li et al.
have demon-
strated that in the presence of metal catalysts such as
copper or iron salts and oxidants such as hydrogen peroxide,
oxygen, and tert-butylhydroperoxide, unfunctionalized sp3
tions[8,9] prompted us to study the typical CDC transforma-
3
À
tion of sp C H bonds adjacent to nitrogen by using organic
À
À
centers of C H bonds can couple to other C H bonds with-
photocatalysts. In this work, eosin Y, a famous organic dye,
was used as a photocatalyst on account of its broad, high
visible-light absorption and economic advantage over nota-
ble metal catalysts.[10] Moreover, the rich spectroscopic prop-
erties of eosin Y are expected to allow for the detection of
the intermediate during irradiation.[11] With this system, we
were able to achieve the oxidative coupling products of N-
aryl tetrahydroisoquinolines with either nitroalkanes or di-
methyl malonate and even acetone in good to excellent
yields under mild conditions. Spectroscopic study and prod-
uct analysis demonstrate for the first time that photoinduced
electron transfer from N-aryl tetrahydroisoquinolines to
eosin Y takes place to generate eosin Y radical anions,
which can subsequently react with nitroalkanes and molecu-
lar oxygen. More strikingly, electron spin resonance (ESR)
out preactivation. Very recently, Stephenson et al.[6] found
[a] Dr. Q. Liu, Y.-N. Li, H.-H. Zhang, Dr. B. Chen, Prof. Dr. C.-H. Tung,
Prof. Dr. L.-Z. Wu
Key Laboratory of Photochemical Conversion
and Optoelectronic Materials
Technical Institute of Physics and Chemistry
The Chinese Academy of Sciences
Beijing 100190 (P. R. China)
Fax : (+86) 10-8254-3580
E-mail: lzwu@mail.ipc.ac.cn
[b] Dr. Q. Liu, Y.-N. Li
State Key Laboratory of Applied Organic Chemistry
College of Chemistry and Chemical Engineering
Lanzhou University, Lanzhou 730000 (P. R. China)
620
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 620 – 627

FULL PAPER
measurements provide direct evidence for the formation of
um salt in nitromethane was not good for the reaction, we
changed the photocatalyst to organosoluble eosin Y bis(te-
trabutylammonium salt) (TBA-eosin Y). As shown in
entry 4 of Table 1, 92% conversion of 1a and 86% yield of
CDC product were obtained after 24 h irradiation. With
2 mol% TBA-eosin Y, complete conversion was observed in
20 h (entry 5). Strikingly, molecular oxygen was found to ac-
celerate the reaction remarkably. In the presence of oxygen,
100% conversion of 1a was achieved after just 4 h irradia-
tion (entry 6). Keeping the initially irradiated sample in the
dark under stirring for an additional 12 h caused a signifi-
cant increase of the yield from 75 to 92% (entry 7). The
system also worked well when oxygen was replaced by air,
but much longer irradiation time was required (entry 8). To
further confirm the participation of molecular oxygen, the
aerobic reaction was investigated by means of oxygen-con-
sumption experiments. It was noted that under the standard
reaction conditions a full conversion of 0.2 mmol 1a con-
sumed approximately 0.15 mmol of oxygen as shown in
Figure 1. Clearly, oxygen plays an important role in the oxi-
ÀC
superoxide radical anions (O2 ) rather than singlet oxygen
(1O2) during visible-light irradiation. This active species is
therefore believed to be responsible for the large rate of ac-
celeration of the aerobic photocatalytic reactions. As a
result, a mild, simple, and efficient metal-free photocatalytic
3
3
À
system for the facile construction of sp –sp C C bonds be-
À
tween tertiary amines and activated C H bonds with the aid
of molecular oxygen and visible light was established.
Results and Discussion
Our preliminary studies focused on the reaction of N-
phenyl-1,2,3,4-tetrahydroisoquinoline (1a) with nitrome-
thane. Typically, a solution that contained 1a and eosin Y
(1 mol%) in degassed nitromethane was excited by a 500 W
high-pressure Hanovia mercury lamp. A glass filter was
used to cut off light below 450 nm, thus guaranteeing that
only eosin Y was irradiated, whereas the substrates of 1a
and nitromethane were silent. To our delight, the desired
CDC product was produced in 82% yield (26% conversion)
as eosin Y disodium salt was irradiated for 24 h (Table 1,
entry 1). The absence of eosin Y, however, resulted in negli-
gible conversion of 1a under the same conditions (entry 2).
Moreover, no conversion could be observed when the reac-
tion was conducted in the dark (entry 3). All of the results
suggest that both light and eosin Y are essential for the reac-
À
tion and eosin Y as a photocatalyst facilitates the C C bond
formation. Given that the poor solubility of eosin Y disodi-
Table 1. Optimization of reaction conditions.
Figure 1. Oxygen uptake experiment: 1a (0.2 mmol), TBA-eosin
Y
(0.004 mmol), CH3NO2 (10 mL). The sample was saturated with a stream
of O2 for 20 min and sealed in a Pyrex tube before irradiation. The
amount of oxygen was determined by gas chromatograph analysis.
dative coupling reaction. In addition, attempts to decrease
the amount of nitromethane also led to the low yield of the
CDC reaction (entry 9).
Entry Conditions[a]
Irradiation Conv. Yield
time [h]
[%][b] [%][c]
With this initial success, we screened the reaction scope
with the aid of TBA-eosin Y and oxygen. As tabulated in
Table 2, a series of substituted 1,2,3,4-tetrahydroisoquinoline
derivatives were able to undergo the CDC reaction with ni-
tromethane efficiently, thus resulting in the desired coupling
products in good to excellent yields (Table 2, entries 1–9).
The use of nitroethane as a nucleophile also gave the de-
sired compounds in good yields (the ratios of the two diaste-
reoisomers are 3:2) (entries 10–12), whereas the less effi-
cient reaction of nitropropane may be due to the steric
effect of the nucleophile (entries 13–15).
To shed light on the primary process of the photocatalytic
CDC reaction, a flash-photolysis investigation was per-
formed in a degassed CH3CN solution at room temperature.
Upon laser excitation by 532 nm light, a strong negative
bleach of the ground-state absorption of TBA-eosin Y at ap-
1
2
3
4
5
6
7
8
9
eosin Y (1 mol%)
no catalyst
24
24
–
26
2
0
92
100
100
100
100
100
82
trace
0
86
88
no light, eosin Y (1 mol%)
TBA-eosin Y (1 mol%)
TBA-eosin Y (2 mol%)
TBA-eosin Y (2 mol%)[d]
TBA-eosin Y (2 mol%)[d]
TBA-eosin Y (2 mol%) in air
TBA-eosin Y (2 mol%), CH3NO2
(5 equiv), CH3CN (10 mL)[d]
24
20
4
75
4[e]
5[e]
5[e]
92(86)[f]
91
34
[a] Reaction conditions: 1a (0.2 mmol), CH3NO2 (10 mL). The reaction
was degassed with argon before irradiation unless indicated otherwise.
[b] Conversion rates were determined by H NMR spectroscopic analysis.
[c] Yields were based on the conversion of 1a and determined by
1H NMR spectroscopy using an internal standard. [d] The solvent was sa-
turated with oxygen before irradiation. [e] The irradiated sample was
stirred in the dark at room temperature for 12 h. [f] Isolated yield after
purification by chromatography on silica gel.
1
Chem. Eur. J. 2012, 18, 620 – 627
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
621

L.-Z. Wu et al.
Table 2. CDC reaction of nitroalkanes with tetrahydroisoquinolines using TBA-eosin Y as photocatalyst.[a]
were immediately replaced by a
series of new absorptions with a
maximum at 370 nm in addition
to the strong triplet-state ab-
sorptions of TBA-eosin Y in
the region of 500–650 nm. Fol-
lowing from spectroscopic stud-
ies of eosin Y derivatives,[11] the
transient species that absorbed
at 370 nm is ascribed to the re-
Entry
Product
Yield
[%][b]
Entry
Product
Yield
[%][b]
1
86
84
81
75
85
77
75
84
9
79
duced TBA-eosin
Y radical
anion. From the kinetics probed
at 370 nm, a fast rise phase fol-
lowed by a slow decay suggest
that the photoinduced electron
transfer from 1a to the triplet
state of TBA-eosin Y led to the
formation and disappearance of
the TBA-eosin Y radical anion.
The rise grows quickly with the
electron-transfer rate constant
(kET) of 5.4ꢁ104 sÀ1 (18.2 ms),
and the back charge recombina-
2a
2b
2c
2d
2e
2 f
2g
2h
2i
2j
2
3
4
5
6
7
8
10
11
12
13
14
15
76[c]
78[c]
64[c]
73[d]
60[d]
46[d]
2k
2l
tion (kCR
) derived from the
decay phase is rather slow with
a
lifetime of 410 ms (2.4ꢁ
103 sÀ1). Prolonged irradiation
of the solution of TBA-eosin Y
with 1a in CH3CN resulted in
no permanent change, thereby
2m
2n
2o
indicating the TBA-eosin
Y
radical anion formed by the
photoinduced electron transfer
was quite stable.
It is known that eosin Y can
react with molecular oxygen to
generate either superoxide radi-
ÀC
or singlet
cal anion (O2
)
oxygen (1O2).[12] To assess the
generation ability of the active
species of oxygen in the photo-
catalytic TBA-eosin Y system,
5,5-dimethyl-1-pyrroline-N-
[a] Reaction conditions: 1 (0.2 mmol), TBA-eosin Y (0.004 mmol), nitroalkane (10 mL), irradiated at ambient oxide (DMPO) and 2,2,6,6-tet-
temperature in the presence of oxygen. [b] Yield after column chromatography. [c] The ratios of the two dia-
stereoisomers are 3:2. [d] The ratios of the two diastereoisomers are 7:4.
ramethylpiperidine
(TEMP)
were employed as a probe to
ÀC
1
react with O2 and O2, respec-
tively. The adducts can be easily detected by electron spin
resonance (ESR) spectroscopy.[13] It is clearly shown in
Figure 3 that when the solution of DMPO, TBA-eosin Y,
and 1a in air-saturated CH3CN was irradiated with the laser
at 532 nm, a single radical was trapped (Figure 3a), the spec-
trum and hyperfine coupling constants of which are in
proximately 530 nm and characteristic absorptions at 580 nm
were observed immediately, the decay of which throughout
the absorption region and the recovery of the bleach occurs
on the same timescale and can be thoroughly described by a
monoexponential function with a lifetime of 16 ms, which is
consistent with that of the triplet excited state of eosin Y de-
rivatives in the literature.[11] Figure 2 displays the time-re-
solved absorption difference spectra for TBA-eosin Y and
for TBA-eosin Y with 1a, respectively. When 1a was intro-
duced into the solution of TBA-eosin Y, the absorptions
ÀC
agreement with the reported values for the adduct of O2
with DMPO.[13] By contrast, when TEMP, an O2 scavenger,
was used instead of DMPO in the same air-saturated solu-
tion, the nitroxide radical TEMPO was hardly detected (Fig-
1
622
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 620 – 627

Cross-Dehydrogenative Coupling Reaction
FULL PAPER
Figure 2. a) Transient absorption difference spectra of TBA-eosin Y in
~
!
*
^
CH3CN at room temperature; =0.46 ms, =5.90 ms, =11.35 ms,
=
27.70 ms. b) Transient absorption difference spectra of TBA-eosin Y with
1a (1.80ꢁ10À3 molLÀ1). [TBA-eosin Y]=1.80ꢁ10À5 molLÀ1; lex =532 nm.
~
!
*
^
=2.28 ms, =15.90 ms, =29.52 ms, =111.24 ms.
Scheme 1. Possible pathways for the aerobic photocatalytic CDC reac-
tions.
ÀC
[15]
ide radical anion (O2 ) or radical anion of nitroalkane.
ÀC
The generated O2 radical anion may undergo protonation
C
to populate HOO radical, which can further react with 1a
C
by means of hydrogen abstraction to afford 1a radical along
with the formation of H2O2.[16] On the other hand, the fast
deprotonation of 1a+ radical cation furnishes 1a radical,
C
C
which has a low oxidization barrier.[17] Once again, the pho-
C
toinduced electron transfer from 1a radical to the triplet
TBA-eosin Y produced iminium ion 4 and TBA-eosin Y
radical anion (EY ), respectively, which is similar to the re-
Figure 3. a) ESR spectrum of
a solution of TBA-eosin Y (1.0ꢁ
ÀC
10À4 molLÀ1), 1a (1.5ꢁ10À3 molLÀ1), and DMPO (2.0ꢁ10À2 molLÀ1) in
air-saturated CH3CN upon irradiation for 20 s. b) ESR spectrum of a so-
lution of TBA-eosin Y (1.0ꢁ10À4 molLÀ1), 1a (1.5ꢁ10À3 molLÀ1), and
TEMP (0.12 molLÀ1) in air-saturated CH3CN upon irradiation for 20 s.
c) ESR spectrum of a solution of TBA-eosin Y (1.0ꢁ10À4 molLÀ1) and
TEMP (0.12 molLÀ1) upon irradiation for 20 s in air-saturated CH3CN.
action between a-amino radical and the [Ru
N
2,2’-bipyridyl) excited state reported by MacMillan et al.[17]
The nucleophilic addition of the azinic acid tautomer of ni-
tromethane to iminium 4 completes the reaction, thereby
giving rise to 1-nitromethyltetrahydroisoquinoline 2a. Be-
cause stirring the irradiated solution in the dark can further
enhance the yield of product 2a, a tetrahydroisoquinoline
hydroperoxide intermediate 3 is likely involved in the cou-
pling reaction. The transformation of hydroperoxide 3 to
iminium 4 therefore results in the continuous production of
2a and H2O2 in the dark.[18]
ure 3b), whereas in the absence of 1a this ESR signal was
clearly observed (Figure 3c). Although triplet eosin Y has
been reported to be an efficient sensitizer in the production
1
of O2 by an energy-transfer pathway,[14] the present case in-
dicates that this pathway is highly suppressed by the effec-
tive electron transfer between triplet TBA-eosin Y and 1a
so that the generated radical anion of TBA-eosin Y can sub-
sequently react with molecular oxygen to produce O2 by
an electron-transfer pathway.
With the understanding of reaction mechanism, the pres-
ent photocatalytic CDC method was further extended to the
coupling of tetrahydroisoquinolines and dimethyl malonate
(Table 3). Under visible-light irradiation, the N-phenyl tetra-
hydroisoquinoline derivatives 1 were treated smoothly with
dimethyl malonate under an oxygen atmosphere to afford
the desired products 5 in moderate to good yields. N-Aryl
tetrahydroisoquinolines with an electron-withdrawing group
located at the phenyl ring gave slightly better results.
Similarly, the photocatalytic aerobic CDC reaction was
also applicable to the oxidative Mannich reaction between
N-aryl tetrahydroisoquinolines 1 and acetone (Table 4).
With a combination of organic photocatalyst TBA-eosin Y
ÀC
On the basis of the above results, the aerobic CDC reac-
tion can be rationalized in terms of the mechanism shown in
Scheme 1. The photoinduced electron transfer from tetrahy-
droisoquinoline 1a to the triplet TBA-eosin Y results in the
formation of 1a+ cation radical and TBA-eosin Y radical
C
ÀC
ÀC
anion (EY ). Subsequent electron transfer from EY radi-
cal anion either to molecular oxygen or nitroalkane regener-
ates TBA-eosin Y, and at the same time produces superox-
Chem. Eur. J. 2012, 18, 620 – 627
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
623

L.-Z. Wu et al.
Table 3. The CDC reaction of tetrahydroisoquinolines with malonate by organophoto-
catalyst.[a]
from TBA-eosin Y radical anion either to molecu-
lar oxygen or nitroalkane regenerates TBA-eosin Y,
and at the same time produces a superoxide radical
ÀC
anion (O2 ) or a radical anion of nitroalkane. The
generated superoxide radical anion, a highly reac-
tive species, can accelerate the reaction remarkably.
Compared to the precious-metal-based CDC reac-
tion and visible-light photoredox catalysis of recent
years, systems by pure organophotocatalysts are
still in high demand. More strikingly, the revelation
of the mechanism of photocatalytic reactions is an-
ticipated to be useful for designing more atom-eco-
nomic and energy-efficient reactions.[20]
Product (yield [%])[b]
5a (65)
5b (51)
5c (68)
[a] Reaction conditions: 1 (0.2 mmol), TBA-eosin Y (0.004 mmol), dimethyl malonate
(1.0 mmol), dissolved in CH2Cl2 (10 mL), irradiated at ambient temperature in the
presence of oxygen. [b] Yield after column chromatography.
Experimental Section
General: 1H NMR spectra were recorded using
a Bruker
Table 4. The Mannich reaction of tetrahydroisoquinolines with acetone by organopho-
tocatalyst.[a]
Avance DPX 400 MHz instrument with tetramethylsilane
(TMS) as an internal standard. 13C NMR spectra were ob-
tained at 100 MHz and referenced to the internal solvent sig-
nals. Mass spectra were recorded using a Trio-2000 GC-MS
spectrometer. Steady-state emission spectra were recorded
using a Perkin–Elmer LS50B spectrofluorimeter. ESR spectra
were recorded at room temperature using a Bruker ESP-300E
spectrometer at 9.8 GHz, X-band, with 100 Hz field modula-
tion. Samples were quantitatively injected into specially made
quartz capillaries for ESR analysis before being purged with
argon or oxygen for 30 min in the dark and illuminated directly
in the cavity of the ESR spectrometer with a Nd:YAG laser
(532 nm, 5–6 ns pulse width, 10 Hz repetition frequency, 10 mJ
pulse energy). All reagents were weighed and handled in air,
and backfilled under an inert atmosphere of argon at room
temperature. Commercially available reagents and solvents
were used without further purification. All the N-aryl tetrahy-
droisoquinolines 1 needed for CDC reactions were prepared
by using the reported procedure[4c] and purified through
column chromatography.
Product (yield [%])[b]
6a (51)
6b (53)
6c (57)
[a] Reaction conditions:
1
(0.2 mmol), TBA-eosin
Y
(0.004 mmol), l-proline
(0.04 mmol), acetone (6 mL), CH3OH (4 mL), irradiated at ambient temperature in
the presence of oxygen. [b] Yield after column chromatography.
Oxygen uptake experiment: A 15 mL Pyrex tube equipped
with a rubber septum and magnetic stir bar was charged with
TBA-eosin Y (4.5 mg, 0.004 mmol), 2-phenyl-1,2,3,4-tetrahydroisoquino-
line (42 mg, 0.2 mmol), and CH3NO2 (10 mL). The mixture was bubbled
with a stream of oxygen for 20 min. CH4 (500 mL) was injected as internal
standard for quantitative GC analysis. The tube was then sealed and irra-
diated by a 500 W high-pressure mercury lamp at ambient temperature,
and a glass filter was employed to cut off light with wavelength below
450 nm. The residual oxygen molecular of the systems was measured
using a GC-14B instrument (Shimadzu) with nitrogen as the carrier gas,
molecular sieve 5 ꢂ columns (30 mꢁ0.53 mm), and a thermal conductivi-
ty detector. The response factor for O2/CH4 was about 11.2 under experi-
mental conditions, which was established by calibration with known
amounts of O2 and CH4, and determined before and after a series of
measurements.
and cocatalyst l-proline, the reaction gave the desired
amino ketones 6 in synthetically useful yields. Despite the
fact that the yields are modest, the present system being per-
formed by pure organocatalysts adds significantly to previ-
ous methodologies.[7,19]
Conclusion
In summary, we provide a simple and effective aerobic,
À
metal-free catalytic CDC reaction for the direct C C bond
formation of N-aryl tetrahydroisoquinolines by means of
visible-light irradiation. By combining organic photocatalyst
TBA-eosin Y and the most economic oxidant molecular
oxygen, the active participants in this coupling reaction have
been broadened to nitroalkanes, dialkyl malonate deriva-
tives, and even nonactivated simple ketones. Mechanistic
studies demonstrate for the first time that photoinduced
electron transfer from N-aryl tetrahydroisoquiline to the
triplet TBA-eosin Y dominates the primary process of the
oxidative coupling reaction. Subsequent electron transfer
General procedure for the CDC reaction of nitroalkanes with tetrahy-
droisoquinolines: A 15 mL Pyrex tube equipped with a rubber septum
and magnetic stir bar was charged with TBA-eosin
Y (4.5 mg,
0.004 mmol), 2-phenyl-1,2,3,4-tetrahydroisoquinoline (42 mg, 0.2 mmol),
and CH3NO2 (10 mL). The mixture was bubbled with a stream of oxygen
for 20 min. The tube was then sealed and irradiated by a 500 W high-
pressure mercury lamp at ambient temperature. A glass filter was em-
ployed to cut off light with wavelength below 450 nm. The progress of
the reaction was monitored by thin-layer chromatography at regular in-
tervals. Generally, the conversion was close to 100% after 4 h of irradia-
tion. The irradiated sample was then stirred in the dark at the room tem-
perature for 12 h. Upon removal of solvent under vacuum, the residue
624
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 620 – 627

Cross-Dehydrogenative Coupling Reaction
FULL PAPER
was purified by flash chromatography on alkalescence silica gel to afford
the corresponding products.
129.6, 147.9, 148.7, 148.9 ppm; EIMS: m/z (%): 328 (30) [M+], 268 (100),
104 (15), 77 (36).
1-Nitromethyl-2-phenyl-1,2,3,4-tetrahydroisoquinoline (2a): 1H NMR
(400 MHz, CDCl3): d=2.82 (dt, J=16.4, 4.9 Hz, 1H), 3.06–3.13 (m, 1H),
3.61–3.69 (m, 2H), 4.57 (dd, J=11.9, 6.6 Hz, 1H), 4.89 (dd, J=12.0,
8.0 Hz, 1H), 5.56 (t, J=8.0 Hz, 1H), 6.87 (t, J=7.3 Hz, 1H), 6.99 (d, J=
8.2 Hz, 2H), 7.14 (d, J=7.2 Hz, 1H), 7.18–7.29 ppm (m, 5H); 13C NMR
(100 MHz, CDCl3): d=26.7, 42.3, 58.4, 79.0, 115.3, 119.7, 126.9, 127.2,
128.3, 129.4, 129.7, 133.2, 135.5, 148.6 ppm; EIMS: m/z (%): 268 (43)
[M+], 208 (100), 77 (5).
1-Nitromethyl-2-p-tolyl-1,2,3,4-tetrahydroisoquinoline (2b): 1H NMR
(400 MHz, CDCl3): d=2.25 (s, 3H), 2.73 (dt, J=16.0, 4.0 Hz, 1H), 3.01–
3.05 (m, 1H), 3.53–3.60 (m, 2H), 4.54 (dd, J=12.0, 6.4 Hz, 1H), 4.83 (dd,
J=12.0 Hz, 8.0 Hz, 1H), 5.48 (t, J=8.0 Hz, 1H), 6.88 (d, J=8.6 Hz, 2H),
7.06 (d, J=8.6 Hz, 2H), 7.11–7.25 ppm (m, 4H); 13C NMR (100 MHz,
CDCl3): d=0.5, 26.4, 42.5, 58.6, 79.0, 116.1, 126.8, 127.2, 128.2, 129.3,
129.5, 130.2, 133.2, 135.6, 146.6 ppm; EIMS: m/z (%): 282 (60) [M+], 222
(100), 118 (64), 91 (66), 77(12).
6,7-Dimethoxy-2-(4-methoxyphenyl)-1-nitromethyl-1,2,3,4-tetrahydroiso-
quinoline (2i): 1H NMR (400 MHz, CDCl3): d=2.57 (dt, J=4.4, 16.0 Hz,
1H), 2.88–2.96 (m, 1H), 3.51–3.57 (m, 1H), 3.75 (s, 3H), 3.86 (s, 6H),
4.56 (dd, J=5.7, 12.0 Hz, 1H), 4.81 (dd, J=8.0, 12.0 Hz, 1H), 5.29 (dd,
J=5.7 Hz, 8.6 Hz, 1H), 6.60 (s, 1H), 6.62 (s, 1H), 6.81 (d, J=8.0 Hz,
2H), 6.91 ppm (d, J=8.0 Hz, 2H); 13C NMR(100 MHz, CDCl3): d=25.3,
43.4, 55.7, 56.0, 56.2, 58.9, 79.1, 109.6, 112.0, 114.8, 119.4, 124.6, 127.7,
143.3, 147.9, 148.9, 154.2 ppm; EIMS: m/z (%): 358 (78) [M+], 298 (92),
296 (100), 282 (80), 254 (39), 149 (42), 77 (8).
1-(1-Nitroethyl)-2-phenyl-1,2,3,4-tetrahydroisoquinoline (2j): 1H NMR
(400 MHz, CDCl3): d=[1.53 (d, J=8.0 Hz), 1.69 (d, J=8.0 Hz), 3H],
[2.83–2.94 (m), 2.99–3.09 (m), 2H], [3.51–3.61 (m), 3.80–3.86 (m), 2H],
[4.84–4.92 (m), 5.01–5.08 (m), 1H], 5.22–5.26 (m, 1H), 6.79–6.84 (m,
1H), 6.97–7.01 (m, 2H), 7.08–7.29 (m, 6H) ppm; 13C NMR (100 MHz,
CDCl3): d=(16.4, 17.4), (26.4, 26.7), (42.7, 43.5), (61.1, 62.7), (85.4, 88.9),
(114.5, 115.4), (118.8, 119.3), 126.1, 126.6, 127.2, 128.2, 128.3, 128.7, 129.1,
129.3, 129.4, 129.6, 132.0, 133.8, 134.8, 135.6, 148.9, 49.2 ppm; EIMS: m/z
(%): 282 (17) [M+], 208 (100), 104 (46), 77 (55).
1-(1-Nitroethyl)-2-p-tolyl-1,2,3,4-tetrahydroisoquinoline (2k): 1H NMR
(400 MHz, CDCl3): d=[1.52 (d, J=6.8 Hz), 1.68 (d, J=6.8 Hz), 3H],
[2.23 (s), 2.26 (s), 3H], [2.76–2.91 (m), 2.95–3.08 (m), 2H], [3.48–3.59
(m), 3.76–3.83 (m), 2H], [4.87 (dq, J=6.8, 13.6 Hz), 5.03 (dq, J=6.6,
13.3 Hz), 1H], 5.11–5.22 (m, 1H), 6.83–6.95 (m, 2H), 6.99–7.27 ppm (m,
6H); 13C NMR (100 MHz, CDCl3): d=(16.4, 17.3), 20.3, (26.2, 26.5),
(43.0, 43.9), (61.4, 62.9), (85.5, 88.9), (115.1, 116.0), 126.0, 126.5, 127.2,
128.1, 128.3, 128.8, 128.9, 129.1, 129.8, 129.9, 132.0, 133.8, 134.8, 135.7,
146.8, 147.1 ppm; EIMS: m/z (%): 296 (14) [M+], 222 (100), 149 (38), 91
(31), 77 (10).
2-(4-Methoxyphenyl)-1-nitromethyl-1,2,3,4-tetrahydroisoquinoline (2c):
1H NMR (400 MHz, CDCl3) d=2.69 (dt, J=16.0, 4.0 Hz, 1H), 2.96–3.02
(m, 1H), 3.50–3.56 (m, 2H), 3.74 (s, 3H), 4.55 (dd, J=12, 5.8 Hz, 1H),
4.81 (dd, J=12, 8.6 Hz, 1H), 5.38 (dd, J=5.8, 8.6 Hz, 1H), 6.81 (d, J=
9.0 Hz, 2H), 6.91 (d, J=9.0 Hz, 2H), 7.09–7.33 ppm (m, 4H); 13C NMR
(100 MHz, CDCl3): d=25.8, 43.1, 55.5, 58.9, 78.9, 114.7, 118.8, 126.6,
126.9, 127.9, 129.4, 132.9, 135.4, 143.0, 153.9 ppm; EIMS: m/z (%): 298
(73) [M+], 239 (100), 223 (55), 115 (50), 91(12), 77 (18).
2-(2-Methoxyphenyl)-1-nitromethyl-1,2,3,4-tetrahydroisoquinoline (2d):
1H NMR (400 MHz, CDCl3) d=2.71 (ddd, J=2.4, 3.8 Hz, 16.5 Hz, 1H),
2.94–2.98 (m, 1H), 3.44–3.61 (m, 2H), 3.82 (s, 3H), 4.53 (dd, J=5.2,
12.0 Hz, 1H), 4.82 (dd, J=8.0, 12.0 Hz, 1H), 5.50 (dd, J=8.3, 5.1 Hz,
1H), 6.81–6.88 (m, 3H), 6.98–7.05 (m, 1H), 7.12–7.30 ppm (m, 4H);
13C NMR (100 MHz, CDCl3): d=27.1, 43.2, 56.0, 58.4, 79.4, 112.8, 121.3,
122.2, 124.3, 126.6, 129.7, 133.9, 135.6, 139.2, 153.4 ppm; EIMS: m/z (%):
298 (62) [M+], 239 (95), 222 (100), 115 (33), 91(11), 77 (21).
2-(4-Bromophenyl)-1-(1-nitroethyl)-1,2,3,4-tetrahydroisoquinoline (2l):
1H NMR (400 MHz, CDCl3): d=[1.55 (d, J=8.0 Hz), 1.67 (d, J=8.0 Hz),
3H], [2.85–2.96 (m), 3.01–3.08 (m), 2H], [3.45–3.60 (m), 3.78–3.84 (m),
2H], [4.83–4.90 (m), 4.97–5.04 (m), 1H], 5.13–5.21 (m, 1H), 6.82–6.87
(m, 2H), 7.10–7.37 ppm (m, 6H); 13C NMR (100 MHz, CDCl3): d=(16.8,
17.5), (26.4, 26.9), (43.0, 43.9), (61.3, 62.9), (85.6, 89.0), (116.3, 117.2),
126.5, 127.0, 127.2, 127.4, 128.5, 128.6, 128.9, 129.4, 129.6, 132.0, 132.2,
132.3, 132.7, 133.7, 134.7, 135.5, 148.1, 148.4 ppm; EIMS: m/z (%): 362
(8), 360 (8) [M+], 314 (24), 312 (20), 288 (100), 206 (26), 129 (54), 115
(43), 91 (10), 77 (14).
1-(1-Nitropropyl)-2-phenyl-1,2,3,4-tetrahydroisoquinoline (2m): 1H NMR
(400 MHz, CDCl3): d=0.91–0.96 (m, 3H), [1.77–1.89 (m), 2.04–2.16 (m),
2H], [2.83–2.93 (m), 3.02–3.11 (m) 2H], [3.48–3.69 (m), 3.81–3.88 (m),
2H], [4.64–4.70 (m), 4.83–4.89 (m), 1H], [5.12 (d, J=9.5 Hz), 5.23 (d, J=
9.5 Hz), 1H], 6.76–6.83 (m, 1H), 6.92–7.00 (m, 2H), 7.13–7.29 ppm (m,
6H); 13C NMR (100 MHz, CDCl3): d=10.7, (24.6, 25.0), (25.7, 26.8),
(42.3, 43.5), (60.7, 62.2), (93.0, 96.1), (114.1, 115.8), (118.6, 119.4), 125.9,
126.6, 127.2, 128.2, 128.6, 128.7, 129.2, 129.3, 129.4, 132.6, 133.9, 134.7,
135.5, 149.0, 149.1 ppm; EIMS: m/z (%): 296 (36) [M+], 209 (100), 115
(78), 104 (82), 77 (81).
1-(1-Nitropropyl)-2-p-tolyl-1,2,3,4-tetrahydroisoquinoline (2n): 1H NMR
(400 MHz, CDCl3): d=0.91–0.95 (m, 3H), [1.77–1.87 (m), 2.01–2.19 (m),
2H], 2.12 (s, 3H), [2.78–2.89 (m), 2.99–3.08 (m), 2H], [3.46–3.64 (m),
3.78–3.86 (m), 2H], [4.63–4.69 (m), 4.81–4.87 (m), 1H], [5.04 (d, J=
12.0 Hz), 5.15 (d, J=12.0 Hz), 1H], 6.81–6.89 (m, 2H), 6.97–7.25 ppm
(m, 6H); 13C NMR (100 MHz, CDCl3): d=10.7, (20.2, 20.3), (24.6, 25.0),
(25.5, 26.6), (42.5, 43.8), (60.9, 62.3), (93.1, 96.2), (114.7, 116.4), 125.8,
126.5, 127.2, 128.1, 128.6, 128.7, 128.9, 129.4, 129.7, 129.9, 132.5, 133.9,
134.7, 135.6, 146.9 ppm; EIMS: m/z (%): 310 (32) [M+], 223 (100), 207
(34), 118 (57), 115 (52), 91 (84), 77 (12); HRMS (EI): m/z calcd for
C19H22N2O2: 310.1681; found: 310.1684.
2-(4-Fluorophenyl)-1-nitromethyl-1,2,3,4-tetrahydroisoquinoline
(2e):
1H NMR (400 MHz, CDCl3) d=2.71 (dt, J=16.0, 4.4 Hz, 1H), 2.98–3.04
(m, 1H), 3.59 (dd, J=9.1, 4.4 Hz, 2H), 4.56 (dd, J=12.0, 5.8 Hz, 1H),
4.83 (dd, J=12.0, 8.6 Hz, 1H), 5.42 (dd, J=8.6, 5.8 Hz, 1H), 6.88–6.92
(m, 4H), 7.12–7.27 ppm (m, 4H); 13C NMR (100 MHz, CDCl3): d=25.7,
29.7, 42.8, 58.7, 78.8, 115.8 (d,
7.4 Hz), 126.7, 126.9, 128.1, 129.4, 132.5, 135.2, 145.3, 157.1 ppm (d, J-
ACHTUNGTRENNUNG
(C,F)=239.2 Hz); EIMS: m/z (%): 286 (63) [M+], 227 (100), 115 (70), 95
JACTHUNGTRENNU(G C,F)=22.2 Hz), 117.9 (d, JACHTUGNTREN(NUNG C,F)=
(58), 91 (12), 77 (8); HRMS (EI): m/z calcd for C16H15FN2O2: 286.1118;
found: 286.1117.
2-(4-Chlorophenyl)-1-nitromethyl-1,2,3,4-tetrahydroisoquinoline
(2 f):
1H NMR (400 MHz, CDCl3): d=2.76 (dt, J=4.4, 16.0 Hz, 1H), 3.05
(ddd, J=15.1, 8.4, 6.3 Hz, 1H), 3.46–3.73 (m, 2H), 4.55 (dd, J=6.3,
12.0 Hz, 1H), 4.82 (dd, J=8.0, 12.0 Hz, 1H), 5.47 (t, J=8.0 Hz, 1H), 6.88
(d, J=9.1 Hz, 2H), 7.10–7.26 ppm (m, 6H); 13C NMR (100 MHz,
CDCl3): d=26.3, 42.4, 58.4, 78.8, 116.7, 124.6, 127.0, 127.2, 128.4, 129.5,
132.7, 135.3, 147.3 ppm; EIMS: m/z (%): 302 (94) [M+], 244 (100), 149
(64), 115 (72), 111 (50), 77 (14).
2-(4-Bromophenyl)-1-nitromethyl-1,2,3,4-tetrahydroisoquinoline
(2g):
1H NMR (400 MHz, CDCl3) d=2.79 (dt, J=4.8, 16.0 Hz, 1H), 3.01–3.15
(m, 1H), 3.57–3.65 (m, 1H), 4.57 (dd, J=6.4, 12.0 Hz, 1H), 4.82 (dd, J=
8.0, 12.0 Hz, 1H), 5.47 (t, J=8.0 Hz, 1H), 6.84 (d, J=9.1 Hz, 2H), 7.16–
7.31 (m, 4H), 7.34 ppm (d, J=9.1 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d=26.1, 42.0, 58.1, 78.6, 111.5, 116.7, 126.8, 126.9, 128.2, 129.2, 132.2,
132.4, 135.0, 147.5 ppm; EIMS: m/z (%): 348 (62), 346 (65) [M+], 288
(100), 118 (99), 90 (25), 77 (12).
6,7-Dimethoxy-1-nitromethyl-2-phenyl-1,2,3,4-tetrahydroisoquinoline
(2h): 1H NMR (400 MHz, CDCl3): d=2.68 (dt, J=4.4, 16.0 Hz, 1H),
2.96–3.04 (m, 1H), 3.54–3.61 (m, 1H), 3.65–3.70 (m, 1H), 3.85 (s, 6H),
4.56 (dd, J=6.4, 12.0 Hz, 1H), 4.85 (dd, J=8.0, 12.0 Hz, 1H), 5.46 (t, J=
8.0 Hz, 1H), 6.60 (s, 1H), 6.65 (s, 1H), 6.85 (t, J=8.0 Hz, 1H), 6.87 (d,
J=8.0 Hz, 2H), 7.24–7.28 ppm (m, 2H); 13C NMR (100 MHz, CDCl3):
d=25.9, 42.2, 56.0, 56.2, 58.1, 78.9, 109.8, 111.9, 115.7, 119.7, 124.7, 127.6,
2-(4-Bromophenyl)-1-(1-nitropropyl)-1,2,3,4-tetrahydroisoquinoline (2o):
1H NMR (400 MHz, CDCl3) d=0.91–0.96 (m, 3H), [1.73–1.84 (m), 1.95–
2.21 (m), 2H], [2.83–2.95 (m), 2.98–3.10 (m), 2H], [3.41–3.48 (m), 3.76–
3.86 (m), 1H], [3.53–3.62 (m), 1H], [4.62–4.68 (m), 4.79–4.85 (m), 1H],
[5.05 (d, J=12.0 Hz), 5.17 (d, J=12.0 Hz), 1H], [6.80 (d, J=9.1 Hz), 6.84
(d, J=9.1 Hz), 2H], 7.14–7.30 ppm (m, 6H); 13C NMR (100 MHz,
CDCl3): d=10.8, (24.9, 25.1), (25.8, 26.9), (42.6, 43.9), (60.8, 62.3), (93.1,
Chem. Eur. J. 2012, 18, 620 – 627
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
625

L.-Z. Wu et al.
96.1), (93.1, 96.1), (110.7, 111.6), (115.8, 117.5), 126.2, 127.0, 127.3, 128.6,
128.8, 129.5, 132.1, 132.3, 132.4, 133.7, 134.6, 135.4, 148.2 ppm; EIMS: m/
z (%): 376 (5) [M+], 374 (6), 289 (67), 289 (67), 288 (100), 287 (74), 286
(76), 222 (33), 207(37), 184 (31), 182 (28), 115 (45), 103 (10), 77 (9);
HRMS (EI): m/z calcd for C18H19N2O2Br: 374.0630; found: 374.0630.
118.4, 126.2, 126.6, 126.8, 128.9, 134.3, 138.2, 143.7, 153.3, 207.3 ppm;
EIMS: m/z (%): 295 (46) [M+], 239 (100), 223 (33), 115 (14).
1-[2-(4-Chlorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]propan-2-one
(6c): 1H NMR (400 MHz, CDCl3): d=2.08 (s, 3H), 2.78–2.85 (m, 2H),
3.00–3.07 (m, 2H), 3.47–3.62 (m, 2H), 5.34 (t, J=8.0 Hz, 1H), 6.83–6.87
(m, 2H), 7.12–7.18 ppm (m, 6H); 13C NMR (100 MHz, CDCl3): d=26.6,
30.7, 41.8, 49.8, 54.4, 115.4, 122.6, 126.0, 126.4, 126.6, 128.3, 128.7, 133.8,
137.5, 147.1, 206.6 ppm; EIMS: m/z (%): 299 (46) [M+], 242 (100), 227
(30), 138 (40), 115 (61), 111 (39), 77 (14).
General procedure for the photocatalytic CDC reaction of dimethyl mal-
onate with tetrahydroisoquinolines: A 15 mL Pyrex tube equipped with a
rubber septum and magnetic stir bar was charged with TBA-eosin Y
(4.5 mg, 0.004 mmol), 2-phenyl-1,2,3,4-tetrahydroisoquinoline (42 mg,
0.2 mmol), dimethyl malonate (132 mg, 1.0 mmol), and CH2Cl2 (10 mL).
The mixture was bubbled with a stream of oxygen for 20 min. The tube
was then sealed and irradiated by a 500 W high-pressure mercury lamp at
ambient temperature. A glass filter was employed to cut off light with
wavelength below 450 nm. After 4 h of irradiation, the sample was then
stirred in the dark at the room temperature for 12 h and then concentrat-
ed under vacuum. Purification of the residue by flash column chromatog-
raphy on silica gel gave the corresponding products.
Acknowledgements
Financial support from the Ministry of Science and Technology of China
(2009CB220008 and 2007CB808004), the National Natural Science Foun-
dation of China (21090343 and 20732007), Solar Energy Initiative of the
Knowledge Innovation Program of the Chinese Academy of Sciences
(KGCXZ-YW-389), and the Bureau for Basic Research of the Chinese
Academy of Sciences is gratefully acknowledged
Dimethyl 2-(1,2,3,4-tetrahydro-2-phenylisoquinolin-1-yl)malonate (5a):
1H NMR (400 MHz, CDCl3): d=2.87 (dt, J=16.5, 5.1 Hz, 1H), 3.07
(ddd, J=15.6, 8.9, 6.3 Hz, 1H), 3.54 (s, 3H), 3.77–3.57 (m, 5H), 3.95 (d,
J=9.4 Hz, 1H), 5.70 (d, J=9.4 Hz, 1H), 6.76 (t, J=7.3 Hz, 1H), 6.98 (d,
J=8.1 Hz, 2H), 7.31–7.06 ppm (m, 7H); 13C NMR (100 MHz, CDCl3):
d=26.22, 42.34, 52.70, 58.34, 59.28, 76.91, 77.23, 77.55, 115.36, 118.79,
126.21, 127.21, 127.80, 129.15, 129.27, 134.95, 135.83, 148.94, 167.57,
168.45 ppm; EIMS: m/z (%): 339 (47) [M+], 209 (100), 193 (56), 115
(66), 77(74).
[1] For example, see: a) V. Ritleng, C. Sirlin, M. Pfeffer, Chem. Rev.
2002, 102, 1731–1770; b) L. Ackermann, Top. Organomet. Chem.
2007, 24, 35–60; c) C.-L. Sun, B.-J. Li, Z.-J. Shi, Chem. Rev. 2011,
111, 1293–1314.
[2] C.-J. Li, Acc. Chem. Res. 2009, 42, 335–344.
Dimethyl 2-[1,2,3,4-tetrahydro-2-(4-methoxyphenyl)isoquinolin-1-yl] mal-
onate (5b): 1H NMR (400 MHz, CDCl3): d=2.75 (dt, J=16.6, 4.4 Hz,
1H), 3.00 (ddd, J=16.6, 10.2, 6.4 Hz, 1H), 3.52–3.70 (m, 2H), 3.61 (s,
3H), 3.64 (s, 3H), 3.73 (s, 3H), 3.96 (d, J=9.4 Hz, 1H), 5.49 (d, J=
9.4 Hz, 1H), 6.82–6.69 (m, 2H), 6.99–6.86 (m, 2H), 7.23–7.06 ppm (m,
4H); 13C NMR (100 MHz, CDCl3) d=25.6, 43.1, 52.59, 52.63, 55.7, 59.3,
114.5, 118.4, 126.1, 127.2, 127.6, 129.3, 134.9, 135.5, 143.6, 153.4, 167.6,
168.4 ppm; EIMS: m/z (%): 369 (73) [M+], 239 (100), 223 (81), 195 (28),
115 (63), 101 (74), 77 (17), 59 (53).
[3] S.-I. Murahashi, N. Komiya, H. Terai, T. Nakae, J. Am. Chem. Soc.
2003, 125, 15312–15313.
[4] a) Z. Li, C.-J. Li, Org. Lett. 2004, 6, 4997–4999; b) Z. Li, C.-J. Li, J.
Am. Chem. Soc. 2005, 127, 3672–3673; c) Z. Li, D. S. Bohle, C.-J. Li,
Proc. Natl. Acad. Sci. USA 2006, 103, 8928–8933.
[5] a) O. Baslꢃ, C.-J. Li, Green Chem. 2007, 9, 1047–1050; b) Z. Li, L.
Cao, C.-J. Li, Angew. Chem. 2007, 119, 6625–6627; Angew. Chem.
Int. Ed. 2007, 46, 6505–6507; c) O. Baslꢃ, N. Borduas, P. Dubois,
J. M. Chapuzet, T.-H. Chan, J. Lessard, C.-J. Li, Chem. Eur. J. 2010,
16, 8162–8166.
Dimethyl 2-[2-(4-chlorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]malo-
nate (5c): 1H NMR (400 MHz, CDCl3): d=2.90 (dt, J=16.4, 5.4 Hz,
1H), 3.05 (ddd, J=14.9, 8.6, 6.1 Hz, 1H), 3.61–3.50 (m, 4H), 3.72–3.62
(m, 4H), 3.91 (d, J=9.5 Hz, 1H), 5.64 (d, J=9.5 Hz, 1H), 6.99–6.78 (m,
2H), 7.24–7.09 ppm (m, 6H); 13C NMR (100 MHz, CDCl3): d=26.2, 42.7,
52.8, 58.4, 59.3, 116.3, 123.5, 126.4, 127.2, 129.1, 134.8, 135.6, 147.5, 167.5,
168.4 ppm; EIMS m/z (%): 373 (77) [M+], 242 (100), 138 (36), 115 (46);
HRMS (EI): m/z calcd for C20H20NO4Cl: 373.1081, found: 373.1081.
[6] A. G. Condie, J. C. Gonzalez-Gomez, C. R. J. Stephenson, J. Am.
Chem. Soc. 2010, 132, 1464–1465.
[7] M. Rueping, C. Vila, R. M. Koenigs, K. Poscharny, D. C. Fabry,
Chem. Commun. 2011, 47, 2360–2362.
[8] a) D. Zhang, L.-Z. Wu, L. Zhou, X. Han, Q. Z. Yang, L.-P. Zhang,
C.-H. Tung, J. Am. Chem. Soc. 2004, 126, 3440–3441; b) D.-H.
Wang, M.-L. Peng, Y. Han, B. Chen, C.-H. Tung, L.-Z. Wu, Inorg.
Chem. 2009, 48, 9995–9997; c) Q. Liu, Y.-N. Li, H.-H. Zhang, B.
Chen, C.-H. Tung, L.-Z. Wu, J. Org. Chem. 2011, 76, 1444–1447.
[9] a) D. Zhang, L.-Z. Wu, Q.-Z. Yang, X.-H Li, L.-P. Zhang, C.-H.
Tung, Org. Lett. 2003, 5, 3221–3224; b) K. Feng, R.-Y. Zhang, L.-Z.
Wu, B. Tu, M.-L. Peng, L.-P. Zhang, D. Zhao, C.-H. Tung, J. Am.
Chem. Soc. 2006, 128, 14685–14690.
[10] a) T. Lazarides, T. McCormick, P. Du, G. Luo, B. Lindley, R. Eisen-
berg, J. Am. Chem. Soc. 2009, 131, 9192–9194; b) M. Neumann, S.
Fꢄldner, B. Kçnig, K. Zeitler, Angew. Chem. 2011, 123, 981–985;
Angew. Chem. Int. Ed. 2011, 50, 951–954.
[11] a) L. Flamigni, J. Phys. Chem. 1992, 96, 3331–3337; b) E. Joselevich,
I. Willner, J. Phys. Chem. 1995, 99, 6903–6912; c) S. Hazebroucq, F.
Labat, D. Lincot, C. Adamo, J. Phys. Chem. A 2008, 112, 7264–
7270.
[12] C.-H. Tung, L.-Z. Wu, L.-P. Zhang, B. Chen, Acc. Chem. Res. 2003,
36, 39–47, and references therein.
[13] a) Z.-Z. Ou, J.-R. Chen, X.-S. Wang, B.-W. Zhang, Y. Cao, New. J.
Chem. 2002, 26, 1130–1136; b) J. Ma, J. Zhao, L. Jiang, Photochem.
Photobiol. 2001, 74, 143–148.
[14] A. I. Meyers, R. L. Nolen, E. W. Collington, T. A. Narwid, R. C.
Strickland, J. Org. Chem. 1973, 38, 1974–1982.
[15] The possible pathway for decomposition of nitroalkane radical
anion had been thoroughly discussed in Ref. [4]; see also: B. Raju,
R. Ragul, B. N. Sivasankar, Indian J. Chem. Sect. B: Org. Chem.
Incl. Med. Chem. 2009, 48, 1315–1318.
General procedure for the Mannich reaction of acetone with tetrahydroi-
soquinolines: A 15 mL Pyrex tube equipped with a rubber septum and
magnetic stir bar was charged with TBA-eosin Y (4.5 mg, 0.004 mmol), 2-
phenyl-1,2,3,4-tetrahydroisoquinoline (42 mg, 0.2 mmol), l-proline
(4.6 mg, 0.04 mmol), acetone (6 mL), and CH3OH (4 mL). The mixture
was bubbled with a stream of oxygen for 20 min. The tube was then
sealed and irradiated by a 500 W high-pressure mercury lamp at ambient
temperature. A glass filter was employed to cut off light with wavelength
below 450 nm. After 4 h of irradiation, the sample was then stirred in the
dark at the room temperature for 12 h. Upon removal of solvent under
vacuum, the residue was purified by flash chromatography on silica gel to
afford corresponding products.
1-(2-Phenyl-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one
(6a):
1H NMR (400 MHz, CDCl3): d=2.06 (s, 3H), 2.82 (dt, J=4.0, 16.0 Hz,
2H), 3.01–3.08 (m, 2H), 3.49–3.56 (m, 1H), 3.61–3.67 (m, 1H), 5.40 (t,
J=8.0 Hz, 1H), 6.77 (t, J=8.0 Hz, 1H), 6.93 (d, J=8.0 Hz, 2H), 7.11–
7.27 ppm (m, 6H); 13C NMR (100 MHz, CDCl3): d=27.2, 31.1, 42.0, 50.2,
54.8, 114.7, 118.2, 126.4, 126.7, 126.8, 128.6, 129.3, 134.4, 138.3, 148.8,
207.2 ppm; EIMS: m/z (%): 265 (23) [M+], 208 (100), 115 (32), 77 (43).
1-[2-(4-Methoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]propan-2-one
(6b): 1H NMR (400 MHz, CDCl3): d=2.05 (s, 3H), 2.70–2.79 (m, 2H),
2.96–3.04 (m, 2H), 3.42–3.56 (m, 2H), 3.74 (s, 3H), 5.24 (t, J=8.0 Hz,
1H), 6.79–6.83 (m, 2H), 6.86–6.93 (m, 2H), 7.09–7.13 ppm (m, 4H);
13C NMR (100 MHz, CDCl3): d=26.7, 30.8, 42.8, 49.9, 55.6, 55.9, 114.6,
626
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 620 – 627

Cross-Dehydrogenative Coupling Reaction
FULL PAPER
[16] The generation of H2O2 was evidenced by the iodometric titration
experiments. For the detailed procedures, see: R. D. Mair, A. J.
Graupner, Anal. Chem. 1964, 36, 194–204.
[20] During the publication of this article, similar papers have appeared:
D. Prasad Hari, B. Kçnig, Org. Lett. 2011, 13, 3852–3855; Y. Pan, C.
Wee Kee, L. Chen, C.-H. Tan, Green Chem. 2011, 13, 2682–2685.
[17] D. A. Nicewicz, D. W. C. Macmillan, Science 2008, 322, 77–80.
[18] ꢅ. Pintꢃr, A. Sud, D. Sureshkumar, M. Klussmann, Angew. Chem.
2010, 122, 5124–5128; Angew. Chem. Int. Ed. 2010, 49, 5004–5007.
[19] a) A. Sud, D. Sureshkumar, M. Klussmann, Chem. Commun. 2009,
3169–3171; b) X.-Z. Shu, Y.-F. Yang, X.-F. Xia, K.-G. Ji, X.-Y. Liu,
Y.-M. Liang, Org. Biomol. Chem. 2010, 8, 4077–4079.
Received: July 26, 2011
Published online: December 8, 2011
Chem. Eur. J. 2012, 18, 620 – 627
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
627