Porphyrin-Catalyzed Oxidation of N-Substituted Tetrahydroisoquinolines to Dihydroisoquinolones

Article abstract of DOI:10.1055/a-1345-3491

A visible-light-induced direct α-oxygenation of N-substituted 1,2,3,4-Tetrahydroisoquinoline derivatives has been successfully developed. Tetraphenylporphyrinatozinc(II) has been identified as an effective and inexpensive photocatalyst for this transformation with a wide range of substrates. This protocol provides a convenient route to the desired products in moderate to good yields at room temperature under air.

Full text of DOI:10.1055/a-1345-3491

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 32, 679–684
letter
679
en
A. Li et al.
Letter
Synlett
Porphyrin-Catalyzed Oxidation of N-Substituted Tetrahydroiso-
quinolines to Dihydroisoquinolones
Ao Li◊a
Bin Pan◊b
Chao Mua
Na Wangb
Yu-Long Li*a
Qin Ouyang*b
a College of Chemistry and Environmental Engineering,
Sichuan University of Science and Engineering, Zigong
643000, P. R. of China
yu_longli@aliyun.com
b College of Pharmacy, Third Military Medical University,
Chongqing 400038, P. R. of China
ouyangq@tmmu.edu.cn
◊These authors contributed equally
Corresponding Authors
Received: 03.12.2020
Accepted after revision: 04.01.2021
Published online: 04.01.2021
Because amines and lactams form a large group of bio-
active substances, -oxidation of amines to form lactams is
a useful oxidative transformation.7 Dihydroisoquinolone
moieties are present in many natural products and biologi-
cally active molecules.8 Many efficient methods have been
developed for the construction of dihydroisoquinolo-
nes.2a,8b,9 Among the reported methods, the -oxidation of
tetrahydroisoquinolines is a particularly direct and attrac-
tive strategy.10 Besides conventional metal oxidants, the use
of metal-free oxidants to achieve this synthesis has attract-
ed much attention; examples include oxidation by NaClO2
and an aerobic oxidation catalyzed by cobalt(II) porphy-
rins.11 In particular, recently reported oxygen oxidations us-
ing 5-methylfuran-2(3H)-one or a binuclear copper com-
DOI: 10.1055/a-1345-3491; Art ID: st-2020-b0618-l
Abstract A visible-light-induced direct -oxygenation of N-substitut-
ed 1,2,3,4-tetrahydroisoquinoline derivatives has been successfully de-
veloped. Tetraphenylporphyrinatozinc(II) has been identified as an ef-
fective and inexpensive photocatalyst for this transformation with a
wide range of substrates. This protocol provides a convenient route to
the desired products in moderate to good yields at room temperature
under air.
Key words photocatalysis, oxidation, porphyrins, zinc catalysis, dihy-
droisoquinolones
Oxidation is one of the most important reactions in or-
ganic synthesis. Most reported oxidation reactions rely on
stoichiometric amounts of such oxidants as metal oxidants,
DDQ, PhI(OAc)2, or peroxides.1 Air, as a natural oxidant,
plays an important role in various life processes to provide
energy, and is also widely used in oxidation reactions.2 One
of the desired goals of green chemistry is to make rational
use of air to realize conversions of specific substances to re-
place conventional oxidation.
Porphyrin derivatives exist widely in Nature, serving as
photosensitizers in photosynthesis3 as well as oxidative re-
action centers of heme enzymes, such as peroxidases, cata-
lases, and cytochromes P450, which show excellent charac-
teristics in the utilization of light and oxygen.4 As photo-
sensitizers, porphyrins can be easily prepared and
modified5, and they have recently been used to catalyze the
epoxidation of ,-unsaturated ketones and the oxidation
of primary amines and secondary amines.6 More environ-
mentally friendly oxidative reactions using porphyrin as
photosensitizer and air as oxidant need to be explored.
Cu(Sal)2(NCMe)]2 (1 mol%), O2 (balloon)
VB1 analogue (20 mol%), TBAC (2 mol%)
CH3CN, 30 °C
R2
N
R1
O
5-methyl-2(3H)-furanone (25 mol%)
DABCO (3 equiv), O2, THF, 25 °C
R2
R2
N
N
R1
R1
R1
O
O
eosin Y (5 mol%), O2 (1 atm)
K2CO3 (1.5 equiv), NaN3 (2.0 equiv)
DMSO, green LEDs, rt
R2
N
R1
rose bengal (3–6 mol%), O2 (balloon)
DBN (1.5–2.5 equiv), DMF, blue LED, rt
R2
N
O
ZnTPP (1 mol%), air
CsF (3.0 equiv)
DMF, blue LEDs, rt
This Work:
air as the oxidant
R2
N
R1
mild reaction conditions
porphyrin as photoredox catalyst
O
Scheme 1 Methods for the synthesis of dihydroisoquinolones by -ox-
idation with dioxygen
© 2021. Thieme. All rights reserved. Synlett 2021, 32, 679–684
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

680
A. Li et al.
Letter
Synlett
plex combined with a vitamin B1 analogue as catalysts, as
well visible-light-induced oxidations, have attracted much
attention (Scheme 1).7d,12 Among these, visible-light-in-
duced -oxidations have been shown to be effective and en-
vironmentally friendly metal-free strategies. Therefore,
there is great interest in developing simple and environ-
mentally friendly photocatalytic oxidation reactions. Here
we report an efficient aerobic oxidation of N-substituted
1,2,3,4-tetrahydroisoquinolines to 3,4-dihydroisoquinolin-
1(2H)-ones through organophotocatalysis using a porphy-
rin as a photosensitizer under mild conditions.
Initially, we selected N-phenyl-1,2,3,4-tetrahydroiso-
quinoline (1a) as a model substrate and oxygen (air) as a
green oxidant to explore the feasibility of the target -car-
bonylation (Table 1). When the reaction was performed in
the presence of tetraphenylporphyrinatozinc(II) (ZnTPP) in
DMF with irradiation by a 5 W blue LED for 12 hours at
room
temperature,
N-phenyl-3,4-dihydroisoquinolin-
Table 1 Screening of Conditions for Visible-Light-Induced Direct -Oxygenation of the N-Substituted Tetrahydroisoquinoline 1aa
cat.(1 mol%), additive (x equiv)
N
N
Ph
blue LEDs, rt, air, 12 h
Ph
O
1a
2a
COONa
Br
COONa
NO2
Br
O2N
NaO
NaO
O
O
O
O
N
N
Br
Br
Br
Br
M
eosin B
eosin Y
N
N
Cl
Cl
Cl
Cl
COOEt
COONa
I
I
NaO
N
H
O
N
H
M = H2 TPP
M = Zn ZnTPP
O
O
Cl
I
I
rhodamine 6G
rose bengal
Entry
Catalyst
Additive (equiv)
Solvent
Yieldb (%)
1
2
ZnTPP
–
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
MeCN
CH2Cl2
THF
23
71
15
25
15
45
41
62
62
60
41
29
54
ZnTPP
CsF (3.0)
NaF (3.0)
KF (3.0)
3
ZnTPP
4
ZnTPP
5
ZnTPP
Na2CO3 (3.0)
K2CO3 (3.0)
Cs2CO3 (3.0)
CsF (1.0)
CsF (5.0)
CsF (3.0)
CsF (3.0)
CsF (3.0)
CsF (3.0)
CsF (3.0)
CsF (3.0)
CsF (3.0)
CsF (3.0)
CsF (3.0)
6
ZnTPP
7
ZnTPP
8
ZnTPP
9
ZnTPP
10
11
12
13
14
15
16
17
18
TPP
eosin Y
eosin B
rose bengal
rhodamine 6G
ZnTPP
c
–
41
9
ZnTPP
ZnTPP
8
ZnTPP
6
a Reaction conditions: 1a (0.10 mmol), photocatalyst (0.001 mmol), additive, solvent (1.0 mL), 5 W blue LEDs, rt, 12 h, air atmosphere.
b Determined by 1H NMR with Ph2CHCN as an internal standard.
c No reaction.
© 2021. Thieme. All rights reserved. Synlett 2021, 32, 679–684

681
A. Li et al.
Letter
Synlett
1(2H)-one (2a) was obtained in 23% yield (Table 1, entry 1).
To our delight, on addition of 3.0 equivalents of CsF, an ob-
vious enhancement in the yield of 2a to 71% (entry 2) was
detected. Subsequently, other additives, such as NaF, KF,
and Cs2CO3 were also tested, but did not improve the reac-
tion yield (entries 3–7). Other organophotocatalysts were
then tested in this reaction at room temperature. Eosin B,
eosin Y, and rose bengal provided the desired product 2a in
yields of 41, 29, and 54%, respectively (entries 11–13),
whereas rhodamine 6G did not promote the formation of
the target product. Compared with ZnTPP as a photocata-
lyst, the free base TPP gave a lower 60% yield (entry 10).
Various solvents such as dimethyl sulfoxide (DMSO), aceto-
nitrile, dichloromethane, and tetrahydrofuran (THF) were
also surveyed (entries 15–18), but the results were unsatis-
factory. Our results showed that the photocatalyst, oxygen
(air), and visible light are all essential for the ortho--oxy-
genation reaction.
Subsequently, we investigated the visible-light-induced
direct -oxygenation of various N-substituted tetrahy-
droisoquinolines 1 in the presence of ZnTPP (1 mol%) and
CsF (3 equiv) in DMF at room temperature for 12 hours
(Scheme 2). Tetrahydroisoquinolines bearing various N-aryl
groups with either electron-donating or electron-with-
drawing substituents afforded the corresponding products
2a–t in yields of 54–84%. Substrates containing various
para-substituted N-phenyl groups gave similar yields; for
example, yields of 2b, 2f, 2j, and 2o were moderate, ranging
from 54 to 61%, although both electron-donating (methyl in
2b, and methoxy in 2o) and electron-withdrawing substitu-
ents (halogen in 2f and 2j) were involved. Interestingly, sub-
strate 1r with an electron-withdrawing para-cyano substit-
uent gave 2r in a higher yield of 76%. On the other hand, in
the case of substrates with meta-substituted N-phenyl
groups, those with electron-rich substituents gave higher
yields than those with electron-withdrawing ones (e.g., 1c
and 1n versus 1i and 1p). We also obtained good yield of
products with ortho-substituted N-phenyl groups (2e and
2m; 65% yield), an N-2-naphthyl group (2s; 62%), and an N-
2-pyridyl group (2q; 62%). We then explored the effects of
substituents on the tetrahydroisoquinoline moiety. Yields
of 2v and 2w, (78 and 71%, respectively) were slightly high-
er than those of the corresponding substrates with no sub-
stituents on the tetrahydroquinoline moiety 2g (73%) and
2b (61%), probably indicating that substituents on the tetra-
hydroisoquinolines ring have an important effect on this re-
action. Compared with the reaction using eosin Y as photo-
sensitizer and NaN3 as the additive,12a the reaction using
ZnTPP as a photosensitizer gave the dihydroisoquinolones
in lower yields, but under conditions that were more envi-
ronmentally friendly, without using the toxic substance
NaN3.
Based on our experience with direct -oxidation of ter-
tiary amines to lactams, we became interested in applying
this method to the synthesis of pharmaceuticals. In particu-
lar, dihydroisoquinolone derivatives can inhibit mitochon-
drial branched-chain aminotransferase (BCATm).13 Targeted
drug molecules were synthesized under our optimized re-
ZnTPP(1 mol%)
CsF (3 equiv)
R
R
N
N
Ar
Ar
DMF, blue LEDs, air, 12 h
O
1
2
F
N
N
N
N
N
N
O
O
O
O
O
O
tBu
F
2b, 61%
2c, 73%
2d, 69%
2a, 71% a
2e, 65%
2f, 59%
N
N
N
N
Br
N
Cl
N
O
O
O
O
O
O
Br
CF3
OCF3
Cl
2i, 72%
2j, 58%
2k, 68%
2l, 71%
2g, 73%
2h, 66%
OMe
N
N
OMe
N
N
NO2
N
N
N
O
O
O
O
O
O
OMe
CN
2m, 65%
2p, 58%
2n, 84%
2o, 54%
2q, 62%
2r, 76%
MeO
MeO
MeO
MeO
MeO
MeO
N
N
N
N
N
O
O
O
O
O
2u, 68%
2v, 78%
2s, 62%
2t, 67%
2w,71%
Cl
Scheme 2 Substrate scope of the visible-light-induced direct -oxygenation. Reagents and conditions: 1a (0.10 mmol), ZnTPP (0.001 mmol), CsF (3
equiv), DMF (1.0 mL), 5 W blue LEDs, rt, 12 h, air atmosphere. Isolated yields are reported. a A 51% yield was obtained and 17% of 1a was recovered
when the reaction was conducted on a 5 mmol scale.
© 2021. Thieme. All rights reserved. Synlett 2021, 32, 679–684

682
A. Li et al.
Letter
Synlett
action conditions (Scheme 3). To our delight, both of the de-
sired inhibitors 2x and 2y were obtained efficiently in
yields of 50 and 56%, respectively from the corresponding
N-aryl-substituted tetrahydroisoquinolines in one-step un-
der our mild conditions. Compared with the previously re-
ported methods involving two-step reactions,13 the synthe-
sis through direct -oxidation is more efficient with a high-
er yield. These results showed that this method has the
potential for broad application in the functionalization of
drug molecules and natural products.
thermore, the reaction was significantly inhibited in the
presence of the singlet-oxygen inhibitor 1,4-diazabicyc-
lo[2,2,2] octane (DABCO) (entry 6). Therefore, singlet oxy-
gen might be responsible for the oxygenation reaction. Ad-
ditionally, we also found that adding large amounts of wa-
ter to the reaction system had only a slight effect on the
yield, suggesting the reaction conditions are not too rigor-
ous.
To obtain further information on the photocatalytic
mechanism, we performed Stern–Volmer fluorescence-
quenching experiments (Figure 1). As the substrate concen-
tration was increased, a dramatic decrease in the fluores-
cence intensity was observed. In contrast, added CsF and di-
oxygen did not interact with the excited state of the photo-
catalyst. These results suggested that the luminescence of
ZnTPP was quenched by N-phenyl-1,2,3,4-tetrahydroiso-
quinoline (1a).
ZnTPP (1 mol%)
CsF (3.0 equiv)
N
N
DMF, blue LEDs, rt
air, 24 h
O
R
R
N
N
NH2
O
O
O
N
NH
2x, 50%
Scheme 3 Synthesis of bioactive chemicals
2y, 56%
To gain some insight into the reaction mechanism, we
conducted several control experiments (Table 2). The reac-
tion did not proceed under an argon atmosphere, indicating
that the added oxygen atoms in the desired product were
mainly obtained from molecular oxygen (Table 2, entry 1).
The reaction did not proceed in the absence of light or a
photocatalyst (entries 2 and 3), suggested that both light
and the photocatalyst are driving forces for this -oxygen-
Figure 1 (A) Stern–Volmer luminescence quenching experiments us-
ing a 20 μM solution of ZnTPP and various concentrations of 1a and CsF
in DMF. (B) The fluorescence spectra for titration of 1a with ZnTPP (20
M) in DMF.
ation
reaction.
When
(2,2,6,6-tetramethyl-1-piper-
idinyl)oxyl (TEMPO) or 2,6-di-tert-butyl-4-methylphenol
(BHT) was added to the model reaction, the oxidation pro-
cess was completely suppressed (entries 4 and 5), indicat-
ing that the reaction might involve a radical process. Fur-
On the base of the above experimental results and pre-
vious reports in the literature,12a a possible mechanism for
this oxidation reaction is proposed in Scheme 4. First, the
photocatalyst is excited by visible-light irradiation to gener-
ate an excited-state species ZnTPP*. A single-electron trans-
fer from ZnTPP* to 1a provides two radicals, I and ZnTPP·–.
Singlet oxygen (1O2) and superoxide radical anion(O2·–) are
produced from O2 through energy transfer from ZnTPP·–.
O2·– reacts with the aminyl cation radical I to give interme-
diate II and a peroxide radical (HOO·). Subsequently, the re-
action between the peroxide radical and radical II results in
the formation of intermediate III. Finally, the desired prod-
uct 2a is obtained by elimination of a water molecule.
In conclusion, we have successfully developed a sustain-
able and cost-effective method for -oxygenation of cyclic
tertiary amines by a photocatalyzed reaction of N-aryltetra-
hydroisoquinolines in the presence of ZnTPP under visible-
light irradiation.13 Under the optimal reaction conditions, a
broad range of substrates were tolerated well, providing
highly practical access to various valuable dihydroisoquino-
lone compounds in moderate to good yields. More signifi-
cantly, this is a potent method for the oxygenation of natu-
ral products and for the synthesis of bioactive chemicals. In
Table 2 Control Experimentsa
ZnTPP (1 mol%)
CsF (3 equiv)
N
N
Ph
Ph
DMF, blue LEDs, air, 12 h
O
1a
2a
Entry
Controlled parameter
Yield (%)
1
2
3
4
5
6
7
8
Ar instead of air
no light
trace
–
no catalyst
–
TEMPO (10 equiv)
BHT (10 equiv)
DABCO (2.5 equiv)
H2O (5 equiv)
H2O (25 equiv)
58
22
26
68
61
a Reaction conditions: 1a (0.10 mmol), ZnTPP (0.001 mmol), CsF (0.30
mmol), DMF (1.0 mL), 5 W blue LEDs, rt, 12 h, air atmosphere.
© 2021. Thieme. All rights reserved. Synlett 2021, 32, 679–684

683
A. Li et al.
Letter
Synlett
(3) (a) Fenwick, O.; Sprafke, J. K.; Binas, J.; Kondratuk, D. V.; Di
Stasio, F.; Anderson, H. L.; Cacialli, F. Nano Lett. 2011, 11, 2451.
(b) Hirai, Y.; Sasaki, S.-i.; Tamiaki, H.; Kashimura, S.; Saga, Y.
J. Phys. Chem. B 2011, 115, 3240.
SET
N
N
Ph
Ph
I
1a
*
ZnTPP
(4) (a) Collman, P.; Chien, A.; Eberspacher, T. A.; Brauman, J. I. J. Am.
Chem. Soc. 2000, 122, 11098. (b) Manoj, K. M.; Lakner, F. J.;
Hager, L. P. J. Mol. Catal. B: Enzym. 2000, 9, 107. (c) Dunne, J.;
Caron, A.; Menu, P.; Alayash, A. I.; Buehler, P. W.; Wilson, M. T.;
Silaghi-Dumitrescu, R.; Faivre, B.; Cooper, C. E. Biochem. J. 2006,
399, 513. (d) Cooper, C. E.; Silaghi-Dumitrescu, R.; Rukengwa,
M.; Alayash, A. I.; Buehler, P. W. Biochim. Biophys. Acta, Proteins
Proteomics 2008, 1784, 1415.
(5) (a) Rothemund, P. J. Am. Chem. Soc. 1935, 57, 2010. (b) Adler, A.
D.; Sklar, L.; Longo, F. R.; Finarelli, D.; Finarelli, M. G. J. Hetero-
cycl. Chem. 1968, 5, 669. (c) Pawlicki, M. Synlett 2020, 31, 1.
(d) Brewster, J.; Anguera, G.; Sessler, J. Synlett 2019, 30, 765.
(6) (a) Wu, Y.; Zhou, G.; Meng, Q.; Tang, X.; Liu, G.; Yin, H.; Zhao, J.;
Yang, F.; Yu, Z.; Luo, Y. J. Org. Chem. 2018, 83, 13051. (b) Jiang, J.;
Liang, Z.; Xiong, X.; Zhou, X.-T.; Ji, H.-B. ChemCatChem 2020, 12,
3523.
ZnTPP
1O2
hν
ZnTPP
O2
O2
HOO
Ph
N
H
N
N
Ph
Ph
O
O
II
OH
III
2a
Scheme 4 Proposed reaction mechanism
(7) (a) Klobukowski, E. R.; Mueller, M. L.; Angelici, R. J.; Woo, L. K.
ACS Catal. 2011, 1, 703. (b) Khusnutdinova, J. R.; Ben-David, Y.;
Milstein, D. J. Am. Chem. Soc. 2014, 136, 2998. (c) Jin, X.;
Kataoka, K.; Yatabe, T.; Yamaguchi, K.; Mizuno, N. Angew. Chem.
Int. Ed. 2016, 55, 7212. (d) Liu, Y.; Wang, C.; Xue, D.; Xiao, M.;
Liu, J.; Li, C.; Xiao, J. Chem. Eur. J. 2017, 23, 3062.
addition, porphyrins are easily prepared and modified, and
therefore have great potential in photocatalytic reactions.
Further research on the application of porphyrins in other
types of photocatalytic reactions is currently underway in
our laboratory.
(8) (a) Chiarugi, A.; Meli, E.; Calvani, M.; Picca, R.; Braonti, R.;
Camaioni, E.; Costantino, G.; Marinozzi, M.; Pellegrini-Giampi-
etro, D. E.; Pellicciari, R.; Moroni, F. J. Pharmacol. Exp. Ther. 2003,
3, 943. (b) Renaud, J.; Bischoff, S. F.; Buhl, T.; Floersheim, P.;
Fournier, B.; Halleux, C.; Kallen, H.; Schlaeppi, J.-M.; Stark, W.
J. Med. Chem. 2003, 46, 2945. (c) Lorenc-Koci, E.; Sokołowska,
M.; Kwiecień, I.; Włodek, L. Brain Res. 2005, 1049, 133. (d) Sun,
M.; Li, J.; Chen, W.; Wu, H.; Yang, J.; Wang, Z. Synthesis 2020, 52,
1253.
Funding Information
The National Key R&D program of China (2018YFA0507900), the
Chongqing Young Top Talents Training Plan, Chongqing Postdoctoral
Innovation Project Funding (cstc2019jcyj-bsh0019), and Sichuan Pro-
vincial Human Resource and Social Security Department.
N
a
ti
o
n
a
l
K
e
y
Research
a
n
d
D
e
ve
l
o
p
me
n
t
Progra
m
o
f
C
h
i
na(2
0
1
8
Y
F
A
0
5
0
7
9
0)
(9) (a) Liu, P.; Zhou, C.-Y.; Xiang, S.; Che, C.-M. Chem. Commun.
2010, 46, 2739. (b) Kohls, P.; Jadhav, D.; Pandey, G.; Reiser, O.
Org. Lett. 2012, 14, 672. (c) Ratnikov, M. O.; Xu, X.; Doyle, M. P. J.
Am. Chem. Soc. 2013, 135, 9475. (d) Xie, W.; Gong, B.; Ning, S.;
Liu, N.; Zhang, Z.; Che, X.; Zheng, L.-Y.; Xiang, J.-B. Synlett 2019,
30, 2077.
Acknowledgment
The authors are grateful for the support from Third Military Medical
University.
(10) So, M.-H.; Liu, Y.-G.; Ho, C.-M.; Che, C.-M. Chem. Asian J. 2009, 4,
1551.
Supporting Information
(11) (a) Song, A.-R.; Yu, J.; Zhang, C. Synthesis 2012, 44, 2903.
(b) Mandal, A. K.; Iqbal, J. Tetrahedron 1997, 53, 7641.
(12) (a) Aganda, K. C.; Hong, B.; Lee, A. Adv. Synth. Catal. 2018, 361,
1124. (b) Thatikonda, T.; Deepake, S. K.; Das, U. Org. Lett. 2019,
21, 2532. (c) Zhang, Y.; Schilling, W.; Riemer, D.; Das, S. Nat.
Protoc. 2020, 15, 822.
Supporting information for this article is available online at
https://doi.org/10.1055/a-1345-3491.
S
u
p
p
orti
n
gI
n
f
orm
a
ti
o
n
S
u
p
p
orti
n
gI
n
f
orm
a
ti
o
n
References and Notes
(13) Borthwick, J. A.; Ancellin, N.; Bertrand, S. M.; Bingham, R. P.;
Carter, P. S.; Chung, C.-w.; Churcher, I.; Dodic, N.; Fournier, C.;
Francis, P. L.; Hobbs, A.; Jamieson, C.; Pickett, S. D.; Smith, S. E.;
Somers, D. O.; Spitzfaden, C.; Suckling, C. J.; Young, R. G. J. Med.
Chem. 2016, 59, 2452.
(14) 3,4-Dihydroisoquinolin-1(2H)-ones 2a–t; General Procedure
The appropriate N-aryltetrahydroquinoline 1 (0.1 mM, 1 equiv),
ZnTPP (0.001 mM, 1% equiv, 0.68 mg), and CsF (0.3 mM, 3 equiv,
46 mg) were added to DMF (0.1 M), and the mixture was stirred
at rt and irradiated by blue LEDs under air overnight. The
mixture was then extracted with CH2Cl2 and the extracts were
washed with H2O. The combined organic phases were dried
(Na2SO4) and concentrated under reduced pressure, and the
crude product was purified by column chromatography (silica
(1) (a) Schumacher, R. F.; Rosário, A. R.; Souza, A. C. G.; Menezes, P.
H.; Zeni, G. Org. Lett. 2010, 12, 1952. (b) Shen, Z.; Dai, J.; Xiong,
J.; He, X.; Mo, W.; Hu, B.; Sun, N.; Hu, X. Adv. Synth. Catal. 2011,
353, 3031. (c) Kang, Y.-B.; Gade, L. H. J. Am. Chem. Soc. 2011, 133,
3658. (d) Wang, Q.; Dong, X.; Xiao, T.; Zhou, L. Org. Lett. 2013,
15, 4846.
(2) (a) Jin, R.; Patureau, F. W. ChemCatChem 2015, 7, 223. (b) Dugal,
M.; Sankar, G.; Raja, R.; Thomas, J. M. Angew. Chem. Int. Ed.
2000, 39, 2310. (c) Sawatari, N.; Yokota, T.; Sakaguchi, S.; Ishii,
Y. J. Org. Chem. 2001, 66, 7889. (d) Yuan, Y.; Ji, H.; Chen, Y.; Han,
Y.; Song, X.-F.; She, Y.-B.; Zhong, R.-G. Org. Process Res. Dev.
2004, 8, 418. (e) Hu, R.-M.; Lai, Y.-H.; Xu, D.-Z. Synlett 2020, 31,
1753.
© 2021. Thieme. All rights reserved. Synlett 2021, 32, 679–684

684
A. Li et al.
Letter
Synlett
gel, PE–EtOAc).
2-Phenyl-3,4-dihydroisoquinolin-1(2H)-one (2a)
J = 6.4 Hz, 2 H), 4.00 (t, 3.15 (t, J = 6.4 Hz, 2 H). 13C NMR (150
MHz, CDCl3):  = 164.2, 143.1, 138.3, 132.0, 129.7, 128.9, 128.7,
127.2, 126.9, 126.2, 125.3, 49.4, 28.6. HRMS (ESI): m/z [M + Na]+
calcd for C15H13NNaO: 246.0895; found: 246.0889.
White solid; yield: 15.8 mg (71%); mp 100–101 °C. 1H NMR (600
MHz, CDCl3):  = 8.16 (d, J = 7.4 Hz, 1 H), 7.47 (t, J = 7.4 Hz, 1 H),
7.40 (dq, J = 16.8, 8.0 Hz, 5 H), 7.25 (d, J = 10.5 Hz, 2 H), 4.00 (t,
© 2021. Thieme. All rights reserved. Synlett 2021, 32, 679–684