Regioselective and Switchable meso-Aminations and Couplings of 5,15-Diarylchlorins

Article abstract of DOI:10.1021/acs.orglett.7b01739

Controllable chemo- and regiodivergent amination reactions of anilines and chlorins are accomplished by employing different oxidants and substrates, constructing aminated chlorin monomers and dimers with high structural diversity. Importantly, besides pre

Full text of DOI:10.1021/acs.orglett.7b01739

Letter
pubs.acs.org/OrgLett
Regioselective and Switchable meso-Aminations and Couplings of
5,15-Diarylchlorins
Qi Cheng,† Yu-Hao Qiu,† Sheng-Lin Luo,‡ Li Shuai,† Yi Yuan,† Ying-Chun Chen,*,†,§
and Qin Ouyang*,†
†College of Pharmacy, Third Military Medical University, Chongqing 400038, China
‡Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Department of Preventive Medicine,
Third Military Medical University, Chongqing 400038, China
§Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
S
* Supporting Information
ABSTRACT: Controllable chemo- and regiodivergent ami-
nation reactions of anilines and chlorins are accomplished by
employing different oxidants and substrates, constructing
aminated chlorin monomers and dimers with high structural
diversity. Importantly, besides preferential 20-meso-position,
the oxidative amination was also realized at the inactive 10-
meso-position by using phenyliodine bis(trifluoroacetate)
(PIFA) and gold(III)-based reagents.
orphyrin and chlorin derivatives have attracted significant
derivatives.7 Direct modifications at preferred 20-meso-position
Pattention due to their numerous applications, such as flanking the pyrroline ring of chlorins were rarely reported except
bromination7b,8 and direct coupling reactions.9 The 10-meso-
artificial photosynthetic systems, sensors, and nonlinear optical
(NLO) devices.1 Chlorins, structurally more similar to photo-
position of chlorins was considered as an inactive site in
comparison with 7,8-β-positions for the bromination,8c though
synthetic pigments, are especially valuable as photosensitizers for
its functionalization might affect the physicochemical properties
due to the short distance to the core of the ring. Developing a
facile method to directly introduce meso-substituents, especially
via amination reactions at inactive 10-position, would be
extremely attractive, since amino groups are useful for dye-
sensitized solar cell development as electron donating groups10
and are favorable for drug discovery owing to their ubiquity in a
variety of pharmaceuticals and natural products.
photodynamic therapy (PDT) owing to their strong absorptions
in red band (600−700 nm).2 Several chlorin derivatives, such as
Verteporfin,3 Temoporfin,4 and Talaporfin5 (Figure 1), have
been approved for clinical use to treat cancer, skin disease, and
abnormal blood vessels, respectively.
A variety of gold(III)-based catalysts have been reported to
promote C−H aminations.11 Specifically, an oxidative strategy by
using phenyliodine diacetate (PIDA) and NaAuCl4·2H2O was
presented to conduct the meso-amination of 5,10,20-trisubsti-
tuted porphyrins; however, for the amination of 5,15-diaryl-
porphyrins, various porphyrin oligomers were generated.12
Recently, as an environmentally friendly approach, hypervalent
iodine(III) reagents have been successfully applied to synthesize
meso-meso directly linked diporphyrins,13 fused diporphyins,14
and regioselective 20−20′ linked chlorin dimers.9 Although
numerous methods to construct C−N bonds for some kinds of
special substrates have been reported using a metal-free oxidative
strategy,15 simplex hypervalent iodine(III) reagents failed to
Figure 1. Chlorin photosensitizers approved for clinical use.
In addition to the natural extraction and derivation of
chlorophyll, chemical synthesis has been proven as a powerful
approach to produce new chlorin derivatives for photosensitizer
discovery.6 Beside modifying the pyrrole ring of porphyrins,
introduction of substituted pyrroles before constructing chlorin
rings was reported as a common synthetic strategy to generate
multifarious meso- or β-substituted chlorin skeletons and
Received: June 9, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01739
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
promote the amination of porphyrins.12 Compared with
porphyrins, chlorins are easier to be oxidized due to their
lower first oxidation potential,9 and have more diverse active sites
to conduct amination, coupling, decomposition, or polymer-
ization reactions. Thus, the reactions of chlorins and anilines by
using oxidation strategies have more possibilities and challenges.
Here we report our preliminary results by using hypervalent
iodine(III) reagents or gold(III) salts for the preparation of
chemo- and regioselective meso-aminated chlorin monomers and
dimers. Importantly, besides preferential 20-meso-position, the
amination was also conducted at the inactive 10-meso-position.
The initial reaction of chlorin 1 and p-toluidine 2a proceeded
rapidly at room temperature in the presence of PIDA/NaAuCl4·
2H2O (1:1). Unfortunately, few products were generated by
using conventional saturated sodium thiosulfate solution to
quench the reaction.12 However, as previously reported,14
NaBH4/CH3OH were used to terminate the reaction, producing
an unusual 10,10′-diaminated, 20,20′-linked chlorin dimer 3a in
36% yield and 20-aminated chlorin 4a in 20% yield (Table 1,
obtained as the major product in the reactions using AgSbF6 or
DDQ. Moreover, the amination could not be promoted in other
solvents, such as THF, acetonitrile, and ethanol.
Beside the oxidant-controlled reaction, the substrates also
played an important role in regulating the chemoselectivity. The
reaction of 1 and N-methyl p-toluidine 2b produced 10,20-
diaminated chlorin 5a in a good yield with NaAuCl4·H2O, and
trace amounts of chlorin dimer 3a were isolated (entry 9).
Surprisingly, by using PIFA, a 10,10′-diaminated and 20,20′-
linked chlorin dimer 3b was generated in a good yield, and minor
diaminated chlorin 5a was also isolated (Table 1, entry 10).
Other possible products, such as 10,10′- or 10,20′-linked chlorin
dimers were not observed and identified. The coupling reaction
of 20-aminated chlorin 4a could not be further promoted by
adding PIFA or gold(III) salt. In addition, we also tried similar
amination reactions for other metal chlorins. PIFA failed to
promote the amination of PdII and NiII chlorin (1-NiII, and 1-
PdII, respectively), and self-coupling dimer also was not
observed. In contrast, by using NaAuCl4·H2O as the oxidant,
the reaction of NiII chlorin and 2a resulted in complex products,
while 1-PdII and 2a produced a mixture of 10,20-diaminated PdII
chlorin 5a-PdII and diaminated PdII porphyrin [for more details,
see the Supporting Information (SI)].
Table 1. Screening Studies of Oxidative Reactions of Chlorin
a
1 and Anilines 2
The structures of these chlorins were confirmed by their NMR
1
data and mass spectrometry. A complete H NMR assignment
for the individual protons of 3a, 4a, and 5a was achieved by 2D-
NMR studies (for more details, see the SI). Compared with 1, the
signals of H-10 and H-20 of 3a disappeared (Figure 2). Beside
b
entry
oxidant (equiv)
R
t
yield (%)
1
2
3
4
5
6
7
8
9
10
PIDA/NaAuCl4·2H2O (1:1)
PIDA/NaAuCl4·2H2O (1:4)
NaAuCl4·2H2O (1.5)
PIDA (1)
H
1 min
1 min
1 min
12 h
3a, 36; 4a, 20
3a, 50; 4a, 25
3a, 68; 4a, < 5
H
H
c
H
trace
d
PIFA (1)
H
1 min
1 min
1 min
1 min
1 min
1 min
4a, 40
d
PIFA (0.25)
H
4a, 15
PIFA (1.5)
H
4a, 65
Figure 2. 1H NMR spectra of 3a, 4a, 5a, and 1 in CDCl3.
PIFA (3)
H
decomposition
3b, < 5; 5a, 60
3b, 61; 5a,17
NaAuCl4·2H2O (1.5)
PIFA (1.5)
CH3
CH3
the upfield shifts of the proton signals near the 20-position (H-18
and H-2) due to the 20−20 connection, other β-Hs in 3a,
especially H-13 and H-7, showed obvious upfield shifts resulting
from the introduction of N-substituent at the 10-position.
Additionally, the interaction between H-2 and H-18 can be found
in the 1H-NOESY NMR spectra of 3a and 3b (see the SI), which
a
Unless otherwise noted, reactions were performed with 1 (0.05
mmol), 2 (0.25 mmol), and oxidant in CH2Cl2 (30 mL) and quenched
by NaBH4/CH3OH (10 mg/2 mL). Isolated yield. 53% of 1 was
b
c
d
recovered. Together with 1.
1
entry 1). A higher yield of 3a was obtained by increasing the
amounts of NaAuCl4·2H2O (entry 2), and better selectivity with
68% yield of 3a was observed by using NaAuCl4·2H2O
independently (entry 3). No expected products were generated
with PIDA (entry 4); however, phenyliodine bis-
(trifluoroacetate) (PIFA) promoted the reaction effectively,
and interestingly, 20-aminated chlorin 4a was produced in a
moderate yield (entry 5). The yield of 4a could be improved to
65% by employing 1.5 equiv of oxidants (entry 7). Further
addition of oxidants produced a complex mixture probably
because of decomposition (entry 8). Other oxidants, such as
AgSbF6, FeCl3, O2, 2,3-dicyano-5,6-dichlorobenzoquinone
(DDQ), PIDA/Cu(OAc)2 (1:0.2), and PIDA/Sc(CF3SO3)2
(1:0.2), failed to promote this amination, while porphyrin was
further confirmed the linkage at 20-position. In the H NMR
spectrum of 4a, the signal of H-20 disappeared and the signals of
β-Hs-2,3,17,18 showed obvious upfield shifts due to the
amination at 20-position. In contrast, beside the disappeared
signals of H-10 and H-20, two signals of N-CH3 and more upfield
shifting signals of β-Hs in the 1H NMR spectrum of 5a proved
that the chlorin ring was diaminated at 10,20-meso-positions.
In addition to PIFA-promoted self-coupling of chlorin,9 we
also found 20−20′-linked chlorin dimer 6 could be synthesized
regioselectively from NaAuCl4·2H2O and 1 in CH2Cl2 within 1
min in 45% yield in the presence of K2CO3. Subsequently,
chlorin dimer 6 reacted with 2a or 2b under the optimized
oxidative conditions. PIFA promoted the formation of C−N
bond with secondary amine 2b in a good yield (Table 2, entry 1),
B
DOI: 10.1021/acs.orglett.7b01739
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
contrast, using substrate with an electron-withdrawing group
resulted in a poorer yield due to its lower εHOMO (entry 3).
Nevertheless, aniline with a 4-ester group failed to give the
amination product, probably due to its low energy of HOMO
(entry 4). The substituent position also affected the reaction, as
using o-toluidine produced the aminated chlorin 4d in a fair yield
(entry 5). Additionally, NaAuCl4·2H2O was used to produce
diaminated chlorins 5 in moderate yields (entries 6−11). It is
worth noting that minor aminated chlorin 4e was isolated along
with 5c, since 4-fluoro-N-methylaniline has a relatively lower
εHOMO (−5.65 eV). It suggested that the oxidant might activate
the meso-Hs at 10- and 20-positions sequentially. In addition to
εHOMO, the steric hindrance also affected the reaction. Except that
N-benzyl-p-toluidine could be used for the amination in a low
yield (entry 11), other compounds with large steric hindrance or
low εHOMO were not able to promote the amination, such as
diphenylamine, carbazole, and N-(p-tolyl)acetamide. In addition
to the literature reported single-electron transfer (SET)
oxidation of chlorin,12,17 the εHOMO depended results suggested
that the possible reaction mechanism may also involve the
oxidation of aniline to a radical.
The natural population analysis (NPA) charges were further
calculated to understand the regioselectivity.16 The meso-carbon
at 20-position was evaluated to have higher electron density with
a charge of −0.334, implying its activity for amination and self-
coupling. In contrast, the meso-carbon at 10-position, selectively
proceeding amination rather than self-coupling,9 had a lower
charge with a value of −0.184. Similarly, meso-carbon at 10-
position of 6 and 4a had similar charges (−0.176 and −0.170,
respectively). However, the charges of 10-meso-carbons in these
compounds were less negative than those of 7,8-β-carbons,
which were consistent with the regioselectivity of bromination
that involved a process of cation radical.8c Due to the unusual
selectivity, we proposed the formation of a complex radical from
chlorin radical and aniline anion, in which the N atom of aniline
was coordinated with the Zn atom of chlorin. The shorter
distance between meso-C atom and coordinated N atom may be
the possible reason for the unusual selectivity at inactive 10-
position (see the SI). As the amination could be conducted for
20- and 10-carbons sequentially, structural diversity may come
from the competition between amination and self-coupling
reaction at electron-rich 20-carbons.
Table 2. Oxidative meso-Amination of Chlorin Dimer 6 and
Anilines 2
a
b
entry
oxidant (equiv)
R
t
yield (%)
1
2
3
4
NaAuCl4·2H2O (1.5)
PIFA (1.5)
H
1 min
1 min
1 min
1 min
3a, 70
3a, 49
3b, 67
3b, 79
H
NaAuCl4·2H2O (1.5)
PIFA (1.5)
CH3
CH3
a
Unless otherwise noted, reactions were performed with chlorin dimer
6 (0.05 mmol), aniline 2 (0.25 mmol), and oxidant (0.075 mmol) in
CH2Cl2 (30 mL) and quenched by NaBH4/CH3OH (10 mg/2 mL).
b
Isolated yield.
while the reaction of 6 and 2a resulted in a low yield (entry 2). In
contrast, gold(III) salt showed high activity for the amination
reaction of 6 with either 2a or 2b, efficiently producing 3a and 3b
in high yields (entries 3 and 4). These results suggested that the
formation of aminated chlorin dimer might proceed through the
self-coupling reaction at 20-meso-position and sequential C−N
bond formation at 10-meso-position. As a result, a step by step
strategy using PIFA and gold(III) salt could be considered as a
general protocol for preparing the aminated chlorin dimers with
different aniline substrates.
According to density functional theory (DFT) calculations16
and experiments, we found that the reactivity of anilines, in a
certain degree, depended on the energy of HOMO (εHOMO). For
the reaction of N-unsubstituted anilines and chlorin by using
PIFA, introducing an electron-donating methoxy group with
higher εHOMO facilitated the reaction (Table 3, entry 2). In
Table 3. Substrate Scope and Limitations of the meso-
a
Amination of Chlorin
As outlined in Figure 3, compared to 1, the absorption
spectrum of 3a showed a broadened Soret band with a shoulder
and a broadened Q bond ranging from 630−800 nm. Similar
broadened and red-shift bonds were found in the spectrum of 4a.
These broad bonds may result from their self-assemble behavior,
εHOMO
b
entry
R
R1
4-Me
(eV)
oxidant
PIFA
yield (%)
4a, 65
1
2
H
−5.36
−5.10
−5.63
−5.97
−5.48
−5.21
−5.16
−5.65
−5.86
−5.45
H
H
H
H
4-OMe
4-F
PIFA
PIFA
PIFA
PIFA
4b, 71
4c, 40
mixture
4d, 49
3
4
4-COOMe
2-Me
5
6
CH3 4-Me
NaAuCl4·2H2O 5a, 60
7
CH3 4-OMe
CH3 4-F
NaAuCl4·2H2O 5b, 45
NaAuCl4·2H2O 5c, 42; 4e, 20
8
c
9
CH3 4-COOMe
NaAuCl4·2H2O mixture
10
Bn
4-Me
NaAuCl4·2H2O 5d, 26
a
Unless otherwise noted, reactions were performed with chlorin 1
(0.05 mmol), aniline 2 (0.25 mmol), and oxidant (0.075 mmol) in
CH2Cl2 (30 mL) and quenched by NaBH4/CH3OH (10 mg/2 mL).
b
c
Isolated yield. 40% of 1 was recovered.
Figure 3. UV−vis spectra of 3a, 3b, 4a, 5a, and 1 in CH2Cl2.
C
DOI: 10.1021/acs.orglett.7b01739
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
40, 340. (d) Sadanala, K. C.; Chaturvedi, P. K.; Seo, Y. M.; Kim, J. M.; Jo,
Y. S.; Lee, Y. K.; Ahn, W. S. Anticancer Res. 2014, 34, 4657.
(3) For selected examples, see: (a) Karim, S. P.; Adelman, R. A. Clin.
because they become sharper when adding a little DMSO into
CH2Cl2 (see the SI). In contrast, sharper bonds were observed in
the spectra of 3b and 5a, since the N-substituents might block the
self-assembly by steric hindrance. Meanwhile, 3b and 5a showed
obvious red-shift for both Soret and Q bands. The Q bands’
maximum absorption wavelength of 3b and 5a were 641 and 627
nm, respectively, while that of 1 was 613 nm. Moreover, the DFT
calculations showed that introducing meso-N-substituents would
lead to lower energies of LUMO and LUMO−1, which might be
the reason for the red-shifted Q bands.16 Additionally, we also
tested the relative fluorescence quantum yield and phototoxic
activity of these synthesized chlorins, suggesting the amination of
chlorin might be useful for developing potential new photo-
sensitizers (see the SI).
Ophthalmol. 2013, 7, 1867. (b) Zhang, H. B.; Ramakrishnan, S. K.;
̋
Triner, D.; Centofanti, B.; Maitra, D.; Gyorffy, B.; Sebolt-Leopold, J. S.;
Dame, M. K.; Varani, J.; Brenner, D. E.; Fearon, E. R.; Omary, M. B.;
Shah, Y. M. Sci. Signaling 2015, 8, ra98.
(4) For recent reviews, see: (a) Senge, M. O.; Brandt, J. C. Photochem.
Photobiol. 2011, 87, 1240. (b) Senge, M. O. Photodiagn. Photodyn. Ther.
2012, 9, 170. (c) de Visscher, S. A.; Dijkstra, P. U.; Tan, I. B.;
Roodenburg, J. L.; Witjes, M. J. Oral Oncol. 2013, 49, 192.
(5) For selected examples, see: (a) Wang, S.; Bromley, E.; Xu, L.; Chen,
J. C.; Keltner, L. Expert Opin. Pharmacother. 2010, 11, 133. (b) Miki, Y.;
Akimoto, J.; Hiranuma, M.; Fujiwara, Y. J. Toxicol. Sci. 2014, 39, 821.
(6) For a comprehensive review, see: Taniguchi, M.; Lindsey, J. S.
Chem. Rev. 2017, 117, 344.
In conclusion, we have investigated the reactions of anilines
and chlorins by using different oxidants. Regioselective 20-
aminated products are efficiently produced by using PIFA
oxidation of N-unsubstitued anilines and chlorins. Diamination
reactions between N-substituted anilines and chlorins at 10- and
20-positions are successfully finished by employing NaAuCl4·
2H2O. Interestingly, diaminated chlorin dimers have been
obtained in the reactions of ZnII chlorin monomers and p-
toluidine with NaAuCl4·2H2O or N-methyl-p-toluidine with
PIFA. It is worth mentioning that the amination could be
conducted at the inactive 10-meso-position. These results should
be helpful for producing more chlorin derivatives as structurally
diverse meso-substituted photosensitizers. Additional results will
be reported in due course.
(7) For a recent review, see: (a) Detty, M. R.; Gibson, S. L.; Wagner, S.
J. J. Med. Chem. 2004, 47, 3897. (b) Lindsey, J. S. Chem. Rev. 2015, 115,
6534. For selected examples, see: (c) Bruckner, C.; Gotz, D. C. G.; Fox,
S. P.; Ryppa, C.; McCarthy, J. R.; Bruhn, T.; Akhigbe, J.; Banerjee, S.;
Daddario, P.; Daniell, H. W.; Zeller, M.; Boyle, R. W.; Bringmann, G. J.
Am. Chem. Soc. 2011, 133, 8740. (d) Ke, X.-S.; Chang, Y.; Chen, J.-Z.;
Tian, J. W.; Mack, J.; Cheng, X.; Shen, Z.; Zhang, J.-L. J. Am. Chem. Soc.
2014, 136, 9598.
(8) (a) Muthiah, C.; Ptaszek, M.; Nguyen, T. M.; Flack, K. M.; Lindsey,
J. S. J. Org. Chem. 2007, 72, 7736. (b) Fan, D. Z.; Taniguchi, M.; Lindsey,
J. S. J. Org. Chem. 2007, 72, 5350. (c) Muthiah, C.; Lahaye, D.;
Taniguchi, M.; Ptaszek, M.; Lindsey, J. S. J. Org. Chem. 2009, 74, 3237.
(d) Xiong, R. S.; Arkhypchuk, A. I.; Kovacs, D.; Orthaber, A.; Borbas, K.
E. Chem. Commun. 2016, 52, 9056.
(9) Ouyang, Q.; Yan, K.-Q.; Zhu, Y.-Z.; Zhang, C.-H.; Liu, J.-Z.; Chen,
C.; Zheng, J.-Y. Org. Lett. 2012, 14, 2746.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b01739.
(10) For recent reviews, see: (a) Urbani, M.; Gratzel, M.; Nazeeruddin,
M. K.; Torres, T. Chem. Rev. 2014, 114, 12330. (b) Higashino, T.;
Imahori, H. Dalton Trans. 2015, 44, 448.
(11) For recent reviews, see: (a) Li, Z.; Brouwer, C.; He, C. Chem. Rev.
2008, 108, 3239. (b) Corma, A.; Leyva-Perez, A.; Sabater, M. J. Chem.
Rev. 2011, 111, 1657.
■
S
Experimental procedures and characterization data for
new compounds (PDF)
(12) Shen, D.-M.; Liu, C.; Chen, X.-G.; Chen, Q.-Y. J. Org. Chem. 2009,
74, 206.
(13) Jin, L.-M.; Chen, L.; Yin, J.-J.; Guo, C.-C.; Chen, Q.-Y. Eur. J. Org.
Chem. 2005, 2005, 3994.
(14) Ouyang, Q.; Zhu, Y.-Z.; Zhang, C.-H.; Yan, K.-Q.; Li, Y.-C.;
Zheng, J.-Y. Org. Lett. 2009, 11, 5266.
(15) For selected examples, see: (a) Antonchick, A. P.; Samanta, R.;
Kulikov, K.; Lategahn, J. Angew. Chem., Int. Ed. 2011, 50, 8605.
(b) Samanta, R.; Bauer, J. O.; Strohmann, C.; Antonchick, A. P. Org. Lett.
2012, 14, 5518. (c) Chen, H.; Kaga, A.; Chiba, S. Org. Lett. 2014, 16,
6136. (d) Manna, S.; Serebrennikova, P. O.; Utepova, I. A.; Antonchick,
A. P.; Chupakhin, O. N. Org. Lett. 2015, 17, 4588. (e) Zenzola, M.;
Doran, R.; Degennaro, L.; Luisi, R.; Bull, J. A. Angew. Chem., Int. Ed.
2016, 55, 7203.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: ycchen@scu.edu.cn
*E-mail: ouyangq@tmmu.edu.cn
ORCID
Ying-Chun Chen: 0000-0003-1902-0979
Qin Ouyang: 0000-0002-1161-5102
Notes
The authors declare no competing financial interest.
(16) DFT calculations were carried out with the GAUSSIAN 09
packages. See the SI.
ACKNOWLEDGMENTS
We are grateful for financial support from the NSFC (21202201)
and Third Military Medical University (2015XZH05).
(17) For selected recent examples, see: (a) Hou, K. P.; Qi, M.; Liu, J. J.;
Bao, X. G.; Schaefer, H. F. J. Org. Chem. 2015, 80, 5795. (b) Hartmann,
M.; Li, Y.; Muck-Lichtenfeld, C.; Studer, A. Chem. - Eur. J. 2016, 22,
3485. (c) Morimoto, K.; Sakamoto, K.; Ohshika, T.; Dohi, T.; Kita, Y.
Angew. Chem., Int. Ed. 2016, 55, 3652.
■
REFERENCES
■
́
(1) For recent reviews, see: (a) Auwarter, W.; Ecija, D.; Klappenberger,
̈
F.; Barth, J. V. Nat. Chem. 2015, 7, 105. (b) Ding, Y.; Zhu, W.-H.; Xie, Y.
Chem. Rev. 2017, 117, 2203. (c) Lu, H.; Kobayashi, N. Chem. Rev. 2016,
116, 6184. (d) Bhupathiraju, N. V.; Rizvi, W.; Batteas, J. D.; Drain, C. M.
Org. Biomol. Chem. 2016, 14, 389. (e) Jiang, L.; Gan, C. R.; Gao, J.; Loh,
X. J. Small 2016, 12, 3609.
(2) For recent reviews, see: (a) Nyman, E. S.; Hynninen, P. H. J.
Photochem. Photobiol., B 2004, 73, 1. (b) Garland, M. J.; Cassidy, C. M.;
Woolfson, D.; Donnelly, R. F. Future Med. Chem. 2009, 1, 667.
(c) Ethirajan, M.; Chen, Y.; Joshi, P.; Pandey, R. K. Chem. Soc. Rev. 2011,
D
DOI: 10.1021/acs.orglett.7b01739
Org. Lett. XXXX, XXX, XXX−XXX