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Intramolecular radical cyclization approach to
access highly substituted indolines and 2,3-
dihydrobenzofurans under visible-light†
Cite this: RSC Adv., 2018, 8, 12879
a
Clarice A. D. Caiuby, a Akbar Ali,a Vinicius T. Santana,b Francisco W. de S. Lucas,
a
b
Marilia S. Santos,a Arlene G. Correa,
Otaciro R. Nascimento,
Hao Jianga
ˆ
a
*
and Marcio W. Paixao
´
˜
The combination of visible-light and tris(trimethylsilyl)silane promoting intramolecular reductive cyclization
protocol for the synthesis of functionalized indolines and 2,3-dihydrobenzofurans has been developed. The
transformations occur in the absence of transition metal and additional photocatalyst. In addition, quantum
yield (F) was determined and electron paramagnetic resonance spectroscopy was performed to better
understand the reaction pathway.
Received 28th February 2018
Accepted 21st March 2018
DOI: 10.1039/c8ra01787e
rsc.li/rsc-advances
Aside from these approaches, free-radical mediated reac-
tions have been developed to access these unique heterocyclic
cores.11 However, a large number of the seminal single-electron-
Introduction
Oxygen- and nitrogen-containing heterocyclic scaffolds are
important components of a variety of important natural prod-
ucts and prevalent structural motifs in biologically active
molecules, agrochemicals and designed materials.1
transfer strategies requires stoichiometric quantities of
hazardous reagents (e.g. tributyltin hydride or AIBN) as radical
generators – in which implicates environmental concerns.12
Nevertheless, the eld of synthetic organic photochemistry is
rapidly growing in importance as it represents an efficient and
environment-friendly alternative to the previous described
methods.13 The photon energy allows to access reactive inter-
mediates that cannot be accessed by other strategies employing
a clean energy source under mild conditions. Under this
concept, either UV or visible light mediated approaches have
been described to access indolines and dihydrobenzofurans
(Scheme 1).
In particular, indolines and 2,3-dihydrobenzofurans have
attracted considerable interest from both synthetic and
medicinal chemistry due to the presence of these privileged
scaffolds in pharmaceutical2 and naturally occurring alkaloids3
(Fig. 1). Under this scenario, highly decorated architectures
containing those systems exhibit noteworthy anti-HIV inhib-
itor,4 antihypertensive5 and anti-inammatory6 activities.
As a consequence of their high biological potentials, signif-
icant effort has been devoted to the development of efficient
protocols for the synthesis of these heterocyclic frameworks.7
Towards this end, some traditional methods involves oxidation
processes,8 Lewis or Bronsted acids9 and transition-metal-
catalyzed reactions – for example, the intramolecular hydro
functionalization of alkenes, aryl functionalization, the heter-
oannulation of 1,3-dienes and transition-metal-catalyzed
dicarbofunctionalization of unactivated olens via tandem
cross-coupling/cyclization process to afford a variety of oxygen
and nitrogen heterocycles.10
Very recently, Li and co-workers introduced an elegant metal-
free carboiodination protocol for the syntheses of highly deco-
rated indolines and 2,3-dihydrobenzofurans under UV
radiation.14
On the other hand, the use of visible-light as a source of
energy for promoting chemical transformation has emerged as
an interesting topic in organic synthesis.15 In this sense,
different research groups have demonstrated the syntheses of
nitrogen- and oxygen-containing heterocyclic scaffolds using
Cu(I),16 Ir(III)17 and Ru(II)18 based complexes under visible-light
irradiation. Moreover, Jamison and coworkers have described
the combination of nickel- and photoredox-catalysis (Ni/Ru) for
the regioselective synthesis of 3-substituted indolines from
alkenes and 2-iodoacetanilides.19
aCenter of Excellence for Research in Sustainable Chemistry (CERSusChem),
˜
Department of Chemistry, Federal University of Sao Carlos – UFSCar, Rodovia
´
˜
˜
Washington Luıs, km 235 – SP-310, Sao Carlos, Sao Paulo, Brazil 13565-905.
E-mail: mwpaixao@ufscar.br
b
´
˜
Group of Molecular Biophysics “Sergio Mascarenhas”, Sao Carlos Institute of Physics
Although the advances of metal promoted photoredox
strategies in the activation of small molecules, these
approaches also revealed some drawbacks such as catalysts
cost, removal from the reaction medium and the need of an
˜
˜
˜
– IFSC/USP, University of Sao Paulo, Avenida Trabalhador Sao Carlense, 400, Sao
Carlos, SP, 13560-970, Brazil
† Electronic supplementary information (ESI) available: Procedures, additional
experiments, characterisation of products, and copies of 1H and 13C NMR
spectra. See DOI: 10.1039/c8ra01787e
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Fig. 1 Selected examples of biologically active indolines and 2,3-dihydrobenzofurans.
Scheme 1 Photo-promoted strategies for synthesis of indolines and 2,3-dihydrobenzofurans.
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excess of additive. In this context, electron donor–acceptor found that with 2 equiv. proved benecial to the yield of the
(EDA) complex have been explored as an alternative.20
desired product (Table 1, entry 3).
Nevertheless, in spite of the considerable advances that have
To our delight, using white-light LEDs as the source of visible
been made in this eld, the design of general and mild photo- irradiation showed a signicant effect on chemical efficiency –
chemical strategies that improves efficiency, lower cost and thus providing indoline 2a in 90% yield (Table 1, entry 4). Under
decrease waste are highly desirable.21 In this regard, our UV-irradiation (254 nm) for 30 min at room temperature, the
research group has recently described a metal-free photo- model reaction provides product 2a in 65% along with
chemical protocol for the synthesis of N-heterocyclic byproducts. These ndings were attributed to high energy of the
compounds.22 Encouraged by this work, which took advantage irradiation which can decrease the reaction selectivity (Table 1,
of the EDA complex formation – herein, we report the extension entry 5). Moreover, the inuence of the organosilane was also
of this approach towards the synthesis of highly substituted investigated. Meanwhile, when Et3SiH and PhSiH3 were used
indolines and 2,3-dihydrobenzofurans.
instead of TTMSS, the reaction did not occur, and the starting
material were completely recovered (Table 1, entries 6 and 7).
It is worth mentioning that the TTMSS-based radical can also
be generated under aerobic conditions,23 therefore, control
experiments were conducted with light absence to evaluate this
parallel pathway for the tandem reductive/cyclization process.
Conducting the reaction at room temperature and in the dark-
ness delivered the indoline ring in 70% aer a long reaction
time (72 hours, Table 1, entry 8).
When the reaction temperature was increased to 50 ꢀC,
similar range of chemical efficiency could be observed in a short
reaction period (Table 1, entry 9). Although the generation of
the TTMSS-based radical under thermal conditions was
feasible, it showed to be less effective than the photochemical
process. It is well reported that molecular oxygen – even under
air atmosphere conditions – can spontaneously react with
TTMSS at room temperature to generate a silyl-centered
radical.24 Having that in mind, we then evaluated the inu-
ence of oxygen in the radical generation of the described
methodology. When the reaction was carried out under
degasied solvent, argon atmosphere and blue LEDs irradia-
tion, the desired indoline 1a could be obtained in 89% chemical
yield (Table 1, entry 10). Furthermore, performing the reaction
under air atmosphere, low temperature and darkness, there was
no product formation and the starting material could be
completely recovered (see ESI† for details). These results
provided strong evidences that support the essential role of the
visible-light in the radical generation event of this protocol.
Next, complementary experiments showed that the combina-
tion of TTMSS and visible light were essential for this trans-
formation (Table 1, entries 11 and 12).
Results and discussion
We began our investigation performing a screening of different
solvents and the starting material (see ESI Tables S2 and S4†).
The N-allyl-N-2-haloanilines were evaluated, considering the
halogen atom and nature of the substituent on the nitrogen.
The N-allyl-N-(2-iodophenyl)acetamide 1a was chosen as model
substrate, employing reaction conditions similar to our previ-
ously reported synthesis of the privileged indole and oxindole
scaffolds (Table 1, for complete details see ESI†). Pleasing, the
reaction of 1a in the presence of 1 equiv. of tris(trimethylsilyl)
silane (TTMSS), acetonitrile as solvent under a compact uo-
rescent lamp (CFL) irradiation for 24 hours provided 47% of the
targeted indoline 2a (Table 1, entry 1). The addition of ethanol
(5 equiv.) as hydrogen source did not change the reaction yield
(Table 1, entry 2). We also evaluated the amount of TTMSS and
Table 1 Optimization study for the intramolecular cyclization photo-
promoted synthesis of indolinea
Entry
Silane
hn
Temp
Time (h)
Yieldb (%)
1c,d
2c,e
3c
TTMSS
TTMSS
TTMSS
TTMSS
TTMSS
Et3SiH
PhSiH3
TTMSS
TTMSS
TTMSS
—
CFL
CFL
CFL
LEDs
UV
LEDs
LEDs
Darkness
Darkness
LEDs
Darkness
LEDs
rt
rt
rt
rt
rt
rt
rt
rt
24
24
24
24
0.5
48
48
72
5
47
50
70
92
65
—
—
70
72
89
—
—
We then sought to determined the wavelength required for
an efficient silane-mediated atom transfer process of 1a
(Table 2).
4f
5g
6f
The use of a red-light LEDs (632 nm) resulted in a low yield
aer 12 hours (Table 2, entry 1) – meanwhile, under a green-
light LEDs (520 nm) irradiation, the reaction was completed
aer 7 hours with an increment on the chemical yield (Table 2,
entry 2). To our delight, the highest yield was achieved
employing blue-light LEDs irradiation (Table 2 – entry 3),
therefore, under the model reaction conditions the desired
product was obtained in 98% yield aer 5 h.
7f
8
9
50 ꢀ
rt
C
C
10h
11
12f
5
48
48
50 ꢀ
rt
—
a
Unless otherwise specied reactions were performed using 1a (0.20
b
mmol), silane (2 equiv.), MeCN (4 mL). Yield of isolated products.
c
d
Reaction vessel placed between two 12 W CFL lamp. 1 equiv. of
With the optimized reaction conditions in hand, we exam-
ined the generality of the reaction protocol (Table 3). In general,
e
TTMSS was used. Reaction was performed with 1 equiv. of TTMSS
and 5 equiv. of EtOH. Irradiated with a white light-emitting diode
(LEDs) strip. UV radiation (40 W). Irradiated with a blue LEDs strip
f
g
h
the
N-allyl-2-iodophenyl-acetamides
bearing
electron-
under argon atmosphere and degasied solvent.
withdrawing groups on the aromatic ring (2b–2e) reacted
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Table
evaluationa
2 Optimization of the reaction conditions: wavelength Table 3 Scope of the intramolecular cyclization photo-promoted
synthesis of indolinesa,b
Entry
lb (nm)
Solvent
Time (h)
Yieldc (%)
1
2
3
4
632
520
450
450
MeCN
MeCN
MeCN
Acetone
12
7
5
46
85
98
93
24
a
Unless otherwise specied reactions were performed using 1a (0.20
mmol), TTMSS (2 equiv., 0.40 mmol) and specied solvent (4 mL).
b
Irradiated with a LEDs strip. c Yield of isolated products.
efficiently to afford the corresponding indoline products in
moderate to excellent yields. To our delight, substrates bearing
additional halogen e.g. Cl – functionality that allow subsequent
functionalization by transition metal mediated cross-coupling
reactions25 – underwent the reaction efficiently, affording the
corresponding product in good yield (2f ¼ 78% y). Subse-
quently, we observed that the substitution pattern on the
aromatic ring of the substrate did not affect the chemical effi-
ciency (compared 2f vs. 2g), however a substantial difference in
the reaction times were necessary. The protocol was also
compatible with substrates bearing electron-donating groups,
thus rendering products 2j and 2k in 60% and 83% respectively.
As an important demonstration of the reactivity, N-allyl-2-
bromophenyl-acetamide derivatives where also effective under
our reaction conditions, providing the cyclization products 2i
and 2l, albeit in diminished yields.
To further assess the functional-group tolerance of the
metal-free photo-initiated synthesis of indolines, we explored
the reactivity of different substrates having different substitu-
ents on the olenic portion. Notably, a series of b-mono
substituted olens bearing different functional group, such as
methyl (2m and 2n), aryl (2o) and methyl ester (2p and 2q) are
compatible with this reaction conditions, and all the reaction
produced desired products in moderate to good yields.
Substrates having two substituents on the terminal carbon of
the olen provided the products 2r and 2s in good yields.
Finally, a-disubstituted substrates were converted into the
desired indoline products 2t and 2u in good yields.
Based on the encouraging results for the synthesis of the
indoline framework, we envisioned to extended the TM-free
visible-light-induced photochemical methodology to the
synthesis of 2,3-dihydrobenzofurans. To this end, a brief opti-
mization was further performed, especially regarding the
wavelength range of the light source. Among those screened,
white LEDs provided optimum yield of the 2,3-dihy-
drobenzofuran (for details see the ESI†). Subjecting the
substrate (1-(allyloxy)-2-iodobenzene) to a slightly modied
version of the optimized conditions – however, in the absence of
both TTMSS and visible light, no conversion to the desired
a
Unless otherwise specied reactions were performed using 1a–u (0.20
mmol), TTMSS (2 equiv., 0.40 mmol), and MeCN (0.4 mL) in a 4 mL vial
irradiated with a blue LEDs strip for 5 to 72 hours at room temperature
(see ESI for conditions). Yield of isolated products.
b
cyclization product were observed, with the starting material
being fully recovered.
At this point, our attention turned toward the preparation of
some examples of oxygen-heterocycle in the optimized condi-
tions (Table 4). For substrate bearing terminal alkene, high
conversion was observed. With respect to the alkene component
elaboration, the reaction was also tolerant to alkyl-substitution
partners (4b and 4c).
The double bond was also amenable further structural vari-
ations, therefore, 4d having a terminal electron withdrawing
group undergoes sequential reduction/cyclization in high yield.
Finally, the potential of this methodology was further demon-
strated in the synthesis of dihydrobenzofuran 4e which
contains a quaternary center.
In order to gain further insight into the mechanism of this
reaction, a series of control experiments were also pursued.
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Table 4 Intramolecular cyclization photo-promoted synthesis of 2,3-
donor–acceptor association between 1a and TTMSS (EDA
dihydrobenzofuransa,b
complex), and therefore acts as
transformation.
a
promoter of the
Complementarily, fraction of light absorbed experiments
revealed the reaction mixture absorbs almost 100% of the light
fraction at 450 nm, supporting the experimental data in which
the reaction is promoted efficiently by blue LEDs light. These
ndings added to lower irradiance of the green and red LEDs
(85% and 3% respectively) corroborate the lower yield and
reactivity observed for the reaction under these light sources
(for details see ESI†).
Trapping experiments were performed and afforded strong
evidence that the reaction proceeds via a single electron
pathway. When the reaction was accomplished in the presence
of a radical scavenger – 2,2,6,6-tetramethyl-1-piperidinyloxy
a
Unless otherwise specied reactions were performed using 3a–e (0.20
mmol), TTMSS (2 equiv., 0.40 mmol), and MeCN (0.4 mL) in a 4 mL vial (TEMPO) – there was a complete inhibition of the desired
irradiated with two white LEDs lamps (12 W) for 5 to 72 hours at room
temperature (see ESI for conditions). All yields refer to isolated
products.
transformation. Furthermore, MS analysis of the reaction
mixture showed the presence of the starting material 1a (which
b
was fully recovered) along with the formation of the TTMSS
adduct with TEMPO, implying the formation of silyl-centered
radical under visible-light irradiation.
Additionally, spin trapping experiments were also per-
formed. In this study, compound 1a was used as model
substrate and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as spin
trap.26 Thus, carrying out the reaction either in the darkness or
in the absence of TTMSS no signal was observed. On the other
hand, subjecting substrate 1a to a blue LEDs irradiation, in the
presence of TTMSS and DMPO, resulted in the EPR spectrum
(red line) presented in Fig. 3. In the same gure, the simulated
spectrum (black line) using the EasySpin package27 is presented.
The hyperne splitting observed was rst simulated
considering a spin-1/2 (NOc radical) coupled to the closest N
and H nuclei of the DMPO molecule, resulting in the hyperne
coupling constants a14N ¼ 1.33 mT, a1H ¼ 0.94 mT with a 0.4 mT
Therefore, we started by performing UV-visible spectroscopic
studies to investigate the behavior of all the components of the
reaction under visible light. Individual solutions of 1a, TTMSS,
indoline 2a and reaction mixture were prepared and the
absorbances were measured (Fig. 2). The solutions were
prepared in duplicate, one of which was kept under light irra-
diation and the other in the light absence (see ESI† for further
details). The solid lines represent all measurement performed
in the darkness, whereas dashed lines correspond to the spectra
of the solutions exposed to the irradiation. Firstly, the indi-
vidual evaluation of compounds 1a (red lines), TTMSS (black
lines) and 2a (blue lines) did not showed a signicant change in
the absorbance spectra aer exposure to the blue LEDs irradi-
ation (Fig. 2).
However, a new absorption band (l ¼ 356 nm) was detected
for the reaction mixture composed by TTMSS and 1a (RM, green
lines) upon the radiation incidence – which suggests the
formation of an intermediate that absorbs nearly the visible
light region. This species would be generated through electron
Fig. 3 EPR spectra of the reaction mixture with DMPO under blue
LEDs radiation (30 W).
Fig. 2 Absorbance spectra for TTMSS solutions (0.02 mol Lꢁ1, black
lines), 1a (0.01 mol Lꢁ1, red lines), 2a (0.01 mol Lꢁ1, blue lines) and the
reaction mixture of TTMSS (0.02 mol Lꢁ1) + 1a (0.01 mol Lꢁ1) (RM,
green lines). SM: starting material, RM: reaction mixture.
Scheme 2 Reaction between 1a and the trapping reagent DMPO.
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Fig. 4 Mechanistic proposal for photo-promoted indolines synthesis.
linewidth. However, considering the possible products formed generates the silicon-centered radical (I). Then, a dehalogena-
between the DMPO and the intermediary radicals of the reac- tion reaction of the substrate 1a occurs through the abstraction
tion, several steps were taken into account in order to improve of the iodine by the silicon radical, forming an aryl radical (II).
the simulation.
The intermediate II passes through a 5-exo-trig cyclisation, to
The best simulation was obtained considering two addi- generate the alkyl radical III, followed by abstraction of
tional hydrogen atoms that are closer to the bond of the trapped hydrogen to form the nal product 2a.
radical with the DMPO (position 3) and a more distant nitrogen
(both nitrogen- and hydrogens atoms provided from 2a), that
must also be in the trapped radical. The hyperne coupling
Conclusions
constants that best t the data are a1H ¼ 0.0981 mT, a1H ¼ 0.152
In summary, we have described a mild and metal-free visible
light mediated protocol for the synthesis of highly substituted
mT, and a14N ¼ 0.088 mT with a linewidth of 0.17 mT. The
radical species captured by the DMPO may be the alkyl radical
intermediate, leading to the formation of the adduct 5
(Scheme 2). The nuclei used in the simulation are highlighted
in the adduct 5. Moreover, no EPR signal was detected aer
irradiation of a TTMSS solution in acetonitrile.
indolines that proceeds via formation of an EDA complex
between N-allyl-2-haloanilines and the organosilane reagent,
TTMSS. Several functional groups were well tolerated affording
the nitrogen heterocycles mostly in good to excellent yields. The
methodology has also been expanded to oxygen-containing
substrates for the synthesis of 2,3-dihydrobenzofurans. Mech-
anistic insights were obtained through UV-visible spectroscopy,
quantum yield, and EPR analysis indicating that the association
substrate-TTMSS is essential to start the photo-transformation,
which proceeds through a radical chain propagation. The
features of this methodology such as environmentally friendly
radical generation and highly valued structures reveal the
potential of this chemistry to access a variety of complex
scaffolds.
Likewise, quantum yield experiments were performed to
provide additional insights about radical chain propagation.
The quantum yield of the specied photo reaction between 1a
and TTMSS to provide 2a, was obtained using the photode-
composition of potassium trioxalatoferrate(III) trihydrate as the
actinometer. The quantum yield average for the reaction was F
¼ 28.37, which suggests that a single photon triggers 28 radical
steps, indicating that transformation can occur through radical-
chain process.28 This fact corroborates the hypothesis that
TTMSS has an important role as a radical initiator.
In light of these experimental results and previous work,22
Conflicts of interest
plausible radical/SET pathway based on excited EDA
a
complexes is outlined in Fig. 4. Upon light irradiation, the
photochemical transformation would occur via a reactive
excited complex (1a – TTMSS)*. The generation of such
complex, can be rationalized through two distinct mechanisms
– (a) the formation of an electron donor–acceptor association
(EDA complex) which is irradiated at the wavelength of its CT
band, or (b) local irradiation of individual bands of either
components, leads to excited form, which can combine with its
nonexcited counterpart, thus leading to the corresponding
exciplex. Sequentially, over either an electron-transfer or energy-
transfer events the homolytic cleavage of the Si–H bond
There are no conicts to declare.
Acknowledgements
C. A. D. Caiuby and A. Ali acknowledge CNPq for their Master
and PhD fellowships, respectively. FAPESP is also acknowledged
for the postdoctoral fellowship to F. W. de S. Lucas and M. S.
˜
ˆ
Santos. M. W. Paixao and A. G. Correa gratefully acknowledge
´
nancial support from CNPq (INCT – Catalise) and FAPESP (13/
07600-3, 14/50249-8 and 15/17141-1). The authors also
acknowledge GSK for the nancial support.
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M. Hartmann and A. Studer, Angew. Chem., Int. Ed., 2014,
53, 8180–8183.
Notes and references
12 (a) J. N. Johnston, M. A. Plotkin, R. Viswanathan and
E. N. Prabhakaran, Org. Lett., 2001, 3, 1009–1011; (b)
H. Fuwa and M. Sasaki, Org. Lett., 2007, 9, 3347–3350; (c)
Y. Ueno, X. Chino and M. Okawara, Tetrahedron Lett., 1982,
23, 2575–2576.
1 (a) X. X. Guo, D. W. Gu, Z. Wu and W. Zhang, Chem. Rev.,
2015, 115, 1622–1651; (b) B. Eekhari-Sis, M. Zirak and
A. Akbari, Chem. Rev., 2013, 113, 2958–3043; (c)
N. R. Candeias, L. C. Branco, P. M. P. Gois, C. A. M. Afonso
and A. F. Trindade, Chem. Rev., 2009, 109, 2703–2802; (d)
C. A. Carson and M. A. Kerr, Chem. Soc. Rev., 2009, 38,
3051–3060.
2 (a) J. E. Wilson, R. Kurukulasuriya, M. Reibarkh, M. Reiter,
A. Zwicker, K. Zhao, F. Zhang, R. Anand, V. J. Colandrea,
A. M. Cumiskey, A. Crespo, R. A. Duffy, B. A. Murphy,
K. Mitra, D. G. Johns, J. L. Duffy and P. Vachal, ACS Med.
Chem. Lett., 2016, 7, 261–265; (b) P. Mayer, P. Brunel and
T. Imbert, Bioorg. Med. Chem. Lett., 1999, 9, 3023–3026.
3 D. Zhang, H. Song and Y. Qin, Acc. Chem. Res., 2011, 44, 447–
457.
13 (a) D. Ravelli, D. Dondi, M. Fagnonia and A. Albini, Chem.
Soc. Rev., 2009, 38, 1999–2011; (b) J. R. Chen, X. Q. Hu,
L. Q. Lu and W. J. Xiao, Acc. Chem. Res., 2016, 49, 1911–
1923; (c) D. A. Nicewicz and D. W. C. MacMillan, Science,
2008, 322, 77–80; (d) N. A. Romero and D. A. Nicewicz,
Chem. Rev., 2016, 116, 10075–10266; (e) T. Peglow,
S. Blechert and E. Steckhan, Chem. Commun., 1999, 433–
434; (f) H. Kim and C. Lee, Angew. Chem., Int. Ed., 2012, 51,
12303–12306; (g) W. Guo, L.-Q. Lu, Y. Wang, Y.-N. Wang,
J.-R. Chen and W.-J. Xiao, Angew. Chem., Int. Ed., 2015, 53,
2265–2269; (h) X.-D. Xia, Y.-L. Ren, J.-R. Chen, X.-L. Yu,
L.-Q. Lu, Y.-Q. Zou, J. Wan and W.-J. Xiao, Chem.–Asian J.,
2015, 10, 124–128; (i) X.-D. Xia, L.-Q. Lu, W.-Q. Liu,
D.-Z. Chen, Y.-H. Zheng, L.-Z. Wu and W.-J. Xiao, Chem.–
Eur. J., 2016, 22, 8432–8437.
4 I. S. Abd-Elazem, H. S. Chen, R. B. Bates and R. C. C. Huang,
Antiviral Res., 2002, 55, 91–106.
5 A. Rakhit, M. E. Hurley, V. Tipnis, J. Coleman, A. Rommel
and H. R. Brunner, J. Clin. Pharmacol., 1986, 26, 156–164.
6 E. D. Coy, L. E. Cuca and M. Seow, Bioorg. Med. Chem. Lett.,
2009, 19, 6922–6925.
14 X. Yang, W. Liu, L. Li, W. Wei and C. J. Li, Chem.–Eur. J.,
2016, 22, 15252–15256.
´
7 L. Pouysegu, A. V. Avellan and S. Quideau, J. Org. Chem.,
15 (a) M. H. Shaw, J. Twilton and D. W. C. MacMillan, J. Org.
Chem., 2016, 81, 6898–6926; (b) C. K. Prier, D. A. Rankic
and D. W. C. MacMillan, Chem. Rev., 2013, 113, 5322–5363;
(c) T. P. Yoon, M. A. Ischay and J. Du, Nature, 2010, 2, 529–
532; (d) E. R. Welin, C. Le, D. M. Arias-Rotondo,
J. K. McCuske and D. W. C. MacMillan, Science, 2017, 355,
380–385; (e) D. Griffin, M. A. Zeller and D. A. Nicewicz, J.
Am. Chem. Soc., 2015, 137, 11340–11348.
16 B. Michelet, C. Deldaele, S. Kajouj, C. Moucheron and
G. Evano, Org. Lett., 2017, 19, 3576–3579.
17 (a) H. Kim and C. Lee, Angew. Chem., Int. Ed., 2012, 51,
12303–12306; (b) S. K. Pagire and O. Reiser, Green Chem.,
2017, 19, 1721–1725.
2002, 67, 3425–3436.
8 (a) S. J. Gharpure and Y. G. Shelke, Org. Lett., 2017, 19, 5406–
5409; (b) M. Rueping, C. Brinkmann, A. P. Antonchick and
I. Atoresei, Org. Lett., 2010, 12, 4604–4607.
9 (a) For Pd-catalyzed reactions see:E. D. Coy, L. Jovanovic and
M. Seow, Org. Lett., 2010, 12, 1976–1979; (b)
A. R. O. Venning, P. T. Bohan and E. J. Alexanian, J. Am.
Chem. Soc., 2015, 137, 3731–3734; (c) For Cu-catalyzed
reaction see:J. Huang, Y. Chen, J. Chan, M. L. Ronk,
R. D. Larsen and M. M. Faul, Synlett, 2011, 1419–1422; (d)
For Ru-catalyzed reaction see:M. K. Manna, S. K. Bhunia
and R. Jana, Chem. Commun., 2017, 53, 6906–6909; (e) For
Rh-catalyzed reaction see:T. A. Davis, C. Wang and
T. Rovis, Synlett, 2015, 26, 1520–1524.
18 T. R. Blum, Y. Zhu, S. A. Nordeen and T. P. Yoon, Angew.
Chem., Int. Ed., 2014, 53, 11056–11059.
10 (a) D. Liu, G. Zhao and L. Xiang, Eur. J. Org. Chem., 2010,
3975–3984; (b) A. M. Hyde and S. L. Buchwald, Angew.
Chem., Int. Ed., 2008, 47, 177–180; (c) M. D. Ganton and
M. A. Kerr, Org. Lett., 2005, 7, 4777–4779; (d) M. S. Pinaud,
P. Diaz, J. Martinez and F. Lamaty, Tetrahedron Lett., 2007,
63, 3340–3349; (e) J. lnanaga, O. Ujikawa and
M. Yamaguchi, Tetrahedron Lett., 1991, 32, 1737–1740; (f)
R. W. Charnley, B. W. Puffer and P. H. Dussault, J. Am.
Chem. Soc., 2014, 136, 5821–5823; (g) S. G. Newman and
M. Lautens, J. Am. Chem. Soc., 2011, 133, 1778–1780; (h)
C. Chen, J. Hu, J. Su and X. Tong, Tetrahedron Lett., 2014,
55, 3229–3231; (i) T. T. Schempp, B. E. Daniels,
S. T. Staben and C. E. Stivala, Org. Lett., 2017, 19, 3616–3619.
11 For selected reviews see: (a) D. P. Curran, C. H. T. Chen,
S. J. Geib and A. J. B. Lapierre, Tetrahedron, 2004, 60,
4413–4424; (b) A. Studer and D. P. Curran, Angew. Chem.,
Int. Ed., 2016, 55, 58–102For a recent example see:(c)
19 S. Z. Tasker and T. F. Jamison, J. Am. Chem. Soc., 2015, 137,
9531–9534.
20 For a review on photoreactions via EDA complexes see: (a)
C. Lima, T. Lima, M. Duarte, I. D. Jurberg and
˜
M. W. Paixao, ACS Catal., 2016, 6, 1389–1407For selected
´
exemples see: (b) E. Arceo, I. D. Jurberg, A. Alvarez-
´
Fernandez and P. Melchiorre, Nat. Chem., 2013, 5, 750–
756; (c) E. Arceo, A. Bahamonde, G. Bergonzini and
P. Melchiorre, Chem. Sci., 2014, 5, 2438–2442; (d)
A. Bahamonde and P. Melchiorre, J. Am. Chem. Soc., 2016,
138, 8019–8030; (e) Y.-Y. Liu, X.-Y. Yu, J.-R. Chen,
M.-M. Qiao, X. Qi, D.-Q. Shi and W. Xiao, Angew. Chem.,
Int. Ed., 2017, 56, 9527–9531; (f) R. Wang, W. Guan,
Z.-B. Han, F. Liang, T. Suga, X. Bi and H. Nishide, Org.
Lett., 2017, 19, 2358–2361; (g) V. Quint, F. Morlet-Savary,
´
J.-F. Lohier, J. Lalevee, A.-C. Gaumont and S. Lakhdar, J.
Am. Chem. Soc., 2016, 138, 7436–7441.
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RSC Advances
Paper
´
21 H. Jiang, J. R. Bak, F. J. Lopez-Delgado and K. A. Jørgensen, 25 (a) P. Ruiz-Castillo, D. G. Blackmond and S. L. Buchwald, J.
Green Chem., 2013, 15, 3355–3359.
22 G. P. Silva, A. Ali, R. C. Silva, H. Jiang and M. Paixao, Chem.
Commun., 2015, 51, 15110–15113.
23 (a) C. Chatgilialoglu, Acc. Chem. Res., 1992, 188, 188–194; (b)
C. Chatgilialoglu, Chem.–Eur. J., 2008, 14, 2310–2320.
Am. Chem. Soc., 2015, 137, 3085–3092; (b) R. A. Green and
J. F. Hartwig, Angew. Chem., Int. Ed., 2015, 54, 3768–3772;
(c) L. Li, S. Zhao, A. J. Pangu, M. Diane and M. R. Biscoe, J.
Am. Chem. Soc., 2014, 136, 14027–14030.
˜
26 E. G. Janzen, Acc. Chem. Res., 1971, 4, 31–40.
24 A. B. Zaborovskiy, D. S. Lutsyk, R. E. Prystansky, 27 S. Stoll and A. Schweiger, J. Magn. Reson., 2006, 178, 42–55.
V. I. Kopylets, V. I. Timokhin and C. Chatgilialoglu, J. 28 M. A. Cismesia and T. P. Yoon, Chem. Sci., 2015, 6, 5426–
Organomet. Chem., 2004, 689, 2912–2919.
5434.
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