Visible Light Promoted Synthesis of Indoles by Single Photosensitizer under Aerobic Conditions

Article abstract of DOI:10.1021/acs.orglett.7b01367

The construction of substituted indole skeletons is always an important concern of synthetic chemists because of its prevalent structure found in natural products and biological molecules. Here, we succeeded in preparing indoles and their derivatives from

Full text of DOI:10.1021/acs.orglett.7b01367

Letter
pubs.acs.org/OrgLett
Visible Light Promoted Synthesis of Indoles by Single
Photosensitizer under Aerobic Conditions
Wen-Qiang Liu,†,‡ Tao Lei,†,‡ Zi-Qi Song,†,‡ Xiu-Long Yang,†,‡ Cheng-Juan Wu,†,‡ Xin Jiang,†,‡
Bin Chen,†,‡ Chen-Ho Tung,†,‡ and Li-Zhu 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
‡University of Chinese Academy of Sciences, Beijing 100049, P. R. China
S
* Supporting Information
ABSTRACT: The construction of substituted indole skeletons is always an
important concern of synthetic chemists because of its prevalent structure
found in natural products and biological molecules. Here, we succeeded in
preparing indoles and their derivatives from a wide variety of simple enamines
via radical cyclization only with catalytic amounts of an iridium(III)
photosensitizer (PS) in DMSO solution under air atmosphere. The
mechanistic investigation suggests that the reaction involves a radical course to accomplish the conversion of enamines to
indoles under visible light irradiation.
ndoles are an important kind of heterocyclic compounds,
which widely exist in pharmaceuticals, agrochemicals, natural
Taking advantage of visible light as a renewable energy source,
photoredox catalysis has recently made significant progress in
organic synthesis.9 Rueping and our group combined a
photosensitizer with metal palladium10 or cobalt catalysts11 to
achieve a range of indoles synthesis (Scheme 1b). In contrast to
the previous work, we report herein a new strategy for the
synthesis of indoles, which relies on a single photosensitizer in
DMSO to afford multisubstituted indoles via radical cyclization
of enamines in air without adding any metal catalysts and bases
(Scheme 1).
We started our investigations with the easily prepared N-aryl
enamine 1a as the substrate. When dissolving the mixture of fac-
Ir(ppy)3 (tris(2-phenylpyridine)iridium(III)) and enamine
substrate in DMSO under blue LEDs irradiation for 5 h at
room temperature in air, the desired indole compound was
obtained in a yield of 81% monitored by 1H NMR analysis (Table
1, entry 1). In order to improve the reaction efficiency, we
studied the effect of reaction temperature, photosensitizers, and
solvents and achieved an excellent yield of 99% at the reaction
temperature of 75 °C (Table 1, entry 2). Among a series of
common photosensitizers, fac-Ir(ppy)3 had the best catalytic
efficiency (Table 1, entries 3−7), and the amount of photo-
sensitizer showed no much effect on the yields (Table 1, entries
8−9). The most striking observation is that DMSO is the best
solvent among the tested solvents like DMF, MeCN, MeOH,
and ClCH2CH2Cl (Table 1, entries 10−13), even at higher
concentration (Table 1, entry 14). Control experiments
confirmed that the photosensitizer and visible light were essential
to the reaction (Table 1, entries 15−16) and that the presence of
air greatly enhanced the yield of 16% under inert argon to 99%
(Table 1, entry 17). Under the optimized conditions, i.e.,
I
products, and materials science.1 The traditional indole synthesis
is mainly based on annulation reactions of anilines with alkynes,2
cyclization reactions of o-alkynylanilines,3 or vinylanilines,4
cyclization reactions via C−N bond formation,5 and so on.6
However, most of these approaches suffer from the lack of
starting material availability and functional group tolerance. In
2008, Glorius7 and co-workers were the first to disclose a direct
oxidative synthesis of indoles, employing N-aryl enamines as the
starting materials with the help of Pd(OAc)2 as the catalyst
(Scheme 1a). The availability of raw materials and the tolerance
Scheme 1. Representative Synthesis of Indoles via
Intramolecular Cyclization of Enamines
of functional groups make the reaction better.8 Nonetheless, the
use of stoichiometric amounts of metal salts as the oxidants leads
to undesirable byproducts and residual metals. Developing green
and sustainable reaction systems is essential for indole synthesis
in chemistry and pharmaceuticals.
Received: May 7, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01367
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a,b
Table 1. Optimization of the Reaction Conditions
Scheme 2. Substrates of Enamines
b
entry
PS
solvent
yield (%)
c
1
fac-Ir(ppy)3
fac-Ir(ppy)3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
81
>99
23
68
17
15
0
2
3
4
5
6
7
Ir(ppy)2(dtbpy)PF6
(Ir[dF(CF3)ppy]2(dtbpy))PF6
Ru(bpy)3Cl2
Ru(bpy)3(PF6)2
Acr+-Mes·ClO4
−
d
8
e
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
−
>99
>99
0
9
10
11
12
13
MeCN
MeOH
DCE
0
0
0
f
14
DMSO
DMSO
DMSO
DMSO
66
0
15
g
16
fac-Ir(ppy)3
0
h
17
fac-Ir(ppy)3
16
a
Reaction conditions (unless otherwise specified): a mixture of 1a (0.1
mmol) and photosensitizer (2 mol %) in solvent (2 mL) irradiated
b
1
with 3 W blue LEDs for 5 h at 75 °C in air. Yields detected by H
c
d
e
NMR. At room temperature. 1 mol % of fac-Ir(ppy)3. 3 mol % of
fac-Ir(ppy)3. 1 mL of DMSO. In the absence of light. In argon.
f
g
h
a
Reaction conditions: a mixture of 1 (0.1 mmol) and fac-Ir(ppy)3 (1
mol %) in DMSO (2 mL) irradiated with 3 W blue LEDs for 5 h at 75
°C in air. Isolated yields. Scale up to 1.0 mmol for 6 h.
b
c
enamine 1 (0.1 mmol) with 1 mol % fac-Ir(ppy)3 in DMSO (2
mL), irradiated by blue LEDs for 5 h at 75 °C in air (Table 1,
entry 8), the reaction proceeded efficiently.
hindrance tert-butyl at the para-position of N-aryl enamine, 93%
yield could be achieved (2s). Moreover, a good yield of 78% was
obtained when the template reaction scaled up to 1.0 mmol
under the irradiation of blue LEDs for 6 h.
Next, we examined the ethyl benzoylacetate moiety with
different substituents of the N-aryl enamines (Scheme 3). The N-
aryl enamine containing methoxy group gave the desired indole
in 68% yield (2t), and the N-aryl enamines with electron-
withdrawing groups such as −F and −Cl also performed well
with good yields (2u−2v, 83−85%). However, the enamine
bearing a strong electron-withdrawing group of −NO2 did not
With the optimized conditions in hand, we attempted to
explore the scope of the reaction (Table 1, 8). Most of the N-aryl
enamines bearing electron-donating or electron-withdrawing
groups could afford their corresponding indoles in high yields
under optimized conditions. Incorporation of electron-donating
(−OMe, −SMe) groups of N-aryl enamine was tolerated
affording the products in high yields (2b−2c, 89−99%).
Trimethoxy-substituted N-aryl enamine could also give the
indole in a yield of 78% (2d). It was noteworthy that highly
reactive hydroxyl substituted N-aryl enamine produced the
product in 69% yield (2e). Substrate with naphthyl group
afforded the desired product in a moderate 58% yield (2f). When
replacing ethoxycarbonyl to butoxycarbonyl (2g), we achieved
an excellent yield of 86%. As shown in Scheme 2, the N-aryl
enamines with a strong electron-withdrawing trifluoromethyl
group and cyano-group could yield the indoles in 78% and 82%
yield, respectively (2h−2i). The N-aryl enamines with an ester-
group and acetyl group could successfully produce the indoles in
89−97% yields (2j−2k). The N-aryl enamines with −F, −Cl, and
−Br enabled to have their indoles up to 85% yield (2l−2n),
which would be conducive to further modification of indoles.
Despite the steric hindrance of the substituents, methyl-
monosubstituted enamines could produce their corresponding
indoles in high yields. N-Aryl enamines bearing the methyl group
at the ortho (2o)-, para (2p)-, and meta-position (2q and 2q′)
afforded the indoles in a yield of 95%, 88%, and 96%, respectively.
In addition, meta-methyl-substituted N-aryl enamine 1q gave two
regioisomers (2q and 2q′) at the ratio of 2.6:1. In the case of N-
aryl enamine with two meta-methyl-substituents, the indole
product was obtained (2r) only in 71% yield. With the large steric
a,b
Scheme 3. Substrates of Enamines
a
Reaction conditions: a mixture of 1 (0.1 mmol) and fac-Ir(ppy)3 (1
mol %) in DMSO (2 mL) irradiated with 3 W blue LEDs for 5 h at 75
b
°C in air. Isolated yields.
B
DOI: 10.1021/acs.orglett.7b01367
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
produce any desired product due to substrate decomposition
detected by TLC (2w). In addition, we examined the reactivity of
N-methyl substituted enamine 2x and obtained its corresponding
indole in a yield of 70% under the template reaction conditions.
This result suggested that the presence of the N−H bond is not
imperative for the synthesis of indoles from enamines under this
reaction condition.
dioxetane intermediate, which subsequently decomposes into
two carbonyl fragments.14 This is consistent with the fact that
substrate 1a decomposed completely after 5 h of irradiation in
DMF, MeOH, MeCN, and ClCH2CH2Cl. In DMSO when the
typical 1O2 photosensitizer Eosin Y or Rose Bengal was used, no
desired indole 2 could be detected, but the above reaction
proceeded smoothly in the presence of a strong physical
quencher of 1O2, 1,4-diazabicyclo[2.2.2]-octane (DABCO)
To understand the reaction process of the system, we carefully
designed a number of control experiments and found that when
DMF, MeOH, MeCN, or ClCH2CH2Cl was the solvent under
standard reaction conditions, enamine substrate 1a decomposed
completely after irradiation with blue LEDs for 5 h. Only with
catalytic amounts of fac-Ir(ppy)3 in DMSO solution could we
produce the indole skeleton from simple enamines under air
atmosphere, indicating that DMSO might serve as the oxidant in
this reaction. However, this assumption is not the case because
emission of fac-Ir(ppy)3 was not quenched by DMSO (Figure
S1), and the sulfur free radical was not captured by electron spin
resonance (ESR) (Figure S8). Notably, the solution color
changed from bright yellow to brown except for DMSO during
the reaction process. To monitor the reaction in different
solvents, steady-state spectroscopy was subsequently employed
(Figure S2−5). With respect to the absorption spectral changes
as a function of illumination time, the use of only DMSO as the
reaction solvent enabled the reaction system to be stable.
To clarify the role of DMSO solvent, we determined the
oxidation/reduction potentials of fac-Ir(ppy)3 and substrate in
different solvents. It was surprising to note that the oxidation/
reduction potentials of fac-Ir(ppy)3 and enamine substrate
changed a lot in different solvents, especially in DMSO (Table
S1). The oxidation potential of substrate 1a was dramatically
increased to 0.90 V vs SCE. As a result, the excited fac-Ir(ppy)3*
and resulting IrIV are unable to oxidize enamine 1a but react with
oxygen yielding a superoxide radical anion (O2•−), which reacts
(Scheme 4).15 All of the results clearly demonstrate that O2
1
was not involved in the formation of indoles, and the real active
oxygen species is the superoxide radical anion (O2•−) in DMSO.
Scheme 4. Mechanistic Experiments
On the basis of previous work and the above results, we
proposed a plausible mechanism for this transformation. As
shown in Scheme 5, fac-Ir(ppy)3 is initially pumped to reach its
Scheme 5. Proposed Mechanism
with enamine 1a for the following transformation. Indeed, we
)
12 (Figure 1b) and
•−
could trap the superoxide radical anion (O2
carbon radical13 (Figure 1f) signals. At the same time, the signal
of singlet oxygen (1O2) was also detected (Figure S10). It is well-
known that enamines with an electron-rich double bond are easy
1
to react with O2 under visible light irradiation and to yield
excited state *IrIII by visible light. The electron-transfer *IrIII to
molecular oxygen (O2) leads to the formation of O2•− and IrIV.
Because *IrIII and IrIV are not oxidative enough to abstract an
electron from N-aryl enamine 1 in DMSO (Table S1), the
generated O2•− is the most likely species in charge of oxidation of
1a to produce the radical intermediate A, with the generation of
HOO−. The resulting radical intermediate A undergoes radical
cyclization to afford B, which is further oxidized by IrIV and
deprotonated to give the desired indole 2 with the completion of
the photocatalytic cycle. The fact that the introduction of a
radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO) into the reaction solution resulted in no conversion
of substrate 1a to indole 2a (Scheme 4) further confirmed that
radicals are involved in our reaction system. No hydrogen
peroxide (H2O2) was detected by in situ 1H NMR analysis after
irradiation of the reaction mixture in DMSO-d6 for 5 h in air at
Figure 1. Electron spin resonance (ESR) spectrum: a solution of
DMPO and fac-Ir(ppy)3 in air-saturated DMSO (a) without irradiation
and (b) upon irradiation with blue LEDs for 10 s; a solution of enamine
1a, DMPO, and fac-Ir(ppy)3 in deaerated DMSO (c) without irradiation
and (d) upon irradiation with blue LEDs for 30 s; a solution of enamine
1a, DMPO, and fac-Ir(ppy)3 in air-saturated DMSO (e) without
irradiation and (f) upon irradiation with blue LEDs for 30 s.
C
DOI: 10.1021/acs.orglett.7b01367
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(2) (a) Shen, M.; Li, G.; Lu, B. Z.; Hossain, A.; Roschangar, F.; Farina,
V.; Senanayake, C. H. Org. Lett. 2004, 6, 4129−4132. (b) Ackermann,
L.; Sandmann, R.; Villar, A.; Kaspar, L. T. Tetrahedron 2008, 64, 769−
777. (c) Cui, X.; Li, J.; Fu, Y.; Liu, L.; Guo, Q.-X. Tetrahedron Lett. 2008,
49, 3458−3462. (d) Stuart, D. R.; Bertrand-Laperle, M.; Burgess, K. M.
N.; Fagnou, K. J. Am. Chem. Soc. 2008, 130, 16474−16475. (e) Shi, Z.;
Zhang, C.; Li, S.; Pan, D.; Ding, S.; Cui, Y.; Jiao, N. Angew. Chem., Int. Ed.
2009, 48, 4572−4576. (f) Ackermann, L.; Lygin, A. V. Org. Lett. 2012,
14, 764−767.
(3) (a) Gogoi, A.; Guin, S.; Rout, S. K.; Patel, B. K. Org. Lett. 2013, 15,
1802−1805. (b) Xia, X.-F.; Zhang, L.-L.; Song, X.-R.; Niu, Y.-N.; Liu, X.-
Y.; Liang, Y.-M. Chem. Commun. 2013, 49, 1410−1412. (c) Gogoi, A.;
Modi, A.; Guin, S.; Rout, S. K.; Das, D.; Patel, B. K. Chem. Commun.
2014, 50, 10445−10447. (d) Chen, Y.-Y.; Chen, J.-H.; Zhang, N.-N.; Ye,
L.-M.; Zhang, X.-J.; Yan, M. Tetrahedron Lett. 2015, 56, 478−481.
(4) (a) Hegedus, L. S.; Allen, G. F.; Waterman, E. L. J. Am. Chem. Soc.
1976, 98, 2674−2676. (b) Hegedus, L. S.; Allen, G. F.; Bozell, J. J.;
Waterman, E. L. J. Am. Chem. Soc. 1978, 100, 5800−5807. (c) Odle, R.;
Blevins, B.; Ratcliff, M.; Hegedus, L. S. J. Org. Chem. 1980, 45, 2709−
2710. (d) Tietze, L. F.; Buhr, W. Angew. Chem., Int. Ed. Engl. 1995, 34,
1366−1368. (e) Latham, E. J.; Stanforth, S. P. Chem. Commun. 1996,
2253−2254. (f) Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105, 2873−
2920.
room temperature (Figure S14), while the water peak (H2O)
increased suggesting that the molecular oxygen was finally
converted to H2O rather than H2O2. The generated H2O2 could
participate in the catalytic cycle and ultimately convert to H2O as
the byproduct (see details in Figure S13−15).
In summary, we have developed a straightforward strategy for
indole synthesis via radical intramolecular cyclization in DMSO
solution under extremely mild reaction conditions, using fac-
Ir(ppy)3 as the single photosensitizer in air without any additives.
Investigations of the mechanism demonstrates that the super-
oxide radical anion (O2•−) generated by single electron transfer
from the photosensitizer to molecular oxygen is essential to
initiate the cyclization of enamines. Among various solvents used
in this work, DMSO is unique because it enhances the oxidation
potential of enamines, thus facilitating the electron transfer
•−
process to generate O2 and simultaneously preventing the
1
enamines from destruction by O2 to keep the stability of the
reaction system. Because of these attributes, various N-aryl
enamines can be successfully converted to their corresponding
indoles in good to excellent yields. Compared with traditional
methods, our strategy is a simple, mild, green, and practical tool
for the synthesis of an indole skeleton that is widely pursued in
chemistry and pharmaceutical industries.
(5) (a) Du, Y.; Liu, R.; Linn, G.; Zhao, K. Org. Lett. 2006, 8, 5919−
́ ́
5922. (b) Barluenga, J.; Jimenez-Aquino, A.; Aznar, F.; Valdes, C. J. Am.
Chem. Soc. 2009, 131, 4031−4041. (c) Tan, Y.; Hartwig, J. F. J. Am.
Chem. Soc. 2010, 132, 3676−3677. (d) Gu, L.; Jin, C.; Wang, W.; He, Y.;
Yang, G.; Li, G. Chem. Commun. 2017, 53, 4203−4206.
ASSOCIATED CONTENT
* Supporting Information
■
S
(6) (a) Wagaw, S.; Yang, B. H.; Buchwald, S. L. J. Am. Chem. Soc. 1998,
120, 6621−6622. (b) Stokes, B. J.; Liu, S.; Driver, T. G. J. Am. Chem. Soc.
2011, 133, 4702−4705. (c) Nanjo, T.; Tsukano, C.; Takemoto, Y. Org.
Lett. 2012, 14, 4270−4273. (d) Wei, Y.; Deb, I.; Yoshikai, N. J. Am.
Chem. Soc. 2012, 134, 9098−9101. (e) Liu, B.; Song, C.; Sun, C.; Zhou,
S.; Zhu, J. J. Am. Chem. Soc. 2013, 135, 16625−16631. (f) Yan, H.; Wang,
H.; Li, X.; Xin, X.; Wang, C.; Wan, B. Angew. Chem., Int. Ed. 2015, 54,
10613−10617. (g) Li, X.; Liang, D.; Huang, W.; Zhou, H.; Li, Z.; Wang,
B.; Ma, Y.; Wang, H. Tetrahedron 2016, 72, 8442−8448.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b01367.
Experimental procedures, methods, and product charac-
terizations (PDF)
AUTHOR INFORMATION
■
(7) (a) Wurtz, S.; Rakshit, S.; Neumann, J. J.; Droge, T.; Glorius, F.
Corresponding Author
*E-mail: lzwu@mail.ipc.ac.cn.
ORCID
̈
̈
Angew. Chem., Int. Ed. 2008, 47, 7230−7233. (b) Neumann, J. J.;
Rakshit, S.; Droge, T.; Wurtz, S.; Glorius, F. Chem. - Eur. J. 2011, 17,
̈
̈
7298−7303.
(8) (a) Bernini, R.; Fabrizi, G.; Sferrazza, A.; Cacchi, S. Angew. Chem.,
Int. Ed. 2009, 48, 8078−8081. (b) Yu, W.; Du, Y.; Zhao, K. Org. Lett.
2009, 11, 2417−2420. (c) Guan, Z.-H.; Yan, Z.-Y.; Ren, Z.-H.; Liu, X.-
Y.; Liang, Y.-M. Chem. Commun. 2010, 46, 2823−2825.
(9) (a) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev.
2013, 113, 5322−5363. (b) Romero, N. A.; Nicewicz, D. A. Chem. Rev.
2016, 116, 10075−10166. (c) Shaw, M. H.; Twilton, J.; MacMillan, D.
W. C. J. Org. Chem. 2016, 81, 6898−6926.
Xin Jiang: 0000-0002-7836-1784
Bin Chen: 0000-0003-0437-1442
Chen-Ho Tung: 0000-0001-9999-9755
Li-Zhu Wu: 0000-0002-5561-9922
Notes
The authors declare no competing financial interest.
(10) Zoller, J.; Fabry, D. C.; Ronge, M. A.; Rueping, M. Angew. Chem.,
Int. Ed. 2014, 53, 13264−13268.
ACKNOWLEDGMENTS
■
(11) Wu, C.-J.; Meng, Q.-Y.; Lei, T.; Zhong, J.-J.; Liu, W.-Q.; Zhao, L.-
M.; Li, Z.-J.; Chen, B.; Tung, C.-H.; Wu, L.-Z. ACS Catal. 2016, 6,
4635−4639.
(12) (a) Dikalov, S.; Jiang, J.; Mason, R. P. Free Radical Res. 2005, 39,
825−836. (b) Liu, Q.; Li, Y.-N.; Zhang, H.-H.; Chen, B.; Tung, C.-H.;
Wu, L.-Z. Chem. - Eur. J. 2012, 18, 620−627. (c) Wu, C.-J.; Zhong, J.-J.;
Meng, Q.-Y.; Lei, T.; Gao, X.-W.; Tung, C.-H.; Wu, L.-Z. Org. Lett. 2015,
17, 884−887.
Financial support for this research from the Ministry of Science
and Technology of China (2013CB834804, 2014CB239402, and
2013CB834505), the National Natural Science Foundation of
China (21390404 and 91427303), the Strategic Priority
Research Program of the Chinese Academy of Science
(XDB17030400), and the Chinese Academy of Sciences is
gratefully acknowledged.
(13) (a) Barr, D. P.; Mason, R. P. J. Biol. Chem. 1995, 270, 12709−
12716. (b) Zhang, G.; Zhang, L.; Yi, H.; Luo, Y.; Qi, X.; Tung, C.-H.;
Wu, L.-Z.; Lei, A. Chem. Commun. 2016, 52, 10407−10410.
(14) Sun, H.; Yang, C.; Gao, F.; Li, Z.; Xia, W. Org. Lett. 2013, 15, 624−
627.
(15) (a) Ouannes, C.; Wilson, T. J. Am. Chem. Soc. 1968, 90, 6527−
6528. (b) Silverman, S. K.; Foote, C. S. J. Am. Chem. Soc. 1991, 113,
7672−7675. (c) Sun, J.-G.; Yang, H.; Li, P.; Zhang, B. Org. Lett. 2016,
18, 5114−5117.
REFERENCES
■
(1) (a) Somei, M.; Yamada, F. Nat. Prod. Rep. 2004, 21, 278−311.
(b) Somei, M.; Yamada, F. Nat. Prod. Rep. 2005, 22, 73−103. (c) Smart,
B. P.; Oslund, R. C.; Walsh, L. A.; Gelb, M. H. J. Med. Chem. 2006, 49,
2858−2860. (d) Kruger, K.; Tillack, A.; Beller, M. Adv. Synth. Catal.
̈
2008, 350, 2153−2167. (e) Kochanowska-Karamyan, A. J.; Hamann, M.
T. Chem. Rev. 2010, 110, 4489−4497. (f) Stuart, D. R.; Alsabeh, P.;
Kuhn, M.; Fagnou, K. J. Am. Chem. Soc. 2010, 132, 18326−18339.
(g) Vicente, R. Org. Biomol. Chem. 2011, 9, 6469−6480.
D
DOI: 10.1021/acs.orglett.7b01367
Org. Lett. XXXX, XXX, XXX−XXX