Tandem iridium-catalyzed decarbonylative c-h activation of indole: Sacrificial electron-rich ketone-assisted bis-arylsulfenylation

Article abstract of DOI:10.1021/acs.orglett.1c00829

Described herein is a decarbonylative tandem C-H bis-arylsulfenylation of indole at the C2 and C4 C-H bonds through the use of pentamethylcyclopentadienyl iridium dichloride dimer ([Cp?IrCl2]2) catalyst and disulfides. A new sacrificial electron-rich adamantoyl-directing group facilitates indole C-H bis-functionalization with a traceless in situ removal. Various differently substituted disulfides can be easily accommodated in this reaction by a coordination to Ir(III) through the formation of six- and five-membered iridacycles at the C2 and C4 positions, respectively. Mechanistic studies show that a C-H activation-induced C-C activation is involved in the catalytic cycle.

Full text of DOI:10.1021/acs.orglett.1c00829

pubs.acs.org/OrgLett
Letter
Tandem Iridium-Catalyzed Decarbonylative C−H Activation of
Indole: Sacrificial Electron-Rich Ketone-Assisted Bis-arylsulfenylation
Subban Kathiravan,* Prasad Anaspure, Tianshu Zhang, and Ian A. Nicholls*
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ABSTRACT: Described herein is a decarbonylative tandem C−H bis-arylsulfenylation of indole at the C2 and C4 C−H bonds
through the use of pentamethylcyclopentadienyl iridium dichloride dimer ([Cp*IrCl2]2) catalyst and disulfides. A new sacrificial
electron-rich adamantoyl-directing group facilitates indole C−H bis-functionalization with a traceless in situ removal. Various
differently substituted disulfides can be easily accommodated in this reaction by a coordination to Ir(III) through the formation of
six- and five-membered iridacycles at the C2 and C4 positions, respectively. Mechanistic studies show that a C−H activation-induced
C−C activation is involved in the catalytic cycle.
ndoles are the fourth most-prominent heterocyclic motif
present in currently marketed drugs and pharmaceuticals.1
H functionalization using readily removable directing groups
remains a highly desirable challenge.
I
The transition-metal-catalyzed C−H functionalization of
indole provides access to a broad array of functionalities,2
and indole is of strategic importance, as it overcomes
limitations associated with classical reactions by circumventing
the need for prefunctionalization, and it provides an efficient
atom and step economy.3
Thioethers are frequently found in pharmaceutical agents,
polymeric materials, and biologically active natural products.13
Over the past few years the use of C−H activation reactions
has emerged as a powerful tool for thioether preparation.14 Yu
and co-workers have reported ligand-promoted Rh(III)-
catalyzed aryl thiolation reactions using amide directing
groups,15 and Daugulis presented an aryl sulfenylation of
benzoic acid derivatives using bidendate aminoquinoline
directing groups.16 Despite these advances the examples of
the arylthiolation of indoles remain extremely limited, with the
regiocontrolled C2/C4 methyl thiolation of indoles under Rh-
catalyzed conditions using oxime as a directing group by
Samatha et al. the only example reported.17 With the above
background, we envisioned that a removable directing group
for the arylsulfenylation using an iridium catalyst would
provide a new complementary method for indole C−H
functionalization. However, there are a number of challenges
associated with this proposal, including (1) the deactivation of
reactive iridacycles through sulfur ligation, (2) the competition
between five- and six-membered iridacycle pathways involving
the C2 and C4 positions, respectively, and (3) the possibility
of undesired side-product formation.
Many of the methods used for the C−H functionalization of
indole at the C2 or C4 positions involve nonremovable
directing-group assistance.4 For example, a Pd-catalyzed C−H
alkenylation at the C4 position has been described by Jia using
an amino acid as a directing group.5 Prabhu and co-workers
have demonstrated a Ru-catalyzed C−H alkenylation using the
formyl group to control the selectivity at the C4 position.6
Later they studied Rh- and Ru-catalyzed C−H alkenylations
using complementary acetyl and trifluoromethylacetyl groups
for the regioselective C−H activation reaction for controlling
selectivity at C2 and C4.7 Zhang has shown decarboxylative
C2/C4 C−H alkenylation reactions using a Rh catalyst.8 An
iridium-catalyzed C4 C−H amination has been disclosed
independently by Prabhu and You.9 The Pd-catalyzed C4
arylation was studied by Zhi, and the acetyl-directing group has
been removed in a separate step.10 Recently, Miura et al.
reported the use of thiomethyl ether as an efficient directing
group for C4 C−H functionalization.11 In another study, You
described a pivaloyl group-assisted C2/C4 heteroarylation of
indoles by a controlled metalation tuning.12 However, in all the
above cases stoichiometric quantities of reagents are required
to remove the directing group, which significantly limits the
utility of these approaches in a synthesis. Accordingly, the
development of clean and user-friendly methods for indole C−
Received: March 9, 2021
Published: April 28, 2021
© 2021 The Authors. Published by
American Chemical Society
https://doi.org/10.1021/acs.orglett.1c00829
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Thus far, the established indole C−H functionalization
directing groups have predominantly afforded six-membered
metallacycles rather than their less stable five-membered
counterparts.18 Inspired by the electron-rich ketone-assisted
sp2 C−H activation of ortho C−H bonds, we hypothesized
that the readily accessible and inexpensive adamantoyl group
could be used to generate dual metallacycles to facilitate a C−S
bond formation (Scheme 1). This choice was further
Table 1. Optimization of Reaction Conditions and Control
Experiments
a
b
entry
deviation from above
yield (%)
1
2
3
PivOH
1-AdCOOH
Ag2O
17
35
15
Scheme 1. This Work ProposalIridium-Catalyzed C−H
Activation of Indole
4
AgOAc
28
5
6
7
8
AgF
NR
55
16
NR
35
Cu(OAc)2
DCM as solvent
under air
9
at 60 °C
10
11
12
at RT
[RuCl2(p-cymene)2]2
[RhCp*Cl2]2
NR
NR
50
a
Reaction conditions: 1a (0.17 mmol), 2a (0.25 mmol), [IrCp*Cl2]2
motivated by its utility as a directing group in C−H activation
reactions for iridium-catalyzed amination and palladium-
catalyzed amidation, among others.19 Its use in conjunction
with indole C−H functionalization was yet to be examined.
Here, we explored and demonstrated the iridium(III)-
catalyzed decarbonylative direct arylsulfenylation of indole at
C2/C4 C−H bonds.
(5 mol %), AgNTf2 (30 mol %), Ag2CO3 (2.0 equiv), 1,2-DCE (2
mL), 120 °C, 22 h. Isolated yield; NR = no reaction.
b
dium dichloride dimer ([RhCp*Cl2]2), both known for their
capacity to catalyze C−H transformations, were investigated,
but neither gave the product in a better yield (Table 1, entries
12 & 13).
At the outset, to test the hypothesis we chose 1a as test
substrate to probe the reactivity of iridium(III) catalysis (using
pentamethylcyclopentadienyl iridium dichloride dimer
([IrCp*Cl2]2)) in the arylsulfenylation of 1a with disulifide
2a, AgNTf2 as a silver additive, and silver carbonate as a
terminal oxidant. To our surprise, when the initial reactions
were performed using anhydrous 1,2-dichloroethane (DCE) as
solvent at 120 °C for 22 h, the bis-aryl sulfenylated C−H
activation product 3a was obtained in 68% isolated yield with
no evidence (thin-layer chromatography (TLC)) of mono-
substituted indole products. The addition of acidic additives,
L-MPAA ligands,20 which are commonly used in 3d and 4d
metal catalysis to promote electrophilic metalation processes,
gave lower isolated yields indicating that this reaction does not
follow an electrophilic metallation pathway (Table 1, entries 1
& 2). Changing the oxidant from silver carbonate to Ag2O or
to AgOAc reduced the product formation (Table 1, entries 3 &
4), whereas the use of AgF gave no product (Table 1, entry 5).
Silver carbonate could be replaced with Cu(OAc)2, albeit with
a reduced yield, suggesting that the acetate ligand is not
required for the coordination of the metal center (Table 1,
entry 7). Changing the solvent from DCE to dichloromethane
also resulted in a lower yield (Table 1, entry 8). When the
reaction was performed under air, no consumption of starting
materials was observed (Table 1, entry 9). A decrease of the
reaction temperature to 60 °C lowered the yield to 35% (Table
1, entry 10), and at room temperature no reaction was
observed (Table 1, entry 11). Two different catalysts, namely,
[RuCl2(p-cymene)2]2 and pentamethylcyclopentadienyl rho-
Having established optimal conditions for this iridium(III)-
catalyzed C−H activation, we focused our attention on
exploring the scope of the directing ketones on the reaction
by using a series of carbonyl substituents. To our delight, the
more electron-rich adamantoyl derivative gave the product in
the highest yield, 68%. The acetyl and pivaloyl groups gave the
expected products in 6 and 25% yields, respectively, thus
illustrating the importance of having an electron-rich ketone
for generating five- and six-membered metallacycles. Interest-
ingly, the formyl group also delivered the decarbonylative aryl
sulfenated product in 33% yield.
With the optimized reaction conditions in hand, we first
examined the effect of substitution of the disulfide on reaction
with the model substrate 1a (Table 2). Both electron-donating
and electron-withdrawing groups were tolerated under the
reaction conditions, and the reaction efficiency was found to be
significantly affected by disulfide aromatic ring substituents.
The 2-Me (3b) group substitutions gave the product in 34%
yield, but the less sterically hindered 3-Me (3c) and 4-Me (3d)
gave 50% and 55% yields. We then explored the influence of
halogenated (Cl, Br, & F) disulfides and found that,
irrespective of their position (ortho, meta, or para), all gave
the products (3e−3l) in moderate to good yields (38−70%),
the products being amenable for further transformations. The
reaction proceeded smoothly with trifluoromethyl (3m, 43%)
and tert-butyl (3n, 37%) substituted disulfides. Furthermore,
the use of disubstituted bulky disulfides provided the products
(3o−3s) in moderate yields (48−60%). To our surprise, we
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a b
,
a b
,
Table 2. Scope of Disulfides
Table 3. Scope of Indoles
a
Reaction conditions: substrate 1 (0.17 mmol, 1 equiv), disulfide 2
(0.25 mmol, 2 equiv), [IrCp*Cl2]2 (5 mol %), AgNTf2 (30 mol %),
Ag2CO3 (0.65 mmol, 2 equiv), 1,2-DCE (2 mL), 120 °C, 22 h.
b
Isolated yield.
and electron-deficient substituted disulfides (2d & 2m) with
1a showed that an inherently higher reactivity was observed
with the electron-deficient disulfide. Additionally, we did not
observe the cross-sulfenylation product. This indicates that the
reaction does not proceed via a concerted metallation/
deprotonation (CMD) (Scheme 2a). We also found that the
use of thiol (5) under these oxidative conditions generated the
disulfide (6) as the only major product, and starting material
(1a) was recovered, which further indicates that the disulfides
are oxidatively added to the metal center during the C−H
activation (Scheme 2b). Finally, reactions in deuterated
solvents were performed (Scheme 2c). We observed 10%
deuteration at C2 and 15% deuteration at C4 in the absence of
silver carbonate, which suggests that the silver carbonate
functions as both a promoter and an oxidant (Scheme 2c-1).
Interestingly, when we studied the reaction in the presence of
Ag2CO3, 82% of the D/H exchange was observed at the C4/
C2 positions. This is indicative of the efficient formation of six-
and five-membered iridacycles (Scheme 2c-2). This further
emphasizes the role of silver carbonate in the mechanism, as
this reaction needed a second silver additive in stoichiometric
quantities to initiate the cyclometalation. The extent of the D/
H exchange observed when using the electron-deficient ketone
N-methyl-3-acetyl indole was lower at C2 (16%) than at C4
(51%). This suggests that the acetyl directing group
preferentially forms the more stable six-membered iridacycle
(Scheme 2c-3). We also extended this study to include the
pivaloyl indole derivative, in which case a C4/C2 D/H
exchange comparable to that of the more electron-rich
adamantyl derivative was observed (Scheme 2c-4). We made
several attempts to obtain the crystal structure of an iridacycle,
a
Reaction conditions: substrate 1 (0.17 mmol, 1 equiv), disulfide 2
(0.25 mmol, 2 equiv), [IrCp*Cl2]2 (5 mol %), AgNTf2 (30 mol %),
Ag2CO3 (0.65 mmol, 2 equiv), 1,2-DCE (2 mL), 120 °C, 22 h.
b
Isolated yield.
used various aliphatic disulfides and 2-pyridine disulfide in this
study but without success (see the Supporting Information).
Encouraged by the broad scope of disulfides accepted by the
model substrate 1a, we proceeded to explore the reaction
tolerance to an indole substitution (Table 3). To our delight,
indoles bearing Cl (4b), Br (4c), I (4d), F (4e), CN (4f), and
COOMe (4g) at the C5 position were all tolerated. C6
substituted indoles (1h−1j) with electron-donating and
electron-withdrawing groups were all compatible and provided
the products (4h−4j) in 70−71% yields. The C7 methyl-
substituted indole also gave the product (4k) in 32% yield.
Given the synthetic applicability of the decarbonylative
iridium(III)-catalyzed C−H activation, we devised a series of
control experiments in order to delineate the mechanism
underlying this reaction (Scheme 2). To this end, an
intermolecular competition experiment between electron-rich
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Scheme 2. Mechanistic Studies and Proposed Mechanism
to characterize the intermediate, but without success. The
robustness of the iridium(III) catalysis was demonstrated by its
use in a gram-scale (1 mmol) reaction, where no significant
loss of catalytic activity was observed and with the product
isolated in 52% (0.21 g) yield (Scheme 2d).
On the basis of the evidence from these mechanistic studies
and in combination with reported data,21 we propose that the
mechanism proceeds through a tandem pathway. Initially, the
catalyst coordinates with either the C4 or C2 C−H bond and
the electron-rich ketone to form either the corresponding six-
membered (A, preferred) or five-membered (D) metallacycle,
respectively. The oxidative addition of disulfide 2a affords the
complex B or E, which upon reductive elimination generates
either complex C or F. After the reaction by both pathways, the
iridacycle G is obtained following a carbonyl group dislocation.
The high temperature can be anticipated to play a crucial role
in decarbonylation.12 In the final step reductive elimination
provides the product 3a, and the reoxidation by silver
regenerates the active catalyst (Scheme 2e).
CONCLUSIONS
■
In summary, we have reported the first tandem decarbonylative
arylsulfenylation of indoles at the C2/C4 positions through an
iridium(III) catalyst. The electron-rich adamantyl ketone
directing group presented here facilitates the formation of
both six- and five-membered iridacycles and is amenable to
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2015, 89, 421−441. (f) Bandini, M.; Eichholzer, A. Catalytic
functionalization of indoles in a new dimension. Angew. Chem., Int.
Ed. 2009, 48, 9608−9644. (g) Humphrey, G. R.; Kuethe, J. T.
Practical methodologies for the synthesis of indoles. Chem. Rev. 2006,
106, 2875−2911.
reaction with a broad scope of disulfides with good yields.
Further efforts to develop decarbonylative transition-metal-
catalyzed regioselective C−H functionalizations are currently
underway in our laboratory.
(2) (a) Lebrasseur, N.; Larrosa, I. Recent Advances in the C2 and
C3 regioselective direct arylation of indoles. Adv. Heterocycl. Chem.
2012, 105, 309. (b) Sandtorv, A. H. Transition metal-catalyzed C-H
activation of indoles. Adv. Synth. Catal. 2015, 357, 2403−2435.
(c) Toutov, A. A.; Liu, W.-B.; Betz, K. N.; Fedorov, A.; Stoltz, B. M.;
Grubbs, R. H. Silylation of C-H bonds in aromatic heterocycles by an
earth-abundant metal catalyst. Nature 2015, 518, 80. (d) Jiao, L.;
Herdtweck, E.; Bach, T. Pd(II)-catalysed regioselective 2-alkylation of
indoles via a norbornene mediated C-H activation: Mechanism and
applications. J. Am. Chem. Soc. 2012, 134, 14563−14572.
(3) (a) Rej, S.; Chatani, N. Rhodium-catalyzed C(sp2) or C(sp3)-H
bond functionalization assisted by removal directing groups. Angew.
Chem., Int. Ed. 2019, 58, 8304−8329. and references cited therein.
(b) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Rhodium-catalyzed C-
C bond formation via heteroatom-directed C-H bond activation.
Chem. Rev. 2010, 110, 624−655.
(4) (a) Leitch, J. A.; Bhonoah, Y.; Frost, C. G. Beyond C2 and C3:
Transition-metal-catalyzed C-H functionalization of indole. ACS
Catal. 2017, 7, 5618−5627. (b) Kalepu, J.; Gandeepan, P.;
Ackermann, L.; Pilarski, L. T. C4H indole functionalization:
precedent and prospects. Chem. Sci. 2018, 9, 4203−4216.
(5) Liu, Q.; Li, Q.; Ma, Y.; Jia, Y. Direct olefination at the C-4
position of tryptophan via C-H activation: Application to biomimetic
synthesis of Clavicipitic acid. Org. Lett. 2013, 15, 4528−4531.
(6) Lanke, V.; Ramaiah Prabhu, K. Regioselective synthesis of 4-
substituted indoles via C-H activation: A ruthenium catalyzed novel
directing group strategy. Org. Lett. 2013, 15, 6262−6265.
(7) Lanke, V.; Bettadapur, K. R.; Prabhu, K. R. Electronic nature of
ketone directing group as a key to control C-2 vs C-4 alkenylation of
indoles. Org. Lett. 2016, 18, 5496−5499.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c00829.
■
sı
Details of synthetic procedures, NMR & HRMS spectra
(PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Subban Kathiravan − Bioorganic & Biophysical Chemistry
Laboratory, Linnaeus University Centre for Biomaterials
Chemistry, Department of Chemistry & Biomedical Chemical
Sciences, Linnaeus University, Kalmar 39182, Sweden;
orcid.org/0000-0003-0774-2528;
Email: suppan.kathiravan@lnu.se
Ian A. Nicholls − Bioorganic & Biophysical Chemistry
Laboratory, Linnaeus University Centre for Biomaterials
Chemistry, Department of Chemistry & Biomedical Chemical
Sciences, Linnaeus University, Kalmar 39182, Sweden;
orcid.org/0000-0002-0407-6542; Email: ian.nicholls@
lnu.se
Authors
Prasad Anaspure − Bioorganic & Biophysical Chemistry
Laboratory, Linnaeus University Centre for Biomaterials
Chemistry, Department of Chemistry & Biomedical
Chemical Sciences, Linnaeus University, Kalmar 39182,
Sweden
Tianshu Zhang − Bioorganic & Biophysical Chemistry
Laboratory, Linnaeus University Centre for Biomaterials
Chemistry, Department of Chemistry & Biomedical
Chemical Sciences, Linnaeus University, Kalmar 39182,
Sweden
(8) Chen, H.; Lin, C.; Xiong, C.; Liu, Z.; Zhang, Y. One-pot
synthesis of fluorescent 2,4-dialkenylindoles by rhodium-catalyzed
dual C-H functionalization. Org. Chem. Front. 2017, 4, 455−459.
(9) (a) Lanke, V.; Prabhu, K. R. Iridium(III) catalyzed regioselective
amidation of indoles at the C4-position using weak coordinating
groups. Chem. Commun. 2017, 53, 5117−5120. (b) Chen, S.; Feng,
B.; Zheng, X.; Yin, J.; Yang, S.; You, J. Iridium-catalyzed direct
regioselective C4-amidation of indoles under mild conditions. Org.
Lett. 2017, 19, 2502−2505.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c00829
(10) Yang, Y.; Gao, P.; Zhao, Y.; Shi, Z. Regiocontrolled direct C-H
arylation of indoles at the C4 and C5 positions. Angew. Chem., Int. Ed.
2017, 56, 3966−3971.
Notes
(11) (a) Kona, C.; Nishii, Y.; Miura, M. Thioether-directed selective
C4 C-H alkenylation of indoles under rhodium catalysis. Org. Lett.
2018, 20, 4898−4901.
The authors declare no competing financial interest.
(12) Chen, S.; Zhang, M.; Su, R.; Chen, X.; Feng, B.; Yang, Y.; You,
J. C2/C4 regioselective heteroarylation of indoles by tuning C-H
metalation modes. ACS Catal. 2019, 9, 6372−6379.
ACKNOWLEDGMENTS
■
We thank Linnaeus University, the Swedish Research Council,
(2014-4573), the Crafoord Foundation (2019-0925) (2020-
0775), and the Helge Ax:son Johnsons Foundation (2019-
0318) for generous funding.
(13) (a) Hoyle, C. E.; Lowe, A. B.; Bowman, C. N. Thiol-click
chemistry: a multifaceted toolbox for small molecule and polymer
synthesis. Chem. Soc. Rev. 2010, 39, 1355−1387.
(14) (a) Gandeepan, P.; Koeller, J.; Ackermann, L. Expedient C-H
chalcogenation of indolines and indoles by positional selective copper
catalysis. ACS Catal. 2017, 7, 1030−1034. (b) Liu, C.; Fang, Y.;
Wang, S.-Y.; Ji, S.-J. RhCl3.3H2O-catalyzed ligand-enabled highly
regioselective thiolation of acrylic acids. ACS Catal. 2019, 9, 8910−
8915. For a comprehensive list, see ref 15.
(15) Kang, Y.-S.; Zhang, P.; Li, M.-Y.; Chen, Y.-K.; Xu, H.-J.; Zhao,
J.; Sun, W. Y.; Yu, J.-Q.; Lu, Y. Ligand-promoted Rh(III)-catalyzed
thiolation of benzamides with a broad disulfide scope. Angew. Chem.,
Int. Ed. 2019, 58, 9099−9103.
(16) Tran, L. D.; Popov, I.; Daugulis, O. Copper-promoted
sulfenylation of sp2 C-H bonds. J. Am. Chem. Soc. 2012, 134,
18237−18240.
REFERENCES
■
(1) (a) Kawasaki, T.; Higuchi, K. Simple indole alkaloids and those
with a nonrearranged monoterpenoid unit. Nat. Prod. Rep. 2005, 22,
761−793. (b) Sharma, V.; Kumar, P.; Pathak, D. J. Biological
importance of the indole nucleus in recent years: A comprehensive
review. J. Heterocycl. Chem. 2010, 47, 491−502. (c) Taylor, R. D.;
MacCoss, M.; Lawson, A. D. G. Rings in Drugs. J. Med. Chem. 2014,
57, 5845−5859. (d) Kochanowska-Karamyan, A. J.; Hamann, M. T.
Marine indole alkaloids: Potential new drug leads for the control of
depression and anxiety. Chem. Rev. 2010, 110, 4489−4497.
(e) Zhang, M.-Z.; Chen, Q.; Yang, G.-F. A review on recent
developments of indole-containing antiviral agents. Eur. J. Med. Chem.
3335
https://doi.org/10.1021/acs.orglett.1c00829
Org. Lett. 2021, 23, 3331−3336

Organic Letters
pubs.acs.org/OrgLett
Letter
(17) Maity, S.; Karmakar, U.; Samanta, R. Regiocontrolled direct C4
and C2 methyl thiolation of indoles under rhodium-catalyzed mild
conditions. Chem. Commun. 2017, 53, 12197−12200.
(18) (a) Borah, A. J.; Shi, Z. Palladium-catalyzed regioselective C-H
fluoroalkylation of indoles at the C4 position. Chem. Commun. 2017,
53, 3945−3948. (b) Pradhan, S.; De, P. B.; Punniyamurthy, T. Weak
cordincation-guided regioselective direct redox-neutral C4 allylation
of indoles with Morita-Baylis-Hillman adducts. Org. Lett. 2019, 21,
9898−9903.
(19) (a) Kim, H.; Shin, K.; Chang, S. Iridium-catalysed C-H
amination with anilines at room temperature: Compatibility of
iridacycles with external oxidants. J. Am. Chem. Soc. 2014, 136, 5904−
5907. (b) Xiao, B.; Gong, T.-J.; Xu, J.; Liu, Z.-J.; Liu, L. Palladium
catalysed intermolecular directed C-H amidation of aromatic ketones.
J. Am. Chem. Soc. 2011, 133, 1466−1474.
(20) Li, G.; Leow, D.; Wan, L.; Yu, J.-Q. Ether-directed ortho-C-H
olefination with a palladium(II)/Monoprotected amino acid catalyst.
Angew. Chem., Int. Ed. 2013, 52, 1245−1247.
(21) Liu, X.; Li, X.; Liu, H.; Guo, Q.; Lan, J.; Wang, R.; You, J.
Aldehyde as a traceless directing group for Rh(III)-catalysed C-H
activation: A facile access to diverse indolo[1,2-a]quinolines. Org. Lett.
2015, 17, 2936−2939.
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