Cobalt-Catalyzed Direct Carbonylative Synthesis of Free (NH)-Benzo[ cd]indol-2(1 H)-ones from Naphthylamides

Article abstract of DOI:10.1021/acs.orglett.9b02037

A cobalt-catalyzed C-H carbonylation of naphthylamides for the synthesis of benzo[cd]indol-2(1H)-one scaffolds has been developed. The reaction employs a traceless directing group and uses benzene-1,3,5-triyl triormate as the CO source, affording various free (NH)-benzo[cd]indol-2(1H)-ones in moderate to high yields (up to 88%). Using this protocol, the total synthesis of BET bromodomain inhibitors A and B was accomplished as well.

Full text of DOI:10.1021/acs.orglett.9b02037

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Cobalt-Catalyzed Direct Carbonylative Synthesis of Free
(NH)‑Benzo[cd]indol-2(1H)‑ones from Naphthylamides
Jun Ying,† Lu-Yang Fu,† Guoqiang Zhong,† and Xiao-Feng Wu*,†,‡
†Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People’s Republic of China
‡Leibniz-Institut fu
̈
r Katalyse e. V. an der Universitat Rostock, Albert-Einstein-Straβe 29a, 18059 Rostock, Germany
̈
S
* Supporting Information
ABSTRACT: A cobalt-catalyzed C−H carbonylation of naphthylamides for the synthesis of benzo[cd]indol-2(1H)-one
scaffolds has been developed. The reaction employs a traceless directing group and uses benzene-1,3,5-triyl triormate as the CO
source, affording various free (NH)-benzo[cd]indol-2(1H)-ones in moderate to high yields (up to 88%). Using this protocol,
the total synthesis of BET bromodomain inhibitors A and B was accomplished as well.
enzo[cd]indol-2(1H)-ones are frequently found as a
significant scaffold in a wide range of pharmaceuticals,
prepared from the reaction of 1,8-naphthalic anhydride with
hydroxylammonium chloride.1a,5f,6 However, this reaction is
limited to a very narrow substrate scope. On the other hand,
transition-metal-catalyzed carbonylative transformation of a
C−H bond is a powerful tool in the construction of carbonyl-
containing compounds.7,8 In 2016, Lei and co-workers
reported a novel PdCl2 (10 mol %) and Cu(OAc)2 (30 mol
%) co-catalyzed aerobic C−H bond activation/N-dealkylative
carbonylation of naphthylamines to access benzo[cd]indol-
2(1H)-ones.9 It is noted that C−H bond activation occurs
selectively at the C8 position of the naphthylamines in this
reaction. Under a carbon monoxide and oxygen (2:1)
atmosphere, N,N-dialkylnaphthylamines were transformed
into the corresponding N-alkyl-substituted benzo[cd]indol-
2(1H)-ones in 37−71% yields.
B
dyes, natural products, and biologically active compounds.1−5
For example, as shown in Scheme 1, compounds A and B
Scheme 1. Selected Pharmaceuticals and Natural Products
of Benzo[Cd]indol-2(1H)-ones
In order to enrich the availability of benzo[cd]indol-2(1H)-
ones and overcome the existing challenges, we report here a
cobalt-catalyzed C−H carbonylation of naphthylamides for the
synthesis of various free (NH)-benzo[cd]indol-2(1H)-ones.
With TFBen as a solid and easy manipulation CO source,
moderate to high yields of the desired products can be isolated.
Additionally, this procedure has been applied successfully in
the total synthesis of BET bromodomain inhibitors A and B as
well.
Initially, N-(naphthalen-1-yl)picolinamide 1a was chosen as
the model substrate for the catalytic system establishing
studies. We used 1a to react with TFBen (3.0 equiv) in the
presence of CoCl2 (30 mol %) as the catalyst and Ag2CO3/air
as the oxidant at 130 °C for 20 h. Fortunately, the expected
product 2a was obtained in 38% yield (Table 1, entry 1). The
reaction with Co(OAc)2·4H2O and Co(acac)2 (Table 1,
represent a new and potent class of BET bromodomain
inhibitors exhibiting antitumor and anti-inflammatory activ-
ities.1 Compound C is a lysosome-targeted agent with dual
bioimaging and antimetastatic features in cancer therapy.2
Aristolactams, naturally occurring phenanthrene lactam alka-
loids, have been used as folk medicines with various biological
activities (Scheme 1).3a
Due to the extraordinary structure of benzo[cd]indol-2(1H)-
ones, only a few synthetic approaches have been realized for
their synthesis. Traditionally, benzo[cd]indol-2(1H)-ones are
Received: June 13, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02037
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Letter
a
half conversion after 1 h; the prolonged reaction time is to
make sure the conversion is complete.
Table 1. Screening of the Reaction Conditions
With the optimal reaction conditions in hand, we began
exploring the scope of this carbonylative transformation of
naphthylamides, and the results are summarized in Scheme 2.
a
b
Scheme 2. Scope of Naphthylamides
yield
(%)
entry
catalyst
CoCl2
oxidant
base
addition
1
Ag2CO3/
air
Ag2CO3/
air
Ag2CO3/
air
Ag2CO3/
air
Ag2CO3/
air
Ag2CO3/
air
Ag2CO3/
N2
Et3N
38
16
30
0
2
3
4
5
6
7
Co(OAc)2·
4H2O
Co(acac)2
CoCl2
Et3N
Et3N
CsCO3
KOtBu
DMAP
Et3N
CoCl2
trace
11
CoCl2
CoCl2
42
8
9
10
CoCl2
CoCl2
CoCl2
Ag2O/N2
BQ/N2
Ag2CO3/
N2
Ag2CO3/
N2
Ag2CO3/
N2
Ag2CO3/
N2
Ag2CO3/
N2
Ag2CO3/
N2
Et3N
Et3N
Et3N
13
trace
55
c
cd
,
11
12
13
14
15
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
Et3N
Et3N
Et3N
Et3N
Et3N
TFA
trace
50
cd
,
AcOH
PivOH
cd
e
,
82 (79 )
cd
,
PhCO2H 46
PivOH 69
cdf
,
,
a
Reaction conditions: 1a (0.2 mmol), TFBen (3.0 equiv), catalyst (30
mol %), oxidant (1.5 equiv), base (3.0 equiv), solvent (2.0 mL), 130
b
°C, 20 h. Yields were determined by 1H NMR using 1,3,5-
c
trimethoxybenzene as the internal standard. Oxidant (2.5 equiv).
d
e
f
Additive (1.0 equiv). Isolated yield. Catalyst (20 mol %).
entries 2 and 3) gave reduced yields. Next, a set of bases was
tested, and much lower yields of 2a were achieved (Table 1,
entries 4−6). In addition, when other solvents were used
instead of 1,4-dioxane, inferior results were observed. No
product could be detected when DMSO or THF was used as
the solvent. In the cases of using toluene and MeCN as the
reaction media, 27% and 20% yields can be obtained,
respectively. It was noteworthy that using Ag2CO3 as a sole
oxidant under N2 atmosphere improved the yield to 42%
(Table 1, entry 7). Moreover, changing the oxidant to Ag2O or
BQ hampered the reaction (Table 1, entries 8 and 9). We were
delighted to find that increasing the amount of Ag2CO3 (2.5
equiv) enhanced the reaction outcome, and 55% yield could be
reached (Table 1, entry 10). Finally, a series of acidic additives
were screened (Table 1, entries 11−14). Gratifyingly, employ-
ing PivOH as the additive significantly promoted the reaction
to access 2a in 79% isolated yield (Table 1, entry 13). When
the amount of CoCl2 was reduced, a lower yield of 2a was
produced, even in the presence of ligands (Table 1, entry 15).
Notably, the model system was tested at 110 and 150 °C as
well. A decreased yield (75%) was obtained at 110 °C, and the
yield could be slightly improved by performing the reaction at
150 °C (85%). However, considering the energy cost, we
decided to continue with 130 °C. The reaction can provide
a
Reaction conditions: 1 (0.2 mmol), TFBen (3.0 equiv), CoCl2 (30
mol %), Ag2CO3 (2.5 equiv), Et3N (3.0 equiv), 1,4-dioxane (2.0 mL),
130 °C, 20 h, isolated yields.
Naphthylamides with electron-donating groups at the C4
position could undergo the reaction smoothly to give the
desired products 2b and 2d in high yields. Interestingly, a
compound bearing a methyl group at the C2 position gave
only a trace amount of product 2c, suggesting that the steric
effect plays an important role in this directing-group-assisted
carbonylation. For compounds with halogen substituents, the
reaction can also gave the expected products 2e and 2f in good
yields. It was found that the reaction of substrates with other
electron-withdrawing functional groups such as −CF3, −NO2,
−OCOMe, −OCOEt, and −Ts proceeded well to afford the
corresponding products 2g−k in 36−64% yields. Both
electron-donating and electron-withdrawing groups on the
benzene ring of 4-phenyl-substituted naphthylamides were well
tolerated to give the desired products 2l−2p in high yields.
When 4-naphthyl-substituted naphthylamides were subjected
to the reaction conditions, good yields of the corresponding
B
DOI: 10.1021/acs.orglett.9b02037
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products 2q and 2r were achieved. Notably, compounds
containing furan and thiophene led to the formation of the
desired products 2s and 2t in good yields as well. The reaction
of substrate bearing an alkyne unit at the C4 position afforded
the desired product 2u in 88% yield. For compounds (1v and
1w) having more conjugated systems, product 2v and 2w were
obtained in 88% and 51% yields, respectively. Additionally,
disubstituted naphthylamide gave the expected product 2x in
55% yield. Remarkably, the reaction conditions could be
applied to substrates with a quinoline and isoquinoline
scaffold, albeit in low yields (2y and 2z).
Scheme 4. Effect of Directing Groups in C−H
Carbonylation of Naphthylamides
To demonstrate the scalability and utility of this method, we
conducted a gram-scale experiment and also completed the
total synthesis of BET bromodomain inhibitors A and B
(Scheme 3). The naphthylamide 1a (1.0 g) was treated with
only a trace of 2a, which could be attributed to the steric
hindrance. It was notable that no reaction occurred when Bz as
the directing group was employed. These results indicated that
the coordination of the cobalt catalyst with a N atom on the
directing group was crucial in C−H carbonylation of
naphthylamides. Additionally, the reactions of compounds
bearing other directing groups such as Ts or Boc failed to
proceed.
Scheme 3. Large-Scale Reaction and Total Synthesis of BET
a
Bromodomain Inhibitors A and B
In order to gain some insight into the reaction mechanism,
several control experiments were performed (Scheme 5). First,
Scheme 5. Control Experiments
a
Reagents and conditions: (a) CH3CH2I, NaH, DMF, rt; (b)
HSO3Cl, CHCl3, 0−50 °C; (c) pyrrole, DiPEA, CH2Cl2, rt; (d)
HNO3, AcOH, 0−50 °C, 1 h; (e) Fe, NH4Cl, AcOH, 50 °C, 30 min;
(f) 5-bromo-2-methoxybenzenesulfonyl chloride, CH2Cl2, pyridine, rt.
TFBen (1.75 equiv) under our standard conditions, furnishing
the expected (NH)-benzo[cd]indol-2(1H)-one 2a in 60% yield
(0.4 g; Scheme 3, eq 1). Then alkylation of 2a resulted in
formation of the N-substituted benzo[cd]indol-2(1H)-one 3a.
In the total synthesis of BET bromodomain inhibitors A and B,
treatment of 3a with chlorosulfonic acid gave the sulfonyl
chloride 4a, which was then reacted with pyrrole to access BET
inhibitor A in 55% yield in two steps (Scheme 3, eq 2a).
Additionally, 3a was reacted with nitric acid to produce 5a in
69% yield. Subsequent nitro reduction of 5a with iron formed
6a in 81% yield. Finally, when 6a was treated with 5-bromo-2-
methoxybenzenesulfonyl chloride, BET inhibitor B was
achieved smoothly in 50% yield in three steps (Scheme 3, eq
2b).
Furthermore, we then turned to investigate the effect of
directing groups in this C−H carbonylation of naphthylamides.
A variety of directing groups were introduced to free
naphthylamine and subjected to the standard conditions
(Scheme 4). It showed that pyrazine 1a′ containing an
additional N atom on the pyridine ring afforded the product 2a
in 47% yield. Interestingly, quinolone-2-carboxamide 1b′ gave
with the addition of 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO) as the radical scavenger under our standard
reaction conditions, the desired product 2a was obtained in
77% yield (Scheme 5, eq 1). This results indicating that radical
process did not involve in this reaction. Second, the kH/kD
value of 1.29 was observed when two parallel reactions with 1a
and 1a-d7 were carried out (Scheme 5, eq 2). Finally, the
intermolecular competition experiment afforded the corre-
sponding products 2a and 2a-d6 and gave the kH/kD value of
1.27 (Scheme 5, eq 3). These KIE experiments indicated that
the C−H bond-cleavage step might not be involved in the rate-
determining step.
C
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Organic Letters
Letter
On the basis of the previous reports10−12 and the control
experiments, a plausible mechanism is proposed to account for
the C−H carbonylation of naphthylamides (Scheme 6).
ACKNOWLEDGMENTS
■
We acknowledge financial support from the Zhejiang Natural
Science Fund for Young Scholars (LQ18B020008), Zhejiang
Sci-Tech University (17062078-Y), and National Natural
Science Foundation of China (21772177).
Scheme 6. Plausible Reaction Mechanism
REFERENCES
■
(1) (a) Xue, X.; Zhang, Y.; Liu, Z.; Song, M.; Xing, Y.; Xiang, Q.;
Wang, Z.; Tu, Z.; Zhou, Y.; Ding, K.; Xu, Y. Discovery of
Benzo[cd]indol-2(1H)-ones as Potent and Specific BET Bromodo-
main Inhibitors: Structure-Based Virtual Screening, Optimization, and
Biological Evaluation. J. Med. Chem. 2016, 59, 1565−1579. (b) Feng,
Y.; Xiao, S.; Chen, Y.; Jiang, H.; Liu, N.; Luo, C.; Chen, S.; Chen, H.
Design, Synthesis and Biological Evaluation of Benzo[cd]indol-
2(1H)-ones Derivatives as BRD4 Inhibitors. Eur. J. Med. Chem.
2018, 152, 264−273.
(2) Li, J.; Tian, R.; Ge, C.; Chen, Y.; Liu, X.; Wang, Y.; Yang, Y.;
Luo, W.; Dai, F.; Wang, S.; Chen, S.; Xie, S.; Wang, C. Discovery of
the Polyamine Conjugate with Benzo[cd]indol-2(1H)-one as a
Lysosome-Targeted Antimetastatic Agent. J. Med. Chem. 2018, 61,
6814−6829.
(3) (a) Youn, S. W.; Ko, T. Y.; Kim, Y. H.; Kim, Y. A. Pd(II)/
Cu(II)-Catalyzed Regio- and Stereoselective Synthesis of (E)-3-
Arylmethyleneisoindolin-1-ones Using Air as the Terminal Oxidant.
Org. Lett. 2018, 20, 7869−7874. (b) Benesch, L.; Bury, P.; Guillaneux,
D.; Houldsworth, S.; Wang, X.; Snieckus, V. Directed ortho
Metalation-cross Coupling Connections. Remote Lateral Metalation-
cyclization of 2-Imino-2′-methyl Biaryls to 9-Aminophenanthrenes. A
Synthesis of the Alkaloid Piperolactam C. Tetrahedron Lett. 1998, 39,
961−964.
(4) Strzelczyk, R.; Michalski, R.; Podsiadly, R. Synthesis and
Application of Dyes Derived from Benz[cd]indol-2(1H)-one as
Visible-light-Absorbing Polymerisation Photoinitiators. Color. Technol.
2016, 132, 320−326.
(5) (a) Appelt, K.; Bacquet, R. J.; Bartlett, C. A.; Booth, C. L. J.;
Freer, S. T.; Fuhry, M. A. M.; Gehring, M. R.; Herrmann, S. M.;
Howland, E. F. Design of Enzyme Inhibitors using Iterative Protein
Crystallographic Analysis. J. Med. Chem. 1991, 34, 1925−1934.
(b) Varney, M. D.; Marzoni, G. P.; Palmer, C. L.; Deal, J. G.; Webber,
S.; Welsh, K. M.; Bacquet, R. J.; Bartlett, C. A.; Morse, C. A. Crystal-
structure-based Design and Synthesis of Benz[cd]indole-containing
Inhibitors of Thymidylate Synthase. J. Med. Chem. 1992, 35, 663−
676. (c) Yin, H.; Xu, Y.; Qian, X. Novel Antitumor Agent Family of
1H-Benzo[c,d]indol-2-one with Flexible Basic Side Chains: Synthesis
and Biological Evaluation. Bioorg. Med. Chem. 2007, 15, 1356−1362.
Initially, the Co(II) catalyst coordinates with the naphthyla-
mide 1a and is then oxidized by Ag(I) salt to generate the
Co(III) complex A′. Subsequently, selective C−H bond
activation at the C8 position of 1a leads to the formation of
intermediate B′. Then coordination of CO, generated in situ
from TFBen, gives the acyl Co(III) species C′, which can
undergo reductive elimination to form the Co(I) complex D′.
Finally, hydrolysis of D′ affords the expected product 2a and
releases the Co(I) species. Oxidation of the Co(I) species by
Ag(I) salt regenerates the active Co(II) catalyst.
In conclusion, we have developed an interesting traceless
directing-group-assisted cobalt-catalyzed C−H carbonylation
of naphthylamides using TFBen as the CO source to access
free (NH)-benzo[cd]indol-2(1H)-ones.13 This protocol fea-
tures a wide substrate scope and provides a facile and efficient
method for the total synthesis of BET bromodomain inhibitors
A and B. Further mechanistic studies and synthetic
applications are ongoing in our laboratory.
́
́
(d) Lopez-Rodríguez, M. L.; Porras, E.; Morcillo, M. J.; Benhamu, B.;
Soto, L. J.; Lavandera, J. L.; Ramos, J. A.; Olivella, M.; Campillo, M.;
Pardo, L. Optimization of the Pharmacophore Model for 5-HT7R
Antagonism. Design and Synthesis of New Naphtholactam and
Naphthosultam Derivatives. J. Med. Chem. 2003, 46, 5638−5650.
(e) Li, X.; Wang, Q.; Qing, Y.; Lin, Y.; Zhang, Y.; Qian, X.; Cui, J.
Novel DNA intercalators without basic side chains as efficient
antitumor agents: Design, synthesis and evaluation of benzo-[c,d]-
indol-malononitrile derivatives. Bioorg. Med. Chem. 2010, 18, 3279−
3284. (f) Kamal, A.; Ramakrishna, G.; Nayak, V. L.; Raju, P.; Rao, A.;
S, V.; Viswanath, A.; Vishnuvardhan, M. V. P. S.; Ramakrishna, S.;
Srinivas, G. Design and Synthesis of Benzo[c,d]indolone-pyrroloben-
zodiazepine Conjugates as Potential Anticancer Agents. Bioorg. Med.
Chem. 2012, 20, 789−800.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02037.
General comments, general procedure, optimization
details, analytic data and NMR spectra (PDF)
AUTHOR INFORMATION
(6) Marzoni, G.; Varney, M. D. An Improved Large-Scale Synthesis
of Benz[cd]indol-2(1H)-one and 5-Methylbenz[cd]indol-2(1H)-one.
Org. Process Res. Dev. 1997, 1, 81−84.
■
Corresponding Author
*E-mail: xiao-feng.wu@catalysis.de.
ORCID
(7) For selected reviews on oxidative carbonylation, see: (a) Wu, X.-
F.; Neumann, H.; Beller, M. Palladium-Catalyzed Oxidative Carbon-
ylation Reactions. ChemSusChem 2013, 6, 229−241. (b) Gabriele, B.;
Mancuso, R.; Salerno, G. Oxidative Carbonylation as a Powerful Tool
for the Direct Synthesis of Carbonylated Heterocycles. Eur. J. Org.
Chem. 2012, 2012, 6825−6839. (c) Liu, Q.; Zhang, H.; Lei, A.
Xiao-Feng Wu: 0000-0001-6622-3328
Notes
The authors declare no competing financial interest.
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Letter
Oxidative Carbonylation Reactions: Organometallic Compounds (R-
M) or Hydrocarbons (R-H) as Nucleophiles. Angew. Chem., Int. Ed.
2011, 50, 10788−10799.
(8) For selected examples of carbonylative C−H activation, see:
(a) Fu, L.-Y.; Ying, J.; Qi, X.; Peng, J.- B.; Wu, X.-F. J. Org. Chem.
2019, 84, 1421−1429. (b) Cabrera-Pardo, J. R.; Trowbridge, A.;
Nappi, M.; Ozaki, K.; Gaunt, M. J. Angew. Chem., Int. Ed. 2017, 56,
11958−11962. (c) Wen, J.; Tang, S.; Zhang, F.; Shi, R.; Lei, A. Org.
Lett. 2017, 19, 94−97. (d) Willcox, D.; Chappell, B. G. N.; Hogg, K.
F.; Calleja, J.; Smalley, A. P.; Gaunt, M. J. Science 2016, 354, 851−
857. (e) Shi, B. F.; Maugel, N.; Zhang, Y. H.; Yu, J. Q. Angew. Chem.,
Int. Ed. 2008, 47, 4882−4886. (f) Chen, M.; Ren, Z.-H.; Guan, Z.-H.
J. Am. Chem. Soc. 2012, 134, 17490−17493. (g) Chen, M.; Ren, Z.-
H.; Wang, Y.-Y.; Guan, Z.-H. Angew. Chem., Int. Ed. 2013, 52, 14196−
14199.
(9) Shi, R.; Lu, L.; Xie, H.; Yan, J.; Xu, T.; Zhang, H.; Qi, X.; Lan, Y.;
Lei, A. C8−H Bond Activation vs. C2−H Bond Activation: From
Naphthyl Amines to Lactams. Chem. Commun. 2016, 52, 13307−
13310.
(10) (a) Williamson, P.; Galvan, A.; Gaunt, M. J. Cobalt-Catalysed
C−H Carbonylative Cyclisation of Aliphatic Amides. Chem. Sci. 2017,
8, 2588−2591. (b) Ling, F.; Zhang, C.; Ai, C.; Lv, Y.; Zhong, W.
Metal-Oxidant-Free Cobalt-Catalyzed C(sp2)−H Carbonylation of
ortho-Arylanilines: An Approach toward Free (NH)-Phenanthridi-
nones. J. Org. Chem. 2018, 83, 5698−5706. (c) Ling, F.; Ai, C.; Lv, Y.;
Zhong, W. Traceless Directing Group Assisted Cobalt-Catalyzed C−
H Carbonylation of Benzylamines. Adv. Synth. Catal. 2017, 359,
3707−3712. (d) Barsu, N.; Bolli, S. K.; Sundararaju, B. Cobalt
Catalyzed Carbonylation of Unactivated C(sp3)−H Bonds. Chem. Sci.
2017, 8, 2431−2435. (e) Zeng, L.; Tang, S.; Wang, D.; Deng, Y.;
Chen, J.-L.; Lee, J.-F.; Lei, A. Cobalt-Catalyzed Intramolecular
Oxidative C(sp3)−H/N−H Carbonylation of Aliphatic Amides.
Org. Lett. 2017, 19, 2170−2173.
(11) For pioneering examples, see: (a) Zaitsev, V. G.; Shabashov, D.;
Daugulis, O. Highly Regioselective Arylation of sp3 C−H Bonds
Catalyzed by Palladium Acetate. J. Am. Chem. Soc. 2005, 127, 13154−
13155. (b) Grigorjeva, L.; Daugulis, O. Cobalt-Catalyzed, Amino-
quinoline-Directed C(sp2)-H Bond Alkenylation by Alkynes. Angew.
Chem., Int. Ed. 2014, 53, 10209−10212.
(12) For an excellent review on this topic, see: Kommagalla, Y.;
Chatani, N. Cobalt(II)-catalyzed C-H Functionalization using an
N,N’-Bidentate Directing Group. Coord. Chem. Rev. 2017, 350, 117−
135.
(13) Yin, Z.; Wu, X.-F. The Design of an In−Ex Tube for Gas
Related Organic Reactions. Org. Process Res. Dev. 2017, 21, 1869−
1871.
E
DOI: 10.1021/acs.orglett.9b02037
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