Synthesis of Redox-Active Phenanthrene-Fused Heteroarenes by Palladium-Catalyzed C-H Annulation

Palladium-Catalyzed C −H Annulation

Letter

Synthesis of Redox-Active Phenanthrene-Fused Heteroarenes by

Jin Hyeok Jang, Seongmo Ahn, Soo Eun Park, Soeun Kim, Hye Ryung Byon,* and Jung Min Joo*

Cite This: https://dx.doi.org/10.1021/acs.orglett.9b04545

Read Online

ACCESS

Metrics & More

Article Recommendations

sı Supporting Information

ABSTRACT: Pd-catalyzed C−H annulation reactions of halo- and

aryl-heteroarenes were developed using readily available o-bromo-

biaryls and o-dibromoaryls, respectively. A variety of ﬁve-membered

heteroarenes rapidly provided the corresponding phenanthrene-fused

heteroarenes, which led to the identiﬁcation of phenanthro-pyrazole

and thiazole as new, stable −2 V redox couples. The ﬂexible

syntheses and tunability of the redox potentials of these azole-fused

phenanthrenes over a wide range are expected to facilitate their application as redox-active organic functional materials.

he design and synthesis of new redox-active cores are

be successfully applied to phenanthroimidazoles cannot be

12,13

critical undertakings in the development of organic

readily applied to other heteroaromatic systems.

functional materials as electron transfer mediators. Electro-

chemical redox mediators have been extensively utilized in

various electrochemical energy storage systems in recent years.

This includes their use as negative- and positive-potential

To provide a diverse library of phenanthroheteroarenes, the

C−H functionalization of heterocycles has been recognized as

4,15

one of the most straightforward approaches.

Many

difunctionalized biaryl building blocks have been developed

for the C−H annulation of heteroarenes, including cyclic

charge carriers in redox-ﬂow batteries, redox shuttle additives

diaryliodoniums, dibenzosiloles, dibenzogermoles, and

^f^o^r^lⁱ^t^hⁱ^u^m^-ⁱ^oⁿ^b^a^t^t^e^rⁱ^e^s^,4 mobile molecular catalysts for

diiodobiaryls (Figure 1A). However, most of these building

blocks are prohibitively expensive with limited availability and

lithium−oxygen batteries, and solid-state organic electrode

materials for aqueous zinc-ion batteries. The organic materials

provide distinctive tunability, and thus, the desired phys-

icochemical and electrochemical properties can be achieved by

structural modiﬁcation. However, to optimize the electro-

chemical performance, the radical species generated by

electron transfer must be stable and undergo the reversible

reaction rapidly, which has been one of the most challenging

characteristics to attain.

Polycyclic aromatic hydrocarbons (PAHs) are promising

scaﬀolds for redox-active materials as they can delocalize

unpaired electrons in π-conjugated systems. As a redox-active

core, PAHs oﬀer extremely negative potentials that are even

comparable to those of alkali ions, such as Li , Na , and K

(

−3.44, −3.11, and −3.33 V vs Fc/Fc , respectively, converted

7−9

from the standard hydrogen electrode).

In addition, the

incorporation of a heteroaromatic ring provides the unique

opportunity to implement another redox-active core, while

retaining the fast electron transfer rate enabled by the PAH

Figure 1. (A) C−H annulation using difunctionalized aryls. (B) C−H

annulation using monofunctionalized biaryls. (C) C−H annulation of

one- and two-heteroatom-containing heteroarenes for the synthesis of

phenanthroheteroarenes.

framework. For example, Little and co-workers demonstrated

that the fused planar framework increased the electron transfer

rate and improved the stability of the corresponding radical

cations of phenanthroimidazoles, leading to the development

Received: December 18, 2019

of reversible oxidative electron transfer mediators. In these

applications, the redox potentials of phenanthroimidazoles

were tuned by modiﬁcation of substituents through con-

densation reactions. However, condensation reactions that can

XXXX American Chemical Society

Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters

Letter

thus not practical for the synthesis of electronically and

sterically varied phenanthroheteroarenes. Alternatively, a

couple of examples using o-dibromobenzene were reported,

yet its potential in the synthesis of π-extended heteroarenes has

Scheme 1. C−H Annulation of 4-Bromo-1-methylpyrazole

not been fully demonstrated. In addition, readily available,

inexpensive o-halobiaryls have been used for the annulation of

20,21

aromatic compounds (Figure 1B).

However, compared to

haloarenes, heteroaromatic counterparts possess relatively

activated C−H bonds and electronically varying C−X bonds,

making it challenging to develop a general protocol for

heterocoupling over dimerization and trimerization. Recog-

nizing the opportunity to develop redox-active materials by

exploiting the rigid, π-conjugated phenanthroheteroarenes, we

developed a convergent approach using C−H annulation

reactions of readily available heteroarenes with o-bromobiaryls

and o-dibromoarenes (Figure 1C). The rapid access to

phenanthroheteroarenes facilitated investigation of their

electrochemical properties.

See Table 1 for reaction conditions. (A) DMF was used instead of

1,4-dioxane. (B) o-Bromobiaryls were not added.

for the synthesis of the phenanthropyrazole. In the absence

of 2-bromobiphenyl, trimerization of the pyrazole was

operative, in addition to the formation of dimer 1b′ (Scheme

1B). Presumably, the oxidative addition of 4-bromopyrazole 1b

followed by C−H arylation at the C5 position of another

pyrazole provided intermediate 1b′, which served as an o-

bromobiaryl unit to ultimately generate 5. This result was

similar to trimerization of thiazole and oxazole but was not

On the basis of the recent reports that o-halobiphenyls

readily undergo dimerization, we envisioned that the choice of

halides would be critical for promoting heterocoupling

reactions. Pyrazole was selected as a representative hetero-

cycle for optimization studies because it would be feasible to

compare the electrochemical properties of pyrazole-fused

phenanthrene with those of the other two-nitrogen-containing

extended to pyrrole and indole (Scheme S1).

Bromopyrazoles having various N substituents were used to

11a,23

azole, imidazole-fused counterpart.

A series of experi-

synthesize phenanthropyrazoles (Scheme 2, 6a−h). The

ments with 4-halopyrazoles and 2-halobiphenyls showed that

the balance between the two halide functions was important

for the formation of phenanthropyrazole 2 (Table 1). When 4-

Scheme 2. C−H Annulation of 4-Bromopyrazoles with o-

Bromobiaryls (method A)

Table 1. Eﬀects of Halides on C−H Annulation of 4-

Halopyrazoles

yield (%)

entry

X¹

X²

1a−c

3a−c

Cl (1a)

Br (1b)

I (1c)

Br (1b)

I (1c)

54 (3a)

0 (3b)

0 (3c)

10 (3b)

0 (3c)

82 (82)

Reaction conditions: pyrazole (0.50 mmol), o-halobiaryl (0.75

mmol), Pd(OAc)₂(0.025 mmol), PCy H·BF (0.050 mmol),

Cs CO (1.5 mmol), 1,4-dioxane (0.50 M), 16 h, 140 °C. H NMR

See Table 1 for reaction conditions.

yield. Isolated yield in parentheses.

presence of a methyl group at the C3 position was also

tolerated (6i). In addition to the biphenyl group, other

symmetrical biaryl groups were smoothly attached to the

pyrazole ring (6j and 6k). However, the use of an

unsymmetrical o-biaryl produced a mixture of inseparable

regioisomers due to 1,4-migration of the Pd intermediates (6l

chloropyrazole 1a was employed, the corresponding C5

arylation product 3a was predominantly formed (entry 1).

In contrast, the combination of 4-bromopyrazole 1b and 2-

bromobiphenyl produced the desired annulation product 2 in

2% yield (entry 2), whereas the other mismatched cases

aﬀorded decreased yields of 2 and increased yields of the

undesired dimer 4 (entries 3−5). When the solvent was

switched from 1,4-dioxane to DMF, a considerable amount of

the C5 arylation product 3b was obtained (Scheme 1A; also

see Table S1 for optimization studies). The resubjection of 3b

to the reaction in 1,4-dioxane enabled ring closure, suggesting

that stepwise, double C−H arylation is one of viable pathways

and 6l′).

As a complement to the annulation with o-bromobiaryls, o-

dibromoarenes could be used to diversify the polycyclic ring

system (Scheme 3). By using a catalytic system similar to

that developed for the reaction of the 4-bromopyrazoles, the 4-

phenylpyrazole was subjected to C−H annulation with o-

dibromobenzene to aﬀord 2, albeit in a moderate conversion

Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters

Letter

Scheme 3. C−H Annulation of 4-Arylpyrazoles with o-

Scheme 4. C−H Annulation for the Synthesis of

Phenanthrene-Fused Heteroarenes (methods A and B)

Dibromoaryls (method B)

Reaction conditions: pyrazole (0.75 mmol), o-dibromoarene (0.50

mmol), Pd(OAc)₂(0.025 mmol), PCy H·BF (0.0375 mmol),

K CO (2.0 mmol), DMA (0.50 M), 16 h, 140 °C. A reduced

amount of pyrazole was used (0.50 mmol).

Method A: heteroarene (1.0 mmol), 2-bromobiphenyl (0.50 mmol),

Table S2 ). It was envisioned that using π-extended or

Pd(OAc) (0.025 mmol), PCy H·BF (0.050 mmol), Cs CO (1.5

substituted dibromoarenes could lead to further expansion and

substitution of the heterocyclic framework. o-Dibromoarenes

having dimethyl and dimethoxy groups and o-dibromonaph-

thalene were employed to give 7a−c, respectively. Suzuki

coupling of bromopyrazoles enabled various aryl groups to be

preinstalled at the pyrazole core, which smoothly underwent

annulation (7d−h). When an m-methoxy group was present at

the C4 aryl ring, 6l was obtained by C−H arylation at the less

sterically hindered position. In this way, the heterocyclic ring

was extended with diﬀerent π-conjugated networks, generating

unsymmetrically substituted heterocycle derivatives in a

selective and systematic manner.

mmol), 1,4-dioxane (0.50 M), 16 h, 140 °C. Method B: heteroarene

(

0.75 mmol), 1,2-dibromobenzene (0.50 mmol), Pd(OAc) (0.025

mmol), PCy H·BF (0.0375 mmol), K CO (2.0 mmol), DMA (0.50

M), 16 h, 140 °C. For azoles 8a−c and 8i, the amounts of reactants

were changed because of a separation issue. See the Supporting

Information for details.

their limited syntheses. We examined the reversibility of the

reaction of the pyrazole and thiazole derivatives in redox

processes. Cyclic voltammograms (CVs) were obtained for 2,

8a, and 8b in 0.10 M tetrabutylammonium bis-

(triﬂuoromethanesulfonyl)imide/N,N-dimethylacetamide

(TBATFSI/DMA) under an argon atmosphere (Figure 2 and

Methods A and B developed for the annulative C−H

activation of pyrazoles were both generally applicable for the π-

extension of other ﬁ ve-membered heteroaromatic rings

Table 2). The reduction peak potential (E ) of phenan-

red

(Scheme 4 and Table S5). Notably, the developed approach

thropyrazole 2 was −3.03 V versus Fc/Fc for one-electron

allowed the general synthesis of 2-aryl phenanthrothiazoles

that were not previously readily accessible (8a−c).

transfer, which is comparable to those of triphenylene,

15b,c,26

phenanthrene, and biphenyl (−3.04, −3.02, and −3.20 V vs

When 4-bromothiazole having two reactive C−H bonds at the

heterocyclic core was used, C−H arylation took place at both

positions (8c, method A). Furthermore, phenanthrothiophenes

were synthesized from readily available thiophene derivatives

and dibromobenzene, as a complement to the annulation of

bromothiophenes and 9-stannaﬂuorenes that are not readily

Fc/Fc , respectively), which are known to have some of the

most negative reduction potentials among aromatic com-

pounds (Figure S1 ). The electrochemical redox ability of 2

appears to improve with the corresponding radical anion of the

phenanthrene ring. The bicyclic benzo-fused pyrazole, 1-

methylindazole, and pyrazole trimer 5 did not exhibit any

redox ability (Figure S2 ), supporting the idea that the pyrazole

ring alone was redox-inactive.

available (8d−g). In addition, oxygen-containing hetero-

cycles as well as a pyrrole underwent annulation to aﬀord 8h−

j. The annulation was also applied to halopyridines, where 2-

and 4-bromopyridines resulted in low yields and 3-bromopyr-

idine formed both regioisomers (Scheme S2). These

inexpensive halo(hetero)arenes can be readily purchased and

assembled in a modular fashion, greatly expanding the scope of

accessible polycyclic heteroaromatic compounds.

When 2-phenyl and 2-(pyridin-4-yl)thiazole were fused with

phenanthrene (8a and 8b, respectively), E emerged at −2.42

red

V for 8a and −2.12 V for 8b (vs Fc/Fc ). Their ﬁrst redox

waves were considerably stable, as demonstrated by the

constant peak current ratio (i_p_,_o_x/i_p_,_r_e_d) of 0.97, which was

−

maintained for 100 cycles at a rate of 10 mV s (Figure 2).

Our convergent methods allowed access to a variety of new

phenanthrene-fused heteroaromatic compounds. The electro-

chemical properties of the pyrazole- and thiazole-fused

counterparts are largely enigmatic, presumably because of

For 8b, which contains a pyridine, the second electron transfer

occurred at an E_r_e_d_,₂of −2.76 V versus Fc/Fc (Figure S3). In

addition, both 8a and 8b showed reasonably high diﬀusion

−

−1

coeﬃcients [6−8 × 10 cm s (Figure S4)] and rate

Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters

The Supporting Information is available free of charge at

Letter

noting that both phenanthro-pyrazole and thiazole did not

show any (quasi)reversible redox event in the positive

potential range (Figure S6) unlike the phenanthroimidazole

11a

(

0.88 V vs Ag/AgNO₃) because of the diﬀerent electronic

character of the heterocycles. In contrast, phenanthroxazole 8d

showed a decrease in the cathodic current over 100 cycles

(

Table 2 and Figure S7 ). Thiophene 8g also displayed unstable

CV curves (Figure S8), indicating the occurrence of an

electrochemical reaction followed by an undesired chemical

reaction (EC process). These results indicate that the type and

arrangement of heteroatoms dramatically impact the redox

properties and stability of the ﬁve-membered heterocyclic

family.

In conclusion, Pd-catalyzed C−H annulation reactions of

heteroarenes were developed for the synthesis of redox-active

phenanthroheteroarenes using readily available (di)-

bromoarenes. A wide range of ﬁve-membered heteroarenes,

such as pyrazole, thiazole, oxazole, thiophene, furan, and

pyrrole, were transformed to the corresponding phenanthrene-

fused heteroarenes. The position of the substituents and the

number of aromatic rings were systematically controlled to

provide various polycyclic heteroaromatic compounds. Nota-

bly, this comprehensive approach enabled the preparation of

phenanthro-pyrazoles and thiazoles, which were found to

undergo reversible reduction reactions. The stability of the

redox processes of the rigid, planar π-conjugated structures of

phenanthrene was demonstrated, in combination with a

multitude of electronic eﬀects of the ﬁve-membered hetero-

arenes. This is expected to facilitate the application of these

scaﬀolds in redox-active organic materials, including organic

electrode materials and redox-ﬂow batteries, aﬀording high

energy density.

Figure 2. CV proﬁles of 2, 8a, and 8b for the ﬁrst (black) and 100th

(red) cycles after scanning over a wide potential range. The dashed

curve indicates the blank electrolyte solution (0.10 M TBATFSI/

DMA) as the background signal. The arrows indicate the scanning

direction. The y scale indicates the current density (milliamperes per

square centimeter). The working, counter, and reference electrodes

were glassy carbon, a platinum wire, and a leak-free Ag/AgCl

−

electrode, respectively. The scan rate was 10 mV s , and all CVs were

acquired in an argon-ﬁlled glovebox.

Table 2. Summary of Electrochemical Characteristics of

Phenanthrene-Fused Heteroarenes

ASSOCIATED CONTENT

sı Supporting Information

■

https://pubs.acs.org/doi/10.1021/acs.orglett.9b04545.

Full experimental details and characterization data

(PDF)

AUTHOR INFORMATION

■

Corresponding Authors

Hye Ryung Byon − Department of Chemistry at Korea

Advanced Institute of Science and Technology (KAIST) and

Advanced Battery Center at KAIST Institute for NanoCentury,

Daejeon 34141, Republic of Korea; orcid.org/0000-0003-

3692-6713 ; Email: hrbyon@kaist.ac.kr

Jung Min Joo − Department of Chemistry and Chemistry

Institute for Functional Materials, Pusan National University,

Busan 46241, Republic of Korea; orcid.org/0000-0003-

Each redox molecule (10 mM) was tested in 0.10 M TBATFSI/

−

DMA at a scan rate of 10 mV s . ΔE , D , and k indicate the peak-

red

to-peak separation, the diﬀusion coeﬃcient for redox molecules, and

the standard heterogeneous rate constant, respectively. The data in

parentheses indicate the value at the 100th cycle.

645-3322 ; Email: jmjoo@pusan.ac.kr

constants [0.8−1.0 × 10⁻³cm s⁻¹(Table 2 and the Supporting

Information)].

The redox-active cores of 8a and 8b were 2-phenyl

benzothiazole and 2-(pyridine-4-yl) benzothiazole, respec-

tively. The phenanthrene ring was idle in this potential

range, whereas this π-conjugated structure aided in prompt

Authors

Jin Hyeok Jang − Department of Chemistry and Chemistry

Institute for Functional Materials, Pusan National University,

Busan 46241, Republic of Korea

Seongmo Ahn − Department of Chemistry at Korea Advanced

Institute of Science and Technology (KAIST) and Advanced

Battery Center at KAIST Institute for NanoCentury, Daejeon

34141, Republic of Korea

electron transfer, demonstrating a Δ E smaller than those for

the parent benzothiazoles (Figure S5 and Table S6). It is worth

Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters

10) Ste p ̧ ien, M.; Gonka, E.; Zy ł a, M.; Sprutta, N. Heterocyclic

Letter

Soo Eun Park − Department of Chemistry and Chemistry

Institute for Functional Materials, Pusan National University,

Busan 46241, Republic of Korea

Soeun Kim − Department of Chemistry at Korea Advanced

Institute of Science and Technology (KAIST) and Advanced

Battery Center at KAIST Institute for NanoCentury, Daejeon

(9) Haynes, W. M. CRC Handbook of Chemistry and Physics, 96th

ed.; CRC Press: Boca Raton, FL, 2015.

́ ́

Nanographenes and Other Polycyclic Heteroaromatic Compounds:

Synthetic Routes, Properties, and Applications. Chem. Rev. 2017, 117,

11) (a) Francke, R.; Little, R. D. Optimizing Electron Transfer

479−3716.

4141, Republic of Korea

Mediators Based on Arylimidazoles by Ring Fusion: Synthesis,

Electrochemistry, and Computational Analysis of 2-Aryl-1-

methylphenanthro[9,10-d ]imidazoles. J. Am. Chem. Soc. 2014, 136,

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.orglett.9b04545

427 −435. (b) Lu, N.-n.; Yoo, S. J.; Li, L.-J.; Zeng, C.-C.; Little, R. D.

A Comparative Study of Organic Electron Transfer Redox Mediators:

Electron Transfer Kinetics for Triarylimidazole and Triarylamine

Mediators in the Oxidation of 4-Methoxybenzyl Alcohol. Electrochim.

Acta 2014, 142, 254 −260. (c) Johnson, B. M.; Francke, R.; Little, R.

D.; Berben, L. A. High Turnover in Electro-Oxidation of Alcohols and

Ethers with a Glassy Carbon-Supported Phenanthroimidazole

Mediator. Chem. Sci. 2017 , 8 , 6493 −6498. Also, see: (d) Tagare,

J.; Vaidyanathan, S. Recent Development of Phenanthroimidazole-

Based Fluorophores for Blue Organic Light-Emitting Diodes

Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

■

This work is supported by the Samsung Research Funding &

Incubation Center of Samsung Electronics under Project

SRFC-MA1702-05. The authors thank Prof. Haesik Yang at

Pusan National University for helpful discussions.

Shestopalov, A. A.; Steel, P. J. Cyclization of α -Oxo-oximes to 2-

OLEDs): an Overview. J. Mater. Chem. C 2018, 6, 10138−10173.

(

12) For the synthesis of phenanthroxazoles by condensation, see:

REFERENCES

(a) Katritzky, A. R.; Wang, Z.; Hall, C. D.; Akhmedov, N. G.;

Substituted Benzoxazoles. J. Org. Chem. 2003, 68, 9093−9099.

■

1) Francke, R.; Little, R. D. Redox Catalysis in Organic

Electrosynthesis: Basic Principles and Recent Developments. Chem.

Soc. Rev. 2014, 43, 2492−2521.

2) (a) Wei, X.; Pan, W.; Duan, W.; Hollas, A.; Yang, Z.; Li, B.; Nie,

(b) Skonieczny, K.; Ciuciu, A. I.; Nichols, E. M.; Hugues, V.;

Blanchard-Desce, M.; Flamigni, L.; Gryko, D. T. Bright, Emission

Tunable Fluorescent Dyes Based on Imidazole and π -Expanded

Imidazole. J. Mater. Chem. 2012 , 22 , 20649 −20664. (c) Sarkar, R.;

Mukhopadhyay, C. A Convenient Strategy to 2,4,5-Triaryl and 2-

Alkyl-4,5-Diaryl Oxazole Derivatives through Silver-Mediated Oxida-

tive CO Cross Coupling/Cyclization. Tetrahedron Lett. 2015, 56,

(

Z.; Liu, J.; Reed, D.; Wang, W.; Sprenkle, V. Materials and Systems for

Organic Redox Flow Batteries: Status and Challenges. ACS Energy

Lett. 2017 , 2 , 2187 −2204. (b) Armstrong, C. G.; Toghill, K. E.

Stability of Molecular Radicals in Organic Non-Aqueous Redox Flow

Batteries: A Mini Review. Electrochem. Commun. 2018 , 91 , 19 −24.

(

872−3876.

13) For the synthesis of phenanthropyrazoles by condensation, see:

a) Wang, Q.; Zhang, Z.; Du, Z.; Hua, H.; Chen, S. One-pot Synthesis

c) Luo, J.; Hu, B.; Hu, M.; Zhao, Y.; Liu, T. L. Status and Prospects

of Organic Redox Flow Batteries toward Sustainable Energy Storage.

ACS Energy Lett. 2019 , 4 , 2220 −2240. (d) Singh, V.; Kim, S.; Kang,

J.; Byon, H. R. Aqueous Organic Redox Flow Batteries. Nano Res.

019, 12, 1988−2001.

3) Haregewoin, A. M.; Wotango, A. S.; Hwang, B.-J. Electrolyte

Additives for Lithium Ion Battery Electrodes: Progress and

Perspectives. Energy Environ. Sci. 2016, 9, 1955−1988.

4) Landa-Medrano, I.; Lozano, I.; Ortiz-Vitoriano, N.; Ruiz de

of 2 H -Phenanthro[9,10-c ]pyrazoles from Isoflavones by Two

Dehydration Processes. Green Chem. 2013, 15 , 1048 −1054.

(b) Olivera, R.; SanMartin, R.; Domínguez, E. A Combination of

Tandem Amine-Exchange/Heterocyclization and Biaryl Coupling

Reactions for the Straightforward Preparation of Phenanthro[9,10-

d ]pyrazoles. J. Org. Chem. 2000 , 65 , 7010 −7019. (c) Olivera, R.;

SanMartin, R.; Domínguez, E. A Straightforward Synthetic Pathway to

Phenanthro[9,10-d ]heterocycles. Synlett 2000, 2000, 1028−1030.

(

Larramendi, I.; Rojo, T. Redox Mediators: A Shuttle to Efficacy in

Metal −O Batteries. J. Mater. Chem. A 2019, 7 , 8746 −8764.

(14) For reviews of C−H functionalization for the synthesis of

heterocycles, see: (a) He, J.; Wasa, M.; Chan, K. S. L.; Shao, Q.; Yu,

5) Fang, G.; Zhou, J.; Pan, A.; Liang, S. Recent Advances in

J.-Q. Palladium-Catalyzed Transformations of Alkyl C −H Bonds.

Chem. Rev. 2017 , 117 , 8754 −8786. (b) Ito, H.; Ozaki, K.; Itami, K.

Annulative π -Extension (APEX): Rapid Access to Fused Arenes,

Heteroarenes, and Nanographenes. Angew. Chem., Int. Ed. 2017 , 56 ,

Aqueous Zinc-Ion Batteries. ACS Energy Lett. 2018, 3, 2480−2501.

6) (a) Sevov, C. S.; Brooner, R. E. M.; Chenard, E.; Assary, R. S.;

Moore, J. S.; Rodríguez-Lopez, J.; Sanford, M. S. Evolutionary Design

of Low Molecular Weight Organic Anolyte Materials for Applications

in Nonaqueous Redox Flow Batteries. J. Am. Chem. Soc. 2015, 137,

(

1144 −11164. (c) Segawa, Y.; Maekawa, T.; Itami, K. Synthesis of

Extended π -Systems through C −H Activation. Angew. Chem., Int. Ed.

015 , 54 , 66 −81. (d) Mei, T.-S.; Kou, L.; Ma, S.; Engle, K. M.; Yu, J.-

4465 −14472. (b) Hu, B.; Tang, Y.; Luo, J.; Grove, G.; Guo, Y.; Liu,

T. L. Improved Radical Stability of Viologen Anolytes in Aqueous

Organic Redox Flow Batteries. Chem. Commun. 2018, 54, 6871−

874. (c) Wei, X.; Xu, W.; Huang, J.; Zhang, L.; Walter, E.; Lawrence,

Q. Heterocycle Formation via Palladium-Catalyzed C −H Function-

alization. Synthesis 2012 , 44 , 1778 −1791. (e) Ackermann, L.; Vicente,

R.; Kapdi, A. R. Transition-Metal-Catalyzed Direct Arylation of

(Hetero)Arenes by C −H Bond Cleavage. Angew. Chem., Int. Ed.

C.; Vijayakumar, M.; Henderson, W. A.; Liu, T.; Cosimbescu, L.; Li,

B.; Sprenkle, V.; Wang, W. Radical Compatibility with Nonaqueous

Electrolytes and its Impact on an All-Organic Redox Flow Battery.

Angew. Chem., Int. Ed. 2015 , 54 , 8684 −8687.

2009 , 48 , 9792 −9826. (f) Hagui, W.; Doucet, H.; Soule, J.-F.

7) Steckhan, E. Indirect Electroorganic Syntheses A Modern

Chapter of Organic Electrochemistry. Angew. Chem., Int. Ed. Engl.

986, 25, 683−701.

8) (a) Cong, G.; Wang, W.; Lai, N.-C.; Liang, Z.; Lu, Y.-C. A High-

Rate and Long-Life Organic −Oxygen Battery. Nat. Mater. 2019, 18,

90−396. (b) Rodríguez-Perez, I. A.; Bommier, C.; Fuller, D. D.;

Application of Palladium-Catalyzed C(sp )−H Bond Arylation to the

Synthesis of Polycyclic (Hetero)Aromatics. Chem 2019, 5, 2006−

2078. (g) Liu, B.; Han, Y.-O.; Hu, F.; Shi, B.-F. Palladium-Catalyzed

(h) Zhang, Q.; Shi, B. F. From Reactivity and Regioselectivity to

Directed Arylation of Unactivated C(sp )−H Bonds. In Strategies for

Palladium-Catalyzed Non-Directed and Directed C−H Bond Function-

alization; Kapdi, A. R., Maiti, D., Eds.; Elsevier, 2017; pp 167 −203.

Stereoselectivity: An Odyssey of Designing PIP Amine and Related

Directing Groups for C −H Activation. Chin. J. Chem. 2019, 37, 647−

656.

Leonard, D. P.; Williams, A. G.; Ji, X. Toward Higher Capacities of

Hydrocarbon Cathodes in Dual-Ion Batteries. ACS Appl. Mater.

Interfaces 2018, 10, 43311−43315. (c) Wang, G.; Huang, B.; Liu, D.;

Zheng, D.; Harris, J.; Xue, J.; Qu, D. Exploring Polycyclic Aromatic

Hydrocarbons as an Anolyte for Nonaqueous Redox Flow Batteries. J.

Mater. Chem. A 2018, 6, 13286−13293.

(15) For stepwise C−H arylation to prepare phenanthroid

thiophenes, thiazoles, and oxazoles in three steps from the parent

Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters

heterocycles, see: (a) Schnapperelle, I.; Bach, T. Modular Synthesis of

Letter

Phenanthro[9,10-c ]thiophenes by a Sequence of C −H Activation,

Suzuki Cross-Coupling and Photocyclization Reactions. Chem. - Eur.

J. 2014 , 20 , 9725 −9732. (b) Shi, X.; Soule, J.-F.; Doucet, H. Synthesis

of Phenanthrothiazoles and 1,2-Di(heteroaryl)benzenes through

and its Application to the Synthesis of Indazoles. Angew. Chem., Int.

Ed. 2017, 56, 16262−16266. (c) Kim, O. S.; Jang, J. H.; Kim, H. T.;

Han, S. J.; Tsui, G. C.; Joo, J. M. Synthesis of Fluorescent Indazoles

by Palladium-Catalyzed Benzannulation of Pyrazoles with Alkynes.

Org. Lett. 2017, 19, 1450−1453. (d) Padhi, B.; Kang, G.; Kim, E.; Ha,

J.; Kim, H. T.; Lim, J.; Joo, J. M. Pd-Catalyzed C −H Annulation of

Five-Membered Heteroaryl Halides with Norbornene Derivatives.

ACS Catal. 2020, 10, 1792−1798.

Successive Pd-Catalyzed Direct Arylations. J. Org. Chem. 2017, 82,

886 −3894. (c) Bouzayani, B.; Ben Salem, R.; Soule, J.-F.; Doucet, H.

Intermolecular Followed by Intramolecular Palladium-Catalyzed

Direct Arylation for the Synthesis of π -Extended Aromatic

Compounds Containing One or Two Heteroelements. Eur. J. Org.

(24) (a) Goikhman, R.; Jacques, T. L.; Sames, D. C −H Bonds as

Ubiquitous Functionality: A General Approach to Complex Arylated

Pyrazoles via Sequential Regioselective C -Arylation and N -Alkylation

Enabled by SEM-Group Transposition. J. Am. Chem. Soc. 2009, 131,

3042 −3048. (b) Mateos, C.; Mendiola, J.; Carpintero, M.; Mínguez, J.

M. Regioselective Palladium-Catalyzed Arylation of 4-Chloropyr-

azoles. Org. Lett. 2010 , 12 , 4924 −4927.

Chem. 2019 , 2019 , 4581 −4588. (d) Shi, X.; Soule, J.-F.; Doucet, H.

Reaction Conditions for the Regiodivergent Direct Arylations at C2-

or C5-Positions of Oxazoles Using Phosphine-Free Palladium

Catalysts. Adv. Synth. Catal. 2019, 361, 4748−4760.

(16) (a) Wu, Y.; Peng, X.; Luo, B.; Wu, F.; Liu, B.; Song, F.; Huang,

P.; Wen, S. Palladium Catalyzed Dual C −H Functionalization of

Indoles with Cyclic Diaryliodoniums, an Approach to Ring Fused

Carbazole Derivatives. Org. Biomol. Chem. 2014, 12, 9777−9780.

(25) Ma, S.; Gu, Z. 1,4-Migration of Rhodium and Palladium in

Catalytic Organometallic Reactions. Angew. Chem., Int. Ed. 2005, 44,

(

512−7517.

26) CV proﬁles of 2-alkyl phenanthrothiazoles showed irreversible

behavior, not suitable for electrochemical applications.

27) (a) Nagao, I.; Shimizu, M.; Hiyama, T. 9-Stannafluorenes: 1,4-

(b) Lee, J. B.; Jeon, M. H.; Seo, J. K.; von Helden, G.; Rohde, J.-U.;

Zhao, B. S.; Seo, J.; Hong, S. Y. Annulative π -Extension of

Unactivated Benzene Derivatives through Nondirected C −H

Arylation. Org. Lett. 2019, 21, 7004−7008.

Dimetal Equivalents for Aromatic Annulation by Double Cross-

Coupling. Angew. Chem., Int. Ed. 2009, 48, 7573−7576. Also, see:

(17) Ozaki, K.; Matsuoka, W.; Ito, H.; Itami, K. Annulative π -

(b) Albrecht, F.; Pavlicek, N.; Herranz-Lancho, C.; Ruben, M.; Repp,

Extension (APEX) of Heteroarenes with Dibenzosiloles and

J. Characterization of a Surface Reaction by Means of Atomic Force

Microscopy. J. Am. Chem. Soc. 2015, 137 , 7424 −7428. (c) Hu, T.; Xu,

K.; Ye, Z.; Zhu, K.; Wu, Y.; Zhang, F. Two-in-One Strategy for the

Pd(II)-Catalyzed Tandem C −H Arylation/Decarboxylative Annula-

tion Involved with Cyclic Diaryliodonium Salts. Org. Lett. 2019, 21,

Dibenzogermoles by Palladium/o -Chloranil Catalysis. Org. Lett.

18) (a) Matsuoka, W.; Ito, H.; Itami, K. Rapid Access to

017, 19, 1930−1933.

Nanographenes and Fused Heteroaromatics by Palladium-Catalyzed

Annulative π -Extension Reaction of Unfunctionalized Aromatics with

Diiodobiaryls. Angew. Chem., Int. Ed. 2017, 56, 12224 −12228.

7233−7237.

(b) Kitano, H.; Matsuoka, W.; Ito, H.; Itami, K. Annulative π -

Extension of Indoles and Pyrroles with Diiodobiaryls by Pd Catalysis:

Rapid Synthesis of Nitrogen-Containing Polycyclic Aromatic

Compounds. Chem. Sci. 2018, 9, 7556−7561.

(

19) For examples of C−H annulation using o -dihalobenzenes, see:

a) Dodonova, J.; Tumkevicius, S. Fused Pyrrolo[2,3-d ]pyrimidines

7-Deazapurines) by Palladium-Catalyzed Direct N −H and C −H

Arylation Reactions. Synthesis 2017, 49, 2523−2534. (b) Shi, X.; Mao,

S.; Roisnel, T.; Doucet, H.; Soule, J.-F. Palladium-Catalyzed

Successive C −H Bond Arylations and Annulations toward the π -

Extension of Selenophene-Containing Aromatic Skeletons. Org. Chem.

Front. 2019, 6, 2398−2403.

(20) For the use of 2-iodobiphenyl in C−H arylation of iodoarenes

to give triphenylene derivatives, see: (a) Pan, S.; Jiang, H.; Zhang, Y.;

Chen, D.; Zhang, Y. Synthesis of Triphenylenes Starting from 2-

Iodobiphenyls and Iodobenzenes via Palladium-Catalyzed Dual C −H

Activation and Double C −C Bond Formation. Org. Lett. 2016, 18,

192−5195. Also, see: (b) Jiang, H.; Zhang, Y.; Chen, D.; Zhou, B.;

Zhang, Y. An Approach to Tetraphenylenes via Pd-Catalyzed C −H

Functionalization. Org. Lett. 2016, 18, 2032−2035.

21) (a) Koga, Y.; Kaneda, T.; Saito, Y.; Murakami, K.; Itami, K.

Synthesis of Partially and Fully Fused Polyaromatics by Annulative

Chlorophenylene Dimerization. Science 2018, 359, 435−439. (b) Zhu,

C.; Wang, D.; Wang, D.; Zhao, Y.; Sun, W.-Y.; Shi, Z. Bottom-up

Construction of π -Extended Arenes by a Palladium-Catalyzed

Annulative Dimerization of o -Iodobiaryl Compounds. Angew. Chem.,

Int. Ed. 2018, 57, 8848−8853.

(22) For trimerization of bromo-thiazoles and oxazoles, see: Xu, Z.;

Oniwa, K.; Kikuchi, H.; Bao, M.; Yamamoto, Y.; Jin, T.; Terada, M.

Pd-Catalyzed Consecutive C −H-Arylation-Triggered Cyclotrimeriza-

tion: Synthesis of Star-Shaped Benzotristhiazoles and Benzotrisox-

azoles. Chem. - Eur. J. 2018, 24, 9041−9050.

(23) For C−H annulation of pyrazoles, see: (a) Yang, W.; Ye, S.;

Fanning, D.; Coon, T.; Schmidt, Y.; Krenitsky, P.; Stamos, D.; Yu, J.-

Q. Orchestrated Triple C −H Activation Reactions Using Two

Directing Groups: Rapid Assembly of Complex Pyrazoles. Angew.

Chem., Int. Ed. 2015, 54, 2501−2504. (b) Kim, H. T.; Ha, H.; Kang,

G.; Kim, O. S.; Ryu, H.; Biswas, A. K.; Lim, S. M.; Baik, M.-H.; Joo, J.

M. Ligand-Controlled Regiodivergent C −H Alkenylation of Pyrazoles