Oxidative Electrocyclization of Diradicaloids: C-C Bonds for Free or How to Use Biradical Character for π-Extension

Article abstract of DOI:10.1021/acs.orglett.0c01717

Herein, we show that biradical character and appropriate distribution of spin density can be used for synthetic purposes. We demonstrate the rational domino annulation that includes dehydrative π-extension (DPEX) as the initiation step and subsequent oxid

Full text of DOI:10.1021/acs.orglett.0c01717

pubs.acs.org/OrgLett
Letter
Oxidative Electrocyclization of Diradicaloids: C−C Bonds for Free or
How to Use Biradical Character for π‑Extension
Mikhail Feofanov,* Vladimir Akhmetov, Dmitry I. Sharapa, and Konstantin Amsharov*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c01717
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: Herein, we show that biradical character and appropriate distribution of spin density can be used for synthetic
purposes. We demonstrate the rational domino annulation that includes dehydrative π-extension (DPEX) as the initiation step and
subsequent oxidative electrocyclizations (EC) promoted by favorable localization of the unpaired electrons enabling up to four C−C
bonds formed during the reaction. Contradicting to the Woodward−Hoffmann rules, the reaction proceeds at room temperature,
whereas termination occurs when biradical character vanishes.
ynthesis of polycyclic aromatic compounds has become
a subclass of pericyclic reactions that play an important role in
Sone of the most relevant branches in modern materials both synthetic and theoretical chemistry.28−30 According to
science.1,2 The possibility to manage the physical properties
through the size, shape, and edge topology3 allows the design
of materials for a wide variety of optoelectronic applica-
tions.4−11 C−C bond formation techniques serve as the main
tools in the bottom-up construction of the desired materials
with atomical precision. It is, therefore, crucial to develop new
synthetic tools and to broaden the scope of the existing
methods such as annulative π-extension (APEX),12,13 Scholl
reaction, alkyne annulation,14,15 aryne trimerizations,16 palla-
dium-catalyzed reactions,17,18 etc. To achieve this goal, it is
vital to understand how different substrates behave upon
exposure to different reaction conditions. However, it can be
not as trivial as it seems. Among vivid examples demonstrating
this fact is the Scholl reaction, which has been known for over
Woodward−Hoffmann rules, this reaction can proceed
through photochemical or thermal activation.31 The second
often requires extremely high temperatures, particularly in the
case of unactivated hexatrienes.32 Unlike them, open-shell
structures play by different rules. They undergo thermal
electrocyclization at ambient temperatures. This is connected
with low HOMO−LUMO gaps resulting in the partial
occupation of HOMO and LUMO in the ground state.
This transformation represents a challenge for chemists due
to the overall complexity of pristine biradicals’ synthesis and
poor control over degradation pathways that unstable
diradicaloids undergo. Several recent reports have studied the
mechanistic aspects of 6π-electrocyclization of phenalenyl-
based diradicaloids.33−37 Despite valuable insights, the
mechanism of the reaction remains not fully understood.38
While these works have been foreshadowing new synthetic
methods to be developed, to the best of our knowledge there
are no direct synthetic applications that emerged from the area.
Herein, we demonstrate such a synthetic application
exploiting DPEX and the Clar model for effective cascade
reactions. Thus, the DPEX reaction can generate biradical
moieties suitable for the “forbidden” 6π-electrocyclization.
100 years, and despite comprehensive studies by Mullen et
̈
al.19 this transformation continues to reveal new examples of
intricate transformations.20−22
Recently, we have contributed to the field by developing the
dehydrative π-extension (DPEX) reaction.6,23 Ambient con-
ditions and the simplicity of the protocol provide rapid access
toward polycyclic aromatic hydrocarbons (PAHs) and nano-
graphenes with zigzag edges and high biradical character. The
latter leads to low chemical stability, as open-shell systems tend
to undergo uncontrollable oligomerization in solution.24,25 It
is, indeed, a complicated task to gain control over the reactivity
of such species.26,27
Received: May 20, 2020
However, as we envision, if the radicals are localized in the
“right” places, this tendency can be used to promote
intramolecular processes. Among them is 6π-electrocyclization,
https://dx.doi.org/10.1021/acs.orglett.0c01717
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
Meanwhile, the precursor design can be rationalized by using
the Clar model, which can predict the favored position of the
radicals and explain the outcome of the reaction. This
reasoning is also supported by the fractional occupation
number weighted electron density (FOD) analysis and DFT-
calculated energy barriers. From a synthetic standpoint, this
domino reaction gives rapid access to violanthrenes and π-
extended 5-helicenes unavailable via alternative methods.
The concept of the domino annulation is shown in Figure 1.
The intermediate obtained after DPEX can be represented via
Figure 2. Domino reaction including DPEX as the initiation step and
subsequent oxidative electrocyclization of diradicaloids. Reaction
conditions: SnCl2/i-PrOH, H2SO4, DCM, room temperature, over-
night.
Figure 1. Concept of the report illustrated by the example of
violanthrene (1) synthesis.
three isomeric structures (1-trans, D1, and 1-cis). D1 has
several resonance forms, the most stable of which are depicted
in Figure 1. As it will be shown later, the efficiency of
intramolecular electrocyclization at room temperature corre-
lates with the stability of the resonance form having radical
centers localized on carbon atoms directly participating in the
new bond formation. The respective resonance forms are
indicated as the Most Contributing Resonance Structure
(MCRS).
We have initiated our studies with three simplest model
intermediates (obtained from P1, P1a, and P2) containing two
interconnected benzophenalenyls, i.e., the smallest fragments
which can be constructed via the DPEX reaction. This choice
is also justified by similarities to the previously studied
phenalenyl fragments.34,35
The syntheses of the symmetric precursors P1 and P1a were
performed in two steps including mono-Suzuki reaction and
subsequent dimerization via Miyaura conditions in the
presence of strong base.39 The asymmetric P2 was obtained
via a three-step procedure (see the Supporting Information
(SI)). The diradicaloids were generated under conditions of
DPEX reaction. For simplicity, only MCRSs of the respective
diradicaloids (RS1, RS1a, and RS2) are shown in Figure 2. In
the case of P1 and P2, the initiation step was followed by in
situ electrocyclization and oxidation yielding violanthrene (1)
and isoviolanthrene (2) as main products, respectively.
Noteworthy, no traces of 1 were found in the case of P1a
(inseparable mixture of different products was formed).
This outcome can be explained via simple qualitative
reasoning.40 To achieve higher efficiency, it is desirable to
have unpaired electrons localized on the corresponding carbon
atoms (Figure 2).
Despite several possible resonance forms, it is the form
containing the biggest number of Clar’s sextets (CS) that
mainly contributes to the preferred positions of radicals. Thus,
it can be seen from Figure 2 that the more sextets that are
involved in the MCRS, the better the yields that are achieved.
Therefore, P2 represents the best precursor in this series as it
has four sextets in the MCRS. However, even in this case, the
unpaired electrons are significantly delocalized (Figure 1). To
address the issue, we have designed the precursor P3 that gives
diradicaloid RS3 in which spin density is concentrated on the
“correct” carbon atoms. Therefore, the yield of the domino
reaction increases to 76%. An intriguing aspect of this
transformation is that it terminates at the π-extended 5-
helicene 3 due to the formation of the closed-shell system.
To investigate whether the approach can be extrapolated to
induce longer domino reactions we have prepared precursor
P4 which gives diradicaloid 4a (Figure 3). Oxidative electro-
cyclization of 4a leads to diradicaloid 4b, which finally
transforms into tetrabenzobisanthrene (TBBA, 4). Thus, this
cascade enables the transformation of the linear oligopheny-
lene P4 into π-extended helicene TBBA in 60% yield, which
corresponds to 88% per C−C bond.
Although it has been recently shown that bulky substituents
can prevent TBBA from the cyclization under Scholl
conditions,41 pristine molecules bearing a fjord-region cannot
be obtained via this reaction. Contrary to hexabenzocor-
onene,42 the distortion in 4 caused by the helical moiety
enhances solubility and allows not only measurement of the
B
https://dx.doi.org/10.1021/acs.orglett.0c01717
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Table 1. Plots of the FOD Density (σ = 0.01 e/bohr3) of
Diradicaloids, Their Biradical Characters, Barriers of
Electrocyclization, and Length of C−C Bonds in Transition
States
Figure 3. Synthesis and characterization of TBBA: (a) Domino
reaction including DPEX and two subsequent oxidative electro-
cyclizations. (b) UV−vis spectrum of TBBA in toluene. (c) DFT-
calculated structure of TBBA. (d) Comparison of DFT-calculated and
1
recorded (300 MHz, C2D2Cl4) H NMR spectrum of TBBA. The
calculated spectrum was scaled by a factor of 0.88. The assignment of
signals is based on DFT.
UV−vis spectrum but also recording of the 1H NMR spectrum
(Figure 3).
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01717.
To support our qualitative model, we have performed DFT
calculations investigating the electronic structures and the
transformations of the diradicaloids RS1a, RS1, RS2, and RS3
(computation details can be found in the SI). The distributions
of the biradical density obtained from the FOD analysis (Table
1) are in perfect agreement with the prediction based on the
Clar model (Figure 2). The applicability of the FOD analysis
and its comparison with other alternative methods have been
discussed previously.23,43 Based on the data for RS1, RS1a, and
RS2, a strong correlation between N_FOD, biradical character
y,44 the reaction barrier, and the length of the forming C−C
bond in transition states can be noticed. This observation can
be interpreted as follows: a higher biradical character
(measured as y or N_FOD) induces an earlier TS and
therefore a lower barrier. Although this trend fits for RS1,
RS1a, and RS2, the larger systems (RS3, 4a, 4b) are
significantly more complex, e.g., chemically irrelevant lengths
■
sı
Details of the synthetic procedures, DFT calculations,
copies of NMR, mass, UV−vis, and HPLC chromato-
grams (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Mikhail Feofanov − Institute of Chemistry, Organic Chemistry,
Martin-Luther-University Halle-Wittenberg, D-06120 Halle,
Germany; Department of Chemistry and Pharmacy, Organic
Chemistry II, Friedrich-Alexander University Erlangen-
Nuernberg, 91058 Erlangen, Germany; orcid.org/0000-
0003-4733-5636; Email: feofanovmn@gmail.com
Konstantin Amsharov − Institute of Chemistry, Organic
Chemistry, Martin-Luther-University Halle-Wittenberg, D-
06120 Halle, Germany; South Ural State University, 454080
Chelyabinsk, Russia; orcid.org/0000-0002-2854-8081;
Email: konstantin.amsharov@chemie.uni-halle.de
of the C−C contacts in the corresponding TSs were found.
36
́
̌
Recent work of Juricek et al. demonstrates that even
CASSCF treatment of such diradicaloid reactions does not
provide barriers quantitatively comparable with the exper-
imental results. Thus, despite all the efforts applied to the
investigation of the electronic structures and qualitative
agreement with the experimentally obtained yields, the
presented results should be taken as a semiquantitative
evaluation.
Authors
Vladimir Akhmetov − Institute of Chemistry, Organic
Chemistry, Martin-Luther-University Halle-Wittenberg, D-
06120 Halle, Germany; Department of Chemistry and
Pharmacy, Organic Chemistry II, Friedrich-Alexander
University Erlangen-Nuernberg, 91058 Erlangen, Germany;
orcid.org/0000-0001-8153-5477
In summary, we present how DPEX together with a simple
empirical model provides rapid access to intricate PAHs. While
DPEX enables the effective generation of diradicaloid
intermediates, the Clar model allows the rational design of
the domino reaction enabling up to four C−C bonds formed in
one step.
Dmitry I. Sharapa − Institut fu
-technologie, Karlsruhe Institute of Technology, 76344
̈
r Katalyseforschung und
C
https://dx.doi.org/10.1021/acs.orglett.0c01717
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(15) Gonzalez-Rodriguez, E.; Abdo, M. A.; dos Passos Gomes, G.;
Ayad, S.; White, F. D.; Tsvetkov, N. P.; Hanson, K.; Alabugin, I.
Twofold π-Extension of Polyarenes via Double and Triple Radical
Alkyne Peri-Annulations: Radical Cascades Converging on the Same
Aromatic Core. J. Am. Chem. Soc. 2020, 142, 8352.
Eggenstein-Leopoldshafen, Germany; orcid.org/0000-0001-
9510-9081
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01717
́
́
(16) Pozo, I.; Guitian, E.; Perez, D.; Pena, D. Synthesis of
̃
Funding
Nanographenes, Starphenes, and Sterically Congested Polyarenes by
Aryne Cyclotrimerization. Acc. Chem. Res. 2019, 52 (9), 2472−2481.
Funded by the Deutsche Forschungsgemeinschaft (DFG) −
Projektnummer 182849149-SFB 953 A6 and by Act 211
Government of the Russian Federation, Contract No.
02.A03.21.0011.
́
(17) Hagui, W.; Doucet, H.; Soule, J. F. Application of Palladium-
Catalyzed C(Sp2)-H Bond Arylation to the Synthesis of Polycyclic
(Hetero)Aromatics. Chem. 2019, 5 (8), 2006−2078.
(18) Koga, Y.; Kaneda, T.; Saito, Y.; Murakami, K.; Itami, K.
Synthesis of Partially and Fully Fused Polyaromatics by Annulative
Chlorophenylene Dimerization. Science (Washington, DC, U. S.) 2018,
359 (6374), 435−439.
Notes
The authors declare no competing financial interest.
(19) Wang, X. Y.; Yao, X.; Mu
1099.
̈
llen, K. Sci. China: Chem. 2019, 62,
ACKNOWLEDGMENTS
■
The authors are thankful to Dr. Harald Maid (Friedrich-
Alexander University Erlangen-Nuernberg, Erlangen, Ger-
many) for NMR measurements and spectra interpretations.
(20) Kawasumi, K.; Zhang, Q.; Segawa, Y.; Scott, L. T.; Itami, K. A
Grossly Warped Nanographene and the Consequences of Multiple
Odd-Membered-Ring Defects. Nat. Chem. 2013, 5 (9), 739−744.
(21) Liu, J.; Narita, A.; Osella, S.; Zhang, W.; Schollmeyer, D.;
REFERENCES
Beljonne, D.; Feng, X.; Mullen, K. Unexpected Scholl Reaction of
̈
■
6,7,13,14-Tetraarylbenzo[k]Tetraphene: Selective Formation of Five-
Membered Rings in Polycyclic Aromatic Hydrocarbons. J. Am. Chem.
Soc. 2016, 138 (8), 2602−2608.
(1) Mu
Graphene Nanoribbons; Mu
̈
llen, K.; Feng, X. From Polyphenylenes to Nanographenes and
llen, K., Feng, X., Eds.; Advances in
̈
Polymer Science; Springer International Publishing: Cham, 2017; Vol.
́
278.
(22) Fernandez-García, J. M.; Evans, P. J.; Medina Rivero, S.;
(2) Mullen, K.; Feng, X. In Chemistry of Carbon Nanostructures;
̈
́
Fernandez, I.; García-Fresnadillo, D.; Perles, J.; Casado, J.; Martín, N.
Muellen, K., Feng, X., Eds.; De Gruyter: Berlin, Boston, 2017.
(3) Ai, Q.; Jarolimek, K.; Mazza, S.; Anthony, J. E.; Risko, C.
Delimited Polyacenes: Edge Topology as a Tool to Modulate Carbon
Nanoribbon Structure, Conjugation, and Mobility. Chem. Mater.
2018, 30 (3), 947−957.
(4) Lee, J. H.; Chen, C. H.; Lee, P. H.; Lin, H. Y.; Leung, M. K.;
Chiu, T. L.; Lin, C. F. Blue Organic Light-Emitting Diodes: Current
Status, Challenges, and Future Outlook. J. Mater. Chem. C 2019, 7
(20), 5874−5888.
(5) Aumaitre, C.; Morin, J. F. Polycyclic Aromatic Hydrocarbons as
Potential Building Blocks for Organic Solar Cells. Chem. Rec. 2019, 19
(6), 1142−1154.
π-Extended Corannulene-Based Nanographenes: Selective Formation
of Negative Curvature. J. Am. Chem. Soc. 2018, 140 (49), 17188−
17196.
(23) Feofanov, M.; Akhmetov, V.; Sharapa, D. I.; Amsharov, K.
Modular Approach to the Synthesis of Two-Dimensional Angular
Fused Acenes. Org. Lett. 2020, 22 (5), 1698−1702.
(24) Sun, Z.; Wu, J. Open-Shell Polycyclic Aromatic Hydrocarbons.
J. Mater. Chem. 2012, 22 (10), 4151−4160.
(25) Hu, P.; Wu, J. Modern Zethrene Chemistry. Can. J. Chem.
2017, 95 (3), 223−233.
(26) Fu, X.; Zhao, D. Cyclo-Oligomerization of 6,12-Diethynyl
Indeno[1,2-b]Fluorenes via Diradical Intermediates. Org. Lett. 2015,
17 (22), 5694−5697.
(6) Lungerich, D.; Papaianina, O.; Feofanov, M.; Liu, J.; Devarajulu,
M.; Troyanov, S. I.; Maier, S.; Amsharov, K. Dehydrative π-Extension
to Nanographenes with Zig-Zag Edges. Nat. Commun. 2018, 9 (1),
4756.
(27) Sahara, K.; Abe, M.; Zipse, H.; Kubo, T. Duality of Reactivity of
a Biradicaloid Compound with an O-Quinodimethane Scaffold. J. Am.
Chem. Soc. 2020, 142 (11), 5408−5418.
̈
(7) Wohrle, T.; Wurzbach, I.; Kirres, J.; Kostidou, A.; Kapernaum,
(28) Bian, M.; Li, L.; Ding, H. Recent Advances on the Application
of Electrocyclic Reactions in Complex Natural Product Synthesis.
Synthesis 2017, 28 (19), 4383−4413.
N.; Litterscheidt, J.; Haenle, J. C.; Staffeld, P.; Baro, A.; Giesselmann,
F.; et al. Discotic Liquid Crystals. Chem. Rev. 2016, 116 (3), 1139−
1241.
(29) Fleming, I. Molecular Orbitals and Organic Chemical Reactions;
John Wiley & Sons, Ltd: Chichester, UK, 2010.
(8) Kim, S.; Kim, B.; Lee, J.; Shin, H.; Park, Y. Il; Park, J. Design of
Fluorescent Blue Light-Emitting Materials Based on Analyses of
Chemical Structures and Their Effects. Mater. Sci. Eng., R 2016, 99,
1−22.
(9) Kaur, N.; Singh, M.; Pathak, D.; Wagner, T.; Nunzi, J. M.
Organic Materials for Photovoltaic Applications: Review and
Mechanism. Synth. Met. 2014, 190, 20−26.
(30) Beaudry, C. M.; Malerich, J. P.; Trauner, D. Biosynthetic and
Biomimetic Electrocyclizations. Chem. Rev. 2005, 105 (12), 4757−
4778.
(31) Woodward, R.B.; Hoffmann, R.. The Conservation of Orbital
Symmetry; Elsevier, 1971.
(32) Yu, T. Q.; Fu, Y.; Liu, L.; Guo, Q. X. How to Promote Sluggish
Electrocyclization of 1,3,5-Hexatrienes by Captodative Substitution. J.
Org. Chem. 2006, 71 (16), 6157−6164.
(10) Mei, J.; Diao, Y.; Appleton, A. L.; Fang, L.; Bao, Z. Integrated
Materials Design of Organic Semiconductors for Field-Effect
Transistors. J. Am. Chem. Soc. 2013, 135 (18), 6724−6746.
(11) Wang, C.; Dong, H.; Hu, W.; Liu, Y.; Zhu, D. Semiconducting
π-Conjugated Systems in Field-Effect Transistors: A Material Odyssey
of Organic Electronics. Chem. Rev. 2012, 112 (4), 2208−2267.
(12) Ito, H.; Ozaki, K.; Itami, K. Annulative π-Extension (APEX):
Rapid Access to Fused Arenes, Heteroarenes, and Nanographenes.
Angew. Chem., Int. Ed. 2017, 56 (37), 11144−11164.
(13) Ito, H.; Segawa, Y.; Murakami, K.; Itami, K. Polycyclic Arene
Synthesis by Annulative π-Extension. J. Am. Chem. Soc. 2019, 141 (1),
3−10.
(33) Steiner, R. P.; Michl, J. π,π-Biradicaloid Hydrocarbons. The
Pleiadene Family. 3.1 A Facile Symmetry-Forbidden Thermal
Conversion of a Polycyclic Butadiene Moiety to a Cyclobutene. J.
Am. Chem. Soc. 1978, 100 (20), 6413−6415.
̈
(34) Ravat, P.; Solomek, T.; Rickhaus, M.; Haussinger, D.;
̌
Neuburger, M.; Baumgarten, M.; Jurícek, M. Cethrene: A Helically
Chiral Biradicaloid Isomer of Heptazethrene. Angew. Chem., Int. Ed.
2016, 55 (3), 1183−1186.
(35) Uchida, K.; Ito, S.; Nakano, M.; Abe, M.; Kubo, T.
Biphenalenylidene: Isolation and Characterization of the Reactive
Intermediate on the Decomposition Pathway of Phenalenyl Radical. J.
Am. Chem. Soc. 2016, 138 (7), 2399−2410.
(14) Senese, A. D.; Chalifoux, W. A. Nanographene and Graphene
Nanoribbon Synthesis via Alkyne Benzannulations. Molecules 2019,
24 (1), 118.
D
https://dx.doi.org/10.1021/acs.orglett.0c01717
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
̌
̌
(36) Solomek, T.; Ravat, P.; Mou, Z.; Kertesz, M.; Jurícek, M.
Cethrene: The Chameleon of Woodward-Hoffmann Rules. J. Org.
Chem. 2018, 83 (8), 4769−4774.
̌
̈
̌
(37) Ravat, P.; Solomek, T.; Haussinger, D.; Blacque, O.; Jurícek, M.
Dimethylcethrene: A Chiroptical Diradicaloid Photoswitch. J. Am.
Chem. Soc. 2018, 140 (34), 10839−10847.
̌
̌
(38) Solomek, T.; Ravat, P.; Jurícek, M. ‘Forbidden’ Electro-
cyclizations of Diradicaloids. Trends Chem. 2019, 1 (7), 705−706.
̈
(39) Nising, C. F.; Schmid, U. K.; Nieger, M.; Brase, S. A New
Protocol for the One-Pot Synthesis of Symmetrical Biaryls. J. Org.
Chem. 2004, 69 (20), 6830−6833.
(40) Sola, M. Forty Years of Clar’s Aromatic π-Sextet Rule. Front.
̀
Chem. 2013, 1 (October), 4−11.
(41) Jux, N.; Martin, M. M.; Hampel, F. A Hexabenzocoronene-
Based Helical Nanographene. Chem. - Eur. J. 2020, 13 (3),
chem.202001471.
(42) Herwig, P. T.; Enkelmann, V.; Schmelz, O.; Mullen, K.
̈
Synthesis and Structural Characterization of Hexa-Tert-Butyl- Hexa-
Peri-Hexabenzocoronene, Its Radical Cation Salt and Its Tricarbo-
nylchromium Complex. Chem. - Eur. J. 2000, 6 (10), 1834−1839.
(43) Grimme, S.; Hansen, A. A Practicable Real-Space Measure and
Visualization of Static Electron-Correlation Effects. Angew. Chem., Int.
Ed. 2015, 54 (42), 12308−12313.
(44) Kamada, K.; Ohta, K.; Shimizu, A.; Kubo, T.; Kishi, R.;
Takahashi, H.; Botek, E.; Champagne, B.; Nakano, M. Singlet
Diradical Character from Experiment. J. Phys. Chem. Lett. 2010, 1 (6),
937−940.
E
https://dx.doi.org/10.1021/acs.orglett.0c01717
Org. Lett. XXXX, XXX, XXX−XXX