Electrophilic substitution of asymmetrically distorted benzenes within triptycene derivatives

Article abstract of DOI:10.1021/acs.orglett.1c00970

Herein, we disclose a unique directing effect of 9-substituted triptycenes in electrophilic substitution to achieve the regioselective functionalization of the triptycene core. The Hirshfeld population analysis was adopted to predict the selectivity in el

Full text of DOI:10.1021/acs.orglett.1c00970

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Letter
Electrophilic Substitution of Asymmetrically Distorted Benzenes
within Triptycene Derivatives
Keisuke Ueno, Yuji Nishii,* and Masahiro Miura*
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ABSTRACT: Herein, we disclose a unique directing effect of 9-substituted triptycenes in electrophilic substitution to achieve the
regioselective functionalization of the triptycene core. The Hirshfeld population analysis was adopted to predict the selectivity in
electrophilic substitution. TMS and t-Bu groups were found to considerably accelerate the reaction at C2 positions to produce C3-
symmetric isomers. Correlation between distortion and charge distribution within benzene rings was systematically examined.
Scheme 1. Synthetic Methods for Functionalized Triptycene
Derivatives
riptycene is a paddle-wheel-shaped aromatic hydrocarbon
Tin which three benzene rings are fused within a barrelene
core.1 Functionalized triptycene derivatives have exhibited
privileged structures in many research areas involving material
science, supramolecular chemistry, molecular machines, etc.,2,3
owing to their unique three-dimensional rigid architecture.
Accordingly, significant interest has focused on the develop-
ment of efficient and controllable synthetic methods for
manufacturing functionalized triptycenes.
A conventional synthetic method is the Diels−Alder
reaction of anthracenes with benzynes (Scheme 1a). This
strategy is not suitable for synthesizing functionalized
triptycenes because it is hardly possible to control the
regioselectivity of the cycloaddition event.4,5 Moreover,
cumbersome multistep synthesis would be inevitable for the
preparation of substituted reactants. Alternatively, electrophilic
substitution has been a practical tool for directly introducing
functionalities onto the periphery of the triptycene core.6 The
transannular π−π interaction between the remote benzene
rings has been well-established,7 but this interaction exerts
negligible effects on site selectivity. Therefore, the three
benzene rings independently react with electrophiles to form
all possible isomers whose distribution is statistically governed
(Scheme 1b). Iridium-catalyzed C−H borylation has also been
utilized to directly install functionalities to the triptycene core.8
The selectivity in this method can be treated like the
electrophilic substitution and give the same result. Obviously,
it is highly challenging to break the D3h symmetry of this
molecule and systematically construct C3-symmetric aromatic
scaffolds, and a new synthetic approach should be required to
overcome the statistical limitation.9
Meanwhile, we recently introduced a triptycene-based Lewis
base catalyst Trip-SMe (Trip = 9-triptycenyl) for electrophilic
Received: March 21, 2021
Published: April 23, 2021
https://doi.org/10.1021/acs.orglett.1c00970
© 2021 American Chemical Society
Org. Lett. 2021, 23, 3552−3556
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halogenation of unactivated aromatics using N-halosuccini-
mides.10 This catalyst forms a corresponding halo-sulfonium
complex in situ; its enhanced charge-separated ion character
contributes the high catalytic activity, and AgSbF6 was
employed as a source of weakly coordinating anions. During
the study, we found that the bromination of Trip-SMe
proceeded with considerable regioselectivity to give the C3-
symmetric isomer as a major product (Scheme 1c).
Scheme 2. (a) Installation and Removal of the TMS
Directing Group and (b) Scale-up Reaction
This result indicates that the substituent at the bridgehead
position can modulate the positional selectivity in functionaliz-
ing the aromatic moiety, leading to an efficient synthetic
method for Janus-type triptycene derivatives. Herein, we
evaluated the unprecedented directing effect for a series of 9-
substituted triptycenes. The Hirshfeld population analysis was
adopted to predict the selectivity in aromatic electrophilic
reactions. Additionally, a unique trend between the distortion
within a benzene ring and the charge distribution was
theoretically examined.
At the outset, we conducted a computational study to
evaluate the unexpected C2 selectivity observed in the
bromination of Trip-SMe (1b). In 2019, Galabov established
a quantitative correspondence between the σ0 substituent
constants of benzene derivatives and the Hirshfeld charge on
ring carbon atoms.11 This method was adopted to estimate the
reactivity and regioselectivity of 1b as well as several triptycene
derivatives (1c−1f). Geometry optimizations and frequency
calculations were carried out at the M06X-2/6-311+G(d,p)
level of theory with IEF-PCM (DCE) solvation. The Hirshfeld
population analysis was conducted at the B3LYP/6-311+G-
(3df,2pd) level. The charge differences according to a
reference triptycene (1a, where R = H and Δq = 0) are
summarized in Figure 1. Note that the lower Δq values
correspond to the higher nucleophilicity of carbon atoms.
suggesting its low reactivity toward electrophiles. Intriguingly,
installation of a TMS (1e) or t-Bu (1f) group at the
bridgehead carbon established considerable negative charges
on C2 atoms, whereas C3 atoms were almost neutral as
compared to that of triptycene (1a). These results prompted
speculation that the electrophilic substitution of Trip-TMS
(1e) and Trip-t-Bu (1f) proceeds with better regioselectivity.
With this picture in mind, we evaluated the regioselectivity
in bromination adopting a Trip-SMe/AgSbF6 catalyst system.
A series of triptycene derivatives were treated with NBS under
the standard conditions (Table 1). The reaction of triptycene
a
Table 1. Optimization Study
b
b
entry
R
yield of 2 and 3
note
c
1
SMe (1b)
H (1a)
OMe (1c)
Br (1d)
TMS (1e)
t-Bu (1f)
2b (53%), 3b (17%)
not detected
not determined
<10% in total
2e 64% (61%), 3e 22%
2f 80% (51%)
--
2
3
4
5
6
1a 44%, mono 60%
complex mixture
mono 27%, di 59%
<20% other isomers
<20% other isomers
a
Reaction conditions: 1 (0.2 mmol), NBS (0.72 mmol), Trip-SMe
(1.0 mol %), and AgSbF6 (1.0 mol %) in DCE solvent (2.0 mL).
b
Estimated by NMR and GC-MS analyses. Isolated yield in
c
parentheses. Data from ref 10.
Figure 1. Summary of the difference in Hirschfeld charges calculated
at the B3LYP/6-311+G(3df,2pd) level.
(1a) ended up in 60% monobromination probably because of
its poor solubility in DCE (entry 2). Trip-OMe (1c) afforded a
complex mixture of isomers, and the yield of 2c and 3c could
not be determined (entry 3). Trip-Br (1d) reacted rather
sluggishly to give the target products in only low yield (≤10%
in total, entry 4). To our delight, the C2 position was
preferentially brominated for Trip-TMS (1e) (C2/C3 = 85/
15), and the corresponding C3-symmetric molecule 2e was
obtained in 64% yield along with 22% of a minor isomer 3e
(entry 5). Further improvement in selectivity was observed for
the reaction of Trip-t-Bu (1f) to produce 2f in 80% yield
(entry 6), and the formation of other isomers was considerably
reduced. The structures of 2e and 2f were unambiguously
determined by two-dimensional NMR and X-ray crystallo-
All of the triptycene derivatives have staggered conforma-
tions as the energy minima. Accordingly, inequivalent benzene
rings were considered for Trip-SMe (1b) and Trip-OMe (1c):
two rings close to the methyl group (C2 and C3) and the other
one opposite the methyl group (C2′ and C3′).12 The
calculated charges for Trip-SMe (1b) indicated that the C2
position is more nucleophilic than the other three carbon
atoms. This is consistent with the selectivity observed in the
halogenation (Scheme 2b). On the contrary, the C3′ atom was
somewhat activated for Trip-OMe (1c). Trip-Br (1d)
exhibited positive charges on both C2 and C3 atoms,
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graphic analyses (CCDC 2067724 and 2067725). These
outcomes correspond well to the charge analysis (Figure 1).
In particular, the directing effect of the TMS group is
synthetically valuable for obtaining a statistically minor isomer.
Trip-TMS (1e) was readily prepared from commercially
available Trip-Br (1d) in one step (Scheme 2). Bromination
product 2e was isolated by regular silica-gel column
chromatography, and the directing group was quantitatively
removed upon treatment with TBAF (tetrabutylammonium
fluoride), affording 2,7,14-tribromotriptycene (4) in 59% yield
over three steps. A conventional method for this compound
has required cumbersome multistep processes via nitration
with concentrated HNO3, Raney Ni reduction of the minor
isomer, and Sandmeyer halogenation (total 13% yield).13
Notably, the bromination of 1e could be conducted on a 2.0
mmol scale, and the desired product could be isolated in 50%
yield by recrystallization from the crude material without
chromatographic purification. Although Trip-t-Bu (1f) ex-
hibited better selectivity in the bromination (Table 1, entry 6),
its preparation suffers from low efficiency (total 15% yield over
three steps).14 Moreover, purification of 2f from the crude
reaction mixture is not easy [51% isolated yield (Table 1, entry
6)], and it is hardly possible to remove the t-Bu directing
group afterward.
to the limited availability of suitable building blocks such as 4
and 8.
The directing effect of the TMS group was also examined for
other electrophiles (Scheme 4). The C2/C3 selectivity was
Scheme 4. Reaction of 1e with Other Electrophiles
72/28 for trifluoromethylthiolation using SCF3-saccharin16 to
produce 10 in 35% yield. On the contrary, a lower selectivity
was observed for nitration (C2/C3 = 57/43),17 giving target
product 11 in 11% yield. These results indicated that the
regioselectivity considerably depends on the electrophile as
well as the reaction conditions employed (for details, see the
Supporting Information).18
Next, we examined some derivatizations of 4 to highlight the
synthetic utility (Scheme 3). Under the standard Sonogashira
a
Scheme 3. Derivatization of 4
Triptycene (1a) is a molecule with a typical Mills−Nixon
effect,19 exhibiting a considerable bond alternation within the
benzene rings: C1−C2, C3−C4, and C5−C6 bonds have
single-bond character. As a result, the enhanced positional
selectivity in the electrophilic substitution was observed at β
carbons (C2 and C3) rather than α carbons (C1 and C4).
Additionally, substituents at the bridgehead position of
triptycene derivatives 1b−1f would asymmetrically distort
the ring (for details, see the Supporting Information). To
elucidate correlation between such a strain and the charge
distribution, we calculated Hirshfeld atomic charges for
“distorted o-xylenes” quarried from the optimized geometries
of 1b−1f (Figure 2).
Trip-SMe (1b), Trip-OMe (1c), and Trip-Br (1d) showed
no clear trend. In sharp contrast, each C2 atom of Trip-TMS
(1e) and Trip-t-Bu (1f) carried significant negative charges,
whereas C3 atoms were positively charged. Because TMS and
t-Bu groups exert minimal inductive effects on the triptycene
a
Reaction conditions: (a) TMS-acetylene (7.5 equiv), Pd(PPh3)4 (15
mol %), CuI (10 mol %), and i-Pr2NH (7.5 equiv) in toluene at 85 °C
for 18 h; (b) phenol (3.3 equiv), Pd(OAc)2 (15 mol %), t-BuXPhos
(20 mol %), and K2CO3 (6.0 equiv) in toluene at 100 °C for 24 h; (c)
di(p-tolyl)amine (3.3 equiv), Pd(OAc)2 (15 mol %), dppf (45 mol
%), and t-BuONa (9.0 equiv) in toluene at 100 °C for 18 h; (d)
B2pin2 (3.3 equiv), PdCl2(PPh3)2 (10 mol %), and KOAc (3.3 equiv)
in 1,4-dioxane at 120 °C for 18 h; (e) (2-bromophenyl)methyl
sulfoxide (3.9 equiv), Pd(PPh3)4 (10 mol %), TBAB (10 mol %), and
aqueous K2CO3 in THF at 70 °C for 24 h; (f) TfOH in DCE at rt for
24 h, then pyridine and H2O, reflux for 4 h.
conditions, three alkyne units were efficiently introduced into
the triptycene core (5, 78% yield). The corresponding aryl
ether 6 and amine 7 were synthesized by Buchwald−Hartwig
coupling reactions in 42% and 78% yields, respectively.15 It is
noteworthy that a thiophene-fused three-dimensional π
architecture (9) was readily constructed via the sequential
borylation (8, 71% yield), cross-coupling reaction, and acid-
mediated intramolecular cyclization. Synthesis of these
isomerically uniform molecules has been scarce probably due
Figure 2. Summary of the difference in Hirschfeld charges calculated
at the B3LYP/6-311+G(3df,2pd) level.
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Author
core, the high C2 selectivity observed for Trip-TMS (1e) and
Trip-t-Bu (1f) can be mainly attributed to the structural
distortion by the steric effect.20 As compared to the benchmark
triptycene (1a), these two molecules have elongated bonds
close to the R group (C5−C6 and C6−C1) and shortened
bonds distant from it (C2−C3 and C3−C4). This might lead
to increased diene character over C2−C5 atoms within
benzene rings; thereby, the terminal C2 atom preferentially
reacted with electrophiles. We emphasize that such a selectivity
induced by asymmetrical distortion has not been investigated,
and the triptycene scaffold would be a suitable model for the
study.
Conventionally, the site selectivity in aromatic substitution
reactions has been discussed on the basis of the stability of
corresponding σ complexes.21 We acquired relative energies for
C2- and C3-protonated species of Trip-TMS (1e) as well as
Trip-t-Bu (1f) at the M06X-2/6-311+G(d,p) level. In both
cases, the energy of the C2 adduct was lower than that of the
C3 adduct by 2.25 kcal/mol for 1e and 1.63 kcal/mol for 1f.
The positive charge within each complex considerably
localized at the para position to the sp3 carbon. This is also
consistent with the observed regioselectivity.
Keisuke Ueno − Department of Applied Chemistry, Graduate
School of Engineering, Osaka University, Suita, Osaka 565-
0871, Japan
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c00970
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by JSPS KAKENHI Grant JP
19K15586 (Grant-in-Aid for Young Scientists) to Y.N., the
Foundation for the Promotion of Ion Engineering (Y.N.), and
JSPS KAKENHI Grant JP 17H06092 (Grant-in-Aid for
Specially Promoted Research) to M.M. The authors thank
Dr. Hiroaki Iwamoto (Osaka University) for his assistance with
DFT calculations.
REFERENCES
■
(1) For seminal works, see: (a) Bartlett, P. D.; Ryan, M. J.; Cohen, S.
G. Triptycene (9,10-o-Benzenoanthracene). J. Am. Chem. Soc. 1942,
64, 2649−2653. (b) Wittig, G.; Ludwig, R. Triptycen aus Anthracen
und Dehydrobenzol. Angew. Chem. 1956, 68, 40−41. (c) Wittig, G.;
Benz, E. Eine neue Triptycen-Synthese. Angew. Chem. 1958, 70, 166.
(d) Craig, A.; Wilcox, C., Jr. Communications: A New Synthesis of
Triptycene. J. Org. Chem. 1959, 24, 1619.
In conclusion, we disclosed a unique directing effect of 9-
substituted triptycene derivatives for electrophilic substitution.
Hirshfeld population analysis was utilized to predict the
selectivity in bromination reactions, and Trip-TMS (1e) and
Trip-t-Bu (1f) were found to produce C3-symmetric isomers as
major products. In addition to the Mills−Nixon effect,
structural distortion of benzene rings was found to be a key
factor to enhance the positional selectivity.
(2) For selected recent reviews, see: (a) Swager, T. M. Iptycenes in
the Design of High Performance Polymers. Acc. Chem. Res. 2008, 41,
1181−1189. (b) Chong, J. H.; MacLachlan, M. J. Iptycenes in
supramolecular and materials chemistry. Chem. Soc. Rev. 2009, 38,
3301−3315. (c) Jiang, Y.; Chen, C.-F. Recent Developments in
Synthesis and Applications of Triptycene and Pentiptycene
Derivatives. Eur. J. Org. Chem. 2011, 2011, 6377. (d) Han, Y.;
Meng, Z.; Ma, Y.-X.; Chen, C.-F. Iptycene-Derived Crown Ether
Hosts for Molecular Recognition and Self-Assembly. Acc. Chem. Res.
2014, 47, 2026−2040. (e) Chen, C.-F.; Han, Y. Triptycene-Derived
Macrocyclic Arenes: From Calixarenes to Helicarenes. Acc. Chem. Res.
2018, 51, 2093−2106. (f) Locke, G. M.; Bernhard, S. S. R.; Senge, M.
O. Nonconjugated Hydrocarbons as Rigid-Linear Motifs: Isosteres for
Material Sciences and Bioorganic and Medicinal Chemistry. Chem. -
Eur. J. 2019, 25, 4590−4647.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c00970.
Experimental procedures, computational method, prod-
uct identification data, and copies of NMR spectra
(PDF)
(3) For recent selected examples, see: (a) Ishiwari, F.; Okabe, G.;
Ogiwara, H.; Kajitani, T.; Tokita, M.; Takata, M.; Fukushima, T.
Terminal Functionalization with a Triptycene Motif That Dramati-
cally Changes the Structural and Physical Properties of an Amorphous
Polymer. J. Am. Chem. Soc. 2018, 140, 13497−13502. (b) Peurifoy, S.
R.; Russell, J. C.; Sisto, T. J.; Yang, Y.; Roy, X.; Nuckolls, C. Designing
Three-Dimensional Architectures for High-Performance Electron
Accepting Pseudocapacitors. J. Am. Chem. Soc. 2018, 140, 10960−
10964. (c) Mahmood, J.; Kim, S.-J.; Noh, H.-J.; Jung, S.-M.; Ahmad,
I.; Li, F.; Seo, J.-M.; Baek, J.-B. A Robust 3D Cage-like Ultra-
microporous Network Structure with High Gas-Uptake Capacity.
Angew. Chem., Int. Ed. 2018, 57, 3415−3420. (d) Ikai, T.; Yoshida, T.;
Shinohara, K.; Taniguchi, T.; Wada, Y.; Swager, T. M. Triptycene-
Based Ladder Polymers with One-Handed Helical Geometry. J. Am.
Chem. Soc. 2019, 141, 4696−4703. (e) Hu, B.-L.; An, C.; Wagner, M.;
Ivanova, G.; Ivanova, A.; Baumgarten, M. Three-Dimensional Pyrene-
Fused N-Heteroacenes. J. Am. Chem. Soc. 2019, 141, 5130−5134.
(f) Xu, W.; Yang, X.-D.; Fan, X.-B.; Wang, X.; Tung, C.-H.; Wu, L.-Z.;
Cong, H. Synthesis and Characterization of a Pentiptycene-Derived
Dual Oligoparaphenylene Nanohoop. Angew. Chem., Int. Ed. 2019, 58,
3943−3947. (g) Li, H.; Ding, J.; Guan, X.; Chen, F.; Li, C.; Zhu, L.;
Xue, M.; Yuan, D.; Valtchev, V.; Yan, Y.; Qiu, S.; Fang, Q. Three-
Dimensional Large-Pore Covalent Organic Framework with stp
Topology. J. Am. Chem. Soc. 2020, 142, 13334−13338. (h) Li, Z.;
Atomic coordinates of all calculated molecules (XYZ)
Accession Codes
CCDC 2067724−2067725 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Authors
Yuji Nishii − Department of Applied Chemistry, Graduate
School of Engineering, Osaka University, Suita, Osaka 565-
0871, Japan; orcid.org/0000-0002-6824-0639;
Email: y_nishii@chem.eng.osaka-u.ac.jp
Masahiro Miura − Department of Applied Chemistry,
Graduate School of Engineering, Osaka University, Suita,
Osaka 565-0871, Japan; orcid.org/0000-0001-8288-
6439; Email: miura@chem.eng.osaka-u.ac.jp
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Sheng, L.; Wang, H.; Wang, Z.; Li, M.; Xu, Y.; Cui, H.; Zhang, H.;
Liang, H.; Xu, H.; He, X. Three-Dimensional Covalent Organic
Framework with ceq Topology. J. Am. Chem. Soc. 2021, 143 (1), 92−
96.
(14) (a) Parish, R. C.; Stock, L. M. 9-t-Butylanthracene. J. Org.
Chem. 1966, 31, 4265−4267. (b) Seki, S.; Morinaga, T.; Kikuchi, H.;
Mitsuhashi, T.; Yamamoto, G.; Oki, M. Reactivities of Stable
Rotamers. VI. Manifestation of Differential Reactivities of the Methyls
in a t-Butyl Group in Radical Halogenations. Bull. Chem. Soc. Jpn.
1981, 54, 1465−1469.
(15) (a) Burgos, C. H.; Barder, T. E.; Huang, X.; Buchwald, S. L.
Significantly Improved Method for the Pd-Catalyzed Coupling of
Phenols with Aryl Halides: Understanding Ligand Effects. Angew.
Chem., Int. Ed. 2006, 45, 4321−4326. (b) Chang, Y. J.; Chow, T. J.
Triaryl linked donor acceptor dyads for high-performance dye-
sensitized solar cells. Tetrahedron 2009, 65, 9626−9632.
(16) Xu, C.; Ma, B.; Shen, Q. N-Trifluoromethylthiosaccharin: An
Easily Accessible, Shelf-Stable, Broadly Applicable Trifluoromethylth-
iolating Reagent. Angew. Chem., Int. Ed. 2014, 53, 9316−9320.
(17) Calvo, R.; Zhang, K.; Passera, A.; Katayev, D. Facile access to
nitroarenes and nitroheteroarenes using N-nitrosaccharin. Nat.
Commun. 2019, 10, 3410.
(4) For selected examples, see: (a) Elbert, S. M.; Rominger, F.;
Mastalerz, M. Synthesis of a Rigid C3v-Symmetric Tris-salicylaldehyde
as a Precursor for a Highly Porous Molecular Cube. Chem. - Eur. J.
2014, 20, 16707. (b) Seiki, N.; Shoji, Y.; Kajitani, T.; Ishiwari, F.;
Kosaka, A.; Hikima, T.; Takata, M.; Someya, T.; Fukushima, T.
Rational synthesis of organic thin films with exceptional long-range
structural integrity. Science 2015, 348, 1122−1126. (c) Xiao, Y.;
Mague, J. T.; Pascal, R. A., Jr. An Exceptionally Close, Non-Bonded
Hydrogen−Hydrogen Contact with Strong Through-Space Spin−
Spin Coupling. Angew. Chem., Int. Ed. 2018, 57, 2244−2247.
(5) Cycloaddition of ynolates with benzynes was reported to
proceed regioselectively: (a) Umezu, S.; dos Passos Gomes, G.;
Yoshinaga, T.; Sakae, M.; Matsumoto, K.; Iwata, T.; Alabugin, I.;
Shindo, M. Regioselective One-Pot Synthesis of Triptycenes via
Triple-Cycloadditions of Arynes to Ynolates. Angew. Chem., Int. Ed.
2017, 56, 1298−1302. (b) Yoshinaga, T.; Fujiwara, T.; Iwata, T.;
Shindo, M. Synthesis of Distorted 1,8,13-Trisilyl-9-hydroxytriptycenes
by Triple Cycloaddition of Ynolates to 3-Silylbenzynes. Chem. - Eur. J.
2019, 25, 13855−13859. (c) Iwata, T.; Yoshinaga, T.; Shindo, M.
Flow Synthesis of Triptycene via Triple Cycloaddition of Ynolate to
Benzyne. Synlett 2020, 31, 1903−1906. (d) Sun, J.; Iwata, T.; Shindo,
M. Synthesis of 9-Hydroxytriptycenes Bearing a Functionalized
Substituent at the C-10 Position through a Triple Cycloaddition
Reaction of Ynolates Derived from 2,6-Di-tert-butylphenyl Esters.
Chem. Lett. 2020, 49, 1084−1087.
(6) For recent selected examples, see: (a) Bura, T.; Nastasi, F.;
Puntoriero, F.; Campagna, S.; Ziessel, R. Ultrafast energy transfer in
triptycene-grafted bodipy scaffoldings. Chem. - Eur. J. 2013, 19, 8900−
8912. (b) Granda, J. M.; Grabowski, J.; Jurczak, J. Synthesis,
Structure, and Complexation Properties of a C3-Symmetrical
Triptycene-Based Anion Receptor: Selectivity for Dihydrogen
Phosphate. Org. Lett. 2015, 17, 5882−5885. (c) Talipov, M. R.;
Navale, T. S.; Rathore, R. The HOMO Nodal Arrangement in
Polychromophoric Molecules and Assemblies Controls the Inter-
chromophoric Electronic Coupling. Angew. Chem., Int. Ed. 2015, 54,
14468−14472. (d) Zhou, H.; Tao, F.; Liu, Q.; Zong, C.; Yang, W.;
Cao, X.; Jin, W.; Xu, N. Microporous Polyamide Membranes for
Molecular Sieving of Nitrogen from Volatile Organic Compounds.
Angew. Chem., Int. Ed. 2017, 56, 5755−5759. See the Supporting
Information for additional references.
(18) We also examined the bromination of Trip-TMS (1e) using
Br2, but a complex mixture of isomers was obtained.
(19) (a) Taylor, R. Electrophilic aromatic substitution. Part III. The
effect of strain on the electrophilic reactivity of fluorene,
dibenzofuran, dibenzothiophen, and carbazole. J. Chem. Soc. B
1968, 1559−1562. (b) Stanger, A. Is the Mills-Nixon Effect Real? J.
Am. Chem. Soc. 1991, 113, 8277−8280. (c) Siegel, J. S. Mills-Nixon
Effect: Wherefore Art Thou? Angew. Chem., Int. Ed. Engl. 1994, 33,
1721−1723. (d) Rathore, R.; Lindeman, S. V.; Kumar, A. S.; Kochi, J.
K. Novel Synthesis and Structures of Tris-Annelated Benzene Donors
for the Electron-Density Elucidation of the Classical Mills-Nixon
́
Effect. J. Am. Chem. Soc. 1998, 120, 6012−6018. (e) Eckert-Maksic,
́
M.; Glasovac, Z.; Novak Coumbassa, N.; Maksic, Z. B. The Mills-
Nixon effect and chemical reactivity−methyl cation affinity of some
cycloalkabenzenes. J. Chem. Soc., Perkin Trans. 2001, 2, 1091−1098.
(20) Other silyl groups such as TES, TIPS, and TBDMS could not
be introduced onto the bridgehead position probably because of their
steric bulk.
(21) We attempted to acquire the transition states for electrophilic
addition but were not successful, implying that TS structures resemble
closely the σ complexes.
(7) Nakazawa, T.; Murata, I. The 9,10-Dihydro-9,10-(1,2-tropylio)
anthracene Tetrafluoroborate. Transannular π-π Interaction between
Tropylium Ion and Remote Benzene Rings. J. Am. Chem. Soc. 1977,
99, 1996−1997.
(8) Peurifoy, S. R.; Castro, E.; Liu, F.; Zhu, X.-Y.; Ng, F.; Jockusch,
S.; Steigerwald, M. L.; Echegoyen, L.; Nuckolls, C.; Sisto, T. J. Three-
Dimensional Graphene Nanostructures. J. Am. Chem. Soc. 2018, 140,
9341−9345.
(9) We recently reported a copper-catalyzed site-selective direct
arylation with the aid of a directing group: Ueno, K.; Nishii, Y.; Miura,
M. Copper-Catalyzed Site-Selective Direct Arylation of Triptycene.
Chem. Lett. 2020, 49, 689−692.
(10) Nishii, Y.; Ikeda, M.; Hayashi, Y.; Kawauchi, S.; Miura, M.
Triptycenyl Sulfide: A Practical and Active Catalyst for Electrophilic
Aromatic Halogenation Using N-Halosuccinimides. J. Am. Chem. Soc.
2020, 142, 1621−1629.
(11) Nikolova, V.; Cheshmedzhieva, D.; Ilieva, S.; Galabov, B.
Atomic Charges in Describing Properties of Aromatic Molecules. J.
Org. Chem. 2019, 84, 1908−1915.
(12) Three methyl groups of Trip-t-Bu (1f) were optimized as
inequivalent, and thus, average values were used in this study.
(13) Zhang, C.; Chen, C.-F. Synthesis and Structure of 2,6,14- and
2,7,14-Trisubstituted Triptycene Derivatives. J. Org. Chem. 2006, 71,
6626−6629.
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