A Trefoil Macrocycle Synthesized by 3-Fold Benzannulation

Article abstract of DOI:10.1021/acs.orglett.8b03099

A new trefoil-shaped molecular architecture consisting of three conjugated macrocycles was synthesized through an unprecedented 3-fold copper catalyzed [4 + 2] benzannulation. DFT calculations indicate that the most stable conformation of this trefoil macrocycle is D₃-symmetric. In agreement with the calculated results, the trefoil macrocycle in single crystals exists as a pair of enantiomers with D₃-symmetry and exhibits interesting honeycomb-like supramolecular structures.

Full text of DOI:10.1021/acs.orglett.8b03099

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
A Trefoil Macrocycle Synthesized by 3‑Fold Benzannulation
Xuejin Yang, Luyan Yuan, Ziyi Chen, Zhifeng Liu, and Qian Miao*
Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
S
* Supporting Information
ABSTRACT: A new trefoil-shaped molecular architecture consisting of three
conjugated macrocycles was synthesized through an unprecedented 3-fold copper
catalyzed [4 + 2] benzannulation. DFT calculations indicate that the most stable
conformation of this trefoil macrocycle is D3-symmetric. In agreement with the
calculated results, the trefoil macrocycle in single crystals exists as a pair of
enantiomers with D3-symmetry and exhibits interesting honeycomb-like supra-
molecular structures.
yclic assemblies of aromatic units through covalent bonds
result in shape-persistent macrocycles,1 which have
[4 + 2] benzannulation reaction of o-alkynylbenzaldehyde (2)
with alkynes11 (Scheme 1a) proved to be an efficient method
for the synthesis of naphthalene derivatives,12 resulting in a
variety of molecular architectures containing multiple naph-
thalene moieties.13,14 When the substrate contained two
aldehyde groups, the 2-fold benzannulation reaction of 3
gave the corresponding anthracene derivative as shown in
Scheme 1b.15 On the basis of these reactions, we envisioned
that hexasubstituted triphenylene derivatives could be prepared
by a 3-fold benzannulation reaction (Scheme 1c) of 2,4,6-
tris(phenylethynyl)benzene-1,3,5-tricarbaldehyde (4), which
was synthesized following the reported procedures with
minor modification.16 To verify this hypothesis, a model
reaction of 4 with diphenylacetylene as catalyzed by Cu(OTf)2
in the presence of CF3CO2H gave hexaphenyltriphenylene 5 in
a yield of 25%, which corresponds to a yield of 63% for each
benzannulation. This 3-fold benzannulation reaction appears
to be a new approach to hexasubstituted triphenylene
derivatives.17
Scheme 2 shows the synthesis of trefoil macrocycles 1a/b
starting from 3,6-dibromo-9,10-dialkyloxyphenathrene (6a/
b),13,18 which reacted with acetylenedicarboxylic acid in a
decarboxylative Sonogashira coupling19 giving 7a/b in fairly
good yields. A large excess (10 equiv) of 6a or 6b was used in
this reaction so that only one C−Br bond in each substrate
molecule reacted. The 3-fold benzannulation reaction of 4 with
7a/b as catalyzed by Cu(OTf)2 under acidic conditions
resulted in hexaphenanthrenylated triphenylene 8a or 8b, in
yields of ca. 33%, which corresponds to a yield of 69% for each
aldehyde group. In comparison to trialdehyde 4, mono-
aldehyde 2 reacted with 7b under the same conditions giving
the corresponding naphthalene derivative 9b (Scheme S2a in
C
become an important class of π-conjugated molecules having
their optical and electronic properties readily modified by
changing the type, number, and connection mode of aromatic
building blocks. These conjugated macrocycles are regarded as
monomeric and well-defined precursors to graphene nano-
meshes.2 For example, surface-assisted polymerization of
iodinated cyclohexa-m-phenylene resulted in regular porous
graphenes.3 Other known applications of the conjugated
macrocycles include supramolecular hosts, fluorescent materi-
als for sensing,4 and organic semiconductors in electronic
devices.5 Benzene is the most commonly employed aromatic
building block for the construction of conjugated macrocycles,
such as cyclo-m-phenylenes6 and cyclo-p-phenylenes,7 while
polycyclic aromatic building blocks offer structural versatility
and optical/electronic properties that are not available to
macrocycles consisting exclusively of benzene units.8 Connect-
ing conjugated macrocycles into larger molecular architectures,
such as polyphenylene spoked wheels9 and geodesic frame-
works of phenine,10 is a promising bottom-up approach to
porous carbon-rich nanomaterials, which, however, remain
largely unexplored. Herein, we report a new molecular
architecture that consists of three conjugated macrocycles
fused together and thus is shaped like a trefoil. As shown in
Figure 1, this trefoil macrocycle (1a/b) contains six
phenanthrene subunits surrounding a triphenylene moiety
and can be mapped onto a porous graphene. The π-backbone
of 1a/b is not flat, but helical at the three o-diphenylbenzene
moieties that are highlighted in yellow in Figure 1a because of
atom crowding in these regions. Detailed below are the
synthesis, stereochemistry, and assembly of 1a/b.
To synthesize 1a/b, an unprecedented 3-fold copper-
catalyzed benzannulation reaction was utilized as a key step
to construct the central triphenylene moiety. Copper-catalyzed
Received: September 27, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03099
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Scheme 2. Synthesis of 1a and 1b
Figure 1. (a) Structure of trefoil macrocycle 1a/b; (b) the π-
backbone of 1a/b as mapped onto a porous graphene.
20% and 23%, respectively. Attempted treatment of 1b with
FeCl3, MoCl5, Sc(OTf)3, or DDQ/MeSO3H for cyclo-
dehydrogenation did not yield 12b with formation of three
more C−C bonds, but led to decomposition of the starting
material. The unsuccessful Scholl reaction of 1b could be
explained with the Mulliken spin density of 1b•+, which is
essentially not located at the desired reaction sites20 as shown
in Figure S1 in the SI. Moreover, 1b appeared almost innert
toward photocyclization although o-terphenyl was reported to
photocyclize into triphenylene under the same conditions.21
Scheme 1. Copper-Catalyzed Benzannulation Reactions of
Mono-, Di-, and Trialdehydes for Synthesizing Derivatives
of Naphthalene (a), Anthracene (b), and Triphenylene (c),
Respectively
1
The H NMR spectra of 1a and 1b exhibited three singlets
and four doublets in the aromatic region, in agreement with a
structure of 3-fold symmetry. The almost colorless solutions of
1a and 1b exhibited nearly identical UV−vis absorption
spectra with the longest absorption maximum at 370 nm
(Figure S4 in the SI), which bathochromically shifts relative to
9,10-dihexyloxyphenathrene13 and triphenylene,22 as a result of
conjugation along the cyclic π-backbone. When excited with
UV light of 370 nm, the solutions of 1a and 1b were
resplendently blue-emissive with an emission peak at about
441 nm. By comparison with 9,10-diphenylanthracene, the
photoluminescence quantum yields of 1a and 1b were
determined to be 58% and 57%, respectively.
The trefoil macrocycle in 1a/b can, in principle, exist as two
pairs of enantiomers depending on the helicity of the three o-
diphenylbenzene regions (highlighted in yellow in Figure 1a).
The homochiral pair, (P,P,P) and (M,M,M), have a D3-
symmetry and are shaped like a three-blade propeller, while the
heterochiral pair, (M,P,P) and (P,M,M), have a C2-symmetry.
The stereochemistry of this trefoil macrocycle was studied with
density functional theory (DFT) calculations and X-ray
crystallography. To reduce computational cost, 1c, a simplified
model molecule with methoxy groups replacing the longer
the Supporting Information (SI)) in a yield of 94%, and
dialdehyde 10 (Scheme S2b) reacted with 7b under the same
conditions giving the corresponding anthracene derivative 11b
(Scheme S2b) in a yield of 51%, which corresponds to a yield
of 71% for each aldehyde group. The relatively low yield for
the 3-fold benzannulation of 4 may be attributed to a possible
side reaction that is not applicable to the mono- and
dialdehyde as shown in Scheme S5 in the SI, although the
hypothetic byproducts (18a−b) were not isolated. The
subsequent 3-fold intramolecular Yamamoto coupling reac-
tions of 8a and 8b afforded macrocycles 1a and 1b in yields of
B
DOI: 10.1021/acs.orglett.8b03099
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alkoxy groups in 1a/b, was calculated at the B3LYP/6-31G*
level of DFT. Structural optimization of 1c revealed the D3-
symmetric isomers, (P,P,P) and (M,M,M)-1c, as the global
energy minimum and the C2-symmetric heterochiral isomers as
the local energy minimum as shown in Figure 2. The D3-
of 7.26 × 10−3 s−1 at 25 °C, as estimated using the Eyring
equation k = κ(kBT/h) exp(−ΔG‡/RT) and assuming a value
of unity for the transmission coefficient (κ).23 The
interconversion of the (M,P,P) and (P,M,M) isomers occurs
through meso-TS with a smaller energy barrier of 17.30 kcal/
mol.
Single crystals of 1b were obtained by slow diffusion of ethyl
acetate and acetonitrile into a solution of 1b in chloroform. X-
ray crystallography revealed the racemic crystal containing a
pair of enantiomers of 1b with D3-symmetry. As shown in
Figure 4a, the π-backbone of (P,P,P)-1b is shaped like a three-
Figure 2. Molecular models of (P,P,P)-1c (a) and (M,P,P)-1c (b) as
calculated at the B3LYP/6-31G* level of DFT with the symmetric
axes. (Hydrogen atoms are removed for clarity, and the helical o-
diphenylbenzene regions are highlighted.)
isomers are more stable than the C2-isomers by 4.82 kcal/mol
in Gibbs free energy, which corresponds to an equilibrium
constant of 3.41 × 103 at 25 °C or 5.62 × 102 at 110 °C. This
indicates that the D3-isomers are dominant from 25 to 110 °C,
1
in agreement with the fact that the H NMR spectra of 1b as
recorded in this temperature range (Figure S5 in the SI) were
essentially the same exhibiting a 3-fold symmetry. Figure 3
Figure 4. (a) (P,P,P)-1b in the crystal; (b) the honeycomb-like
assembly of 1b in the crystal as viewed along the c axis of the unit cell
with (P,P,P)- and (M,M,M)-1b shown in red and blue, respectively.
(All the hexyl groups and hydrogen atoms are removed for clarity, and
carbon and oxygen atoms in (a) are shown as ellipsoids at 50%
probability level.)
blade propeller. The three helical o-diphenylbenzene regions
exhibit the same dihedral angle of 60.68° between the
corresponding orange and yellow benzene rings. The central
triphenylene subunit in 1b is not flat, but contorted with three
identical torsion angles (C4−C4a−C4b−C5, C8−C8a−C8b−
C9, and C12−C12a−C12b−C1) of 11.30°. An interesting
finding from the crystal structure of 1b is an unusual
honeycomb-like supramolecular structure, which is formed
by stacking one layer of (P,P,P)-1b (colored in red) over one
layer of (M,M,M)-1b (colored in blue) with π−π interactions
as shown in Figure 4b. The phenanthrene subunits of two
enantiomers of 1b overlap with a π-to-π distance of 3.47 Å as
shown in Figure S2 (SI). The purple regions surrounded by
Figure 3. Calculated pathway for enantiomerization of (P,P,P)-1c.
(The structures of intermediates and transition states were calculated
at the B3LYP/6-31G* level of DFT, and hydrogen atoms in the
models are removed for clarity.)
shows the calculated pathway for enantiomerization of (P,P,P)-
1c, where (M,P,P) and (P,M,M)-1c are the intermediates. This
pathway has three transition states, P-TS and M-TS as a pair of
enantiomers and meso-TS as a meso isomer. (P,P,P)-1c
converts to (M,P,P)-1c through P-TS and the (M,M,M)-1c
converts to (P,M,M)-1c through M-TS with the same energy
barrier of 20.37 kcal/mol, which corresponds to a rate constant
C
DOI: 10.1021/acs.orglett.8b03099
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In summary, the above study has put forth a new trefoil-
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The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03099.
Details of synthesis and characterization, DFT calcu-
lations, optical properties, NMR spectra, and crystallo-
graphic information for 1b (PDF)
Baumgarten, M.; Wagner, M.; Mu
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Accession Codes
CCDC 1859405 contains the supplementary crystallographic
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 Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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AUTHOR INFORMATION
(11) Asao, N.; Nogami, T.; Lee, S.; Yamamoto, Y. J. Am. Chem. Soc.
2003, 125, 10921−10925.
■
Corresponding Author
*E-mail: miaoqian@cuhk.edu.hk.
ORCID
(12) (a) Lehnherr, D.; Alzola, J. M.; Lobkovsky, E. B.; Dichtel, W. R.
Chem. - Eur. J. 2015, 21, 18122−18127. (b) Hein, S. J.; Lehnherr, D.;
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(13) He, Z.; Xu, X.; Zheng, X.; Ming, T.; Miao, Q. Chem. Sci. 2013,
4, 4525−4531.
Qian Miao: 0000-0001-9933-6548
Notes
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Ms. Hoi Shan Chan (the Chinese University of
Hong Kong) for the single-crystal crystallography. This work
was supported by the Research Grants Council of Hong Kong
(CRF C4030-14G).
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