ortho-Phenylene-Based Macrocyclic Hydrocarbons Assembled Using Olefin Metathesis

Article abstract of DOI:10.1002/ejoc.202000950

While many foldamer systems reliably fold into well-defined secondary structures, higher order structure remains a challenge. A simple strategy for the organization of folded subunits in space is to link them together within a macrocycle. Previous work has shown that o-phenylenes can be co-assembled with rod-shaped linkers into twisted macrocycles, showing an interesting synergy between folding and thermodynamically controlled macrocyclization. In these systems the foldamer units were largely decoupled from each other both conformationally and electronically. Here, we show that hydrocarbon macrocycles, with very short ethenylene linkers, can be assembled from o-phenylenes using olefin metathesis. Characterization by NMR spectroscopy, X-ray crystallography, and ab initio calculations shows that the products are approximately triangular trimer macrocycles with helical o-phenylene corners in a heterochiral configuration. Their photophysics are dominated by the 4,4'-diphenylstilbene moieties, the longest conjugated segments, with further conjugation broken by the twisting of the o-phenylenes.

Full text of DOI:10.1002/ejoc.202000950

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: ortho-Phenylene-based macrocyclic hydrocarbons assembled
using olefin metathesis
Authors: Viraj C. Kirinda, Briana R. Schrage, Christopher J. Ziegler,
and Christopher Scott Hartley
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
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published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000950
Link to VoR: https://doi.org/10.1002/ejoc.202000950
0
1/2020

European Journal of Organic Chemistry
10.1002/ejoc.202000950
FULL PAPER
ortho-Phenylene-based macrocyclic hydrocarbons assembled
using olefin metathesis
[
a]
[b]
[b]
[a]
Viraj C. Kirinda, Briana R. Schrage, Christopher J. Ziegler, and C. Scott Hartley*
[
[
a]
b]
V. C. Kirinda, Dr. C. S. Hartley
Department of Chemistry & Biochemistry
Miami University
Oxford, OH 45056 (USA)
E-mail: scott.hartley@miamioh.edu
Homepage: https://www.hartleygroup.org
B. R. Schrage, Dr. C. J. Ziegler
Department of Chemistry
University of Akron
Akron, OH 44325 (USA)
Supporting information for this article is given via a link at the end of the document.
Abstract: While many foldamer systems reliably fold into well-defined
secondary structures, higher order structure remains a challenge. A
simple strategy for the organization of folded subunits in space is to
link them together within a macrocycle. Previous work has shown that
o-phenylenes can be co-assembled with rod-shaped linkers into
twisted macrocycles, showing an interesting synergy between folding
and thermodynamically controlled macrocyclization. In these systems
the foldamer units were largely decoupled from each other both
conformationally and electronically. Here, we show that hydrocarbon
macrocycles, with very short ethenylene linkers, can be assembled
from o-phenylenes using olefin metathesis. Characterization by NMR
spectroscopy, X-ray crystallography, and ab initio calculations shows
that the products are approximately triangular trimer macrocycles with
helical o-phenylene corners in a heterochiral configuration. Their
photophysics are dominated by the 4,4′-diphenylstilbene moieties, the
longest conjugated segments, with further conjugation broken by the
twisting of the o-phenylenes.
foldamer
moieties
within
conformationally
restricted
macrocycles.[22–24] To synthesize these targets, folding can be
combined with thermodynamically controlled self-assembly,
raising questions about how the two concepts together can yield
products with emergent structural complexity. For helical
foldamers, the products will be twisted macrocycles that combine
the features of globally folded macrocycles[25–31] with those with
conformationally rigid axially chiral subunits.[32–39]
Our work has focused on the ortho-phenylenes, a simple class
of aromatic foldamers.[40] They are well-suited to the study of
folding combined with self-assembly because of their
straightforward conformational behavior, and because of the
predictable dependence of their NMR spectra on their geometries,
which allows solution-phase folding states to be deduced and
quantified. We have previously shown that amine-functionalized
o-phenylenes can be co-assembled with aldehyde-functionalized
rod-shaped linkers.[22–24] In these systems, the combination of
assembly and folding yields new behavior: for example, because
only certain o-phenylene conformers will fit within a macrocycle of
a particular size, the process of macrocyclization can distort them
into folds that are not observed for the unconstrained acyclic
oligomers.
Introduction
The hierarchical structure of biomacromolecules has long inspired
chemists to design abiotic foldamers, oligomers that adopt well-
defined conformations because of noncovalent interactions.[1–5]
Foldamers exhibiting molecular recognition,[6–9] catalysis,[10,11]
interesting electronic properties,[12–14] self-assembly,[15] and
biological activity[16–18] are now known. Ultimately, the goal is to
complement biological systems, achieving analogous structural
sophistication, and thus function, but using structural motifs with
distinct properties. In abiotic foldamer systems, secondary
structure, especially the helix, is now fairly well represented.
Higher-order structure remains rare, especially in non-peptidic
foldamers, even though tertiary and quaternary structure are key
to function in analogous biological systems. Only a handful of
examples are currently known.[19–21]
In this previous work, assembly occurred very effectively, but
the o-phenylenes were conformationally and electronically
decoupled from each other by their linkers. Questions remain
about the tolerance of self-assembly to short restrictive linkers
and the possibility of electronic coupling between the o-
phenylenes. Here, we report the synthesis and characterization of
the unsubstituted ortho-phenylene macrocycles (oP4)
and (oP6)
3
3
,
shown in Scheme 1. The macrocycles were assembled using ring
closing metathesis (RCM), a well-known and efficient method for
the synthesis of macrocycles[41–46] and cages.[47,48] These
conjugated hydrocarbon macrocycles are reminiscent of systems
with Möbius π systems,[36] including an example prepared by
alkyne metathesis,[49] which can lead to antiaromaticity. However,
the π systems of the two macrocycles reported here are formally
A
simple view of higher-order structure is molecular
continuous (i.e., formally aromatic), and their twisting will
architectures that place folded subunits into well-defined positions.
A minimal approach to this challenge is the incorporation of
attenuate conjugation (especially for (oP6)
).[50–52]
3
1
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European Journal of Organic Chemistry
10.1002/ejoc.202000950
FULL PAPER
ethenylene linkers of the olefin systems. Increased steric
congestion could lead to either kinetic trapping or less-efficient
self-assembly because of strain. To test whether the product
distributions in Figure 1 represent equilibrium, we carried out
experiments where the isolated macrocycles were treated with
Grubbs catalyst and allowed to react for 24 h (i.e., to see whether
the same product distributions would be obtained when starting
with the macrocycles). Unfortunately, the results were
inconclusive as the macrocycles simply decomposed to lower-
molecular-weight species.
Scheme 1. Assembly of macrocycles (oP4)
and (oP6)
.
3
3
Results and Discussion
4
6
Figure 1. Monitoring of the macrocyclization of oP and oP .
Synthesis
The macrocycles were synthesized from vinyl-substituted ortho-
Structural analysis of (oP4)
3
4
6
phenylene precursors oP and oP , whose synthesis is described
in the Supporting Information. As shown in Scheme 1, these
precursors (5 mM) were subjected to macrocyclization by olefin
metathesis using the second-generation Grubbs catalyst in 1,2,4-
trichlorobenzene at room temperature. The reactions were carried
out under vacuum to remove the ethylene byproduct. Aliquots
from the reaction mixtures were analyzed by analytical gel
permeation chromatography (GPC). Similar product distributions,
shown in Figure 1, were obtained in both cases, although there
The structures of the macrocycles can be understood in the
context of the acyclic o-phenylenes. As shown in Figure 2, an o-
phenylene tetramer will rapidly interconvert, via rotation about the
central biaryl bond, between a “closed” conformer “A”, which is
stabilized by a single aromatic stacking interaction, and an
extended “open” conformer “B”. In chloroform, aromatic stacking
is not strong enough to completely bias the system toward the
folded state. The fit of an o-phenylene within a quasi-triangular
[
3+3] macrocycle can be quantified through the bite angle (ꢀ)
4
were differences in reactivity. The oP system shows peaks in the
made by the terminal positions of the oligomer (i.e., the angle
between the vectors passing through the points of attachment at
the oligomer termini, brought to a common origin).[55] In the A state
chromatograms corresponding to higher molecular weight
species after only 5 min, with consumption of most of the starting
4
oP after 4 h. While the total amount of products continues to
∘
∘
ꢀ
≈ 70 , whereas in the B state ꢀ ≈ 120 for an o-phenylene
increase, the relative proportions of higher molecular weight
species do not change significantly after the 4 h mark. The
reaction of oP6 proceeds more slowly, with significant starting
material still visible for at least 8 h. In both systems, the product
distribution is unchanging after 24 h, and no change was
observed after adding fresh catalyst and reacting for an additional
tetramer. Thus, as we have previously shown, only the A state fits
∘
within a triangular macrocycle (which requires ꢀ ≈ 60 ) and
macrocyclization induces folding.[22] For (oP4)
3
, we therefore
expect a roughly triangular macrocycle with three twisted o-
phenylene corners. This can exist, in principle, in either
homochiral (PPP or MMM) or heterochiral (PPM or MPP)
configurations.
2
4 h.
Macrocycles (oP4)
and (oP6)
could be isolated from the
3
3
reaction mixtures by flash chromatography followed by semi-
preparative GPC in 25% and 27% yields, respectively (GPC
traces in Figure 1).[53] In both cases, mass spectrometry
confirmed that the major products were the 3+3 macrocycles.
Analysis of fractions corresponding to higher molecular weight
species indicated the presence of higher macrocycles, although
given the breadth of the peaks it is very likely that acyclic
oligomers were also present.[54]
As judged by the GPC monitoring experiments, the self-
assembly of these macrocycles is much less effective than that of
comparable imine-based macrocycles with long linking groups,
which typically give product distributions dominated by [3+3]
macrocycles.[22,24] This is not so surprising given the very short
Figure 2. Conformers of tetra(o-phenylene). The enantiomers of these
conformers will of course also be present and equally populated.
2
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European Journal of Organic Chemistry
10.1002/ejoc.202000950
FULL PAPER
Figure 3. Characterization of (oP4)
by (a) NMR spectroscopy (oP top and (oP )
4
4
bottom, CDCl
3
3
3
, 500 MHz, rt) and (b) X-ray crystallography.
Like other o-phenylenes, considerable structural information
can be obtained through analysis of the NMR spectra of the
macrocycles, particularly when compared to acyclic analogues
by 4.0 kcal/mol. As was observed in the crystal structures, the
DFT calculations predict that the o-phenylene moieties are
compressed on macrocyclization. However, the effect is much
smaller in the calculations (roughly 0.1 Å computationally vs 0.6
Å by crystallography). The difference is in the geometry of oP4,
where the centroid-to-centroid distance between terminal rings is
underestimated (3.67 Å vs 4.25 Å).
4
6
[22,24,40]
4
(
i.e., oP and oP ).
The spectrum of precursor oP , shown
in Figure 3a, is a good match to that of the parent tetra(o-
phenylene),[51] confirming that it does behave according to Figure
2
, with rapid exchange on the NMR time scale. In contrast, the
spectrum of cyclized (oP4)
is complex. Through COSY, HSQC,
The conformational dynamics of the (oP4)
system were
3
3
HMBC, and NOESY/EXSY experiments, it was possible to fully
assign the spectrum (Figure 3 and Supporting Information). All of
the proton signals in the spectrum are split into three (e.g., protons
briefly explored by variable-temperature (VT) 1H NMR
spectroscopy, with the spectra shown in the Supporting
Information. As the temperature was decreased from room
1
a, 1′a, 1′′a), indicating that (oP4)
solution. We therefore conclude that it adopts the heterochiral C
symmetric geometry, and not the higher-symmetry homochiral,
-symmetric configuration. Comparing analogous protons
3
has only twofold symmetry in
3
temperature to 233 K (CDCl ), the internal protons of the o-
2
-
phenylenes (rings 2, Figure 3a) did not show significant chemical
shift or peak shape changes. In contrast, the signals for the
terminal ring protons (rings 1) broadened. This suggests that
rotation about the terminal biaryl bonds slows, as has been
observed for some acyclic o-phenylenes with stronger aromatic
stacking interactions.[57] Interestingly, the effect is more significant
for the protons on rings 1 and 1′ (i.e., the o-phenylenes with the
predominant twist senses). There is relatively little effect as the
temperature is increased to 347 K, although there is some
sharpening of the signal for proton 1′a, suggesting that its
broadened appearance at room temperature results from
conformational exchange at an intermediate rate, and that
inversion of the o-phenylene moieties (e.g., MPP ⇌ MMP) is slow
on the NMR time scale.
D
3
between macrocyclic (oP4)
and acyclic oP , there are significant
4
3
differences in chemical shifts (indicated in Figure 3), suggesting a
change in conformational distribution for the o-phenylene
moieties. In particular, the upfield shifts of protons 1a and
downfield shifts of protons 2e indicate that, in the macrocycle, the
o-phenylenes favor the compact A conformer as the nuclei move
into and away from the shielding zones of nearby aromatic rings,
respectively.[22]
We were able to grow X-ray-quality crystals of both (oP4)
3
,
with the structure shown in Figure 3b, and oP4 (Supporting
Information).[56] The crystal structure confirms the heterochiral
configuration deduced from the 1H NMR analysis of the bulk
solution; a freshly dissolved crystal shows an identical spectrum.
Comparison of the two structures shows that the o-phenylenes
are more tightly folded in the macrocycle, with a mean centroid-
to-centroid distance between the terminal rings (1, 1′, 1′′) of 3.67
Å in (oP4)
, compared to 4.25 Å in oP . The central dihedral angle
4
3
in the o-phenylenes is correspondingly reduced to 60° from 62°.
This compression of the o-phenylene moieties, and the
corresponding strain, may at least partly explain the modest
efficiency of self-assembly of (oP4)
longer, more flexible linkers.[22]
compared to systems with
3
Figure 4. Conformations of hexa(o-phenylene).
DFT geometry optimizations at the PCM(CHCl
pVDZ level were performed to further understand the
conformational preferences of (oP4)
. Both heterochiral and
3
)/B97-D/cc-
Structural analysis of (oP6)
3
3
The conformational behavior of o-phenylene hexamers is much
homochiral configurations and all four possible orientations of the
trans-ethenylene groups were explicitly considered (see
Supporting Information). Consistent with the NMR and
crystallography results, the most-stable heterochiral conformation
is predicted to be preferred over the best homochiral conformation
more complex than that of tetramers. As shown in Figure 4,
hexa(o-phenylene) can fold into a helix stabilized by three
aromatic stacking interactions, called the “AAA” conformer.[57] The
next most stable conformer is the “AAB” state, which differs in
3
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European Journal of Organic Chemistry
10.1002/ejoc.202000950
FULL PAPER
Figure 5. (a) Characterization of (oP6)
by DFT optimization at the PCM(CHCl
by H NMR spectroscopy (oP top and (oP )
1
6
6
3
bottom, CDCl
, 500 MHz, rt). (b) Most-stable conformer of (oP6)
3
3
3
, as determined
3
)/B97-D/cc-pVDZ level.
rotation about one of the key biaryl bonds, resulting in the loss of
a single stacking interaction. Unlike o-phenylene tetramers,
interconversion between these more sterically congested
conformers is typically slow on the NMR time scale (but fast on
the lab time scale). Like the tetramers, the bite angle, and thus
the fit within a macrocycle of a given size, is dependent on the
conformation, with only the well-folded AAA state compatible with
(oP6) and oP6 are small (<0.2 ppm); confirming that the o-
3
phenylenes remain similarly folded (were that not the case, many
proton signals would shift by >1 ppm[24]). We cannot, unfortunately,
determine whether there is a greater bias toward the AAA
conformation in (oP6)
over oP , as had been observed in
6
3
analogous systems,[24] using the available data.
At elevated temperatures (343 K), the 1H NMR signals of
∘
(oP6)
a [3+3] macrocycle (ꢀ ≈ 68 ).
3
broaden
and
coalesce,
indicating
significant
We were, unfortunately, unable to grow crystals of (oP6)
conformational flexibility. Relatively little change in the spectrum
is observed as the temperature is decreased, consistent with the
oligomers already being in a slow regime for conformational
exchange at room temperature.
3
suitable for X-ray diffraction, despite many attempts. However,
analysis of its NMR spectra and computational optimization
provide insight into its structure. For reference, the NMR spectrum
6
Candidate geometries of (oP6)
PCM(CHCl
)/B97-D/cc-pVDZ level. As for (oP4)
3
of the acyclic oP is shown in Figure 5a (top). At room temperature,
3
were optimized at the
, heterochiral
its spectrum is a combination of sharp signals associated with the
perfectly folded (helical) conformation and smaller broad peaks
corresponding to misfolded states, as verified by EXSY
3
configurations of the macrocycle are predicted to be significantly
more stable than homochiral configurations, by at least 3.8
kcal/mol. The most stable geometry is shown in Figure 5b. The o-
phenylenes are well-accommodated by the macrocycle structure,
with biaryl dihedrals along the o-phenylene backbone of
approximately 53°, a close match to those of the parent hexa(o-
phenylene) optimized at the same level of theory (also 53°).[24]
1
spectroscopy. As is typical for o-phenylenes, its H signals could
be assigned through COSY, HSQC, and HMBC spectroscopy; the
assigned chemical shifts of the major conformer (see Supporting
Information) are a good match to those of the parent hexa(o-
phenylene).[51] By analogy, we conclude that oP is predominantly
well-folded into the AAA state.
6
1
6
The H NMR spectrum of (oP )
3
, shown in Figure 5a (bottom),
is significantly more complex than that of the smaller (oP4)
3
. The
spectrum shows minor signals corresponding to misfolded o-
phenylenes, as expected.[24] The assignment of these signals to
misfolded conformations, as opposed to impurities, is confirmed
by EXSY spectroscopy, which shows exchange peaks with
signals in the major conformers,[58] and VT NMR, which shows
coalescence of signals at elevated temperature (see Supporting
Information). As before, the chemical shifts of the major
conformation were assigned using standard 2D NMR spectra.
Unfortunately, while it is clear that there are multiple symmetry-
inequivalent protons in the predominant geometry, it was not
possible to distinguish specific inequivalent o-phenylene moieties.
Nevertheless, we can draw several conclusions on the basis of
the spectra. First, since separate signals can be identified for
Figure 6. UV–vis (solid lines) and fluorescence (dotted lines) spectra of (oP4)
3
and (oP6)
3
in chloroform.
3
many of the protons, it is clear that a D -symmetric homochiral
conformer does not predominate. Second, since the signals for
each proton do tend to be clustered together within roughly 0.1
ppm, the o-phenylenes must favor a single twofold-symmetric
geometry as opposed to a mixture of distinct folding states. Third,
the chemical shift differences for analogous protons between
Photophysics
UV–vis and fluorescence spectra of (oP4)
and (oP6)
3
3
are shown
in Figure 6. In principle, these macrocycles are fully conjugated
around their peripheries, with 42 and 54 electrons in the shortest
conjugated paths around the rings. They are therefore both
4
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European Journal of Organic Chemistry
10.1002/ejoc.202000950
FULL PAPER
formally aromatic. However, folded ortho-phenylenes lack
extended π-conjugation.[50,52] Consequently, the two macrocycles
show similar photophysical properties despite the different
oligomer lengths. Their UV–vis spectra are similar in shape, with
maximum absorption wavelengths (ꢁmax) of 335 nm and 337 nm
(crystallography) would like to acknowledge the University of
Akron for support of this research.
Keywords: conformation analysis • hydrocarbons • chirality •
foldamers • self-assembly
for (oP4) and (oP6)
, respectively. These spectra are a close
3 3
match to that of (E)-4,4′-diphenylstilbene (ꢁmax = 342 nm),[59,60]
which represents a single side of each macrocycle excluding
conjugation through the o-phenylene moieties. Curiously, despite
[
[
1] S. H. Gellman, Acc. Chem. Res. 1998, 31, 173–180.
2] G. Guichard, I. Huc, Chem. Commun. 2011, 47, 5933–5941.
[3] D. J. Hill, M. J. Mio, R. B. Prince, T. S. Hughes, J. S. Moore, Chem. Rev.
2001, 101, 3893–4011.
the structural and spectral similarities, the macrocycles show
6
significantly different absorptivities ( ꢂ ), with that of (oP )
3
[4] I. Saraogi, A. D. Hamilton, Chem. Soc. Rev. 2009, 38, 1726–1743.
[5] B. A. F. Le Bailly, J. Clayden, Chem. Commun. 2016, 52, 4852–4863.
[6] G. Lautrette, B. Wicher, B. Kauffmann, Y. Ferrand, I. Huc, J. Am. Chem. Soc.
4
4
−1
3
approximately double that of (oP ) ((7.9 ± 0.6) × 10 M vs (3.8
4
−1
±
0.3) × 10 M ).
TD-DFT calculations at the CAM-B3LYP/6-311+G(2d,2p)
2
016, 138, 10314–10322.
7] R. B. Prince, S. A. Barnes, J. S. Moore, J. Am. Chem. Soc. 2000, 122, 2758–
762.
[
level do a good job of matching the experimental spectra in terms
of ꢁmax , although the difference in ꢂ is not reproduced. The
absorbance spectra for both macrocycles consist primarily of
transitions to the first three excited states. In both cases, the
orbitals contributing to these excited states are indeed primarily
located on the 4,4′-diphenylstilbene moieties (Supporting
Information).
2
[8] J.-m. Suk, V. R. Naidu, X. Liu, M. S. Lah, K.-S. Jeong, J. Am. Chem. Soc.
2011, 133, 13938–13941.
[9] Y. Hua, Y. Liu, C.-H. Chen, A. H. Flood, J. Am. Chem. Soc. 2013, 135,
14401–14412.
[
10] Z. C. Girvin, M. K. Andrews, X. Liu, S. H. Gellman, Science 2019, 366,
528–1531.
1
[
11] D. Bécart, V. Diemer, A. Salaün, M. Oiarbide, Y. R. Nelli, B. Kauffmann, L.
The fluorescence spectra (Figure 6) are likewise similar and a
good match to that of 4,4′-diphenylstilbene.[60] Both macrocycles
are strongly fluorescent, with quantum yields of 0.88 and 0.81 for
Fischer, C. Palomo, G. Guichard, J. Am. Chem. Soc. 2017, 139, 12524–
1
2532.
[
12] A. Marcos Ramos, S. C. J. Meskers, E. H. A. Beckers, R. B. Prince, L.
(
oP4)
3
and (oP6)
3
, respectively (which are indistinguishable within
Brunsveld, R. A. J. Janssen, J. Am. Chem. Soc. 2004, 126, 9630–9644.
experimental uncertainty). Fluorescence lifetimes were
determined by time-correlated single photon counting. Both
compounds gave good monoexponential fits with lifetimes of 1.4
[13] X. Li, N. Markandeya, G. Jonusauskas, N. D. McClenaghan, V. Maurizot,
S. A. Denisov, I. Huc, J. Am. Chem. Soc. 2016, 138, 13568–13578.
[
14] S. P. Morcillo et al., Chem. Sci. 2016, 7, 5663–5670.
ns and 1.1 ns for (oP4)
and (oP6)
[15] U. Lewandowska, W. Zajaczkowski, L. Chen, F. Bouillière, D. Wang, K.
3
3
.
Koynov, W. Pisula, K. Müllen, H. Wennemers, Angew. Chem., Int. Ed.
2
014, 53, 12537–12541.
[
[
[
[
[
16] J. S. Laursen, J. Engel-Andreasen, C. A. Olsen, Acc. Chem. Res. 2015, 48,
2696–2704.
Conclusion
17] C. M. Goodman, S. Choi, S. Shandler, W. F. DeGrado, Nat. Chem. Biol.
2007, 3, 252–262.
Twisted macrocycles (oP4) and (oP6)
have been synthesized
3 3
18] R. Gopalakrishnan, A. I. Frolov, L. Knerr, W. J. Drury III, E. Valeur, J. Med.
Chem. 2016, 59, 9599–9621.
and characterized. Assembly by olefin metathesis is reasonably
efficient, considering their sterically congested structures and the
strain introduced on macrocyclization by the very short linkers.
Characterization by NMR spectroscopy and X-ray crystallography
19] D. Mazzier, S. De, B. Wicher, V. Maurizot, I. Huc, Angew. Chem., Int. Ed.
2
020, 59, 1606–1610.
20] D. Mazzier, S. De, B. Wicher, V. Maurizot, I. Huc, Chem. Sci. 2019, 10,
984–6991.
shows that macrocycle (oP4)
favors a C -symmetric, heterochiral
3 2
6
geometry in both solution and the solid-state. DFT optimization
confirms that this is indeed the most stable conformer for this
system. Both X-ray crystallography and the DFT calculations
[21] S. De, B. Chi, T. Granier, T. Qi, V. Maurizot, I. Huc, Nat. Chem. 2018, 10,
51–57.
[
22] Z. J. Kinney, C. S. Hartley, J. Am. Chem. Soc. 2017, 139, 4821–4827.
show that the o-phenylene moieties are compressed in (oP4)
indicating strain that may explain the relatively low yield. Similar
behavior is observed for (oP6)
. The macrocycle predominantly
[23] Z. J. Kinney, C. S. Hartley, Org. Lett. 2018, 20, 3327–3331.
3
,
[
[
24] Z. J. Kinney, V. C. Kirinda, C. S. Hartley, Chem. Sci. 2019, 10, 9057–9068.
25] Z. Zhang, W.-Y. Cha, N. J. Williams, E. L. Rush, M. Ishida, V. M. Lynch, D.
Kim, J. L. Sessler, J. Am. Chem. Soc. 2014, 136, 7591–7594.
26] B. Liu, C. G. Pappas, E. Zangrando, N. Demitri, P. J. Chmielewski, S. Otto,
J. Am. Chem. Soc. 2019, 141, 1685–1689.
3
adopts a heterochiral configuration of well-folded o-phenylene
moieties, although misfolded states are observed by NMR
spectroscopy. The photophysical properties of the two systems
are very similar, with nearly identical absorbance and
fluorescence spectra that can be assigned to 4,4′-
diphenylstilbene chromophores, indicating that the twisted o-
phenylenes break conjugation.
[
[27] P. Reiné et al., J. Org. Chem. 2018, 83, 4455–4463.
[28] K. Urushibara, Y. Ferrand, Z. Liu, H. Masu, V. Pophristic, A. Tanatani, I.
Huc, Angew. Chem., Int. Ed. 2018, 57, 7888–7892.
[
[
[
[
[
[
29] R. Katoono, Y. Tanaka, K. Fujiwara, T. Suzuki, J. Org. Chem. 2014, 79,
0218–10225.
30] F. Chen, T. Tanaka, Y. Hong, W. Kim, D. Kim, A. Osuka, Chem.—Eur. J.
016, 22, 10597–10606.
1
2
31] T. Hjelmgaard, L. Nauton, F. De Riccardis, L. Jouffret, S. Faure, Org. Lett.
2018, 20, 268–271.
Acknowledgements
32] M. Caricato, S. D. González, I. Arandia Ariño, D. Pasini, Beilstein J. Org.
Chem. 2014, 10, 1308–1316.
CSH and VCK (synthesis, NMR spectroscopy, computational
chemistry, photophysics) thank the National Science Foundation
33] M. Widhalm, P. Wimmer, G. Klintschar, J. Organomet. Chem. 1996, 523,
1
67–178.
(
CHE-1608213 and CHE-1904236) for support of this work and
34] S. Castro-Fernández, M. M. Cid, C. S. López, J. L. Alonso-Gómez, J. Phys.
Chem. A 2015, 119, 1747–1753.
the Volwiler Distinguished Research Professorship. CJZ and BRS
5
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.202000950
FULL PAPER
[
35] P. Rivera-Fuentes, F. Diederich, Angew. Chem., Int. Ed. 2012, 51, 2818–
828.
2
[
36] G. R. Schaller, F. Topić, K. Rissanen, Y. Okamoto, J. Shen, R. Herges, Nat.
Chem. 2014, 6, 608–613.
[
[
37] S. W. Sisco, J. S. Moore, Chem. Sci. 2014, 5, 81–85.
38] A. U. Malik, F. Gan, C. Shen, N. Yu, R. Wang, J. Crassous, M. Shu, H. Qiu,
J. Am. Chem. Soc. 2018, 140, 2769–2772.
[
39] G. Naulet, L. Sturm, A. Robert, P. Dechambenoit, F. Röhricht, R. Herges,
H. Bock, F. Durola, Chem. Sci. 2018, 9, 8930–8936.
[
[
[
[
[
40] C. S. Hartley, Acc. Chem. Res. 2016, 49, 646–654.
41] W. Zhang, J. S. Moore, J. Am. Chem. Soc. 2005, 127, 11863–11870.
42] C. W. Lee, R. H. Grubbs, J. Org. Chem. 2001, 66, 7155–7158.
43] Y. E. Bergman et al., Org. Lett. 2009, 11, 4438–4440.
44] O. M. Ogba, N. C. Warner, D. J. O’Leary, R. H. Grubbs, Chem. Soc. Rev.
2
018, 47, 4510–4544.
45] Y. Jin, A. Zhang, Y. Huang, W. Zhang, Chem. Commun. 2010, 46, 8258–
260.
[
[
[
8
46] C. Yu, Y. Jin, W. Zhang, in Dynamic Covalent Chemistry (Eds.: W. Zhang,
Y. Jin), John Wiley & Sons, Ltd, Chichester, UK, 2017, pp. 121–163.
47] T. P. Moneypenny II, N. P. Walter, Z. Cai, Y.-R. Miao, D. L. Gray, J. J.
Hinman, S. Lee, Y. Zhang, J. S. Moore, J. Am. Chem. Soc. 2017, 139,
3
259–3264.
[
[
[
48] H. Ding, R. Chen, C. Wang, in Dynamic Covalent Chemistry (Eds.: W.
Zhang, Y. Jin), John Wiley & Sons, Ltd, Chichester, UK, 2017, pp. 165–
2
05.
49] X. Jiang, S. D. Laffoon, D. Chen, S. Pérez-Estrada, A. S. Danis, J.
Rodrıguez-López, M. A. Garcia-Garibay, J. Zhu, J. S. Moore, J. Am.
́
Chem. Soc. 2020, 142, 6493–6498.
50] J. He, S. M. Mathew, S. D. Cornett, S. C. Grundy, C. S. Hartley, Org. Biomol.
Chem. 2012, 10, 3398–3405.
[
[
51] S. M. Mathew, C. S. Hartley, Macromolecules 2011, 44, 8425–8432.
52] S. Ando, E. Ohta, A. Kosaka, D. Hashizume, H. Koshino, T. Fukushima, T.
Aida, J. Am. Chem. Soc. 2012, 134, 11084–11087.
[
3
53] There is a small shoulder at higher retention time for the purified (oP6) .
We do not believe this represents a significant impurity as it is not present
in the GPC traces of the crude mixtures. Regardless, the chromatogram
demonstrates that the macrocycle can be separated from higher
molecular weight species.
[
[
[
54] C. S. Hartley, E. L. Elliott, J. S. Moore, J. Am. Chem. Soc. 2007, 129, 4512–
4
513.
55] The separation of the oligomer termini can be ignored in the calculation of
as this does not affect the fit within the macrocycle.
ꢀ
56] CCDC 1996399-1996400 contain the supplementary crystallographic data
for this paper. The data can be obtained free of charge from The
Cambridge
www.ccdc.cam.ac.uk/structures.
57] S. Mathew, L. A. Crandall, C. J. Ziegler, C. S. Hartley, J. Am. Chem. Soc.
014, 136, 16666–16675.
Crystallographic
Data
Centre
via
[
[
[
[
2
58] For example, the small doublets from 5.85–6.15 ppm can be assigned to
protons 2e or 3e in less-populated conformers.
59] Z. Fengqiang, J. Motoyoshiya, Y. Nishii, H. Aoyama, A. Kakehi, M. Shiro, J.
Photochem. Photobiol., A 2006, 184, 44–49.
60] E. A. Andreeshchev, V. S. Viktorova, S. F. Kilin, Y. P. Kushakevich, I. M.
Rozman, Opt. Spektrosk. 1968, 24, 387–390.
6
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European Journal of Organic Chemistry
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Entry for the Table of Contents
Macrocycles have been assembled from vinyl-substituted ortho-phenylenes using olefin metathesis. The major products are trimers
with congested, twisted structures. Characterization by NMR spectroscopy, X-ray crystallography, and DFT calculations show that
heterochiral configurations are favored. Photophysical properties are also discussed.
Key topic: Foldamer macrocycles
Institute and/or researcher Twitter usernames: @TheHartleyLab, @viraj_chana
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