π-Extension of Strained Benzenoid Macrocycles Using the Scholl Reaction

Article abstract of DOI:10.1021/acs.orglett.8b02979

A series of bent p-terphenyl-containing macrocycles have been synthesized and then regioselectively brominated, arylated, and subsequently subjected to a Scholl-based cyclodehydrogenation reaction. Shortening the alkyloxy bridging unit of these macrocycle

Full text of DOI:10.1021/acs.orglett.8b02979

Letter
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
π‑Extension of Strained Benzenoid Macrocycles Using the Scholl
Reaction
†
†
Nirob K. Saha, Nirmal K. Mitra, Kara F. Johnson, and Bradley L. Merner*
Department of Chemistry and Biochemistry, Auburn University, Auburn, Alabama 36849, United States
*
S Supporting Information
ABSTRACT: A series of bent p-terphenyl-containing macrocycles have been synthesized and then regioselectively brominated,
arylated, and subsequently subjected to a Scholl-based cyclodehydrogenation reaction. Shortening the alkyloxy bridging unit of
these macrocycles increases the bend in the p-terphenyl unit, as well as the strain energy (SE) of the central para-phenylene ring
system. For the first time, incremental increases in SE of the macrocyclic structure of this class of benzenoid compounds have
been investigated in the context of π-extension to strained polycyclic aromatic hydrocarbon systems using the Scholl reaction.
he synthesis of polycyclic aromatic hydrocarbons (PAHs)
from substituted benzenoid systems, using a cyclo-
Several groups have attempted to use the Scholl reaction to
stitch together substituent aromatic rings to backbone arene
units within the macrocyclic framework of [n]CPPs; however,
T
dehydrogenation (Scholl) reaction protocol, has proven to be
1
somewhat unpredictable. Regioisomeric products that result
these efforts have been met with limited success. Mullen and co-
̈
from undesired and, in some cases, nonobvious cyclization
workers have reported the successful synthesis of a hexabenzo-
coronene (HBC)-incorporated [21]CPP via the introduction of
strategically placed methyl groups at para-phenylene units
2
modes have been reported. For example, Durola and co-
workers observed that 2,2″-bis(4-tert-butylphenyl)-p-terphenyl
1) undergoes a cyclodehydrogenation reaction in the presence
(
within the macrocyclic backbone of a [21]CPP (SE = 1.3 kcal/
pp
7
of iron(III) chloride to afford [5]helicene 3 in preference to 2
mol) derivative to circumvent 1,2-phenyl shifts. The
3
(
Scheme 1A). Despite the crowded and congested transition
application of this strategy to a homologous, but more strained,
state that must be attained to furnish the twisted PAH 3, the
cisoid mode of cyclization proved to be major. A similar
annulation reaction was computationally investigated by Hilt
[
15]CPP (SEpp = 2.7 kcal/mol) failed to produce the HBC-
incorporated macrocycle. Similarly, a polyphenylated [9]CPP
SEpp = 7.4 kcal/mol) derivative did not undergo π-extension
(
4
and co-workers, who showed that the preferred, congested
8
when subjected to Scholl reaction conditions. Jasti and co-
workers have investigated a Scholl-based annulation protocol for
the π-extension of arylated [12]CPP and [8]CPP (SEpp = 9.2
kcal/mol) derivatives; however, only mixtures of isomeric
mode of cyclization can be attributed to the uneven distribution
of orbital coefficients about the central ring (after a single
annulation), with the site of the second annulation reaction
exhibiting a larger orbital coefficient. In the absence of the bulky
tert-butyl groups, formation of a carbon−carbon bond across the
9
macrocycles and ring-opened products were obtained.
2
Although these studies have demonstrated that direct π-
extension of nonplanar benzenoid systems to strained PAH
systems using a cyclodehydrogenation reaction is challenging,
they are limited to only a few arene-substituted CPPs. As such,
an investigation to explore the usefulness of this strategy and its
potential limitations was designed using a series of polyarylated
p-terphenyl-containing macrocycles (Scheme 1B). The central
para-phenylene, which is bent, allows for a detailed analysis of
how strain affects the desired annulation and to what extent pre-
bay region of 3 is possible to form PAHs such as 4. If this type of
annulation reaction could be called upon to convert a nonplanar
benzenoid macrocyclic system into a nonplanar PAH-contain-
ing macrocycle, it would represent a viable π-extension strategy
for the synthesis of carbon nanotube (CNT) sidewall segments.
In the context of an [n]cycloparaphenylene ([n]CPP),
connecting adjacent arene vertices of the nanohoop backbone
to arene vertices of appended phenyl or aryl substituents would
5
provide entry to carbon nanobelts (CNBs). The latter would
provide entry to size-selective and structurally uniform armchair
CNTs using programmed or controlled C−C bond-forming
Received: September 18, 2018
6
reactions.
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02979
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 1. π-Extension of Congested p-Terphenyls
Scheme 2. Scholl-Based π-Extension Reaction of Model p-
Terphenyl
to the successful synthesis of helicene 8 to 23−25 gave a single
1
PAH-containing macrocycle in 80−90% yield. The H NMR
spectra of the PAH produced from the Scholl reactions of 23−
2
5 showed nine aromatic signals, with a pair of low-field singlets
at ∼9.5 and 9.2 ppm. This pointed to the structure of
tetrabenz(a,c,h,j)anthracene-containing macrocycles 29B, 30B,
and 31B, which would result from a 1,2-aryl shift reaction at
some point along the reaction pathway. The desired cisoid π-
extension product would produce only eight aromatic signals in
existing and bent π-systems can be extended using this
1
methodology.
the H NMR spectra of 29A−31A, as well as a shielded singlet
3
Inspired by the work of Durola and co-workers, we sought to
for the tert-butyl protons of the desired helicene (see Supporting
Information (SI)). The PAH structures of 29B−31B were
ultimately confirmed to be that of tetrabenz(a,c,h,j)anthracene
exploit the 4-tert-butylphenyl group as the arene unit for π-
extension at the bent p-terphenyl system of 6 (Scheme 1B). To
ensure that the introduction of electron-rich arene units within
the p-terphenyl unit does not lead to undesired, unwanted, or
uncontrollable rearrangement reactions, which have been
10 when a BBr -mediated cleavage of the alkyloxy bridging unit
3
of 29B, followed by methylation of the resulting diol, produced a
PAH that was virtually identical to that of 8 (Scheme 2) with the
exception of two low-field (bay region) singlets at 10.00 and 9.73
ppm (see SI for details).
10
observed by others, a non-macrocyclic homologue of 5 was
1
1
synthesized. Indeed, treatment of 7 with 8.0 equiv of iron(III)
chloride as a solution in 1:9 nitromethane/dichloromethane led
to the formation of [5]helicene 8 in 65% yield and tetrabenz-
At this juncture, homologues containing a central para-
phenylene unit with greater than 4.9 kcal/mol of SE led only to
the formation of tetrabenz(a,c,h,j)anthracene-containing macro-
cycles. The remaining three homologues, 26−28, contain longer
alkyloxy bridging units and thus less strained para-phenylene
rings (SEpp = 2.5−4.3 kcal/mol). Subjecting macrocycles 27
(SE = 3.0 kcal/mol) and 28 (SE = 2.5 kcal/mol) to the Scholl
(
(
a,c,h,j)anthracene (transoid cyclization) derivative 9 in 7% yield
83:17 rr, Scheme 2). The formation of 10, which is the result of
para- to meta-phenylene rearrangement, followed by cyclo-
dehydrogenation, was not observed.
A four-stage, six-step synthetic protocol for the preparation of
bent p-terphenyl-containing macrocycles with alkyloxy bridging
pp
pp
reaction conditions described above resulted in the formation of
desired annulation products 33A and 34A as single regioisomers
in 80% yield (Scheme 3). No rearrangement or transoid
cyclization was observed for these homologues. In the case of
arylated macrocycle 26 (SEpp = 4.3 kcal/mol), π-extension to
afford the desired PAH-containing macrocycle 32A takes place;
however, it is accompanied by the formation 32B. The ratio of
12
units of 4−8 atoms was developed in our laboratory. This
strategy was used to synthesize four new homologues (n = 9−
13
1
2) for the present study. Only homologues that do not
succumb to protic acid-mediated rearrangements were sub-
12b
jected to these investigations (SEpp = 2.5−13.2 kcal/mol).
Regioselective bromination of 11−16 was accomplished by
heating a bromine solution of these macrocycles in ortho-
dichlorobenzene at 80 °C for 3−12 h. Tetrabromides 17−22
were afforded in 80−95% yield as the sole products of these
reactions. A four-fold Suzuki cross-coupling reaction of 17−22
with 4-tert-butylphenylboronic acid proceeded in high yield
1
annulation products was determined to be 83:17 ( H NMR
analysis) in favor of the rearranged isomer. Nonetheless,
regioisomeric macrocycles 32A (9%) and 32B (43%) could be
separated and characterized. To test the stability of 32A, it was
resubjected to identical reaction conditions under which it was
formed. No decomposition or subsequent rearrangement was
observed, and 32A was quantitatively recovered.
(
70−92%) to furnish six arylated precursors for the Scholl
reaction study. Employing the same reaction conditions that led
B
DOI: 10.1021/acs.orglett.8b02979
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. Synthesis of Arylated Macrocycles 23−28 and an
Investigation of Their Scholl Reactions
bridging the PAH structure, respectively. The end-to-end bend
of the dibenzo[f,j]picene unit of 32A is 31.8°, and the SE of this
π-system is 46.9 kcal/mol. The former was calculated by
measuring the angle between the two most distant carbon atoms
of the PAH and the centroid of the central aromatic ring of 32A
(
Figure 1). The latter was obtained by using a method
14
previously reported by Ho
Upon annulation about the bent p-terphenyl backbone of 26,
7.7 kcal/mol of SE is introduced into the macrocyclic structure
̈
ger, Grimme, and co-workers.
2
of 32A (SE(26) = 19.2 kcal/mol). The torsional twist angle (θ)
of the dibenzo[5]helicene unit is 23.3°, which is smaller than θ
15
(
25.1°) for the unperturbed dibenzo[5]helicene 8. Bending
the dibenzo[5]helicene unit of 32A compresses the angle θ and
brings the tert-butyl groups closer together, which should raise
the activation barrier for the annulation reaction of 26 and
related homologues, relative to that of 8. The distance between
the fjord region carbon atoms for 32A is only slightly smaller
than that of 8 (cf. 3.03−3.04 Å). The absorption spectra for 8
and 32A show four absorption bands with λ of 365 and 368
max
nm, respectively (Figure 2). Unlike other bent PAHs, which are
−
5
Figure 2. UV−vis and fluorescence spectra of 32A (blue, 2.0 × 10 M)
−
6
and 8 (orange, 5.0 × 10 M). Fluorescence spectra were measured
All attempts to grow crystals suitable for X-ray crystallo-
graphic analysis of 32A were unsuccessful. However, an
optimized geometry was obtained using density functional
theory calculations with the B3LYP functional and 6-31G* basis
set (Figure 1). The structure of 32A is both twisted and bent due
to the presence of the [5]helicene moiety and the octyloxy group
with 365 nm excitation.
typically blue-shifted relative to the unperturbed, planar
compound, the dibenzo[f,j]picene, or dibenzo[5]helicene, unit
of 32A is only slightly red-shifted. Time-dependent DFT
calculations (B3LYP/6-31G* level of theory) predict a red shift
in the electronic absorption spectra of 32A relative to that of 8,
with λmax of 351 and 345 nm, respectively. The fluorescence
spectra of 32A and 8 show two emission bands with a λmax of 438
nm for both compounds. The fluorescence quantum yields
(
emission efficiencies) of 32A and 8 were measured to be 0.25
and 0.12, respectively. The increased emission efficiency of 32A
is likely due to constraints imposed by the alkyloxy bridging unit,
which makes for a more ridged dibenzo[5]helicene fluorophore.
To the best of our knowledge, 32A is the first example of a bent
analogue of this PAH, and it appears that bending an already
twisted PAH unit does not have a pronounced effect on the
photophysical properties of dibenzo[f,j]picene.
In conclusion, a series of bent p-terphenyl-containing
macrocycles have been synthesized and regioselectively arylated.
For the first time, successful annulation onto a strained para-
phenylene unit using the Scholl reaction has been correlated to
Figure 1. Optimized geometry of 32A (DFT-B3LYP 6-31G*).
the SE of the para-phenylene ring (SE ). Furthermore,
pp
C
DOI: 10.1021/acs.orglett.8b02979
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
intermediates that result from rearrangement reactions under
these π-extension conditions have been unequivocally identified
and characterized. These studies suggest that π-extension of
(7) Quernheim, M.; Golling, F. E.; Zhang, W.; Wagner, M.; Rad
̈
er, H.-
J.; Nishiuchi, T.; Mu
̈
llen, K. Angew. Chem., Int. Ed. 2015, 54, 10341−
10346.
(
8) Nishiuchi, T.; Feng, X.; Enkelmann, V.; Wagner, M.; Mu
Chem. - Eur. J. 2012, 18, 16621−16625.
9) (a) Sisto, T. J.; Zakharov, L. N.; White, B. M.; Jasti, R. Chem. Sci.
̈
llen, K.
bent para-phenylene units is possible when the SE is less than
pp
4
.3 kcal/mol. When the SEpp is less than 3.0 kcal/mol, no
(
rearrangement is observed. The structure of 32A represents a
rare example of a macrocyclic helicene system that is both
twisted and bent, with an end-to-end bend angle of 31.8° and
2
2
(
016, 7, 3681−3688. (b) Sisto, T. J.; Tian, X.; Jasti, R. J. Org. Chem.
012, 77, 5857−5860.
10) Dou, X.; Yang, X.; Bodwell, G. J.; Wagner, M.; Enkelmann, V.;
4
6.9 kcal/mol (an additional 27.7 kcal/mol starting from 26) of
Mullen, K. Org. Lett. 2007, 9 (13), 2485−2488.
̈
SE. We hope that these results will serve as a guide for future
synthetic efforts aimed toward π-extension of benzenoid
macrocycles and their conversion into PAH-containing macro-
cycles, such as CNBs. Finally, mechanistic investigations of the
Scholl reactions presented here to better understand the
observed rearrangement reactions, as well as the synthesis of
analogues of 32A, are underway in our laboratory and will be
reported in due course.
(11) For the synthesis of 7, see Scheme SI-2 in the Supporting
Information.
(
12) (a) Mitra, N. K.; Meudom, R.; Gorden, J. D.; Merner, B. L. Org.
Lett. 2015, 17, 2700−2703. (b) Mitra, N. K.; Meudom, R.; Corzo, H.
H.; Gorden, J. D.; Merner, B. L. J. Am. Chem. Soc. 2016, 138, 3235−
3
3
(
(
240. (c) Mitra, N. K.; Corzo, H. H.; Merner, B. L. Org. Lett. 2016, 18,
278−3281.
13) For details, see Scheme SI-1 in the Supporting Information.
14) Ohlendorf, G.; Mahler, C. W.; Jester, S.- S.; Schnakenburg, G.;
Grimme, S.; Ho
(15) Ravat, P.; Hinkelmann, R.; Steinebrunner, D.; Prescimone, A.;
Bodoky, I.; Jurícek, M. Org. Lett. 2017, 19, 3707−3710.
̈
ger, S. Angew. Chem., Int. Ed. 2013, 52, 12086−12090.
ASSOCIATED CONTENT
■
̌
*
S
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.8b02979.
Experimental procedures, characterization data, including
1
13
H and C NMR spectra for all new compounds, and
crystallographic data (PDF)
AUTHOR INFORMATION
■
*
Corresponding Author
E-mail: blm0022@auburn.edu.
ORCID
Bradley L. Merner: 0000-0002-0543-3708
Author Contributions
†N.K.S. and N.K.M. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This material is based upon work supported by the National
Science Foundation under Grant No. CHE-1654691. The
authors are also grateful to Auburn University, the College of
Sciences and Mathematics, and the Department of Chemistry
and Biochemistry. Umicore is also thanked for generous catalyst
donations.
REFERENCES
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DOI: 10.1021/acs.orglett.8b02979
Org. Lett. XXXX, XXX, XXX−XXX