A route to a cyclobutane-linked double-looped system: Via a helical macrocycle

Article abstract of DOI:10.1039/c9cc01201j

Macrocycles built of carbazole and pyridine fragments with alkene/alkane linkers constitute a helical structure as documented structurally and spectroscopically. The 'solid-state' prearrangement observed for two CC bonds leads to unprecedented transformation to a cyclobutane in a head-to-tail (rtct) geometry with two macrocyclic loops in a perpendicular orientation.

Full text of DOI:10.1039/c9cc01201j

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Reactivity differences of Sc
first methanofullerene derivatives of Sc
3
N@C2n (2n
=
68 and 80). Synthesis of the
3
N@D5h-C80
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DOI: 10.1039/C9CC01201J
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A Route to a Cyclobutane-Linked Double-Looped System via a
Helical Macrocycle
†
†
*a
Jan Klajn, Wojciech Stawski, Piotr J. Chmielewski, Joanna Cybińska and Miłosz Pawlicki
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
1
Macrocycles build of carbazole and pyridine fragments with final molecule creating i.a. the helical structures, but also
alkene/alkane linkers constitute a helical structure as documented potentially mimicking the solid state orientation of highly
structurally
and
spectroscopically.
The
‘solid-state’ reactive fragments opening a possibility of extraordinary
prearrangement observed for two C=C bonds leads to reactivity including the formation of highly strained fragments
unprecedented transformation to a cyclobutane in a head-to-tail (e.g. cyclobutane) unavailable for any other type of
(rtct) geometry with two macrocyclic loops in a perpendicular preorganization in solution.
orientation.
Following these observations here we report the studies on the
influence of the degree of linkers saturation on a helicity within
the skeletons merging carbazole and pyridines. In addition the
orientation of C-C units leads to a figure-eight structure with the
organization of unsaturated bonds allowing an unprecedented
cyclization eventually forming a cyclobutane linked double
looped structure.
Macrocyclic structures continue their attractiveness as
molecules with a wide scope of applicability and structural
motifs allowing testing many aspects of reactivity unavailable
for linear molecules e.g. helicity. Helical structures constructed
of aromatic subunits (i.a. helicenes) occupy an important place
in modern research nevertheless usually formation of such
motifs requires application of very stiff building blocks
tBu
tBu
tBu
1
2
1
7
18
3
4
1
5
6
stabilizing 3D organization. On the other hand the highly
N
N
16
CHO
N
N
N
N
intramolecular 15
strained structures and conjugated macrocycles have been
reported as motifs where an internal reactivity can result in
unexpected transformations. Depending on the size of
macrocycle many aspects of possible properties but also several
reactivity paths leading to modifications unavailable without a
NH
14
1
131
H
7
H
N
a
8
3
12
N
CHO
9
81
82
1
32
11 10
tBu
111
101
tBu tBu
tBu
1
3
3-H2
intermolecular
a
2
macrocyclic prearrangement have been explored. A significant
34
5
33
311
35
4
6
81
tBu
tBu
tBu
difference has been observed for structures with decreased
macrocyclic conjugation where the local effects become
influential and the control on the regio- or stereoselectivity
could be addressed in post-synthetic transformations, i.a.
photochemical. Nonetheless the application of photoinduced
2
91
N
N
N
101
N
N
2
20
19
NH
HN
NH
X
HN
1
2
81
111
N
N
N
17
22
261
131
tBu tBu
tBu
tBu
24
15
23
16
-
.
.
=
3
2
2 H X = -C C-
2
reactions for a controlled modification of macrocycles is rare,
-
2
4
-
H
X = -C C-
even if such modification has been reported as very efficient
and selective for the solid state transformations of predefined
derivatives of bis-pyridylethylene structures with a designed
orientation during crystalisation.4,5 Still the shape persistence of
macrocyclic structures covers both of discussed aspects as
unsaturated building-blocks introduce a significant rigidity to
tBu
tBu
N
H
H
N
HN
N
intramolecular
b
NH
H
N
tBu
H
tBu
4
Scheme 1. Synthetic approach to formation of target macrocycles (conditions: a)
TiCl , Zn, C N, dioxane, reflux); b) CH(D)Cl , 365 nm, 72 h).
4
5
H
5
3
a.Wydział Chemii, Uniwersytet Wrocławski, F. Joliot-Curie 14, 50-383 Wrocław,
Poland
milosz.pawlicki@chem.uni.wroc.pl
http://mjplab.org/
These authors contributed equally.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
The McMurry coupling as a convenient way for formation of
alkenes leads also to structures containing saturated bonds
opening the way for obtaining structures where the rigidity of
final skeletons will influence the observed behaviour. Thus we
6
7
†
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have subjected dialdehyde
1
to low valent titanium coupling in N-H-N hydrogen bond within the coordination cavity that
View Article Online
DOI: 10.1039/C9 C1 1C 01201J
1
,4-dioxane (Scheme 1) receiving reproducibly two types of strongly affects the radiative channel during excitation.
products: intramolecular
intermolecular ( (3%), -H
the comparing experiment performed for phenyl derivative steric confinements of
Scheme S1) showed solely the intramolecular variant of ethylene bridge as documented in the crystal structure (Figure
(
3
(15%),
3
-H
(6%)). To our surprise macrocycles is consistent with spectroscopic conclusions. The
result in a strong deformation of
2
(12%)) and
The X-Ray analysis performed for pyridine based
2
2
2
(3%) and -H
2
4
3
(
reactivity with formation of highly strained Z-isomer (Figure S8). 2A). The bond lengths of formed C2-bridge (C(1)-C(2) 1.388(7)
All macrocyclic structures remain locally aromatic according to Å, C(1)-C(18) 1.459(7) C(2)-C(3) 1.476(8) Å) are not showing
magnetic criterion8 and the spectroscopic properties are much differences from typical sp -sp double bond and a sp -sp
2
2
2
2
consistent with rather negligible macrocyclic delocalisation single interaction.
9
observed comparing to other macrocycles of similar size but
also involving a carbazole10 what can lead to expected
intramolecular reactivity in a controlled way.
Figure 2. Crystal structure of
3 (A, thermal ellipsoids present 30% probability) and
3
-H (B, thermal ellipsoids present 50% probability).
2
Nevertheless the bond angles are drastically deformed
2
2
comparing to those of ideal trigonal geometry of an sp -sp
linkage (C(1)-C(2)-C(3) 140.5°, H(1)-C(1)-C(2) 109.7° and (H(2)-
C(2)-C(3) 109.7°) what is caused by the small size of the
macrocyclic core (Figure 2A) along with the presence of
hydrogen and a repulsion with neighbouring nitrogens. The
1
Figure 1
3
. H NMR spectra of 3 (A), 2 (B) and 4 (C) (CDCl , 600MHz, 300K).
3
3
Assignment follows the numbering system presented in Scheme 1.
presence of saturated sp -sp linker documented in the crystal
structure of -H (Figure 2B) changes geometry and results in
less planar conformation consistent with the character of the C-
3 suggested a dissimilar environment of both C bridge and the spectroscopic predictions.
3
2
The C(H)=C(H) ethylene singlets recorded at
and = 6.95 for
ethene bridges. The C chemical shift for the same positions
= 131.2 ppm = 132.4 ppm ) undoubtedly confirmed a (Figure 3) with the E-orientation of pyridines and helical
presence of double bond in both structures. The existence of orientation. The C=C linkers in and -H present geometry
single bonds in -H -H and -H was manifested by specific close to the expected construction of a trans-substituted alkene
resonance on H NMR spectra at = 3.50 ppm, = 3.41 ppm (Figure 3A,B) and the bond lengths of C(1)-C(2) 1.354(8) Å, C(1)-
and = 3.35 ppm, respectively. A substantial down-field shift of C(18) 1.468(5) C(2)-C(3) 1.476(5) Å for and C(1)-C(2) 1.396(7)
resonances observed for and = 12.8ppm and = 17.8 ppm Å, C(1)-C(18) 1.495(7) C(2)-C(3) 1.495(5) Å for -H . Also the C-C
respectively, Figure 1) eventually assigned to NH groups of linkers in -H and -H (Figure 3B,C) present geometric factors
carbazole are consistent with a strong interaction of hydrogen characteristic for saturated bonds C(19)-C(20) 1.434(7) Å, C(19)-
confined between three nitrogens. The introduction of C(18) 1.505(4) Å for 2- and C(1)-C(2) 1.510(12) Å, C(1)-C(18)
saturated bonds in all macrocycles noticeably shifts the 1.509(8) Å for -H
resonances assigned to NH groups ( = 12.32 ppm ( -H ), As observed in the crystals (Figure 3)
= 11.88 ppm ( -H ), = 16.32 ppm ( -H )) while comparing to present helical conformation,
their unsaturated origins consistently with expected higher chromatographic analysis with a chiral support has shown a
global flexibility. presence of two well separated fractions that presented
The absorbance spectra of obtained macrocycles (Figure S39- identical spectroscopic properties (NMR, UV-Vis) with
1) showed an absorbance at = 400 nm for and = 425 nm complementary Cotton effects (Figure 4) solely for suggesting
for as the most red-shifted transition. All macrocycles do not a crucial influence of two unsaturated linkers in stabilization of
δ = 7.66 ppm for 2
δ
13
2 4
2, 2-H and 2-H present very similar arrangement in crystals
(δ
2
,
δ
3
2
2
2
2
2
,
2
4
3
2
1
δ
δ
δ
2
2
3
(δ
δ
2
2
2
2
2
4
H
2
2
4
.
δ
2
2
2
,
2
-H
2
,
2
-H
4
and
3
-H
2
δ
2
4
δ
3
2
nevertheless
the
4
λ
2
λ
2
3
1
show any emission consistently with H NMR analysis of strong helical conformation in solution. The presence of N-H-N
hydrogen bonding in the cavity as documented in NMR and X-
2
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DOI: 10.1039/C9CC01201J
Figure 3. Crystal structure of 2 (A), 2-H
2
(B) and 2-H
4
(C) (all projections present M isomer, thermal ellipsoids at 30% probability).
3
Ray analyses is insufficient to hold the structure in CHCl ) has shown (Figure S38) the separation of two
conformational stiffness in solution. The final assignment of unsaturated bonds of 3.685 Å still keeping that in the range
enantiomers have been achieved based on theoretical postulated by Schmidt and co-workers as crucial for such
1
2
predictions where a fair correlation between observed and transformation.
predicted spectra was observed ((TDDFT calculations, see SI). Thus we have exposed a freshly prepared sample of
air-free CDCl to the UV light (365 nm) observing a gradual
disappearance of and formation of target molecule (Scheme
, Figure S1) with a full conversion to after 70h of irradiation.
The recorded process is quantitative and the only formed
product is as an intramolecular variant of potential reactivity.
The UV-Vis properties of are consistent with the previously
2
in the
3
2
1
4
4
4
observed including the lack of emission (Figure S39). The NMR
analysis of the final compound showed a significantly up-field
shifted bridging CH unit (
1
δ
= 7.66 ppm →
δ
= 4.97 ppm, Figure
C) along with the change of C chemical shift ( = 131.2 ppm
= 51.0 ppm) consistent with formation of a cyclobutane
13
δ
→
δ
especially that the mass spectrum recorded for the final product
showed the m/z signal at 915.5088 the same as for
2 and
+
consistent with [C64
H
32
N
6
+H] proving isomerisation of the
Figure 4. CD spectra (298 K, DCM) of separated enantiomers of
2 along with stick
representations of their skeletons and assignments of helicity senses.
starting material. The 2D NMR analysis has shown a presence of
strong NOE contact between the bridging unit and internal NH
signal (see Figure S14) confirming a short distance between
both hydrogens.
Photodimerization of unsaturated C-C bonds with formation
of i.a. cyclobutanes according to principles of Schmidt and co-
workers requires a specific orientation of two double bonds (i.e.
separation of reacting fragments up to 4 Å).12 Such processes
have been explored in the solid-state where the proximity of
double bonds is forced by the crystal net. Nevertheless a careful
analysis of crystal structures showed a close proximity of two
In contrast to
the photodimerisation product
2
where the D
2
symmetry can be distinguished
remains silent in CD
4
experiments (Figure S35) what supports the formation of
13
cyclobutane in the head-to-tail organization and the rctc
orientation of substituents what imposes a C2v symmetry in the
2 4
C‧‧‧C linkers in 2, 2-H and 2-H (Figure 3) with much shorter
final molecule. The X-Ray analysis of
4 (Figure 5) is consistent
separation than those reported for [2+2] photodimerisation
observed in solid state of pyridine derivative[ and close to the
sum of van der Waals radii of carbon (3.4 Å). Thus two
with spectroscopic conclusions. The linking central unit shows
bond lengths of ca. 1.55 Å and angles close to those expected
4,5]
14
for cyclobutane (~88º, (Figure 5)). The depth of pucker in
4
has
unsaturated bonds in
to a cyclobutane containing skeleton. As documented in the CD
experiments, keeps the helical conformation also in the
solution and the proximity of both double bonds is sustained.
The DFT optimized geometry of with B3LYP-6-31G(d,p) (PCM,
2
are in perfect orientation for isomerizing
o
been recorded as 19 what, while comparing to cyclobutane is
smaller by ~10 . The formation of new linker increases the N-
o 14
2
N distances in the macrocyclic core(s) to about 3.9 Å between
pyridines and 2.8 Å between carbazole and pyridines. Both
2
macrocyclic fragments in
4
are nearly perpendicular as
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o
2
a) M. Suzuki, A. Osuka J. Am. Chem. Soc. 2007, 1Vi2ew9,A4rti6cl4e-O4n6lin5e;
documented by the dihedral angle of 89.3 between mean
planes of each part of the molecule (Figure 5, inset) consistent
with C2v symmetry and lack of chirality.
b) M. Pawlicki, D. Bykowski, L. Szterenberg, L. Latos-Grażyński,
DOI: 10.1039/C9CC01201J
Angew. Chem. Int. Ed. 2012, 51, 2500-2504; c) M. Umetani, T.
Tanaka, T. Kim, D. Kim, A. Osuka, Angew. Chem. Int. Ed. 2016,
5
5
,8095–8099.
a) Y. Xu, M.D. Smith, J. A. Krause, L.S. Shimizu, J. Org. Chem.
009, 74, 4874-4877; b) T. Nagai, A. Takiguchi, M. Ueda, K.
Oda, S. Hiroto, H. Shinokubo J. Am. Chem. Soc. 2018, 140
392-8395.
3
4
5
2
,
8
M.-M. Gan, J.-G. Yu, Y.-Y. Wang, Y.-F. Han Cryst. Growth
Des., 2018, 18, 553–565; b) S. Poplata, A. Tröster, Y.-Q. Zou, T.
Bach Chem. Rev. 2016, 116, 9748-9815; c) V. Ramamurthy, J.
Sivaguru Chem. Rev. 2016, 116, 9914-9993.
a) S.M. Oburn, D.C. Swenson, S.V.S. Mariappan, L.R.
MacGillivray J. Am. Chem. Soc. 2017, 139, 8452-8454; b) M.
Nagarathinam, A.M.P. Peedikakkal, J.J. Vittal Chem. Commun.
2
4
9
008, 5277-5288, c) L.R. MacGillivray Cryst. Eng. Comm. 2002,
, 37-41; d) K. Biradha, R. Santra Chem. Soc. Rev. 2013, 42
,
50-967.
6
a) M. Ephritikhine Chem. Commun., 1998, 2549–2554; b) A.
F
ü
2
rstner, B. Bogdanovic Angew Chem. lnr. Ed. Engl. 1996, 35
442-2469; c) Y. Nakakuki, T. Hirose, H. Sotome, H. Miyasaka,
H.; K. Matsuda J. Am. Chem. Soc. 2018, 140, 4317−4326.
K. Matsumoto, H. Minami, T. Kawase, M. Oda Org. Biomol.
Chem. 2004, , 2323-2326.
M. Pawlicki, L. Latos-Grażyński Chem. Asian J. 2015, 10, 1438-
451.
,
7
8
9
2
1
a) D. Kuzuhara, Y. Sakakibara, S. Mori, T. Okujima, H. Uno, H.
Yamada Angew. Chem. Int. Ed. 2013, 52, 3360-3363; b) D.
Kuzuhara, Z. Xue, S. Mori, T. Okujima, H. Uno, N. Aratani, H.
Yamada Chem. Commun. 2013, 49, 8955-8957; c) M. Pawlicki,
K. Hurej, L. Szterenberg, L. Latos-Grażyński Angew. Chem. Int.
Ed. 2014, 53, 2992-2996, d) M. Pawlicki, M. Garbicz, L.
Szterenberg, L. Latos-Grażyński Angew. Chem. Int. Ed. 2015,
Figure 5. X-Ray structure of
4 (thermal ellipsoids present 30% probability). Insets
present bond length and angles in cyclobutane linker and a perpendicular
orientation of both loops.
In conclusion we have presented a rational approach for
formation of two types of cyclic structures involving carbazole
and pyridine units showing a possibility of forming highly
strained molecules with a Z-ethylene bridge obtained in a way
of intramolecular reaction. The intermolecular variant leads to
formation of macrocycles where two 2-pyridyl subunits are
linked by differently saturated E-bridges. As documented in CD
experiments two ethylene linkers are crucial for keeping the
helicity in solution. In addition the spatial arrangement with a
close proximity of two ethylene bridges allowed the
photodimerisation eventually creating the first example of a
cyclobutane structure linking two nitrogen(s) containing loops
and showing a potential for further functionalization with
formation of non-trivial structures unavailable in any other
approach. Further experiments for extending the scope of
applicability and exploring the potential of presented structures
are under way in our lab.
55, 1906-1909; e) K.S. Anju, S. Ramakrishnan, A. Srinivasan,
Org. Lett. 2011, 13, 2498–2501.
1
1
0 a) L. Arnold, H. Norouzi-Arasi, M. Wagner, V. Enkelmann, K.
Müllen Chem. Commun. 2011, 47, 970-972; b) Ch. Maeda, T.
Yoneda, N Aratani, M.-C. Yoon, J.M. Lim, D. Kim, N. Yoshioka,
A. Osuka Angew. Chem. Int. Ed. 2011, 50, 5691-5694.
1 a) A. L. Sobolewski, M. Gil, J. Dobkowski, J. Waluk J. Phys.
Chem. A, 2008, 113, 7714-7716; b) Y. Iima, D. Kuzuhara, Z.-L.
Xue, S. Akimoto, H. Yamada, K. Tominaga, K. Phys. Chem.
Chem. Phys. 2014, 16, 13129-13135; c) K. Hurej, W. Stawski,
L. Latos-Grażyński, M. Pawlicki Chem. Asian J. 2016, 11, 3329–
3
333; d) K.S. Kim, J. M. Lim, R. Myśliborski, M. Pawlicki, L.
Latos-Grażyński, D. Kim J. Phys. Chem. Lett. 2011,
2 G. M. Schmidt J. Chem. Soc. 1964, 1996–2000.
2, 477-481.
1
1
3 A.M.P. Peedikakkal, J. J. Vittal Chem. Eur. J. 2008, 14, 5329-
5334.
1
4
E.V. Anslyn, D.A. Dougherty Modern Physical Organic
Chemistry University Science Books, 2006, University Science
Books: Sausalito, CA, USA 2006.
Financial support from the National Science Centre, Poland
(2015/17/B/ST5/01437) is kindly acknowledged. The Wrocław
Supercomputer Centre (KDM WCSS) is kindly acknowledged for
sharing computation resources necessary for DFT calculations.
Conflicts of interest
There are no conflicts to declare.
Notes and references
1
A. Robert, P. Dechambenoit, E.A. Hillard, H. Bock, F. Durola,
Chem. Commun. 2017, 53, 11540-11543.
4
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