Preparation and characterization of a halogen-bonded shape-persistent chiral alleno-acetylenic inclusion complex

Article abstract of DOI:10.1021/ol403778f

A chiral bidentate inclusion complex has been formed by halogen-bond interaction between the pyridyl moieties of a pyridoallenoacetylenic host and octafluorodiiodobutane. X-ray crystallography showed that the guest adopts a chiral conformation inside the molecular channels formed by stacking of the host units. A 10 ppm shielding of the ¹⁵N NMR resonance for the pyridil units provided evidence of the formation of the halogen-bond complex in solution.

Full text of DOI:10.1021/ol403778f

Letter
pubs.acs.org/OrgLett
Preparation and Characterization of a Halogen-Bonded Shape-
Persistent Chiral Alleno-acetylenic Inclusion Complex
́ ́ ́
dez, Inmaculada R. Lahoz, Antonio L. Llamas-Saiz, Jose Lorenzo Alonso-Gom
ez,†
†
†
‡
Silvia Castro-Fernan
María-Magdalena Cid,* and Armando Navarro-Vaz
,†
,†
́
quez*
†
Department of Organic Chemistry, Facultade de Química, Universidade de Vigo, 36310 Vigo, Spain
‡
Unidade de Raios X. RIAIDT. Edificio CACTUS. Campus Vida. Universidade de Santiago de Compostela, 15782 Santiago de
Compostela, Spain
S Supporting Information
*
ABSTRACT: A chiral bidentate inclusion complex has been
formed by halogen-bond interaction between the pyridyl moieties
of a pyridoallenoacetylenic host and octafluorodiiodobutane. X-
ray crystallography showed that the guest adopts a chiral
conformation inside the molecular channels formed by stacking
1
5
of the host units. A 10 ppm shielding of the N NMR resonance
for the pyridil units provided evidence of the formation of the
halogen-bond complex in solution.
1
−5
a
hape-persistent macrocycles (SPMs),
on acetylenic structural units, present as one of their
principal characteristics their ability to self-assemble in solution,
commonly based
Scheme 1. Synthesis of Enantiopure (P,P,P,P)-1
S
6
−8
giving rise to liquid crystal phases, or when crystallized form
molecular channels by suited alignment of the macrocycles
cavities. Most of the reported SPMs have an achiral nature
9
since they are based on nonstereogenic arene-acetylene or
arene-bisacetylene motifs. However, the introduction of a
stereogenic allene unit leads to chiral allenoacetylenic or
10−16
allenophanic structures.
Noteworthy, these allene-based
structures present very intense Cotton bands in their electronic
1
7,18
circular dichroism (ECD) spectra,
which makes them
suitable as potential chiral sensors, especially if polar groups,
pointing toward the inner cavity, were present in the molecule
as, for instance, in our previously reported allenoacetylenic
1
9
20
(
2,5)- and (2,6)-substituted pyridine rings. Recently, the
a
formation of chiral molecular channels in the solid state from
an allenoacetylenic macrocyle decorated with phenols in its
periphery has been reported by the group of Diederich.
Reagents and conditions: (a) [PdCl (PPh ) ], CuI, TMEDA,
2 3 2
toluene, 110 °C, 20 h, 79%; (b) NaOH, toluene, 110 °C, 2 h, 80%;
21
(c) CuCl , CuCl, pyridine, 25 °C, 72 h, 57%.
2
Allenoacetylenic or allenophanic SPMs have been postulated in
many cases as potential hosts for formation of inclusion
complexes. So far, reported examples have been limited to
yield. Similarly, the enantiomer (M,M,M,M)-1 was obtained
from the corresponding (M)-2 allene. It is worth noting the
stability of homochiral 1, which did not show signs of
20−22
solvent inclusion in crystallized compounds.
We report
here the preparation of (2,6)-pyridophane in an enantiopure
homochiral form, either (P,P,P,P)-1 or (M,M,M,M)-1, and its
use as a host for the formation of a chiral bidentate inclusion
complexes through halogen-bonding interaction with octa-
fluorodiiodobutane.
1
decomposition or isomerization on its H NMR spectrum
after weeks at room temperature under day light.
20
Computational AM1 studies showed that (P,P,P,P)-1 has
three conformations very close in energy, namely, C boat, C
2
2
chair, and the highest symmetry D twist form (Figure 1a−c).
As the first step of the synthesis toward (P,P,P,P)-1 (Scheme
2
Here we reoptimized and computed vibrational frequencies at
1), Sonogashira cross-coupling reaction between 2,6-dibromo-
the DFT CAM-B3LYP/6-31G* level for these three con-
pyridine with enantiopure allene (P)-2 afforded (P,P)-3 in 79%
yield (Scheme 1). Removal of the acetonide protecting group
gave (P,P)-4 in 80% yield. Intermolecular ring closure under
Breslow conditions afforded the desired (P,P,P,P)-1 in 62%
Received: December 31, 2013
Published: February 10, 2014
©
2014 American Chemical Society
1136
dx.doi.org/10.1021/ol403778f | Org. Lett. 2014, 16, 1136−1139

Organic Letters
Letter
Figure 3. Packing diagram along the channel direction, b (left) and a
(
right) axes, displaying the π−π stacking of aromatic pyridine rings
and the layers of hydrophobic interactions in the ab plane.
24
nitriles, and others, to the σ-hole of a X−C bond (X = I, Br,
Figure 1. DFT CAM-B3LYP/6-31G* geometries for (a) C boat, (b)
25
2
Cl). Halogen bonds are becoming more and more useful as
C chair, (c) D twist (P,P,P,P)-1, and (d) C F I -(P,P,P,P)-1 inclusion
2
2
4 8 2
part of the “non-covalent interaction toolkit” in the design of
complex.
26
27
crystals structures, liquid crystal and jelly phases, and even
medicinal chemistry.
28
formations, confirming that they are true minima in the
potential energy surface (see Supporting Information).
Modeling of several halogen-bond bidentate complexes with
different diiodinated and dibrominated guests was carried out
through AM1 semiempirical computations. After trying several
possible guests, we found that octafluoro-1,4-diiodobutane
perfectly fitted the molecular cavity of (P,P,P,P)-1 resulting in a
Crystallization of (P,P,P,P)-1 from a CHCl /hexane solution
3
afforded suitable crystals that after X-ray diffraction analysis
show that (P,P,P,P)-1 adopts the highest symmetry D twist
2
form in the solid state. The macrocycle molecules pack piling
on top of each other, giving rise to elongated cavities that
extend through the whole crystal dimension along the direction
of the b unit cell axis forming a channel (Figure 2). The
bidentate halogen-bonded complex of C symmetry in the AM1
2
potential surface as well as in higher level DFT CAM-B3LYP
computations (see Figure 1d and Supporting Information for
details).
When (M,M,M,M)-1 was allowed to crystallize from a C D
6
6
solution in the presence of an excess of the diiodinated guest,
suitable small crystals were obtained for X-ray diffraction
analysis, which showed the formation of a 1:1 complex between
(
M,M,M,M)-1 and C F I with a molecular geometry very
4 8 2
similar to that obtained in the DFT computations. The C F I
4
8 2
guest adopts an extended conformation inside the host cavity
with a N−I distance of 3.0 Å. The unit cell is formed by two
equivalent C forms that can be interconverted by rotation
2
around a C axis, which passes through the two nitrogen atoms
2
of the host (Figure 4). Interestingly, the guest diiodo
Figure 2. Three perpendicular views of the channel surface in
crystallized (P,P,P,P)-1.
morphology of the channel was analyzed with the Caver 3.0
2
3
software by using a sphere of radius 1.2 Å as a probe. The
channel is formed by a sequence of ellipsoidal voids located in
the centroid of the cyclic molecule, with an approximate
3
volume of 290 Å . Due to blocking by the tert-butyl moieties,
the void cavities are interconnected by three small pores, the
widest being the one in the middle. Along the c axis, the
adjacent macrocycle pyridil group intercalates between the
piled molecules (Figure 3), leading to optimal π-stacking with a
distance between aromatic moieties of ∼3.5 Å.
Figure 4. View of the unit cell formed by two units of the C F I −
4
8 2
(
M,M,M,M)-1 complex.
The face-to-face orientation of the pyridine lone-pairs toward
compound adopts a chiral conformation inside the complex
with a I−C1−C4−I torsion angle of 167°. The packing of the
macrocycle units is very similar to that observed for the free
host crystal, being now the described molecular channels filled
by the fluorinated guest.
the channel void in the D conformation strongly suggested a
2
great potential for the use of homochiral 1 as a bidentate host,
especially for guests with linear or nearly linear geometries.
Two types of noncovalent interactions come then to mind:
formation of hydrogen bonds with acidic guests or the use of
halogen-bond interactions. Halogen bonds are formed by
donation from a lone-pair -containing donor such as amines,
2
9
NMR spectroscopy provided strong evidence of the
presence of the C F I -1 complex also in solution. A C D
4
8 2
6
6
solution of (M,M,M,M)-1 was titrated with 30, 60, 90, and 120
1
137
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Organic Letters
Letter
1
molar equiv of the diiodo compound. H NMR spectrum
showed some nonmonotonic changes in the chemical shifts of
the pyridyl proton signals on increasing C F I concentration
AUTHOR INFORMATION
Corresponding Authors
■
*
*
4
8 2
E-mail: mcid@uvigo.es.
E-mail: armando.deus@gmail.com.
(
see spectra in the Supporting Information). We curiously
observed that at the highest concentration (120 equiv) of the
guest the meta protons of the pyridyl group become
nonequivalent, while only a single set of resonances is observed
in the 13C spectrum. This seems to indicate breaking of the
magnetic equivalence but not of chemical equivalence. This fact
is remarkable since rapid exchange of guest-degenerated
dispositions inside the cavity should average both J-couplings
and chemical shifts in the host.
A stronger evidence of complex formation was obtained
through analysis of the N chemical shift, obtained, by means
of HMBC H− N experiments, at the different titration points
Figure 5). The N shielding goes as high as 9.8 ppm with 120
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(
We thank Spanish Ministerio de Economıa
CTQ2011- 28831) for research funding and a Ramon
research contract to A.N.-V. J.L.A.-G thanks Xunta de Galicia
for a “Parga Pondal” research contract. We thank the Galician
supercomputer center (CESGA) for computer time.
́
y Competitividad
y Cajal
́
1
5
1
15
15
(
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