Molecular gyroscope with a trans-cyclohexane-1,4-diimine rotor unit: Isolation and characterization of a geometric isomer as a formal intermediate of hindered rotation

Article abstract of DOI:10.1246/cl.2012.79

Condensation reactions of macrocyclic diamines 1 and cyclohexane-1,4- dicarbaldehydes 2 with the substituents at 1,4- positions gave a series of macrocage molecules that can be considered molecular gyroscopes. The gyro-rotational behavior of the cyclohexane rotor is largely affected by the degree of steric requirement of the substituents, and isolation of synisomer suggests stepwise motion in the macrocages attached with bulky substituents on the rotor.

Full text of DOI:10.1246/cl.2012.79

doi:10.1246/cl.2012.79
Published on the web December 30, 2011
79
Molecular Gyroscope with a trans-Cyclohexane-1,4-diimine Rotor Unit:
Isolation and Characterization of a Geometric Isomer
as a Formal Intermediate of Hindered Rotation
Hiroyoshi Sugino,1 Hidetoshi Kawai,*1,2 Kenshu Fujiwara,1 and Takanori Suzuki*1
1Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, Hokkaido 060-0810
2Department of Chemistry, Faculty of Science, Tokyo University of Science, Shinjuku-ku, Tokyo 162-8601
(Received October 11, 2011; CL-110827; E-mail: tak@sci.hokudai.ac.jp)
Condensation reactions of macrocyclic diamines 1 and
cyclohexane-1,4-dicarbaldehydes 2 with the substituents at 1,4-
positions gave a series of macrocage molecules that can be
considered molecular gyroscopes. The gyro-rotational behavior
of the cyclohexane rotor is largely affected by the degree of
steric requirement of the substituents, and isolation of syn-
isomer suggests stepwise motion in the macrocages attached
Scheme 1. Gyro-rotation in molecular gyroscope with small
substituents (Type-1).
with bulky substituents on the rotor.
Macrocyclic molecules having a rotating unit in the center
have attracted much attention in terms of their unique structures,
dynamics, and functions.1 Such macrocages are often called
molecular gyroscopes or turnstiles as first proposed by Garcia-
Garibay2 and Moore,3 respectively. Such cage molecules can
serve as a useful motif for studying the internal motion of
molecules, since the way and ease of the motion can be modified
by the macrocycle/rotor structures.1-3 Here we describe a new
series of macrocyclic compounds bridged with a trans-cyclo-
hexane-1,4-diimine unit, which exhibit characteristic rotational
behavior (gyro-rotaion) depending on the steric bulkiness of the
substituents on the cyclohexane rotor unit.
Scheme 2. Gyro-rotation in molecular gyroscope with me-
dium-sized substituents (Type-2).
As shown in Scheme 1, the substituents on the rotor are
accommodated in the macrocyclic cavity to adopt the planar-
conformation as an energy-minimized geometry when the
substituents are small enough (type-1). Very small activation
energy is expected for the gyro-rotation for this class. As the
substituents on the rotor become larger, the rotation of the
cyclohexane unit is gradually slowed. The macrocages are prone
to prefer another conformation, in which the substituents are
directed to the opposite sides of the macrocycle (anti-conforma-
tion) (Scheme 2). The rotational motion of the cyclohexane unit
in these type-2 compounds occurs via the planar-conformation,
which corresponds to the transition state of gyro-rotation. Due to
the limitation of the cavity size, much larger substituents can no
longer go through the cavity (Scheme 3), and the syn-confor-
mation would be involved as the intermediate of the rotational
motion in type-3, in which the substituents are located on the
same side of the macrocycle. The system undergoing stepwise
partial-rotations is interesting from the viewpoint of unique
intramolecular motion such as unidirectional rotation.4
Scheme 3. Hindered rotation in molecular gyroscope with
very large substituent (Type-3).
In this work, bis(m-terphenyl)-type diamines 1A and 1B5
are chosen as the macrocyclic outer rings to study the rotational
behavior depending on the substituent bulkiness as depicted
above. We have succeeded in isolating both anti- and syn-
conformations as stable species by attaching large enough
substituents such as biphenyl-4-ylmethyl at the 1,4-positions of
cyclohexane rotor units (type-3). In contrast, a cyclohexane rotor
Figure 1. Structures of macrocycles 1A and 1B and cyclo-
hexane units 2a and 2b.
unit with smaller substituents such as methoxycarbonyl is freely
rotating within the same macrocycle to exhibit gyro-rotation
(type-1). The details are described herein (Figure 1).
Chem. Lett. 2012, 41, 79-81
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80
(a)
(b)
Figure 3. X-ray structure of diimine 3Ba. (a) Front view and
(b) top view.
(298 K, CDCl3). For example, the 8 protons assigned as Ar-O-
CH2- units are observed as a sharp singlet (4.80 ppm) in 3Aa
or as a triplet (4.02 ppm, J = 6.0 Hz) in 3Ba, which can be
accounted for only by assuming the time-averaged higher
symmetry. Thus, it can be concluded that the gyro-rotation in
3Aa and 3Ba is faster than the NMR time-scale at 298 K in
solution (Figures S3 and S411).
Scheme 4. Synthesis of macrocyclic diimines 3Aa and 3Ba.
(a)
(b)
Next we turned our attention to generate the macrocyclic
cage 3Ab and 3Bb, in which gyro-rotation is hindered due to the
bulkiness of biphenyl-4-ylmethyl groups at the 1,4-positions of
the cyclohexane unit. To further modify the terminal group of
biphenyl unit later, 4¤-TBSO groups are installed on the rotor
precursor 2b. As expected from Scheme 3, condensation of
macrocycle 1A and 2b (refluxing benzene, TFA) afforded a
mixture of two isomeric products 3Ab/3Ab¤ (1:1)7 in a
combined yield of 37%. By starting with flexible macrocycle
2B, isomeric mixture of 3Bb/3Bb¤ were formed in about 2:1-
3:1 ratio, which were separated by chromatography on Al2O3
(y. 31% and 12%, respectively).7 At this moment, it is not
clear which component of 3Bb/3Bb¤ corresponds to the syn- or
anti-isomer. However, the structural identity was unambigu-
ously determined by the end-capping/hydrolysis technique5 as
follows.
The key feature we focused on is that only the anti-isomer
has the structure in which the long rotor unit is threaded through
the macrocyclic outer ring. Both of the syn- or anti-isomers
3Bb/3Bb¤ could be hydrolyzed under the acidic conditions to
regenerate 1B and 2b. In contrast, after attaching end-caps at the
biphenyl termini, which is large enough to prevent dethreading,
only syn-isomer can be hydrolyzed into the two components (1B
and terminal-modified-2b), since the interlocked structure would
be formed upon hydrolysis of anti-isomer (Scheme 5).
By the reaction of 3Bb (major) and 3Bb¤ (minor) with ¡-
bromo-¡¤-{4-[tris(4¤-tert-butylbiphenyl-4-yl)methyl]phenoxy}-
p-xylene (5)5 in the presence of TBAF/Cs2CO3, the terminal-
modified compounds 4Bb (major) and 4Bb¤ (minor) were
obtained (See Supporting Information). In the case of 4Bb, the 8
protons assigned as Ar-O-CH2- units are observed as four
multiplet signals around 4.15, 4.00, 3.47, and 3.25 ppm, whereas
the same 8 protons are observed as one multiplet signal (3.72
ppm) in 4Bb¤. These results can be accounted for by supposing
that cyclohexane units in 4Bb and 4Bb¤ do not rotate. The
1H NMR spectral changes under acidic hydrolytic conditions
clearly indicate that 4Bb derived from the major component 3Bb
gave 1B and terminal-modified-2b (Figure 4), thus 3Bb is the
syn-isomer. On the other hand, the minor component 3Bb¤ is
proven to be the anti-isomer, since 4Bb¤ derived from 3Bb¤
showed only marginal spectral changes under hydrolytic con-
ditions (Figure 5). Isolation of syn-isomer 3Bb along with anti-
Figure 2. X-ray structure of diimine 3Aa. (a) Front view and
(b) top view.
Upon condensation of trans-dimethyl 1,4-diformylcyclo-
hexane-1,4-dicarboxylate (2a)6 with rigid macrocycle 1A with
hexadiyne parts connecting two aminoterphenyl units under
acidic dehydrating conditions (refluxing benzene, TFA), macro-
cage diimine 3Aa7 was obtained in 15% yield,8 which is
sensitive to hydrolysis (Scheme 4).
According to the X-ray analysis on 3Aa,9 the molecule
adopts the characteristic geometry of a type-1 molecular
gyroscope and the two ester groups are accommodated within
the cavity (Figure 2). A noteworthy structural feature is that
ester groups larger than the imine units are located at the axial
positions of cyclohexane. Such conformation is not favorable in
terms of 1,3-diaxial interactions10 but is suitable to connect the
two amine groups of the outer macrocycle with a greater
separation (N-N: 7.24 ¡) than in the case of another conforma-
tion in which the two ester groups adopt the equatorial positions.
Yet, the separation is still much narrower than the free
macrocycle 1A (8.52 ¡) or benzene solvate (1A¢(benzene)3)
(8.45 ¡) determined by the X-ray analyses (Figures S1 and
S2),9,11 and the strain in the outer macrocycle of 3Aa could
account for its high sensitivity toward hydrolysis.
When another macrocycle 1B, in which two aminoterphenyl
units are connected by flexible hexamethylene chains, is
condensed with the cyclohexane unit 2a,7 the ester groups
may be located at the equatorial positions to reduce 1,3-diaxial
interactions in molecular cage 3Ba (Scheme 4).7 This is the
case, and the X-ray analysis9 revealed the geometry in which
two nitrogen atoms are connected by much smaller separation
(6.00 ¡) by locating the imine groups at the axial positions
(Figure 3). Accordingly, the cyclohexanedicarboxylate unit in
3Ba is more voluminous than in 3Aa, but the ester groups can be
still be accommodated in the cavity thanks to the flexible nature
of the hexamethylene chains in the outer ring.
In solution, free rotation of the cyclohexane unit in
molecular cages 3Aa and 3Ba is expected from the above X-
1
ray structures, which was confirmed by H NMR spectroscopy
Chem. Lett. 2012, 41, 79-81
© 2012 The Chemical Society of Japan
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81
divergent. The large substituents require the system to adopt the
intermediate for the gyro-rotation as in type-3, for which the
isomer can be isolated when the rotation is completely hindered.
This work was party supported by the Global COE Program
(Project No. B01: Catalysis as the Basis for Innovation in
Materials Science). We are very grateful to Grant-in-Aid for
Scientific Research on Innovative Areas: Organic Synthesis
Based on Reaction Integration from MEXT, Japan.
References and Notes
1
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Gladysz, Angew. Chem., Int. Ed. 2004, 43, 5537. d) G. S.
Kottas, L. I. Clarke, D. Horinek, J. Michl, Chem. Rev. 2005,
105, 1281. e) W. Setaka, K. Sato, A. Ohkubo, C. Kabuto, M.
Kira, Chem. Lett. 2006, 35, 596. f) W. Setaka, S. Ohmizu, C.
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J.-P. Launay, R. Poteau, G. Rapenne, Chem.®Eur. J. 2008,
14, 8147. h) A. Guenet, E. Graf, N. Kyritsakas, M. W.
Hosseini, Chem.®Eur. J. 2011, 17, 6443.
Scheme 5. Hydrolysis of (a) syn-isomer and (b) anti-isomer in
wet CDCl3. Shaded circles indicate 4-{4-[tris(4¤-tert-butylbi-
phenyl-4-yl)methyl]phenoxymethyl}benzyl groups.
2
a) C. E. Godinez, G. Zepeda, M. A. Garcia-Garibay, J. Am.
Chem. Soc. 2002, 124, 4701. b) Z. Dominguez, H. Dang,
M. J. Strouse, M. A. Garcia-Garibay, J. Am. Chem. Soc.
2002, 124, 7719. c) S. D. Karlen, C. E. Godinez, M. A.
Garcia-Garibay, Org. Lett. 2006, 8, 3417. d) T.-A. V. Khuong,
H. Dang, P. D. Jarowski, E. F. Maverick, M. A. Garcia-
Garibay, J. Am. Chem. Soc. 2007, 129, 839.
3
4
5
T. C. Bedard, J. S. Moore, J. Am. Chem. Soc. 1995, 117,
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M. K. J. ter Wiel, R. A. van Delden, A. Meetsma, B. L.
Feringa, J. Am. Chem. Soc. 2005, 127, 14208.
a) H. Kawai, T. Umehara, K. Fujiwara, T. Tsuji, T. Suzuki,
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2009, 455, 30.
ppm
Figure 4. 1H NMR spectra (300 MHz, CDCl3) of diimine 4Bb
(a) and its hydrolyzed mixture (b). (c) and (d) were measured
after GPC separation of the hydrolyzed sample, which cor-
responds to (c) terminal-modified-2b and (d) macrocycle 1B,
respectively.
6
7
8
C. R. Davis, D. C. Swenson, D. J. Burton, J. Org. Chem.
1993, 58, 6843.
Experimental procedures and selected spectral data are given
in the Supporting Information.
Although trans-2a used in the above reaction contains 20%
of cis-isomer due to the less selective reduction of the
tetraester precursor by DIBALH,6 no product was isolated
having the cis-diimine substructure.
ꢀ
9
1A: triclinic, P1, a = 7.751(10), b = 12.548(15), c =
19.64(2) ¡, ¡ = 71.35(4), ¢ = 78.69(5), £ = 90.10(6)°,
V = 1771(3) A3, Z = 2, R = 0.0929; 1A¢(benzene)3: tri-
clinic, P1, a = 10.028(5), b = 10.661(5), c = 13.261(7) ¡,
ꢀ
ppm
¡ = 102.519(5), ¢ = 109.719(7), £ = 101.017(7)°, V =
1247.8(11) A3, Z = 1, R = 0.0723; 3Aa: orthorhombic,
Pccn, a = 30.06(12), b = 17.33(8), c = 8.98(4) ¡, V =
Figure 5. 1H NMR spectra (300 MHz, CDCl3) of diimine 4Bb¤
(a) before and (b) after an addition of TFA.
3
ꢀ
4678(37) A , Z = 4, R = 0.0615; 3Ab: triclinic, P1, a =
8.635(3), b = 10.814(3), c = 14.111(5) ¡, ¡ = 71.45(2),
¢ = 80.22(3), £ = 75.87(3)°, V = 1205.2(6) A3, Z = 1, R =
0.109.
isomer 3Bb¤ clearly shows that the hindered gyro-rotation of
anti-3Bb¤ would occur, if at all, in a stepwise manner by
involving syn-isomer 3Bb as the intermediate.
10 S. Hirano, S. Toyota, M. Kato, F. Toda, Chem. Commun.
In summary, the rotational motion of macrocage molecules,
that mimic gyroscopes/turnstiles, are largely affected by the
steric requirement of the rotor unit. By attaching the substituents
with a different size, the mechanism of gyro-rotation would be
2005, 3646.
11 Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
Chem. Lett. 2012, 41, 79-81
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/