Synthesis of a triply-bridged molecular gyroscope by a directed meridional cyclization strategy

Article abstract of DOI:10.1021/ol071379y

A crystalline triply bridged molecular gyroscope has been prepared and analyzed by single-crystal X-ray diffraction. A convergent synthetic strategy was developed to control the direction of the three bridges, from the preferred two zonal and one meridion

Full text of DOI:10.1021/ol071379y

ORGANIC
LETTERS
2007
Vol. 9, No. 18
3559-3561
Synthesis of a Triply-Bridged Molecular
Gyroscope by a Directed Meridional
Cyclization Strategy
Jose E. Nun˜ez, Arunkumar Natarajan, Saeed I. Khan, and
Miguel A. Garcia-Garibay*
Department of Chemistry and Biochemistry, UniVersity of California,
Los Angeles, California 90095-1569
mgg@chem.ucla.edu
Received June 11, 2007
ABSTRACT
A crystalline triply bridged molecular gyroscope has been prepared and analyzed by single-crystal X-ray diffraction. A convergent synthetic
strategy was developed to control the direction of the three bridges, from the preferred two zonal and one meridional arrangement of a
one-step cylclization process to the directed three meridional bridges achieved by a north−south desymmetrization.
Growing interest in artificial molecular machinery1 has led
to the design and exploration of amphidynamic crystals as a
new class of materials with physical properties that depend
on the internal dynamics of mobile molecular components.2
Our initial contributions have centered on molecules with
shapes and functions analogous to those of macroscopic
gyroscopes,2a-e,3 such as compounds 1a-c (Figure 1). They
consist of an intrinsically barrierless4 1,4-dialkynylbenzene
rotator as the dynamic component (red) and two triaryl-
methyl (trityl) or triptycyl groups acting as a stator (blue).
In addition to providing steric shielding, the stator serves as
a frame of reference to define the dynamics of the rotator in
the crystal.2a-e
(∼1012 s-1),2e 2-fold flipping frequencies measured by solid-
state NMR depend on the structure of the stator. At 298 K,
While steric hindrance in crystals results in rotational
frequencies slower than those expected in the gas phase
(1) (a) Balzani, V.; Credi, A.; Raymo, F.; Stoddart, F. Angew. Chem.,
Int. Ed. 2000, 39, 3348. (b) Kottas, G. S.; Clarke, L. I.; Horinek, D.; Michl,
J. Chem. ReV. 2005, 105, 1281. (c) Bedard, T.C.; Moore, J. A. J. Am. Chem.
Soc., 1995, 117, 10662. (d) Kay, E. R.; Leigh, D. A.; Zerbetto, F. Angew.
Chem., Int. Ed. 2007, 46, 72. (e) Feringa, B. L.; Koumura, N.; Delden, R.
A.; TerWiel, M. K. J. Appl. Phys. A, 2002, 75, 301. (f) Sestelo, J. P.; Kelly,
T. R. Appl. Phys. A 2002, 75, 337. (g) Shirai, Y.; Morin, J.-F.; Sasaki, T.;
Guerrero, J. M.; Tour, J. M. Chem. Soc. ReV. 2006, 35, 1043. (h) Marsella,
M. J.; Rahbarnia, S.; Wilmont, N. Org. Biomol. Chem. 2007, 5, 391.
Figure 1. Gyroscope consisting of a rotating mass (rotator) linked
by an axle to a shielding enclosure (stator). Molecular analogues
consist of a phenylene rotator, a dialkyne axle (red), and a bis-
trityl stator (blue).
10.1021/ol071379y CCC: $37.00
© 2007 American Chemical Society
Published on Web 08/02/2007

they vary from ca. 800 Hz for 1a (R1 ) R2 ) H)2d and 5
kHz for 1b (R1 ) OMe, R2 ) H),5a,b up to >100 MHz for
1c (R1 ) R2 ) tBu).5c Now, in order to better emulate the
structure and function of a macroscopic gyroscope, we set
out to synthesize compound 2 (Figure 1). It is anticipated
that fully encapsulated rotators with polar groups (-F, NO2,
etc.) will exhibit interesting dielectric properties, as these
are expected to respond to electric, magnetic, and optic
stimuli.2a-c,3,6
As a first step toward a general synthesis of triply bridged
structures, we explored the functionalization of hexa-m-
phenol 3. We noticed that reaction of the hexaphenolate with
6 equiv of n-bromobutane or n-bromohexadecane in DMSO
at 363 K produced derivatives 4a and 4b in ca. 80% yield
within 15 min (Scheme 1). Encouraged by this and by
with 3.0 equiv of 1,8- and 1,10-dibromoalkanes. While the
reactions proceeded rapidly and cleanly, triple cyclization
led to the “open” structures 5a and 5b, with one meridional
(north-south) and two zonal (east-west) bridges. These
compounds were characterized by NMR and mass spectrom-
etry, and the structure was confirmed by single-crystal X-ray
diffraction in the case of 5b (Scheme 1).7
Recognizing the success of Gladysz et al.8 on the synthesis
of metal-centered gyroscopes (6a-c, Scheme 1) through
metathesis reactions,9 we decided to synthesize the ω-al-
kenyloxy derivatives 4c and 4d. We selected 6 and 10
ω-alkenyl carbon chains to explore the effect of the ring
closing metathesis reaction on the formation of 10 and 18
carbon bridges to form the required 28- and 36-membered
macrocyles. Unfortunately, metathesis reactions with PhCHd
RuCl2(PCy3)2 or PhCHdRuCl2(ImesH2)(PCy3)9 followed by
PdC-catalyzed hydrogenation yielded compounds 5b and 5c,
respectively, with zonal and meridional bridges. Given the
drawbacks of the symmetrically functionalized precursor,
next we investigated a directed meridional approach with
the asymmetric precursor 7 (Scheme 2).
Scheme 1
Scheme 2
molecular models suggesting that 8- and 10-carbon chains
should have no obvious strain, we explored a one-pot reaction
(2) (a) Khuong, T.-A.; Nun˜ez, J. E.; Godinez, C. E.; Garcia-Garibay,
M. A. Acc. Chem. Res. 2006, 39, 413. (b) Garcia-Garibay, M. A. Proc.
Natl. Acad. Sci. U.S.A. 2005, 102, 10771. (c) Garcia-Garibay, M. A. Top.
Curr. Chem. 2006, 262, 179. (d) Dominguez, Z.; Dang, H.; Strouse, M. J.;
Garcia-Garibay, M. A. J. Am. Chem. Soc. 2002, 124, 7719. (e) Godinez,
C. E.; Zepeda, G.; Garcia-Garibay, M. A. J. Am. Chem. Soc. 2002, 124,
4701. (f) Gardinier, J. R.; Pellechia, P. J.; Smith, M. D. J. Am. Chem. Soc.
2005, 127, 12448. (g) Zhu, H. F.; Wang, X. F.; Okamura, T. A.; Sun, W.
Y.; Ueyama, N. J. Coord. Chem. 2006, 59, 429. (h) Vaughan, O. P. H.;
Williams, F. J.; Bampos, N.; Lambert, R. M. Angew. Chem., Int. Ed. 2006,
45, 3779. (i) Setaka, W.; Sato, K.; Ohkubo, A.; Kabuto, C.; Kira, M. Chem.
Lett. 2006, 35, 596. (j) Horike, S.; Matsuda, R.; Tanaka, D.; Matsubara, S.;
Mizuno, M.; Endo, K.; Kitagawa, S. Angew. Chem., Int. Ed. 2006, 45, 7226.
(k) Sato, D.; Akutagawa, T.; Takeda, S.; Noro, S.; Nakamura, T. Inorg.
Chem. 2007, 46, 363.
(3) Analogous structures with polar rotators have properties analogous
to macroscopic compasses: (a) Dominguez, Z.; Khuong, T.-A. V.; Dang,
H.; Sanrame, C. N.; Nun˜ez, J. E.; Garcia-Garibay, M. A. J. Am. Chem.
Soc. 2003, 125, 8827. (b) Horansky, R. D.; Clarke, L. I.; Price, J. C.;
Khuong, T.-A. V.; Jarowski, P. D.; Garcia-Garibay, M. A. Phys. ReV. B
2005, 72, 014302. (c) Horansky, R. D.; Clarke, L. I.; Winston, E. B.; Price,
J. C.; Karlen, S. D.; Jarowski, P. D.; Santillan, R.; Garcia-Garibay, M. A.
Phys. ReV. B 2006, 74, 054306.
(4) (a) Abramenkov, A. V.; Almenningen, A.; Cyvin, B. N.; Cyvin, S.
J.; Jonvik, T.; Khaikin, L. S.; Roemming, C.; Vilkov, L. V. Acta Chem.
Scand. 1988, A42, 674. (b) Sipachev, V. A.; Khaikin, L. S.; Grikina, O. E.;
Nikitin, V. S.; Traettberg, M. J. Mol. Struct. 2000, 523, 1.
(5) (a) Nun˜ez, J. E.; Khuong, T.-A. V.; Campos, L. M.; Farfan, N.; Dang,
H.; Karlen, S. D.; Garcia-Garibay, M. A. Cryst. Growth Des. 2006, 6. 866.
(b) Khuong, T.-A. V.; Dang, H.; Jarowski, P. D.; Maverick, E. F.; Garcia-
Garibay, M. A. J. Am. Chem. Soc. 2007, 129, 839. (c) Khuong, T.-A. V.;
Zepeda, G.; Ruiz, R.; Khan, S. I.; Garcia-Garibay, M. A. Cryst. Growth
Des. 2004, 4, 15.
We envisioned the synthesis of compound 7 by Pd(0)-
catalyzed coupling of terminal alkyne 8 with iodophenylene
(6) Rozenbaum, V. M. SoV. Phys. JETP 1991, 72, 1028.
(7) Compound 2: C78H88O6, C7H8, 0.5 (C7H8), 0.15 (C6H6), colorless
plates, MW ) 1267.20, triclinic, P1h, a ) 11.6972(16) Å, b ) 18.1228(3)
Å, c ) 18.781(2)Å, R ) 111.3840(16)°, â ) 96.2430(3)°, γ ) 90.9480-
(3)°, Z ) 2, F_000 ) 1367, λ ) 0.71073, T ) 100(2) K, crystal size ) 0.2
× 0.2 × 0.1, R1 ) 0.0621, wR2 ) 0.1639 (all data). 5b. While plate-like
crystals of 5b from CHCl3 failed to give good data refinement, we were
able to obtain the connectivity and a reasonable packing arrangement:
C78H88O6, colorless plates, MW ) 1121.48, tetragonal, P-4, a ) 16.9165-
(7) Å, b ) 16.9165(7) Å, c ) 11.7976(10) Å, R ) 90.0°, â ) 90.0°, γ )
90.0°, Z ) 2, λ ) 0.71073, T ) 100(2) K, crystal size ) 0.3 × 0.2 × 0.1.
(8) (a) Wang, L.; Hampel, F.; Gladysz, J. A. Angew. Chem., Int. Ed.
2006, 45, 4372. (b) Narwara, A. J.; Shima, T.; Hampel, F.; Gladysz, J. A.
J. Am. Chem. Soc. 2006, 128, 4962. (c) Shima, T.; Hampel, F.; Gladysz, J.
A. Angew. Chem., Int. Ed. 2004, 43, 5537.
3560
Org. Lett., Vol. 9, No. 18, 2007

9, both being available from known tris(m-methoxy)trityl
alkyne 10.5a For the successful implementation of Scheme
2 we made the key observation that the BBr3 removal of the
methyl groups cannot be accomplished with a terminal
alkyne. Therefore, 10 was reacted with a 2.5-fold excess of
1,4-diiodobenzene under Sonogashira conditions before it
was submitted to demethylation with BBr310 and subsequent
alkylation with a large excess (18 equiv) of 1,10-dibromo-
decane. The desired tris(ω-bromoalkoxy) precursor 9 was
obtained in 25% yield over three steps. Similarly, triphenol
8 was obtained by protection of 10 with TBDMS-Cl11 prior
Figure 2. (Left) Space-filling model from the X-ray structure of
2 with the dialkynyl phenylene and oxygens shown in red, alkyl
bridges in blue, and solvent molecules in magenta (toluene) and
purple (benzene). (Right) Representation of the environment of the
central phenylene viewed along its 1,4-axis illustrating the cage
formed by its own alkyl chains, those of neighboring molecules
(in green), and solvent molecules. The disorder in the structure is
not shown (see text).
10
to removal of the methyl groups with BBr3 and removal
of TBDMS with TBAF.12 Sonogashira coupling of tribromide
9 with triphenol 8 gave compound 7, a heavy oil, in 67%
yield. Finally, reaction of 7 with 3 equiv of NaH in DMF
for 19 h at 0-25 °C provided the desired meridional bridges
of molecular gyroscope 2. Satisfyingly, the three 28-
membered macrocycles of the novel tricyclic structure are
obtained in 27% isolated yield, for an average yield of 65%
per cyclization step.
molecular point group C1. As illustrated in the right side of
Figure 2, the steric shielding provided by three alkyl chains
is not ideal. While the three bridges (in blue) curve away
from the center to maximize the space around the rotator,
bridges from neighboring molecules (in green) and included
solvent molecules (in purple and magenta) reduce the free
volume about the prospective rotator. The molecular and
crystal structure of 2 suggests that bulkier chains will be
required to create the shielding needed to prevent close
packing interactions and the inclusion of solvent molecules.
With a promising directed strategy now in place, a wide
range of triply bridged derivatives are now in preparation
for dynamic testing.
Molecular gyroscope 2 is a crystalline solid that dissolves
well in boiling CH2Cl2 and CHCl3 and only poorly in
1
aromatic solvents. The solution H and 13C NMR of 2 are
consistent with a rapidly equilibrating structure with a time-
averaged C3h point group. X-ray diffraction data from single
crystals grown in mixtures of toluene and benzene were
solved in the space group P1h as a nonstoichiometric mixed
clathrate.7 The chemical formula of the asymmetric unit is
C78H88O6, 1.5C6H5CH3, 0.15C6H6, with one molecule of 2,
one toluene molecule in a general position, and half of
another toluene molecule at an inversion center7 (Figure 2).
One of the three bridges and the central phenylene are
disordered over two positions with relative occupancies of
15% and 85% that correlate well with the presence or absence
of substoichiometric benzene. The trityl groups of each
molecule adopt propeller conformations of the same chirality
but with aryl groups having different torsion angles for a
Acknowledgment. This work was supported by the
National Science Foundation through Grant Nos.
DMR0307028, DMR0605688, and DGE-0114443 [NSF
IGERT: Materials Creation Training Program (MCTP)].
Supporting Information Available: Syntheses and char-
acterization of 2 and 5a-c. Crystallographic information for
2 (CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
(9) (a) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996,
118, 100. (b) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18.
(10) Shultz, D. A.; Kumar, R. K. J. Am. Chem. Soc. 2001, 123, 6431.
(11) Ockey, D. A.; Lewis, M. A.; Schore, N. E. Tetrahedron 2003, 59,
5377.
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70, 4233.
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