Self-assembly of an amphiphilic [2]rotaxane incorporating a tetrathiafulvalene unit

Article abstract of DOI:10.1021/ol006387s

(matrix presented) The template-directed synthesis of a [2]rotaxane, in which a π-electron deficient ring component - cyclobis(paraquat-p-phenylene) - is assembled around a π-electron rich asymmetric monopyrrolotetrathiafulvalene unit on the rod section o

Full text of DOI:10.1021/ol006387s

ORGANIC
LETTERS
2000
Vol. 2, No. 23
3547-3550
Self-Assembly of an Amphiphilic
[2]Rotaxane Incorporating a
Tetrathiafulvalene Unit
,†
Jan Oskar Jeppesen,†,‡ Julie Perkins,† Jan Becher,‡ and J. Fraser Stoddart*
Department of Chemistry and Biochemistry, UniVersity of California, Los Angeles,
405 Hilgard AVenue, Los Angeles, California 90095-1569, and Department of
Chemistry, Odense UniVersity (UniVersity of Southern Denmark), CampusVej 55,
DK-5230, Odense M, Denmark
stoddart@chem.ucla.edu
Received July 27, 2000
ABSTRACT
The template-directed synthesis of a [2]rotaxane, in which a π-electron deficient ring componentscyclobis(paraquat-p-phenylene)sis assembled
around a π-electron rich asymmetric monopyrrolotetrathiafulvalene unit on the rod section of an amphiphilic dumbbell component that is
terminated by a hydrophilic dendritic stopper at one end and a hydrophobic tetraarylmethane stopper at the other end, is reported.
Catenanes and rotaxanes1 are multicomponent functional
assemblies comprisingsin addition to covalent bondss
mechanical and noncovalent bonds that can become key
elements in the operation of molecular devices.2,3 In the case
of rotaxanes, where a dumbbell component is encircled by
a ring component, amphiphilic character, together with the
presence of redox-active units in the two components, are
desirable features that allows single-molecule-thick electro-
chemical junctions to be fabricated.3 On account of their
unique π-electron donating properties, tetrathiafulvalene
(TTF) and their derivatives have found widespread use in
materials chemistry.4 Although a considerable range of
catenanes and pseudorotaxanes,1 incorporating a TTF unit
in conjunction with the π-electron accepting tetracationic
cyclophane,5 cyclobis(paraquat-p-phenylene) (CBPQT4+),
have been reported,6 a very few rotaxanes employing these
particular components have been described to date in the
literature.6a,e,n In addition, to the best of our knowledge,
rotaxanes incorporating TTF units in dumbbell components
† University of California, Los Angeles.
‡ Odense University (University of Southern Denmark).
(1) (a) Fyfe, M. C. T.; Stoddart, J. F. Acc. Chem. Res. 1997, 30, 393-
401. (b) Ja¨ger, R.; Vo¨gtle, F. Angew. Chem., Int. Ed. Engl. 1997, 36, 930-
944. (c) Molecular Catenanes, Rotaxanes and Knots; Sauvage, J.-P.,
Dietrich-Buchecker, C. O., Eds.; VCH-Wiley: Weinheim, 1999. (d)
Raymo, F. M.; Stoddart, J. F. Chem. ReV. 1999, 99, 1643-1663.
(2) For a [2]catenane-based solid-state electronically reconfigurable
switch, see: (a) Asakawa, M.; Higuchi, M.; Mattersteig, G.; Nakamura,
T.; Pease, A. R.; Raymo, F. M.; Shimizu, T.; Stoddart, J. F. AdV. Mater.
2000, 12, 1099-1102. (b) Collier, C. P.; Mattersteig, G.; Wong, E. W.;
Luo, Y.; Beverly, K.; Sampaio, J.; Raymo, F. M.; Stoddart, J. F.; Heath, J.
R. Science 2000, 289, 1172-1175.
(3) For electronically configurable molecular-based logic gates, see: (a)
Collier, C. P.; Wong, E. W.; Belohradsky, M.; Raymo, F. M.; Stoddart, J.
F.; Kuekes, P. J.; Williams, R. S.; Heath, J. R. Science 1999, 285, 391-
394. (b) Wong, E. W.; Collier, C. P.; Belohradsky, M.; Raymo, F. M.;
Stoddart, J. F.; Heath, J. R. J. Am. Chem. Soc. 2000, 122, 5831-5840.
(4) For TTF reviews, see: (a) Adam, M.; Mu¨llen, K. AdV. Mater. 1994,
6, 439-459. (b) Jørgensen, T.; Hansen, T. K.; Becher, J. Chem. Soc. ReV.
1994, 23, 41-51. (c) Bryce, M. R. J. Mater. Chem. 1995, 5, 1481-1496.
(d) Garin, J. AdV. Heterocycl. Chem. 1995, 62, 249-304. (e) Schukat, G.;
Fangha¨nel, E. Sulfur Rep. 1996, 18, 1-294. (f) Bryce, M. R. J. Mater.
Chem. 2000, 10, 589-598. (g) Nielsen, M. B.; Lomholdt, C.; Becher, J.
Chem. Soc. ReV. 2000, 29, 153-164.
(5) (a) Philp, D.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. F.; Williams,
D. J. J. Chem. Soc., Chem. Commun. 1991, 1584-1586. (b) Asakawa, M.;
Dehaen, W.; L′abbe´, G.; Menzer, S.; Nouwen, J.; Raymo, F. M.; Stoddart
J. F.; Williams, D. J. J. Org. Chem. 1996, 51, 9591-9595.
10.1021/ol006387s CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/27/2000

comprising two different stoppers have been unknown
hitherto, most likely because of the lack of an appropriate
TTF building block. Now that such a building block in the
shape of the pyrrolo[3,4-d]tetrathiafulvalene ring system7 is
available, we have self-assembled an asymmetric [2]rotaxane
with a dumbbell component incorporating this asymmetric
TTF unit situated in the rod section between a hydrophilic
and hydrophobic stopper and encircled by CBPQT4+. Here,
we report this accomplishment.
Scheme 3. Synthesis of the Hydrophilic Stopper
The asymmetric TTF building block 3 was synthesized
as outlined in Scheme 1. Cross-coupling of (1,3)-dithiolo-
Scheme 1. Synthesis of the Asymmetric TTF Building Block
[4,5-c]pyrrole-2-one7 (1) with 2 equiv of 4-(2-cyanoethyl-
thio)-5-methylthio-1,3-dithiole-2-thione8 (2) in neat P(OEt)3
gave 3 (64%) in gram quantities after column chromatog-
raphy.9
The hydrophobic stopper 6 was obtained (Scheme 2) in
84% yield by a modification of the procedure already
by Percec and co-workers.13 Methyl 4-hydroxybenzoate (9)
was alkylated with toluene-4-sulfonic acid 2-(2-methoxy-
ethoxy)ethyl ester14 (10) in MeCN in the presence of K2CO3.
The ester 11 was reduced with LiAlH4 in THF, and the
resulting benzyl alcohol was chlorinated with SOCl2 in dry
CH2Cl2, affording 12 in 60% overall yield for the three steps.
Etherification of methyl 3,4,5-trihydroxybenzoate (13) with
the benzyl chloride 12 was carried out in DMF in the
Scheme 2. Synthesis of the Hydrophobic Stopper
(6) For examples of catenanes, rotaxanes and pseudorotaxanes containing
TTF, see: (a) Ashton, P. R.; Bissell, R. A.; Spencer, N.; Stoddart, J. F.;
Tolley, M. S. Synlett 1992, 923-926. (b) Jørgensen, T.; Becher, J.;
Chambron, J.-C.; Sauvage, J.-P. Tetrahedron Lett. 1994, 35, 4339-4342.
(c) Li, Z.-T.; Stein, P. C.; Svenstrup, N.; Lund, K. H.; Becher, J. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2524-2528. (d) Li, Z.-T.; Becher, J. Chem.
Commun. 1996, 639-640. (e) Li, Z.-T.; Stein, P. C.; Becher, J.; Jensen,
D.; Mørk, P.; Svenstrup, N. Chem. Eur. J. 1996, 2, 624-633. (f) Asakawa,
M.; Ashton, P. R.; Balzani, V.; Credi, A.; Mattersteig, G.; Matthews, O.
A.; Montalti, N.; Spencer, N.; Stoddart, J. F.; Venturi, M. Chem. Eur. J.
1997, 3, 1992-1996. (f) Li, Z.-T.; Becher, J. Synlett 1997, 557-560. (g)
Nielsen, M. B.; Li, Z.-T.; Becher. J. J. Mater. Chem. 1997, 7, 1175-1187.
(h) Asakawa, M.; Ashton, P. R.; Balzani, V.; Credi, A.; Hamers, C.;
Mattersteig, G.; Montalti, N.; Shipway, A. N.; Spencer, N.; Stoddart, J. F.;
Tolley, M. S.; Venturi, M.; White, A. J. P.; Williams, D. J. Angew. Chem.,
Int. Ed. 1998, 37, 333-337. (i) Nielsen, M. B.; Thorup, N.; Becher, J. J.
Chem. Soc., Perkin Trans. 1 1998, 1305-1308. (j) Credi, A.; Montalti,
M.; Balzani, V.; Langford, S. J.; Raymo, F. M.; Stoddart, J. F. New J. Chem.
1998, 22, 1061-1065. (k) Asakawa, M.; Ashton, P. R.; Balzani, V.; Boyd,
S. E.; Credi, A.; Mattersteig, G.; Menzer, S.; Montalti, M.; Raymo, F. M.;
Ruffilli, C.; Stoddart, J. F.; Venturi, M.; Williams, D. J. Eur. J. Org. Chem.
1999, 985-994. (l) Lau, J.; Nielsen, M. B.; Thorup, N.; Cava, M. P.; Becher,
J. Eur. J. Org. Chem. 1999, 3335-3341. (m) Balzani, V.; Credi, A.;
Mattersteig, G.; Matthews, O. A.; Raymo, F. M.; Stoddart, J. F.; Venturi,
M.; White, A. J. P.; Williams, D. J. J. Org. Chem. 2000, 65, 1924-1936.
(n) Damgaard, D.; Nielsen, M. B.; Lau, J.; Jensen, K, B.; Zubarev, R.;
Levillian, E.; Becher, J. J. Mater. Chem. 2000, 10, 2249-2258.
reported in the literature.10 4-[Bis(4-tert-butylphenyl)(4-
ethylphenyl)methyl]phenol11 (4) was alkylated with [2-(2-
chloroethoxy)ethoxy]tetrahydropyran12 (5) in n-butanol, fol-
lowed by removal of the THP protecting group with aqueous
HCl. Tosylation (53%) of 6, and subsequent treatment of 7
with NaI, gave (99%) the hydrophobic stopper 8.
The synthesis of the hydrophilic stopper which is outlined
in Scheme 3 follows a synthetic methodology first described
3548
Org. Lett., Vol. 2, No. 23, 2000

Scheme 4. Synthesis of the Dumbbell 21 and Self-Assembly of the [2]Rotaxane 24‚4PF6
presence of K2CO3, giving 14 in 58% yield. Compound 15
Finally, 17 was chlorinated, using conditions similar to those
used for the preparation of 15, in 94% yield.
was prepared in 62% overall yield from (i) reduction of 14
with LiAlH4, followed by (ii) chlorination of the benzyl
alcohol by SOCl2 in dry CH2Cl2 with 2,6-di-tert-butyl-4-
methylpyridine (DTBMP) as proton trap. Compound 17 was
obtained in 61% yield by the reaction of 4-hydroxybenzyl
alcohol (16) with 15 in DMF in the presence of K2CO3.
The synthesis of the dumbbell 21 was achieved as outlined
in Scheme 4. A solution of 3 in THF was treated with 1
equiv of CsOH‚H2O. This procedure generated the TTF-
monothiolate, which was subsequently alkylated with 1 equiv
of the hydrophobic stopper 8, affording the TTF derivative
19 in 88% yield. Removal of the tosyl protecting group was
carried out in near quantitative yield by refluxing 19 in a
1:1 mixture of THF-MeOH in the presence of an excess of
NaOMe. An 80% yield of the dumbbell15 21 was obtained
following N-alkylation of the pyrrole unit in 20 with the
hydrophilic stopper 18 in DMF containing NaH. Finally, the
[2]rotaxane16 24‚4PF6 was self-assembled in 8% yield17 using
the dumbbell 21 as the template for the formation of
interlocked cyclobis(paraquat-p-phenylene) tetracation from
the dicationic precursor18 22‚2PF6 and 1,4-bis(bromomethyl)-
benzene (23) (Scheme 4).
(7) Recently, two of us developed an efficient synthesis of the pyrrolo-
[3,4-d]tetrathiafulvalene ring system using a simple and nonclassical pyrrole
synthesis. See: (a) Jeppesen, J. O.; Takimiya, K.; Jensen, F.; Becher, J.
Org. Lett. 1999, 1, 1291-1294. (b) Jeppesen, J. O.; Takimiya, K.; Jensen,
F.; Brimert K.; Nielsen, K.; Thorup, N.; Becher J. J. Org. Chem. 2000, 65,
5794-5805.
(8) Simonsen, K. B.; Svenstrup, N.; Lau, J.; Simonsen, O.; Mørk, P.;
Kristensen, G. J.; Becher, J. Synthesis 1996, 407-418.
(9) Although the synthesis of 3 has been described before in the literature
(see ref 7b), it was prepared by a different route and only on a very small
scale.
(10) Ashton, P. R.; Ballardini, R.; Balzani, V.; Belohradsky, M.; Gandolfi,
M. T.; Philp, D.; Prodi, L.; Raymo, F. M.; Reddington, M. V.; Spencer,
N.; Stoddart, J. F.; Venturi, M.; Williams, D. J.J. Am. Chem. Soc. 1996,
118, 4931-4951.
(11) Although we have previously used (see ref 10) compound 4 as its
potassium salt in alkylations, we now prefer to isolate it directly as the
phenol after an acid-catalyzed reaction between bis(4-tert-butylphenyl)-4-
ethylphenylmethanol and phenol, followed by silica gel column chroma-
tography and recrystallization from hexane.
(12) Gibson, H. W.; Lee, S.-H.; Engen, P. T.; Lecavalier, P.; Sze, J.;
Shen, Y. X.; Bheda, M. J. Org. Chem. 1993, 58, 3748-3756.
(13) Percec, V.; Cho. W.-D.; Mosier, P. E.; Ungar, G.; Yeardley, D. J.
P. J. Am. Chem. Soc. 1998, 120, 11061-11070 and references therein.
(14) Satoru, I.; Hideo, M.; Kiyoshi, T. J. Chem. Soc., Perkin Trans. 1
1997, 1357-1360.
1
(15) Data for dumbbell 21: H NMR (400 MHz, CD3COCD3, 298 K)
δ 1.17 (t, J ) 7.6 Hz, 3H), 1.26 (s, 18H), 2.39 (s, 3H), 2.57 (q, J ) 7.6 Hz,
2H), 3.02 (t, J ) 6.3 Hz, 2H), 3.26 (s, 9H), 3.44-3.49 (m, 6H), 3.59-3.64
(m, 6H), 3.72 (t, J ) 6.3 Hz, 2H), 3.76-3.81 (m, 8H), 4.05-4.13 (m, 8H),
4.88 (s, 2H), 4.97 (s, 2H), 5.00 (s, 2H), 5.01 (s, 4H), 6.70 and 6.72 (AB q,
J ) 2.1 Hz, 2H), 6.79 (d, J ) 8.7 Hz, 4H), 6.84 (s, 2H), 6.89-6.94 (m,
6H), 7.03-7.16 (m, 12H), 7.25-7.33 (m, 6H), 7.37 (d, J ) 8.8 Hz, 4H);
MS(FAB) m/z 1736 (M+). Anal. Calcd for C98H113NO15S6 (1737.3): C,
67.75; H, 6.56; N, 0.81. Found: C, 67.61; H, 6.46; N, 0.80.
Org. Lett., Vol. 2, No. 23, 2000
3549

The fast atom bombardment mass spectrum (FAB-MS)
of the [2]rotaxane 24‚4PF6 is illustrated in Figure 1 and
In summary, we have devised and completed the synthesis
of a dumbbell-shaped component employing the recently
developed7 asymmetric monopyrrolo-TTF unit in its rod
section to direct the attachment in a stepwise manner of first
a hydrophobic and then second a hydrophilic stopper. This
dumbbell was used subsequently as a template in self-
assembling a [2]rotaxane. While these new amphiphilic
redox-active components are being assessed for their abilities
to self-organize into monolayerssas a prelude to their
introduction into devices3swith single-molecule-thick elec-
trochemical junctions, we are extending the synthetic meth-
odology disclosed in this Letter to the construction of more
elaborate amphiphilic [2]rotaxanes containing additional
recognition sites in their rod components so that ring
components can be induced to shuttle mechanically between
two states, thereby functioning as an array of electronic
switches.
Figure 1. FAB-MS spectrum of the [2]rotaxane 24‚4PF6.
Acknowledgment. We thank DARPA and Hewlett-
Packard for generous financial support and the University
of Odense for a Ph.D. Scholarship to J.O.J.
shows peaks corresponding to the [M - PF6]+, [M - 2PF6]+,
and [M - 3PF6]+ as well as for [M - 2PF6]2+, [M - 3PF6]2+,
1
and [M - 4PF6]2+ ions. A comparison of the H NMR
spectra (CD3COCD3, 298 K) of the dumbbell 21 and the
[2]rotaxane 24‚4PF6 revealed (Table 1) significant changes
Supporting Information Available: Experimental pro-
cedures for 21 and 24‚4PF6. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL006387S
1
Table 1. Selected H NMR Spectroscopic Data (δ and ∆δ
Values in ppm) for the Dumbbell 21 and the [2]Rotaxane
24‚4PF6 in CD3COCD3 at 298 K
(16) Data for [2]rotaxane 24•4PF6: 1H NMR (400 MHz, CD3COCD3,
298 K) δ 1.19 (t, J ) 7.6 Hz, 3H), 1.28 (s, 18H), 2.60 (q, J ) 7.6 Hz, 2H),
2.64 (s, 3H), 3.28 (s, 6H), 3.29 (s, 3H), 3.29 (t, J ) 6.4 Hz, 2H), 3.47-
3.50 (m, 6H), 3.61-3.65 (m, 6H), 3.77-3.81 (m, 6H), 3.95 (t, J ) 6.4 Hz,
2H), 3.98-4.01 (m, 2H), 4.08-4.14 (m, 6H), 4.23-4.25 (m, 2H), 4.69 (s,
2H), 4.80 (s, 4H), 4.97 (s, 2H), 5.18 (s, 2H), 5.98-6.08 (m, 8H), 6.43 and
6.45 (AB q, J ) 2.1 Hz, 2H), 6.78 (s, 2H), 6.83-6.85 (m, 4H), 6.94 (d, J
) 8.7 Hz, 4H), 7.07-7.12 (m, 10H), 7.18 (d, J ) 8.6 Hz, 2H), 7.26-7.31
(m, 10H), 7.38 (bs, 4H), 7.69 (d, J ) 8.7 Hz, 2H), 7.94-8.06 (m, 8H),
8.45 (bs, 4H), 9.16 (bs, 4H), 9.48 (bs, 4H); MS(FAB) m/z 2691 (M - PF6)+,
2546 (M - 2PF6)+, 2401 (M - 3PF6)+, 1736 (dumbbell)+, 1273 (M -
2PF6)2+, 1200.5 (M - 3PF6)2+, 1128 (M - 4PF6)2+; UV-vis (Me2CO)
compd
21
24‚4PF6
SCH3 SCH2CH2O SCH2CH2O NCH2Ar Pyr-H
2.39
2.64
3.02
3.29
3.72
3.95
4.88
5.18
6.71
6.44
-0.27
+0.25
+0.27
+0.23
+0.30
in the chemical shift of the signals associated with the protons
located close to the TTF unit. Furthermore, the UV-vis
spectrum of the [2]rotaxane 24‚4PF6 recorded in Me2CO
shows a broad charge transfer (CT) absorption band centered
on 810 nm, which is characteristic of structures containing
a TTF unit located “inside” the tetracationic cyclophane19
CBPQT4+. These observations clearly suggest, that, in
solution at least, the tetracationic cyclophane encircles the
TTF unit in the [2]rotaxane 24‚4PF6.
λ
max 810 nm, (ꢀ 1400 L mol-1 cm-1). Anal. Calcd for C134H145F24N5O15P4S6‚
2H2O (2837.6): C, 56.00; H, 5.23; N, 2.44. Found: C, 56.07; H, 5.06; N,
2.28.
(17) Unreacted dumbbell can be recovered and reused.
(18) Anelli, P.-L.; Ashton, P. R.; Ballardini, R.; Balzani, V.; Delgado,
M.; Gandolfi, M. T.; Goodnow, T. T.; Kaifer, A. E.; Philp, D.; Pietrasz-
kiewicz, M.; Prodi, L.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.;
Stoddart, J. F.; Vicent, C.; Williams, D. J. J. Am. Chem. Soc. 1992, 114,
193-218.
(19) Devonport, W.; Blower, M. A.; Bruce, M. R.; Goldenberg, L. M.
J. Org. Chem. 1997, 62, 885-887.
3550
Org. Lett., Vol. 2, No. 23, 2000