Triphenylphosphonium-stoppered [2]rotaxanes

Article abstract of DOI:10.1021/ol990049d

(equation presented) The template-directed syntheses of two [2]rotaxanes, one carrying one and the other two triphenylphosphonium stoppers, have been achieved using a threading-followed-by-stoppering approach. Either one or two benzylic bromide functions-

Full text of DOI:10.1021/ol990049d

ORGANIC
LETTERS
1999
Vol. 1, No. 1
129-132
Triphenylphosphonium-Stoppered
[2]Rotaxanes
Stuart J. Rowan, Stuart J. Cantrill, and J. Fraser Stoddart*
Department of Chemistry and Biochemistry, UniVersity of California, Los Angeles,
405 Hilgard AVenue, Los Angeles, California 90095-1569
stoddart@chem.ucla.edu
Received April 15, 1999
ABSTRACT
The template-directed syntheses of two [2]rotaxanes, one carrying one and the other two triphenylphosphonium stoppers, have been achieved
using a threading-followed-by-stoppering approach. Either one or two benzylic bromide functionsslocated at the para-positions of
dibenzylammonium-based ions, which become encircled by dibenzo[24]crown-8 macrocycles during the initial thermodynamically controlled
phases that mark the recognition eventssserve as sites for nucleophilic attack by triphenylphosphine during the subsequent kinetic stages
that lead to the formation of the two [2]rotaxanes.
Rotaxanes1 are molecules that are created when one or more
beadlike species become trapped mechanicallysusually with
some supramolecular assistance2son a dumbbell-shaped
entity. Recently, a number of protocols based on self-
assembly3 have been developed4 for the syntheses of these
mechanically interlocked compounds. The most successful
protocol has probably been the threading-followed-by-
stoppering one.4a It involves (Scheme 1) the passage of a
rodlike component through the beadlike one at the behest
of stabilizing noncovalent bonding interactions. The
[2]pseudorotaxane that is generated is then transformed into
a [2]rotaxane by a reaction that plants bulky stoppers at the
ends of the encircled rod. In recent times, we have developed
a variety of approaches that lead to the formation of rotaxanes
(1) (a) Amabilino, D. A.; Stoddart, J. F. Chem. ReV. 1995, 95, 2725-
2828. (b) Ja¨ger, R.; Vo¨gtle, F. Angew. Chem., Int. Ed. Engl. 1997, 36, 930-
944. (c) Nepogodiev, S. A.; Stoddart, J. F. Chem. ReV. 1998, 98, 1959-
1976. (d) Chambron, J.-C.; Sauvage, J.-P. Chem. Eur. J. 1998, 4, 1362-
1366.
(2) Fyfe, M. C. T.; Stoddart, J. F. Acc. Chem. Res. 1997, 30, 393-401.
(3) Philp, D.; Stoddart, J. F. Angew. Chem., Int. Ed. Engl. 1996, 35,
1154-1196.
(4) (a) Ashton, P. R.; Glink, P. T.; Stoddart, J. F.; Tasker, P. A.; White,
A. J. P.; Williams, D. J. Chem. Eur. J. 1996, 2, 729-736. (b) Solladie´, N.;
Chambron, J.-C.; Dietrich-Buchecker, C. O.; Sauvage, J.-P. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 906-909. (c) 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. (d) Lane, A. S.; Leigh, D. A.;
Murphy, A. J. Am. Chem. Soc. 1997, 119, 11092-11093. (e) Lyon, A. P.;
Macartney, D. H. Inorg. Chem. 1997, 36, 729-736. (f) Anderson, S.; Aplin,
R. T.; Claridge, T. D. W.; Goodson, T., III; Maciel, A. C.; Rumbles, G.;
Ryan, J. F.; Anderson, H. L. J. Chem. Soc., Perkin Trans. 1 1998, 2383-
2398. (g) Rowan, A. E.; Aarts, P. P. M.; Koutstaal, K. W. M. Chem.
Commun. 1998, 611-612. (h) Kolchinski, A. G.; Alcock, N. W.; Roesner,
R. A.; Busch, D. H. Chem. Commun. 1998, 1437-1438. (i) Loeb, S. J.;
Wisner, J. A. Chem. Commun. 1998, 2757-2758. (j) Hu¨bner, G. M.; Gla¨ser,
J.; Seel, C.; Vo¨gtle, F. Angew. Chem., Int. Ed. 1999, 38, 383-386.
(5) Ashton, P. R.; Ballardini, R.; Balzani, V.; Baxter, I.; Credi, A.; Fyfe,
M. C. T.; Gandolfi, M. T.; Go´mez-Lo´pez, M.; Mart´ınez-D´ıaz, M.-V.;
Piersanti, A.; Spencer, N.; Stoddart, J. F.; Venturi, M.; White, A. J. P.;
Williams, D. J. J. Am. Chem. Soc. 1998, 120, 11932-11942.
(6) Cantrill. S. J.; Fulton, D. A.; Fyfe, M. C. T.; Stoddart, J. F.; White,
A. J. P.; Williams, D. J. Tetrahedron Lett. 1999, 40, 3669-3672.
(7) Cantrill, S. J.; Matthews, O. A.; Stoddart, J. F., unpublished results.
(8) Cantrill, S. J.; Rowan, S. J.; Stoddart, J. F., manuscript in preparation.
(9) (a) Ashton, P. R.; Chrystal, E. J. T.; Glink, P. T.; Menzer, S.; Schiavo,
C.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.; White, A. J. P.; Williams,
D. J. Chem. Eur. J. 1996, 2, 709-728. (b) Ashton, P. R.; Fyfe, M. C. T.;
Hickingbottom, S. K.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. J.
Chem. Soc., Perkin Trans. 2 1998, 2117-2128. (c) Ashton, P. R.; Baxter,
I.; Cantrill, S. J.; Fyfe, M. C. T.; Glink, P. T.; Stoddart, J. F.; White, A. J.
P.; Williams, D. J. Angew. Chem., Int. Ed. 1998, 37, 1294-1297.
10.1021/ol990049d CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/24/1999

the possibility of generating phosphorus ylides and studying
their subsequent reactions with aldehydes and ketones
becomes a reality.
Scheme 1
The synthesis of the [2]rotaxane 4-H‚3PF6 is outlined in
Scheme 2. Bis(4-methoxycarbonylbenzyl)amine4a 1 was
Scheme 2
using this particular protocol. Thus, triazole,4a pyridinium,5
urea,6 carbamate7 and imine formation8 all yield [2]rotaxanes
from [2]pseudorotaxanes formed9 between appropriately
functionalized dibenzylammonium (DBA+) cations that
spontaneously penetrate the cavity of dibenzo[24]crown-8
(DB24C8). Here, we report an important new stoppering
procedure for the synthesis of [2]rotaxanes that relies upon
this particular form of supramolecular assistance, prior to
the formation of triphenylphosphonium stoppers, when
benzylic p-bromomethyl groups on the DBA+ derivatives
become the sites for nucleophilic attack by triphenylphos-
phine. Clearly, if this synthetic goal can be achieved, then
(10) For leading references on this method, see: Adrian, J. C.; Wilcox,
C. S. J. Am. Chem. Soc. 1991, 113, 678-680.
(11) Sample Procedure for the Preparation of 4-H‚3PF6 and 5-H‚
3PF6. Triphenylphosphine (297 mg, 1.1 × 10-3 mol) was added to a solution
of the bis(bromomethyl) derivative 3-H‚PF6 (200 mg, 3.8 × 10-4 mol) and
DB24C8 (508 mg, 6.6 × 10-4 mol) in MeCN/CH2Cl2 (3.8 mL, 1:1). The
reaction was then left to stir at room temperature overnight. The resulting
white precipitate was filtered off and washed with CH2Cl2. The organic
layer was then removed and the resulting solid redissolved in CH2Cl2 and
any insoluble material removed by filtration and added to the white solid
obtained from the previous filtration after anion exchange. This white solid
was shown to be the free dumbbell-shaped compound 5-H‚3PF6 (179 mg,
33%). Et2O was then added to the CH2Cl2 solution, and the resulting white
precipitate was filtered and washed with more Et2O. This white solid was
then dissolved in MeCN, and saturated aqueous NH4PF6 was added until
no further precipitation was observed. This precipitate was filtered, washed
with water, and then dried under vacuum. Further purification was carried
out by flash chromatography with CH2Cl2/MeOH (100: 0, 99:1, ..., 95:5),
resulting in a white solid of 4-H‚3PF6 (340 mg, 55%). Rotaxane 4-H‚
reduced (LiAlH4/THF), yielding the diol 2 (90%), which was
converted (69%) into the protonated dibromide 3-H‚PF6 with
aqueous HBr (48%), followed by counterion exchange
(NH4PF6/H2O). It is important for subsequent rotaxane
formation that 3-H‚PF6 binds DB24C8 in a pseudorotaxane
fashion. On account of the fact that the free species and the
1
pseudorotaxane are in slow exchange on the H NMR time
scale, the single-point method10 was used to establish Ka
values of 352 and 1778 M-1 for the 1:1 complex formed in
CD3CN and CD2Cl2/CD3CN (1:1), respectively.
The synthesis11 of the [2]rotaxane 4-H‚3PF6 was conse-
quently carried out (Scheme 2) in the mixed solvent by
simply adding PPh3 to a 100 mM solution of 3-H‚PF6 and
DB24C8. After counterion exchange, 4-H‚3PF6 was isolated
in 55% yield, along with 33% of the dumbbell-shaped
compound 5-H‚3PF6. Although 3-H‚PF6 is insoluble in
CH2Cl2, when DB24C8 is added to a suspension, the
dibromide dissolves slowly, presumably as a result of
pseudorotaxane formation. This observation led to the [2]-
rotaxane 4-H‚3PF6 being synthesized in 70% yield in CH2-
Cl2 solution.
1
3PF6: H NMR (400 MHz, CD3CN) δ ) 7.83-7.87 (m, 6H), 7.61-7.66
(m, 12H), 7.45-7.50 (m, 12H), 7.13 (d, J ) 8 Hz, 4H), 6.80 (m, 4H),
6.66-6.70 (m, 8H), 4.60 (m, 4H), 4.42 (d, J ) 14.8 Hz, 4H), 3.91-3.93
(m, 8H), 3.65-3.66 (m, 8H), 3.51 (s, 8H); 13C NMR (100 MHz, CD3CN)
δ ) 147.1, 135.4 (JPC ) 3 Hz), 134.1 (JPC ) 9.7 Hz), 132.6 (JPC ) 3.8
Hz), 131.2 (JPC ) 5.4 Hz), 130.2 (JPC ) 12.5 Hz), 129.8, 128.0 (JPC ) 8.3
Hz), 121.3, 117.4 (JPC ) 85.7 Hz), 112.2, 70.6, 70.1, 67.6, 51.9, 29.4 (JPC
) 48.5 Hz); 31P NMR (162 MHz, CD3CN) δ ) 22.8 (PhP+), -143.6 (septet,
J ) 708 Hz, PF6-); MS (FAB) 1486 (M - PF6)+, 1341 (M - 2PF6)+,
1
1196 (M - 3PF6)+. Dumbbell-Shaped Compound 5-H‚3PF6: H NMR
(400 MHz, CD3CN) δ ) 7.84-7.89 (m, 6H), 7.65-7.69 (m, 12H), 7.50-
7.56 (m, 12H), 7.29 (d, J ) 8 Hz, 4H), 6.99 (dd, J ) 2.4, 8 Hz, 4H), 4.65
(d, J ) 14.9 Hz, 4H), 4.12 (brs, 4H); 13C NMR (100 MHz, CD3CN) δ )
135.4 (JPC ) 3 Hz), 134.1 (JPC ) 9.8 Hz), 131.5 (JPC ) 5.4 Hz), 131.1
(JPC ) 3.9), 130.9, 130.2 (JPC ) 12.5 Hz), 129.0 (JPC ) 8.4 Hz), 117.3
(JPC ) 85.8 Hz), 50.7, 29.4 (JPC ) 48.5 Hz); 31P NMR (162 MHz, CD3-
CN) δ ) 23.7 (PhP+), -143.6 (septet, J ) 708 Hz, PF6-); MS (FAB)
1038 (M - PF6)+, 893 (M - 2PF6)+.
During the synthesis of the rotaxane, a white precipitate
of the salt 5-H‚3X (X ) Br, PF6) is formed, thus reducing
130
Org. Lett., Vol. 1, No. 1, 1999

the yield of the [2]rotaxane, anticipated on the basis of the
high stability of the [2]pseudorotaxane precursor in the
reaction solvent. As soon as Ph3P displaces Br- ions from
3-H‚PF6, counterion exchange can take place, resulting in
the formation of a tight ion pair between the Br- and 5-H+
ions. The consequence of this competition will be to hinder
formation of 4-H+ and encourage the production of 5-H+.
The synthesis of the [2]rotaxane 8-H‚2PF6 was carried out
(Scheme 3) in a manner similar to that described above for
by adding Ph3P to a 100 mM solution of 7-H‚PF6 and
DB24C8 in CH2Cl2. Unlike 5-H‚3PF6, the corresponding
dumbbell-shaped compound 9-H‚2PF6 did not precipitate out
of solution, and therefore was never isolated, from this
reaction mixture. However, by simple addition of triphen-
ylphosphine to 7-H‚PF6 in MeCN, without any DB24C8
present, 9-H‚2PF6 could be obtained easily.
1
Figure 1 shows the partial H NMR spectra recorded in
CD3CN of both the [2]rotaxane 8-H‚2PF6 and the corre-
sponding free dumbbell-shaped compound 9-H‚2PF6. As
expected, the biggest chemical shift differences are the
downfield ones of 0.42 and 0.62 ppm for the two sets of
Scheme 3
+
CH2NH2 protons on going from 9-H‚2PF6 to 8-H‚2PF6.
There is also a significant upfield shift of 0.25 ppm for
+
the CH2PPh3 protons. The signal for these methylene
protons in the [2]rotaxane is particularly sensitive to the
environment: δ values of 4.30, 4.64, and 5.03 have been
noted in CDCl3, CD3CN, and CD3SOCD3, respectively.
Smaller changes in chemical shifts are also observed for the
protons on both the para-substituted aromatic rings.
13C NMR spectra of all four phosphorus-containing
compounds show strong P-C couplings, ranging from 85
Hz for the phosphorus coupling to the ipso carbons on the
phenyl rings to 3 Hz for the coupling of the phosphorus over
five bonds through to the “internal” quaternary carbon atoms
on the benzylic rings. Assignments of the resonances in the
13C NMR spectra were based on HMQC experiments, as well
as on comparisons with known compounds.13 The Ph3P+
signals in the 31P NMR spectra14 of both dumbbell-shaped
compounds, and their related rotaxanes, reveal shifts of
around 1 ppm when rotaxane formation occurs.
In conclusion, we have demonstrated a novel approach to
the synthesis2 of rotaxanes that relies upon the supramo-
lecular assistance inherent in the recognition4 between a
secondary dialkylammonium center and the cavity of a crown
ether. The new [2]rotaxanes 4-H‚3PF6 and 8-H‚2PF6 have
the potential to undergo further covalent modifications on
4-H‚3PF6. 4-tert-Butylbenzyl-4′-hydroxymethylbenzylamine
(6) was prepared in 74% overall yield from (i) condensation
of 4-tert-butylbenzaldehyde with 4-methoxycarbonylbenzy-
lammonium chloride in the presence of anhydrous MgSO4
followed by (ii) reduction of the resulting imine with NaBH4
in MeOH and (iii) reduction of the ester function to a
hydroxymethyl group with LiAlH4 in THF. Conversion of
6 to the bromomethyl salt 7-H‚PF6 required a four-step
procedure. Reaction of the alcohol 6 with aqueous 48% HBr
resulted in the formation of 4-tert-butylbenzyl-4′-hydroxym-
ethylbenzylammonium bromide (6-H‚Br) as a white precipi-
tate. Following counterion exchange (NH4PF6/H2O) and
treatment of this hexafluorophosphate salt with methanolic
48% HBr, 4-tert-butylbenzyl-4′-bromomethylbenzylammo-
nium hexafluorophosphate (7-H‚PF6) was obtained after yet
another counterion exchange with aqueous ammonium
hexafluorophosphate. The complexation of 7-H‚PF6 by
DB24C8 was reflected in a Ka value of 400 M-1 in CD3CN,
i.e., slightly more than the comparable binding constant for
the dibromide 3-H‚PF6. The template-directed synthesis of
the [2]rotaxane 8-H‚2PF612 was accomplished in 80% yield
(12) Data for Rotaxane 8-H‚2PF6: 1H NMR (400 MHz, CD3CN) δ )
7.83-7.87 (m, 3H), 7.61-7.66 (m, 6H), 7.43-7.49 (m, 6H,), 7.23 (s, 4H),
7.15 (d, J ) 8 Hz, 2H), 6.82 (m, 4H), 6.73 (m, 4H), 6.64 (dd, J ) 2.4, 8
Hz, 2H), 4.72 (m, 2H), 4.49 (m, 2H), 4.39 (d, J ) 14.8 Hz, 2H), 3.94-
4.00 (m, 8H), 3.59-3.75 (m, 8H), 3.45-3.55 (s, 8H), 1.22 (s, 9H); 13C
NMR (100 MHz, CD3CN) δ ) 152.3, 147.3, 135.3 (JPC ) 3 Hz), 134.1
(JPC ) 9.7 Hz), 133.0 (JPC ) 3.8 Hz), 131.0 (JPC ) 5.3 Hz), 130.2 (JPC
)
12.5 Hz), 129.8, 129.2, 128.7, 127.6 (JPC ) 8.3 Hz), 125.6, 121.3, 117.1
(JPC ) 85.7 Hz), 112.3, 70.6, 70.1, 67.8, 52.2, 51.7, 34.2, 30.5, 29.4 (JPC
) 48.2 Hz); 31P NMR (162 MHz, CD3CN) δ ) 22.6 (PhP+), -143.6 (septet,
J ) 708 Hz, PF6-); MS (FAB) 1122 (M - PF6)+, 977 (M - 2PF6)+. Data
for Dumbbell-Shaped Compound 9-H‚2PF6: 1H NMR (400 MHz, CD3-
CN) δ ) 7.86-7.89 (m, 3H), 7.66-7.71 (m, 6H), 7.52-7.57 (m, 6H), 7.47
(AB, J ) 8 Hz), 7.42 (AB, J ) 8 Hz, 2H), 7.33 (d, J ) 8 Hz, 2H), 6.97 (m,
2H), 4.64 (d, J ) 14.8 Hz, 2H), 4.10 (m, 2H), 4.07 (m, 2H), 1.31 (s, 9H);
13C NMR (100 MHz, CD3CN) δ ) 152.4, 135.3 (JPC ) 3 Hz), 134.1 (JPC
) 9.7 Hz), 131.9 (JPC ) 3.8 Hz), 131.3 (JPC ) 5.3 Hz), 130.8, 130.2 (JPC
) 12.5 Hz), 129.9, 128.4 (JPC ) 8.3 Hz), 128.0, 125.9, 117.2 (JPC ) 85.7
Hz), 50.2, 49.7, 34.3, 30.5, 29.4 (JPC ) 48.8 Hz); 31P NMR (162 MHz,
CD3CN) δ ) 23.6 (PhP+), -143.6 (septet, J ) 708 Hz, PF6-); MS (FAB)
528 (M - 2PF6)+.
(13) (a) Albright, T. A.; Freeman, W. J.; Schweizer, E. E. J. Am. Chem.
Soc. 1975, 97, 2942-2950. (b) Verstuyft, A. W.; Redfield, D. A.; Cary, L.
W.; Nelson, J. H. Inorg. Chem. 1977, 16, 2776-2786.
(14) All 31P NMR spectra were measured in CD3CN at room temperature
and referenced to external PPh3 in CDCl3 (δ ) -5.31). See: Davies, J. A.;
Dutremez, S.; Pinkerton, A. A. Inorg. Chem. 1991, 30, 2380-2387.
Org. Lett., Vol. 1, No. 1, 1999
131

Figure 1. Partial 1H NMR (400 MHz, CD3CN) spectra of (a) the [2]rotaxane 8-H‚2PF6 and of (b) the free dumbbell compound 9-H‚2PF6
account of the obvious reactivities associated with the
benzylic centers adjacent to their triphenylphosphonium
stoppers. We are now in a position to study the reactivity of
the ylide centers generated, in these new rotaxanes, upon
the addition of base. In principle, we now have ways of
converting rotaxanes into other, more intricate, interlocked
molecular compounds. Work is currently in progress to
unleash this potential.
Acknowledgment. We thank UCLA for generous finan-
cial support.
Supporting Information Available: 1H and 13C NMR
spectra for compounds 4-H‚3PF6, 5-H‚3PF6, 8-H‚2PF6, and
9-H‚2PF6. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL990049D
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Org. Lett., Vol. 1, No. 1, 1999