Rotaxanes via Michael addition

Article abstract of DOI:10.1021/ol990350u

(equation presented) The application of a template effect to the classical Michael addition of heteronucleophiles to various Michael acceptor systems leads in good yields to a new trapping synthesis of [2]rotaxanes with conjugated functional groups in the

Full text of DOI:10.1021/ol990350u

ORGANIC
LETTERS
Rotaxanes via Michael Addition†
Carin Reuter and Fritz Vo1gtle*
2000
Vol. 2, No. 5
593-595
Kekule´-Institut fu¨r Organische Chemie und Biochemie der UniVersita¨t Bonn,
Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany
Voegtle@uni-bonn.de
Received December 13, 1999
ABSTRACT
The application of a template effect to the classical Michael addition of heteronucleophiles to various Michael acceptor systems leads in good
yields to a new trapping synthesis of [2]rotaxanes with conjugated functional groups in their axles.
Rotaxanes and catenanes are molecules that consist of
noncovalently interlocked building blocks. They are of
current interest as model systems for molecular recognition
and as precursors for molecular devices.1 Efficient rotaxane
syntheses make use of template assistance based on a
molecular recognition process of the reacting components.2
Template effects support the preorganization of the reactants
by hydrogen bonding, hydrophobic and donor-acceptor
interactions, or metal coordination.3 A recent improvement
in rotaxane syntheses was the development of an anion
template process which led to generally high yields of [2]-
and [3]rotaxanes with ether, ester, and other axles via
nucleophilic substitution reactions.4 This encouraged us to
extend this template effect to other essential reactions in
organic chemistry. Here we report on the successful applica-
tion of anion template synthesis to the Michael addition of
heteronucleophiles to various Michael acceptors. This allows
creation of rotaxanes with conjugated functional groups in
their axles.5
First we synthesized semiaxles based on acrylic (2) and
propiolic acid motifs (3) (Figure 1). These Michael acceptors
† Dedicated to Prof. Dr. Gu¨nther Wulff on the occasion of his 65th
birthday.
(1) (a) Rotaxanes are molecules that consist of one or more wheels and
penetrating axles; these are mechanically bound together and sterically
prevented from dethreading by bulky stopper groups at both ends of the
axles. Harrison, I. T.; Harrison, S. J. Am. Chem. Soc. 1967, 89, 5723-
5724. (b) For reviews of molecular engineering, see: Balzani, V.; Go´mez-
Lo´pez, M.; Stoddart, J. F. Acc. Chem. Res. 1998, 31, 405-414. (c) Bissell,
R. A.; Co´rdova, E.; Stoddart, J. F.; Tolley, M. S.; Venturi, M.; White, A.
J. P.; Williams, D. J. Chem. Eur. J. 1997, 3, 152-170.
(2) For reviews, see: (a) Schill, G. Catenanes, Rotaxanes, and Knots;
Academic Press: New York, 1971. (b) Amabilino, D. B.; Stoddart, J. F.
Chem. ReV. 1995, 95, 2725-2825. (c) Gibson, H. W. In Large Ring
Molecules; Semlyen, J. A., Ed.; Wiley: Chichester, 1996; pp 191-262.
(d) Ja¨ger, R.; Vo¨gtle, F. Angew. Chem., Int. Ed. Engl. 1997, 36, 930-944.
(e) Sauvage, J. P., Dietrich-Buchecker, C. O., Eds. Molecular Catenanes,
Rotaxanes and Knots; VCH-Wiley: Weinheim, 1999.
(3) (a) Anderson, S.; Anderson, H. L.; Sanders, J. K. M. Acc. Chem.
Res. 1993, 26, 469-475. (b) Hoss, R.; Vo¨gtle, F. Angew. Chem., Int. Ed.
Engl. 1995, 33, 375-384. (c) Diederich, F.; Stang, P. J. Templated Organic
Synthesis; Wiley-VCH: Weinheim, 1999. (d) Gerbeleu, N. V.; Arion, V.
B.; Burgess, J.; Template Synthesis of Macrocyclic Compounds; VCH-
Wiley: Weinheim, 1999. (e) Hubin, T. J.; Kolchinski, A. G.; Vance, A.
L.; Busch, D. H. In AdVances in Supramolecular Chemistry, Vol. 5; JAI
Press Inc.: 1999.
Figure 1.
were then to be reacted with tritylphenolate (1a) or tritylthio-
phenolate (1b) anions in the presence of the tetralactam wheel
4 under basic conditions as shown in Scheme 1.6 For the
10.1021/ol990350u CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/15/2000

In analogy to the base-catalyzed hetero-Michael addition
described in the literature,9 the addition of the oxygen
nucleophile 1a to propiolate 3a resulted mainly in (E)-7a
while with the sulfur nucleophile 1b (Z)-adducts were
preferably formed (Table 1). The isomers could be easily
Scheme 1. Synthesis of [2]Rotaxanes via Michael Addition
1
distinguished by the H NMR coupling constants of the
olefinic protons. Integration of the signals of the free axle
7a revealed an (E/Z) ratio of 63:37 (3J(E) ) 12.1-12.2 Hz,
3J(Z) ) 8.5-8.6 Hz) whereas 7b was isolated with an (E/Z)
3
ratio of 29:71 (3J(E) ) 15.1-15.2 Hz, J(Z) ) 9.8-10.2 Hz
71-78%). 7c was formed exclusively as the (Z) adduct in
the reaction of 1b with 3b.10 In all cases the ratios of the
corresponding rotaxanes were very similar to those of the
free axles. This means that despite the steric hindrance of
the supramolecular nucleophiles [1‚4], there seems to be no
significant control of the (E/Z) selectivity by the wheel 4.
This is particularly remarkable in the case of the (Z)-only
addition of [1b‚4] to 3a.
Using dichloromethane instead of chloroform as the
solvent, we isolated the corresponding acetal[2]rotaxanes 8
bearing a methylene unit in their axles as byproducts with
yields of 81% (8a) and 23% (8b) (Scheme 2).11
formation of the crucial supramolecular nucleophiles7 [1‚
4], nonpolar solvents such as dichloromethane or chloroform,
high concentrations, and room temperature are favorable.
According to NMR experiments, molecular recognition
through hydrogen bonds is almost quantitative under these
conditions.4a
Scheme 2. Synthesis of the Acetal[2]rotaxanes 8
For comparison we first performed the addition of the
stoppers to the semiaxles in the absence of the wheel 4.
Neither of the stoppers 1 yielded the corresponding free axle
with the acrylic acid derivatives 2. However, the phenolate
1a formed 7a with the more electrophilic propiolate 3a in
41% yield. Phenolate 1a did not react with the less reactive
propiolamide 3b. p-Thiophenolate 1b, which is the stronger
nucleophile, was added to both propiolic acid derivatives to
give 24% and 53% yields, respectively (Table 1). The same
The attempted catalytic hydrogenation of 6a with Pd/C
did not lead to the desired [2]rotaxane with an aliphatic axle
5a. Instead the axle was cleaved into p-tritylphenol 1a and
Table 1. (E/Z) Isomer Ratio in Percent of the Free Axles 7
and the [2]Rotaxanes 6
(4) (a) Hu¨bner, G. M.; Gla¨ser, J.; Seel, C.; Vo¨gtle, F. Angew. Chem.,
Int. Ed. 1999, 38, 383-386. (b) Reuter, C.; Wienand, W.; Hu¨bner, G. M.;
Seel, C.; Vo¨gtle, F. Chem. Eur. J. 1999, 5, 2692-2697. (c) Schmieder, R.;
Hu¨bner, G. M.; Seel, C.; Vo¨gtle, F. Angew. Chem., Int. Ed. 1999, 38, 3528-
3530. (d) Hu¨bner, G. M.; Reuter, C.; Seel, C.; Vo¨gtle, F. Synthesis 2000,
103-108.
Michael adduct
yield [%]
(E/Z) ratio [%]
7a
7b
7c
6a
6b
6c
41
24
53
13
19
35
63:37
29:71
0:100
66:34
22:78
0:100
(5) For the end-capping of pseudorotaxanes under radical conditions,
see: Takata, T.; Kawasaki, H.; Asai, S.; Furusho, Y.; Kihara, N. Chem.
Lett. 1999, 223-224.
(6) Because of the low acidity of common CH acids, it was not possible
to use carbon nucleophiles; the strong bases needed for their deprotonation
also led to a deprotonation of the carbonamide groups of wheel 4.
(7) For complexes such as [1‚4] the term supramolecular nucleophiles
was coined, see ref 4a. The molecular recognition of the anionic stoppers
results from hydrogen bonding with one of the two isophthalamide units
of the wheel 4, whose hydrogens are pointing toward the cycle’s center, as
shown by X-ray structure analyses: (a) Fischer, C.; Nieger, M.; Mogck,
O.; Bo¨hmer, V.; Ungaro, R.; Vo¨gtle, F. Eur. J. Org. Chem. 1998, 155-
161. (b) See also: Adams, H.; Carver, F. J.; Hunter, C. A.; Osborne, N. J.
A. Chem. Commun. 1998, 2449-2450. (c) Clegg, W.; Gimenez-Saiz, C.;
Leigh, D. A.; Murphy, A.; Slawin, A. M. Z.; Teat, S. J. J. Am. Chem. Soc.
1999, 121, 4124-4129.
chemical selectivities were observed in the presence of the
wheel 4 leading to the rotaxanes 6, but with somewhat
reduced yields (13-35%). Again, no reaction was observed
with the acrylic acid derivatives 2 nor did 1a react with 3b.
The higher yield of rotaxane 6c as compared to those of
6a and 6b might in part result from hydrogen bonding
between the amide group of the semiaxle 3b and the amide
groups of the wheel 4 in addition to the host/guest interac-
tions of the wheel 4 and the thiolate 1b.8
(8) For the binding of amides by hosts such as 4, see ref 7b and Seel,
C.; Parham, A. H.; Safarowsky, O.; Hu¨bner, G. M.; Vo¨gtle, F. J. Org. Chem.
1999, 64, 7236-7242.
594
Org. Lett., Vol. 2, No. 5, 2000

p-tritylphenyl propionate under the more vigorous reaction
conditions (60 °C, 3.5 bar) required. Also, as already
observed with other rotaxane systems, the double bond of
the rotaxane reacts more slowly as compared to the double
bond in the corresponding free axle.12
for the trapping syntheses of [2]rotaxanes and to improve
and extend the scope of a new synthetic approach to
supramolecular systems. In addition to the previously
reported substitution reactions of benzyl bromides or car-
bonyl chlorides with anionic heteronucleophiles, this new
template synthesis opens new possibilities for rotaxane
syntheses and provides the basis for further developments
of hitherto unknown template-controlled formations of ro-
taxanes, catenanes, and knots.
In conclusion, it is possible to use hetero-Michael addition
(9) For the addition of phenolates, see: (a) Winterfeld, E.; Preuss, H.
Chem. Ber. 1966, 99, 450-458. (b) Winterfeld, E.; Krohn, W.; Preuss, H.
Chem. Ber. 1966, 99, 2572-2578. (c) Ciganek, E. J. Org. Chem. 1980, 45,
1497-1505. (d) Bates; D. J.; Rosenblum, M.; Samuels, S. B. J. Organomet.
Chem. 1981, 209, C55. (e) Vo-Quang, Y.; Marais, D.; Vo-Quang, L.; Le
Goffic, F. Tetrahedron Lett. 1983, 24, 5209-5210. (f) Ferguson, G.; Fisher,
K. J.; Ibrahim, B. E.; Ishang, C. Y.; Iskader, G. M.; Katritzki, A. R.; Parvez,
M. J. Chem. Soc., Chem. Commun. 1983, 1216-1217. For the addition of
thiophenolates, see: (g) Truce, W. E.; Goldhamer, D. L. J. Am. Chem. Soc.
1959, 81, 5798-5800. (h) Truce, W. E.; Goldhamer, D. L.; Kruse, R. B. J.
Am. Chem. Soc. 1959, 81, 4931-4934. (i) Pfaendler, H. R.; Gosteli, J.;
Woodward, R. B. J. Am. Chem. Soc. 1979, 101, 6306-6310. (j) Wadsworth,
D. A.; Detty, M. R. J. Org. Chem. 1980, 45, 4611-4615. (k) Corbett, D.
F. J. Chem. Soc., Chem. Commun. 1981, 803-804. (l) Detty, M. R.; Murray,
B. J. J. Am. Chem. Soc. 1983, 105, 883-890. (m) Detty, M. R.; Murray,
B. J.; Smith, D. L.; Zumbulyadis, N. J. Am. Chem. Soc. 1983, 105, 875-
882.
Acknowledgment. This work was supported by the
Deutsche Forschungsgemeinschaft. Special thanks are due
to Dr. C. Schalley and Dr. C. Seel for advice.
Supporting Information Available: Experimental pro-
cedures and full characterization for compounds 2, 3, and
5-8. This material is available free of charge via the Internet
at http://pubs.acs.org.
OL990350U
(10) This is similar to the (Z)-addition of thioisocyanate to N-methyl-
propiolamide: Crow, W. D.; Leonard, N. J. J. Org. Chem. 1965, 30, 2660-
2665.
(12) Parham, A. H.; Windisch, B.; Vo¨gtle, F. Eur. J. Org. Chem. 1999,
1233-1238.
(11) 8a, see ref 4b; 8b, see Supporting Information.
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