Synthesis of [2]rotaxanes by the copper-mediated threading reactions of aryl iodides with alkynes

Article abstract of DOI:10.1021/ol400992p

The catalytic activity of the macrocyclic phenanthroline-copper(I) complex is utilized for the Sonogashira-type reaction to synthesize [2]rotaxanes. Thus, [2]rotaxanes were prepared by reactions between terminal alkynes and aryl iodides in the presence of

Full text of DOI:10.1021/ol400992p

ORGANIC
LETTERS
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Vol. XX, No. XX
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Synthesis of [2]Rotaxanes by the
Copper-Mediated Threading Reactions
of Aryl Iodides with Alkynes
Kenta Ugajin,† Eiko Takahashi,† Ryu Yamasaki,† Yuichiro Mutoh,† Takeshi Kasama,‡
and Shinichi Saito*,†
Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka,
Shinjuku, Tokyo, 162-8601, Japan, and Research Center for Medical and Dental
Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku,
Tokyo, 113-8510, Japan
ssaito@rs.kagu.tus.ac.jp
Received April 10, 2013
ABSTRACT
The catalytic activity of the macrocyclic phenanthrolineꢀcopper(I) complex is utilized for the Sonogashira-type reaction to synthesize
[2]rotaxanes. Thus, [2]rotaxanes were prepared by reactions between terminal alkynes and aryl iodides in the presence of the macrocyclic
copper complex. Bulky substituents were introduced to the substrates to stabilize the rotaxane. The bond-forming reaction proceeded selectively
inside the macrocyclic complex so that the rotaxanes could be synthesized.
Rotaxane is a well-known example of mechanically inter-
locked compounds, which consists of a cyclic component and
a linear component with bulky substituents located at both
ends. With sufficiently large substituents, rotaxanes would
exist as a stable molecule and two components would not
dissociate easily. Various approaches have been reported for
the synthesis of rotaxanes, and the template method has been
widely used.1
and catenanes.3 Thus, the catalytic activity of the macro-
cyclic metal complex has been utilized for the efficient
synthesis of interlocked compounds. Since the bond forma-
tion reaction proceeded selectively inside the macrocyclic
ring, the interlocked compounds were isolated in good to
high yields. This approach has been recently applied to the
synthesis of highly functionalized molecules.4
Recently, a new approach has been reported for the
synthesis of interlocked compounds such as rotaxanes2
€
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ꢀ
† Tokyo University of Science.
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J. D.; Goldup, S. M.; Hanni, K. D.; Lee, A.-L.; Leigh, D. A. Angew.
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‡ Tokyo Medical and Dental University.
Chem., Int. Ed. 2007, 46, 5709–5713. (d) Crowley, J. D.; Hanni, K. D.;
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r
10.1021/ol400992p
XXXX American Chemical Society

Table 1. Reaction of the Alkyne with Aryl Iodides in the Presence
of Macrocyclic PhenanthrolineꢀCopper(I) Catalyst (1)
We were interested in the catalytic activity of macro-
cyclic phenanthrolineꢀcopper(I) complexes and reported
the synthesis of rotaxanes by the copper-mediated oxida-
tive homocoupling reaction of alkynes.2b,k The study in-
dicated that the copper complexes could be used as the
catalysts for other coupling reactions, and rotaxanes with
(3) (a) Sato, Y.; Yamasaki, R.; Saito, S. Angew. Chem., Int. Ed. 2009,
48, 504–507. (b) Goldup, S. M.; Leigh, D. A.; Long, T.; McGonigal,
P. R.; Symes, M. D.; Wu, J. J. Am. Chem. Soc. 2009, 131, 15924–15929.
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Thompson, A. L.; Anderson, H. L. Chem. Sci. 2011, 2, 1897–1901. (c)
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Figure 1. 1H NMR spectra of 9a, 10a, and 12 (500 MHz, CDCl3).
various axle components could be prepared. In this paper
we report the synthesis of [2]rotaxane by a Sonogashira-
type cross-coupling reaction5 mediated by a macrocyclic
phenanthrolineꢀcopper(I) complex.
We examined the catalytic activity of a macrocyclic
phenanthrolineꢀcopper(I) complex 12b for the cross-coupling
reactions between 4-(octyloxy)phenylacetylene 2 and iodo-
benzoates 3, and the results are summarized in Table 1. The
reaction between 2 and methyl 2-iodobenzoate 3a proceeded
in the presence of 1 and K2CO3, and the product was isolated
(5) For examples of the Cu-catalyzed Sonogashira-type reactions,
see: (a) Bates, C. G.; Saejueng, P.; Venkataraman, D. Org. Lett. 2004, 6,
1441–1444. (b) Monnier, F.; Turtaut, F.; Duroure, L.; Taillefer, M. Org.
Lett. 2008, 10, 3203–3206.
B
Org. Lett., Vol. XX, No. XX, XXXX

Table 2. Synthesis of [2]Rotaxanes by the Sonogashira-Type Cross-Coupling Reaction
entry
aryl iodide
time (h)
producta (yield)
1
2
3
7a
7b
7c
24
54
33
9a (52%)b
9b (24%)b
9c (24%)b
10a (44%)c
10b (37%)c
10c (33%)c
11 (7%)b
11 (16%)b
11 (14%)b
a Compounds 9a,n10a are ortho-isomers; 9b, 10b are meta-isomers; and 9c, 10c are para-isomers. b The yields were based on 1. c The yields were based on 8.
reaction of 2 with the para-isomer 3c proceeded, the yield of
the product was disappointing (entry 3). These results imply
that the coordination of the carbonyl group to the Cu atom of
Scheme 1. Synthesis of Iodobenzoates with a Bulky Substituent
the aryl copper species, which would be formed by the
reaction of aryl iodide with the copper complex, would play
an important role (vide infra).
To apply this reaction for the synthesis of rotaxanes,
substrates with bulky substituents were required. We chose
the tris(40-ethylbiphenyl)methyl group as the bulky sub-
stituent and introduced this substituent to iodobenzoates.
The synthesis of the precursors 7aꢀc was carried out by the
condensation of the iodobenzoic acid with an alcohol 62k
under standard conditions (Scheme 1). The reactions
proceeded smoothly, providing the corresponding esters
in good to high yields.
The synthesis of [2]rotaxanes was studied by the reaction
of 1, 7aꢀc, and 8.2b The results are summarized in Table 2.
in good yield (entry 1). When ethyl 3-iodobenzoate 3b was
used, the yield of the product decreased (entry 2). Though the
A mixture of 1 (1.0 equiv), 7 (2.2 equiv), 8 (2.0 equiv),
and K2CO3 (4.0 equiv) was heated at 120 °C under Ar.
Org. Lett., Vol. XX, No. XX, XXXX
C

The mixture was cooled to rt and treated with aqueous
ammonia6 to remove the copper ion. When the ortho-isomer
(7a) was used as the substrate, [2]rotaxane 9a was isolated
in 52% yield (based on 1). The cross-coupling product 10a
and [2]rotaxane 11,2k which was formed by the oxidative
dimerization of alkyne 8, were also isolated (entry 1).
When 3-iodobenzoate 7b was used, [2]rotaxane 9b was
obtained in 24% yield (entry 2). The reaction of 4-iodo-
benzoate 7c also gave the [2]rotaxane 9c in 24% yield
(entry 3). It is noteworthy that the yields of 9aꢀc do not
correlate well with the yields of the model reactions
reported in Table 1: the yield of 9a was better, as expected,
though the yields of 9b,c were higher than we anticipated
by the results shown in Table 1.7
Scheme 2. A Plausible Mechanism of the Cross-Coupling
Reaction
The structures of the rotaxanes were elucidated by
spectroscopic methods. The 1H NMR spectra of 9a, 10a,
and 128 are shown in Figure 1. Inthe NMR spectrum of 9a,
the upfield shifts of the protons of the phenanthroline
moiety (Ha ꢀ He) were observed. The methylene protons
adjacent tothe oxygenatom (H3, H4, Hf, Hg) also shifted to
higher fields. These shifts are frequently observed for other
rotaxanes we synthesized in previous studies. The splitting
of the protons of the resorcinol moiety (Hh, Hi) of 9a is
another strong indicator for the formation of the rotaxane.
The structures of the rotaxanes were further confirmed by
mass spectroscopy (see Supporting Information).
A plausible mechanism5 of the cross-coupling reaction is
described in Scheme 2. In the presence of a base, the reaction
of Cu(I) complex with the alkyne would proceed to yield a
Cu(I) acetylide intermediate. Next, a Cu(III) complex was
generated by the oxidative addition of aryl iodide to the
acetylide. This process might be accelarated by the presence
of a carbonyl group located at the ortho position (i.e., in the
reaction of 7a) since the coordination of the carbonyl group
to the copper atom would stabilize the Cu(III) complex.
Finally, the formation of a new CꢀC bond would proceed by
reductive elimination. When this process proceeded inside
the ring, the rotaxane would be isolated as the final product.
In summary, we succeeded in the synthesis of [2]rotaxanes
by the Sonogashira-type cross-coupling reaction between
a terminal alkyne and aryl iodides. The macrocyclic
phenanthrolineꢀcopper(I) complex 1 was observed to be
suitable for this transformation, and a series of isomeric
rotaxanes were prepared. The study provided a new and
unique method for the synthesis of rotaxanes.
Acknowledgment. We thank the UBE foundation for
financial support.
(6) Jackson, D.; Megiatto, Jr.; Schuster, D. I. Org. Lett. 2011, 13,
1808–1811.
(7) Trace amounts of the starting materials were also recovered. The
1,3-diyne product, which would be formed by the oxidative dimerization
of 8, was not isolated probably because the amount of the product was
very small.
Supporting Information Available. Detailed experimen-
tal procedures and spectral data for 4ꢀ10. This material is
available free of charge via the Internet at http://pubs.acs.org.
(8) Saito, S.; Nakazono, K.; Takahashi, E. J. Org. Chem. 2006, 71,
7477–7480.
The authors declare no competing financial interest.
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