Synthesis of [2]catenanes by oxidative intramolecular diyne coupling mediated by macrocyclic copper(I) complexes

Article abstract of DOI:10.1002/anie.200804864

(Chemical Equation Presented) Right said thread: Oxidative intramolecular coupling reactions of α,ω-diynes in the presence of macrocyclic phenanthroline Cu^I complexes allows the synthesis of [2]catenanes in up to 64% yield (see scheme). The bon

Full text of DOI:10.1002/anie.200804864

Communications
DOI: 10.1002/anie.200804864
Catenanes
Synthesis of [2]Catenanes by Oxidative Intramolecular Diyne Coupling
Mediated by Macrocyclic Copper(I) Complexes**
Yuta Sato, Ryu Yamasaki, and Shinichi Saito*
Mechanically interlocked compounds, such as catenanes and
rotaxanes, are challenging synthetic targets which are
expected to be important components of molecular
machines[1] and switches.[2] Although catenanes were initially
synthesized in low yields by the statistical approach[3] and the
“directed” approach,[4] efficient synthesis of more complex
molecules was achieved only when the components were
preorganized by various interactions. Thus, a large number of
catenanes were synthesized by the assembly of two or more
components by template strategies. For example, Sauvage and
co-workers achieved a high yield catenane synthesis by
preorganization of the constituent parts as ligands around a
CuI template.[5] The groups of Stoddart[6a,b] and Fujita[6c]
applied p–p donor–acceptor interactions in very efficient
syntheses of interlocked molecules. Hydrogen bonding was
also utilized in the process of self-assembly by the groups of
Vꢀgtle[7a,b] and Leigh[7c] (Scheme 1). However, these methods
tions of macrocyclic Cu complexes. In Leighꢁs system, a
substoichiometric amount of the Cu species could be
employed to isolate the rotaxanes in good yields.[11]
A
common notable feature of these reactions is that efficient
threading was achieved by the reactions catalyzed (or
mediated) by the macrocyclic complexes.
The successful synthesis of [2]rotaxanes by a threading
reaction (Glaser coupling)[9] led us to study the synthesis of
another important class of interlocked molecules, [2]cate-
nanes. Herein, we report the first synthesis of [2]catenanes by
the oxidative intramolecular homocoupling of a,w-diynes
with macrocyclic CuI–phenanthroline complexes (Scheme 2).
Scheme 2. Synthesis of [2]catenanes by the oxidative homocoupling of
terminal diynes.
We synthesized a series of a,w-diynes[12] with bisphenol A
as a linker and examined the relationship between the
structure of the diyne and the yield of the [2]catenanes in
the presence of 1A.[9] The results are summarized in
Table 1.[13]
Scheme 1. Synthesis of catenanes by template method.
involve mutual interactions between the components and
therefore the structures of the products are under many
restrictions. The development of a new synthetic method
would increase the availability of interlocked compounds and
contribute to the progress of the study of molecular topology.
Recently, Leigh and co-workers reported a new method
for the synthesis of rotaxanes,[8] utilizing catalytic reactions of
macrocyclic Pd complexes to carry out bond-forming reac-
tions inside the macrocycle. Only a catalytic amount of metal
was required since the metal was transferred between the
macrocyclic ligands. Our group,[9] as well as that of Leigh,[10]
also reported the synthesis of rotaxanes by threading reac-
Table 1: Synthesis of [2]catenanes by intramolecular oxidative coupling
of 2a–d.
Entry
1
Diyne
Alkyne
Product
Yield [%]
16
[*] Y. Sato, Dr. R. Yamasaki, Dr. S. Saito
Department of Chemistry, Faculty of Science
Tokyo University of Science
2a
3aA
Kagurazaka, Shinjuku, Tokyo 162-8601 (Japan)
E-mail: ssaito@rs.kagu.tus.ac.jp
Homepage: http://www.rs.kagu.tus.ac.jp/sslab/
2
3
4
2b
2c
2d
3bA
3cA
3dA
18
13
[**] We thank the Yamada Science Foundation and the UBE Foundation
for the financial support of this work.
trace
Supporting Information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200804864.
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Chemie
Most precursors reacted to give the desired [2]catenanes
by the intramolecular coupling reaction. The a,w-diynes with
2-alkoxyphenylacetylene moiety were good substrates for the
synthesis of [2]catenanes, and the products were isolated in
16–18% yields (Table 1, entries 1 and 2). However, the yields
of [2]catenanes decreased when other diynes were used as the
substrates (Table 1, entries 3 and 4). Compound 2d turned
out to be an especially inferior substrate for the reaction
(Table 1, entry 4). We assume that the yields of the products
were influenced significantly by the conformation of the
diynes. When the diynes were terminated with 2-alkoxyphe-
nylacetylene moiety, the conformation of the substrate was
more suitable for the formation of [2]catenanes, and the
product was isolated in better yields.
that yields of the [2]catenanes might be influenced by the
bond angle of the linkers. Thus, the two diyne units were
preorganized in a favorable position for the intramolecular
cyclization of 2h (dibenzofuran linker) to proceed smoothly.
Conversely, the angles in which other linkers preorganize the
reacting diyne groups might be too small or too large.
Since 4,6-dihydroxydibenzofuran turned out to be the best
linker, we synthesized a,w-diynes with different spacers using
4,6-dihydroxydibenzofuran as a linker and they were utilized
for the synthesis of catenanes, but diynes with shorter or
longer spacers both resulted in decreased catenane yields
(Table 2, entries 4 and 5). a,w-Diynes terminated with differ-
ent alkyne groups were also inferior substrates for the
synthesis of [2]catenanes, affording very low yields (Table 2,
entries 6 and 7). The desired intramolecular cyclization of the
diynes competes with intermolecular oligomerization reac-
tions, suggesting that diynes 2h–k would not adopt a
favorable conformation for the intramolecular coupling.
Finally, we examined the relationship between the size of
the metal-coordinated macrocycle and the yield of the
[2]catenanes, by carrying out the reaction using phenanthro-
line-based macrocycles with linker moieties of different
lengths. The results are summarized in Table 3.
Next, we synthesized a,w-diynes[12] with different linkers
and examined the relationship between the structure of the
linker and the yield of [2]catenanes. The results are summar-
ized in Table 2.
Table 2: Synthesis of [2]catenanes by the oxidative intramolecular
homocoupling of 2e–k.
Table 3: Relationship between the ring size of the phenanthroline-based
macrocycle and the yield of [2]catenanes.
Entry Diyne Linker (X)
Alkyne
Product Yield [%]
1
2
2e
2 f
3eA
3 fA
13
12
Entry
Cu complex
Conditions[a]
Product
Yield [%]
1
2
3
4
5
6
7
8
1A (n=6)
1B (n=8)
1C (n=10)
1D (n=12)
1A
1B
1C
1D
A
A
A
A
B
B
B
B
3gA
3gB
3gC
3gD
3gA
3gB
3gC
3gD
27
26
9
3
4
5
2g
2h
2i
3gA
3hA
3iA
27
16
10
9
64
58
27
34
[a] Conditions A: diyne (1.0 equiv), K2CO3 (3.0 equiv), I2 (1.0 equiv),
48 h. Conditions B: diyne (5.0 equiv), K2CO3 (15.0 equiv), I2 (5.0 equiv),
6 days.
6
7
2j
3jA
8
2k
3kA
trace
When CuI complexes of smaller macrocycles (n = 6, n = 8)
were treated with diyne 2g, the resultant [2]catenanes were
isolated in 26–27% yields (Table 3, entries 1 and 2). The
yields of the catenanes decreased when CuI complexes of
larger macrocycles (n = 10, n = 12) were used as the substrates
(Table 3, entries 3 and 4). Owing to the increased flexibility of
the larger complexes the favorable conformation for catenane
formation is not retained. Nonetheless, it is possible to
improve the yields by exploiting the “catalytic” nature of the
reaction. Thus, by using 5 equivalents of 2g as the substrate,
a,w-Diynes linked with resorcinol, 4,5-dihydroxyxan-
thene, or 4,6-dihydroxydibenzofuran reacted with 1A to
give the corresponding [2]catenanes. Resorcinol (diyne 2e,
Table 2, entry 1) and 4,5-dihydroxyxanthene (diyne 2 f,
Table 2, entry 2) were inferior linkers compared to that in
2a, but 4,6-dihydroxydibenzofuran was a more successful
linker moiety for the cyclization, and [2]catenane 3gA was
isolated in 27% yield (Table 2, entry 3). This result indicated
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Communications
revealed that a new class of [2]catenanes is
accessible by utilizing bond-forming reac-
tions catalyzed by the macrocyclic com-
plexes. Further studies directed toward the
synthesis of complex interlocked structures
are ongoing.
Experimental Section
Synthesis of [2]catenane 3gA: I2 (5.1 mg,
0.020 mmol) was added with stirring to a mixture
of macrocyclic phenanthroline–copper(I) complex
1A[9] (16.6 mg, 0.020 mmol), diyne 3g (13.2 mg,
0.020 mmol) and K2CO3 (8.4 mg, 0.060 mmol) in
dry xylene (1.0 mL). The mixture was heated to
1308C and stirred at this temperature for 48 h.
After the mixture had cooled to room temper-
ature, CH3CN (2 mL), CH2Cl2 (2 mL), KCN
(10 mg) and H2O (1 mL) were added and the
resulting mixture was stirred at room temperature
for 3 h. The organic layer was separated, and the
aqueous layer was extracted with CH2Cl2 (2 ꢂ
5 mL). The combined organic layer was washed
with water, dried over Na2SO4 and concentrated
under reduced pressure. The residue was purified
by column chromatography on silica gel with
hexane/CH2Cl2 (1:1 v/v) as eluent, and then fur-
ther purified by gel permeation chromatography
using CHCl3 to yield [2]catenane 3gA (6.9 mg,
27%) as a yellow amorphous solid. 1H NMR
(600 MHz, C6D6): d = 8.91–8.90 (d, J = 7.8 Hz,
4H), 8.14–8.12 (d, J = 8.4 Hz, 2H), 7.99–7.98 (d,
J = 8.4 Hz, 2H), 7.71–7.69 (d, J = 7.8 Hz, 2H), 7.62
(s, 2H), 7.53–7.51 (dd, J = 7.8, 1.2 Hz, 2H), 7.27–
7.23 (m, 6H), 7.20–7.18 (m, 2H), 6.92–6.89 (m, 2H), 6.77–6.76 (d, J =
8.4 Hz, 2H), 6.74–6.72 (dd, J = 8.4, 2.4 Hz, 2H), 6.61–6.59 (t, J =
7.2 Hz, 2H), 6.37–6.36 (d, J = 8.4 Hz, 2H), 3.98–3.96 (t, J = 6.6 Hz,
4H), 3.85–3.83 (t, J = 6.0 Hz, 4H), 3.66–3.63 (t, J = 7.8 Hz, 4H), 3.53–
3.50 (t, J = 7.2 Hz, 4H), 1.65–1.52 (m, 12H), 1.42–1.40 (m, 4H), 1.23–
1.18 (m, 4H), 1.16–1.10 (m, 8H), 0.82 (m, 4H), 0.70 ppm (m, 8H);
13C NMR (150 MHz, C6D6): d = 161.5, 161.3, 161.0, 156.2, 147.0, 146.1,
137.0, 135.1, 132.3, 130.6, 130.4, 129.7, 129.6, 128.4, 128.3,127.5, 126.6,
Scheme 3. Proposed mechanism for the formation of [2]catenanes.
we isolated catenane 3gA in 64% yield. Similarly, [2]cate-
nanes 3gB, 3gC, 3gD were isolated in 58, 27 and 34% yields,
respectively (Table 3, entries 6, 7 and 8). The improved yields
of the catenanes in the presence of a large amount of the
diynes can be reasonably explained by supposing that the Cu
complex was regenerated when the catenane forming reaction
failed (Scheme 3). Thus, the reaction of the diyne with the Cu-
phenanthroline complex might proceed to give various
intermediates, such as dialkynyl complex 4,[14] spiro complex
5, and pseudocatenane complex 6. The [2]catenane would be
isolated from 6 on reductive elimination. If, however, other
complexes were formed, the Cu complex would be regen-
erated by the reductive elimination of the diyne and
reoxidation by iodine. This “catalytic cycle” would continue
until the diyne was consumed or the Cu complex was
completely converted into the [2]catenane.[15,16]
1
The partial H NMR spectra of 1A, 3gA, and a cyclic
diyne are shown in Figure 1. As a result of the interaction
between the components, the spectrum of 3gA was different
from those of the components. For example, the signals
corresponding to the phenanthroline moiety of 1A were at
d = 7.70 and 7.32 ppm, whereas those of 3gA were at d = 8.06
and 7.62 ppm, respectively. Compared to the signals of 1A,
many signals were shifted downfield in the spectrum of the
catenane (3gA), in contrast to the tendency for [2]rotaxanes
with similar structural features.[9]
In summary, we developed a novel approach for the
synthesis of [2]catenanes by the reactions mediated by the
macrocyclic Cu-phenanthroline complexes. The study
Figure 1. 1H NMR spectra (600 MHz, C6D6) of a) macrocyclic phenan-
throline (1A), b) [2]catenane (3gA), and c) a cyclic diyne.
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Angewandte
Chemie
125.9, 124.1, 120.3, 119.0, 115.3, 113.0, 112.0, 111.9, 110.8, 107.9, 101.5,
80.2, 79.1, 69.5, 68.7, 68.1, 67.7, 30.2, 29.93, 29.91, 29.7, 29.5, 29.2, 28.9,
26.8, 26.1, 26.0, 25.8 ppm; IR (KBr): n˜ = 2927, 2854, 1594, 1488, 1277,
1249, 1175, 1015, 838, 750 cmÀ1; HR-MS calcd for C86H88N2O9:
1315.6382; found: 1315.6383.
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[8] J. Bernꢄ, J. D. Crowley, S. M. Goldup, K. D. Hꢅnni, A. L. Lee,
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[9] S. Saito, E. Takahashi, K. Nakazono, Org. Lett. 2006, 8, 5133 –
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Received: October 6, 2008
Published online: December 9, 2008
[10] V. Aucagne, K. D. Hꢅnni, D. A. Leigh, P. J. Lusby, D. B. Walker,
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Keywords: catenanes · C–C coupling · copper · macrocycles ·
NMR spectroscopy
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