Selective enclathration of linear alkanols by a self-assembled coordination cage. Application to the catalytic wacker oxidation of ω-alkenols

Article abstract of DOI:10.1246/cl.2005.1392

Linear alkanols were efficiently enclathrated by a self-assembled cage (1) to give a 1:2 host-guest complex as confirmed by NMR and crystallographic analyses. Cage 1 also enclathrated an ω-alkenol, 8-nonen-1-ol, and, upon heating, Wacker-type oxidation took place with a catalytic amount of 1 to give 9-hydroxynonan-2-one in a good yield. Copyright

Full text of DOI:10.1246/cl.2005.1392

1392
Chemistry Letters Vol.34, No.10 (2005)
Selective Enclathration of Linear Alkanols by a Self-assembled Coordination Cage.
Application to the Catalytic Wacker Oxidation of !-Alkenols
Michito Yoshizawa, Naoko Sato, and Makoto Fujitaꢀ
Department of Applied Chemistry, School of Engineering, The University of Tokyo and CREST,
Japan Science and Technology Agency (JST), 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656
(Received July 27, 2005; CL-050977)
Linear alkanols were efficiently enclathrated by a self-as-
sembled cage (1) to give a 1:2 host–guest complex as confirmed
by NMR and crystallographic analyses. Cage 1 also enclathrated
an !-alkenol, 8-nonen-1-ol, and, upon heating, Wacker-type
oxidation took place with a catalytic amount of 1 to give 9-
hydroxynonan-2-one in a good yield.
Because of their flexible conformation, long alkyl chain
compounds are poorly recognized by synthetic receptors.1,2
Therefore, subsequent chemical transformation within the recep-
tors has been hardly explored.3 In nature, lipoxygenases4 demon-
strate both the selective recognition and the chemical reaction
(oxidation) of long alkyl chain compounds within their binding
pockets. To mimic the nature’s system, we have examined the
binding and the subsequent reaction of long alkyl chain com-
pounds within self-assembled coordination cage 1, which we
have developed as a molecular flask during the last decade.5
We have found that cage 1 binds linear alkanols and !-alkenols
quite efficiently and, in case of the !-alkenols, subsequent
Wacker-type oxidation is smoothly catalyzed by cage 1
(Scheme 1).
While binding a variety of relatively rigid organic com-
pounds,6 cage 1 hardly recognizes simple linear alkanes mainly
because of a large entropy cost for binding these substrates. By
simply attaching a hydroxyl group, we found the efficient bind-
ing of long alkyl chain compounds by cage 1. When an excess
amount (ca. 20 equiv.) of 1-nonanol (2) was suspended in an
aqueous solution of 1 (5 mM) at 80 ꢁC for 1 h, the quantitative
formation of 1 ꢂ ð2Þ2 complex was observed by 1H NMR
(Figure 1). The proton signals of 2 were significantly shifted
upfield (ꢀꢀ ¼ ca. ꢃ0:8ꢄꢃ2:4 ppm). Protons Ha{i were fully as-
signed by H–H COSY NMR. From the integral ratio, the forma-
tion of a 1:2 host–guest complex was indicated. Similarly, longer
alkanols (C10–C13) as well as decanoic acid (3) were also en-
Figure 1. 1H NMR spectrum (500 MHz, rt, D2O, TMS as exter-
nal standard) of 1 ꢂ ð2Þ2 complex.
clathrated within 1 giving rise to 1:2 complexes.7 Since linear
alkanes such as n-nonane were hardly enclathrated by cage 1,
the hydroxyl group is essential for binding linear alkyl chain
compounds.
The formation of 1 ꢂ ð2Þ2 complex was clearly displayed by
crystallographic analysis. Pale yellow crystals suitable for X-ray
crystallographic analysis grew from an aqueous solution of 1 ꢂ
ð2Þ2 by the very slow evaporation of water for two months.8 The
crystal structure revealed the orthogonal packing of two mole-
cules of 2 in the cavity of cage 1 (Figure 2). The terminal hy-
droxyl group was situated at the opening of 1 being away from
ꢁ
a Pd(II) center of 1 by ca. 5.1 A. This distance indicated no inter-
action between the hydroxyl group and the cage. Probably, the
hydroxyl group stabilized the 1 ꢂ ð2Þ2 complex through hydro-
gen bonding with outside water molecules at the opening.8 This
Figure 2. Crystal structure of 1 ꢂ ð2Þ2 complex. Two mole-
cules of 2 are orthogonally packed in the cavity of 1.
Scheme 1.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.10 (2005)
1393
agreed with the fact that the structural isomers, 3- and 4-nona-
nols, were poorly enclathrated by 1.
to the geometry fixation of 4 in the cavity. In analogy to the X-
ray geometry of 2, the terminal CH2=CH– group is expected to
be very close to the Pd(II) center of the cage to facilitate the re-
action. Under the same conditions, 9-decen-1-ol and 10-unde-
cen-1-ol were less efficiently oxidized into 10-hydroxydecan-
2-one and 11-hydroxyundecan-2-one in only 32 and 9% yields,
respectively,9 due probably to wrong orientation of the olefin
moiety with respect to the Pd(II) center.
In summery, we have achieved the recognition of long alkyl
chain compounds at a fixed position of the hydrophobic cavity of
1. The subsequent catalytic oxidation of !-alkenols is reminis-
cent of nature’s system, where a substrate is recognized at the
binding pocket and a metal center promotes a reaction at a spe-
cific position, and the product is excluded from the pocket.4
We paid our attention to the proximity of the terminal meth-
yl group to a Pd(II) corner of the cage, and examined the enclath-
ration of !-alkenols in expectation of the interaction of the
olefin moiety with the Pd(II) center. When a large excess of
8-nonen-1-ol (4) (20 equiv. mol) was suspended in the aqueous
solution of 1 at 80 ꢁC for 5 h, we observed the Wacker-type ox-
idation of 4. Namely the CH2=CH– group of 4 was catalytically
converted into a CH3CO– group to give 9-hydroxynonan-2-one
(5) in 66% yield.9 Since the substrate 4 was insoluble in water,
the reaction proceeded in an organic-aqueous two-phase system.
1H NMR monitoring of the aqueous phase clearly revealed the
efficient binding of 4 by the cage followed by the smooth trans-
formation of 4 into 5. At the beginning, the formation of inclu-
sion complex 1 ꢂ ð4Þ2 was confirmed (Figure 3a). Upon heating,
new signals assignable to 5 appeared around 3.5–0.9 ppm
(Figure 3b). The chemical shifts of 5 were not shifted upfield, in-
dicating that 5 was excluded and replaced by more hydrophobic
4. Large integral ratio of 5 in Figure 3b showed moderate water
solubility of 5.
References and Notes
1
2
3
J. L. Atwood, J. E. D. Davies, D. D. Macnicol, and F. Vogtle,
¨
‘‘Comprehensive Supramolecular Chemistry, Vol. 3, Cyclodex-
trins,’’ ed. by J. Szejtli and T. Osa, Pergamon, Oxford, U.K.
(1996); T. Bojinova, Y. Coppel, N. L. Viguerie, A. Milius, I.
Rico-Lattes, and A. Lattes, Langmuir, 19, 5233 (2003).
Enclathration of long alkyl chain compounds: T. Fujimoto, R.
Yanagihara, K. Kobayashi, and Y. Aoyama, Bull. Chem. Soc.
Jpn., 68, 2113 (1995); L. Trembleau and J. Rebek, Jr., Science,
301, 1219 (2003); A. Scarso, L. Trembleau, and J. Rebek, Jr.,
Angew. Chem., Int. Ed., 43, 963 (2004).
Recent reviews for self-assembled cages: A. Lutzen, Angew.
¨
Chem., Int. Ed., 44, 1000 (2005); D. M. Vriezema, M. C.
`
Aragones, J. A. A. Elemans, J. J. L. M. Cornelissen, A. E.
Rowan, and R. J. M. Nolte, Chem. Rev., 105, 1445 (2005).
M. J. Knapp, F. P. Seebeck, and J. P. Klinman, J. Am. Chem.
Soc., 123, 2931 (2001).
M. Yoshizawa and M. Fujita, Pure Appl. Chem., 77, 1107
(2005).
4
5
6
7
T. Kusukawa and M. Fujita, J. Am. Chem. Soc., 124, 13576
(2002).
1 ꢂ (3)2, 1 ꢂ (1-decanol)2, 1 ꢂ (1-undecanol)2, 1 ꢂ (1-do-
decanol)2, and 1 ꢂ (1-tridecanol)2 were formed in ca. 100, 80,
80, 55, and 30% yields, respectively, under the same conditions.
Crystal data for 1 ꢂ (2)2: C113H161N45O97Pd6, MW ¼ 4344:40,
Figure 3. Catalytic Wacker oxidation of 8-nonen-1-ol (4) into
9-hydroxynonan-2-one (5) in the aqueous solution of 1
(5 mol %) at 80 ꢁC for 5 h. 1H NMR spectra (500 MHz, rt,
D2O, TMS as external standard) of the aqueous phase (a) before
and (b) after the reaction (light gray circle: 4, dark gray circle: 5).
8
ꢁ
tetragonal, space group I41=a, a ¼ b ¼ 26:1979ð14Þ A, c ¼
ꢁ
ꢁ 3
31:687ð3Þ A, V ¼ 21747ð3Þ A , T ¼ 80ð2Þ K, Z ¼ 4, Dcalcd
¼
1:327 g cmꢃ3, ꢁ (Mo Kꢂ) ¼ 0:71073 A, 125649 reflections
measured, 12513 unique (Rint ¼ 0:0295) which were used in
all calculations. The structure was solved by direct method
(SHELXL-97) and refined by full-matrix least-squares methods
on F2 with 582 parameters. R1 ¼ 0:0758 (I > 2ꢃðIÞ) and wR2 ¼
0:2173, GOF 1.134; max./min. residual density 1.531/ꢃ1:049
ꢁ
The observed catalytic turnover indicated the involvement
of both inclusion and exclusion steps in the catalytic cycle.
The inclusion step should be driven by the efficient hydrophobic
interaction between substrate 4 and cage 1 as revealed by the
X-ray structure (Figure 2). The exclusion step should be driven
by the reduced host–guest hydrophobic interaction due to the
conversion of the hydrophobic CH2=CH– moiety into the
hydrophilic CH3CO– moiety. Since the Pd(II) component,
(tmed)Pd(NO3)2,10 hardly showed the catalytic activity (only
2% yield), the present reaction was obviously catalyzed by the
Pd(II)-containing cage 1 itself. Interestingly, Pd(0) species that
should be formed in the Wacker-type oxidation seemed to be
aerobically reoxidized into Pd(II) without using reoxidizing co-
reagent such as a Cu(II) salt.
ꢁ ꢃ3
eA . Crystallographic data reported in this manuscript have
been deposited with Cambridge Crystallographic Data Centre
as supplementary publication no. CCDC-279341. Copies of
the data can be obtained free of charge via http://www.ccdc.
cam.ac.uk/conts/retrieving.html (or from the Cambridge Crys-
tallographic Data Centre, 12, Union Road, Cambridge, CB2
1EZ, UK; fax: +44 1223 336033; or deposit@ccdc.cam.ac.uk).
Near the hydroxyl group of 2, a water molecule was observed
ꢁ
within a hydrogen bonding distance (OꢅꢅꢅO: 2.85 A).
9
The yield was estimated by NMR after 4 and 5 were extracted
with CDCl3 from the reaction mixture.
Previously, we reported the catalytic Wacker oxidation of
styrene promoted by cage 10 and (en)Pd(NO3)2.11,12 Since 10
did not show any catalysis, co-existence of (en)Pd(NO3)2 was
essential. In the present case, the oxidation was efficiently pro-
moted by cage 1 alone. The catalysis of cage 1 itself is ascribed
10 tmed = N,N,N0,N0-tetramethylethylenediamine.
11 Cage 10 is an analogue of 1 where tmed is replaced by ethylene-
diamine (=en). M. Fujita, D. Oguro, M. Miyazawa, H. Oka, K.
Yamaguchi, and K. Ogura, Nature, 378, 469 (1995).
12 H. Ito, T. Kusukawa, and M. Fujita, Chem. Lett., 2000, 598.
Published on the web (Advance View) September 10, 2005; DOI 10.1246/cl.2005.1392