Molecular-architecture-based administration of catalysis in water: Self-assembly of an amphiphilic palladium pincer complex

Article abstract of DOI:10.1002/anie.201100827

Testing the waters: An architecture-based system for transition-metal catalysis consisting of a self-assembled amphiphilic pincer palladium complex bearing hydrophilic and hydrophobic chains has been developed. Self-assembly of the bilayer vesicles of the complex, concentration of the organic substrates within the hydrophobic region of the bilayer membrane, and catalytic transformation of the substrate all occur sequentially in water (see scheme). Copyright

Full text of DOI:10.1002/anie.201100827

Communications
DOI: 10.1002/anie.201100827
Vesicular Catalyst
Molecular-Architecture-Based Administration of Catalysis in Water:
Self-Assembly of an Amphiphilic Palladium Pincer Complex**
Go Hamasaka, Tsubasa Muto, and Yasuhiro Uozumi*
Biological membranes are known to play a key role in
controlling life-related molecular functions (e.g., active/
passive transport, diffusion, filtration, selective permeation,
etc.). Lipid bilayer membrane vesicles (i.e., liposomes) are
small assemblies of amphiphilic molecules bearing both
hydrophilic and hydrophobic groups and they offer promising
prospects for the understanding of biological membranes. If
less-catalytically active small molecules can self-assemble to
form bilayer vesicles and, in so doing, gain unique catalytic
functions for a given molecular transformation, this process
could conceivably be used in a catalysis-driven system.[1–3] We
report herein the formation of a bilayer membrane vesicle
from an amphiphilic palladium complex through self-assem-
bly to realize palladium-catalyzed carbon–carbon bond-
forming reactions under ambient conditions (in water,
under air, at room temperature), wherein the vesicle archi-
tecture is essential for the catalysis. The formation of a
catalytically active vesicle and the vesicle-catalyzed organic
transformations were both promoted in water by the hydro-
phobic properties of the substrates and catalysts, as opposed
to conventional artificial organic chemical reaction systems
(i.e., standard flask reactions) that are often promoted with
external driving forces (e.g., heat, pressure, light, etc.).
The pincer palladium complex 1[4,5] having pairs of
Scheme 1. Formation of vesicle 1vscl by self-assembly of the pincer
palladium complex 1.
hydrophobic dodecyl chains and hydrophilic tri(ethylene
glycol) (TEG) chains located opposite to one another on
the rigid planar backbone, was designed and prepared for use
in the self-assembly formation[6] of vesicles exhibiting cata-
lytic activity in water (Scheme 1; see the Supporting Infor-
mation). After the complex 1, which was obtained as an
amorphous nanopowder (1amps; Figure 1a), was treated in
water at 608C for 4 hours, the resulting aqueous mixture was
cooled and subjected to a dynamic light scattering (DLS)
study (Figure 1c) to demonstrate the formation of the vesicle
1vscl (average diameter= 550 nm).[7] Vesicle 1vscl was isolated
by centrifugation and decantation in 10–40% yield based on
the recovery of 1 as an amorphous powder from the super-
natant. Transmission electron microscopy (TEM) and atomic
force microscopy (AFM) images of the isolated vesicle 1vscl
are shown in Figures 1b and d, respectively.[8] These micro-
scopic studies revealed that 1vscl was obtained as hard
vesicles.[9] Their spherical form was confirmed by AFM
(Figure 1d), and the thickness of the vesicle membrane was
determined to be 6 nm by TEM methods (Figure 1b). These
data are consistent with those of the bilayer membranous
structure of 1mono having a monomer length of approximately
2.8 nm in the structure (Scheme 1).[10] The incorporation of
the fluorescent reagent, fluorescein, into the 1vscl revealed a
hollow structure with an inner hydrophobic region in the
exterior membrane.[11] Thus, when the isolated 1vscl was
exposed to fluorescein under aqueous conditions, the fluo-
rescent vesicles, 1vscl/fluorescein, were isolated after rinsing
with water. The fluorescence microscopic image and the
[*] Dr. G. Hamasaka, T. Muto, Prof. Dr. Y. Uozumi
Institute for Molecular Science
Myodaiji, Okazaki 444-8787 (Japan)
Fax: (+81)564-59-5574
E-mail: uo@ims.ac.jp
Homepage: http://groups.ims.ac.jp/organization/uozumi_g/
T. Muto, Prof. Dr. Y. Uozumi
The Graduate School for Advanced Studies
Myodaiji, Okazaki 444-8787 (Japan)
Prof. Dr. Y. Uozumi
Riken
Hirosawa, Wako 351-0198 (Japan)
[**] We acknowledge the JSPS (Grant-in-Aid for Scientific Research no.
20655035; Grant-in-Aid for Scientific Research on Innovative Area
no. 2105) for partial financial support of this work. We also thank Dr.
R. Tero (Toyohashi University of Technology (Japan)) for AFM and
fluorescence microscopy measurements. Confocal images were
acquired at Spectrography and Bioimaging Facility, NIBB Core
Research Facilities.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201100827.
4876
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 4876 –4878

Figure 1. a) TEM image of 1amps (amorphous powder). b) TEM image of 1vscl. c) A histogram of the size distribution of 1vscl formed in water as
observed by dynamic light scattering. d) AFM image of 1vscl. e) Fluorescence microscopic image of 1vscl/fluorescein. f) CLSM image of 1vscl
fluorescein. g) Fluorescence microscopic image of 1vscl/Nile Red.
/
confocal laser scanning microscopic (CLSM) image are shown
in Figures 1e and f, respectively.[12]
The fluorescent stain of fluorescein in the membrane
observed by CLSM revealed a hydrophobic inner region in
the bilayer membrane(Figure 1 f). The fluorescein dye was
replaced with another fluorescent dye, Nile Red; the isolated
1vscl/fluorescein was exposed to Nile Red in water to give 1vscl/
Nile Red (Figure 1g). These experiments demonstrate that a
hydrophobic organic molecule can diffuse into the membra-
nous region of 1vscl and be exchanged with another external
hydrophobic organic molecule in water.
With the desired vesicles of the palladium-pincer complex
in hand, we next explored their catalytic potential for
arylating oxirane ring-opening reactions[13] of the vinyl
epoxide (2) with phenylboronic acid (3; Figure 2a). A
mixture of the epoxide
2 and phenylboronic acid 3
(1.2 equiv) was stirred in water with 2 mol% palladium
within the vesicle 1vscl for 12 hours. The reaction mixture was
extracted with tert-butyl methyl ether to give an 84% yield
(determined by NMR analysis) of the arylated product 4
along with its regioisomer 5. The catalyst 1 was recovered
[14]
from the organic extracts as its amorphous form 1amps
.
Figure 2. a) Palladium-catalyzed oxirane ring opening with PhB(OH)2.
[a] 1vscl was generated in situ without being isolated in water. b) Sche-
matic image of the concept of catalysis within the bilayer membrane of
However, under similar reaction conditions, the reaction
with nano-suspension of the amorphous powder 1amps (Fig-
ure 1a) did not proceed as efficiently. Neither 1vscl nor 1amps
catalyzed the arylation in organic solvents, because both the
vesicle 1vscl and the amorphous 1amps disassembled/dissolved
into the catalytically less active monomer 1mono. Thus, vesicle
formation is essential for the amphiphilic pincer complex 1 to
acquire the necessary catalytic property in water. The organic
substrate 2 should be concentrated within the hydrophobic
region of the bilayer membrane under aqueous conditions,
where the potentially catalytic palladium species is located in
immediate proximity. This concept is shown schematically in
Figure 2b.
the 1vscl
.
The architecture-based catalysis was also performed in
one pot without isolation of the catalytically active vesicle
1vscl. Thus, a mixture of 1amps of in water was preheated at
1008C for 4 hours prior to being used in the catalysis. During
this time, the vesicles 1vscl should have formed in situ. After
the mixture was cooled, the oxirane 2 and phenylboronic acid
3 were added to the aqueous mixture at ambient temperature
(258C, 12 h) to give 4/5 in 87% yield (4/5 = 53:47). However,
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Communications
Table 1: Miyaura–Michael reaction of a,b-unsaturated ketones 6 and 7
Keywords: heterogeneous catalysis · palladium · self-assembly ·
vesicular catalysts · water chemistry
.
with sodium tetraarylborates 8.[a]
[1] Very recently, studies on the self-assembly of polymer-supported
enzymes have appeared, see: a) G. Delaittre, I. C. Reynhout,
J. J. L. M. Cornelissen, R. J. M. Nolte, Chem. Eur. J. 2009, 15,
12600 – 12603; b) D. M. Vriezema, P. M. L. Garcia, N. S. Oltra,
N. S. Hatzakis, S. M. Kuiper, R. J. M. Nolte, A. E. Rowan,
J. C. M. van Hest, Angew. Chem. 2007, 119, 7522 – 7526;
Angew. Chem. Int. Ed. 2007, 46, 7378 – 7382.
[2] For a review on self-assembled architectures serving as nano-
reactors for catalytic molecular transformations, see: D. M.
Vriezema, M. C. Aragonꢀs, J. A. A. W. Elemans, J. J. L. M.
Cornelissen, A. E. Rowan, R. J. M. Nolte, Chem. Rev. 2005,
105, 1445 – 1489.
[3] Selected examples for catalytic applications of self-assembled
architectures, see: a) M. S. Goedheijt, B. E. Hanson, J. N. H.
Reek, P. C. J. Kamer, P. W. N. M. van Leeuwen, J. Am. Chem.
Soc. 2000, 122, 1650 – 1657; b) M. Ferreira, H. Bricout, N.
Azaroual, C. Gaillard, D. Landy, S. Tilloy, E. Monflier, Adv.
Synth. Catal. 2010, 352, 1193 – 1203.
Entry Catalyst Product
Conv. [%][b] Yield [%][b] Selectivity [%]
1
2
3
4
5
6
7
8
1vscl
1amps
1vscl
1amps
1vscl
1amps
1vscl
9a (X=H) 85
9a (X=H) 23
9b (X=F)
9b (X=F)
10a (X=H) 39
10a (X=H) 18
10b (X=F) 17
83
7
98
30
66
3
63
<1
95
n.a.
39
3
14
5
>99
17
82
71
1amps
10b (X=F)
7
[a] Reaction conditions: cycloalkenone (6 or 7; 1 equiv), sodium
tetraarylborate (8; 1.5 equiv), water, palladium (2 mol%) using either
[4] K. Takenaka, M. Minakawa, Y. Uozumi, J. Am. Chem. Soc. 2005,
127, 12273 – 12281.
[5] The method for the synthesis of 1 is given in the Supporting
Information.
1
vscl or 1amps, 258C, 12–24 h. [b] Determined by 1H NMR analysis using an
internal standard (Cl2CHCHCl2).
[6] Examples for self-assembly of amphiphilic molecules, see:
a) S. H. Seo, J. Y. Chang, G. N. Tew, Angew. Chem. 2006, 118,
7688 – 7692; Angew. Chem. Int. Ed. 2006, 45, 7526 – 7530; b) J. P.
Hill, W. Jin, A. Kosaka, T. Fukushima, H. Ichihara, T.
Shimomura, K. Ito, T. Hashizume, N. Ishii, T. Aida, Science
2004, 304, 1481 – 1483.
[7] Recent examples of vesicle formation by self-assembly under
thermal conditions, see: a) G. P. Robbins, M. Jimbo, J. Swift,
M. J. Therien, D. A. Hammer, I. J. Dmochowski, J. Am. Chem.
Soc. 2009, 131, 3872 – 3874; b) W. Cai, G.-T. Wang, Y.-X. Xu, X.-
K. Jiang, Z.-T. Li, J. Am. Chem. Soc. 2008, 130, 6936 – 6937;
c) F. J. M. Hoeben, I. O. Shklyarevskiy, M. J. Pouderoijen, H.
Engelkamp, A. P. H. J. Schenning, P. C. M. Christianen, J. C.
Maan, E. W. Meijer, Angew. Chem. 2006, 118, 1254 – 1258;
Angew. Chem. Int. Ed. 2006, 45, 1232 – 1236; d) Y. J. Jeon, P. K.
Bharadwaj, S. W. Choi, J. W. Lee, K. Kim, Angew. Chem. 2002,
114, 4654 – 4656; Angew. Chem. Int. Ed. 2002, 41, 4474 – 4476.
[8] Additional microscopic images of 1vscl (AFM, TEM, SEM,
fluorescence microscopy, confocal laser scanning microscopy)
are given in the Supporting Information.
[9] a) M. Yang, W. Wang, F. Yuan, X. Zhang, J. Li, F. Liang, B. He, B.
Minch, G. Wegner, J. Am. Chem. Soc. 2005, 127, 15107 – 15111;
b) T. Rehm, S. Vladimir, Z. Xin, Wꢁrthner, F. Grꢂhn, K. Klein,
C. Schmuck, Org. Lett. 2008, 10, 1469 – 1472; c) C. Cai, J. Lin, T.
Chen, X. Tian, Langmuir 2010, 26, 2791 – 2797.
[10] The molecular structure of 1mono was preliminarily simulated by
RHF/STO-3G.
[11] See Ref. [7b].
[12] The encapsulating vesicle formation experiment with the
fluorescent reagent Rhodamine B was examined (see the
Supporting Information).
[13] J. Kjellgren, J. Aydin, O. A. Wallner, I. V. Saltanova, K. J. Szabꢃ,
Chem. Eur. J. 2005, 11, 5260 – 5268.
[14] Decomposition of the pincer complex 1 (e.g., formation of
palladium nanoparticles, hydrolysis of the pincer ligand moiety,
etc.) was not observed under the reaction conditions.
[15] For recent reviews on Miyaura–Michael reactions, see: a) N.
Miyaura, Synlett 2009, 2039 – 2050; b) N. Miyaura, Bull. Chem.
Soc. Jpn. 2008, 81, 1535 – 1553.
the 1amps did not promote the ring-opening reaction without
preheating.
The architecture-based production of catalysts, wherein
the self-assembly for vesicle formation, self-concentration of
the substrate inside the bilayer membrane, and the catalytic
transformation of the substrate with the palladium species
took place sequentially, was demonstrated in the Miyaura–
Michael reaction (Table 1).[15] Thus, the vesicle 1vscl (2 mol%
Pd) catalyzed the Miyaura–Michael reaction of cyclohexe-
none (6) with sodium tetraphenylborate (8a, 1.5 equiv) in
water to give the desired arylated product 9a in 83% yield
with 98% reaction selectivity after 12 hours (entry 1),
whereas the amorphous 1amps afforded only a 7% yield of
9a with much lower selectivity (entry 2). The reaction of
cyclohexenone (6) with sodium tetrakis(4-fluorophenyl)bo-
rate (8b) also proceeded to afford 9b in 63% yield and 95%
selectivity, whereas 1amps did not promote the reaction
(entries 3 and 4). Significant acceleration of the reaction
with the vesicle 1vscl was also observed in the reaction of
cycloheptenone (7) with sodium tetraarylborates (8a, 8b;
entries 5–8).
In conclusion, we have developed an architecture-based
system of transition-metal catalysis using an amphiphilic
pincer palladium complex 1 bearing hydrophilic and hydro-
phobic chains. This system involves 1) the self-assembly of
bilayer vesicles of 1, 2) the self-concentration of organic
substrates within the hydrophobic region of the bilayer
membrane, and 3) the catalytic transformation of the sub-
strate with the palladium species located within close
diffusion proximity, all of which occur sequentially in water.
Various types of catalysis are being developed using this
approach in our laboratory and will be reported in due course.
Received: February 1, 2011
Published online: March 31, 2011
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Angew. Chem. Int. Ed. 2011, 50, 4876 –4878