Fluorous biphasic catalysis without perfluorinated solvents: Application to Pd-Mediated Suzuki and Sonogashira couplings

Article abstract of DOI:10.1002/1521-3773(20021202)41:23<4474::AID-ANIE4474>3.0.CO;2-S

With and now without: Perfluoro-tagged catalysts immobilized on fluorous reversed-phase silica gel can be used for Suzuki and Sonogashira C-C coupling reactions (see scheme; R¹ = e.g., phenyl, 4-MeOC₆H₄, R² e.g., 4-NO₂C₆H₄, 4-MeCOC₆H₄, X = Br, I) without the need for perfluorinated solvents. After the reaction the products were isolated by decantation and the Pd catalysts were recovered and reused.

Full text of DOI:10.1002/1521-3773(20021202)41:23<4474::AID-ANIE4474>3.0.CO;2-S

COMMUNICATIONS
Supramolecular Amphiphiles: Spontaneous
Formation of Vesicles Triggered by Formation
of a Charge-Transfer Complex in a Host**
Young Jin Jeon, Parimal K. Bharadwaj,
SooWhan Choi, Jae Wook Lee, and Kimoon Kim*
Studies on vesicles have received much attention in recent
years as they are important building blocks of all living
systems and are potentially useful in many areas of chemistry,
biology, and material science: for example, in the develop-
ment of light-harvesting systems, artificial ion channels, drug/
[1±±3
gene deliverys ys tems, and new smart materials.
Over the
last decade a wide varietyof s ny thetic amphiphiles with
different polar head groups and hydrophobic tails have been
Scheme 1. Formation of stable ternarycomplexes 1, 2, and 3.
reported.[
2,±3
With onlya few exceptions,
[43
however, these
amphiphiles are single molecules prepared byconventional
covalent synthesis. Herein we report, for the first time, the
spontaneous formation of giant vesicles triggered bythe
formation of a stable ternaryinclusion complex that behaves
as a large supramolecular amphiphile. Furthermore, the
disruption of the vesicles can be easilytriggered bya redox
process.
or turbid solution with a violet color corresponding to 2 and 3,
[123
respectively. A broad absorption band centered at about
50 nm in their UV/Vis spectra,[1±3 as in 1, indicates the
5
formation of charge-transfer complexes inside CB[83
2þ
(
Scheme 1). Without CB[83, binarymixtures of C VC
(or
1
12
2þ
C VC ) and DHNp do not produce anycolor change, which
1
16
Cucurbit[63uril (CB[63), a macrocyclic cavitand comprising
six glycoluril units, has a hydrophobic cavity that is accessible
through two identical carbonyl-fringed portals. It has been
supports the theorythat these charge-transfer complexes are
indeed formed inside the CB[83 cavity. Conclusive evidence
for the formation of stable 1:1:1 ternarycomplexes were
[5,63
widelyused as a s yn thetic receptor
and as a building block
1
further obtained from H NMR and ESI mass measure-
[73
for supramolecular architectures. Our recent synthesis of
[123
1
ments. For example, in the H NMR spectrum of 2, the
new cucurbituril homologues,[ cucurbit[n3uril (CB[n3, n ¼ 5,
83
2þ
signals for the bipyridinium unit of C VC
up-field, whereas those for the alkyl tail of C VC
and DHNp shift
1
12
7, and 8) containing five, seven, and eight glycoluril units,
2þ
1
12
respectively, has opened up new opportunities in supra-
(
particularlythose for the meth lye ne units close to the
molecular chemistry.[
9,103
For example, CB[83, which has a
bipyridinium unit) shift down-field relative to those in their
free forms. This observation is consistent with the formation
of a charge-transfer complex between the bipyridinium unit of
cavitycomparable to that of g-cyclodextrin, can form a stable
2
þ
1
:1:1 complex (1) with methyl viologen (MV ) and 2,6-
[9a3
dihydroxynaphthalene (DHNp) (Scheme 1). The formation
of the ternarycomplex is driven bycharge-transfer interaction
between the electron-deficient and electron-rich guest mole-
cules inside the hydrophobic cavity of CB[83. This discovery
prompted us to explore supramolecular assemblies of higher
hierarchybased on formation of a ternarycomplex.
2þ
C VC
1
and DHNp inside CB[83, and the presence of a
12
2þ
signal at m/z 914.±0 [M 3 in the ESI mass spectrum exactly
matching the formula mass of 2 (m/z 942.86 for 3) further
confirms the formation of a ternarycomplex.
Most interestingly, the ternary complexes 2 and 3 form
large vesicles, which has been confirmed bylight microscopy,
Sonication of an equimolar mixture of CB[83, a viologen
[1±3
TEM, and SEM measurements.
The TEM images
2
þ
2þ
with a C12 or C16 alkyl chain (C VC
or C VC
,
1
12
1
16
(Figure 1a) of 2, which has a C12 hydrophobic tail, reveal
nearlymonodispersed vesicles with an average diameter of
respectively),[113 and DHNp in water results in a transparent
2
0 nm. On the other hand, 3, which has a C16 hydrophobic tail,
forms relativelylarge vesicles with a diameter ranging from
0 nm to 1.2 mm (TEM images, Figure 1b). A high-resolution
[
*3 Prof. Dr. K. Kim, Y. J. Jeon, Prof. Dr. P. K. Bharadwaj, Dr. S. Choi,
Dr. J. W. Lee
National Creative Research Initiative Center for Smart Supramole-
cules and
2
[1±3
TEM image of the vesicles shows their hollow structures.
Dynamic light scattering data of 3 in water indicate the
presence of supramolecular aggregates with an average
diameter of 870 nm. The SEM images (Figure 1c) of 3 also
show large spheres with a diameter ranging from 20 nm to
Department of Chemistry, Division of Molecular and Life Sciences
Pohang Universityof Science and Technology
San ±1 Hyojadong, Pohang 790±784 (Republic of Korea)
Fax : (þ 82)54±279±8129
E-mail: kkim@postech.ac.kr
1.2 mm; the typical vesicle size lies between 400 and 950 nm.
[
**3 We gratefullyacknowledge the Creative Research Initiative Program
of the Korean Ministryof Science and Technologyfor support of this
work and the Brain Korea 21 Program of the Korean Ministryof
Education for a graduate studentship (Y.J.J.). We thank Drs. Hee-Joon
Kim and Young Ho Ko for helpful suggestions and help, respectively,
in the NMR study. We also thank Prof. Hee-Tae Jung of KAIST for
helpful discussions on the TEM experiments.
The SEM images also demonstrate that the vesicles are robust
as theymaintain the spherical shape even when theyare dried
on a solid surface. This observation is in sharp contrast to most
vesicle systems made of natural or synthetic amphiphiles,
which are flattened on a surface under similar conditions.[
The origin of the extraordinarystabilityof the present vesicles
2a3
Supporting information for this article is available on the WWW under
http://www.angewandte.org or from the author.
2þ
is, however, not yet clear. We must point out that C VC
1
12
4474
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0044-8249/02/412±-4474 $ 20.00+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 2±

COMMUNICATIONS
2þ
2þ
The two components, DHNp and C VC
(or C VC ),
1
1
12
16
which reside inside the cavityof CB[83 in 2 (or 3) are redox
active. Therefore, we anticipated that oxidation of DHNp or
2
þ
2þ
reduction of C VC
(or C VC ) would result in destruc-
1
1
12
16
tion of the ternarycomplex as a result of the loss of charge-
transfer interaction between the two guests, which mayin turn
cause collapse of the vesicles. With this idea in mind, we
treated 2 and 3 with cerium(iv) ammonium nitrate (CAN)
which can oxidize DHNp to naphthoquinone. The charge-
transfer band at 550 nm disappears in the UV/Vis spectrum of
2
or 3 upon treatment with CAN which indicates destruction
[1±3
of the charge-transfer complex inside CB[83. The collapse
of vesicles of 3 has been confirmed bySEM; the previously
observed spherical objects no longer exist in the SEM images
of the CAN-treated sample.[ We are currentlyexploring
other methods to disrupt the vesicles under mild conditions.
In conclusion, we have demonstrated the spontaneous
formation of giant vesicles triggered byformation of a stable
ternaryinclusion complex that behaves as a large supra-
molecular amphiphile. Since the ternarycomplex is stabilized
bycharge-transfer interaction of an electron donor±acceptor
pair inside a host, redox chemistrycan be used to trigger the
collapse of the vesicles. These novel vesicles mayfind useful
applications in manyareas including development of smart
materials. We are currentlyexploring these possibilities.
163
Figure 1. a) TEM image of ternarycomplex 2. b) TEM image of ternary
complex 3. c) SEM image of ternarycomplex 3. Samples (concentration ¼
ꢀ4
6
.9 î 10 m) were negativelystained with uran yl acetate (2 wt% in water)
for observation byTEM.
2
þ
and C VC
itself form onlymicellar aggregates at the same
1
16
ꢀ
4
concentration (6.9 î 10 m, critical micelle concentration
cmc) ¼ ca. 1 î 10 m). Therefore, the formation of vesicles
is triggered bythe formation of the ternarycomplexes CB[83-
ꢀ
4
[143
(
2
þ
2þ
DHNp-C VC
(or C VC ), which behave as supramo-
1
1
12
16
lecular amphiphiles with a large polar head group and a
hydrophobic tail. Such spontaneous formation of vesicles
triggered bythe formation of a ternarycomplexes is
unprecedented.
Further evidence for the formation of vesicles of 2 and 3 is
provided byencapsulation of the fluorescent d ye sulforhoda-
mine G (S) within the interior of the vesicles. Figure 2 (inset)
is a representative fluorescence microscopyimage of 3, which
has been prepared in the presence of S and purified by
dialysis, and shows the entrapment of S in the vesicle 3. The
stabilityof the vesicles is also demonstrated byveryslow
release of the fluorescent dye trapped inside the vesicles
Received: August 6, 2002 [Z198983
[
13 a) J. H. Fendler, Membrane Mimetic Chemistry, Wiley, New York,
982; b) T. Kunitake, Angew. Chem. 1992, 104, 692; Angew. Chem. Int.
Ed. Engl. 1992, 31, 709.
1
[23 a) Y. Tanaka, M. Miyachi, Y. Kokube, Angew. Chem. 1999, 111, 565;
Angew. Chem. Int. Ed. 1999, 38, 504; b) Y. Einaga, O. Sato, T. Iyoda,
A. Fujishima, K. Hashimoto, J. Am. Chem. Soc. 1999, 121, ±745; c) Q.
Cheng, T. Peng, R. C. Stevens, J. Am. Chem. Soc. 1999, 121, 6767;
d) Y. R. Vandenberg, B. D. Smith, M. N. Pÿrez-Payµn, A. P. Davis, J.
Am. Chem. Soc. 2000, 122, ±252; e) S. Kolusheva, T. Shahal, R.
Jelinek, J. Am. Chem. Soc. 2000, 122, 776; f) A. Veronese, P. L. Luisi, J.
Am. Chem. Soc. 1998, 120, 2662; g) T. Renkes, H. J. Sch‰fer, P. M.
Siemens, E. Neumann, Angew. Chem. 2000, 112, 2566; Angew. Chem.
Int. Ed. 2000, 39, 2515; h) P. Ghosh, S. Sengupta, P. K. Bharadwaj,
Langmuir 1998, 14, 5712; i) P. Bandyopadhyay, P. K. Bharadwaj,
Langmuir 1998, 14, 75±7.
[±3 a) B. J. Ravoo, R. Darcy, Angew. Chem. 2000, 112, 4494; Angew.
Chem. Int. Ed. 2000, 39, 4±24; b) M. Brettreich, S. Burghardt, C.
Bˆttler, T. Bayerl, S. Bayerl, A. Hirsch, Angew. Chem. 2000, 112, 1915;
Angew. Chem. Int. Ed. 2000, 39, 1845; c) A. M. Cassell, C. C. Asplund,
J. M. Tour, Angew. Chem. 1999, 111, 2565; Angew. Chem. Int. Ed.
(
Figure 2). Addition of Triton X-100, which is known to
solublize vesicles, triggers a quick release of the dye. The dye-
entrapment experiment, which is known to provide a clue to
the lamellarityof vesicles, [ suggests that the vesicle 3 is
153
unilamellar rather than multilamellar.[1±3
1
999, 38, 240±; d) M. Hetzer, H. Clausen-Schaumann, S. Bayerl, T. M.
Bayerl, X. Camps, O. Vostrowsky, A. Hirsch, Angew. Chem. 1999, 111,
10±; Angew. Chem. Int. Ed. 1999, 38, 1962; e) S. Zhou, C. Burger, B.
2
Chu, M. Sawamura, N. Nagahama, M. Toganoh, U. E. Hackler, H.
Isobe, E. Nakamura, Science 2001, 291, 1944.
[
43 a) V. Marchi-Artzner, L. Jullien, T. Gulik-Krzywicki, J.-M. Lehn,
Chem. Commun. 1997, 117; b) F. Ilhan, T. H. Galow, M. Gray, G.
Clavier, V. M. Rotello, J. Am. Chem. Soc. 2000, 122, 5895.
[
53 For reviews of cucurbituril, see a) W. L. Mock, Comprehensive
Supramolecular Chemistry, Vol. 2, (Ed.: F. Vˆgtle) Pergamon, Oxford,
1
1
996, p477; b) P. Cintas, J. Inclusion Phenom. Mol. Recognit. Chem.
994, 17, 205.
[
63 a) Y.-M. Jeon, J. Kim, D. Whang, K. Kim, J. Am. Chem. Soc. 1996, 118,
790; b) D. Whang, J. Heo, J. H. Park, K. Kim, Angew. Chem. 1998,
9
Figure 2. Confocal fluorescence microscope images of vesicle 3 containing
entrapped sulforhodamine G (inset) and release profile of the dye from the
vesicle.
110, 8±; Angew. Chem. Int. Ed. 1998, 37, 78; c) H.-J. Kim, J. Heo, W. S.
Jeon, E. Lee, J. Kim, S. Sakamoto, K. Yamaguchi, K. Kim, Angew.
Chem. 2001, 113, 1574; Angew. Chem. Int. Ed. 2001, 40, 1526.
Angew. Chem. Int. Ed. 2002, 41, No. 2±
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0044-8249/02/412±-4475 $ 20.00+.50/0
4475

COMMUNICATIONS
[
73 a) D. Whang, Y.-M. Jeon, J. Heo, K. Kim, J. Am. Chem. Soc. 1996, 118,
1±±±; b) D. Whang, K. Kim, J. Am. Chem. Soc. 1997, 119, 451; c) D.
Whang, K.-M. Park, J. Heo, K. Kim, J. Am. Chem. Soc. 1998, 120,
899; d) S.-G. Roh, K.-M. Park, G.-J. Park, S. Sakamoto, K.
Yamaguchi, K. Kim, Angew. Chem. 1999, 111, 672; Angew. Chem.
Int. Ed. 1999, 38, 6±8; e) E. Lee, J. Heo, K. Kim, Angew. Chem. 2000,
Is Fluoride Bonded to Two Pd Acceptors Still
Basic? Three CH Cl Molecules Encapsulating
1
2
2
4
a Pd (m-F) Square and New Implications for
2
2
Catalysis**
1
12, 2811; Angew. Chem. Int. Ed. 2000, 39, 2699; f) E. Lee, J. Kim, J.
Vladimir V. Grushin* and William J. Marshall
Heo, D. Whang, K. Kim, Angew. Chem. 2001, 113, 41±; Angew. Chem.
Int. Ed. 2001, 40, ±99; g) J. W. Lee, Y. H. Ko, S.-H. Park, K.
Yamaguchi, K. Kim, Angew. Chem. 2001, 113, 768; Angew. Chem.
Int. Ed. 2001, 40, 746; h) K.-M. Park, D. Whang, E. Lee, J. Heo, K.
Kim, Chem. Eur. J. 2002, 8, 498; i) K.-M. Park, S.-Y. Kim, J. Heo, D.
Whang, S. Sakamoto, K. Yamaguchi, K. Kim, J. Am. Chem. Soc. 2002,
Organotransition-metal fluoro complexes have recently
received much attention due to their useful, uncommon
properties,[ and potential use in the synthesis of highly
13
[2±43
desired, selectivelyfluorinated organic molecules,
in
1
24, 2140; j) K. Kim, Chem. Soc. Rev. 2002, 31, 96.
catalysis,[ and in CꢀH activation. Further progress in this
new, promising area will depend on firm knowledge of the
nature and reactivityof the metal±fluorine bond. As a ligand
for the catalytically important platinum group metals, fluoride
still remains scantilyexplored. Thus, being ubiquitous in
catalysis, palladium has been shown[ to form isolable fluoro
complexes onlyrecentl .y Here we report on the s yn thesis,
unexpectedlystrong basicit ,y and peculiar reactivityof the
first dinuclear organopalladium m-fluorides and their mono-
5,63
[73
[
[
83 J. Kim, I.-S. Jung, S.-Y. Kim, E. Lee, J.-K. Kang, S. Sakamoto, K.
Yamaguchi, K. Kim, J. Am. Chem. Soc. 2000, 122, 540.
93 a) H.-J. Kim, J. Heo, W. S. Jeon, E. Lee, J. Kim, S. Sakamoto, K.
Yamaguchi, K. Kim, Angew. Chem. 2001, 113, 1574; Angew. Chem.
Int. Ed. 2001, 40, 1526; b) S.-Y. Kim, I.-S. Jung, E. Lee, J. Kim, S.
Sakamoto, K. Yamaguchi, K. Kim, Angew. Chem. 2001, 113, 2177;
Angew. Chem. Int. Ed. 2001, 40, 2119; c) S. Y. Jon, Y. H. Ko, S. H.
Park, H.-J. Kim, K. Kim, Chem. Commun. 2001, 19, 19±8; d) H.-J.
Kim, W. S. Jeon, Y. H. Ko, K. Kim, Proc. Natl. Acad. Sci. USA, 2002,
6,83
9
9, 5007.
103 a) A. Day, A. P. Arnold, R. J. Blanch, B. Snushall, J. Org. Chem. 2001,
6, 8094; b) R. J. Blanch, A. J. Sleeman, T. J. White, A. P. Arnold, A. I.
[
nuclear analogues stabilized by(alk yl ) P ligands.
±
6
Using our previouslydeveloped methods [ we prepared a
series of new Pd fluorides 1±6 [Eq. (1) and (2)3, which were
characterized byanal yt ical, spectroscopic, and X-raydiffrac-
6,83
Day,Nano Lett. 2002, 2, 147; c) A. I. Day, R. J. Blanch, A. P. Arnold, S.
Lorenzo, G. R. Lewis, I. Dance, Angew. Chem. 2002, 114, 285; Angew.
Chem. Int. Ed. 2002, 41, 275; d) C. Marqiez, W. M. Nau, Angew. Chem.
2
001, 113, 4515; Angew. Chem. Int. Ed. 2001, 40, 4±87.
[93
tion data (see Supporting Information for details).
[
[
113 a) Y. Lei, J. K. Hurst, J. Phys. Chem. 1991, 95, 7918; b) K. L. Kovacs,
A. Der, Biochimie 1986, 68, 211.
123 The vesicles were prepared as follows: A small amount of THF (0.±±
0
.5 mL) and distilled water (10 mL) were added to a vial containing an
equimolar ratio (6.9 mmol) of three components: CB[83, viologen with
2þ
2þ
1 1
a long alkyl chain (C VC12 or C VC16 ), and 2,6-dihydroxynaph-
thalene. The resulting suspension was sonicated at 608C for 1 h to
remove the initiallyadded THF and then kept overnight at room
temperature to give a transparent (2) or turbid (3) solution. The
formation of 1:1:1 ternarycomplexes in 2 and 3 has been confirmed by
1
UV/Vis and H NMR spectroscopyas well as ESI mass spectrometry.
1
2
: H NMR (500MHz, D
2
O, 25 8C, TMS) d ¼ 8.81 (2H, brs), 8.54 (2H,
brs), 7.7± (2H, brs), 7.25 (2H, brs), 6.87 (±H, brs), 6.64 (±H, brs), 6.45
2H, brs), 5.89 (2H, brs), 5.75 (16H, d), 5.47 (16H, s), 4.54 (±H, s),
(
4
.17 (16H, d), 2.26 (2H, brs), 1.75±1.15 (18H, brs), 0.86 (±H, brs);
2
þ
UV/Vis (H
2
O): lCT ¼ 552 nm; ESI-MS: m/z (%): 914.±0 (100) [M 3. 3:
O, 25 8C, TMS) d ¼ 9.02 (2H, brs), 8.49 (2H,
1
H NMR (500MHz, D
2
brs), 7.56 (2H, brs), 7.21 (2H, brs), 7.10±6.04 (6H, brs), 5.74 (16H, d),
5
l
2
.46 (16H, s), 4.16 (16H, d), 2.42±0.65 (±4H, brs); UV/Vis (H O):
CT ¼ 548 nm; ESI-MS: m/z (%): 942.86 (70) [M 3.
2
þ
Considering the particularlystrong p basicityof coordi-
nated terminal fluoride[
1,6,10±123
and the enhanced donating
[
[
1±3 See Supporting Information.
143 a) A. Diaz, P. A. Quintela, J. M. Schuette, A. E. Kaifer, J. Phy. Chem.
988, 92, ±5±7; b) Y. Lee, C. Lee, Bull. Korean Chem. Soc. 1999, 20, 1.
properties of iPr P (compared to Ph P), PdꢀF d ±p filled/
±
±
p
p
1
filled repulsions in 1 and 3 were expected to be stronger than
[
153 Preparation of the dye-entrapped vesicles and calculation of the dye-
entrapped volume were carried out byconventional experimental
procedures used for liposomes: R. C. C. New, Liposomes: A practical
approach, Oxford University, Oxford, 1990.
163 Addition of CAN to an aqueous solution of sulforhodamine G results
in immediate quenching of its fluorescence as a consequence of the
rapid oxidation of the dye; therefore, the release of the dye from the
dye-entrapped vesicle triggered by CAN could not be monitored.
[83
in their Ph P analogue [(Ph P) PdPh(F)3, resulting in
±
±
2
elongation rather than shortening of the PdꢀF bond. Surpris-
ingly, the PdꢀF bond lengths in both 1 (Figure 1; 2.050(2) and
[
2
.057(2) ä for two structurallysimilar molecules in the
asymmetric unit), and 3 (Figure 2; 2.057(2) ä) are shorter
[
*3 Dr. V. V. Grushin, W. J. Marshall
Central Research and Development
E. I. DuPont de Nemours & Co., Inc.
Experimental Station
Wilmington, Delaware 19880±0±28 (USA)
Fax : (þ 1)±02-695-8281
E-mail: vlad.grushin-1@usa.dupont.com
[
**3 Contribution No. 8±±1. We thank Dr. D. Christopher Roe for variable-
temperature NMR experiments.
Supporting information for this article is available on the WWW under
http://www.angewandte.org or from the author.
4476
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0044-8249/02/412±-4476 $ 20.00+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 2±