Instantaneous carbon-carbon bond formation using a microchannel reactor with a catalytic membrane

Article abstract of DOI:10.1021/ja066697r

Instantaneous catalytic carbon-carbon bond forming reactions were achieved in a microchannel reactor having a polymeric palladium complex membrane. The catalytic membrane was constructed inside the microchannel via self-assembling complexation at the interface between the organic and aqueous phases flowing laminarly, where non-cross-linked polymer-bound phosphine and ammonium tetrachloropalladate dissolved, respectively. A palladium-catalyzed coupling reaction of aryl halides and arylboronic acids was performed using the microchannel reactor to give quantitative yields of biaryls within 4 s of retention time in the defined channel region. Copyright

Full text of DOI:10.1021/ja066697r

Published on Web 12/01/2006
Instantaneous Carbon-Carbon Bond Formation Using a Microchannel
Reactor with a Catalytic Membrane
Yasuhiro Uozumi,*,† Yoichi M. A. Yamada,† Tomohiko Beppu,† Naoshi Fukuyama,†
Masaharu Ueno,‡ and Takehiko Kitamori‡
Institute for Molecular Science (IMS) and the Graduate UniVersity for AdVanced Studies, Higashi-yama 5-1,
Myodaiji, Okazaki 444-8787, Japan, and Department of Applied Chemistry, Graduate School of Engineering,
The UniVersity of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
Received September 16, 2006; E-mail: uo@ims.ac.jp
Table 1. Suzuki-Miyaura Coupling Using the Microchannel
Instantaneous catalytic molecular transformation is an important
goal in chemical synthesis. Recently, microreactor systems offering
many fundamental as well as practical advantages have been
considered as innovative devices for chemical experimentation.1-3
Molecular transformations with catalyst-immobilized microflow
reactors are representative examples of these systems, in which the
efficiency of various reactions has been found to increase because
of the vast interfacial area and the close distance of the molecular
diffusion path in the narrow space of the microreactors.4,5 More
recently, Kobayashi et al. developed a microchannel reactor bearing
a palladium catalyst immobilized on the wall to realize highly
efficient hydrogenation under triphase (solid (catalyst)-liquid
(substrate solution)-gas (molecular hydrogen)) conditions.6 Con-
sidering that the majority of chemical reactions are carried out by
mixing two unique solutions of reactants, it is not surprising that
the catalyst-immobilized microreactor for liquid-solid-liquid
triphase reaction systems would be an eagerly awaited device. If a
catalyst were installed as a membranous composite at the center of
the microchannel, two reactants could be oppositely charged into
and flow through the divided channel all the while in contact with
the vast interfacial surface of the catalytic membrane from both
front and back sides, thereby realizing an instantaneous chemical
reaction. This concept is shown schematically in Figure 1, where
a catalytic cross-coupling reaction is depicted as a typical example.
We report here the introduction of the polymer membrane of a
palladium complex inside a microchannel reactor via a self-
assembling complexation of a polymeric phosphine ligand and a
palladium species at the interface of two parallel laminar layers
flowing through the microchannel. Its use in the palladium-catalyzed
carbon-carbon bond forming reactions of aryl halides and aryl-
boronic acids under microflow conditions, where the instantaneous
production of biaryl compounds was achieved quantitatively
within 4 s of residence time in the defined channel region, is also
discussed.
Reactor Having a Catalytic Membrane.a
entry
Ar
Ar
′
yield (%) of Ar−Ar′
1b
2
3
4
5
C6H5
4-MeOC6H4
3-MeC6H4
2-MeC6H4
4-MeOC6H4
99c
96
99
3-EtOCOC6H4
3-ClC6H4
4-CF3C6H4
99
88
6
99cd
a Aryl iodide (6.3 mM in CH3CO2C2H5/i-C3H7OH (2/5); flow rate: 2.5
µL/min), arylboronic acids (9.4 mM in 18.3 mM aq Na2CO3; flow rate:
5.0 µL/min), 50 °C, residence time ) 4 s. b Aryl iodide (12.5 mM in
i-C3H7OH), arylboronic acids (18.8 mM in 37.5 mM aq Na2CO3). c TOF
) 600 h-1 d A total of 240 µg/h of the coupling product was isolated by
use of 1 microreactor.
charged the ethyl acetate solution of PA-TAP (5.0 mM; solution
A) and the aqueous solution of (NH4)2PdCl4 (1.7 mM; solution B)
oppositely into the microchannel at 25 °C for 10 min with a flow
rate of 5.0 µL/min. Two-phase parallel laminar flow was formed
under the flowing conditions and a polymer membrane was
precipitated at the interface between the two parallel flows. Parts
C and D of Figure 2 show the microscopic images of the membrane
of PA-TAP-Pd from the top and cross sections, respectively.10
To explore the utility of the microchannel bearing the PA-TAP-
Pd membrane in catalytic organic transformations, we preliminarily
elected to study the palladium-catalyzed cross-coupling of aryl
halides with arylboronic acids (the so-called Suzuki-Miyaura
reaction).11 Representative results are shown in Table 1. We were
very pleased to find that the coupling reaction proceeded smoothly
in the channel and was completed within only 4 s to give a
quantitative yield of the desired biaryl product. Thus, a solution of
aryl iodide in EtOAc/2-PrOH (6.3 mM; solution C)) and an aqueous
solution arylboronic acid with Na2CO3 (9.4 mM; solution D) were
oppositely introduced into the membrane-divided channels at 50
°C with a flow rate of 2.5 µL/min (for solution C) and 5.0 µL/min
(for solution D), respectively, and two parallel laminar layers flowed
to pass through the channel in 4 s.12 The resulting organic/aqueous
microstream was collected from the outlet of the channel to afford
a quantitative yield of the corresponding biaryls (Table 1). The
chemical yield and structure of the products were determined by
GC13 and 1H NMR. Electron-deficient as well as electron-rich aryl
halides readily coupled with arylboron reagents bearing para, meta,
and ortho EWG- and EDG-substituents to give the corresponding
biaryls in 88-99% yield. This coupling reaction includes two
Polymer deposition at the laminar interface was originally
reported by Whitesides et al. for the acid-base reaction of a
polymeric sulfonate salt and a polymeric ammonium salt,7 but, to
the best of our knowledge, nothing has appeared so far on the
interfacial deposition of transition-metal complexes with the view
of using them as catalytic membranes. The formation of the
palladium-complex membrane, poly(acrylamide)-triarylphosphine-
palladium (PA-TAP-Pd) (Figure 2a),8 was carried out with a
microchannel reactor9 having a channel pattern of 100 µm width,
40 µm depth, 140 mm length, and a Y-junction (Figure 2 B). We
† Institute for Molecular Science (IMS) and the Graduate University for
Advanced Studies.
‡ Department of Applied Chemistry.
9
15994
J. AM. CHEM. SOC. 2006, 128, 15994-15995
10.1021/ja066697r CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Figure 1. Concept of a microchannel-flow reaction system divided by a catalytic membrane.
Figure 2. Formation of catalytic membrane inside a microchannel: (A) metallo-cross-linking formation of PA-TAP-Pd polymer; (B) reaction apparatus;
(C) microscopic view of the membrane formation (top view); (D) microscopic (SEM) view of the membrane inside the channel (cross section).
intermolecular reaction stepss(i) oxidative addition forming the
arylpalladium intermediate on the membrane and (ii) reaction of
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rate. By using this catalytic membrane-divided microchannel
reactor, the fine optimization of the reaction conditions was made
possible easily by changing the concentration of each reactant
solution as well as the individual parallel laminar flow rates.
Compared to the conventional flask reaction system, this method
of performing a catalytic reaction involving multiple intermolecular
steps offers a great advantage.
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The microchannel reactor equipped with a catalytic membrane
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(10) The physical properties of the membrane are as follows: thickness ) 1.3
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(12) The coupling reaction did not proceed without the catalytic membrane
under similar conditions.
Acknowledgment. This work was supported by the CREST
program, sponsored by the JST. We also thank the JSPS and the
MEXT for partial financial support of this work.
(13) Several fractions were collected as random snapshots for each reaction
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Supporting Information Available: Experimental details and
characterization data for the catalytic membrane and the cross-coupling
reactions. This material is available free of charge via the Internet at
http://pubs.acs.org.
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J. AM. CHEM. SOC. VOL. 128, NO. 50, 2006 15995