in Handbook of Combinatorial Chemistry, ed. K. C. Nicolaou,
R. Hanko and W. Hartwig, Wiley-VCH, Weinheim, 2002, ch. 19;
(b) Y. Uozumi, Top. Curr. Chem., 2004, 242, 77; (c) Z. Wang,
G. Chen and K. Ding, Chem. Rev., 2009, 109, 322; (d) J. Lu and
P. H. Toy, Chem. Rev., 2009, 109, 815.
2 (a) Y. M. A. Yamada, Chem. Pharm. Bull., 2005, 53, 723 (review);
(b) Y. M. A. Yamada, H. Guo and Y. Uozumi, Org. Lett., 2007, 9,
1501; (c) Y. M. A. Yamada and Y. Uozumi, Tetrahedron, 2007, 63,
8492; (d) Y. M. A. Yamada, Y. Maeda and Y. Uozumi, Org. Lett.,
2006, 8, 4259; (e) Y. M. A. Yamada and Y. Uozumi, Org. Lett.,
2006, 8, 1375.
Scheme 3 Microscopic observation of l-device 1 after the reaction
(120 min) of 4a and 5a.
3 (a) J.-i. Yoshida, A. Nagaki and T. Yamada, Chem.–Eur. J., 2008,
14, 7450; (b) C. Wiles and P. Watts, Eur. J. Org. Chem., 2008, 1655;
(c) J. Kobayashi, Y. Mori and S. Kobayashi, Chem.–Asian J.,
2006, 1, 22–35; (d) K. Jahnisch, V. Hessel, H. Lowe and M. Baerns,
¨
¨
Angew. Chem., Int. Ed., 2004, 43, 406; (e) H. Pennemann, V. Hessel
and H. Lowe, Chem. Eng. Sci., 2004, 59, 4789; (f) P. D. I. Fletcher,
¨
S. J. Haswell, E. Pombo-Villar, B. H. Warrington, P. Watts,
S. Y. F. Wong and X. Zhang, Tetrahedron, 2002, 58, 4735;
(g) S. J. Haswell, R. J. Middleton, B. O’Sullivan, V. Skelton,
P. Watts and P. Styring, Chem. Commun., 2001, 391.
Scheme 4 Intermolecular substitution vs. intramolecular elimination.
4 For recent reports on flow-reactors bearing immobilized palladium
catalysts, see: (a) G. M. Greenway, S. J. Haswell, D. O. Morgan,
V. Skelton and P. String, Sens. Actuators, B, 2000, 63, 153;
(b) G. Jas and A. Kirschning, Chem.–Eur. J., 2003, 9, 5708;
(c) J. Kobayashi, Y. Mori, K. Okamoto, R. Akiyama, M. Ueno,
T. Kitamori and S. Kobayashi, Science, 2004, 304, 1305;
Representative results of the allyl–aryl coupling of a variety
of allyl esters and arylborate reagents are shown in Table 1.
Coupling with PhB(OH)2–Na2CO3 (aqueous flow) showed
moderate reactivity under otherwise similar conditions to give
6a in 43% yield (entry 4). Both the regioisomeric 1-acetoxy-1-
phenyl-2-propene (7) and cinnamyl methyl carbonate (4b) also
reacted with 5a under the same conditions to give quantitative
yields of 6a in 1 second (entries 5 and 6). The microflow
reaction of 4a with sodium tetrakis(4-fluorophenyl)borate (5b)
under similar conditions gave 1-(4-fluorophenyl)-3-phenyl-2-
propene (6b) in 94% yield (entry 7).
(d) U. Kunz, H. Schonfeld, W. Solodenko, G. Jas and
¨
A. Kirschning, Ind. Eng. Chem. Res., 2005, 44, 8458;
(e) A. Kirschning, W. Solodenko and K. Mennecke, Chem.–Eur.
J., 2006, 12, 5972; (f) I. R. Baxendale, C. M. Griffiths-Jones,
S. V. Ley and G. K. Tranmer, Chem.–Eur. J., 2006, 12, 4407;
(g) T. Fukuyama, M. T. Rahman, M. Sato and I. Ryu, Synlett,
2008, 151.
5 (a) P. J. A. Kenis, R. F. Ismagilov, S. Takayama and
G. M. Whitesides, Acc. Chem. Res., 2000, 33, 841; (b) P. J. A.
Kenis, R. F. Ismagilov and G. M. Whitesides, Science, 1999, 285,
83; (c) B. Zhao, N. O. L. Viernes, J. S. Moore and D. J. Beebe,
J. Am. Chem. Soc., 2002, 124, 5284; (d) H. Hisamoto, Y. Shimizu,
K. Uchiyama, M. Tokeshi, Y. Kikutani, A. Hibara and
T. Kitamori, Anal. Chem., 2003, 75, 350.
It is noteworthy that the methyl vinyl carbinol esters 8a and
8b underwent the palladium-catalyzed allyl–aryl coupling to
give the corresponding coupling product 9 with excellent
selectivity, though, under identical conditions, the chemical
yield was moderate (33 and 57% yield, respectively). The
reaction of methyl vinyl carbinol esters must proceed via
the corresponding p-allylpalladium intermediate bearing a
b-sp3-hydride which often suffers from b-elimination under
the palladium-catalyzed conditions to give the undesired
1,3-dienes (Scheme 4).10,11, However, no trace of the 1,3-diene,
phenylbutadiene, was observed in the reactions using l-device
1, presumably due to the extremely fast intermolecular
coupling pathway (vs. intramolecular b-elimination).
6 Y. Uozumi, Y. M. A. Yamada, T. Beppu, N. Fukuyama, M. Ueno
and T. Kitamori, J. Am. Chem. Soc., 2006, 128, 15994–15995.
7 Purchased from Institute of Microchemical Technology, Co., Ltd.
(Kanagawa, Japan; URL: http://www.i-mt.co.jp).
8 Preparation of PA-TAP-Pd for the Suzuki–Miyaura reaction and
Mizoroki–Heck reaction, see: (a) Y. M. A. Yamada, K. Takeda,
H. Takahashi and S. Ikegami, Tetrahedron, 2004, 60, 4087;
(b) Y. M. A. Yamada, K. Takeda, H. Takahashi and S. Ikegami,
J. Org. Chem., 2003, 68, 7733; (c) Y. M. A. Yamada, K. Takeda,
H. Takahashi and S. Ikegami, Tetrahedron Lett., 2003, 44, 2379;
(d) Y. M. A. Yamada, K. Takeda, H. Takahashi and S. Ikegami,
Org. Lett., 2002, 4, 3371.
9 (a) H. Tsukamoto, M. Sato and Y. Kondo, Chem. Commun., 2004,
1200; (b) C. Najera, J. Gil-Molto and S. Karlstrom, Adv. Synth.
´ ´
¨
In conclusion, a variety of palladium membranes were
installed inside microchannel reactors via the ‘‘ship-in-a-bottle’’
protocol of our molecular convolution method to provide micro-
reaction devices. The m-devices were applied to the instantaneous
allyl–aryl coupling reaction of allylic esters with tetraarylborates
to afford the corresponding coupling products in quantitative
yields within 1 second of residence time. Extension of catalytic
membrane-installed microchannel reactors to other organic
transformations is currently in progress.
Catal., 2004, 346, 1798; (c) K. Manabe, K. Nakada, N. Aoyama and
S. Kobayashi, Adv. Synth. Catal., 2005, 347, 1499; (d) M. Moreno-
Manas, R. Pleixats and S. Villarroya, Organometallics, 2001, 20, 4524;
(e) G. W. Kabalka, G. Dong and B. Venkataiah, Org. Lett., 2003, 5,
893; (f) E. Paetzold and G. Oehme, J. Mol. Catal. A: Chem., 2000,
152, 69; (g) E. Blart, J. P. Genet, M. Safi, M. Savignac and D. Sinou,
Tetrahedron, 1994, 50, 505.
10 Palladium-catalyzed arylation of secondary allylic acetates
possessing b-sp2 or sp3-hydride, see: (a) G. Ortar, Tetrahedron
Lett., 2003, 44, 4311; (b) D. Bouyssi, V. Gerusz and G. Balme, Eur.
J. Org. Chem., 2002, 2445; (c) J.-Y. Legros and J.-C. Flaud,
Tetrahedron Lett., 1990, 31, 7453.
Notes and references
11 Resin-supported Pd catalyzed arylation of secondary allylic esters
possessing b-sp2 or sp3-hydride, see: Y. Uozumi, H. Danjo and
T. Hayashi, J. Org. Chem., 1999, 64, 3384.
1 For a recent review of solid-phase reactions using palladium
catalysts, see: (a) Y. Uozumi and T. Hayashi, ‘‘Solid-Phase
Palladium Catalysis for High-throughput Organic Synthesis’’,
ꢁc
This journal is The Royal Society of Chemistry 2009
5596 | Chem. Commun., 2009, 5594–5596