Hydroxyapatite-bound cationic ruthenium complexes as novel heterogeneous Lewis acid catalysts for Diels-Alder and aldol reactions

Article abstract of DOI:10.1021/ja0302533

Creation of a stable and well-defined active center on a solid surface is a promising protocol for designing more efficient hybrid-catalysts that bridge the gap between homogeneous and heterogeneous catalysis. Treatment of a hydroxyapatite-bound Ru complex (RuHAP) with an aqueous solution of AgX (X = SbF₆-, TfO-) afforded a new type of cationic Ru phosphate complex, having potentially vacant coordination sites. These cationic RuHAPs exhibited Lewis acidity toward carbonyl and cyano groups, promoting Diels-Alder and Aldol reactions with high efficiencies. Moreover, no Ru leaching was detected in the above organic reactions, and then the catalysts were recyclable. Copyright

Full text of DOI:10.1021/ja0302533

Published on Web 08/30/2003
Hydroxyapatite-Bound Cationic Ruthenium Complexes as Novel
Heterogeneous Lewis Acid Catalysts for Diels-Alder and Aldol Reactions
Kohsuke Mori, Takayoshi Hara, Tomoo Mizugaki, Kohki Ebitani, and Kiyotomi Kaneda*
Department of Chemical Science and Engineering, Graduate School of Engineering Science, Osaka UniVersity,
1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan
Received April 25, 2003; E-mail: kaneda@cheng.es.osaka-u.ac.jp
The design of promising Lewis acid catalysts has attracted
considerable interest in organic synthesis because of their unique
catalytic performances across a diverse array of carbon-carbon
bond-forming reactions.1 Despite the advantages of homogeneous
metal complex catalysts,2 difficulties in recovering the expensive
catalyst metals and ligands from the reaction mixtures severely limit
their industrial applications. Attempts to overcome these problems
have so far been directed toward the anchoring of efficient soluble
systems on insoluble matrixes. These hybrid-catalysts, however,
have been inadequate due to (i) inferior activities, as compared to
homogeneous analogues, (ii) tedious multistep preparations, and
(iii) leaching of active components.
Figure 1. Proposed structures of (A) RuHAP, (B) cationic RuHAP-(I) and
-(II) (I, X ) SbF6; II, X ) OTf), and (C) Ru-enolate intermediate (X )
OTf).
Table 1. RuHAP-(I)-Catalyzed Diels-Alder Reactiona
Our alternative strategy for the design of the hybrid-catalysts
focuses on the utilization of hydroxyapatites (HAP), having a
promising ability as a macroligand for catalytically active centers.3
Recently, by using the cation-exchange method, we have success-
fully created a stable monomeric Ru phosphate complex on the
surface of the hydroxyapatite (RuHAP) as a versatile catalyst with
superior activity for the selective oxidation reactions and possessing
high reusability.3a-c Herein, we present a new type of hydroxya-
patite-bound cationic Ru complex with potentially vacant coordina-
tion sites that are generated by simple modulation of the neutral
RuHAP using silver salts. By acting as a Lewis acid toward
carbonyl and cyano groups, these cationic RuHAPs exhibited
effective catalytic activities for Diels-Alder and aldol reactions
under mild and neutral conditions.
c
entry
diene
dienophile
time (h)
yield (%)b
endo/exo
1
2d
3
4
5
6
7
1a
1a
1a
1a
1b
1c
1c
2a
2a
2b
2c
2d
2d
2e
4
4
5
4
6
6
6
92
82
92
91
89
83
93
90/10
91/9
91/9
100/0
100/0
a Reaction conditions: diene (1.2 mmol), dienophile (1 mmol), ni-
tromethane (5 mL), cationic RuHAP-(I) (0.05 g, Ru: 0.05 mmol), room
temperature. b Determined by GC based on dienophile using an internal
standard technique. c Determined by H NMR. d Cationic RuHAP-(II).
1
Treatment of a hydroxyapatite, Ca10(PO4)6(OH)2, with an aqueous
RuCl3‚nH2O solution at room temperature yielded the RuHAP (Ru
content: 0.97 mmol g-1). Characterizations by means of elemental
analysis, XPS, EDX, and Ru-K edge XAFS demonstrated the
occurrence of an equimolar substitution of Ru3+ for Ca2+ to generate
a monomeric Ru3+ species surrounded by four oxygen atoms and
one chlorine atom (Figure 1A).3a The cationic RuHAP-(I) and -(II)
were prepared by treatment of the RuHAP, at room temperature
under argon atmosphere, with an aqueous solution of AgX (1.1
room temperature. For example, reaction between cyclopentadiene
1a and methyl vinyl ketone 2a proceeded smoothly to afford
5-acetyl-2-norbornene in 92% yield with a favorable endo:exo
selectivity (entry 1). In marked contrast to the homogeneous
-
[RuIII(salen)(NO)H2O]+SbF6 complex, the RuHAP-(I) was ap-
plicable to a less reactive dienophile of methyl acrylate 2b (entry
3).6a It is generally known that product inhibition is a crucial
drawback in traditional Al-, Ti-, or B-based Lewis acid catalysis.
When the above reaction of 1a with 2b was completed, two
substrates were added, and a new mixture was allowed to further
react. The subsequent three reactions gave the corresponding
cycloadduct in over 92% yields at essentially the same rates,
showing that the present catalyst can keep its inherent activity during
the successive reactions.
From practical and environmental considerations, the develop-
ment of water-tolerant Lewis acid catalysts is particularly attractive.7
The cationic RuHAP-(II) has proved to be a useful catalyst for the
aldol reaction of nitriles with carbonyl compounds in water,
affording the corresponding R,â-unsaturated nitriles in excellent
yields.8 Representative results are summarized in Table 2. The
present catalyst exhibited a specific activity only toward nitriles as
aldol donors; other active methylene compounds such as 2,4-
pentanedione, dimethyl malonate, and nitroethane, whose pKa values
-
equiv of Ru; X ) SbF6 and TfO-, respectively). The absence of
chlorine was confirmed by XPS analysis of the cationic RuHAPs.4
The Ru K-edge XANES spectrum was quite similar to that of the
parent RuHAP, showing that the Ru species exists in the 3+
oxidation state.4 In the Fourier transform (FT) of k3-weighted Ru
K-edge EXAFS, there were no peaks around 3.5 Å due to the
presence of contiguous Ru sites. The inverse FTs of the cationic
RuHAPs were well fitted by replacing the Ru-Cl bond (2.32 Å)
in the RuHAP with a Ru-O bond (2.10 Å) assignable to a weakly
coordinated aqua ligand.5 Consequently, a well-defined cationic Ru
phosphate complex can be created on the hydroxyapatite surface,
as illustrated in Figure 1B.
As can be seen from Table 1, several Diels-Alder reactions were
successfully accelerated by the use of the cationic RuHAP-(I) as
an effective heterogeneous Lewis acid catalyst in nitromethane at
9
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J. AM. CHEM. SOC. 2003, 125, 11460-11461
10.1021/ja0302533 CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Table 2. RuHAP-(II)-Catalyzed Aldol Reaction Using Nitrilesa
with the formation of a Ru-enolate species surrounded by three
oxygens, as shown in Figure 1C. It is reasonable to suggest that
the cationic RuHAP-(II)-catalyzed aldol reaction using nitriles
involves the Ru-enolate intermediate, which is generated through
the cooperative catalysis between the cationic Ru species and the
basic phosphate ligand; the former activates the nitrile as a Lewis
acid, while the latter phosphate abstracts an acidic R-proton of the
nitrile to generate an enolate species. The Diels-Alder reaction
can be induced by the Lewis acid site that originates from the
cationic Ru species. Furthermore, the hydroxyapatite effectively
serves as a suitable macroligand for the catalytically active Ru
center, which allows strict steric control of the reaction intermediate.
Vide supra, the high trans stereoselectivity of 7 (trans:cis ) 9:1),
as compared to those of other homogeneous systems,9,11 and the
effective suppression of product inhibition in the Diels-Alder
reaction can be attributed to the steric hindrance imposed by solid
surface.
In summary, the design of novel Lewis acid catalysts and their
effectiveness for useful carbon-carbon bond-forming reactions were
demonstrated. No Ru leaching in the reaction media was observed,
and then the catalyst was recyclable. Our protocol based on
hydroxyapatites as a macroligand represents an opportunity for the
nanoscale design of functionalized catalysts, and further extension
to asymmetric catalysis remains to be explored.
donor
acceptor
entry
R )
1
R )
2
R )
3
time (h)
yield (%)b
1
CO2Et (3a)
CO2Et (3a)
CONH2 (3b)
CO2Et (3a)
CO2Et (3a)
CO2Et (3a)
CN (3c)
Ph
Ph
Ph
H (4a)
H (4a)
H (4a)
H (4b)
H (4c)
H (4d)
Me (4e)
4
4
4
8
3
5
6
3
5
>99
78
2c
3
98
95
95
92
4d
5d
6d
7e
8e
9e
PhCHdCH
n-C3H7
3-cyclohexene
Ph
82
CN (3c)
CN (3c)
-C5H10- (4f)
-C4H8- (4g)
>99
91
a Reaction conditions: nitrile (1.0 mmol), carbonyl compound (1.2
mmol), cationic RuHAP-(II) (0.05 g, Ru: 0.05 mmol), H2O (5 mL), room
temperature. b Determined by GC based on nitrile using an internal standard
technique. c Cationic RuHAP-(I). d 50 °C. e 80 °C.
Scheme 1
Scheme 2
Acknowledgment. We thank Dr. S. Nishiyama (Kobe Univer-
sity), Dr. T. Shishido (Tokyo Gakugei University), and Dr. T. Uruga
(JASRI) for XAFS measurements.
Supporting Information Available: Experimental procedures,
XAFS analysis, and IR measurements (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
are similar to that of ethylcyanoacetate 3a, did not yield aldol
products under the above conditions. It is notable that treatment of
R,â-unsaturated carbonyl compounds 5a-b with 3c gave the 1,2-
addition products in high yields, as shown in Scheme 1; attack of
an enolate species on the carbonyl function exclusively occurred
without the 1,4-addition. This phenomenon is quite distinct from
that of the RuIIH2(PPh3)4-catalyzed reaction, whose products are
predominantly a result of the 1,4-addition.8d In terms of the HSAB
principle, a trivalent Ru enolate species generated from the RuHAP
may behave as a harder nucleophile than that from the divalent Ru
species, which allows a favorable interaction with the carbonyl
groups to enhance the 1,2-addition. Furthermore, the present
catalytic system is highly suitable for large-scale operations. A 100
mmol scale reaction of 3a with 4a using 0.2 mol % of the Ru
catalyst provided 94% of (E)-ethyl 2-cyano-3-phenyl-2-propenoate
within 24 h. More significantly, no Ru leaching even under aqueous
conditions was detected by ICP analysis whose detection limit is
0.03 ppm. The recovered catalyst could be reused without loss of
its activity; over 97% yields were attained for the three recycling
reactions of 3a with 4a.
References
(1) (a) SelectiVites in Lewis Acid Promoted Reactions; Schinzer, D., Ed.;
Kluwer Academic Publishers: Dordrecht, The Netherlands, 1989. (b)
Santelli, M.; Pons, J.-M. Lewis Acids and SelectiVity in Organic Synthesis;
CRS Press: Boca Raton, FL, 1995. (c) Lewis Acids in Organic Synthesis;
Yamamoto, H., Ed.; Wiley-VCH: Weinheim, 2000.
(2) (a) Bosnich, B. Aldrichimica Acta 1998, 31, 76. (b) Murahashi, S.-I.;
Takaya, H. Acc. Chem. Res. 2000, 33, 225.
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Am. Chem. Soc. 2000, 122, 7144. (b) Mori, K.; Yamaguchi, K.; Mizugaki,
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(4) For XPS and XAFS analyses, sodium salts such as NaSbF6 and NaOTf
were used instead of silver salts to avoid an interference of insoluble AgCl.
(5) See Supporting Information.
(6) For some recent reports on Lewis acid-catalyzed Diels-Alder reaction,
see: (a) Odenkirk, W.; Rheingold, A.-L.; Bosnich, B. J. Am. Chem. Soc.
1992, 114, 6392. (b) Zhu, Z.; Espenson, J. H. J. Am. Chem. Soc. 1997,
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Viton, F.; Bernardinelli, G. Angew. Chem., Int. Ed. 2001, 40, 4481.
(7) For example, see: Kobayashi, S.; Manabe, K. Acc. Chem. Res. 2002, 35,
209.
(8) For leading references of transition metal complex-catalyzed aldol reaction
of nitriles, see: (a) Lin, Y.; Zhu, X.; Xiang, M. J. Organomet. Chem.
1993, 448, 215. (b) Hirano, M.; Ito, Y.; Hirai, M.; Fukuoka, A.; Komiya,
S. Chem. Lett. 1993, 2057. (c) Nemoto, H.; Kubota, Y.; Yamamoto, Y. J.
Chem. Soc., Chem. Commun. 1994, 1665. (d) Murahashi, S.-I.; Naota,
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(9) It is said that the base abstracts a proton of isonitriles coordinating to the
metals, see: (a) Nesper, R.; Pregosin, P. S.; Pu¨ntener, K.; Wo¨rle, M. HelV.
Chim. Acta 1993, 76, 2239. (b) Stark, M. A.; Richards, C. J. Tetrahedron
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(10) (a) Joris, S. J.; Amberg, C. H. J. Phys. Chem. 1971, 75, 3172. (b) Elliott,
J. C. Structure and Chemistry of the Apatites and Other Calcium
Orthophosphates; Elsevier: Amsterdam, 1994.
For the aldol reaction of methyl isocyanoacetate 6 with 4a, the
cationic RuHAP-(II) gave the corresponding oxazoline 7 in 90%
yield without any additives (Scheme 2), whereas the [Ru(salen)-
-
(NO)H2O]+SbF6 complex required a Hunig’s base (i-Pr2NEt) to
complete the catalytic cycle.9 The IR spectrum of the cationic
RuHAP-(II), upon treatment with 3b, showed a shift of the ν(CN)
band toward 2093 cm-1 in comparison with the free cyano group
at 2260 cm-1, along with a new peak at 870 cm-1 assigned to the
2-
P-OH group of a HPO4 ion on the hydroxyapatite surface.5,10
The FT-EXAFS analysis for the above treated sample indicated
the decrease of the coordination number of the nearest neighboring
Ru-O bond (1.98 Å) from 4 to 3, and the appearance of an
additional second Ru-O bond (2.28 Å) attributable to a weak
interaction between Ru and P-OH.5 These results are in agreement
(11) Steric repulsion between the phenyl groups of 4a and the isocyano moiety
bound to the Ru phosphate complex in synclinal configuration severely
limits the formation of cis-isomer.
JA0302533
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