An efficient, ligand-free, heterogeneous supported copper hydroxide catalyst for the synthesis of N,N-bicyclic pyrazolidinone derivatives

Article abstract of DOI:10.1002/chem.201002793

Truly heterogeneous with retention of its high performance: The 1,3-dipolar cycloaddition of azomethine imines to terminal alkynes was efficiently promoted by the easily prepared, inexpensive, supported copper hydroxide, Cu(OH) _x/Al₂O₃. Various kinds of azomethine imines and terminal alkynes could be utilized as dipoles and dipolarophiles, respectively, to form the corresponding N,N-bicyclic pyrazolidinone derivatives in high yields.

Full text of DOI:10.1002/chem.201002793

COMMUNICATION
DOI: 10.1002/chem.201002793
An Efficient, Ligand-Free, Heterogeneous Supported Copper Hydroxide
Catalyst for the Synthesis of N,N-Bicyclic Pyrazolidinone Derivatives
Kazuaki Yoshimura, Takamichi Oishi, Kazuya Yamaguchi, and Noritaka Mizuno*[a]
The synthesis of pyrazolidinone and pyrazolone heterocy-
cles is of great importance because they have been used as
dyes, color pigments, pharmaceuticals, and agricultural
chemicals.[1] In particular, N,N-bicyclic pyrazolidinone deriv-
atives show very important bioactivities and have been
widely investigated as pesticides, herbicides, and analogues
of b-lactam antibiotics such as penicillin and cephalospor-
in.[2] The 1,3-dipolar cycloaddition of azomethine imines to
alkynes (an analogous reaction to the Huisgen 1,3-dipolar
cycloaddition[3]), first reported by Dorn and Otto in 1968,[4]
is one of the most useful procedures for the synthesis of
N,N-bicyclic pyrazolidinone derivatives because many func-
tional groups remain intact in the presence of azomethine
imines and alkynes.[2] However, this uncatalyzed cycloaddi-
tion gives a mixture of regioisomers in the case of unsym-
metrically substituted alkynes;[5] for example, when the ther-
mally induced cycloaddition of 1-benzylidene-3-oxo-1-pyra-
zolidinium-2-ide (1a) to ethyl propiolate (2a) was carried
out under the conditions described in Equation (1), a regioi-
someric mixture of 3aa and 3aa’ was obtained.
tion is a powerful method for the synthesis of N,N-bicyclic
pyrazolidinone derivatives, only a few catalysts have been
reported until now; for example, CuI/nitrogen-based li-
gands,[7] [Cu
ACHTNUGTRENNUG(m-OH)ACHTUNGTRNE(NUGN tmen)]2Cl2 (tmen=N,N,N’,N’-tetrame-
thylethylenediamine),[8] and copper(I)-exchanged zeolites.[9]
In addition, these systems have shortcomings such as 1) low
turnover frequency (TOF) and turnover number (TON), 2)
difficulty in catalyst/product(s) separation and catalyst
reuse, and/or 3) indispensability of additives such as stabiliz-
ing ligands. Therefore, the development of efficient catalysts
(in particular, heterogeneous catalysts are desirable[10]) for
the cycloaddition is still a challenging subject.
Herein, we report that the 1,3-dipolar cycloaddition is ef-
ficiently promoted by the easily prepared inexpensive sup-
ported copper hydroxide catalyst, Cu(OH)x/Al2O3.[11] Vari-
ous kinds of azomethine imines and terminal alkynes could
be utilized as dipoles and dipolarophiles, respectively, to
form the corresponding N,N-bicyclic pyrazolidinone deriva-
tives in moderate to high yields. In addition, the observed
catalysis was truly heterogeneous, and Cu(OH)x/Al2O3 could
be reused with retention of its high catalytic performance.
Initially, the catalytic activities for the 1,3-dipolar cycload-
dition of 1a to 2a were compared for various copper-based
catalysts. The supported copper hydroxide Cu(OH)x/Al2O3
(see the Experimental Section for the preparation and char-
acterization) showed the highest catalytic activity and gave
the corresponding N,N-bicyclic pyrazolidinone 3aa in an
almost quantitative yield (Table 1, entry 1). It was confirmed
1
Generally, it is widely accepted that the 1,3-dipolar cyclo-
addition of organic azides to terminal alkynes proceeds re-
gioselectively in the presence of copper catalysts and that a
(in situ generated) copper(I) acetylide is the catalytically
active species.[6] Similarly, Fu and co-workers reported for
the first time that the 1,3-dipolar cycloaddition of azome-
thine imines to terminal alkynes also proceeds regioselec-
tively in the presence of copper(I) salts and certain nitro-
gen-based ligands.[7] Although copper-catalyzed cycloaddi-
by the H NMR analysis that the Cu(OH)x/Al2O3-catalyzed
cycloaddition exclusively gave 3aa without the formation of
the regioisomer 3aa’. The cycloaddition hardly proceeded in
the absence of the catalysts (Table 1, entry 10) or in the
presence of Al2O3 (Table 1, entry 9). The catalyst precursor
CuCl2·2H2O and commonly utilized copper salts such as
CuCl and CuSO4·5H2O were not effective for the cycloaddi-
tion (Table 1, entries 3–5). The catalytic activity of
Cu(OH)x/Al2O3 was much higher than those of CuO, unsup-
ported Cu(OH)2, and a physical mixture of Cu(OH)2 and
Al2O3 (Table 1, entries 6–8). The catalytic activity of
Cu(OH)x/Al2O3 was higher than that of CuCl2 supported on
Al2O3 prepared without the base treatment (CuCl2/Al2O3,
see the Supporting Information for the preparation)
(Table 1, entry 1 vs. entry 2). These results suggest that the
generation of the “highly dispersed copper hydroxide spe-
cies” on the surface of supports is very important to achieve
high catalytic performance.
[a] K. Yoshimura, T. Oishi, Dr. K. Yamaguchi, Prof. Dr. N. Mizuno
Department of Applied Chemistry, School of Engineering
The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
Fax : (+81)3-5841-7220
E-mail: tmizuno@mail.ecc.u-tokyo.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002793.
Chem. Eur. J. 2011, 17, 3827 – 3831
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Table 1. 1,3-Dipolar cycloaddition reaction of 1a to 2a with various
Table 2. Cu(OH)x/Al2O3-catalyzed 1,3-dipolar cycloaddition of azome-
thine imines (dipoles) to terminal alkynes (dipolarophile).[a]
copper catalysts.[a]
Entry
Catalyst
Yield of 3aa[b] [%]
1
2
3
4
Cu(OH)x/Al2O3
CuCl2/Al2O3
CuCl2·2H2O
CuCl
95
45
2
3
5
6
CuSO4·5H2O
CuO
1
3
Entry
Dipole
Dipolarophile
Product
t [h]
Yield[b] [%]
7
Cu(OH)2
Cu(OH)2 + Al2O3
Al2O3
<1
4
4
1
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
1 f
1g
2a
2a
2a
2b
2c
2d
2e
2a
2a
2a
2a
2a
2a
3aa
3aa
3aa
3ab
3ac
3ad
3ae
3ba
3ca
3da[d]
3ea
3 fa
3ga
2.5
2.5
2.5
2.5
4.5
24
3.5
4.5
2
4
12
2.5
12
95
94
93
96
97
55
88
93
92
98
80
88
85
8[c]
9[d]
10
2[c]
3[c]
4
none
3
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.55 mmol), catalyst (Cu:
1.5 mol% with respect to 1a), [D8]toluene (2 mL), 408C, Ar (1 atm),
2.5 h. [b] Yields (based on 1a) were determined by 1H NMR spectrosco-
py. [c] A mixture of Cu(OH)2 (Cu: 1.5 mol%) and Al2O3 (30 mg). [d]
Al2O3 (30 mg).
5
6
7
8
9
10
11
12
13
To examine whether the observed catalysis is derived
from the solid Cu(OH)x/Al2O3 catalyst or leached copper
species, the cycloaddition of 1a to 2a was carried out under
the conditions described in Table 1, and the Cu(OH)x/Al2O3
catalyst was removed from the reaction mixture by filtration
at approximately 50% conversion of substrates. After re-
moval of the Cu(OH)x/Al2O3 catalyst, 1a (0.25 mmol) was
newly added to the filtrate, and the resulting solution was
again heated at 408C under an Ar atmosphere. In this case,
no further production of 3aa was observed. In addition, it
was confirmed by inductively coupled plasma atomic emis-
sion spectroscopy that copper species were hardly detected
in the filtrate (below 7 ppm after the cycloaddition). These
results rule out any contribution to the observed catalysis
from copper species that leached into the reaction solution,
and the observed catalysis is heterogeneous.[12]
Next, the scope of the Cu(OH)x/Al2O3-catalyzed cycload-
dition was examined. The cycloaddition of azomethine
imine 1a (as a dipole) to various terminal alkynes bearing
electron-withdrawing groups (as dipolarophiles) including
propargylic esters (2a and 2b), propargylic ketones (2c and
2d), and tosylacetylene (2e) gave the corresponding N,N-bi-
cyclic pyrazolidinone derivatives in moderate to high yields
(Table 2, entries 1 and 4–7). Various kinds of azomethine
imines could be utilized as dipoles for the present cycloaddi-
tion. As for the azomethine imines with para-substituted
benzylidene groups at the dipole ends (1a–1c), the reaction
rates of the dipoles with electron-withdrawing substituents
were larger than those with electron-donating ones (Table 2,
entries 1, 8, and 9). Monomethyl- (1d) and dimethyl-substi-
tuted (1e) dipoles at the 5-positions also gave the corre-
sponding N,N-bicyclic pyrazolidinone derivatives in high
yields (Table 2, entries 10 and 11), whereas these reactions
required longer reaction times in comparison with that of
unsubstituted 1a because of the steric hindrance of methyl
groups in 1d and 1e. The cycloaddition of monomethyl-sub-
[a] Reaction conditions: dipole (0.5 mmol), dipolarophile (0.55 mmol),
Cu(OH)x/Al2O3 (Cu: 1.5 mol% with respect to dipoles), [D8]toluene
(2 mL), 408C, Ar (1 atm). [b] Yields (based on dipoles) were determined
by 1H NMR spectroscopy. [c] Reuse experiments; entry 2 (the 1st reuse)
and entry 3 (the 2nd reuse). [d] syn/anti=86:14. The ratio was deter-
1
mined by H NMR spectroscopy.
stituted 1d to 2a showed a high syn diastereoselectivity for
the methyl and phenyl groups in 3da (syn/anti=86:14)
(Table 2, entry 10), suggesting that the addition of an alkyne
(acetylide species) mainly takes place anti to the methyl
group in 1d. Also, dipoles with alkyl groups at the dipole
ends (1 f and 1g) worked well as reaction partners of dipo-
larophiles (Table 2, entries 12 and 13). The Cu(OH)x/Al2O3
catalyst retrieved after the cycloaddition could be reused
without an appreciable loss of its high catalytic perfor-
mance; for the cycloaddition of 1a to 2a with the retrieved
catalyst under the conditions described in Table 2, 94% and
93% yields of 3aa were obtained for the 1st and the 2nd
reuse experiments, respectively (Table 2, entries 2 and 3).
Notably, the amount catalyst required could be reduced
considerably; in a 5 mmol-scale cycloaddition of 1a to 2a
using only 0.15 mol% of Cu(OH)x/Al2O3 (at 408C), the
TOF was 46 hÀ1, and the TON reached up to 646 [Eq. (2)].
These values were much higher than those previously re-
ported for the copper-based heterogeneous catalyst of cop-
per(I)-exchanged zeolite (TOF: 4.5 hÀ1, TON: 18 at 608C).[9]
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Heterogeneous Cycloaddition
COMMUNICATION
The Cu(OH)x/Al2O3 catalyst (Cu: 1.4 mol% with respect
to 2a) was treated with 2a in [D8]toluene (0.27m, 2 mL) at
408C for 1 h under an Ar atmosphere, and the UV/Vis spec-
trum of the retrieved catalyst was measured. The intensity
of the absorption band around 700 nm assignable to the d–d
transition of copper(II) species[13] decreased considerably
(Figure 1, inset). Furthermore, it was confirmed by the GC-
Scheme 1. A possible reaction mechanism for the present Cu(OH)x/
Al2O3-catalyzed cycloaddition.
The cycloaddition of 1a to deuterated ethyl propiolate 2a’
(D content at the terminal position: 94%)[18] gave 3aa in
88% yield, and the deuterium content at the 3-position of
3aa was 32% [Eq. (4)]. When the 1,3-dipolar cycloaddition
of 1a to 2a’ was carried out in the presence of Cu(OH)x/
Al2O3 pretreated with D2O (see the Supporting Informa-
tion), the deuterium was introduced at the 3-position of 3aa,
and the content was 78% [Eq. (5)]. Therefore, the hydrogen
at the 3-position of 3aa mainly comes from water (or
proton) on the catalyst.[19] The results of the deuterium-la-
beling experiments are consistent with the above-mentioned
possible mechanism involving the acetylide formation (via
Figure 1. The UV/Vis spectra of the fresh Cu(OH)x/Al2O3 catalyst (spec-
trum A) and the catalyst retrieved after the treatment with 2a (spectrum
B).
MS analysis that the corresponding diyne (4aa)[14] was pro-
duced during the treatment. These results suggest that the
following reduction of copper(II) to copper(I) species by an
alkyne likely proceeds at the initial stage of the cycloaddi-
tion (step (i) in Scheme 1) [Eq. (3)].[15]
À
cleavage of the terminal C H bond) and the ligand ex-
change between the vinyl copper intermediate and water (or
proton).
In addition to a decrease in the intensity of the d–d transi-
tion band, a new broad absorption band around 450 nm as-
signable to copper(I) acetylide species appeared
(Figure 1),[16] suggesting that the reaction of the copper(I)
species with an alkyne takes place to generate the catalyti-
cally active copper(I) acetylide species (step (ii) in
Scheme 1).[17] Upon treatment of the catalyst (treated with
2a) with 1a (two equiv) in [D8]toluene (2 mL) at 408C for
2.5 h, the absorption band due to the acetylide species disap-
peared with the formation of an almost equimolar amount
of 3aa (37.1 mmol) with respect to the copper species used
(33.5 mmol). The reaction of the acetylide species with an
azomethine imine likely proceeds to form the corresponding
vinyl copper species (step (iii) in Scheme 1),[9] followed by
the ligand exchange between the vinyl copper species and
proton (or water) to form the corresponding N,N-bicyclic
pyrazolidinone and the copper(I) species (step (iv) in
Scheme 1), and the catalytic cycle is completed.
In conclusion, Cu(OH)x/Al2O3 could act as an efficient
heterogeneous catalyst for the 1,3-dipolar cycloaddition re-
action of azomethine imines to terminal alkynes. The ob-
served catalysis was intrinsically heterogeneous, and the cat-
alyst was reusable without significant loss of its catalytic ac-
tivity. The in situ generated copper(I) species is the catalyti-
cally active species for the present cycloaddition. The pres-
ent systems have the following significant advantages; 1)
Chem. Eur. J. 2011, 17, 3827 – 3831
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N. Mizuno et al.
[2] a) S. Radl in Bicyclic Systems with Two Ring Junction Nitrogen
Atom: Comprehensive Heterocyclic Chemistry II, Vol 8 (Eds.: A. R.
Katritzky, C. W. Rees, E. F. V. Scriven), Elsevier, Oxford, 1996,
p. 747–832; b) M. I. Konaklieva, B. J. Plotlin, Curr. Med. Chem.
Anti-Infect. Agents 2003, 2, 287–302; c) S. Hanessian, G. McNaugh-
ton-Smith, H.-G. Lombart, W. D. Lubell, Tetrahedron 1997, 53,
12789–12854, and references therein.
applicability to various dipoles and dipolarophiles, 2) much
higher catalytic activities than those of the previously re-
ported heterogeneous catalyst,[9] 3) no use of stabilizing li-
gands, 4) easy catalyst/product separation, and 5) reusability
of the Cu(OH)x/Al2O3 catalyst.
[3] a) R. Huisgen in 1,3-Dipolar Cycloaddition Chemistry (Ed.: A.
Padwa) Wiley, New York, 1984, p. 1–176; b) K. V. Gothelf, K. A.
Jørgensen, Chem. Rev. 1998, 98, 863–910; c) Synthetic Applications
of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and
Natural Products (Eds.: A. Padwa, W. H. Pearson) Wiley, New
York, 2003.
[4] a) H. Dorn, A. Otto, Chem. Ber. 1968, 101, 3287–3301; b) H. Dorn,
A. Otto, Angew. Chem. 1968, 80, 196; Angew. Chem. Int. Ed. Engl.
1968, 7, 214–215.
Experimental Section
The supported copper hydroxide Cu(OH)x/Al2O3 was prepared according
to the literature procedure.[11] The aqueous solution (60 mL) of
CuCl2·2H2O (0.085 g, 8.3 mm) containing the Al2O3 powder (2.0 g) cal-
cined at 5508C was vigorously stirred at room temperature. After 15 min,
the pH of the solution was quickly adjusted to 12 by addition of an aque-
ous solution of NaOH (1.0m, base treatment), and the resulting slurry
was further stirred for 24 h. The solid was then filtered off, washed with a
large amount of water, and dried in vacuo to afford Cu(OH)x/Al2O3
(2.0 g) as a light blue powder. This powder contained 1.6 wt% copper
and approximately 10 wt% water. The XRD pattern of Cu(OH)x/Al2O3
was the same as that of the parent Al2O3 support and no signals due to
copper metal (clusters) and copper oxides were observed. The XPS spec-
trum of Cu(OH)x/Al2O3 showed the binding energies of Cu 2p3/2 at
933.8 eV (full width at the half maximum: 3.7 eV) with the shakeup satel-
lite peak at 942.3 eV, suggesting that the oxidation state of the copper
species is +2.[20] No chlorine was detected in Cu(OH)x/Al2O3 by the XPS
measurement. In the radial distribution functions from the Fourier trans-
formation of the k3-weighed EXAFS for Cu(OH)x/Al2O3, the signals due
to Cu–O–Cu and Cu–Cu shells were hardly observed. The absence of
these shell signals suggests that no networks of linked copper species
exist in Cu(OH)x/Al2O3. All these results suggest that copper(II) hydrox-
ide is highly dispersed on Al2O3.
[5] a) L. N. Jungheim, S. K. Sigmund, J. Org. Chem. 1987, 52, 4007–
4013; b) L. N. Jungheim, S. K. Sigmund, N. D. Jones, J. K. Swartzen-
druber, Tetrahedron Lett. 1987, 28, 289–292; c) C. Turk, B. Stanov-
ˇ
ˇ
ˇ
ˇ
nik, L. Golic, S. Golic-Grdadolik, A. Golobic, L. Selic, Helv. Chim.
Acta 2001, 84, 146–156.
[6] a) V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless,
Angew. Chem. 2002, 114, 2708–2711; Angew. Chem. Int. Ed. 2002,
41, 2596–2599; b) C. W. Tornøe, C. Christensen, M. Meldal, J. Org.
Chem. 2002, 67, 3057–3064; c) V. D. Bock, H. Hiemstra, J. H. van
Maarseveen, Eur. J. Org. Chem. 2006, 51–68, and references there-
in.
[7] a) R. Shintani, G. C. Fu, J. Am. Chem. Soc. 2003, 125, 10778–10779;
b) A. Suꢁrez, C. W. Downey, G. C. Fu, J. Am. Chem. Soc. 2005, 127,
11244–11245.
[8] T. Oishi, K. Yoshimura, K. Yamaguchi, N. Mizuno, Chem. Lett.
2010, 39, 1086–1987.
[9] Although copper(I)-exchanged zeolite can easily be retrieved from
the reaction mixture and reused several times, it has not been re-
ported in the following reference that the reaction proceeds with the
filtrate after the removal of the catalyst or not: M. Keller, A. S. S.
Sido, P. Pale, J. Sommer, Chem. Eur. J. 2009, 15, 2810–2817.
[10] The development of easily recoverable and recyclable heterogene-
ous catalysts by filtration or centrifugation can solve the problems
of the homogeneous systems and has received particular interest for
the synthesis of fine chemicals: R. A. Sheldon, H. van Bekkum,
Fine Chemical through Heterogeneous Catalysis, Wiley, Weinheim,
2001.
[11] Quite recently, we have reported that the supported copper hydrox-
ides can act as efficient heterogeneous catalysts for the oxidative ho-
mocoupling of alkynes and the 1,3-dipolar cycloaddition of organic
azides to alkynes: a) T. Katayama. K. Kamata, K. Yamaguchi, N.
Mizuno, ChemSusChem 2009, 2, 59–62; b) T. Oishi, T. Katayama,
K. Yamaguchi, N. Mizuno, Chem. Eur. J. 2009, 15, 7539–7542; c) K.
Yamaguchi, T. Oishi, T. Katayama, N. Mizuno, Chem. Eur. J. 2009,
15, 10464–10472.
The 1,3-dipolar cycloaddition was carried out as follows. Into a glass vial
were successively placed Cu(OH)x/Al2O3 (Cu: 1.5 mol% with respect to
an azomethine imine), an azomethine imine (0.5 mmol), an alkyne
(0.55 mmol), and a solvent (2 mL). Then, the resulting solution was
stirred at 408C under an Ar atmosphere. The yields were determined by
1H NMR analysis. After the reaction was completed, Cu(OH)x/Al2O3 was
separated by filtration and was further washed with toluene. The filtrate
was passed through a short silica gel column, and then evaporated in
vacuo to give 3aa (93% isolated yield). The retrieved Cu(OH)x/Al2O3
was washed with toluene and dried in vacuo before recycling. The prod-
ucts were confirmed by the comparison of their NMR spectra with those
of authentic data.[7–9]
Acknowledgements
This work was supported in part by the Global COE Program (Chemistry
Innovation through Cooperation of Science and Engineering), Japan
Chemical Innovation Institute (JCII), and Grants-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science and
Technology.
[12] R. A. Sheldon, M. Wallau, I. W. C. E. Arends, U. Shuchardt, Acc.
Chem. Res. 1998, 31, 485–493.
[13] B. J. Hathaway, D. E. Billing, Coord. Chem. Rev. 1970, 5, 143–207.
[14] Compound 4aa: MS (EI): m/z (%): 194 (1.2) [M+], 150 (40), 149
(85), 148 (23), 106 (43), 105 (17), 104 (18), 78 (17), 77 (100), 76 (27),
51 (11).
[15] The treatment of a [D8]toluene solution of 2a’ (D content at the ter-
minal position: 94%, 0.27m, 2 mL) with Cu(OH)x/Al2O3 (Cu:
1.4 mol% with respect to 2a’) at 208C for 1 h resulted in a decrease
in the deuterium content from 94% to 42%. Also, Al2O3 took part
in the H/D exchange reactions. Thus, the H/D exchange readily
takes place on Cu(OH)x/Al2O3.
Keywords: alkynes · azomethine imines · copper hydroxide ·
heterogeneous catalysis · N,N-bicyclic pyrazolidinone
[1] a) T. Eicher, S. Hauptmann, The Chemistry of Heterocycles, 2nd ed.,
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[16] In the UV/Vis spectrum of copper(I) phenyl acetylide [CuI
A
ꢀ
CPh)]n, a similar broad absorption band was observed around 400–
460 nm.[11c]
[17] The 1,3-dipolar cycloaddition of 1a to ethyl 2-butynoate (internal
alkyne) under the conditions described in Table 2 did not proceed,
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Heterogeneous Cycloaddition
COMMUNICATION
also suggesting that the copper species in Cu(OH)x/Al2O3 is termi-
nally bound to an alkyne to form the copper acetylide species.
[18] Compound 2a’ was synthesized according to the literature proce-
dure: T. Schwier, V. Gevorgyan, Org. Lett. 2005, 7, 5191–5194.
[19] It was confirmed that no H/D exchange reaction of the hydrogen at
the 3-position of non-deuterated 3aa proceeded in the presence of
Cu(OH)x/Al2O3 pretreated with D2O.
[20] a) D. Briggs, M. P. Seah, Practical Surface Analysis by Auger and X-
ray Photoelectron Spectroscopy, Wiley, Chichester, 1983; b) G. P.
Williams in CRC Handbook of Chemistry and Physics, 82nd Ed.
(Eds.: D. R. Lida) CRC Press, Washington DC, 2001, Section 10,
p. 200–205.
Received: September 29, 2010
Published online: February 24, 2011
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