La/Ag heterobimetallic cooperative catalysis: A catalytic asymmetric conia-ene reaction

Article abstract of DOI:10.1002/anie.201102114

A dual catalyst system: The cooperative function of a hard and soft Lewis acid (La^III and Ag^I, respectively) in a catalyst system that includes an amide-based ligand 1 is crucial for simultaneous activation of intramolecular 1,3-dicarbonyl and alkyne moieties to afford enantioenriched cyclopentane derivatives (see scheme). Copyright

Full text of DOI:10.1002/anie.201102114

Communications
DOI: 10.1002/anie.201102114
Homogeneous Catalysis
La/Ag Heterobimetallic Cooperative Catalysis:
A Catalytic Asymmetric Conia-Ene Reaction**
Akinobu Matsuzawa, Tomoyuki Mashiko, Naoya Kumagai,* and Masakatsu Shibasaki*
Cooperative catalysis continues to attract growing interest as
a particularly effective strategy to promote specific bond
formation under mild reaction conditions.[1] This intriguing
approach allows for the activation of not only a single
functionality through multiple coordination, but also chemi-
cally distinct multiple functionalities in a simultaneous
manner. The latter option, under an asymmetric environment,
is particularly powerful to assemble the multiple function-
alities with a high degree of stereocontrol. A carbonyl group
and an alkyne group represent hard and soft Lewis basic
functionalities, respectively, and their simultaneous activation
by hard and soft Lewis acid cooperative catalysis can be best
manifested by a Conia-ene reaction.[2–5] Pioneering work on
the catalytic asymmetric Conia-ene reaction of b-keto esters
and 1,3-diketones with a hard Lewis acid (Yb(OTf)3)/chiral
soft Lewis acid (DTBM-Segphos/PdII) bimetallic catalytic
system was reported by Corkey and Toste.[6] Subsequently,
Dixon and co-workers reported a distinct approach with
chiral amine base/soft Lewis acid (CuOTf) cooperative
catalysis.[7] Meanwhile, our research group developed a
La(NO3)3/amide-based ligand 1a/amine ternary catalyst that
promotes the catalytic asymmetric amination of malonamates
to azodicarboxylates. In this reaction a La/1a/amine ternary
complex formed under equilibrium acts as a chiral Lewis acid
(Scheme 1).[8,9] We envisioned that endowing a soft Lewis acid
function to the La/1a catalytic system would produce a hard
Lewis acid/soft Lewis acid heterobimetallic cooperative
catalyst.[1] In this catalyst system, the enolate is generated
through activation of a carbonyl group by a hard Lewis acid,
which subsequently couples with an electrophilically acti-
vated alkyne by a soft–soft interaction under an asymmetric
environment (Scheme 2). Herein, we report that a chiral La/
Scheme 2. Conia-ene reaction through hard Lewis acid/soft Lewis acid
heterobimetallic cooperative catalysis.
Ag heterobimetallic cooperative catalyst on a chiral amide-
based ligand promotes an enantioselective Conia-ene reac-
tion of alkyne-tethered malonamates and b-keto esters. This
approach furnishes enatioenriched cyclopentane derivatives
bearing exocyclic olefin and two distinct a-carbonyl groups at
a quaternary stereogenic center.[10]
Initial attempts at the catalytic asymmetric Conia-ene
reaction of alkyne-tethered malonamate 2a were conducted
using the La(NO3)3/1a/H-l-Val-OtBu (1:1:3) ternary cata-
lyst,[8a] which is effective for prochiral face selection of the
enolate derived from 2a. Combined use of various soft Lewis
acids was evaluated and the results are summarized in
Table 1. In the presence of 10 mol% of the La catalyst and
[Ni(acac)2], the Conia-ene reaction of 2a slowly proceeded at
508C and gave the desired product 3a in low yield with
marginal enantioinduction (Table 1, entry 1). The soft Lewis
acids [Pd(CH3CN)4](BF4)2 and [Rh(CH3CN)2(cod)]BF4 were
totally ineffective and no formation of 3a was detected
(Table 1, entries 2 and 3). Metal salts of Group 11 elements
exhibited higher catalytic performance, and afforded 3a in
21% with CuOTf, albeit with virtually no enantioinduction
(Table 1, entry 4). Degradation of the catalyst, likely owing to
the precipitation of silver salts, was circumvented in the
presence of phosphine ligand 5, and AgOAc outperformed
AgOTf (Table 1, entries 5 and 6). Concomitant alkyne
hydration was observed when AgOAc/5 was used as a soft
Lewis acid catalyst and gave ketone 4a in 12% yield (Table 1,
entry 6). This pathway became even more dominant in the
reaction using [AuCl(PPh3)]/AgSbF6 (Table 1, entry 7).
Scheme 1. The structure of amide-based ligand 1.
[*] A. Matsuzawa, T. Mashiko, Dr. N. Kumagai, Prof. Dr. M. Shibasaki
Institute of Microbial Chemistry, Tokyo
3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan)
Fax: (+81)3-3447-7779
E-mail: nkumagai@bikaken.or.jp
mshibasa@bikaken.or.jp
Homepage: http://www.bikaken.or.jp/research/group/shibasaki/
shibasaki-lab/index.html
A. Matsuzawa, T. Mashiko
Graduate School of Pharmaceutical Sciences
The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
[**] This work was financially supported by Grant-in-Aid for Scientific
Research (S) from the JSPS. T.M. thanks the JSPS for a predoctoral
fellowship. Dr. M. Shiro is gratefully acknowledged for X-ray
crystallographic analysis of 3a.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201102114.
7616
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 7616 –7619

Table 1: Initial Screening of the catalyst.[d]
Table 2: Initial screening of the catalyst.
Entry
RE
x
Solvent
T
[8C]
t
[h]
Yield
[%][a]
ee
[%][b]
Entry
Soft Lewis acid
t [h]
Yield [%][a]
ee [%][b]
[mol%]
3a
4a
1
2
3
4
Y
10
10
10
10
10
10
20
20
20
THF
THF
THF
THF
THF
THF
AcOEt
AcOEt
AcOEt
50
50
50
50
50
50
50
RT
0
21
21
21
21
21
21
21
21
48
58
92
83
55
64
À2
37
25
0
1
2
3
4
[Ni(acac)2·2H2O]
70
70
70
70
66
66
9
7
nd
nd
21
27
55
18
–
–
–
–
–
À14
–
La
Nd
Gd
Er
La
La
La
La
[Rh(CH3CN)2(cod)]BF4
[Pd(CH3CN)4](BF4)2
–
CuOTf·1= C6H6
À2
À3
7
2
5
À4
5[c]
6[c]
7
AgOTf/5
AgOAc/5
[AuCl(PPh3)]/AgSbF6
6[c]
7
93
3
12
78
quant.
96
63
82
90
9
8
9
[a] Determined by 1H NMR analysis. [b] Determined by HPLC on a chiral
stationary phase. [c] Ag salt/5 (1/1). [d] acac=acetylacetonate, cod=
1,5-cyclooctadiene, nd=not determined, Tf=trifluoromethanesulfonyl.
63
[a] Determined by 1H NMR analysis. [b] Determined by HPLC on a chiral
stationary phase. [c] 5 was used instead of PPh3. THF=tetrahydrofuran.
Table 3: Scope of catalytic asymmetric Conia-ene reaction promoted by
La(OiPr)3/1a/AgOAc/PPh3 catalyst.[g]
Owing to the possibility of unavoidably deactivating the
soft Lewis acid through coordination of the primary amino
group of H-l-Val-OtBu, the RE(OiPr)3/1a (RE = rare-earth
metal) catalytic system with a soft Lewis acid component
AgOAc/PPh3 was next examined (Table 2). Screening of rare-
earth-metal alkoxides revealed that La was optimal as a hard
Lewis acid with an amide-based ligand 1a, in terms of both
chemical yield and enantioselectivity (Table 2, entries 1–5).
Of particular note was the absence of by-product 4a in the
RE(OiPr)3/1a/AgOAc/PPh3 catalytic system. Although the
reaction using bidentate ligand 5 significantly decreased the
enantioselectivity (Table 2, entries 2 vs. 6), employing AcOEt
as the reaction solvent enhanced the enantioselectivity to
63% ee (Table 2, entry 7). Further improvement of the
enantioselectivity was observed at lower temperatures at
the expense of chemical yield. Thus the reaction at 08C
afforded 3a with 90% ee (Table 2, entry 9).
The scope of the Conia-ene reaction using the La(OiPr)3/
1a/AgOAc/PPh3 heterobimetallic catalytic system is summar-
ized in Table 3.[11,12] In addition to malonamate 2a (Table 3,
entry 1), the present hard Lewis acid/soft Lewis acid hetero-
bimetallic system was also applicable to the Conia-ene
reaction of b-keto esters. a-Benzoyl esters 2b and 2c were
converted into the corresponding Conia-ene products with
high enantioselectivity, irrespective of the ester group. The
reaction using aromatic b-keto esters was dependent on the
electronic nature of the substituent on the aromatic ring; the
reaction proceeded smoothly with aromatic b-keto esters 2d
and 2e with high enantioselectivity (Table 3, entries 4–6),
whereas low conversion was observed with b-keto ester 2 f
bearing an electron-donating methoxy substituent, even after
an extended reaction time (Table 3, entry 7). Aliphatic b-keto
esters exhibited higher reaction efficiency and the reaction of
Entry
Substrate 2
Ligand
x
t
Prod. Yield
[%][a]
ee
R1
R2
[mol%] [h]
[%][b]
1[d]
2
3
2a NH2
2b Ph
2c Ph
2d 2-naph
2e p-FC6H4
2e p-FC6H4
2 f p-
OMe 1a
OEt 1a
OBn 1a
OEt 1a
OEt 1a
OEt 1a
OEt 1a
10
10
10
10
10
5
48 3a
63[c] 90
quant. 91
118 3b
64 3c
64 3d
68 3e
75 3e
120 3 f
79
70
82
92
26
86
90
91
87
93
4
5
6[b]
7
10
MeOC6H4
8[d,e] 2g Me
OMe 1a
OMe 1a
OEt 1b
OEt 1b
OBn 1b
OMe 1b
OMe 1b
OEt 1b
OMe 1a
5
0.5
5
5
5
5
2.5
5
5
19 3g
65 3g
14 3h
12 3h
12 3i
15 3j
45 3j
24 3k
61 3l
89[c] 92
quant.[c] 96
quant.[c] 84
quant.[c] 91
quant. 83
86[c] 90
9[f]
10
11
12
13
14
15
16
2g Me
2h Me
2h Me
2i Me
2j Et
2j Et
2k Et
2l nPr
96[c] 83
98[c] 87
92
83
[a] Yield of isolated product. [b] Determined by HPLC or GC on a chiral
stationary phase. [c] Determined by 1H NMR analysis. [d] Double the amount
of PPh3 was used. [e] The reaction was carried out in air. [f] Substrate was
added over 24 h. [g] Bn=benzyl, naph=naphthyl.
2g was achieved even with only 0.5 mol% catalyst loading
(Table 3, entry 9). The present heterobimetallic catalyst
system was robust and the reaction was performed in air
with comparable yield and enantioselectivity (Table 3,
entry 8). The ester group marginally impacted on the
enantioselectivity and the use of amide-based ligand 1b
bearing a bulkier substituent derived from l-tert-butylglycine
Angew. Chem. Int. Ed. 2011, 50, 7616 –7619
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
7617

Communications
enhanced the enantioselectivity in the reaction of ethyl ester
2h (Table 3, entries 10 and 11). Both reactivity and enantio-
selectivity diminished as the steric bulk around the ketone
moiety increased (Table 3, entry 13–16). The enantioselectiv-
ity of the reaction with n-propyl ketone 2l decreased to
83% ee (Table 3, entry 16).
The cooperative nature of the present catalyst system is
suggested by results of the control experiments outlined in
Scheme 3. When the reaction of 2g was run without the
Scheme 4. Opposite stereoselection using amide-based ligand 1c
bearing a soft Lewis basic sulfide substituent.
The coexistence of alkyne and Ag salts may produce an
unreactive Ag acetylide species and halt the desired catalytic
process. To probe this possibility, deuterated alkyne [D]-6
(87% deuterated) was subjected to the La/Ag heterobime-
tallic catalyst system in the presence of the proton donor
methyl acetoacetate (7), which is chemically analogous to the
1,3-dicarbonyl substrate 2. Stirring at 08C with 7 led to a
significant H/D exchange of [D]-6 (Scheme 5, conditions A).
Scheme 3. Control experiment. Optimal conditions: La(OiPr)3
(5 mol%)/1a(10 mol%)/AgOAc(5 mol%)/PPh3(5 mol%);
conditions A: La(OiPr)3(5 mol%)/1a(10 mol%);
conditions B: 1a(10 mol%)/AgOAc(5 mol%)/PPh3(5 mol%).
AgOAc/PPh3 component or La(OiPr)3 under otherwise
identical conditions, no formation of the Conia-ene product
3g was detected, thus indicating that simultaneous activation
of the 1,3-dicarbonyl group by hard Lewis acidic La and the
alkyne group by soft Lewis acidic Ag is crucial to promote the
reaction.
To gain insight into the actual active catalyst, 31P and
1H NMR analyses of La(OiPr)3/1a/AgOAc/PPh3 (1:2:1:1)
heterobimetallic catalyst were conducted. The 31P NMR
spectrum of the same heterobimetallic catalyst in CDCl3
was nearly identical to that of AgOAc/PPh3, thus suggesting
that the La(OiPr)3/1a component did not form a stable
complex with the Ag cation.[13] Broad signals were observed in
Scheme 5. H/D exchange of acetylenic proton by the La/Ag heterobi-
matallic catalyst system. Conditions A: La(OiPr)3(10 mol%)/1a
(20 mol%)/AgOAc(10 mol%)/PPh3(20 mol%), 7 (1 equiv);
conditions B: La(OiPr)3(10 mol%)/1a(20 mol%)/AgOAc(10 mol%)/
PPh3(20 mol%); conditions C: La(OiPr)3(10 mol%)/1a(20 mol%); 7
(1 equiv).
1
the H NMR spectrum of La(OiPr)3/1a (1:2) in CDCl3, thus
indicating that complexation of La(OiPr)3 and 1a was in
equilibrium as demonstrated in previous studies.[8b] These
spectroscopic patterns remained unchanged upon the addi-
tion AgOAc/PPh3, as expected from 31P NMR analysis. Taken
together, these findings suggest that the hard Lewis acid
component La(OiPr)3/1a and the soft Lewis acid component
AgOAc/PPh3 were not inherently associative and thus
associated on hard and soft Lewis basic substrate 2 to function
together in the transition state.
An amide-based ligand 1c bearing a soft Lewis basic
sulfide substituent (Scheme 1), derived from l-methionine,
likely interacts with the Ag cation as well as with the La cation
to drastically change the stereochemical course of the
reaction. Indeed, with 2j the Conia-ene product (S)-3j was
obtained in 53% ee with the catalyst prepared from 1c
(Scheme 4b). Thus opposite enantioselection was produced
when 1b was used (Scheme 4a). The 31P NMR spectrum of
La(OiPr)3/1c/AgOAc/PPh3 (1:2:1:1) displayed an upfield
shift compared to that of AgOAc/PPh3 (1:1), and is thus
indicative of the formation of the 1c/AgOAc/PPh3 complex,
which would account for the opposite enantioselectivity.
Comparable level of H/D exchange was detected in the
absence of 7, and was likely due to proton exchange with the
amide-based ligand 1a (Scheme 5, conditions B). No H/
D exchange proceeded in the absence of the soft Lewis acid
component AgOAc/PPh3 (Scheme 5, conditions C). These
findings can be ascribed to silver-assisted deprotonation of
the acetylenic proton of 6 to form silver acetylide and
reprotonation through proton exchange with 7, which occured
in equilibrium as a nonproductive pathway.[14]
In summary, we have developed La(OiPr)3/1/AgOAc/
PPh3, a heterobimetallic hard Lewis acid/soft Lewis acid
cooperative catalyst system, to promote an asymmetric
Conia-ene reaction of malonamates and b-keto esters.
Cooperative activation of a 1,3-dicarbonyl and alkyne moi-
eties induced by the La/Ag heterobimetallic catalyst pro-
moted the desired reaction with as little as 0.5 mol% catalyst
loading. Applications of this cooperative catalyst for the
7618
www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 7616 –7619

6244; g) A. B. Leduc, T. P. Lebold, M. A. Kerr, J. Org. Chem.
2009, 74, 8414; h) T. P. Lebold, A. B. Leduc, M. A. Kerr, Org.
Lett. 2009, 11, 3770.
asymmetric assembly of substrates bearing hard and soft
Lewis basic functionalities are underway.
[6] B. K. Corkey, F. D. Toste, J. Am. Chem. Soc. 2005, 127, 17168.
[7] T. Yang, A. Ferrali, F. Sladojevich, L. Campbell, D. J. Dixon, J.
Am. Chem. Soc. 2009, 131, 9140.
Received: March 25, 2011
Published online: June 6, 2011
[8] a) T. Mashiko, N. Kumagai, M. Shibasaki, Org. Lett. 2008, 10,
2725; b) T. Mashiko, N. Kumagai, M. Shibasaki, J. Am. Chem.
Soc. 2009, 131, 14990.
[9] For the utility of amide-based ligand 1a, see: a) A. Nojiri, N.
Kumagai, M. Shibasaki, J. Am. Chem. Soc. 2009, 131, 3779; b) Y.
Kawato, N. Takahashi, N. Kumagai, M. Shibasaki, Org. Lett.
2010, 12, 1484; c) A. Matsuzawa, A. Nojiri, N. Kumagai, M.
Shibasaki, Chem. Eur. J. 2010, 16, 5036.
[10] For reviews on catalytic asymmetric synthesis of tetrasubstituted
stereogenic centers, see: a) E. J. Corey, A. Guzman-Perez,
Angew. Chem. 1998, 110, 402; Angew. Chem. Int. Ed. 1998, 37,
388; b) J. Christoffers, A. Mann, Angew. Chem. 2001, 113, 4725;
Angew. Chem. Int. Ed. 2001, 40, 4591; c) C. J. Douglas, L. E.
Overman, Proc. Natl. Acad. Sci. USA 2004, 101, 5363; d) B. M.
Trost, C. Jiang, Synthesis 2006, 369; e) P. G. Cozzi, R. Hilgraf, N.
Zimmermann, Eur. J. Org. Chem. 2007, 5969; f) M. Bella, T.
Gasperi, Synthesis 2009, 1583.
[11] The absolute configuration of 3a was determined by X-ray
crystallographic analysis. CCDC 817622 3a contains the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Summary
of crystallographic analysis and the crystal structure was
provided in the Supporting Information.
Keywords: cooperative catalysis · heterobimetallic complexes ·
homogeneous catalysis · lanthanum · silver
.
[1] Recent reviews on cooperative catalysis: a) J.-A. Ma, D. Cahard,
Angew. Chem. 2004, 116, 4666; Angew. Chem. Int. Ed. 2004, 43,
4566; b) H. Yamamoto, K. Futatsugi, Angew. Chem. 2005, 117,
1958; Angew. Chem. Int. Ed. 2005, 44, 1924; c) T. Ikariya, K.
Murata, R. Noyori, Org. Biomol. Chem. 2006, 4, 393; d) D. H.
Paull, C. J. Abraham, M. T. Scerba, E. Alden-Danforth, T.
Lectka, Acc. Chem. Res. 2008, 41, 655; e) J.-K. Lee, M. C. Kung,
H. H. Kung, Top. Catal. 2008, 49, 136; f) Y. J. Park, J.-W. Park,
C.-H. Jun, Acc. Chem. Res. 2008, 41, 222; g) M. Shibasaki, M.
Kanai, S. Matsunaga, N. Kumagai, Acc. Chem. Res. 2009, 42,
1117.
[2] R. Bloch, P. Le Perchec, F. Rouessac, J. M. Conia, Tetrahedron
1968, 24, 5971.
[3] For a review, see: J. M. Conia, P. Le Perchec, Synthesis 1975, 1.
[4] Selected examples of Lewis acid catalyzed Conia-ene reactions:
a) M. A. Boaventura, J. Drouin, J. M. Conia, Synthesis 1983, 801;
b) F. E. McDonald, T. C. Olson, Tetrahedron Lett. 1997, 38, 7691;
c) D. Bouyssi, N. Monteiro, G. Balme, Tetrahedron Lett. 1999, 40,
1297; d) O. Kitagawa, H. Fujiwara, T. Suzuki, T. Taguchi, M.
Shiro, J. Org. Chem. 2000, 65, 6819; e) J. J. Kennedy-Smith, S. T.
Staben, F. D. Toste, J. Am. Chem. Soc. 2004, 126, 4526; f) S. T.
Staben, J. J. Kennedy-Smith, F. D. Toste, Angew. Chem. 2004,
116, 5464; Angew. Chem. Int. Ed. 2004, 43, 5350; g) Q. Gao, B.-F.
Zheng, J.-H. Li, D. Yang, Org. Lett. 2005, 7, 2185; h) N.
Mꢀzailles, L. Ricard, F. Gagosz, Org. Lett. 2005, 7, 4133; i) Y.
Kuninobu, A. Kawata, K. Takai, Org. Lett. 2005, 7, 4823; j) A.
Ochida, H. Ito, M. Sawamura, J. Am. Chem. Soc. 2006, 128,
16486; k) Y. Itoh, H. Tsuji, K.-I. Yamagata, K. Endo, I. Tanaka,
M. Nakamura, E. Nakamura, J. Am. Chem. Soc. 2008, 130,
17161; l) Y. Liu, R.-J. Song, J.-H. Li, Synthesis 2010, 3663; m) L.
Liu, L. Wei, Y. Lu, J. Zhang, Chem. Eur. J. 2010, 16, 11813; n) S.
Montel, D. Bouyssi, G. Balme, Adv. Synth. Catal. 2010, 352, 2315;
o) H. K. Grover, T. P. Lebold, M. A. Kerr, Org. Lett. 2011, 13,
220.
[5] A Conia-ene type reaction of nitrogen- or oxygen- tethered
acetylenic 1,3-dicarbonyl substrates: a) X. Marat, N. Monteiro,
G. Balme, Synlett 1997, 845; b) B. Clique, N. Monteiro, G. Balme,
Tetrahedron Lett. 1999, 40, 1301; c) M. Cavicchioli, X. Marat, N.
Monteiro, B. Hartmann, G. Balme, Tetrahedron Lett. 2002, 43,
2609; d) M. Nakamura, C. Liang, E. Nakamura, Org. Lett. 2004,
6, 2015; e) S. Morikawa, S. Yamazaki, Y. Furusaki, N. Amano, K.
Zenke, K. Kakiuchi, J. Org. Chem. 2006, 71, 3540; f) K.
Takahashi, M. Midori, K. Kawano, J. Ishihara, S. Hatakeyama,
Angew. Chem. 2008, 120, 6340; Angew. Chem. Int. Ed. 2008, 47,
[12] 3g,h,j,k are volatile compounds and as a result the yield of
isolated material fluctuated.
[13] See the Supporting Information.
[14] On the basis of the independent nature of La(OiPr)3/1a and
AgOAc/PPh3 components, the present catalytic asymmetric
Conia-ene reaction likely proceeded through a formal trans
carbometalation via a 5-exo-dig cyclization mode. 5-Endo-dig
cyclization proceeded with substrate 2m bearing an internal
alkyne under optimized reaction conditions (La(OiPr)3
(5 mol%)/1b(10 mol%)/AgOAc(5 mol%)/PPh3(10 mol%),
AcOEt, 40 h) at room temperature, and afforded endocyclic
cyclopentene 3m in 65% yield and 52% ee. Product 3m is not
accessible via a cis carbometalation pathway, and trans carbo-
metalation would be more likely for substrates 2a–l. However,
the possibility that trans carbometalation proceeded only with
2m via the 5-endo-dig cyclization mode cannot be ruled out. The
determination of the absolute configuration of 3m is detailed in
the Supporting Information.
Angew. Chem. Int. Ed. 2011, 50, 7616 –7619
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
7619