Design of a combinational magnesium catalyst for the stereocontrolled cross reaction of enones

Article abstract of DOI:10.1002/chem.201403183

The first stereocontrolled cross reaction of enones has been realized. A novel combinational magnesium catalyst was designed to address the enantioselectivity problem between reaction partners with an intermolecular symmetric structure and bearing identical functional groups. This new catalytic strategy was proven to be effective to introduce high levels of enantioselectivity in the cross reaction of enones.

Full text of DOI:10.1002/chem.201403183

DOI: 10.1002/chem.201403183
Communication
&
Asymmetric Synthesis
Design of a Combinational Magnesium Catalyst for the
Stereocontrolled Cross Reaction of Enones
Dongxu Yang,[a] Linqing Wang,[a] Fengxia Han,[a] Depeng Zhao,[a] and Rui Wang*[a, b]
Abstract: The first stereocontrolled cross reaction of
enones has been realized. A novel combinational magne-
sium catalyst was designed to address the enantioselectiv-
ity problem between reaction partners with an intermo-
lecular symmetric structure and bearing identical function-
al groups. This new catalytic strategy was proven to be ef-
fective to introduce high levels of enantioselectivity in the
cross reaction of enones.
Figure 1. a) A challenge for the catalyst: selecting a specific activation
Carbonyl compounds are thoroughly studied nucleophiles and
hold fundamentally pivotal positions in asymmetric synthesis.
In this area, the direct remote functionalization of carbonyl
groups has been intensely studied and provided step economy
advantages for the construction of complex molecules.[1] In
recent years, aminocatalysis has provided a powerful platform
for the activation of g- and e-position of unsaturated aldehydes
or ketones and allowed direct synthetic access to obtain high
levels of structural complexity.[2] And the direct activation of g-
carbons of other carbonyl compounds such as esters, amides,
and acetyl chlorides were also successfully achieved by using
particular organocatalytic strategies.[3] On the other hand,
metal catalysts were also applied to g-functionalization trans-
formations that mainly concerned g-butenolides-type nucle-
philes.[4] Recently, we have also realized the direct site-specific
g-deprotonation process of linear enones employing a magnesi-
um catalyst.[5] Given these well-established methods for direct
g-functionalization reactions, we found that there are remark-
able advances in the development of several effective catalytic
systems to give more flexibility in the selection of diverse
types of carbonyl compounds as nucleophiles. However, an un-
usual challenge is encountered when choosing some special
partners as electrophiles. To date, there is still no successful ex-
ample using reaction partners equipped with exactly the same
electron withdrawing group (EWG) within the direct enantiose-
lective g-functionalization reactions. As shown in Figure 1, two
sequence of the substrate bearing the same electron withdrawing group.
b) The intermolecular symmetric structure between the reaction partners
increases the difficulty in the enantioselective process.
Table 1. Screening of the reaction conditions for the cross reaction of
enones.
Entry[a]
P
Yield [%][b]
d.r.[c]
ee[d]
1
2
3
4
5
6
7
8
P1
P2
P3
P4
P5
P6
P7
P8
P6
P6
52
40
33
37
49
75
62
64
76
73
14:1
8:1
7:1
55
À11
À7
À5
60
83
75
83
86
7:1
12:1
16:1
16:1
15:1
17:1
17:1
9[e]
10[e,f]
[a] D. Yang, L. Wang, F. Han, D. Zhao, Prof. Dr. R. Wang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province
Lanzhou University, Lanzhou, 730000 (P. R. China)
E-mail: wangrui@lzu.edu.cn
90
[a] Reactions were performed with 2a (0.35 mmol) and 1a (0.1 mmol) in
toluene (1.0 mL) in the presence of N1 (20 mol%), P (20 mol%), and
MgBu2 (20 mol%) at 608C for 24 h. [b] Yield of the isolated product.
[b] Prof. Dr. R. Wang
State Key Laboratory for Oxo Synthesis and Selective Oxidation
Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences
Lanzhou, 730000 (P. R. China)
1
[c] Diastereomeric ratios were determined by HNMR (300 MHz). [d] Enan-
tiomeric excesses of the major diastereomer were analyzed by chiral sta-
tionary phase HPLC. [e] The reaction was carried out in p-xylene. [f] The
reaction was performed at 358C for 72 h.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201403183.
Chem. Eur. J. 2014, 20, 1 – 6
1
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
key challenges with this type of transformations remain: 1) It is
especially hard for the catalyst to select a specific activating se-
quence of the substrates when the nucleophile and electro-
phile bear an identical functional group, which would probably
lead to racemic products. 2) The intermolecular symmetric
structure between the reaction partners could also increase
the difficulty in the enantioselective process. In fact, this type
of challenge has also been noted by the Jørgensen’s group;
they have published a paper very recently discussing the acti-
vation problem between reaction partners, and aminocatalysis
is shown to expand the classical reactivity pattern by activation
of the electrophiles. However, the reaction also has to use nu-
cleophiles bearing different elec-
acid (P1) and quinidine (N1) in the presence of MgBu2 success-
fully led to the formation of 3a with moderate yield and enan-
tioselective induction (Table 1, entry 1). Inspired by this positive
result, we imagined that higher enantioselectivities values
should be easily obtained by increasing the size of 3,3’-sub-
stituents in the phosphoric acids. However, unexpected results
were generated when equipping various logical designed sub-
stituents such as pheny l, 2-naphthyl in the phosphoric acids.
It is surprising to observe the total configuration inversion of
the product using these bulky groups in phosphoric acids (en-
tries 2–4). Based on these results, we believe that the steric
effect of the combinational catalyst should be very different
tron withdrawing groups with
electrophiles.[6]
Table 2. Substrate scopes of the cross reaction of enones.
Frankly, we have not noted
this unusual challenge when we
set out of our preliminary inves-
tigations of the cross reaction of
enones, and we have got
a series of unsuccessful results
when using some C2-symmetric
ligands embracing MgBu2 as ac-
tivator.[7] Based on the knowl-
edge of the g-activation mode
of linear enones in our previous
work,[5] herein we set out to de-
velop a new catalytic system to
address the enantioselective
problem in this cross reaction of
enones. In recent years, the suc-
cessful employments of chiral
phosphate metal salts were
found to be effective in catalyz-
ing enantioselective transforma-
tions.[8,9] At the same time, it is
well known that cinchona scaf-
Entry[a]
R[b]
Yield ([%])[c]
d.r.[d]
17:1
>20:1
>20:1
14:1
ee [%][e]
1
2
3
4
5
–
3a (73)
3b (75)
3c (73)
3d (42)
3e (53)
90
91
90
92
95
R1 =4-Me-Ph
R1 =4-MeO-Ph
R1 =2-Cl-Ph
R1 =3-MeO-Ph
R1 =
>20:1
6
3 f (39)
12:1
98
R1 =
R1 =
R1 =
7
8
9
3g (51)
3h (64)
3i (55)
>20:1
>20:1
>20:1
95
92
76
folds combined with
a wide
range of metal ions have also
led to the development of new
stereocontrolled reactions.[10] In
light of these achievements, we
envisioned that the combination
of these two types of privileged
chiral scaffolds together linking
by a metal center, could serve as
a powerful tool in asymmetric
synthesis.
R1 =
10
11
3j (36)
3k (70)
3l (63)
3m (79)
3n (74)
>20:1
>20:1
15:1
91
91
84
75
72
R2 =3-Cl-Ph
R2 =
12[f]
13
14
R3 =Me
R3, R4 =
>20:1
>20:1
15
16
17
18
19
R4 =2-F-Ph
3o (32)
3p (76)
3q (83)
3r (79)
3s (27)
18:1
>20:1
>20:1
>20:1
>20:1
93
89
90
84
96
To validate our hypothesis, we
initially endeavored to examine
the stereocontrol ability of our
proposed combinational catalyt-
ic strategy in the cross reaction
between enones 1a and 2a. As
shown by the representative re-
sults illustrated in Table 1, the
R4 =3-Me-Ph
R5 =4-F-Ph
R5 =3-MeO-Ph
R5 =2-Me-Ph
[a] Reactions were performed with 2 (0.35 mmol) and 1 (0.1 mmol) in p-xylene (1.0 mL) in the presence of N1
(20 mol%), P6 (20 mol%) and MgBu2 (20 mol%) at 358C for 72 h. [b] For the changing group in substrates
1 and 2. [c] Yield of the isolated product. [d] Diastereomeric ratios were determined by 1HNMR (300 MHz).
[e] Enantiomeric excesses of the major diastereomer were analyzed by chiral stationary phase HPLC. [f] The re-
action was conducted using P7 instead of P6 as ligand.
combination of
a phosphoric
&
&
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
2
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
from the monocatalytic way. So some infrequently used phos-
phoric acids were synthesized and applied into the present
cross reaction. Halo-substituted phosphoric acids were found
to give better enantioselectivity and the screening effort led to
the fortunate identification of the optimal bromine-substituted
ligand P6 (entries 5–8). Further refinement was achieved by
optimizing of solvents and reaction temperature, and the reac-
tion in p-xylene afforded good diastereoselectivity and high
enantioselectivity at 358C for 72 h (entry 10).
Then the combinational strategy for the cross reaction of
enones was subjected to a rigorous test of the substrate
scope. First of all, b-monosubstituted enones with various sub-
stituents afforded the corresponding [4+2]-cyclization prod-
ucts with excellent diastereoselectivities and enantioselectivi-
ties (Table 2, entries 2–5 and 11). Heteroaromaticenones were
also tolerable in the present transformation with high ee values
and moderate yields (entries 6–8, 10 and 12). It should be
noted that enones with a naphthyl group (entry 6) in the b-po-
sition or an ortho-substituted phenyl (entry 4) showed reduced
reactivity. The use of b-aliphatic enones could not provide the
desired products and there was no reaction between the reac-
tion partners. Moreover, the b-cinamylchalcone was also inves-
tigated and generated the corresponding cyclization adduct in
moderate yield and ee value (entry 9). Furthermore, b, b-disub-
stituted enones were also tested under similar conditions. The
nucleophilic partners bearing different aryl groups were com-
patible in the reaction and leading to the desired products
with good enantioselectivities (entries 15–19). The ortho-substi-
tuted groups at either the b- or a’-positions also attenuated
the reactivity and gave a lower conversion (entries 15 and 19).
Notably, different substituents at the g-position of b, b-disub-
stitutedenones were also tested and giving relatively lower
enantioselectivies (entries 13 and 14).
Scheme 1. a) The g-H site specific selectivity and the change in the size of
the R group in the nucleophilic enones have no obvious effect on the enan-
tioselectivity. b) The g-H site specific selectivity and the change in the size of
the R group in the electrophilic enones have obvious effect on the enantio-
selectivity.
Table 3. Control experiments of the cross-reaction of enones.
Entry[a]
N/P
Yield [%]
d.r.
ee [%]
1
2
3
4
5
6
7
8
N1/(R)-P2
N1/(S)-P2
N2/(S)-P2
N2/(R)-P2
N1/(R)-P6
N1/(S)-P6
N2/(R)-P6
N1/–
–/(S)-P6
N1/–
–/(S)-P6
N1/(S)-P6’
35
40
54
47
53
75
65
79
<5
81
<5
83
12:1
8:1
7:1
10:1
14:1
16:1
14:1
1:2.6
–
1:1.8
–
4:1
13
À11
À11
21
À77
83
Our next stage of investigation focused on the site-selectivi-
ty experiments. The g-site specific activation was observed for
both of the b-monosubstituted enones and b,b-disubstituted-
enones containing other active nucleophilic site. More impor-
tantly, an interesting phenomenon was observed during our
experiments. As shown in Scheme 1, changing the R group in
the nucleophilic b,b-disubstitutedenones did not give obvious
influence on the enantioselectivities. On the contrary, increas-
ing the size of the R group in the electrophilic enones led to
a change of the ee values of the products from 3 to 83%. By
analyzing this result, we speculated that the nucleophilic
enones should coordinate to the metal center of the catalyst
at first, and then the attack direction of the electrophilic
enones determined the stereocontrolled results of the combi-
national catalyst.
À79
7/15
9
–
4/–
3
10[b]
11[b]
12[c]
17
[a] Reactions were performed with 0.35 mmol of 2a and 0.1 mmol of 1a
in toluene (1.0 mL) in the presence of N (20 mol%), P (20 mol%), and
MgBu2 (20 mol%) at 608C for 24 h. [b] Using 40 mol% ligand. [c] (S)-P6’
was purified on silica gel without washing with HCl.
To gain deeper comprehension of the activation mode and
the stereocontrol ability of the combinational catalyst, a serial
of control experiments were carried out. As illustrated in
Table 3, the stereochemistry is consistent with the configura-
tion of phosphoric acids, while changing of cinchona scaffolds
only slightly affects the ee values and has no decisive influence
on the absolute configuration of the product (Table 3, en-
tries 1–7). However, when the phosphoric acid (S)-P6 and
MgBu2 were employed in the absence of cinchona alkaloids,
almost no product was generated (entries 8, 10). On the con-
trary, by the use of quinine and MgBu2 as combinational cata-
lysts in the cross reaction led to the cyclization adduct with un-
satisfactory diastereoselectivity and low ee values (entries 9,
11). Moreover, it should be noted that the use of phosphoric
acid (S)-P6’ that was purified on silica gel and not washed with
HCl led to a product with dramatically decreased enantioselec-
tivity (entry 12). With these data in hand, we could draw some
preliminary conclusions of the combinational catalyst as fol-
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
3
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
2012, 14, 5590; l) G. Bencivennia, P. Galzeranoa, A. Mazzantia, G. Barto-
lia, P. Melchiorre, Proc. Natl. Acad. Sci. USA 2010, 107, 20642; m) G. Ber-
gonzini, S. Vera, P. Melchiorre, Angew. Chem. 2010, 122, 9879; Angew.
Chem. Int. Ed. 2010, 49, 9685; n) J.-L. Li, T.-R. Kang, S.-L. Zhou, R. Li, L.
Wu, Y.-C. Chen, Angew. Chem. 2010, 122, 6562; Angew. Chem. Int. Ed.
2010, 49, 6418; o) R. M. de Figueiredo, R. Frçhlich, M. Christmann,
Angew. Chem. 2008, 120, 1472; Angew. Chem. Int. Ed. 2008, 47, 1450;
p) S. Bertelsen, M. Marigo, S. Brandes, P. Dinꢃr, K. A. Jørgensen, J. Am.
Chem. Soc. 2006, 128, 12973.
lows: 1) The cinchona alkaloid in the combinational catalysis
plays the role of promoter in the cross reaction. 2) The abso-
lute configuration was determined by the phosphoric acid
which should be linked to the cinchona scaffold by the metal
center, so the phosphoric acid could be deprived of C2-symme-
try which was the key factor to introduce high enantioselectivi-
ty between the almost C2-symmetry reaction partners.
3) During the activation process, the coordination sequence of
the substrates to the metal center was affirmatory, because the
nucleophile enones need to be activated by the promoter (cin-
chona alkaloid), so the b,b-disubstitutedenones must coordi-
nate to the metal center firstly and deprotonated by the
Brønsted base of the cinchona scaffold, then the product
could be furnished after the coordination of electrophile
enones. So the cinchona scaffold was important for guarantee-
ing the generation of the chiral cyclization adducts by depriv-
ing the combinational catalyst of the C2-symmetry and ascer-
taining the coordination sequence of the substrates.[11]
[3] For selected examples, see: a) J. Xu, Z. Jin, Y. R. Chi, Org. Lett. 2013, 15,
5028; b) J. Mo, X. Chen, Y. R. Chi, J. Am. Chem. Soc. 2012, 134, 8810;
c) H. Ube, N. Shimada, M. Terada, Angew. Chem. 2010, 122, 1902; Angew.
Chem. Int. Ed. 2010, 49, 1858; d) J. Luo, H. Wang, X. Han, L.-W. Xu, J.
Kwiatkowski, K.-W. Huang, Y. Lu, Angew. Chem. 2011, 123, 1901; Angew.
Chem. Int. Ed. 2011, 50, 1861; e) H. Huang, Z. Jin, K. Zhu, X. Liang, J. Ye,
Angew. Chem. 2011, 123, 3290; Angew. Chem. Int. Ed. 2011, 50, 3232;
f) C. Curti, G. Rassu, V. Zambrano, L. Pinna, G. Pelosi, A. Sartori, L. Battis-
tini, F. Zanardi, G. Casiraghi, Angew. Chem. 2012, 124, 6304; Angew.
Chem. Int. Ed. 2012, 51, 6200; g) X. Jiang, L. Liu, P. Zhang, Y. Zhong, R.
Wang, Angew. Chem. 2013, 125, 11539; Angew. Chem. Int. Ed. 2013, 52,
11329; h) J. Zhang, X. Liu, X. Ma, R. Wang, Chem. Commun. 2013, 49,
9329; i) P. S. Tiseni, R. Peters, Angew. Chem. 2007, 119, 5419; Angew.
Chem. Int. Ed. 2007, 46, 5325; j) L. Shen, L. Sun, S. Ye, J. Am. Chem. Soc.
2011, 133, 15894; k) L. Shen, W.-Q. Jia, S. Ye, Angew. Chem. 2013, 125,
613; Angew. Chem. Int. Ed. 2013, 52, 585.
[4] a) B. M. Trost, J. Hitce, J. Am. Chem. Soc. 2009, 131, 4572; b) A. Yamagu-
chi, S. Matsunaga, M. Shibasaki, Org. Lett. 2008, 10, 2319; c) N. E. Shep-
herd, H. Tanabe, Y. Xu, S. Matsunaga, M. Shibasaki, J. Am. Chem. Soc.
2010, 132, 3666; d) L. Yin, H. Takada, N. Kumagai, M. Shibasaki, Angew.
Chem. 2013, 125, 7451; Angew. Chem. Int. Ed. 2013, 52, 7310; e) L. Lin, J.
Zhang, X. Ma, X. Fu, R. Wang, Org. Lett. 2011, 13, 6410.
[5] D. Yang, L. Wang, F. Han, D. Zhao, B. Zhang, R. Wang, Angew. Chem.
2013, 125, 6871; Angew. Chem. Int. Ed. 2013, 52, 6739.
[6] L. Dell’Amico, Ł. Albrecht, T. Naicker, P. H. Poulsen, K. A. Jørgensen, J.
Am. Chem. Soc. 2013, 135, 8063.
In summary, we have developed an efficient combinational
catalyst employing two types of privileged chiral scaffolds in
the magnesium mediated cross reactions of enones. The g-site
specific selectivity and the achievement of stereocontrol in the
transformation between the intermolecular symmetry sub-
strates bearing same activation group relies on the perfect col-
laboration of the bifunctional combinational catalyst. Still,
a precise understanding of the activation mode of the cross re-
action of enones and the origin of enantioselectivity in the
combinational catalytic system await further investigations.
[7] See the Supporting Information for our preliminary studies on screen-
ing of ligands.
[8] For selected recent examples, see: a) M. Terada, F. Li, Y. Toda, Angew.
Chem. 2014, 126, 239; Angew. Chem. Int. Ed. 2014, 53, 235; b) K. Saito, Y.
Kajiwara, T. Akiyama, Angew. Chem. 2013, 125, 13526; Angew. Chem. Int.
Ed. 2013, 52, 13284; c) S.-Y. Yu, H. Zhang, Y. Gao, L. Mo, S. Wang, Z.-J.
Yao, J. Am. Chem. Soc. 2013, 135, 11402; d) R. J. Phipps, F. D. Toste, J.
Am. Chem. Soc. 2013, 135, 1268; e) W. Chen, J. F. Hartwig, J. Am. Chem.
Soc. 2013, 135, 2068; f) B. Xu, S.-F. Zhu, Z.-C. Zhang, Z. Yu, Y. Ma, Q.-L.
Zhou, Chem. Sci. 2014, 5, 1442; g) G. L. Li, T. Liang, L. Wojtas, J. C. Anti-
lla, Angew. Chem. 2013, 125, 4726; Angew. Chem. Int. Ed. 2013, 52, 4628;
h) J. Lv, L. Zhang, S. Z. Luo, J.-P. Cheng, Angew. Chem. 2013, 125, 9968;
Angew. Chem. Int. Ed. 2013, 52, 9786; i) Y.-M. Wang, J. Wu, C. Hoong, V.
Rauniyar, F. D. Toste, J. Am. Chem. Soc. 2012, 134, 12928; j) A. Alix, C.
Lalli, P. Retailleau, G. Masson, J. Am. Chem. Soc. 2012, 134, 10389; k) E. L.
McInturff, E. Yamaguchi, M. J. Krische, J. Am. Chem. Soc. 2012, 134,
20628; l) Z. Chai, T. J. Rainey, J. Am. Chem. Soc. 2012, 134, 3615; m) J. R.
Zbieg, E. Yamaguchi, E. L. Mclnturff, M. J. Krische, Science 2012, 336,
324; n) V. Rauniyar, A. D. Lackner, G. L. Hamilton, F. D. Toste, Science
2011, 334, 1681; o) Z. Zhang, W. Zheng, J. C. Antilla, Angew. Chem.
2011, 123, 1167; Angew. Chem. Int. Ed. 2011, 50, 1135; p) W. Zheng, Z.
Zhang, M. J. Kaplan, J. C. Antilla, J. Am. Chem. Soc. 2011, 133, 3339; q) V.
Rauniyar, Z. Wang, H. E. Burks, F. D. Toste, J. Am. Chem. Soc. 2011, 133,
8486; r) G. Jiang, R. Halder, Y. Fang, B. List, Angew. Chem. 2011, 123,
9926; Angew. Chem. Int. Ed. 2011, 50, 9752; s) M. Hatano, K. Moriyama,
T. Maki, K. Ishihara, Angew. Chem. 2010, 122, 3911; Angew. Chem. Int. Ed.
2010, 49, 3823; t) S. Liao, B. List, Angew. Chem. 2010, 122, 638; Angew.
Chem. Int. Ed. 2010, 49, 628; u) R. L. LaLonde, Z. Wang, M. Mba, A. D.
Lackner, F. D. Toste, Angew. Chem. 2010, 122, 608; Angew. Chem. Int. Ed.
2010, 49, 598; v) C. Li, C. Wang, B. Villa-Marcos, J. Xiao, J. Am. Chem.
Soc. 2008, 130, 14450; w) S. Mukherjee, B. List, J. Am. Chem. Soc. 2007,
129, 11336; x) G. L. Hamilton, E. Kang, M. Mba, F. D. Toste, Science 2007,
317, 496.
Acknowledgements
This work was supported by the NSFC (Nos. 91213302,
21272102, 21202071) and the National S&T Major Project of
China (No. 2012ZX09504001-003).
Keywords: cyclization
· enantioselectivity · intermolecular
symmetric structure · magnesium catalysts · site specific
selectivity
[1] For recent reviews on vinylogous processes of carbonyl compounds,
see: a) G. Casiraghi, L. Battistini, C. Curti, G. Rassu, F. Zanardi, Chem. Rev.
2011, 111, 3076; b) J. Clayden, Chem. Soc. Rev. 2009, 38, 817; c) S. F.
Martin, Acc. Chem. Res. 2002, 35, 895; d) S. E. Denmark, J. R. Heem-
stra, Jr., G. L. Beutner, Angew. Chem. 2005, 117, 4760; Angew. Chem. Int.
Ed. 2005, 44, 4682.
[2] For recent reviews, see: a) K. L. Jensen, G. Dickmeiss, H. Jiang, Ł. Al-
brecht, K. A. Jørgensen, Acc. Chem. Res. 2012, 45, 248; b) J.-L. Li, T.-Y.
Liu, Y.-C. Chen, Acc. Chem. Res. 2012, 45, 1491; c) H. Jiang, Ł. Albrecht,
K. A. Jørgensen, Chem. Sci. 2013, 4, 2287; d) I. Jurberg, I. Chatterjee, R.
Tannert, P. Melchiorre, Chem. Commun. 2013, 49, 4869; for selected
recent representative examples: e) H. Jiang, D. C. Cruz, Y. Li, V. H. Laurid-
sen, K. A. Jørgensen, J. Am. Chem. Soc. 2013, 135, 5200; f) X. Feng, Z.
Zhou, C. Ma, X. Yin, R. Li, L. Dong, Y.-C. Chen, Angew. Chem. 2013, 125,
14423; Angew. Chem. Int. Ed. 2013, 52, 14173; g) D. Bastida, Y. Liu, X.
Tian, E. Escudero-Adꢁn, P. Melchiorre, Org. Lett. 2013, 15, 220; h) Ł. Al-
brecht, G. Dickmeiss, F. C. Acosta, C. Rodrꢂguez-Escrich, R. L. Davis, K. A.
Jørgensen, J. Am. Chem. Soc. 2012, 134, 2543; i) G. Talavera, E. Reyes,
J. L. Vicario, L. Carrillo, Angew. Chem. 2012, 124, 4180; Angew. Chem. Int.
Ed. 2012, 51, 4104; j) J.-L. Li, S.-L. Zhou, P.-Q. Chen, L. Dong, T.-Y. Liu, Y.-
C. Chen, Chem. Sci. 2012, 3, 1879; k) C. Cassani, P. Melchiorre, Org. Lett.
[9] For ion-paired chiral catalyst combining chiral phosphate and ammoni-
um, see: a) K. Ohmatsu, M. Ito, T. Kunieda, T. Ooi, J. Am. Chem. Soc.
2013, 135, 590; b) X. Feng, Z. Zhou, R. Zhou, Q.-Q. Zhou, L. Dong, Y.-C.
&
&
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
4
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
Chen, J. Am. Chem. Soc. 2012, 134, 19942; c) T. Xu, C. Cassani, Y. Liu, Y.
Moran, A. Urakawa, P. Galzerano, E. Arceo, P. Melchiorre, J. Am. Chem.
Soc. 2011, 133, 17934; d) N. J. A. Martin, B. List, J. Am. Chem. Soc. 2006,
128, 13368; e) S. Mayer, B. List, Angew. Chem. 2006, 118, 4299; Angew.
Chem. Int. Ed. 2006, 45, 4193.
S. Gou, X. Huang, X. Liu, X. Feng, Angew. Chem. 2007, 119, 8620; Angew.
Chem. Int. Ed. 2007, 46, 8468; i) F. M. Koch, R. Peters, Angew. Chem.
2007, 119, 2739; Angew. Chem. Int. Ed. 2007, 46, 2685; j) F. Yang, D.
Zhao, J. Lan, P Xi, L. Yang, S. Xiang, J. You, Angew. Chem. 2008, 120,
5728; Angew. Chem. Int. Ed. 2008, 47, 5646; k) S. Cui, S. D. Walker, J. C. S.
Woo, C. J. Borths, H. Mukherjee, M. J. Chen, M. M. Faul, J. Am. Chem.
Soc. 2010, 132, 436; l) J. Erb, D. H. Paull, T. Dudding, L. Belding, T.
Lectka, J. Am. Chem. Soc. 2011, 133, 7536; m) D. Yang, L. Wang, D. Zhao,
F. Han, B. Zhang, R. Wang, Chem. Eur. J. 2013, 19, 4691.
[10] For an elegant review, see: a) L. Stegbauer, F. Sladojevich, D. J. Dixon,
Chem. Sci. 2012, 3, 942; for selected examples: b) S. Kobayashi, Y. Tsu-
chiya, T. Mukaiyama, Chem. Lett. 1991, 20, 541; c) R. M. Kamble, V. K.
Singh, Tetrahedron Lett. 2003, 44, 5347; d) C. Zhu, X. Shen, S. G. Nelson,
J. Am. Chem. Soc. 2004, 126, 5352; e) L. Liu, R. Wang, Y.-F. Kang, C. Chen,
Z.-Q. Xu, Y.-F. Zhou, M. Ni, H.-Q. Cai, M.-Z. Gong, J. Org. Chem. 2005, 70,
1084; f) S. France, M. H. Shah, A. Weatherwax, H. Wack, J. P. Roth, T.
Lectka, J. Am. Chem. Soc. 2005, 127, 1206; g) Z. Liu, A. S. Wasmuth, S. G.
Nelson, J. Am. Chem. Soc. 2006, 128, 10352; h) J. Wang, X. Hu, J. Jiang,
[11] A proposed mechanism is summarized in the Supporting Information.
Received: April 21, 2014
Published online on && &&, 0000
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
COMMUNICATION
&
Asymmetric Synthesis
D. Yang, L. Wang, F. Han, D. Zhao,
R. Wang*
&& – &&
Design of a Combinational
Magnesium Catalyst for the
Stereocontrolled Cross Reaction of
Enones
The first stereocontrolled cross reac-
tion of enones has been realized. A
novel combinational magnesium cata-
lyst was designed to address the enan-
tioselectivity problem between reaction
partners with an intermolecular sym-
metric structures and bearing identical
functional groups. This new catalytic
strategy was proven to be effective to
introduce high level of enantioselectivi-
ty in the cross reaction of enones (see
scheme; QD=quinidine).
&
&
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!