Asymmetric calcium catalysis: Highly enantioselective carbonyl-ene and friedel-crafts reactions for the synthesis of quaternary α-hydroxy esters bearing a trifluoromethyl group

Article abstract of DOI:10.1002/asia.201200063

Enantioselective calcium-catalyzed addition reactions of styrene and indole derivatives with trifluoropyruvates have been developed. The alkaline-earth metal-catalyzed reactions proceed smoothly to afford the corresponding products in high yields and with good to excellent enantioselectivities under mild reaction conditions. Copyright

Full text of DOI:10.1002/asia.201200063

DOI: 10.1002/asia.201200063
Asymmetric Calcium Catalysis: Highly Enantioselective Carbonyl-Ene and
Friedel–Crafts Reactions for the Synthesis of Quaternary a-Hydroxy Esters
Bearing a Trifluoromethyl Group
Magnus Rueping,* Teerawut Bootwicha, Supakeat Kambutong, and Erli Sugiono[a]
Introduction
The development of efficient catalytic asymmetric reactions
that allow the preparation of enantiopure organic molecules
still constitutes a major challenge in organic chemistry. Con-
siderable attention has been devoted to the development of
new routes or methods to access these compounds. Most ex-
isting methods rely on the application of chiral transition
metal catalysts, and a variety of highly enantioselective reac-
tions have been reported. Recently, chiral alkaline-earth
metal catalysts have been found to be promising alternative
catalysts in chemical transformations.[1,2,3a,b] Among the
chiral alkaline-earth metal catalysts reported, chiral calcium
catalysts are of great interest as they can readily be pre-
Figure 1. Chiral binol-derived Brønsted acids and their calcium salts.
pared and exhibit outstanding stereoselective induction.[1d]
During the synthesis of chiral 2,2’-dihydroxy-1,1’-bi-
naphthyl (binol)-derived N-triflylphosphoramides 1 we ob-
served the formation of calcium salts 2.[3b,7b] This was at first
sight intriguing as no calcium derivatives were used in the
synthesis or work-up procedure. However, we noticed that
silica gel contains traces of calcium and thus the purification
by column chromatography was responsible for the forma-
tion of the chiral calcium complexes. The calcium salts 2
turned out to be less effective catalysts, and this may be due
to the chelating properties of the triflylphosphoramide li-
gands (Figure 1). Acidic workup resulted in the chiral triflyl-
phosphoramides, which are highly acidic Brønsted acid cata-
lysts 1 that generally exhibit higher reactivity and selectivi-
ty.[3d] Similar observations have also been made for the cor-
responding chiral phosphoric acids 3[4,5] and their calcium
salts 4 in imine activations.[2f] However, in this case, often
only little difference in reactivity has been observed and ste-
reoselectivities of the acid and calcium salt are compara-
ble.[6,2f]
Results and Discussion
Recently, we reported a highly enantioselective carbonyl-
ene reaction[7–9] using various styrene derivatives. In this re-
action, the calcium phosphoramide complexes 2 were poor
catalysts, while the metal-free phosphoramides 1 proved to
be highly effective Brønsted acid catalysts.[7b]
However, the high acidity of the triflylphosphoramides
1 (pKa 6–7 in acetonitrile) led to by-product formation
through elimination, and in certain cases, styrene dimeriza-
tion was observed. In order to suppress the side reactions
we decided to employ milder catalysts.[7b]
Here we report a highly enantioselective carbonyl-ene re-
action of trifluoropyruvate with styrene derivatives cata-
lyzed by a chiral calcium phosphate catalyst. We began our
studies by examining various binol-derived phosphoric acid
catalysts (pKa 13-14 in acetonitrile) and their calcium salts.
Interestingly, the calcium salts showed both better reactivity
and selectivity in the reaction of methylstyrene with trifluor-
opyruvate and the corresponding a-hydroxy-a-trifluoro-
methyl esters were obtained in good yields and with excel-
lent enantioselectivities if the reactions were performed in
aromatic solvents (Table 1). Of various binol and [H8]-binol
[a] Prof. Dr. M. Rueping, T. Bootwicha, S. Kambutong, Dr. E. Sugiono
Institute of Organic Chemistry
phosphoric acid-derived calcium salts tested, the CaACHTUNGTRENNUNG[4e]n
RWTH-Aachen University
Landoltweg 1, 52074 Aachen (Germany)
Fax : (+49)241-8092665
showed the best results, thus providing the desired product
in 90% ee (Table 1, entry 5). Lower yields and enantioselec-
tivities were obtained when the reactions were carried out
in o-xylene (65% yield, 87% ee) or CF3-benzene (66%
yield, 82% ee; Table 1, entries 6 and 7). Lowering the reac-
E-mail: magnus.rueping@rwth-aachen.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201200063.
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Table 1. Optimization of the enantioselective carbonyl-ene reaction.[a]
ent styrene derivatives (5a–j) bearing electron-donating and
electron-withdrawing substituents could effectively be em-
ployed in this mild calcium-catalyzed procedure and the de-
sired a-hydroxy-a-trifluoromethyl esters were isolated in
good yields and with excellent enantioselectivities (Table 2,
entries 1–10). Interestingly, just 0.5 mol% of catalyst was
sufficient for a successful reaction.
Based on this success and to further explore the synthetic
utility of chiral calcium binol phosphate catalysts we decided
to also examine the asymmetric Friedel–Crafts alkyla-
tion.[10,11] The calcium-catalyzed reaction of indole 8a with
ethyl trifluoropyruvate 6 was selected as the model reaction.
The influence of the catalyst structure, catalyst loading, and
solvents are summarized in Table 3. Our initial experiments
Entry Ca[4]n [mol%] Solvent
T [8C] Yield [%][b] ee [%][c]
1
2
3
4
5
6
7
8
9
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
E
toluene
toluene
toluene
toluene
toluene
o-xylene
À20
À20
À20
À20
À20
À20
53
52
53
49
72
65
66
68
60
67
3
84
64
90
87
82
94
94
Table 3. Optimization of the enantioselective Friedel–Crafts alkylation.[a]
CF3-benzene À20
toluene
toluene
À40
À60
[a] Reaction conditions: 5a (1.5 equiv), 6 (1.0 equiv), CaACTHUNRTGENNUG[4a]n–CaACHTUTGNREN[NUNG 4e]n
(0.5–1 mol%), in 0.25m solution of solvent for 48 h. [b] Yield of the iso-
lated product after column chromatography. [c] Determined by HPLC
analysis on a chiral column (CHIRALPAK AS-H).
tion temperature to À408C gave the product in higher enan-
tiomeric excess but lower chemical yield (68% yield, 94%
ee; Table 1, entry 8 vs. entry 5). Further decrease in the reac-
tion temperature to À608C did not improve the enantiose-
lectivity of the reaction (Table 1, entry 9). Importantly, the
mild reaction conditions and neutral acidity resulted in no
by-product formation, and neither elimination nor dimeriza-
tion of styrene was observed.
Entry
Ca[4]n [mol%]
Solvent
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
A
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
ClCH2CH2Cl
ClCH2CH2Cl
CHCl3
CF3-benzene
Toluene
benzene
93
83
98
85
82
83
89
83
90
92
87
93
83
66
49
50
49
45
63
77
73
72
83
46
76
69
58
42
E
E
R
R
N
N
Having established the optimal reaction conditions, we
next focused on the scope of this first asymmetric calcium-
catalyzed carbonyl-ene reaction (Table 2). In general, differ-
R
9
R
10[d]
11
12
13
14
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
G
Table 2. Scope of the chiral calcium phosphate-catalyzed carbonyl-ene
reaction.[a]
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
[a] Reaction conditions: indole 8a (1.0 equiv), 6 (1.5 equiv), Ca
ACHTUNGTRENNUNG[4 f]n–Ca-
AHCTUNGTRENNUNG
30 min. [b] Yield of the isolated product after column chromatography.
[c] Determined by HPLC analysis on a chiral column (CHIRALPAK
OD-H). [d] The reaction was performed at À308C for 24 h.
Entry
R
7
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
9
Ph
7a
7b
7c
7d
7e
7 f
7g
7h
7i
68
62
56
68
68
77
75
53
50
75
94
89
90
84
84
86
91
95
91
87
p-MeC6H4
m-MeC6H4
p-EtC6H4
p-tBuC6H4
p-iPrC6H4
m,p-Me2C6H3
p-FC6H4
were conducted at room temperature using various calcium
binol phosphate cataylsts such as Ca
the chiral calcium catalysts evaluated, 1-naphthyl-substituted
[H8]-binol calcium phosphate Ca[4k]n was the best catalyst,
ACHUTNGTRENUNG[4 f]n–CaCAHTUNGTERN[NUGN 4l]n. Among
AHCTUNGTRENNUNG
providing the corresponding product 9a in good yield and
good enantioselectivity (Table 3, entry 6). By lowering the
catalyst loading to 2 mol% resulted in a slight reduction in
the ee without affecting the chemical yield (Table 3, entry 8
vs. entry 6). Next we investigated the effect of reaction
media (Table 3, entries 8–14). In general, the reaction can
2-naphthyl
6-tetralinyl
10
7j
[a] Reaction conditions: 5 (1.5 equiv), 6 (1.0 equiv), CaACTHNUTRGNEUNG[4e]n (0.5 mol%),
in 0.25m solution of toluene at À408C for 48 h. [b] Yield of the isolated
product after column chromatography. [c] Determined by HPLC analysis
on a chiral column.
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Highly Enantioselective Carbonyl-Ene and Friedel–Crafts Reactions
be performed in various solvents in the presence of catalytic
amounts of the catalyst CaACTHNUTRGNE[UNG 4k]n, thus giving the product in
good to excellent yields. The choice of the solvents showed
noticeable impact on the enantioselectivity. With catalyst
in organic synthesis. Thus, the newly developed transition-
metal-free protocol addresses this challenge and provides
a valuable and mild method for the generation of esters
comprising an a-trifluoromethyl as well as a-hydroxy
moiety, a substitution pattern which mimics a carboxylic
acid.
CaACHTUNGTRENNUNG[4k]n higher enantiomeric excess was obtained when the
reactions were performed in halogenated solvents. The best
result in terms of chemical yield and enantioselectivity was
obtained when the reaction was carried out in dichloro-
ethane and the product was isolated in 90% yield and 83%
enantiomeric excess (Table 3, entry 9). Lowering the reac-
tion temperature from room temperature to À308C resulted
in prolonged reaction time and lower enantiomeric excess
(Table 3, entry 10 vs. entry 9).
Experimental Section
General Procedure for the Enantioselective Carbonyl-Ene Reaction of
Trifluoropyruvate with a-Methyl Styrene
In a screw capped reaction tube, a mixture of a-methyl styrene
5
(0.3 mmol, 1.5 equiv) and catalyst Ca[4e]n (0.5 mol%) was dissolved in
AHCTUNGTRENNUNG
With the optimal reaction conditions in hand, the scope of
the asymmetric calcium phosphate-catalyzed Friedel–Crafts
alkylation was investigated (Table 4). The reaction generally
toluene (0.8 mL) and ethyl trifluoropyruvate 6 (0.2 mmol, 1.0 equiv) was
added at À408C. The resulting solution was stirred for 48 h. The crude
reaction mixture was directly charged on silica gel and purified by
column chromatography (n-hexane/ethyl acetate, 95.5) to afford the de-
sired product 7.
Table 4. Scope of the asymmetric Friedel–Crafts alkylation.[a]
General Procedure for the Enantioselective Friedel–Crafts Alkylation of
Indole with Trifluoropyruvate
Indole 8 (0.077 mmol, 1.0 equiv), catalyst CaACTHNURTGNENUG[4k]n (5 mol%), and ethyl
trifluoropyruvate 6 (0.116 mmol, 1.5 equiv) were suspended in dichloro-
ethane (0.3 mL) in a screw capped vial. The resulting mixture was al-
lowed to stir at room temperature for 30 min. The crude reaction mixture
was directly purified by column chromatography on silica gel (n-hexane/
dichloromethane/ethyl acetate, 10:9:1) to give the desired product 9.
Entry
R
9
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
H
5-F
5-Cl
5-Br
5-I
5-CN
6-F
6-Cl
5-CH3
5-OCH3
7-CH3
7-C2H5
9a
9b
9c
9d
9e
9 f
9g
9h
9i
92
94
93
98
98
90
96
98
99
98
99
98
83
84
84
85
79
87
89
87
82
82
87
84
Acknowledgements
The authors acknowledge European Research Council for a starting
grant.
9
10
11
12
9j
9k
9l
Keywords: 1,2-addition reactions · asymmetric synthesis ·
brønsted acids · calcium · chirality
[a] Reaction conditions: indole
8 (1.0 equiv), 6 (1.5 equiv), CaACHTGUNTREN[NUNG 4k]n
(5 mol%), in 0.26m solution of dichloroethane at room temperature for
30 min. [b] Yield of the isolated product after column chromatography.
[c] Determined by HPLC analysis on a chiral column.
[1] For reviews of asymmetric reactions using alkaline-earth metal cata-
lysts, see: a) S. Kobayashi, R. Matsubara, Chem. Eur. J. 2009, 15,
10694–10700; b) U. Kazmaier, Angew. Chem. 2009, 121, 5902–5904;
Angew. Chem. Int. Ed. 2009, 48, 5790–5792; c) S. Harder, Chem.
Rev. 2010, 110, 3852–3876; d) S. Kobayashi, Y. Yamashita, Acc.
Chem. Res. 2011, 44, 58–71; e) Y. Yamashita, T. Tsubogo, S. Ko-
bayashi, Chem. Sci. 2012, 3, 967–975.
proceeds well with various indoles bearing electron-with-
drawing or electron-donating groups to afford the products
in excellent yields and with enantiomeric excesses up to
89%. Interestingly, the calcium salts compare favorably to
the earlier reported metal-free Brønsted acid catalysts.[12]
[2] Recent examples of chiral alkaline-earth and metal binol phosphate
catalysts, see: a) M. Hatano, T. Ikeno, T. Matsumura, S. Torii, K. Ish-
ihara, Adv. Synth. Catal. 2008, 350, 1776–1780; b) K. Shen, X. Liu,
Y. Cai, L. Lin, X. Feng, Chem. Eur. J. 2009, 15, 6008–6014; c) T.
Yue, M.-X. Wang, D.-X. Wang, G. Masson, J. P. Zhu, J. Org. Chem.
2009, 74, 8396–8399; d) M. Klussmann, Angew. Chem. 2009, 121,
7260–7261; Angew. Chem. Int. Ed. 2009, 48, 7124–7125; e) F.
Drouet, C. Lalli, H. Liu, G. Masson, J. Zhu, Org. Lett. 2011, 13, 94–
97; f) M. Hatano, K. Ishihara, Synthesis 2010, 3785–3801; g) M.
Hatano, K. Moriyama, T. Maki, K. Ishihara, Angew. Chem. 2010,
122, 3911–3914; Angew. Chem. Int. Ed. 2010, 49, 3823–3826; h) M.
Klussmann, L. Ratjen, S. Hoffmann, V. Wakchaure, R. Goddard, B.
List, Synlett 2010, 2189–2192; i) J. Lv, X. Li, L. Zhong, S. Luo, J.-P.
Cheng, Org. Lett. 2010, 12, 1096–1099; j) Z. Zhang, W. Zheng, J. C.
Antilla, Angew. Chem. 2011, 123, 1167–1170; Angew. Chem. Int.
Ed. 2011, 50, 1135–1138; k) U. Hennecke, C. H. Mꢁller, R. Frçhlich,
Org. Lett. 2011, 13, 860–863; l) G. K. Ingle, Y. Liang, M. G. Mormi-
no, G. Li, F. R. Fronczek, J. C. Antilla, Org. Lett. 2011, 13, 2054–
Conclusions
In summary, we here report the first asymmetric calcium-
catalyzed addition reactions of styrene as well as indole de-
rivatives to trifluoropyruvates. The corresponding products
are obtained in high yields and with good to excellent enan-
tioselectivities. The procedure allows direct access to biolog-
ically relevant fluorine-containing molecules, which are of
interest for medicinal and agrochemical chemistry. The syn-
thesis of quaternary stereocenters still remains a challenge
Chem. Asian J. 2012, 00, 0 – 0
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COMMUNICATION
2057; m) S. E. Larson, G. Li, G. B. Rowland, D. Junge, R. Huang,
H. L. Woodcock, J. C. Antilla, Org. Lett. 2011, 13, 2188–2191; n) J.
Lv, L. Zhang, Y. Zhou, Z. Nie, S. Luo, J.-P. Cheng, Angew. Chem.
2011, 123, 6740–6744; Angew. Chem. Int. Ed. 2011, 50, 6610–6614;
o) M. Rueping, T. Bootwicha, E. Sugiono, Synlett 2011, 323–326;
p) M. Terada, K. Kanomata, Synlett 2011, 1255–1258; q) W. Zheng,
Z. Zhang, M. J. Kaplan, J. C. Antilla, J. Am. Chem. Soc. 2011, 133,
3339–3341; r) J. Lv, L. Zhang, S. Hu, J.-P. Cheng, S. Luo, Chem.
Eur. J. 2012, 18, 799–803; s) S. Zhou, S. Fleischer, K. Junge, M.
Beller, Angew. Chem. 2011, 123, 5226–5230; Angew. Chem. Int. Ed.
2011, 50, 5120–5124.
Ed. 2005, 44, 7257–7260; d) S. Doherty, J. G. Knight, C. H. Smyth,
R. W. Harrington, W. Clegg, J. Org. Chem. 2006, 71, 9751–9764;
e) S. Doherty, J. G. Knight, C. H. Smyth, R. W. Harrington, W.
Clegg, Organometallics 2007, 26, 5961–5966; f) J.-F. Zhao, T.-B. W
Tjan, B.-H. Tan, T.-P. Loh, Org. Lett. 2009, 11, 5714–5716; g) H.-K.
Luo, Y.-L. Woo, H. Schumann, C. Jacob, M. van Meurs, H.-Y. Yang,
Y.-T. Tan, Adv. Synth. Catal. 2010, 352, 1356–1364; h) K. Zheng, Y.
Yang, J. Zhao, C. Yin, L. Lin, X. Liu, X. Feng, Chem. Eur. J. 2010,
16, 9969–9972.
[9] For recent reviews on enantioselective carbonyl-ene reactions, see:
a) K. Mikami, M. Terada in Comprehensive Asymmetric Catalysis,
Vol. 3 (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer,
Berlin, 1999, pp. 1143–1176; b) M. L. Clarke, M. B. France, Tetrahe-
dron 2008, 64, 9003–9031.
[10] Reviews on catalytic enantioselective Friedel–Crafts alkylations,
see: a) M. Bandini, A. Umani-Ronchi, Catalytic Asymmetric Frie-
del–Crafts Alkylations, Wiley-VCH, Weinheim, 2009; b) S.-L. You,
Q. Cai, M. Zeng, Chem. Soc. Rev. 2009, 38, 2190–2201; c) M. Ruep-
ing, B. J. Nachtsheim, Beilstein J. Org. Chem. 2010, 6, No. 6; d) V.
Terrasson, R. M. de Figueiredo, J. M. Campagne, Eur. J. Org. Chem.
2010, 2635–2655.
[3] a) M. Rueping, R. M. Koenigs, I. Atodiresei, Chem. Eur. J. 2010, 16,
9350–9365; b) M. Rueping, B. J. Nachtsheim, R. M. Koenigs, W.
Ieawsuwan, Chem. Eur. J. 2010, 16, 13116–13126; c) M. Rueping,
B. J. Nachtsheim, W. Ieawsuwan, I. Atodiresei, Angew. Chem. 2011,
123, 6838–6853; Angew. Chem. Int. Ed. 2011, 50, 6706–6720.
[4] For reviews on binol phosphoric acids, see: a) T. Akiyama, J. Itoh,
K. Fuchibe, Adv. Synth. Catal. 2006, 348, 999–1010; b) G. Adair, S.
Mukherjee, B. List, Aldrichimica Acta 2008, 41, 31–39; c) M.
Terada, Chem. Commun. 2008, 4097–4112; d) M. Terada, Bull.
Chem. Soc. Jpn. 2010, 83, 101–119; e) M. Terada, Synthesis 2010,
1929–1982; f) D. Kampen, C. M. Reisinger, B. List, Top. Curr.
Chem. 2010, 291, 395–456; g) A. Zamfir, S. Schenker, M. Freund,
S. B. Tsogoeva, Org. Biomol. Chem. 2010, 8, 5262–5276; h) M.
Rueping, A. Kuenkel, I. Atodiresei, Chem. Soc. Rev. 2011, 40, 4539–
4549.
[5] Selected examples on Brønsted acid-catalyzed reactions from our
group, see: a) M. Rueping, E. Sugiono, C. Azap, Angew. Chem.
2006, 118, 2679–2681; Angew. Chem. Int. Ed. 2006, 45, 2617–2619;
b) M. Rueping, A. P. Antonchick, T. Theissmann, Angew. Chem.
2006, 118, 3765–3768; Angew. Chem. Int. Ed. 2006, 45, 3683–3686;
c) M. Rueping, C. Azap, Angew. Chem. 2006, 118, 7996–7999;
Angew. Chem. Int. Ed. 2006, 45, 7832–7835; d) M. Rueping, W.
Ieawsuwan, A. P. Antonchick, B. J. Nachtsheim, Angew. Chem. 2007,
119, 2143–2146; Angew. Chem. Int. Ed. 2007, 46, 2097–2100; e) M.
Rueping, E. Sugiono, F. R. Schoepke, Synlett 2007, 1441–1445; f) M.
Rueping, A. P. Antonchick, Angew. Chem. 2008, 120, 10244–10247;
Angew. Chem. Int. Ed. 2008, 47, 10090–10093; g) M. Rueping, B. J.
Nachtsheim, S. A. Moreth, M. Bolte, Angew. Chem. 2008, 120, 603–
606; Angew. Chem. Int. Ed. 2008, 47, 593–596; h) M. Rueping, A. P.
Antonchick, E. Sugiono, K. Grenader, Angew. Chem. 2009, 121,
925–927; Angew. Chem. Int. Ed. 2009, 48, 908–910; i) M. Rueping,
W. Ieawsuwan, Adv. Synth. Catal. 2009, 351, 78–84; j) M. Rueping,
C. Brinkmann, A. P. Antonchick, I. Atodiresei, Org. Lett. 2010, 12,
4604–4607; k) M. Rueping, F. Tato, F. R. Schoepke, Chem. Eur. J.
2010, 16, 2688–2691; l) M. Rueping, M.-Y. Lin, Chem. Eur. J. 2010,
16, 4169–4172; m) M. Rueping, T. Theissmann, Chem. Sci. 2010, 1,
473–476; n) M. Rueping, E. Sugiono, A. Steck, T. Theissmann, Adv.
Synth. Catal. 2010, 352, 281–287; o) M. Rueping, U. Uria, M.-Y. Lin,
I. Atodiresei, J. Am. Chem. Soc. 2011, 133, 3732–3735.
[11] Examples of asymmetric Friedel–Crafts alkylations catalyzed by
binol phosphoric acids, see: a) D. Uraguchi, K. Sorimachi, M.
Terada, J. Am. Chem. Soc. 2004, 126, 11804–11805; b) Y.-X. Jia, J.
Zhong, S.-F. Zhu, C.-M. Zhang, Q.-L. Zhou, Angew. Chem. 2007,
119, 5661–5663; Angew. Chem. Int. Ed. 2007, 46, 5565–5567; c) Q.
Kang, Z.-A. Zhao, S.-L. You, J. Am. Chem. Soc. 2007, 129, 1484–
1485; d) G. Li, G. B. Rowland, E. B. Rowland, J. C. Antilla, Org.
Lett. 2007, 9, 4065–4068; e) M. Terada, K. Sorimachi, J. Am. Chem.
Soc. 2007, 129, 292–293; f) M. Terada, S. Yokoyama, K. Sorimachi,
D. Uraguchi, Adv. Synth. Catal. 2007, 349, 1863–1867; g) J. Itoh, K.
Fuchibe, T. Akiyama, Angew. Chem. 2008, 120, 4080–4082; Angew.
Chem. Int. Ed. 2008, 47, 4016–4018; h) Q. Kang, X.-J. Zheng, S.-L.
You, Chem. Eur. J. 2008, 14, 3539–3542; i) H.-Y. Tang, A.-D. Lu, Z.-
H. Zhou, G.-F. Zhao, L.-N. He, C.-C. Tang, Eur. J. Org. Chem. 2008,
1406–1410; j) M. J. Wanner, P. Hauwert, H. E. Schoemaker, R. de
Gelder, J. H. van Maarseveen, H. Hiemstra, Eur. J. Org. Chem.
2008, 180–185; k) M. Zeng, Q. Kang, Q.-L. He, S.-L. You, Adv.
Synth. Catal. 2008, 350, 2169–2173; l) Q. Cai, Z.-A. Zhao, S.-L. You,
Angew. Chem. 2009, 121, 7564–7567; Angew. Chem. Int. Ed. 2009,
48, 7428–7431; m) S. Nakamura, Y. Sakurai, H. Nakashima, N. Shi-
bata, T. Toru, Synlett 2009, 1639–1642; n) Y.-F. Sheng, Q. Gu, A.-J.
Zhang, S.-L. You, J. Org. Chem. 2009, 74, 6899–6901; o) Y.-F.
Sheng, G.-Q. Li, Q. Kang, A.-J. Zhang, S.-L. You, Chem. Eur. J.
2009, 15, 3351–3354; p) F.-L. Sun, M. Zeng, Q. Gu, S.-L. You,
Chem. Eur. J. 2009, 15, 8709–8712; q) D. Enders, M. Seppelt, T.
Beck, Adv. Synth. Catal. 2010, 352, 1413–1418; r) T. Sakamoto, J.
Itoh, K. Mori, T. Akiyama, Org. Biomol. Chem. 2010, 8, 5448–5454;
s) L. Simꢂn, J. M. Goodman, J. Org. Chem. 2010, 75, 589–597; t) T.
Wang, G.-W. Zhang, Y. Teng, J. Nie, Y. Zheng, J.-A. Ma, Adv. Synth.
Catal. 2010, 352, 2773–2777; u) T. Hirata, M. Yamanaka, Chem.
Asian J. 2011, 6, 510–516; v) M. Rueping, S. Raja, A. NfflÇez, Adv.
Synth. Catal. 2011, 353, 563–568; w) D. Wilcke, E. Herdtweck, T.
Bach, Synlett 2011, 1235–1238; x) Q. Yin, S.-L. You, Chem. Sci.
2011, 2, 1344–1348.
[6] D. Uraguchi, M. Terada, J. Am. Chem. Soc. 2004, 126, 5356–5357.
[7] Organocatalyzed enantioselective carbonyl-ene reactions, see:
a) M. L. Clarke, C. E. S. Jones, M. B. France, Beilstein J. Org. Chem.
2007, 3, No. 24; b) M. Rueping, T. Theissmann, A. Kuenkel, R. M.
Koenigs, Angew. Chem. 2008, 120, 6903–6906; Angew. Chem. Int.
Ed. 2008, 47, 6798–6801.
[8] Metal-catalyzed enantioselective carbonyl-ene reaction with trifluor-
opyruvates, see: a) K. Aikawa, S. Kainuma, M. Hatano, K. Mikami,
Tetrahedron Lett. 2004, 45, 183–185; b) K. Mikami, K. Aikawa, S.
Kainuma, Y. Kawakami, T. Saito, N. Sayo, H. Kumobayashi, Tetra-
hedron: Asymmetry 2004, 15, 3885–3889; c) K. Mikami, H. Kakuno,
K. Aikawa, Angew. Chem. 2005, 117, 7423–7426; Angew. Chem. Int.
[12] a) J. Nie, G. W. Zhang, L. Wang, D. H. Zheng, Y. Zheng, J. A. Ma,
Eur. J. Org. Chem. 2009, 3145–3149; b) W. Kashikura, J. Itoh, K.
Mori, T. Akiyama, Chem. Asian J. 2010, 5, 470–472.
Received: January 18, 2012
Published online: && &&, 0000
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www.chemasianj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 0000, 00, 0 – 0
ÝÝ These are not the final page numbers!

COMMUNICATION
Asymmetric Catalysis
Magnus Rueping,*
Teerawut Bootwicha,
Supakeat Kambutong,
Erli Sugiono
&&&& — &&&&
Asymmetric Calcium Catalysis: Highly
Enantioselective Carbonyl-Ene and
Friedel–Crafts Reactions for the
Synthesis of Quaternary a-Hydroxy
Esters Bearing a Trifluoromethyl
Group
Enantioselective calcium-catalyzed
addition reactions of styrene and
indole derivatives with trifluoropyru-
vates have been developed. The alka-
line-earth metal-catalyzed reactions
proceed smoothly to afford the corre-
sponding products in high yields and
with good to excellent enantioselectivi-
ties under mild reaction conditions.
Chem. Asian J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
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These are not the final page numbers! ÞÞ