Enantioselective carbonyl-ene reactions of arylglyoxals with a chiral palladium(II)-BINAP catalyst

Article abstract of DOI:10.1002/adsc.200600361

The palladium(II)-BINAP-catalyzed enantioselective carbonyl-ene reactions between ten arylglyoxals and five alkenes were systematically investigated and demonstrated good to excellent enantioselectivities with high ee values of up to 93.8%. The results sh

Full text of DOI:10.1002/adsc.200600361

FULL PAPERS
DOI: 10.1002/adsc.200600361
Enantioselective Carbonyl-Ene Reactions of Arylglyoxals with a
Chiral Palladium(II)-BINAP Catalyst
He-Kuan Luo,a,* Lim Bee Khim,a Herbert Schumann,b Christina Lim,a
Tan Xiang Jie,a and Hai-Yan Yanga
a
Institute of Chemical and Engineering Sciences, 1 Pesek Road, Jurong Island, Singapore 627833
Fax : (+65)-6316-6182; e-mail: luo_hekuan@ices.a-star.edu.sg
Institut für Chemie, Technische Universität Berlin, Straße des 17, Juni 135, 10623 Berlin, Germany
b
Received: July 18, 2006; Revised: March 30, 2007
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The palladium(II)-BINAP-catalyzed enan- tivity is improved. When using dienes (1,4-diisopro-
tioselective carbonyl-ene reactions between ten aryl- penylbenzene and 1,3-diisopropenylbenzene) as sub-
glyoxals and five alkenes were systematically investi- strates in this reaction, only one of the two carbon-
gated and demonstrated good to excellent enantiose- carbon double bonds participated into the reaction
lectivities with high ee values of up to 93.8%. The re- affording tetrafunctional organic compounds with
sults showed that both arylglyoxals and alkenes exert moderate enantioselectivities of up to 83.8% ee. The
evident effects on the enantioselectivity. Particularly, chiral Lewis acid palladium(II) catalyst incorporating
the ortho-methyl substituents of the substrates could (R)-BINAP, which is a conformationally restricted
increase the enantioselectivity. The achieved excel- chiral ligand, is very stable in ionic liquids and could
lent enantioselectivities may be due to the corre- be recycled 21 times with retention of the high enan-
sponding substrate matches well fitting the chiral tioselectivity.
space created by the chiral palladium(II)-BINAP
catalyst. The ortho-methyl substituents may improve
the fitting of the substrate match to the chiral space Keywords: alkenes; arylglyoxals; carbonyl-ene reac-
created by the chiral catalyst, hence the enantioselec- tion; enantioselectivity; palladium
Introduction
methylenecyclohexane to give (S)-ethyl 3-(1’-cyclo-
hexenyl)-2-hydroxypropionate with 78% ee and 88%
As one of the most fundamental carbon-carbon bond- yield at room temperature. Mikami[6b] and co-workers
forming reactions in organic synthesis and asymmetric also
reported
that
the
chirally
dynamic
catalysis to prepare optically active homoallylic alco- diphenylphosphinoferrocene
AHCTREUNG
hols, the enantioselective carbonyl-ene reaction has used to prepare enantio- and diastereomerically pure
attracted much attention in the past two decades, and metal complexes by coordination with enantiopure di-
various transition metal catalysts incorporated with aminobinaphthyl (DABN) to control the axial chirali-
different ligands have been actively studied.[1–7] Some ty of DPPF-M complexes, and demonstrated that
of them could achieve high enantioselectivity, such as Ni(II)-DPPF with DABN affords much higher enan-
organoaluminum catalysts,[1] Ti-BINOL catalysts[2] tioselectivities for the glyoxylate-ene reactions in
Cu-BOX catalysts,[4] optically active b-ketoiminato comparison with the Pd(II) and Pt(II) counterparts.
cationic cobalt
N
À
For the group of Pd(II)-diphosphine catalysts, Mika- were also efficient and enantioselective catalysts for
mi[6a] and co-workers firstly studied the palladium(II) the glyoxylate-ene reaction between ethyl glyoxylate
complexes of (S)-BINAP, (S)-Tol-BINAP and (S)- and methylenecyclohexane with ees up to 85%, and
xylyl-BINAP in the glyoxylate-ene reactions between the addition of achiral acidic phenol additives could
ethyl glyoxylate and alkenes, and demonstrated that increase the rate of the OTf-based catalysts by dis-
{Pd
N
(SbF6)2 is an efficient rupting contact ion pairs and sequestering traces of
Adv. Synth. Catal. 2007, 349, 1781 – 1795
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1781

He-Kuan Luo et al.
FULL PAPERS
platinum complex of tropos-BIPHEP [BIPHEP=2,2’- from 96% to 88%, and the yield dropped from 86%
bis(diphenylphosphino)-1,1’-biphenyl] can be resolved to 53%. Ohta[8c] and co-workers reported that, in the
with (S)-BINOL, thus the d- and l-{(BIPHEP)Pt[(S)- asymmetric transfer hydrogenation of acetophenone,
BINOL]} systems could each be isolated to give the the Lewis acid catalyst TsDPEN-coordinated Ru(II)
corresponding single diastereoismer from which the complex [TsDPEN=N-(p-toluenesulfonyl)-1,2-diphe-
Lewis acid fragments d- and l-[(BIPHEP)Pt]2+ can be nylethylenediamine] could be recycled in [BMIM]
obtained by liberating (S)-BINOL via different meth- [PF6] through five cycles. Although the conversion
ods. The obtained Pt(II)-BIPHEP Lewis acid is an ef- evidently decreased from 96% to 63%, the high
ficient and enantioselective catalyst for the carbonyl- enantioselectivity (93% ee) remained constant. Con-
ene reactions of ethyl glyoxylate and phenylglyoxal cerning catalyst recycle for enantioselective carbonyl-
with alkenes affording ee values as high as 94%[6e] ene reactions, Ikegami[2d] and co-workers developed a
since the coordination of BIPHEP to the substitution- reusable heterogeneous catalyst prepared from a self-
inert metal platinum(II) significantly slows the atro- assembly of Ti(O-i-Pr)4 and non-cross-linked copoly-
G
pinversion. Recently Doherty[6f] and co-workers re- mers with (R)-BINOL pendant groups, which was
ported that the enantiopure platinum(II) complexes reused four times for the enantioselective carbonyl-
of conformationally flexible NUPHOS diphosphines, ene reaction between ethyl glyoxylate and a-methyl-
À
d- and l-[(NUPHOS)Pt](X)2 (X=OTfÀ, SbF6 ) are styrene with almost no loss of activity (around 85%
highly efficient catalysts for the carbonyl-ene reac- yield), but the ee dropped from 88% to 81%. Particu-
tions of ethyl glyoxylate and phenylglyoxal with vari- larly, Doherty[6f] and co-workers have demonstrated
ous alkenes affording ee values as high as 95%; The that the in situ generated d-[(NUPHOS)Pt](OTf)2
G
in situ activation of d- and l-{(NUPHOS)Pt[(S)- from BINOLate precursors can be used three times
BINOL]} with triflic acid generated a most efficient with almost no loss of enantioselectivity in the ionic
catalyst in the ionic liquid [EMIM]
G
G
methylimidazolium bis(trifluoromethylsulfonyl)- dropped evidently. For example, for the monocyclic
amide] affording marked enhancements in enantiose- NUPHOS-Pt(II)-catalyzed reaction between phenyl-
lectivity compared with the corresponding reactions glyoxal and methylenecyclohexane, the enantioselec-
in dichloromethane; Particularly, platinum(II) cata- tivity remained constant (87% ee, 87% ee, 86% ee
lysts based on monocyclic NUPHOS can compete for three cycles, respectively), but the isolated yields
with their BINAP counterparts.
dropped from 38% to 13% over these three cycles;
Homogeneous asymmetric catalysis using chiral For the reaction between ethyl glyoxylate and methyl-
Lewis acid catalysts has the evident advantages of enecyclohexane, the enantioselectivity also remained
high efficiency and high enantioselectivity. However, constant (71% ee, 70% ee, 70% ee for three cycles,
most homogeneous catalysts for asymmetric reactions respectively), but the isolated yield also dropped from
are not practical because the chiral catalysts are very 74% to 43% over these cycles.
expensive and the catalyst loadings are very high, nor-
Because all of the catalysts were reported to be
mally 2 mol% to 20 mol%. Therefore recycling the water-sensitive, strictly anhydrous reaction conditions
expensive chiral catalysts is extremely important for are needed, including drying of solvents, substrates
industrial applications. Beside heterogenization of ho- and reactors, etc. One of the two substrates is an aryl-
mogeneous catalysts to make solid catalysts which glyoxal that is usually prepared, purified and trans-
usually results in decreased enantioselectivity and/or ported as the monohydrate form.[9] The dry arylglyox-
activity, recently some reports have demonstrated al has to be prepared by drying the arylglyoxal mono-
that ionic liquids could be used to recycle the chiral hydrate under vacuum and at elevated temperature
catalysts by phase separation for five cycles with re- because the chiral catalysts are water-sensitive. This
tention of high enantioselectivities and good activi- caused much inconvenience in the study of enantiose-
ties.[8] Jessop[8a] and co-workers reported that the lective carbonyl-ene reactions and, as a consequence,
asymmetric hydrogenation of tiglic acid in only phenylglyoxal was studied. Recently, we found
[BMIM]PF6/H2O (BMIM=1-butyl-3-methylimidazoli- that palladium(II)- and platinum(II)-BINAP catalysts
um) gave 85% ee. After the product had been ex- are water-tolerant in the enantioselective carbonyl-
tracted with scCO2, the ionic liquid-immobilized cata- ene reactions, so the arylglyoxal monohydrate could
lyst was reused for four times with an average ee of be used directly as substrate achieving good to excel-
89% which is higher than the original ee of 85% ob- lent enantioselectivities.[10] This provided us with a
tained from the first cycle; at the same time the con- versatile and convenient method to study different ar-
version dropped only slightly from 99% to 97%. ylglyoxals in this reaction, to investigate the effect of
Song[8b] and co-workers reported that
(salen)Mn catalyst could be recycled for four times in tegrated with alkenes. In the present studies, we sys-
[BMIM][PF6] for the asymmetric epoxidation of 2,2- tematically investigated the Pd(II)-BINAP-catalyzed
dimethylchromene, after five cycles, the ee dropped enantioselective carbonyl-ene reactions of ten aryl-
a chiral substrates systematically by matching arylglyoxals in-
ACHTREUNG
1782
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1781 – 1795

Enantioselective Carbonyl-Ene Reactions of Arylglyoxals
FULL PAPERS
glyoxals with five alkenes and two dienes. The effect
of the substrates on enantioselectivity is discussed;
We also studied the recycle of the palladium(II) cata-
lyst with (R)-BINAP that is a conformationally re-
stricted chiral diphosphine ligand in the ionic liquid
[BdMIM]
ACHTREUNG
catalyst is very stable in [BdMIM]
AHCTREUNG
recycled 21 times with retention of the high enantio-
selectivity and no loss of isolated yield for the first 11
cycles.
Results
Scheme 2. Enantioselective carbonyl-ene reactions catalyzed
Pd(II)-BINAP-Catalyzed Enantioselective Carbonyl-
Ene Reactions between Ten Arylglyoxals and Five
Alkenes
by the chiral catalyst {[(R)-BINAP]Pd}(SbF6)2.
A
nylglyoxal, 4-bromophenylglyoxal, 2,4,6-trimethylphe-
In order to study the effect of the substrates, here we nylglyoxal, 2-naphthylglyoxal, 4-fluorophenylglyoxal,
selected ten arylglyoxals and five alkenes with differ- 4-trifluoromethylphenylglyoxal, 2,4-difluorophenyl-
ent molecular structures. The ten arylglyoxals include glyoxal and 3,4-difluorophenylglyoxal (1–10 in
phenylglyoxal, 4-methylphenylglyoxal, 4-chlorophe- Scheme 1). The five alkenes include methylenecyclo-
hexane, 2,3-dimethyl-1-butene, 2,4,4-trimethyl-1-pen-
tene, a-methylstyrene and a,2-dimethylstyrene (a–e in
Scheme 1). The Pd(II)-BINAP-catalyzed enantiose-
lective carbonyl-ene reactions between the above ten
arylglyoxals and the five alkenes were systematically
investigated and demonstrated good to excellent
enantioselectivities with ee values between 72.8% and
93.8% (Table 1 and Scheme 2). Both the arylglyoxals
and the alkenes could evidently affect the enantiose-
lectivity, indicating that the Pd(II)-BINAP-catalyzed
enantioselective carbonyl-ene reactions are highly
substrate-dependent. In general, the reactions of both
2,3-dimethyl-1-butene and a,2-dimethylstyrene dem-
onstrate excellent enantioselectivities with all the ten
arylglyoxals (entries 11–20 and 41–50). The reactions
of both methylenecyclohexane and 2,4,4-trimethyl-1-
pentene demonstrate relatively lower but still high
enantioselectivities (1–10 and 21–30), while the reac-
tions of a-methylstyrene demonstrate the lowest
enantioselectivities (entries 31–40).
Enantioselective Carbonyl-Ene Reactions of Dienes
Two dienes, 1,4-diisopropenylbenzene and 1,3-diiso-
propenylbenzene (f and g in Scheme 3) were investi-
Scheme 1. Substrates employed in the enantioselective car-
bonyl-ene reactions.
Scheme 3. Structures of 1,4-diisopropenylbenzene and 1,3-
diisopropenylbenzene.
Adv. Synth. Catal. 2007, 349, 1781 – 1795
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1783

He-Kuan Luo et al.
FULL PAPERS
Table 1. Enantioselective carbonyl-ene reactions of ten arylglyoxals with five alkenes.[a]
Entry
Alkene
Arylglyoxal
Product
No.
Structure
Time [h]
Yield[b] [%]
ee[c] [%]
88.0 (S)
85.5 (S)
85.2 (S)
1
2
3
a
a
a
1
2
3
1a
2a
3a
1
1
2
51
47
35
4
a
4
4a
3
39
84.2 (S)
5
6
7
a
a
a
5
6
7
5a
6a
7a
2
2
2
41
50
43
91.2 (S)
73.6 (S)
87.8 (S)
8
9
a
a
8
9
8a
9a
2
41
42
86.0 (S)
85.0 (S)
1.5
10
11
12
13
a
b
b
b
10
1
10a
1b
2
2
1
2
37
50
37
43
85.2 (S)
93.0 (S)
91.8 (S)
91.6 (S)
2
2b
3
3b
1784
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1781 – 1795

Enantioselective Carbonyl-Ene Reactions of Arylglyoxals
FULL PAPERS
Table 1. (Continued)
Entry
Alkene
Arylglyoxal
Product
No.
Structure
Time [h]
Yield[b] [%]
ee[c] [%]
14
15
16
17
b
b
b
b
4
5
6
7
4b
5b
6b
7b
3
2
2
2
35
50
34
34
89.5 (S)
93.4 (S)
91.6 (S)
92.8 (S)
18
19
b
b
8
9
8b
9b
2
2
41
30
92.0 (S)
91.8 (S)
20
21
22
23
b
c
c
c
10
1
10b
1c
2
2
1
3
34
56
49
59
91.6 (S)
88.0 (S)
86.8 (S)
76.4 (S)
2
2c
3
3c
24
25
26
27
c
c
c
c
4
5
6
7
4c
5c
6c
7c
3
2
2
2
46
36
48
37
85.1 (S)
92.6 (S)
84.0 (S)
87.2 (S)
Adv. Synth. Catal. 2007, 349, 1781 – 1795
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1785

He-Kuan Luo et al.
FULL PAPERS
Table 1. (Continued)
Entry
Alkene
Arylglyoxal
Product
No.
Structure
Time [h]
Yield[b] [%]
ee[c] [%]
85.0 (S)
87.3 (S)
81.8 (S)
80.0 (S)
82.8 (S)
28
c
c
c
d
d
8
8c
2
51
41
46
40
32
29
9
9c
1.5
2
30
10
1
10c
1d
2d
31
1
32
2
1
33
34
d
d
3
4
3d
4d
1
31
33
74.8 (S)
76.0 (S)
0.5
35
36
d
d
5
6
5d
6d
0.5
0.5
20
21
75.2 (S)
78.4 (S)
37
38
39
40
d
d
d
d
7
7d
0.5
0.5
0.5
0.5
22
27
17
18
78.0 (S)
75.0 (S)
82.4 (S)
72.8 (S)
8
8d
9
9d
10
10d
1786
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1781 – 1795

Enantioselective Carbonyl-Ene Reactions of Arylglyoxals
FULL PAPERS
Table 1. (Continued)
Entry
41
Alkene
Arylglyoxal
Product
No.
Structure
Time [h]
0.5
Yield[b] [%]
ee[c] [%]
93.6 (S)
93.8 (S)
e
e
1
2
1e
2e
21
22
42
0.5
43
44
e
e
3
4
3e
4e
0.5
0.5
25
21
93.0 (S)
93.6 (S)
45
46
e
e
5
6
5e
6e
0.5
0.5
35
22
92.8 (S)
93.6 (S)
47
48
49
e
e
e
e
7
7e
0.5
0.5
0.5
0.5
19
18
28
16
93.8 (S)
91.4 (S)
93.6 (S)
90.0 (S)
8
8e
9
9e
50
10
10e
[a]
Reaction conditions: All the reactions were run under room temperature. Catalyst {[(R)-BINAP]Pd}
(5 mol%); arylglyoxal monohydrate, 0.25 mmol; alkene, 0.25 mmol.
Isolated yield with flash chromatography.
Determined by HPLC with a Chiralcel OD-H column for products 1a, 2a, 1b, 2b, 1c, 2c; with a Chiralpak AD-H column
for products 3a, 4a, 3b, 4b, 3c, 4c, 8c, 9c; with a Chiralpak AS-H column for products 5a–10a, 5b–10b, 5c–7c, 10c, 5d–10d;
with a Chiralcel OB-H column for products 1d, 2d, 3d, 4d. The absolute configurations of the carbonyl-ene products were
determined by comparing the HPLC retention times with those reported in the literature, or by comparison with the
analogous products reported in the literature.
A
[b]
[c]
gated in the enantioselective carbonyl-ene reactions. reaction affording tetrafunctional organic compounds
The results revealed that only one of the two carbon- with moderate enantioselectivities (see Table 2 and
carbon double bonds of the diene participated in the Table 3). Even when the molar ratio of arylglyoxal to
Adv. Synth. Catal. 2007, 349, 1781 – 1795
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1787

He-Kuan Luo et al.
FULL PAPERS
Table 2. Enantioselective carbonyl-ene reactions between arylglyoxals and 1,4-diisopropenylbenzene.[a]
Entry
Arylglyoxal
Product
No.
Structure
Time
Yield[b] [%]
ee[c] [%]
72.4 (S)
1
1
1f
2f
3f
30 min
23
9
2
3
2
3
30 min[d]
15 min
66.0 (S)
73.8 (S)
29
4
5
6
7
4
5
6
7
4f
5f
6f
7f
20 min
10 min
10 min
10 min
18
15
13
18
68.8 (S)
67.2 (S)
74.4 (S)
65.8 (S)
8
8
8f
15 min
28
71.3 (S)
[a]
Reaction conditions: All the reactions were run at room temperature. Catalyst {[(R)-BINAP]Pd}
mol%); arylglyoxal monohydrate, 0.25 mmol; diene, 0.25 mmol.
Isolated yield with flash chromatography.
Determined by HPLC with a Chiralpak AS-H column. The absolute configurations of the carbonyl-ene products were de-
termined by comparing with the analogous product reported in the literature.
Reaction at 08C.
A
[b]
[c]
[d]
diene is as high as 3 to give the arylglyoxal in a large bonds in the diene. Furthermore, the enentioselectivi-
excess, the second carbon-carbon double bond still ties remain almost the same when the substrate molar
cannot participate in the reaction. This may be due to ratio was varied from 1 to 3 (see Table 4). In compari-
the close vicinity of the two carbon-carbon double son, diene g with a meta-disubstituted phenyl group
1788
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1781 – 1795

Enantioselective Carbonyl-Ene Reactions of Arylglyoxals
FULL PAPERS
Table 3. Enantioselective carbonyl-ene reactions between arylglyoxals and 1,3-diisopropenylbenzene.[a]
Entry
Arylglyoxal
Product
No.
Structure
Time
Yield[b] [%]
ee[c] [%]
80.0 (S)
83.8 (S)
1
2
1
2
1g
2g
30 min
50 min[d]
36
16
3
4
3
4
3g
4g
10 min
10 min
23
21
78.4 (S)
78.0 (S)
5
6
5
6
5g
6g
10 min
10 min
41
21
80.2 (S)
82.8 (S)
7
7
8
7g
8g
15 min
15 min
20
27
77.0 (S)
74.7 (S)
8
[a]
Reaction conditions: All the reactions were run at room temperature. Catalyst {[(R)-BINAP]Pd}(SbF6)2 0.0125 mmol (5
A
mol%); arylglyoxal monohydrate, 0.25 mmol; diene, 0.25 mmol.
Isolated yield with flash chromatography.
[b]
[c]
Determined by HPLC with a Chiralpak AS-H column. The absolute configurations of the carbonyl-ene products were de-
termined by comparing with the analogous product reported in the literature.
Reaction at 08C.
[d]
shows higher enantioselectivity than diene f with a Catalyst Recycle in Ionic Liquid
para-disubstituted phenyl group (average ee with
eight glyoxals in Table 3 and Table 2: 79.4% vs.
G
[NTf2]
[1-butyl-2,3-dimethylimidazolium
70.0%). This may be because the two meta-isopropen- bis(trifluoromethylsulfonyl) amide, see Scheme 4] is a
yl substituents in diene g are much closer than the more chemically inert room temperature ionic liquid
two para-isopropenyl substituents in diene f. Hence in compared with “C-2-unmodified” imidazolium-based
diene g when one isopropenyl is participating in the ionic liquids,[11a] such as [BMIM]
[NTf2] and [EMIM]
G
reaction with arylglyoxal, the other isopropenyl is [NTf2]. In order to minimize the negative effect of
close to the reaction site and therefore shows higher the ionic liquid on the reaction, here we selected
influence to afford higher enantioselectivity.
[BdMIM]
ACHTREUNG
pensive chiral catalyst {[(R)-BINAP]Pd}
AHCTREUNG
Scheme 2). Three reactions of phenylglyoxal with
three alkenes including methylenecyclohexane, 2,3-di-
Adv. Synth. Catal. 2007, 349, 1781 – 1795
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1789

He-Kuan Luo et al.
FULL PAPERS
Table 4. Variation of substrate ratio (n) in enantioselective
carbonyl-ene reactions between phenylglyoxal and 1,4-diiso-
propenylbenzene/1,3-diisopropenylbenzene.[a]
the turnover had cumulated up to 156.5 mol product/
(mol catalyst) (see Table 5 and Figure 1). For the re-
action between phenylglyoxal and 2,3-dimethyl-1-
butene, the ee had slightly dropped from 91.8% to
Substrates
Entry Phenylglyoxal/ Yield[b] ee[c]
Diene (n)
[%]
[%]
Phenylglyoxal/1,4-dii-
sopropenylbenzene
1
2
3
4
5
6
1
2
3
1
2
3
23
29
43
36
41
38
72.4
72.8
72.4
80.0
80.2
80.0
Phenylglyoxal/1,3-dii-
sopropenylbenzene
[a]
Reaction conditions: All the reactions were run at room
temperature for 30 min. Catalyst {[(R)-BINAP]Pd}-
A
[b]
[c]
Isolated yield with flash chromatography.
Determined by HPLC with a Chiralpak AS-H column.
Figure 1. The correlation of ee and cumulative turnover with
the number of cycle for enantioselective carbonyl-ene reac-
tion between phenylglyoxal monohydrate and methylenecy-
clohexane in [BdMIM][NTf2].
G
91.0% after 22 cycles, the yield had cumulated up to
808%, while the turnover had cumulated up to 161.6
mol product/(mol catalyst) (see Table 6 and Figure 2).
For the reaction between phenylglyoxal and 2,4,4-tri-
Scheme 4. Schematic structure of the ionic liquid [BdMIM]-
[NTf2].
ACHTREUNG
methyl-1-butene and 2,4,4-trimethyl-1-pentene, were methyl-1-pentene, the ee remained the same (85.8%)
investigated. over 22 cycles, the yield had cumulated up to 1057%
All the three reactions were recycled 21 times. For and the turnover had cumulated up to 211.4 mol
the reaction between phenylglyoxal and methylenecy- product/(mol catalyst) (see Table 7 and Figure 3). It
clohexane, after the catalyst being recycled for 21 can be concluded that, for all the three reactions, the
times, the ee had only slightly dropped from 87.4% to Pd(II)-BINAP catalyst can be recycled many times
86.4%, the yield had cumulated up to 781%, while (up to 22 cycles) with retention of the high enantiose-
Table 5. Catalyst recycle in [BdMIM][NTf2] for enantioselective carbonyl-ene reaction between phenylglyoxal monohydrate
G
and methylenecyclohexane.[a]
Cycle
1
2
3
4
5
6
7
8
9
10
11
ee [%][b]
87.4
33
86.3
46
86.2
53
86.2
39
86.4
33
86.4
34
86.0
45
86.4
31
87.2
38
87.8
34
86.0
40
Yield [%][c]
Cumulative Yield [%]
Turnover
Cumulative Tunover
33
6.6
6.6
79
9.2
15.8
132
10.7
26.5
171
7.7
34.2
204
6.6
40.8
238
6.8
47.6
283
9.0
56.6
314
6.3
62.9
352
7.6
70.5
386
6.9
77.4
426
8.1
85.5
Cycle
12
13
14
15
16
17
18
19
20
21
22
ee [%][b]
86.1
38
86.0
38
85.8
38
86.0
35
85.8
37
86.4
31
85.8
28
86.4
31
85.8
29
86.2
26
86.4
24
Yield [%][c]
Cumulative Yield [%]
Turnover
464
7.6
502
7.5
540
7.7
575
7.1
612
7.3
643
6.3
671
5.7
702
6.2
731
5.7
757
5.1
781
4.8
Cumulative Tunover
93.1
100.6
108.3
115.4
122.7
129.0
134.7
140.9
146.6
151.7
156.5
[a]
Reaction conditions: All the reactions were run under room temperature for 1 hour. Catalyst {[(R)-BINAP]Pd}
0.0125 mmol (5 mol%); phenylglyoxal monohydrate, 0.25 mmol; methylenecyclohexane, 0.25 mmol; ionic liquid
[BdMIM][NTf2], 0.5 mL.
Determined by HPLC with a Chiralcel OD-H column.
Isolated yield with flash chromatography.
A
ACHTREUNG
[b]
[c]
1790
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1781 – 1795

Enantioselective Carbonyl-Ene Reactions of Arylglyoxals
FULL PAPERS
Table 6. Catalyst recycle in [BdMIM][NTf2] for enantioselective carbonyl-ene reaction between phenylglyoxal monohydrate
A
and 2,3-dimethyl-1-butene.[a]
Cycle
1
2
3
4
5
6
7
8
9
10
11
ee [%][b]
91.8
36
91.8
44
91.6
46
91.6
48
91.8
46
91.6
49
91.6
51
91.6
41
91.6
41
91.4
39
91.2
37
Yield [%][c]
Cumulative Yield [%]
Turnover
Cumulative Tunover
36
7.2
7.2
80
8.8
16.0
126
9.2
25.2
174
9.6
34.8
220
9.2
44.0
269
9.8
53.8
320
10.2
64.0
361
8.2
72.2
402
8.2
80.4
441
7.8
88.2
478
7.4
95.6
Cycle
12
13
14
15
16
17
18
19
20
21
22
ee [%][b]
91.9
35
92.0
34
91.4
34
91.5
34
91.6
32
91.7
30
91.8
29
91.6
28
91.6
27
91.9
26
91.0
21
Yield [%][c]
Cumulative Yield [%]
Turnover
513
7.0
547
6.8
581
6.8
615
6.8
647
6.4
677
6.0
706
5.8
734
5.6
761
5.4
787
5.2
808
4.2
Cumulative Tunover
102.6
109.4
116.2
123.0
129.4
135.4
141.2
146.8
152.2
157.4
161.6
[a]
Reaction conditions: All the reactions were run under room temperature for 2 h. Catalyst {[(R)-BINAP]Pd}
0.0125 mmol (5 mol%); phenylglyoxal monohydrate, 0.25 mmol; 2,3-dimethyl-1-butene, 0.25 mmol; ionic liquid
[BdMIM][NTf2], 1.0 mL.
Determined by HPLC with a Chiralcel OD-H column.
Isolated yield with flash chromatography.
A
ACHTREUNG
[b]
[c]
lectivity; the isolated yield did not drop for the first
11 cycles and then dropped slowly for the second 11
cycles. These results clearly show that immobilizing
conformationally stable chiral Lewis acid catalysts in
chemically inert ionic liquids is a powerful strategy to
recycle expensive chiral catalysts, combining the ad-
vantages of homogeneous and heterogeneous cataly-
sis. To improve the recycling of d-[(NUPHOS)Pt]
(OTf)2 in the ionic liquid [EMIM][NTf2] for three cy-
U
cles,[6f] in the present catalyst recycle studies we fo-
cused on the following points: 1) We selected the
cheaper metal palladium instead of platinum. 2) (R)-
Figure 2. The correlation of ee and cumulative turnover with
the number of cycles for enantioselective carbonyl-ene reac-
BINAP is a conformationally restricted ligand that tion between phenylglyoxal monohydrate and 2,3-dimethyl-
1-butene in [BdMIM][NTf2].
AHCTREUNG
does not have the problem of racemization in the re-
Table 7. Catalyst recycle in [BdMIM][NTf2] for enantioselective carbonyl-ene reaction between phenylglyoxal monohydrate
G
and 2,4,4-trimethyl-1-pentene.[a]
Cycle
1
2
3
4
5
6
7
8
9
10
11
ee [%][b]
85.8
50
86.2
58
86.0
54
85.6
56
86.1
56
86.2
52
85.4
54
84.8
54
85.6
51
86.0
51
85.6
52
Yield [%][c]
Cumulative Yield [%]
Turnover
Cumulative Tunover
50
10.0
10.0
108
11.6
21.6
162
10.8
32.4
218
11.2
43.6
274
11.2
54.8
326
10.4
65.2
380
10.8
76.0
434
10.8
86.8
485
10.2
97.0
536
10.2
107.2
588
10.4
117.6
Cycle
12
13
14
15
16
17
18
19
20
21
22
ee [%][b]
85.6
50
85.2
48
86.0
45
86.0
43
86.2
47
86.2
39
86.0
42
86.0
41
86.4
41
85.8
38
85.8
35
Yield [%][c]
Cumulative Yield [%]
Turnover
Cumulative Tunover
638
10.0
127.6
686
9.6
137.2
731
9.0
146.2
774
8.6
154.8
821
9.4
164.2
860
7.8
172.0
902
8.4
180.4
943
8.2
188.6
984
8.2
196.8
1022
7.6
204.4
1057
7.0
211.4
[a]
Reaction conditions: All the reactions were run under room temperature for 2 h. Catalyst {[(R)-BINAP]Pd}
0.0125 mmol (5 mol%); phenylglyoxal monohydrate, 0.25 mmol; 2,4,4-trimethyl-1-pentene, 0.25 mmol; ionic liquid
[BdMIM][NTf2], 1.0 mL.
Determined by HPLC with a Chiralcel OD-H column.
Isolated yield with flash chromatography.
A
ACHTREUNG
[b]
[c]
Adv. Synth. Catal. 2007, 349, 1781 – 1795
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1791

He-Kuan Luo et al.
FULL PAPERS
Discussion
The Effect of Substrates
From the enantioselective carbonyl-ene reactions of
ten arylglyoxals with five alkenes listed in Table 1, the
average ee values of one arylglyoxal with five alkenes
and one alkene with ten arylglyoxals were calculated
and sorted in order from high to low in Table 8 and
Table 9, respectively. In comparison, alkenes demon-
strate greater influence on the enantioselectivity than
arylglyoxals (Dee: 15.4% vs. 4.8%). The average ees
of the ten arylglyoxals are between 89.0% and
84.2%, the order is arylglyoxal 5>arylglyoxal 1>ar-
ylglyoxal 2>arylglyoxal 9>arylglyoxal 7>arylglyoxal
8>arylglyoxal 4>arylglyoxal 10>arylglyoxal 3=ar-
ylglyoxal 6. The average ees of the five alkenes are
between 92.9% and 77.5%, the order is alkene e>
Figure 3. The correlation of ee and cumulative turnover with
the number of cycles for enantioselective carbonyl-ene reac-
tion between phenylglyoxal monohydrate and 2,4,4-trimeth-
yl-1-pentene in [BdMIM][NTf2].
G
cycling process comparing with tropos- or conforma- alkene b>alkene c>alkene a>alkene d. Among the
tionally flexible ligands.[6d,f] 3) The ionic liquid ten arylglyoxals, 2,4,6-trimethylphenylglyoxal demon-
[BdMIM][NTf2] is a more chemically inert ionic strates the highest average ee values of up to 89.0%;
A
liquid compared to “C-2-unmodified” imidazolium- Among the five alkenes, a,2-dimethylstyrene demon-
based ionic liquids.[11a] 4) Phenylglyoxal monohydrate strates the highest average ee values of up to 92.9%.
was used directly as substrate instead of freshly dried These results showed that both arylglyoxal and alkene
phenylglyoxal. Based on the above four points, we demonstrated evident effects on enantioselectivity.
achieved 22 cycles with retention of the high enantio-
selectivity and no loss of isolated yields for the first
11 cycles. Therefore we have made the Pd(II)-
BINAP-catalyzed enantioselective carbonyl-ene reac-
Table 9. Average ee of one alkene with ten arylglyoxals(from
tions more practical, and to the best of our knowl-
high to low).
edge, this is the best result of catalyst recycle in any
enantioselective carbonyl-ene reaction.
Alkene
e
b
c
a
d
Dee
For the chiral diphosphine-Pd(II)- and Pt(II)-cata-
lyzed enantioselective carbonyl-ene reactions, in some
cases the yields are low.[6] One reason is that the reac-
tion is not fast enough, there are still some unreacted
substrates left when terminating the reaction. Anoth-
er reason is that the product is a multi-functional or-
ganic molecule that is very active and could undergo
parallel side reactions resulting in the product being
consumed. This is supported by the result that a short
reaction time (such as 0.5–2 h) usually gives higher
yields and more pure products than a long reaction
time (such as overnight). In the catalyst recycle stud-
ies, although the yield for each reaction cycle is not
high, the catalyst recycle of 22 times has made the ex-
pensive chiral catalyst much more productive in com-
parison to the corresponding enantioselective carbon-
yl-ene reactions in dichloromethane.
Average ee
92.9
91.9
85.4
85.2
77.5
15.4
Scheme 5. The effect of an ortho-methyl group.
Table 8. Average ee of one arylglyoxal with five alkenes(from high to low).
Arylglyoxal
5
1
2
9
7
8
4
10
3
6
Dee
4.8
Average ee
89.0
88.5
88.1
88.0
87.9
85.9
85.7
84.3
84.2
84.2
1792
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1781 – 1795

Enantioselective Carbonyl-Ene Reactions of Arylglyoxals
FULL PAPERS
The Effect of ortho-Methyl Substituents of Both
Arylglyoxals and Alkenes
highly consistent with that of the Pd(II)-BINAP cata-
lyst.
The average ee of a,2-dimethylstyrene is much higher
than the average ee of a-methylstyrene (92.9% vs. Mechanistic Considerations on the Effect of
77.5%), clearly indicating that only one ortho-methyl Substrates
substituent could significantly increase the enantiose-
lectivity (Scheme 5). The average ee of 2,4,6-trime- Mikami and his co-workers have proposed that the
thylphenylglyoxal is higher than the average ee of 4- coordination of ethyl glyoxylate with the chiral cata-
methylphenylglyoxal (89.0% vs. 88.1%), indicating lyst forms the key intermediate.[6a] Gagne and his co-
that the two ortho-methyl substituents could also in- workers proposed the same kind of intermediate to
crease the enantioselectivity (Scheme 5). The promot- interpret the counterion-dependent additive and di-
ing effect of the ortho-methyl substituent on enantio- phosphine electronic effects.[6c] In order to interpret
selectivity may be due to the close vicinity of the the substrate effect, here we propose a catalytic cycle
ortho-methyl to the reaction site.
(Scheme 6) involving the intermediate (A) which is
formed from the coordination of the chiral catalyst
with arylglyoxal and intermediate (C) which is a com-
plex of the chiral catalyst with the product. The sub-
strate effect may be closely related to the fitness of
the substrate match to the chiral space created by the
Pt(II)-BINAP-Catalyzed Enantioselective
Carbonyl-Ene Reactions
In order to further prove the promoting effect of chiral catalyst, and better fitness results in higher
ortho-methyl substituent, the Pt(II)-BINAP-catalyzed enantioselectivity. The achieved excellent enantiose-
carbonyl-ene reactions of a-methylstyrene (d) and lectivities of the carbonyl-ene reactions shown in
a,2-dimethylstyrene (e) with phenylglyoxal (1) and 4- Table 1 may be due to the corresponding substrate
methylphenylglyoxal (2) were investigated (Table 10). matches well fitting the chiral space created by palla-
For the reactions with both phenylglyoxal (entries 1 dium(II)-BINAP catalyst when the alkene is ap-
and 2) and 4-methylphenylglyoxal (entries 3 and 4), proaching the coordinated arylglyoxal to form the
a,2-dimethylstyrene demonstrates much higher enan- product (B in Scheme 6). The intermediate (C) releas-
tioselectivities than a-methylstyrene (90.2% ee vs. es the chiral product which is an optically active ho-
78.0% ee; 93.0% ee vs. 76.2% ee). This significant moallylic alcohol, meanwhile the palladium(II)-
promoting effect of the Pt(II)-BINAP catalyst is BINAP catalyst reverts to intermediate (A) by coor-
dinating with arylglyoxal again. The ortho-methyl sub-
stituents are close to the reaction site and they may
Table 10. Pt(II)-BINAP-catalyzed enantioselective carbonyl-
improve the fitness of the substrate match to the
chiral space, therefore the enantioselectivity is in-
creased. Comparing the arylglyoxals in Scheme 1 re-
vealed that, although both the fluoro substituent
which is a strong electron-withdrawing group and the
methyl substituent which is an electron-donating
group, are attached to the phenyl ring, arylglyoxals 1,
2, 9, 7 have almost the same ee values(average ee
88.5%, 88.1%, 88.0%, 87.9%, respectively), only the
bulky methyl at the ortho position could increase the
enantioselectivity(arylglyoxal 5: average ee 89.0%).
This may further imply that the promoting effect of
ortho-methyl group is because of a steric effect, not
ene reactions of a-methylstyrene and a,2-dimethylstyrene
with phenylglyoxal and 4-methylphenylglyoxal.[a]
Entry Alkene Arylglyoxal Product Time Yield[b] ee[c]
[h]
[%]
[%]
1
2
3
4
d
e
d
e
1
1
2
2
1d
1e
2d
2e
2
76
78.0
(R)
90.2
(R)
76.2
(R)
93.0
(R)
0.5
1.5
0.5
70
70
64
[a]
Reaction conditions: All the reactions were run under an electronic effect.
room temperature. Catalyst {[(S)-BINAP]Pt}(SbF6)2,
AHCTREUNG
0.0125 mmol (5 mol%); arylglyoxal monohydrate,
0.25 mmol; alkene, 0.25 mmol.
Isolated yield with flash chromatography.
Conclusions
[b]
[c]
Determined by HPLC with a Chiralcel OB-H column for
products 1d, 2d; with a Chiralpak AS-H column for
products 1e, 2e. The absolute configurations of the car-
bonyl-ene products were determined by comparing the
HPLC retention times with those reported in the litera-
ture, or by comparing with the analogous products re-
ported in the literature.
The palladium(II)-BINAP-catalyzed enantioselective
carbonyl-ene reactions between ten arylglyoxals and
five alkenes were systematically investigated and
demonstrated good to excellent enantioselectivities
with ee values of up to 93.8%. Both arylglyoxals and
alkenes demonstrate evident effects on the enantiose-
Adv. Synth. Catal. 2007, 349, 1781 – 1795
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1793

He-Kuan Luo et al.
FULL PAPERS
Scheme 6. Proposed catalytic cycle to interpret the effect of substrates on enantioselectivity in the Pd(II)-BINAP-catalyzed
enantioselective carbonyl-ene reactions.
liquid chromatography (HPLC) was performed on an Agi-
lectivity. The achieved excellent enantioselectivities
lent 110 Series HPLC equipped with a UV detector using a
chiral column selected from Chiralcel OD-H, Chiralcel OB-
may be due to the corresponding substrate matches
well fitting the chiral space created by the chiral pal-
ladium(II)-BINAP catalyst.
H, Chiralpak AD-H and Chiralpak AS-H columns. Elemen-
tal analysis was performed on a EuroEA3000 Series Ele-
mental Analyzer. Purification of reaction products was car-
ried out by flash column chromatography on silica gel. Phe-
nylglyoxal monohydrate was purchased from Sigma–Al-
drich, all the other aryglyoxal monohydrates were purchased
from SynChem. All the alkenes including methylenecyclo-
hexane, 2,3-dimethyl-1-butene, 2,4,4-trimethyl-1-pentene, a-
methylstyrene and a,2-dimethylstyrene were purchased
form Sigma–Aldrich and used without pretreatment. The
two dienes, 1,4-diisopropenylbenzene and 1,3-diisopropenyl-
benzene, were purchased from TCI. The ionic liquid
The ortho-methyl substituents of the substrates
could increase the enantioselectivity. This may be due
to the fact that the ortho-methyl group could improve
the fitness of the substrate match to the chiral space
created by the chiral catalyst.
Using a diene (1,4-diisopropenylbenzene and 1,3-
diisopropenylbenzene) as substrate in the enantiose-
lective carbonyl-ene reactions, only one of the two
carbon-carbon double bonds participated in the reac-
tion affording tetrafunctional organic compounds with
moderate enantioselectivities of up to 83.8% ee.
The chiral Lewis acid Pd(II) catalyst incorporated
with (R)-BINAP that is a conformationally restricted
chiral ligand, is very stable in an ionic liquid; it could
be recycled for 21 times with retention of the high
enantioselectivity.
[BdMIM] [NTf2] was prepared following
a reported
method.[11]
Catalyst Activation
A small Schlenk flask was charged with 0.0125 mmol [(R)-
BINAP]PdCl2 and AgSbF6 (2.5 equivs.), after which 2 mL
dichloromethane were added. The resulting mixture was
stirred for 30 min under a nitrogen or argon atmosphere at
room temperature, giving an in situ activated catalyst solu-
tion of {[(R)-BINAP]Pd}(SbF6)2.
A
Experimental Section
General Procedure for Enantioselective Carbonyl-
Ene Reactions
General Considerations
The manipulations were carried out under an atmosphere of
nitrogen or argon by using standard Schlenk line techniques.
1H NMR and 13C NMR were recorded in CDCl3 on a
Bruker 400 spectrometer. Analytical high-performance
To a solution of the in situ prepared catalyst in dichlorome-
thane according to the above described activation method,
was added 0.25 mmol of the corresponding arylglyoxal mono-
1794
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1781 – 1795

Enantioselective Carbonyl-Ene Reactions of Arylglyoxals
FULL PAPERS
hydrate and 0.25 mmol of the alkene. The resulting mixture References
was stirred for required time at room temperature. The re-
action mixture was firstly concentrated and then diluted
with 1 mL of hexane. The mixture was immediately loaded
onto a silica gel column, and eluted with hexane/ethyl ace-
tate mixture to give the corresponding product. The isolated
compound was characterized with 1H NMR and 13C NMR
(CDCl3, 400 MHz). The enantiomeric excess was deter-
mined by HPLC with a chiral column.
[1] For a catalyst based on Al, see: K. Maruoka, Y. Hoshi-
no, T. Shirasaka, H. Yamamoto, Tetrahedron Lett. 1988,
29, 3967–3970.
[2] For catalysts based on Ti, see: a) K. Mikami, M.
Terada, T. Nakai, J. Am. Chem. Soc. 1989, 111, 1940–
1941; b) K. Mikami, M. Terada, T. Nakai, J. Am. Chem.
Soc. 1990, 112, 3949–3954; c) K. Mikami, Pure Appl.
Chem. 1996, 68, 639–644; d) Y. M. A. Yamada, M. Ichi-
nohe, H. Takahashi, S. Ikegami, Tetrahedron Lett. 2002,
43, 3431–3434; e) Y. Yuan, X. Zhang, K. Ding, Angew.
Chem. Int. Ed. 2003, 42, 5478–5480; f) H. Guo, X.
Wang, K. Ding, Tetrahedron Lett. 2004, 45, 2009–2012.
[3] For catalysts based on Ln, see: a) C. Qian, T. Huang,
Tetrahedron Lett. 1997, 38, 6721–6724; b) C. Qian, L.
Wang, Tetrahedron: Asymmetry 2000, 11, 2347–2357.
[4] For catalysts based on Cu, see: a) D. A. Evans, C. S.
Burgey, N. A. Paras, T. Vojkovsky, S. W. Tregay, J. Am.
Chem. Soc. 1998, 120, 5824–5825; b) D. A. Evans, S. W.
Tregay, C. S. Burgey, N. A. Paras, T. Vojkovsky, J. Am.
Chem. Soc. 2000, 122, 7936–7943.
General Procedure for Catalyst Recycle in Ionic
Liquid
The in situ activated catalyst solution in dichloromethane
was transferred through a small filter into another small
Schlenk flask which was already charged with 0.5 mL or
1 mL of ionic liquid. Then 0.25 mmol of phenylglyoxal mon-
ohydrate was added and the resulting mixture was stirred
for several minutes until the phenylglyoxal monohydrate
had dissolved completely. After removing the dichlorome-
thane under vacuum, 0.25 mmol of alkene was added and
the reaction was run for the required time at room tempera-
ture. Then the reaction mixture was extracted with ether
(2 mL”3). Removal of the ether gave a residue which was
[5] For a catalyst based on Co, see: S. Kezuka, T. Ikeno, T.
Yamada, Org. Lett. 2001, 3, 1937–1939.
then dissolved into 1.5 mL of hexane/ethyl acetate(9:1),
G
[6] For catalysts based on Pd and Pt, see: a) J. Hao, M.
Hatano, K. Mikami, Org. Lett. 2000, 2, 4059–4062;
b) K. Mikami, K. Aikawa, Org. Lett. 2002, 4, 99–101;
c) J. H. Koh, A. O. Larsen, M. R. GagnØ, Org. Lett.
2001, 3, 1233–1236; d) J. J. Becker, P. S. White, M. R.
GagnØ, J. Am. Chem. Soc. 2001, 123, 9478–9479; e) H.-
K. Luo, H. Schumann, J. Mol. Cat. A: Chem. 2006, 248,
42–47; f) S. Doherty, P. Goodrich, C. Hardacre, H.-K.
Luo, M. Nieuwenhuyzen, R. K. Rath, Organometallics
2005, 24, 5945–5955.
loaded onto a silica gel column, and eluted with hexane/
ethyl acetate mixture (9:1) to give the corresponding prod-
uct. The isolated material was checked with 1H NMR
(CDCl3, 400 MHz). The enantiomeric excess was deter-
mined by HPLC with a chiral column. After being extract-
ed, the reaction mixture (i.e., ionic liquid layer) was dried
under vacuum to remove the residual ether. According to
the above procedure, the reaction was repeated for 21 times
to evaluate the capabilities of the ionic liquid immobilized
chiral catalyst.
[7] For a catalyst based on Sc, see: D. A. Evans, J. Wu, J.
Am. Chem. Soc. 2005, 127, 8006–8007.
[8] a) R. A. Brown, P. Pollet, E. McKoon, C. A. Eckert,
C. L. Liotta, P. G. Jessop, J. Am. Chem. Soc. 2001, 123,
1254–1255; b) C. E. Song, E. J. Roh, Chem. Commun.
2000, 837–838; c) I. Kawasaki, K. Tsunoda, T. Tsuji, T.
Yamaguchi, H. Shibuta, N. Uchida, M. Yamashita, S.
Ohta, Chem. Commun. 2005, 2134–2136.
SupportingInformation
Detailed descriptions of the procedures for the preparation
and characterization of products 1a–g, 2a–g, 3a–g, 4a–g, 5a–
g, 6a–g, 7a–g, 8a–g, 9a–e and 10a–e are given in the Support-
ing Information.
[9] R. Bousset, Bull. Soc. Chim. 1939, 6, 986–988.
[10] H.-K. Luo, H.-Y Yang, X. J. Tan, S. C. Ong, H. Schu-
mann, B. K. Lim, C. Lim, J. Mol. Cat. A: Chem. 2007,
261, 112–119.
[11] a) M.-C. Tseng, Y.-M. Liang and Y.-H. Chu, Tetrahe-
dron Lett. 2005, 46, 6131–6136; b) L. Cammarata, S. G.
Kazarian, P. A. Salter, T. Welton, Phys. Chem. Chem.
Phys. 2001, 3, 5192–5200.
Acknowledgements
This work was supported by Institute of Chemical and Engi-
neering Sciences (ICES) A-STAR, Singapore.
Adv. Synth. Catal. 2007, 349, 1781 – 1795
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1795