Water-tolerant enantioselective carbonyl-ene reactions with palladium(II) and platinum(II) Lewis acid catalysts bearing BINAP

Article abstract of DOI:10.1016/j.molcata.2006.07.068

Palladium(II) and platinum(II) Lewis acid catalysts bearing BINAP have been proved to be water-tolerant in enantioselective carbonyl-ene reactions, thus arylglyoxal monohydrate could be used directly as substrate achieving good to excellent enantioselectivities as high as 95.4% e.e.. The enantioselective carbonyl-ene reactions using phenylglyoxal monohydrate as substrate with four alkenes including methylenecyclohexane, 2,3-dimethyl-1-butene, 2,4,4-trimethyl-1-pentene and alpha-methylstyrene, were investigated demonstrating comparable or even higher yields and enantioselectivities in comparison with the corresponding carbonyl-ene reactions using dry phenylglyoxal as substrate for both palladium(II)-BINAP catalyst and platinum(II)-BINAP catalyst. The palladium(II) and platinum(II)-BINAP catalyzed enantioselective carbonyl-ene reactions between 4-methylphenylglyoxal monohydrate and the four alkenes were also investigated affording enantioselectivities between 76.2% and 91.8% e.e.. A mechanism involving the coordination of arylglyoxal and 2,2-dihydroxy-1-phenylethanone with chiral catalyst was proposed to interpret the enantioselective carbonyl-ene reactions using arylglyoxal monohydrate as substrate.

Full text of DOI:10.1016/j.molcata.2006.07.068

Journal of Molecular Catalysis A: Chemical 261 (2007) 112–119
Water-tolerant enantioselective carbonyl-ene reactions with palladium(II)
and platinum(II) Lewis acid catalysts bearing BINAP
He-Kuan Luoa,∗, Hai-Yan Yanga, Tan Xiang Jiea, Ong Siong Chiewa,
Herbert Schumannb, Lim Bee Khima, Christina Lima
a Institute of Chemical and Engineering Sciences (ICES), 1 Pesek Road,
Jurong Island, Singapore 627833, Singapore
b Institut fu¨r Chemie, Technische Universita¨t Berlin (TU-Berlin),
Straße des 17, Juni 135, D-10623 Berlin, Germany
Received 14 June 2006; received in revised form 25 July 2006; accepted 26 July 2006
Available online 7 September 2006
Abstract
Palladium(II) and platinum(II) Lewis acid catalysts bearing BINAP have been proved to be water-tolerant in enantioselective carbonyl-ene
reactions, thus arylglyoxal monohydrate could be used directly as substrate achieving good to excellent enantioselectivities as high as 95.4% e.e..
The enantioselective carbonyl-ene reactions using phenylglyoxal monohydrate as substrate with four alkenes including methylenecyclohexane,
2,3-dimethyl-1-butene, 2,4,4-trimethyl-1-pentene and alpha-methylstyrene, were investigated demonstrating comparable or even higher yields and
enantioselectivities in comparison with the corresponding carbonyl-ene reactions using dry phenylglyoxal as substrate for both palladium(II)-
BINAP catalyst and platinum(II)-BINAP catalyst. The palladium(II) and platinum(II)-BINAP catalyzed enantioselective carbonyl-ene reactions
between 4-methylphenylglyoxal monohydrate and the four alkenes were also investigated affording enantioselectivities between 76.2% and 91.8%
e.e.. A mechanism involving the coordination of arylglyoxal and 2,2-dihydroxy-1-phenylethanone with chiral catalyst was proposed to interpret
the enantioselective carbonyl-ene reactions using arylglyoxal monohydrate as substrate.
© 2006 Elsevier B.V. All rights reserved.
Keywords: Enantioselective; Carbonyl-ene; Palladium; Platinum; Phenylglyoxal
1. Introduction
The enantioselective carbonyl-ene reaction catalyzed by chi-
ral Lewis acid is an important methodology for carbon–carbon
bond construction to prepare optically active homoallylic alco-
hols. For this reaction a variety of chiral Lewis acid catalysts
based on various metals and ligands have been studied [2–8],
some of them were reported demonstrating high efficiency and
high enantioselectivity, such as organoaluminum catalyst [2], Ti-
BINOL catalyst [3], Cu-BOX catalyst [5] and optically active
␤-ketoiminato cationic cobalt(III) catalyst [6] etc.. However
all of them were reported to be water-sensitive, hence prop-
erly dried solvents, substrates and reactors have to be used.
Particularly, as one of the most common substrates for enan-
tioselective carbonyl-ene reactions, dry phenylglyoxal has to be
made by drying phenylglyoxal monohydrate which is usually
prepared, purified and transported as monohydrate form because
phenylglyoxal monohydrate is loose white powder therefore
it could be easily handled (see Picture 1A, left) [9]. Phenyl-
glyoxal monohydrate has not been used directly in enantios-
Water-tolerant catalystsand catalyticprocesses do notrequire
dehydrative drying of substrates, solvents and reactors etc.,
hence they are more easily to be used in industry. Moreover,
water has been reported to have beneficial effect on enan-
tioselectivities and activities in a few Lewis acid catalyzed
asymmetric catalytic reactions. For example, in hetero-Diels-
Alder reaction with Danishefsky’s diene using chiral lanthanide
bis(bisfluoromethanesulfonyl)amide (bis-trifylamide) catalyst,
the presence of a small amount of water as an additive can
increase the enantioselectivity [1]. Therefore developing water-
tolerant asymmetric catalysis is of general interests.
∗
Corresponding author. Tel.: +65 6796 3827; fax: +65 6316 6182.
E-mail address: luo hekuan@ices.a-star.edu.sg (H.-K. Luo).
1381-1169/$ – see front matter © 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2006.07.068

H.-K. Luo et al. / Journal of Molecular Catalysis A: Chemical 261 (2007) 112–119
113
hydrate with four alkenes including methylenecyclohexane,
2,3-dimethyl-1-butene, 2,4,4-trimethyl-1-pentene and alpha-
methylstyrene, demonstrating good to excellent enantioselec-
tivities with e.e. values as high as 95.4%.
2. Results and discussions
2.1. Enantioselective carbonyl-ene reactions between
phenylglyoxal monohydrate and alkenes (see Table 1)
The [(R-BINAP)Pd]2+ Lewis acid catalyzed enantioselec-
tive carbonyl-ene reactions using phenylglyoxal monohydrate
directly as substrate were firstly studied and compared with
the corresponding carbonyl-ene reactions using dry phenylgly-
oxal as substrate (see Table 1). The first reaction we studied
was the palladium(II)-BINAP catalyzed carbonyl-ene reaction
between phenylglyoxal and methylenecyclohexane. We found
that phenylglyoxal monohydrate did not kill the catalyst or
stop the reaction, but could give higher yield and enantiose-
lectivity as compared with dried phenylglyoxal (see entries 1
and 2 in Table 1, 51% yield, 88.0% ee versus 36% yield and
86.5% e.e.). In order to confirm this result, we run the reac-
tion for six times and the data presented are average values of
six runs. For the palladium(II)-BINAP catalyzed carbonyl-ene
reactions of the other three alkenes including 2,3-dimethyl-
1-butene, 2,4,4-trimethyl-1-pentene and alpha-methylstyrene,
phenylglyoxal monohydrate also demonstrated comparable or
higher yields and enantioselectivities as compared with dried
phenylglyoxal (see entries 7, 8, 13, 14, 19, 20) with e.e. values
as high as 93.0%.
Picture1. Phenylglyoxalmonohydrate(A, left)anddryphenylglyoxal(B, right).
elective catalytic reactions just because all the existing chiral
Lewis acid catalysts were reported to be water-sensitive and
most of the phenylglyoxal is in the form of 2,2-dihydroxy-
1-phenylethanone(PhC(O)CH(OH)2) (see Scheme 1). On the
other hand, pure and dry phenylglyoxal is brown oil under high
temperature, such as 90 ◦C, or very sticky and thick semi-solid
under low temperature, such as 30 ◦C (see Picture 1B, right),
which is much more difficult to be handled and may undergo
dimerization or polymerization. Therefore phenylglyoxal has to
be freshly dried prior to use. This may greatly hinder the use
of phenylglyoxal in catalytic processeses in which the catalysts
are water-sensitive. Therefore it is very useful to develop water-
tolerant enantioselective catalytic reactions by using phenylgly-
oxal monohydrate directly as substrate to prepare chiral chemi-
cals.
[(S-BINAP)Pt]2+ catalyst was also studied for all the four
enantioselective carbonyl-ene reactions between phenylgly-
oxal and the four alkenes including methylenecyclohexane,
2,3-dimethyl-1-butene, 2,4,4-trimethyl-1-pentene and alpha-
methylstyrene. As we expected, phenylglyoxal monohydrate
also demonstrated higher yields and enantioselectivities in dif-
ferent degrees as compared with dried phenylglyoxal (see entries
3–6, 9–12, 15–18, 21, 22). In order to make a clear compari-
son, we run the reactions of phenylglyoxal monohydrate with
three alkenes including methylenecyclohexane, 2,3-dimethyl-1-
butene and 2,4,4-trimethyl-1-pentene for 10 min, and compared
with dried phenylglyoxal. As shown in Table 1, phenylglyoxal
monohydrate demonstrated higher yields and enantioselectivi-
ties than dired phenylglyoxal (51% yield and 88% e.e. versus
39% yield and 86.4% e.e.; 47% yield and 95.4% e.e. versus
45% yield and 95.0% e.e.; 59% yield and 91.0% e.e. versus
48% yield and 90.0% e.e., see entries 4, 5, 10, 11, 16, 17). For
the platinium(II)-BINAP catalyzed enantioselective carbonyl-
ene reactions between phenylglyoxal and alpha-methylstyrene,
phenylglyoxal monohydrate also demonstrated higher yield and
enantioselectivity than dried phenylglyoxal (76% yield and 78.0
% e.e. versus 43% yield and 77.1% e.e., see entries 21, 22).
The above results proved that [(R-BINAP)Pd]2+ and [(S-
BINAP)Pt]2+ are water-tolerant in enantioselective carbonyl-
ene reactions in dichloromethane, phenylglyoxal monohydrate
could be used directly as substrate achieving good to excellent
enantioselectivities.
Palladium catalyst of bis(diphenylphosphino)-type ligand
has been proved to be water-tolerant in some catalytic reac-
tions. For example, the palladium catalyst incorporated with
1,3-bis(diphenylphosphino)propane could catalyze the alternat-
ing copolymerization of CO and ethylene in methanol–water
or in acetic acid–water solvents demonstrating high activity
[10]. Therefore the palladium catalyst of (R)/(S)-(+)/(−)-2,2ꢀ-
bis(diphenylphosphino)-1,1ꢀ-binaphthalene(BINAP) could be
water-tolerant catalyst for asymmetric catalysis. However, pre-
vious reports demonstrated that the enantioselective glyoxylate-
ene reactions between ethyl glyoxylate and alkenes was water-
sensitive, trace water (H2O:ethyl glyoxylate = 2:3) could stop
the reaction completely [7d].
In the present studies, we proved that [(R-BINAP)Pd]2+ and
[(S-BINAP)Pt]2+ are water-tolerant chiral Lewis acid catalysts
for the enantioselective carbonyl-ene reactions. Here we report
our studies on [(R-BINAP)Pd]2+ and [(S-BINAP)Pt]2+ cat-
alyzed water-tolerant enantioselective carbonyl-ene reactions of
phenylglyoxal monohydrate and 4-methylphenylglyoxal mono-
Scheme 1. Equilibration between phenylglyoxal and 2,2-dihydroxy-1-
phenylethanone.

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H.-K. Luo et al. / Journal of Molecular Catalysis A: Chemical 261 (2007) 112–119
Table 1
Comparison of enantioselective carbonyl-ene reactions using phenylglyoxal monohydrate and dry phenylglyoxal as substrate with four alkenes
Catalytic reaction
Entry
Phenyl glyoxal
Product
Time
Catalayst
Yielda (%)
e.e.b (%)
1c
2c
3
4
5
Monohydrate
Dried
Monohydrate
Monohydrate
Dried
1a
1a
1a
1a
1a
1a
1 h
1 h
30 min
10 min
10 min
2 h
Pd
Pd
Pt
Pt
Pt
Pt
51
36
72
51
39
63
88.0(S)d
86.5(S)
87.0(R)
88.0(R)
86.4(R)
86.4(R)
6
Dried
7
8
9
10
11
12
Monohydrate
Dried
Monohydrate
Monohydrate
Dried
1b
1b
1b
1b
1b
1b
2 h
2 h
30 min
10 min
10 min
2 h
Pd
Pd
Pt
Pt
Pt
Pt
50
50
64
47
45
66
93.0(S)
93.0(S)
95.2(R)
95.4(R)
95.0(R)
94.9(R)
Dried
13
14
15
16
17
18
Monohydrate
Dried
Monohydrate
Monohydrate
Dried
1c
1c
1c
1c
1c
1c
2 h
2 h
30 min
10 min
10 min
2 h
Pd
Pd
Pt
Pt
Pt
Pt
56
50
88
59
48
54
88.0(S)
87.6(S)
91.0(R)
91.0(R)
90.0(R)
88.2(R)
Dried
19
20
21
22
Monohydrate
Dried
Monohydrate
Dried
1d
1d
1d
1d
1 h
1 h
2 h
2 h
Pd
Pd
Pt
40
27
76
43
80.0(S)
78.8(S)
78.0(R)
77.1(R)
Pt
Reactionconditions:allthereactionswererunatroomtemperature. Catalyst[(R-BINAP)Pd](SbF6)2 or[(S-BINAP)Pt](SbF6)2 0.0125 mmol(5 mol%);phenylglyoxal,
0.25 mmol; alkene, 0.25 mmol.
a
Isolated yield with flash chromatography.
Determined by HPLC with a Chiralcel OD-H column for products 1a, 1b and 1c, with a Chiralcel OB-H column for products 1d.
Average of six runs, the others are average values of three runs.
The absolute configurations of the carbonyl-ene products were determined by comparing the HPLC retention times with those reported in the literature.
b
c
d
Table 2
Enantioselective carbonyl-ene reactions between 4-methylphenylglyoxal monohydrate and alkenes
Catalytic reaction
Entry
Product
Time (h)
Catalyst
Yielda (%)
e.e.b (%)
1
2
2a
2a
1
2
Pd
Pt
47
75
85.5(S)c
87.2(R)
3
4
2b
2b
1
2
Pd
Pt
37
76
91.8(S)
88.0(R)
5
6
2c
2c
1
2
Pd
Pt
49
51
86.8(S)
88.2(R)
7
8
2d
2d
1
Pd
Pt
32
70
82.8(S)
76.2(R)
1.5
Reaction conditions: all the reactions were run at room temperature. Catalyst [(R-BINAP)Pd](SbF6)2 or [(S-BINAP)Pt](SbF6)2, 0.0125 mmol (5 mol%); 4-
methylphenylglyoxal monohydrate, 0.25 mmol; alkene, 0.25 mmol.
a
Isolated yield with flash chromatography.
Determined by HPLC with a Chiralcel OD-H column for products 2a, 2b and 2c, with a Chiralcel OB-H column for products 2d.
The absolute configurations of the carbonyl-ene products were determined by comparing with the products in Table 1. Average of three runs.
b
c

H.-K. Luo et al. / Journal of Molecular Catalysis A: Chemical 261 (2007) 112–119
115
Scheme 2. Proposed catalytic mechanism for enantioselective carbonyl-ene reactions of arylglyoxal monohydrate and alkene.
2.2. Enantioselective carbonyl-ene reactions
between 4-methylphenylglyoxal monohydrate
and alkenes (see Table 2)
demonstrated comparable or even higher yields and enantios-
electivities in comparison with the corresponding carbonyl-ene
reactionsusingdryphenylglyoxalassubstrate, clearlyindicating
that [(R-BINAP)Pd]2+ and [(S-BINAP)Pt]2+ are water-tolerant
in dichloromethane for carbonyl-ene reactions. For example, for
the palladium(II)-BINAP catalyzed enantioselective carbonyl-
enereactionbetweenphenylglyoxalandmethylenecyclohexane,
dry phenylglyoxal demonstrated only 36% yield and 86.5%
e.e. for 1 h run, however phenylglyoxal monohydrate demon-
strated increased yield and enantioselectivity (51% yield and
88.0% e.e. for 1 h run). Since the increase was not signifi-
cant, we run the reaction for six times to confirm the results,
and the above data are average values of six runs; For the
platinium(II)-BINAP catalyzed enantioselective carbonyl-ene
reactions between phenylglyoxal and alkenes, phenylglyoxal
monohydrate also demonstrated higher yields and enantioselec-
tivities than dried phenylglyoxal. This result is a sharp contrast
against the {[(S)-MeOBIPHEP]Pt}(SbF6)2 catalyzed enantios-
elective glyoxylate-ene reactions between ethyl glyoxylate and
alkenes, in which trace water (H2O:ethyl glyoxylate = 2:3) could
stop the reaction completely [7d].
In order to interpret the enantioselective carbonyl-ene reac-
tions of arylglyoxal monohydrate, here a catalytic mechanism
was proposed and shown in Scheme 2. Previously it has been
proposed that, in the enantioselective carbonyl-ene reactions
[7a,d,e], phenylglyoxal is firstly activated by coordination with
chiral catalyst to form a key intermediate (A) (see Scheme 2),
which is then attacked by alkene and the carbonyl-ene reaction
occurs (see intermediate B) forming intermediate (C) which is a
complex of chiral catalyst and product. Finally, intermediate (C)
releases chiral product and backs to intermediate (A) by subse-
quent coordination with the second molecule phenylglyoxal.
In our studies, since we are using phenylglyoxal monohydrate
as substrate, in dichloromethane solution there is a equilibration
As a very common substrate, 4-methylphenylglyoxal has
not been studied for enantioselective carbonyl-ene reac-
tions. The development of water-tolerant enantioselective
carbonyl-ene reactions provided us a convenient protocol to
study the enantioselective carbonyl-ene reactions using 4-
methylphenylglyoxal monohydrate as substrate with the four
alkenes using [(R-BINAP)Pd]2+ and [(S-BINAP)Pt]2+ Lewis
acid catalysts. As shown in Table 2, the results are close to
the enantioselective carbonyl-ene reactions of phenylglyoxal
monohydrate with alkenes. Both [(R-BINAP)Pd]2+ and [(S-
BINAP)Pt]2+ catalysts demonstrated very high e.e. values for
the carbonyl-ene reaction of 4-methylphenylglyoxal monohy-
drate and 2,3-dimethyl-1-butene (91.8% e.e. and 88.0% e.e.,
respectively), also demonstrated very good enantioselectivi-
ties for the carbonyl-ene reactions of 4-methylphenylglyoxal
monohydrate with 2,4,4-trimethyl-1-pentene (86.8% e.e. and
88.2% e.e., respectively) and methylenecyclohexane (85.5% e.e.
and 87.2% e.e., respectively). For the carbonyl-ene reaction of
4-methylphenylglyoxal monohydrate and alpha-methylstyrene,
[(R-BINAP)Pd]2+ and [(S-BINAP)Pt]2+ demonstrated relatively
low e.e. values (82.8% e.e. and 76.2% e.e., respectively).
2.3. Mechanism of [(R-BINAP)Pd]2+ and
[(S-BINAP)Pt]2+ Lewis acid catalyzed
enantioselective carbonyl-ene reactions
As shown in Tables 1 and 2, for all the enantioselec-
tive carbonyl-ene reactions of phenylglyoxal monohydrate and
4-methylphenylglyoxal monohydrate with the four alkenes,
both palladium(II)-BINAP and platinum(II)-BINAP catalysts

116
H.-K. Luo et al. / Journal of Molecular Catalysis A: Chemical 261 (2007) 112–119
showed that in dichloromethane solution, only a small amount
of the compound is in the form of free phenylglyoxal, most
of the compound should be in the form of 2,2-dihydroxy-1-
phenylethanone. Under such conditions, if only pure phenyl-
glyoxal could undergo carbonyl-ene reaction, 2,2-dihydroxy-1-
phenylethanone will shift to phenylglyoxal during the reaction.
Obviously, this process may result in low activity. More impor-
tantly, beside 2,2-dihydroxy-1-phenylethanone, using phenyl-
glyoxal monohydrate as substrate introduces some water into
the reaction system, water could coordinate with palladium(II)
and platinum(II) [11], therefore it is considered as a competi-
tive inhibitor for catalysis to decrease the catalytic activity or
even stop a reaction completely [7d] (see Scheme 3). But in
fact, for some of the carbonbyl-ene reactions using phenyl-
glyoxal monohydrate, the isolated yield was higher than the
corresponding reaction using dry phenylglyoxal. Therefore here
we propose the second catalytic cycle (see cycle 2 in Scheme 2).
Acetal-ene reaction was also reported to occur easily when
promoted with Lewis acid catalyst [12]. Since 2,2-dihydroxy-1-
phenylethanone is structurally similar to acetal, here we propose
that 2,2-dihydroxy-1-phenylethanone may also undergo enan-
tioselective reaction with alkene as shown in cycle 2 like acetal-
ene reaction. Firstly, intermediate (D) was formed by coordi-
nation of chiral catalyst with 2,2-dihydroxy-1-phenylethanone.
Then the alkene may approach the coordinated 2,2-dihydroxy-
1-phenylethanone (see intermediate E) and form the product,
meanwhile one molecule H2O is given out (see intermediate
F). After releasing the product and subsequent coordination
with the second molecule of 2,2-dihydroxy-1-phenylethanone,
the catalyst backs to intermediate (D). In summary, the pal-
ladium(II) and platinum(II)-BINAP catalyzed enantioselective
carbonyl-ene reaction involves catalytic cycle 1 and cycle 2.
This mechanism could help us to understand the enantioselec-
Fig. 1. Comparison of 1H NMR(CD2Cl2, 400 MHz) of phenylglyoxal mono-
hydrate (A) and dried phenylglyoxal (B).
between phenylglyoxal and 2,2-dihydroxy-1-phenylethanone,
the 1H-NMR(CD2Cl2, 400 MHz) of phenylglyoxal monohy-
drate revealed that the peak of aldehyde-H at 9.57 ppm is very
small and the ratio of phenyl-H to aldehyde-H is 115.71:1.00(see
A in Fig. 1). After phenylglyoxal was dried under 90 ◦C in
vacuum, the peak of aldehyde-H was significantly enhanced,
and the ratio of phenyl-H to aldehyde-H was decreased to
1
27.14:1.00 (see B in Fig. 1). Theoretically, in the H-NMR of
free phenylglyoxal, the ratio of phenyl-H to aldehyde-H is 5:1.
Therefore the 1H-NMR of phenylglyoxal monohydrate clearly
Scheme 3. Competitive coordination on the metal center of the chiral catalyst.

H.-K. Luo et al. / Journal of Molecular Catalysis A: Chemical 261 (2007) 112–119
117
tive carbonyl-ene reaction using phenylglyoxal monohydrate
as substrate. In dried phenylglyoxal, the ratio of phenyl-H to
aldehyde-H is 27.14:1.00 which is still higher than the ratio of
5:1 for free phenylglyoxal. This may indicate that it is very hard
to remove all the water from the system by heating at 90 ◦C in
vacuum, therefore small amount of water is always existing in
the system. Although the exact amount of water is not known,
it may play a beneficial role in the reaction according to the
proposed mechanism shown in Scheme 2.
phy on silica gel. Dry dichloromethane was purified using
MBRAUN-SPS solvent purification system. 0.25 mM phenyl-
glyoxal solution of dichloromethane was prepared by dissolving
freshly dried phenylglyoxal (under 90 ◦C in vacuum) in dry
dichloromethane. Phenylglyoxal monohydrate and alkenes were
purchased from Sigma–Aldrich. 4-Methylphenylglyoxal mono-
hydrate was purchased from SynChem. R-BINAP((R)-(+)-2,2ꢀ-
bis(diphenylphosphino)-1,1ꢀ-binaphthalene) and S-BINAP((S)-
(−)-2,2ꢀ-bis(diphenylphosphino)-1,1ꢀ-binaphthalene) were pur-
chased from Sigma–Aldrich. (R-BINAP)PdCl2 and (S-
BINAP)PtCl2 were prepared according to a reported method
[13] by reaction of BINAP (1 equiv.) in dichloromethane with
dichloro(␩4-1,5-cyclooctadiene)palladium(II) or dichloro(␩4-
1,5-cyclooctadiene)platinum(II) (1 equiv.) which were also pre-
pared according to reported methods [14].
3. Summary
Both palladium(II) and platinum(II)-BINAP Lewis acid cat-
alysts have been demonstrated to be water-tolerant in enan-
tioselective carbonyl-ene reactions between arylglyoxals and
alkenes. Thus arylglyoxal monohydrate could be used directly
as substrate achieving comparable or even higher yields
and enantioselectivities as compared with the corresponding
carbonyl-ene reactions using dry phenylglyoxal as substrate.
The enantioselective carbonyl-ene reactions using phenylgly-
oxal monohydrate and 4-methylphenylglyoxal monohydrate
as substrates with four alkenes including methylenecyclo-
hexane, 2,3-dimethyl-1-butene, 2,4,4-trimethyl-1-pentene and
alpha-methylstyrene, were investigated affording good to excel-
lent enantioselectivities between 76.2% and 95.4% e.e.. A
mechanism involving the coordination of arylglyoxal and 2,2-
dihydroxy-1-phenylethanone with chiral catalyst was proposed
to interpret the enantioselective carbonyl-ene reaction using
arylglyoxal monohydrate as substrate. To the best of our knowl-
edge, this is the first report on water-tolerant enantioselective
carbonyl-ene reactions using arylglyoxal monohydrate as sub-
strate.
The development of water-tolerant enantioselective
carbonyl-ene reactions using arylglyoxal monohydrate as sub-
strate provided us a convenient and versatile protocol to study
the enantioselective carbonyl-ene reactions between various
arylglyoxals and alkenes. The studies on enantioselective
carbonyl-ene reactions using more substituted and functional-
ized aryglyoxals monohydrate are in process. meanwhile we
are also studying the catalyst recycle of palladium(II)-BINAP
catalyst in ionic liquid. All these research works will be
published later in due course.
4.2. Catalyst activation
A small Schlenk flask was charged with 0.0125 mmol (R-
BINAP)PdCl2 or (S-BINAP)PtCl2 and AgSbF6 (2.5–3.0 equiv),
after 2 mL dichloromethane was added, the resulting mixture
was stirred for 30 min under nitrogen or argon atmosphere at
room temperature, giving in situ activated catalyst solution of
[(R-BINAP)Pd](SbF6)2 or [(S-BINAP)Pt](SbF6)2.
4.3. General procedure for enantioselective carbonyl-ene
reactions
To a solution of the in situ prepared catalyst in
dichloromethane according to the above described activation
method, wasadded0.25 mmolcorrespondingarylglyoxalmono-
hydrate and 0.25 mmol alkene. The resulting mixture was stirred
for required time at room temperature. Then the mixture was
loaded onto a silica gel, and eluted with hexane/ethyl acetate
mixture to give the corresponding compound. The isolated prod-
uct was characterized with 1H-NMR and 13C-NMR(CDCl3,
400 MHz). Enantiomeric excess was determined by HPLC with
a chiral column.
4.4. Preparation of 3-(1ꢀ-cyclohexenyl)-
2-hydroxy-1-phenylpropan-1-one (1a)
The title compound was prepared according to the general
procedure using 0.25 mmol phenylglyoxal monohydrate and
0.25 mmol methylenecyclohexane. Pure product was obtained
by column chromatography over silica gel eluted with hex-
ane/ethyl acetate (9:1). The obtained product was checked with
1H-NMR and 13C-NMR(CDCl3, 400 MHz), which is consistent
with the reported results. Enantiomeric excess was determined
by HPLC with a Chiralcel OD-H column (1.0% 2-propanol in
hexane, flow 1.0 mL/min, (S)enantiomer RT = 13.2 min(major),
(R)enantiomer RT = 20.1 min(minor)).
4. Experimental
4.1. General considerations
In case of water-free reactions, the manipulations were car-
ried out under an atmosphere of nitrogen or argon by using
standard Schlenk line techniques in dried glassware. 1H-NMR
and 13C-NMR were recorded in CDCl3 on a BRUCKER 400
spectrometer. Analytical high-performance liquid chromatogra-
phy (HPLC) was performed on an Agilent 110 Series HPLC
equipped with a UV detector using a Chiralcel OD-H or Chi-
ralcel OB-H column. Elemental analysis was performed on a
EuroEA3000 Series Elemental Analyzer. Purification of reac-
tion products was carried out by flash column chromatogra-
4.5. Preparation of 4-isopropyl-2-hydroxy-1-phenyl-4-
penten-1-one (1b)
The title compound was prepared according to the general
procedure using 0.25 mmol phenylglyoxal monohydrate and

118
H.-K. Luo et al. / Journal of Molecular Catalysis A: Chemical 261 (2007) 112–119
0.25 mmol 2,3-dimethyl-1-butene. Pure product was obtained
by column chromatography over silica gel eluted with hex-
ane/ethyl acetate (9:1). The obtained product was checked with
1H-NMR and 13C-NMR(CDCl3, 400 MHz), which is consistent
with the reported results. Enantiomeric excess was determined
by HPLC with a Chiralcel OD-H column (0.8% 2-propanol in
hexane, flow 1.0 mL/min, (S)enantiomer RT = 27.5 min(major),
(R)enantiomer RT = 58.6 min(minor)).
hexane, flow 1.0 mL/min, (S)enantiomer RT = 8.3 min(major),
(R)enantiomer RT = 11.2 min(minor)).
4.9. Preparation of 4-isopropyl-2-hydroxy-1-
(4-methylphenyl)-4-penten-1-one (2b)
The title compound was prepared according to the general
procedure using 0.25 mmol 4-methylphenylglyoxal monohy-
drate and 0.25 mmol 2,3-dimethyl-1-butene. Pure product was
obtained by column chromatography over silica gel eluted
with hexane/ethyl acetate (9:1). 1H-NMR(CDCl3, 400 MHz,
δ): 1.020, 1.029(d), 1.037, 1.046(d) (–CH3, 6H), 2.161,
2.184, 2.199, 2.222(dd, –CH2CH(OH)–, 1H), 2.282–2.350(m,
–CH(CH3)2, 1H), 2.433(S, Ph-CH3, 3H), 2.585, 2.591, 2.623,
2.629(dd, –CH2CH(OH)–, 1H), 3.687, 3.704(d, –OH, 1H),
4.901, 4.936(s, s, –C CH2, 2H), 5.169–5.216(m, –CH(OH)–,
1H), 7.292, 7.312(d), 7.817, 7.838(d) (Ph-H, 4H). 13C-
NMR(CDCl3, 400 MHz, δ): 21.56, 21.78, 33.57, 41.14, 72.16,
109.63, 128.69, 129.40, 129.59, 131.13, 145.01, 151.37, 201.28.
C15H20O2 (232.33): Calcd. C 77.55%, H 8.68%; found C
77.22%, H 8.97%. Enantiomeric excess was determined by
HPLC with a Chiralcel OD-H column (1.0% 2-propanol in
hexane, flow 1.0 mL/min, (S)enantiomer RT = 7.2 min(major),
(R)enantiomer RT = 9.5 min(minor)).
4.6. Preparation of 6,6-dimethyl-2-hydroxy-4-methylene-1-
phenylheptan-1-one (1c)
The title compound was prepared according to the gen-
eral procedure using 0.25 mmol phenylglyoxal monohydrate
and 0.25 mmol 2,4,4-trimethyl-1-pentene. Pure product was
obtained by column chromatography over silica gel eluted
with hexane/ethyl acetate (9:1). The obtained product was
checked with 1H-NMR and 13C-NMR(CDCl3, 400 MHz),
which is consistent with the reported results. Enantiomeric
excess was determined by HPLC with a Chiralcel OD-H column
(1.0% 2-propanol in hexane, flow 1.0 mL/min, (S)enantiomer
RT = 10.2 min(major), (R)enantiomer RT = 14.3 min(minor)).
4.7. Preparation of 1,4-diphenyl-2-hydroxy-4-
penten-1-one (1d).
4.10. Preparation of 6,6-dimethyl-2-
hydroxy-4-methylene-1-(4-methylphenyl)-heptan-1-one (2c)
The title compound was prepared according to the gen-
eral procedure using 0.25 mmol phenylglyoxal monohydrate
and 0.25 mmol alpha-methylsyrene. Pure product was obtained
by column chromatography over silica gel eluted with hex-
ane/ethyl acetate (9:1). The obtained product was checked with
1H-NMR and 13C-NMR(CDCl3, 400 MHz), which is consistent
with the reported results. Enantiomeric excess was determined
by HPLC with a Chiralcel OB-H column (3.0% 2-propanol in
hexane, flow 1.0 mL/min, (R)enantiomer RT = 20.5 min(minor),
(S)enantiomer RT = 27.4 min(major)).
The title compound was prepared according to the gen-
eral procedure using 0.25 mmol 4-methylphenylglyoxal mono-
hydrate and 0.25 mmol 2,4,4-trimethyl-1-pentene. Pure prod-
uct was obtained by column chromatography over silica
1
gel eluted with hexane/ethyl acetate (9:1). H-NMR(CDCl3,
400 MHz, δ): 0.882(s, –C(CH3)3, 9H), 1.963, 1.996, 2.016,
2.049(q, –CH2C(CH3)3, 2H), 2.197, 2.219, 2.234, 2.256(dd,
–CH2CH(OH)–, 1H), 2.434(s, Ph-CH3, 3H), 2.599, 2.606,
2.636, 2.642(dd, –CH2CH(OH)–, 1H), 3.676, 3.693(d, –OH,
1H), 4.868, 5.012(s, s, –C CH2, 2H), 5.154–5.200(m,
–CH(OH)–, 1H), 7.290, 7.310(d) and 7.818, 7.839(d) (Ph-
H, 4H). 13C-NMR(CDCl3, 400 MHz, δ): 21.76, 29.88, 31.61,
44.24, 49.49, 72.44, 116.31, 128.70, 129.56, 131.14, 143.05,
145.02, 201.20. C17H24O2 (260.38):Calcd. C78.42%, H9.29%;
found C 78.76%, H 9.11%. Enantiomeric excess was determined
by HPLC with a Chiralcel OD-H column (1.0% 2-propanol in
hexane, flow 1.0 mL/min, (S)enantiomer RT = 6.1 min(major),
(R)enantiomer RT = 8.0 min(minor)).
4.8. Preparation of 3-(1ꢀ-cyclohexenyl)-
2-hydroxy-1-(4-methylphenyl)-propan-1-one (2a)
The title compound was prepared according to the gen-
eral procedure using 0.25 mmol 4-methylphenylglyoxal mono-
hydrate and 0.25 mmol methylenecyclohexane. Pure product
was obtained by column chromatography over silica gel eluted
with hexane/ethyl acetate (9:1). 1H-NMR(CDCl3, 400 MHz,
δ): 1.532–1.587(m) and 1.602–1.639(m) (–CH2CH2–, 4H),
2.036–2.042(m, –CH2–C C–, 4H), 2.110, 2.131, 2.146,
2.167(dd, –CH2CH(OH)–, 1H), 2.430(S, Ph-CH3, 3H), 2.459,
2.495(d, –CH2CH(OH)–, 1H), 3.660, 3.677(d, –OH, 1H),
5.133–5.179(m, –CH(OH)–, 1H), 5.475(s, –C CH–, 1H), 7.283,
7.303(d) and 7.806, 7.826(d)(Ph-H, 4H). 13C-NMR(CDCl3,
400 MHz, δ): 21.74, 22.16, 22.83, 25.28, 28.79, 44.66, 72.03,
124.89, 128.72, 129.51, 131.33, 133.36, 144.87, 201.54.
C16H20O2 (244.34): Calcd. C 78.65%, H 8.25%; found C
78.24%, H 8.06%. Enantiomeric excess was determined by
HPLC with a Chiralcel OD-H column (1.0% 2-propanol in
4.11. Preparation of 4-phenyl-1-
(4-methylphenyl)-2-hydroxy-4-penten-1-one (2d)
The title compound was prepared according to the gen-
eral procedure using 0.25 mmol 4-methylphenylglyoxal
monohydrate and 0.25 mmol alpha-methylsyrene. Pure
product was obtained by column chromatography over
silica gel eluted with hexane/ethyl acetate (9:1). 1H-
NMR(CDCl3, 400 MHz, δ): 2.419(s, Ph-CH3, 3H), 2.605,
2.626, 2.641, 2.663(dd, –CH2CH(OH)–, 1H), 3.046, 3.053,

H.-K. Luo et al. / Journal of Molecular Catalysis A: Chemical 261 (2007) 112–119
119
3.082, 3.090(dd, –CH2CH(OH)–, 1H), 3.657, 3.674(d, –OH,
[4] For catalysts based on Ln, see;
(a) C. Qian, T. Huang, Tetrahedron Lett. 38 (1997) 6721;
(b) C. Qian, L. Wang, Tetrahedron: Asymmetry 11 (2000) 2347.
[5] For catalysts based on Cu, see;
1H), 5.067–5.114(m, –CH(OH)–, 1H), 5.165, 5.346(s, s,
–C CH2, 2H), 7.240–7.353(m) and 7.684, 7.704(d), (Ph-H,
9H). 13C-NMR(CDCl3, 400 MHz, δ): 21.76, 42.18, 71.50,
116.07, 126.63, 127.71, 128.39, 128.67, 129.52, 131.24,
140.67, 144.14, 145.01, 201.13. C18H18O2 (266.34): Calcd. C
81.17%, H 6.81%; found C 80.76%, H 6.52%. Enantiomeric
excess was determined by HPLC with a Chiralcel OB-H column
(3.0% 2-propanol in hexane, flow 0.5 mL/min, (S)enantiomer
RT = 21.7 min(major), (R)enantiomer RT = 28.8 min(minor)).
(a) D.A. Evans, C.S. Burgey, N.A. Paras, T. Vojkovsky, S.W. Tregay, J. Am.
Chem. Soc. 120 (1998) 5824;
(b) D.A. Evans, S.W. Tregay, C.S. Burgey, N.A. Paras, T. Vojkovsky, J.
Am. Chem. Soc. 122 (2000) 7936.
[6] For catalysts based on Co, see;
S. Kezuka, T. Ikeno, T. Yamada, Org. Lett. 3 (2001) 1937.
[7] For catalysts based on Pd and Pt, see;
(a) J. Hao, M. Hatano, K. Mikami, Org. Lett. 2 (2000) 4059;
(b) K. Aikawa, S. Kainuma, M. Hatano, K. Mikami, Tetrahedron Lett. 45
(2004) 183;
(c) J.J. Becker, P.S. White, M.R. Gagne, J. Am. Chem. Soc. 123 (2001)
9478;
Acknowledgement
This work was supported by Institute of Chemical and Engi-
neering Sciences (ICES) A-STAR, Singapore.
(d) J.H. Koh, A.O. Larsen, M.R. Gagne, Org. Lett. 3 (2001) 1233;
(e) H.-K. Luo, H. Schumann, J. Mol. Catal. A: Chem. 248 (2006) 42.
[8] For catalysts based on Sc, see;
D.A. Evans, J. Wu, J. Am. Chem. Soc 127 (2005) 8006.
[9] R. Bousset, Bull. Soc. Chim. 6 (1939) 986.
[10] (a) A. Vavasori, L. Toniolo, G. Cavinato, F. Vistentin, J. Mol. Catal. A:
Chem. 204 (2003) 295;
(b) A. Vavasori, L. Toniolo, G. Cavinato, J. Mol. Catal. A: Chem. 215
(2004) 63.
[11] P.J. Stang, D.H. Cao, G.T. Poulter, A.M. Arif, Organometallics 14 (1995)
1110.
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