Palladium(II) complexes of C2-bridged chiral diphosphines: Application to enantioselective carbonyl-ene reactions

Article abstract of DOI:10.1002/adsc.200900888

(11bR,11′bR)-4,4′-(1,2-Phenylene)bis[4,5-dihydro-3H- dinaphtho[2,1-c:1′,2′-e] phosphepin] [abbreviated as (R)-BINAPHANE], (3R,3′R,4S,4′S,11bS,11′bS)-4,4′-bis(1,1-dimethylethyl)- 4,4′,5,5′-tetrahydro-3,3′-bi-3H-dinaphtho[2,1-c:1′, 2′-e]phosphepin [(S)-BINAPINE], (1S,1′S,2R,2′R)-1,1′- bis(1,1-dimethylethyl)-2,2′-biphospholane [(S,S,R,R)TANGPHOS] and (2R,2′R,5R,5′R)-1,1′-(1,2-phenylene)bis[2,5-bis(1-methylethyl) phospholane] [(R,R)-i-Pr-DUPHOS] are C₂-bridged chiral diphosphines that form stable complexes with palladium(II) and platinum(II) containing a five-membered chelate ring. The Pd(II)-BINAPHANE catalyst displayed good to excellent enantioselectivities with ee values as high as 99.0% albeit in low yields for the carbonyl-ene reaction between phenylglyoxal and alkenes. Its Pt(II) counterpart afforded improved yields while retaining satisfactory enantioselectivity. For the carbonyl-ene reaction between ethyl trifluoropyruvate and alkenes, the Pd(II)-BINAPHANE catalyst afforded both good yields and extremely high enantioselectivities with ees as high as 99.6%. A comparative study on the Pd(II) catalysts of the four C₂bridged chiral diphosphines revealed that Pd(II)-BINAPHANE afforded the best enantioselectivity. The ee values derived from Pd(II)-BINAPHANE are much higher than those derived from the other three Pd(II) catalysts. A comparison of the catalyst structures shows that the Pd(II)-BINAPHANE catalyst is the only one that has two bulky (R)-binaphthyl groups close to the reaction site. Hence it creates a deep chiral space that can efficiently control the reaction behavior in the carbonyl-ene reactions resulting in excellent enantioselectivity.

Full text of DOI:10.1002/adsc.200900888

FULL PAPERS
DOI: 10.1002/adsc.200900888
Palladium(II) Complexes of C2-Bridged Chiral Diphosphines:
Application to Enantioselective Carbonyl-Ene Reactions
He-Kuan Luo,a,* Yuan-Ling Woo,a Herbert Schumann,b Chacko Jacob,a
Martin van Meurs,a Hai-Yan Yang,a and Yen-Ting Tana
a
Institute of Chemical and Engineering Sciences, A*STAR (Agency for Science, Technology and Research), 1 Pesek Road,
Jurong Island, Singapore 627833
Fax : (+65)-6316-6182; e-mail: luo_hekuan@ices.a-star.edu.sg
Institut fꢀr Chemie, Technische Universitꢁt Berlin, Straße des 17. Juni 135, 10623 Berlin, Germany
b
Received: December 22, 2009; Revised: April 19, 2010; Published online: May 5, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900888.
Abstract: (11bR,11’bR)-4,4’-(1,2-Phenylene)bis[4,5- and alkenes, the Pd(II)-BINAPHANE catalyst af-
dihydro-3H-dinaphtho[2,1-c:1’,2’-e]phosphepin] [ab- forded both good yields and extremely high enantio-
breviated
(3R,3’R,4S,4’S,11bS,11’bS)-4,4’-bis(1,1-dimethylethyl)- tive study on the Pd(II) catalysts of the four C2-
4,4’,5,5’-tetrahydro-3,3’-bi-3H-dinaphtho[2,1-c:1’,2’- bridged chiral diphosphines revealed that Pd(II)-BI-
as
(R)-BINAPHANE], selectivities with ees as high as 99.6%. A compara-
e]phosphepin [(S)-BINAPINE], (1S,1’S,2R,2’R)-1,1’- NAPHANE afforded the best enantioselectivity. The
bis(1,1-dimethylethyl)-2,2’-biphospholane [(S,S,R,R)- ee values derived from Pd(II)-BINAPHANE are
TANGPHOS]
and
(2R,2’R,5R,5’R)-1,1’-(1,2- much higher than those derived from the other three
Pd(II) catalysts. A comparison of the catalyst struc-
phenylene)bis[2,5-bis(1-methylethyl)phospholane]
ACHTUNGTRENNUNG
[(R,R)-i-Pr-DUPHOS] are C2-bridged chiral diphos- tures shows that the Pd(II)-BINAPHANE catalyst is
phines that form stable complexes with palladium(II) the only one that has two bulky (R)-binaphthyl
and platinum(II) containing a five-membered chelate groups close to the reaction site. Hence it creates a
ring. The Pd(II)-BINAPHANE catalyst displayed deep chiral space that can efficiently control the re-
good to excellent enantioselectivities with ee values action behavior in the carbonyl-ene reactions result-
as high as 99.0% albeit in low yields for the carbon- ing in excellent enantioselectivity.
yl-ene reaction between phenylglyoxal and alkenes.
Its Pt(II) counterpart afforded improved yields while
retaining satisfactory enantioselectivity. For the car- Keywords: asymmetric catalysis; carbonyl-ene reac-
À
bonyl-ene reaction between ethyl trifluoropyruvate tion; C C bond formation; diphosphines; palladium
Introduction
of chiral catalysts is stable and generally cannot be
racemized under the reaction conditions.
An investigation of the correlation between catalyst
The chiral Lewis acid-catalyzed enantioselective
structure and enantioselectivity is one of the key carbonyl-ene reaction continue to attract much atten-
issues in fundamental asymmetric catalysis. For this tion in asymmetric synthesis because it is an atom-
reason, the concept of chiral space has been proposed economical tool to synthesize optically active homoal-
to understand and guide the design of new chiral cata- lylic alcohols that are important building blocks in or-
lysts including both molecular chiral catalysts and het- ganic synthesis, especially for use in the pharmaceuti-
erogeneous chiral catalysts.[1] The chiral space can be cal industry. Among the various chiral Lewis acid cat-
reshaped by modifying the chiral ligands or chiral alysts studied so far,[2–10] palladium(II) and platin-
modifiers in order to achieve high enantioselectivity
ACHTUNGTRENuUNNG m(II) complexes of C4-bridged chiral diphosphines,
for a specific asymmetric reaction. Among the differ- such as atropos-BINAP {BINAP=1,1’-[1,1’-binaph-
ent strategies to make chiral catalysts studied so far, thalene]-2,2’-diylbis[1,1-diphenylphosphine]}, atropos-
the use of conformationally restricted chiral ligands is BIPHEP
{BIPHEP=1,1’-[[1,1’-biphenyl]-2,2’-diyl]-
still dominating this research area, because this kind bis[1,1-diphenylphosphine]} and atropos-SEGPHOS-
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Palladium(II) Complexes of C2-Bridged Chiral Diphosphines
type {SEGPHOS=1,1’-[4,4’-bi-1,3-benzodioxole]-5,5’-
diylbis[1,1-diphenylphosphine]} ligands, have been in-
vestigated for the enantioselective carbonyl-ene reac-
tions. For example, Mikami[7a] and co-workers report-
ed that {Pd
Tol-BINAP=1,1’-(1S)-[1,1’-binaphthalene]-2,2’-diyl-
bis[1,1-bis(4-methylphenyl)phosphine]} was an effi-
ACHTUNGTRENNUNG(CH3CN)2[(S)-Tol-BINAP]} (SbF6)2 {(S)-
A
ACHTUNGTRENNUNG
cient catalyst for the reaction between ethyl glyoxy-
late and methylenecyclohexane affording 88% yield
and 78% ee at room temperature. Gagnꢃ[7b] and co-
workers showed À that {[(S)-MeO-BIPHEP]Pt}(X)2
(X=OTfÀ, SbF6 ) {(S)-MeO-BIPHEP=1,1’-[(1S)-
6,6’-dimethoxy[1,1’-biphenyl]-2,2’-diyl]bis[1,1-
diphenylACHTUNGTRENNUNGphosphine]} afforded ee values up to 85% for
the same carbonyl-ene reaction. Mikami[7c–e] and co-
workers also reported that a “naked” palladium(II)
complex with the chiral atropos-SEGPHOS and an
atropos-platinum complex with BIPHEP are efficient
catalysts for the carbonyl-ene reactions of ethyl tri-
fluoropyruvate and alkenes affording ee values be-
tween 84% and 98%. Later, the Pd(II)-BINAP cata-
lyzed enantioselective carbonyl-ene reactions between
various aryglyoxals and alkenes were investigated by
us affording good to excellent enantioselectivity with
ee values as high as 93%.[7f]
Besides C4-bridged chiral diphosphines, C2-bridged
chiral diphosphines are another class of privileged li-
gands that have been used in asymmetric reactions af-
fording good to excellent enantioselectivity, such as
asymmetric cyclization and asymmetric hydrogena-
tion.[11] One advantage of C2-bridged chiral diphos-
phines is that they form a stable five-membered che-
late ring with the metal, thus providing a robust cata-
lyst. Another advantage is that each of the two phos-
phorus atoms is attached to a chiral centre. These two
chiral centres create a chiral space which can be re-
shaped by modifying the chiral centreꢄs shape and
size. Hence this provides us an opportunity to investi-
gate the correlation between catalyst structure and
enantioselectivity. Here we investigate the palladiu-
m(II) complexes of four C2-bridged chiral diphos-
phines (see Scheme 1) for the enantioselective car-
Scheme 1. Pd(II) group catalysts of C2-bridged chiral diphos-
phines.
bonyl-ene reactions. The employed four ligands are Results and Discussion
(R)-BINAPHANE {(11bR,11’bR)-4,4’-(1,2-pheny-
lene)bis[4,5-dihydro-3H-dinaphtho[2,1-c:1’,2’-e]phos- Comparison of Palladium(II) Complexes of C2-
A
phepin]}, (S)-BINAPINE {(3R,3’R,4S,4’S,11bS,11’bS)- Bridged Chiral Diphosphines
4,4’-bis(1,1-dimethylethyl)-4,4’,5,5’-tetrahydro-3,3’-bi-
3H-dinaphtho[2,1-c:1’,2’-e]phosphepin},
TANGPHOS {(1S,1’S,2R,2’R)-1,1’-bis(1,1-dimethyl- chiral diphosphines are shown in Scheme 1. One
ethyl)-2,2’-biphospholane} and (R,R)-i-Pr-DUPHOS common feature of these complexes is that they con-
{(2R,2’R,5R,5’R)-1,1’-(1,2-phenylene)bis[2,5-bis(1- tain a stable five-membered chelate ring. Each chiral
methylethyl)phospholane]}. The correlation between diphosphine ligand has a pair of chiral centres that
(S,S,R,R)- The four palladium(II) complexes of C2-bridged
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
chiral space and enantioselectivity is discussed.
are different in shape and size for different ligands,
thus creating different chiral spaces. The Pd-(R)-BI-
NAPHANE (Pd-1) has two bulky (R)-binaphthyl
groups close to the reaction site, hence it creates a
deep chiral space with the reaction site inside.[11a] The
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He-Kuan Luo et al.
FULL PAPERS
Pd-(S)-BINAPINE (Pd-2) also has two bulky (R)-bi-
naphthyl groups, however they are relatively far away
from the reaction site, and cannot significantly affect
the asymmetric reaction. Therefore the chiral space of
Pd-2 is mainly created by the two tert-butyl groups
which are much smaller than the (R)-binaphthyl
group, hence Pd-2 has a relatively smaller chiral
space for asymmetric reaction. Both Pd-(S,S,R,R)-
TANGPHOS (Pd-3) and Pd-(R,R)-iPr-DUPHOS
(Pd-4) cannot create chiral spaces as deep as that of
Pd-1 because the chiral centres of Pd-3 and Pd-4 are
smaller than those of Pd-1. Therefore in comparison,
Pd-1 is the only catalyst that provides a deep chiral
space for asymmetric reaction.
A catalytic mechanism has been proposed to inter-
pret the palladium(II)-catalyzed enantioselective car-
bonyl-ene reactions.[7] In the catalytic cycle, the dicar-
bonyl compound is first activated by coordination to
the palladium to form an intermediate. This key inter-
mediate will be attacked by an alkene to initiate the
carbonyl-ene reaction. Therefore the catalyst should
have a chiral space that is deep enough to affect both
Scheme 3. Substrates employed in the enantioselective car-
bonyl-ene reactions.
of the substrates, so that the reaction behavior can be long reaction time usually resulted in the formation
well controlled to achieve high enantioselectivity. This of some impurities. The impurities are increasing with
may indicate that Pd-1 with a deep chiral space can the reaction time and finally resulting in decreased
display high enantioselectivity for the carbonyl-ene yield. For example, for the Pd-1-catalyzed reaction of
reaction.
phenylglyoxal with 1b, 1c or 1d, the color changed
from light orange yellow to dark green or greenish
brown. After 16 h of an overnight run, TLC indicated
that the impurities were clear and strong, but the
product became very weak. Flash chromatography af-
forded only a trace of impurities. In comparison, a 2 h
Enantioselective Carbonyl-Ene Reactions of
Phenylglyoxal with Alkenes
All the chiral Pd(II) and Pt(II) catalysts shown in run can afford a clean product albeit in low yields
Scheme 1 were investigated for the enantioselective (14%, 29% and 39% yields for 1b–1d, entries 3–5,
carbonyl-ene reactions of phenylglyoxal (2a) with five Table 1). Hence the reactions were usually run for a
alkenes including methylenecyclohexane (1a), 2,3-di- short time of maximally 2 h in this study, in order to
methyl-1-butene (1b), 2,3,3-trimethyl-1-butene (1c), obtain a cleaner product and/or a better yield.
2,4,4-trimethyl-1-pentene (1d) and a-methylstyrene
The results show that Pd-1 displayed good to excel-
(1e) (see Scheme 2 and Scheme 3). In order to make lent enantioselectivity with ee values of 81.1%,
the enantioseletive carbonyl-ene reactions more prac- 90.2%, 99.0%, 89.0% and 87.1% for alkenes 1a–1e
tical, here we used equimolar amounts of carbonyl (see entries 1, 3–6, Table 1). However, compared to
compound and alkene to run the reaction. Hence the Pd-1, Pd-2 displayed much lower enantioselectivity
isolated yields are more useful compared to those de- with ee values of 26.7%, 61.3%, 60.1%, 61.1% and
rived from the reactions using a large excess of car- 50.8% for alkenes 1a–1e (see entries 12–16, Table 1).
bonyl compound. For the phenylglyoxal-based reac- Pd-3 displayed moderate to good enantioselectivity
tions, with the prolongation of reaction time, the with ee values of 41.7%, 80.2%, 83.5%, 84.0% and
color of the reaction mixture became darker and 77.3% for alkenes 1a–1e (see entries 17–21, Table 1).
darker. TLC and flash chromatography showed that a However these ee values are still much lower than
those of Pd-1. Pd-4 displayed very low enantioselec-
tivity with ee values of 29.6%, 28.0%, 29.0%, 32.2%
and 39.3% for alkenes 1a–1e (see entries 22–26,
Table 1). These results are consistent with the struc-
tural analysis. Pd-1 with a deep chiral space displayed
the best enantioselectivity among the four Pd(II)
complexes of C2-bridged chiral diphosphine ligands.
Pt(II)-(R)-BINAPHANE (Pt-1) was also investigat-
ed for the enantioselective carbonyl-ene reactions of
Scheme 2. Enantioselective carbonyl-ene reactions.
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Palladium(II) Complexes of C2-Bridged Chiral Diphosphines
Table 1. Enantioselective carbonyl-ene reactions of phenyl-
Enantioselective Carbonyl-Ene Reactions of 2b and
2c with Alkenes
glyoxal with alkenes.[a]
Entry Cata- Alkene Prod- Time Yield[b] ee[c]
Because Pd-1 is a highly enantioselective catalyst, it
was also investigated for the carbonyl-ene reactions
of ethyl trifluoropyruvate with the five alkenes (see
Scheme 2 and Scheme 3). Compared to the phenyl-
glyoxal-based reactions with low yields (14%–39%),
ethyl trifluoropyruvate-based reactions afforded sig-
nificantly improved yields (60%–78%, Table 2) be-
cause ethyl trifluoropyruvate is a more active sub-
strate compared to phenylglyoxal. More importantly,
all the ethyl trifluoropyruvate-based reactions afford-
ed excellent enantioselectivity with ee values of
99.4%, 99.3%, 99.6%, 98.8% and 91.2% for alkenes
1a–1e. In comparison, these ee values are much
higher or comparable relative to the corresponding
phenylglyoxal-based reactions. It should be noted that
alkene 1b afforded only one product 3b when reacted
with phenylglyoxal. However it afforded two products
lyst
uct
[h]
[%]
[%]
1
Pd-1
Pd-1
Pd-1
Pd-1
Pd-1
Pd-1
Pt-1
Pt-1
Pt-1
Pt-1
Pt-1
Pd-2
Pd-2
Pd-2
Pd-2
Pd-2
Pd-3
Pd-3
Pd-3
Pd-3
Pd-3
Pd-4
Pd-4
Pd-4
Pd-4
Pd-4
1a
1a
1b
1c
1d
1e
1a
1b
1c
1d
1e
1a
1b
1c
1d
1e
1a
1b
1c
1d
1e
1a
1b
1c
1d
1e
3a
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
2
1
2
2
2
1
2
2
2
2
2
1
2
2
2
1
1
2
2
2
1
1
2
2
2
1
25
27
14
29
39
26
64
58
44
58
42
10
30
39
42
14
14
29
25
40
16
21
13
13
32
25
81.1 (R)
81.4 (R)
90.2 (R)
99.0 (R)
89.0 (R)
87.1 (R)
84.9 (R)
90.8 (R)
91.0 (R)
78.2 (R)
79.3 (R)
26.7 (S)
61.3 (S)
60.1 (S)
61.1 (S)
50.8 (S)
41.7 (S)
80.2 (S)
83.5 (S)
84.0 (S)
77.3 (S)
29.6 (R)
28.0 (R)
29.0 (R)
32.2 (R)
39.3 (R)
2[d]
3
4
5
6[d]
7
8
9
10
11
12[d]
13
14
15
16[d]
17[d]
18
19
20
21[d]
22[d]
23
24
25
26[d]
1
(4b:4b’=2.5:1 calculated from H NMR) when react-
ed with ethyl trifluoropyruvate, and both of the prod-
ucts have extremely high ee values (99.3% and 99.6%
for 4b and 4b’).
Further studies showed that Pd-1 and Pt-1 can also
catalyze the reaction of ethyl glyoxylate and a-meth-
ylstyrene affording good enantioselectivities (see en-
tries 6 and 7, Table 2). For a 2 h run at room tempera-
ture, Pd-1 displayed a higher ee value, but a lower
yield (86.8% ee, 38% yield) compared to Pt-1 (70.6%
[a]
Reaction conditions: All the reactions were run at room
temperature. Pd(II) or Pt(II) catalyst, 0.0125 mmol ee, 46% yield). The results in Table 1 and Table 2
(5 mol%); solution of phenylglyoxal in dichloromethane
(0.25M), 1 mL; alkene, 0.25 mmol.
Isolated yield with flash chromatography.
Determined by HPLC with a Chiralcel OD-H column
for products 3a–3d, with a Chiralcel OB-H column for
product 3e. The absolute configurations of the carbonyl-
ene products (3a–3e) were determined by comparing the
HPLC retention times with those reported in the litera-
ture, or by comparison with analogous products reported
in the literature.
show that Pd-1 is versatile to catalyze the enantiose-
lective carbonyl-ene reactions between different kinds
of carbonyl compounds and alkenes.
[b]
[c]
Mechanistic Considerations for the Formation of 4b
and 4b’
Among the five alkenes shown in Scheme 3, 2,3-di-
[d]
Using 0.25 mmol phenylglyoxal monohydrate instead of methyl-1-butene (1b) is the smallest molecule, while
1 mL solution of phenylglyoxal in dichloromethane.
ethyl trifluoropyruvate is also smaller than phenyl-
glyoxal. Hence when considering the catalytic mecha-
nism,[7] the chiral catalyst (Pd-1) may still have suffi-
cient space to allow 1b to approach the coordinated
ethyl trifluoropyruvate in two ways (see paths A and
phenylglyoxal with the five alkenes (see entries 7–11, B, Scheme 4) producing two products 4b and 4b’. Be-
Table 1). Compared to its palladium counterpart, Pt-1 cause of its lower steric hindrance, path A still domi-
afforded higher isolated yields under identical condi- nates the catalytic cycle to afford the major product
tions (Pt-1: 42%–64% yields vs Pd-1: 14%–39% 4b in a ratio of 4b:4b’=2.5:1.
yields, see entries 1–11, Table 1). However, Pt-1 dis-
played lower enantioselectivity for the reactions of
phenylglyoxal with alkenes 1c–1e (Pt-1: 91.0%, The Water Tolerance of Pd-1
78.2%, 79.3% vs. Pd-1: 99.0%, 89.0%, 87.1%), albeit
Pt-1 displayed a slightly higher enantioselectivity for When the solid compound Pd-1 or even its CD2Cl2 so-
the reactions of phenylglyoxal with alkenes 1a and 1b lution was exposed in the air for one day, its 31P NMR
(Pt-1: 84.9%, 90.8% vs. Pd-1: 81.1%, 90.2%).
had no shift, indicating an air-stable compound. For
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He-Kuan Luo et al.
FULL PAPERS
Table 2. Enantioselective carbonyl-ene reactions of 2b and 2c with alkenes.[a]
Entry
Catalyst
Alkene
Carbonyl compound
Product
Time [h]
Yield[b] [%]
ee[c] [%]
1
2
Pd-1
Pd-1
1a
1b
2b
2b
4a
4b
4b’
4c
4d
4e
5e
5e
1
1
78
99.4
99.3
99.6
99.6
98.8
91.2
86.8
70.6
60 (4b:24’=2.5)
3
4
5
6
7
Pd-1
Pd-1
Pd-1
Pd-1
Pt-1
1c
1d
1e
1e
1e
2b
2b
2b
2c
2c
1
1
2
2
2
64
76
64
38
46
[a]
Reaction conditions: All the reactions were run at room temperature. Pd-1 or Pt-1 catalyst, 0.0125 mmol (5 mol%);
alkene, 0.25 mmol; for entries 1–5, 0.25 mmol ethyl trifluoropyruvate was used; For entries 6–7, 0.5 mmol ethyl glyoxylate
(50% solution in toluene) was used.
Isolated yield with flash chromatography.
Determined by GC with a Varian CP7502 chiral column (cp-Chirasil-dexB capillary 25.0 mꢅ250 mmꢅ0.25 mm nominal)
for products 4a–4d, by HPLC with a Chiralpak AS-H column for product 4e and 5e.
[b]
[c]
tioselective catalyst for both the phenylglyoxal-based
reactions and ethyl trifluoropyruvate-based reactions
with ee values as high as 99.6%. Pt(II)-BINAPHANE
also afforded satisfactory enantioselectivity with im-
proved yields as compared to its Pd(II) counterpart.
However, the other three Pd(II) catalysts of (S)-BI-
NAPINE, (S,S,R,R)-TANGPHOS and (R,R)-i-Pr-
DUPHOS afforded much lower ee values compared
to Pd-BINAPHANE. A comparison of catalyst struc-
ture reveals that Pd(II)-BINAPHANE is the only cat-
alyst that has two bulky (R)-binaphthyl groups close
to the reaction site. Hence it creates a deeper chiral
space relative to the other three chiral palladium(II)
catalysts. The deep chiral space of Pd-BINAPHANE
may efficiently control the reaction behavior of the
two substrates resulting in excellent enantioselectivi-
ties.
Experimental Section
General Considerations
Scheme 4. The mechanism of forming two products.
All manipulations were carried out under an atmosphere of
nitrogen or argon using standard Schlenk line techniques.
1H NMR, 13C NMR and 19F NMR were recorded in CDCl3
or CD2Cl2 on a Bruker 400 spectrometer. 19F NMR data
were measured against (trifluoromethyl)benzene (d=
À62.9 ppm). Analytical high-performance liquid chromatog-
the 1 h reaction of phenylglyoxal monohydrate and
methylenecyclohexane, Pd-1 gave 27% yield and
81.4% ee (entry 2, Table 1) which is comparable to
the ee value using dehydrated phenylglyoxal (81.1% raphy (HPLC) was performed on an Agilent 110 Series
HPLC system equipped with a UV detector using a chiral
column selected from Chiralcel OD-H, Chiralcel OB-H and
Chiralpak AS-H columns. Chiral GC analysis was per-
formed on an Agilent 6890N Network GC system using a
Varian CP7502 chiral column (cp-Chirasil-dexB capillary
25.0 mꢅ250 mmꢅ0.25 mm nominal). Elemental analysis was
performed on a EuroEA3000 Series Elemental Analyzer.
High resolution mass spectra were obtained on an Agilent
LC-MS TOF. Purification of reaction products was carried
out by flash column chromatography on silica gel. Phenyl-
ee, entry 1, Table 1). Therefore, Pd-1 is tolerant to
traces of water present in the reaction.
Conclusions
We have investigated the palladium(II) complexes of
four C2-bridged chiral diphosphines as catalysts for
the enantioselective carbonyl-ene reactions. Pd-
BINAACHTUNGTRENNUNGPHANE was demonstrated to be a highly enan- glyoxal monohydrate was purchased from Sigma–Aldrich,
1360
asc.wiley-vch.de
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1356 – 1364

Palladium(II) Complexes of C2-Bridged Chiral Diphosphines
dried under vacuum at 908C and used as a 0.25M dichloro-
methane solution. Ethyl trifluoropyruvate was purchased
from Alfa Aesar and used without pretreatment. Ethyl
glyoxylate (50% in toluene) was purchased from Sigma-
Alpha. All the alkenes including methylenecyclohexane, 2,3-
dimethyl-1-butene, 2,3,3-trimethyl-1-butene, 2,4,4-trimethyl-
1-pentene and a-methylstyrene were purchased from
Sigma–Aldrich and used without pretreatment. (R)-BINA-
PHANE, (S)-BINAPINE, (S,S,R,R)-TANGPHOS and
(R,R)-i-Pr-DUPHOS were purchased from STREM. [(R,R)-
i-Pr-DUPHOS]PdCl2 was synthesized by the reaction of
(COD)PdCl2 with (R,R)-i-Pr-DUPHOS following the re-
ported method.[12] Instead of the synthetic procedure by
treatment of (CH3CN)2PdCl2 with (R)-BINAPHANE,[11a]
here [(R)-BINAPHANE]PdCl2 was also synthesized by the
reaction of (COD)PdCl2 with (R)-BINAPHANE. The race-
alyst. The crude product was dissolved in dichloromethane
(5 mL) and layered with diethyl ether (15 mL) at room tem-
perature. The obtained white solid was washed with pentane
(10 mL) and dried under vacuum affording 199 mg of the
product. The solution mixture was dried giving a residue
that was dissolved in dichloromethane (2 mL) and layered
with diethyl ether (10 mL) affording a second batch of the
product (38 mg). Total yield: 69%. 31P{1H} NMR (CD2Cl2,
162 MHz): d=59.2 (t,
J ACHTUNTGNRUEGN
Pt,P =1737 Hz); 1H{31P} NMR
(CD2Cl2, 400 MHz): d=3.12 (dd, CH2, 2H, J=14.7 Hz, J=
5.6 Hz), 3.64 (dd, CH2, 2H, J=14.1 Hz, J=5.6 Hz), 3.80 (t,
CH2, 2H, J=14.9 Hz), 4.25 (t, CH2, 2H, J=14.5 Hz), 6.40–
6.44 (m, Ar-H, 2H), 6.97 (d, Ar-H, 2H, J=8.5 Hz), 7.09–
7.13 (m, Ar-H, 6H), 7.18–7.22 (m, Ar-H, 4H), 7.39 (t, Ar-H,
2H, J=7.5 Hz), 7.44 (t, Ar-H, 2H, J=7.5 Hz), 7.68 (d, Ar-
H, 2H, J=8.4 Hz), 7.89–7.95 (m, Ar-H, 8H); 13C{1H}-
mic
carbonyl-ene
products
were
prepared
with
{31P} NMR (CD2Cl2, 100 MHz): d=33.28, 34.14, 125.68,
ACHTUNGTRENNUNG
(Ph3P)2PdCl2.
125.89, 126.09, 126.53, 126.67, 127.17, 128.19, 128.34, 128.35,
128.59, 128.91, 130.00, 130.09, 130.90, 132.02, 132.31, 132.65,
132.72, 133.24, 133.45, 134.48, 139.63; anal. calcd. for
C50H36Cl2P2Pt (964.75): C 62.25%, H 3.76%; found: C
62.09%, H 4.21%.
General Procedure for the Synthesis of Chiral
Palladium Group Complexes
In a 50-mL Schlenk tube, a desired amount of (COD)PdCl2
or (COD)PtCl2 was dissolved in dichloromethane (10 mL),
to which a solution of an equimolar amount of the chiral di-
phosphine in dichloromethane (10 mL) was added dropwise
under vigorous stirring. The resulting solution was stirred
overnight at room temperature, then dichloromethane was
removed under vacuum affording a yellow powder for the
Pd(II) complex or a white powder for Pt(II) complex. The
obtained crude product was washed with ether (10 mLꢅ2)
and dried under vacuum.
[(S)-BINAPINE]PdCl2
(S)-BINAPINE (500 mg, 0.68 mmol) and an equimolar
amount of (COD)PdCl2 were used to synthesize the title
catalyst. The obtained crude product was dissolved in di-
chloromethane (10 mL), layered with pentane (15 mL) and
stored in a freezer (~À208C). The obtained pale yellow
solid was washed with pentane (5 mL) and dried under
vacuum affording 198 mg of the product. The solution mix-
ture was dried giving a residue that was dissolved in di-
chloromethane (6 mL), layered with pentane (10 mL) and
stored in a freezer affording a second batch of the product
(189 mg). Total yield: 62%. 31P{1H} NMR (CD2Cl2,
[(R)-BINAPHANE]PdCl2
(R)-BINAPHANE (250 mg, 0.36 mmol) and an equimolar
amount of (COD)PdCl2 were used to synthesize the title
catalyst. The obtained crude product was dissolved in di-
chloromethane (10 mL) and layered with pentane (15 mL)
at room temperature. The obtained pale yellow solid was
washed with pentane (10 mL) and dried under vacuum af-
fording 172 mg of the product. The solution mixture was
dried giving a residue that was dissolved in dichloromethane
(5 mL) and layered with pentane (10 mL) affording a
ACTHNUTRGNEUNG
162 MHz): d=119.1 (s); 1H{31P} NMR (CD2Cl2, 400 MHz):
d=0.55 (s, CH3, 18H), 2.95 (d, CH2, 2H, J=13.2 Hz), 3.45
(s, CH, 2H), 3.79 (d, CH2, 2H, J=13.2 Hz), 6.69 (d, Ar-H,
2H, J=8.5 Hz), 6.95 (d, Ar-H, 2H, J=8.6 Hz), 7.16–7.20
(m, Ar-H, 2H), 7.29 (d, Ar-H, 2H, J=8.4 Hz), 7.43–7.47 (m,
Ar-H, 2H), 7.50–7.55 (m, Ar-H, 2H), 7.60–7.64 (m, Ar-H,
4H), 7.84 (d, Ar-H, 2H, J=8.1 Hz), 7.89 (d, Ar-H, 2H, J=
ACTHNUTRGNEUNG
8.4 Hz), 8.08 (d, Ar-H, 4H, J=8.4 Hz); 13C{1H}{31P} NMR
second batch of the product (64 mg). Total yield: 75%.
(CD2Cl2, 100 MHz): d=27.90, 28.52, 37.34, 53.07, 126.23,
126.28, 126.40, 126.43, 126.82, 127.09, 127.99, 128.45, 129.13,
129.39, 130.17, 130.34, 130.87, 132.66, 132.99, 133.04, 133.39,
133.46, 133.72, 135.16; anal. calcd. for C52H48Cl2P2Pd
(912.21): C 68.47%, H 5.30%; found: C 68.19%, H 5.50%.
1
31P{1H} NMR (CD2Cl2, 162 MHz): d=84.2 (s); H
G
(CD2Cl2, 400 MHz): d=3.30 (d, CH2, 2H, J=14.7 Hz), 3.65
(d, CH2, 2H, J=14.2 Hz), 3.87 (d, CH2, 2H, J=14.3 Hz),
4.43 (d, CH2, 2H, J=14.6 Hz), 6.43–6.45 (q, Ar-H, 2H, J=
3.2 Hz), 7.08 (d, Ar-H, 2H, J=8.5 Hz), 7.18 (d, Ar-H, 2H,
J=8.4 Hz), 7.22–7.27 (m, Ar-H, 4H), 7.31–7.38 (m, Ar-H,
4H), 7.50–7.60 (m, Ar-H, 4H), 7.84 (d, Ar-H, 2H, J=
AHCTUNTGREG[NNNU (S,S,R,R)-TANGPHOS]PdCl2
ACTHNUTRGNEUNG
8.5 Hz), 7.99–8.08 (m, Ar-H, 8H); 13C{1H}{31P} NMR
AHCTUNGTREG(NNUN S,S,R,R)-TANGPHOS (250 mg, 0.87 mmol) and an equimo-
lar amount of (COD)PdCl2 were used to synthesize the title
catalyst. The crude product was dissolved in dichlorome-
thane (10 mL), layered with ether (10 mL) and stored in a
freezer (~À208C). The obtained pale yellow solid was
washed with pentane (5 mL) and dried under vacuum af-
fording 105 mg of the product. The solution mixture was
dried giving a residue that was dissolved in dichloromethane
(5 mL), layered with diethyl ether (10 mL) and stored in a
freezer affording a second batch of the product (98 mg).
Total yield: 50%. 31P{1H} NMR (CD2Cl2, 162 MHz): d=
(CD2Cl2, 100 MHz): d=34.47, 34.60, 125.74, 125.90, 126.17,
126.59, 126.65, 127.18, 128.16, 128.34, 128.37, 128.58, 128.94,
130.04, 130.37, 131.06, 132.26, 132.49, 132.77, 132.97, 133.26,
133.29, 133.60, 134.55, 139.50; anal. calcd. for C50H36Cl2P2Pd
(876.09): C 68.55%, H 4.14%; found: C 68.32%, H 4.40%.
[(R)-BINAPHANE]PtCl2
(R)-BINAPHANE (250 mg, 0.36 mmol) and an equimolar
amount of (COD)PtCl2 were used to synthesize the title cat-
Adv. Synth. Catal. 2010, 352, 1356 – 1364
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1361

He-Kuan Luo et al.
FULL PAPERS
1
121.6 (s); H
{31P} NMR (CD2Cl2, 400 MHz): d=1.43 (s, CH3,
OD-H column [0.8% 2-propanol in hexane, flow
18H), 1.59–1.76 (m, CH2, 4H), 2.11–2.16 (m, CH2, 2H),
2.29–2.35 (m, CH2, 2H), 2.45–2.49 (m, CH2, 4H), 2.63–2.68
0.5 mLminÀ1, (S)-enantiomer Rt =27.5 min
ACHTNGUTERN(UNG minor), (R)-
enantiomer Rt =58.6 minACTHNUGRTENUNG(major)].
ACTHNUTRGNEUNG
(m, CH, 2H); 13C{1H}{31P} NMR (CD2Cl2, 100 MHz): d=
26.65, 27.00, 29.26, 34.70, 35.68, 45.85; anal. calcd. for
C16H32Cl2P2Pd (463.70): C 41.44%, H 6.96%; found: C
41.20%, H 6.78%.
2-Hydroxy-5,5-dimethyl-4-methylene-1-phenyl-1-hex-
anone (3c)
The title compound was prepared according to the general
procedure using 0.25 mmol of phenylglyoxal and 0.25 mmol
of 2,3,3-trimethyl-1-butene. The pure product was obtained
by column chromatography over silica gel eluted with
General Procedure for Catalyst Activation
A small Schlenk tube was charged with 0.0125 mmol of the
desired [chiral diphosphine]MCl2 (M=Pd, Pt) and AgSbF6
(2.5 equivalents), followed by the addition of dichlorome-
thane (1 mL). The resulting mixture was stirred for 30 min
under a nitrogen or argon atmosphere at room temperature,
giving the in situ activated catalyst solution of {[chiral
1
hexane/ethyl acetate (9:1). H NMR (CDCl3, 400 MHz): d=
0.97 [s, CACTHUNGTRNEUNG(CH3)3, 9H], 2.09 [dd, CH2C(OH), 1H, J=16.3 Hz,
J=9.7 Hz], 2.52 [dt, -CH2C(OH), 1H, J=16.5 Hz, J=
1.0 Hz], 3.61 (s, broad, OH, 1H), 5.05 (s, C=CH2, 1H), 5.06
(s, C=CH2, 1H), 5.21 [dd,-CH(OH), 1H, J=9.7 Hz, J=
1.9 Hz], 7.42–7.46 (m, Ar-H, 2H), 7.53–7.57 (m, Ar-H, 1H),
7.85–7.88 (m, Ar-H, 2H); 13C NMR (CDCl3, 100 MHz): d=
29.06, 36.16, 37.33, 72.48, 108.36, 128.62, 128.91, 133.63,
134.02, 153.19, 202.03. The enantiomeric excess was deter-
mined by HPLC with a Chiralcel OD-H column [1.0% 2-
propanol in hexane, flow 1.0 mLminÀ1, (S)-enantiomer Rt =
7.9 min (minor), (R)-enantiomer Rt =11.7 min (major)].
diphosphine]M}ACHTUNGTRENNUNG(SbF6)2 (M=Pd, Pt).
General Procedure for Enantioselective Carbonyl-
Ene Reactions
To a solution of the in situ prepared catalyst in dichlorome-
thane according to the above described activation method,
was added a dichloromethane solution of phenylglyoxal
(1 mL, 0.25 mmol/mL) or 0.25 mmol ethyl trifluoropyruvate
or 0.5 mmol ethyl glyoxylate (50% in toluene), followed by
0.25 mmol of the desired alkene. The resulting mixture was
stirred for 1 or 2 h at room temperature. Then the reaction
mixture was concentrated under vacuum and diluted with
hexane (1.5 mL). The mixture was immediately loaded onto
silica gel, and eluted with a hexane/ethyl acetate mixture to
give the corresponding compound. The isolated product was
2-Hydroxy-6,6-dimethyl-4-methylene-1-phenyl-1-hept-
anone (3d)
The title compound was prepared according to the general
procedure using 0.25 mmol of phenylglyoxal and 0.25 mmol
of 2,4,4-trimethyl-1-pentene. The pure product was obtained
by column chromatography over silica gel eluted with
hexane/ethyl acetate (9:1). The 1H NMR and 13C NMR of
the product were consistent with the reported data.[6a] The
enantiomeric excess was determined by HPLC with a Chir-
alcel OD-H column [1.0% 2-propanol in hexane, flow
1.0 mLminÀ1, (S)-enantiomer Rt =10.2 min (minor), (R)-
enantiomer Rt =14.3 min (major)].
1
characterized with H NMR, 13C NMR and 19F NMR spec-
trosocopy. The enantiomeric excess was determined by
HPLC or GC with a chiral column.
The following details for the synthesis and analysis of
compounds 3a–3e and 4a–4e were obtained using Pd-1 as
the catalyst.
2-Hydroxy-1,4-diphenyl-4-penten-1-one (3e)
3-(1-Cyclohexenyl)-2-hydroxy-1-phenyl-1-propanone
(3a)
The title compound was prepared according to the general
procedure using 0.25 mmol of phenylglyoxal and 0.25 mmol
of a-methylsyrene. The pure product was obtained by
column chromatography over silica gel eluted with hexane/
The title compound was prepared according to the general
procedure using 0.25 mmol of phenylglyoxal and 0.25 mmol
of methylenecyclohexane. The pure product was obtained
by column chromatography over silica gel eluted with
hexane/ethyl acetate (9:1). The 1H NMR and 13C NMR of
the product were consistent with the reported data.[6a]. The
enantiomeric excess was determined by HPLC with a Chir-
alcel OD-H column [1.0% 2-propanol in hexane, flow
1.0 mLminÀ1, (S)-enantiomer Rt =13.2 min (minor), (R)-
enantiomer Rt =20.12 min (major)].
1
ethyl acetate (9:1). The H NMR and 13C NMR of the prod-
uct were consistent with the reported data.[7e] The enantio-
meric excess was determined by HPLC with a Chiralcel
OB-H column [3.0% 2-propanol in hexane, flow
1.0 mLminÀ1, (R)-enantiomer Rt =20.5 min (major), (S)-
enantiomer Rt =27.4 min (minor)].
Ethyl 2-(Cyclohexenylmethyl)-3,3,3-trifluoro-2-hy-
droxypropanoate (4a)
2-Hydroxy-5-methyl-4-methylene-1-phenyl-1-hexan-
one (3b)
The title compound was prepared according to the general
procedure using 0.25 mmol of ethyl trifluoropyruvate and
0.25 mmol of methylenecyclohexane. The pure product was
obtained by column chromatography over silica gel eluted
with hexane/ethyl acetate (5:1). 1H NMR (CDCl3,
400 MHz): d=1.27 (t, CH3, 3H, J=7.2 Hz), 1.41–1.53 (m,
CH2CH2, 4H), 1.75–2.05 (m, CH2C=C, 4H), 2.43 [d,
CH2C(OH), 1H, J=13.9 Hz], 2.59 [d, CH2-C(OH), 1H, J=
13.9 Hz], 3.72 (broad, OH, 1H), 4.20–4.32 (m, COOCH2,
The title compound was prepared according to the general
procedure using 0.25 mmol of phenylglyoxal and 0.25 mmol
of 2,3-dimethyl-1-butene. The pure product was obtained by
column chromatography over silica gel eluted with hexane/
1
ethyl acetate (9:1). The H NMR and 13C NMR of the prod-
uct were consistent with the reported data.[6a] The enantio-
meric excess was determined by HPLC with a Chiralcel
1362
asc.wiley-vch.de
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1356 – 1364

Palladium(II) Complexes of C2-Bridged Chiral Diphosphines
2H), 5.48 (s, -C=CH-, 1H]; 13C NMR (CDCl3, 100 MHz):
d=13.98, 21.93, 22.85, 25.40, 29.77, 39.60, 63.55, 78.22 (q,
(CDCl3, 100 MHz): d=13.79, 28.91, 30.79, 36.49, 63.64, 77.97
(q, JC,F =28.0 Hz), 108.84, 123.50 (q, JC,F =287.5 Hz), 150.46,
169.78; 19F{1H} NMR (CDCl3, 376 MHz): d=À79.56; HR-
MS (ESI): m/z=291.1166, calcd. for C12H19F3O3Na [M+
Na]+: 291.1179. The enantiomeric excess was determined by
GC using a Varian CP7502 column (508C for 2 min; ramp
to 1108C at 108CminÀ1 and hold 20 min; then ramp to
1808C at 108CminÀ1 and hold 5 min, gas flow: 1 mLminÀ1):
Rt of the major enantiomer=13.0 min, Rt of the minor enan-
tiomer=13.7 min.
J
C,F =28.5 Hz), 123.38 (q, JC,F =286.3 Hz), 127.69, 130.88,
169.73; 19F{1H} NMR (CDCl3, 376 MHz) d=À78.73; HR-
MS (ESI): m/z=289.1011, calcd. for C12H17F3O3Na [M+
Na]+: 289.1022. The enantiomeric excess was determined by
GC using a Varian CP7502 column [508C for 2 min; ramp to
1108C at 108CminÀ1 and hold 30 min; then ramp to 1808C
at 108CminÀ1 and hold 20 min, gas flow: 1 mLminÀ1); Rt of
the major enantiomer=23.4 min, Rt of the minor enantio-
mer=25.5 min.
Ethyl 2-Hydroxy-6,6-dimethyl-4-methylene-2-(tri-
fluoromethyl)-heptanoate (4d)
Ethyl 2-Hydroxy-5-methyl-4-methylene-2-(trifluoro-
methyl)-hexanoate (4b) and Ethyl 2-Hydroxy-4,5-
dimethyl-2-(trifluoromethyl)-4-hexenoateACTHNUGTRNEUNG( 4b’)
The title compound was prepared according to the general
procedure using 0.25 mmol of ethyl trifluoropyruvate and
0.25 mmol of 2,4,4-trimethyl-1-pentene. The pure product
was obtained by column chromatography over silica gel
eluted with hexane/ethyl acetate (15:1). 1H NMR (CDCl3,
The title compounds were prepared according to the general
procedure using 0.25 mmol of ethyl trifluoropyruvate and
0.25 mmol of 2,3-dimethyl-1-butene. The products of two
couples of enantiomers were obtained by column chroma-
tography over silica gel eluted with hexane/ethyl acetate
400 MHz): d=0.83 [s, C
J=7.2 Hz), 1.81 [d, CH2-C
CH2-C(CH3)3, 1H, J=13.1 Hz], 2.57 [dd, CH2-C(OH), 1H,
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
1
(15:1). H NMR (CDCl3, 400 MHz, mixture of 4b and 4b’):
J=14.1 Hz, J=0.7 Hz], 2.68 [d, CH2-C(OH), 1H, J=
14.1 Hz], 3.77 (broad, -OH, 1H), 4.19–4.34 (m, COOCH2,
2H), 4.81 (t, C=CH2, 1H, J=0.8 Hz), 4.95 (s, C=CH2, 1H);
13C NMR (CDCl3, 100 MHz): d=13.91, 29.66, 31.68, 38.39,
d=0.937 (d, CHCH3 of 4b, 3H, J=6.8 Hz), 0.943 (d,
CHCH3 of 4b, 3H, J=6.8 Hz), 1.24–1.28 (m, CH2CH3 of 4b
and 4b’), 1.57 (s, CH3 of 4b’, 3H), 1.59 (s, CH3 of 4b’, 3H),
1.62 (s, CH3 of 4b’, 3H), 2.22 [sept, CHACTHUNGTRNEUNG(CH3)2 of 4b, 1H, J=
50.39, 63.64, 78.35 (q, JC,F =28.2 Hz), 118.29, 123.32 (q, JC,F
=
6.8 Hz], 2.59, 2.67, 2.76 (d,d,d, CH2 of 4b and 4b’, J=
14.5 Hz, J=14.3 Hz, J=14.1 Hz), 3.64 (s broad, OH of 4b’,
1H), 3.79 (s broad, OH of 4b, 1H), 4.12–4.36 (m, OCH2 of
4b and 4b’), 4.80 (s, C=CH2 of 4b, 1H), 4.85 (s, C=CH2 of
286.5 Hz), 140.36, 169.51; 19F{1H} NMR (CDCl3, 376 MHz):
d=À78.85; HR-MS (ESI): m/z=305.1325, calcd. for
C13H21F3O3Na [M+Na]+: 305.1335. The enantiomeric excess
was determined by GC using a Varian CP7502 column
(508C for 2 min; ramp to 1108C at 108CminÀ1 and hold
20 min; then ramp to 1808C at 108CminÀ1 and hold 5 min,
gas flow: 1 mLminÀ1): Rt of the major enantiomer=
15.5 min, Rt of the minor enantiomer=16.5 min.
1
4b, 1H). The ratio of 4b to 4b’ calculated from H NMR is
2.5. 13C NMR (CDCl3, 100 MHz, mixture of 4b and 4b’):
data of 4b: d=13.83, 21.37, 21.81, 34.11, 35.66, 63.62, 78.22
(q, JC,F =28.4 Hz), 111.56, 123.37 (q, JC,F =286.7 Hz), 148.95,
169.51; data of 4b’: d=13.76, 19.38, 20.91, 20.97, 36.18,
63.50, (a group of small peaks are hidden in between the
strong solvent peaks, its d and J cannot be accurately calcu-
lated), 119.80, 123.60 (q, JC,F =286.1 Hz), 131.58, 170.09;
19F{1H} NMR (CDCl3, 376 MHz, mixture of 4b and 4b’): d=
À78.66 (4b’), À79.02 (4b); HR-MS (ESI): m/z=277.1009,
calcd. for C11H17F3O3Na [M+Na]+: 277.1022. The enantio-
meric excess was determined by GC using a Varian CP7502
column (508C for 2 min; ramp to 1108C at 108CminÀ1 and
hold 20 min; then ramp to 1808C at 108CminÀ1 and hold
5 min, gas flow: 1 mLminÀ1): for product 4b, Rt of the major
enantiomer=10.8 min, Rt of the minor enantiomer=
11.1 min; for product 4b’, Rt of the major enantiomer=
12.6 min, Rt of the minor enantiomer=13.1 min.
Ethyl 2-Hydroxy-4-phenyl-2-(trifluoromethyl)pent-4-
enoate (4e)
The title compound was prepared according to the general
procedure using 0.25 mmol of ethyl trifluoropyruvate and
0.25 mmol of a-methylstyrene. The pure product was ob-
tained by column chromatography over silica gel eluted with
hexane/ethyl acetate (15:1). 1H NMR (CDCl3, 400 MHz):
d=1.03 (t, OCH2CH3, 3H, J=7.2 Hz), 2.96 [dd, CH2-
C(OH), 1H, J=14.0 Hz, J=0.7 Hz], 3.21 [d, CH2-C(OH),
1H, J=14.0 Hz], 3.51–3.59 (m, COOCH2, 1H), 3.72 (s,
broad, OH, 1H), 3.91–3.99 (m, COOCH2, 1H), 5.21 (d, C=
CH2, 1H, J=0.9 Hz), 5.31 (d, C=CH2, 1H, J=1.3 Hz), 7.18–
7.25 (m, Ph-H, 5H); 13C NMR (CDCl3, 100 MHz): d=13.55,
37.03 (q,
JC,F =1.1 Hz), 63.49, 77.11 (q, JC,F =28.7 Hz),
Ethyl 2-Hydroxy-5,5-dimethyl-4-methylene-2-(tri-
fluoromethyl)-hexanoate (4c)
119.45, 123.38 (q, JC,F =286.1 Hz), 126.78, 127.73, 128.16,
141.02, 141.04, 168.95; 19F{1H} NMR (CDCl3, 376 MHz): d=
À78.62; HR-MS (ESI): m/z=311.0857, calcd. for
C14H15F3O3Na [M+Na]+: 311.0866. The enantiomeric excess
was determined by HPLC with a Chiralpak AS-H column
(0.5% 2-propanol in hexane, flow 0.3 mLminÀ1): Rt of the
major enantiomer=16.0 min, Rt of the minor enantiomer=
17.2 min).
The title compound was prepared according to the general
procedure using 0.25 mmol of ethyl trifluoropyruvate and
0.25 mmol of 2,3,3-trimethyl-1-butene. The pure product was
obtained by column chromatography over silica gel eluted
with hexane/ethyl acetate (15:1). 1H NMR (CDCl3,
400 MHz): d=1.06 [s, CACHTUNTRGNENG(U CH3)3, 9H], 1.30 (t, OCH2CH3, 3H,
J=7.2 Hz), 2.66 [dt, CH2C(OH), 1H, J=16.5 Hz, J=
1.5 Hz], 2.80 [d, CH2C(OH), 1H, J=16.5 Hz], 3.88 (broad,
OH, 1H), 4.22–4.39 (m, COOCH2, 2H), 4.94 (t, C=CH2,
1H, J=1.2 Hz), 4.97 (d, C=CH2, 1H, J=1.3 Hz); 13C NMR
Adv. Synth. Catal. 2010, 352, 1356 – 1364
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1363

He-Kuan Luo et al.
FULL PAPERS
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Ethyl 2-Hydroxy-4-phenyl-4-pentenoate (5e)
The title compound was prepared according to the general
procedure using 0.5 mmol ethyl glyoxylate (50% in toluene)
and 0.25 mmol a-methylstyrene. The pure product was ob-
tained by column chromatography over silica gel eluted with
heyane/ethyl acetate (5:1). The 1H NMR and 13C NMR
spectra of the product were consistent with reported
data.[5a,b] The enantiomeric excess was determined by HPLC
with a chiral AS column (5.0% 2-propanol in hexane, flow
1.0 mLminÀ1): (S)-enantiomer Rt =11 min (minor), (R)-
enantiomer Rt =17 min (major).
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Supporting Information
1H NMR, 13C NMR, 19F{H} NMR, HPLC and GC traces of
products 3cꢀand 4a–4e are given in the Supporting Informa-
tion.
[7] For catalysts based on Pd and Pt with chiral diphos-
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Acknowledgements
This work was supported by Institute of Chemical and Engi-
neering Sciences, A*STAR, Singapore.
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1364
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ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1356 – 1364