Asymmetric bis(alkoxycarbonylation) reaction of terminal olefins catalyzed by palladium in the presence of copper(I) triflate and a chiral bioxazoline ligand

Article abstract of DOI:10.1246/bcsj.74.955

A palladium-catalyzed asymmetric bis(alkoxycarbonylation) reaction of terminal olefins in the presence of copper(I) triflate was achieved by using a chiral bioxazoline ligand, (4S,4′S)-4,4′-dibenzyl-4,4′,5,5′-tetrahydro- 2,2′-bioxazole, under normal press

Full text of DOI:10.1246/bcsj.74.955

c. Jpn.
© 2001 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 74, 955—958 (2001)
955
e Chemical
ciety of Ja-
n
e Chemical
ciety of Ja-
n
Asymmetric Bis(alkoxycarbonylation) Reaction of Terminal Olefins
Catalyzed by Palladium in the Presence of Copper(I) Triflate and a
Chiral Bioxazoline Ligand
Asymmetric Bis(alkoxycarbonylation)
S. Takeuchi et al.
01
5
Susumu Takeuchi, Yutaka Ukaji,* and Katsuhiko Inomata*
8
Department of Chemical Science, Graduate School of Natural Science and Technology, Kanazawa University,
Kakuma, Kanazawa, Ishikawa 920-1192
SJA8
09-2673
361
tober
(Received October 13, 2000)
00
00
.1
A palladium-catalyzed asymmetric bis(alkoxycarbonylation) reaction of terminal olefins in the presence of cop-
per(I) triflate was achieved by using a chiral bioxazoline ligand, (4S,4′S)-4,4′-dibenzyl-4,4′,5,5′-tetrahydro-2,2′-biox-
azole, under normal pressure of carbon monoxide and oxygen at 25 ˚C to give the corresponding optically active mono-
substituted succinates with enantioselectivity up to 66% ee.
An asymmetric carbonylation reaction of olefins catalyzed
by transition metals provides one of the most efficient methods
to produce optically active carbonyl compounds, which are
very important synthons for biologically active compounds.
There have been intensive researches on the asymmetric
monocarbonylation of prochiral olefins, that is, hydroformyla-
tion,1 hydrocarboxylation,2 hydro(alkoxycabonylation),3 and
carbonyl-copolymerization.4 To the contrary, a limited number
of the asymmetric biscarbonylation was reported. The palladi-
um-catalyzed carbonylation reaction of styrene using atropiso-
meric diphosphanes gave the optically active dimethyl
phenysuccinate along with oligomers containing two terminal
methoxycarbonyl groups.5a Bis(alkoxycabonylation) of sty-
rene in the presence of Chiraphos sulfide was also reported to
proceed with low enantioselectivity.5b Thus, the asymmetric
biscarbonylation of olefins is still regarded as one of the chal-
lenging problems in asymmetric carbonylation.
yield. The optical yield of the obtained diester 2a was deter-
mined to be 16% ee by a HPLC analysis (Entry 1 in Table 1).
When allylpalladium chloride dimer was used instead of
PdCl2, the stereoselectivity was scarcely changed (Entry 2).
To our disappointment, the carbonylation reaction utilizing
CuOTf(C6H6)0.5 instead of CuCl on combination with allylpal-
ladium chloride dimer, by which the best result was realized in
the asymmetric bis(alkoxycarbonylation) reaction of homoal-
lylic alcohols,8 did not proceed (Entry 3). It was found that the
combination of PdCl2 and
a 0.5 molar amount of
CuOTf(C6H6)0.5 afforded 2a with enhanced enantioselectivity
of 64% ee (Entry 4). Using a 1.0 molar amount of
CuOTf(C6H6)0.5 decreased the chemical yield (Entry 5). In the
present bis(alkoxycarbonylation), a small amount of methyl
cinnamate was produced accompanied by 2a; for example,
10% yield in the case of Entry 4.
We have already reported on selective mono- and bis(alkox-
ycarbonylation) reactions catalyzed by palladium in the pres-
ence of copper(II) or copper(I) chloride to prepare esters and γ-
butyrolactones from terminal olefins and homoallylic alcohols,
respectively.6,7 Furthermore, the asymmetric intra- and inter-
molecular bis(alkoxycarbonylation) of homoallylic alcohols
catalyzed by palladium(II) and copper(I) salts was developed
to afford the corresponding optically active γ-butyrolactones.8
Herein, we wish to report on the bis(alkoxycarbonylation) re-
action of terminal olefins catalyzed by palladium(II) and cop-
per(I) salts under normal pressure of carbon monoxide and ox-
ygen atmosphere to afford the corresponding optically active
mono-substituted succinates.
(1)
Next, several other bioxazolines, 3B-D and ent-3E, were
used as chiral ligands for the bis(alkoxycarbonylation) reaction
(Fig. 1). Although the carbonylation reactions proceeded,
First, a bis(alkoxycarbonylation) of styrene (1a) was exam-
ined on a combination of the palladium(II) and copper(I) salts
in the presence of (4S,4′S)-4,4′-dibenzyl-4,4′,5,5′-tetrahydro-
2,2′-bioxazole (3A) under a carbon monoxide and oxygen (ca.
1/1, v/v, 1 atm) atmosphere in MeOH at 25 ˚C (Eq. 1). A reac-
tion using a 0.02 molar amount of PdCl2 and 1.5 molar
amounts of CuCl gave dimethyl phenylsuccinate (2a) in 42%
Fig. 1.

956 Bull. Chem. Soc. Jpn., 74, No. 5 (2001)
Asymmetric Bis(alkoxycarbonylation)
Table 1.
Entry
Asymmetric Bis(alkoxycarbonylation) Reaction of Styrene (1a) under Various Conditions
[Pd(II)]
[Cu(I)]
(Molar
Ligand
Co-solvent
Time/d
Yield of
ee/%a)
amounts)
2a/%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
PdCl2
(C3H5PdCl)2
(C3H5PdCl)2
PdCl2
CuCl
CuCl
1.5
1.5
0.5
0.5
1.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
3A
3A
3A
3A
3A
3B
—
—
—
—
—
—
—
—
—
11
19
7
5
7
15
3
14
7
4
12
6
6
5
5
5
5
5
42
47
—
53
41
47
27
36
35
51
34
34
73
62
67
64
36
57
16
17
—
64
64
27
48
12
42d)
41
4
60
66
44
60
40
6
b)
b)
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
CuOTf(C6H6)0.5
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
3C
3D
ent-3Ec)
4
—
—
5
3A
3A
3A
3A
3A
3A
3A
Et2O
THF
DME
dioxane
CH2Cl2
CHCl3
C6H6
20
a) Enantiomeric excess was determined by an HPLC analysis (Daicel Chiralcel OD-H). b) 0.01 molar amount of (C3H5PdCl)2 was
used. c) Enantiomer of 3E was used ass a chiral ligand. d) (S)-Enantiomer was mainly obtained.
enantioselectivities were lower than that in the case of the ben-
zyl substituted ligand 3A (Entries 4, 6–9). The 5,5,5′,5′-tet-
ramethyl substituted bioxazoline 4 appeared to be less selec-
tive than 3A (Entry 10). By using a benzyl substituted
bis(oxazoline) 5, little enantioselectivity was realized (Entry
11).
Further, the effect of a co-solvent in MeOH was examined
(Entries 4, 12–18). Although the optical yields were not sig-
nificantly influenced by the co-solvent, except for CHCl3 and
benzene (Entries 17 and 18), the chemical yield was rather im-
proved by using THF among the co-solvents examined (Entry
13).
Next, the bis(alkoxycarbonylation) reaction of several ter-
minal olefins 1 was carried out by using a 0.02 molar amount
of PdCl2 and a 0.5 molar amount of CuOTf(C6H6)0.5 in the
presence of a 0.04 molar amount of bioxazoline 3A under a
carbon monoxide and oxygen (ca. 1/1, v/v, 1 atm) atmosphere
in MeOH/THF (1/1, v/v) at 25 ˚C (Eq. 2). The results are sum-
marized in Table 2. In the reaction of aromatic olefins 1b, c,
similar results to 1a were obtained (Entries 1–3). Not only the
aromatic olefins 1a–c, but aliphatic terminal olefins 1d, e could
be the substrates of the bis(alkoxycarbonylation) (Entries 4
and 5).
Although the precise mechanism of the present reaction is
still an open question, one possible reaction pathway is shown
in Scheme 1. In the present carbonylation, copper might work
not only as an oxidant, but also as a co-catalyst to generate ac-
tive species.11 That is, copper(I) triflate reacts with CO and
MeOH successively to give the CuCO2Me species 6,12 and the
methoxycarbonyl group was transferred to palladium chloride
complex 10 with the chiral ligand 3 to generate complex 7.
Further, copper(I) triflate also reacts with 7 to afford a cationic
palladium intermediate 8, in which olefin can, strongly coordi-
nate to the palladium metal. An attack of palladium upon in-
ternal carbon of the olefin (T1 and T2 in Fig. 2) might be more
favorable than that on terminal carbon (T3 and T4 in Fig. 2) to
avoid a direct repulsion between a substituent R in olefin and
the methoxycarbonyl group. This was supported by the forma-
tion of methyl cinnamate as a side product in a reaction with
styrene 2a (R ꢀ Ph). Further, a steric hindrance between R
and the substituent at C-4 of the bioxazoline ligand would dis-
favor the transition state T1; thus, the transition state T2 was
most favored to produce an optically active mono-substituted
succinate 2 along with palladium(0) complex 9. Based on the
Table 2.
Asymmetric Bis(alkoxycarbonylation) Reaction
of Terminal Olefins 1
Entry
1
R
Time/d Yield of 2/%
ee/%
(2)
1
2
3
4
5
a
b
c
d
e
Ph
2-Np
4-(tBu)C6H4
PhCH2
PhCH2CH2
6
73
43
74
35
53
66a)
64a)
60a)
59a)
46b)
11
8
The absolute configurations of succinates 2a and 2d were
determined to be R and S, respectively, by a comparison with
the reported specific rotations,9,10 which suggests that both car-
bonylations predominantly proceeded from a re-face of 1a and
1d. The absolute configurations of products 2b, 2c and 2e
were tentatively determined to be R, R, and S, respectively,
based on the above fact.
16
11
a) Enantiometric excess was determined by an HPLC anal-
ysis (Daicel Chiralcel OD-H).
b) Enantiometric excess was determined by an HPLC anal-
ysis (Daicel Chiralcel OB-H).

S. Takeuchi et al.
Bull. Chem. Soc. Jpn., 74, No. 5 (2001) 957
Scheme 1.
fact that alkoxycarbonylation reaction of methyl cinnamate did
not proceed under similar conditions, the pathway via α,β-un-
saturated ester as an intermediate could be excluded. The pal-
ladium(II) catalyst 10 is regenerated by the oxidation of 9 by
oxygen in the presence of copper(I) salt. During this oxidation
step, copper(I) triflate might be partially produced again and
recycled. By using a large amount of copper(I) triflate, liberat-
ed trifluoromethanesulfonic acid (11) might decompose the re-
active palladium intermediate to decrease the chemical yield
(Table 1, Entry 5). In the case of palladium complex with
bis(oxazoline) ligand 5, the 6-membered ring moiety consist-
ing of palladium atom and bis(oxazoline) ligand 5 might adopt
a distorted non-planar conformation in a transition state corre-
sponding to 8, in which the bis(oxazoline) ligand moiety is no
longer C2 symmetric.13 Therefore, the carbonylation reaction
using ligand 5 could proceed with little enantioselectivity.
In summary, palladium-catalyzed asymmetric bis(alkoxy-
carbonylation) of terminal olefins was achieved utilizing the
chiral bioxazoline ligand. This method provides a new entry
for preparing optically active mono-substituted succinates.
Experimental
The melting point was determined with a micro melting ap-
paratus (Yanagimoto-Seisakusho) and was uncorrected. The
1H NMR spectra were recorded on a JEOL JNM-GX 400 or a
JEOL Lambda 400 spectrometer with tetramethylsilane as an
internal standard. The IR spectra were measured with a JAS-
CO FT/IR-230 spectrometer. The MS spectra were measured
with a Hitachi M-80, or a JMS-SX102A mass spectrometer.
The specific optical rotations were recorded on a JASCO DIP-
370 spectrometer. THF and Et2O were freshly distilled from
sodium diphenylketyl. All other solvents were distilled and
stored over drying agents. Column chromatography and thin-
layer chromatography (TLC) were performed on Wakogel C-
300 and Merck’s silica gel 60 PF254 (Art. 7749), respectively.
Chiral ligands 3, 4 and 5 were prepared by the methods pre-
viously reported.8,14
The Representative Procedure of Asymmetric Bis(alkoxy-
carbonylation) for Styrene (1a):
To a mixture of PdCl2
(1.77 mg, 0.01 mmol), (4S,4′S)-4,4′-dibenzyl-4,4′,5,5′-tetrahy-
dro-2,2′-bioxazole (3A) (6.44 mg, 0.02 mmol), and
CuOTf(C6H6)0.5 (63 mg, 0.25 mmol), a MeOH (2 mL) solution
Fig. 2.

958 Bull. Chem. Soc. Jpn., 74, No. 5 (2001)
Asymmetric Bis(alkoxycarbonylation)
of styrene (1a) (52 mg, 0.50 mmol) was added under an argon
atmosphere, followed by the addition of THF (2 mL). The ar-
gon atmosphere was replaced with CO/O2 (ca. 1/1, v/v) and
the reaction mixture was stirred for 6 d at 25 ˚C. Sat. aqueous
NaHCO3 was added and the insoluble substance was filtered
off through Celite. After the filtrate was extracted with ethyl
acetate several times, the combined extracts were washed with
water and brine, dried over Na2SO4, and condensed in vacuo.
The residue was purified by TLC (SiO2, hexane/ethyl acetate
ꢀ 8/1, v/v) to give dimethyl (R)-phenylsuccinate (2a) (81 mg,
73%, 66% ee).
2H), 2.76 (dd, J ꢀ 9.15, 16.48 Hz, 1H), 2.88 (m, 1H), 3.67 (s,
3H), 3.71 (s, 3H), 7.16–7.21 (m, 3H), 7.26-7.30 (m, 2H).
References
1
K. Nozaki, F. Shibahara, and T. Hiyama, Chem. Lett., 2000,
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2
(1990).
3
H. Alper and N. Hamel, J. Am. Chem. Soc., 112, 2803
Dimethyl (R)-Phenylsuccinate (2a):
Mp 54–55 ˚C
(from hexane), (Ref. 15, 58–59 ˚C); [α]D25 ꢁ95˚ (c 0.8, CHCl3;
66% ee), (Ref. 9 (S)-isomer: [α]D24 ꢂ50.7˚ (c 0.95, CHCl3; 38%
ee)); MS m/z (rel intensity) 222 (Mꢂ, 1.26), 191 (17.10), 190
(68.59), 162 (88.14), 121 (100.00), 103 (39.33), 91 (17.15), 77
(25.95); IR (KBr) 3030, 2958, 1730, 1600, 1493, 1437, 1310,
1196, 1154, 997, 870, 728, 698 cmꢁ1; 1H NMR (CDCl3) δ 2.67
(dd, J ꢀ 5.50, 17.09 Hz, 1H), 3.21 (dd, J ꢀ 10.07, 17.09 Hz,
1H), 3.67 (s, 3H), 3.68 (s, 3H), 4.09 (dd, J ꢀ 5.50, 10.07 Hz,
1H), 7.26–7.35 (m, 5H).
P. Cao and X. Zhang, J. Am. Chem. Soc., 121, 7708 (1999);
W.-Y. Yu, C. Bensimon, and H. Alper, Chem. Eur. J., 3, 417
(1997); H. Alper and N. Hamel, J. Chem. Soc., Chem. Commun.,
1990, 135.
4
K. Nozaki, N. Sato, Y. Tonomura, M. Yasutomi, H. Takaya,
T. Hiyama, T. Matsubara, and N. Koga, J. Am. Chem. Soc., 119,
12779 (1997); Z. Jiang and A. Sen, J. Am. Chem. Soc., 117, 4455
(1995); M. Brookhart, M. I. Wagner, G. G. A. Balavoine, and H.
A. Haddou, J. Am. Chem. Soc., 116, 3641 (1994), and references
cited therein.
In a similar manner, other succinates 2b–e were prepared
from the corresponding olefins 1b–e.
5
a) S. C. A. Nefkens, M. Sperrle, and G. Consiglio, Angew.
Chem., Int. Ed. Engl., 32, 1719 (1993). b) M. Hayashi, H.
Takezaki, Y. Hashimoto, K. Takaoki, and K. Saigo, Tetrahedron
Lett., 39, 7529 (1998).
Dimethyl (R)-(2-Naphthyl)succinate (2b): An oil; [α]D25
ꢁ95˚ (c 0.6, CHCl3; 64% ee); MS m/z (rel intensity) 272 (Mꢂ,
20.55), 240 (27.81), 212 (100.00), 182 (0.86), 171 (47.75), 153
(30.19), 128 (7.23); IR (neat) 3056, 2952, 1738, 1600, 1508,
6
K. Inomata, S. Toda, and H. Kinoshita, Chem. Lett., 1990,
1567; S. Toda, M. Miyamoto, H. Kinoshita, and K. Inomata, Bull.
Chem. Soc. Jpn., 64, 3600 (1991).
1
1437, 1336, 1268, 1164, 1008, 861, 819, 752 cmꢁ1; H NMR
(CDCl3) δ 2.77 (dd, J ꢀ 5.49, 17.09 Hz, 1H), 3.31 (dd, J ꢀ
10.07, 17.09 Hz, 1H), 3.68 (s, 3H), 3.69 (s, 3H), 4.27 (dd, J ꢀ
5.49, 10.07 Hz, 1H), 7.40 (dd, J ꢀ 1.83, 8.54 Hz, 1H), 7.45–
7.51 (m, 2H), 7.74 (d, J ꢀ 1.83 Hz, 1H), 7.80–7.82 (m, 3H).
7
Related intra- and intermolecular bis(alkoxycarbonyla-
tion): Y. Tamaru, M. Hojo, and Z. Yoshida, J. Org. Chem., 56,
1099 (1991).
8
Y. Ukaji, M. Miyamoto, M. Mikuni, S. Takeuchi, and K.
Inomata, Bull. Chem. Soc. Jpn., 69, 735 (1996).
2a: J. Lehmann and G. C. Lloyd-Jones, Tetrahedron, 51,
Dimethyl
(R)-[4-(1,1-Dimethylethyl)phenyl]succinate
(2c): An oil; [α]D25 ꢁ64˚ (c 1.1, CHCl3; 60% ee); MS m/z (rel
intensity) 278 (Mꢂ, 8.97), 263 (6.80), 246 (100.00), 231
(29.05), 218 (83.19), 203 (99.92), 177 (81.13), 145 (36.40),
117 (19.10), 91 (10.27); IR (neat) 2956, 1739, 1510, 1437,
9
8863 (1995).
10 2d: E. Guibé-Jampel, G. Rousseau, and J. Salaün, J. Chem.
Soc., Chem. Commun., 1987, 1080.
1364, 1253, 1196, 1162, 1007, 849, 831 cmꢁ1 1H NMR
;
11 In the O2 oxidation reaction of olefins catalyzed by palladi-
um–copper systems, it has been proposed that copper works not as
an oxidant of palladium but as co-catalyst cooperated with palladi-
um to generate active species: T. Hosokawa and S.-I. Murahashi,
Acc. Chem. Res., 23, 49 (1990).
(CDCl3) δ 1.30 (s, 9H), 2.65 (dd, J ꢀ 5.19, 17.09 Hz, 1H),
3.20 (dd, J ꢀ 10.38, 17.09 Hz, 1H), 3.68 (s, 6H), 4.07 (dd, J ꢀ
5.19, 10.38 Hz, 1H), 7.19 (d, J ꢀ 8.24 Hz, 2H), 7.34 (d, J ꢀ
8.24 Hz, 2H).
12 Copper(I) compounds is well-known to absorb carbon
monoxide to generate carbonyl complexes. Furthermore, carbon-
ylation reactions of alcohols, amines, and water have been known
to be catalyzed by Group 11 metals, in which alkoxycarbonyl-,
carbamoyl-, and carboxyl-metal species are supposed as interme-
diates, respectively.16 Thus, the CuCO2Me species might be a pos-
sible intermediate in the present reaction.
13 The distortion from planarity in the (1,3-diphenylallyl)pal-
ladium complex with the ligand ent-5 was reported: M. Zehnder,
M. Neuburger, P. von Matt, and A. Pfaltz, Acta Crystallogr., Sect.
C, C51, 1109 (1995).
14 D. Müller, G. Umbricht, B. Weber, and A. Pfaltz, Helv.
Chim. Acta, 74, 232 (1991); U. Leutenegger, G. Umbricht, C.
Fahrni, P. Matt, and A. Pfaltz, Tetrahedron, 48, 2143 (1992); A.
Pfaltz, Acc. Chem. Res., 26, 339 (1993).
15 D. E. James and J. K. Stille, J. Am. Chem. Soc., 98, 1810
(1976).
Dimethyl (S)-Benzylsuccinate (2d): An oil; [α]D25 ꢁ18˚
(c 0.1, CHCl3; 59% ee), (Ref. 10 (S)-isomer: [α]D ꢁ27.3˚ (c
4.5, CHCl3; > 98% ee)); MS m/z (rel intensity) 236 (Mꢂ,
18.24), 204 (19.92), 176 (78.70), 163 (40.52), 145 (28.42), 131
(52.68), 117 (100.00), 91 (91.33); IR (neat) 3029, 2952, 1736,
1604, 1497, 1438, 1362, 1165, 1032, 1006, 746, 702 cmꢁ1; 1H
NMR (CDCl3) δ 2.41 (dd, J ꢀ 4.89, 16.79 Hz, 1H), 2.68 (dd, J
ꢀ 9.16, 16.79 Hz, 1H), 2.76 (dd, J ꢀ 8.22, 13.41 Hz, 1H), 3.05
(dd, J ꢀ 6.41, 13.41 Hz, 1H), 3.10–3.17 (m, 1H), 3.64 (s, 3H),
3.67 (s, 3H), 7.15 (d, J ꢀ 7.32 Hz, 2H), 7.20–7.32 (m, 3H).
Dimethyl (S)-(2-Phenylethyl)succinate (2e):
An oil;
[α]D25 ꢁ10˚ (c 0.9, CHCl3; 46% ee); MS m/z (rel intensity) 251
(Mꢂꢂ1, 5.36), 250 (Mꢂ, 8.96), 187 (57.43), 146 (100.00), 144
(11.01), 117 (11.51), 114 (77.49), 104 (31.50), 91 (24.76); IR
(neat) 3027, 2952, 1737, 1604, 1496, 1437, 1364, 1262, 751,
1
701 cmꢁ1; H NMR (CDCl3) δ 1.80–1.87 (m, 1H), 1.95–2.04
16 M. I. Bruce, J. Organometal. Chem., 44, 209 (1972).
(m, 1H), 2.48 (dd, J ꢀ 5.18, 16.48 Hz, 1H), 2.61–2.67 (m,