Phosphinite thioglycosides derived from natural D-sugars as useful P/S ligands for the synthesis of both enantiomers in palladium-catalyzed asymmetric substitution

Article abstract of DOI:10.1055/s-2005-918963

Phosphinite thioglycosides I for which a modular synthetic approach is reported, were found highly efficient catalyst precursors for palladium(0)-catalyzed asymmetric substitution. Both enantiomers of the allylated products have been obtained with high ee

Full text of DOI:10.1055/s-2005-918963

LETTER
2963
Phosphinite Thioglycosides Derived from Natural D-Sugars as Useful
P/S Ligands for the Synthesis of Both Enantiomers in Palladium-Catalyzed
Asymmetric Substitution
M
ixe
d
P/S
Ligand
o
s
D
erivedfro
u
m
N
atural
D
r
a
Instituto de Investigaciones Químicas, C.S.I.C-Universidad de Sevilla, c/. Américo Vespucio 49, Isla de la Cartuja, 41092 Sevilla, Spain
Fax +34(95)4460565; E-mail: khiar@iiq.csic.es
b
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, c/ Profesor García González 2,
41012 Sevilla, Spain
E-mail: inmaff@us.es
Received 18 July 2005
Following the seminal work of Evans,5 in this communi-
cation we report the first synthesis of mixed P/S ligands I
derived from carbohydrates (Scheme 1), and their
preliminary applications in a highly enantioselective
palladium(0)-catalyzed allylic substitution. In our ap-
proximation both enantiomers of the allylated products
have been obtained using pseudo-enantiomeric natural
sugars as catalyst precursors.6
Abstract: Phosphinite thioglycosides I for which a modular
synthetic approach is reported, were found highly efficient catalyst
precursors for palladium(0)-catalyzed asymmetric substitution.
Both enantiomers of the allylated products have been obtained with
high ee (up to 96%) using natural sugars as catalyst precursors.
Key words: P/S ligands, carbohydrates, both enantiomers, allylic
substitution
A fundamental characteristic of the phosphinite thio-
glycoside I is that upon coordination to the metal the ano-
meric sulfur atom becomes stereogenic. The close
proximity of the chiral sulfur atom to the coordination
sphere of the transition metal anticipates a good enantio-
selective discrimination in the catalytic process, provided
that the low inversion barrier of the sulfur metal bond can
be surmounted.5,7 We have recently reported the prepara-
tion of C2-symmetric bis-thioglycosides as new homo-
donor S/S ligands in Pd(0)-catalyzed allylic alkylation of
1,3-diphenylpropenylacetate with dimethyl malonate.8 A
subsequent study of the corresponding Pd(II) complexes
has indicated that the good enantioselectivity achieved
was a consequence of an efficient stereocontrol of the sul-
fur atom exerted by the exo-anomeric effect.9 In the case
of phosphinite thioglycosides I metal complexes, where
the exo-anomeric effect is not operative, good stereocon-
trol of the sulfur atom is also predicted taking into account
the strong steric and stereoelectronic interactions of the
substituent at sulfur and the endocyclic oxygen of the
pyranose ring.
The difficulty to predict the structural requirements of a
ligand for acting as a successful catalyst explains the
enduring need to develop new ligands which combine
efficiency, wide scope and easy synthesis.1 Therefore,
modular synthetic designs allowing a rapid optimization
of the ligand structure for a high activity and/or selectivity
in a precise chemical transformation are greatly desirable.
Carbohydrates, which are amongst the cheapest and most
abundant chiral starting materials, hold a range of struc-
tural characteristics that make them very appealing for
such venture.2 Notably, carbohydrates possess various
hydroxyl groups in different orientations, allowing easy
tuning of steric, electronic and three-dimensional struc-
ture of carbohydrate based ligands.3 Conceptually, the
utilization of carbohydrates in asymmetric synthesis is
severely limited when both enantiomers are needed, as L-
sugars are exceedingly expensive. While this problem has
been elegantly solved by RajanBabu4 in the case of homo-
donor P/P ligands, up to now there is no solution in the
case of mixed ligands with two different heteroatoms.
R
S
O
R´
PO
PPh2
O
OP
I
Nu
OAc
Ph
I
I
Nu
Ph
+
NuH
Ph
Ph
Ph
[Pd(η3-C3H5)Cl]2
[Pd(η3-C3H5)Cl]2
Ph
Scheme 1
SYNLETT 2005, No. 19, pp 2963–2967
0
1
.1
2
.2
0
0
5
Advanced online publication: 27.10.2005
DOI: 10.1055/s-2005-918963; Art ID: D20005ST
© Georg Thieme Verlag Stuttgart · New York

2964
N. Khiar et al.
LETTER
OAc
O
OH
OAc
O
AcO
AcO
O
AcO
AcO
Me2C
ii–iii
i
O
S
S
OAc
O
R
R
OAc
2: R = p-Tol (C1β
3: R = t-Bu (C1α
4: R = t-Bu (C1β
OH
5: R = p-Tol (C1β
6: R = t-Bu (C1α
OAc
)
)
1
)
)
7: R = t-Bu (C1β
)
)
OCOR'
OCOR'
O
O
O
Me2C
iv
Me2C
v
O
O
S
O
S
O
R
R
OH
8: R = p-Tol, R' = t-Bu (C1β
9: R = p-Tol, R' = CH3 (C1β
10: R = t-Bu, R' = CH3 (C1α
11: R = t-Bu, R' = CH3 (C1β
PPh2
)
12: R = p-Tol, R' = t-Bu (C1β
13: R = p-Tol, R' = CH3 (C1β
14: R = t-Bu, R' = CH3 (C1α
15: R = t-Bu, R' = CH3 (C1β
)
)
)
)
)
)
)
Scheme 2 Reagents and conditions: (i) RSH, BF3·OEt2, CH2Cl2, 0 °C or r.t. (80–95%); (ii), MeONa, MeOH; (iii) DMP, CSA, acetone (75–
80% for the 2 steps); (iv) R¢COCl, pyridine or collidine, CH2Cl2, –78 °C; (v) PPh2Cl, Et3N–THF (70–80%).
Condensation of a thiol with galactose pentaacetate (1) in ee, a-thioglycoside 14 led to the product in a very low ee
the presence of boron trifluoride afforded the correspond- (Table 1, entry 3). Aromatic thioglycosides 12 and 13 led
ing thioglycosides 2–4 in high chemical yields (85–95%, to 17S with the same moderate enantioselectivity around
Scheme 2).10 Surprisingly, while this reaction is reported 60% ee (Table 1, entries 1 and 2). Bulkier alkyl thioglyco-
to be highly diastereoselective, leading to the 1,2-trans- sides, such as the tert-butyl thioglycoside 15, afforded the
thioglycoside, we have found that when tert-butanethiol desired product 17S in up to 92% ee. Lowering the tem-
was used as glycosyl acceptor the stereochemical out- perature has a beneficial effect on the enantioselectivity
come of the reaction was highly dependent on the reaction allowing the preparation of the S isomer in an excellent
conditions. Condensation of tert-butanethiol with 1 at 0 96% ee at –20 °C. Owing to the success of these ligands
°C afforded b-thioglycoside 4 as the main product in only in palladium-catalyzed asymmetric allylation of dimethyl
one hour. In contrast, when conducted at room tempera- malonate, they were assayed in the allylation of benzyl
ture the reaction was found to be thermodynamically con- amine. The results of the allylic amination employing the
trolled, affording a- and b-thioglycosides 3 and 4 in a 2:1 same conditions as before are given in Table 2. Aromatic
ratio. Fortunately, the two diastereoisomers 3 and 4 have thioglycoside 13 (Table 2, entry 1) and axial thiogly-
high separation factors, allowing their preparation in high coside 14 (Table 2, entry 2) afforded the allylated amine
yields. A Zemplen deacetylation, followed by acid- 18 with low ee, while the equatorial tert-butyl thioglyco-
catalyzed acetalation with 2,2-dimethoxypropane (DMP) side 15 afforded the product in good ee. As it can be seen
afforded the 3,4-acetals 5–7 in 75–80% yield. A regiose- from Table 2, the aminated product 18R was obtained in
lective acylation of primary alcohol with pivaloyl chloride an excellent 93% yield and good 90% ee at 0 °C (Table 2,
in pyridine, or acetyl chloride in methylene chloride using entry 4), lowering the temperature to –20 °C afforded the
collidine as base at –78 °C afforded the monoalcohols 8– R isomer in 96% ee albeit in low yield (Table 2, entry 5).
11 in good yields.11 Finally, the installation of the phos-
As stated in the introduction, one of the drawbacks when
using carbohydrates as chiral ligands in asymmetric catal-
phinite moiety has been carried out in a 1:1 mixture THF–
Et3N, using DMAP as catalyst in 80–90% yield.12 Thus, in
ysis is the difficulty to access to the other enantiomer. Ac-
only 5 high yielding steps the phosphinite thioglycosides
cordingly, while D-glucose is the cheapest commercially
available chiral starting material (1.2 Eu/mol), the corre-
12–15 were obtained on a multigram scale (Scheme 2).13
The ability of the prepared phosphinite thioglycosides to sponding enantiomer, L-glucose is prohibitively expen-
act as chiral ligands in asymmetric catalysis was firstly sive (8650 Eu/mol), ruling out any possibility of using L-
assayed in the palladium-catalyzed allylic alkylation of sugars even in catalytic amount. Using b-D-glucopyrano-
1,3-diphenylpropenylacetate (16) with dimethyl mal- side as the chiral backbone,4 RajanBabu has demonstrated
onate. The reactions were conducted in methylene chlo- in the case of Rh(I)-catalyzed hydrogenation, that the 3,4-
ride using 3 mol% of Pd and 4.3 mol% of ligands, and the diphosphinite derivatives behave as pseudo-enantiomers
results are given in Table 1.14
to the 2,3-diphosphinite derivatives previously developed
by Selke.15
As can be seen from Table 1, phosphinite thioglycosides
are efficient precursors of the Pd(0) catalyst for the allyla-
tion of dimethyl malonate, as the desired product 17 was
always obtained in good chemical yield. The enantio-
selectivity is highly dependent on the stereochemistry of
the anomeric center and on the substituent of the sulfur.
Significantly, while b-thioglycosides 12, 13 and 15 af-
forded the desired product with good yield and variable
OH
O
HO
OH
HO
HO
O
O
OH
OH
OH
HO
HO
α-D-arabinose
HO
OH
OH
β-D-galactose
Figure 1
Synlett 2005, No. 19, 2963–2967 © Thieme Stuttgart · New York

LETTER
Mixed P/S Ligands Derived from Natural D-Sugars
2965
Table 1 Pd-Catalyzed Allylic Alkylation of 1,3-Diphenylpropenyl Acetate 16 with Dimethyl Malonate Using Ligands 12–15
1.5 mol%
[Pd(allyl)Cl]2
4.3 mol% L*
MeO2C
Ph
CO2Me
Ph
OAc
Ph
CH2(CO2Me)2
+
Ph
BSA, KOAc,
CH2Cl2, temp
17
16
OAc
O
OAc
O
O
OPiv
O
O
OAc
O
Me2C
O
Me2C
Me2C
O
Me2C
S
O
O
S
O
S
O
L*
O
O
t-Bu
O
S
O
Ph2P
Ph2P
t-Bu
Ph2P
Ph2P
12
13
14
15
Entry
Liganda
12
Temp (°C)
Yield (%)b
ee (%)c
61
1
2
3
4
5
6
7
r.t.
r.t.
r.t.
r.t.
r.t.
0
78
73
82
76
93
72
62
13
65
14
14
15
82
15
92d
94
15
15
–20
96
a All reactions were conducted in CH2Cl2 using 4.3 mol% of the ligand and 1.5 mol% of [PdCl(C3H5)]2.
b Isolated yield.
c Determined by HPLC using chiral column Chiralpack-AD.
d Reagents: 8.6 mol% of the ligand and 3 mol% of [PdCl(C3H5)]2.
Table 2 Pd-Catalyzed Allylic Amination of 1,3-Diphenylpropenyl
Acetate 16 Using Ligands 13–15
Nevertheless, this strategy cannot be applied in our case
taking into account the nature of our ligands with two dif-
ferent heterodonating atoms, one of them at the anomeric
position. In order to solve this problem, we have noticed
that a-D-arabinose, a cheap commercially available D-
pentopyranose, which exists mainly in the 1C4 conforma-
tion, is a quasi mirror image of b-D-galactose (Figure 1).16
1.5 mol%
[Pd(allyl)Cl]2
4.3 mol% L*
Ph
HN
OAc
Ph
PhCH2NH2
+
Ph
Ph
Ph
BSA, KOAc,
CH2Cl2, temp
18
16
Entry
Liganda
13
Temp (°C) Yield (%)b ee (%)c
t-Bu
t-Bu
O
O
S
i–iii
O
O
S
iv
O
OAc
OAc
1
2
3
4
5
r.t.
r.t.
r.t.
0
89
71
76
93
29
46
32
86
90
96
O
PPh2
OH
OAc
O
O
AcO
C
14
C
19
20
21
Me2
Me2
15
Scheme 3 Reagents and conditions: (i) t-BuSH, BF3·OEt2, CH2Cl2,
0 °C (80–95%); (ii) MeONa, MeOH; (iii) DMP, CSA, acetone (65%
for the 3 steps); (iv) PPh2Cl, Et3N–THF, DMAP (70–80%).
15
15
–20
a All reactions were conducted in CH2Cl2 using 4.3 mol% of the
ligand and 1.5 mol% of [PdCl(C3H5)]2.
We then wondered if phosphinite thioglycosides derived
from arabinose could act as enantiomers to those derived
from galactose. To do so, the synthesis of phosphinite
thioarabinopyranoside related to 15 was planned. Starting
from arabinose tetraacetate 19, the desired 2-phosphinite
tert-butyl thioarabinopyranoside 21 was obtained in only
b Isolated yield.
c Determined by HPLC using chiral column Chiralpack-AD.
four high yielding steps and on a multigram scale, of palladium, 4.3 mol% of 21) and dimethyl malonate as
(Scheme 3). The ligand 21 was then assayed in the Pd(0)- soft nucleophile afforded 17R, which is the opposite
catalyzed allylic substitution of 1,3-diphenyl propenyl- isomer to the one obtained with ligand 15, in 72% yield
acetate 16. Using the same conditions as before (3 mol% and an interesting 84% ee (Scheme 4).
Synlett 2005, No. 19, 2963–2967 © Thieme Stuttgart · New York

2966
N. Khiar et al.
LETTER
1.5 mol%
[Pd(allyl)Cl]2
4.3 mol% 21
1.5 mol%
[Pd(allyl)Cl]2
4.3 mol% 21
MeO2C
Ph
CO2Me
Ph
OAc
Ph
Ph
Ph
NH
Ph
Ph
CH(CO2Me)2
BSA, KOAc,
CH2Cl2, –20 °C
PhCH2NH2
BSA, KOAc,
CH2Cl2, –20 °C
18S
16
17R
84% ee
88% ee
t-Bu
O
O
S
O
PPh2
O
C
21
Me2
Scheme 4
When the nucleophile used was benzylamine, again the In conclusion, the preliminary results reported in this
opposite isomer 18S was obtained in an excellent 88% ee work illustrate the high potential of phosphinite thiogly-
albeit in low yield (29%), and in 78% ee and 67% yield at cosides I in asymmetric catalysis and suggest their wider
0 °C (Scheme 4). Thus even though derived from natural utility in other catalytic processes. The tuning of other pa-
D-sugars, ligands 15 and 21 behave as enantiomers in rameters implemented in the synthetic design, such as the
Pd(0)-catalyzed asymmetric substitutions. The lower electronic character of the phosphinite moiety, and the
enantioselectivity observed with ligand 21 compared to conformation of the pyranose ring may certainly lead to
15 can be rationalized by a greater flexibility of the ara- more efficient catalysts. On the other hand the modular
binopyranose vs. the galactopyranose rings.
synthetic design developed will allow rapid attachment of
these ligands to a solid support, while the hydrophilic na-
ture of the sugar residue may allow the synthesis of water
soluble catalysts, allowing their facile recovery and recy-
cle. Work along these lines is currently under active inves-
tigation in our group.
The stereocontrol of the stereogenic sulfur metal center
and its relation to the enantioselectivity of the substitution
process was next probed. Thus, representative phosphin-
ite thioglycosides Pd(II)-complexes 22, 23 and 24 were
synthesized and studied (Scheme 5).
OAc
Acknowledgment
O
OAc
O
Me2C
O
Cl2Pd(CH3CN)2
Me2C
O
We thank the Dirección General de Investigación Científica y
Técnica (grant No. PB BQU2003-00937 and CTQ2004-01057) and
La Fundación Ramón Areces for financial support.
O
O
O
CH2Cl2
80%
S
t-Bu
Pd Cl
Cl
t-Bu
O
Ph
P
S
Ph2P
14
Ph
[2 isomers (60:40)]
22
References
O
OAc
OAc
O
O
Me2C
Ph
S
Me2C
O
(1) (a) Chiral Auxiliaries and Ligands in Asymmetric Synthesis;
Seyden-Penne, J., Ed.; Wiley Interscience: New York,
1995. (b) Comprehensive Asymmetric Catalysis, Vol. 1-3;
Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer:
Berlin, 1999.
O
t-Bu
Cl
O
O
Cl2Pd(CH3CN)2
S
Pd
Cl
t-Bu
PPh2
15
P
O
Ph
CH2Cl2
84%
23 (one isomer)
(2) (a) Dieguez, M.; Pàmies, O.; Claver, C. Chem. Rev. 2004,
104, 3189. (b) Steiborn, D.; Junicke, H. Chem. Rev. 2000,
100, 4283. (c) Rajanbabu, T. V.; Casalnuovo, A. L.; Ayers,
T. A. In Advances in Catalytic Processes, Vol. 2; Doyle, M.
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(3) (a) Casalnuovo, A. L.; RajanBabu, T. V.; Ayers, T. A.;
Warren, T. H. J. Am. Chem. Soc. 1994, 116, 9869.
(b) Selke, R.; Swarze, M.; Baudisch, H.; Grassert, I.;
Michalik, M.; Oehme, G.; Stoll, N.; Costisella, B. J. Mol.
Catal. 1993, 84, 223. (c) Dieguez, M.; Ruiz, A.; Claver, C.
J. Org. Chem. 2002, 67, 3796. (d) Reetz, M. T.; Goosen, L.
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(4) (a) Rajanbabu, T. V.; Ayers, T. A.; Casalnuovo, A. L. J. Am.
Chem. Soc. 1994, 116, 4101. (b) Ayers, T. A.; RajanBabu,
T. V. U. S. Patent 5510507, 1996.
(5) Evans, D. A.; Campos, K. R.; Tedrow, J. S.; Michael, F. E.;
Gagné, M. R. J. Am. Chem. Soc. 2000, 122, 7905.
(6) This work has been presented in part in the ISOCS-XXI,
Madrid, Spain, 4-9 July 2004.
t-Bu
t-Bu
Cl
O
O
S
O
Pd
Ph
O
O
S
O
Cl2Pd(CH3CN)2
PPh2
P
Ph
Cl
O
O
CH2Cl2
88%
C
C
Me2
24 (one isomer)
Me2
21
Scheme 5
Significantly, while two diastereoisomers were obtained
in the case of 22 in a 2:3 ratio, only one isomer was ob-
tained in the case of 23 and 24. 1H and 31P dynamic NMR
studies of 23 from –70 °C to 40 °C confirmed that a single
isomer exists in solution, revealing an efficient control of
the sulfur stereochemistry by the sugar residue and that
the enantioselectivity achieved was intimately related to
the stereocontrol of the sulfur atom.
Synlett 2005, No. 19, 2963–2967 © Thieme Stuttgart · New York

LETTER
Mixed P/S Ligands Derived from Natural D-Sugars
2967
(7) (a) Molander, G.; Burke, J.; Carrol, P. J. J. Org. Chem. 2004,
69, 8062. (b) Mancheño, O. G.; Gomez Arrayas, R.;
Carretero, J. C. J. Am. Chem. Soc. 2004, 126, 456. (c) Yan,
Y. Y.; RajanBabu, T. V. Org. Lett. 2000, 2, 199.
(d) Albinati, A.; Pregosin, P. S.; Wick, K. Organometallics
1996, 15, 2419.
(8) Khiar, N.; Araújo, C. S.; Alvarez, E.; Fernández, I.
Tetrahedron Lett. 2003, 44, 3401.
(9) Khiar, N.; Araújo, C. S.; Suárez, B.; Álvarez, E.; Fernández,
I. Chem. Commun. 2004, 44, 714.
J
PC = 2.7 Hz), 128.2 (d, JPC = 7.0 Hz), 128.1 (d, JPC = 7.0
Hz), 109.7, 81.3 (d, JPC = 5.6 Hz), 77.8 (d, JPC = 18.8 Hz),
75.6 (d, JPC = 5.0 Hz), 73.8, 66.6, 63.5, 43.8, 31.3, 27.9,
26.3, 20.8 ppm. 31P NMR (121.4 MHz, CDCl3): d = 117.5
ppm.
Compound 15: 1H NMR (500 MHz, CDCl3): d = 7.56–7.47
(m, 4 H), 7.34–7.29 (m, 6 H), 4.51 (d, 1 H, J = 9.5 Hz), 4.33–
4.26 (m, 3 H), 4.15 (dd, 1 H, J = 1.8, 5.6 Hz), 3.96–3.88 (m,
2 H), 2.03 (s, 3 H), 1.42 (s, 3 H), 1.29 (s, 3 H), 1.22 (s, 9 H)
ppm.13C NMR (125 MHz, CDCl3): d = 170.8, 142.9 (d,
JPC = 18.4 Hz), 142.1 (d, JPC = 15.2 Hz), 131.3 (d, JPC = 22.1
Hz), 130.5 (d, JPC = 21.3 Hz), 129.0 (d, JPC = 32.5 Hz), 128.0
(d, JPC = 6.4 Hz), 127.9 (d, JPC = 7.2 Hz), 110.5, 83.1 (d,
(10) (a) Ferrier, R. J.; Furneaux, R. H. Methods Carbohydr.
Chem. 1980, 8, 251. (b) Khiar, N.; Martin-Lomas, M. J.
Org. Chem. 1995, 60, 7017.
(11) Ishihara, K.; Kurihara, H.; Yamamoto, H. J. Org. Chem.
1993, 58, 3791.
(12) Yonehara, K.; Hashizume, T.; Mori, K.; Ohe, K.; Uemura, S.
J. Org. Chem. 1999, 64, 5593.
JPC = 3.3 Hz), 80.6 (d, JPC = 18.7 Hz), 79.3 (d, JPC = 2.7 Hz),
73.6 (2 C), 63.9, 44.1, 31.3, 27.7, 26.4, 20.8 ppm. 31P NMR
(121.4 MHz, CDCl3): d = 119.8 ppm.
Compound 21: 1H NMR (500 MHz, CDCl3): d = 7.54–7.46
(m, 4 H), 7.33–7.29 (m, 6 H), 4.76 (d, 1 H, J = 6.9 Hz), 4.28–
4.26 (m, 1 H), 4.22 (t, 1 H, J = 5.7 Hz), 4.10–4.01 (m, 1 H),
3.70 (dd, 1 H, J = 4.4, 12.7 Hz), 1.47 (s, 3 H), 1.30 (s, 3 H),
1.19 (s, 9 H) ppm.13C NMR (125 MHz, CDCl3): d = 131.2
(13) Compound 12: 1H NMR (500 MHz, CDCl3): d = 7.60–7.50
(m, 4 H), 7.38 –7.31 (m, 6 H), 7.21 (d, 2 H, J = 7.9 Hz), 7.02
(d, 2 H, J = 8.0 Hz), 4.58 (d, 1 H, J = 10.0 Hz), 4.35 (dd, 1
H, J = 4.5, 11.7 Hz), 4.29 (dd, 1 H, J = 7.7, 11.7 Hz), 4.23 (t,
1 H, J = 5.9 Hz), 4.13 (d, 1 H, J = 5.5 Hz), 4.02–3.93 (m, 2
H), 2.30 (s, 3 H), 1.43 (s, 3 H), 1.29 (s, 3 H), 1.19 (s, 9 H)
ppm. 13C NMR (125 MHz, CDCl3): d = 178.3, 137.7, 132.4,
131.1 (d, JPC = 11.8 Hz), 130.7 (d, JPC = 11.8 Hz), 129.3 (d,
(d, JPC = 22.1 Hz), 130.5 (d, JPC = 21.4 Hz), 129.1 (d, JPC
31.7 Hz), 128.1 (d, JPC = 5.9 Hz), 128.0 (d, JPC = 6.7 Hz),
=
110.1, 84.5, 82.6 (d, JPC = 4.2 Hz), 80.3 (d, JPC = 19.2 Hz),
72.2, 63.2, 44.0, 31.3, 27.8, 26.3 ppm. 31P NMR (121.4
MHz, CDCl3): d = 118.6 ppm.
J
J
PC = 26.0 Hz), 128.1 (d, JPC = 6.8 Hz), 110.5, 88.4 (d,
PC = 4.1 Hz), 80.4 (d, JPC = 28.4 Hz), 79.1, 74.0, 73.7, 63.7,
(14) Typical Procedure.
38.7, 27.8, 27.1, 26.4, 21.2 ppm. 31P NMR (121.4 MHz,
CDCl3): d = 119.5 ppm.
To a solution of the ligand (4.3 mol%) in dry deoxygenated
CH2Cl2 (0.5 mL), [PdCl(C3H5)]2 (1.5 mol%) was added
under argon. The reaction mixture was stirred for 1 h at r.t.,
then a catalytic amount of KOAc (0.5 mg) was added,
followed by BSA (3 mol equiv) and a solution of 1,3-
diphenyl-2-propenyl acetate (16, 1 mol equiv) in dry
deoxygenated CH2Cl2 (0.7 mL). The temperature was then
adjusted to the desired one (see Table 1) and dimethyl
malonate (3 equiv) was added. Once the reaction finished as
judged by TLC, the solvent was evaporated and the residue
purified by column chromatography, affording the desired
product 17 as a viscous oil, which solidify on standing. The
ee was determined by chiral HPLC using a Chiralpack AD
column (1 mL/min, i-PrOH–hexane, 5:95, 30 °C). Retention
times: (R)-17: tR = 14.2 min, (S)-17: tR = 19.5 min.
(15) (a) Selke, R. React. Kinet. Catal. Lett. 1980, 14, 463.
(b) Selke, R. J. Organomet. Chem. 1989, 370, 249.
(16) Kunz, H.; Pfrengle, W.; Sager, W. Tetrahedron Lett. 1989,
30, 4109.
Compound 13: 1H NMR (500 MHz, CDCl3): d = 7.58–7.49
(m, 4 H), 7.36–7.32 (m, 6 H), 7.23 (d, 2 H, J = 7.9 Hz), 7.03
(d, 2 H, J = 7.9 Hz), 4.56 (d, 1 H, J = 9.4 Hz), 4.33 (d, 2 H,
J = 6.1 Hz), 4.23 (t, 1 H, J = 5.9 Hz), 4.13 (dd, 1 H,
J = 5.5, 1.5 Hz), 4.03–3.91 (m, 2 H), 2.31 (s, 3 H), 2.07 (s, 3
H), 1.41 (s, 3 H), 1.28 (s, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): d = 170.8, 142.6 (d, JPC = 18.5 Hz), 141.9 (d,
JPC = 15.4 Hz), 137.7, 132.6, 130.9 (d, JPC = 21.8 Hz), 130.8
(d, JPC = 21.8 Hz), 130.2, 129.3 (d, JPC = 30.2 Hz), 128.1 (d,
JPC = 6.9 Hz), 110.6, 87.9 (d, JPC = 4.2 Hz), 80.0 (d,
JPC = 18.4 Hz), 79.1, 73.9, 73.6, 63.8, 27.7, 26.4, 21.1, 20.8
ppm. 31P NMR (121.4 MHz, CDCl3): d = 119.4 ppm.
Compound 14: 1H NMR (500 MHz, CDCl3): d = 7.57–7.50
(m, 4 H), 7.35–7.32 (m, 6 H), 5.56 (d, 1 H, J = 5.1 Hz), 4.70–
4.67 (m, 1 H), 4.34–4.11 (m, 5 H), 2.02 (s, 3 H), 1.41 (s, 3
H), 1.30 (s, 12 H) ppm. 13C NMR (125 MHz, CDCl3): d =
170.7, 141.8 (d, JPC = 19.4 Hz), 141.7 (d, JPC = 16.0 Hz),
130.9 (d, JPC = 21.8 Hz), 130.7 (d, JPC = 21.7 Hz), 129.3 (d,
Synlett 2005, No. 19, 2963–2967 © Thieme Stuttgart · New York