Imidazolium-tagged ferrocenyl diphosphanes in allylic substitution with heteroatom nucleophiles

Article abstract of DOI:10.1016/j.tetasy.2009.07.039

Imidazolium-tagged ferrocenyl diphosphanes are useful ligands in palladium-catalyzed allylic substitutions with heteroatom nucleophiles. Substitution with phthalimide proceeds with high enantioselectivity (up to 92% ee) in various ionic liquids. Reaction with p-cresol as nucleophile affords allylation product in up to 62% ee, while using tolylsulfinate as a nucleophile gives a product with very little or no enantioselectivity. Under these reaction conditions, catalyst recyclability is challenging, and decrease in activity as well as enantioselectivity was observed.

Full text of DOI:10.1016/j.tetasy.2009.07.039

Tetrahedron: Asymmetry 20 (2009) 1892–1896
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Imidazolium-tagged ferrocenyl diphosphanes in allylic substitution
with heteroatom nucleophiles
*
ˇ
Radovan Šebesta , Filip Bilcík
Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina, 84215 Bratislava, Slovakia
a r t i c l e i n f o
a b s t r a c t
Article history:
Imidazolium-tagged ferrocenyl diphosphanes are useful ligands in palladium-catalyzed allylic substitu-
tions with heteroatom nucleophiles. Substitution with phthalimide proceeds with high enantioselectivity
(up to 92% ee) in various ionic liquids. Reaction with p-cresol as nucleophile affords allylation product in
up to 62% ee, while using tolylsulfinate as a nucleophile gives a product with very little or no enantiose-
lectivity. Under these reaction conditions, catalyst recyclability is challenging, and decrease in activity as
well as enantioselectivity was observed.
Received 22 June 2009
Accepted 28 July 2009
Available online 31 August 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
tion.7 Polyethylene glycol (PEG)-supported catalysts again appear
as interesting soluble alternatives to cross-linked polymer sup-
Enantioselective catalytic carbon–carbon and carbon–hetero-
atom bond formations are important tools for the construction of
complex molecules. From a large array of available methods, nucle-
ophilic attack on a transition metal-stabilized allylic cation has been
a greatly studied reaction, because it leads to many useful structural
motifs.1 From among many metals capable of catalyzing allylic
substitution, palladium occupies a prominent position. Numerous
asymmetric ligands have been successfully utilized in this reac-
tion,2 including a range of chiral ferrocene derivatives.3
One of the important issues in modern asymmetric catalysis is a
question of catalyst recycling or practical product separation. Het-
erogeneous catalysis offers solutions to some of the issues.4 On the
other hand, heterogeneous systems often suffer from decreased
activities compared to homogeneous catalysts. Therefore, a con-
cept of homogeneous-supported catalysis was suggested as an
interesting alternative to address this problem, and was aimed at
combining positive features of both heterogeneous and homoge-
neous catalyses. These catalytic systems, usually in connection
with an appropriate reaction medium such as fluorous solvents,
soluble polymers or ionic liquids, offer interesting possibilities
for the development of efficient recyclable catalysts.5 In this con-
text, diverse ionically tagged catalysts have been successfully used
for a variety of asymmetric catalytic reactions in ionic liquids.6
However, little attention has been devoted to asymmetric allylic
substitution in this direction. Several polymer-supported palla-
dium catalysts have been shown to be active in allylic substitu-
ports. Bandini and Ding prepared PEG-supported palladium cata-
lysts for allylic substitution.8 Gavrilov and Reetz described ionic
phosphites which were used in asymmetric hydrogenation as well
as allylic substitution.9 Using an ionic-tag strategy, we prepared
soluble imidazolium ferrocenyl phosphanes, which also proved to
be useful ligands in Pd-catalyzed allylic alkylation of 1,3-diphenyl-
propenyl acetate with dimethyl malonate.10 At the same time, the
imidazolium cation was also attached to Josiphos diphosphanes but
the resulting ligands were used for Rh-catalyzed hydrogenation.11
Our BPPFA 1-derived imidazolium diphosphane 3 afforded an ally-
lation product with high enantioselectivity (92% ee). However, we
also noted problems with recyclability of these catalysts.10 Encour-
aged by the initial results we decided to explore the allylic substi-
tution reaction with heteroatom nucleophiles. Herein we report
that imidazolium-tagged ferrocenyl diphosphanes are useful li-
gands in Pd-catalyzed allylic substitution with heteroatom nucleo-
philes. We also tried to address the issue of catalyst recycling by
modification of its structure.
2. Results and discussion
Imidazolium-tagged ferrocenyl diphosphanes 3 and 4 (Scheme
1) were prepared from the BPPFA ligand12 by a procedure devel-
oped in our laboratory.10 Ligand 4 was suggested as a possible
improvement of ligand 3. The acidic proton at the 2-position was
replaced by a methyl group to prevent carbene formation under
basic conditions.13
As a prototype reaction, we chose allylic substitution with
potassium phthalimide as a nucleophile (Scheme 2). A palladium
* Corresponding author. Tel.: +421 2 60296603; fax: +421 2 60296337.
E-mail address: sebesta@fns.uniba.sk (R. Šebesta).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.07.039

ˇ
R. Šebesta, F. Bilcík / Tetrahedron: Asymmetry 20 (2009) 1892–1896
1893
Table 2
O
Allylic substitution with potassium phthalimide
Me
NMe2
Br
Time (h) Yieldc (%) eed (%)
N
Entry Ligand Solvent
4
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
3
3
4
3
3
3
3
3
3
3
3
4
4
4
3
4
3
[emim]EtOSO3/CH2Cl2
[emim]EtOSO3/CH2Cl2
[emim]EtOSO3/CH2Cl2
[emim]EtOSO3/THF
[emim]EtOSO3/CH3CN
[bmim]PF6/CH2Cl2
[bdmim]PF6/CH2Cl2
rec. [bdmim]PF6/CH2Cl2
[bdmim]PF6/THF
[bdmim]NTf2/CH2Cl2
rec. [bdmim]NTf2/CH2Cl2
[bdmim]NTf2/CH2Cl2
rec. [bdmim]NTf2/CH2Cl2
[bdmim]NTf2/CH2Cl2 (1:4)
[Bu3EtP](EtO)2PO2/CH2Cl2
[emim]EtOSO3/EtOAc
[1-Bu-3-Me-pyr]PF6
4.5
48
18
24
20
72
21
168
120
72
67
47
84
39
70
49
70
<5
24
15
15
47
9
92
91
89
88
92
90
92
n.d.
90
92
92
91
90
91
78
88
91
a
PPh2
PPh2
b
Fe
Fe
PPh2
PPh2
2
1
O
R
R
Me
72
N
N
168
168
72
20
168
48
Me
4
N
N
N
Me
1.
50
67
<5
20
A
MWI
PPh2
PPh2
Fe
2. LiNTf2 or KPF6
H2O
3, R = H, A = PF6
4, R = Me, A = NTf2
a
b
c
Reaction was performed at 0 °C.
5 mol % of catalyst was used.
Isolated yield of pure compound 6.
Scheme 1.
d
Determined by HPLC on Chiralcel OD-H, hexane/i-PrOH, 90:10; 0.75 mL/min.
O
a)
EtOSO3, other imidazolium ionic liquids are abbreviated similarly;
[bdmim] stands for 1-butyl-2,3-dimethylimidazolium) and CH2Cl2
or CH3CN (Table 2, entries 1–5). It is also noteworthy that ligand 3
in ionic liquids performs better than the parent BPPFA ligand 1 in
terms of both chemical yield and enantioselectivity (Table 1, entry
8 cf. Table 2 entry 6). After consumption of all the starting material,
followed by TLC, the reaction mixture was extracted with toluene to
obtain crude product 6. In ionic liquids immiscible with water, the
unreacted potassium phthalimide together with potassium acetate
was removed by extraction with water. The catalytic system, com-
prised the palladium complex of ligand 3 dissolved in ionic liquid
and was, before reuse, dried in vacuum and degassed. Unfortunately,
the recycled catalytic system with ligand 3 was considerably less ac-
tive (Table 2, entries8 and 11). The situationdid not improvein other
ionic liquids, at lower temperatures or excesses of organic solvent.
We hypothesized that the presence of a large amount of basic potas-
sium phthalimide can be a problem, leading to ligand or ionic liquid
degradation. For this reason we prepared ligand 4 with a 1,2-di-
methylimidazoliummoiety, whichshouldbe more resistant tobasic
conditions. In our reaction, ligand 4 behavessimilarly to ligand 3, but
there was no improvement in the recycled experiments (Table 2, en-
try 13). Even a combination of 2-methyl-substituted imidazolium
ionic liquids, such as [bdmim]PF6 and [bdmim]NTf2, and ligand 4
did not improve the situation (Table 2, entries 12–14).
NK
O
2 mol % Pd/L*
OAc
O
N
O
IL, solvent, r.t.
Ph
Ph
O
b)
Ph
Ph
5
NH
6
O
BSA, KOAc
2 mol % Pd/L*
IL, solvent, r.t.
Scheme 2.
complex of BPPFA afforded compound 6 in small to medium yields
and with enantioselectivities from 37 to 90% ee (Table 1, entry 3).
The strong influence of the reaction medium on the reactivity and
enantioselectivity should be noted (Table 1).
Table 1
Allylic substitution with potassium phthalimide using BPPFA ligand
Entry
Solvent
Time (h)
Yielda (%)
eeb (%)
In order to minimize the amount of the base present in the reac-
tion mixture, we tried to use phthalimide with bis(trimethyl-
silyl)acetamide (BSA) and a catalytic amount of KOAc, a well
known strategy for the generation of stabilized anions from active
methylene compounds (Scheme 2, procedure b). Interestingly, the
reaction proceeded well in some ionic liquids, such as [emim]EtOS-
O3. Product 6 was isolated in up to 68% yield and 92% ee (Table 3,
entries 1 and 5). However recycling was again difficult because this
ionic liquid is miscible with water (Table 3, entry 3).
As a representative oxygen nucleophile, we chose 4-methyl-
phenolate. Lithium alkoxide was generated from the corresponding
alcohol and BuLi in THF. The resulting THF solution was added into
the ionic liquid containing the Pd-complex of ligand 3 (Scheme 3).
In [emim]EtOSO3, compound 7 was formed in medium yields but
with only 62% ee (Table 4, entry 2). Using [bdmim]NTf2 as the reac-
tion medium, the enantioselectivity decreased to 54% ee but partial
recycling of catalytic system was possible (Table 4, entries 5 and 6).
However catalytic activity as well as enantioselectivity decreased.
We attempted to use BSA and KOAc for the generation of a better
1
2
3
4
5
6
7
8
CH2Cl2
THF
EtOAc
Toluene
ClCH2CH2Cl
[emim]EtOSO3/H2O
[emim]EtOSO3/EtOH
[bdmim]PF6/CH2Cl2
24
160
120
120
120
168
168
48
19
5
50
5
22
34
10
55
70
37
90
68
80
60
70
70
a
Isolated yield of pure compound 6.
Determined by HPLC on Chiralcel OD-H, hexane/i-PrOH, 90:10; 0.75 mL/min.
b
When ionic liquids and ionic ligand 3 were used in this reaction,
product 6 was isolated in up to 84% yield with high enantioselectiv-
ities (up to 92% ee). The small solubility of potassium phthalimide in
ionic liquid led to the formation of very viscous reaction mixtures,
resulting in inadequate stirring. In order to avoid this problem we
added a polar organic solvent, miscible with the ionic liquid, into
the reaction mixture (Table 2). The best results were obtained with
ionic liquid 1-ethyl-3-methylimidazolium ethylsulfate ([emim]

ˇ
R. Šebesta, F. Bilcík / Tetrahedron: Asymmetry 20 (2009) 1892–1896
1894
Table 3
Me
SO2Na
Ligand 3 in Pd-catalyzed allylic substitution with phthalimide, BSA, and KOAc
Entry
Solvent
Time (h)
Yielda (%)
eeb (%)
O
S
OAc
Ph
Me
2 mol % Pd/L*
O
1
2
3
4
5
[emim]EtOSO3/CH2Cl2
[bmim]PF6/CH2Cl2
rec. [bmim]PF6/CH2Cl2
[bmim]PF6/CH2Cl2 (1:4)
[emim]EtOSO3/CH2Cl2 (1:4)
32
72
168
120
48
64
6
5
7
68
90
92
92
92
91
Ph
Ph
Ph
IL, solvent, r.t.
5
9
Scheme 4.
a
Isolated yield of pure compound 6.
Determined by HPLC on Chiralcel OD-H, hexane/i-PrOH, 90:10; 0.75 mL/min.
b
Table 5
Allylic substitution with sodium p-tolylsulfinate.
OM
OH
RM
Entry Solvent
Mol % of 3 Time (h) Yielda (%) eeb (%)
THF
1
2
3
4
5
6
[bmim]PF6/CH2Cl2
[bmim]PF6/CH2Cl2
2
3
3
3
2
3
24
20
168
16
24
96
53
81
15
86
33
75
15
10
26
0
29
7
Me
Me
RM = BuLi, MeMgBr, Et2Zn
rec. [bmim]PF6/CH2Cl2
[emim]EtOSO3/CH2Cl2
[bdmim]NTf2/THF
Me
c
[bmim]PF6/CH2Cl2
a
b
c
Isolated yield of pure compound 9.
Determined by HPLC on Chiralcel OD-H, hexane/i-PrOH, 90:10; 0.75 mL/min.
Pd2dba3.CHCl3 was used as palladium source.
OM
O
7
OAc
Me
Ph
Me
Ph
+
Ph
Ph
2 mol % Pd/L*
IL, solvent, r.t.
we increased the ligand to palladium ratio from 1:1 to 1.5:1, how-
ever, the enantioselectivity of the reaction did not improve.
The NMR experiments confirmed that imidazolium diphos-
phane ligands form palladium complexes in ionic liquid. Figure 1
shows 31P NMR of the free ligand 4 (a) and its Pd-complex in
[bdmim]NTf2 (b). The spectrum displays a typical shift from nega-
tive to positive chemical shift values, thus confirming complexa-
tion of both phosphorus atoms to palladium. NMR spectrum (c)
of ionic liquid phase after reaction and extraction of product shows
significant ligand decomposition.
Recycling experiments as well as NMR studies suggest that imi-
dazolium-tagged ferrocenyl diphosphanes are sensitive under the
reaction conditions of allylic substitution. Substitution of the
hydrogen at the 2-position with a methyl group did not lead to sig-
nificant improvement. This could be explained by the possible for-
mation of C4-carbene under basic conditions.14
5
OH
8
Ph
Ph
Scheme 3.
nucleophile from p-cresol but no product 7 was isolated (Table 4,
entry 7). When phenolate was generated with MeMgBr instead of
BuLi, a typical product of allylic substitution with phenolate, ether
7, was only isolated as a minor component. The major product,
compound 8, resulted from Friedel–Craft alkylation of phenolate
in position 2 by allyl cation (Table 4, entries 8 and 9). Compound
8, however, was usually obtained with low enantioselectivity or
as a racemate. Using Et2Zn as a base product 7 was isolated in
35% yield but with no enantioselectivity. The results with p-cresol
are summarized in Table 4.
3. Conclusions
With sodium p-tolylsulfinate as a nucleophile, product 9 can be
obtained in good yield but with little (up to 29% ee) to no enanti-
oselectivity (Scheme 4) (Table 5). Competitive complexation of the
nucleophile to palladium could be a possible explanation for the
small enantioselectivity. In an attempt to minimize this effect,
We have demonstrated that allylic substitution with hetero-
atom nucleophiles in ionic liquids can be conveniently performed.
Allylation products with nitrogen and oxygen nucleophiles were
formed with high enantioselectivities (up to 92% ee and 62% ee,
Table 4
Allylic substitution with 4-methylphenolate using ligand 3.
Entry
Base
Solvent
Time (h)
7b,c (yield/ee)
8d,e (yield/ee)
1a
2
3
4
5
6
7
8
9
BuLi
BuLi
BuLi
BuLi
BuLi
BuLi
BSA/KOAc
MeMgBr
MeMgBr
Et2Zn
[emim]EtOSO3/THF
[emim]EtOSO3/THF
[bmim]PF6/THF
rec. [bmim]PF6/THF
[bmim]NTf2/THF
rec. [bmim]NTf2/THF
[emim]EtOSO3/THF
[bmim]PF6/THF
24
43
18
42
43
72
168
18
18
18
79/50
41/62
46/46
16/14
43/54
25/24
0
12/0
0
35/0
-
-
37/34
22/3
-
-
0
74/2
65/0
39/0
rec. [bmim]PF6/THF
[bmim]NTf2/THF
10
a
b
c
BPPFA was used as a ligand.
Isolated yield of pure compounds 7.
Enantiomeric excess determined by HPLC on Chiralcel OD-H column, hexane/i-PrOH, 98:2; 0.5 mL/min).
Isolated yield of pure compounds 8.
Enantiomeric excess determined by HPLC on Chiralcel OD-H column, hexane/i-PrOH, 80:20; 0.75 mL/min)
d
e

ˇ
R. Šebesta, F. Bilcík / Tetrahedron: Asymmetry 20 (2009) 1892–1896
1895
79%) as a yellow solid. Mp 71–74 °C. 1H NMR (300 MHz, CDCl3):
(peaks of minor amide rotamer shown in italics) d 1.04–1.20 (m,
2H, CH2), 1.31 (d, J = 6.9 Hz, 3H CH3), 1.32–1.47 (m, 2H, CH2),
1.48–1.64 (m, 2H, CH2), 1.65–1.84 (m, 2H, CH2), 2.14, 2.19 (s, 3H,
N–CH3), 2.58, 2.63 (s, 3H, Im–CH3), 3.59 (m, 1H), 3.62 (m, 1H),
3.79, 3.82 (s, 3H, Im–CH3), 4.03 (m, 2H, CH2); 4.14 (m, 3H, Fc),
4.45 (m, 1H, Fc), 4.50 (m, 1H, Fc), 5.23, 6.01 (dd, J = 13.4, 7.0 Hz,
1H, FcCH), 7.00–7.12 (m, 2H, Ph), 7.13–7.35 (m, 18H, Ph + Im),
7.36–7.48 (m, 2H, Ph). 13C NMR (75 MHz, CDCl3): (peaks of minor
amide rotamer shown in italics) d 170.7, 170.6 (CO), 143.8, 143.7
(qC), 139.0 (d, J = 8.4 Hz), 138.3 (d, J = 9.0 Hz), 136.6 (d, J = 8.1 Hz),
135.0, 134.9 (d, J = 21.4 Hz), 133.63, 133.61 (d, J = 20.0 Hz), 133.1,
133.0 (d, J = 19.1 Hz), 132.4 (d, J = 19.6 Hz), 131.9, 128.9 (d, J =
32.0 Hz), 128.2 (d, J = 42.2 Hz), 128,16, 128.15 (d, J = 15.8 Hz),
128.09 (d, J = 15.8 Hz), 122,4, 122.0, 121.0, 120.9 (Ph, Im), 94.1, 93.7
(d, J = 25.5 Hz, CFc), 77.2 (CHFc), 76.8 (d, J = 9.2 Hz), 75.5, 75.4 (d,
J = 19.7 Hz), 74.5 (dd, J = 4.5, 1.8 Hz, CHFc); 73.4, 73.2 (d, J = 4.8 Hz,
CFc), 73.1, 72.4 (d, J = 4.6 Hz, CHFc), 71.2 (d, J = 2.4 Hz, CHFc), 48.5,
48.4 (CH2), 35.4, 35.37 (CH3), 32.1 (CH2), 29.7, 29.3 (CH2), 28.6
(CH3), 25.8, 25.7 (CH2), 23.5, 23.3 (CH2), 15.9, 15.6 (CH3), 9.7, 9.66
(CH3). 31P NMR (121 MHz, CDCl3): d À17.9, À18.2; À26.9, À27.0.
Figure 1. NMR spectra of free ligand 4 (a), its Pd-complex (b), and ionic liquid after
reaction and work-up (c).
respectively). Magnesium alcoholate undergoes interesting Fri-
edel–Crafts alkylation with allyl cation. The efficient recycling of
the catalytic system is a challenging task, presumably due to the
decomposition of the catalyst in the inherently basic conditions
present. However further work in this area is currently underway
in our laboratory.
[a
]
D = À212 (c 0.51, CHCl3). HRMS calcd for C48H52FeN3OP2:
804.2930; found: 804.2842.
4.3. (R)-(E)-2-(1,3-Diphenylprop-1-enyl)isoindolin-1,3-dione 6
4.3.1. Procedure a
4. Experimental
4.1. General
Ligand (0.02 mmol) and [Pd(allyl)Cl]2 (3.7 mg, 0.01 mmol) were
dissolved in degassed ionic liquid (2 mL), and the resulting solution
was stirred for 30 min at rt. Then acetate 5 (252 mg, 1.0 mmol) in
CH2Cl2 (2 mL) was added to this solution and the mixture was
stirred for additional 15 min at rt. Solid potassium phthalimide
(371 mg, 2 mmol) was added and the reaction mixture was stirred.
The reaction was monitored by TLC and stopped when no starting
material was detected or after the selected time. The mixture was
then washed with water (3 Â 10 mL). The reaction product was ex-
tracted with small portions of toluene and the combined organic
extracts were concentrated. The crude product was purified by col-
umn chromatography (SiO2; hexane/EtOAc, 8:1).
All reactions were carried out under an inert atmosphere of N2.
The solvents were purified by standard methods. Ionic liquids were
purchased from Merck. NMR spectra were recorded on Varian Mer-
cury plus instrument (300 MHz for 1H, 75 MHz for 13C, and
121.5 MHz for 31P). Chemical shifts (d) are given in ppm relative
to tetramethylsilane for 1H NMR; to residual solvent peak for 13C
NMR and to H3PO4 as external standard for 31P NMR. Specific
rotations were measured on Perkin–Elmer instrument and are
given in deg cmÀ3 gÀ1 dmÀ1. Flash chromatography was performed
on Merck Silica Gel 60. Thin-layer chromatography was performed
on Merck TLC-plates Silica Gel 60, F-254. Enantiomeric excesses
were determined by HPLC on Chiralpak AD-H (Daicel Chemical
Industries) column using hexane/iPrOH = 9:1 as a mobile phase
and detection with UV-detector at 254 nm. Mass spectrum was re-
corded on Waters Premium QTOF instrument. Compound 2 was
prepared according to the literature procedure.10 The absolute con-
figuration of compound 6 was assigned by comparison of the sign
of the specific rotation with the literature values. Configurations of
compound 7, 8, and 9 were assigned in analogy to compound 6.
4.3.2. Procedure b
The ligand (0.02 mmol) and [Pd(allyl)Cl]2 (3.7 mg, 0.01 mmol)
were dissolved in an ionic liquid (2 mL), and the resulting solution
was stirred for 30 min at room temperature. Acetate 5 (252 mg,
1.0 mmol) in an appropriate solvent (2 mL) was added to this solu-
tion and the resulting solution was stirred for additional 15 min at
room temperature. Then phthalimide (294 mg, 2 mmol), BSA
(0.49 mL, 407 mg, 2.0 mmol), and KOAc (5 mg, 0.05 mmol) were
added, and the resulting mixture was stirred. The reaction was
monitored by TLC and stopped when no starting material was de-
tected or after the selected time. The mixture was then washed
with water (3 Â 10 mL) and the product was extracted with tolu-
ene. The combined organic extracts were concentrated and the
crude product was purified by column chromatography (SiO2; hex-
ane/EtOAc 8:1). 1H NMR (300 MHz, CDCl3): d 6.13 (d, J = 8.6 Hz, 1H,
CH), 6.72 (d, J = 15.9 Hz, 1H, CH), 7.07 (dd, J = 15.9, 8.6 Hz, CH),
7.20–7.39 (m, 6H, Ph), 7.40–7.53 (m, 4H, Ph), 7.67–7.75 (m, 2H,
Ph-Phtal), 7.80–7.89 (m, 2H, Ph-Phtal). NMR data are in agreement
4.2. Preparation of ligand 4
Compound 2 (355 mg, 0.450 mmol) and 1,2-dimethylimidazole
(1.08 g, 11.2 mmol) were dissolved in CH2Cl2 and the solution was
concentrated. The residue was subjected to microwave irradiation
(6 Â 10 s, 300 W) and (2 Â 10 s, 500 W). After cooling, the resulting
mixture was washed with t-BuOMe (5 Â 5 mL). The oily residue
was dissolved in MeOH (10 mL), the solution was filtered through
Celite, and the filtrate was concentrated. The crude product was
dissolved in degassed deionized H2O (30 mL) and MeOH (0.5 mL).
Into this solution, LiNTf2 (194 mg, 0.675 mmol) in H2O (5 mL)
was added and the resulting mixture was stirred for 5 h at rt.
The pale yellow precipitate was filtered off and washed with H2O
(100 mL). Purification of the crude product by column chromatog-
raphy (SiO2, CH2Cl2/MeOH 95:5) afforded pure ligand 4 (387 mg,
withtheliterature.15
CHCl3). HPLC (Chiralcel OD-H, hexane/i-PrOH, 90:10; 0.75 mL/min):
tR(minor) 11.8 min, tR(major) 14.5 min.
[
a]
D = À20(c1.7, CHCl3);Lit.16
[a
]
D = À17(c1.7,
4.4. (E)-3-(4-Methylphenyloxy)-1,3-diphenylprop-1-ene 7
Ligand 2 (0.02 mmol) and [Pd(allyl)Cl]2 (3.7 mg, 0.01 mmol)
were dissolved in an ionic liquid (2 mL), and the resulting solution

ˇ
R. Šebesta, F. Bilcík / Tetrahedron: Asymmetry 20 (2009) 1892–1896
1896
was stirred for 30 min at rt. Acetate 5 (252 mg, 1.0 mmol) was
added to this solution and the resulting mixture was stirred for
additional 15 min at rt. Into a THF (2 mL) solution of 4-methylphe-
nol (324 mg, 3 mmol), cooled to 0 °C in an ice-bath, BuLi was added
dropwise (1.6 M in hexane, 0.75 mL, 1.2 mmol); alternatively
MeMgBr (3 M in Et2O) or Et2Zn (1 M in toluene) was used). This
solution was stirred for 15 min and then added via syringe pump
to the reaction mixture over 3 h. The reaction was monitored by
TLC and stopped when no starting material was detected or after
the selected time. The product was extracted with toluene and
the combined extracts were concentrated. The crude product was
purified by column chromatography (SiO2; hexane/EtOAc 8:1) to
give ether 7 and alcohol 8.
Acknowledgments
Financial support from Slovak Ministry of Education, Grant No.
MVTS-COST/UK/07, and Slovak Grant Agency VEGA, Grant No.
VEGA 1/3569/06 is gratefully acknowledged. NMR measure-
ments were provided by Slovak State Programme Project No.
2003SP200280203. Dr. Branislav Horvath is thanked for 31P NMR
experiments in ionic liquids. Dr. Jozef Marák is gratefully acknowl-
edged for performing HRMS measurements. Professor Štefan Toma
is thanked for valuable discussions.
References
Compound 7: mp 66–67.5 °C. 1H NMR (300 MHz, CDCl3): d 2.25
(s, 3H, CH3), 5.75 (d, J = 6.4 Hz, 1H, CH), 6.43 (dd, J1 = 15.9 Hz,
J2 = 6.4 Hz, 1H, CH), 6.66 (d, J = 15.9 Hz, 1H, CH), 6.83–6.91 (m,
2H, Ph-cresol), 6.99–7.07 (m, 2H, Ph-cresol), 7.18–7.50 (m, 10H,
Ph). 13C NMR (75 MHz, CDCl3): d 20.5 (CH3), 80.9 (CH-O), 116.1
(CH), 126.6 (CH), 127.79 (CH), 127.82 (CH), 129.4 (CH), 129.8
(CH), 130.3(qC), 131.4 (CH), 136.4 (qC), 140.5 (qC), 155.7 (qC).
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are in agreement with the literature.17
[a]D = +2.6 (c 1.0, CHCl3,
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29% ee). HPLC (Chiralcel OD-H, hexane/i-PrOH, 90:10; 0.75 mL/
min): tR = 24.5, tR = 29.9 min.