Chiral Phosphinophenyloxazolines bearing alkoxymethyl substituants: Synthesis and application in the palladium catalyzed allylic substitution reactions

Article abstract of DOI:10.1002/jccs.200500115

The chiral phos phine-oxazoline ligands 3 and 4 bearing 4-alkoxymethyl sub stitu ents on the oxazoline ring with (R)-configuration were prepared from L-serine methyl ester in 66% and 33% yields, respectively. Along this synthetic path way, the β-hydroxyla

Full text of DOI:10.1002/jccs.200500115

Journal of the Chinese Chemical Society, 2005, 52, 819-826
819
Chiral Phosphinophenyloxazolines Bearing Alkoxymethyl Substituents:
Synthesis and Application in the Palladium Catalyzed Allylic Substitution
Reactions
Rong-Jiunn Chen (
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan, R.O.C.
) and Jim-Min Fang* (
)
The chiral phosphine-oxazoline ligands 3 and 4 bearing 4-alkoxymethyl substituents on the oxazoline
ring with (R)-configuration were prepared from L-serine methyl ester in 66% and 33% yields, respectively.
Along this synthetic pathway, the b-hydroxylamides derived from L-serine methyl ester and 2-halobenzoyl
chlorides were expediently converted to the corresponding oxazolines by using diethylaminosulfur trifluoride
as the activation agent. Potassium diphenylphosphide was the reagent of choice for replacing the bromine
atom on the phenyl ring, giving the desired oxazoline-phosphine ligands 3 and 4. Together with [Pd(h3-
allyl)Cl]2, ligands 3 and 4 induced an enantioselective allylic substitution reaction of 1,3-diphenyl-2-pro-
penyl acetate by dimethyl malonate. Although ligands 3 and 4 exhibit the (R)-configuration, differing from
the (S)-configuration of Pfaltz-Helmchen-Williams phosphine-oxazoline ligands, all these ligands led to the
same enantiotopic preference in the allylic substitution reaction. To facilitate the recovery and reuse of the
phosphine-oxazoline ligand, immobilization on Merrifield resin was attempted, albeit in low loading.
Keywords: Phosphine; Oxazoline; Palladium; Chiral ligands; Allylic substitution.
INTRODUCTION
The chiral ligands prepared by connection of phosphine
control in organic transformation, such as the Pd-mediated
allylic substitution reactions.5
and oxazoline moieties have been successfully used to pro-
mote a variety of metal catalyzed asymmetric organic reac-
tions.1 For example, Pfaltz,2 Helmchen,3 and Williams4 groups
have independently found the highly enantioselective substi-
tution reaction of 1,3-diphenyl-2-propenyl acetate with di-
methyl malonate by the catalysis of a palladium complex 2
that is prepared in situ from the phosphine-oxazoline ligand 1
and [Pd(h3-allyl)Cl]2.5 The (S)-configuration of the chiral
ligand 1 originates from (S)-valinol. We report herein the
synthesis of the P,N-ligands 3 and 4 that bear 4-alkoxymethyl
substituents on the oxazoline ring. In addition to the phospho-
rus and nitrogen atoms, the 4-alkoxymethyl group may also
serve as a coordination site for a metal ion to render a stereo-
RESULTS AND DISCUSSION
The condensation reaction of L-serine methyl ester (as
the hydrochloric salt 5) with 2-chlorobenzoyl chloride (6) in
the presence of Et3N gave an amide 7 in 78% yield (Scheme
I). Several attempts to form oxazoline by activation of the
hydroxyl group in 7 failed to give the desired cyclization
product. For example, treatment of 7 with p-TsCl or SOCl2
in the presence of Et3N gave only the elimination product 8.6
In another approach, the hydroxylamide 7 was heated with
PPh3/CCl4 in the presence of Et3N to afford a mixture of
alkene 8 and the desired oxazoline 9 in 27% and 30% yields,
O
O
O
O
Ph
P
Ph
Ph
Ph
P
N
Ph
P
N
P
N
N
H
O
R
H
H
S
Ph
Pd Ph
H
MeO
R
Ph
1
3
X
2
PhCH2O
4
Dedicated to Professor Ching-Erh Lin on the Occasion of his 66th Birthday and his Retirement from National Taiwan University
* Corresponding author. Fax: +886-2-23636359; E-mail: jmfang@ntu.edu.tw

820 J. Chin. Chem. Soc., Vol. 52, No. 4, 2005
Chen and Fang
respectively. Finally, diethylaminosulfur trifluoride (DAST)
turned out to be the reagent of choice for the transformation
of hydroxylamide 7 into oxazoline 9.7 Thus, treatment of 7
with DAST at -78 °C in the presence of K2CO3 gave 9 exclu-
sively in 99% yield, without complication of the side-product
8. Unlike the valinol derived oxazolines, e.g., compound 1,
the oxazoline 9 containing an electron-withdrawing ester
group renders the proton at C-4 susceptible to alkaline condi-
tions. Indeed, oxazoline 9 was readily changed to alkene 8
upon treatment with a base, e.g., NaOH and NaH, presumably
via the H-4 abstraction to cause a rupture of the oxazoline
ring (Scheme I).
Scheme II
H
N
NH3+Cl-
ii
i
HO
MeO
HO
+
HO
MeO
O
O
Br
O
Br
10
O
5
11
iii
iv
O
O
O
N
Br
N
Br
N
Br
MeO
MeO
HO
14
13
O
12
vi
v
O
O
Scheme I
N
X
N
PPh2
O
1'
MeO
3
1'
H
NH3+Cl-
15 X = Br
Et3N
1"
HO
MeO
v
N
PhCH2O
Cl
+
HO
MeO
4 X = PPh3
O
O
Cl
O
Cl
O
5
Reagents and conditions: (i) SOCl2, 25 °C, 3 h; Et3N, CH2Cl2,
25 °C, 4 h; 85%. (ii) DAST, CH2Cl2, -78 °C, 1 h; K2CO3, -78
°C, 3 h; 99%. (iii) LiAlH4/Et2O, THF, 25 °C, 4 h; 95%. (iv)
NaH, MeI, THF, 25 °C, 3 h; 96%. (v) KPPh2, THF, 25 °C, 24 h;
86% for 3 and 75% for 4. (vi) NaH, PhCH2OC6H4(CH2)3Br,
Ag2CO3, THF/DMF (5:1), 0 °C, 5 h; 58%.
6
7 (78%)
H
see the Text
O
N
+
4
N
H
Cl
9
O
Cl
MeO
O
MeO
O
8
The alkylation reaction of alcohol 13 with 1-benzyloxy-4-
(3-bromopropyl)benzene was achieved in THF/DMF (5:1)
solution by the assistance of Ag2CO3, giving ether 15 in 58%
yield. Substitution of bromine atom with diphenylphosphine
group was not trivial as one would expect. We have tried sev-
eral methods using different combinations of reagents, e.g.,
BuLi (or t-BuLi)/Ph2PCl in tetramethylethylenediamine
(TMEDA), Li (or Mg)/Ph2PCl (or PPh3) in various condi-
tions, and even with catalysts of CuI or Pd(PPh3)2Cl2, but
failed to procure the desired substitution product.8 Finally,
the bromophenyl compounds 14 and 15 were reacted with
KPPh2 to afford the desired oxazoline-phosphine ligands 3
and 4.9 The 1H NMR spectra indicated that the aromatic pro-
tons (H3”) at the ortho-position of the PPh2 group appeared at
the relatively high fields of d 6.49 (for 3) and 6.86 (for 4), pre-
sumably due to the shielding effect of the phenyl group in a
pseudo-equatorial orientation (Fig. 1, see below). The methy-
lene protons (H1’) adjacent to the methoxy group in 3 also ap-
peared at the relatively high fields of d 2.44 and 2.66, presum-
ably due to the shielding effect of the pseudo-axial phenyl
group. The optimal yields of 3 (86%) and 4 (75%) were pro-
cured by stirring 14 and 15, respectively, with 5 equiv of
KPPh2 in THF at room temperature for 24 h. Use of less
B
O
4
N
H
Cl
MeO
O
B
By a procedure similar to that for amide 7, the acyl
chloride derived from 2-bromobenzoic acid (10) was reacted
in situ with the serine derivative 5 to give the amide 11 in 85%
yield (Scheme II). The direct amidation reaction of acid 10
with 5 was also carried out, albeit in modest yields (50-75%),
by using dicyclohexylcarbodiimide (DCC) or 1-(3-dimethyl-
aminopropyl)-3-ethylcarbodiimide (EDCI) as the dehydrat-
ing agents and Et3N and 4-dimethylaminopyridine (DMAP)
as the reaction promoters. Hydroxylamide 11 was then treated
with DAST in the presence of K2CO3 to afford the desired
oxazoline 12 in a quantitative yield.7
The reduction of ester 12 with LiAlH4 at room tempera-
ture afforded the alcohol 13, which was treated with NaH and
MeI to give the ether 14 in a 92% overall yield (Scheme II).
One should avoid using excessive amounts of LiAlH4; other-
wise, the bromophenyl moiety in 12 would also be reduced.

Chiral Alkoxymethyl Phosphinophenyloxazolines
J. Chin. Chem. Soc., Vol. 52, No. 4, 2005 821
amounts (1-3 equiv) of KPPh2 resulted in lower yields. When
15 was heated with KPPh2 in refluxing THF (68 °C), a com-
plicated product mixture containing the alcohol 13 and 3-(4-
benzyloxyphenyl)propanol, in addition to the desired phos-
phine product 4, was obtained in considerable amounts. The
cleavage of ether linkage in 15 might result from the nucleo-
philic attack at the carbinyl carbons (C-1¢ and C-1²) by di-
phenylphosphine or bromine anions.
[Pd(h3-allyl)Cl]2, 1 mol % of CsOAc and 10 equiv of BSA in
CH2Cl2 solution. By comparison with the previous reports,13
the optically active product 19 with levorotation predomi-
nated in the (S)-enantiomer. The ee value was determined by
HPLC analysis on a Chiralcel OD column, where the (S)-en-
antiomer was more polar than the (R)-enantiomer. Using
ligand 4 for the allylic substitution reaction resulted in the
same stereoselectivity, albeit in modest enantioselectivity (£
65% ee).
MeO2C
CO2Me
O
O
air, Pd/C, H+
PhCH2O
OAc
Ph
CH2(CO2Me)2, [Pd(allyl)Cl]2
Ligand, Base, BSA
Ph
Ph
P
Ph
N
P
N
H
Ph
O
Ph
Ph
Ph
O
O
18
(S)-19
PhCH2O
4
16
In comparison, the (R)-configuration in ligands 3 and 4
Phosphine 4 were partially oxidized in the air by the ca-
(the alkoxymethyl substituents shown on the a-face) differs
from the (S)-configuration in ligand 1 (the isopropyl substi-
tutent shown on the b-face). However, either the (S)-ligand 1
or the (R)-ligands 3/4 induced the same enantiotopic prefer-
ence in the allylic substitution reaction, giving (S)-19 as the
dominant product. The rationale for the stereoselectivity us-
ing ligand 1 has been proposed by Helmchen and cowork-
ers.3,5 Their proposed transition state (Fig. 1a) includes sev-
eral important features: (i) the isopropyl substituents on the
oxazoline ring forces the triarylphosphine scaffold to tilt to-
ward the p-allyl moiety, (ii) the p-allyl moiety prefers the exo-
orientation to minimize the steric effect against the pseudo-
equatorial phenyl group on the phosphorus center, and (iii)
the nucleophilic attack of dimethyl malonate occurs at C-1
that is trans to the phosphorus atom. On the other hand, the
alkoxy group in ligand 3 (or 4) can coordinate to the palla-
dium, and thus exposes the less hindered exo-face to accom-
modate the p-allyl moiety (Fig. 1b). These two working mod-
els interpret well how the allylic substitution reaction occurs
in a highly stereoselective manner to afford the product pre-
talysis of Pd/C under acidic conditions,10 e.g., in AcOH/MeOH
solution (1:10), to give the corresponding phosphine oxide
16. The characteristic trivalent phosphorus signal in 4 oc-
curred at d -22.96 in the 31P NMR spectrum, whereas the
pentavalent phosphorus in 16 appeared at a much lower field
of d 32.76.
Interestingly, treatment of the chlorophenyl oxazoline
9 with t-BuLi/Ph2PCl in Et2O (-78 to 25 °C, 18 h) gave a 32%
yield of 17 with retention of the chlorine atom. By the chela-
tion effect of the neighboring oxazoline moiety,11 compound
9 might undergo the ortho-lithiation, and then react with
Ph2PCl to afford the product 17.
Ph2P
O
O
t-BuLi, Ph2PCl
N
Cl
N
Cl
Et2O, -78 oC to rt
O
O
PhCH2O
PhCH2O
9
17
With compounds 3 and 4 in hand, a wide range of asym-
metric organic reactions with catalysis of transition metals
could be assessed by using these chiral oxazoline-phosphine
ligands.1-5 To demonstrate this possible application of com-
pounds 3 and 4, we firstly investigated the substitution reac-
tion of 1,3-diphenyl-2-propenyl acetate (18) with dimethyl
malonate by the catalysis of [Pd(h3-allyl)Cl]2.5 According to
the previously reported reaction protocol,12 N,O-bis(trimeth-
ylsilyl)acetamide (BSA) and a base (KOAc or CsOAc) were
also used as the promoters in addition to the chiral ligands (3
or 4). The best result (entry 4, Table 1), in 96% chemical yield
and 90% ee, was obtained from the reaction using 3 equiv
of dimethyl malonate, 20 mol % of ligand 3, 5 mol % of
(a)
(b)
less hindered
exo-face
pseudo-axial
O
i-Pr
H
1'
R
O
Ph
Ph
H
1
Nu
Nu
O
N
N
Pd
Ph
Pd
Ph
H
H
P
P
3
H
H
H3"
pseudo-
equatorial
Fig. 1. Working models for the enantioselective allylic
substitution reactions: (a) using (S)-ligand 1,
and (b) using (R)-ligand 3 or 4.

822 J. Chin. Chem. Soc., Vol. 52, No. 4, 2005
Chen and Fang
Table 1. Allyllic substitution reactions of 1,3-diphenyl-2-propenyl acetate (18) with dimethyl malonate using [Pd(h3-
allyl)Cl]2 and chiral ligand (3 or 4), giving product 19a
Ligand [Pd(allyl)Cl]2
Base
(mol %)
BSA
(equiv)
Reaction Yield
time (h) (%)
Ee
(%)
Entry
Solvent
Config.b
(mol %)
(mol %)
1
2
3
4
5
6
7
8
9
3 (10)
3 (10)
3 (10)
3 (20)
3 (20)
4 (20)
4 (20)
4 (20)
4 (20)
5
5
5
5
5
10
10
5
KOAc (150)
KOAc (5)
KOAc (5)
CsOAc (1)
CsOAc (1)
KOAc (5)
KOAc (5)
CsOAc (1)
CsOAc (1)
0
3
3
10
10
1.5
1.5
10
2
CH2Cl2
CH2Cl2
CH2Cl2/DMF
CH2Cl2
72
48
48
48
48
40
54
06
02
00
21
70
96
98
96
63
97
98
-
-
NDc
S
03
49
90
79
53
65
42
10
S
CH3CN
CH2Cl2
THF
CH2Cl2
CH3CN
S
S
S
S
5
S
a The reaction was conducted with 3 equiv of dimethyl malonate at 25 °C.
b Configuration of major enantiomer.
c Not determined.
dominating in the (S)-isomer. In comparison with the present
study, somewhat higher enantioselectivity in the previously
reports3,5 may be accounted for by the slight orientation twist
of the pseudo-equatorial phenyl groups in the two transition
states.
palladium catalyzed asymmetric allylic substitution reaction.
We are currently searching for an improved preparation of
the immobilized oxazoline-phosphine ligands that may be
applied to facilitate catalytic asymmetric reactions.
Immobilization on polymer and other supports is a gen-
eral method for facilitation of the recovery and reuse of the
ligand and metal catalyst.14 In one approach, the benzyl pro-
tecting group in 4 was removed by treatment with AlCl3 and
N,N-dimethylaniline,15 and the resulting phenol product 20
was reacted with Merrifield resin (chloromethylated polysty-
rene) in the presence of Cs2CO3 in DMF to give the resin-
supported oxazoline-phosphine ligand 21.16 However, the
loading of oxazoline-phosphine ligands was rather low, 0.33
mmol/g as estimated by elemental analysis of the nitrogen
content.
EXPERIMENTAL
General Procedures
All reactions requiring anhydrous conditions were con-
ducted in flame-dried apparatus under an atmosphere of ar-
gon or nitrogen. Syringes and needles for the transfer of re-
agents were dried at 100 °C and allowed to cool in a desicca-
tor over P2O5 before use. Ethers were distilled from sodium
benzophenone ketyl; (chlorinated) hydrocarbons, and amines
from CaH2. Reactions were monitored by TLC using pre-
coated with a 0.25 mm layer of silica gel containing a fluores-
cent indicator. Column chromatography was carried out on
Kieselgel 60 (40-63 mm). Melting points are uncorrected. Op-
tical rotations were measured on a digital polarimeter with a
cuvette of 10 cm length. [a]D Values are given in 10-1 deg cm2
O
Ph
P
Ph
N
H
O
g-1. Chemical shifts of H, 13C and 31P NMR spectra are re-
1
O
20 R = H
21 R = Merrifield resin
ported relative to CHCl3 [dH 7.24, dC (central line of t) 77.0]
and H3PO4 (dP = 0). Distortionless enhancement polarization
transfer (DEPT) spectra were taken to determine the types of
carbon signals.
R
CONCLUSION
Methyl (S)-2-(2-Chlorobenzamido)-3-hydroxypropanoate
(7)
In summary, we have devised an efficient method for
the synthesis of chiral oxazoline-phosphine ligands bearing
an alkoxymethyl group as the additional coordination site.
The use of these chiral ligands has been demonstrated in a
A mixture of 2-chlorobenzoic acid (11.6 g, 74 mmol)
and SOCl2 (52 g, 224 mmol) was stirred at room temperature
for 3 h and then concentrated under reduced pressure to give

Chiral Alkoxymethyl Phosphinophenyloxazolines
J. Chin. Chem. Soc., Vol. 52, No. 4, 2005 823
the corresponding 2-chlorobenzoyl chloride. A solution of
L-serine methyl ester hydrochloride (10 g, 67 mmol) in
CH2Cl2 (150 mL) and Et3N (18.9 g, 186 mmol) were added.
The reaction mixture was stirred for 4 h at room temperature,
and quenched by addition of water (100 mL). The aqueous
phase was separated and then extracted with CH2Cl2 (100
mL). The combined organic phase was dried (MgSO4), fil-
tered, concentrated, and chromatographed on a silica gel col-
umn with elution of EtOAc/hexane (3:7) to give amide 7
(14.8 g, 86%).
(M+ + H): 240.0349, found: m/z 240.0427.
Methyl (S)-2-(2-bromobenzamido)-3-hydroxypropanoate
(11)
Amidation of 2-bromobenzoic acid with L-serine meth-
yl ester hydrochloride, by a procedure similar to that for 7,
gave 11 in 85% yield. TLC (EtOAc/hexane, 1:1) Rf = 0.50;
[a]D23 = +26.9 (c = 1.0, CH2Cl2); IR (KBr, cm-1) 3401, 3345,
2961, 1750, 1619, 1542, 1376, 1057; 1H NMR (CDCl3, 400
MHz) d 3.09 (br s, OH), 3.73 (s, 3H), 3.92-4.07 (m, 2H), 4.76
(m, 1H), 7.06 (d, J = 5.6 Hz, NH), 7.18-7.30 (m, 2H), 7.47
TLC (EtOAc/hexane, 1:1) Rf = 0.50; [a]23 = +26.2 (c =
D
1.0, CH2Cl2); IR (KBr, cm-1) 3347, 2962, 1750, 1619, 1546,
1377, 1217, 1060; 1H NMR (CDCl3, 400 MHz) d 2.75 (t, J =
5.9 Hz, OH), 3.78 (s, 3H), 4.00-4.10 (m, 2H), 4.83 (m, 1H),
7.15-7.40 (m, 4H), 7.62-7.65 (dd, J = 1.2, 8.0 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) d 52.9, 55.3, 63.3, 127.1, 130.30,
130.38, 130.9, 131.7, 134.0, 166.5, 170.6; HR-FAB-MS
calcd for C11H1335ClNO4 (M+ + H): 258.0455, found: m/z
258.0526.
(dd, J = 1.8, 7.5 Hz, 1H), 7.53 (dd, J = 1.2, 7.9 Hz, 1H); 13
C
NMR (CDCl3, 100 MHz) d 52.6, 55.0, 62.7, 119.3, 127.4,
129.4, 131.4, 133.3, 136.7, 167.7, 170.5; HR-FAB-MS calcd
for C11H1279BrNO4 (M+ + H): 301.9950, found: m/z 302.0028.
(S)-2-(2-Bromophenyl)-4-methoxycarbonyl-4,5-dihydro-
1,3-oxazole (12)
A solution of hydroxylamide 11 (232 mg, 0.77 mmol)
and DAST (0.12 mL, 0.93 mmol) in CH2Cl2 (30 mL) was
stirred at -78 °C for 1 h and then to which was added K2CO3
(0.21 g, 1.6 mmol). The mixture was stirred for 3 h at -78 °C,
warmed to room temperature, and quenched by slow addition
of an aqueous NaHCO3 solution (5%, 50 mL). The mixture
was extracted with CH2Cl2 (30 mL ´ 2). The combined or-
ganic phase was dried (MgSO4), filtered, concentrated, and
chromatographed on a silica gel column with elution of
EtOAc/hexane (3:7) to give oxazoline 12 (216 mg, 99%).
Methyl 2-(2-Chlorobenzamido)-2-propenoate (8) and
(S)-2-(2-Chlorophenyl)-4-methoxycarbonyl-4,5-dihydro-
1,3-oxazole (9)
A mixture of hydroxylamide 7 (200 mg, 0.77 mmol),
PPh3 (300 mg, 1.2 mmol) and Et3N (120 mg, 1.2 mmol) in
CCl4 (30 mL) was heated under reflux for 24 h. The mixture
was concentrated and chromatographed on a silica gel col-
umn by elution with EtOAc/hexane (2:8) to give alkene 8 (50
mg, 27%) and oxazoline 9 (56 mg, 30%).
TLC (EtOAc/hexane, 1:1) Rf = 0.71; [a]23 = +90.6 (c = 0.1,
D
Hydroxylamide 7 was treated with DAST, by a proce-
dure similar to that for 12, to give oxazoline 9 in a quantita-
tive yield.
CH2Cl2); IR (KBr, cm-1) 2957, 1745, 1648, 1592, 1437, 1361,
1211, 1027; 1H NMR (CDCl3, 400 MHz) d 3.80 (s, 3H), 4.60
(m, 1H), 4.71 (m, 1H), 4.98 (dd, J = 8.0, 10.6 Hz, 1H), 7.24-
7.34 (m, 2H), 7.61 (dd, J = 1.0, 8.0 Hz), 7.72 (dd, J = 1.8, 7.6
Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 52.8, 68.7, 69.8,
121.9, 127.1, 128.9, 131.7, 132.1, 133.9, 165.9, 171.3; HR-
FAB-MS calcd for C11H11BrNO3 (M+ + H): 283.9844, found:
m/z 283.9922.
Alkene 8: TLC (EtOAc/hexane, 3:7) Rf = 0.53; IR (KBr,
1
cm-1) 3383, 2968, 1728, 1679, 1532, 1336, 1213, 1050; H
NMR (CDCl3, 400 MHz) d 3.85 (s, 3H), 6.00 (br s, 1H), 6.79
(br s, 1H), 7.33-7.44 (m, 3H), 7.69 (dd, J = 7.4, 1.8 Hz, 1H),
8.50 (br s, NH); 13C NMR (CDCl3, 100 MHz) d 53.1, 109.7,
127.2, 130.2, 130.5, 130.7, 130.9, 131.8, 134.5, 164.4, 164.8;
HR-FAB-MS calcd for C11H11ClNO3 (M+ + H): 240.0349,
found: m/z 240.0428.
(S)-2-(2-Bromophenyl)-4-hydroxymethyl-4,5-dihydro-1,3-
oxazole (13)
Oxazoline 9: TLC (EtOAc/hexane, 3:7) Rf = 0.22; [a]23
A solution of ester 12 (4.41 g, 15.6 mmol) in THF (150
mL) was treated with LiAlH4 (18.7 mL of 1 M solution in
Et2O) at room temperature for 1 h. After sequential addition
of water (1 mL), aqueous NaOH (15%, 1 mL) and water (3
mL), the mixture was filtered through a pad of Celite, and
washed with CH2Cl2 (50 mL) and MeOH/CH2Cl2 (5:95, 50
mL). The organic phase was concentrated and then chro-
matographed on a silica gel column with elution of EtOAc to
D
= +26.9 (c = 0.1, CH2Cl2); IR (KBr, cm-1) 2958, 1733, 1694,
1594, 1439, 1318, 1267, 1053; 1H NMR (CDCl3, 400 MHz) d
3.74 (s, 3H), 4.53 (dd, J = 8.8, 10.6 Hz, 1H), 4.63 (dd, J = 8.2,
8.6 Hz, 1H), 4.92 (dd, J = 8.1, 10.7 Hz, 1H), 7.21-7.39 (m,
3H), 7.72 (dd, J = 1.7, 7.7 Hz, 1H); 13C NMR (CDCl3, 100
MHz) d 52.6, 68.6, 69.5, 126.4, 126.5, 130.6, 131.5, 131.9,
133.4, 165.1, 171.2; HR-FAB-MS calcd for C11H11ClNO3

824 J. Chin. Chem. Soc., Vol. 52, No. 4, 2005
Chen and Fang
give alcohol 13 (3.78 g, 95%). TLC (EtOAc/hexane, 8:2) Rf =
0.26; [a]2D2 = +58.3 (c = 1.0, CH2Cl2); IR (KBr, cm-1) 3351,
2939, 1653, 1591, 1434, 1362, 1250, 1027; 1H NMR (CDCl3,
400 MHz) d 3.55 (m, 1H), 3.57 (br s, OH), 3.72 (m, 1H), 4.20
(m, 1H), 4.35 (m, 1H), 7.16-7.24 (m, 2H), 7.52-7.56 (m, 2H);
13C NMR (CDCl3, 100 MHz) d 63.8, 68.3, 69.6, 121.6, 127.0,
128.2, 129.4, 131.1, 131.7, 133.6, 164.8; HR-FAB-MS calcd
for C10H11BrNO2 (M+ + H): 255.9895, found: m/z 255.9974.
(R)-4-Methoxymethyl-2-(2-diphenylphosphino)phenyl-4,5-
dihydro-1,3-oxazole (3)
Under an atmosphere of argon, KPPh2 (1.05 mmol, 2.1
mL of 0.5 M solution in THF) was added to a solution of the
bromophenyl compound 14 (56 mg, 0.21 mmol) in THF (3
mL). The mixture was stirred at room temperature for 24 h,
and then to which was added water (20 mL) and CH2Cl2 (20
mL). The aqueous phase was separated and then extracted
with CH2Cl2 (30 mL). The combined organic phase was dried
(MgSO4), filtered, concentrated, and chromatographed on a
silica gel column with elution of EtOAc/pentane (1:9) to give
(R)-4-Methoxymethyl-2-(2-bromophenyl)-4,5-dihydro-1,3-
oxazole (14)
A solution of alcohol 13 (3.00 g, 11.8 mmol) in THF (30
mL) was stirred with NaH (14.2 mmol, 60% dispersion in
mineral oil washed with anhydrous hexane before use) at
room temperature for 10 min. A solution of MeI (1.68 g, 11.8
mmol) in THF (30 mL) was added dropwise. The mixture was
stirred for 3 h, filtered through a pad of Celite, and washed
with EtOAc (50 mL). The organic phase was concentrated
and then chromatographed on a silica gel column with elution
of EtOAc/hexane (3:7) to give ether 14 (3.04 g, 96%). TLC
3 (68 mg, 86%). TLC (EtOAc/hexane, 3:7) Rf = 0.34; [a]22
=
D
+33.3 (c = 1.0, CH2Cl2); IR (KBr, cm-1) 2928, 1643, 1536,
1486, 1299, 1120; 1H NMR (CDCl3, 400 MHz) d 2.44 (dd, J =
13.9, 7.4 Hz, 1H), 2.60 (dd, J = 13.9, 6.7 Hz, 1H), 3.27 (s,
3H), 3.50 (dd, J = 9.4, 4.1 Hz, 1H), 3.62 (dd, J = 9.4, 3.3 Hz,
1H), 4.42 (m, 1H), 6.49 (d, J = 8.0 Hz, 1H), 7.24-7.65 (m,
13H); 13C NMR (CDCl3, 100 MHz) d 48.0, 58.8, 73.6, 73.7,
126.8, 128.33, 128.38, 128.4, 128.51, 128.58, 128.6, 128.7,
131.3, 132.61, 132.66, 132.80, 132.85, 134.3, 137.6, 137.7,
138.3, 138.4, 166.5; 31P NMR (CDCl3, 162 MHz) d -22.87;
HR-FAB-MS calcd for C23H23NO2P (M+ + H): 376.1388,
found: m/z 376.1618.
(EtOAc/hexane, 1:1) Rf = 0.33; [a]22 = +64.4 (c = 1.0,
D
CH2Cl2); IR (KBr, cm-1) 2931, 1651, 1593, 1472, 1358, 1245,
1
1031; H NMR (CDCl3, 400 MHz) d 3.37 (s, 3H), 3.45 (m,
1H), 3.66 (m, 1H), 4.29 (m, 1H), 4.42-4.53 (m, 2H), 7.22 (m,
1H), 7.29 (m, 1H), 7.59 (dd, J = 7.9, 1.3 Hz, 1H), 7.66 (dd, J =
7.6, 1.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 58.9, 66.3,
70.3, 74.1, 121.3, 126.6, 129.4, 131.0, 131.3, 133.3, 163.8;
HR-FAB-MS calcd for C11H13BrNO2 (M+ + H): 270.0051,
found: m/z 270.0129.
(R)-4-[3-(4-Benzyloxyphenyl)propoxy]methyl-2-(2-diphen-
ylphosphino)phenyl-4,5-dihydro-1,3-oxazole (4)
Treatment of the bromophenyl compound 15 with
KPPh2, by a procedure similar to that for 3, gave compound 4
in 75% yield. TLC (EtOAc/hexane, 3:7) Rf = 0.54; [a]23
=
D
-12.5 (c = 1.0, CH2Cl2); IR (KBr, cm-1) 3064, 2926, 1641,
1512, 1485, 1241, 1027; 1H NMR (CDCl3, 400 MHz) d 1.83
(m, 2H), 2.47 (dd, J = 7.6, 13.8 Hz, 1H), 2.53-2.69 (m, 3H),
3.32-3.45 (m, 2H), 3.54 (m, 1H), 3.72 (m, 1H), 4.42 (m, 1H),
5.01 (s, 2H), 6.86 (d, J = 8.4 Hz, 1H), 6.88 (d, J = 8.7 Hz, 2H),
7.05 (d, J = 8.7 Hz, 2H), 7.27-7.63 (m, 18H); 13C NMR
(CDCl3, 100 MHz) d 31.2, 31.3, 48.2, 70.0, 70.3, 71.6, 71.7,
114.7, 126.8, 127.4, 127.8, 128.4, 128.49, 128.55, 128.62,
128.65, 128.7, 129.2, 131.3, 132.6, 132.7, 132.8, 132.9, 137.1,
138.4, 157.0, 166.6; 31P NMR (CDCl3, 162 MHz) d -22.96;
HR-FAB-MS calcd for C38H37NO3P (M+ + H): 586.2433,
found: m/z 586.2503.
(R)-4-{[3-(4-benzyloxyphenyl)propoxy]methyl}-2-(2-
bromophenyl)-4,5-dihydro-1,3-oxazole (15)
Alcohol 13 treated with NaH, Ag2CO3 (1 equiv) and
1-benzyloxy-4-(3-bromopropyl)benzene in THF/DMF (5:1)
solution for 5 h at room temperature, by a procedure similar
to that for 14, gave ether 15 in 58% yield. TLC (EtOAc/hex-
ane, 3:7) Rf = 0.45; [a]24 = +20.0 (c = 1.0, CH2Cl2); IR (KBr,
D
1
cm-1) 2928, 1652, 1512, 1456, 1356, 1240, 1025; H NMR
(CDCl3, 400 MHz) d 1.87 (m, 2H), 2.63 (t, J = 7.3 Hz, 2H),
3.47-3.52 (m, 3H), 3.74 (dd, J = 7.7, 2.5 Hz, 1H), 4.35-4.40
(m, 1H), 4.46-4.55 (m, 2H), 5.02 (s, 2H), 6.89 (d, J = 8.6 Hz,
2H), 7.08 (d, J = 8.6 Hz, 2H), 7.24-7.45 (m, 7H), 7.62 (dd, J =
7.7, 1.0 Hz, 1H), 7.69 (dd, J = 7.7, 1.7 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) d 31.24, 31.28, 66.7, 69.9, 70.5, 70.7,
72.5, 114.6, 121.6, 126.9, 127.3, 127.7, 128.4, 129.2, 129.7,
131.2, 131.5, 133.6, 134.1, 137.1, 156.9, 164.2; HR-FAB-MS
calcd for C26H27BrNO3 (M+ + H): 480.1096, found: m/z
480.1165.
(R)-4-[3-(4-Benzyloxyphenyl)propoxy]methyl-2-(2-diphen-
ylphosphorino)phenyl-4,5-dihydro-1,3-oxazole (16)
Phosphine 4 in MeOH/AcOH (10:1) solution was stirred
in the air for 18 h to give phosphine oxide 16. TLC (EtOAc/
hexane, 8:2) Rf = 0.34; [a]23 = -13.7 (c = 1.0, CH2Cl2); IR
D
(KBr, cm-1) 3063, 1658, 1514, 1439, 1322, 1236, 1177, 1117;

Chiral Alkoxymethyl Phosphinophenyloxazolines
J. Chin. Chem. Soc., Vol. 52, No. 4, 2005 825
1H NMR (CDCl3, 400 MHz) d 1.79 (m, 2H), 2.53 (t, J = 7.6
Hz, 2H), 2.68 (m, 1H), 2.95 (m, 1H), 3.12 (m, 1H), 3.26 (m,
1H), 3.40 (t, J = 8.6 Hz, 1H), 3.68 (m, 1H), 4.52 (m, 1H), 5.01
(s, 2H), 6.85 (d, J = 8.5 Hz, 2H), 7.03 (d, J = 8.4 Hz, 2H), 7.15
(m, 1H), 7.24-7.50 (m, 10H), 7.62-7.89 (m, 7H), 8.02 (m,
1H); 13C NMR (CDCl3, 100 MHz) d 31.3, 31.4, 46.9, 70.0,
70.2, 71.0, 71.1, 114.7, 127.1, 127.4, 127.8, 128.24, 128.36,
128.43, 128.53, 128.67, 128.7, 128.8, 128.9, 129.2, 130.3,
130.4, 130.7, 130.8, 131.1, 131.2, 131.4, 131.9, 133.9, 134.1,
137.1, 156.9, 166.8; 31P NMR (CDCl3, 162 MHz) d 32.76 ppm;
HR-FAB-MS calcd for C38H37BrNO4P (M+ + H): 602.2382,
found: m/z 602.2610; Anal. Calcd for C38H36NO4BrP: C,
75.86; H, 6.03; N, 2.33. Found: C, 75.97; H, 6.12; N, 1.98.
mg, 0.6 mmol) and KOAc (1 mg, 0.01 mmol). The mixture
was stirred at room temperature for 40 h, and taken up with
Et2O (80 mL). The ethereal solution was washed with satu-
rated NH4Cl (20 mL ´ 2), dried (MgSO4), filtered, concen-
trated, and chromatographed on a silica gel column with elu-
tion of EtOAc/hexane (1:9) to give dimethyl 2-(1,3-diphen-
yl-2-propenyl)malonate (19). A sample of 19 was analyzed
by HPLC on a Chiralcel column (25 cm ´ 0.46 cm) with elu-
tion of 2-propanol/hexane (1:120, flow rate 0.9 mL) using RI
and UV (254 nm) detectors. tR = 13.7 min (R-19) and 14.6
min (S-19).
(R)-4-[3-(4-Hydroxyphenyl)propoxy]methyl-2-(2-diphenyl-
phosphino)phenyl-4,5-dihydro-1,3-oxazole (20)
(R)-4-[3-(4-Benzyloxyphenyl)propoxy]methyl-2-(2-chloro-
6-diphenylphosphino)phenyl-4,5-dihydro-1,3-oxazole (17)
To a solution of 9 (502 mg, 2.1 mmol) in Et2O (20 mL)
was added dropwise t-BuLi (1.6 mL of 1.5 M solution in
THF) at -78 °C. The mixture was stirred for 3 h; a solution of
ClPPh2 (946 mg, 4.3 mmol) in Et2O (10 mL) was added
dropwise at -78 °C. The reaction mixture was stirred at room
temperature for 18 h, quenched by addition of water (30 mL),
and extracted with CH2Cl2 (40 mL ´ 2). The organic phase
was dried (MgSO4), filtered, concentrated, and chromato-
graphed on a silica gel column with elution of EtOAc/hexane
(2:8) to give compound 17 (416 mg, 32%). TLC (EtOAc/hex-
To a solution of 4 (500 mg, 0.85 mmol) and AlCl3 (0.34
g, 2.56 mmol) in CH2Cl2 (30 mL) was added N,N-dimethyl-
aniline (1 g, 8.5 mmol). The mixture was stirred at room tem-
perature for 1 h, filtered through a pad of Celite, and washed
with CH2Cl2 (20 mL) and EtOAc/hexane (1:1, 30 mL). The
combined organic phase was concentrated and chromato-
graphed on a silica gel column with elution of EtOAc/hexane
(1:9) to give phenol 20 (328 mg, 78%). TLC (EtOAc/hexane,
3:7) Rf = 0.33; [a]23 = -23.0, (c = 1.0, CH2Cl2); IR (KBr, cm-1)
D
3343, 3022, 1653, 1516, 1439, 1352, 1218; 1H NMR (CDCl3,
400 MHz) d 1.78-1.85 (m, 2H), 2.48 (dd, J = 7.4, 14.0 Hz,
1H), 2.55 (m, 2H), 2.84 (m, 1H), 3.27-3.42 (m, 2H), 3.54 (m,
1H), 3.67 (dd, J = 3.3, 9.5 Hz, 1H), 4.40-4.47 (m, 1H), 6.37
(br s, OH), 6.58 (d, J = 8.2 Hz, 1H), 6.73 (d, J = 8.2 Hz, 2H),
6.90-6.98 (m, 2H), 7.23-7.63 (m, 13H); 13C NMR (CDCl3, 100
MHz) d 30.8, 31.2, 48.0, 70.4, 71.6, 71.7, 115.2, 126.9, 128.4,
128.50, 128.57, 128.62, 128.69, 128.8, 128.9, 129.3, 131.5,
132.6, 132.8, 133.2, 134.2, 154.2, 166.9; 31P NMR (CDCl3,
162 MHz) d -22.45; HR-FAB-MS calcd for C31H31NO3P (M+
+ H): 496.1963, found: m/z 496.2187.
ane, 3:7) Rf = 0.54; [a]22 = +40.1 (c = 1.0, CH2Cl2); IR (KBr,
D
cm-1) 2965, 1652, 1513, 1460, 1222, 1037; 1H NMR (CDCl3,
400 MHz) d 1.85 (m, 2H), 2.62 (t, J = 7.3 Hz, 2H), 3.36 (t, J =
8.4 Hz, 1H), 3.45 (m, 2H), 3.65 (dd, J = 4.6, 9.4 Hz, 1H), 4.17
(m, 2H), 4.38 (m, 1H), 5.03 (s, 2H), 6.89-6.92 (m, 3H), 7.08-
7.11 (m, 2H), 7.22-7.24 (m, 2H), 7.31-7.43 (m, 15H); 13C
NMR (CDCl3, 100 MHz) d 31.2, 31.3, 66.6, 69.9, 70.4, 70.9,
72.5, 114.6, 127.4, 127.8, 128.42, 128.46, 128.48, 128.49,
128.5, 128.9, 129.2, 129.3, 129.6, 130.5, 131.7, 133.4,
133.71, 133.73, 133.81, 133.88, 133.92, 133.94, 134.1,
136.09, 136.11, 136.21, 136.22, 137.1, 140.5, 140.7, 156.9,
162.4; 31P NMR (CDCl3, 162 MHz) d -8.33; HR-FAB-MS
calcd for C38H36ClNO3P (M+ + H): 620.2043, found: m/z
620.2120.
A Polymer-Supported Ligand 21
Merrifield resins (2% cross-linked, 2-2.5 meq Cl/g,
200-400 mesh) were dried under reduced pressure before use.
Under an atmosphere of N2, a mixture of alcohol 20 (500 mg,
1.0 mmol), Merrifield resins (367 mg, 0.73-0.91 mmol) and
Cs2CO3 (359 mg, 1.1 mmol) in DMF (10 mL) was agitated at
60 °C for 24 h. The mixture was cooled and the resins were
collected by filtration and washed successively with 1:1
H2O/THF (3 ´ 25 mL), MeOH (3 ´ 25 mL), and THF (3 ´ 25
mL). The product was dried to yield 710 mg of 21. Elemental
analysis showed the average nitrogen content of 0.46 ±
0.09% (three measurements), equivalent to an average load-
ing of 0.33 mmol/g.
Representative Procedure for the Palladium Catalyzed
Asymmetric Allylic Substitution Reaction (Table 1)
A mixture of ligand 4 (24 mg, 0.04 mmol) and
[Pd(allyl)Cl]2 (7.2 mg, 0.02 mmol) in CH2Cl2 (10 mL) was
stirred for 10 min. A solution of 1,3-diphenyl-2-propenyl ac-
etate (50 mg, 0.2 mmol) in CH2Cl2 (10 mL) was added, fol-
lowed by dimethyl malonate (78 mg, 0.6 mmol), BSA (122

826 J. Chin. Chem. Soc., Vol. 52, No. 4, 2005
Chen and Fang
ton Trans. 2003, 1669-1674.
ACKNOWLEDGEMENT
6. Peer, M.; de Jong, J. C.; Kiefer, M.; Langer, T.; Rieck, H.;
Schell, H.; Sennhenn, P.; Sprinz, J.; Steinhagen, H.; Wiese,
B.; Helmchen, G. Tetrahedron 1996, 52, 7547-7583.
7. Phillips, A. J.; Uto, Y.; Wipf, P.; Reno, M. J.; Williams, D. R.
Org. Lett. 2000, 2, 1165-1168.
We thank the National Science Council for financial
support.
8. (a) Brown, J. M.; Baker, K. V.; Hughs, N.; Skarnulis, A. J.;
Sexton, A. J. Org. Chem. 1991, 56, 698-703. (b) Koch, G.;
Lloyd-Jones, G. C.; Loiseleur, O.; Pfaltz, A.; Pretot, R.;
Schaffner, S.; Schnider, P.; von Matt, P. Recl. Trav. Chim.
Pays-Bas 1995, 114, 206-210. (c) Overmann, L. E.; Owen, C.
E.; Zipp, G. G. Angew. Chem. Int. Engl. 2002, 41, 3884-
3887.
9. (a) Allen, J. V.; Dawson, G. J.; Frost, C. G.; Williams, J. M. J.
Tetrahedron 1994, 50, 799-808. (b) Nagel, U.; Nedden, H. G.
Chem. Ber. Recueil 1997, 130, 385-397. (c) Haenel, M. W.;
Oevers, S.; Bruckmann, J.; Kuhnigk, J.; Krueger, C. Synlett
1998, 301-303.
10. Read, G.; Urgelles, M. J. Chem. Soc., Dalton Trans. 1986,
1383-1388.
11. (a) Snieckus, V. Chem. Rev. 1990, 90, 879-933. (b) Snieckus,
V. NATO ASI Series E: Applied Sciences 1996, 320, 191-
221. (c) Hartung, C. G.; Snieckus, V. (Ed., Astruc, D.) Mod-
ern Arene Chemistry 2002, 330-367.
12. For review of palladium-catalyzed enantioselective allylic
substitution reactions: (a) Sesay, S. J.; Williams, J. M. J. Adv.
Asym. Syn. 1998, 3, 235-271. (b) Acemoglu, L.; Williams, J.
M. J. (Ed., Negishi, E.) Handbook of Organopalladium
Chemistry for Organic Synthesis 2002, 2, 1945-1979. For re-
lated examples: (c) Trost, B. M.; Murphy, D. J. Organo-
metallics 1985, 4, 1143. (d) Loiseleur, O.; Elliott, M. C.; von
Matt, P.; Pfaltz, A. Helv. Chim. Acta 2000, 83, 2287-2294.
(e) Gibson, C.; Rebek, J., Jr. Org. Lett. 2002, 4, 1887-1890.
13. (a) Evans, D. A.; Campos, K. R.; Tedrow, J. S.; Michael, F.
E.; Gagné, M. R. J. Am. Chem. Soc. 2000, 122, 7905-7920.
(b) Fukuda, T.; Takehara, A.; Iwao, M. Tetrahedron: Asym-
metry 2001, 12, 2793-2799.
Received February 21, 2005.
REFERENCES
1. For reviews, see: (a) Helmchen, G.; Pfaltz, A. Acc. Chem.
Res. 2000, 33, 336-345. (b) Pfaltz, A.; Drury, W. J., III. Proc.
Natl. Acad. Sci. USA 2004, 101, 5723-5726. For related rep-
resentative ligands, see: (c) Strangeland, E. L.; Sammakia, T.
Tetrahedron 1997, 53, 16503-16510. (d) Gilbertson, S. R.;
Chang, C.-W. T. J. Org. Chem. 1998, 63, 8424-8431. (e)
Nishibayashi, Y.; Takei, I.; Uemura, S.; Hidai, M. Organo-
metallics 1998, 17, 3420-3422. (f) Zhang, W.; Yoneda, Y.;
Kida, T.; Naktshji, Y.; Ikeda, I. Tetrahedron: Asymmetry
1998, 9, 3371-3380. (g) Yonehara, K.; Hashimume, T.; Mori,
K.; Ohe, K.; Uemura, S. J. Org. Chem. 1999, 64, 9374-9380.
(h) Jiang, Y.; Jiang, Q.; Zhu, G.; Zhang, X. Tetrahedron Lett.
1997, 38, 215-218. (i) Ahn, K. H.; Cho, C.-W.; Park, J.; Lee,
S. Tetrahedron: Asymmetry 1997, 8, 1179-1185. (j)
Ogasawara, M.; Yoshida, K.; Kamei, H.; Kato, K.; Uozumi,
Y.; Hayashi, T. Tetrahedron: Asymmetry 1998, 9, 1779-
1787. (k) Wiese, B.; Helmchen, G. Tetrahedron Lett. 1998,
39, 5727-5730. (l) Hou, D.-R.; Reibenspies, J. H.; Burgess,
K. J. Org. Chem. 2001, 66, 206-215. (m) Blankenstein, J.;
Pfaltz, A. Angew. Chem., Int. Ed. 2001, 40, 4445-4447. (n)
Bernardinelli, G. H.; Kundig, E. P.; Meier, P.; Pfaltz, A.;
Radkowski, K.; Zimmermann, N.; Neuburger-Zehnder, M.
Helv. Chim. Acta 2001, 84, 3233-3246. (o) Cozzi, P. G.; Zim-
mermann, N.; Hilgraf, R.; Schaffner, S.; Pfaltz, A. Adv.
Synth. Cat. 2001, 343, 450-454.
14. For the polymer-supported oxazoline ligands: (a) Bolm, C.;
Hermanns, N.; Claßen, A.; Muñiz, K. Bioorg. Med. Chem.
Lett. 2002, 12, 1795-1798. (b) Burguete, M. I.; Díez-Barra,
E.; Fraile, J. M.; García, J. I.; García-Verdugo, E.; Garcia-
Verdugo, E.; Gonzalez, R.; Herrerias, C. I.; Luis, S. V.; May-
oral, J. A. Bioorg. Med. Chem. Lett. 2002, 12, 1821-1824. (c)
Jonsson, C.; Hallman, K.; Andersson, H.; Stemme, G.;
Malkoch, M.; Malmstrom, E.; Hult, A.; Moberg, C. Bioorg.
Med. Chem. Lett. 2002, 12, 1857-1861.
15. (a) Akiyama, T.; Hirofuji, H.; Ozaki, S. Tetrahedron Lett.
1991, 32, 1321-1324. (b) Akiyama, T.; Hirofuji, H.; Hirose,
A.; Ozaki, S. Synth. Commun. 1994, 24, 2179-2185.
16. (a) Dorwald, F. Z. Organic Synthesis on Solid Phase: Sup-
ports, Linkers, Reactions; Wiley-VCH: Weinheim, 2002. (b)
Talukdar, S.; Chen, R.-J.; Chen, C.-T.; Lo, L.-C.; Fang, J.-M.
J. Comb. Chem. 2001, 3, 341-345.
2. von Matt, P.; Pfaltz, A. Angew. Chem., Int. Engl. 1993, 32,
566-568.
3. Sprinz, J.; Helmchen, G. Tetrahedron Lett. 1993, 34,
1769-1772.
4. Dawson, G. J.; Frost, C. G.; Williams, J. M. J. Tetrahedron
Lett. 1993, 34, 3149-3150.
5. (a) Helmchen, G. J. Organomet. Chem. 1999, 576, 203-214.
Steinhagen, H.; Reggelin, M.; Helmchen, G. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 2108-2110. (b) Kollmar, M.; Goldfuss,
B.; Reggelin, M.; Rominger, F.; Helmchen, G. Chem. Eur. J.
2001, 7, 4913-4927. (c) Kollmar, M.; Steinhagen, H.;
Janssen, J. P.; Goldfuss, B.; Malinovskaya, S. A.; Vazquez,
J.; Rominger, F.; Helmchen, G. Chem. Eur. J. 2002, 8,
3103-3114. (d) Vazquez, J.; Goldfuss, B.; Helmchen, G. J.
Organomet. Chem. 2002, 641, 67-70. (e) Apfelbacher, A.;
Braunstein, P.; Brissieux, L.; Welter, R. J. Chem. Soc., Dal-