4-ferrocenyl-1,3-oxazoline derivatives as ligands for catalytic asymmetric allylation reactions

Article abstract of DOI:10.1016/S0022-328X(02)01737-0

Bis(oxazolines) and 2-(2-phosphinoaryl)oxazolines derived from highly enantiopure 2-amino-2-ferrocenylethanol have been tested as ligands in the asymmetric Pd(0)-catalysed allylic alkylation reaction. Essentially complete enantioselectivity (99.8:0.2 er) has been achieved in the nucleophilic substitution of 1,3-diphenyl-2-propenyl acetate by dimethyl malonate anion. The absolute configuration of the ligands has been unambiguously established by chiroptical methods.

Full text of DOI:10.1016/S0022-328X(02)01737-0

Journal of Organometallic Chemistry 660 (2002) 62Á70
/
www.elsevier.com/locate/jorganchem
4-Ferrocenyl-1,3-oxazoline derivatives as ligands for catalytic
asymmetric allylation reactions
Rosa Ma. Moreno, Agust´ı Bueno, Albert Moyano *
Unitat de Recerca en S´ıntesi Asime`trica (URSA), Departament de Qu´ımica Orga`nica, Facultat de Qu´ımica, Universitat de Barcelona, Mart´ı i Franque`s
1-11, 08028 Barcelona, Spain
Received 28 May 2002; received in revised form 5 July 2002; accepted 24 July 2002
Abstract
Bis(oxazolines) and 2-(2-phosphinoaryl)oxazolines derived from highly enantiopure 2-amino-2-ferrocenylethanol have been tested
as ligands in the asymmetric Pd(0)-catalysed allylic alkylation reaction. Essentially complete enantioselectivity (99.8:0.2 er) has been
achieved in the nucleophilic substitution of 1,3-diphenyl-2-propenyl acetate by dimethyl malonate anion. The absolute configuration
of the ligands has been unambiguously established by chiroptical methods. # 2002 Elsevier Science B.V. All rights reserved.
Keywords: Asymmetric synthesis; Ferrocenes; Induced circular dichroism; Oxazolines
1. Introduction
show that the use of an allyl palladium complex derived
from 3 as a catalyst in asymmetric allylic alkylations
gives rise to extraordinarily high selectivities (up to
99.8:0.2 enantiomer ratio (er)).
The use of chiral ferrocene derivatives as ligands for
asymmetric catalysis has been receiving an increasing
attention in the last decade [1]. While planar chiral 1,1?-
disubstituted or 1,2-disubstituted ferrocenes have been
extensively studied, much less attention has been paid to
central chiral derivatives such as a,b-disubstituted
ferrocenes [2]. We have recently described in this Journal
[3] the highly enantioselective synthesis of 2-amino-2-
ferrocenyl ethanol (1) in both enantiomeric forms, as
well as its conversion into the oxazoline-based ligands 2
and 3.
Subsequently to the acceptance of our article, Patti et
al. [4] have reported an alternative preparation of amino
alcohol (ꢀ
/
)-1 and of phosphinooxazoline (ꢁ)-3, to-
/
gether with a single example of the application of 3 to
asymmetric catalysis. Prompted by the publication of
this paper, we wish now to disclose our own results on
the use of ligands 2 and 3 in the Pd(0)-catalysed allylic
alkylation reaction. In particular, we present for the first
time conclusive evidence for the assignation of an (S)
absolute configuration to amino alcohol (ꢁ)-1, and we
/
* Corresponding author. Tel.: ꢁ
7878
E-mail address: amoyano@qo.ub.es (A. Moyano).
/
34-93-402-1245; fax: ꢁ34-93-339-
/
0022-328X/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 3 2 8 X ( 0 2 ) 0 1 7 3 7 - 0

R.M. Moreno et al. / Journal of Organometallic Chemistry 660 (2002) 62Á
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63
2. Results and discussion
Further evidence for the (S) absolute configuration of
amino alcohol (ꢁ)-1 was obtained by conversion of the
derived oxazolidinone 5 [3] into the N-acylated com-
/
2.1. Absolute configuration of ferrocene-based ligands 2
and 3
pound 6 (Scheme 1). Treatment of a THF solution of 6
with sodium hexamethyldisilazane at ꢀ78 8C, followed
/
by addition of excess methyl iodide afforded the N-(3-
phenyl-2-methylpropanoyl)oxazolidinone 7 with excel-
lent diastereoselectivity (94:6 diastereomer ratio (dr),
measured by HPLC). When this compound was reacted
with lithium benzyloxide in the conditions described by
Evans the levorotatory ester 8, of known (2R) config-
uration [11], was obtained. This is the expected product
from the attack of the alkyl halide to the less hindered
face of the chelated sodium (Z)-enolate, assuming an
(S) configuration for oxazolidinone 5. Methylation of
the sodium enolate derived from (R)-4-phenyl-N-(3-
phenylpropanoyl)oxazolidinone (10) took place, as ex-
pected, in a completely parallel way (predominant
formation of the (2R) isomer) but with substantially
lower diastereoselectivity (70:30 dr), showing that the
ferrocenyl group exerts a higher stereodiscriminating
effect than the phenyl one.
Bis(oxazoline) (ꢀ
were prepared in high enantiomeric purity (]
through the intermediacy of amino alcohol (ꢁ)-1, from
(ꢁ)-1-ferrocenylethane-1,2-diol (4) [5] by the procedures
reported in our previous article [3]. It is worth noting,
however, that the assignation of an (S) configuration to
/
)-2 and phosphinooxazoline (ꢀ
/
)-3
/99:1 er),
/
/
diol (ꢁ
/
)-4 (and, therefore, to the derived compounds
(ꢁ)-1, (ꢀ
/
/
)-2 and (ꢀ)-3) ultimately relied on the
/
application of the ‘mnemonic device’ for the osmium-
catalysed asymmetric dihydroxylation of alkenes [6].
Since several exceptions to this rule have been reported
in the literature [7], we felt that it was necessary to
confirm this assignation by an alternative procedure.
Recently, Salvadori et al. [8] have shown that the
absolute configuration of chiral acyclic 1,2-diols can
be reliably ascertained by analysis of the induced
circular dichroism spectrum of their complexes with
dimolybdenum tetraacetate in DMSO solution, accord-
ing to the method initially developed by Snatzke [9]. By
application of the empirical rule developed by Salvadori,
for which no exceptions are known [10], we should
2.2. Catalytic asymmetric allylation reactions
expect an intense negative Cotton effect at ca. 305Á310
/
With compounds 2 and 3 in hand, and having firmly
established their absolute configuration, we set out to
study their applicability in asymmetric catalysis. Li-
gands 2 and 3 were initially tested in the Pd(0)-catalysed
asymmetric allylic alkylation [12] of rac-(E)-1,3-diphe-
nyl-2-propenyl acetate 12 using dimethyl malonate as
the nucleophile, a benchmark reaction that has been
traditionally used to assess the efficiency of new ligands
[13] (Scheme 2).
The results of this study are summarised in Table 1.
The required catalysts were either generated in situ
(conditions A and B in Table 1) or in a previous step
(conditions C and D). Allylpalladium complexes 14 and
15 were readily prepared by reacting allylpalladium
chloride dimer with one equivalent of ligands 2 and 3,
respectively, based on palladium, and were isolated as
the hexafluorophosphate salts [14].
nm (band IV according to Snatzke’s nomenclature) in
the induced circular dichroism spectrum of the (S)
enantiomer of diol 4. We were pleased to observe that
the stationary state induced circular dichroism spectrum
of a 4:3 mixture of dimolybdenum tetraacetate and diol
(ꢁ
/
)-4 in DMSO solution exhibited a strong negative
2.15) at lꢂ315 nm, a zone in
Cotton effect (Do?ꢂ
/
ꢀ
/
/
which the circular dichroism spectrum of the uncom-
plexed diol showed no significant absorption. This
negative Cotton effect is indicative of a negative sign
for the OÃ
derivative of (ꢁ
the assignment of an (S) configuration to the stereo-
genic centers of compounds 1Á4, and establishing that
/
CÃ
/
CÃ
/
O dihedral angle in the Cottonogenic
/)-4 (Fig. 1), therefore, confirming
/
the Sharpless’ ‘mnemonic rule’ for asymmetric dihy-
droxylations can be safely applied to 1-ferrocenyl
alkenes [5].
Fig. 1. Induced circular dichroism spectrum at stationary conditions of compound (ꢁ
/
)-4 in solution of dimolybdenum tetraacetate in DMSO, and
relation between the absolute configuration of the substrate and the sign of the OÃCÃ
/
/
CÃO dihedral in the Cottonogenic derivative.
/

64
R.M. Moreno et al. / Journal of Organometallic Chemistry 660 (2002) 62Á70
/
Scheme 1. Reagents and conditions: (a) 1.1 equivalents n-BuLi, THF, 0 8C; 1.1 equivalents 3-phenylpropanoyl chloride, 0 8C to room
temperature (b) 1.5 equivalents sodium bis(trimethylsilyl)amide, THF, ꢀ78 8C, 30 min; five equivalents methyl iodide, ꢀ78 8C, 3Á7 h. (c) 1.5
/
/
/
equivalents lithium benzyloxide, THF, 0 8C, 23 h.
entry 2). Not unexpectedly [12b], better results were
obtained with the phosphinooxazoline ligand 3. In this
case, both good yields and enantioselectivities (entry 4)
were achieved in dichloromethane solution, although
tetrahydrofuran also appears to be a suitable solvent
(entry 6). The preformed catalyst 15, both in dichlor-
omethane and in tetrahydrofuran, afforded extraordi-
narily high enantioselectivities (entries
8 and 9,
respectively), but was less reactive that the catalyst
prepared in situ. Interestingly enough, when the reaction
was performed at 70 8C in tetrahydrofuran solution,
the results obtained with the allylpalladium complex 15
(entry 10) were essentially equivalent to those achieved
with the catalyst generated in situ in dichloromethane at
room temperature. The use of toluene as a solvent (entry
11) led to a significant decrease of the enantioselectivity
of the process. In all instances, the major enantiomer of
product 13 was the (R) one, an stereochemical outcome
that can be explained by assuming a nucleophilic attack
of the malonate anion to the more sterically crowded
terminus of the diphenylallyl moiety in the exo-diaster-
eomer of the allylpalladium intermediate (Fig. 2) [12].
We have also briefly examined the behaviour of
catalyst 15 in the allylic substitution of rac-1,3-dimethy-
lallyl acetate (16) (Scheme 3) and of rac-2-cyclohexenyl
acetate (18) (Scheme 4) by dimethyl malonate. In both
Some reactivity trends are readily apparent from the
data gathered in Table 1. First of all, it can be seen that
the catalytic activity of the bis(oxazoline) ligand 2 is
relatively low, since even after prolonged reaction times
the allylic malonate (R)-13 was isolated in minor
amounts (9Á/20% yield), albeit with good optical purity
(upto 96:4 er using dichloromethane as the solvent, see
Scheme 2. Asymmetric allylic alkylation reaction of diphenylpropenyl acetate 12 using catalysts derived from ligands (S,S)-2 and (S)-3. See Table 1
for the reaction conditions.

R.M. Moreno et al. / Journal of Organometallic Chemistry 660 (2002) 62Á
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65
Table 1
Asymmetric Pd(0)-catalysed allylic alkylation reactions with 4-ferrocenyl-1,3-oxazoline ligands
a
b
c
Entry
Catalyst
Solvent
Temperature
Time
Yield of 13 (%)
Er of 13
1
A
A
B
C
Et2O
Room temperature
Room temperature
Room temperature
Room temperature
Room temperature
Room temperature
Room temperature
Room temperature
Room temperature
70 8C
26 h
26 h
9
94:6
96:4
2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
15
20
80
59
72
74
63
48
78
48
3
92 h
17 h
94:6
94:6
4
d
5
C
18 h
16 h
95:5
97:3
6
C
C
7
Toluene
CH2Cl2
THF
19 h
94:6
e
8
D
7 days
7 days
20 h
99.8:0.2
98.4:1.6
94:6
e
9
D
10
11
D
D
THF
toluene
Room temperature
4 days
86:14
a
A (2% [Pd(C3H5)Cl]2, 6% 2); B (2% 14); C (2% [Pd(C3H5)Cl]2, 6% 3); D (2% 15).
Yield of isolated product after chromatographic purification.
Measured by HPLC (Chiralcel-ODH column).
b
c
d
e
KAcO was used instead of LiAcO.
A 5% of 15 was used in this case.
cases, when the reaction was run in dichloromethane
similar to those obtained in general with phosphinoox-
azoline ligands [12].
solution at room temperature, conversion was extremely
low even after several days. The process was much faster
in tetrahydrofuran at 70 8C, and complete conversions
were achieved after a few hours. Under these conditions,
the (R)-enantiomer of the allyl malonate 17 was
produced with moderate enantioselectivity (72:28 er),
while (S)-(2-cyclohexenyl) malonate (18) was obtained
with very low enantioselectivity. These results are
In summary, we have shown that 4-ferrocenyl-1,3-
oxazolines can give rise to highly enantioselective
ligands for asymmetric allylic alkylations, although
some structural variation of the 4-ferrocenyl-1,3-oxazo-
line moiety appears to be necessary in order to improve
the applicability scope of the derived catalysts. Work
along these lines is underway in our laboratory.
Fig. 2. Rationalisation of the stereochemical outcome of the allylic alkylation reactions mediated by ligands 2 and 3.

66
R.M. Moreno et al. / Journal of Organometallic Chemistry 660 (2002) 62Á70
/
Scheme 3. Asymmetric allylic alkylation reaction of dimethylpropenyl acetate (16) using catalyst 15.
3.2. Induced circular dichroism spectrum of (ꢁ)-4
/
To a 1.52 mM DMSO solution of Mo2(AcO)4 (0.038
mmol in 25 ml), (ꢁ)-1-ferrocenylethane-1,2-diol (4) (7.0
/
mg, 0.029 mmol) was added in one portion. The CD
spectrum of the mixture was recorded every 10 min, and
the stationary state was reached after 1 h at r.t. ICD
bands according to Snatzke’s nomenclature [9]: l (nm),
Scheme 4. Asymmetric allylic alkylation reaction of 2-cyclohexenyl
acetate (18) using catalyst 15.
Do?: V, 277,ꢁ
/
1.19; IV, 315, ꢀ2.15.
/
3.3. (S)-4-Ferrocenyl-N-(3?-phenylpropanoyl)-1,3-
oxazolidin-2-one, (6)
3. Experimental
To a cold (0 8C), stirred solution of (S)-4-ferrocenyl-
1,3-oxazolidin-2-one (5) (0.100 g, 0.37 mmol) in anhy-
drous THF (5 ml), 0.32 ml (0.41 mmol) of a 1.3 M
solution of n-butyl lithium in hexanes were added with a
calibrated syringe, and stirring was maintained for 0.5 h
at the same temperature. At this point, 92 ml (0.41
mmol) of 3-phenylpropanoyl chloride was added in one
portion. The reaction mixture was then slowly warmed
to r.t., and after 1 h TLC analysis showed that no
starting material remained. The reaction was quenched
by the addition of aqueous saturated ammonium
chloride solution (2 ml), and extracted with CH2Cl2
3.1. General and analytical methods
Melting points were determined in an open capillary
tube and are uncorrected. Optical rotations were
measured at room temperature (r.t.) (23 8C) on a
PerkinÁElmer 241 MC polarimeter. Concentrations
/
are given in g 100 mlꢀ1. CD spectra were recorded
using a JASCO 720 spectropolarimeter, with a 0.1 cm
cell in DMSO and at r.t. Infrared spectra were recorded
in a Fourier transform mode, using NaCl film or KBr
1
(3ꢃ
/
10 ml). The combined organic layers were washed
pellet techniques. The H-NMR spectra were recorded
with 1 M aqueous NaOH (2ꢃ
ml), dried over MgSO4 and evaporated at reduced
pressure to afford a crude product that upon chromato-
/
10 ml) and with brine (10
at 200 or at 300 MHz (sꢂ
/
singlet, dꢂ
/
doublet, tꢂ
/
triplet, mꢂmultiplet, brꢂ
/
/
broad), and the 13C-NMR
spectra were recorded at 50.3 or at 75.4 MHz. 31P-NMR
spectra were recorded at 121 MHz. Chemical shifts are
given in ppm and referenced to Me4Si (1H), CHCl3 (13C)
or H3PO4 (31P). J values are given in Hz. Carbon
multiplicities were established by DEPT experiments.
graphic purification (silica gel, C6H14ÁEtOAc mixtures
/
of increasing polarity) yielded 0.118 g (79%) of pure (S)-
4-ferrocenyl-N-(3-phenylpropanoyl)-1,3-oxazolidin-2-
one (6) as a yellow solid.
M.p. 150.5Á
/
152.5 8C. [a]Dꢂ
/
ꢀ
/
162.5 (cꢂ0.57,
/
Mass spectra (MS) were run on a HewlettÁPackard HP-
/
CH2Cl2). IR (KBr): nꢂ/3089, 2927, 1777, 1702, 1379,
5988 A spectrometer, using CI, EI or FAB ionisation
techniques. Exact mass measurements (HRMS) were
performed by the ‘Unidade de Espectrometria de Masas
de la Universidade de Santiago de Compostela’. All
reactions were run in flame or oven-dried glassware
under a N2 atmosphere. Reaction progress was followed
by TLC (Merck DC-Alufolien KIESELGEL 60 F254).
1331, 1248, 1190, 1057, 821 cmꢀ1. 1H-NMR (200 MHz,
CDCl3): d (ppm) 2.91 (m, 2H, 3?-CH2), 3.16 (m, 2H, 2?-
CH2), 4.21 (m, 8H, Fc), 4.43 (m, 1H, Fc), 4.64 (m, 2H, 5-
CH2), 5.33 (m, 1H, 4-CH), 7.20 (m, 5H, Ph). 13C-NMR
(50 MHz, CDCl3): d (ppm) 30.2 (3?-CH2), 37.1 (2?-CH2),
53.4 (4-CH), 65.4 (Fc-CH), 68.5 (Fc-CH), 68.3 (5-CH2),
68.8 (Fc-CH), 68.9 (Fc-CH), 70.7 (Fc-CH), 84.7 (Fc-
Cq), 120.6 (Ph-CH), 128.3 (Ph-CH), 128.4 (Ph-CH),
140.3 (Ph-Cq), 158.0 (1?-Cq), 171.8 (2-Cq). MS (CI,
Silica gel (70Á/230 mesh) was used for column chroma-
tography. Compounds 1Á/5 were prepared as previously
1ꢁ, 11%], 421 [Mꢁ18ꢁ, 100%].
/
described by us [3]. Compounds 9 [15], 12 [16], 16 [17]
and 18 [17] were obtained according to published
procedures.
NH3) m/eꢂ
/
404 [Mꢁ
/
HRMS (CI) Calcd. for C22H22FeNO3: 404.0935. Found:
404.0949.

R.M. Moreno et al. / Journal of Organometallic Chemistry 660 (2002) 62Á
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67
3.4. (R)-4-Phenyl-N-(3?phenylpropanoyl)-1,3-
oxazolidin-2-one (10)
Chiralcel-OD column, 95% C6H14*
hol, Fꢂ Tꢂ
0.5 ml minꢀ1
tR(2?S,4S) 65.6 min, tR (2?R,4S) 84.3 min.
M.p. 109.5Á111.0 8C. [a]Dꢂ 186.5 (cꢂ
CH2Cl2). IR (KBr): nꢂ2925, 1775, 1701, 1379, 1329,
1231, 1186, 1105, 1030, 957, 820 cmꢀ1. H-NMR (200
MHz, CDCl3): d (ppm) 1.05 (d, Jvic(CH3,2?-CH) 6.6 Hz,
/
5% isopropyl alco-
/
,
/
25 8C, lꢂ254 nm,
/
ꢂ
/
ꢂ
/
To a cold (0 8C), stirred solution of (R)-4-phenyl-1,3-
oxazolidin-2-one (9) (0.500 g, 3.1 mmol) in anhydrous
THF (10 ml), 2.0 ml (3.4 mmol) of a 1.6 M solution of n-
butyl lithium in hexanes were added with a calibrated
syringe, and stirring was maintained for 0.5 h at the
same temperature. At this point, 0.78 ml (5.6 mmol) of
3-phenylpropanoyl chloride were added in one portion,
and the reaction mixture was slowly warmed to r.t.
When TLC analysis showed that no starting material
remained, the reaction was quenched by the addition of
aqueous saturated ammonium chloride solution (5 ml),
/
/
ꢀ
/
/0.50,
/
1
ꢂ
/
?
3H, CH3), 2.64 (dd, Jgem(3?-CHH)
ꢂ
/
13.4 Hz, Jvic(3?-CH,2?-
13.4
4.2 (m,
5-CHH), 4.61
CH)ꢂ7.2 Hz, 1H, 3?-CHH), 2.98 (dd, Jgem(3?-CHH)
/
ꢂ
/
?
Hz, Jvic(3?-CH?,2?-CH)
9H, Fcꢁ2?-CH), 4.3Á
(dd, Jgem(5-CHH) 8.6 Hz, Jvic(5-CH,4-CH)
5-CHH), 5.21 (dd, Jvic(4-CH,5-CH)
CH?)ꢂ
ꢂ
/
7.8 Hz, 1H, 3?-CHH), 3.9Á
/
/
/
4.4 (m, 2H, Fcꢁ
/
?
ꢂ
/
ꢂ
/
2.6 Hz, 1H,
?
ꢂ
/
8.0 Hz, Jvic(4-CH,5-
/
2.4 Hz, 1H, 4-CH), 7.25 (m, 5H, Ph). 13C-NMR
and extracted with CH2Cl2 (3ꢃ
organic layers were dried over MgSO4 and evaporated
at reduced pressure to afford a crude product that upon
/
20 ml). The combined
(50 MHz, CDCl3): d (ppm) 16.9 (CH3), 39.2 (2?-CH),
39.6 (3?-CH2), 53.5 (4-CH), 65.2 (Fc-CH), 68.3 (5-CH2),
68.5 (Fc-CH), 68.6 (Fc-CH), 68.7 (Fc-CH), 70.2 (Fc-
CH), 84.9 (Fc-Cq), 126.2 (Ph-CH), 128.2 (Ph-CH), 129.1
(Ph-CH), 139.2 (Ph-Cq), 152.7 (1?-Cq), 175.8 (2-Cq).
chromatographic purification (silica gel, C6H14ÁEtOAc
/
mixtures of increasing polarity) yielded 0.859 g (93%) of
the desired (R)-4-phenyl-N-(3-phenylpropanoyl)-1,3-
oxazolidin-2-one (10) as a colourless solid.
MS (CI, NH3) m/eꢂ
/
417 [Mꢁ, 72%], 418 [Mꢁ1ꢁ,
/
100%]. HRMS (CI) Calcd. for C23H24FeNO3: 418.1105.
Found: 418.1089.
M.p. 122.9Á
/
123.8 8C. [a]Dꢂ
/
ꢀ
/
61.0 (cꢂ1.08,
/
CH2Cl2). IR (KBr): nꢂ2923, 1779, 1701, 1653, 1559,
/
1
1456, 1383, 1259, 1200, 1055, 801 cmꢀ1. H-NMR (200
MHz, CDCl3): d (ppm) 2.93 (m, 2H, 3?-CH2), 3.27 (m,
3.6. (R)-4-Phenyl-N-(3?-phenyl-(R)-2?-
methylpropanoyl)-1,3-oxazolidin-2-one (11)
2H, 2?-CH2), 4.27 (dd, Jgem(5-CHH)
ꢂ8.8 Hz,
/
?
Jvic(5-CH, 4-CH)ꢂ
/
3.8 Hz, 1H, 5-CHH), 4.67 (t,
?
Jgem(5-CHH)
5.42 (dd, Jvic(4-CH, 5-CH)
Hz, 1H, 4-CH), 7.2Á
ꢂ
/
Jvic(5-CH, 4-CH)ꢂ
/
8.8 Hz, 1H, 5-CHH),
?
To a cold (ꢀ78 8C) solution of Na[(Me3Si)2N] (0.579
/
ꢂ
/
8.5 Hz, Jvic(4-CH, 5-CH?)
ꢂ
/
3.8
g, 3.18 mmol) in anhydrous THF (10 ml), a solution of
the N-acyloxazolidinone (10) (0.627 g, 2.12 mmol) was
added slowly via syringe. After stirring for 30 min at the
same temperature, a solution of CH3I (0.62 ml, 10
mmol) in anhydrous THF (5 ml) was added via syringe.
/
7.3 (m, 10H, Ph). 13C-NMR (50
MHz, CDCl3): d (ppm) 30.1 (3?-CH2), 37.1 (2?-CH2),
57.5 (4-CH), 69.9 (5-CH2), 125.8 (Ph-CH), 126.1 (Ph-
CH), 128.3 (Ph-CH), 129.1 (Ph-CH), 138.9 (Ph-Cq),
140.2 (Ph-Cq), 154.0 (1?-Cq), 171.7 (2-Cq). MS (CI,
The mixture was stirred at ꢀ78 8C for 3 h, the reaction
/
NH3) m/eꢂ
/
295 [Mꢁ, 7%], 296 [Mꢁ
/
1ꢁ, 100%]. HRMS
was quenched by addition of aqueous saturated ammo-
nium chloride solution (5 ml), and extracted with EtOAc
(CI) Calcd. for C18H18NO3: 296.1287. Found: 296.1290.
(3ꢃ20 ml). The combined organic phases were dried
/
3.5. (S)-4-Ferrocenyl-N-(3?-phenyl-(R)-2?-
methylpropanoyl)-1,3-oxazolidin-2-one (7)
over MgSO4 and evaporated at reduced pressure to
afford a crude product (dr 70:30, according to 1H-NMR
spectroscopy), that upon chromatographic purification
To a cold (ꢀ
/
78 8C) solution of Na[(Me3Si)2N] (50
(silica gel, C6H14ÁEtOAc mixtures of increasing polar-
/
mg, 0.25 mmol) in anhydrous THF (5 ml), a solution of
the N-acyloxazolidinone (6) (70 mg, 0.17 mmol) was
added slowly via syringe. After stirring for 30 min at the
same temperature, a solution of CH3I (53 ml, 0.85 mmol)
in anhydrous THF (5 ml) was added via syringe. The
ity) gave 0.284 g (43%) of the title compound 11 as a
colourless solid.
M.p.
88.9Á
/
90.0 8C.
[a]Dꢂ
/
ꢀ
/
122.5
(cꢂ1.00,
/
CH2Cl2). IR (KBr): nꢂ2923, 1779, 1703, 1603, 1454,
/
1383, 1236, 1198, 1041, 953 cmꢀ1. 1H-NMR (200 MHz,
mixture was stirred at ꢀ
quenched by addition of aqueous saturated ammonium
chloride solution (5 ml), and extracted with EtOAc (3ꢃ
15 ml). The combined organic phases were dried over
MgSO4 and evaporated at reduced pressure to afford a
crude product (94:6 dr) that upon chromatographic
/
78 8C for 7 h, the reaction was
CDCl3): d (ppm) 1.14 (m, 3H, CH3), 2.64 (m, 1H, 3?-
CHH), 3.01 (m, 1H, 3?-CHH), 4.18 (m, 2H, 2?-CHꢁ
/
5-
?
Jvic(5-CH,4-CH)
/
CHH), 4.48 (t, Jgem(5-CHH)
1H, 5-CHH), 5.29 (dd, Jvic(4-CH,5-CH)
ꢂ
/
ꢂ
/
8.8 Hz,
ꢂ
/
8.8 Hz,
?
Jvic(4-CH,5-CH?)
ꢂ
/
3.6 Hz, 1H, 4-CH), 7.19Á
/7.35 (m,
10H, Ph). 13C-NMR (50 MHz, CDCl3): d (ppm) 17.1
(CH3), 39.4 (3?-CH2), 39.6 (2?-CH), 57.6 (4-CH), 69.7
(5-CH2), 125.6 (Ph-CH), 128.2 (Ph-CH), 129.1 (Ph-CH),
139.0 (Ph-Cq), 139.2 (Ph-Cq), 153.2 (1?-Cq), 175.9
purification (silica gel, C6H14ÁEtOAc mixtures of in-
/
creasing polarity) gave 17 mg (24%) of the title
compound 7 as a yellow solid. Conditions for the
HPLC determination of the diastereomeric purity of 7:
(2-Cq). MS (EI) m/eꢂ91 (100%), 118 (83%), 309
/

68
R.M. Moreno et al. / Journal of Organometallic Chemistry 660 (2002) 62Á70
/
[Mꢁ, 12%]. HRMS (EI) Calcd. for C19H19NO3:
309.1365. Found: 309.1374.
M.p. 132.0Á
IR (KBr): nꢂ2923, 1734, 1699, 1653, 1620, 1554, 1541,
1506, 1437, 1119, 837 cmꢀ1 1H-NMR (300 MHz,
CDCl3): d (ppm) 2.8Á3.3 (br, 2H, allyl-CH2), 3.38 (br
s, 1H, Fc), 3.71 (m, 1H, allyl-CHH), 4.00 (br s, 1H, Fc),
4.12 (s, 5H, Fc), 4.24 (br s, 1H, Fc), 4.28 (br s, 1H, Fc),
/
135.2 8C. [a]Dꢂ
/
ꢀ
/
284 (cꢂ
/
0.33, EtOH).
/
.
/
3.7. [(S,S)-4-Ferrocenyl-2-(1-methyl-1-
(ferrocenyl(1,3-oxazolin-2-yl)ethyl)-1,3-oxazole]-[p-
allyl]palladium(II) hexafluorophosphate (14)
?
Jvic(5-CH,4-CH)
4.79 (t, Jgem(5-CHH)
CHH), 4.99 (br, 1H, allyl-CHH), 5.14 (t, Jgem(5-
ꢂ
/
ꢂ9.9 Hz, 1H, 5-
/
To a stirred suspension of di-m-chloro-bis(p-allyl)pal-
ladium (28 mg, 0.074 mmol) in absolute EtOH (2 ml), a
solution of bis(oxazoline) 2 (78 mg, 0.140 mmol) in
absolute EtOH (2 ml) was added via cannula at r.t. The
resulting mixture was stirred for 1 h at r.t., at which
point an homogeneous orange-coloured solution was
obtained. Solid ammonium hexafluorophosphate (25
mg, 0.142 mmol) was added in one portion, and the
mixture was left in the refrigerator (4 8C) for 24 h. The
precipitate was isolated by filtration, washed with cold
(0 8C) absolute EtOH and dried in vacuo to afford 39
mg (33%) of the title compound 14 as a yellow crystal-
line solid.
?
Jvic(5-CH,4-CH)
CHH)ꢂ
/
ꢂ
/
9.9 Hz, 1H, 5-CHH), 5.31 (dd,
?
10.0 Hz, Jvic(4-CH,5-CH?)
Jvic(4-CH,5-CH)
CH), 5.64 (br, 1H, allyl-CH), 7.03 (m, 2H, Ar-CH), 7.20
ꢂ
/
ꢂ6.9 Hz, 1H, 4-
/
(m, 2H, Ar-CH), 7.37 (m, 2H, Ar-CH), 7.4Á7.5 (m, 5H,
/
Ar-CH), 7.67 (m, 2H, Ar-CH), 8.20 (dd, Jvic (3?-CH,4?-
CH)ꢂ
/
ꢂ
4.2 Hz, 1H, 3?-CH). 13C-NMR
/
?
7.5 Hz, 4JC-P
(75 MHz, CDCl3): d (ppm) 56.0 (br, allyl-CH2), 65.3 (4-
CH), 68.5 (Fc-CH), 68.9 (Fc-CH), 69.2 (Fc-CH), 69.9
(Fc-CH), 74.6 (5-CH2), 81.0 (br, allyl-CH2), 87.0 (Fc-
Cq), 121.5 (allyl-CH), 127.3 (Ar-Cq), 127.9 (Ar-Cq),
129.4 (Ar-CH), 133.0 (Ar-CH), 133.6 (Ar-CH), 133.7
(Ar-Cq), 133.9 (Ar-CH), 134.1 (Ar-CH), 163.4 (2-Cq).
31P-NMR (121 MHz, CDCl3): d (ppm) 20.0 (s). HRMS
(FAB) Calcd. for C34H31FeNOPPd: 662.0517. Found:
661.8481.
M.p. 155.0Á
IR (KBr): nꢂ2925, 1736, 1699, 1684, 1651, 1559, 1474,
1460, 1136, 839, 665 cmꢀ1 1H-NMR (300 MHz,
CDCl3): d (ppm) 1.69 (br s, 6H, 2ꢃCH3), 2.61 (d,
Jtrans 12.3 Hz, 1H, allyl-CHH), 2.64 (d, Jtrans 12.6
6.0 Hz, 1H, allyl-
1.5 Hz, 1H, allyl-
/
156.0 8C. [a]Dꢂ
/
ꢀ
/
269 (cꢂ/0.63, EtOH).
/
.
/
3.9. Pd-catalysed allylic substitution of (E)-1,3-
diphenyl-2-propenyl acetate (12)
ꢂ
/
ꢂ
/
Hz, 1H, allyl-CHH), 3.26 (d, Jcis
ꢂ
ꢂ
/
?
C?HH), 3.85 (dd, Jcis
ꢂ
/
6.6 Hz, Jallyl
/
3.9.1. With ligand 3 in THF
C?HH), 4.18 (br s, 14H, Fc), 4.25 (br s, 2H, Fc), 4.31 (br
s, 2H, Fc), 4.85 (br, 2H, CHHO), 4.99 (br, 4H, CHHOꢁ
Phosphinooxazoline 3 (15 mg, 0.03 mmol), di-m-
chloro-bis(p-allyl)palladium (4 mg, 0.01 mmol) and
LiOAc (0.6 mg, 0.01 mmol) were dissolved in anhydrous
THF (1 ml). After 30 min of stirring at r.t., a solution of
the allyl acetate 12 (123 mg, 0.49 mmol) in anhydrous
THF (1 ml) was added and stirring was maintained for 1
h. BSA (0.36 ml, 1.46 mmol) and dimethyl malonate
(0.17 ml, 1.46 mmol) were added with the aid of a
calibrated syringe and the solution was stirred at r.t. for
16 h. At this point, TLC showed that only a trace of the
starting acetate was present in the reaction mixture, that
was diluted with CH2Cl2 (5 ml) and washed with water
/
?
CHN), 5.24 (tt, Jtrans
ꢂ
/
12.6 Hz, Jcis
ꢂ6.9 Hz, 1H, allyl-
/
CH). 13C-NMR (75 MHz, CDCl3): d (ppm) 23.5 (CH3),
27.1 (CH3), 40.5 (Cq, C(CH3)2), 61.5 (allyl-CH2), 61.7
(allyl-C?H2), 66.3 (CHN), 67.8 (Fc-CH), 68.3 (Fc-CH),
68.8 (Fc-CH), 69.7 (Fc-CH), 75.8 (CH2O), 87.0 (Fc-Cq),
115.7 (allyl-CH), 172.1 (oxazoline-Cq). HRMS (FAB)
Calcd. for C32H35FeN2O2Pdꢁ
/
: 697.0427. Found:
696.9149.
3.8. [(S)-Diphenyl-(2?-(4-ferrocenyl(1,3-oxazolin-2-
yl)phenyl))phosphine]-[p-allyl]palladium(II)
hexafluorophosphate (15)
(3ꢃ
concentrated in vacuo. The crude product was purified
by column chromatography (silica gel, C6H14ÁEtOAc
mixtures of increasing polarity). Compound (ꢁ)-13 was
/
2 ml). The organic layer was dried over MgSO4 and
/
To a stirred suspension of di-m-chloro-bis(p-allyl)pal-
ladium (19 mg, 0.051 mmol) in absolute EtOH (2 ml), a
solution of phosphinooxazoline 3 (50 mg, 0.097 mmol)
in absolute EtOH (2 ml) was added via cannula at r.t.
The resulting mixture was stirred for 1 h at r. t., at which
point a homogeneous orange-coloured solution was
obtained. Solid ammonium hexafluorophosphate (17
mg, 0.089 mmol) was added in one portion, and the
mixture was left in the refrigerator (4 8C) for 48 h. The
precipitate was isolated by filtration, washed with cold
(0 8C) absolute EtOH and dried in vacuo to afford 36
mg (46%) of the title compound 15 as an orange
crystalline solid.
/
isolated as a colourless oil (115 mg, 72% yield, 97:3 er).
3.9.2. With preformed catalyst 15 in CH2Cl2
To a stirred solution of complex 15 (11.3 mg, 0.014
mmol) and LiOAc (0.4 mg, 0.006 mmol) in anhydrous
CH2Cl2 (1 ml) a solution of the allyl acetate 12 (70 mg,
0.28 mmol) in anhydrous CH2Cl2 (1 ml) was added and
stirring was maintained for 30 min at r. t.. BSA (0.21 ml,
0.83 mmol) and dimethyl malonate (96 ml, 0.83 mmol)
were added with the aid of a calibrated syringe and the
solution was stirred at r.t. for 7 days. The reaction
mixture was diluted with CH2Cl2 (5 ml) and washed

R.M. Moreno et al. / Journal of Organometallic Chemistry 660 (2002) 62Á
/70
69
with water (3ꢃ/2 ml). The organic layer was dried over
column chromatography (silica gel, C6H14Á
/
EtOAc mix-
MgSO4 and concentrated in vacuo. The crude product
was purified by column chromatography (silica gel,
tures of increasing polarity). Compound (ꢀ
isolated as a colourless oil (93 mg, 100% yield, 56:44 er).
The absolute configuration of (ꢀ)-19 was assigned by
comparison of the optical rotation value ([a]Dꢂ 3.6
(cꢂ1.66, CHCl3)). with literature data [19]. Conditions
for the GC determination of the enantiomeric purity of
19: b-DEX column, Tꢂ120 8C, tR(S) 96.6 min,
tR(R) 98.0 min.
/
)-19 was
C6H14Á
pound (ꢁ
63% yield, 99.8:0.2 er). The absolute configuration of
(ꢁ)-13 was assigned by comparison of the optical
rotation value ([a]Dꢂ 18.0 (cꢂ1.1, EtOH)). with
/EtOAc mixtures of increasing polarity). Com-
/
/)-13 was isolated as a colourless oil (57 mg,
/
ꢀ
/
/
/
/
ꢁ
/
/
/
ꢂ
/
literature data [14]a, [18]. Conditions for the HPLC
determination of the enantiomeric purity of 13: Chir-
ꢂ
/
alcel-ODH column, 99% C6H14Á
Fꢂ 25 8C, lꢂ
0.3 ml minꢀ1, Tꢂ
min, tR(S) 42.7 min.
/
1% isopropyl alcohol,
/
/
/
254 nm, tR(R) 39.7
ꢂ
/
Acknowledgements
ꢂ
/
We gratefully acknowledge financial support from
DGI (grant BQU2000-0648) and from DURSI (grant
2000SGR-00019). A.B. and R.M. are grateful to the
University of Barcelona and to the Generalitat de
Catalunya (DURSI), respectively, for predoctoral fel-
lowships.
3.10. Pd-catalysed allylic substitution of (E)-3-pentenyl
acetate (16)
To a stirred solution of complex 15 (17.6 mg, 0.022
mmol) and LiOAc (1.4 mg, 0.02 mmol) in anhydrous
THF (1 ml) a solution of the allyl acetate 16 (140 mg,
1.09 mmol) in anhydrous THF (1 ml) was added and
stirring was maintained for 1 h at r.t. BSA (0.80 ml, 3.27
mmol) and dimethyl malonate (0.38 ml, 3.27 mmol)
were added with the aid of a calibrated syringe and the
solution was heated and stirred at 70 8C until TLC
showed that the starting acetate 16 had disappeared (2
h). After cooling to r.t., the reaction mixture was diluted
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showed that the starting acetate 18 had disappeared (5
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/
The organic layer was dried over MgSO4 and concen-
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