Modular bis(oxazoline) ligands for palladium catalyzed allylic alkylation: Unprecedented conformational behaviour of a bis(oxazoline) palladium η3-1,3-diphenylallyl complex

Article abstract of DOI:10.1002/1521-3765(20020916)8:18<4164::AID-CHEM4164>3.0.CO;2-G

New families of enantiopure bis(oxazolines) with 4,5-trans (5a - g) or 4,5-cis (6c) stereochemistry at the individual rings have been prepared in high yield. Their η³-allyl palladium complexes (8a-g, 9c and 10) have been used as catalytic precu

Full text of DOI:10.1002/1521-3765(20020916)8:18<4164::AID-CHEM4164>3.0.CO;2-G

FULL PAPER
Modular Bis(oxazoline) Ligands for Palladium Catalyzed Allylic
Alkylation: Unprecedented Conformational Behaviour of a
Bis(oxazoline) Palladium h3-1,3-Diphenylallyl Complex
Miquel Angel Perica¡s,*[a] Cristina Puigjaner,[a] Antoni Riera,[a] Anton Vidal-Ferran,[a]
Montserrat Go¬mez,[b] Francisco Jime¬nez,[b] Guillermo Muller,*[b] and Merce¡ Rocamora[b]
Abstract: New families of enantiopure bis(oxazolines) with 4,5-trans (5a g) or 4,5-
cis (6c) stereochemistry at the individual rings have been prepared in high yield.
Their h3-allyl palladium complexes (8a g, 9c and 10) have been used as catalytic
precursors in allylic alkylation reactions with excellent enantioselectivities (up to
96%) for the trans oxazoline derivatives, while Pd/6c system was inactive.NMR
studies on palladium h3-1,3-diphenylallyl intermediates (11a, c and e) showed the
presence of syn/syn- and syn/anti-allyl isomers in solution; this resembles the first
example of h3-h1-h3 isomerism in Pd allylic complexes containing bis(oxazolines)
derived from malonic acid.
Keywords: allyl isomerism ¥ asym-
metric catalysis
ligands NMR spectroscopy
¥ palladium
¥
bis(oxazoline)
¥
It is thus advisable that the toolkit of the synthetic chemist
contains families of ligands with slightly different steric
characteristics, so that enantioselectivity can be fine-tuned
for a particular substrate.[3]
For historical reasons, enantiopure chiral ligands have been
taken from the shelf of nature and used either directly or after
some simple manipulation.Those belonging to one of the
most successful types, b-amino alcohols, can be derived from
amino acids by reduction protocols; however, there are some
limitations due to both enantiomer availability and structural
type.[4]
We have shown that synthetic yet enantiopure epoxides,
readily available through well established reactions of very
broad scope, such as the Sharpless[5] and the Jacobsen
epoxidations,[6] are a most convenient source of structurally
diverse amino alcohols through regioselective ring-opening/
protection sequences (Scheme 1).[7]
These amino alcohols are devoid of the limitations encoun-
tered in those derived from natural amino acids, and we have
succeeded in developing optimal ligands for a variety of
processes and substrates through its structural fine-tuning.[8]
Introduction
Chiral ligands play a fundamental role in the complex
phenomenon of asymmetric catalysis.[1] Thus, they are not
only responsible for the activation of the metal atom where
the catalytic activity resides, but also for the generation of a
disymmetric environment around the metal atom which is in
the origin of the enantioselectivity of the process.
In most cases, the molecular recognition between the
metal ligand aggregate and the reacting molecule goes
beyond a simple interaction between functional groups.Even
the interaction between purely skeletal regions of these
species can contribute in a significant manner to the differ-
entiation between diastereomeric transition states and, hence,
to the enantioselectivity of the reactions.
Because of this, universally useful ligands are rare and
optimal ligands often vary, even within a single reaction type,
from one substrate to another.[2]
¡
[a] Prof.M.A.Perica s, Dr.C.Puigjaner, Dr.A.Riera, Dr.A.Vidal-Ferran
¡
Departament de QuÌmica Organica
Universitat de Barcelona
Parc CientÌfic de Barcelona, Josep Samitier 1-5
08028 Barcelona (Spain)
Sources of diversity
Fax : (‡34) 93-4037095
E-mail: mpericas@pcb.ub.es
NR21
O
¬
¬
[b] Prof.G.Muller, Dr.M.Go mez, Sr.F.Jime nez, Dr.M.Rocamora
Ar
OH
Ar
OR2
¡
Departament de QuÌmica Inorganica
OH
Universitat de Barcelona
1
2
¡
MartÌ i Franques 1-11, 08028 Barcelona (Spain)
Fax : (‡34) 93-4907725
Scheme 1.Regioselective ring-opening/protection sequences of enantio-
pure epoxides.
E-mail: guillermo.muller@qi.ub.es
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Chem. Eur. J. 2002, 8, No. 18

4164 4178
This is, in fact, greatly facilitated by the completely modular
nature of 2.
Results and Discussion
Amino alcohols 3, bearing a free amino group, are also
readily available in enantiopure form from epoxides 1 and still
present two elements of structural diversity.In fact, their
ruthenium complexes have been developed as efficient
mediators for transfer hydrogenation,[9] while the derived
oxazaborolidines 4 have been structurally optimized as
ligands for the catalytic enantioselective borane reduction of
prochiral ketones.[10]
Synthesis of the bis(oxazoline) ligands: According to our
synthetic plan, amino alcohols 3a g are the starting materials
for the preparation of bis(oxazolines) 5 6.
These amino alcohols were readily prepared from epoxy-
alcohols 1 through a well-documented procedure involving
the initial conversion to a family of diverse epoxy ethers 13,
subsequent regioselective and stereospecific ring-opening of
the epoxides with azide in the presence of lithium perchlo-
rate[13] and final reduction of the intermediate azido alcohols
14 (Scheme 2).Whereas amino alcohols 3a e have been
previously reported and used as oxazaborolidine precursors
(3 f, g),[10] incorporating aryl groups other than phenyl as a
further source of diversity, have been designed and prepared
for the purposes of this research.
Sources of diversity
H
NH2
Ar
N
B
R2
Ar
OR1
N
O
OH
OR1
3a: R1 = CH3, Ar = Ph
3b: R1 = CH2Ph, Ar = Ph
3c: R1 = CHPh2, Ar = Ph
3d: R1 = CPh3, Ar = Ph
4
O
O
a)
b)
Ar
OCHPh2
Ar
OH
3e: R1 = (CH2)2OCH3, Ar = Ph
3f: R1 = CHPh2, Ar = mesityl
3g: R1 = CHPh2, Ar = 1-naphthyl
13f: 70%
13g: 87%
1f: Ar = mesityl (>99% ee)
1g: Ar = 1-naphthyl (86% ee)
NH2
Ar
N3
c)
As a continuation of these efforts, we planned to investigate
the use of amino alcohols 3 for the preparation of bis(oxazo-
lines) 5 and 6.
OCHPh2
Ar
OCHPh2
OH
OH
3f: 42% (conv. 51%) (>99% ee)
3g: 70% (>99% ee)
14f
14g
O
O
O
O
Scheme 2.Synthesis of chiral amino alcohols 3 from epoxyalcohols 1.
a) NaH, DMF, BrCHPh2, 08C, 17 h; b) NaN3, LiClO4, CH3CN, 558C, 24 h;
c) NaBH4, THF/MeOH, 55 608C, 22 h.
N
N
N
N
R1O
R1O
OR1
OR1
Ar
Ar
Ar
Ar
5
6
The formation of epoxyethers 13a d, bearing alcohol
protecting groups of increasing size, and 13e, with a protecting
group with chelating ability, took place uneventfully by the
reported procedure.[10] For the synthesis of 13 f, g, in turn, the
corresponding epoxyalcohols 1 f[14] and 1g[15] were treated
with benzhydryl bromide in the presence of NaH in DMF at
08C.This led to the formation of 13 f, g in 70 and 87% yield,
respectively.The regioselective and stereospecific ring-open-
ing step of these epoxyethers was carried out under Crotti×s
conditions, which involve the use of sodium azide in a 5m
LiClO4 solution in acetonitrile.Under these conditions, the
intermediate azido alcohols 14 f, g were obtained in quanti-
tative yield and were further converted into the final amino
alcohols 3 f, g without purification.The azido group in these
intermediates was reduced with sodium borohydride in THF/
MeOH, as these conditions turned out to be harmless to
benzylic ethers.Amino alcohol 3g was obtained in good yield
(70%) and enantiomerically pure (>99%) after enantiomeric
enrichment by selective crystallization of the racemate from
pentane/dichloromethane (1:1).However, the reduction of
14 f leading to 3 f posed some problem.After 22 hours at 55
608C, conversion was only 51%, although the reaction
proceeded very cleanly (83% selectivity; 42% yield).An
increase in the temperature (808C) and in the reaction time
(2 d) did not improve this result.Most probably, the difficul-
ties observed in reduction of this azide can be attributed to the
Metal complexes of bis(oxazolines) 7, ultimately derived
from amino acids, have successfully been employed as
catalysts in a variety of enantioselective processes.[11] Among
them, the palladium-catalyzed allylic substitution appeared as
especially well suited for the purpose of this research,[12] since
Ar and OR1 groups of different steric and electronic nature in
5 and 6 could, in principle, exert a tuning of the catalytic
activity and enantioselectivity of the corresponding p-allyl
palladium complexes 8 12.
O
R
O
O
O
N
N
R1O
OR1
N
N
Pd
Ar
Ar
X
R
R
R
7
8-12
In line with these ideas, we report herein the synthesis of a
diverse family of bis(oxazolines) 5 and 6, bearing Ar and OR1
groups of different size, from the corresponding enantiopure
amino alcohols 3.An NMR study of p-allyl palladium
complexes involving symmetrically substituted allyl residues
(11, 12) and the use of the unsubstituted p-allyl complexes
(8 10) as catalysts in the alkylation of rac-1,3-diphenylprop-
2-enyl acetate with dimethyl malonate are also reported.
Chem. Eur. J. 2002, 8, No. 18
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M.A.Perica s, G.Muller et al.
FULL PAPER
Table 1.Yields for the synthesis of trans 5a g bis(oxazolines).
presence of the two methyl groups in the ortho position of the
mesityl group, which could strongly hinder the approach of
the nucleophile to the reacting carbon.
O
O
N
N
R1O
OR1
With the family of amino alcohols 3a g at hand, their
conversion into bis(oxazolines) was studied next.Interest-
ingly the substitution scheme in 3 offers the possibility of
systematic variations of steric, electronic, and binding char-
acteristics of the target ligands as well as the selection of the
stereochemistry (cis or trans) in the individual oxazoline rings
in order to achieve improved catalytic behaviour.Up to now,
examples of bis(oxazolines) with a 4,5-disubstitution scheme
in the individual rings, as those being the target of our
research,[12b, 16] have been scarce.However, stereodivergent
methodology for the preparation of cis- or trans-substituted
derivatives from a single, stereodefined amino alcohol has
already been developed.[16a]
Ar
Ar
5a: R1 = CH3, Ar = Ph
5b: R1 = CH2Ph, Ar = Ph
5c: R1 = CHPh2, Ar = Ph
5d: R1 = CPh3, Ar = Ph
5e: R1 = (CH2)2OCH3, Ar = Ph
5f: R1 = CHPh2, Ar = mesityl
5g: R1 = CHPh2, Ar = 1-naphthyl
Bis(oxazoline)
A[a]
[%]
B‡C[a]
Overall yield
[%]
[%]
5a
5b
5c
5d
5e
5 f
5g
95
80
97
99
92
96
91
96
89
95
93
87
77
88
95
72
95
93
Studies directed to the conversion of amino alcohols 3a
g
81
into the corresponding trans bis(oxazolines) 5 were first
undertaken.These are, in fact, the expected products in the
usual preparation of mono- and bis(oxazolines) from amino
alcohols, which usually involves inversion at the hydroxyl-
bearing carbon atom.Thus, the usual three-step process
beginning with the condensation of malonic acid derivatives
with amino alcohols to form bis(hydroxyamide) intermediates
15 was followed (Scheme 3).The activation of the free
hydroxy groups in 15 allows a subsequent base-induced
cyclization taking place through SN2 mechanism which leads
to the target bis(oxazolines) 5.The major variations within
this general method lie in the use of diverse activating
agents[17] as well as different bases[17c] to affect the ring-closure
step.After some exploratory experiments, activation as
mesylate[17c] and the use of 5% KOH/MeOH to induce
cyclization were selected as the most appropriate for amino
alcohols 3a g.
100
100
[a] See Scheme 3.
acid[17b] induced a selective reaction.Fortunately, treatment
of the bis(hydroxyamides) 15a g with 2.2 equivalents of
methanesulfonyl chloride and 4.4 equivalents of triethylamine
in CH2Cl2 at 08C for two hours,[17c] afforded the corresponding
bis(mesylates) 16a g in quantitative yield.Due to limited
stability, it is advisable to perform the base-induced cycliza-
tion of 16 inmediately after its preparation.Potassium
hydroxide in MeOH (5%)[17c] at room temperature provided
excellent results in the cyclization of 16 leading to bis(oxazo-
lines) 5.Somewhat surprisingly, other bases such as NaOH in
H2O/MeOH failed to induce cyclization.
Quite interestingly, bis(oxazolines) 5a g obtained by this
procedure were notably pure, so that further purification of
these highly polar materials was not necessary.[18] The derived
p-allyl palladium complexes could be prepared directly from
the crude reaction products and, thanks to its high crystallinity
(8, 9c, 10), allowed further purification whenever necessary
(see below).
a)
Cl
O
O
Cl
OH
OH
NH2
b)
B
NH HN
O
O
Ar
OR1
OR1 Ar
Ar OR1
A
OH
The relative trans stereochemistry of the chiral centres in
the individual oxazoline rings of 5 was confirmed by means of
a NOESY experiment on 5c, where an NOE signal could be
observed between CH-N and the single CH2 unit (Figure 1).
3
15
O
O
O
O
OMs
OMs
c)
NH HN
N
N
OR1
C
R1O
Note the mean overall yield for the preparation of 5a
from 3a g by the discussed procedure is 87%.
g
OR1 Ar
Ar OR1
Ar
Ar
16
5
As we have already mentioned, the trans stereochemistry in
the individual oxazoline rings in 5a g arises from the fact that
the cyclization step takes place with inversion of configuration
at C-2, where the hydroxyl substituent has been previously
activated as a mesylate.Therefore, the preparation of
bis(oxazolines) 6, with cis stereochemistry at the individual
rings, requires a synthetic route taking place with retention of
configuration at C-2.Among the different methods fulfilling
this requirement,[19] the Desimoni methodology,[19d] which
involves the use of a catalytic amount of Bu2SnCl2 to affect
both the activation and the cyclization of a bis(hydroxyamide)
intermediate, was selected.Starting from 15c, heating in
xylene under reflux for 48 hours in the presence of a catalytic
Scheme 3.Three-step synthesis of bis(oxazolines) 5 from amino alcohols
3.a) Et 3N, CH2Cl2; RT, 20 h; b) 2.2 equiv MsCl, 4.4 equiv Et3N, CH2Cl2,
08C ! RT, 2 h; c) 5% KOH/MeOH, RT, 15 h.
The initial condensation of 3a g with dimethylmalonyl
dichloride was carried out in the presence of triethylamine at
room temperature for 20 h.[17a] The resulting bis(hydroxy-
amides) 15 were obtained in excellent yields in all cases
(Table 1) and were used as starting materials for the next step
without further purification.Next, the activation of the free
hydroxyl groups in 15a g was studied.Neither the use of
thionyl chloride[17a] nor treatment with methanesulfonic
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Catalyzed Allylic Alkylation
4164 4178
methodology previously described.[12b, 12h] These allyl com-
pounds were obtained as monometallic complexes of general
formula [Pd(h3-allyl)(L)]PF6, where the ligand is N,N-bonded
to the metallic centre, see below.
O
O
O
O
N
N
N
N
R1O
Ph2HCO
OR1
PF6
OCHPh2
PF6
Pd
Pd
Ar
Ph
Ar
Ph
9c
8a: R1 = CH3, Ar = Ph
8b: R1 = CH2Ph, Ar = Ph
8c: R1 = CHPh2, Ar = Ph
8d: R1 = CPh3, Ar = Ph
O
O
8e: R1 = (CH2)2OCH3, Ar = Ph
8f: R1 = CHPh2, Ar = mesityl
8g: R1 = CHPh2, Ar = 1-naphthyl
N
N
Pd
Ph
Ph
PF6
10
O
O
O
O
N
N
N
N
R1O
H3CO
OR1
PF6
OCH3
PF6
Pd
Pd
Ph
Ph
Ph
Ph
Ph
Ph
Figure 1.Part of the NOESY spectrum (35. 5 ppm) of 5c (arrows indicate
NOE contacts between H3 and H4 protons).
11a: R1 = CH3
12a
11c: R1 = CHPh2
amount of Bu2SnCl2 afforded bis(oxazoline) 6c (Scheme 4).
The preparation of its p-allyl palladium complex allowed a
complete purification of the crude.
11e: R1 = (CH2)2OCH3
Type-11 complexes, contain-
ing the more sterically demand-
ing 1,3-diphenylallyl ligand
were obtained in low yields as
oils.Only 11e could be isolated
as an orange foam and fully
characterized by NMR spectro-
scopy and mass spectrometry
(see Experimental Section).
O
O
O
O
HO
OH
a)
N
N
Ph2HCO
NH HN
OCHPh2
OCHPh2
Ph2HCO
Ph
Ph
Ph
Ph
6c
15c
Scheme 4.Synthesis of bis(oxazoline) 6c from bis(hydroxyamide) 15c.a) Bu 2SnCl2, xylene, reflux, 48 h.
Most probably, the difficulties met in the formation of these
complexes respond to an increased steric interaction between
the substituents on the oxazoline rings and the allyl ligand.In
this respect, it is worth noting that 6c does not form a h3
complex with the 1,3-diphenylallyl group, and this fact could
be attributed to a conformational change in the phenyl
substituents at C-4 in the oxazolines, due to the increased
interaction with the alkoxyalkyl substituent at C-5, leading to
an even stronger interaction with the allyl ligand.
The poor catalytic results obtained with 6c, as it will be
discussed later, did not warrant the continuation of synthetic
efforts towards the preparation of related molecules with the
same stereochemistry.They could be important, however, as
catalytic ligands for different processes and, in that case, other
members of the same family could be readily obtained by the
same procedure.[11]
Allylic palladium complexes–NMR studies: Ionic palladium
complexes containing the non-substituted allyl (8a g, 9c and
10), 1,3-diphenylallyl (11a, c and e) and cyclohexenyl (12a)
groups were prepared from standard palladium dimer mate-
rials and the appropriate chiral ligand in the presence of
ammonium hexafluorophosphate (Scheme 5), following the
The complexes were fully characterized by the usual
techniques.The IR spectra showed a strong signal in the
range 1660 1665 cmÀ1 assigned to the C N stretching of the
ˆ
oxazoline moiety, in similar position to that observed in the
free ligands.Positive FAB mass spectra exhibited, in all cases,
the peak at highest m/z ratio for the ™[Pd(h3-allyl)(L)]∫
fragment.
a)
[Pd(η3-allyl)(L)]PF6
[Pd(η3-allyl)(µ-X)]2
+
2 L
The NMR spectroscopy has been the most useful technique
to determine the structure of these complexes in solution.[20]
The relevant 1H NMR data are summarized in Tables 2 and 3.
Unfortunately, it was not possible to obtain any crystal of
sufficient quality to perform X ray diffraction measurements.
(X = Cl, Br)
8a-g, 9c, 10: allyl = C3H5
11a,c,e: allyl = 1,3-Ph2-C3H3
12a: allyl = cyclo-C6H9
Scheme 5.Synthesis of allyl complexes ( 8a g, 9c, 10, 11a, 11c, 11e, 12a)
containing bis(oxazolines).a) NH PF6.
4
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¡
M.A.Perica s, G.Muller et al.
FULL PAPER
Table 2.Selected 1H NMR (CDCl3, 298 K, 500 MHz) data[a] (d in ppm) for complexes 8a g, 9c and 10.
5
Hcentral
1
O
O
6
2
4
Hsyn
N
N
RO
OR
3
Hanti
'R
R'
Com- 2[b]
3
4
5
central
syn
anti
other
plex
8a
4.62 (m, 2H)
5.25
(d, 7.0, 1H)
5.15
(d, 7.5, 1H)
5.19
(brs, 2H)
3.79
(brd, 4, 2H)
3.75 (dd,
4.5, 3.5, 2H)
3.90 (dd, 11.1,
3.3, 2H)
3.84 (dd, 11.1,
4.5, 2H)
3.92
(dd, 12, 4, 1H)
3.88
1.89
(s, 3H)
1.85
(s, 3H)
1.81
(s, 6H)
4.99 (tt,
12.0, 7.5, 1H)
3.42
2.61
R ˆ CH3:
(brd, 6.5, 1H)
2.83 (dd,
7.0, 2.0, 1H)
3.41
(brd, 7.8, 1H)
2.83
(d, 13.0, 1H) 3.50 (s, 3H)
1.89
(d, 12.0, 1H)
2.57
(d, 12.3, 1H) 4.65 (s, 4H)
1.89
(d, 12.6, 1H)
2.61
3.47 (s, 3H)
8b[c]
4.61
(m, 2H)
4.97
(tt, 12.6, 7, 1H)
R ˆ CH2(Ph):
(dd, 7, 1.9, 1H)
3.41
8c
4.64
(m, 2H)
5.24
(d, 6.5, 1H)
5.15
1.82
(s, 3H)
1.75
5.02
R ˆ CH(Ph)2:
(tt, 12.6, 6.9, 1H) (brd, 7.2, 1H)
2.88
(d, 12.5, 1H) 5.54 (s, 1H)
1.95
5.51 (s, 1H)
(d, 6.5, 1H)
(dd, 12, 4, 1H)
3.81
(s, 3H)
(dd, 6.9, 3.5, 1H) (d, 12.5, 1H)
(dd, 12, 4, 1H)
3.76
(dd, 12, 4, 1H)
3.69
8d[c]
4.49
(m, 2H)
5.06
(d, 7.2, 1H)
5.03
1.94
5.06 4.9
(m, 1H)
3.37
(brd, 6, 1H)
2.84
2.57
(dd, 11.5, 3.3, 2H) (s, 7H)[d]
3.56
(d, 12.3, 1H)
[d]
(m, 1H)
5.20
(brs, 2H)
3.87
(dd, 11.5, 4.8, 2H)
3.89
(m, 2H)
(brd, 6.6, 1H)
3.42
(tt, 12.3, 6.9, 1H) (brd, 6.9, 1H)
8e[c]
4.64
(m, 2H)
1.87
(s, 6H)
4.98
2.6
R ˆ
(d, 12.6, 1H) (CH2)2OCH3
2.83
1.89
(d, 12.6, 1H)
3.76 3.57
(m, 8H)
(CH2)2OCH3
3.37
(m, 2H)
(dd, 7.2, 1.8, 1H)
(s, 6H)
8 f[c]
4.77
(m, 1H)
4.75
5.76
(d, 8.4, 1H)
5.59
3.90
1.75
(s, 3H)
1.72
5.03
(tt, 12.5, 7, 1H)
2.56
(dd, 7.0, 2, 1H)
3.35
2.41
(d, 12.5, 1H) 5.47 (s, 2H)
1.88 mesityl
(d, 12.5, 1H) Me
2.05, 2.12, 2.22
R ˆ CHPh2:
(dd, 11, 2.5, 2H)
3.73
(dd, 11, 2.5, 2H)
(m, 1H)
(d, 9.3, 1H)
(s, 3H)
(dd, 6.5, 2, 1H)
(each: s, 6H)
CH
6.7 (s, 4H)
R ˆ CHPh2:
5.67 (s, 2H)
8g
4.73
(brd, 4.1, 2H)
6.14
(brs, 2H)
4.09 (dd, 10.5,
4.2, 2H)
3.99 (dd, 10.5,
4.2, 2H)
3.25 3.20
(m, 4H)
1.89
(s, 6H)
4.89
(tt, 12.5, 7, 1H)
2.96
(brd, 7, 1H)
2.51
(brd, 7, 1H)
4.11
2.6
(d, 12, 1H)
1.70
(d, 12, 1H)
2.57
9c[c]
5.40 5.27
(m, 2H)
5.64
(d, 10.5, 1H)
5.53
1.84 (s, 3H) 4.88
1.77 (s, 3H) (tt, 12.3, 7.3, 1H) (d, 4.8, 1H)
2.72
R ˆ CH(Ph)2
(d, 12.3, 1H) 4.97 (s, 1H)
1.72
4.94 (s, 1H)
(d, 10.5, 1H)
(dd, 6.9, 1.8, 1H) (d, 12.6, 1H)
10[e]
5.00 (m, 3H)[f] 5.53
4.30 (m, 2H)
1.88 (s, 3H) 5.00 (m, 3H)[f]
1.84 (s, 3H)
3.43
2.57
(dd, 10.4, 7.0, 1H)
5.42
(d, 6.6, 1H)
2.85
(d, 12.4, 1H)
1.93
(dd, 10.4, 7.7, 1H)
(d, 6.0, 1H)
(d, 12.5, 1H)
[a] Multiplicity (br, broad; d, doublet; m, multiplet; q, quartet; s, singlet; t, triplet), coupling constants (in Hz), and relative integration in parentheses.[b] see
formala for labeling scheme.[c] 300 MHz spectrum. [d] One anti proton overlapped with H5 protons.[e] 250 MHz spectrum.[f] Two H2 protons and H
central
proton are overlapped.
Upon coordination of the C2 symmetrical ligands to the
metal, the loss of ligand symmetry is observed in H NMR
anti protons are observed for each of the allyl complexes.Allyl
protons of type-11 complexes appear shifted downfield
compared with the corresponding non-substituted allyl com-
pounds, type-8, probably due to the presence of the phenyl
substituents.
Variable temperature NMR experiments indicate a dynam-
ic behaviour of the allyl complexes.For complex 8a, 1H NMR
spectra were recorded in the temperature range À35 558C
(Figure 2).Concerning the bis(oxazoline) ligand, the protons
1
spectra, because some proton signals are duplicated relative
to the free ligands.Therefore, methyl protons H5 appear as
two singlets (8a, c, 9c, 10, 11a, c, e, 12a); protons H3, as two
doublets (8a, c, d, f, h, 9c, 11a, c, e, 12a); and diastereotopic
protons H4 are split in up to four set of signals for 8c and 11c
complexes.Obviously, this asymmetry is also shown in the
allyl moiety.Therefore, two set of signals for each syn and/or
4168
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Catalyzed Allylic Alkylation
4164 4178
Table 3.Selected 1H NMR (298 K, 500 MHz, CDCl3) data[a] (d in ppm) for complexes 11a, c, e and 12.
Complex
2[b]
3
4
5
central
syn
anti
other
[Ccentral
]
[Cterminal
]
[Cterminal]
syn/syn-11a[c]
4.37
(m, 2H)
4.26
(d, 3.5, 1H)
4.04
3.57
(m, 2H)
3.42
1.98
(s, 3H)
1.67
5.73 (dd, 12.5,
10.5, 1H)
5.33
(d, 12.5, 1H)
3.82
R ˆ CH3:
3.48 (s, 3H)
3.36 (s, 3H)
(d, 2, 1H)
4.54
(d, 3.5, 1H)
4.22
(m, 2H)
3.73
(dd, 10, 7.5, 1H)
3.58
(s, 3H)
1.75
(s, 3H)
1.49
(d, 10.5, 1H)
5.31
(d, 12.5, 1H)
3.65
syn/syn-11c
4.35
(m, 2H)
5.68 (dd, 12.5,
10.5, 1H)
R ˆ CH(Ph)2:
5.64 (s, 1H)
5.25 (s, 1H)
(d, 4, 1H)
(dd, 10, 5, 1H)
3.51
(s, 3H)
(d, 10.5, 1H)
(dd, 11, 3.5, 1H)
3.31
(dd, 11, 3, 1H)
3.71 3.42
(m)[d]
syn/syn-11e
syn/anti-11e
12a
4.35 4.32
(m, 2H)
4.22
(d, 4.0, 1H)
3.98
1.87
(s, 3H)
1.58
5.66
5.25
(d, 13, 1H)
[85.2]
R ˆ
(dd, 13,
10.5, 1H)
[107.4]
(CH2)2OCH3
3.36
(d, 4, 1H)
(s, 3H)
3.70
(s, 3H)
3.29
(dd, 10.5, 1, 1H)
[72.2]
3.8
(d, 12, 1H)
[76.0]
(s, 3H)
R ˆ
4.61
5.16
(d, 6.5, 1H)
3.88
3.82
1.81
(s, 3H)
1.67
5.03
(dd, 12, 8, 1H)
[105.0]
4.58
(d, 8, 1H)
[80.7]
[d]
(ddd, 6.5, 3,
3, 1H)
4.35
(m, 2H)
(CH2)2OCH3
3.29
[d]
(d, 5.5, 1H)
(s, 3H)
(s, 3H)
3.26
(s, 3H)
R ˆ CH3:
(m, 1H)
4.57
(m, 2H)
5.19
(d, 7.0, 1H)
5.13
3.79
(t, 4.0, 2H)
3.70
1.87
(s, 3H)
1.84
5.09
(t, 6.5, 1H)
4.67
(m, 1H)
3.56
3.48 (s, 3H)
3.43 (s, 3H)
cyclohexenyl
CH2 groups:
0.07; 0.53; 0.89;
1.18; 1.31; 1.44
(each: m, 1H)
(d, 7.0, 1H)
(m, 2H)
(s, 3H)
(m, 1H)
[a] Multiplicity (d, doublet; m, multiplet; q, quartet; s, singlet; t, triplet), coupling constants (in Hz), and relative integration in parentheses.In brackets, 13C
chemical shifts.[b] See Table 2 for labeling.[c] 300 MHz spectrum.[d] Diastereotopic 4 and (CH2)2 protons of the R substituent of the syn/syn and syn/anti
isomer appear overlapped in the 3.72 3.42 ppm range.
observed, neither between the
pairs of the syn or anti protons
nor among them.
In order to elucidate the
solution structure of these com-
plexes and their dynamic be-
haviour, some NOE NMR ex-
periments were carried out.
From NOE contacts, we could
associate the allyl protons with
the bis(oxazoline) protons
nearby to the allyl moiety, as
shown in Figure 3 for 8c, allow-
ing a complete correlation.
In addition to the NOE con-
tacts, exchange signals between
some protons (H3 and H3' or
Figure 2.Variable temperature 1H NMR spectra of 8a.
Hanti and Hanti') confirm the
presence of two movements, a
of the two oxazoline rings (H2, H3, H4, H5) give rise to two
sets of signals below 08C, but above 458C, only one set of
broad signals is observed, indicating that the movement at
high temperature in solution is fast relative to the NMR time-
scale.However, the number of signals for the allyl protons is
independent of the temperature and no coalescence is
faster apparent allyl rotation around the palladium-allyl bond
and a slower h3-h1-h3 process.[21]
It is important to note that, type-11 complexes containing
the 1,3-diphenylallyl group, can give rise to several isomers,
depending on the stereochemical relationship between the
phenyl substituents of the allyl group and the central allyl
Chem. Eur. J. 2002, 8, No. 18
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M.A.Perica s, G.Muller et al.
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5.54
Ph
Me5
o'H
MeO(H2C)2O
2'
Ph
4,4
2
O
4.22
O
3
3.92
O
Me5
Me5'
Me5'
4.64
N
N
Ho
Pd
4',4'
O
O
3.81
5.24
3'
3.76
O
3.95
Ha
5.25
H'a
3.70
O(CH2)2OMe'
N
N
Pd
2.6 Ha
3.88
4.64
1.95
Ha'
5.15
Ph
Ph
5.51
Hc
Hs'
3.41
Hs
2.88
Ph'
'Ph
Hc
syn/syn-11e
Figure 3.Relevant NOE contacts from NOESY experiment of 8c (proton
chemical shifts in ppm).
Me5
MeO(H2C)2O
2'
4,4
2
O
O
hydrogen: syn/syn; syn/anti and anti/anti.For P-donor ligands
in addition to the major syn/syn isomers, syn/anti isomers are
generally observed.But for bis(oxazolines) derived malonic
acids, only syn/syn isomers for (h3-1,3-diphenylallyl)-palla-
dium(ii) complexes have been described in the literature,[12b, f]
although we have recently observed syn/anti isomers for
analogous complexes containing chiral biphenyl-bis(oxazoli-
nes).[12i]
3
Me5'
3.88
N
N
Pd
4',4'
3'
Hc
5.16
O(CH2)2OMe'
Ph
H's
4.58
Ha
3.8
Ph
syn/anti-11e
Here, syn/syn and syn/anti isomers (ca.ratio 85/15, respec-
tively) are also detected in solution by NMR spectroscopy for
type-11 complexes (11a, c and e), but only for 11e the signals
of both isomers could be unambigously assigned (Table 3).
The combined use of two-dimensional COSY, HSQC and
NOESY experiments allows the assignment of all relevant
proton signals for 11e (Figure 4).The values of the coupling
constants between central and terminal allyl protons (13.0 and
10.5 Hz) and the presence of NOE interactions between both
terminal protons of the allyl group in the major isomer, allow
us to assign syn/syn isomer to the major species.The minor
isomer shows other values for the coupling constants (12.0 and
8.0 Hz) and no NOE contacts between terminal protons, thus
suggesting a syn/anti conformation.The central allyl proton
shows an NOE interaction with ortho hydrogens of both
phenyl groups of the allyl ligand in the syn/syn isomer, while
in the syn/anti isomer this interaction appears only with one
phenyl substituent.Moreover, both isomers show interesting
NOE contacts between allyl and oxazoline hydrogens in the
3-position.NOE contacts are observed between both methyl
groups in the 5-position and ortho hydrogens of the oxazoline
phenyl groups.Such interaction can be explained by assuming
a boat-like conformation for the chelate ring with the methyl
in a pseudoaxial position near the phenyl substituent and
interconversion with a second conformation in which the
boat-like chelate ring is inverted as reported by Pfaltz.[12b]
Interesting exchange signals between major syn/syn and
minor syn/anti isomers are observed in NOESY spectra.
Exchange between Hanti (3.70 ppm) of the major isomer and
Figure 4.Relevant NOE contacts from NOESY experiment of 11e
isomers (proton chemical shifts in ppm).
À
(85.5 ppm) of the major isomer. Therefore, the opened Pd C
bond belongs to the more electrophilic carbon atom contain-
ing the substituent that suffers the biggest steric hindrance
with the oxazoline fragment (see below, Scheme 7).In
addition, exchange signals between some protons (H3 and
H3', H2 and H2', H4 and H4') reveal that the well-known
À
apparent allyl rotation around the palladium allyl bond is
also present.[21]
For 11c an exhaustive NMR study has only been possible
for the major isomer (Table 3).According to the value of the
coupling constants for Hcentral Hanti, a syn/syn configuration is
suggested.NOESY experiments show correlative NOE inter-
actions between protons of the oxazoline ligand H3
(4.54 ppm) H4 (3.73 ppm; 3.58 ppm) H6 (5.64 ppm), and
H3' (4.22 ppm) H4' (3.31 ppm; 3.51 ppm) H6' (5.25 ppm)
as well as contacts between the allyl and the oxazoline ligands,
Hanti (5.31 ppm) H3 (4.54 ppm) and Hanti' (3.65 ppm) H3'
(4.22 ppm). Similar exchange signals between oxazoline
protons as those observed for 11e complex (H3 and H3', H4
and H4', H6 and H6') suggest the presence of the allyl rotation
mechanism.
1H NMR spectra of the complex with cyclic allyl group, 12a,
show the same pattern as the open chain ones described
above.It is noteworthy that all non allyl hydrogens of the
cyclic fragment display different chemical shifts (0.07 and
0.89 ppm, 0.53 and 1.18 ppm, 1.31 and 1.44 ppm; Table 3).
NOESY experiments show interactions between geminal
protons, allowing to assign each pair of hydrogen atoms to
one carbon.Moreover for 12a, NOE interactions between
Hsyn (4.67 ppm) Hcyclohexenyl (0.07 ppm and 0.89 ppm) H3
(5.13 ppm) as well as in the other moiety of the complex,
Hsyn (3.56 ppm) Hcyclohexenyl (1.31 ppm and 1.44 ppm) H3
(3.19 ppm) allows to describe the relative position of the allyl
H
syn (4.58 ppm) of the minor one suggests h3-h1-h3 movement.
The fact that no other Hanti Hsyn exchange is observed points
to that the exchange mechanism takes place by opening
À
selectively one of the terminal Pd C bond, leading to the
formation of the less hindered syn/anti isomer.HSQC
spectrum shows correlation between Hanti (3.70 ppm) and
terminal C (72.2 ppm), and Hanti (5.25 ppm) and terminal
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Catalyzed Allylic Alkylation
4164 4178
group and the phenyl substituent in the 3-position of the
oxazoline ligand.
Thus, rac-3-acetoxy-1,3-diphenyl-1-propene was alkylated in
dichloromethane at room temperature in the presence of 8a
g, 9c or 10 (Scheme 6), the nucleophile being generated from
dimethyl malonate, BSA, and a catalytic amount of potassium
acetate.[22] The results of the enantioselective allylic alkylation
are collected in Table 5.
Allylic alkylations catalyzed by Pd/bis(oxazoline) complexes:
When the catalytic results obtained with several bis(oxazo-
lines) derived from dimethylmalonic acid in the alkylation of
rac-3-acetoxy-1,3-diphenyl-1-propene with dimethyl malo-
nate are compared (Table 4), it is readily observed that
among ligands unsubstituted at C-5 (R2 ˆ H, entries 1 5), the
best asymmetric induction is achieved with the phenyl and the
isopropyl substituted ligands (entries 1 and 2, respectively),
while more conformationally flexible substituents (entries 3
5) lead to lower enantiomeric excesses.These results warrant
the specification of the chain substituent in our acyclic amino
alcohol precursors 3 as aryl groups, while suggesting that the
enantioselectivity of the reaction is (at least partially)
controlled by steric interactions between the R1 group in the
bis(oxazoline) and the phenyl substituents on the allyl ligands
in the palladium intermediate species.These interactions
would induce a desymmetrization of the allyl termini with
respect to palladium and ultimately determine the more
electrophilic terminal allylic carbon towards which the
external nucleophilic attack is directed.
OAc
CH(COOMe)2
a)
+
CH2(COOMe)2
*
Ph
Ph
Ph
* Ph
Scheme 6.Asymmetric allylic alkylation catalyzed by 8a g, 9c and 10.
a) 8a g, 9c, 10, BSA, KOAc, CH2Cl2, RT.
Table 5.Results of asymmetric allylic alkylation of rac-3-acetoxy-1,3-
diphenyl-1-propene with dimethyl malonate catalyzed by type-8, 9c and 10
complexes.[a]
Entry
Precursor
Conv.[b]
ee [%][c]
1
2
3
4
5[d]
6
7
8
8a
8b
8c
8d
8e
8f
8g
9c
10
26
16
60
94
81
8
100
0
23
94 (R)
95 (R)
96 (R)
96 (R)
93 (R)
50 (R)
96 (R)
9
95 (R)
Table 4.Asymmetric allylic alkylation of rac-3-acetoxy-1,3-diphenyl-1-
propene with dimethyl malonate catalyzed by Pd/bis(oxazoline) systems.
[a] Catalytic conditions: 0.02 mmol of complex 8, 9c, or 10, 1 mmol rac-1,3-
diphenyl-2-propenyl acetate, 3 mmol dimethyl malonate, 3 mmol BSA and
a catalytic amount of KOAc in 4 mL CH2Cl2 at rt for 48 h.[b] Conversion
percentage based on the substrate.[c] ee values determined by HPLC on a
Chiralcel-OD column.Absolute configuration, in parentheses, determined
by optical rotation: U.Leutenegger, G.Umbricht, C.Fahrni, P.V.Matt, A.
Pfaltz, Tetrahedron 1992, 48, 2143 2156.[d] 160 h.
O
O
R2
R2
N
N
R1
R1
Entry
Ligand[a]
ee (%)
Ref.
1
2
3
4
5
6
R2 ˆ H, R1 ˆ Ph
R2 ˆ H, R1 ˆ iPr
95[b]
94[c]
88[c]
90[c]
92[c]
97[c]
this work
[12b]
When 2 mol% of catalyst was used, the conversion of the
allylic acetate to the desired product was complete after 48
240 h at room temperature.The amount of catalyst could be
lowered to 1 mol%, but the required reaction times corre-
spondingly increased.To compare the activities of the differ-
ent bis(oxazolines), data on conversion and enantioselectivity
recorded with the studied ligands after 48 h are provided.As it
can be readily seen, catalytic activity notably increases
(conversion varies from 16 to 94%) with the size of the C-5
substituent on the oxazoline fragment in cases where the C-4
substituent is phenyl: CH2Ph <CH3 < CHPh2 < CPh3
(entries 1 4).All these catalytic systems induced high
enantioselectivities (94 96%) and, while the highest values
are recorded with ligands containing the bulkier alkoxy
groups, the differences are probably not significative.In line
with these results, when the ligand derived from phenyl-
glycinol, bearing no substituent at C-5 is studied (precursor
10, entry 9), the recorded enantioselectivity is similar to that
recorded with 8a d and the catalytic activity lies among
those of 8a and 8b.[23] This tends to indicate the existence of a
threshold value in the bulk of the C-5 substituent for its
translation into increased activity.
[12b]
[12g]
[12f]
[12b]
R2 ˆ H, R1 ˆ CH2Ph
R2 ˆ H, R1 ˆ CH(Ph)(OCOPh)
R2 ˆ H, R1 ˆ CH(Ph)(OH)
R2 ˆ Ph, R1 ˆ CH2OSi(tBu)Me2
[a] See formula.[b] Determined by HPLC on a chiral column.[c] Deter-
mined by H NMR spectroscopy with shift reagent [Eu(hfc)3].
1
Concerning the effect of substituents at the sterogenic C-5,
only one system is reported in the literature (entry 6, Table 4).
When the results in entries 3, 4 and 5 are compared with those
in entry 6, a benefitial contribution on enantioselectivity of
the substituent at C-5 is observed, despite of the rather long
distance between this part of the molecule and the region
where the reaction events take place.The high enantioselec-
tivity observed with the bis(oxazoline) developed by Pfaltz
suggested that the alkoxyalkyl substituent (CH2OR1) in the
bis(oxazolines) 5a g (i.e., the R2 substituent in Table 4),
could also exert an important influence on the reactivity and
enantioselectivity of the derived h3-allylpalladium complexes,
so that its study is a matter of interest.
To test the effect of structural variation (CH2OR1 group) in
the modular amino alcohol precursors 3 on the catalytic
activity and enantioselectivity induced by the derived bis(ox-
azoline) ligands 5 6, palladium complexes (8a g, 9c and 10)
containing an unsubstituted allyl moiety were used as catalytic
precursors in model asymmetric allylic alkylation reactions.
For the study of the influence of the aryl substituent in the
amino alcohol skeleton (C-4 substituent in the oxazoline
ring), the alkoxymethyl substituent at C-5 was specified as
benzhydryloxymethyl since, in this way, our starting point (8c)
depicts an intermediate value of activity, likely to be sensitive
Chem. Eur. J. 2002, 8, No. 18
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M.A.Perica s, G.Muller et al.
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to structural variation.When the results for 8c are compared
with those recorded for 8 f (Arˆ mesityl) and 8g (Arˆ 1-
naphthyl), the 1-naphthyl substituted ligand gave complete
conversion in 48 hours, and 96% ee (entry 7), while the
mesityl substituted ligand was the less active and the poorest
in inducing enantioselectivity (entry 6).Presumably in this
case, other palladium species are formed, because of the
O
O
Nu
Nu
Ph
a
b
N
N
OR
RO
Ph
Ph
Ph
Ph
72.2
Ph
Ph
Pd
85.2
Major product
Minor product
(R)
Ph
(S)
b
a
syn/syn-11e
À
palladium assisted C H activation of the ortho-methyl groups
of the mesityl moiety.[24] Thus, the aryl groups which are
slightly more sterically demanding than phenyl are beneficial
in the considered catalytic system; however, the sterically
crowded aryls probably prevent the achievement of the
transition state geometry in the enantioselective reaction
path.
O
O
N
N
OR
RO
Ph
Ph
Pd
Ph
Ph
Somewhat surprisingly, 9c turned out to be inactive.In this
case, where the substituents on the two stereogenic centres
are in cis arrangement, decomposition towards palladium
metal was immediately observed.In order to understand the
different behaviour of trans-5c and cis-6c ligands, and since
[Pd(h3-1,3-diphenylallyl)(6c)]PF6 could not be isolated ex-
perimentally, the diphenylallyl intermediate complexes de-
rived from these bis(oxazolines) were studied by means of
theoretical calculations, at the PM3 (tm) level.[25] The
calculated formation enthalpy of both complexes
(80.97 kcalmolÀ1 for the trans complex and 85.47 kcalmolÀ1
for the cis complex) shows that the cis is significantly less
stable than the trans arrangement, because of the steric
interactions between the oxazoline substituents.In practice,
these interactions are probably responsible for the observed
decomposition in solution when using 9c.
An additional aspect of these alkylation reactions deserve
comment.It is well known that the enantioselectivity in the
Pd-catalyzed allylic alkylation with soft reagents is controlled
by the nucleophilic attack to the more electrophilic terminal
carbon of the allyl ligand in the PdII intermediates such as 11.
As described above, 11a, c and e are, in solution, mixtures of
two isomers (syn/syn and syn/anti) and this isomerism is
observed at the more electrophilic carbon (the one exhibiting
the highest 13C chemical shifts).For 11e in particular, if both
species reacted at the same rate, the enantiomeric excess of
the reaction product would be lower (the de of the active
species is 70%) than the observed one (ee 93%), because the
nucleophilic attack on the more electrophilic carbon atoms
leads to opposite enantiomers: R configuration for syn/syn-
11e and S for syn/anti-11e (Scheme 7).The high enantiose-
lectivity observed with our ligands provides an indication that
syn/anti to syn/syn interconversion should be faster than
nucleophilic attack to the syn/anti stereoisomer.
O
O
Nu
Ph
Ph
a
b
N
N
OR
RO
Ph
Nu
not observed
Ph
Ph
Ph
Ph
Pd
(S)
80.7
Ph
76.0
a
b
syn/anti-11e
Scheme 7.Selectivity of the dimethyl malonate attack on the terminal
allylic carbon atoms of type-11 species.
derived from dimethylmalonyl dichloride, have been detected
in solution.Two-dimensional NMR experiments have shown
that the p-s-p isomerization process takes place by opening
selectively the Pd C bond containing the carbon atom which
suffers the biggest steric hindrance with the oxazoline frag-
ment.
À
According to the results reported here, both the alkox-
ymethyl moiety in the starting amino alcohols (the oxazoline
C-5 substituent) and the aryl substituent in the amino alcohol
skeleton (the oxazoline C-4 substituent) are important in
determining the catalytic activity of the palladium complexes
of trans-disubstituted oxazolines.Thus, the recorded order of
reactivity indicates that when the steric bulk of the alkoxy
methyl group increases, the aryl substituent on the same
oxazoline ring experiences a conformational change in order
to minimize the increased steric hindrance.The conforma-
tional change in the C-4 substituent, in turn, probably
provokes an increased interaction with the allyl moiety.In
response to that, the allyl group desymmetrizes with respect to
palladium, leading to a more electrophilic carbon atom more
efficiently attacked by the malonate anion.
This interpretation also explains the behaviour of the cis-
substituted bis(oxazoline) 6c.In response to the increased
steric interaction, the type-11 complex containing 6c cannot
be isolated nor generated under catalytic conditions.
In spite of the existence of syn/syn and syn/anti isomerism in
the intermediate 1,3-diphenylallyl palladium complexes, very
high enantioselectivities have been reported and this fact
provides an indication that: a) the syn/syn isomer reacts much
faster than the syn/anti one, and b) the isomerization of the
syn/anti isomer is fast relative to its alkylation.
Conclusion
In summary, a new family of bis(oxazolines) (5a g, 6c)
derived from modular, enantiopure amino alcohol has been
prepared.
Pd-allyl complexes with 5a g and 6c ligands have been
fully studied by means of NMR spectroscopy.For the first
time, syn/anti allyl isomers for type-11 compounds, containing
the disubstituted 1,3-diphenylallyl group and bis(oxazolines)
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Catalyzed Allylic Alkylation
4164 4178
EtOAc (99:1/98:2).[ a]2D3 ˆ À2.2 (c ˆ 0.75 gmLÀ1 in CHCl3); 1H NMR
(200 MHz): d ˆ 7.40 7.24 (m, 10H), 6.81 (s, 2H), 5.50 (s, 1H), 3.87 3.80
(m, 2H), 3.69 (dd, J ˆ 10.9, 5.1 Hz, 1H), 3.25 3.19 (m, 1H), 2.35 (s, 6H),
2.25 (s, 3H); 13C NMR (50 MHz): d ˆ 142.5 (C), 133.5 (C), 131.9 (C), 129.2
(CH), 129.0 (CH), 128.6 (CH), 128.1 (CH), 127.6 (CH), 127.5 (CH), 126.8
(CH), 126.4 (CH), 123.4 (CH), 122.8 (CH), 84.5 (CH), 69.3 (CH2), 60.7
Experimental Section
CAUTION: Tin compounds are highly toxic. Azide salts are toxic and may
explode if heated.
General methods: All compounds were prepared under a purified nitrogen
atmosphere using standard Schlenk and vacuum-line techniques.The
solvents were purified by standard procedures[26] and distilled under
(CH), 55.0 (CH); IR (film): nÄ ˆ 3029, 2923, 1493, 1451, 1096, 741, 702 cmÀ1
;
‡
‡
MS (CI, NH3): m/z (%): 376 (18) [M‡NH4] , 359 (22) [M‡H] , 358 (80)
nitrogen.[Pd( h3-C3H5)(m-Cl)]2,[27] [Pd(h3-1,3-Ph2-C3H3)(m-Cl)]2,[12b] and
‡
‡
[M] , 167 (100) [Ph2CH] ; HRMS (EI): calcd for C25H25O2: 357.1855;
[28]
[Pd(h3-cyclohexenyl)(m-Cl)]2
were prepared as previously described.
‡
found: 357.1863 [M À H] .
Ligand 7 (R ˆ Ph), 2,2-bis[2-(4S-phenyl-3,4-dihydrooxazol-2-yl)]propane
was prepared as described by Corey et al.[17a] Hydrogen peroxide additions
were carried out by a authomatic Metrohm 665 Dossimat syringe.NMR
spectra were recorded on Varian XL-500 (1H, standard SiMe4), Bruker
DRX 500 (1H, standard SiMe4), Varian Gemini (13C, 50 MHz, standard
SiMe4) and Bruker DRX 250 spectrometers in CDCl3 unless otherwise
cited.IR spectra were recorded on a Nicolet 520 FT-IR, Nicolet 510 FT-IR
and FTIR Nicolet Impact 400 spectrometers.FAB mass spectra were
obtained on a Fisons V6-Quattro instrument.The GC analysis were
performed on a Hewlett Packard5890 SeriesII gas chromatograph (50 m
Ultra 2 capillary column 5% phenylmethylsilicone and 95% dimethylsi-
licone) with a FID detector.The GC/MS analysis were performed on a
Hewlett Packard5890 SeriesII gas chromatograph (50 m Ultra2 capillary
column) interfaced to a Hewlett Packard5971 mass selective detector.
Optical rotations were measured on a Perkin Elmer241MC spectropo-
larimeter.Enantiomeric excess were determined by HPLC on a Hewlettt
Packard1050 Series chromatograph (Chiralcel-OD chiral column) with a
(1R,2R)-1-Amino-1-(1-naphthyl)-3-diphenylmethoxy-2-propanol (3g): A
solution of 13g (2.94 g, 8.0 mmol), LiClO4 (21.0 g, 0.198 mol), and NaN3
(2.6 g, 40 mmol) in acetonitrile (40 mL) was stirred at 558C for 24 h under
N2. H2O (480 mL) was added, and the aqueous layer was extracted with
Et2O.The combined organic extracts were dried and concentrated under
vacuum to give 14g (3.24 g) as an oil that was used in the next step without
further purification.A solution of 14g (3.24 g, 7.91 mmol) and sodium
borohydride (954 mg, 23.5 mmol) in THF (18.7 mL) was heated at 55
608C under N2.MeOH (39. mL) was added during 1 h.After the mixture
was heated at this temperature for 22 h, H2O (345 mL) was added, and the
aqueous layer was extracted with CH2Cl2.The combined organic extracts
were dried and concentrated under vacuum.The residual oil was
chromatographed through a short silica gel column using hexane/EtOAc
(60:40) as eluent to give 3g (2.12 g, 70%) and the starting product 14g
(0.3 g, 9%). Product 3g was obtained enantiomerically pure (>99%,
HPLC OD: 1 mLminÀ1, hexane/isopropanol 80:20; tR (1R,2R) ˆ 11.5 min;
tR ˆ (1S,2S) ˆ 20.8 min) after enantiomeric enrichment by selective crys-
UV detector, and by GC on
a Hewlett Packard5890 SeriesII gas
tallization of the racemate from pentane/dichloromethane 1:1.[ a]D23
ˆ
chromatograph (25 m FS-cyclodex-b-I/P column: heptakis(2,3,6-tri-O-
methyl)-b-cyclodextrin/polysiloxan) with a FID detector.Elemental anal-
À77.4 (c ˆ 1.05 gmLÀ1 in CHCl3); 1H NMR (200 MHz): d ˆ 8.11 (dd, J ˆ
6.2, 3.4 Hz, 1H), 7.85 (dd, J ˆ 6.2, 3.4 Hz, 1H), 7.75 (d, J ˆ 8 Hz, 1H), 7.63
(d, J ˆ 6.8 Hz, 1H), 7.49 7.19 (m, 13H), 5.22 (s, 1H), 5.08 (d, J ˆ 5.2 Hz,
1H), 4.23 (ddd, J ˆ 5.2, 5.2, 5.2 Hz, 1H), 3.52 3.37 (m, 2H), 2.29 (brs, 3H);
13C NMR (50 MHz): d ˆ 141.8 (C), 138.0 (C), 133.7 (C), 131.1 (C), 128.9
(CH), 128.4 (CH), 128.3 (CH), 127.7 (CH), 127.6 (CH), 127.4 (CH), 127.0
(CH), 126.6 (CH), 126.1 (CH), 125.5 (CH), 125.4 (CH), 123.6 (CH), 122.9
(CH), 84.4 (CH), 72.8 (CH), 70.2 (CH2), 53.7 (CH); IR (film): n ˆ 3371,
3062, 3029, 2921, 2867, 1598, 1493, 1453, 1077, 1028, 781, 741, 702 cmÀ1; MS
¡
yses were carried out by the Serveis CientÌfico-Tecnics de la Universitat de
Barcelona in an Eager1108 microanalyzer.
3-Acetoxy-1-cyclohexene: This product was prepared following the meth-
od described in the literature with minor modifications.[29] To a stirred
mixture of cyclohexene (15.0 g, 183 mmol), palladium acetate (42 mg,
0.18 mmol), and benzoquinone (0.59 g, 5.5 mmol) dissolved in 150 mL of
acetic acid, hydrogen peroxide (33%, 22.5 mL) was added within 6 h at
508C by a automatic syringe (0.25 mL each 4 minutes). Then, the mixture
was kept at the same temperature for 6 h.At room temperature, the
mixture was filtered over celite and extracted three times with pentane/
diethyl ether 1:1 (50 mL).The organic phases were washed with 2 m NaOH
solution (3 Â 50 mL), dried over anhydrous Na2SO4, filtered off, and the
solvent removed at room temperature, under reduced pressure.The
colourless oil was purified by flash chromatography (silica gel, hexane/
diethyl ether 1:1) to yield the title compound (11.5 g, 45%).
‡
‡
(CI, NH3): m/z (%): 401 (1) [M‡NH4] , 384 (100) [M‡H] ; HRMS (EI):
‡
calcd for C26H25NO2: 383.1885, found: 383.1892 [M] .
(1R,2R)-1-Amino-1-(2,4,6-trimethylphenyl)-3-diphenylmethoxy-2-propa-
nol (3 f): Compound 1 f (3.0 g, 8.4 mmol), LiClO4 (22.0 g, 0.207 mol), and
NaN3 (2.7 g, 41.8 mmol) in acetonitrile (42 mL) were treated as described
for 3g during 24 h.The workup was identical to the one described for 3g to
give 14 f (3.36 g) as an oil that was used in the next step without further
purification.
(2S,3S)-3-(1-Naphthyl)-2-diphenylmethoxymethyloxirane (13g): A solu-
tion of (2S,3S)-2,3-epoxy-3-(1-naphthyl)propanol 1g (1.87 g, 9.3 mmol) in
DMF (11.2 mL) was added through a cannula to a suspension of sodium
hydride (0.477 g, ca. 10.9 mmol) in DMF (11.2 mL) at 08C under N2.The
mixture was stirred for 20 min, and diphenylmethylbromide (2.93 g,
11.9 mmol) was added into the mixture with a syringe. The mixture was
stirred for 17 h at 08C.MeOH (116 mL) and brine (116 mL) were added.
The aqueous solution was extracted with Et2O.The combined organic
extracts were dried and concentrated under vacuum.The residual oil was
chromatographed using hexane/EtOAc (100:0/98:2) as eluent to give 13g
(2.96 g, 87%)as an oil. [a]2D3 ˆ ‡38.3 (c ˆ 1.4 g mLÀ1 in CHCl3); 1H NMR
(200 MHz): d ˆ 8.12 8.08 (m, 1H), 7.90 7.85 (m, 1H), 7.79 (dd, J ˆ 7,
2.2 Hz, 1H), 7.54 7.24 (m, 14H), 5.56 (s, 1H), 4.44 (d, J ˆ 2.2 Hz, 1H), 3.91
(dd, J ˆ 11, 3.7 Hz, 1H), 3.82 (dd, J ˆ 11, 5 Hz, 1H), 3.29 3.24 (m, 1H);
13C NMR (50 MHz): d ˆ 142.5 (C), 133.5 (C), 131.9 (C), 129.2 (CH), 129.0
(CH), 128.6 (CH), 128.1 (CH), 127.6 (CH), 127.5 (CH), 126.8 (CH), 126.4
(CH), 123.4 (CH), 122.8 (CH), 84.5 (CH), 69.3 (CH2), 60.7 (CH), 55.0
(CH); IR (film): nÄ ˆ 3062, 3029, 2861, 2825, 1511, 1493, 1453, 1098, 1030,
A solution of 14 f (3.36 g, 8.4 mmol), and sodium borohydride (1.01 g,
25.2 mmol) in THF (19.2 mL) was heated at 55 608C under N2.MeOH
(4.2 mL) was added during 1 h, and the mixture was heated at this
temperature for 22 h.A workup identical to the one described for 3g
followed by chromatography through a short silica gel column using
hexane/EtOAc (60:40) as eluent yielded the starting product 14 f (1.65 g,
49%) and 3 f (1.2 g, 42%). [a]2D3 ˆ À2.53 (c ˆ 0.95 gmLÀ1 in CHCl3);
1H NMR (200 MHz): d ˆ 7.39 7.25 (m, 10H), 6.83 (s, 2H), 5.47 (s, 1H),
4.52 (d, J ˆ 6.4 Hz, 1H), 4.20 (ddd, J ˆ 8.8, 5.4, 3 Hz, 1H), 3.83 (dd, J ˆ 10.2,
3 Hz, 1H), 3.72 (dd, J ˆ 9.9, 5.4 Hz, 1H), 2.41 (s, 6H), 2.24 (s, 3H), 1.64 (brs,
3H); 13C NMR (75 MHz): d ˆ 142.1 (C), 142.0 (C), 136.9 (C), 136.5 (C),
135.4 (C), 130.4 (C), 128.5 (CH), 128.4 (CH), 127.6 (CH), 127.5 (CH), 127.0
(CH), 126.8 (CH), 84.3 (CH), 73.3 (CH), 71.4 (CH2), 53.5 (CH), 21.2 (CH3),
20.7 (CH3); IR (KBr): n ˆ 3303, 3029, 2925, 1493, 1455, 1117, 1069, 1030,
‡
743, 706 cmÀ1; MS (CI, NH3): m/z (%): 376 (100) [M‡H] ; elemental
analysis calcd (%) for C25H29NO2: C 79.96, H 7.78, N 3.73; found: C 79.85, H
7.81, N 3.81.
‡
801, 780, 743, 702 cmÀ1; MS (CI, NH3): m/z (%): 384 (100) [M‡NH4] , 367
General procedure for the synthesis of compounds 8a
h3-Allyl [(4R,4'R,5S,5'S)-2,2'-(1-methylethylidene)bis(4-phenyl-5-methox-
ymethyl-4,5-dihydrooxazole)-N,N]-palladium(ii) hexafluorophosphate
g
‡
(25) [M‡H] ; HRMS (EI): calcd for C26H22O2: 366.1620; found: 366.1635
‡
[M] .
(2S,3S)-3-(2,4,6-Trimethylphenyl)-2-diphenylmethoxymethyloxirane
(13 f): Compound 1 f (2.5 g, 13 mmol) in DMF (15.7 mL), sodium hydride
(0.665 g, ca. 15.2 mmol) in DMF (15.7 mL), and diphenylmethylbromide
(4.08 g, 16.5 mmol) were treated as described for 13g with stirring 17 h at
08C to give 13 f (3.28 g, 70%) as an oil after chromatography using hexane/
(8a): Preparation of bis(hydroxyamide) 15a: A solution of dimethylma-
lonyl dichloride (0.47 g, 2.76 mmol) in CH2Cl2 (2.76 mL) was added
through
a cannula to a cold (08C) solution of (1R,2R)-1-amino-3-
methoxy-1-phenyl-2-propanol (3a; 1.00 g, 5.52 mmol) and Et3N (0.77 mL,
5.52 mmol) in CH2Cl2 (4 mL).The reaction mixture was allowed to warm to
Chem. Eur. J. 2002, 8, No. 18
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0818-4173 $ 20.00+.50/0
4173

¡
M.A.Perica s, G.Muller et al.
FULL PAPER
‡
room temperature and stirred for 20 h.The reaction mixture was diluted
with CH2Cl2 (18.4 mL) and washed with 2n HCl (3 Â 11.5 mL) and
saturated aqueous NaHCO3 (3 Â 11.5 mL). The organic extracts were dried
(Na2SO4) and concentrated under vacuum to afford the crude dihydroxy
diamide 15a (1.2 g, 95%) as a yellow foam which was used in the next
reaction without further purification. 1H NMR (200 MHz): d ˆ 7.92 (d, J ˆ
8.2 Hz, 2H), 7.33 7.19 (m, 10H), 5.25 (dd, J ˆ 8.2, 4.6 Hz, 2H), 4.01 (ddd,
1100, 733, 700 cmÀ1; MS (CI, NH3): m/z (%): 628 (3) [M‡NH4] , 611 (41)
‡
‡
[M‡H] , 610 (100) [M] .
Formation of bis(oxazoline) 5b: A solution of dihydroxy diamide 15b
(0.58 g, 0.95 mmol), Et3N (0.58 mL, 4.16 mmol) and MsCl (0.165 mL,
2.12 mmol) in CH2Cl2 (7.8 mL) was treated as described in the general
procedure.The workup was identical to the one described for 16a to give
16b (697 mg, 96%) as a white foam which was used in the next step without
further purification.Bis(mesylate) 16b (697 mg, 0.91 mmol) was treated
with KOH (15.8 mL of a 5% methanolic solution in weight, 11.25 mmol)
for 15 h as described for 5a to afford 5b (501 mg, 96%) as a yellow oil
which was used in the next reaction without further purification. 1H NMR
(200 MHz): d ˆ 7.34 7.22 (m, 20H), 4.98 (d, J ˆ 6.6 Hz, 2H), 4.59 4.50 (m,
2H), 4.57 (s, 4H), 3.67 3.65 (m, 4H), 1.68 (s, 6H); 13C NMR (50 MHz):
J ˆ 4.2, 4.2, 4.2 Hz, 2H), 3.33 (s, 6H), 3.38 3.17 (m, 4H), 1.51 (s, 6H);
13
ˆ
C NMR (50 MHz): d ˆ 173.6 (C O), 138.4 (C), 128.6 (CH), 127.4 (CH),
126.7 (CH), 73.3 (CH2), 72.0 (CH), 59.3 (CH3), 57.1 (CH), 50.0 (C), 23.6
(CH3); IR (film): nÄ ˆ 3386, 3033, 2929, 1663, 1517, 1455, 1106, 735, 700 cmÀ1
;
‡
‡
MS (CI, NH3): m/z (%): 476 (63) [M‡NH4] , 459 (100) [M‡H] .
Formation of bis(oxazoline) 5a: Methanesulfonyl chloride (0.30 mL,
3.88 mmol, 2.2 equiv) was added dropwise to a cold (08C) solution of
dihydroxy diamide 15a (0.80 g, 1.74 mmol) and Et3N (1.07 mL, 7.65 mmol)
in CH2Cl2 (14.4 mL) was added. The reaction mixture was allowed to warm
to room temperature and stirring was continued for 2 h.The reaction
mixture was then poured into saturated aqueous NH4Cl solution (16 mL).
The organic layer was separated and the aqueous layer was extracted with
CH2Cl2 (3 Â 10 mL).The combined organic extracts were washed with
brine (1 Â 10 mL), dried (Na2SO4) and concentrated under reduced
pressure to afford the crude bis(mesylate) 16a quantitatively as a yellow
oil which was used in the next reaction without further purification.The
bis(mesylate) 16a (1.05 g, 1.71 mmol) was treated with KOH (30 mL of a
5% methanolic solution in weight, 21.2 mmol, 12.4 equiv) for 15 h at room
temperature.The reaction mixture was then poured into water (17 mL).
The organic layer was separated and the aqueous layer was extracted with
CH2Cl2 (3 Â 17 mL).The combined organic layers were dried (Na 2SO4) and
concentrated under reduced pressure to afford the crude bis(oxazoline) 5a
(0.66 g, 92%) as a yellow oil which was used in the next reaction without
further purification.[ a]2D3 ˆ ‡132.0 (c ˆ 0.9 gmLÀ1 in CHCl3); 1H NMR
(200 MHz): d ˆ 7.33 7.24 (m, 10H), 4.92 (d, J ˆ 6.6 Hz, 2H), 4.52 (ddd, J ˆ
5.6, 5.6, 5.6 Hz, 2H), 3.67 3.60 (m, 2H), 3.59 3.52 (m, 2H), 3.42 (s, 6H),
ˆ
d ˆ 169.6 (C N), 142.0 (C), 137.8 (C), 128.6 (CH), 128.5 (CH), 128.4 (CH),
127.7 (CH), 127.5 (CH), 127.4 (CH), 126.6 (CH), 86.3 (CH), 73.3 (CH2), 71.9
(CH), 70.9 (CH2), 39.0 (C), 24.4 (CH3); IR (film): nÄ ˆ 1659, 1455, 1113, 737,
698 cmÀ1; MS (CI, NH3): m/z (%): 592 (3) [M‡NH4] , 575 (43) [M‡H] ,
‡
‡
‡
574 (100) [M] .
Preparation of 8b: A solution of [Pd(h3-C3H5)(m-Cl)]2 (44 mg, 0.12 mmol),
the bis(oxazoline) 5b (120 mg, 0.21 mmol) in EtOH (2 mL) and NH4PF6
(36 mg, 0.22 mmol) were treated as described in the general procedure for
14 h and then kept in the refrigerator, resulting in the separation of an
orange oil.The liquid was decanted and the oil was washed with cold EtOH
and dried under vacuum to give 8b as an orange foam (96 mg, 53%).[ a]D23
ˆ ‡ 64.2 (c ˆ 0.85 gmLÀ1 in CHCl3); 1H NMR (300 MHz): d ˆ 7.39 7.15
(m, 20H), 5.19 (brs, 2H), 4.97 (tt, J ˆ 12.6, 7.7 Hz, 1H), 4.65 (s, 4H), 4.63
4.60 (m, 2H), 3.90 (dd, J ˆ 11.1, 3.3 Hz, 2H), 3.84 (dd, J ˆ 11.1, 4.5 Hz, 2H),
3.41 (brd, J ˆ 7.8 Hz, 1H), 2.83 (dd, J ˆ 7, 1.9 Hz, 1H), 2.57 (d, J ˆ 12.3 Hz,
1H), 1.89 (d, J ˆ 12.6 Hz, 1H), 1.81 (s, 6H); 13C NMR (75 MHz): d ˆ 172.7
ˆ
(C N), 139.5 (C), 137.4 (C), 129.5 (CH), 128.9 (CH), 128.5 (CH), 128.0
(CH), 127.9 (CH), 126.6 (CH), 126.3 (CH), 116.1 (CH), 87.7 (CH), 87.5
(CH), 74.7 (CH), 74.5 (CH), 73.6 (CH2), 69.6 (CH2), 69.5 (CH2), 61.6 (CH2),
61.1 (CH2), 40.9 (C), 26.2 (CH3), 24.8 (CH3); IR (film): nÄ ˆ 3033, 1659, 1474,
1455, 1135, 1028, 837, 739, 700 cmÀ1; MS (FAB): m/z (%): 721 (100) [M À
1.69 (s, 6H); 13C NMR (50 MHz): d ˆ 169.7 (C N), 142.0 (C), 128.6 (CH),
ˆ
127.5 (CH), 126.6 (CH), 86.2 (CH), 73.6 (CH2), 71.8 (CH), 59.4 (CH3), 39.0
‡
PF6] .
(C), 24.3 (CH3); IR (film): nÄ ˆ 3064, 3031, 2985, 2935, 2881, 1659, 1455,
h3-Allyl [(4R,4'R,5S,5'S)-2,2'-(1-methylethylidene)bis(5-diphenylmethox-
‡
1133, 1113, 700 cmÀ1; MS (CI, NH3): m/z (%): 423 (100) [M‡H] .
ymethyl-4-phenyl-4,5-dihydrooxazole)-N,N]-palladium(ii)
phosphate (8c)
hexafluoro-
Preparation of 8a: A solution of [Pd(h3-C3H5)(m-Cl)]2 (183 mg, 0.50 mmol)
and crude bis(oxazoline) 5a (0.40 g, 0.95 mmol) in EtOH (3 mL) was
stirred at room temperature for 1 h and then NH4PF6 (158 mg, 0.97 mmol)
was added.The reaction mixture was stirred for 14 h and kept in the
refrigerator, resulting in the precipitation of the complex 8a as a white solid
(0.44 g, 65%) which was filtered and washed with cold EtOH. [a]2D3 ˆ ‡36.6
(c ˆ 1.0 g mLÀ1 in CHCl3); 1H NMR (500 MHz): d ˆ 7.44 7.15 (m, 10H),
5.25 (d, J ˆ 7 Hz, 1H), 5.15 (d, J ˆ 7.5 Hz, 1H), 4.99 (tt, J ˆ 12, 7.5 Hz, 1H),
4.66 4.59 (m, 2H), 3.79 (brd, J ˆ 4 Hz, 2H), 3.75 (dd, J ˆ 4.5, 3.5 Hz, 2H),
3.50 (s, 3H), 3.47 (s, 3H), 3.42 (br d, J ˆ 6.5 Hz, 1H), 2.83 (dd, J ˆ 7, 2 Hz,
Preparation of bis(hydroxyamide) 15c: (1R,2R)-1-Amino-1-phenyl-3-di-
phenylmethoxy-2-propanol (3c; 1.5 g, 4.5 mmol) and Et3N (0.63 mL,
4.5 mmol) in CH2Cl2 (3.3 mL) were treated with dimethylmalonyl dichlor-
ide (0.38 g, 2.25 mmol) in CH2Cl2 (2.3 mL) as described in the general
procedure.After the usual workup, dihydroxy diamide 15c was obtained as
a white foam (1.67 g, 97%) which was used in the next reaction without
further purification. 1H NMR (200 MHz): d ˆ 7.66 (d, J ˆ 8.4 Hz, 2H),
7.30 7.12 (m, 30H), 5.26 5.2 (m, 2H), 5.21 (s, 2H), 4.08 4.00 (m, 2H),
1H), 2.61 (d, J ˆ 13 Hz, 1H), 1.89 (s, 3H), 1.89 (d, J ˆ 12 Hz, 1H), 1.85 (s,
3.33 (dd, J ˆ 9.7, 3.9 Hz, 2H), 3.41 (dd, J ˆ 10, 4.4 Hz, 2H), 1.18 (s, 6H);
13
13
ˆ
3H); C NMR (75 MHz): d ˆ 172.8 (C N), 139.5 (C), 139.4 (C), 129.5
ˆ
C NMR (50 MHz): d ˆ 173.5 (C O), 141.1 (C), 140.8 (C), 138.1 (C), 128.4
(CH), 128.9 (CH), 126.6 (CH), 126.3 (CH), 116.1 (CH), 87.8 (CH), 87.6
(CH), 74.5 (CH), 74.4 (CH), 72.0 (CH2), 71.9 (CH2), 61.7 (CH2), 61.1 (CH2),
59.6 (CH3), 40.9 (C), 26.3 (CH3), 24.8 (CH3); IR (KBr): n ˆ 3033, 2838,
1663, 1455, 1127, 1096, 1032, 878, 837, 760, 704 cmÀ1; MS (FAB): m/z (%):
(CH), 127.7 (CH), 127.6 (CH), 127.4 (CH), 127.2 (CH), 127.0 (CH), 126.8
(CH), 84.9 (CH), 72.1 (CH), 70.4 (CH2), 56.6 (CH), 49.9 (C), 23.4 (CH3); IR
(film): nÄ ˆ 3398, 3031, 2921, 1663, 1495, 1453, 1098, 1028, 733, 698 cmÀ1; MS
‡
(FAB): m/z (%): 764 (100) [M‡H] .
‡
570 (100) [M À PF6] ; elemental analysis calcd (%)for C28H35F6N2O4PPd: C
Formation of bis(oxazoline) 5c: A solution of dihydroxy diamide 15c
(527 mg, 0.691 mmol), Et3N (0.424 mL, 3.04 mmol) and MsCl (0.118 mL,
1.52 mmol) in CH2Cl2 (5.5 mL) was treated as described in the general
procedure.After the usual workup, bis(mesylate) 16c was obtained
quantitatively as a white foam which was used in the next step without
further purification.The bis(mesylate) 16c (598 mg, 0.65 mmol) was
treated with KOH (11.4 mL of a 5% methanolic solution in weight,
8.03 mmol) for 15 h as described for 5a to afford 5c (432 mg, 91%) as a
white solid.The product was recrystallized from Et 2O.[ a]2D3 ˆ ‡143.05 (c ˆ
0.66 gmLÀ1 in CHCl3); 1H NMR (500 MHz): d ˆ 7.26 7.16 (m, 30H), 5.31
(s, 2H), 4.97 (d, J ˆ 6.4 Hz, 2H), 4.48 (ddd, J ˆ 5, 5, 5 Hz, 2H), 3.58 (dd, J ˆ
10, 5 Hz, 2H), 3.54 (dd, J ˆ 10, 4.8 Hz, 2H), 1.59 (s, 6H); 13C NMR
47.04, H 4.93, N 3.92; found: C 46.81, H 4.98, N 4.08.
h3-Allyl [(4R,4'R,5S,5'S)-2,2'-(1-methylethylidene)bis(5-benzyloxymethyl-
4-phenyl-4,5-dihydrooxazole)-N,N]-palladium(ii)
hexafluorophosphate
(8b)
Preparation of bis(hydroxyamide) 15b: (1R,2R)-1-Amino-1-phenyl-3-phe-
nylmethoxy-2-propanol (3b; 1.00 g, 3.89 mmol) and Et3N (0.54 mL,
3.89 mmol) in CH2Cl2 (2.82 mL) were treated with dimethylmalonyl
dichloride (0.33 g, 1.94 mmol) in CH2Cl2 (1.94 mL) as described in the
general procedure.The workup was identical to the one described for 15a
to give 15b (952 mg, 80%)as a white foam which was used in the next step
without further purification. 1H NMR (200 MHz): d ˆ 7.84 (d, J ˆ 8.0 Hz,
2H), 7.31 7.12 (m, 20H), 5.24 (dd, J ˆ 8.4, 4.4 Hz, 2H), 4.48 (d, J ˆ 11.3 Hz,
2H), 4.38 (d, J ˆ 11.3 Hz, 2H), 4.00 (ddd, J ˆ 4.0, 4.0, 4.0 Hz, 2H), 3.41 (dd,
J ˆ 10.0, 3.3 Hz, 2H), 3.28 (dd, J ˆ 10.0, 4.0 Hz, 2H), 1.30 (s, 6H); 13C NMR
ˆ
(75 MHz): d ˆ 169.7 (C N), 142.2 (C), 141.8 (C), 141.7 (C), 128.6 (CH),
128.4 (CH), 128.3 (CH), 127.6 (CH), 127.5 (CH), 127.4 (CH), 127.0 (CH),
126.9 (CH), 126.6 (CH), 86.3 (CH), 83.9 (CH), 72.0 (CH), 69.6 (CH2), 39.0
(C), 24.3 (CH3); IR (film): nÄ ˆ 3062, 3029, 2937, 1659, 1495, 1453, 1111, 743,
ˆ
(50 MHz): d ˆ 173.6 (C O), 138.4 (C), 137.2 (C), 128.5 (CH), 128.3 (CH),
‡
128.0 (CH), 127.3 (CH), 126.7 (CH), 73.8 (CH2), 72.0 (CH), 71.0 (CH2), 57.0
698 cmÀ1; MS (FAB): m/z (%): 727 (100) [M] ; elemental analysis calcd
(CH), 49.9 (C), 23.4 (CH3); IR (film): nÄ ˆ 3394, 3031, 2869, 1663, 1515, 1455,
(%) for C49H46N2O4: C 80.96, H 6.38, N 3.85; found: C 80.97, H 6.40, N 3.83.
4174
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0818-4174 $ 20.00+.50/0
Chem. Eur. J. 2002, 8, No. 18

Catalyzed Allylic Alkylation
4164 4178
Preparation of 8c: A solution of [Pd(h3-C3H5)(m-Cl)]2 (44 mg, 0.12 mmol),
bis(oxazoline) 5c (158 mg, 0.217 mmol) in EtOH (2.5 mL) and NH4PF6
(36 mg, 0.22 mmol) were treated as described in the general procedure for
14 h and kept in the refrigerator, resulting in the precipitation of the
complex 8c as a white solid (115 mg, 52%).[ a]2D3 ˆ ‡96.9 (c ˆ 0.5 gmLÀ1 in
CHCl3); 1H NMR (500 MHz): d ˆ 7.41 7.1 (m, 30H), 5.54 (s, 1H), 5.51 (s,
1H), 5.24 (d, J ˆ 6.5 Hz, 1H), 5.15, (d, J ˆ 6.5 Hz, 1H), 5.02 (tt, J ˆ 12.6,
6.9 Hz, 1H), 4.68 4.66 (m, 2H), 3.92 (dd, J ˆ 12, 4 Hz, 1H), 3.88 (dd, J ˆ
12, 4 Hz, 1H), 3.81 (dd, J ˆ 12, 4 Hz, 1H), 3.76 (dd, J ˆ 12, 4 Hz, 1H), 3.41
(brd, J ˆ 7.2 Hz, 1H), 2.88 (dd, J ˆ 6.9, 3.5 Hz, 1H), 2.61 (d, J ˆ 12.5 Hz,
1H), 1.95 (d, J ˆ 12.5 Hz, 1H), 1.82 (s, 3H), 1.75 (s, 3H); 13C NMR
Preparation of bis(hydroxyamide) 15e: (1R,2R)-1-Amino-3-[2-(meth-
oxy)ethoxy]-1-phenyl-2-propanol (3e; 0.60 g, 2.66 mmol) and Et3N
(0.372 mL, 2.66 mmol) in CH2Cl2 (1.9 mL) were treated with dimethylma-
lonyl dichloride (0.225 g, 1.33 mmol) in CH2Cl2 (1.34 mL) as described in
the general procedure for 20 h.After the usual workup, dihydroxy diamide
15e was obtained as an orange oil (0.589 g, 81%) which was used in the
next reaction without further purification. 1H NMR (200 MHz): d ˆ 7.81 (d,
J ˆ 8.8 Hz, 2H), 7.36 7.20 (m, 10H), 5.48 (dd, J ˆ 8.6, 4.6 Hz, 2H), 3.94
3.92 (m, 2H), 3.82 3.32 (m, 12H), 3.51 (s, 6H), 1.50 (s, 6H); 13C NMR
ˆ
(50 MHz): d ˆ 173.6 (C O), 139.2 (C), 128.4 (CH), 127.9 (CH), 127.0 (CH),
126.8 (CH), 126.3 (CH), 72.1 (CH), 71.8 CH2), 71.5 (CH2), 70.5 (CH2), 58.6
(CH3), 57.5 (CH), 50.3 (C), 23.7 (CH3); IR (film): nÄ ˆ 3390, 3064, 3031, 2894,
1667, 1515, 1455, 1200, 1104, 735, 702 cmÀ1; MS (CI, NH3): m/z (%): 564
ˆ
(75 MHz): d ˆ 172.8 (C N), 141.3 (C), 139.3 (C), 129.5 (CH), 128.9 (CH),
128.5 (CH), 127.8 (CH), 127.7 (CH), 127.1 (CH), 126.9 (CH), 116.2 (CH),
87.5 (CH), 84.2 (CH), 75.0 (CH), 68.7 (CH2), 61.6 (CH2), 61.2 (CH2), 40.9
‡
‡
(19) [M‡NH4] , 547 (100) [M‡H] .
(C), 26.1 (CH3); IR (KBr): n ˆ 3031, 1659, 1455, 1133, 839, 749, 700 cmÀ1
;
Formation of bis(oxazoline) 5e: A solution of dihydroxy diamide 15e
(0.5 g, 0.915 mmol), Et3N (0.559 mL, 4.0 mmol) and MsCl (0.157 mL,
2.0 mmol) in CH2Cl2 (7.6 mL) was treated as described in the general
procedure.After the usual workup, bis(mesylate) 16e was obtained
quantitatively as an orange oil which was used in the next step without
further purification.The bis(mesylate) 16e (0.64 g, 0.915 mmol) was
treated with KOH (15.9 mL of a 5% methanolic solution in weight,
11.25 mmol) for 15 h as described for 5a to afford bis(oxazoline) 5e
(415 mg, 89%) as an orange oil which was used in the next reaction without
further purification. 1H NMR (200 MHz): d ˆ 7.35 7.20 (m, 10H), 4.94 (d,
‡
MS (ESP, MeOH): m/z (%): 873 (100) [M À PF6] ; elemental analysis calcd
(%) for C52H51F6N2O4PPd: C 61.27, H 5.04, N 2.75; found: C 60.29, H 5.09,
N 2.58.
h3-Allyl [(4R,4'R,5S,5'S)-2,2'-(1-methylethylidene)bis(4-phenyl-5-triphe-
nylmethoxymethyl-4,5-dihydrooxazole)-N,N]-palladium(ii)
hexafluoro-
phosphate (8d)
Preparation of bis(hydroxyamide) 15d: (1R,2R)-1-Amino-1-phenyl-3-tri-
phenylmethoxy-2-propanol (3d; 1.00 g, 2.44 mmol) and Et3N (0.34 mL,
2.44 mmol) in CH2Cl2 (1.8 mL) were treated with dimethylmalonyl
dichloride (0.206 g, 1.22 mmol) in CH2Cl2 (1.2 mL) as described in the
general procedure for 20 h.The usual work up afforded the crude
dihydroxy diamide 15d (1.1 g, 99%) as a yellow foam which was used in
the next reaction without further purification. 1H NMR (200 MHz): d ˆ
7.37 7.0 (m, 42H), 5.12 (dd, J ˆ 8, 4 Hz, 2H), 4.16 4.08 (m, 2H), 3.02
J ˆ 6.6 Hz, 2H), 4.54 (ddd, J ˆ 5, 5, 5 Hz, 2H), 3.73 3.52 (m, 12H), 3.38 (s,
13
ˆ
6H), 1.68 (s, 6H); C NMR (50 MHz): d ˆ 169.6 (C N), 142.1 (C), 128.6
(CH), 127.5 (CH), 126.6 (CH), 86.4 (CH), 72.4 (CH2), 72.0 (CH2), 72.0
(CH), 71.0 (CH2), 59.0 (CH3), 39.0 (C), 24.4 (CH3); IR (film): nÄ ˆ 2879,
1659, 1495, 1455, 1111, 1030, 994, 700 cmÀ1; MS (CI, NH3): m/z (%): 546
‡
(100) [M ‡ 2 NH4] .
2.98 (m, 4H), 1.38 (s, 6H); 13C NMR (50 MHz): d ˆ 173.0 (C O), 143.3 (C),
ˆ
137.3 (C), 128.5 (CH), 128.2 (CH), 127.8 (CH), 127.2 (CH), 127.0 (CH), 87.1
(C), 72.1 (CH), 69.2 (CH2), 56.1 (CH2), 49.6 (C), 23.9 (CH3); IR (KBr): n ˆ
3409, 1661, 1495, 1449, 1077, 745, 700 cmÀ1; MS (FAB): m/z (%): 938 (100)
Preparation of 8e: A solution of [Pd(h3-C3H5)(m-Cl)]2 (137 mg, 0.37 mmol),
bis(oxazoline) 5e (362 mg, 0.71 mmol) in EtOH (4 mL) and NH4PF6
(122 mg, 0.75 mmol) were treated as described in the general procedure
for 14 h and kept in the refrigerator, resulting in the separation of an orange
oil.The liquid was decanted and the oil was washed with cold EtOH and
dried under vacuum to give the complex 8e as an orange foam (0.3 g, 53%).
‡
[M‡Na] .
Formation of bis(oxazoline) 5d: A solution of dihydroxy diamide 15d
(1.09 g, 1.19 mmol), Et3N (0.73 mL, 5.25 mmol) and MsCl (0.2 mL,
2.63 mmol) in CH2Cl2 (9.8 mL) was treated as described in the general
procedure.After the usual workup, bis(mesylate) 16d was obtained
quantitatively (1.27 g) as a white foam which was used in the next step
without further purification.The bis(mesylate) 16d (510 mg, 0.475 mmol)
was treated with KOH (8.9 mL of a 5% methanolic solution in weight,
6.32 mmol) for 15 h as described for 5a to afford 5d (0.4 g, 96%) as a white
foam which was recrystallized from EtOH.[ a]2D3 ˆ ‡120.85 (c ˆ 1.05 gmLÀ1
in CHCl3); 1H NMR (300 MHz): d ˆ 7.5 7.20 (m, 40H), 5.0 (d, J ˆ 6.9 Hz,
2H), 4.53 4.47 (m, 2H), 3.42 (dd, J ˆ 10.2, 4.2 Hz, 2H), 3.31 (dd, J ˆ 10.2,
1
[a]2D3 ˆ ‡50.9 (c ˆ 1.01 gmLÀ1 in CH2Cl2); H NMR (300 MHz): d ˆ 7.42
7.2 (m, 10H), 5.20 (brs, 2H), 4.98 (tt, J ˆ 12.3, 6.9 Hz, 1H), 4.68 4.63 (m,
2H), 3.89 3.87 (m, 4H), 3.76 3.57 (m, 8H), 3.42 (brd, J ˆ 6.9 Hz, 1H),
3.37 (s, 6H), 2.83 (dd, J ˆ 7.2, 1.8 Hz, 1H), 2.6 (d, J ˆ 12.6 Hz, 1H), 1.89 (d,
J ˆ 12.6 Hz, 1H), 1.87 (s, 6H); 13C NMR (75 MHz): d ˆ 172.8 (C N), 139.4
ˆ
(C), 129.4 (CH), 128.8 (CH), 126.4 (CH), 116.0 (CH), 87.6 (CH), 74.5 (CH),
71.7 (CH2), 70.9 (CH2), 70.6 (CH2), 61.5 (CH2), 61.0 (CH2), 58.9 (CH3), 40.8
(C), 25.6 (CH3); IR (film): nÄ ˆ 2927, 1659, 1495, 1457, 1221, 1129, 839, 756,
‡
702 cmÀ1; MS (FAB): m/z: 658 (100) [M À PF6] .
4.6 Hz, 2H), 1.76 (s, 6H); 13C NMR (75 MHz): d ˆ 169.8 (C N), 143.6 (C),
h3-Allyl [(4R,4'R,5S,5'S)-2,2'-(1-methylethylidene)bis(5-diphenylmethoxy-
methyl-4-(2,4,6-trimethylphenyl)-4,5-dihydrooxazole)-N,N]-palladium(ii)
hexafluorophosphate (8 f)
ˆ
142.3 (C), 128.6 (CH), 128.5 (CH), 127.8 (CH), 127.4 (CH), 127.1 (CH),
126.7 (CH), 86.8 (CH), 86.6 (CH), 71.9 (CH), 64.4 (CH2), 39.1 (C), 24.5
(CH3); IR (film): nÄ ˆ 1655, 1449, 1117, 911, 733, 700 cmÀ1; MS (FAB): m/z
(%): 880 (100); HRMS (FAB): calcd for C61H55N2O4: 879.4162, found:
Preparation of bis(hydroxyamide) 15 f: (1R,2R)-1-Amino-1-mesityl-3-di-
phenylmethoxy-2-propanol (3 f; 0.8 g, 2.13 mmol) and Et3N (0.297 mL,
2.13 mmol) in CH2Cl2 (1.54 mL) were treated with dimethylmalonyl
dichloride (0.18 g, 1.065 mmol) in CH2Cl2 (1.1 mL) as described in the
general procedure for 20 h.After the usual workup, dihydroxy diamide 15 f
was obtained quantitatively as an orange foam which was used in the next
reaction without further purification. 1H NMR (200 MHz): d ˆ 7.41 (d, J ˆ
8.0 Hz, 2H), 7.32 7.25 (m, 20H), 6.68 (s, 4H), 5.53 5.39 (m, 2H), 5.39 (s,
2H), 4.12 4.03 (m, 2H), 3.60 (dd, J ˆ 9.9, 3.7 Hz, 2H), 3.50 (dd, J ˆ 10.2,
5.2 Hz, 2H), 2.23 (s, 18H), 1.11 (s, 6H); 13C NMR (50 MHz): d ˆ 172.5
‡
879.4190 [M‡H] .
Preparation of 8d:
A
solution of [Pd(h3-C3H5)(m-Cl)]2 (21.7 mg,
0.059 mmol), the bis(oxazoline) 5d (100 mg, 0.114 mmol) in EtOH
(1 mL) and NH4PF6 (20 mg, 0.123 mmol) were treated as described in the
general procedure for 14 h and kept in the refrigerator, resulting in the
precipitation of the complex 8d as a white solid (68 mg, 51%).[ a]D23
ˆ
1
‡72.9 (c ˆ 1.8 g mLÀ1 in CH2Cl2); H NMR (300 MHz): d ˆ 7.45 7.01 (m,
40H), 5.04 (d, J ˆ 7.2 Hz, 1H), 5.06 4.9 (m, 1H), 4.52 4.46 (m, 2H), 3.69
(dd, J ˆ 11.5, 3.3 Hz, 2H), 3.56 (dd, J ˆ 11.5, 4.8 Hz, 2H), 3.37 (brd, J ˆ
ˆ
(C O), 141.3 (C), 136.5 (C), 131.2 (C), 128.4 (CH), 127.6 (CH), 127.0 (CH),
6 Hz, 1H), 2.84 (brd, J ˆ 6.6 Hz, 1H), 2.57 (d, J ˆ 12.3 Hz, 1H), 1.94 (s,
126.9 (CH), 84.8 (CH), 71.5 (CH), 71.0 (CH2), 52.3 (CH), 49.1 (C), 23.7
13
ˆ
7H); C NMR (75 MHz): d ˆ 172.8 (C N), 143.1 (C), 139.2 (C), 129.5
(CH3), 20.8 (CH3); IR (film): nÄ ˆ 3408, 3064, 3029, 1669, 1509, 1453, 1094,
‡
(CH), 129.0 (CH), 128.5 (CH), 127.5 (CH), 126.4 (CH), 126.3 (CH), 88.1
(C), 87.3 (CH), 74.8 (CH), 63.6 (CH2), 61.7 (CH2), 61.3 (CH2), 41.1 (C), 25.8
(CH3); IR (film): nÄ ˆ 3060, 1656, 1492, 1449, 1131, 839, 749, 700 cmÀ1; MS
735, 702 cmÀ1; MS (FAB): m/z (%): 848 (100) [M‡H] .
Formation of bis(oxazoline) 5 f: A solution of dihydroxy diamide 15 f (0.9 g,
1.06 mmol), Et3N (0.65 mL, 4.67 mmol) and MsCl (0.18 mL, 2.34 mmol) in
CH2Cl2 (8.7 mL) were treated as described in the general procedure. After
the usual workup, bis(mesylate) 16 f was obtained quantitatively as a yellow
foam which was used in the next step without further purification.The
bis(mesylate) 16 f (1.02 g, 1.02 mmol) was treated with KOH (17.7 mL of a
5% methanolic solution in weight, 12.7 mmol, 12.4) for 15 h as described
for 5a to afford bis(oxazoline) 5 f (0.78 g, 95%) as a yellow foam which was
‡
(ESP, MeOH): m/z (%): 1025 (100) [M À PF6] ; elemental analysis calcd
(%) for C64H59F6N2O4PPd: C 65.62, H 5.08, N 2.39; found: C 64.24, H 5.18,
N 2.70.
h3-Allyl [(4R,4'R,5S,5'S)-2,2'-(1-methylethylidene)bis(5-methoxyethoxy-
methyl-4-phenyl-4,5-dihydrooxazole)-N,N]-palladium(ii) hexafluorophos-
phate (8e)
Chem. Eur. J. 2002, 8, No. 18
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0818-4175 $ 20.00+.50/0
4175

¡
M.A.Perica s, G.Muller et al.
FULL PAPER
used in the next reaction without further purification.A fraction of the
crude was chromatographed through a silica gel/2.5% Et3N column using
hexane/EtOAc (95:5/90:10) as eluent to give a sample pure for the
complete characterisation.[ a]2D3 ˆ ‡118.8 (c ˆ 0.54 gmLÀ1 in CH2Cl2);
1H NMR (200 MHz): d ˆ 7.28 7.26 (m, 20H), 6.76 (s, 4H), 5.45 (d, J ˆ
9.2 Hz, 2H), 5.33 (s, 2H), 4.70 4.63 (m, 2H), 3.64 (dd, J ˆ 10.8, 3.4 Hz,
(d, J ˆ 5.6 Hz, 2H), 5.41 (s, 2H), 4.61 (ddd, J ˆ 4.9, 4.9, 4.9 Hz, 2H), 3.81
(dd, J ˆ 10.2, 4.8 Hz, 2H), 3.72 (dd, J ˆ 10.6, 4.4 Hz, 2H), 1.82 (s, 6H);
13
ˆ
C NMR (50 MHz): d ˆ 170.1 (C N), 141.7 (C), 141.6 (C), 137.3 (C), 133.8
(C), 130.7 (C), 128.7 (CH), 128.5 (CH), 128.3 (CH), 127.9 (CH), 127.7 (CH),
127.5 (CH), 127.2 (CH), 126.8 (CH), 126.0 (CH), 125.6 (CH), 125.4 (CH),
124.3 (CH), 123.1 (CH), 85.6 (CH), 84.1 (CH), 69.1 (CH2), 67.9 (CH), 39.3
(C), 24.5 (CH3); IR (film): nÄ ˆ 3062, 1661, 1611, 1495, 1453, 1148, 1119, 909,
2H), 3.54 (dd, J ˆ 10.7, 5.1 Hz, 2H), 2.25 (s, 12H), 2.22 (s, 6H), 1.63 (s, 6H);
13
‡
C NMR (50 MHz): d ˆ 168.4 (C N), 141.7 (C), 141.6 (C), 137.3 (C), 136.9
778, 735, 702 cmÀ1; MS (FAB): m/z (%): 828 (100) [M] ; HRMS (FAB):
ˆ
‡
(C), 132.7 (C), 130.1 (C), 128.3 (CH), 128.2 (CH), 127.5 (CH), 127.4 (CH),
127.0 (CH), 126.9 (CH), 84.0 (CH) 83.9 (CH), 69.7 (CH2), 67.6 (CH), 39.0
(C), 24.0 (CH3), 20.8 (CH3), 20.5 (CH3); IR (film): nÄ ˆ 3029, 2927, 2858,
1656, 1611, 1495, 1455, 1108, 1030, 911, 737, 702 cmÀ1; MS (FAB): m/z (%):
calcd for C57H50N2O4: 827.3804; found: 827.3837 [M] .
Preparation of 8g: [Pd(h3-C3H5)(m-Cl)]2 (23 mg, 0.064 mmol), bis(oxazo-
line) 5g (0.1 g, 0.121 mmol) in EtOH (2 mL) and NH4PF6 (21 mg,
0.13 mmol) were treated as described in the general procedure for 14 h
and kept in the refrigerator, resulting in the precipitation of the complex 8g
as a white solid (89 mg, 66%) which was filtered and washed with cold
EtOH.[ a]2D3 ˆ ‡92.6 (c ˆ 0.45 gmLÀ1 in CHCl3); 1H NMR (500 MHz): d ˆ
7.88 (d, J ˆ 8.1 Hz, 2H), 7.84 (d, J ˆ 8.1 Hz, 2H), 7.72 (d, J ˆ 8.4 Hz, 2H),
7.51 7.29 (m, 28H), 6.14 (brs, 2H), 5.67 (s, 2H), 4.89 (tt, J ˆ 12.5, 7 Hz,
1H), 4.73 (brd J ˆ 4.1 Hz, 2H), 4.09 (dd, J ˆ 10.5, 4.2 Hz, 2H), 3.99 (dd, J ˆ
10.5, 4.2 Hz, 2H), 2.96 (brd, J ˆ 7 Hz, 1H), 2.60 (d, J ˆ 12 Hz, 1H), 2.51
(brd, J ˆ 7 Hz, 1H), 1.89 (s, 6H), 1.70 (d, J ˆ 12 Hz, 1H); 13C NMR
‡
812 (100) [M‡H] ; HRMS (FAB): calcd for C55H58N2O4: 811.4430, found:
‡
811.4432 [M] .
Preparation of 8 f: [Pd(h3-C3H5)(m-Cl)]2 (26 mg, 0.071 mmol), bis(oxazo-
line) 5 f (109 mg, 0.134 mmol) in EtOH (2 mL) and NH4PF6 (23 mg,
0.142 mmol) were treated as described in the general procedure for 14 h
and kept in the refrigerator, resulting in a poor precipitation of the complex
8 f.Then, the reaction mixture was concentrated under vacuum, CH 2Cl2
was added.The organic phase was washed with water, separated,
subsequently dried (MgSO4), filtered and concentrated under reduced
pressure.Hexane (2 mL) was added resulting in the precipitation of the
complex 8 f as a white solid (110 mg, 74%).[ a]2D3 ˆ ‡122.2 (c ˆ 0.9 gmLÀ1
in CHCl3); 1H NMR (300 MHz): d ˆ 7.33 7.30 (m, 20H), 6.79 (s, 4H), 5.76
(d, J ˆ 8.4 Hz, 1H), 5.59 (d, J ˆ 9.3 Hz, 1H), 5.49 (s, 2H), 5.04 (tt, J ˆ 12.4,
6.9 Hz, 1H), 4.80 4.77 (m, 2H), 3.90 (dd, J ˆ 11, 2.5 Hz, 2H), 3.73 (dd, J ˆ
11, 2.5 Hz, 2H), 3.35 (dd, J ˆ 6.5, 2 Hz, 1H), 2.56 (dd, J ˆ 7.0, 2.0 Hz, 1H),
2.41 (d, J ˆ 12.5 Hz, 1H), 2.22 (s, 6H), 2.12 (s, 6H), 2.05 (s, 6H), 1.88 (d, J ˆ
12.5 Hz, 1H), 1.75 (s, 3H), 1.72 (s, 3H); 13C NMR (75 MHz): d ˆ 171.4
ˆ
(75 MHz): d ˆ 172.8 (C N), 141.5 (C), 141.2 (C), 134.6 (C), 133.8 (C), 129.9
(CH), 129.2 (CH), 128.7 (CH), 128.5 (CH), 128.0 (CH), 127.7 (CH), 127.4
(CH), 127.1 (CH), 127.0 (CH), 126.2 (CH), 121.8 (CH), 116.3 (CH), 86.9
(CH), 84.2 (CH), 70.8 (CH), 68.5 (CH2), 61.5 (CH2), 60.9 (CH2), 41.1 (C),
25.4 (CH3); IR (KBr): n ˆ 3064, 1661, 1474, 1455, 1133, 839, 778, 743,
‡
702 cmÀ1; MS (FAB): m/z (%): 974 (100) [M À PF6] ; elemental analysis
calcd (%) for C58H63F6N2O4PPd: C 63.13, H 5.75, N 2.59; found: C 63.48, H
5.82, N 2.69.
h3-Allyl
[(4R,4'R,5R,5'R)-2,2'-(1-methylethylidene)bis(5-diphenylme-
ˆ
(C N), 141.1 (C), 138.9 (C), 138.6 (C), 137.4 (C), 137.2 (C), 136.9 (C, 130.5
thoxymethyl-4-phenyl-4,5-dihydrooxazole)-N,N]-palladium(ii) hexafluoro-
phosphate (9c)
(C), 131.9 (C), 129.8 (CH), 128.6 (CH), 128.5 (CH), 128.4 (CH), 128.0 (CH),
127.9 (CH), 127.8 (CH), 127.7 (CH), 127.4 (CH), 127.3 (CH), 126.9 (CH),
116.3 (CH), 85.5 (CH), 85.1 (CH), 84.3 (CH), 70.7 (CH), 70.1 (CH), 68.5
(CH2), 68.0 (CH2), 60.6 (CH2), 60.2 (CH2), 40.9 (C), 25.8 (CH3), 23.4 (CH3),
20.8 (CH3), 20.7 (CH3), 20.6 (CH3), 20.0 (CH3); IR (KBr): n ˆ 3031, 2925,
1654, 1611, 1495, 1455, 1131, 1090, 1030, 841, 733, 704 cmÀ1; MS (FAB): m/z
Formation of bis(oxazoline) 6c: A solution of dihydroxy diamide 15c
(0.5 g, 0.655 mmol) in anhydrous xylene (13 mL) was heated under reflux in
a Dean-Stark apparatus with dibutyl tin dichloride (13 mg) for 48 h.The
solvent was distilled off and the crude bis(oxazoline) 6c was used in the
next reaction without further purification.
‡
(%): 958 (100) [M À PF6] ; elemental analysis calcd (%) for
C60H55F6N2O4PPd: C 64.38, H 4.95, N 2.50; found: C 65.41, H 5.14, N 2.65.
Preparation of 9c: A solution of [Pd(h3-C3H5)(m-Cl)]2 (50 mg, 0.137 mmol),
bis(oxazoline) 6c (0.18 g, 0.248 mmol) in EtOH (3 mL) and NH4PF6
(44 mg, 0.27 mmol) were treated as described in the general procedure
for 14 h and kept in the refrigerator, resulting in the separation of an orange
oil.The liquid was decanted and the oil was washed with cold EtOH and
h3-Allyl [(4R,4'R,5S,5'S)-2,2'-(1-methylethylidene)bis(5-diphenylmethoxy-
methyl-4-(1-naphthyl)-4,5-dihydrooxazole)-N,N]-palladium(ii) hexafluoro-
phosphate (8g)
Preparation of bis(hydroxyamide) 15g: (1R,2R)-1-Amino-1-(1-naphthyl)-
3-diphenylmethoxy-2-propanol (3g; 0.5 g, 1.3 mmol) and Et3N (0.182 mL,
1.3 mmol) in CH2Cl2 (0.95 mL) were treated with dimethylmalonyl
dichloride (0.11 g, 0.65 mmol) in CH2Cl2 (0.65 mL) as described in the
general procedure for 20 h.After the usual workup, dihydroxy diamide 15g
was obtained quantitatively as an orange foam which was used in the next
reaction without further purification. 1H NMR (200 MHz): d ˆ 8.13 8.08
(m, 2H), 7.89 7.81 (m, 4H), 7.71 (d, J ˆ 7.8 Hz, 2H), 7.46 7.41 (m, 8H),
7.30 7.17 (m, 20H), 6.16 (dd, J ˆ 8, 4.4 Hz, 2H), 5.16 (s, 2H), 4.27 4.25 (m,
2H), 3.42 (dd, J ˆ 10.1, 3.5 Hz, 2H), 3.27 (dd, J ˆ 10, 3.4 Hz, 2H), 1.18 (s,
dried under vacuum to give 9c as an orange foam (80 mg, 32%).[ a]D23
ˆ
À48.1 (c ˆ 0.55 gmLÀ1 in CHCl3); H NMR (300 MHz): d ˆ 7.33 7.13 (m,
30H), 5.64 (d, J ˆ 10.5 Hz, 1H), 5.53 (d, J ˆ 10.5 Hz, 1H), 5.40 5.27 (m,
2H), 4.97 (s, 1H), 4.94 (s, 1H), 4.88 (tt, J ˆ 12.3, 7.3 Hz, 1H), 4.11 (d, J ˆ
4.8 Hz, 1H), 3.25 3.20 (m, 4H), 2.72 (dd, J ˆ 6.9, 1.8 Hz, 1H), 2.57 (d, J ˆ
12.3 Hz, 1H), 1.84 (s, 3H), 1.77 (s, 3H), 1.72 (d, J ˆ 12.6 Hz, 1H); 13C NMR
1
ˆ
(75 MHz): d ˆ 172.9 (C N), 141.2 (C), 141.1 (C), 134.8 (C), 134.7 (C), 128.8
(CH), 128.5 (CH), 128.3 (CH), 128.0 (CH), 127.8 (CH), 127.6 (CH), 127.5
(CH), 126.8 (CH), 126.7 (CH), 116.1 (CH), 84.3 (CH), 83.2 (CH), 83.0
(CH), 74.1 (CH), 73.9 (CH), 67.4 (CH2), 67.3 (CH2), 61.8 (CH2), 60.8 (CH2),
40.9 (C), 26.0 (CH3), 25.1 (CH3); IR (film): nÄ ˆ 3031, 1659, 1495, 1455, 1135,
6H); 13C NMR (50 MHz): d ˆ 173.6 (C O), 140.9 (C), 140.7 (C), 134.5 (C),
ˆ
133.7 (C), 130.9 (C), 128.7 (CH), 128.4 (CH), 128.0 (CH), 127.8 (CH), 127.6
(CH), 127.4 (CH), 126.9 (CH), 126.4 (CH), 125.6 (CH), 125.2 (CH), 123.5
(CH), 122.9 (CH), 85.2 (CH), 71.1 (CH), 70.5 (CH2), 53.4 (CH), 50.0 (C),
23.4 (CH3); IR (film): nÄ ˆ 3394, 3062, 1663, 1513, 1453, 1100, 778, 741,
‡
1096, 839, 739, 702 cmÀ1; MS (FAB): m/z (%): 873 (100) [M À PF6] .
h3-Allyl [(4R,4'R)-2,2'-(1-methylethylidene)bis(4-phenyl)-4,5-dihydrooxa-
zole)-N,N]-palladium(ii) hexafluorophosphate (10): Analogous complex
with SbF6 as an outer-anion described by Rush et al.[30] Crude bis(oxazo-
line) 7 (R ˆ Ph) (0.641 g, 1.92 mmol) in acetone/dichloromethane 1:1
(20 mL) was stirred and cooled to 08C.A solution of [Pd( h3-C3H5)(m-Cl)]2
(0.346 g, 0.96 mmol) in 20 mL of the same mixture of solvents was added,
followed by addition of NH4PF6 (3.12 g, 19.2 mmol) dissolved in 20 mL of
the same mixture of solvents.The mixture was stirred for 1 h at room
temperature.Then, the solvent was evaporated and the solid obtained was
washed with water and recrystallized from absolute ethanol/pentane
(0.99 g, 83%). 1H NMR (250 MHz): d ˆ 7.46 7.14 (m, 10H), 5.53 (dd,
J ˆ 10.4, 7.0 Hz, 1H), 5.42 (dd, J ˆ 10.4, 7.7 Hz, 1H), 5.00 (m, 3H), 4.30 (m,
2H), 3.43 (d, J ˆ 6.6 Hz, 1H), 2.85 (d, J ˆ 6.0 Hz, 1H), 2.57 (d, J ˆ 12.4 Hz,
1H), 1.93 (d, J ˆ 12.5 Hz, 1H), 1.88 (s, 3H), 1.84 (s, 3H); 13C NMR
‡
700 cmÀ1; MS (FAB): m/z (%): 864 (100) [M‡H] .
Formation of bis(oxazoline) 5g: A solution of dihydroxy diamide 15g
(620 mg, 0.718 mmol), Et3N (0.435 mL, 3.12 mmol) and MsCl (0.123 mL,
1.59 mmol) in CH2Cl2 (5.9 mL) were treated as described in the general
procedure.After the usual workup, bis(mesylate) 16g was obtained
quantitatively as a yellow foam which was used in the next step without
further purification.The bis(mesylate) 16g (0.7 g, 0.69 mmol) was treated
with KOH (11.9 mL of a 5% methanolic solution in weight, 8.6 mmol) for
15 h as described for 5a to afford bis(oxazoline) 5g (0.53 g, 93%) as a
yellow foam which was used in the next reaction without further
purification.A fraction of the crude was chromatographed through a silica
gel/2.5% Et3N column using hexane/EtOAc (100:0/80:20) as eluent to give
sample pure for the complete characterisation.[ a]2D3 ˆ ‡12.0 (c ˆ
(50 MHz): d ˆ 173.4 (C N), 139.9 (C), 139.7 (C), 129.3 (CH), 128.8 (CH),
ˆ
a
0.63 gmLÀ1 in CHCl3); 1H NMR (200 MHz): d ˆ 7.97 (d, J ˆ 8.8 Hz, 2H),
126.7 (CH), 126.4 (CH), 115.8 (CH), 76.5 (CH2), 72.8 (CH), 72.4 (CH), 61.2
7.83 (d, J ˆ 7.8 Hz, 2H), 7.72 (d, J ˆ 8.0 Hz, 2H), 7.45 7.23 (m, 28H), 5.92
(CH2), 60.9 (CH2), 40.8 (C), 26.6 (CH3), 24.7 (CH3); IR (KBr): nÄ ˆ 1566,
4176
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0818-4176 $ 20.00+.50/0
Chem. Eur. J. 2002, 8, No. 18

Catalyzed Allylic Alkylation
4164 4178
‡
839 cmÀ1; MS (FAB): m/z (%): 483 (100) [M À PF6] ; elemental analysis
calcd (%) for C24H27F6N2O2PPd: C 45.98, H 4.34, N 4.47; found: C 44.65, H
4.50, N 4.52.
(silica gel; ethyl acetate).The enantiomeric excesses were determined by
GC on a FS-cyclodex-b-I/P column.
h3-1,3-Diphenylallyl [(4R,4'R,5S,5'S)-2,2'-(1-methylethylidene)bis(5-me-
thoxyethoxymethyl-4-phenyl-4,5-dihydrooxazole)-N,N]-palladium(ii) hexa-
fluorophosphate (11e):
Acknowledgement
A
solution of [Pd(h3-1,3-Ph2-C3H3)(m-Cl)]2
(56 mg, 0.084 mmol) and crude bis(oxazoline) 5e (0.1 g, 0.196 mmol) in
CH2Cl2/THF/MeOH 6:5:5 (16 mL) was stirred at room temperature for 1 h
and then NH4PF6 (32 mg, 0.198 mmol) was added. After stirring the
reaction mixture for one week, it was washed with water, dried (MgSO4)
and concentrated under vacuum to give the crude complex.EtOH was
added resulting in the separation of an oil.The liquid was decanted and the
oil was washed wih cold EtOH and dried under vacuum to give the complex
11e as an orange foam (0.1 g, 54%). [a]2D3 ˆ À45.4 (c ˆ 0.47 gmLÀ1 in
CHCl3); 1H NMR (500 MHz): d (major) ˆ 7.39 6.63 (m, 20H), 5.66 (dd,
J ˆ 13, 10.5 Hz, 1H), 5.25 (d, J ˆ 13 Hz, 1H), 4.35 4.32 (m, 2H), 4.22 (d,
J ˆ 4 Hz, 1H), 3.98 (d, J ˆ 4 Hz, 1H), 3.71 3.42 (m, 12H), 3.70 (dd, J ˆ
10.5, 1 Hz, 1H), 3.36 (s, 3H), 3.29 (s, 3H), 1.87 (s, 3H), 1.58 (s, 3H);
minorˆ 7.48 6.84 (m, 20H), 5.16 (d, J ˆ 6.5 Hz, 1H), 5.03 (dd, J ˆ 12, 8 Hz,
1H), 4.61 (ddd, J ˆ 6.4, 3.1, 3.1 Hz, 1H), 4.58 (d, J ˆ 8 Hz, 1H), 4.37 4.33
(m, 1H), 3.88 (d, J ˆ 5.5 Hz, 1H), 3.81 (d, J ˆ 12 Hz, 1H), 3.82 3.79 (m,
¬
We would like to thank the Spanish Ministerio de Educacion y Cultura
(BQU2001-3358 and PB98-1246) and Generalitat de Catalunya, DURSI
(2000SGR00019 and 1999SGR00045) Cristina Puigjaner thanks CIRIT
for a fellowship, and A.V.-F. thanks Ministerio de Educacion y Cultura for a
¬
¬
ƒ
contract under the program, Acciones para la Incorporacion a Espana de
¬
Doctores y Tecnologos.
[1] For general references on asymmetric catalysis, see: a) R.Noyori,
Asymmetric Catalysis in Organic Synthesis, Wiley, New York, 1994;
b) Comprehensive Asymmetric Catalysis, Vol. I III (Eds.: E. N.
Jacobsen, A.Pfaltz, H.Yamamoto), Springer, Berlin,
1999; c) I.
Ojima, Catalytic Asymmetric Synthesis, Wiley, New York, 2000.
[2] In the well-studied addition of diethylzinc to aldehydes, for instance,
ligands performing very well with substrates heavily substituted at the
a carbon give less satisfactory results with linear substrates, and vice
versa.Compare, for instance, the results obtained with DAIB (M.
Kitamura, S.Suga, K.Kawai, R.Noyori, J. Am. Chem. Soc. 1986, 108,
6071 6072) with those obtained with norephedrine derived amino
alcohols (K.Soai, S.Yokoyama, T.Hayasaka, J. Org. Chem. 1991, 56,
4264 4268).
2H), 3.72 3.42 (m, 8H), 3.29 (s, 3H), 3.26 (s, 3H), 3.27 3.25 (m, 2H), 1.81
13
ˆ
(s, 3H), 1.67 (s, 3H); C NMR (75 MHz): d (major) ˆ 173.7 (C N), 172.7
ˆ
(C N), 139.6 (C), 139.2 (C), 138.4 (C), 135.6 (C), 129.2 (CH), 129.1 (CH),
128.9 (CH), 128.5 (CH), 128.3 (CH), 128.1 (CH), 125.3 (CH), 124.6 (CH),
107.4 (CH), 87.2 (CH), 87.0 (CH), 85.2 (CH), 72.2 (CH), 71.8 (CH2), 71.7
(CH2), 71.2 (CH2), 70.9 (CH2), 70.8 (CH2), 70.1 (CH), 69.4 (CH), 58.9
ˆ
(CH3), 40.5 (C), 26.7 (CH3), 24.1 (CH3); minorˆ 173.2 (C N), 139.4 (C),
[3] For recent examples see: a) M.J. Burk, Acc. Chem. Res. 2000, 33,
363 372; b) U.Nettekoven, M.Widhalm, H.Kalchhauser, P.C.J.
138.9 (C), 137.6 (C), 129.6 (CH), 128.9 (CH), 128.2 (CH), 128.0 (CH), 127.9
(CH), 127.8 (CH), 126.5 (CH), 125.7 (CH), 105.0 (CH), 87.7 (CH), 86.8
(CH), 80.7 (CH), 76.0 (CH), 73.0 (CH), 70.5 (CH2), 69.9 (CH), 58.9 (CH3),
40.5 (C), 27.0 (CH3), 23.6 (CH3); IR (film): nÄ ˆ 2925, 1655, 1492, 1451, 1123,
Kamer, P.W.N.M.van Leeuwen, M.Lutz, A.L.Spek,
J. Org. Chem.
2001, 66, 759 770; c) for a review on combinatorial approaches to
ligand optimization, see: K.D. Shimizu, M.L. Snapper, A.H.
Hoveyda, in Comprehensive Asymmetric Catalysis, Vol. III (Eds.:
‡
839, 758, 698 cmÀ1; MS (FAB): m/z (%): 809 (100) [M À PF6] .
(h3-Cyclohexenyl)-[(4R,4'R,5R,5'R)-2,2'-(1-methylethylidene)bis(5-phe-
nyl-4-methoxymethyl-4,5-dihydrooxazole)-N,N]-palladium(ii) hexafluoro-
phosphate (12a) Preparation of 12a: [Pd(h3-cyclohexenyl)(m-Cl)]2 (90 mg,
0.168 mmol), bis(oxazoline) 5a (0.16 g, 0.37 mmol) in EtOH (3 mL) and
NH4PF6 (60 mg, 0.37 mmol) were treated as described in the general
procedure for 14 h and kept in the refrigerator, resulting in the precip-
itation of the complex 12a as a white solid (152 mg, 70%) which was
filtered and washed with cold EtOH. 1H NMR (500 MHz): d ˆ 7.45 7.15
(m, 10H), 5.19 (d, J ˆ 7 Hz, 1H), 5.13 (d, J ˆ 7 Hz, 1H), 5.09 (t, J ˆ 6.5 Hz,
1H), 4.67 (m, 1H), 4.57 (m, 2H), 3.79 (t, J ˆ 4.0 Hz, 2H), 3.70 (m, 2H), 3.56
(m, 1H), 3.48 (s, 3H), 3.43 (s, 3H), 1.87 (s, 3H), 1.84 (s, 3H), 1.44 (m, 1H),
E.N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, Berlin,
pp.1389 1399.
1999,
[4] For compilations of natural and unnatural ligands and auxiliaries, see:
a) H.U.Blaser, Chem. Rev. 1992, 92, 935 952; b) J.Seyden-Penne,
Chiral Auxiliaries and Ligands in Asymmetric Synthesis, Wiley, New
York, 1995; c) F.Fache, E.Schulz, M.L.Tommasino, M.Lemaire,
Chem. Rev. 2000, 100, 2159 2231.
[5] T.Katsuki, V.S.Martin, Org. React. 1996, 48, 1 299.
[6] E.N. Jacobsen, M.H. Wu, in Comprehensive Asymmetric Catalysis,
Vol. II (Eds:. EN. .Jacobsen, A.Pfaltz, H.Yamamoto), Springer,
Berlin, 1999, pp.649 677.
1.31 (m, 1H), 1.18 (m, 1H), 0.89 (m, 1H), 0.53 (m, 1H), 0.07 (m, 1H);
¡
[7] A.Vidal-Ferran, A.Moyano, M.A.Perica s, A.Riera, J. Org. Chem.
13
ˆ
ˆ
C NMR (62.9 MHz): d ˆ 173.1 (C N), 172.7 (C N), 139.7 (C), 139.4 (C),
129.7 (CH), 129.5 (CH), 129.0 (CH), 126.8 (CH), 126.4 (CH), 125.9 (C),
106.1 (CH), 88.0 (CH), 87.7 (CH), 78.8 (CH2), 75.2 (CH2), 74.6 (CH), 74.4
(CH), 72.0 (CH2), 59.6 (CH3), 40.7 (C), 28.2 (CH2), 27.2 (CH2), 26.7 (CH3),
1997, 62, 4970 4982.
¡
[8] a) A.Vidal-Ferran, A.Moyano, M.A.Perica s, A.Riera, Tetrahedron
Lett. 1997, 38, 8773 8776; b) A.Vidal-Ferran, N.Bampos, A.
¡
Moyano, M.A. Perica s, A.Riera, J.K.M.Sanders,
J. Org. Chem.
‡
24.4 (CH3), 19.3 (CH2); MS (FAB): m/z (%): 610 (100) [M À PF6] ;
1998, 63, 6309 6318; c) C.Jimeno, A.Vidal-Ferran, A.Moyano,
elemental analysis calcd (%) for C31H39F6N2O4PPd: C 49.32, H 5.21, N 3.70;
found: C 48.70, H 5.60, N 3.74.
¡
M.A.Perica s, A.Riera, Tetrahedron Lett. 1999, 40, 777 780.
¬
¡
[9] M.Pasto , M.A. Perica s, A.Riera, Eur. J. Org. Chem. 2002, 2337
2341.
General procedure for palladium-catalyzed allylic alkylation
¡
[10] C.Puigjaner, A.Vidal-Ferran, A.Moyano, M.A.Perica s, A.Riera, J.
Org. Chem. 1999, 64, 7902 7911.
[11] For
Allylic alkylation of rac-3-acetoxy-1,3-diphenyl-1-propene: The complex
8a g, 9c or 10 (0.02 mmol) was dissolved in CH2Cl2 (2 mL). rac-3-
Acetoxy-1,3-diphenyl-1-propene (252 mg, 1 mmol), dissolved in CH2Cl2
(2 mL), was added followed by dimethyl malonate (396 mg, 3 mmol),
BSA (610 mg, 3 mmol), and a catalytic amount of KOAc.The mixture was
stirred at room temperature for 48 h (unless stated otherwise).Then, the
solution was diluted with diethyl ether, filtered over Celite, and washed
with water (4 Â 10 mL).The organic phase was dried over anhydrous
Na2SO4, filtered off, and solvent removed under reduced pressure.
Purification of the product was done by column chromatography (silica
gel; ethyl acetate), followed by heating treatment at 1308C under vacuum.
The enantiomeric excesses were determined by HPLC on a Chiralcel OD
column, using hexane/isopropanol 9:1, in a flow of 0.5 mLminÀ1 and
pressure 14 bar.
a review, see: AK. .Ghosh, P.Mathivanan, J.Cappiello,
Tetrahedron: Asymmetry 1998, 9, 1 45.
[12] For previous use of bis(oxazoline) ligands in palladium-catalyzed
allylic alkylation, see: a) D.Muller, G.Umbricht, B.Weber, A.Pfaltz,
Helv. Chim. Acta 1991, 74, 232 240; b) P.von Matt, G.C.Lloyd-
Jones, A.B.E. Minidis, A. Pfaltz, L. Macko, M. Neuburger, M.
Zehnder, H.Ruegger, P.S.Pregosin, Helv. Chim. Acta 1995, 78, 265
284; c) W.Zhang, T.Hirao, I.Ikeda, Tetrahedron Lett. 1996, 37, 4545
4548; d) W.Zhang, T.Kida, Y.Nakatsuji, I.Ikeda,
Tetrahedron Lett.
1996, 37, 7995 7998; e) KH. .Ahn, C-.W.Cho, J.Park, S.Lee,
Tetrahedron: Asymmetry 1997, 8, 1179 1185; f) O.Hoarau, H.Aiet-
Haddou, J-.C.Daran, D.Cramailere, G.G.A.Balavoine,
Organo-
metallics 1999, 18, 4718 4723; g) O.Hoarau, H.AÔt-Haddou, M.
Castro, G.A.Balavoine, Tetrahedron: Asymmetry 1997, 8, 3755 3764;
h) M.Go mez, S.Jansat, G.Muller, M.A.Maestro, J.MahÌa, M.Font-
Allylic alkylation of rac-3-acetoxy-1-cyclohexene: The procedure was
analogous to the one described for the rac-3-acetoxy-1,3-diphenyl-1-
propene.Purification of the product was done by column chromatography
¬
BardÌa, X.Solans, J. Chem. Soc. Dalton Trans. 2001, 1432 1439; i) M.
Chem. Eur. J. 2002, 8, No. 18
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0818-4177 $ 20.00+.50/0
4177

¡
M.A.Perica s, G.Muller et al.
FULL PAPER
¬
Gomez, S.Jansat, G.Muller, MA. .Maestro, J.MahÌa,
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¡
[14] E.Medina, A.Moyano, M.A.Perica
s, A.Riera, Helv. Chim. Acta
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¡
[15] E.Medina, A.Vida-Ferran, A.Moyano, M.A.Perica
s, A.Riera,
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malonate was also tested, using 8a and 10 as catalytic precursors.
After 48 h, 8a system gave very low conversion of substrate (10%)
and very low asymmetric induction (14% ee).Under analogous
conditions, 10 was inactive.
[16] a) G.Desimoni, G.Faita, M.Mella,
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Received: February 14, 2002 [F3877]
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