Chiral thiazoline ligands: Application in Pd-catalysed allylic substitution

Article abstract of DOI:10.1016/j.tet.2004.07.048

A series of thiazoline ligands, analogues of well-known oxazolines, easily prepared from chiral aminoalcohols and appropriate dithioesters, was tested in the Pd-catalysed allylic substitution. A systematic comparison with the corresponding oxazolines (usi

Full text of DOI:10.1016/j.tet.2004.07.048

Tetrahedron 60 (2004) 9263–9272
Chiral thiazoline ligands: application in Pd-catalysed
allylic substitution
*
Isabelle Abrunhosa, Lise Delain-Bioton, Annie-Claude Gaumont, Mihaela Gulea
*
and Serge Masson
´ ´ ´
Laboratoire de Chimie Moleculaire et Thioorganique (UMR CNRS 6507), ENSICAEN-Universite, 6 Bd. Marechal Juin,
F-14050 Caen, France
Received 7 May 2004; revised 1 July 2004; accepted 22 July 2004
Available online 26 August 2004
Abstract—A series of thiazoline ligands, analogues of well-known oxazolines, easily prepared from chiral aminoalcohols and appropriate
dithioesters, was tested in the Pd-catalysed allylic substitution. A systematic comparison with the corresponding oxazolines (using literature
data or our own tests) has been made for each case. Some important differences (between their catalytic activity and enantioselectivity) were
noted for the two types of ligands, especially in the case of bis(thiazolines) and bis(oxazolines).
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
2.1. Synthesis of thiazolines
In comparison with the widely applied oxazolines ligands in
asymmetric catalysis1, their sulfur analogues, the thiaz-
olines, are less known and have been rarely used for this
purpose. However, since the first example published by
Helmchen2 and which concerned the use of metal-
complexes of chiral bis(thiazolines) as catalysts, the interest
in thiazoline ligands seem to increase and other authors
reported the syntheses and applications of new structures of
these compounds.3,4 Comparative studies,2,4e in some well
known metal-catalysed asymmetric reactions between
oxazolines and thiazolines, appear necessary for further
development of the latter, bringing out the different
behaviors of the two heterocycles towards metal chelation.
However, studies related to the thiazoline ligands were
limited so far by the difficult access to a large variety of
enantiopure structures. In our previous work,3 we described
a versatile method to prepare thiazolines as easily as
oxazolines by using chiral aminoalcohols and appropriate
dithioesters (Scheme 1) together with a preliminary test
using one of them in Pd-catalysed allylic substitution. We
report here our full study on the efficiency, as ligands in this
model reaction, of all the synthesized thiazolines (Fig. 1). A
systematic comparison with the corresponding already
known oxazolines has been made for each case.
The general syntheses of thiazolines 1, 2, 3, 4 and 12 are
already described in our previous paper,3 starting from the
corresponding dithioesters and commercial enantiopure
aminoalcohols. The synthetic pathways used five steps
(from the isopropyl or cyclohexyl dithioester) for the
bis(thiazolines) 1 and 2 and two steps (from pyridyl or
quinolyl dithioester) for the thiazolines 3, 4 and 12.5 Two
new types of structures have been added to the thiazoline
ligand family and are reported here: the 8-quinolyl
thiazolines 5 (Scheme 2), analogues of the reported
8-quinolyl oxazolines6 and the phosphine-thiazoline 9b
(Scheme 3), analogue of the widely known phosphine-
oxazoline.7
Similarly to the 2-quinolyl thiazolines, 8-quinolyl thiazo-
lines 5 were prepared in two steps (with 81-86% overall
yield) starting from the 8-quinolyl dithioester 138 via the
corresponding thioamides 14 (Scheme 2).
Keywords: Thiazolines; Oxazolines; Chiral ligands; Asymmetric catalysis;
Allylic substitution.
* Corresponding authors. Tel.: C33231452898; fax: C33231452877
(M.G.); tel.: C33-2-31452891 (S.M.);
e-mail addresses: gulea@ismra.fr; masson@ismra.fr
Scheme 1.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.07.048

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I. Abrunhosa et al. / Tetrahedron 60 (2004) 9263–9272
Figure 1.
Scheme 2.
Phosphine-thiazoline 9b was prepared starting from the 2-
fluoro-phenylthiazoline 8b by reaction with potassium
diphenylphosphide.9 Thiazoline 8b was obtained in two
steps (thioacylation, then cyclization of 7b) from 2-fluoro-
benzene dithioester 68 and S-valinol. The overall yield for
the three steps was 68% (Scheme 3).
2.2. Pd-catalysed allylic substitution using thiazolines
and comparison with oxazolines
We chose as a model reaction the version of the Pd-
catalysed allylic substitution which is often used to test new
ligands10 the enantioselective substitution of the acetyloxy
group of the racemic 1,3-diphenylpropenyl acetate 10 by the
carbanion of the dimethyl malonate. The latter is generated
using the couple bis(trimethylsilyl)-acetamide (BSA)/
potassium acetate (KOAc), in presence of allylpalladium
dimer. This affords the (E)-2-methoxycarbonyl-3,5-
diphenylpent-4-enoate 11 (Scheme 5).
Scheme 5.
First, the effects of solvent (Et2O, THF, CH2Cl2, toluene,
CH3CN), temperature (20, 0 8C, reflux of toluene or
CH2Cl2) and amounts of reagents and catalyst were
examined for each type of thiazoline ligand.11 We selected
and summarized here the results obtained under optimal
conditions (CH2Cl2 at room temperature, see Section 3).
The comparison with the corresponding oxazolines has
Scheme 3.
It should be noted that we recently reported a new high
yielding method to synthesize all required aromatic and
heteroaromatic dithioesters, precursors of thiazolines 3, 4, 5,
8 and 128 (Scheme 4).
Scheme 4.

I. Abrunhosa et al. / Tetrahedron 60 (2004) 9263–9272
9265
Generally, bis(thiazolines) (Table 1, entries 1–4, 6–8) had
better catalytic activity (see the reaction time) than the
corresponding bis(oxazolines) and gave higher ee % for 11.
The only exception was found for the benzyl substituted
ligand 1e for which the results were nearly comparable, but
favourable to oxa-1e (Table 1, entries 5 and 9). For most
cases, enantiomer (R)-11 was the major enantiomer
obtained using ligands 113 or 2 with (R,R) configuration,
while (S)-11 comes from (S,S) ligands 1 or 2. One exception
emerged for thia-1d with (S,S) configuration, which led to
(R)-11. Moreover, in the case of bis(thiazolines), the
enantiomeric excess of 11 decreases from thia-1a to thia-
1b, with the increase of the steric hindrance of the
substituent R on the heterocycle, leading even to an
inversion of configuration in the case of thia-1d, when
RZtBu, in contrast to the bis(oxazolines) series (Graph 1).
Figure 2.
been made using literature data or our own experimental
results.
In order to make easier the analysis of the following results,
prefixes thia and oxa will be employed respectively for
thiazolines and oxazolines ligands, the same number n
indicating the analogy of their structures (Fig. 2).
Graphs 1 and 2 facilitate the comparison between the
enantiomeric excesses obtained with the different ligands.
A possible explanation for this specific behavior of
bis(thiazolines) could be a competition between nitrogen
and sulfur in the chelation of palladium.4e Indeed, compared
to oxygen, sulfur, due to its voluminous HOMO orbital, is
able to coordinate soft metals like Pd. Based on already
described models,12,14 we suggest the co-existence of three
p-allylic palladium complexes (intermediates in the reac-
tion mixture): the complex A-(N,N), in which Pd is chelated
by the two nitrogen atoms and the two diastereomeric
complexes B1-(N,S) syn–syn (endo) and B2-(N,S) syn–syn
(exo), in which Pd is chelated by one nitrogen and one sulfur
atoms (Scheme 6).
2.2.1. Bis(thiazolines) 1 and 2. In this series, all catalytic
tests were done in our laboratory, except for oxa-1e, for
which data were extracted from the literature.12
The analysis of Table 1 and Graph 1 discloses some
amazing differences between the two types of ligands.
The reaction involving the complex A-(N,N) should
proceed as for bis(oxazolines).12,14 In this case, a strong
interaction between the substituent R of one heterocycle and
one phenyl group of the allylic substrate, directs the attack
of the nucleophile preferentially on the more sterically
congested carbon center (C1 in Scheme 6) leading to a major
(R) product for a (R,R) configuration of the ligand. It is
possible that an important increase of the steric interaction
in A-(N,N) (with a more bulky R substituent), causes a
rotation of one of the thiazoline cycles, releasing the
constraint and allowing the Pd-chelation by one sulfur atom
to give B1-(N,S) complex. The C2 symmetric bis(thiazoline)
Graph 1. Comparative graph: ee % of 11 with ligands 1 (Table 1, entries 1,
2, 4–9); (R)-11 ee % are given in positive values and (S)-11 ee % in negative
values; for an easier reading of the graph we extrapolated the data for the
(S,S) ligands oxa and thia-1d and 1e and considered them of (R,R)
configuration).
Graph 2. Comparative graph: ee% of 11 with ligands 3 (Table 2, entries 1, 2, 4–7) and 4 (Table 3, entries 1, 2, 4–8); (R)-11 ee % are given in positive value)
and for an easier reading of the graph we extrapolated the data for the (S) ligands and considered them of (R,R) configuration.

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Table 1. Pd-catalysed asymmetric allylic substitution with bis(thiazolines) thia-1 and 2 and bis(oxazolines) oxa-1
Entry
Ligand
Config. of the
ligand
R
Time (h)
Conv. %
ee %
Config. of 11
1
2
3
4
5
thia-1a
thia-1b
thia-1c
thia-1d
thia-1e
(R,R)
(S,S)
(R,R)
(S,S)
(S,S)
Et
30
42
42
30
72
95
95
95
90
94
88
42
42
31
70
(R)
(S)
(R)
(R)
(S)
iPr
iPr
tBu
Bn
6
7
oxa-1a
oxa-1b
oxa-1d
oxa-1e
(R,R)
(S,S)
(S,S)
(S,S)
Et
168
168
168
68
7
8
20
97
4
(R)
(S)
(S)
(S)
iPr
tBu
Bn
19
33
88
8
9a
10
11
thia-2a
thia-2c
(R,R)
(R,R)
Et
iPr
48
72
95
95
51
41
(R)
(R)
a
Literature data.
Figure 3.
thia-1a–d/[Pd(C3H3Ph2)]CPF6 but, unfortunately, the
complexes had low stability and crystals could not be
isolated. However, one of them, the complex thia-1a/
[Pd(C3H3Ph2)]CPF6K (Fig. 3) could be characterized by 1H
NMR (see Section 3). The highest chemical shifts of the
CH–N protons let supposed in this case the chelation of Pd
by the two nitrogen atoms. The lack of the 13C NMR did not
allow us to have the Dd(13C) between the signals of C1 and
C3, indicating the electronic difference around these atoms
coordinated to Pd.12a
K
On the other hand, we succeeded in the isolation of a single
crystal of the complex thia-2a/PdCl2 (Fig. 3) and deter-
mined its structure by X-ray diffraction analysis.
Scheme 6.
could now behave as a heterofunctinal hemilabile N,S-
ligand.15 In this case, the Pd-complex could exist in two
diastereomeric forms in equilibrium, B1-(N,S) syn–syn
(endo) and B2-(N,S) syn–syn (exo), the selectivity of the
nucleophilic attack being dependent upon the difference
between their reactivities.7d,16 Therefore, the ligand can be
considered relatively similar to the a-sulfanyl oxazolines
ligands reported by Williams17,18 for which, on the p-allylic
intermediate complexes, an attack trans to the sulfur atom
(C3 in Scheme 6) is observed. Thus, complex B1-(N,S)
would lead to (S)-11, while A-(N,N) and B2-(N,S) to (R)-11,
explaining the decrease of the enantiomeric excess, as well
as the inversion of the enantioselection, with a bulkier R
substituent. The possibility of the metal-chelation by two
sulfur atoms cannot be completely excluded, but in that
case, the chiral effect around the sulfur would be probably
too small to generate enantioselectivity.
The structure showed in Figure 4, clearly discloses the N,N
coordination. However, this complex is not the real reaction
intermediate, so it does not exclude our previous hypotheses
related to the participation of sulfur in the chelation of the
p-allylic palladium complex.
2.2.2. Pyridyl thiazolines 3. In this series, we have tested
the thiazolines ligands and compared two of them with the
corresponding oxazolines for which data have been already
reported in the literature.19
The analysis of Table 2 shows that the catalytic activity of
pyridyl oxazolines oxa-3b,f is better than that of their
analogues thiazolines thia-3b,f. About 2 h are needed for the
formers to give a good conversion, while 3–4 days are
needed using the latters. Enantiomeric excesses are nearly
similar, with a small superiority for the thiazolines (Table 2,
Graph 2). The best result in the thiazolines series is 81% ee,
obtained with thia-3d (RZtBu).
In order to examine the Pd-chelation with bis(thiazolines)
and to rationalize the experimental results, we have
undertaken to analyse some Pd-complexes with bis(thiazo-
lines) and tried to obtain crystallographic analyses. First, we
attempted to prepare the postulated reaction intermediates
The enantioselection was the same for both oxazolines and

I. Abrunhosa et al. / Tetrahedron 60 (2004) 9263–9272
9267
been successfully used as ligands in the cyclopropanation
with diazoesters catalysed by ruthenium.
2.2.4. 2- and 8-Quinolyl thiazolines 4 and 5. The behavior
of the 2-quinolyl thiazolines 4 as ligands in the allylic
substitution was found to be very similar to that of the
pyridyl thiazolines 3. Their catalytic activity was found
lower than the one of the pyridyl oxazolines reported in the
literature.19 Thus, about 72 to 144 h (Table 3, entries 1–5)
are necessary for a good conversion using thiazolines,
compared to 5 to 17 h (Table 3, entries 6–8) with the
oxazoline analogues. Analysis of the results indicated in
Table 3 (entries 1–8) and Graph 2 shows that the
enantiomeric excesses are nearly similar and grow in this
series with the steric hindrance of the R substituent. The best
result was obtained in both cases with the most bulky
substituent (RZtBu), 85% ee with thia-4d and 92% ee with
oxa-4d. The enantioselection for thia-4d was close to that
observed for the corresponding pyridyl thiazoline thia-3d
and let suppose a reaction intermediate similar in both cases
(Scheme 7).
Figure 4.
thiazolines: the enantiomer (R)-11 was obtained using
ligands (R)-3, while (S)-11 comes from (S)-3. This suggests
that the reaction intermediates with thiazolines are similar to
those proposed for the pyridyl oxazolines,19 the Pd being
complexed by the two nitrogen atoms of the pyridine and
thiazoline heterocycles. Thus, the attack of the nucleophile
should take place preferentially on the terminal carbon C3
trans to the thiazoline nitrogen of the p-allylic Pd-complex
syn–syn endo, for an S configuration of the ligand (Scheme 7).
In a second series of experiments, we compared the
2-quinolyl thiazolines thia-4 (Table 3, entries 1–5) and the
8-quinolyl thiazolines thia-5 (Table 3, entries 9–12), which
could form respectively with the Pd, a five- or a six-
membered chelate ring. Then, the 8-quinolyl thiazolines
thia-5 were compared with the corresponding oxazolines6.
The literature data show that for the quinolyl oxazolines, the
8-substituted derivatives oxa-5 (Table 3, entries 13–15) are
more reactive than the 2-substituted ones oxa-4 (Table 3,
entries 6–8). Compared to both 2-quinolyl thiazolines thia-4
and their oxygenated analogues oxa-5, the 8-quinolyl
thiazolines thia-5 have been found to be rather inefficient,
giving only 8–20% conversion after 10 days and 13–48%
enantiomeric excesses.
2.2.5. 2-Diphenylphosphino-phenylthiazoline 9. Unlike
the phosphine-oxazoline analogue, well known for its high
efficiency as ligand in the Pd-catalysed allylic substitution,7
thia-9b (RZiPr) showed very disappointing results. Testing
the two ligands in our reaction conditions (in dichloro-
methane at room temperature), a total conversion after 48 h
and 93% ee were observed with the commercial oxa-9b,
while only 8% conversion and 24% ee were obtained with
thia-9b. Moreover, the enantioselection was reversed, the
major enantiomer (S)-11 being produced with (S)-oxa-9b,
while (R)-11 was preferentially obtained with (S)-thia-9b
ligand.
Scheme 7.
2.2.3. 2,6-Pyridyl bis(thiazolines) 12. Only the (S,S)-2,6-
pyridyl bis(thiazoline) 12b (with RZiPr) has been tested in
this series. Whatever the conditions tested (different
solvents and temperatures), the catalyst with this ligand
proved to be completely inefficient in this reaction. The
corresponding oxazoline (the Pybox) has been described
giving 80% conversion after 2 days in refluxing dichloro-
methane and only 26% ee.20 Besides, it is interesting to note
that both oxazolines21 and thiazolines22 of this series have
In conclusion, a new family of ligands, the thiazolines, has
Table 2. Pd-catalysed asymmetric allylic substitution with pyridyl -thiazolines and -oxazolines 3
Entry
Ligand
Config. of the
ligand
R
Time (h)
Conv. %
ee %
Config. of 11
1
2
3
4
5
thia-3a
thia-3b
thia-3c
thia-3d
thia-3f
(R)
(S)
(R)
(S)
(R)
Et
96
96
42
30
72
95
95
95
90
94
38
34
42
81
64
(R)
(S)
(R)
(S)
(R)
iPr
iPr
tBu
Ph
6a
oxa-3b
oxa-3f
(S)
(R)
iPr
Ph
1
1.5
84
86
24
55
(S)
(R)
7a
a
Literature data.

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Table 3. Pd-catalysed asymmetric allylic substitution with 2- and 8-quinolyl- thiazolines and oxazolines 4 and 5
Entry
Ligand
Config. of the
ligand
R
Time (h)
Conv. %
ee %
Config. of 11
1
2
3
4
5
thia-4a
thia-4b
thia-4c
thia-4d
thia-4f
(R)
(S)
(R)
(S)
(R)
Et
144
144
96
144
72
95
95
95
70
53
59
65
66
85
78
(R)
(S)
(R)
(S)
(R)
iPr
iPr
tBu
Ph
6a
7a
8a
oxa-4b
oxa-4d
oxa-4f
(S)
(S)
(R)
iPr
tBu
Ph
4.5
15
17
88
85
93
62
92
68
(S)
(S)
(R)
9
thia-5a
thia-5b
thia-5d
thia-5f
(R)
(S)
(S)
(R)
Et
240
240
240
240
19
20
15
8
13
21
22
48
(R)
(S)
(S)
(R)
10
11
12
iPr
tBu
Ph
13a
14a
15a
oxa-5b
oxa-5d
oxa-5f
(S)
(S)
(R)
iPr
tBu
Ph
0.5
1
2
96
88
94
42
77
59
(S)
(S)
(R)
a
Literature data.
been tested in Pd-catalysed allylic substitution and the
results were compared with those of the known oxazolines
analogues. In several cases, the behavior of the two types of
ligands was very different, as far as catalytic activities and
enantiomeric excesses are concerned. Bis(thiazolines) were
found to be globally more active than bis(oxazolines) and
furnished good enantioselectivity (up to 88%). Pyridyl- and
quinolyl-thiazolines were found to behave quite similarly to
the corresponding oxazolines concerning the enantioselec-
tive induction, but were less active. Lastly, while the
phosphine-oxazoline is one of the best ligands for this
reaction, the phosphine-thiazoline was inefficient. In some
cases, a competition between nitrogen and sulfur in the
palladium chelation is suspected but further studies are still
needed to confirm this hypothesis. Investigations related to
other metal-catalyzed reactions are in progress, in our
laboratory or in collaboration with other research groups, in
order to expand the application scope of these thiazolines
chiral ligands in asymmetric catalysis.
Compounds 1a,c (1b is the enantiomer of 1c); 2a,c; 3a,c,f;
4a,c,d,f and 12d,f have been already synthesized and
characterized.3
3.2. Preparation of bis(thiazolines) 1d and 1e
Bis(thiazolines) 1d and 1e have been prepared using the
general procedure described for bis(thiazolines),3 in five
steps, starting from isopropyl methyldithioester and the
corresponding aminoalcohol (S-(C)-tert-leucinol and
respectively S-(C)-phenylalaninol). They were purified by
silica gel flash chromatography (pentane/diethyl ether: 70/
30).
3.2.1. (S,S)-2,20-(1-Methylethylidene)-bis[4,5-dihydro-4-
tert-butylthiazole] 1d. Viscous yellow oil, [a]2D0ZK29 (c
1, acetone), overall yieldZ62%. 1H NMR (400 MHz,
CDCl3): 0.98 (s, 18H, 2!(CH3)3C), 1.52 (s, 6H,
C(CH3)2), 3.10–3.16 (m, 4H, 2!CH2S), 4.16 (t, 2H, JZ
9.0 Hz, 2!CHN). 13C NMR (62.9 MHz, CDCl3): 26.3 (2!
CH3), 27.0 (2!CH3), 27.1 (2!CH3), 30.1 (2!(CH3)3C),
34.6 ((CH3)2C), 34.6 (2!CH2), 47.8 (C(CH3)2), 87.3 (2!
CHN), 173.1 (2!C]N). IR (NaCl): 2960, 2920, 2870,
1620 (nC]N), 1450, 1370. Mass m/z: 326 (MC, 15) 269
(100), 255 (17), 211 (8), 187 (6), 153 (41), 126 (13), 41 (12).
Anal. Calcd for C17H30N2S2: C, 62.52; H, 9.26; N, 8.58.
Found: C, 62.67; H, 9.45; N, 8.15.
3. Experimental
3.1. General remarks
Most of the reactions were carried out under nitrogen
atmosphere with magnetic stirring, unless otherwise speci-
fied and monitored by TLC using silica plates. Synthesized
products were purified by flash column chromatography on
silica gel or recrystallised if needed. Solvents were dried by
distillation prior to use. The NMR spectra were recorded in
CDCl3, with a ‘Brucker AC 250’ or a ‘Brucker AC 400’
spectrometer. The chemical shifts d are expressed in ppm,
conventional abbreviations are used. Optical rotation values
were measured on a Perkin–Elmer-241 polarimeter for the
sodium D line at 20 8C. Melting points are uncorrected. The
infrared spectra were recorded with a Perkin–Elmer 16 PC
spectrometer, n(cmK1) are given. Mass spectra were
recorded with a Nermag R 10 10H spectrometer in
electronic impact at 70 eV, m/z and relative abundance are
given. HRMS were obtained with a JEOL JMS-AX 500
mass spectrometer. Elemental microanalyses were per-
formed at Caen with an automatic apparatus CHNS-O
ThermoQuest.
3.2.2. (S,S)-2,20-(1-Methylethylidene)bis[4,5-dihydro-4-
benzylthiazole] 1e. yellow oil, overall yieldZ58%. 1H
NMR (400 MHz, CDCl3):1.58 (s, 6H, C(CH3)2), 2.73 (dd,
2H, JZ13.6, 9.3 Hz, 2!CHHPh), 3.06 (dd, 2H, JZ11.8,
5.4 Hz, 2!CHHS), 3.19 (dd, 2H, JZ13.6, 5.0 Hz, 2!
CHHPh), 3.22 (dd, 2H, JZ11.8, 6.0 Hz, 2!CHHS), 4.73–
4.80 (m, 2H, 2!CHN), 7.22–7.34 (m, 10H, Harom). 13C
NMR (62.9 MHz, CDCl3): 26.9 (C(CH3)2), 37.8 (2!H2C–
Ph), 40.1 (2!CH2S), 47.9 (C(CH3)2), 78.3 (2!CHN),
126.8 (2!CHarom), 128.9 (2!CHarom), 129.8 (2!CHarom),
138.9 (2!Carom), 174.9 (2!C]N). IR (NaCl): 3010, 2960,
2920, 1600 (nC]N), 1450, 1350. Mass m/z: 394 (MC, 18),
303 (100), 245 (2), 218 (2), 153 (45), 126 (12), 91 (25), 65
(7). Anal. Calcd for C23H26N2S2: C, 70.01; H, 6.64; N, 7.10.
Found: C, 69.71; H, 6.32; N, 6.95.

I. Abrunhosa et al. / Tetrahedron 60 (2004) 9263–9272
9269
3.3. Preparation of 2-pyridyl thiazoline 3d
7.3 Hz, CHN), 7.31 (dd, 1H, JZ8.3, 4.2 Hz, H3), 7.57 (dd,
1H, JZ8.1, 7.5 Hz, H6), 7.77 (d, 1H, JZ8.1 Hz, H5), 8.04
(dd, 1H, JZ8.3, 1.7 Hz, H4), 8.25 (d, 1H, JZ7.4 Hz, H7),
8.90 (dd, 1H, JZ4.2, 1.7 Hz, H2). 13C NMR (62.9 MHz,
CDCl3): 11.5 (CH3CH2), 28.4 (CH2CH3), 38.6 (CH2S), 77.9
(CHN), 121.7, 126.4, 128.6, 130.8, 130.8, 133.0, 136.7,
145.9, 150.1, 165.5 (S–C]N). IR (KBr): 2960, 2920, 1650
(nC]N), 1570, 1490, 1460, 1380, 1310, 1250. Calcd for
C14H14N2S: C, 69.39; H, 5.82; N, 11.56. Found: C, 69.93;
H, 5.52; N, 11.17.
Thiazoline 3d has been prepared using the general
procedure described for the 2-pyridyl thiazolines,3 in two
steps, starting from methyl pyridine-2-dithiocarboxylate8
and S-tert-leucinol. It was purified by silica gel flash
chromatography (pentane/diethyl ether: 70/30).
3.3.1. 2-[(S)-4,5-dihydro-4-tert-butyl-2-thiazolyl]pyri-
dine 3d. Yellow solid, mp 44 8C, [a]2D0ZK51 (c 1,
acetone), overall yieldZ81%. 1H NMR (400 MHz,
CDCl3): 1.08 (s, 9H, (CH3)3C), 3.21 (dd, 1H, JZ11.0,
10.4 Hz, CHHS), 3.33 (dd, 1H, JZ11.0, 9.3 Hz, CHHS),
4.46 (dd, 1H, JZ10.4, 9.3 Hz, CHN), 7.37 (dd, 1H, JZ7.7,
4.9 Hz, H4), 7.77 (dt, 1H, JZ7.7, 1.4 Hz, H5), 8.13 (d, 1H,
3.5.2. 8-[(S)-4,5-Dihydro-4-isopropyl-2-thiazolyl]quino-
line 5b. Brown solid, mp 55 8C, [a]2D0ZK141 (c 1,
acetone), overall yieldZ81%. 1H NMR (400 MHz,
CDCl3): 1.15 (d, 6H, JZ6.8 Hz, CH(CH3)2), 2.22 (sept,
1H, JZ6.8 Hz, CH(CH3)2), 3.14 (t, 1H, JZ10.7 Hz,
CHHS), 4.43 (dd, 1H, JZ10.7, 8.6 Hz, CHHS), 4.45 (ddd,
1H, JZ10.4, 8.6, 6.8 Hz, CH]N), 7.46 (dd, 1H, JZ8.3,
4.2 Hz, H3), 7.60 (dd, 1H, JZ8.1, 7.3 Hz, H6), 7.92 (d, 1H,
JZ8.1, 1.4 Hz, H5), 8.21 (dd, 1H, JZ8.3, 1.8 Hz, H4), 8.38
(dd, 1H, JZ7.3, 1.4 Hz, H7), 9.03 (dd, 1H, JZ4.2, 1.8 Hz,
H2). 13C NMR (62.9 MHz, CDCl3): 19.4, 20.3 ((CH3)2CH),
33.6 (CH2S), 36.3 (CH(CH3)2), 82.2 (CHN), 121.7, 126.5,
128.6, 130.7, 130.7, 133.2, 136.6, 146.0, 150.1, 165.5 (S–
C]N). IR (KBr): 2970, 2850, 1610 (nS–C]N), 1550, 1490,
1460, 1380, 1310, 1250. Calcd for C15H16N2S: C, 70.27; H,
6.29; N, 10.93. Found: C, 70.32; H, 6.29; N, 11.12.
3
JZ7.7 Hz, H6), 8.65 (dd, 1H, JZ4.9, 1.4 Hz, H3). 13C
NMR (62.9 MHz, CDCl3): 27.2 ((CH3)3C), 33.4 (CH2S),
35.8 ((CH3)3C), 88.8 (CHN), 122.0, 125.6, 136.7, 149.6,
151.8, 177.9 (SC]N) IR (NaCl): 2950, 2870, 1610 (nC]N),
1460, 1380, 1270. Anal. Calcd for C12H16N2S: C, 65.41; H,
7.32; N, 12.71; S, 14.55. Found: C, 65.08; H, 7.40; N, 12.42;
S, 14.33.
3.4. Preparation of pyridine-2,6-bis(thiazoline) 12b
Thiazoline 12b has been prepared using the general method
already described for analogous compounds with RZtBu,
Ph,3 in two steps, starting from dimethyl 2,6-pyridine
bis(dithiocarboxylate)8 and two equivalents of S-valinol. It
was purified by silica gel flash chromatography (pentane/
diethyl ether).
3.5.3. 8-[(S)-4,5-Dihydro-4-tert-butyl-2-thiazolyl]quino-
line 5d. Brown solid, mp 75 8C, [a]2D0ZK157 (c 1,
1
acetone), overall yieldZ85%. H NMR (400 M1H NMR
(400 MHz, CDCl3): 1.12 (s, 9H, (CH3)3C), 3.11 (t, 1H, JZ
11.5 Hz, CHHS), 3.34 (dd, 1H, JZ11.5, 8.7 Hz, CHHS),
4.34 (dd, 1H, JZ11.5, 8.7 Hz, CHN), 7.43 (dd, 1H, JZ8.3,
4.2 Hz, H3), 7.57 (dd, 1H, JZ8.1, 7.4 Hz, H6), 7.89 (dd, 1H,
JZ8.1, 1.2 Hz, H5), 8.16 (dd, 1H, JZ8.3, 1.7 Hz, H4), 8.38
(dd, 1H, JZ7.4, 1.2 Hz, H7), 8.99 (dd, 1H, JZ4.2, 1.7 Hz,
H2). 13C NMR (62.9 MHz, CDCl3): 27.5 ((CH3)3C), 35.1
(CH2S), 35.6 (C(CH3)3), 85.8 (CHN), 121.7, 126.5, 128.6,
130.8, 130.7, 133.2, 136.7, 146.0, 150.0, 165.2 (S–C]N).
IR (KBr): 2970, 2850, 1610 (nS–C]N), 1520, 1490, 1380,
1310, 1250. Mass m/z: 270 (MC, 6), 213 (100), 155 (16),
128 (7), 101 (5), 59 (8). Calcd for C16H18N2S: C, 71.07; H,
6.71; N, 10.36; S, 11.86. Found: C, 70.76; H, 6.89; N, 10.10;
S, 11.49.
3.4.1. 2,6-Bis[(S)-4,5-dihydro-4-isopropyl-2-thiazolyl]-
pyridine 12b. Yellow solid, mp 190 8C, [a]2D0ZK125 (c
1, acetone), overall yieldZ61%. 1H NMR (400 MHz,
CDCl3): 1.08 (t, 12H, JZ6.7, Hz, 2!CH(CH3)2), 2.13
(oct, 2H, JZ6.7 Hz, 2!CH(CH3)2), 3.11 (t, 2H, JZ
10.4 Hz, 2!CHHS), 3.38 (dd, 2H, JZ10.4, 9.3 Hz, 2!
CHHS), 4.53 (ddd, 2H, JZ10.4, 9.3, 6.7 Hz, 2!CHN), 7.83
(t, 1H, JZ7.7 Hz, H4), 8.16 (d, 2H, JZ7.7 Hz, H4 and H5).
13C NMR (62.9 MHz, CDCl3): 19.4 and 19.7 (2!
(CH3)2CH), 33.4 (2!CH(CH3)2), 34.1 (2!CH2S), 84.0
(2!CHN), 122.7, 136.9, 150.6, 167.9 (S–C]N). IR (KBr):
2960, 2870, 1600 (nS–CZN), 1450, 1360, 1310, 1020. Calcd
for C17H23N3S2: C, 61.22; H, 6.95; N, 12.60. Found: C,
60.91; H, 6.92; N, 12.78.
3.5. Preparation of 8-quinolyl thiazolines 5
3.5.4. 8-[(R)-4,5-Dihydro-4-phenyl-2-thiazolyl]quinoline
5f. Orange solid, mp 62 8C, [a]2D0ZK3.1 (c 1, acetone),
overall yieldZ82%. H NMR (400 MHz, CDCl3): 3.29 (t,
1
The 8-quinolyl thiazolines 5a,b,d,f have been prepared
using the general procedure described for the 2-quinolyl
thiazolines 43, in two steps, starting from dithioester 138 and
the corresponding aminoalcohol (R-2-aminobutanol,
S-valinol, S-tert-leucinol and, respectively, R-phenylglyci-
nol). They were purified by silica gel flash chromatography
(pentane/diethyl ether: 70/30).
1H, JZ10.9 Hz, CHHS), 3.81 (dd, 1H, JZ10.9, 8.7 Hz,
CHHS), 5.70 (dd, 1H, JZ10.9, 8.7 Hz, CHN), 7.24–7.54
(m, 6H, H3 and C6H5), 7.62 (dd, 1H, JZ8.0, 7.4 Hz, H6),
7.94 (dd, 1H, JZ8.0, 1.3 Hz, H5), 8.21 (dd, 1H, JZ8.3,
1.7 Hz, H4), 8.52 (dd, 1H, JZ7.4, 1.3 Hz, H7), 9.03 (dd, 1H,
JZ4.2, 1.7 Hz, H2). 13C NMR (62.9 MHz, CDCl3): 42.0
(CH2S), 78.7 (CHN), 121.8, 126.5, 127.2, 127.8, 128.7,
129.0, 131.0, 131.1, 132.6, 136.8, 142.9, 145.9, 150.1, 167.6
(C]N). IR (KBr): 1650 (nS–C]N), 1610, 1510, 1490, 1380,
1310, 1250. HRMS (MHC) calcd for C18H15N2S: 291.0956.
Found: 291.0951. Calcd for C18H14N2S: C, 74.45; H, 4.86;
N, 9.65; S, 11.04. Found: C, 73.73; H, 4.75; N, 9.60; S,
11.04.
3.5.1. 8-[(R)-4,5-Dihydro-4-ethyl-2-thiazolyl]quinoline
5a. Viscous dark red oil, [a]2D0ZC138 (c 1, acetone),
1
overall yieldZ79%. H NMR (400 MHz, CDCl3): 1.13 (t,
3H, JZ7.3 Hz, CH3CH2), 1.74 (m, 1H, CH2CH3), 1.92 (m,
1H, CH2CH3), 3.07 (dd, 1H, JZ10.8, 9.0 Hz, CHHS), 3.48
(dd, 1H, JZ10.8, 8.5 Hz, CHHS), 4.56 (dt, 1H, JZ8.5,

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I. Abrunhosa et al. / Tetrahedron 60 (2004) 9263–9272
3.6. Synthesis of (S)-(2-fluoro-phenyl)-4-isopropyl
4,5-dihydro-thiazole 8b
JZ10.6, 8.4 Hz, CHHS), 4.83 (ddd, 1H, JZ10.6, 8.4,
6.8 Hz, CHN), 6.92 (ddd, 1H, JZ3.8, 7.6, 1.2 Hz, Harom),
7.19 (dt, 1H, JZ7.6, 1.3 Hz, Harom), 7.23–7.34 (m, 10H,
A mixture of dithioester 68 (1.5 mmol) and S-valinol
(1.5 mmol) was stirred at room temperature for 12 h.
Then, the mixture was concentrated under reduced pressure,
providing thioamide 7b which was sufficiently pure
H
arom), 7.39 (m, 1H, Harom), 7.73 (ddd, 1H, JZ7.8, 3.6,
1.3 Hz, Harom). 31P NMR (101.2 MHz, CDCl3): K6.95. 13
C
NMR (62.9 MHz, CDCl3): 19.6 and 20.4 ((CH3)2CH), 33.6
((CH3)2CH), 36.7 (CH2S), 85.3 (CHN), 128.5 (d, JZ1.9 Hz,
1
according to H NMR to be used without purification in
the next step.
C
arom), 128.63, 128.64, 128.68, 128.7, 130.2, 130.6 (d, JZ
3.1 Hz, Carom), 134.2 (d, JZ10.1 Hz, Carom), 134.5 (d, JZ
10.7 Hz, Carom), 134.9, 138.2 (d, JZ20.1 Hz, Carom), 138.3
(d, JZ23.7 Hz, Carom), 139.1 (d, JZ24.5 Hz, Carom), 139.2
(d, JZ1.9 Hz, Carom), 165.4 (S–C]N). IR (KBr): 3050,
2960, 2910, 2870, 1600 (nS–C]N), 1550, 1460, 1430, 1380,
1360, 1260. Calcd for C24H24NPS: C, 74.01; H, 6.21; N,
3.60; S, 8.23. Found: C, 73.72; H, 6.32; N, 3.54; S, 7.78.
3.6.1. 2-Fluorobenzenethioamide 7b. Crude product:
viscous green-yellow oil: 1H NMR (400 MHz, CDCl3):
1.07 and 1.09 (2d, 6H, JZ6.7 Hz, CH(CH3)2), 1.99 (s, 1H,
OH), 2.17 (sept, 1H, JZ6.7 Hz, CH(CH3)2), 3.87 (dd, 1H,
JZ11.1, 4.4 Hz, CHHOH), 3.94 (dd, 1H, JZ11.1, 2.1 Hz,
CHHOH), 4.76 (m, 1H, CHNH), 7.09 (ddd, 1H, JZ11.8,
8.3, 1.2 Hz, H3), 7.22 (dt, 1H, JZ7.6, 1.2 Hz, H5), 7.42 (m,
1H, H4), 8.08 (dd, 1H, JZ1.8 Hz, JZ7.6 Hz, H6), 8.11 (s,
1H, NH).
3.8. Synthesis of complex thia-1a/[Pd(C3H3Ph2)]CPF6
K
The same procedure as described in the literature for a
used.12
bis(oxazolines)
was
From
[Pd(1,3-
diphenylallyl)Cl]2 (0.1 mmol), AgPF6 (0.2 mmol) and
thia-1a (0.2 mmol), the complex thia-1a/[Pd(C3H3Ph21)]-
CPF6 was obtained in 66% yield, as an orange solid. H
NMR (400 MHz, CDCl3), d 0.89 (t, 6H, JZ6.7, Hz, 2!
CH3CH2), 1.56 (s, 6H, (CH3)2C), 2.13–2.42 (m, 4H, 2!
CH3CH2), 3.14 (dd, 1H, JZ6.3, 11.3, Hz, CHHS), 3.48 (dd,
1H, JZ9.5, 11.3, Hz, CHHS), 4.84 (d, 1H, JZ11.4 Hz,
CH), 4.92 (m, 1H, NCH), 5.24 (d, 1H, JZ11.4 Hz, CH),
6.35 (t, 1H, JZ11.4 Hz, CH), 7.34–7.45 (m, 4H, Harom),
7.63–7.73 (m, 6H, Harom).
To crude 7b diluted in 10 mL of THF, mesylchloride
(2 mmol) was added. Then, NEt3 (4 mmol) was added
dropwise, at room temperature. Stirring was maintained for
10 min then water (10 mL) was added and the mixture
extracted with dichloromethane (2!10 mL). The organic
phase was dried (MgSO4), solvents were evaporated and the
residual oil was purified by flash chromatography on silica
gel (pentane/diethyl ether: 80/20) to provide 2-fluorobenz-
ene thiazoline 8b.
Compound 8b. Yellow oil, yieldZ78%. 1H NMR
(400 MHz, CDCl3): 1.05 and 1.13 (2d, 6H, JZ6.7 Hz,
CH(CH3)2), 2.14 (sept, 1H, JZ6.7 Hz, CH(CH3)2), 3.17
(dd, 1H, JZ10.9, 9.7 Hz, CHHS), 4.14 (dd, 1H, JZ10.9,
9.1 Hz, CHHS), 4.83 (m, 1H, CHN), 7.11 (ddd, JZ10.6,
8.1, 0.8 Hz, Harom), 7.19 (dt, 1H, JZ7.8, 0.8 Hz, Harom),
7.42 (m, 1H, Ar–Harom), 7.88 (dd, 1H, JZ7.8, 1.7 Hz,
3.9. Synthesis of complex thia-2a/PdCl2 and crystal
structure determination
1.5 g of (PdCl2)n were stirred with 40 mL of acetonitrile, at
room temperature, for 24 h, under nitrogen. The orange
solid was filtered, washed with diethyl ether and dried.
Pd[Cl2(CH3CN)2] was obtained as an orange solid in 91%
yield (2 g). A mixture of Pd[Cl2(CH3CN)2] (0.5 mmol) and
ligand thia-2a (0.5 mmol) in dichloromethane (5 mL) was
stirred at room temperature, for 24 h, under nitrogen. After
evaporation of the solvent the crude thia-2a/PdCl2, an
orange solid, was characterized in 1H NMR. Then, the
complex was crystallized and one monocrystal was
analysed by X-ray diffraction.
H
arom). 19F NMR (235.3 MHz, CDCl3): K111.94 (m). 13C
NMR (62.9 MHz, CDCl3): 19.9 and 19.7 ((CH3)2CH), 33.1
((CH3)2CH), 35.3 (d, JZ3.3 Hz, CH2S), 83.0 (CHN), 116.3
(d, JZ22.0 Hz, C3), 121.7 (d, JZ11.4 Hz, Carom), 124.0 (d,
JZ3.6 Hz, Carom), 130.6 (d, JZ2.5 Hz, Carom), 132.1 (d,
JZ8.6 Hz, Carom), 160.5 (d, JZ254.5 Hz, FCarom), 161.1 (d,
JZ4.9 Hz, S–C]N). IR (KBr): 2960, 2870, 1600 (nS–C]N),
1590, 1480, 1450, 1380, 1270.
3.7. Synthesis of (S)-(2-diphenylphosphino-phenyl)-4-
isopropyl 4,5-dihydro-thiazole 9b
3.9.1. (R,R)-2,20-Cyclohexylidene bis[4-ethyl-4,5-
dihydrothiazoline]/PdCl2 (thia-2a/PdCl2). 1H NMR
(250 MHz, CDCl3): 0.94 (t, 6H, JZ7.4 Hz, 2!CH3CH2),
1.52–1.95 (m, 10H, (CH2)5), 2.15 (m, 2H, CH3CHH), 2.45
(m, 2H, CH3CHH), 3.22 (dd, 2H, JZ11.4, 11.3 Hz, 2!
CHHS), 3.35 (dd, 2H, J1Z11.3, 11.2 Hz, 2!CHHS), 4.95–
5.20 (m, 2H, 2!CHN).
A commercial 0.5 M solution of Ph2PK in THF (1.1 mmol,
2.16 mL) was diluted with THF (4 mL) and refluxed under
nitrogen. A solution of 8b in 3 mL of THF was added
dropwise and the mixture refluxed for 20 min. After cooling
down to room temperature, hydrolysis with water and
extraction with dichloromethane, the solution was dried
with MgSO4, filtered and evaporated. The product was
purified by flash chromatography on silica gel with pentane,
affording pure compound 9b.
The crystal structure of thia-2a/PdCl2 has been registered at
the Cambridge Crystallographic Data Centre and allocated
the deposition number CCDC 236476.
C16H26Cl2N2PdS2, FwZ487.81, orthorhombic, space group
Yellow solid, mp 94 8C, [a]2D0ZK42 (c 1, acetone), overall
yieldZ82%. H NMR (400 MHz, CDCl3): 0.81 and 0.89
(2d, 6H, JZ6.7 Hz, CH(CH3)2), 1.79 (oct, 1H, JZ6.7 Hz,
CH(CH3)2), 2.99 (t, 1H, JZ10.6 Hz, CHHS), 3.27 (dd, 1H,
P212121, aZ10.361 (2) A, bZ13.425 (8) A, cZ14.655
˚
˚
1
K3
˚
˚
(7) A, VZ2038.5(2) A
.
ZZ4, DxZ1.589 Mg/m3,
l(Mo Ka)Z0.71073 A, mZ13.77 cmK1, F(000)Z992,
˚
TZ293 K. The sample (0.35!0.32!0.27 mm3) was

I. Abrunhosa et al. / Tetrahedron 60 (2004) 9263–9272
9271
M. L.; Lemaire, M. Chem. Rev. 2000, 100, 2159. (c) Lutomski,
K. A.; Meyers, A. I. Asymmetric Synthesis via Chiral
Oxazolines Asymmetric Synthesis, Vol. 3; Academic: New
York, 1984; p 213. (d) Pfaltz, A. J. Heterocycl. Chem. 1999,
36, 1437. (e) Johnson, J. S.; Evans, D. A. Acc. Chem. Res.
2000, 33, 325.
studied on an automatic diffractometer CAD4 NONIUS
with graphite monochromated Mo Ka radiation. The cell
parameters are obtained by fitting a set of 25 high-theta
reflections. The data collection (2qmaxZ548, scan u/2qZ1,
tmaxZ60 s, range HKL: h 0,13; k K3,17; l K4,18) gives
4061 unique reflections from which 3110 with IO2.0s(I).
After Lorenz and polarization corrections, the structure was
solved with SIR-97, which reveals the non-hydrogen atoms
of the compound. The whole structure was refined with
SHELXL97 by the full-matrix least-square techniques (use
of F square magnitude; x, y, z, bij for Pd, S, Cl, C and N
atoms, x, y, z in riding mode for H atoms; 209 variables and
3110 observations; calcd wZ1/[s2(Fo2)C(0.21P)2] where
PZ(F2oC2Fc2)/3 with the resulting RZ0.029, RwZ0.073
2. Helmchen, G.; Krotz, A.; Ganz, K.-T.; Hansen, D. Synlett
1991, 257.
3. Abrunhosa, I.; Gulea, M.; Levillain, J.; Masson, S.
Tetrahedron: Asymmetry 2001, 12, 2851.
4. Hideyuki, I. Patent written in Japanese, JP 09194432 A2,
1997; CAN 127, 205573. Hideyuki, I. Patent written in
Japanese, JP 11124373 A2, 1999; CAN 130, 352267.
´
(c) Molina, P.; Tarraga, A.; Curiel, D. Synlett 2002, 3, 435.
and SwZ01.127 (residual Dr%0.67 e AK3). The absolute
˚
´
(d) Molina, P.; Tarraga, A.; Curiel, D.; Bautista, D.
Tetrahedron: Asymmetry 2002, 13, 1621. (e) Du, D. M.; Fu,
B.; Xia, Q. Synthesis 2004, 221.
configuration was unambiguously confirmed by the Flack
parameter (0.02(4)).
5. The spectral data of some new structures like thia-1d,e, thia-3d
and 12b are given in Section 3
3.10. Typical procedure for the Pd-catalysed allylic
substitution
6. Chelucci, G.; Gladiali, S.; Saba, A. Tetrahedron: Asymmetry
1999, 10, 1393.
7. (a) Von Matt, P.; Pfaltz, A. Angew. Chem. Int. Ed. Engl. 1993,
32, 566. (b) Sprinz, J.; Helmchen, G. Tetrahedron Lett. 1993,
34, 1769. (c) Dawson, G.; Frost, C. G.; Williams, J. M. J.;
Coate, S. W. Tetrahedron Lett. 1993, 34, 3149. (d) Steinhagen,
H.; Reggelin, M.; Helmchen, G. Angew. Chem. Int. Ed. 1997,
36, 2108. (e) Peer, M.; de Jong, J. C.; Kiefer, M.; Langer, T.;
Rieck, H.; Schell, H.; Sennhenn, P.; Sprinz, J.; Steinhagen, H.;
Wiese, B.; Helmchen, G. Tetrahedron 1996, 52, 7547.
(f) Koch, G.; Lloyd-Jones, G. C.; Loiseleur, O.; Pfaltz, A.;
Under a nitrogen atmosphere, allylpalladium chloride dimer
(0.012 mmol), the ligand (0.03 mmol) and solid potassium
acetate (0.025 mmol) were mixed in 2 mL of dichloro-
methane for 30 min. Diphenylpropenyl acetate 10
(0.5 mmol), N,O-bis(trimethylsilyl)acetamide (BSA)
(1.5 mmol) and the dimethyl malonate (1.5 mmol) were
then successively added. The reaction mixture was stirred at
20 8C and monitored by TLC (pentane/diethyl ether: 80/20).
The solvent was removed and the residue directly analysed
by HPLC, using a Chiralpak AD analytical column Daicel
(90/10 n-heptane/2-propanol, flow rate 1 mL/min,
252.1 nm). Conversions have been calculated from the
integration of the corresponding peaks of 10 (tZ7.2 min)
and 11. Enantiomeric excesses of (E)-methyl 2-methoxy-
carbonyl-3,5-diphenylpent-4-enoate 11 have been measured
by HPLC; the separation of the two enantiomers was
calibrated using racemic product: (R)-(C)-11, t1Z
14.3 min; (S)-(K)-11, t2Z20.1 min).
´ ˆ
Pretot, R.; Schaffner, S.; Schnider, P.; von Matt, P. Recl. Trav.
Chim. Pays-Bas 1995, 114, 206.
8. Abrunhosa, I.; Gulea, M.; Masson, S. Synthesis 2004, 6, 928.
9. Cope, S. J.; Dawson, G. J. Synlett 1993, 509.
10. Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395.
11. Abrunhosa, I. PhD Dissertation, Caen University, 2003.
12. (a) Von Matt, P.; Lloyd-Jones, G. C.; Minidis, A. B. E.; Pfaltz,
A.; Macko, L.; Neuburger, M.; Zehnder, M.; Ruegger, H.;
Pregosin, P. S. Helv. Chim. Acta 1995, 78, 265. (b) Pfaltz, A.
Acc. Chem. Res. 1993, 26, 339. (c) Leutenegger, U.; Umbricht,
G.; Fahrni, C.; von Matt, P.; Pfaltz, A. Tetrahedron 1992, 48,
2143. (d) Reiser, O. Angew. Chem. Int. Ed.. Engl. 1993, 32,
547.
Acknowledgements
13. A wrong configuration was indicated in our previous paper3
for the major enantiomer of 11 obtained with the ligand thia-1a
and is here corrected.
The authors thank Pr. A. Pfaltz (University of Basel) for
helpful information. Dr. L. Toupet (University of Rennes) is
gratefully acknowledged for the X-ray crystal diffraction
´
analysis. We also thank M. Lemarie for her precious
assistance in HPLC analyses. This work has been performed
ˆ
within the ‘PUNCHOrga’ interregional network (Pole
Universitaire Normand de Chimie Organique). We grate-
`
fully acknowledge the ‘Ministere de la Recherche et des
Nouvelles Technologies’, CNRS (Centre National de la
14. Pfaltz, A. Acta Chem. Scand. 1996, 50, 189.
15. Braunstein, P.; Naud, F. Angew. Chem. Int. Ed. Engl. 2001, 40,
680.
16. Frost, C. G.; Williams, J. M. J. Tetrahedron Lett. 1993, 34,
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17. Dawson, G. J.; Frost, C. G.; Martin, C. J.; Williams,
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