Preparation of axially chiral N,N′-diarylimidazolium and N-arylthiazolium salts and evaluation of their catalytic potential in the benzoin and in the intramolecular stetter reactions

Article abstract of DOI:10.1002/ejoc.200300762

N-Aryl-substituted imidazoles 14b, 15b and thiazoles 17-22, 25 were prepared which contain a stereogenic axis and which can occur as atropisomers. The imidazolium salts 15b could be obtained from 2-isopropylaniline (12b) and diacetyl (11) in three steps (19% yield) whereas the synthesis of their tert-butyl analogues failed. The meso-isomer meso-15b prevailed (dr = 90/10). The chiral thiazolium salts rac-17 (53% yield) and rac-22 (49% yield) were prepared in two steps from 2-tert-butylaniline (12a). The enantiomerically pure thiazolium salt 19 was obtained from α-bromomenthone (23) and the aniline 12a (27% overall yield). In contrast to the imidazolium salts 15b, the thiazolium salts proved to be suitable catalysts in the benzoin condensation of benzaldehyde (1 → 2) and in the intramolecular Stetter reaction of the α,β-unsaturated ester 9a. The best results obtained with catalyst 19 (20 mol %) were 85% yield of product 2 (40% ee) and 75% yield of product 10a (50% ee). The stereogenic axis of catalyst 19 is not configurationally stable in the catalytically active carbene intermediate 28. The catalyst is recovered as a mixture of diastereomeric atropisomers 19 and 26 in a ratio of 70:30 to 75:25. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200300762

FULL PAPER
Preparation of Axially Chiral N,NЈ-Diarylimidazolium and N-Arylthiazolium
Salts and Evaluation of Their Catalytic Potential in the Benzoin and in the
Intramolecular Stetter Reactions
Jens Pesch,[a] Klaus Harms,[b] and Thorsten Bach*[a]
Keywords: Asymmetric catalysis / Atropisomerism / Carbenes / Heterocycles / Umpolung
N-Aryl-substituted imidazoles 14b, 15b and thiazoles 17−22,
25 were prepared which contain a stereogenic axis and
which can occur as atropisomers. The imidazolium salts 15b
could be obtained from 2-isopropylaniline (12b) and diacetyl
(11) in three steps (19% yield) whereas the synthesis of their
able catalysts in the benzoin condensation of benzaldehyde
(1 Ǟ 2) and in the intramolecular Stetter reaction of the α,β-
unsaturated ester 9a. The best results obtained with catalyst
19 (20 mol %) were 85% yield of product 2 (40% ee) and 75%
yield of product 10a (50% ee). The stereogenic axis of cata-
tert-butyl analogues failed. The meso-isomer meso-15b pre- lyst 19 is not configurationally stable in the catalytically act-
vailed (dr = 90/10). The chiral thiazolium salts rac-17 (53%
yield) and rac-22 (49% yield) were prepared in two steps
from 2-tert-butylaniline (12a). The enantiomerically pure thi-
azolium salt 19 was obtained from α-bromomenthone (23)
and the aniline 12a (27% overall yield). In contrast to the
imidazolium salts 15b, the thiazolium salts proved to be suit-
ive carbene intermediate 28. The catalyst is recovered as a
mixture of diastereomeric atropisomers 19 and 26 in a ratio
of 70:30 to 75:25.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
Before discussing our results in detail an overview is
given which describes briefly the development of organocat-
alysts for nucleophilic aldehyde activation. Outstanding re-
sults that have recently been achieved[6,7] prompted us to
disclose our own results.
The study presented in this report is concerned with the
preparation of axially chiral azolium salts of the general
structure A (Figure 1). These compounds are accessible
from the thiones B[1] and can be converted into the carbenes
C by deprotonation at carbon atom C-2. As a major appli-
cation for these compounds we envisaged their use as cata-
lysts for enantioselective CϪC bond-forming reactions such
as the benzoin condensation[2,3] or the Stetter reaction.[4,5]
The fact that the nitrogen atom does not carry a stereogenic
center but is part of the stereogenic element appeared to be
an attractive new concept not yet pursued in this area.
N-Heterocyclic carbenes (NHC)[8] add to aldehydes and
allow for a polarity reversal (Umpolung) at the carbonyl
carbon atom via the corresponding electron-rich enols. The
most prominent CϪC bond-forming reactions charac-
terized by this mechanistic feature are the previously men-
tioned benzoin and Stetter reactions.[9] The thiazolium salt-
catalyzed benzoin condensation has been investigated inten-
sively by Breslow.[10] The mode of action of the thiazolium
salt is fully analogous to the role that natural thiamine (vit-
amin B1) pyrophosphate plays in many biochemical reac-
tions.[11] It was this analogy which led Stetter et al.[4b,5] to
devise 3-benzyl-5-hydroxyethyl-3-methyl-substituted thiazo-
lium salts as catalysts for the addition of aliphatic aldehydes
to electrophiles.
Figure 1. General structure of the axially chiral azolium salts A,
their precursor B and the intermediate carbenes C
[a]
Lehrstuhl für Organische Chemie I, Technische Universität
München
Lichtenbergstr. 4, 85747 Garching
Fax: (internat.) ϩ49-(0)89-28913315
E-mail: thorsten.bach@ch.tum.de
[b]
Crystal Structure Determination, Fachbereich Chemie Philipps-
Universität Marburg
Hans-Meerwein-Str., 35032 Marburg
Scheme 1. The benzoin reaction of benzaldehyde (1) generating the
two enantiomeric products 2 and ent-2
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J. Pesch, K. Harms, T. Bach
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As apparent from the benzoin condensation of benzal- Stetter reactions (vide infra).[16] Leeper et al. studied the
dehyde (1) depicted in Scheme 1, the addition of the alde- enantioselective benzoin condensation (up to 82.5% ee) em-
hyde to a prostereogenic center leads to the formation of ploying the bicyclic triazolium chloride 6 (Figure 3).[17] The
enantiomers. In this simple case, (R)-benzoin (2) and its en- catalyst was designed by applying the previously used con-
antiomer ent-2 are obtained.
cept of a conformationally locked endocyclic stereogenic
In early attempts to conduct the benzoin condensation center to triazolium salts. Excellent results in the benzoin
enantioselectively, Sheehan et al. employed thiazolium salts condensation (up to 95% ee) were eventually achieved by
derived from simple α-chiral primary amines.[12] The best Enders et al. who used triazolium salt 7.[6] A related catalyst
result was obtained with catalyst 3 (Figure 2) which deliv- 8 was designed by Rovis et al.[7] who aimed at enantioselec-
ered the dextrorotatory benzoin ent-2 in 38.5% optical pu- tive intramolecular Stetter reactions.
rity (21% yield). In another experiment, benzoin 2 was ob-
The more complex architecture of the Stetter reaction
tained from ent-3 in 51.5% optical purity (6% yield) after a products obtained by Enders et al.[16] and Rovis et al.[7]
shorter reaction time. The stereochemical result was ex- holds promise for further applications in synthesis. A typi-
plained by invoking (E)-enol 4 as an intermediate. Free ro- cal example of the reaction studied is provided in Scheme 2.
tation around the NϪC bond is restricted due to 1,3-allylic The easily available salicylaldehyde-derived substrate 9
strain. As a consequence the electrophilic aldehyde attacks underwent cyclization to the 4-chromanones 10 and ent-10.
from the top face via transition state 5϶ in which the steric If the reaction was conducted in the presence of catalyst 8
interactions between the substituents at the two prostereog- (20 mol %) the (R)-product 10b was the major enantiomer
enic carbon atoms are minimized. Despite several attempts obtained from 9b in 94% yield with 94% ee.[7]
to achieve higher enantiomeric excesses in the benzoin con-
densation the improvements remained insignificant for
some time.[13] Even the appealing idea to embed the stereog-
enic center into a cyclic array as realized by Leeper et
al.[13d,13e] and by Rawal et al.[13f] did not lead to higher en-
antioselectivities.
Scheme 2. The intramolecular Stetter reaction of ester 9 generating
the two enantiomeric products 10 and ent-10
Results and Discussion
Figure 2. The Sheehan catalyst 3,[12] its enol intermediate 4 and the
potential transition 5϶ state of its enantioselective benzoin conden-
Our research was initiated in 1999[18] and was triggered
by earlier studies we had conducted using axially chiral en-
sation
amides in the PaternoϪBüchi reaction.[19] There was no in-
`
The observation by Teles, Enders et al.[14] that triazolium formation on the rotational barrier around the CarylϪN
salts exhibit higher catalytic activity than thiazolium salts bond in axially chiral carbenes of type C. Based on known
in the benzoin condensation turned out to be the key dis- data for biphenyls[20] and N-aryl-2H-1,3-thiazole-2-
covery for the development of highly enantioselective cata- thiones[21] it was expected that azolium salts A and 2H-1,3-
lysts. Initial studies were conducted with a triazolium salt azole-2-thiones B with a large ortho-alkyl substituent R2,
in which the chiral substituent was attached to the nitrogen ideally tert-butyl, and a substituent R1 that was not H
atom by an exocyclic single bond (up to 86% ee).[15] The would be configurationally stable.
same catalyst delivered up to 71% ee in intramolecular
N,NЈ-Diarylimidazolium Salts
The possibility to obtain C2-symmetric chiral azolium
salts was so attractive that we turned our first synthetic
study towards N,NЈ-diarylimidazolium salts (Scheme 3).
Condensation of diacetyl (11) with ortho-substituted ani-
lines 12 yielded the diimines 13.[22] Whereas the isopropyl-
substituted product 13b could be further converted into the
corresponding thione 14b the tert-butyl-substituted product
13a[22] failed to react under the same reaction conditions.
Other attempts to convert diimine 13a or aniline 12a into
the desired thione 14a, to another cyclic imidazole deriva-
Figure 3. The chiral triazolium catalysts 6,[17] 7,[6] and 8[7]
2026
tive, or directly to the imidazolium salt 15a also failed.
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Axially Chiral N,NЈ-Diarylimidazolium and N-Arylthiazolium Salts
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Figure 4. A molecule of compound meso-15b·DMSO in the crystal[24]
Scheme 3. Synthesis of the imidazolium salt meso-15b
Upon treatment with lithium in THF, the diimine 13b
was converted into its dianion, which was subsequently
quenched with carbon disulfide. Two diastereoisomers were
formed and could be separated by chromatography. There
was no interconversion between the two diastereoisomers.
The racemic dl-product dl-14b was identified by single-crys-
tal X-ray crystallography.[23] The structure of meso-product
meso-14b was consequently assigned to the other dia-
stereoisomer. The subsequent oxidation to the imidazolium
salt was conducted with meta-chloroperbenzoic acid
(mCPBA) and perchloric acid in THF at Ϫ78 °C. Irrespec-
tive of which diastereoisomer was taken as starting material
for the oxidation, the imidazolium ion 15b was always ob-
tained as a mixture of diastereoisomers in which the meso-
product meso-15b prevailed (dr ϭ 90:10). Other oxidation
methods[1] delivered similar results and yielded the meso-
product predominantly. The imidazolium salt meso-15b was
obtained as the perchlorate and gave crystals suitable for
single-crystal X-ray crystallography. The structure of the
imidazolium ion is shown in Figure 4.[24]
Figure 5. Configuration of the N-heterocyclic carbene used as li-
gand in the chiral Ru complex 16[25]
rotation around the CarylϪN bond in the N-heterocyclic
carbene is not restricted.
Work in the area of imidazolium salts was discontinued
as the preparation of N,NЈ-bis(2-tert-butylphenyl)imidazol-
ium salts was not feasible (vide supra). Furthermore, we
observed, in line with previous results by Teles, Enders et
al.,[14a] that the reactivity of N,NЈ-diarylimidazolium salts
in benzoin and Stetter reactions is inferior to the reactivity
of thiazolium salts.
N-Arylthiazolium Salts
Upon dissolving the diastereomerically pure imidazolium
Work in this area centered around three major topics
perchlorate meso-15b there was no equilibration to the dia- which are best illustrated by the target compounds that we
stereomeric mixture. Based on this result and on the pre- attempted to prepare and that are depicted in Figure 6. The
viously mentioned observation that the thiones 14b do not simple N-(2-tert-butylphenyl)thiazolium salt 17 was to be
equilibrate, the interconversion of the dl-diastereoisomer to separated by conventional resolution via the corresponding
the meso-diastereoisomer must have occurred in some inter- diastereomeric salts using a chiral counterion YϪ. A 2H-
mediate involved in imidazolium salt formation. We assume 1,3-thiazole-2-thione of type 18 with a 5-hydroxyethyl (R ϭ
that the free carbene is responsible for the equilibration and H) side chain can be esterified and possibly separated via
that the preference for the meso-diastereoisomer is due to the corresponding diastereoisomers. Oxidation of com-
attractive van der Waals interactions of the lipophilic sub- pounds 18 (R ϭ acyl, alkylsulfonyl) and cleavage of the
stituents. Recent results by Grubbs et al.,[25] who employed ester should lead to enantiomerically pure thiazolium salts.
a C2-symmetric chiral 1,3-bis(2-isopropylphenyl)-4,5-di- Finally, the chiral thiazolium salt 19 was to be obtained as
hydro-4,5-diphenylimidazole-2-ylidene as ligand in a ru- a single enantiomerically pure diastereoisomer due to the
thenium complex (16, Figure 5) support the notion that the chiral menthol-derived backbone. The three topics will be
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J. Pesch, K. Harms, T. Bach
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individually discussed in the sequence in which the com-
pounds 17Ϫ19 are shown in Figure 6.
Figure 6. Structure of three chiral thiazole derivatives 17, 18, and
19 which are potential precursors for axially chiral N-heterocyclic
carbenes
Figure 7. A molecule of compound rac-17 in the crystal;[26] the
counterion (Y ϭ ClO4) is not shown
In an approach to thiazole rac-17, the racemic thione rac-
20 was easily obtained by treating aniline 12a under basic
conditions with carbon disulfide and chloroacetone in
DMSO (Scheme 4). Subsequent condensation under acidic
conditions in ethanol yielded the desired intermediate rac-
20 which was further oxidized to the thiazolium salt. Ion
The second approach towards an enantiomerically pure
thiazolium salt was based on compounds 18 (Figure 6). Un-
fortunately, the attempted resolution of the 5-hydroxyethyl-
2H-1,3-thiazole-2-thione rac-18 (R ϭ H) also failed. The
compound was prepared in analogy to thione rac-20 from
aniline 12a and 3-chloro-5-hydroxy-2-pentanone (49%
yield). Upon esterification with camphorsulfonyl chloride
[NEt3 (CH2Cl2); 78%] and with O-methylmandelic acid
chloride [NEt3 (CH2Cl2); 99%] the diastereomeric thiones
could be detected by NMR spectroscopy as separate com-
pounds but could not be separated either chromatograph-
ically or by crystallization.
exchange with perchlorate gave compound rac-17 (YϪ
ϭ
ClO4Ϫ) in good yield.
More successful was the third strategy which aimed at
the preparation of compound 19 (Figure 6). In a test run
with α-bromocyclohexanone[27] we checked whether the
previously used thiazolethione synthesis starting from α-
chloroketones was applicable to cyclic substrates. This was
proved to be the case (60% yield starting from aniline 12a).
Thione rac-21 was further converted into the thiazolium
salt rac-22 (Scheme 5).
Scheme 4. Synthesis of the thiazolium salt rac-17
All attempts to achieve a fractional crystallization upon
ion exchange with a chiral counterion remained unsuccess-
ful. However, despite this unsatisfactory result there was
also some good news: the crystal structure of compound
rac-17 (Y ϭ ClO4)[26] revealed that the tert-butyl group pro-
vides an extremely efficient shielding of one diastereotopic
face at carbon atom C-2 (Figure 7). In addition, we could
show that the catalytic activity of the thiazolium salt rac-17
is similar to the typical Stetter catalyst 3-benzyl-5-hydroxy-
ethyl-3-methylthiazolium bromide.[5] A conceivable decrease
in reactivity due to the sterically bulky N-(2-tert-butylphe-
nyl) substituent was not observed. In the benzoin conden-
sation (cf. Scheme 1), product rac-2 was obtained in 74%
yield at 80 °C after 1.5 h employing the Stetter catalyst (5
Scheme 5. Synthesis of the thiazolium salt rac-22
For the synthesis of compound 19 the known α-bromo-
mol % catalyst, 30 mol % NEt3 in EtOH). With catalyst rac- menthone (23)[28] was prepared from (Ϫ)-menthone by
17 under otherwise identical conditions, the yield was 75%. treatment with LDA and bromine (89% yield). It was ob-
After 19 h at room temperature, the Stetter catalyst allowed tained as a mixture of diastereoisomers (dr ϭ 58:42). The
for a yield of 96% whereas rac-17 gave 98%.
mixture was taken directly into the thione synthesis which
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Axially Chiral N,NЈ-Diarylimidazolium and N-Arylthiazolium Salts
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was conducted stepwise (Scheme 6). In the first reaction
Conventional oxidation with H2O2 at room temperature
step the dithiocarbamate 24 was generated by treating ani- surprisingly led to a mixture of three diastereoisomers in a
line 12a with carbon disulfide and subsequently with bro- ratio of 60:20:20. Based on X-ray crystallographic[30] and
mide 23. Contrary to the cyclohexanone-derived dithiocar- NMR spectroscopic evidence the two minor diastereoiso-
bamate, dithiocarbamate 24 did not cyclize spontaneously mers were identified as the atropisomer 26 and its epimer
to the corresponding bicyclic N,O-acetal. A solvent change at C-4 27 (Figure 9). Apparently, the hydrogen atom at C-4
to pentane was required to induce a cyclization with HCl is sufficiently acidic to account for an epimerization. The
in diethyl ether. Finally, water was eliminated under acidic fact that the other atropisomer was formed at room tem-
conditions to yield the desired product, after crystallization, perature, possibly via a carbene intermediate, was somewhat
as a mixture of two atropisomers (dr ϭ 97:3). The shown discouraging but we decided to look at some catalysis re-
anti-isomer 25 prevailed. Its relative and absolute configu- sults first. For these experiments, the diastereomerically
ration was proven by single-crystal X-ray analysis.[29] Some pure thiazolium salt 19 was employed. For preliminary
experimentation was required until we found optimal con- studies, we used either the racemic compound rac-22 or the
ditions for the conversion of thione 25 into the desired thia- more easily available diastereomeric mixture obtained by
zolium salt 19. A clean conversion into the diastereomer- oxidation of compound 25.
ically pure product 19 was finally achieved upon treatment
with mCPBA at low temperature. Under these conditions
no epimerization was observed. The configuration of this
product was again proven by X-ray crystallography (Fig-
ure 8).[30]
Figure 9. The diastereoisomers of compound 19, thiazolium salts
26 and 27
Catalysis Experiments
In our search for optimal reaction conditions, the
benzoin condensation (cf. Scheme 1) was conducted first.
Possible solvents were screened using 5 mol % catalyst and
5-mol % NEt3 at ambient temperature. Best conversions
were achieved in EtOH, MeCN or CH2Cl2 (reaction time:
15 h; quantitative yield) but the enantioselectivities were
low. The best enantioselectivity was achieved in THF but
Scheme 6. Synthesis of the thiazolium salt 19
in this case the conversion was not satisfactory (15% yield
after 15 h). A variation of base (tBuOK, NaOEt, KHMDS)
in THF as the solvent did not lead to an improvement. A
successful remedy was to increase the amount of catalyst
and the amount of base to 20 mol %. Under these con-
ditions, benzoin 2 was isolated in 85% yield (reaction time:
18 h at ambient temperature) and with 40% ee (HPLC, col-
umn: Daicel ChiralPak AD). The reaction did not proceed
at lower temperature (0 °C). The absolute configuration of
the major enantiomer was determined from its known
specific rotation.
The Stetter reaction studies conducted with starting ma-
terial 9a (cf. Scheme 2) delivered results similar to the re-
sults obtained in the benzoin condensation. THF was the
superior solvent and NEt3 the base of choice. With 20
mol % of catalyst 19, product 10a was obtained in 75%
yield (reaction time: 16 h) and with 50% ee (HPLC, column:
Daicel ChiralPak AD). The absolute configuration of the
product was determined by comparison of the HPLC reten-
tion times for either enantiomer with known data,[7,16] and
is in agreement with the specific rotation. The enantioselec-
tivity was monitored relative to the reaction time. It was
Figure 8. A molecule of compound 19 in the crystal;[30] the coun-
terion is not shown
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J. Pesch, K. Harms, T. Bach
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essentially constant during the first 10Ϫ15 h but deterio-
The transition states for the formation of enols 29 and
rated significantly after an extended period of time (14% ee 30 should differ energetically to the same extent as the con-
after 48 h). formations 28 and 28Ј. In the benzoin condensation we
The experiments which were conducted with 20 mol % therefore expected 70Ϫ75% of the product to be formed via
catalyst and which aimed at the highest possible enantiose- intermediate 29 and 25Ϫ30% of the product to be formed
lectivity were all performed with the enantio- and dia- via intermediate 30. The face differentiation observed in the
stereomerically pure catalyst 19 obtained from low tem- benzoin condensation is in agreement with intermediate 29
perature oxidation of thione 25. Despite the perfect stereo- being responsible for the formation of the major enanti-
chemical purity of the thiazolium salt the recovered catalyst omer. Assuming a transition state 31϶ similar to 5϶ the nu-
was always recovered as a mixture of atropisomers 19 and cleophilic benzaldehyde carbonyl carbon atom is attacked
26. The ratio varied between 75:25 and 70:30. The phenom- from its Si-face leading to the (R)-configured product 2
enon was studied more closely by treating the pure thiazol- (Figure 10). In full analogy, the prostereogenic β-carbon
ium salt 19 with NEt3 in THF. An isomerization (reaction atom of the α,β-unsaturated ester of substrate 9a is intra-
time: 48 h at ambient temperature) occurred and a mixture molecularly attacked by the enol carbon atom via transition
of atropisomers was detected in a ratio of 75:25 by 1H state 32϶ . Both prostereogenic carbon atoms react at their
NMR spectroscopy. With NaHCO3 an additional epimeriz- Si-face and the (R)-configured product 10a is formed. The
ation at C-4 occurred and four products were identified. mode of face differentiation is in line with previous results
The ratio of products was 60:20:15:5 as determined by inte- obtained for the first generation chiral triazolium salt devel-
1
gration of the H NMR signal of the hydrogen atom at C- oped by Enders et al.[15,16] This catalyst was also used for
2. The three major isomers were identified as compounds both benzoin and Stetter reactions and it was also assumed
19, 26 and 27. The minor isomer is assumed to be the atrop- to shield the Re-face of the nucleophilic enol carbon
isomer of compound 27.
atom.[31]
Discussion
The result described at the end of the preceding section
left little doubt about the fact that the intermediate N-het-
erocyclic carbene 28 formed by deprotonation of thiazolium
salt 19 is not configurationally stable at room temperature.
The rotational barrier around the CarylϪN bond is too low
and allows for an equilibration between the two confor-
mations 28 and 28Ј (Scheme 7). It is reasonable to assume
that the ratio 28/28Ј is equal to the ratio of atropisomers
19/26 present in the equilibrated mixture obtained after the
catalysis experiments or after simple base treatment. It is
the very same steric interaction between the isopropyl
group at C-4 and the 2-tert-butylphenyl group that is re-
sponsible for the thermodynamic preference of 28 over 28Ј
and of 19 over 26.
Figure 10. Possible transition states 31϶ and 32϶ for the enantiose-
lective benzoin and Stetter reaction catalyzed by thiazolium salt 19
In the diastereoisomer 30 of compound 29 the Si-face
is shielded and the Re-face is accessible. This intermediate
consequently accounts for the formation of the other en-
antiomer. In other words, the stereochemical outcome (40%
ee in favor of 2, 50% ee in favor of 10a) of the catalysis
experiments can be semi-quantitatively understood based
on the assumed intermediacy of compounds 28 and 28Ј in
a ratio of 75:25. A further improvement cannot be achieved
unless the ratio of the two atropisomers is significantly
shifted in favor of a single isomer. This could be possibly
achieved by a substituent in the cyclohexane ring which is
bulkier than isopropyl. In line with our expectations the
face differentiation exerted by the tert-butyl substituent on
the phenyl group is excellent.
Conclusion
In summary, axially chiral N-arylthiazolium have been
shown to be catalysts for nucleophilic aldehyde activation.
In the carbene intermediate, the rotation around the stere-
ogenic axis is not sufficiently restricted to suppress a racem-
ization or epimerization. The diastereomerically pure thia-
zolium salt 19 which bears a 2-tert-butylphenyl substituent
at the nitrogen atom was converted into a mixture of 19
Scheme 7. Equilibration of the two atropisomeric carbenes 28 and
28Ј and their reaction with benzaldehyde (1)
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General Procedure for the Synthesis of N,NЈ-Bis(ortho-alkylaryl)bu-
tane-2,3-diimines (GP A): Anilines 12 and a catalytic amount of
formic acid were dissolved in ethanol and diacetyl (11) was slowly
added. After stirring the mixture for 24 h at ambient temperature,
the precipitate was filtered and washed with water. The crude prod-
uct was dissolved in CH2Cl2, dried with MgSO4, filtered and con-
centrated in vacuo.
and its atropisomer 26 (dr ϭ 75:25) upon treatment with
base. The stereogenic center in the intermediate carbene fa-
vors one rotamer 28, which, in turn, is responsible for the
formation of the major diastereoisomer 19 upon repro-
tonation. Upon reaction with benzaldehyde it accounts in
a similar fashion for the formation of the major enol dia-
stereoisomer 29, which, in turn, leads to the major enanti-
omer 2 observed in the benzoin condensation catalyzed by
19. Given recent work in this area[6,7] the results we ob-
tained in the benzoin (up to 40% ee) and in the intramol-
ecular Stetter reaction (up to 50% ee) are certainly not com-
petitive. The concept of axial chirality, however, was proven
to be viable for an efficient chirality transfer. The shielding
of the diastereotopic face in transition states 31϶ and 32϶
is close to perfect. The obstacle to overcome is associated
with the above-mentioned free rotation around the stereog-
N,NЈ-Bis(2-tert-butylphenyl)butane-2,3-diimine (13a):[22] According to
GP A, 2-tert-butylaniline (12a; 6.57 g, 6.87 mL, 44.0 mmol) was
dissolved in ethanol (15 mL) and reacted with diacetyl (11; 1.89 g,
1.93 mL, 22.0 mmol). After evaporation of the solvents in vacuo,
compound 13a (7.69 g, quant.) was obtained as a yellow powder.
4
1H NMR (250 MHz): δ ϭ 7.42 (dd, 3J ϭ 7.8, J ϭ 1.4 Hz, 2 H,
3
Har-6), 7.19 (virt. td, J ഠ 7.8, 4J ഠ 1.5 Hz, 2 H, Har-5), 7.08 (virt.
td, 3J ഠ 7.6, 4J ഠ 1.4 Hz, 2 H, Har-4), 6.51 (dd, 3J ϭ 7.6, 4J ϭ
1.5 Hz, 2 H, Har-3), 2.21 (s, 6 H, CH3), 1.36 [s, 18 H, C(CH3)3]
ppm. 13C NMR (62.9 MHz): δ ϭ 166.8 (CN), 149.3 (Car-1), 139.3
enic axis. If the preference 28 vs. 28Ј or 29 vs. 30 was more (Car-2), 126.4 (CarH), 126.3 (CarH), 124.0 (CarH-3), 119.2 (CarH-
6), 35.1 [C(CH3)3], 29.5 [C(CH3)3] ppm. MS (EI, 70 eV): m/z (%) ϭ
pronounced the enantiomeric excess is likely to increase. A
straightforward idea would for example be to replace the
isopropyl group at carbon atom C-4 by the bulkier 2-phe-
nyl-2-propyl substituent using 8-phenylmenthone as the
starting material.
348 (15) [Mϩ], 291 (19) [Mϩ
Ϫ
C4H9], 174 (100)
[C4H9C6H4NCCH3ϩ], 91 (42) [C7H7ϩ], 55 (8) [C4H7ϩ].
N,NЈ-Bis(2-isopropylphenyl)butane-2,3-diimine (13b): According to
GP A, 2-isopropylaniline (12b; 27.0 g, 28.3 mL, 200 mmol) was dis-
solved in ethanol (100 mL) and reacted with diacetyl (11; 8.61 g,
8.70 mL, 100 mmol). After evaporation of the solvents in vacuo,
compound 13b (28.7 g, 89%) was obtained as a bright-yellow pow-
der. M.p. 83 °C. 1H NMR (360 MHz): δ ϭ 7.31 (dd, 3J ϭ 7.6, 4J ϭ
1.5 Hz, 2 H, Har-6), 7.17 (virt. td, 3J ഠ 7.6, 4J ഠ 1.5 Hz, 2 H, Har-
5), 7.10 (virt. td, 3J ഠ 7.6, 4J ഠ 1.5 Hz, 2 H, Har-4), 6.60 (dd, 3J ϭ
7.6, 4J ϭ 1.5 Hz, 2 H, Har-3), 2.97 [sept, 3J ϭ 7.0 Hz, 2 H,
CH(CH3)2], 2.16 (s, 6 H, CH3), 1.20 [d, 3J ϭ 7.0 Hz, 12 H,
CH(CH3)2] ppm. 13C NMR (90 MHz): δ ϭ 167.6 (CN), 148.3 (Car-
1), 137.8 (Car-2), 126.1 (CarH-6), 125.7 (CarH-5), 124.3 (CarH-3),
117.9 (CarH-4), 28.5 [CH(CH3)2], 22.7 (CH3), 15.6 [CH(CH3)2]
ppm. IR (KBr): ν˜ ϭ 3045 (w, CarH), 2990 (s, CalH), 1632 (s, Cϭ
N), 1481 (m, CarϭCar), 1459 (m, CarϭCar), 1356 (s), 1279 (w), 1115
Experimental Section
General: All reactions involving water-sensitive chemicals were car-
ried out in flame-dried glassware with magnetic stirring under Ar.
Common solvents [pentane (P), diethyl ether (Et2O), tert-butyl
methyl ether (TBME), tetrahydrofuran (THF), dichloromethane,
ethyl acetate (EtOAc), ethanol (EtOH) and methanol (MeOH)]
were distilled prior to use. Anhydrous CH2Cl2 was distilled from
CaH2, and anhydrous THF and Et2O were distilled from K/Na
immediately prior to use. N,N-Diisopropylethylamine was distilled
from calcium hydride. All other chemicals were either commercially
available or prepared according to the cited references. TLC: Merck
glass sheets (0.25 mm silica gel 60, F254), eluent given in brackets.
Detection by UV or coloration with ceric ammonium molybdate
(CAM). Optical rotation: PerkinϪElmer 241 MC. HPLC: Dionex
Pump P580A LPG, UV Detector UVD 340S. Columns: Pheno-
menex Luna Si(2) [250 ϫ 4.60 mm, flow ϭ 1.00 mL·minϪ1], Daicel
ChiralCel OD [250 ϫ 4.60 mm, flow ϭ 1.00 mL·minϪ1], ChiralPak
AD [250 ϫ 4.60 mm, flow ϭ 1.00 mL·minϪ1], Solvents: Merck
LiChrosolv, detection wavelength λ ϭ 254 nm, eluent given in
brackets. Melting points (uncorrected): Reichert hot bench. NMR:
Bruker spectrometers ARX-200, AC-250, AC-300 and AX-500. 1H
and 13C NMR spectra were recorded in CDCl3 at ambient tem-
perature unless stated otherwise. Chemical shifts are reported rela-
tive to tetramethylsilane as internal standard or residual solvent
signals. Apparent multiplets which occur as a result of the acciden-
tal equality of coupling constants of magnetically nonequivalent
protons are marked as virtual (virt.). If there was a missing signal
due to superimposition, the spectrum is marked with an asterisk (*).
IR: Bruker IFS 200 or PerkinϪElmer 1600 FT-IR. MS: Varian
CH7 (EI) or Finnigan MAT 8200 (EI). HRMS: Finnigan MAT
8200 (EI). GC-MS: Agilent 6890 (GC system, flow: 1.3 mL/min,
(m), 1031 (m), 752 (s), 724 cmϪ1 (s). GC-MS (EI, 70 eV, tR
ϭ
21.3 min): m/z (%) ϭ 320 (2) [Mϩ], 277 (55) [Mϩ Ϫ C3H7], 160
(100) [C3H7C6H4NCCH3ϩ], 144 (54), 130 (30), 118 (20), 103 (19),
91 (40), 77 (20). C22H28N2 (320.47): calcd. C 82.45, H 8.81, N 8.74;
found C 82.51, H 8.79, N 8.67.
1,3-Dihydro-1,3-bis(2-isopropylphenyl)-4,5-dimethyl-2H-imidazole-
2-thione (14b): Diimine 13b (2.79 g, 8.70 mmol) was dissolved in
dry THF (20 mL). Lithium (130 mg, 18.0 mmol) was added in
small pieces and the mixture was placed in an ultrasonic bath until
the lithium metal had been fully consumed. The resulting dark red
solution was cooled to 0 °C and dry CS2 (2.53 g, 2.00 mL,
33.0 mmol) was added dropwise. After stirring for 20 h at ambient
temperature, the reaction was stopped by addition of water
(200 mL). The resulting solution was extracted with CH2Cl2 (3 ϫ
100 mL). The combined organic layers were washed with water
(75 mL) and brine (75 mL), dried with MgSO4, and filtered. The
solvent was removed in vacuo. After chromatographic purification
(P/Et2O, 90:10 Ǟ 50:50), compounds 14b (1.40 g, 44%) were ob-
tained as dark brown solids.
column: HP 5MS (30 m), temperature: 50 Ǟ 250 °C at 10 K·minϪ1
10 min at 250 °C), Agilent 5973 (mass-selective detector, EI), Col-
,
dl-1,3-Dihydro-1,3-bis(2-isopropylphenyl)-4,5-dimethyl-2H-imid-
azole-2-thiones (dl-14b): Yield 770 mg (22%); Rf ϭ 0.33 (P/Et2O,
umn: HP 5MS (30 m). Elemental analysis: Elementar vario EL. 60:40); m.p. 110 °C (dec.). 1H NMR (250 MHz): δ ϭ 7.49Ϫ7.41
Flash chromatography:[32] Merck silica gel 60 (230Ϫ400 mesh, ca.
50 g for 1 g of material to be separated), eluent given in brackets.
Eluents [Et2O, pentane (P)] were distilled prior to use.
(m, 4 H, Har-3/4), 7.28Ϫ7.35 (m, 2 H, Har-5), 7.18 (br. d, 3J ഠ
3
7.6 Hz, 2 H, Har-6), 2.80 [sept, J ϭ 6.7 Hz, 2 H, CH(CH3)2], 1.89
3
3
(s, 6 H, CH3), 1.33 [d, J ϭ 6.7 Hz, 6 H, CH(CH3)2], 1.20 [d, J ϭ
Eur. J. Org. Chem. 2004, 2025Ϫ2035
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2031

J. Pesch, K. Harms, T. Bach
FULL PAPER
6.7 Hz, 6 H, CH(CH3)2] ppm. 13C NMR (62.9 MHz): δ ϭ 164.6 dissolved in a 2:1 (v/v) mixture of methanol/water (100 mL). Upon
(CS), 146.8 (Car-2), 134.5 (Car-1), 129.6 (CarH-3), 128.9 (CarH-6), stirring at 0 °C, a white solid precipitated, which was filtered and
126.8 (2
[CH(CH3)2], 23.4 [CH(CH3)2], 9.9 (CH3) ppm. IR (KBr): ν˜ ϭ 3031 After recrystallisation from methanol, compound rac-17 (7.12 g,
(w, CarH), 2957 (s, CalH), 2864 (s, CalH), 1491 (m, CarϭCar), 1451
74%) was obtained as a colorless crystalline solid. M.p. 213 °C. 1H
ϫ CarH), 121.8 (C-4/C-5), 28.3 [CH(CH3)2], 23.9 washed subsequently with water (100 mL) and Et2O (100 mL).
(m, CarϭCar), 1385 (s), 1353 (s), 1277 (m, CϭS), 1083 (w), 768 (s), NMR (250 MHz, [D6]DMSO): δ ϭ 10.39 (d, J ϭ 2.2 Hz, 1 H,
752 cmϪ1 (s). GC-MS (EI, 70 eV, tR ϭ 27.4 min): m/z (%) ϭ 364
ϩCH), 8.34 (s, 1 H, SCHC), 7.97 (d, 3J ϭ 8.2 Hz, 1 H, Har-6), 7.85
3
(19) [Mϩ], 349 (3) [Mϩ Ϫ CH3], 331 (100) [Mϩ Ϫ SH], 321 (25) (virt. t, J ഠ 8.2 Hz, 1 H, Har-5), 7.66 (virt. t, 3J ഠ 7.9 Hz, 1 H,
[Mϩ Ϫ C3H7], 301 (11), 285 (3), 271 (3). HRMS (EI, 70 eV): calcd. Har-4), 7.43 (d, J ϭ 7.9 Hz, 1 H, Har-3), 2.55 (s, 3 H, CH3), 1.37
3
for C23H28N2S: 364.1973; found 364.1972.
[s, 9 H, C(CH3)3] ppm. 13C NMR (62.9 MHz, [D6]DMSO): δ ϭ
160.3 (ϩCH), 147.5 (NCCH3), 144.8 (Car-2), 132.9 (Car-1), 131.7
(CarH-5), 129.9 (CarH-6), 128.2 (CarH-3), 127.7 (CarH-4), 121.7
(SCHC), 35.6 [C(CH3)3], 31.1 [C(CH3)3], 13.8 (CH3) ppm. IR
(KBr): ν˜ ϭ 3113 (s, CarH), 2957 (s, CalH), 2881 (w, CalH), 2017
(w), 1830 (w), 1570 (m, CarϭCar), 1487 (s, CarϭCar), 1441 (s, Carϭ
Car), 1083 (vs, CϭN), 764 (s), 620 cmϪ1 (s, ClO). C14H18ClNO4S
(331.82): calcd. C 50.68, H 5.47, N 4.22; found C 50.47, H 5.53,
N 4.25.
meso-1,3-Dihydro-1,3-Bis(2-isopropylphenyl)-4,5-dimethyl-2H-
imidazole-2-thiones (meso-14b): Yield 770 mg (22%); Rf ϭ 0.11 (P/
Et2O, 60:40); m.p. 112 °C (dec.). 1H NMR (360 MHz): δ ϭ
7.46Ϫ7.48 (m, 4 H, Har-3/Har-4), 7.31Ϫ7.36 (m, 2 H, Har-5), 7.24
(br. d, 3J ϭ 7.5 Hz, 2 H, Har-6), 2.72 [sept, 3J ϭ 7.1 Hz, 2 H,
CH(CH3)2], 1.89 (s, 6 H, CH3), 1.30 [d, 3J ϭ 7.1 Hz, 6 H,
3
CH(CH3)2], 1.20 [d, J ϭ 7.1 Hz, 6 H, CH(CH3)2] ppm. 13C NMR
(90.5 MHz): δ ϭ 164.5 (CS), 146.7 (Car-2), 134.5 (Car-1), 129.8
(CarH-3), 128.8 (CarH-6), 126.9 (2 ϫ CarH), 121.9 (C-4/C-5), 28.4
[CH(CH3)2], 23.6 [CH(CH3)2], 23.4 [CH(CH3)2], 9.9 (CH3) ppm.
IR (KBr): ν˜ ϭ 3032 (w, CarH), 2956 (s, CalH), 2863 (s, CalH), 1491
(m, CarϭCar), 1451 (m, CarϭCar), 1382 (s), 1349 (s), 1278 (w, Cϭ
S), 1080 (w), 1031(w), 767 (s), 751 cmϪ1 (s). GC-MS (EI, 70 eV,
tR ϭ 28.2 min): m/z (%) ϭ 364 (19) [Mϩ], 349 (3) [Mϩ Ϫ CH3],
331 (100) [Mϩ Ϫ SH], 321 (25) [Mϩ Ϫ C3H7], 301 (11), 285 (3),
271 (3). HRMS (EI, 70 eV): calcd. for C23H28N2S: 374.1973;
found 374.1971.
3-(2-tert-Butylphenyl)-1,3-dihydro-5-(2-hydroxyethyl)-4-methyl-2H-
thiazole-2-thione (rac-18):
A solution of aniline 12a (1.49 g,
1.56 mL, 10.0 mmol) in DMSO (5.00 mL) was treated with 20 
aqueous NaOH (0.50 mL, 10.0 mmol) at ambient temperature. The
mixture was cooled to 0 °C and CS2 (838 mg, 0.66 mL, 11.0 mmol)
was added. Upon stirring for 1 h at ambient temperature, a change
of colour occurred from dark-red to orange. The mixture was co-
oled to 0 °C and a freshly prepared solution of 3-chloro-5-hydroxy-
2-pentanone[34] (2.11 g, 10.0 mmol) in 5 mL of 1,4-dioxane was ad-
ded. After stirring for an additional 1 h at ambient temperature,
water (10 mL) was added and an orange viscous oil separated. The
solvent was decanted and the oily residue was dissolved in ethanol
(5.0 mL). 36% Hydrochloric acid (1.0 mL) was added and the mix-
ture was stirred at ambient temperature for 2.5 h. After washing
the mixture with aqueous NaHCO3 solution to pH 7.0, the solvent
was removed in vacuo and the aqueous residue was extracted with
CH2Cl2 (3 ϫ 50 mL). The combined organic layers were dried with
MgSO4, filtered and the solvent was removed in vacuo. After puri-
fication by flash chromatography (Et2O), compound rac-18 (1.50 g,
49%) was obtained as a pale-yellow oil. Rf ϭ 0.33 (Et2O). 1H NMR
1,3-Bis(2-isopropylphenyl)-4,5-dimethylimidazolium Perchlorate
(15b): A solution of thione 14b (91.0 mg, 0.25 mmol) in THF
(2.00 mL) was cooled to Ϫ78 °C. Perchloric acid (75%, 125 mg,
100 µL, 1.25 mmol) and 75% meta-chloroperbenzoic acid (216 mg,
0.87 mmol) were added and the mixture was stirred for 6 h at Ϫ78
°C. After removal of the solvent in vacuo, the residue was sus-
pended in Et2O and stirred for 2 h. The crude product was filtered
and washed with Et2O (3 ϫ 10 mL). After drying in vacuo, com-
pound 15b (49.0 mg, 45%) was obtained as a pale-yellow powder.
dr (meso/dl) ϭ 9:1. M.p. 205 °C. 1H NMR (250 MHz): δ ϭ 8.48 (s,
1 H, dl-CHϩ), 8.31 (s, 1 H, meso-CHϩ), 7.78Ϫ7.80 (m, 2 H, Har),
7.56Ϫ7.63 (m, 2 H, Har), 7.49Ϫ7.52 (m, 2 H, Har), 7.38Ϫ7.45 (m,
3
4
(250 MHz): δ ϭ 7.64 (dd, J ϭ 8.2, J ϭ 1.4 Hz, 1 H, Har-6), 7.44
(virt. td, 3J ഠ 7.8, 4J ഠ 1.4 Hz, 1 H, Har-4), 7.30 (virt. td, 3J ഠ 8.2,
4J ഠ 1.5 Hz, 1 H, Har-5), 6.90 (dd, 3J ϭ 7.8, 4J ϭ 1.5 Hz, 1 H,
Har-3), 3.76 (t, 3J ϭ 6.1 Hz, 2 H, CH2CH2OH), 3.13 (br. s, 1 H,
3
2 H, Har), 2.68 [sept, J ϭ 6.9 Hz, 2 H, dl-CH(CH3)2], 2.47 [sept,
3J ϭ 6.9 Hz, 2 H, meso-CH(CH3)2], 2.16 (s, 6 H, meso-CH3), 2.14
3
(s, 6 H, dl-CH3), 1.30 [d, J ϭ 6.9 Hz, 6 H, meso-CH(CH3)2], 1.27
3
3
CH2CH2OH), 2.82 (dt, J ϭ 6.1, J ϭ 3.1 Hz, 2 H, CH2CH2OH),
1.86 (s, 3 H, CH3), 1.28 [s, 9 H, C(CH3)3] ppm. 13C NMR
(62.9 MHz): δ ϭ 188.1 (CS), 146.6 (Car-2), 136.7 (SCCH2), 134.9
(Car-1), 130.5 (CarH-3), 129.8 (CarH-4), 129.4 (CarH-6), 127.2
(CarH-5), 120.5 (NCCH3), 61.4 (CH2CH2OH), 36.0 [C(CH3)3], 31.4
[C(CH3)3], 29.7 (CH2CH2OH), 14.1 (CH3) ppm. IR (KBr): ν˜ ϭ
3465 (br, OH), 2959 (m, CalH), 2850 (w, CalH), 1609 (s, SCϪNH),
1491 (m, CarϭCar), 1438 (m, CarϭCar), 1358 (s), 1304 (s), 1253 (vs,
CϭS), 1164 (s), 1052 (s), 986 (m), 768 cmϪ1 (s). GC-MS (EI, 70 eV,
tR ϭ 27.27 min): m/z (%) ϭ 307 (11) [Mϩ], 274 (22) [Mϩ Ϫ SH],
250 (100) [Mϩ Ϫ C4H9], 219 (13), 57 (13) [C4H9ϩ]. C16H21NOS2
(307.48): calcd. C 62.50, H 6.88, N 4.56; found C 62.35, H 6.95,
N 4.56.
3
3
[d, J ϭ 6.9 Hz, 6 H, dl-CH(CH3)2], 1.22 [d, J ϭ 6.9 Hz, 6 H, dl-
CH(CH3)2], 1.16 [d, J ϭ 6.9 Hz, 6 H, meso-CH(CH3)2] ppm. 13C
3
NMR (62.9 MHz)*: δ ϭ 145.6 (dl-Car-2), 144.5 (meso-Car-2), 133.7
(C-4/C-5), 132.0 (dl-CHϩ), 131.9 (meso-CHϩ), 130.4 (meso-Car-1),
130.2 (dl-Car-1), 129.5 (dl-CarH), 129.2 (meso-CarH), 128.5 (meso-
CarH), 128.0 (meso-CarH), 127.8 (dl-CarH), 127.7 (dl-CarH), 127.5
(dl-CarH), 126.8 (meso-CarH), 28.3 [meso-CH(CH3)2], 28.0 [dl-
CH(CH3)2], 24.7 [meso-CH(CH3)2], 24.6 [dl-CH(CH3)2], 23.1 [dl-
CH(CH3)2], 22.8 [meso-CH(CH3)2], 9.0 (dl-CH3), 8.9 (meso-CH3)
ppm. IR (KBr): ν˜ ϭ 3425 (br), 3106 (m, CarH), 2986 (s, CalH),
1545 (s, CarϭCar), 1478 (m, CarϭCar), 1453 (m, CarϭCar), 1232 (w),
1083 (br. s, CϭN), 782 cmϪ1 (s). C23H29N2ClO4 (432.94): calcd. C
63.81, H 6.75, N 6.47; found C 63.49, H 6.81, N 6.52.
3-(2-tert-Butylphenyl)-4-methylthiazolium Perchlorate (rac-17): (4S,7R)-3-(2-tert-Butylphenyl)-4-isopropyl-7-methyl-4,5,6,7-tetra-
Thione rac-20 (vide infra)[21f] (7.66 g, 29.1 mmol) was dissolved in
hydrobenzothiazolium Perchlorate (19): The thione 25 (vide infra)
acetic acid (120 mL) and treated with 30% aqueous H2O2 (8.30 mL, (899 mg, 2.50 mmol) was dissolved in THF (10.0 mL) and cooled
96.0 mmol). Upon stirring for 30 min at ambient temperature the
color of the solution turned from pale yellow to orange. The sol-
vent was removed in vacuo. The residue was dissolved in methanol
(20 mL) and treated with a solution of NaClO4 (16.9 g, 120 mmol)
to Ϫ78 °C. 70% Perchloric acid (2.74 g, 1.08 mL, 12.5 mmol) and
75% mCPBA (2.16 g, 8.75 mmol) were added portionwise and the
resulting suspension was stirred for 4 h at Ϫ78 °C. After warming
to ambient temperature, the solvent was removed in vacuo. The
2032
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 2025Ϫ2035

Axially Chiral N,NЈ-Diarylimidazolium and N-Arylthiazolium Salts
FULL PAPER
residue was dissolved in CH2Cl2 (20 mL), washed with water (3 ϫ
20 mL) and the solvent was removed in vacuo. The residual white
solid was suspended in Et2O (50 mL) and stirred for 2 h. The crude
product was filtered and washed thoroughly with Et2O (50 mL).
2-bromocyclohexanone[27] (1.77 g, 10.0 mmol) was added. After
stirring for 3 h at ambient temperature, water (20 mL) was added
and the mixture was stirred for an additional 10 min at 0 °C. The
precipitate was filtered and successively washed with water
After drying in vacuo, compound 19 (880 mg, 82%) was obtained (20 mL), ethanol (5 mL) and pentane (50 mL). The crude cyclis-
1
as a white solid. M.p. 199 °C. H NMR (400 MHz): δ ϭ 10.00 (s, ation product was suspended in 96% ethanol (30 mL), 36% hydro-
1 H, HCϩ), 7.71 (dd, 3J ϭ 8.3, 4J ϭ 1.4 Hz, 1 H, Har-6), 7.61 (ddd,
chloric acid (1.7 mL, 21.0 mmol) was added and the mixture was
3
4
3
3J ϭ 8.3, J ϭ 6.8, J ϭ 1.9 Hz, 1 H, Har-5), 7.39 (ddd, J ϭ 7.9, heated to reflux for 1 h. After cooling to ambient temperature, the
3J ϭ 6.8, 4J ϭ 1.4 Hz, 1 H, Har-4), 7.35 (dd, 3J ϭ 7.9, 4J ϭ 1.9 Hz, solvent was removed in vacuo. The residue was dissolved in CH2Cl2
1 H, Har-3), 3.11Ϫ3.20 (m, 1 H, 7-H), 2.81 (tdd, 3J ϭ 7.1, 3J ϭ (25 mL) and washed with aqueous NaHCO3 (10 mL) and brine
2
3
3
4.2, J ϭ 1.6 Hz, 1 H, 4-H), 2.19 (dddd, J ϭ 13.5, J ϭ 7.0, J ϭ (25 mL). The organic layer was dried with Na2SO4, filtered and the
3
2
3
3
3.9, J ϭ 4.9 Hz, 1 H, 6-H), 1.96 (dddd, J ϭ 14.2, J ϭ 7.1, J ϭ
solvent was removed in vacuo. After flash chromatographic purifi-
cation (P/Et2O, 60:40), compound rac-21 (1.82 g, 60%) was ob-
7.0, 3J ϭ 3.8 Hz, 1 H, 5-H), 1.82 (dddd, 2J ϭ 14.2, 3J ϭ 10.6, 3J ϭ
7.1, J ϭ 3.7 Hz, 1 H, 5-H), 1.59 [dsept, J ϭ 4.2, J ϭ 6.9 Hz, 1 tained as a white solid. Rf ϭ 0.45 (P/Et2O, 60:40); m.p. 119 °C. 1H
3
3
3
3
3
4
H, CH(CH3)2], 1.45 (d, J ϭ 6.9 Hz, 3 H, CH3), 1.36Ϫ1.45 (m, 1 NMR (400 MHz): δ ϭ 7.64 (dd, J ϭ 8.2, J ϭ 1.4 Hz, 1 H, Har-
H, 6-H), 1.15 [s, 9 H, C(CH3)3], 0.73 [d, 3J ϭ 6.9 Hz, 3 H, 6), 7.43 (ddd, 3J ϭ 8.2, 3J ϭ 7.2, 4J ϭ 1.6 Hz, 1 H, Har-5), 7.30
CH(CH3)2], 0.67 [d, J ϭ 6.9 Hz, 3 H, CH(CH3)2] ppm. 13C NMR (virt. td, 3J ഠ 7.9, 4J ϭ 1.4 Hz, 1 H, Har-4), 6.91 (dd, 3J ϭ 7.9,
3
(90 MHz): δ ϭ 159.3 (CS), 147.5 (C-4Ј), 144.9 (Car-2), 144.5 (C-
7Ј), 133.3 (Car-1), 132.0 (CarH-5), 130.8 (CarH-6), 129.2 (CarH-3),
4J ϭ 1.6 Hz, 1 H, Har-3), 2.51Ϫ2.55 (m, 2 H, 4-H), 2.02Ϫ2.08 (m,
2 H, 7-H), 1.82Ϫ1.89 (m, 2 H, 6-H), 1.73Ϫ1.80 (m, 2 H, 5-H), 1.30
127.5 (CarH-4), 39.8 (CH-4), 36.4 [C(CH3)3], 31.5 [C(CH3)3], 30.6 [s, 9 H, C(CH3)3] ppm. 13C NMR (90 MHz): δ ϭ 188.7 (CS), 147.1
(CH-7), 30.1 (CH2-6), 28.2 [CH(CH3)2], 22.4 (CH3), 20.4 (CH2-5), (Car-2), 138.5 (C-4Ј), 134.4 (Car-1), 130.7 (CarH-6), 130.1 (CarH-5),
19.9 [CH(CH3)2], 16.6 [CH(CH3)2] ppm. IR (KBr): ν˜ ϭ 3070 (s,
129.6 (CarH-4), 127.4 (CarH-3), 120.9 (C-7Ј), 36.4 [C(CH3)3], 31.8
CarH), 2962 (s, CalH), 2873 (w, CalH), 1559 (m, CarϭCar), 1489 (s, [C(CH3)3], 25.6 (C-7), 23.2 (C-4), 22.8 (C-6), 21.8 (C-5) ppm. IR
CarϭCar), 1440 (s, CarϭCar), 1097 (vs, ϩCϭN), 759 (s), 622 cmϪ1 (KBr): ν˜ ϭ 3105 (w, CarH), 2951 (vs, CalH), 2868 (w, CalH), 1620
(s, ClO). C21H30ClNO4S (427.99): calcd. C 58.93, H 7.07, N 3.27;
found C 58.82, H 7.06, N 3.25.
(s, SCϪNH), 1488 (s, CarϭCar), 1437 (s, CarϭCar), 1357 (s), 1312
(s), 1291 (vs, CϭS), 1213 (m), 1044 (m), 776 (m), 757 cmϪ1 (s).
GC-MS (EI, 70 eV, tR ϭ 26.00 min): m/z (%) ϭ 303 (9) [Mϩ], 270
(22) [Mϩ Ϫ SH], 246 (100) [Mϩ Ϫ C(CH3)3], 218 (6), 91 (3)
[C6H5Nϩ], 77 (3) [C6H5ϩ]. C17H21NS2 (303.49): calcd. C 67.28, H
6.97, N 4.62; found C 67.38, H 7.00, N 4.56.
3-(2-tert-Butylphenyl)-1,3-dihydro-4-methyl-2H-1,3-thiazole-2-
thione (rac-20):[21f] A solution of aniline 12a (1.49 g, 1.56 mL,
10.0 mmol) in DMSO (5.00 mL) was treated with 20  aqueous
NaOH (0.50 mL, 10.0 mmol) at ambient temperature. The mixture
was cooled to 0 °C and CS2 (761 mg, 0.60 mL, 10.0 mmol) was 3-(2-tert-Butylphenyl)-4,5,6,7-tetrahydrobenzothiazolium Perchlor-
added. Upon stirring for 1 h at ambient temperature, a change of ate (rac-22): Thione rac-21 (287 mg, 0.95 mmol) was dissolved in
colour from dark-red to orange occurred. The mixture was cooled acetic acid (5.00 mL) and 30% H2O2 (83.6 mg, 0.25 mL,
to 0 °C and chloroacetone (925 mg, 0.80 mL, 10.0 mmol) was ad-
ded. After 1 h of stirring at ambient temperature, water (10 mL)
was added and the mixture was stirred for an additional 10 min at
0 °C upon which a yellow solid precipitated. The solid was filtered,
dissolved in ethanol (10 mL) and treated with 36% hydrochloric
acid (0.5 mL) for 1 h at 80 °C. Upon cooling to ambient tempera-
ture the crude product precipitated. After filtration and recrystalli-
3.04 mmol) was added. After stirring the resulting yellow solution
for 30 min at ambient temperature, the solvent was removed in va-
cuo. The residue was dissolved in methanol (2.00 mL) and treated
with a solution of NaClO4 (0.57 g, 4.00 mmol) in a 2:1 mixture of
methanol/water. After stirring for a few minutes at 0 °C, a yellow
solid precipitated. The crude product was filtered and washed with
water (10 mL) and Et2O (20 mL) and dried in vacuo. Compound
zation from 96% ethanol, rac-20 (1.62 g, 62%) was obtained as rac-22 (288 mg, 82%) was obtained as a pale yellow solid. M.p. 203
1
pale-orange crystals. M.p. 102 °C. H NMR (200 MHz): δ ϭ 7.66 °C. 1H NMR (250 MHz, [D6]DMSO): δ ϭ 10.12 (s, 1 H, ϩCH),
(dd, 3J ϭ 8.1, 4J ϭ 1.5 Hz, 1 H, Har-6), 7.44 (virt. td, 3J ഠ 8.1, 7.67 (dd, 3J ϭ 8.0, 4J ϭ 1.4 Hz, 1 H, Har-6), 7.39 (virt. td, 3J ഠ
3
4
4
3
4
4J ഠ 1.5 Hz, 1 H, Har-5), 7.30 (virt. td, J ഠ 7.7, J ഠ 1.5 Hz, 1 8.0, J ϭ 1.6 Hz, 1 H, Har-5), 7.31 (virt. td, J ϭ 7.9, J ϭ 1.4 Hz,
H, Har-4), 6.86 (dd, 3J ϭ 7.7, 4J ϭ 1.5 Hz, 1 H, Har-3), 6.39 (quart,
1 H, Har-4), 6.94 (dd, 3J ϭ 7.9, 4J ϭ 1.6 Hz, 1 H, Har-3), 2.44Ϫ2.49
(m, 2 H, C-4), 2.14Ϫ2.20 (m, 2 H, 7-H), 1.69Ϫ1.89 (m, 4 H, 5-H/
4J ϭ 1.1 Hz, 1 H, SCH), 1.90 (d, J ϭ 1.1 Hz, 3 H, NCCH3), 1.28
4
[s, 9 H, C(CH3)3] ppm. 13C NMR (50 MHz): δ ϭ 189.9 (CS), 146.5 6-H), 1.12 [s,
9
H, C(CH3)3] ppm. 13C NMR (62.9 MHz,
(Car-2), 140.5 (s, NCCH3), 134.0 (Car-1), 130.4 (CarH-3), 129.6 [D6]DMSO): δ ϭ 160.3 (d, CS), 145.9 (Car-2), 140.3 (Car-1), 134.9
(CarH-6), 129.3 (CarH-4), 127.0 (CarH-5), 106.2 (SCH), 35.9 (C-4Ј), 131.9 (CarH-5), 130.0 (CarH-6), 129.5 (CarH-3), 127.0
[C(CH3)3], 31.2 [C(CH3)3], 16.0 (CH3) ppm. IR (KBr): ν˜ ϭ 3106
(CarH-4), 121.4 (C-7Ј), 36.3 [C(CH3)3], 31.7 [C(CH3)3], 25.6 (CH2-
(w, CarH), 2958 (m, CalH), 2866 (w, CalH), 1591 (s, SCϪNH), 1488 7), 23.5(CH2-4), 22.4 (CH2-6), 20.9 (CH2-5) ppm. IR (KBr): ν˜ ϭ
(s, CarϭCar), 1295 (vs, CϭS), 769 (m), 733 cmϪ1 (m). MS (EI, 3104 (s, CarH), 2957 (s, CalH), 1584 (m, CarϭCar), 1493 (m, Carϭ
70 eV): m/z (%) ϭ 263 (17) [Mϩ], 230 (20) [Mϩ Ϫ SH], 206 (100)
[Mϩ Ϫ C4H7]. C14H17NS2 (263.42): calcd. C 63.83, H 6.50, N 5.32;
found C 63.49, H 6.46, N 5.37.
Car), 1448 (m, CarϭCar), 1092 (vs, ϩCϭN), 775 (s), 622 cmϪ1 (s,
ClO). C17H22ClNO4S (371.88): calcd. C 54.91,H 5.96, N 3.77;
found C 54.67, H 6.07, N 3.81.
3-(2-tert-Butylphenyl)-4,5,6,7-2H-tetrahydrobenzothiazole-2-thione (4S,7R)-3-(2-tert-Butylphenyl)-4-isopropyl-7-methyl-4,5,6,7-2H-
(rac-21): A solution of aniline 12a (1.49 g, 1.56 mL, 10.0 mmol) in tetrahydrobenzothiazole-2-thione (25): Aniline 12a (14.4 g, 15.0 mL,
DMSO (50 mL) was treated with 20  aqueous NaOH (0.50 mL, 96.3 mmol) dissolved in DMSO (100 mL) was treated with 24 
10.0 mmol) at ambient temperature. The mixture was cooled to 0
°C and CS2 (838 mg, 0.66 mL, 11.0 mmol) was added. Upon stir-
ring for 1 h at ambient temperature, a change of colour from dark-
red to orange occurred. Again the solution was cooled to 0 °C and
aqueous KOH (3.00 mL, 96.3 mmol) at ambient temperature. The
solution was cooled to 0 °C and CS2 (8.00 g, 6.40 mL, 105 mmol)
was added. Upon stirring for 1 h at ambient temperature, a change
of colour from dark-red to orange occurred. The mixture was co-
Eur. J. Org. Chem. 2004, 2025Ϫ2035
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2033

J. Pesch, K. Harms, T. Bach
FULL PAPER
oled to 0 °C and α-bromomenthone 23[28] (20.4 g, 87.5 mmol) was After flash chromatographic purification (P/Et2O, 80:20 Ǟ 50:50),
added. After stirring for 2 h at ambient temperature, the mixture
was poured into ice water (300 mL) and extracted with Et2O (3 ϫ
chromanone 10a[7,16] (82.0 mg, 75%) was obtained as a pale-yellow
solid in an optical purity of 50% ee. Rf ϭ 0.36 (P/Et2O, 60:40);
250 mL). The combined organic layers were washed with water (2 tR ϭ 15.9/19.4 min [(R)-isomer/(S)-isomer, ChiralPak AD, hexane/
1
3
ϫ 100 mL) and brine (2 ϫ 100 mL), dried with Na2SO4, filtered isopropanol, 95:5]. H NMR (360 MHz): δ ϭ 7.89 (dd, J ϭ 8.0,
and the solvent removed in vacuo. The oily residue was dissolved
4J ϭ 1.6 Hz, 1 H, 5-H), 7.49 (ddd, 3J ϭ 8.3, 3J ϭ 7.0, 4J ϭ 1.6 Hz,
in pentane (100 mL). Upon treatment with a mixture of 1  HCl in 1 H, 7-H), 7.03 (ddd, J ϭ 8.0, J ϭ 7.0, J ϭ 0.9 Hz, 1 H, 6-H),
3
3
4
Et2O (80 mL) and pentane (200 mL) precipitation of the cyclisation
product occurred. The crude product was filtered, washed with
pentane (150 mL) and dissolved in ethanol (abs., 70.0 mL). 98%
6.98 (dd, 3J ϭ 8.3, 4J ϭ 0.9 Hz, 1 H, 8-H), 4.61 (dd, 2J ϭ 11.1,
3
2
3J ϭ 5.2 Hz, 1 H, 2-H), 4.30 (dd, J ϭ 12.0, J ϭ 11.1 Hz, 1 H, 2-
H), 3.73 (s, 1 H, COOCH3), 3.35 (virt. tdd, 3J ഠ 5.2, 3J ϭ 12.0,
Methanesulfonic acid (11.5 g, 7.80 mL, 120 mmol) was added and 3J ϭ 8.0 Hz, 1 H, 3-H), 2.95 (dd, 2J ϭ 17.2, 3J ϭ 5.0 Hz, 1 H,
the solution was heated under reflux for 5 h. One half of the solvent
CH2COOCH3), 2.44 (dd, 2J 17.2, 3J
ϭ ϭ 8.0 Hz, 3 H,
was removed in vacuo and the mixture was cooled to 4 °C. After CH2COOCH3) ppm. 13C NMR (62.9 MHz): δ ϭ 192.6 (C-4), 171.8
two days of crystallization the product was filtered, washed with (COOCH3), 161.6 (C-8Ј), 136.0 (CH-7), 127.3 (CH-5), 121.5 (CH-
ice-cold ethanol (2 ϫ 40 mL) and pentane (200 mL). After drying
in vacuo, compound 25 (10.4 g, 33%) was obtained as white crys-
tals. M.p. 125 °C. 1H NMR (400 MHz): δ ϭ 7.62 (dd, 3J ϭ 8.2,
4J ϭ 1.4 Hz, 1 H, Har-6), 7.42 (ddd, 3J ϭ 8.2, 3J ϭ 7.1, 4J ϭ 1.5 Hz,
6), 120.3 (C-5Ј), 117.8 (CH-8), 70.1 (CH2-2), 52.0 (COOCH3), 42.4
(CH-3), 30.0 (CH2COOCH3) ppm.
3
3
4
1 H, Har-5), 7.26 (ddd, J ϭ 7.9, J ϭ 7.1, J ϭ 1.4 Hz, 1 H, Har-
Acknowledgments
3
4
4), 7.08 (dd, J ϭ 7.9, J ϭ 1.5 Hz, 1 H, Har-3), 2.76Ϫ2.70 (m, 1
This project was supported by the Fonds der Chemischen Industrie.
We would like to thank A. Stengel, T. H. Endl, T. Bartels and A.
Schmid (undergraduate research participants) for skilful technical
assistance.
3
3
3
5
H, 7-H), 2.36 (dddd, J ϭ 7.0, J ϭ 5.8, J ϭ 4.2, J ϭ 1.6 Hz, 1
H, 4-H), 2.03 (dddd, J ϭ 13.4, J ϭ 8.5, J ϭ 5.0, J ϭ 3.7 Hz, 1
3
3
3
3
3
3
3
3
H, 6-H), 1.80 (dddd, J ϭ 14.1, J ϭ 8.5, J ϭ 7.0, J ϭ 3.7 Hz, 1
H, 5-H), 1.66 (dd, 3J ϭ 14.1, 3J ϭ 9.1, 3J ϭ 5.8, 3J ϭ 3.7 Hz, 1 H,
3
3
5-H), 1.49 (septd, J ϭ 7.0, J ϭ 4.2 Hz, CH(CH3)2], 1.37 (dddd,
3J ϭ 13.4, 3J ϭ 9.1, 3J ϭ 7.0, 3J ϭ 3.7 Hz, 1 H, 6-H), 1.26 [s, 9 H,
C(CH3)3], 1.22 [d, 3J ϭ 7.0 Hz, 3 H, CH(CH3)2], 0.68 [d, 3J ϭ
[1] [1a]
Review: J. Liebscher, in Methoden der organischen Chemie
(Ed.: A. de Mejiere), Houben-Weyl, 4th ed., Vol. E8b, Thieme,
[1b]
7.0 Hz, 3 H, CH(CH3)2], 0.62 (d, 3J ϭ 6.8 Hz, 3 H, CH3) ppm. 13
C
Stuttgart 1994, pp. 192Ϫ194.
H.-J. Schönherr, H.-W.
[1c]
Wanzlick, Justus Liebigs Ann. Chem. 1970, 731, 176Ϫ179.
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NMR (62.9 MHz): δ ϭ 188.6 (CS), 146.3 (Car-2), 140.9 (C-4Ј),
134.5 (Car-1), 132.0 (CarH-3), 130.7 (CarH-6), 129.6 (CarH-4), 129.2
(C-7Ј), 126.4 (CarH-5), 39.7 (CH-4), 36.2 [C(CH3)3], 31.7
[C(CH3)3], 30.1 (CH2-6), 29.5 (CH-7), 27.8 [CH(CH3)2], 22.2
(CH3), 20.3 (CH2-5), 20.2 [CH(CH3)2], 17.0 [CH(CH3)2] ppm. IR
(KBr): ν˜ ϭ 3030 (w), 2957 (m, CalH), 2861 (w, CalH), 1604 (s,
SCϪNH), 1489 (m, CarϭCar), 1438 (m, CarϭCar), 1368 (s), 1312
(s), 1283 (s, CϭS), 1192 (s), 1051 (s), 920 (m), 819 (w), 756 cmϪ1
(s). MS (EI, 70 eV): m/z (%) ϭ 359 (13) [Mϩ], 326 (19) [Mϩ Ϫ SH],
302 (100) [Mϩ Ϫ C4H9], 259 (6), 244 (8), 91 (14) [C6H5Nϩ]. HRMS
(EI, 70 eV): calcd. for C21H29NS2: 359.1741; found 359.1739.
[2] [2a]
[2b]
F. Wöhler, J. Liebig, Ann. Pharm. 1832, 3, 249Ϫ301.
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Enantioselective Benzoin Condensation with Thiazolium Salt 19 as
Pre-Catalyst: Thiazolium salt 19 (42.7 mg, 0.10 mmol) and benzal-
dehyde (104 mg, 0.10 mL, 1.00 mmol) were suspended in THF
(0.50 mL). Triethylamine (10.1 mg, 14.0 µL, 0.10 mmol) was added
under vigorous stirring and the solution was stirred for 16 h at
ambient temperature. The mixture was directly poured onto silica
gel to stop the reaction. After flash chromatographic purification
(P/Et2O, 80:20 Ǟ 50:50), (R)-benzoin (2, 88.4 mg, 85%) was ob-
tained as a white solid in an optical purity of 40% ee. Rf ϭ 0.36
(P/Et2O, 60:40). [α]2D5 ϭ Ϫ65 (c ϭ 1.0 in MeOH); tR ϭ 15.4/
20.8 min [(S)-isomer/(R)-isomer, ChiralPak AD, hexane/isopro-
Engl. 1974, 13, 539.
[5]
[6]
[5a]
Reviews:
H. Stetter, Angew. Chem. 1976, 88, 695Ϫ704; An-
gew. Chem. Int. Ed. Engl. 1976, 15, 639Ϫ647. [5b] H. Stetter, H.
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[8a]
M. Regitz, Angew. Chem. 1996, 108,
[8b]
791Ϫ794; Angew. Chem. Int. Ed. Engl. 1997, 35, 724Ϫ728.
W. A. Herrmann, C. Köcher, Angew. Chem. 1997, 109,
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2002, 114, 1342Ϫ1363; Angew. Chem. Int. Ed. 2002, 41,
1
panol, 95:5]. H NMR (360 MHz): δ ϭ 7.93Ϫ7.90 (m, 2 H, Har),
7.55Ϫ7.26 (m, 8 H, Har), 5.95 (s, 1 H, CHOH), 4.55 (br. s, 1 H,
OH) ppm. 13C NMR (90 MHz): δ ϭ 199.0 (CϭO), 139.0 (Car-1),
133.9 (CarH-4), 133.5 (Car-1Ј), 129.1 (CarH-2), 129.0 (CarH-3),
128.7 (CarH-2Ј), 128.6 (CarH-4Ј), 127.8 (CarH-3Ј), 76.2 (CHOH)
ppm.
[8e]
W. A. Herrmann, Angew. Chem.
1290Ϫ1309.
[9]
Review on asymmetric variants of the benzoin and Stetter reac-
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Springer-Verlag, Berlin, Heidelberg, 1999, 1093Ϫ1102.
Enantioselective Intramolecular Stetter Reaction with Thiazolium
Salt 19 as Pre-Catalyst: Thiazolium salt 19 (42.7 mg, 0.10 mmol)
and methyl ester 9a[34] (110 mg, 0.50 mmol) were suspended in
THF (0.50 mL). Triethylamine (10.2 mg, 14.0 µL, 0.10 mmol) was
added and the solution was stirred for 21 h at ambient temperature.
The mixture was directly poured onto silica gel to stop the reaction.
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[10b]
R. Breslow, J. Am. Chem. Soc. 1958, 80, 3719Ϫ3726.
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2034
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 2025Ϫ2035

Axially Chiral N,NЈ-Diarylimidazolium and N-Arylthiazolium Salts
FULL PAPER
charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from
the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax:
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´
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3
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12 Union Road, Cambridge CB2 1EZ, UK; Fax: (internat.)
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Crystal data of compound 25, (C21H29NS2, Mr ϭ 359.57): crys-
tal size 0.39 ϫ 0.30 ϫ 0.21 mm, orthorhombic, space group
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[21] [21a]
Review: R. Gallo, C. Roussel, U. Berg, Adv. Heterocycl.
P212121, a ϭ 880.0(1), b ϭ 1335.1(2), c ϭ 1773.4(1) pm, U ϭ
[21b]
3
2083.5(3) A , ρcalcd. ϭ 1.146 g cmϪ3 Z ϭ 4, F(000) ϭ 776, µ ϭ
˚
Chem. 1988, 43, 173Ϫ299.
Soc., Perkin Trans. 2 1985, 273Ϫ277.
jimi, A. Chemlal, A. Djafri, J. Org. Chem. 1988, 53,
A. Djafri, C. Roussel, J. Chem.
[21c]
2.6 cmϪ1, IPDS2 diffractometer, λ ϭ 0.71073 A, T ϭ 193 K,
˚
C. Roussel, M. Ad-
14302 reflections (h Ϯ10, k Ϯ15, l Ϯ21), 2Θmax. ϭ 24.99°, 3616
independent and 3002 observed reflections [I Ͼ 2σ(I)], 3616
used for refinement, 244 parameters, R1 ϭ 0.0305, wR2 ϭ
[21d]
5076Ϫ5080.
C. Roussel, A. Chemlal, New J. Chem. 1988,
12, 947Ϫ952. [21e] A. Djafri, M. Bouchekara, F. Djafri, F. Bena-
[21f]
0.0805, residual electron density 0.10 e·AϪ3, direct methods,
˚
chenhou, J. Soc., Alger. Chim. 1996, 6, 123Ϫ136.
sel, C. Suteu, J. Chromatogr. A 1997, 761, 129Ϫ138.
C. Rous-
[21g]
A.
hydrogen atoms calculated, ‘‘Flack parameter’’ (absolute struc-
ture) ϭ 0.05(7). CCDC-218997 contains the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html
(or from the CCDC, 12 Union Road, Cambridge CB2
1EZ, UK; Fax: (internat.) ϩ44-1223-336033; E-mail:
deposit@ccdc.cam.ac.uk).
Hirtopeanu, M. Mihai, G. Mihai, C. Roussel, Heterocycles
2000, 53, 1669Ϫ1675. [21h] A. Hirtopeanu, C. Suteu, C. Uncuta,
G. Mihai, C. Roussel, Eur. J. Org. Chem. 2000, 1081Ϫ1090.
D. J. Tempel, L. K. Johnson, R. L. Huff, P. S. White, M. Brook-
hart, J. Am. Chem. Soc. 2000, 122, 6686Ϫ6700.
Crystal data of compound dl-14b: (C23H28N2S, Mr ϭ 364.53):
crystal size 0.54 ϫ 0.45 ϫ 0.27 mm, monoclinic, space group
[22]
[23]
[30]
Crystal data of compounds 19 and 27, (C21H30ClNO4S, Mr ϭ
427.99): crystal size 0.42 ϫ 0.42 ϫ 0.33 mm, triclinic, space
group P1, a ϭ 781.8(1), b ϭ 913.7(1), c ϭ 1729.5(1) pm, α ϭ
P21/n, a ϭ 1334.7(1), b ϭ 1906.8(1), c ϭ 1706.4(1) pm, β ϭ
3
108.39(5)°, U ϭ 4121.0(4) A , ρcalcd. ϭ 1.175 g·cmϪ3 for Z ϭ
˚
8, F(000) ϭ 1568, µ ϭ 1.7 cmϪ1, IPDS-II diffractometer, λ ϭ
92.20(1), β ϭ 101.45(1), γ ϭ 113.94(1)°, U ϭ 1096.91(14) A ,
3
˚
0.71073 A, T ϭ 193 K, 40839 reflections (h Ϯ15, k Ϯ22, l Ϯ20),
ρcalcd. ϭ 1.296 g cmϪ3 for Z ϭ 2, F(000) ϭ 456, µ ϭ 3.0 cmϪ1
,
˚
˚
2Θmax. ϭ 24.94°, 7171 independent and 4775 observed reflec-
tions [I Ͼ 2σ(I)], 7171 reflections used for refinement, 481 par-
ameters, R1 ϭ 0.0341, wR2 ϭ 0.0947, residual electron density
IPDS2 diffractometer, λ ϭ 0.71073 A, T ϭ 193 K, 13116 reflec-
tions (h Ϯ9, k Ϯ10, l Ϯ20), 2Θmax. ϭ 25.0°, 7242 independent
and 6811 observed reflections [I Ͼ 2σ(I)], 7242 reflections used
for refinement, 545 parameters, R1 ϭ 0.0295, wR2 ϭ 0.0780,
0.28 e·AϪ3, direct methods, hydrogen atoms calculated. CCDC-
˚
residual electron density Ϫ0.24 e·AϪ3, direct methods, hydro-
˚
219600 contains the supplementary crystallographic data for
this compound. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC,
12 Union Road, Cambridge CB2 1EZ, UK; Fax: ϩ44-1223-
336033; E-mail: deposit@ccdc.cdm.ac.uk).
Crystal data of compound meso-15b: (C23H29ClN2O4·DMSO,
Mr ϭ 511.06), crystal size 0.24 ϫ 0.24 ϫ 0.09 mm, orthorhom-
gen atoms calculated, ‘‘Flack parameter’’ (absolute struc-
ture) ϭ Ϫ0.02(3). CCDC-218996 contains the supplementary
crystallographic data for compounds 19 and 27 which crys-
tallized in a single crystal. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from
the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax:
(internat.) ϩ44-1223-336033; E-mail: deposit@ccdc.cam.ac.uk).
A referee pointed out that the interpretation for the stereoselec-
tivity in the Stetter reaction (transition state 31϶) could also
be based on an alternative transition state suggested in ref.[17]
W. C. Still, M. Kahn, A. J. Mitra, J. Org. Chem. 1978, 43,
2923Ϫ2925.
[24]
bic, space group Pnma, a ϭ 1347.0(1), b ϭ 1513.6(1), c ϭ
3
[31]
1346.2(1) pm, U ϭ 2744.6(3) A , ρcalcd. ϭ 1.237 g·cmϪ3 for Z ϭ
˚
4, F(000) ϭ 1088, µ ϭ 2.51 cmϪ1, Stoe IPDS diffractometer,
˚
λ ϭ 0.71073 A, T ϭ 193 K, 17814 reflections (h Ϯ16, k Ϯ18,
[32]
[33]
[34]
l Ϯ16), 2Θmax. ϭ 25.97°, 2790 independent and 1605 observed
reflections [I Ͼ 2σ(I)], 2790 reflections used for refinement, 190
parameters, R1 ϭ 0.0517, wR2 ϭ 0.144, residual electron den-
F. J. Leeper, D. H. C. Smith, J. Chem. Soc., Perkin Trans. 1
1995, 861Ϫ873.
sity 0.77 e·AϪ3, direct methods, hydrogen atoms refined.
˚
CCDC-218998 contains the supplementary crystallographic
data for this compound. These data can be obtained free of
E. Ciganek, Synthesis 1995, 1311Ϫ1314.
Received May 5, 2003
Eur. J. Org. Chem. 2004, 2025Ϫ2035
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2035