Enantiospecific synthesis of 4-(4'-methoxyphenyl)-hexan-3-one as precursor for optically active (pS) or (pR) isomer of (Z) or (E)-3-(2'-((N,N-dimethylamino)methylferrocenyl)-4-(4''-methoxyphenyl)-hex-3-ene

Article abstract of DOI:10.1016/S0957-4166(97)00636-8

We describe herein an original method for the preparation of enantiomerically pure (Z)- or (E)-3-(2'-((N,N-dimethylamino)methylferrocenyl)-4-(4''-methoxyphenyl)-hex-3-ene possessing a p(S) or p(R) plane of chirality. The key step of the synthesis lies in obtaining enantiomerically pure (R) or (S) 4-(4'-methoxyphenyl)-hexan-3-one whose reaction with the lithiated N,N-dimethylaminomethylferrocene leads to two enantiomerically pure amino-alcohol diastereomers (pS,3S,4R) and (pR,3S,4R), or (pS,3R,4S) and (pR,3R,4S) respectively. Subsequent dehydration yields a mixture of three olefins, namely, two trisubstituted olefins and either the (Z)- or (E)-tetrasubstituted olefin with respect to the starting amino-alcohol diastereomer. Additionally we obtained the enantiomerically pure (R)- and (S)-4-phenyl-hexan-3-one and the corresponding diastereomeric amino-alcohols.

Full text of DOI:10.1016/S0957-4166(97)00636-8

Pergamon
Tetrahedron: Asymmetry 9 (1998) 259–269
Enantiospecific synthesis of 4-(40-methoxyphenyl)-hexan-3-one
as precursor for optically active (pS) or (pR) isomer of (Z) or
(E)-3-(20-((N,N-dimethylamino)methylferrocenyl)-4-
(400-methoxyphenyl)-hex-3-ene
Bernard Malézieux,a,∗ Michel Gruselle,a Ludmila Troitskaya b and Viatcheslav Sokolovb
aLaboratoire de Chimie des Métaux de transition, URA CNRS 419 Université P. et M. Curie, Case 42, 4, Place Jussieu 75252,
Paris Cédex 05, France
bLaboratory for Organometallic Stereochemistry, Institute of Organoelement Compounds (INEOS), Russian Academy of
Sciences, 28 Vavilov Street, 117813 Moscow, Russia
Received 7 November 1997; accepted 16 December 1997
Abstract
We describe herein an original method for the preparation of enantiomerically pure (Z)- or (E)-3-(20-((N,N-
dimethylamino)methylferrocenyl)-4-(400-methoxyphenyl)-hex-3-ene possessing a p(S) or p(R) plane of chirality.
The key step of the synthesis lies in obtaining enantiomerically pure (R) or (S) 4-(40-methoxyphenyl)-hexan-
3-one whose reaction with the lithiated N,N-dimethylaminomethylferrocene leads to two enantiomerically pure
amino-alcohol diastereomers (pS,3S,4R) and (pR,3S,4R), or (pS,3R,4S) and (pR,3R,4S) respectively. Subsequent
dehydration yields a mixture of three olefins, namely, two trisubstituted olefins and either the (Z)- or (E)-
tetrasubstituted olefin with respect to the starting amino-alcohol diastereomer. Additionally we obtained the
enantiomerically pure (R)- and (S)-4-phenyl-hexan-3-one and the corresponding diastereomeric amino-alcohols.
© 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction
The synthesis of heterobimetallic compounds possessing a conjugated electronic system connecting
the two metallic sites has received considerable attention due to the opportunity for observing cooperative
properties behavior.1 A simple molecular wire might be composed of two metallocenic functions
connected by a double bond. In such a case the charge can be selectively created at one of the two
metallic centers depending on the nature of the metal.
∗
Corresponding author. E-mail: gruselle@ccr.jussieu.fr
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(97)00636-8

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Fig. 1. Aryl ferrocenyl ethylene — type A
In addition, one of the two metallic π-complexes when properly disubstituted can present a plane
of chirality and be obtained in the active form.2 For our purpose the most useful models are the aryl
ferrocenyl ethylenes (type A) (Fig. 1).
Some ferrocenic 1,2 or 1,3 disubstituted compounds are well known in enantiomerically pure forms3
as well as those belonging to the arene complexes series.4 Olefins of type A are generally obtained by a
Wittig reaction starting from optically active 1,2 disubstituted ferrocene carboxaldehydes.5 However, this
reaction yields predominantly the (E)-olefins. Our objective was the synthesis of the (Z) and the (E)-3-
(20-((N,N-dimethylamino)methylferrocenyl)-4-(400 -methoxyphenyl)-hex-3-ene possessing a p(S) or p(R)
plane of chirality6 by using optically active amino-alcohols as precursors.
We have previously described the synthesis of the optically active ferrocenic amino-alcohols7: 3-
(20-((N,N-dimethylamino)methylferrocenyl)-4-(400 -methoxyphenyl)-hexan-3-ols. Their relative config-
urations were unambiguously determined for the racemic compounds by X-ray diffraction studies.7 The
absolute configurations were deduced from the configuration of the starting cyclopalladated ferrocenic
compound previously described in the literature.8 The carbon–carbon bond between the ferrocenic
moiety and the six membered aromatic ring was built by action of the lithiated ((N,N-dimethylamino)-
methyl)-ferrocene (LiDMAMF) on the appropriate ketone (Scheme 1).
Scheme 1. Control of the chirality by asymmetric cyclopalladation
The main characteristic of this nucleophilic addition is the high diastereoselectivity of the reaction
leading to two of the four possible isomers. The configuration of the generated new asymmetric carbon
is, in most of the cases reported in the literature,9 correlated to the configuration of the plane of chirality
in the lithiated substituted ferrocene. In this example, the stereochemical course of the reaction is under
the control of the configuration of the carbon adjacent to the ketone as described earlier for some

B. Malézieux et al. / Tetrahedron: Asymmetry 9 (1998) 259–269
261
nucleophilic attacks.10 In the previous approach7 the control of the chirality was reached using the
classical asymmetric cyclopalladation of DMAMF followed by the iodination and then the lithiation
of the iodide. The optically active (pS) or (pR) lithiated ferrocene moiety reacts diastereoselectively with
the racemic 4-(40-methoxyphenyl)-hexan-3-one to yield two diastereomers (pR,3S,4R) and (pR,3R,4S)
or (pS,3R,4S) and (pS,3S,4R) respectively with moderate enantiomeric excess (65 to 70%) according
to those obtained for the cyclopalladated compounds. Based on these results, we planned to invert the
synthetic strategy, i.e. to use optically pure 4-(40-methoxyphenyl)-hexan-3-one and racemic LiDMAMF.
We anticipated the formation of the target ferrocenic amino-alcohols in high enantiomeric excesses
(Scheme 2).
Scheme 2. Formation of the two diastereomeric amino-alcohol (pR,3R,4S)-5b and (pS,3R,4S)-6b from ketone (4S)-4b
The subsequent formation of the tri- and tetra-substituted olefins from the amino-alcohols was achieved
by acidic treatment. The reaction is very specific in the sense that the geometry (Z) or (E) of the
obtained tetrasubstituted olefins depends solely on the relative configuration of the starting amino-alcohol
(Scheme 3).11
Scheme 3. Formation of the olefins from the amino-alcohols

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2. Results and discussion
Several methods of preparation of 2-aryl-alkylketones as a racemic mixture12 or as optically active
compounds13 were described earlier. They are most commonly formed in the reaction of a lithiated
aliphatic compound with 2-phenylalkanoic acids.14 Metallated chiral hydrazones can be used as interme-
diates in this synthesis.15 Recently enzymatic oxidations of secondary alcohols were also reported.16
We propose therein a new and efficient way to prepare optically active 4-aryl-hexan-3-ones combining
an enzymatic resolution of 2-aryl-butanoic acids followed by classical conversion of the carboyl into a
ketone (Scheme 4).
Scheme 4. Obtention of the ketones from the acids
Different methods have been used to achieve the resolution of aliphatic organic acids by
bioconversion.17 One of the most efficient and useful techniques uses the enzymatic resolution of
the racemic methyl esters by enantioselective hydrolysis.18 This approach, which usually gives good
yields, requires very simple and inexpensive experimental conditions.19 The enantiomerically pure
(R)-or (S)-2-phenyl-(or-(40 -methoxyphenyl))-butanoic acids 1a (or 1b) were prepared from the methyl
esters 2a (or 2b) by using horse liver esterase (HLE). [The reaction is also possible with pig liver esterase
(PLE) but with no satisfactory ee (65% for the unreacted ester) at pH 7.2 at room temperature.] In this
enzymatic reaction the (R) isomer is primarily hydrolyzed under the conditions described by Bloch.20
(Scheme 5).
Scheme 5. Obtention of the optically pure acids 1a or 1b by horse liver esterase

B. Malézieux et al. / Tetrahedron: Asymmetry 9 (1998) 259–269
263
Table 1
The methyl esters with (S) configuration 2a (or 2b) were recovered in 34% yield and 93% ee based on
the literature values of the acids21,22 after three days of enzymatic treatment of the racemic mixtures of
2a (or 2b). Hydrolyses by KOH in aqueous ethanol solution yielded the corresponding acids (S)-1a (or
(S)-1b). The (R) enantiomers of acids 1a (or 1b) were obtained after one step in 60% yield with an ee of
56%. The re-esterification followed by another cycle of enzymatic treatment afforded after one day the
expected (R) isomers with ee of 96% in 35% yield.
The acids 1a (or 1b) were transformed into their corresponding acid chlorides 3a (or 3b) using thionyl
chloride at 80°C for one hour and purified by distillation in vacuo (5 mmHg). Rotation values for 1a and
1b are reported in Table 1 and compared to those found in the literature.
The absence of racemization during the formation of the acid chlorides was confirmed by hydrolysis.
The recovered acids present an identical specific rotation as the initial compounds. Attempts to prepare
optically active ketones by the reaction of ethyl lithium with the corresponding acid 1a (or 1b) according
to literature23 failed, resulting in partially racemized ketone (ee 40–60%) even at low temperature.
The (R) or (S)-4-phenyl-(or-(40 -methoxyphenyl))-hexan-3-one 4a (or 4b) were therefore prepared by
the reaction of bromoethyl magnesium cuprate with the optically active (R) or (S)-2-phenyl-(or-(40 -
methoxyphenyl))-butanoyl chloride 3a (or 3b) according to the method described by Dubois and
Boussu24 for the preparation of hindered ketones. The ketones 4a (or 4b) were obtained by addition of
an ethereal solution of the butanoyl chlorides 3a (or 3b) at low temperature (−60°C) to a stoichiometric
amount of bromoethyl magnesium cuprate. After acidic hydrolysis the ketones were isolated in 78%
yield by flash-chromatography on silica gel (eluent pentane:ether=95:5). The optical rotations of ketones
4a and 4b were recorded in toluene25 and are reported in Table 2. To our knowledge, the optically active
form of 4b has never been reported.
The next step in the synthesis was the reaction of the racemic lithiated DMAMF with the optically
active ketones (R) or (S)-4a (or 4b). This step was described earlier7 and therefore we only report the
optical rotation values, enantiomeric excesses and absolute configurations of each of the amino-alcohols

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Table 2
Table 3
in Table 3: (pR,3R,4S)-5a, (pS,3S,4R)-5a, (pR,3S,4R)-6a (pS,3R,4S)-6a (or 5b, 6b). It is noteworthy that
the relations between the rotations of the amino-alcohols and their corresponding enantiomeric excesses
based on those of the starting ketones, correlate perfectly with our previous results based on the ee of the
starting ferrocenic cyclopalladated compounds.
The absence of racemization during the acidic hydrolysis renders possible the recycling of the starting
ketone. This fact allowed us to obtain an overall yield of 55% of amino-alcohols. This opportunity does
not exist in the asymmetric cyclopalladation approach in which the unreacted optically active material is
lost. Finally, the target olefins (Z)-7b (or (E)-7b) were obtained by reaction of trifluoroacetic acid with
the amino-alcohols 5b (or 6b) in dichloromethane at room temperature (Scheme 2). The yields, specific
rotation values and ees are reported in Table 4. The yields of tetrasubstituted olefins are relatively low,
however, it is possible to increase them by using the corresponding co-products trisubstituted olefins 8b
(Scheme 2) as new starting materials.
3. Conclusion
This work describes the preparation of ferrocenic amino-alcohols with high enantiomeric purity,
exhibiting three elements of chirality including a ferrocenic plane. The key step of this synthesis is the
easy preparation of optically active aryl-alkylketones with high ees and their diastereoselective conden-
sation with the lithiated dimethyl aminomethylferrocene. The resulting amino-alcohols are selectively

B. Malézieux et al. / Tetrahedron: Asymmetry 9 (1998) 259–269
265
Table 4
dehydrated to yield trisubstituted and tetrasubstituted olefins with predictible (Z) or (E) configuration,
for which specific rotation has been determined.
4. Experimental methods
4.1. General information
All reactions were carried out under an atmosphere of dry argon. Solvents were dried and distilled
using standard techniques. Diethyl ether was distilled from sodium:benzophenone, methylene chloride
from sodium hydride, pentane was treated with sulfuric acid and distilled with sodium, triethylamine was
dried with sodium. DMAMF was obtained from Aldrich and was distilled under reduced presure before
use. Horse liver acetone powder was obtained from Sigma and used as received. 1H and 13C spectra were
recorded on a Brucker AM 250 instrument, using standard programmes for proton (299.9 MHz) and
carbon (75 MHz) spectra. NMR chemical shifts are reported in δ (ppm) relative to TMS (1H, 13C) J values
are given in hertz. Elemental analyses were performed by Centre Régional de Microanalyse, Université
Pierre et Marie Curie. Optical rotations were recorded on an Ameria AA-10 polarimeter at a wavelength
of 589 nm (sodium D line) using a 1.0 dm cell with a total volume of 1.3 mL. The enantiomeric excesses
of the methylated acids and the ketones were determined by HPLC using a chiral column (Chiralcel OJ
eluent isopropanol:heptane 0:5 to 1% with a flow of 0.5 to 1 ml/min, detector at 300 nm). The (Z) and
(E) geometries have been determined by NMR analysis using an NOE DIFF programme.
4.2. (R) and (S)-2-Aryl-butanoic-acid 1a (aryl=phenyl) or 1b (aryl=40methoxyphenyl)
4.2.1. General procedure
In an 150 mL Erlenmeyer flask, 3 g (15 mmol) of ester 2b in 90 mL of phosphoric buffer solution
pH 7.2 (for 1 L: 53.7 g Na2HPO4·12H2O; 6.8 g KH2PO4) were stirred with 3 g of horse liver acetone
powder (Sigma) at room temperature for 90 h. The mixture was acidified with 2 mL of conc. HCl and
extracted five times with 50 mL of ether with the help of a centrifuge (5 min at 4000 t/min). The acidic
organic ethereal layer was then basified with 150 mL of saturated Na2CO3 solution and the resulting

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B. Malézieux et al. / Tetrahedron: Asymmetry 9 (1998) 259–269
aqueous layer washed 5 times with ether (200 mL). The basic ethereal layers were filtered through silica
gel and the removal of the solvent gave the optically active (S)-2b ester form (1.02 g, ee 93%; 61%
saponification; yield 34%). The basic aqueous layer was then acidified with conc. HCl until precipitation
was complete, extracted (ether, 3×120 mL) and filtered through silica gel to yield 1.46 g of the (R)-1b
acid form (ee 56%; yield 52%).
The optically enriched acid was re-esterified for another cycle of 24 h with the enzyme (in the ratio:
2 g for 3 g of (R)-(−)-2b) and treated under the same conditions as described above, yielding 0.55 g of
(R)-1b (38% saponification, 95% ee; yield 35%). (R)-1a [α]D=−95 (c=2.18, toluene). (S)-1a [α]D=+88
(c=0.432, toluene). (R)-1b [α]D=−62 (c=0.53, chloroform). (S)-1b [α]D=+61 (c=0.74, chloroform).
4.3. 2-Phenyl-butanoic-acid-methyl ester 2a
Compound 2a was obtained from the commercially available phenylbutanoic acid 1a by refluxing it in
CH3OH in the presence of conc. H2SO4 for 3 h. 1H NMR (CDCl3) δ 0.85 (t, 3, J=7.4); 1.76 (m, 1); 2.07
(m, 1); 3.42 (t, 1, J=7.7); 3.58 (s, 3); 7.20 (m, 5).
4.4. 2-(40-Methoxyphenyl)-butanoic-acid-methyl ester 2b
4-Methoxyphenyl-acetonitrile (Acros) was ethylated according to a previously described method.7 21
g (0.12mol) of 4-methoxyphenyl-butyronitrile was refluxed overnight in 140 mL of ethylene glycol with
130 g of KOH. After cooling to r.t., 200 mL of water were added followed by 100 mL of HCl (2 N). The
white precipitate was filtered off, washed (Et2O), extracted with ether and dried to give 22 g of a crude
pale yellow viscous mixture containing the 2-(40-methoxyphenyl)-butanoic acid 1b and its demethylated
form. The oil was dissolved in 25 mL of EtOH and warmed to 60°C. NaOH (5 g, 0.125 mol) in 7.5 mL
of H2O–Me2SO4 (15 g, 0.12 mol) were added alternately in 5 portions. After the additions, a further 1
g of NaOH in 2 mL H2O was added to ensure an alkaline solution and the solution was heated in an oil
bath at 82°C for 3.5 h. Then the solution was cooled, the ethanol removed and the residue washed (H2O)
and extracted (Et2O). Evaporation of the solvent gave 21.5 g (0.10 mol) of 4-methoxyphenyl-butanoic
acid methyl ester 2b as a pale yellow oil (yield 83%). 1H NMR (CDCl3) δ 0.89 (t, 3, J=7.4); 1.77 (m, 1);
2.06 (m, 1); 3.42 (t, 1, J=7.7); 3.66 (s, 3); 3.79 (s, 3); 6.87 (d, 2, J=6.7); 7.23 (d, 2, J=6.7).
4.5. (R) and (S)-2-Aryl-butanoyl chloride 3a (aryl=phenyl) and 3b (aryl=40-methoxyphenyl)
Acid chlorides 3a (or 3b) were obtained quantitatively by refluxing the acid form 1a (or 1b) for 1 h with
2 eq. of thionyl chloride followed by vacuum distillation. They were stored under argon at −30°C. 3a:
1H NMR (CDCl3) δ 0.98 (t, 3, J=7.4); 1.92 (h, 1, J=7.4); 2.28 (h, 1, J=7.4); 3.94 (t, 1, J=7.5); 7.40 (m,
5). (R)-3a [α]D=−82 (c=2.37, chloroform). (S)-3a [α]D=+71 (c=0.79, chloroform). (R)-3b [α]D=−68
(c=0.64, chloroform). (S)-3b [α]D=+67 (c=0.88, chloroform).
4.6. (R) and (S)-4-Aryl-hexan-3-one 4a or 4b
4.6.1. General procedure
2.2 g (0.02 mol) of CuCl (Acros) were dried for 2 h at 120°C under vacuum. After cooling to −70°C,
15 mL of ether were added dropwise followed by 0.02 mol of ethyl magnesium bromide prepared from
magnesium turnings and ethyl bromide in ether using standard procedures. After 15 min, 1.8 g (9.9 mmol)
of (S)-(+)-3b was directly added with a syringe and the solution was stirred for 15 min before pouring

B. Malézieux et al. / Tetrahedron: Asymmetry 9 (1998) 259–269
267
the mixture into an acidic (150 mL of 5% HCl) ice–water bath. The solution was extracted with ether
(100 mL) dried (MgSO4) evaporated and flash-chromatography carried out on silica gel (Merck 60G)
starting with pure pentane and mixing it with 10% of ether. Removal of solvent led to 1.36 g (7.7 mmol,
yield 78%) of the optically active ketone (S)-(+)-4b. 4a: 1H NMR (CDCl3) δ 0.82 (t, 3, J=7.4); 0.97 (t,
3, J=7.3); 1.66–1.780 (m, 1); 2.01–2.13 (m, 1); 2.31–2.48 (m, 2); 3.55 (t, 3, J=7.4); 7.20–7.35 (m, 5).
13C NMR (CDCl3) δ 8.02, 12.3, 25.5, 35.3, 60.7, 127.2, 128.4, 128.9, 139.4, 211.4. (R)-4a [α]D=−337
(c=2.24, toluene). (S)-4a [α]D=+320 (c=1.13, toluene). 4b: 1H NMR (CDCl3) δ 0.81 (t, 3, J=7.4); 0.95
(t, 3, J=7.3); 1.59–1.76 (m, 1); 1.94–2.09 (m, 1); 2.24–2.48 (m, 2); 3.48 (t, 3, J=7.4); 3.77 (s, 1); 6.85 (d,
2, J=8.7); 7.12 (d, 2, J=8.7). (R)-4b [α]D=−317 (c=0.49, toluene). (S)-4b [α]D=+306 (c=0.50, toluene).
Recently a series of phenylalkylketones was reported for which the ees were determined by HPLC.26
These values are in close agreement to our results. In particular these authors published a value of
[α]D=−48 with 33% ee for the (R)-2-phenyl-pentan-3-one in CHCl3; taking into account the solvent
effects resulting in a two-fold increase of optical rotation values in toluene as compared to chloroform,
and also the similar values for α-methyl and α-ethyl compounds.27
4.7. (pR,3S,4R) and (pS,3S,4R)-3-(20-((N,N-Dimethylamino)methylferrocenyl)-4-aryl-hexan-3-ol (5a
and 6a)(aryl=phenyl) or (5b and 6b)(aryl=400-methoxyphenyl)
4.7.1. General procedure
To 0.80 g (3.3 mmol) of (N,N-dimethylamino)methylferrocene (Strem) in 10 mL anhydrous ether
under argon at room temperature was added 3.1 mmol of butyllithium. After 1 h, 0.6 g (2.9 mmol) of
optically active ketone (R)-(−)-4a dissolved in 2 mL of ether, was added at −40°C. After 15 min the
mixture was poured into an acidic ice–water bath (100 mL, 5% HCl) and extracted 4 times with ether.
This acidic ethereal layer was dried, evaporated and flash-chromatography was carried out to yield 0.21 g
(1 mmol) of unreacted ketone. The aqueous solution was basified by addition of Na2CO3 and extracted 5
times with ether. Removal of solvent gave a dark orange oil which after chromatography on plates (silica
gel 60G, eluent pentane: Et3N 3% Rf 0.45 and 0.40) led to 0.20 g (0.45 mmol) of (pS,3S,4R)-5a (a more
polar isomer) as an oil and 0.17 g (0.38 mmol) of (pR,3S,4R)-6a as an oil (total yield of amino-alcohols
28%).
To ensure a satisfactory separation of the amino-alcohols the plates of silica had to be precoated with
the eluent and dried to prevent tail formation. The separation can be improved by drying the plates after
1
a first migration and operating a second migration. (pS*,3S*,4R*)-5a (aryl=phenyl): H NMR (CDCl3)
δ 0.49 (t, 3, J=7.3); 1.17 (t, 3, J=7.3); 1.24 (m, 1); 1.45 (m, 1); 1.77 (m, 1); 2.08 (m, 1); 2.11 (s, 6); 2.50
(dd, 1, J=11.9, 2.9); 2.51 (d, 1, J=12.2); 3.94 (m, 1); 4.01 (m, 1); 4.11 (t, 1, J=2.5); 4.16 (s, 5); 7.22 (m,
5). 13C NMR (CDCl3) δ 8.9, 13, 24, 29.9, 36.5, 44.5, 44.8, 58.7, 60.1, 66.1, 69.2, 69.6, 70.1, 82.1, 99.1,
126, 127.7, 130.4, 142.5. IR (CCl4) 3188, 2930, 1455 cm−1. Anal. Calcd for C25H33ONFe: C, 71.60;
H, 7.93; found: C, 71.67; H, 7.96. (pR,3R.4S)-5a [α]D=+32 (c=0.54, ethanol, ee 92%). (pS,3S.4R)-5a
[α]D=−71 (c=0.45, ethanol, ee 98%). (pR*,3S*,4R*)-6a: 1H NMR (CDCl3) δ: 0.36 (t, 3, J=7.3); 0.79 (t,
3, J=7.3); 1.31 (m, 2); 2.04 (m, 2); 2.19 (s, 6); 2.73 (d, 1, J=12.4); 2.84 (m, 1); 3.91 (m, 1); 4.11 (m, 1);
4.13 (m, 1); 4.14 (s, 5); 7.23 (d, 2, J=6.9); 7.28, t, 1, J=7.0); 7.36 (d, 2, J=7.1). 13C NMR (CDCl3) δ 8.6,
13, 24.1, 29.9, 37.4, 42.1, 44.8, 58.5, 59.4, 65.4, 68.6, 69.7, 70.9, 82.3, 99, 126.1, 127.9, 130.1, 143.4. IR
(CCl4) 3570, 3192, 2930, 1455 cm−1. Anal. Calcd for C25H33ONFe: C, 71.60; H, 7.93; found: C, 71.54;
H, 8.08. (pR,3S.4R)-6a [α]D=+44 (c=0.37, ethanol, ee 98%). (pS,3R.4S)-6a [α]D=−38 (c=0.40, ethanol,
ee 92%).

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B. Malézieux et al. / Tetrahedron: Asymmetry 9 (1998) 259–269
4.8. Compounds 5b, 6b, 7b and 8b were described early7,11
(pR,3R,4S)-5b [α]D=+54 (c=0.61, ethanol, ee 93%). (pS,3S,4R)-5b [α]D=−55 (c=0.69, ethanol, ee
96%). (pR,3S,4R)-6b [α]D=+48 (c=1.18, ethanol, ee 96%). (pS,3R,4S)-6b [α]D=−46 (c=0.76, ethanol, ee
93%). When compounds 5b and 6b were chromatographed, another more polar isomer was also present
but in very small amounts. 1H NMR (CDCl3) δ: 0.57 (t, 3, J=7.3); 1.29 (t, 3, J=7.3); 1.74 (m, 2); 1.77 (s,
6); 2.23 (q, 2, J=7.9); 2.42 (d, 2, J=12.1); 2.65 (m, 1); 3.70 (s, 3); 3.81 (q, 1, Ha-Hb); 3.90 (m, 1); 3.93
(m, 1); 4.00 (t, 1, J=2.5); 4.10 (s, 5); 6.62 (d, 2, J=8.7); 6.91 (d, 2, J=8.7).
Acknowledgements
This work has received financial supports of INTAS (grant 94-1716). The authors thank the Russian
Academy of Sciences, C.N.R.S. and the University ‘Pierre et Marie Curie’ in Paris.
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