Synthesis and separation of substituted cyclopropane carboxylic acid amide isomers

Article abstract of DOI:10.1016/S0957-4166(01)00232-4

The phase-transfer-catalyzed cyclization of optically active malonic acid allylic ester amides yields bicyclic cyclopropane carboxamide lactone derivatives. The two diastereomers obtained could be separated in some cases by simple column chromatography yielding the pure isomers.

Full text of DOI:10.1016/S0957-4166(01)00232-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1287–1292
Synthesis and separation of substituted cyclopropane carboxylic
acid amide isomers
3
Zolta´n Finta,a Zolta´n Hell,a,* Jo´zsef Ba´lint,a Adrienn Taka´cs,a La´szlo´ Pa´rka´nyib and La´szlo´ Tokea
aDepartment of Organic Chemical Technology, Budapest University of Technology and Economics, H-1521 Budapest,
POB 91, Hungary
bInstitute of Chemistry, Chemical Research Center, H.A.S., H-1525 Budapest, POB 17, Hungary
Received 3 April 2001; accepted 22 May 2001
Abstract—The phase-transfer-catalyzed cyclization of optically active malonic acid allylic ester amides yields bicyclic cyclopropane
carboxamide lactone derivatives. The two diastereomers obtained could be separated in some cases by simple column chromatog-
raphy yielding the pure isomers. © 2001 Elsevier Science Ltd. All rights reserved.
2. Results and discussion
1. Introduction
If R1 and R2 are different, a new stereogenic center is
formed at C(6). The parameters of the reaction were
studied including the effect of the R1, R2 and R3 groups
and the reaction temperature on the stereoselectivity.6
The effect of hydrotalcite, a mineral-like solid base,7
and microwave irradiation8 on the exo–endo selectivity
was discussed.
Cyclopropane carboxylic acid and a number of its
derivatives are useful intermediates in the preparation
of important natural and unnatural compounds having
biological activity; for example, certain aminocyclo-
propane carboxylic acid derivatives and pyrethroid-type
insecticides.1–4 As in many cases, these compounds have
several stereogenic centers and the stereoisomers have
different biological activities; stereoselective synthesis of
these compounds is therefore a useful exercise.
It seemed interesting to examine whether the introduc-
tion of a chiral auxiliary in the starting malonic acid
derivative has any influence on the stereoselectivity of
the reaction. For this purpose we synthesized the amide
derivatives 5 by reacting (R)-(+)-1-phenylethylamine 4a
(Fig. 2, R=phenyl) or (R)-(+)-1-(1-naphthyl)-
ethylamine 4b (R=1-naphthyl) with 6 molar excesses
of diethyl malonate (Fig. 2). The ester-amides 5 thus
obtained were hydrolyzed with aqueous sodium
Recently a phase-transfer catalytic method was devel-
oped for the preparation of cyclopropane carboxylic
acid lactones 2 from malonic acid allylic esters 1 using
solid potassium carbonate, iodine and a lipophilic quat-
ernary ammonium salt (Fig. 1). The reaction is
diastereoselective, the two rings being cis-fused while
the R3 group is always in the exo position.5
Figure 1.
* Corresponding author. E-mail: hell.oct@chem.bme.hu
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00232-4

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Z. Finta et al. / Tetrahedron: Asymmetry 12 (2001) 1287–1292
Figure 2.
hydroxide to the corresponding acids 6, which
were coupled with 3-methyl-but-2-en-1-ol 7a, 2-methyl-
pent-2-en-4-ol 7b, or 4-methyl-1,1,1-trichloro-pent-3-en-
2-ol 7c in dichloromethane in the presence of DCC,
resulting in the desired ester-amides 8, which are suit-
able starting materials for examination of the cycliza-
tion reaction. Due to the two methyl groups in the
alcohols 7a–7c and the diastereoselectivity of the reac-
tion, only two diastereomers would be expected to form
in the cyclization (Fig. 3).
showed that the chiral amide function had no effect on
the stereoselectivity of the reaction.
Attempts were made to separate the obtained
diastereomeric mixtures. Column chromatography of
the crude 9e and 10e mixture using a hexane/ethyl
acetate mixture (4:1) as the eluent yielded the pure
diastereomers 9e and 10e. The absolute configuration of
these isomers could not be determined by 1H NMR
experiments (Double Pulse Filtered Gradient Nuclear
Overhauser Effect, DPFGNOE); there was no effect
when the proton at the annelation point or the amide
proton were irradiated. Since one of these
diastereomers could be obtained in crystalline form, its
absolute configuration was determined by X-ray crys-
tallography. Crystals of 9e suitable for the analysis were
obtained by slow evaporation of the ethereal solution
of the compound. The configuration of this isomer was
(1R,4R,5R,aR) as shown in Fig. 4.
Cyclization of the ester amides was effected5 by stirring
with iodine, solid potassium carbonate and TCMC, in
refluxing toluene. 1H NMR analysis of the crude
product showed two singlets at 2.6–3.2 ppm and, when
the R substituent was phenyl, two doublets were seen at
ca. 7.2 ppm both in a 1:1 ratio, which were assigned as
the C(5) proton and the amide NH, respectively, in the
expected diastereomers 9 and 10. This unambiguously
Figure 3.

Z. Finta et al. / Tetrahedron: Asymmetry 12 (2001) 1287–1292
1289
In the case of 9a and 10a perfect separation could not
be effected, only mixtures were obtained in which the
1
isomeric ratio determined from the H NMR spectra
was 5:1 and 1:5, with 35 and 37% yield, respectively.
The mixtures 9b, 10b and 9d, 10d were found to be
inseparable.
By removing the chiral alkyl group from the amide
function (by for example hydrogenolysis), pure enan-
tiomers of substituted cyclopropane carboxylic acid
lactones could be obtained, which are useful intermedi-
ates for substituted cyclopropane carboxylic acids or
1-aminocyclopropane carboxylic acids. As there was no
possibility for the introduction of any functional group
into the molecules 2 which would help to separate the
isomers, simple resolution with diastereomeric salt for-
mation could not be effected. Using our method the
enantiomers of substituted cyclopropane carboxylic
acids could be easily separated.
Figure 4.
3. Experimental
Melting points were determined in a capillary and are
uncorrected. IR spectra were recorded on a Perkin–
Elmer Spectrum 1600 instrument. Optical rotations
were determined on a Perkin–Elmer 241 polarimeter.
1H NMR spectra were recorded on Bruker AW-250
(250 MHz) spectrometer; chemical shifts are given on
the l scale using TMS as internal standard. l (TMS)=
0 ppm in CDCl3. Thin-layer chromatography was car-
ried out using Merck Kieselgel 60F plates with eluents
hexane/acetone 4:1 or hexane/ethyl acetate 4:1. Column
chromatography was carried out on Merck Kieselgel
60–200 mesh (25 g/0.1 g reaction mixture) with the
same eluents.
3.1. Preparation of monoamides 6
Figure 5.
Amine 4 (25 mmol) was added to diethyl malonate (24
g, 0.15 mol) at 120°C. The mixture was then stirred
under reflux for 2 h. Excess diethyl malonate was
distilled from the mixture under vacuum. A solution of
sodium hydroxide (1.48 g, 0.037 mol) in water (20 mL)
was added to the residue and the mixture was stirred
under reflux for 2 h. The precipitate was removed by
filtration, the filtrate was diluted with distilled water,
acidified with conc. HCl (3.6 mL), the mixture was
extracted with chloroform and the organic phase was
dried over magnesium sulfate. The solvent was evapo-
rated under vacuum and the solid thus obtained was
recrystallized from toluene. The crystalline material was
dissolved in a solution of sodium hydroxide (0.7 g, 18
mmol) in water (20 mL), extracted with chloroform, the
aqueous layer was acidified with conc. HCl (2 mL),
then extracted with chloroform, the organic layer was
dried over magnesium sulfate and the solvent was
evaporated.
Similarly, the pure isomers 9f and 10f could be sepa-
rated by a simple column chromatography with excel-
lent yield. One of these isomers was also crystalline;
X-ray
crystallographic
data
confirmed
its
(1R,4R,5R,aR) configuration (Fig. 5).
1
The H NMR spectra of the crystalline isomers 9e and
9f showed that in both compounds the signals for the
proton at the annelation point were seen at a lower
chemical shift than in the equivalent isomers 10e and
10f, respectively (2.85 for 9e and 2.93 for 10e; while
2.92 for 9f and 2.96 for 10f). Taking this fact into
account we could suppose that the chemical shift of the
hydrogen at the annelation point in compounds 9 (hav-
ing (R) configuration) always appeared at a lower l
value than in compounds 10 (having (S) configuration).
In this way we could determine compounds 9 and 10
1
and their ratio from the H NMR spectra.
3.2. Malonic acid (R)-(+)-1-phenylethylamide 6a
Compounds 9c and 10c could be isolated by column
chromatography; we obtained a 30% yield of both pure
isomers (and a fraction of the diastereomeric mixture).
Yield: 76%, white crystals, mp: 69–71°C (toluene). IR
(KBr): 3347, 3281, 1722, 1641, 1547; 1H NMR (250

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Z. Finta et al. / Tetrahedron: Asymmetry 12 (2001) 1287–1292
MHz, CDCl3): 1.64 (d, 3H, J 6.33), 3.16 (s, 2H), 5.24
(m, 1H), 7.35–7.74 (m, 5H), 7.81 (d, 1H, J 8.16);
[h]2D5=+116.4, c=1, methanol. Anal. found: C, 63.66;
H, 6.28; N, 6.78%. Calcd for C11H13NO3: C, 63.76; H,
6.28; N, 6.76%.
3.8. Malonic acid [(R)-(+)-1-(1-naphthyl)ethylamide]-2-
methyl-2-penten-4-yl ester 8d
Yield: 68%, colorless liquid. IR (film): 3284, 3057, 1745,
1
1655, 1550; H NMR (250 MHz, CDCl3): 1.27 (d, 3H,
J 5.4 Hz) 1.51 (d, 3H, J 6.2), 1.71 (s, 6H), 3.27 (s, 2H),
5.12–5.24 (m, 2H), 5.97 (m, 1H), 7.2–7.6 (m, 7H), 8.06
(s, 1H); [h]2D5=+24.7, c=1, methanol. Anal. found: C,
74.41; H, 7.38; N, 4.15%. Calcd for C21H25NO3: C,
74.33; H, 7.37; N, 4.12%.
3.3. Malonic acid (R)-(+)-1-(1-naphthyl)ethylamide 6b
Yield: 88%, white crystals, mp: 125–127°C (toluene). IR
1
(KBr): 3345.5, 3283.5, 1719, 1637, 1543; H NMR (250
MHz, CDCl3): 1.64 (d, 3H, J 6.33), 3.16 (s, 2H), 5.89
(m, 1H), 7.00 (s, 1H), 7.35–7.74 (m, 7H), 7.98 (d, 1H, J
8.16); [h]2D5=+41.5, c=1, methanol. Anal. found: C,
70.05; H, 5.89; N, 5.41%. Calcd for C15H15NO3: C,
70.05; H, 5.83; N, 5.44%.
3.9. Malonic acid [(R)-(+)-1-phenylethylamide]-4-
methyl-1,1,1-trichloro-3-penten-2-yl ester 8e
Yield: 68%, colorless liquid. IR (film): 3291, 3065, 1755,
1
1650, 1553; H NMR (250 MHz, CDCl3): 1.48 (s, 3H),
3.4. Esterification of carboxylic acids 6
1.51 (s, 3H), 1.86 (d, 3H, J 6.97), 3.43 (s, 2H), 5.13 (m,
1H), 5.31 (d, 1H, J 9.24), 6.08 (d, 1H, J 9.24), 7.2–7.5
(m, 6H); [h]2D5=+64.7, c=1, methanol. Anal. found: C,
51.92; H, 5.02; N, 3.59%. Calcd for C17H20Cl3NO3: C,
51.97; H, 5.09; N, 3.56%.
To a solution of alcohol 7 (2.8 mmol) and acid
monoamide 6 (2.83 mmol) in dichloromethane (15 mL)
was added dicyclohexylcarbodiimide (0.69 g, 3 mmol)
under stirring at 0°C. Then the mixture was further
stirred at room temperature for 6 h. The mixture was
filtered, the precipitate washed with dichloromethane
and the organic phase washed with sodium hydrocar-
bonate solution; the organic layer was dried over mag-
nesium sulfate and the solvent was evaporated. The
residue was purified by column chromatography (with
eluent hexane/acetone 4:1).
3.10. Malonic acid [(R)-(+)-1-(1-naphthyl)ethylamide]-4-
methyl-1,1,1-trichloro-3-penten-2-yl ester 8f
Yield: 59%, colorless liquid. IR: 3324, 3054, 1753, 1647,
1
1557; H NMR (250 MHz, CDCl3): 1.61 (s, 3H), 1.64
(s, 3H), 1.75 (d, 3H, J 7.71), 3.4 (s, 2H), 5.24 (d, 1H, J
9.27), 5.97 (m, 1H), 6.03 (d, 1H, J 9.27), 7.3–7.7 (m,
7H), 8.07 (d, 1H, J 7.71); [h]2D5=+35.7, c=1, methanol.
Anal. found: C, 56.91; H, 4.92; N, 3.19%. Calcd for
C21H22Cl3NO3: C, 56.94; H, 4.97; N, 3.16%.
3.5. Malonic acid [(R)-(+)-1-phenylethylamide]-3-
methyl-2-buten-1-yl ester 8a
Yield: 67%, colorless liquid. IR (film): 3293, 3068, 1749,
1657, 1551; H NMR (250 MHz, CDCl3): 1.49 (s, 3H),
1
3.11. General procedure for cyclization of compounds 8
1.52 (s, 3H), 1.73 (d, 3H, J 13.2), 3.31 (s, 2H), 4.63 (d,
2H, J 7.27), 5.13 (m, 1H), 5.35 (m, 1H), 7.1–7.4 (m,
5H), 7.5 (d, 1H, J 7.32); [h]2D5=+85.8, c=1, methanol.
Anal. found C, 69.85; H, 7.69; N, 5.09%. Calcd for
C16H21NO3: C, 69.81; H, 7.63; N, 5.09%.
To a mixture of potassium carbonate (3.3 g), iodine (3.0
g) and one drop of TCMC in toluene (30 mL), a
solution of esters 8 (5 mmol) in toluene (10 mL) was
added dropwise at 110°C with vigorous stirring. The
mixture was stirred until 8 was completely consumed
(monitored by TLC analysis). The mixture was cooled
and filtered, the solid was washed with toluene, the
filtrate washed with sodium thiosulfate solution then
further washed with water, dried over magnesium sul-
fate and the solvent was evaporated. The oily residue
was purified by column chromatography (with eluent
hexane/ethyl acetate 4:1).
3.6. Malonic acid [(R)-(+)-1-(1-naphthyl)ethylamide]-3-
methyl-2-buten-1-yl ester 8b
Yield: 68%, colorless liquid. IR (film): 3283, 3072, 1725,
1
1678, 1649, 1555; H NMR (250 MHz, CDCl3): 1.48 (s,
3H), 1.5 (s, 3H), 1.73 (d, 3H, J 7.71), 3.31 (s, 2H), 4.63
(d, 2H, J 7.27), 5.35 (m, 1H), 5.97 (m, 1H), 7.35–7.91
(m, 7H), 8.07 (d, 1H, J 7.71); [h]2D5=+21.4, c=1,
methanol. Anal. found: C, 73.86; H, 7.09; N, 4.39%.
Calcd for C20H23NO3: C, 73.84; H, 7.07; N, 4.31%.
3.12. 6,6-Dimethyl-3-oxa-bicyclo[3.1.0]hexan-2-on-1-car-
boxylic acid (R)-(+)-1-phenylethylamide 9a, 10a
3.7. Malonic acid [(R)-(+)-1-phenylethylamide]-2-
methyl-2-penten-4-yl ester 8c
Yield: 67%, colorless liquid. IR (film): 3295, 1782, 1654,
1552; H NMR (250 MHz, CDCl3): 1.31, (s, 3H), 1.34
1
(s 3H), 1.51 (d, 3H, J 7.15), 2.63, 2.66 (d,d, 1H, J 4.94),
4.13 (d, 2H, J 5.38), 5.14 (m, 1H), 7.1–7.35 (m, 5H),
7.98, 7.99 (d, 1H, J 7.32). Anal. found: C, 70.38; H,
6.98; N, 5.19%. Calcd for C16H19NO3: C, 70.32; H,
6.95; N, 5.12%.
Yield: 64%, colorless liquid. IR (film): 3284, 3057, 1745,
1655, 1550; H NMR (250 MHz, CDCl3): 1.27 (d, 3H,
J 5.4 Hz) 1.51 (d, 3H, J 6.2), 1.71 (s, 6H), 3.27 (s, 2H),
5.12–5.18 (m, 2H), 5.71–5.86 (m, 1H), 7.2–7.5 (m, 5H),
7.6 (s, 1H); [h]2D5=+57.7, c=1, methanol. Anal. found:
C, 70.51; H, 7.99; N, 4.85%. Calcd for C17H23NO3: C,
0.58; H, 7.95; N, 4.84%.
1
(1R,4S,5R,aR)-9a/(1S,4R,5S,aR)-10a
[h]2D5=+62.4, c=1, methanol.
1:5
mixture:

Z. Finta et al. / Tetrahedron: Asymmetry 12 (2001) 1287–1292
1291
(1R,4S,5R,aR)-9a/(1S,4R,5S,aR)-10a
[h]2D5=+56.5, c=1, methanol.
5:1
mixture:
3.17. 6,6-Dimethyl-4-trichloromethyl-3-oxa-bicy-
clo[3.1.0]hexan-2-on-1-carboxylic acid (R)-(+)-1-(1-
naphthyl)ethylamide 9f, 10f
3.13. 6,6-Dimethyl-3-oxa-bicyclo[3.1.0]hexan-2-on-1-car-
boxylic acid (R)-(+)-1-(1-naphthyl)ethylamide 9b, 10b
(1R,4R,5R,aR)-9f: Yield: 25%, white crystals, mp:
1
190.5°C. IR (KBr): 3304, 1782, 1653, 1540; H NMR
(400 MHz): 1.41 (s, 3H), 1.43 (s, 3H), 1.67 (d, 3H, J
6.82), 2.92 (s, 1H), 4.6 (s, 1H), 5.95 (m, 1H), 7.3–8.13
(m, 8H); [h]2D5=−6.7, c=1, methanol. Anal. found: C,
57.21; H, 4.52; N, 3.19%. Calcd for C21H20Cl3NO3: C,
57.20; H, 4.54; N, 3.17%.
Mixture of diastereomers, yield: 54%, yellow oil. IR
(film): 3361, 1781, 1666, 1529; 1H NMR (250 MHz,
CDCl3): 1.15 (s, 3H), 1.29 (s, 3H), 1.16 (d, 3H, J 5.49),
2.62, 2.7 (d,d, 2H, J 5.38), 4.13 (d, 2H, J 5.38), 5.96 (m,
1H), 7.6–8.2 (m, 8H); [h]2D5=−0.53, c=1, methanol.
Anal. found: C, 74.33; H, 6.55; N, 4.39%. Calcd for
C20H21NO3: C, 74.31; H, 6.50; N, 4.33%.
(1S,4S,5S,aR)-10f: Yield: 25%, yellow oil. IR (film):
1
3304, 1782, 1653, 1540; H NMR (400 MHz, CDCl3):
1.41 (s, 3H), 1.43 (s, 3H), 1.67 (d, 3H, J 6.82), 2.96 (s,
1H), 4.6 (s, 1H), 5.95 (m, 1H), 7.3–8.13 (m, 8H);
[h]2D5=+13.8, c=1, methanol. Anal. found: C, 57.21; H,
4.52; N, 3.19%. Calcd for C21H20Cl3NO3: C, 57.20; H,
4.54; N, 3.17%.
3.14. 6,6-Dimethyl-4-methyl-3-oxa-bicyclo[3.1.0]hexan-
2-on-1-carboxylic acid (R)-(+)-1-phenylethylamide 9c,
10c
(1R,4S,5R,aR)-9c: yield 32%, [h]2D5=+35.5, c=1,
methanol; (1S,4R,5S,aR)-10c: yield 30%, [h]2D5=+60.4,
c=1,
methanol;
spectroscopic
data
of
the
3.18. X-Ray diffraction studies
diastereomeric mixture: IR (film): 3296, 1788, 1653,
1
1550; H NMR (250 MHz, CDCl3): 1.31, (s, 3H), 1.34
Crystal data for compound 9e: C17H18Cl3NO3, Fwt:
390.67, colorless prism, size: 0.60×0.60×0.35 mm,
(s, 3H), 1.51–1.87 (m, 6H), 2.61, 2.69 (s, s, 1H, J 4.91),
4.12–4.23 (m, 1H), 4.45–4.53 (m, 1H), 5.14 (m, 1H),
7.1–7.41 (m, 5H), 8.02, 8.11 (d, 1H, J 7.32). Anal.
found: C, 71.05; H, 7.39; N, 4.85%. Calcd for
C17H21NO3: C, 71.08; H, 7.31; N, 4.87%.
orthorhombic, space group P212121, a=8.156(1), b=
3
,
,
11.207(1), c=20.600(3) A, V=1882.9(4) A , T=293(2)
K, Z=4, F(000)=808, Dx=1.378 Mg m−3, m=0.501
mm−1.
3.15. 6,6-Dimethyl-4-methyl-3-oxa-bicyclo[3.1.0]hexan-
2-on-1-carboxylic acid (R)-(+)-1-(1-naphthyl)ethylamide
9d, 10d
Cell parameters were determined by least-squares of the
setting angles of 25 (15.035q516.96°) reflections.
Intensity data were collected on an Enraf–Nonius
Mixture of diastereomers, yield: 51%, colorless liquid.
IR (film): 3293, 1792, 1655, 1559; H NMR (400 MHz,
CAD4 diffractometer (graphite monochromator; Mo-
1
,
Ka radiation, u=0.710730 A) at 293(2) K in the range
CDCl3): 1.31, (s, 3H), 1.34 (s, 3H), 1.51–1.87 (m, 6H),
2.63, 2.65 (s, s, 1H, J 4.91), 4.12–4.23 (m, 1H), 4.45–
4.53 (m, 1H) 5.14 (m, 1H), 7.3–8.12 (m, 8H); [h]2D5=
+13.7, c=1, methanol. Anal. found: C, 71.27; H, 6.83;
N, 4.15%. Calcd for C21H23NO3: C, 71.21; H, 6.82; N,
4.15%.
2.695q529.95° using ꢀ/2q scans. The intensities of
three standard reflections were monitored regularly
(every 60 min). The intensities of the standard reflec-
tions indicated a crystal decay of 10% (the data were
corrected for decay).
A total of 6293 reflections were collected of which 5423
were unique [Rint=0.0132, R(|)=0.0404]; intensities of
3200 reflections were greater than 2|(I).9 Completeness
to q=0.991.
3.16. 6,6-Dimethyl-4-trichloromethyl-3-oxa-bicy-
clo[3.1.0]hexan-2-on-1-carboxylic acid (R)-(+)-1-
phenylethylamide 9e, 10e
(1R,4R,5R,aR)-9e: yield: 30%, white crystals, mp:
A psi-scan absorption correction10 was applied to the
data (the minimum and maximum transmission factors
were 0.9145 and 0.9944).
1
121.5°C. IR (KBr): 3291, 1785, 1650, 1553; H NMR
(400 MHz, CDCl3): 1.33 (s, 3H), 1.34 (s, 3H), 1.5 (d,
3H, J 8.24), 2.85 (s, 2H), 4.62 (s, 1H), 5.14 (m, 1H),
7.3–7.7 (m, 5H), 7.73 (d, 1H, J 7.69), 7.84 (d, 1H, J
7.69); [h]2D5=+22.8, c=1, methanol. Anal. found: C,
52.28; H, 4.65; N, 3.59%. Calcd for C17H18Cl3NO3: C,
52.24; H, 4.60; N, 3.58%.
The structure was solved by direct methods11 (and
subsequent difference syntheses). Anisotropic full-
matrix least-squares refinement12 on F2 for all non-
hydrogen atoms yielded R1=0.0392 and wR2=0.0931
for 3200 [I>2|(I)] and R1=0.0806 and wR2=0.1022 for
all (5423) intensity data (number of parameters=220,
goodness-of-fit=0.934, absolute structure parameter
x=0.00(5), the maximum and mean shift/esd is 0.000
and 0.000).
(1S,4S,5S,aR)-10e: yield: 30%, yellow oil. IR (film):
1
3291, 1785, 1650, 1553; H NMR (400 MHz, CDCl3):
1.33 (s, 3H), 1.34 (s, 3H), 1.5 (d, 3H, J 8.24), 2.93 (s,
2H), 4.62 (s, 1H), 5.14 (m, 1H), 7.3–7.7 (m, 5H), 7.73
(d, 1H, J 7.69), 7.84 (d, 1H, J 7.69); [h]2D5=+71.0, c=1,
methanol. Anal. found: C, 52.28; H, 4.65; N, 3.59%.
Calcd for C17H18Cl3NO3: C, 52.24; H, 4.60; N 3.58%.
The maximum and minimum residual electron density
−3
,
in the final difference map was 0.160 and −0.272 e A .

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Z. Finta et al. / Tetrahedron: Asymmetry 12 (2001) 1287–1292
(0.0606P)2] where P=(Fo +2Fc )/3.
2
2
The weighting scheme applied was w=1/[|2(Fo )+
2
(0.0583P)2] where P=(Fo +2Fc )/3.
2
2
Hydrogen atomic positions were calculated from
assumed geometries. Hydrogen atoms were included in
structure factor calculations but they were not refined.
The isotropic displacement parameters of the hydrogen
atoms were approximated from the Ueq value of the
atom they were bonded to. Scattering factors,13 molecu-
lar graphics.14
Hydrogen atomic positions were calculated from
assumed geometries except H13 that was located in
difference maps. Hydrogen atoms were included in
structure factor calculations but they were not refined.
The isotropic displacement parameters of the hydrogen
atoms were approximated from the Ueq value of the
atom they were bonded to.
Crystal data for compound 9f: C21H19Cl3NO3, Fwt:
439.72, colorless prism, size: 0.60×0.50×0.35 mm,
Acknowledgements
orthorhombic, space group P212121, a=9.405(1), b=
3
,
,
10.996(1), c=20.138(2) A, V=2082.6(4) A , T=293(2)
K, Z=4, F(000)=908, Dx=1.402 Mg m−3, m=0.462
mm−1.
This work was supported by the Hungarian Research
Fund Programs (OTKA Grant No. T-023046).
Cell parameters were determined by least-squares of the
setting angles of 25 (15.055q516.90°) reflections.
References
1. Danishefsky, S. Acc. Chem. Res. 1979, 12, 66.
2. Wong, N. C.; Hon, M.-Y.; Tse, C. W.; Yip, Y. C. Chem.
Rev. 1989, 89, 165.
Intensity data were collected on an Enraf–Nonius
CAD4 diffractometer (graphite monochromator; Mo-
,
Ka radiation, u=0.710730 A) at 293(2) K in the range
3. Kondo, K.; Takashima, T.; Tunemoto, D. Chem. Lett.
2.395q531.96° using ꢀ/2q scans. The intensities of
three standard reflections were monitored regularly
(every 60 min). The intensities of the standard reflec-
tions indicated a crystal decay of 4% (the data were
corrected for decay).
1979, 1185.
4. Arlt, D.; Jautelat, M.; Lantzsch, R. Angew. Chem. 1981,
93, 719.
5. To3 ke, L.; Hell, Z.; Szabo´, G. T.; To´th, G.; Bihari, M.;
Rockenbauer, A. Tetrahedron 1993, 49, 5133.
6. Hell, Z.; Finta, Z.; Gru¨nvald, T.; Bo¨cskei, Zs.; Bala´n, D.;
A total of 8210 reflections were collected of which 7161
were unique [Rint=0.0141, R(|)=0.0490]; intensities of
4093 reflections were greater than 2|(I).9 Completeness
to q=0.993.
Keseru3 , Gy. M.; To3 ke, L. Tetrahedron 1999, 55, 1367.
7. Finta, Z.; Hell, Z.; Bala´n, D.; Cwik, A.; Keme´ny, S.;
Figueras, F. J. Mol. Catal. A 2000, 161, 149.
8. Finta, Z.; Hell, Z.; To3 ke, L. J. Chem. Res. (S) 2000, 242.
9. Harms, K. XCAD4 Data Reduction Program for CAD4
Diffractometers, Philipps-Universita¨t Marburg, Ger-
many, 1996.
A psi-scan absorption correction10 was applied to the
data (the minimum and maximum transmission factors
were 0.9947 and 0.9747).
10. North, A. C.; Philips, D. C.; Mathews, F. Acta Crystal-
logr., Sect. A 1968, 24, 350.
The structure was solved by direct methods11 (and
subsequent difference syntheses). Anisotropic full-
matrix least-squares refinement12 on F2 for all non-
hydrogen atoms yielded R1=0.0421 and wR2=0.0932
for 4093 [I>2|(I)] and R1=0.0872 and wR2=0.1034 for
all (7161) intensity data (number of parameters=256,
goodness-of-fit=0.883, absolute structure parameter
x=−0.08(5), the maximum and mean shift/esd is 0.001
and 0.000).
11. SHELXS: Sheldrick, G. M. SHELXS-97 Program for
Crystal Structure Solution, University of Go¨ttingen, Ger-
many, 1997.
12. Sheldrick, G. M. SHELXL-97 Program for Crystal Struc-
ture Refinement, University of Go¨ttingen, Germany,
1997.
13. Neutral atomic scattering factors and anomalous scatter-
ing factors are taken from: International Tables for X-ray
Crystallography, Vol. C.; Wilson, A. C. J., Ed.; Kluwer
Academic: Dordrecht, 1992; Tables 6.1.1.4 (pp. 500–502),
4.2.6.8 (pp. 219–222) and 4.2.4.2 (pp. 193–199).
14. PLATON: Spek, A. L. Acta Crystallogr., Sect. A 1990,
46, C-34.
The maximum and minimum residual electron density
−3
,
in the final difference map was 0.374 and −0.209 e A .
The weighting scheme applied was w=1/[|2(Fo )+
2
.