Enantiomerically pure β-amino acids: A convenient access to both enantiomers of trans-2-aminocyclohexanecarboxylic acid

Article abstract of DOI:10.1002/1099-0690(200209)2002:17<2948::AID-EJOC2948>3.0.CO;2-E

Enantiomerically pure trans-2-aminocyclohexanecarboxylic acid is an important building block for helical β-peptides. We report here that this amino acid can be obtained from trans-cyclohexane-1,2-dicarboxylic acid in good yield by a simple one-pot procedure comprising cyclization to the anhydride, amide formation with ammonia, and a subsequent Hofmann-type degradation with phenyliodine(III) bis(trifluoroacetate) (PIFA) as the oxidant. The N-Fmoc- and N-BOC-protected derivatives were obtained by treatment of the amino acid with Fmoc-OSu and BOC₂O, respectively. The N-BOC derivative could be prepared in even better overall yield by a one-pot procedure leading directly from trans-cyclohexane-1,2-dicarboxylic acid to the N-BOC-protected amino acid. Both enantiomers of the starting trans-1,2-cyclohexanedicarboxylic acid can be obtained easily and in large quantities by separating commercially available racemic trans-1,2-cyclohexanedicarboxylic acid using either (R)- or (S)-1-phenethylamine. X-ray crystallography of the diastereomerically pure salt obtained from (R)-1-phenethylamine revealed that the configuration of the diacid component is (1R,2R), and not (1S,2S) as reported in the literature. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Full text of DOI:10.1002/1099-0690(200209)2002:17<2948::AID-EJOC2948>3.0.CO;2-E

FULL PAPER
Enantiomerically Pure β-Amino Acids: A Convenient Access to Both
Enantiomers of trans-2-Aminocyclohexanecarboxylic Acid
Albrecht Berkessel,*[a] Katja Glaubitz,[a] and Johann Lex[a]
Keywords: Amino acids / Amides / Carboxylic acids / Chiral resolution / Oxidation
Enantiomerically pure trans-2-aminocyclohexanecarboxylic
dicarboxylic acid to the N-BOC-protected amino acid. Both
acid is an important building block for helical β-peptides. We enantiomers of the starting trans-1,2-cyclohexanedicarbox-
report here that this amino acid can be obtained from trans-
cyclohexane-1,2-dicarboxylic acid in good yield by a simple
one-pot procedure comprising cyclization to the anhydride,
amide formation with ammonia, and a subsequent Hofmann-
type degradation with phenyliodine(III) bis(trifluoroacetate)
(PIFA) as the oxidant. The N-Fmoc- and N-BOC-protected
derivatives were obtained by treatment of the amino acid
with Fmoc-OSu and BOC2O, respectively. The N-BOC deriv-
ative could be prepared in even better overall yield by a one-
pot procedure leading directly from trans-cyclohexane-1,2-
ylic acid can be obtained easily and in large quantities by
separating commercially available racemic trans-1,2-cyclo-
hexanedicarboxylic acid using either (R)- or (S)-1-phenethyl-
amine. X-ray crystallography of the diastereomerically pure
salt obtained from (R)-1-phenethylamine revealed that the
configuration of the diacid component is (1R,2R), and not
(1S,2S) as reported in the literature.
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
Introduction
crystallization of 3 or ent-3 is reported to afford varying
yields (10Ϫ41%) of the individual enantiomers of the N-
benzoylated amino acids 3 and ent-3.[5] Finally, it appeared
desirable to avoid the change of the N-protecting group
(benzoyl to BOC).
β-Amino acids have recently attracted considerable atten-
tion, mainly due to the bioactivity of β-peptides, which are
not subject to peptidase degradation, and due to their abil-
ity to form stable tertiary structures.[1Ϫ4] In the latter con-
text, Gellman and co-workers have shown that oligomers of
trans-2-aminocyclohexanecarboxylic acid
2 (Scheme 1)
form stable 14-helices.[5,6] Our interest in β-peptides in gen-
eral, and in the oligomers of the β-amino acids 2 and ent-2
in particular, is related to our work aiming at biomimetic
catalysts based on helical peptide scaffolds.[7] The published
syntheses of enantiomerically pure 2 or ent-2 are based on
the following sequence (Scheme 1): (i) preparation of the
racemic amino acid rac-2 by alkali metal reduction of
anthranilic acid 1, (ii) N-benzoylation to rac-3, (iii) separa-
tion of the enantiomers either by using (Ϫ)-quinine as the
chiral auxiliary or by induced crystallization, (iv) N-de-
benzoylation, (v) introduction of an N-protecting group
suitable for peptide synthesis, such as BOC (Scheme 1).[5,8,9]
In our hands, the reduction of 1 proved tedious and rela-
tively low-yielding (10Ϫ30%). The isolation of pure rac-3
from the benzoylation requires intermediate esterification,
column chromatography and hydrolysis.[5] Furthermore, the
separation of the enantiomers 3 and ent-3 by crystallization
with (Ϫ)-quinine proved capricious,[5] whereas the induced
Scheme 1
It was reported recently that (1S,2S)-trans-cyclohexane-
dicarboxylic acid (ent-5) can be obtained readily in en-
antiomerically pure form by crystallization of the commer-
cially available racemate rac-5 with the inexpensive auxiliary
(R)-1-phenethylamine (6; Scheme 2).[10] In our hands, this
procedure afforded the enantiomerically pure (Ͼ 99% ee)
diacid reproducibly in at least 40% yield on a 0.5 mol scale
and without any problem. In addition, the racemic starting
trans-diacid rac-5 can be obtained in one step from even
cheaper cis-hexahydrophthalic anhydride.[11] We thus rea-
soned that 5 or ent-5 are excellent starting materials for the
preparation of the amino acids 2 and ent-2 on a larger scale.
[a]
Institut für Organische Chemie der Universität zu Köln,
Greinstrasse 4, 50939 Köln, Germany
Fax: (internat.) ϩ49-(0)221/470Ϫ5102
E-mail: berkessel@uni-koeln.de
2948
 WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0917Ϫ2948 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2002, 2948Ϫ2952

A Convenient Access to Both Enantiomers of trans-2-Aminocyclohexanecarboxylic Acid
FULL PAPER
Here we disclose our one-pot procedure for the high- and ent-4 could be performed in a one-pot procedure as
yielding conversion of the diacids 5 and ent-5 to the β-am- well (overall yield 67%).
ino acids 2 and ent-2, respectively. A one-pot conversion
leading directly from the diacids 5 and ent-5 to the N-BOC-
protected amino acids 4 and ent-4 proved possible as well.
Furthermore, X-ray crystallography of the diastereomer-
ically pure salt obtained from the crystallization of racemic
trans-1,2-cyclohexanedicarboxylic acid (rac-5) with (R)-1-
phenethylamine 6 revealed that the configuration of the di-
acid component is in fact (1R,2R) (5, as shown in
Scheme 2), and not (1S,2S) as reported.[10]
Scheme 3
Scheme 2
Results and Discussion
We initially tried to convert the enantiomerically pure di-
acid 5 directly into the BOC-protected amino acid 4 by
treatment with O,O-diphenylphosphoryl azide (DPPA) in
Figure 1. X-ray crystal structure of the amino acid hydrochloride
2·HCl
tert-butyl alcohol.[12] As it turned out, the desired product
could not be isolated in reasonable yields under any of the
many reaction conditions tried. We thus turned our atten-
tion to a Hofmann degradation of the monoamide 8
(Scheme 3). The latter is readily available from 5 by conver-
sion into the trans-anhydride 7[11] and subsequent ring-
opening with ammonia.[14] Of the many reagents examined,
phenyliodine() bis(trifluoroacetate) (PIFA) turned out to
give the best results (77%, Scheme 3).[16] Most importantly,
we found that all three steps necessary for the conversion
of the diacid 5 to the amino acid 2 can be carried out in a
one-pot procedure (Scheme 3): First, the diacid 5 is refluxed
with acetyl chloride. Dissolution of the diacid indicates the
completion of the first step. Excess acetyl chloride and
acetic acid are pumped off, and the anhydride 7 is dissolved
in dichloromethane. Conversion into the amide 8 is effected
within minutes by treatment with gaseous ammonia. Once
the precipitation is complete, the dichloromethane solvent
is replaced by a solution of the oxidant (PIFA) in a mixture
of acetonitrile/water, and the Hofmann degradation pro-
ceeds smoothly at room temperature. After ca. 24 h, the de-
sired amino acid 2 can be isolated in 74% yield as the hydro-
chloride 2·HCl. The X-ray crystal structure of this hydro-
chloride is shown in Figure 1. Finally, introduction of the
Fmoc group is achieved in the usual way by treatment with
Fmoc-OSu, affording the N-protected amino acid 9 in 81%
yield (Scheme 4).[17] Similarly, the N-BOC protected deriv-
ative 4 was obtained in 68% yield by treatment of 2·HCl
with di-tert-butyl pyrocarbonate (BOC2O, Scheme 4, Fig-
ure 2).[5] In fact, the four-step sequence leading from the
Scheme 4
Figure 2. X-ray crystal structure of the N-BOC derivative ent-4
As mentioned in the introduction, (R)-1-phenethylamine
diacids 5 and ent-5 to the N-BOC-protected amino acids 4 6 is reported in the literature to cause the precipitation of
Eur. J. Org. Chem. 2002, 2948Ϫ2952
2949

A. Berkessel, K. Glaubitz, J. Lex
FULL PAPER
6.97. 1H NMR ([D4]methanol): δ ϭ 1.16Ϫ1.37 (m, 4 H), 1.64Ϫ2.05
(m, 4 H), 2.37Ϫ2.51 (m, 2 H) ppm. 13C NMR ([D4]methanol): δ ϭ
26.5, 30.2, 46.3, 178.9 ppm. IR: ν˜ ϭ 2961, 1716, 1458, 1273, 1204,
939 cmϪ1. [α]2D5 ϭ Ϫ18.3 (c ϭ 1.00, acetone) {ref.[13] [α]D25 ϭ Ϫ18.5
(c ϭ 1.00, acetone)}.
the diastereomeric salt with (1S,2S)-cyclohexanedicarbox-
ylic acid ent-5 from the racemate rac-5.[10] In our hands,
the dicarboxylate moiety of the precipitate formed was the
(1R,2R)-isomer, as revealed by X-ray crystallography (Fig-
ure 3). We found the isolated (1R,2R)-cyclohexanedicarbox-
ylic acid 5 to be more than 99% optically pure and to be
levorotatory. The reported procedure[10] also states a nega-
tive specific rotation. Consequently, it appears most likely
that just the descriptors for the configuration of the isolated
trans-cyclohexanedicarboxylic acid were misassigned.[10]
Enantiomerically pure trans-1,2-cyclohexanedicarboxylic acid an-
hydride 7 was prepared according to a procedure published for the
racemic material (rac-7) using acetyl chloride,[11] affording the an-
hydride 7 as a colorless solid, yield: 98%; m.p. 162 °C (ref.[13] m.p.
164 °C).
Enantiomerically pure trans-1,2-cyclohexanedicarboxylic acid
monoamide 8 was prepared according to a procedure published for
the racemic material (rac-8) by ring-opening the anhydride with dry
ammonia gas.[14] The product was separated as a white solid. Yield:
quant., m.p. 197 °C (ref.[15] m.p. 196 °C, racemic mixture).
Hofmann Degradation of the Monoamide 8 (or ent-8) with PIFA:
Phenyliodine() bis(trifluoroacetate) (PIFA) (1.00 g, 2.32 mmol)
was dissolved in acetonitrile/water (8 mL, 1:1 v/v). trans-1,2-Cyclo-
hexanedicarboxylic acid monoamide (8 or ent-8, 400 mg,
2.32 mmol) was added, and the mixture was stirred at room tem-
perature overnight. The solution was then diluted with water (50
mL) and acidified with concentrated HCl (5 mL). Iodobenzene and
unchanged PIFA were extracted with Et2O. The ether layer was
washed with 10% aq. HCl, and the combined aqueous layers were
evaporated, yielding the amino acid hydrochloride 2·HCl (or ent-
2·HCl) as a colorless solid. Recrystallization from EtOH/Et2O af-
forded 320 mg (1.78 mmol, 77%, ee Ͼ 99%) of analytically pure
2·HCl (or ent-2·HCl) as colorless crystals; m.p. 208 °C. For the ee
determination, a sample of 2·HCl (or ent-2·HCl) was converted
into the N-trifluoroacetamide of 2 (or ent-2) by treatment with tri-
fluoroacetic anhydride and analyzed by GC on a 25 m Hydrodex
β-3P column. C7H14ClNO2 (179.6): calcd. C 46.80, H 7.86, N 7.80;
found C 46.83, H 7.54, N 7.92.. 1H NMR ([D6]DMSO): δ ϭ
1.15Ϫ1.46 (m, 4 H), 1.58Ϫ1.73 (m, 2 H), 1.94Ϫ2.06 (m, 2 H),
2.36Ϫ2.45 (m, 1 H), 3.07Ϫ3.18 (m, 1 H) ppm. 13C NMR
([D6]DMSO): δ ϭ 23.1, 24.1, 28.1, 28.9, 45.5, 49.9, 174.4 ppm. IR:
ν˜ ϭ 2862, 2035, 1720, 1623, 1604, 1514, 1453, 1382, 1249, 1219,
1164, 1055, 874, 670 cmϪ1. [α]2D5 ϭ Ϫ46 (c ϭ 1.00, water).
Figure 3. X-ray structure of the salt formed from (R)-1-phenethyla-
mine (6) and (1R,2R)-cyclohexanedicarboxylic acid (5)
Experimental Section
General: Reagents and solvents were purified by standard proced-
ures. Phenyliodine() bis(trifluoroacetate) (PIFA), N-(9-fluorenyl-
methoxycarbonyloxy)succinimide (Fmoc-OSu) and di-tert-butylpy-
rocarbonate (BOC2O) were purchased from standard suppliers and
used as received. Melting points were determined in capillary tubes
and are uncorrected. NMR spectra were recorded on a Bruker AC
300 instrument. IR spectra were recorded on a PerkinϪElmer FT-
IR 1600 spectrometer (CsI discs). Optical rotations were measured
on a PerkinϪElmer polarimeter 343plus. CHN-Analyses were de-
termined on an Elementar Vario EL instrument (Elementarana-
lysen Systeme GmbH). Capillary gas chromatography was carried
out on a HewlettϪPackard-5800 II instrument using a 25 m
Hydrodex β-3P column (MachereyϪNagel) or a 25 m WCOT-FS
CP-Chiralsil-Dex CB column (Chrompack). X-ray structural ana-
lyses were performed on a Nonius Kappa CCD diffractometer.
One-Pot Procedure for the Conversion of the Diacid 5 (or ent-5) to
the Amino Acid Hydrochloride 2·HCl (ent-2·HCl): Acetyl chloride
(25 mL) was added to trans-1,2-cyclohexanedicarboxylic acid (5 or
ent-5, 1.60 g, 9.30 mmol), and the mixture was refluxed until all
solids had dissolved. Excess acetyl chloride was removed under re-
duced pressure, and the solid residue was taken up in dichlorome-
thane (250 mL). Dry ammonia was bubbled through this solution
at room temperature. After completion of the precipitation, the
solvent was again removed under reduced pressure, and a solution
of PIFA (4.00 g, 9.30 mmol) in acetonitrile/water (50 mL, 1:1 v/v)
was added. Stirring was continued at room temperature overnight.
The reaction mixture was then diluted with water (100 mL), acidi-
fied with concentrated HCl (15 mL), and extracted with Et2O. The
ether layer was washed with 10% aq. HCl, and the combined aque-
ous layers were evaporated to yield the amino acid hydrochloride
2·HCl (or ent-2·HCl) as a colorless solid. Recrystallization from
EtOH/Et2O afforded 2·HCl (or ent-2·HCl) as colorless crystals
(1.22 g, 6.85 mmol, 74%); m.p. 208 °C. All analytical data were
identical with those obtained for the material prepared in a step-
wise manner.
trans-1,2-Cyclohexanedicarboxylic acid (rac-5) was obtained in
80% yield as a colorless solid (m.p. 220 °C, ref.[11] m.p. 218Ϫ220
°C) from cis-hexahydrophthalic anhydride, according to a literat-
ure procedure.[11]
Separation of the Enantiomers 5 and ent-5 of trans-1,2-Cyclohexane-
dicarboxylic Acid (rac-5): Racemic trans-1,2-cyclohexanedicarbox-
ylic acid (rac-5; 2.40 g, 13.9 mmol) was added to a solution of (R)-
1-phenethylamine (6; 1.70 g, 14.0 mol) in EtOH (20 mL) at Ϫ78
°C. A colorless precipitate formed, which was filtered off after
warming to room temperature. This solid was recrystallized from
hot EtOH/toluene (1:1, 40 mL) three times. The product thus ob-
tained was dissolved in 1  aq. HCl and extracted three times with
Et2O (50 mL). The combined organic layers were dried over
MgSO4 and evaporated under reduced pressure, affording the en-
antiomerically pure dicarboxylic acid 5 (or ent-5, when ent-6 was
employed) as colorless crystals; yield: 800 mg (4.66 mmol, 33%, ee
Ͼ 99%); m.p. 177 °C (ref.[13] m.p. 179Ϫ183 °C). For the ee deter-
mination, a sample of 5 (or ent-5) was converted into the dimethyl
ester by treatment with an ethereal solution of diazomethane and
analyzed by GC on a 25 m WCOT FS CP-Chiralsil-Dex CB col-
umn. C8H12O4 (172.2): calcd. C 55.81, H 7.02; found C 55.88, H
N-Fmoc-trans-2-aminocyclohexanecarboxylic Acid (9, or ent-9):
trans-2-Aminocyclohexanecarboxylic acid hydrochloride 2·HCl (or
ent-2·HCl; 290 mg, 1.62 mmol) was dissolved in THF (15 mL)
2950
Eur. J. Org. Chem. 2002, 2948Ϫ2952

A Convenient Access to Both Enantiomers of trans-2-Aminocyclohexanecarboxylic Acid
FULL PAPER
whilst stirring. Sodium hydroxide (81.0 mg, 2.00 mmol) was added, ature. After completion of the precipitation, the colorless solid was
followed by Fmoc-OSu (545 mg, 1.62 mmol). Finally, water (7.5 filtered off, dried in vacuo, and added to a solution of PIFA
mL) and additional THF (7.5 mL) were added. After five minutes, (12.8 g, 29.8 mmol) in acetonitrile/water (150 mL, 1:1 v/v). Stir-
sodium bicarbonate (169 mg, 2.0 mmol) and THF (7.5 mL) were ring was continued at room temperature overnight. The reaction
added and the reaction mixture was stirred at room temperature mixture was then diluted with water (250 mL), acidified with con-
overnight. The solution was acidified to pH 1 by addition of 1.5  centrated HCl (50 mL), and extracted with Et2O. The aqueous layer
aqueous hydrochloric acid. A precipitation occurred, and the mix- was concentrated to a volume of 200 mL, and potassium carbonate
ture was extracted thoroughly with EtOAc. The combined organic (29.9 g, 216 mmol) was added, followed by dioxane (400 mL) and
layers were washed with 1.5  aq. hydrochloric acid and water. BOC2O (11.8 g, 54.2 mmol). The reaction mixture was stirred at
After drying over MgSO4, the solvent was evaporated under re- room temperature overnight. It was then acidified to pH 1 by addi-
duced pressure. The solid residue was recrystallized from EtOAc/ tion of 3  HCl and extracted three times with EtOAc (250 mL).
hexane, affording 9 (or ent-9) as a colorless solid. Yield: 480 mg The combined organic layers were dried over MgSO4 and the sol-
(1.31 mmol, 81%); m.p. 222 °C (ref.[17] m.p. 201Ϫ203 °C, racemic vent was removed under reduced pressure. The remaining solid was
mixture). C22H23NO4 (365.4): calcd. C 72.31, H 6.34, N 3.83; found dried at 60 °C and 1 mbar to afford the product 4 (or ent-4) as a
1
C 72.41, H 6.32, N 3.78. H NMR (CDCl3): δ ϭ 1.05Ϫ1.95 (m, 9 colorless powder; yield: 4.44 g, 67%; m.p. 150Ϫ151 °C. The analyt-
H), 2.18Ϫ2.30 (m, 1 H), 4.15Ϫ4.25 (m, 3 H), 7.30Ϫ7.88 (m, 8 H) ical data were identical with those obtained for the material pre-
ppm. 13C NMR (CDCl3): δ ϭ 24.2, 24.4, 28.8, 32.1, 46.7, 48.3, pared in a stepwise manner (see above).
50.7, 65.2, 120.0, 125.1, 125.2, 127.0, 127.5, 175.3 ppm. IR: ν˜ ϭ
X-ray Structural Analyses of the Amino Acid Hydrochloride 2·HCl,
ent-2·HCl, of the N-BOC Derivative ent-4 and of the salt 5·6: Crys-
3332, 2934, 1696, 1559, 1540, 1529, 1451, 1424, 1318, 1261, 1231,
1126, 1057, 760, 741 cmϪ1. [α]D25 ϭ Ϫ42 (c ϭ 1.00, CHCl3).
tals suitable for X-ray structural analyses were obtained by recrys-
N-BOC-trans-2-aminocyclohexanecarboxylic Acid (4, or ent-4): N- tallization as described in the preparations. Experimental para-
Protection of the amino acid hydrochloride 2·HCl (or ent-2·HCl) meters are summarized in Table 1.
with BOC2O was performed according to a literature procedure,[5] CCDC-187726 (5·6), -187727 (ent-2·HCl), -187728 (ent-4) and
affording 4 (or ent-4) as colorless solids. Yield: 68%, m.p. 154 °C -187729 (2·HCl) contain the supplementary crystallographic data
(ref.[5] m.p. 154 °C). All analytical data were identical with the liter- for this paper. These data can be obtained free of charge via
ature values.[5] Crystals suitable for X-ray structural analysis were www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12
obtained by crystallization from hot ethyl acetate/hexane.
Union Road, Cambridge CB2 1EZ, UK; Fax: (internat.) ϩ44-1223/
336-033; E-mail: deposit@ccdc.cam.ac.uk).
One-Pot Procedure for the Conversion of the Diacid 5 (or ent-5) to
the N-BOC-Protected Amino Acid 4 (or ent-4): A mixture of trans-
1,2-cyclohexanedicarboxylic acid 5 (or ent-5) (4.66 g, 27.1 mmol)
Acknowledgments
and acetyl chloride (25 mL) was refluxed until the solid was dis- This work was supported by the European Community (Research
solved. Excess acetyl chloride was removed under reduced pressure, Training Network ‘‘Combinatorial Catalysis’’, HPRN-CT-2000-
and the solid residue was taken up in dichloromethane (500 mL). 00014), by the BASF AG, Ludwigshafen, and by the Fonds der
Dry ammonia was bubbled through this solution at room temper- Chemischen Industrie.
Table 1. Experimental parameters of the X-ray structural analyses of 2·HCl ent-2·HCl, 5·6, ent-4
2·HCl
C7H14ClNO2
179.64
0.2 ϫ 0.15 ϫ 0.15
monoclinic
P21
7.842(1)
6.883(1)
8.803(1)
90
94.81(1)
90
473.48(11)
1.260
ent-2·HCl
C7H14ClNO2
179.64
0.15 ϫ 0.15 ϫ 0.15
monoclinic
P21
7.833(1)
6.883(1)
8.904(1)
90
94.81(1)
90
472.99(11)
1.261
5·6
ent-4
Empirical formula
Mr
C16H23NO4
293.35
0.2 ϫ 0.1 ϫ 0.1
orthorhombic
P212121
6.091(1)
10.006(1)
26.091(1)
90
C12H21NO4
243.30
0.2 ϫ 0.2 ϫ 0.1
orthorhombic
P212121
5.200(1)
20.315(1)
27.003(1)
90
Crystal dimensions [mm]
Crystal system
Space group
˚
a [A]
˚
b [A]
˚
c [A]
α [°]
β [°]
γ [°]
90
90
90
90
2852.5(6)
1.133
8
3
˚
V [A ]
1590.16(31)
1.225
4
ρcalcd. [gcmϪ3
Z
]
2
2
Radiation
Scan mode
2 Θmax [°]
Mo-Kα
ϕ/ω
Mo-Kα
ϕ/ω
Mo-Kα
ϕ/ω
Mo-Kα
ϕ/ω
54
54
54
54
Reflections collected
Independent reflections
Reflections observed
Data/parameters
R1 (F)
3063
1831
1633
1831/156
0.033
0.073
0.185
0.00(6)
3807
1973
1760
1973/156
0.029
0.062
0.122
0.03(5)
8868
3463
1864
3463/283
0.052
0.082
0.133
Ϫ
18526
6011
2051
6011/477
0.069
0.126
R2 (F2)
ρfin. (max) [e·A
Ϫ3
˚
]
0.155
Ϫ
Absolute structure parameter
Eur. J. Org. Chem. 2002, 2948Ϫ2952
2951

A. Berkessel, K. Glaubitz, J. Lex
FULL PAPER
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