On the origin of the facial selectivity of the Sharpless asymmetric dihydroxylation of styrene derivatives

Article abstract of DOI:10.1081/CAR-120019011

Xylose/styrene-based substrates were reacted with Sharpless asymmetric dihydroxylation reagents AD-mix α and AD-mix β. Unlike the previously reported xylose allyl ether, the saccharide unit did not affect the stereochemical outcome of the reaction. Asymme

Full text of DOI:10.1081/CAR-120019011

Journal of Carbohydrate Chemistry
ISSN: 0732-8303 (Print) 1532-2327 (Online) Journal homepage: http://www.tandfonline.com/loi/lcar20
On the Origin of the Facial Selectivity of the
Sharpless Asymmetric Dihydroxylation of Styrene
Derivatives
Nicolas Moitessier , Christophe Henry , Christophe Len , Denis Postelb &
Yves Chapleura
To cite this article: Nicolas Moitessier , Christophe Henry , Christophe Len , Denis Postelb
& Yves Chapleura (2003) On the Origin of the Facial Selectivity of the Sharpless Asymmetric
Dihydroxylation of Styrene Derivatives, Journal of Carbohydrate Chemistry, 22:1, 25-34, DOI:
10.1081/CAR-120019011
To link to this article: http://dx.doi.org/10.1081/CAR-120019011
Published online: 20 Aug 2006.
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JOURNAL OF CARBOHYDRATE CHEMISTRY
Vol. 22, No. 1, pp. 25–34, 2003
On the Origin of the Facial Selectivity of the Sharpless
Asymmetric Dihydroxylation of Styrene Derivatives
Nicolas Moitessier,1 Christophe Henry,1 Christophe Len,2,
*
Denis Postel,2 and Yves Chapleur1
1Groupe SUCRES, UMR CNRS, Universite´ Henri Poincare´,
Nancy-Vandoeuvre, France
2Laboratoire des Glucides, Universite´ de Picardie-Jules Verne, Amiens, France
ABSTRACT
Xylose/styrene-based substrates were reacted with Sharpless asymmetric dihydrox-
ylation reagents AD-mix a and AD-mix b. Unlike the previously reported xylose allyl
ether, the saccharide unit did not affect the stereochemical outcome of the reaction.
Asymmetric dihydroxylation using AD-mix a or AD-mix b of the chiral olefin gave
mainly one diastereoisomer (de: 98%) with S and R configuration respectively. A
modelling study directed at a rationalisation of the asymmetric dihydroxylation data is
described and applied to diversely derivatised styrenes.
Key Words: Asymmetric dihydroxylation; Chiral olefin; Modelling study.
INTRODUCTION
The Sharpless asymmetric dihydroxylation (AD) methodology[1] has evolved into
one of the most powerful tools for enantioselective functionalisation of olefins and
found wide applications in total synthesis and medicinal chemistry. For instance, AD
of 2 successfully afforded intermediates en route to novel nucleoside analogues such
as 1 as inhibitors of reverse transcriptase in the treatment of HIV infection.[2–4] AD
*
Correspondence: Dr. Christophe Len, Laboratoire des Glucides, Universite´ de Picardie-Jules
Verne, F-80039 Amiens, France; E-mail: Christophe.Len@sc.u-picardie.fr.
25
DOI: 10.1081/CAR-120019011
0732-8303 (Print); 1532-2327 (Online)
www.dekker.com
Copyright D 2003 by Marcel Dekker, Inc.

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26
Moitessier et al.
Figure 1. Biological relevant compounds prepared using Sharpless AD as a key step.
of 4a was also a key reaction in the preparation of Adenophostin A analogues
(Figure 1).[5,6]
While optimising the catalysts, Sharpless and Corey have proposed models based
on X-ray crystallographic data and NOE experiments, respectively, to rationalise the
enantiofacial selectivity of the reaction with styrene (Figure 2).[7–9]
A survey of Sharpless AD of achiral styrene derivatives[2,7,10–13] showed that
different substitutions in ortho, meta or para positions of the aromatic ring usually
slightly affect the enantiomeric excess (ee).
Figure 2. (a) L-shaped model with (DHQD)2PHAL.[8] (b) U-shaped model with
(DHQD)2PYDZ.[9] (c) Mnemonic device. (From Ref. [8].)

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Styrene Derivatives
27
In contrast, AD of chiral alkenes is harder to rationalize since a substrate intrinsic
enantiocontrol may be operative.[14] For instance, asymmetric dihydroxylation of allyl
a-D-xylosides such as 4a and 4b highlighted a great double diastereoselection
effect.[5,6,15] Eventfully, the xylose moiety, which can be seen as a chiral auxiliary,
inverted the sense of attack according to the Sharpless mnemonic. We attempted to
account for these observations using molecular dynamics methods and proposed a
model that agreed with the experimental data. We report herein our studies on
asymmetric dihydroxylation of a different xylose derivative featuring a styrene moiety
and the rationalisation of the data.
RESULTS AND DISCUSSION
In previous work,[2–4] we reacted the dioxane derivative 2 to synthesize the
nucleoside 1 via asymmetric dihydroxylation (Figure 1). Although the dihydroxylation
proceeded uneventfully, the separation of enantiomers remained tricky.[2–4] We opted
for the use of a chiral auxiliary such as a monosaccharide to obtain diastereoisomers
and hence to facilitate the separation.[17] For that purpose, the use of a partially
protected xylofuranoside was envisaged, and the suitable dialdehyde was converted
Scheme 1. (a) 1,2-O-isopropylidene-a-D-xylofuranose, p-TSA, THF; (b) BrMePh3P, BuLi, THF;
(c) AD-mix a, tert-BuOH/H2O; (d) BzCl, N(C2H5)3, toluene; (e) AcOH, H2O then MeOH HCl 1%;
(f) AD-mix b, tert-BuOH/H2O.

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Moitessier et al.
into the corresponding cyclic diacetal 5 using standard conditions (Scheme 1). 5 was
next homologated into the styrene derivative 6 by treatment with methyltriphenylpho-
sphonium bromide and butyl lithium in THF. The Wittig adduct 6 was the substrate
for the subsequent Sharpless asymmetric dihydroxylation (AD). Thus, 6 was alter-
natively reacted with AD-mix a and AD-mix b in a mixture of tert-butyl alcohol/
water to afford the expected diols 7a (78%) and 7b (81%), respectively, as single
1
isomers as shown by H and 13C NMR. Further HPLC and GC-MS analysis confirmed
this high selectivity (de: 99.5% for 7a, de: 98% for 7b). Fortunately, the separation of the
isomers became easy, as well as did the preparation of optically pure analogues.
Selective protection of the diols 7a and 7b was accomplished by treatment with benzoyl
chloride in toluene–triethylamine mixture at –20°C to give the esters 8a and 8b,
respectively. The benzoate 8a was treated with HCl 1% in methanol to afford the
benzo[c]furan derivatives 9a and 10a in a 1:1 ratio. Under similar conditions, the hy-
droxyester 8b gave the heterocycles 9b and 10b as an equimolar mixture.
The enantiofacial selectivity in the asymmetric dihydroxylation reaction was de-
termined by X-ray crystallography of diol 7a (Figure 3). The absolute configuration at
the carbon atom created during the oxidation was S with AD-mix a in agreement with
the mnemonic rule.[9]
These high diastereoselections with both AD-mix a and b were striking for several
reasons. First, this data contrasted with the previous observations where the effect of
the sugar moiety was strong and led to the unexpected diol according to Sharpless
mnemonic.[15] Secondly, the corresponding dioxane 2[2–4] was earlier reacted with AD-
mix a and b with similar selectivities, indicating no substrate control of the reaction.
Finally, the asymmetric dihydroxylation of monosaccharides does not usually provides
diols with so high excesses.[19–22]
This high enantiofacial discrimination together with the absence of substrate
induction at the asymmetric dihydroxylation step deserved further investigations.
Earlier, we reported a pure molecular mechanics method based on a simulated
annealing to rationalize the unusual behaviour of 4b.[15] In the present work, an
enhanced version of the protocol based on a genetic algorithm was exploited and
included the computation of the solvation free energy contribution. The full protocol
and its testing on a variety of substrates will be reported in due course.
For the comparison purpose, we thought to apply this enhanced protocol to styrene.
The computation led to two energetically accessible models within 1 kcal.molÀ1, which
Figure 3. Ortep diagram of diol 7a. (From Ref. [18].)

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Styrene Derivatives
29
Figure 4. Computed transition states for the AD with AD-mix b of styrene. Only olefin
hydrogens are shown for clarity.
predicted the observed enantiofacial selectivity (Figure 4). Interestingly, these two
models resemble those alternatively proposed by Sharpless and Corey.[7–9] A closer
look reveals that the assembly conformations differed mainly for the olefin positioning,
the catalyst conformation being roughly similar. Indeed, the catalyst conformation
corroborated that proposed by Sharpless on NMR basis.[9]
The high convergence of the experimentally pictured (Figure 2) and computational
models (Figure 5) was encouraging. We next investigated the AD transition states of 2
and 6. Again, the proposed models were in accordance with the experimental
observations (Figures 5 and 6).
In both cases (with or without the chiral auxiliary), the styrene part of the substrate
fitted in the same zone as did the styrene. However, although the fully protected xylo-
furanoside ring did not have any influence on the stereofacial selection, it was found to
be involved in hydrophobic interactions with a methoxyquinoline moiety (Figure 5).
Consequently, a new spatial arrangement of the catalyst occurred. This additional
interaction might explain the gain in selectivity observed between styrene (97% ee with
both AD-mix a and AD-mix b) and 6 (de: 99.5% with AD-mix a, de: 98% with AD-
mix b). In terms of excess, this difference may be viewed as low. However, in terms of
free energy of activation, the gain is large. For instance a de of 97% requires a
difference in energy between the transition states leading to the minor and major
isomers of 2.3 kcal.mol À 1 while a de of 99.5% is equivalent to DG = 3.2 kcal.molÀ1
.
In contrast, 2 fitted in the ‘‘binding site’’ with roughly identical arrangements to
styrene (Figure 5). Regarding the observed ee’s and the proposed models, we could
conclude about a negligible effect of any small ortho group. Indeed, although this latter is
Figure 5. Computed transition states for the AD-mix b of 6.

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Moitessier et al.
Figure 6. Computed transition states for the AD with AD-mix b of 2.
facing the solvent increasing unfavourable contacts with the polar medium (tert-BuOH/
H2O), it did not sterically clash with the catalyst nor favorably interact with it.
In conclusion, we successfully used the Sharpless asymmetric dihydroxylation as a
key step in the preparation of saccharide analogues 9 and 10. The introduction of a
chiral auxiliary allowed an easier identification and purification of both isomers
produced. Interestingly, unlike the previously reported xylose-based substrate 4a, 6 was
dihydroxylated with high stereoselectivity. These results prompted us to look back to
our initial modelling work on AD. We exploited an enhanced version of this protocol to
account for these last observations. This modelling study highlighted two energetically
accessible models previously proposed by Corey and Sharpless. These two models were
also proposed for AD of styrene derivatives 2 and 6 and shed light on aromatic
stacking, hydrophobic and steric interactions that can explain the experimental data.
Further optimisation of the procedure, test of its versatility and rationalisation of
Sharpless mnemonic device will be presented in due course.
EXPERIMENTAL
Melting points were determined on a digital melting-point apparatus (Electro-
thermal) and are uncorrected. Optical rotations were recorded at 22°C in CHCl3 or
MeOH solutions with a digital polarimeter DIP-370 (JASCO) using a 1dm cell and
.
rotations are given in 10 À 1 deg cm2 gÀ 1 1H NMR and 13C NMR spectra were
recorded in CDCl3 or Me2SO–d6 (internal Me4Si) respectively at 300.13. MHz and at
75.47 MHz (Bruker AM WB-300). Coupling constants (J) are given in Hz. TLC was
performed on Silica F254 (Merck) with detection by UV light at 254 nm or by
charring with phosphomolybdic–H2SO4 reagent. Column chromatography was effected
on Silica Gel 60 (Merck, 230 mesh). Commercial reagents were supplied by Lancaster
or Acros.
Computational simulations were performed with the Insight II1 2000 package
using a modified CFF91 force field and a protocol reported elsewhere.[23] Graphical
displays were printed out from the Insight II1 molecular modeling system.
3,5-O-(S)-(2-Ethenylbenzylidene)-1,2-O-isopropylidene- -D-xylofuranose
(6). A suspension of methyltriphenylphosphonium bromide (7.0 g, 19.59 mmol) in
dry tetrahydrofuran (20 mL) at 0°C under N2 was treated dropwise with n-butyl lithium
(12.3 mL of 1.6 M in hexane, 19.59 mmol), warmed to room temperature for 1 h, and
re-cooled to 0°C during the addition of compound 5[14] (3.0 g, 9.79 mmol) in tetra-

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Styrene Derivatives
31
hydrofuran (10 mL). After 1 h at room temperature, the reaction mixture was quenched
with saturated aqueous NH4Cl (30 mL) and extracted with diethyl ether (2 Â 50 mL).
The extract was worked up, and the crude product was purified by column chroma-
tography (hexane–acetone, 95:5) to afford 6 (2.1 g, 69%) as a white solid, mp 85.3–
1
87.6°C. [a]2D4 À 16.0 (c 1.0, CHCl3); H NMR (300 MHz, CDCl3) d 7.51 (m, 2H, H-3
and H-6), 7.28 (m, 2H, H-4 and H-5), 7.07 (dd, 1H, J 1.0, J 11.0, CHCH2), 6.05 (d, 1H,
J1,2 3.6, H-1), 5.62 (m, 1H, J 17.5, CHCH2), 5.57 (s, 1H, CH), 5.30 (m, 1H, CHCH2),
4.60 (d, 1H, J2,3 0, H-2), 4.44 (d, 1H, J5a,5b 13.4, H-5a), 4.39 (bs, 1H, H-4), 4.12 (bs,
1H, H-3), 4.11 (d, 1H, H-5b), 1.49 (s, 3H, CH3), 1.31 (s, 3H, CH3). 13C NMR (75
MHz, CDCl3) d 136.3 (C-1), 133.9 (2C, C-2, CHCH2), 129.2, 127.6, 126.4 and 126.0
(4C, C-3, C-4, C-5 and C-6), 116.4 (CHCH2), 111.8 (Ciso), 105.6 (C-1), 98.1 (CH),
83.8 (C-2), 78.9 (C-4), 72.1 (C-3), 66.8 (C-5), 26.7 (CH3), 26.1 (CH3).
Anal. Calcd for C17H20O5 (304.34): C 67.09, H 6.62; Found: C 66.97 H 6.78.
3,5-O-(S)[2-((S)-1,2-Dihydroxyethyl)benzylidene]-1,2-O-isopropylidene- -D-
xylofuranose (7a). A mixture of AD-mix a (2.3 g) in tert-butyl alcohol (8.2 mL) and
water (8.2 mL) was stirred at room temperature until both phases were clear. After the
mixture was cooled to 0°C, compound 6 (0.5 g, 1.64 mmol) was added in one portion
and the heterogeneous slurry was stirred vigorously at 0°C for 10 h. The reaction
mixture was quenched by addition of sodium sulfite (2.5 g) at 0°C, warmed to room
temperature and stirred for one hour. The product was extracted with dichloromethane
(20 mL), the extract was concentrated and the crude product was purified by column
chromatography (hexane–acetone, 50:50) to afford 7a (0.45 g, 81%) as a white solid,
D
1
mp 190.2–190.7°C. [a]20 + 29.7 (c 0.5, CHCl3); H NMR (300 MHz, CDCl3) d 7.49
(m, 2H, H-3 and H-6), 7.30 (m, 2H, H-4 and H-5), 6.04 (d, 1H, J1,2 3.6, H-1), 5.59 (s,
1H, CH), 5.17 (dd, 1H, J 3.4, J 8.0, CHOH), 4.55 (d, 1H, J2,3 0, H-2), 4.39 (bd, 1H, H-
5a), 4.38 (bs, 1H, H-4), 4.09 (d, 1H, J3,4 1,7, H-3), 4.08 (dd, 1H, J4,5b 1.7, J5a,5b 13.3,
H-5b), 3.79 (dd, 1H, J 3.3, J 11.2, CHaHbOH), 3.64 (dd, 1H, J 8.0, CHaHbOH), 3.13,
2.00 (bs, 2H, OH), 1.48 (s, 3H, CH3), 1.29 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3) d
139.0 (C-1), 134.4 (C-2), 129.6, 127.8, 127.0, 126.9 (4C, C-3, C-4, C-5 and C-6), 112.0
(Ciso), 105.6 (C-1), 98.8 (CH), 83.7 (C-2), 78.8 (C-4), 71.9 (C-3), 70.8 (CHOH), 67.5
(CH2OH), 66.7 (C-5), 26.6 (CH3), 26.1 (CH3).
Anal. Calcd for C17H22O7 (338.35): C 60.35, H 6.55; Found: C 60.52, H 6.82.
3,5-O-(S)[2-((R)-1,2-Dihydroxyethyl)benzylidene]-1,2-O-isopropylidene- -D-
xylofuranose (7b). Using the same procedure as detailed for compound 6 but using
AD-mix b, the isomer 7b was obtained (0.43 g, 78%) as a white solid, mp 67.0–
D
1
67.4°C. [a]21 À 18.9 (c 0.5, CHCl3); H NMR (300 MHz, CDCl3) d 7.49 (m, 2H, H-
6 and H-3), 7.28 (m, 2H, H-4 and H-5), 6.19 (d, 1H, J1,2 3.6, H-1), 5.56 (s, 1H, CH),
5.39 (dd, 1H, J 3.4, J 8.0, CHOH), 4.59 (d, 1H, J2,3 0, H-2), 4.39 (dd, 1H, J4,5a 1,7,
J5a,5b 10.7, H-5a), 4.38 (bs, 1H, H-4), 4.12 (bs, 1H, H-3), 4.10 (dd, 1H, J4,5b 2.0, H-5b),
3.69 (dd, 1H, J 3.2, J 11.2, CHaHbOH), 3.63 (dd, 1H, J 8.5, CHaHbOH), 3.13, 2.00 (bs,
2H, OH), 1.51 (s, 3H, CH3), 1.33 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3) d 139.9
(C-1), 134.2 (C-2), 129.7, 127.7, 127.5, 127.4 (4C, C-3, C-4, C-5 and C-6), 112.0
(Ciso), 105.7 (C-1), 100.2 (CH), 83.8 (C-2), 78.9 (C-4), 71.9 (C-3), 70.7 (CHOH), 67.8
(CH2OH), 66.7 (C-5), 26.7 (CH3), 26.2 (CH3).
Anal. Calcd for C17H22O7 (338.35): C 60.35, H 6.55; Found: C 60.48, H 6.52.

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Moitessier et al.
3,5-O-(S)[2-((S)-2-Benzoyloxy-1-hydroxyethyl)benzylidene]-1,2-O-isopropyli-
dene- -D-xylofuranose (8a). To a stirred solution of diol 7a (1.0 g, 2.95 mmol) in
anhydrous toluene (4.4 mL) and triethylamine (1.1 mL) at À 20°C benzoyl chloride
(335 mg, 2.95 mmol) was added dropwise. The reaction mixture was stirred for 12 h,
water (10 mL) was added, and the mixture was extracted with diethyl ether (2 Â 10
mL). The extract was worked up, and the crude product was purified by column
chromatography (hexane–acetone, 85:15) to afford 8a (0.9 g, 69%) as a white solid,
D
1
mp 127.9–128.3°C. [a]21 + 13.3 (c 0.9, CHCl3); H NMR (300 MHz, CDCl3) d 8.04
(m, 2H, H-3 and H-6), 7.57–7.37 (m, 7H, H-4, H-5, COPh), 6.03 (d, 1H, J1,2 3.2, H-1),
5.71 (s, 1H, CH), 5.45 (bd, 1H, J 7.7, CHOH), 4.61 (m, 1H, CHaHbO), 4.55 (d, 1H, J2,3
0, H-2), 4.39 (m, 3H, H-4, H-5a and CHaHbO), 4.12 (bd, 1H, J5a,5b 11.7, H-5b), 4.10
(bs, 1H, H-3), 3.10 (bs, 1H, OH), 1.49 (s, 3H, CH3), 1.28 (s, 3H, CH3). 13C NMR (75
MHz, CDCl3) d 166.8 (COPh), 138.1 (C-1), 134.5 (C-2), 133.1 (C-para/OBz), 129.9
(C-i/OBz), 129.7, 129.5, 128.3, 128.1, 126.8, 126.7 (8C, C-ortho/OBz, C-meta/OBz, C-
3, C-4, C-5 and C-6), 111.8 (Ciso), 105.6 (C-1), 98.0 (CH), 83.7 (C-2), 78.8 (C-4), 72.0
(C-3), 69.4 (CHOH), 68.7 (CH2OH), 66.7 (C-5), 26.7 (CH3), 26.1 (CH3).
Anal. Calcd for C24H26O8 (442.46): C 65.15, H 5.92; Found: C 64.97, H 6.19.
3,5-O-(S)[2-((R)-2-benzoyloxy-1-hydroxyethyl)benzylidene]-1,2-O-isopropyli-
dene- -D-xylofuranose (8b). Using the procedure described 8b (0.94, 72%) was ob-
D
1
tained as a white solid, mp 71.5–71.9°C, [a]22 À 10.0 (c 0.5, CHCl3); H NMR (300
MHz, CDCl3) d 8.06 (m, 2H, H-6 and H-3), 7.57–7.36 (m, 9H, H-4, H-5, COPh), 5.97
(d, 1H, J1,2 3.3, H-1), 5.60 (s, 1H, CH), 5.59 (bd, 1H, J 7.5, CHOH), 4.55 (m, 1H,
CHaHbO), 4.50 (d, 1H, J2,3 0, H-2), 4.32 (m, 3H, H-4, H-5a and CHaHbO), 4.10 (bd,
1H, J5a,5b 11.7, H-5b), 4.06 (bs, 1H, H-3), 3.05 (bs, 1H, OH), 1.44 (s, 3H, CH3), 1.16 (s,
3H, CH3). 13C NMR (75 MHz, CDCl3) d 166.7 (COPh), 138.7 (C-1), 134.2 (C-2), 133.1
(C-para/OBz), 129.7 (C-i/OBz), 129.6, 127.9, 127.4, 127.2, (8C, C-ortho/OBz, C-meta/
OBz, C-3, C-4, C-5 and C-6), 111.7 (Ciso), 105.5 (C-1), 99.6 (CH), 83.7 (C-2), 78.9
(C-4), 72.0 (C-3), 69.5 (CHOH), 68.3 (CH2OH), 66.6 (C-5), 26.6 (CH3), 25.8 (CH3).
Anal. Calcd for C24H26O8 (442.46): C 65.15, H 5.92; Found: C 65.04, H 6.17.
(1R,3S)-3-Benzoyloxymethyl-1,3-dihydro-1-methoxybenzo[c]furan (9a) and
(1S,3S)-3-Benzoyloxymethyl-1,3-dihydro-1-methoxybenzo[c]furan (10a). The sac-
charide derivative 8a (300 mg, 0.678 mmol) was taken up in 16.8 mL of 80% acetic
acid and heated at 60°C for 2 hours. After solvent evaporation and co-evaporation with
toluene, the residue was dissolved in methanolic HCl (1%, 3.5 mL), and the mixture
was stirred for 2 h at room temperature. Water (20 mL) was added, and the mixture
was extracted with diethyl ether (2 Â 10 mL). The extract was worked up and purified
by silica gel column chromatography (hexane–acetone, 95:5) to afford 9a and 10a (130
mg, 67%) obtained as a pair of diastereoisomers with a cis/trans ratio of 1:1. Both
diastereoisomers 9a cis and 10a trans had physical data and NMR data identical to
those previously described.[2]
(1S,3R)-Benzoyloxymethyl-1,3-dihydro-1-methoxybenzo[c]furan (9b) and
(1R,3R)-Benzoyloxymethyl-1,3-dihydro-1-methoxybenzo[c]furan (10b). Using the
above procedure 8b (300 mg, 0.678 mmol) was converted to a mixture of 9b and 10b
(128 mg, 66%) obtained as a pair of diastereoisomers with a cis/trans ratio of 1:1. Both

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Styrene Derivatives
33
diastereoisomers 9b and 10b had physical data and NMR data identical to those
previously described.[2]
ACKNOWLEDGMENTS
We thank Pr. G. Nowogrocki for the X-ray studies, Dr. Bernard Maigret for
critically reading this manuscript and ‘‘Le Conseil Re´gional de Picardie’’ for finan-
cial support.
REFERENCES
1. Kolb, H.C.; VanNieuwenhze, M.S.; Sharpless, K.B. Catalytic asymmetric
dihydroxylation. Chem. Rev. 1994, 94, 2483–2547.
2. Ewing, D.F.; Fahmi, N.; Len, C.; Mackenzie, G.; Pranzo, A. Stereoisomeric
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Received February 5, 2002
Accepted October 4, 2002