Enantioselective sulfide oxidation with H2O2: A solid phase and array approach for the optimisation of chiral Schiff base-vanadium catalysts

Article abstract of DOI:10.1055/s-2002-32582

Two libraries of chiral Schiff base ligands were synthesised and screened in the vanadium-catalysed oxidation of alkyl aryl sulfides with hydrogen peroxide as terminal oxidant. The vanadium-chiral Schiff base complex 10, readily prepared from 3,5-diiodo-salicylaldehyde and (S)-tert-leucinol, was found to be highly enantioselective. Optically active sulfoxides could thus be obtained in good yields with up to 97% ee.

Full text of DOI:10.1055/s-2002-32582

LETTER
1055
Enantioselective Sulfide Oxidation with H2O2: A Solid Phase and Array
Approach for the Optimisation of Chiral Schiff Base-Vanadium Catalysts
Enantioselective
é
O
xiadation with 2
t
H
O
2 rice Pelotier,a Mike S. Anson,*a Ian B. Campbell,b Simon J. F. Macdonald,b Ghislaine Priem,b
Richard F. W. Jacksonc
a
GlaxoSmithKline, Medicines Research Centre, Chemical Development, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK
Fax +44(134)8764414; E-mail: msa17004@gsk.com
b
c
GlaxoSmithKline, Medicines Research Centre, Medicinal Chemistry, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK
Department of Chemistry, Dainton Building, University of Sheffield, E-mail: Brook Hill, Sheffield, S3 7HF, UK
Received 21 May 2002
which probably affects the equilibrium between the per-
oxovanadium species.12
Abstract: Two libraries of chiral Schiff base ligands were synthe-
sised and screened in the vanadium-catalysed oxidation of alkyl aryl
sulfides with hydrogen peroxide as terminal oxidant. The vanadi-
um-chiral Schiff base complex 10, readily prepared from 3,5-di-
iodo-salicylaldehyde and (S)-tert-leucinol, was found to be highly
enantioselective. Optically active sulfoxides could thus be obtained
in good yields with up to 97% ee.
As part of our interest in simple oxidation systems using
H2O2 as terminal oxidant, we were attracted by Bolm’s
protocol and decided to launch a systematic study to opti-
mise the Schiff base-derived catalyst structure. Our ap-
proach was to rapidly generate libraries of simple chiral
Schiff bases using solid phase chemistry and parallel syn-
thesis and to screen them in the enantioselective vanadi-
um-catalysed sulfide oxidation. In this paper, we report
our results from these screenings and highlight in particu-
lar that the enantiocontrol is dictated mainly by a single
stereocentre on the Schiff base ligand and that the pre-
ferred catalysts, synthesised in only one or two steps from
commercially available materials, lead to some of the best
ee’s reported to date.
Key words: asymmetric catalysis, Schiff bases, hydrogen perox-
ide, enantioselective sulfoxidation, supported catalysts
Enantiopure sulfoxides are an important class of com-
pounds as synthetic intermediates for asymmetric trans-
formations,1 as chiral ligands in enantioselective
catalysis2 and as bioactive ingredients in the pharmaceuti-
cal industry.3 The asymmetric oxidation of prochiral
sulfides4 has become the method of choice for the synthe-
sis of optically active sulfoxides since Kagan5 and
Modena6 independently reported high enantioselectivities
using modified versions of the Sharpless epoxidation sys-
tem: alkyl hydroperoxide/titanium tetraisopropoxide/di-
ethyl tartrate.
Although originally stoichiometric, catalytic versions of
this titanium-mediated reaction were later described7 and
new catalytic systems have emerged.8–11 Current efforts
are devoted to the development of oxidation reactions us-
ing hydrogen peroxide as terminal oxidant, as this is a
cheap, readily available, environmentally benign and
atom efficient reagent.9–11 In this respect, the catalytic sys-
tem of a vanadium-chiral Schiff base 1 described by Bolm
in 1995 is particularly attractive for its simplicity, high ac-
tivity (0.01–1 mol% of catalyst) and good enantioselec-
tion in asymmetric sulfide oxidation with H2O2, giving up
to 70% ee for thioanisole oxidation (Scheme 1).10a Im-
provements of the selectivity were later achieved using
more complex Schiff bases bearing extra chirality on the
fragment derived from the aldehyde. Thus binaphthyl-de-
rived ligand 210b and biphenyl-derived ligand 310e afforded
methyl phenylsulfoxide in 78% and 88% ee respectively.
In this latter case, the enantioselectivity was further im-
proved by the addition of a slight amount of methanol,
Scheme 1
We first synthesised a library of solid-supported Schiff
bases 7 derived from a large range of readily available
chiral amines and supported salicylaldehyde
6
(Scheme 2). The coupling of a salicylaldehyde unit onto a
solid support was achieved by the synthesis of acid pre-
cursor 5 and alkylation of its cesium salt with Merrifield
Synlett 2002, No. 7, Print: 01 07 2002.
Art Id.1437-2096,E;2002,0,07,1055,1060,ftx,en;D10002ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1056
B. Pelotier et al.
LETTER
resin. Acid 513 was prepared in 4 steps from tert-butylhy- of the substituent to the amine, from 21% ee with a me-
droquinone, by selective alkylation with ethyl-5-bromov- thyl group (Table 1, entry 5) to 52% ee with a tert-butyl
alerate, ortho-directed formylation14 of phenol 4, allyl- group (Table 1, entry 10). Interestingly, the position of the
protection of the free phenol (which was rendered neces- chiral centre, or to the amine, did not affect the selec-
sary for clean coupling to the resin), and saponification of tivity (Table 1, entry 4 vs. 5). It is also worth noting that
the ethyl ester. A deallylation reaction with 10 mol% mainly the (S) enantiomers of the sulfoxide were formed
Pd(PPh3)4 and morpholine led to the supported salicylal- with both ligands 7d and 7e bearing methyl substituents of
dehyde 6, the structure of which was confirmed by MAS- opposite configuration. These results demonstrate firstly
NMR. Various chiral amines, mainly diversely substitut- the role of the hydroxyl function in the chelation with va-
ed aminoalcohols, were then condensed with aldehyde 6. nadium and secondly the importance of substitution on
The structures of the resulting imines 7 were checked by only one face of the resulting vanadium-tridentate Schiff
MAS-NMR as conventional aldehyde colour tests on res- base complex for enantioselectivity.
in provided ambiguous results.15
The best enantioselectivities were obtained with (S)-tert-
leucinol-derived ligand 7j (52% ee) and (1R,2S)-cis-ami-
CO2Et
noindanol-derived ligand 7o (48% ee) containing the
same amines as the best ligands reported in the literature
(cf ligands 1–3) and represent the best results so far in the
sulfide oxidation with solid-supported vanadium cata-
lysts. Control experiments were performed in solution
phase with Schiff bases prepared by condensation of the
ethyl ester analogue of aldehyde 6 and L-allo-threonine,
(1R,2S)-cis-aminoindanol or (S)-tert-leucinol. Compara-
ble results in terms of selectivity order were obtained with
54%, 59% and 63% ee respectively (compared to 40%,
48% and 52% ee with supported ligands 7m, 7o and 7j),
and validated our solid phase approach for the optimisa-
tion of catalyst structures. The loss of enantioselectivity
from solution phase to solid phase catalysis has previously
been reported for other asymmetric transformations17 and
might be explained by the lower accessibility of the cata-
lytic sites on solid support.
tBu
OH
tBu
OH
b,c,d
tBu
a
O
HO
4
O
O
CO2H
O
tBu
e,f
O
OH
OAll
O
O
5
6
g
O
O
O
tBu
OH
N
Table 1 Thioanisole Oxidation with Supported Vanadium-Schiff
Bases 7 as Catalysts and Aqueous H2O2 as Oxidant
R*
7
Scheme 2 Reagents and conditions: a) ethyl-5-bromovalerate,
K2CO3, KI, CH3CN, 55 °C; b) MgCl2, Et3N, CH3CN, r.t. then
(CH2O)n, 40 °C; c) allyl bromide, K2CO3, DMF, r.t.; d) LiOH.H2O,
dioxane-H2O (1:1), r.t., 47% (4 steps); e) Merrifield resin (0.74 mmol/
g), Cs2CO3, KI, DMF, 50 °C; f) Pd(PPh3)4, morpholine, CH2Cl2, r.t.;
g) chiral amine, CH2Cl2, r.t.
Entry Ligand Aminea
Yieldb eeb
Conf.c
S
We next screened our library of 29 chiral supported
ligands in the vanadium-catalysed asymmetric oxidation
of thioanisole, after pre-optimisation of the reaction con-
ditions for this triphasic catalytic system.16 Representative
examples of the library results are reported in Table 1.
Poor enantioselectivities were observed when no hydrox-
yl function was present on the amine backbone (ligands
7a and 7b, Table 1, entries 1 and 2 vs. 9), when the ami-
noalcohol was monosubstituted by another heteroatomic
group (alcohol, amide, ester, cf ligand 7c, Table 1, entry
3), with 1,1,2-trisubstituted aminoalcohols, trans-1,2-dis-
ubstituted aminoalcohols (ligand 7l, Table 1, entry 12 vs.
13) and trans-1,2-disubstituted aminosulfonamides
(ligand 7k, Table 1, entry 11). In contrast, higher enanti-
oselectivities were reached with aminoalcohols substitut-
ed with alkyl or aromatic groups (Table 1, entries 4–10)
and cis-1,2-disubstituted aminoalcohols (Table 1, entries
13–15). The selectivity increased with the steric hindrance
1
7a
82
4
2
3
7b
7c
71
74
6
6
S
R
4
5
7d
7e
77
78
20
21
S
S
Synlett 2002, No. 7, 1055–1060 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Enantioselective Sulfide Oxidation with H2O2
1057
Table 1 Thioanisole Oxidation with Supported Vanadium-Schiff
Bases 7 as Catalysts and Aqueous H2O2 as Oxidant (continued)
We then focused on the aldehyde part of the Schiff base
ligand and decided to screen different aldehyde structures
by parallel synthesis of a library of chiral Schiff bases in
solution. To build the library, we chose cis-aminoindanol
rather than tert-leucinol (best leads from the previous
screening) because of the possibilities this aromatic ami-
noalcohol offers for further structural modifications.
Moreover, at the time of the study, there was no example
in the literature of selective cis-aminoindanol-derived
ligands for asymmetric sulfide oxidation. Chiral Schiff
bases 9 were prepared by condensation of 44 diversely
substituted salicylaldehydes with (1R,2S)-cis-aminoin-
danol (Scheme 3). After 16 h, the imines that had precip-
itated were simply filtered. For those still in solution, the
excess aminoalcohol was scavenged with N-methyl isato-
ic anhydride polystyrene resin. The purity of the crude
Schiff bases was checked by HPLC and 1H NMR and for
41 out of the 44 found to be satisfactory (>90%) and suit-
able for screening without further purification.
Entry Ligand Aminea
Yieldb eeb
Conf.c
6
7f
74
23
R
7
7g
78
32
S
8
9
7h
7i
72
71
34
39
S
S
10
11
7j
76
73
52
6
S
Scheme 3 Synthesis of a library of cis-aminoindanol-derived Schiff
base ligands 9
7k
S
All 41 chiral Schiff bases were tested in the vanadium-ca-
talysed oxidation of thioanisole and representative results
are reported in Table 2. Ligand 9a without a substituent
on the aromatic ring of the aldehyde part gave 55% ee
(Table 2, entry 1), which constituted our reference value
in assessing the influence of substituents on the selectivi-
ty. Surprisingly, bulky substituents such as a tert-butyl
group in ortho position to the phenol did not improve the
selectivity (Table 2, entries 4, 8, 10). Ligand 9j, derived
from the same aldehyde as the one in Bolm’s best ligand
1, led to the same result as the unsubstituted equivalent 9a
(55% ee, Table 2, entry 10). In contrast, a smaller alkyl
substituent such as a methyl group (ligand 9c, Table 2, en-
try 3) afforded the sulfoxide with a better enantioselectiv-
ity of 67% ee. To cross-check these findings, we
synthesised the isopropyl- and phenyl-substituted ana-
logues (ortho to the phenol), of intermediate steric hin-
drance, and we obtained intermediate selectivities of 59%
and 63% respectively, as might be expected.
12
13
14
7l
87
82
85
6
40
39
R
R
R
7m
7n
15
7o
83
48
R
a Amine condensed on supported salicylaldehyde 6.
However, no general conclusions can be drawn as the
enantioselectivity often results from a combination of
both steric and electronic effects of the substituents. For
example, the substitution of a methyl group by a more
electron-donating methoxy group induced the opposite ef-
fect of decreasing the enantioselectivity (41% ee, Table 2,
entry 5). The importance of electronic effects is further il-
lustrated with ligands 9b and 9f; the presence of a halogen
substituent improves the selectivity from 55% to 64%
b Determined by chiral HPLC of the crude mixture with 1,2,3-tri-
methoxybenzene as internal standard (IS) (Chiralcel OD-H, 5% EtOH
in heptane, 1 mL/min, 227 nm). Retention times: 4.2 min (thioani-
sole), 7.1 min (internal standard), 11.7 min (R-methyl-phenylsulfox-
ide), 13.1 min (S-methyl-phenylsulfoxide), 14.3 min (methyl-
phenylsulfone). The sulfone was obtained as by-product in ~10–20%
yield, along with some unreacted thioanisole (up to 10%).
c Configuration of the major enantiomer.
Synlett 2002, No. 7, 1055–1060 ISSN 0936-5214 © Thieme Stuttgart · New York

1058
B. Pelotier et al.
LETTER
Table 2 Thioanisole Oxidation with Vanadium-Schiff Bases 9
Catalysts and Aqueous H2O2 as Oxidanta (continued)
(Table 2, entry 1 vs. 2) and from 41% to 66% (Table 2, en-
try 5 vs. 6). More generally, the presence of one or more
halogen atoms on the aldehyde aromatic ring was benefi-
cial irrespective of their positions (Table 2, entries 9 vs.
10, 2 vs. 1, 6 vs. 5). Unexpectedly, good enantioselectivi-
ties were observed with ligands 9k and 9l (67% and 73%,
Table 2, entries 11 and 12), derived from unsubstituted
naphthaldehydes. Overall, the best enantioselectivities
were achieved with the 3,5-diiodo-substituted ligand 9g
(70% ee, Table 2, entry 7) and with the naphthaldehyde-
derived ligand 9l (73% ee, Table 2, entry 12). 9l is more
selective than Bolm’s ligand 1 even with no substitution
on the aldehyde aromatic system.
Entry
9
Ligand
Aldehydeb
Yieldc
86
Eec
64
9i
10
9j
85
55
Table 2 Thioanisole Oxidation with Vanadium-Schiff Bases 9
Catalysts and Aqueous H2O2 as Oxidanta
11
12
9k
9l
83
80
67
73
Entry
1
Ligand
Aldehydeb
Yieldc
83
Eec
55
9a
2
3
9b
9c
73
82
64
67
a All reactions were performed with 1.5 mol% of ligand (7.5 mmol),
1 mol% of VO(acac)2 (5 mmol), 0.2 equiv of 1,2,3-trimethoxyben-
zene (0.1 mmol), 1 equiv of thioanisole (0.5 mmol) and 1.1 equiv of
27% H2O2 (60 mL) in 1 mL of CH2Cl2.
b Aldehyde condensed on (1R,2S)-cis-aminoindanol.
c Determined by chiral HPLC of the crude mixture with 1,2,3-tri-
methoxybenzene as internal standard (Chiralcel OD-H, 5% EtOH in
heptane, 1 mL/min, 227 nm).
4
9d
80
54
To complete this study, we synthesised a set of pure
ligands derived from the best hits of each library (all com-
binations between (S)-tert-leucinol or (1R,2S)-cis-ami-
noindanol on one hand and 3,5-diiodosalicylaldehyde or
1-hydroxy-2-naphthaldehyde on the other). We also in-
cluded ligands derived from 4-bromo-1-hydroxy-2-
naphthaldehyde18 as this aldehyde combines the main fea-
tures of the two best aldehydes from the screening. In or-
der to find the best reaction conditions with these optimal
ligands, we examined different reaction parameters such
as the temperature, the addition of alcohol and the metal/
ligand ratio. In general, the thioanisole oxidation is more
enantioselective at lower temperature (0 °C) for most
ligands whereas methanol as an additive is only beneficial
in some cases, mainly with (1R,2S)-cis-aminoindanol de-
rivatives. No significant change was observed by modify-
ing the ratio vanadium/ligand from 1:1 to 1:2.
5
6
7
8
9e
9f
82
88
85
79
41
66
70
53
9g
9h
From this optimisation work, ligands 1020 and 1121 (see
Figure) emerged as the best candidates for the vanadium-
catalysed enantioselective oxidation of sulfides. Finally, a
series of experiments was carried out with ligand 10 and
different amounts of oxidant (from 0.9 equiv to 1.4 equiv
Synlett 2002, No. 7, 1055–1060 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Enantioselective Sulfide Oxidation with H2O2
1059
of H2O2), which revealed that the enantioselectivity In conclusion, we have been able to optimise Bolm’s cat-
reached a maximum value when approximately 1.2 equiv alytic system for the oxidation of alkyl aryl sulfides by a
of oxidant was added (88% ee from the crude mixture). systematic screening of the different components of the
This was 7–9% higher than the ones measured for the re- Schiff base ligand. We report the best enantioselectivities
actions with 0.9 equiv and 1.4 equiv of H2O2.
so far with supported vanadium-Schiff base complexes
and demonstrate that high enantioselectivities can be
achieved with simple and readily available (1–2 steps)
chiral Schiff bases bearing only one chiral centre, such as
imine 10.
Acknowledgement
We are grateful to the European Commission for financial support
of this work via Marie Curie Fellowships (B. P. and G. P., HPMI-
CT-1999-00021). We thank Stuart D. Green for his initial contribu-
tions to this work. We also would like to thank Harish S. Trivedi for
his help in solid phase work, Peter J. Moore for his help in MAS-
NMR spectroscopy and Eric G. Hortense for HPLC assistance.
Figure
With these new optimised conditions,22 we performed the
vanadium-catalysed oxidation of various alkyl aryl sul-
fides with our best ligands 10 and 11 (Table 3). The cor-
responding sulfoxides were obtained in good isolated
yields with enantioselectivities of greater than 89%, and
up to 97% for methyl naphthylsulfoxide. In particular,
ligand 10 afforded methyl phenylsulfoxide in 81% yield
and 90% ee, which are comparable results to those ob-
tained with the more complex ligand 3. These are the best
results reported so far with simple chiral Schiff bases
bearing only one chiral centre.
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Table 3 Oxidation of Alkyl Aryl Sulfides with the Preferred Vana-
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Entry Ar
R
Ligand Yieldb eec
1
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5
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7
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C6H5
Me
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a All reactions were performed twice and gave reproducible results.
b Isolated yields after column chromatography on silica gel (EtOAc–
cyclohexane).
c Determined by chiral HPLC: methyl phenylsulfoxide (Chiralcel OD-
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d Reaction carried out with MeOH (20 L) added at the same time as
the sulfide.
Synlett 2002, No. 7, 1055–1060 ISSN 0936-5214 © Thieme Stuttgart · New York

1060
B. Pelotier et al.
LETTER
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250 MHz) = 12.60 (s, 1 H), 9.92 (s, 1 H), 8.49 (d, 1 H, J =
8.5 Hz), 8.19 (d, 1 H, J = 8.5 Hz), 7.80 (t, 1 H, J = 8.5 Hz),
7.80 (s, 1 H), 7.63 (t, 1 H, J = 8.5 Hz); 13C NMR (CDCl3, 62
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Macdonald, S. J. F. Chem. Commun. 2001, 2594.
(12) Bryliakov, K. P.; Karpyshev, N. N.; Fominsky, S. A.;
Tolstikov, A. G.; Talsi, E. P. J. Mol. Catal. A: Chem. 2001,
171, 73.
(19) Boehlow, T. R.; Harburn, J. J.; Spilling, C. D. J. Org. Chem.
2001, 66, 3111.
(20) Compound 10: 1H NMR (CDCl3, 250 MHz) = 14.85 (br. s,
1 H), 8.10 (s, 1 H), 8.00 (d, 1 H, J = 2.0 Hz), 7.51 (d, 1 H, J
= 2.0 Hz), 3.99 (dd, 1 H, J = 11.5, 2.5 Hz), 3.69 (dd, 1 H, J
= 11.5, 9.5 Hz), 3.07 (dd, 1 H, J = 9.5, 2.5 Hz), 1.00 (s, 9 H);
13C NMR (CDCl3, 62 MHz) = 166.5, 164.6, 149.9, 141.0,
117.0, 92.6, 78.2, 75.9, 61.8, 32.9, 26.8 (3 C); MS (ES) m/z
= 474 (M + H+).
(13) Compound 5: 1H NMR (CDCl3, 250 MHz) = 10.30 (s, 1
H), 7.15 (m, 2 H), 6.08 (ddt, 1 H, J = 17.0, 10.5, 5.0 Hz), 5.52
(dd, 1 H, J = 17.0, 1.5 Hz), 5.33 (dd, 1 H, J = 10.5, 1.5 Hz),
4.46 (br. d, 2 H, J = 5.0 Hz), 3.98 (br. t, 2 H, J = 5.0 Hz), 2.46
(br. t, 2 H, J = 7.0 Hz), 1.85 (m, 4 H), 1.41 (s, 9 H); 13C NMR
(CDCl3, 62 MHz) = 190.4, 179.2, 156.5, 154.8, 145.6,
132.7, 130.3, 122.5, 117.5, 108.3, 79.9, 67.7, 35.2, 33.5, 30.7
(3 C), 28.5, 21.4; MS (ES) m/z = 335 (M + H+), 279, 251,
233.
(21) Compound 11: 1H NMR (CDCl3, 250 MHz) = 13.57 (br. s,
1 H), 8.39 (d, 1 H, J = 8.0 Hz), 7.98 (d, 1 H, J = 8.0 Hz), 7.70
(m, 1 H), 7.67 (t, 1 H, J = 8.0 Hz), 7.49 (t, 1 H, J = 8.0 Hz),
7.01 (s, 1 H), 4.06 (dd, 1 H, J = 11.5, 3.0 Hz), 3.76 (br. t, 1
H, J = 10.5 Hz), 3.16 (m, 1 H), 1.07 (s, 9 H); 13C NMR
(CDCl3, 62 MHz) = 177.1, 162.2, 135.9, 131.5, 130.7,
127.7, 126.1, 125.5, 109.4, 107.0, 75.2, 62.3, 33.5, 27.2 (3
C); MS (ES) m/z = 350 and 352 (M + H+).
(22) Typical experimental procedure: To a 0.03 M solution of
ligand in CH2Cl2 (0.25 mL, 7.5 mol, 0.015 equiv) was
added a 0.02 M solution of VO(acac)2 in CH2Cl2 (0.25 mL,
5 mol, 0.01 equiv) and the resulting mixture was stirred at
r.t. for 30 min. A 1 M solution of sulfide in CH2Cl2 (0.5 mL,
0.5 mmol, 1 equiv) was added and after 30 min stirring at r.t.,
the reaction mixture was cooled down to 0 °C. After 15 min
at 0 °C, 27% H2O2 in H2O (65 L, 1.2 mmol, 1.2 equiv) was
added dropwise. The mixture was stirred at 0 °C for 16 h and
the solvent evaporated. The crude residue was purified by
column chromatography (silica gel, EtOAc–cyclohexane).
(14) Hofsløkken, N. U.; Skattebøl, L. Acta Chem. Scand. 1999,
53, 258.
(15) Chiral amino acids failed to react with supported
salicylaldehyde 6.
(16) Typical procedure: Solid supported Schiff base 7 (6 mol,
0.012 equiv) was weighed in an Alltech tube and the resin
was swollen in CH2Cl2 for 1 h. A 0.04 M solution of
VO(acac)2 in CH2Cl2 (1 mL, 40 mol) was added and the
mixture was shaken for 1 h. The solution was filtered and the
resin washed with CH2Cl2 (5 2 mL) and transferred into a
reaction test tube. A 0.5 M solution of thioanisole (1 mL, 0.5
mmol, 1 equiv) and 1,2,3-trimethoxybenzene (0.1 mmol, 0.2
equiv, internal standard) in CH2Cl2 was added, followed by
7% H2O2 in H2O (240 L, 1.1 equiv). The reaction mixture
was stirred for 16 h and analysed by chiral HPLC (Chiralcel
OD-H, 5% EtOH in heptane, 1 mL/min, 227 nm). Retention
Synlett 2002, No. 7, 1055–1060 ISSN 0936-5214 © Thieme Stuttgart · New York