Synthesis and Chemical Reactivity of α-Oxo Aldehyde-Supported Silicas

Article abstract of DOI:10.1002/ejoc.200300347

The synthesis and characterisation of α-oxo aldehyde-supported silicas by the sol-gel procedure is described. The glyoxylyl group was generated after gelation, either by periodic oxidation of gluconamide chains or by deprotection of a diisopropylthioaceta

Full text of DOI:10.1002/ejoc.200300347

FULL PAPER
Synthesis and Chemical Reactivity of α-Oxo Aldehyde-Supported Silicas
Samiran Kar,[a] Pascal Joly,[b] Michel Granier,[a] Oleg Melnyk,*[b] and
Jean-Olivier Durand*[a]
Keywords: Aldehydes / Glyoxylic acid / Silica / Sol-gel processes / Solid support
The synthesis and characterisation of α-oxo aldehyde-sup-
and reactivity of the supported α-oxo aldehyde function was
ported silicas by the sol-gel procedure is described. The investigated in model reactions with hydroxylamine and hy-
glyoxylyl group was generated after gelation, either by peri-
odic oxidation of gluconamide chains or by deprotection of a
diisopropylthioacetal-protected derivative. The accessibility
drazine derivatives.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
the reactivity of the glyoxylyl group inside the silica matrix
and to examine the potential of the COCHO function
chemistry for the preparation of diverse hybrid organic-in-
organic materials.
In this paper we describe trialkoxysilanes precursors
bearing a masked COCHO function and their use for the
preparation of glyoxylyl silicas. The reactivity of the new
materials was examined in model reactions with hy-
droxylamine or 3-methyl-2-benzothiazolinone hydrazone
hydrochloride (MBTH).
Sol-gel chemistry[1] is an important and general route for
the synthesis of modified silicas incorporating organic moi-
eties. Hybrid organic-inorganic[2] silica-based materials are
prepared by sol-gel hydrolysis and condensation of alkoxy-
silylated organic molecules, combining the characteristics of
the inorganic network and of the organic component, both
organic and inorganic units being linked through stable
SiϪC bonds. Many applications have so far been described,
in fields such as catalysis,[3a] nonlinear optics[3bϪ3c] or
biomaterials,[3dϪ3g] as the mild conditions of the sol-gel pro-
cedure preserve the characteristics of sensitive molecules. In
the course of our work on hybrid organic-inorganic materi-
als, we were interested in the preparation of α-oxo aldehyde
(COCHO) functionalised silicas. Indeed, such materials
have scarcely been studied[4] despite the unique reactivity of
the glyoxylyl group in solution,[5] and the procedures de-
scribed need several steps. In solution, the COCHO group
reacts efficiently with hydroxylamines, hydrazine derivatives
or β-aminothiols to give oxime, hydrazone or thiazolidine
adducts under very mild experimental conditions. These re-
actions have been extensively exploited for site-specific bi-
omolecule modification and for the convergent synthesis of
macromolecules.[6] These classical liquid-state reactions are
not necessarily efficient when one of the reactants is con-
fined to a surface[7] and depend on the accessibility at the
surface, the polarity and porosity of the material, and the
steric hindrance of the reactants. We thus set out to examine
Results and Discussion
To overcome time-consuming multi-step syntheses of tri-
alkoxysilane precursors, we first examined the viability of
commercially available and cheap(triethoxysilyl)propylglu-
conamide (GAPS) as a masked glyoxylyl group for the
preparation of the materials.
The NH4F-catalysed nucleophilic co-gelation of GAPS
(solution in ethanol) with tetraethoxysilane was performed
as shown in Scheme 1. The gelation was efficient only for
low values of x (1,2). At high values of x, phase separation
and precipitation occurred.
The gels X1 were analysed by IR and solid-state NMR
spectroscopy. CP MAS 29Si NMR (ppm) shows resonances
at δ ϭ Ϫ111 (Q4) and Ϫ101 ppm (Q3), corresponding to
SiO4 units possessing four and three siloxane bridges,
respectively. Resonances at δ ϭ Ϫ66 (T3) and Ϫ56 ppm (T2)
(minor) correspond to SiO3 units with three and two silox-
ane bridges, respectively. Xerogels X1 are well condensed,
as no units with one siloxane bridge are observed. IR
(cmϪ1) shows resonances at 3500Ϫ3200 (ν OH), 2944 (ν
CH), 2893 (ν CH), 1654 (ν CϭO), 1554 (δ NH), 1200Ϫ1050
and 950 (ν SiϪO). CP MAS 13C NMR shows resonances
at δ ϭ 10 (CH2ϪSi), 23 (CH2), 43 (CH2ϪN), 72 (CHϪOH,
[a]
´
Laboratoire de Chimie Moleculaire et Organisation du Solide,
´
UMR 5637, case 007-Universite Montpellier II,
`
Place Eugene Bataillon, 34095 Montpellier Cedex 05 France
Fax: (internat.) ϩ33-(0)4-67143852
E-mail: durand@univ-montp2.fr
[b]
Institut de Biologie de Lille, UMR 8525,
1, rue du Pr. Calmette, 59021 Lille Cedex France
E-mail: oleg.melnyk@pasteur-lille.fr
4132
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300347
Eur. J. Org. Chem. 2003, 4132Ϫ4139

Synthesis and Chemical Reactivity of α-Oxo Aldehyde-Supported Silicas
FULL PAPER
Scheme 1. Syntheses and reactivities of COCHO xerogels from GAPS precursor
major large signal) and 172 ppm (CϭO). The carbon chain δ ϭ 144 ppm, confirm the formation of the oxime bond.
was not damaged by the sol-gel procedure. Microanalysis on our functionalised solids is rather in-
With the GAPS material to hand, we next examined the exact[11] (Ϯ10%) but it was used to estimate the yield. From
conversion of the gluconamide chain into the glyoxylyl the nitrogen content, we deduced 75% functionalisation, al-
group. We anticipated that oxidative cleavage of the polyol though NMR spectra analyses suggest this is probably
moiety by periodate should provide a COCHO group, since higher. GAPS is thus an efficient precursor for the prep-
diols, α-hydroxy ketones and α-diketones, but not α-keto aration of COCHO supported silicas, and the chemical re-
amides,[9] are readily cleaved under those conditions. Xero- activity of the COCHO function with a small molecule had
gel X1 was therefore treated with aqueous sodium per- been demonstrated. However, the low solubility of Si(OEt)4
iodate[8] and the new material was characterised as above. in ethanolic GAPS proscribed its use for xerogels with low
IR spectroscopy shows resonances at 3500Ϫ3200 (ν OH), proportions of organic component in the solid, due to
2942 (ν CH), 1663 (ν CϭO), 1558 (δ NH), 1085 and 943 (ν phase separation.
SiϪO). The (ν CϭO) band is shifted to higher wavelength
We turned to thioacetal as a protective group for the CO-
after oxidation. CP MAS 13C NMR shows resonances at CHO function to enhance the solubility of the precursor
δ ϭ 10.9 (CH2ϪSi), 22.9 (CH2), 42.3 (CH2ϪN), 87.5 and thus have access to materials of low COCHO content.
[CH(OH)2] and 171.2 ppm (CϭO). The disappearance of This protective group has successfully been used in the
the signals at δ ϭ 72 ppm demonstrates the cleavage of the solid-phase synthesis of COCHO functionalised pep-
polyol chain and, importantly, the appearance of a new sig- tides,[12] aromatic (Scheme 2) and aliphatic precursors
nal at δ ϭ 87.5 ppm confirms the presence of the α-oxo (Scheme 3) having been prepared. Precursor 4 was syn-
aldehyde function in the hydrated form. Indeed, glyoxylic thesised by means of a Heck[13] reaction between 4-styryl-
acid is known to exist essentially in its hydrated form in (trimethoxy)silane[14] and intermediate 1. Intermediate 1 was
water.[5] Signals around δ ϭ 185 ppm, which could have in turn prepared by coupling of 3,4-dihydro-4-oxo-1,2,3-
arisen from partial oxidation of the gluconamide chain, are benzotriazin-3-yl diisopropylthioacetate[12] with 4-iodoani-
not observed.
line in the presence of triethylamine.
The accessibility and reactivity of the supported COCHO
The precursors 5 and 6 were obtained by coupling of 3,4-
function was next examined with hydroxylamine[10] as a dihydro-4-oxo-1,2,3-benzotriazin-3-yl diisopropylthioacet-
model compound for oxime formation (xerogel X3-1, ate[12] with (3-aminopropyl)trimethoxysilane and bis[3-(tri-
Scheme 1). IR spectroscopy shows resonances at methoxysilyl)propyl]amine, respectively, in the presence of
3500Ϫ3200 (ν OH), 2942 (ν CH), 1669 (ν CϭO), 1617 (ν triethylamine. Note that the methoxysilyl groups of 6 were
CϭN), 1552 (δ NH), 1200Ϫ1050 and 970 (ν SiϪO). CP not equivalent (two signals by 29Si NMR) because of the
MAS 13C NMR shows resonances at δ ϭ 10.7 (CH2ϪSi), presence of the tertiary amide.
23 (CH2), 42 (CH2ϪN), 144.5 (CϭN) and 164.2 ppm (Cϭ
Precursors 4, 5 or 6 were then dissolved in a MeOH/THF
O). The data, in particular the disappearance of the hydrate mixture (1:1) in the presence of various amounts of TMOS
at δ ϭ 87.7 ppm and the appearance of a new signal at (y ϭ 1 to 100). No phase separation occurred. After the
Scheme 2. Synthesis of precursor 4
Eur. J. Org. Chem. 2003, 4132Ϫ4139
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4133

S. Kar, P. Joly, M. Granier, O. Melnyk, J.-O. Durand
FULL PAPER
Scheme 3. Synthesis of precursors 5 and 6
nucleophilic gelation procedure (Scheme 4), the protected agreement with well condensed xerogels. Note that in the
N-glyoxylyl silica gels were characterised by EDX, solid- microanalysis for (x Ն 20), the Si and C values are lower
state NMR, IR and microanalysis.
(up to 7%) and H values higher than those obtained from
the theoretical values calculated from total condensation.
This is consistent with the presence of SiOH groups (Q3,
Q2, T2) and water at the surfaces of the materials.
Porosity measurements on X4, X5 and X6 gels were per-
formed by nitrogen sorption,[15] and the specific surface
areas were determined by use of the BET equation (35
points). Evaluation of the porous volume was achieved by
the BJH method and the microporous volume was deter-
mined by analysis of the t-plot diagram. The results are
summarised in Table 1.
Table 1. Porosity measurements of xerogels X4ϪX6
Scheme 4. Synthesis of xerogels X4-X6
Xerogel
Porous
diameter (A)
Microporous
contribution
(% volume)
Specific surface area
(m2/g)
˚
Electron dispersive X-ray analysis (EDX) was used as a
qualitative method to detect Si and S atoms. The technique
shows that the samples are homogeneous on a micrometric
scale, as no variation in the Si/S ratio is observed from one
analysis to another, either on the same particle or on differ-
ent particles. IR spectroscopy shows intense bands charac-
teristic of gel formation at 3500Ϫ3200 (ν SiϪOH),
1150Ϫ1050 and 960 (ν SiϪO). For xerogels X4, the organic
component is observed at 2960Ϫ2866 (ν CH), 1665 (ν CO),
1590 (ν CϭC) and 1520 (ν NH). For xerogels X5, the or-
ganic component is observed at 2965Ϫ2855 (ν CH), 1650
(ν CϭO) and 1540 (ν NH), the aliphatic CO group thus
being observed at lower frequency. For xerogel X6, the or-
X4-50
X5-10
X5-20
X5-50
X5-100
X6-10
X6-20
X6-50
X6-100
38
36
36Ϫ80
38
40
37
38
39
39
33
Ϫ
3
15
13
22
18
24
22
545
284
334
587
805
279
495
656
754
We observed that X4-x presented specific surface area for
ganic component is observed at 2965Ϫ2860 (ν CH), 1635 x Ͼ 20 when the surface area for X5 and X6 at x ϭ 10
(ν CϭO) and 1450 (δ CH). The 13C solid-state NMR spec- was already high. The specific surface area increased with
tra of xerogels X4 show resonances at 170 (CO), 134Ϫ128 increasing x. Xerogel X4-50 presented a type I and IV iso-
(CϭC), 52 (SϪCHϪS), 38 and 24 ppm (CH, CH3). Xerog- therm, with an important microporous contribution and a
els X5 show resonances at 170 (CO), 50 (SϪCHϪS), 42 narrow mesoporous distribution. Xerogels X5-x showed
(CH2-NH) 35, 23 and 10 ppm (CH, CH2, CH3); xerogels different behaviour: xerogels X5-50 and X5-100 presented
X6 show the same type of resonances, with CH2ϪN being type I and type IV isotherms with narrow mesopores and a
shifted downfield and superimposed on the (SϪCHϪS) sig- 15% microporous contribution, while X5-10 presented a
nal at δ ϭ 50 ppm. The carbon skeleton was not damaged type IV isotherm with the hysteresis not closing, which sug-
by the sol-gel procedure, and the signals characteristic of gests that some pores have an ‘‘ink bottle’’ shape with small
the dithioacetal group are present at 50Ϫ52 ppm. The 29Si pore openings that do not facilitate N2 desorption. Xerogel
solid-state NMR spectra show two major resonances, Q4 X5-20 presented a type IV isotherm with a large distri-
and Q3, at Ϫ109 and Ϫ102 ppm and a minor one, Q2, at bution of mesopores from 36 to 80 A. With X6, we did
˚
δ ϭ Ϫ92 ppm. The T3 and T2 resonances are observed at not observe important textural variations, all compounds
Ϫ77 and Ϫ70 ppm for xerogels X4 and at Ϫ62 and presenting type I and type IV isotherms with a narrow dis-
Ϫ55 ppm for xerogels X5 and X6. These analyses are in tribution of mesopores and 20% microporous character.
4134
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4132Ϫ4139

Synthesis and Chemical Reactivity of α-Oxo Aldehyde-Supported Silicas
FULL PAPER
The characteristic of the organic precursor therefore con- for the detection of aldehydes,[16] so we carried out reac-
tributes to the texture of the solid.
tions between MBTH and xerogels X8-X9 (Scheme 7). The
Removal of the dithiane function was next examined. reaction was usually incomplete as determined by 13C
Xerogels X5-(5,10) and X6-(5,10) were treated with N- NMR analyses (50% conversion or less), the best result be-
bromosuccinimide[12] in aqueous CH3CN (Scheme 5). ing obtained with X9-5. In this case the α-oxo aldehyde
Microanalysis showed very low amounts of residual S (Ͻ function of X12-5 is no longer detected, and the 13C NMR
0.5%), indicating that the cleavage was efficient in shows major changes, with the appearance of aromatic car-
90Ϫ95% yield.
bons (δ ϭ 122, 111 ppm), CϭN (δ ϭ 145 ppm) and NϪMe
(δ ϭ 32 ppm). The IR shows a shift in the CO band to
1632, the appearance of CϭN bands (1600), and aromatics
(1539, 1474, 744). From the increases in the N (1.52 for X9-
5 to 4.89 for X12-5) and C contents (12.47 for X9-5 to 19.82
for X12-5), the estimated yield was 85%.
Scheme 5. Deprotection of the dithiane-protected COCHO groups
The IR spectra show a shift of the NCO band to higher
wavelength: from 1650 to 1665 for X8 and from 1632 to
1640 for X9. In the 13C NMR, disappearance of the signals
at δ ϭ 24, 38 and 50 ppm, corresponding to the dithiane
group, is observed, and signals at δ ϭ 189 and 88 ppm ap-
pear, these being attributed to the nonhydrated and hy-
drated forms of aldehyde groups. Aliphatic chains were not
damaged, so the procedure allowed the quasi-total depro-
tection of X5-(5,10) and X6-(5,10). The same glyoxylic xero-
gels X2 and X8 were obtained by two different pathways
(Scheme 1 and Scheme 5). Note that X8-5 was dried at 120
°C for 2 h under vacuum and X2-1 was dried at room temp.,
so X8-5 presented both the aldehyde and hydrated forms of
the COCHO function (13C NMR: δ ϭ 188 and 88 ppm)
while the COCHO function of X2-1 was only in its hydrated
state (δ ϭ 88 ppm).
Scheme 7. Reactivities of X8, X9 with MBTH
The fluorescence emission spectrum of X12-5 confirms
the presence of the conjugated chromophore with λ,em
520 nm (Figure 1).
ϭ
The reactivity of the supported COCHO function was
then studied by treatment with hydroxylamine. Xerogels
X8-5 and X9-10 were treated under the same experimental
conditions as used for X2-1 (Scheme 6). The reaction
worked in every case, and the spectra of X10-5 are similar
to those of X3-1. From the increases in the N content (1.97
for X8-5 to 3.25 for X10-5, and 1.1 for X9-10 to 1.82 for
X11-10), the estimated yield was 80%.
Figure 1. Fluorescence emission spectrum of X9-5 after coupling
with MBTH
The reactivity of the COCHO depends on the accessi-
bility of the function. The texture of the material is essential
in this case, and MBTH seems to be less reactive than
NH2OH, which is smaller and could thus diffuse more eas-
ily at the surface and inside the pores of the solid matrix.
In conclusion, we have described the syntheses of CO-
CHO-functionalised silicas by the sol-gel procedure. The
Scheme 6. Reactivities of X8 and X9 with hydroxylamine
The coupling reaction with more bulky molecules was glyoxylyl group was formed either by periodate oxidation
then examined. MBTH is known to be a sensitive reagent of a gluconamide chain or by removal of a diisopro-
Eur. J. Org. Chem. 2003, 4132Ϫ4139
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4135

S. Kar, P. Joly, M. Granier, O. Melnyk, J.-O. Durand
FULL PAPER
pylthioacetal group. We have shown by solid-state MAS 13
C
Precursor 5: A mixture of (3-aminopropyl)trimethoxysilane (1.07 g,
6 mmol),
3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-yl
diisopro-
NMR that the COCHO function might exist in its hydrated
form on the solids. The supported COCHO functions re-
acted with small molecules such as NH2OH. Work to ex-
ploit this approach for the preparation of sophisticated sil-
ica-based materials is in progress.
pylthioacetate (2.1 g, 6 mmol) and triethylamine (1.25 mL, 9 mmol)
in dichloromethane (40 mL) was stirred at room temperature for
4 h and the solvent was evaporated under vacuum. The resulting
mass was dissolved in dry diethyl ether/pentane (1:3) mixture, the
solution was purified by passage through a short column of sil-
anised silica gel 60 under argon, and the compound (2.125 g, 96%)
was obtained as a liquid after evaporation of the solvent. 1H NMR
(200 MHz, CDCl3): δ ϭ 0.69 (t, 2 H, SiCH2), 1.30Ϫ1.36 (m, 12 H,
CH3), 1.68 (t, 2 H), 3.15 (m, 2 H), 3.32 (m, 2 H), 3.6 (s, 9 H, OMe),
4.36 (s, 1 H, SCHS) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 6.8,
23.1, 23.5, 37.4, 42.6, 50.3, 50.9, 170.0 ppm. 29Si (40 MHz, CDCl3):
δ ϭ Ϫ 42.2 ppm. IR (neat): ν˜ ϭ 3276.2, 3074.8, 2958.4, 2865.8,
2840.0, 1643.7, 1551.8, 1453.7, 1195.0, 1087.9, 820.0 cmϪ1. HRMS
Experimental Section
Manipulations of air-sensitive compounds were carried out under
N2. Solid-state NMR spectra were recorded with Bruker 250 and
400 MHz spectrometers with a MAS 4 (spinning rate 9 kHz) or
MAS 7 (spinning rate 3.5 kHz) probe. Contact time was 5 ms for
CP MAS experiments and decoupling power was 200 W for hpdec
MAS experiments. IR-FT (KBr pellets) were recorded with a Nico-
let instrument. Microanalyses were performed at the central service
of microanalyses (CNRS at Vernaison). High resolution mass spec-
tra (FABϩ) were performed with a JEOL DL-100 spectrometer,
with a nitrobenzyl alcohol (NBA) or a glycerolthioglycerol (GT)
matrix. Surface area measurements (BET) were recorded by use of
a Micromeritics Gemini III 2375 under nitrogen. Fluorescence was
registered with a SLM Aminco 8100 spectrometer, by reflection on
a KBr pellet. A front face sample holder was used and oriented at
60° in order to minimise specular reflection. Appropriate filters
were used to eliminate Rayleigh and Raman scatters from the emis-
sion.
(FABϩ, GT) of C14H31NOS2 [MHϩ] calcd. 370.6299; found
ϩ
370.6280.
Precursor 6:
A mixture of bis[3-(trimethoxysilyl)propyl]amine
(2.05 g, 6 mmol), 3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-yl diiso-
propylthioacetate (2.1 g, 6 mmol) and triethylamine (1.25 mL,
9 mmol) in dichloromethane (40 mL) was stirred at room tempera-
ture for 4 h. and solvent was evaporated under vacuum. The re-
sulting mass was dissolved in dry diethyl ether/pentane (1:3) mix-
ture, The resulting solution was purified by passage through a short
column of silanised silica gel 60 under argon, and the compound
(3.03 g, 95%) was obtained as a liquid after evaporation of the sol-
vent. 1H NMR (200 MHz, CDCl3): δ ϭ 0.64 (t, 4 H, SiCH2),
1.28Ϫ1.36 (m, 12 H), 1.68Ϫ1.72 (m, 4 H), 3.25Ϫ3.36 (m, 6 H),
3.59 (s, 9 H, OMe), 3.60 (s, 9 H, OMe), 4.72 (s, 1 H, SCHS) ppm.
13C NMR (50 MHz, CDCl3): δ ϭ 6.6, 6.8, 20.9, 22.8, 24.0, 24.5,
35.4, 49.3, 50.2, 50.9, 51.0, 168.8 ppm. 29Si NMR (40 MHz,
CDCl3): δ ϭ Ϫ42.0, Ϫ 42.6 ppm. IR (neat): ν˜ ϭ 2964.7, 2844.9,
Precursor 1: A mixture of 4-iodoaniline (1.5 g, 6.8 mmol), 3,4-di-
hydro-4-oxo-1,2,3-benzotriazin-3-yl diisopropylthioacetate (2.42 g,
6.8 mmol) and triethylamine (1.42 mL, 10.2 mmol) in dichloro-
methane (50 mL) was stirred at room temperature for 2 h. The reac-
tion mixture was thoroughly washed with water (3ϫ 50 ml), dried
with MgSO4 and evaporated to gave the corresponding iodo com-
pound, which was crystallised from cyclohexane (2.6 g, 94%). 1H
NMR (200 MHz, CDCl3): δ ϭ 1.36 (2d, J ϭ 6.8 Hz, 12 H, CH3),
3.19 (m, 2 H, iPr), 4.46 (s, 1 H, SCHS), 7.37(d, J ϭ 8.8 Hz, 2 H,
Ar), 7.68 (d, J ϭ 8.8 Hz, 2 H, Ar), 8.5 (s, 1 H, NH) ppm. 13C
NMR (50 MHz, CDCl3): δ ϭ 23.5, 37.8, 50.8, 88.2, 121.8, 137.7,
138.4, 168.3 ppm. IR (KBr): ν˜ ϭ 3288.5, 3250.6, 3183.0, 3114.1,
3059.5, 2949.0, 2929.7, 2861.1, 1660.3, 1607.4, 1585.4, 1538.0,
1487.6, 1458.2, 1393.9, 1335.8, 1236.0, 1172.0, 1155.4, 1053.9,
1643.3, 1458.0, 1425.3, 1365.4, 1191.0, 1087.5, 1011.2, 798.7 cmϪ1
.
HRMS (FABϩ, GT) of C20H46NOS2 [MHϩ] calcd. 532.8911;
found 532.8893.
ϩ
Cogel X1-1: Si(OEt)4 (3.34 mL, 15 mmol) was added with stirring
to a 12 g solution of GAPS (50% in EtOH, 15 mmol). H2O
(0.4 mL) and NH4F (0.25  in H2O, 0.6 mL) were then added.
Gelation occurred after 1 h. After curing for one week, the gel was
washed with EtOH, acetone and Et2O and dried under vacuum.
CP MAS 29Si NMR: δ ϭ Ϫ66.1 (T3), Ϫ101.7 (Q3), Ϫ111.2 (Q4)
ppm. CP MAS 13C NMR: δ ϭ 10.5, 23.8, 43.6, 72.4, 172.04 ppm.
IR (KBr): ν˜ ϭ 3423, 2944, 2893, 1654, 1554, 1453, 1412,
1003.3, 968.1, 934.9, 823.2 cmϪ1
.
HRMS (FABϩ, GT) of
C14H20NOS2Iϩ [Mϩ] calcd. 410.3613; found 410.3625.
1200Ϫ1050, 950 cmϪ1
.
Cogel X1-2: The same procedure was repeated with a 1 g solution
of GAPS (50% in EtOH, 1.3 mmol), Si(OEt)4 (0.55 mL, 2.6 mmol),
NH4F (0.25 , 50 µL) and H2O (64 µL).
Precursor 4: A mixture of trimethoxy(4-vinylphenyl)silane (493 mg,
2.2 mmol), the iodo compound (900 mg, 2.2 mmol), palladium
acetate (50 mg, 0.22 mmol) and trimethylamine (0.03 mL,
22 mmol) in acetonitrile (15 mL) was heated in a sealed tube at 115
°C. After stirring for 44 h at 115 °C, the solution was cooled to
room temperature and the solvent was evaporated under vacuum.
The resulting mass was dissolved in dry toluene (50 mL). The re-
sulting solution was purified by passage through a short column of
silanised silica gel 60 under argon, and the compound was obtained
as a liquid (1.07 g, 92%) after evaporation of the solvent. 1H NMR
Cogel X2-1: Xerogel X1-1 (510 mg) and NaIO4 (2.5 g, 11.7 mmol)
were stirred in H2O (11 mL) and AcOH, (1 mL). After 2 h, the gel
was filtered and the solid was washed thoroughly with H2O, THF
and Et2O. The gel was dried in air. CP MAS 13C NMR: δ ϭ 10.9,
22.9, 30.9 (minor), 42.3, 87.5, 171.2 ppm. IR (KBr): ν˜
ϭ
3500Ϫ3200, 2942, 1664, 1558, 1445, 1200Ϫ1050, 944 cmϪ1
.
(200 MHz, CDCl3): δ ϭ 1.29Ϫ1.38 (m, 12 H, CH3), 3.22 (m, 2 H, Cogel X3-1: Xerogel X2-1 (500 mg) was added to a solution of
iPr), 3.66 (s, 9 H, OMe), 4.49 (s, 1 H, SCHS) 7.11Ϫ7.70 (m,10 H, ClNH3OH (1 g, 14.5 mmol), AcOH, (10 mL), AcONa, (1.26 g),
aromatic), 8.53 (br. s, 1 H, NH) ppm. 13C NMR (50 MHz, CDCl3): H2O (15 mL) and EtOH (10 mL). The reaction mixture was stirred
δ ϭ 23.5, 37.8, 50.9, 51.3, 117.4, 120.1, 126.4127.7, 128.2, 128.8,
for 2 h and filtered, and the solid was washed thoroughly with H2O,
129.5, 134.0, 135.6, 139.9, 168.1 ppm. 29Si (40 MHz, CDCl3): δ ϭ EtOH and Et2O. The solid was washed at 80 °C under vacuum.
Ϫ 54. IR (neat): ν˜ ϭ 3301.1, 2960.3, 2840.8, 1660.1, 1594.8, 1412.1, CP MAS 13C NMR: δ ϭ 10.7, 23.3, 42.6, 144.5, 164.2 ppm. IR
1325.9, 1244.8, 1188.5, 1085.5, 967.0, 820.0, 737.9 cmϪ1. HRMS
(KBr): ν˜ ϭ 3500Ϫ3200, 2942, 1669, 1617, 1553, 1453, 1389,
ϩ
(EI) for C25H35O4NS2 [Mϩ] calcd. 505.7749; found 505.7733.
1200Ϫ1050, 945 cmϪ1
.
4136
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4132Ϫ4139

Synthesis and Chemical Reactivity of α-Oxo Aldehyde-Supported Silicas
Table 2. Synthesis of Co-Gels X4
FULL PAPER
Solid
4 (mg)
y mmol
NH4F (%)
x
TMOS (mg)
mmol
H2O (mL)
Solvent (mL)
X4-1
500
200
200
300
300
200
0.99
1
1
1
1
2
4
1
2
5
10
20
50
150
120
300
900
1805
3010
0.99
0.789
1.97
5.92
11.87
19.8
0.06
3.9
2.3
4.6
12.8
24.5
39.7
X4-2
0.396
0.396
0.594
0.594
0.396
0.023
0.066
0.198
0.421
0.691
X4-5
X4-10
X4-20
X4-50
Table 3. Synthesis of Co-Gels X5
Solid
5 (g)
y mmol
NH4F (%)
x
TMOS (g)
mmol
H2O (mL)
Solvent (mL)
X5-5
0.5
0.5
0.5
0.05
0.05
1.35
1.35
1.35
0.135
0.135
1
1
2
4
4
5
10
20
50
100
1.029
2.059
4.119
1.0298
2.0596
6.775
13.55
27.1
6.775
13.55
0.226
0.470
0.958
0.236
0.469
16
X5-10
X5-20
X5-50
X5-100
29.3
55.9
13.6
26.9
Table 4. Synthesis of Co-Gels X6
Solid
6 (mg)
y mmol
NH4F (%)
x
TMOS (mg)
mmol
H2O (mL)
Solvent (mL)
X6-1
531
531
531
531
53
1
1
1
1
1
1
1
1
1
2
4
4
1
5
10
20
50
152
760
1520
3040
760
1
5
10
20
5
0.0505
0.1945
0.3745
0.7419
0.17
3.95
11.8
21.6
41.3
10
X6-5
X6-10
X6-20
X6-50
X6-100
53
100
1520
10
0.35
19.8
Co-Gels X4, X5 and X6: (Tables 2, 3 and 4) Precursor 4, 5 or 6 X4-50: C22H26NO102.5S2Si51: calcd. C 8.41, H 0.83, N 0.44, S 2.04,
(y mmol) and Si(OMe)4 (y·x mmol) were dissolved in a MeOH/
THF mixture (50:50, concentration of Si species: 0.5 ). After ad-
dition of water [(1.5 ϩ2x)y mmol] and a catalytic amount of NH4F
(0.25 ) in water, transparent gels were formed within few h. After
ageing for 1 week the materials were then powdered and washed
with acetone and diethyl ether to give xerogels and dried at 100 °C
overnight under vacuum.
Si 45.61; found C 5.17, H 2.08, N 0.13, S 1.28, Si 34.52. SBET ϭ
545 m2/g.
X5-5: CP MAS 29Si NMR: δ ϭ Ϫ62 (T3), Ϫ102.8 (Q3), Ϫ108.9
(Q4) ppm. CP MAS 13C NMR: δ ϭ 10.1, 24.0, 37.8, 42.2, 50.3,
172.6 ppm. IR (KBr): ν˜ ϭ 3500Ϫ3200, 2964.3, 2932.1, 2867.8,
1651.5, 1539.0, 1458.6, 1200Ϫ1050, 954.9, 804.8 cmϪ1. SBET ϭ 2
m2/g.
X4-1: CP MAS 29Si NMR:δ ϭ Ϫ68 (T2), Ϫ77.1 (T3), Ϫ100 (Q3),
Ϫ109.7 (Q4) ppm. CP MAS 13C NMR: δ ϭ 23.9, 37.9, 51.7, 128.0,
134.9, 169.7 ppm. IR (KBr): ν˜ ϭ 3500Ϫ3200, 2960, 2924, 2866,
X5-10: IR (KBr): ν˜ ϭ 3500Ϫ3200, 2964, 2921, 2866, 1648, 1539,
1458, 1200Ϫ1050, 956 cmϪ1. C11H22NO22.5S2Si11: calcd. C 14.09,
H 2.36, N 1.31, Si 32.95, S 6.84; found C 13.14, H 2.82, N 2.12, Si
32.00, S, 4.83. SBET ϭ 284 m2/g.
1661, 1593, 1519, 1402, 1312, 1200Ϫ1050, 956, 824 cmϪ1. SBET
ϭ
1.4 m2/g.
X5-20: CP MAS 29Si NMR: δ ϭ Ϫ56.7 (T2), Ϫ63.6 (T3), Ϫ101.3
(Q3), Ϫ109.2 (Q4) ppm. CP MAS 13C NMR: δ ϭ 8.8, 23.0, 37.2,
41.8, 50.0, 175.7 ppm. IR (KBr): ν˜ ϭ 3500Ϫ3200, 2964, 2855, 1643,
1539, 1453, 1200Ϫ1050, 804.2 cmϪ1. C11H22NO42.5S2Si21: calcd. C
8.53, H1.43, N 0.90, Si 38.57, S 4.14; found C 9.89, H 2.44, N 1.20,
Si 35.20, S 2.88. SBET ϭ 334 m2/g.
X4-2: IR (KBr): ν˜ ϭ 3500Ϫ3200, 2960, 2922, 2862, 1663, 1587,
1519, 1413, 1314, 1200Ϫ1050, 963, 829 cmϪ1. SBET ϭ 2 m2/g.
X4-5: IR (KBr): ν˜ ϭ 3500Ϫ3200, 2959, 2930, 2866, 1668, 1596,
1524, 1409, 1316.5, 1200Ϫ1050, 957 cmϪ1. SBET ϭ 13 m2/g.
X4-10: CP MAS 29Si NMR: δ ϭ Ϫ68.6 (T2), Ϫ77.1 (T3), Ϫ91.7
Ϫ100 (Q3), Ϫ109.7 (Q4) ppm. IR (KBr): ν˜ ϭ 3500Ϫ3200, 2967,
X5-50: SBET ϭ 587 m2/g.
X5-100: SBET ϭ 806 m2/g.
2926, 2865, 1663, 1601, 1526, 1458, 1417, 1200Ϫ1050, 960 cmϪ1
.
C22H26NO22.5S2Si11: calcd. C 25.46, H 2.52, N 1.35, Si 29.77, S
6.18; found C 26.52, H 3.24, N 1.57, Si 28.52, S 6.16. SBET ϭ 13
m2/g.
X6-1: CP MAS 29Si NMR: δ ϭ Ϫ56.9 (T2), Ϫ65.7 (T3), Ϫ101.2
(Q3), 109.4 (Q4) ppm. CP MAS 13C NMR: δ ϭ 7.6, 21.1, 32.5,
48.0, 167.5 ppm. IR (KBr): ν˜ ϭ 3500Ϫ3200, 2958, 2916, 1630,
1459, 1368, 1200Ϫ1050, 914, 791 cmϪ1. SBET ϭ 2 m2/g.
X4-20: IR (KBr): ν˜ ϭ 3500Ϫ3200, 2967, 2932, 2871, 1663, 1601,
1526, 1465, 1417, 1200Ϫ1050, 947 cmϪ1. C22H26NO42.5S2Si21:
calcd. C 16.12, H 1.59, N 0.85, Si 35.99, S 3.91; found C 13.63, H
2.34, N 0.56, Si 29.80, S 3.46. SBET ϭ 13 m2/g.
X6-5: CP MAS 29Si NMR: Ϫ58.2 (T2), Ϫ65.6 (T3), Ϫ100.8 (Q3),
Ϫ109.3 (Q4) ppm. CP MAS 13C NMR: δ ϭ 10.3, 23.7, 35.5, 50.5,
Eur. J. Org. Chem. 2003, 4132Ϫ4139
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4137

S. Kar, P. Joly, M. Granier, O. Melnyk, J.-O. Durand
FULL PAPER
169.6 ppm. IR (KBr): ν˜ ϭ 3500Ϫ3200, 2964, 2921, 2858, 1632, tionalised silica gel was dried under vacuum at 120 °C for 2 h. CP-
1458, 1370, 1200Ϫ1050, 962 cmϪ1. SBET ϭ 2 m2/g.
MAS 13C NMR (75 MHz): δ ϭ 9.8, 22.6, 42.2, 143.8, 164.5 ppm.
IR (KBr): ν˜
ϭ 3500Ϫ3200, 2942, 1665, 1610, 1561, 1447,
X6-10: CP MAS 29Si NMR: δ ϭ Ϫ58.8 (T2), Ϫ65.2 (T3), Ϫ91.1
(Q2), Ϫ101.1 (Q3), Ϫ108.6 (Q4) ppm. CP MAS 13C NMR: δ ϭ
10.4, 23.4, 35.9, 50.1, 168.1 ppm. IR (KBr): ν˜ ϭ 3500Ϫ3200, 2964,
2921, 1632, 1458, 1200Ϫ1050, 956, 798 cmϪ1. C14H27NO24S2Si12:
calcd. C 16.89, H 2.73, N 1.40, Si 33.89, S 6.44; found C 15.35, H
3.57, N 1.02, Si 32.83, S 4.90. SBET ϭ 279 m2/g.
1200Ϫ1050, 956 cmϪ1. C5H8N2O13.5Si6: calcd. C 12.50, N 5.82, Si
34.93; found C 9.41, N 3.25, Si 32.20.
Xerogel X11-10: The same procedure was applied with X9-10
(130 mg), NH2OH,HCl (230 mg, 3.32 mmol), sodium acetate
buffer (11 mL, pH 4.5) and EtOH (8 mL). CP MAS 13C NMR
(75 MHz): δ ϭ 10.1, 22.5, 51.2, 144.0, 165.2 ppm. CP MAS 29Si
NMR (60 MHz): δ ϭ Ϫ55.9 (T2), Ϫ64.8 (T3), Ϫ91.2 (Q2), Ϫ101.2
(Q3), Ϫ110.4 (Q4) ppm. IR (KBr): ν˜ ϭ 3500Ϫ3200, 2953, 1643,
1496, 1441, 1200Ϫ1050, 951 cmϪ1. C8H14N2O25Si12: calcd. C 10.98,
N 3.20, Si 38.44; found C 8.68, N 1.82, Si 28.31.
X6-20: IR (KBr): ν˜ ϭ 3500Ϫ3200, 2969, 2916, 1635, 1459, 951, 796
cmϪ1. C14H27NO44S2Si22: calcd. C 10.28, H 1.70, N 0.87, Si 38.73,
S 4.01; found C 9.45, H 2.86, N 0.60, Si 32.83, S 2.89. SBET ϭ 495
m2/g.
X6-50: SBET ϭ 656 m2/g.
X6-100: SBET ϭ 754 m2/g.
MBTH Adduct of Glyoxylyl-Silica Gel: A suspension of xerogel X9-
5 (100 mg), 3-methyl-2-benzothiazolinone hydrazone hydrochloride
hydrate (MBTH, 220 mg, 1.02 mmol) and phosphate buffer (4 mL,
pH 7) in ethanol (6 mL) was stirred at room temperature for 6 h.
The functionalised silica gel was filtered off and washed with water,
ethanol, acetone and diethyl ether. The functionalised silica gel was
dried under vacuum at 120 °C for 2 h. CP MAS 13C NMR
(75 MHz): δ ϭ 10.7, 22.5, 31.7, 51.0, 111.8, 123.0, 145, 165.4 ppm.
IR (KBr): ν˜ ϭ 3500Ϫ3200, 2953, 1632, 1599, 1539, 1474, 1414,
1359, 1200Ϫ1050, 962 cmϪ1. C16H20N4O14SSi12: calcd. C 25.00, N
7.79, S 4.40, Si 27.26; found C 19.81, N 1.97, S 2.81, Si 26.65.
Glyoxylyl-Silica Gel (General Procedure for the Preparation of Sil-
ica Gel): A suspension of X5-x or X6-x in acetonitrile/water (8:2)
was treated at room temperature with solid N-bromosuccinimide
(NBS) in one portion (Table 5 and 6). After 4 h, the functionalised
silica gel was filtered off and washed with water and acetonitrile.
The functionalised silica gel was dried under vacuum at 100 °C
for 8 h.
Table 5. Synthesis of Glyoxylyl-Silica Gels X8
Solid
X5 (mg)
NBS (mg/mmol)
CH3CN/H2O (mL)
X8-5
X8-10
600
840
890/5
800/4.5
16/4
32/8
[1] [1a]
C. J. Brinker, G. W. Scherer, Sol-gel Science: The Physics
and Chemistry of Sol-gel Processing, San Diego, 1990. [1b]L. L.
Hench, J. K. West, Chem. Rev. 1990, 90, 33.
Table 6. Synthesis of Glyoxylyl-Silica Gels X9
[2] [2a]
[2b]
C. Sanchez, F. Ribot, New. J. Chem. 1994, 18, 1007.
U.
Schubert, N. Hüsing, A. Lorenz, Chem. Mater. 1995, 7, 2010.
[2c]
[2d]
Solid
X6 (mg)
NBS (mg/mmol)
CH3CN/H2O (mL)
D. A. Loy, K. J. Shea, Chem. Rev. 1995, 95, 1431.
J.
[2e]
Wen, G. L. Wilkes, Chem. Mater. 1996, 8, 1667.
R. J. P.
Corriu, D. Leclercq, Angew. Chem. Int. Ed. Engl. 1996, 35,
X9-5
X9-10
420
510
600/3.37
700/3.93
16/4
32/8
1420. [2f] R. J. P. Corriu, Angew. Chem. Int. Ed. 2000, 39, 1376.
[2g]
G. Cerveau, R. J. P. Corriu, Coord. Chem. Rev. 1998,
178Ϫ180, 1051.
[3] [3a]
P. M. Price, J. H. Clark, D. J. Macquarrie, Dalton Trans.
[3b]
X8-5: CP MAS 29Si NMR: δ ϭ Ϫ59.9 (T2), Ϫ65.4 (T3), Ϫ102.2
(Q3), Ϫ108.9 (Q4) ppm. CP MAS 13C NMR: δ ϭ 9.6, 21.9, 42.5,
88.3, 171.5, 188.6 ppm. IR (KBr): ν˜ ϭ 3500Ϫ3200, 2943, 1665,
1561.5, 1447, 1200Ϫ1050, 951, 793 cmϪ1. C5H10NO14.5Si6: calcd.
C 12.4, N 2.89, Si 34.71; found C 8.96, N 1.97, Si 30.9, S Ͻ 0.3.
2000, 101.
Chem. Mater. 1997, 9, 1012.
J. Garcia-Macedo, J. Canva, M. Blanchard-Desce, F. Chaput,
B. Lebeau, S. Brasselet, J. Zyss, C. Sanchez,
[3c]
J. Reyes-Esqueda, B. Darracq,
K. Lahlil, J. P. Boilot, A. Brun, Y. Levy, Optics Commun. 2001,
[3d]
´
J. Livage, C. R. Aca. Sci. Paris, T. 322, Serie II b
198, 207.
[3e]
1996, 417.
I. Gill, A. Ballesteros, J. Am. Chem. Soc. 1998,
120, 8587. [3f] D. Avnir, S. Braun, O. Lev, M. Ottolenghi, Chem.
Mater. 1994, 6, 1605.
[4a] J. R. Falsey, M. Renil, S. Park, S. Li, K. S. Lam, Bioconjug-
ate Chem. 2001, 12, 346.
Lett. 2002, 43, 4435.
Hansen, Tetrahedron Lett. 2000, 41, 5147.
X8-10: IR (KBr): ν˜ ϭ 3500Ϫ3200, 2964, 1670, 1556, 1452,
1200Ϫ1050, 951, 842.9 cmϪ1. C5H10NO24.5Si11: calcd. C 7.65, N
1.8, Si 39.20; found C 6.37, N 1.26, Si 35.7, S Ͻ 0.5.
X9-5: CP MAS 13C NMR: δ ϭ 7.2, 18.5, 48.2, 167.2, 189.4 ppm.
IR (KBr): ν˜ ϭ 3500Ϫ3200, 2953.8, 1637.8, 1409, 1200Ϫ1050,
951.3, 798.7 cmϪ1. C8H15NO16Si7: calcd. C 16.6, N 2.40, Si 33.90;
found C 12.47, N 1.52, Si 28.25, S Ͻ0.45.
[3g]
M. T. Reetz, Adv. Mater. 1997, 9, 12.
[4]
[5]
[4b]
Q. Xu, K. S. Lam, Tetrahedron
[4c]
N. Schlienger, M. R. Bryce, T. K.
A. J. L. Cooper, A. G. Redfield, J. Biological Chem. 1975, 250,
527; F. Chastrette, C. Bacoud, M. Chastrette, G. Mattioda, Y.
Christidis, Bull. Soc. Chim. 1985, II-66.
X9-10: IR (KBr): ν˜ ϭ 3500Ϫ3200, 2953, 1643, 1200Ϫ1050, 962
cmϪ1. C8H15NO26Si12: calcd. C 10.9, N 1.6, Si 38.3; found, C 9.25,
N 1.1, Si 30.87, S Ͻ 0.3.
[6] [6a]
O. Melnyk, J. A. Fehrentz, J. Martinez, H. Gras-Masse,
Biopolymers (Peptide Science) 2000, 55, 165. [6b] J. S. Fruchart,
H. Gras-Masse, O. Melnyk, Tetrahedron Lett. 1999, 40, 6225.
[6c]
[6d]
J. Shao, J. P. Tam, J. Am. Chem. Soc. 1995, 117, 3893.
J. P. Tam, J. C. Spetzler, Biomedical Peptides, Proteins and Nu-
Hydroxylamine Adduct of Glyoxylyl-Silica Gel
[6e]
X10-5: A suspension of X8-5 (242 mg, 0.5 mmol), hydroxylamine
hydrochloride (173 mg, 2.5 mmol) and sodium acetate buffer
(12 mL, pH 4.5) in ethanol (8 mL) was stirred at room temperature
for 6 h. The functionalised silica gel was then filtered off and
washed with water, ethanol, acetone and diethyl ether. The func-
cleic Acids 1995, 1, 123.
J. J. Starling, K. L. Law, K. Rose, B. Dufour, R. E. Offord,
S. D. Mikolajczyk, D. L. Meyer,
[6f]
Bioconjugate Chem. 1994, 5, 636.
K. F. Georghegan, J. G.
Stroh, Bioconjugate Chem. 1992, 3, 138.
[7a] C. J. Page, G. A. Neff, Langmuir 1996, 12, 238. [7b] S. Klap-
[7]
4138
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4132Ϫ4139

Synthesis and Chemical Reactivity of α-Oxo Aldehyde-Supported Silicas
FULL PAPER
dohr, K. H. Dötz, W. Assenmacher, W. Hoffbauer, N. Hüsiing,
N. Boggetto, M. Reboud-Ravaux, Bioorg. and Med. Chem.
1997, 5, 707.
[13] [13a]
M. Nieger, J. Pfeiffer, M. Popall, U. Schubert, G. Trimmel,
[7c]
Chem. Eur. J. 2000, 6, 3006.
J. P. Bezombes, C. Chuit, R.
R. F. Heck, Palladium Reagents in Organic Synthesis, Aca-
demic Press, London, 1985. [13b]I. P. Beletskaya, A. V. Chep-
rakov, Chem. Rev. 2000, 100, 3009.
Corriu, C. Reye, J. Mater. Chem. 1999, 9, 1727.
M. Daumax, Y. Vo-Quang, L. Vo-Quang, F. Le Goffic, Syn-
thesis 1989, 64.
Jerry March, Advanced Organic Chemistry 4th edition 1992,
1174.
[8]
[9]
[14]
[15]
A. Hirao, T. Hatayama, T. Nagawa, M. Yamaguchi, K. Yamag-
uchi, S. Nakahama, Macromolecules 1987, 20, 242.
S. Brunauer, P. H. Emmett, E. Teller, J. Am. Chem. Soc. 1938,
60, 309.
[10]
S. S. Samanta, S. C. Ghosh, A. De, J. Chem. Soc., Perkin Trans.
1 1997, 3673.
[16] [16a]
W. H. Chan, S. M. Shuang, M. M. F. Choi, Analyst 2001,
[11]
[16b]
D. J. Macquarrie, S. E. Fairfield, J. Mater. Chem. 1997, 7, 2201.
126, 720.
M. N. Reddy, R. Chinthalapati, Talanta 1998, 47, 85.
Received June 10, 2003
C. S. P. Sastry, P. Y. Naidu, C. S. R. Lakshmi,
[12] [12a]
´
D. Qasmi, L. Rene, B. Badet, Tetrahedron Lett. 1994, 35,
4343. [12b] D. Qasmi, E. De Rosny, L. Rene, B. Badet, I. Vergely,
Eur. J. Org. Chem. 2003, 4132Ϫ4139
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4139