Reaction of Alkenes with Hydrogen Peroxide and Sodium Iodide: A Nonenzymatic Biogenic-Like Approach to Iodohydrins

Article abstract of DOI:10.1002/chem.200305582

An efficient protocol to synthesize iodohydrins from alkenes is presented. Reactions were conducted in aqueous media using safe and readily available sodium iodide (the most abundant form of the element), and a highly convenient oxidant such as hydrogen peroxide. Addition of a protic acid triggers a faster and efficient process, a role formally related to that played by haloperoxidase enzymes in naturally occurring transformations. The successful application of these conditions to multigram scale preparations and over natural products derivatives is also discussed.

Full text of DOI:10.1002/chem.200305582

FULL PAPER
Reaction of Alkenes with Hydrogen Peroxide and Sodium Iodide:
A Nonenzymatic Biogenic-Like Approach to Iodohydrins
Josÿ Barluenga,* MarÌa Marco-Arias, Francisco Gonzµlez-Bobes, Alfredo Ballesteros, and
Josÿ M. Gonzµlez[a]
Abstract: An efficient protocol to synthesize iodohydrins from alkenes is present-
ed. Reactions were conducted in aqueous media using safe and readily available
sodium iodide (the most abundant form of the element), and a highly convenient
oxidant such as hydrogen peroxide. Addition of a protic acid triggers a faster and
efficient process, a role formally related to that played by haloperoxidase enzymes
in naturally occurring transformations. The successful application of these condi-
tions to multigram scale preparations and over natural products derivatives is also
discussed.
Keywords: alkenes
synthesis ¥ electrophilic addition ¥
halogenation ¥ water chemistry
¥
biomimetic
Introduction
scantly considered for the conversion of alkenes to iodohy-
drins.[6] Furthermore, and oppositely to the situation encoun-
tered when preparing halohydrins containing bromine and
chlorine, it has been established that the related iodo-hy-
droxylation process by reaction of an alkene with iodine and
water does not represent an efficient alternative.[7] There-
fore, recent efforts towards the preparation of this class of
valuable iodinated synthetic intermediates have drawn
mainly their attention to the recognition of appropriate
starting materials,[8] better iodine donors,[9] or even alterna-
tive and more elaborated synthetic strategies.[10] Interesting-
ly, an alkyl iodide can be activated and used as a valuable
iodide source to accomplish a synthetically useful conversion
of an alkene to the corresponding iodohydrin.[11] Those lead-
ing findings call for the development of a straight conver-
sion of alkenes to iodohydrins that eventually should be
based on the combination of a convenient oxidant and a
simple salt that acts as the supplier of iodide ions. The valid-
ity and scope of such a conceptually simple methodology
still remains to be covered.[12]
The search for efficient preparations of different types of or-
ganic compounds is associated many times to the develop-
ment of new reagents and/or synthetic strategies. Neverthe-
less, more than often, the consideration of straight ap-
proaches relying on activating basic raw sources providing
the required components remains scarcely investigated and
credited. To this purpose, biomimetic considerations have
proved to be very enlightening, offering simple solutions to
many synthetic problems. Thus, in approaching the prepara-
tion of halogenated compounds halides are of prime inter-
est, as they are key players in those biohalogenation proc-
esses[1] leading to naturally occurring organohalogen com-
pounds.[2] Haloperoxidases are the enzymes responsible for
those reactions[3] and their catalytic activity has been chemi-
cally exploited for different purposes.[4] In this sense, biosyn-
thetic studies in the marine environment assigned an active
role to iodide ions in mediating conversion of alkenes to bi-
functional derivatives.[5] In sharp contrast to this natural
trend, safe and highly convenient sodium iodide has been
Herein, we report on the iodo-hydroxylation reaction of
alkenes 1 with sodium iodide in aqueous media (Scheme 1).
The process uses environmentally benign[13] 33% aqueous
solution of hydrogen peroxide as oxidant.[14]
[a]Prof. Dr. J. Barluenga, M. Marco-Arias, F. Gonzµlez-Bobes,
Dr. A. Ballesteros, Dr. J. M. Gonzµlez
Instituto Universitario de
QuÌmica Organometµlica ™Enrique Moles∫
Unidad Asociada al C.S.I.C., Universidad de Oviedo
C/Juliµn ClaverÌa, 8
Results and Discussion
33006 Oviedo (Spain)
Fax : (+34)98-5103450
E-mail: barluenga@uniovi.es
We initially undertook the search for reaction conditions
that promote the incorporation of iodide ions into the
alkene. Overall, this would allow for a direct iodo-hydroxy-
lation reaction of the unsaturated hydrocarbon. The enzy-
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
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DOI: 10.1002/chem.200305582
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FULL PAPER
Addition of acid was required to promote an efficient
process. First we tested commercially available 35% aque-
ous solution of HBF4, obtaining good results. Entry 8 shows
a reasonably fast process and an excellent yield of isolated
2a, which is generated as a single stereoisomer.[16] The proc-
ess was fairly robust when scaled up to 0.1 mol of 1a, fur-
nishing 19.7 g of 2a (entry 9, Table 1).
Scheme 1. 2-Iodoalkanols 2 from iodo-hydroxylation reaction of alkenes
1 based on biomimetic considerations.
The feasibility of alternative acids was also tested. We
chose indene (1b), being a more labile alkene under acid
conditions, as a convenient substrate to analyze the influ-
ence of this experimental variable. In all the cases tested, a
single adduct (2b) was formed in good yield, and as a single
isomer (see Table 2). Interestingly, the reaction can be also
executed by the addition of several types of acids routinely
used in chemical processes. In general, the observed reaction
rate nicely correlates with the pKa value of the correspond-
ing acid. Thus, stronger acids gave rise to faster reactions
than weaker ones. We observed that even H3PO4, an acid
with a pKa value in the range of 2, is adequate to promote
this iodination chemistry. Remarkably, a solid acid resin
(entry 5, Table 2) can be also conveniently employed to fur-
nish 2b, offering an easily recyclable proton source.
matic synthesis of 2-deoxy-2-halo sugars starting from the
parent glycal and the corresponding halide had been previ-
ously reported.[6b] Along those studies an isolated observa-
tion on the iodo-hydroxylation of d-galactal taking place
without requiring any enzymatic catalysis was noticed.[15] On
this basis, we first evaluated the scope of these non-enzy-
matic conditions over several representative alkenes. Under
those conditions, cyclohexene gave rise to a mixture of com-
pounds, yielding the desired iodohydrin in 31%. Further-
more, 1-hexene afforded exclusively the product that arose
from a competitive 1,2-diiodination process. Methyl cinna-
mate did not react at all, and only traces of the iodo-hy-
droxylated product were observed upon extending the reac-
tion time up to 60 h. Indene furnished a complex reaction
mixture, which suggested that oligomerization reactions
took place under those reaction conditions. Thus, as it was
early proposed,[6a] the catalytic action of an enzyme seems
to be generally required to promote the efficient incorpora-
tion of iodide ions to alkenes, resulting in iodohydrins. The
non-enzymatic conditions above referred are useful when
electron-rich alkenes are used as precursors, such as the case
of the given glycal.[6b] However, significant drawbacks were
found to obtain the desired iodohydrins for the case of
other classes of simple alkenes. Searching for a more general
synthetic methodology, we attempted to overcome those
limitations establishing an alternative way of triggering the
process. We used cyclohexene (1a) as a model compound to
screen the reaction conditions that might simulate the effect
of the enzymatic activation step. A graphic summary of rele-
vant data is presented in Table 1.
Table 2. Iodo-hydroxylation of 1b using NaI and H2O2.[a]
[b]
Entry
Acid
t [h]Yield
[%]
1
2
3
4
5
6
HBF4
H2SO4
2
8
30
30
30
20
83
84
77
oxalic acid
H3PO4
69
Amberlyst 15 (wet)[c]
TFA
65[d]
80
[a]H 2O2 was added to a cooled flask (ice bath) containing a mixture of
NaI, acid and 1b (5 mmol scale) in THF/H2O. [b]Based on isolated
amount of 2b and referred to 1b. [c]Amberlyst 15 (wet) ion-exchange
resin is a registered trademark of Rohm and Haas, and was purchased
from Aldrich. [d]2.5 g of resin used.
Table 1. Iodo-hydroxylation of 1a using NaI and H2O2.[a]
The scope was further explored, and the results are sum-
marized in Table 3 (unless otherwise noticed, the conditions
outlined in Table 1, entry 8, were routinely used).
As depicted, many types of representative alkenes suc-
cessfully reacted with a predictable selectivity, which follows
the already noticed trend for the reactions of 1a and 1b.
The reactivity of mono-substituted alkenes was explored
(Table 1, entries 3 and 4). The nature of the substituent
bounded to the alkene controls the regioselectivity of the
process. Thus, for the case of an alkyl substituent, the reac-
tion product was formed as a mixture of regioisomers, being
Markovnikov×s one the major component (5:1 ratio, by
GC). However, styrene furnished only one regioisomer.
More substituted alkenes were transformed into the corre-
sponding iodohydrin derivatives, including among them an
example of a tri-substituted one. When cyclopentene and cy-
cloheptene were assayed under the above defined condi-
tions, the iodo-hydroxylation reaction occurred, but minor
Entry
Molar ratio[b]
H2O2:HBF4
Reaction time
[h][%]
Yield[d]
[c]
1
2
3
4
5
6
7
8
9
1:
24
24
24
48
24
4.5
4.5
2
1
11
25
27
70
89
90
94
87[e]
1:1
1:2
3:1
3:2
3:3
2:4
3:6
3:6
2.5
[a]H 2O2 (33% aqueous solution) was added to a cooled flask (ice bath)
containing a mixture of NaI and 1a in THF/H2O (12 mL/5 mL, for
5 mmol of 1a). [b]Referred to 1:1 molar ratio for 1a:NaI. [c]Added as
35% commercial aqueous solution. [d]Based on isolated amounts of 2a
and referred to NaI. [e]For 0.1 mol scale of NaI and using 0.11 mol of 1a
(the reaction mixture was mechanically stirred).
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Iodohydrins
1677 1682
Table 3. Iodohydrins 2 from alkenes 1, NaI and H2O2.[a]
amounts of 2-iodoperoxides were detected in crude reaction
mixtures. The reaction was easily optimized by lowering the
amount of H2O2 added. Both electron-rich and electron-de-
ficient olefins are efficient partners in this process; the
nature of the acid and the reaction time being the only vari-
ables that have to be tuned (entries 5 and 7). For the elec-
tron-rich 3,4-dihydro-2H-pyran (1g), the use of the standard
conditions resulted in polymerization reactions. In this case,
the addition of lower amounts of a weaker acid (TFA) was
required to promote an efficient reaction. Under the opti-
mized conditions above established for 1g, the related tri-O-
benzyl-d-glucal (1l) was also smoothly derivatized, yielding
potentially useful iodinated building blocks for carbohydrate
chemistry. In this case, the crude mixture isolated from the
iodination reaction was rapidly treated with Ac2O in Et3N,
rendering the mixture of compounds presented in Scheme 2.
A remarkable 14:1 ratio for the formation of manno over
gluco isomers was determined by HPLC analysis of the mix-
ture upon acylation.[17,18]
Pure samples of 2-deoxy-2-iodo-mannopyrannosyl deriva-
tives, a form 3l and b form 3l’, were isolated by standard
column chromatography, in the yields given in Scheme 2.
A terpene, (+)-3-carene (1m), was easily iodo-hydroxylat-
ed using this approach in nearly quantitative conversion, but
severe decomposition occurred along the standard chroma-
tographic purification leading to only 43% isolated yield of
2m. However, the purity in which 2m is generated in crude
reaction mixtures allows its direct use for further synthetic
elaboration. Thus, as an example, epoxide 3m was prepared
in 70% overall yield from 1m, as outlined in Scheme 3. The
observed stereochemistry for the epoxide nicely comple-
ments that accessible using the direct epoxidation reaction
of 1m with a peracid.[19]
Entry
1
Alkene
1
t
Product
2
Yield[b]
[%]
[h]
2
2
94
83
2
3
5
76[c]
4
5
6
5
60
2
72[d]
81
65
7
6
88[e]
8
9
8
77[f]
85[e]
22
The pattern of reactivity showed by the different alkenes
in these transformations, as well as the regio- and stereo-
chemistry observed are those expected for a reaction involv-
ing the participation of cyclic iodonium ions as reaction in-
termediates. These species should be formed upon interac-
tion of 1 with an electrophilic source of iodine.[20] An appro-
priate process that would contribute to generate iodonium
ions into the given solution could reasonably involve an ini-
tial nucleophilic attack of iodide[21] onto protonated hydro-
gen peroxide.[22] As a result, this would afford an active con-
centration of unstable and productive hypoiodous acid in
solution (Scheme 4). Interaction of HOI, or of its protonat-
ed form,[23] with 1 accounts well for the observed formation
of iodohydrins 2.[24]
10
11
4
4
90[g]
92[g]
[a]Reaction performed with 5 mmol of the corresponding alkene.
[b]Based on isolated amount of 2 and referred to 1. [c]Combined yield
from the amount of each regiosomer isolated in pure form (2c was isolat-
ed in 63% upon column chromatography on silica gel using hexane/ethyl
acetate:10/1, from a crude reaction mixture containing 2c:2c’ in 5:1 ratio
by GC analysis). [d]4 equiv HBF 4 and 4 equiv H2O2 were used.
[e]CF 3CO2H (1.1 equiv) instead of HBF4, and H2O2 (6 equiv) were
added. [f]Based on crude reaction. Upon chromatography Ph 2C=CHI
was isolated. [g]1.5 equiv H 2O2 were used.
Scheme 2. Synthesis of 2-iodo-2-deoxymannopyranosyl derivatives from a protected glucal.
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J. Barluenga et al.
FULL PAPER
(1 equiv, 5 mmol) and THF/H2O (12 mL/5 mL). The mixture was cooled
in an ice-water bath and magnetically stirred. To this vigorously stirred
mixture HBF4 (6.12 mL of 35% aqueous solution, 6 equiv, 30 mmol) and
H2O2 (1.5 mL, 3 equiv, 15 mmol, 33% aqueous solution) were sequential-
ly added. An exothermic reaction and development of a dark red colour
in solution were noticed. After 15 min, the cooling bath was removed
and the reaction mixture further stirred until the solution turned colour-
less (see Table 3 and Scheme 3). THF was then removed under vacuum,
and the resulting mixture was treated with Na2S2O3 (30 mL of 5% aque-
ous solution), and extracted with CH2Cl2 (3î50 mL). The combined or-
ganic layers were washed with brine, dried over Na2SO4 and concentrat-
ed. The crude reaction products were purified by column chromatogra-
phy (hexane/EtOAc) to give pure iodohydrins that gave satisfactory spec-
troscopic and analytical data. Analytical data for compounds 2a,[25] 2b,[9d]
2c,[26] 2 f[27] were in complete accordance with literature values.
Scheme 3. Sequential iodo-hydroxylation/epoxidation reactions of (+)-3-
carene.
(1S,3R,4R,6R)-4-Iodo-3,7,7-trimethylbicyclo[4.1.0]heptan-3-ol
(2m):
Scheme 4. Proposed reaction pathway.
yellow oil; Rf =0.7 (hexane/ethyl acetate 3:1); [a]D =À73 (c=18, CH2Cl2,
208C); 1H NMR (400 MHz, CDCl3): d=4.15 (dd, J=12, 7.2 Hz, 1H;
CH), 2.6 (ddd, J=14.9, 12, 8.5 Hz, 1H; CH2), 2.45 (ddd, J=14.9, 7.2,
0.8 Hz, 1H; CH2), 2.25 (brs, 1H; O-H), 2.1 (dd, J=14.5, 10.1 Hz, 1H;
CH2), 1.35 (m, 1H), 1.25 (dd, J=1.2, 0.5 Hz, 3H; CH3), 0.95 (s, 3H;
CH3), 0.85 (s, 3H; CH3), 0.75 (ddd, J=10.1, 9.1, 4.9 Hz, 1H; CH), 0.45
(ddd, J=9.1, 8.5, 0.8 Hz, 1H; CH); 13C NMR (75 MHz, CDCl3): d=70.8
(C), 49.8 (CH), 34.4 (CH2), 31.1 (CH2), 28.4 (CH3), 24.1 (CH3), 21.9
(CH), 20.1 (CH), 17.5 (C), 15.1 (CH3); HRMS (EI): m/z: calcd for
C10H17O: 153.1275; found: 153.1279 [M +ÀI].
General procedure for the preparation of iodohydrins 2j and 2k: A
lower amount of H2O2 (0.75 mL, 1.5 equiv, 7.5 mmol) was used to avoid
competitive formation of hydroperoxides analogues. Analytical data for
compounds 2j,[28] 2k[28] were in complete accordance with literature
values.
Conclusion
In summary, a truly practicable, efficient and almost unpre-
cedented entry to an important class of iodine containing bi-
functional compounds has been devised and executed on
the basis of biomimetic considerations.
Among other distinctive features of this synthetically val-
uable iodo-hydroxylation process are the use of readily
available starting materials and that of a safe and conven-
ient oxidant, as diluted solutions of hydrogen peroxide. Fur-
thermore, the easiness in which the process was scaled up to
the use of 0.1 mol of starting material represents a worthy
and distinctive synthetic attractiveness of this new approach
for preparing 2-iodoalkanols, imitating biogenic pathways to
functionalize alkenes.
The reaction conditions were successfully applied over a
wide set of alkenes, including natural products derivatives.
Overall, using common chemicals, an aqueous medium and
a very simple synthetic Scheme could now be considered as
a solid alternative for preparing iodohydrins, overcoming
many problems usually faced under previously reported con-
ditions.
General procedure for the preparation of iodohydrins 2g 2i and 2l: The
best results were obtained employing trifluoroacetic acid (0.42 mL,
1.1 equiv, 5.5 mmol). Analytical data for compounds 2g,[29] 2i[12e] were in
complete accordance with literature values.
1-O-Acetyl-3,4,6-tri-O-benzyl-2-deoxy-2-iodo-a-mannopyranose
(3l):
yellow oil; Rf =0.27 (hexane/ethyl acetate 5:1); [a]D =+7.1 (c=7.5,
1
CH2Cl2, 208C); H NMR (300 MHz, CDCl3): d=7.4 7.1 (m, 15H), 6.4 (d,
J=1.4 Hz, 1H; CH), 4.86 (d, J=10.5 Hz, 1H; CH), 4.7 (m, 2H; CH2),
4.5 (m, 3H), 4.4 (dd, J=4, 1.6 Hz, 1H; CH), 4.0 (m, 2H; CH2), 3.78 (dd,
J=11.1, 4 Hz, 1H; CH2), 3.68 (dd, J=11.1, 1.6 Hz, 1H; CH2), 3.22 (dd,
J=8.2, 4 Hz, 1H; CH), 2.05 (s, 3H; CH3); 13C NMR (75 MHz, CDCl3):
d=168.4 (C), 138.1 (C), 137.8 (C), 137.2 (C), 128.4 (CH), 128.3 (CH),
128.2 (CH), 128.0 (2îCH), 127.9 (CH), 127.7 (CH), 127.6 (CH), 127.4
(CH), 95.4 (CH), 76.0 (CH), 75.3 (CH), 75.2 (CH2), 74.7 (CH), 73.4
(CH2), 70.9 (CH2), 68.4 (CH2), 30.9 (CH), 20.4 (CH3); HRMS (EI): m/z:
calcd for C29H31O6: 302.0168; found: 302.0169 [M +ÀI].
1-O-Acetyl-3,4,6-tri-O-benzyl-2-deoxy-2-iodo-b-mannopyranose
(3l’):
yellow oil; Rf =0.24 (hexane/ethyl acetate 5:1); [a]D =À3.7 (c=13.7,
CH2Cl2, 208C); 1H NMR (300 MHz, CDCl3): d=7.4 7.1 (m, 15H), 5.00
(d, J=1.4 Hz, 1H; CH), 4.90 (d, J=10.8 Hz, 1H; CH), 4.70 (m, 3H),
4.60 (dd, J=2.3, 1.4 Hz, 1H; CH), 4.50 (dd, J=11.0, 6.5 Hz, 2H; CH2),
4.00 (m, 1H), 3.78 (m, 2H; CH2), 3.68 (ddd, J=9.7, 4.3, 2.3 Hz, 1H;
CH), 3.20 (dd, J=8.4, 4.3 Hz, 1H; CH), 2.20 (s, 3H; CH3); 13C NMR
(75 MHz, CDCl3): d=168.6 (C), 138.0 (C), 137.9 (C), 137.0 (C), 128.4
(CH), 128.2(2îCH), 127.9 (2îCH), 127.7 (2îCH), 127.6 (CH), 127.4
(CH), 91.2 (CH), 78.9 (CH), 76.9 (CH), 75.2 (CH), 75.1 (CH2), 73.4
(CH2), 70.6 (CH2), 68.4 (CH2), 36.0 (CH), 21.0 (CH3); HRMS (EI): m/z:
calcd for C29H31O6: 302.0168; found: 302.0166 [M +ÀI].
Experimental Section
General: All reactions were carried out under air atmosphere unless oth-
erwise is specified in the text. THF and Et2O were distilled from sodium/
benzophenone under N2. Analytical thin-layer chromatography plates
used were Merck UV-active silica gel 60 F254 on aluminium plates. Flash
column chromatography was carried out on silica gel 60, 230 240 mesh,
using appropriate mixtures of ethyl acetate and hexanes as eluent.
1H NMR (200, 300, 400 MHz) and 13C NMR (50, 75, 100 MHz) spectra
were measured at room temperature on a Bruker AC-200, AC-300 and
AMX-400 instruments with tetramethylsilane (1H NMR) or CDCl3
(13C NMR) as internal standard. Carbon multiplicities were assigned by
DEPT techniques. High resolution mass spectra (HRMS) were deter-
mined on a Finnigan MATT 95 spectrometer. Elemental analysis were
carried out on a Perkin Elmer 2400 microanalyzer. Gas chromatographic
analyses were conducted on an HP6890 using a Beta dex 120 Supelco
(30 mî0.25 mmî0.25 mm) column. HPLC analyses were performed on a
Waters LC Module I plus using a Kromasil 100 C8 5 mm 25î1.0 column.
Melting points were determined on a B¸chi-Tottoli and are uncorrected.
Optical rotations were measured on a Perkin-Elmer 241 polarimeter.
Procedure for the preparation of 2d: HBF4 (4.1 mL of 35% aqueous sol-
ution, 4 equiv, 20 mmol) and H2O2 (2 mL, 4 equiv, 20 mmol, 33% aque-
ous solution) were used. Analytical data for compound 2d[26] were in
complete accordance with literature values.
Synthesis of epoxide 3m: A crude mixture of 2m was treated with NaH
(1.3 g, ꢀ1 equiv, 5 mmol) in a THF/Et2O mixture (1:1, 30 mL) under N2
atmosphere. The reaction was magnetically stirred for 3.5 h and then hy-
drolyzed with ice. The mixture was extracted with Et2O (3î25 mL) and
washed with brine (2î50 mL). The combined organic layers were then
dried over anhydrous sodium sulphate and volatiles were removed under
vacuum. Further purification upon column chromatography (hexane/
General procedure for the preparation of iodohydrins 2a 2c, 2 f, and
2m: A 100 mL flask was charged with NaI (0.75 g, 1 equiv, 5 mmol), 1
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Chem. Eur. J. 2004, 10, 1677 1682

Iodohydrins
1677 1682
EtOAc 50:1) afforded pure 3m (0.53 g, 3.5 mmol, 70%). Analytical data
for compound 3m[30] were in complete accordance with literature values.
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2128.
[12]While chloro- and bromo-hydroxylation reactions of alkenes em-
ploying the corresponding halide salts were proved to be valuable
synthetic methodologies, the scope of the related iodo-hydroxylation
process has not yet been established. For representative studies on
the former reactions, see: a) M. R. Detty, F. Zhou, A. E. Friedman,
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[13]For some applications see: a) S. Juliµ, J. Masana, J. C. Vega, Angew.
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[14]H 2O2 is an environmentally benign oxidant for chemical processes.
a) R. A. Sheldon, Chemtech 1994, 38 47; b) J. H. Clark, Green
Chem. 1999, 1, 1 8.
[15]This iodination-triggered process uses the H 2O2/KI reagents combi-
nation in a citric-phosphate buffer (pH 3). The reaction time em-
ployed for the described iodination was 30 minutes at room temper-
ature.
[16]Compounds 2 and 3 were characterized by NMR spectroscopy and
gave satisfactory analytical and/or HRMS data, in accordance to the
assigned structure.
[17]The mannopyranosyl derivatives were observed in the crude reac-
tion mixture in a ratio of 4:1 for a:b epimers, according to HPLC
analysis.
Acknowledgement
This research was supported by Principado de Asturias (PR-01-GE-9)
and the Spanish DGI (MCT-01-BQU-3853). F.G.-B. thanks Principado de
Asturias for a predoctoral fellowship.
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Received: September 29, 2003
Revised: December 15, 2003 [F5582]
1682
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 1677 1682