Reactions of 1-tosyl-3-substituted indoles with conjugated dienes under thermal and/or high-pressure conditions

Article abstract of DOI:10.1021/jo0057856

The behavior of 1-tosyl-3-acetylindole (1a), N,N-diethyl-17tosyl-3-indoleglyoxylamide (1b), and 1-tosyl-3-nitroindole (1c) as dienophiles in Diels-Alder reactions under thermal and/or high-pressure conditions was explored with different dienes: isoprene (

Full text of DOI:10.1021/jo0057856

3906
J . Org. Chem. 2001, 66, 3906-3912
Rea ction s of 1-Tosyl-3-su bstitu ted In d oles w ith Con ju ga ted Dien es
u n d er Th er m a l a n d /or High -P r essu r e Con d ition s
Betina Biolatto, Mar´ıa Kneeteman, Elisa Paredes, and Pedro M. E. Mancini*
Laboratorio Fester, AÄ rea de Quı´mica Orga´nica, Departamento de Qu´ımica, Facultad de Ingenierı´a
Quı´mica, Universidad Nacional del Litoral, Santiago del Estero 2829, 3000 Santa Fe, Argentina
pmancini@fiqus.unl.edu.ar
Received December 29, 2000
The behavior of 1-tosyl-3-acetylindole (1a ), N,N-diethyl-1-tosyl-3-indoleglyoxylamide (1b), and
1-tosyl-3-nitroindole (1c) as dienophiles in Diels-Alder reactions under thermal and/or high-pressure
conditions was explored with different dienes: isoprene (2), 1-(N-acetyl-N-propylamino)-1,3-
butadiene (3), and 1-methoxy-3-trimethylsilyloxy-1,3-butadiene (Danishefsky’s diene) (4). Compared
to the acylated indoles, the nitro derivative proved to be the best dienophile. In general, the use of
Danishefsky’s diene led to high-yielding reactions under milder conditions. Likewise, high-pressure
conditions proved to be better in producing high yields of products. The advantage of high-pressure
over thermal conditions was the ability of the former to generate highly functionalized adducts in
better yields, which were otherwise very difficult or impossible to obtain. The use of thermal or
high-pressure conditions led to different regio- and/or stereoselectivity in the adducts, allowing
control of the regio- or stereoisomer produced.
In tr od u ction
Recently, it has been shown that 1-tosyl-3-nitroindole
(1c) is a very good dienophile in thermal Diels-Alder
reactions (with normal electron demand) with different
dienamides, leading to mixtures of 1-tosyl-4-substituted
dihydrocarbazoles and 1-tosylcarbazoles. The ease of
thermal extrusion of nitrous acid accompanying the
reaction of this dienophile and the aromatization with
N-alkylamide loss from the resultant dihydrocarbazoles
(to produce highly stable heteroaromatic compounds)
makes this two-step reaction sequence a facile, new
method for dihydrocarbazole and carbazole synthesis.7
Wenkert’s previous observations have already demon-
strated the feasibility of normal Diels-Alder chemistry
with five-membered, aromatic heterocycles bearing elec-
tron-withdrawing groups, as dienophiles,8 and the higher
reactivity of â-substituted compared to R-substituted
substrates.9 Compounds such as furans, N-benzenesulfo-
nylpyrroles, benzofurans, and N-benzenesulfonylindoles
â-substituted with electron-withdrawing groups are in-
volved as dienophiles in normal Diels-Alder reactions
with 1,3-butadiene and isoprene, at elevated tempera-
tures, leading to mixtures of regioisomers in moderate
to high yields. The above-cited characteristics of the high-
pressure conditions would lead to improved yields and
eventual changes in the regio- and stereoselectivity of
these cycloaddition reactions. Moreover, adducts would
retain all of the substituents from the reactants, which
The versatile Diels-Alder [4 + 2] cycloaddition is an
asset in the organic chemist’s toolbox because it simul-
taneously sets ring(s), asymmetric centers, and functional
groups.1 Of the many parameters that could be changed
to effect the success of a synthetic method, there is
renewed interest in high pressure as a method to effect
Diels-Alder reactions.2 Since the Diels-Alder reaction
is characterized by a negative volume of activation (∆Vq),
the application of pressure facilitates the transformation
of the reactants into the relatively more compact transi-
tion state, thereby lowering the activation energy of the
process. Moreover, ∆V for the overall process is also
negative, thus making it kinetically, as well as thermo-
dynamically, favorable. At atmospheric pressure, some
cycloadditions fail since they are reversible and reach a
low equilibrium yield that cannot be improved by raising
the temperature. Pressure, on the other hand, favors the
forward reaction and disfavors the reverse, leading to
higher yields.3-5 Its use for preparative intermolecular
Diels-Alder cycloadditions has been well studied,2 but
no successful examples of high-pressure Diels-Alder
reactions involving heteroaromatic compounds as dieno-
philes have been reported.6
* To whom correspondence should be addressed. Phone: 54-342-
4571166. Fax: 54-342-4571162.
(1) Carruthers, W. Cycloaddition Reactions in Organic Synthesis;
Pergamon Press: Oxford, 1990.
(2) Dauben, W. G.; Kozikowski, A. P. J . Am. Chem. Soc. 1974, 96,
3664-3666.
(3) Isaacs, N. Tetrahedron 1991, 47, 8463-8497.
(4) (a) Matsumoto, K.; Sera, A.; Uchida, T. Synthesis 1985, 1-26.
(b) Matsumoto, K.; Sera, A. Synthesis 1985, 999-1027.
(5) Le Noble, W.; Kelm, H. Angew. Chem. 1980, 19, 841-856.
(6) The first indication of the advantages of high-pressure conditions
in effecting Diels-Alder reactions of aromatic compounds acting as
dienophiles is the reaction between 1-nitronaphthalene and Danishef-
sky’s diene, which shows higher yields than the thermal reaction.
Paredes, E.; Biolatto, B.; Kneeteman, M.; Mancini, P. Tetrahedron Lett.
2000, 41, 8079-8082.
(7) Biolatto, B.; Kneeteman, M.; Mancini, P. Tetrahedron Lett. 1999,
40, 3343-3346.
(8) (a) Wenkert, E.; Piettre, S. J . Org. Chem. 1988, 53, 5850-5853.
(b) Wenkert, E.; Moeller, P. D. R.; Piettre, S. R. J . Am. Chem. Soc.
1988, 110, 7188-7194.
(9) Despite much effort spent on the isolation of a 1:1 adduct in the
methyl 1-tosyl-2-indolecarboxylate/isoprene reaction, none was ob-
served. Under catalyzed conditions (50-90% of AlCl3 or BF3‚Et2O, 100
°C, 24-120 h) the reaction afforded up to 15% of methyl 1-tosyl-3-
prenyl-2-indolecarboxylate. Traces of an unknown product were also
present, but the isolation was impossible to be carried out. NMR
experiments of the crude led us to suppose the presence of a possible
adduct.
10.1021/jo0057856 CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/08/2001

Reactions of 1-Tosyl-3-substituted Indoles
J . Org. Chem., Vol. 66, No. 11, 2001 3907
Ta ble 1. Diels-Ald er Rea ction s of 3-Acylin d oles 1a a n d 1b w ith Isop r en e (2)
entry
indole
diene
catalysis
reaction conditions
resultsa
1
2
3
4
5
6
1a
2, 12 equiv
20 °C, 10 kbar, 16 h
20 °C, 11 kbar, 16 h
40 °C, 11.5 kbar, 72 h
40 °C, 11.5 kbar, 48 h
20 °C, 11.5 kbar, 16 h
40 °C, 11.5 kbar, 72 h
5a :6a , traces; 1a 98%
5a , 55%; 1a , 45%
5a , 46%; 1a , 50%
5b:6b, 20%; 1b, 80%
5b, 72%; 1b, 28%
5b, 55%; 1b, 40%
BF3‚Et2O, 0.5 equiv
BF3‚Et2O, 0.5 equiv
1b
2, 12 equiv
BF3‚Et2O, 0.5 equiv
BF3‚Et2O, 0.5 equiv
a
Products, yield; dienophile, % recovery.
Ta ble 2. Diels-Ald er Rea ction s of 3-Nitr oin d ole 1c w ith
Isop r en e (2)
represents an advantage over the thermal Diels-Alder
reaction of 1-tosyl-3-nitroindole (1c).
Accordingly, the purpose of the present work is to
explore the behavior of 1-tosyl-3-acetylindole (1a ), N,N-
diethyl-1-tosyl-3-indoleglyoxylamide (1b),10 and 1-tosyl-
3-nitroindole (1c) in normal Diels-Alder reactions with
functionalized conjugated dienes. At the same time, this
work aims at determining the regiochemistry and ster-
eochemistry of the adducts obtained under thermal and/
or high-pressure conditions, with a view to discussing the
scope and limitations of this technique.
resultsa
Resu lts a n d Discu ssion
entry indole
diene
reaction conditions
1
2
3
1c
2, 12 equiv 90 °C, 96 h
7:8 (5:1), 30%;
1c, 55%
5c, 22%;
1c, 77%
5c, 75%; 9, 5%;
1c, 20%
To test the efficacy of the Diels-Alder reaction of
electron poor 1-tosylindoles, the following compounds
were used as dienes: isoprene (2), 1-(N-acetyl-N-propy-
lamino)-1,3-butadiene (3), and 1-methoxy-3-trimethylsi-
lyloxy-1,3-butadiene (Danishefsky’s diene) (4).
20 °C, 11.5 kbar,
24 h
40 °C, 11.5 kbar,
72 h
a
Products, yield; dienophile, % recovery.
these cases was lower (Table 1, entries 3 and 6). Accord-
ing to Wenkert,8b the reactions of both indoles with
isoprene at 195 °C led to moderate-to-high yields (63-
87%) of 3:1 mixtures of the above-mentioned regioiso-
mers, whereas the Lewis acid catalysis of the reaction
between 1-tosyl-3-acetylindole and isoprene during 4 h
at 70 °C improved the regioselectivity (24:1 5a :6a ) but
lowered the yields (29%). These results demonstrated the
higher capacity of the combination of high pressure/
catalysis as compared to the combination of temperature/
catalysis, in improving the yield and regioselectivity of
the reaction.
Attempts to produce the nitroadducts in the reaction
between 1c and 2 under mild thermal conditions11 (Table
2, entry 1) were unsuccessful, with only 30% yield of
regioisomeric dihydrocarbazoles 7 and 8 and no carba-
zoles produced. The reaction at high pressure gave a
nitroadduct, single regioisomer 5c in 22% yield (Table
2, entry 2). When the reaction was carried out at 40 °C
during 72 h, the yield of 5c reached 75%, with traces of
carbazole 9 (Table 2, entry 3).12 These results constituted
When 1-tosyl-3-acetylindole (1a ) and N,N-diethyl-1-
tosyl-3-indoleglyoxylamide (1b) were reacted with iso-
prene (2) under high pressures (Table 1, entries 1 and
4), mixtures of regioisomers 5a , 6a and 5b, 6b were
obtained in very low yields. However, under catalyzed
conditions (Table 1, entries 2 and 5), both reactions
furnished over 50% of the single regioisomer 5a and 5b,
respectively. Given the better electron-withdrawing prop-
erties of the glyoxylamide group, the yield of cycloadduct
5b was ca. 15-20% higher than that of 5a . Attempts to
improve yields by increasing either the reaction time and/
or the temperature only led to extensive diene polymer-
ization, which prevented the complete recovery of the
crude material from the reaction vessel. It was presum-
ably due to this problem that the product conversion in
(11) Reproduction of Wenkert’s reaction8b between 1-tosyl-3-nitroin-
dole 1c and isoprene 2 led to the same four-component mixture of
dihydrocarbazoles 7 and 8 and carbazoles 9 and 10.
(12) The presence of carbazole 9 was detected immediately following
decompression by 1H NMR analyses of the crude. The loss of nitrous
acid could occur upon depressurization.
(10) Other choices as 1-tosyl-3-formylindole or methyl 1-tosyl-3-
indoleglyoxylate were discarded due to both the lower reactivity as
dienophiles and the higher instability under reaction conditions such
as elevated temperatures or Lewis acid catalysis.

3908 J . Org. Chem., Vol. 66, No. 11, 2001
Biolatto et al.
Ta ble 3. Diels-Ald er Rea ction s of 3-Acylin d oles 1a a n d
1b w ith Dien a m id e 3
F igu r e 1. (a) Exo and (b) endo approaches of 1-tosyl-3-
substituted indole and a substituted diene.
ity, leading to one of four possible adducts. The steroi-
somer obtained constituted the first indication of an
abnormal exo selectivity of the Diels-Alder reaction
(Figure 1a). It could be thought that a transition state
more compact than product could be responsible for the
predisposition of the previously cited reaction to produce
the exo adduct as the only product. Such speculation
could be due to the unique feature of the secondary
orbital interaction between the aromatic ring of the
dienophile and the butadienic system of the diene,
stronger than that expected between the glyoxylamide
group and the dienic system.
Previous results7 showed the tendency toward thermal
extrusion of nitrous acid in the reaction of 1-tosyl-3-
nitroindole (1c) and dienamide 3 at temperatures higher
than 90 °C. Attempts to produce the nitroadduct under
milder thermal conditions (Table 4, entry 1) again led
the substituted 1-tosyldihydrocarbazole 15, the carbazole
11, and the recovery of unreacted dienophile 1c. In
contrast to the reaction involving isoprene (2) under high-
pressure conditions, the reaction of 1-tosyl-3-nitroindole
(1c) and dienamide 3 at high pressures and 50 °C (Table
4, entry 2) led to the formation of the same substituted
dihydrocarbazole 15 obtained under thermal conditions.
Lowering the temperature and the diene/dienophile ratio,
the reaction furnished a mixture of nitroadducts and
dihydrocarbazole 15 (Table 4, entries 3 and 4). Due to
the ease of nitrous acid extrusion, the chromatographic
purification of the nitroadducts always led to mixtures
with the corresponding dihydrocarbazole 15, preventing
the full identification of the former. Analyses of the
mixture by 1H NMR and 13C NMR experiments and
comparison with those of 14b helped us to determine the
structure of the main nitroadduct as 14c.16
The use of Danishefsky’s diene allowed us to analyze
the influence of bulky substituents on the yields, regio-
chemistry and stereochemistry of the cycloadditions
under thermal and/or high-pressure conditions. Heating
a 12:1 mixture of 1a and Danishefsky’s diene 4 afforded
only traces of a mixture of possible diastereomers 16a
and 17a , after hydrolysis (Table 5, entry 1).14 Attempts
to increase the yields of the reaction under high-pressure
conditions (Table 5, entries 2 and 3) led to only 25% of a
ca. 1:1 (inseparable) mixture of the cited cycloadducts.
Noteworthy, even under high pressure, this dienophile
was not reactive enough to afford good yields in the
reaction with a very good diene. Compared to acetylindole
1a , glyoxylamide 1b proved to be a far better dienophile,
yielding a 40:1 mixture of diastereomers 16b and 17b in
70% yield at 120 °C after hydrolysis (Table 5, entry 4).
The reaction showed a great preference for the endo
entry indole
diene
reaction conditions
resultsa
1
2
3
1a
1b
3, 3 equiv 40 °C, 10 kbar,
110 h
3, 3 equiv 120 °C, 96 h
13a :14a , traces;
1a , 80%
13b:14b, traces;
1b, 73%
40 °C, 11.5 kbar,
48 h
14b, 51%; 1b, 49%
a
Products, yield; dienophile, % recovery.
the first indication of the advantages of high-pressure
conditions in producing highly substituted products (even
with a good leaving group such as nitro), impossible to
obtain at normal pressure because of the thermal insta-
bility of the cycloadducts. In no case was the conversion
into products complete, even under catalyzed conditions.
Obviously, further increases of temperature, reaction
time, or even pressure would result in more extensive
polymerization of the diene and consequently a high
viscosity, preventing the cycloaddition process from oc-
curring.
Exposure of acylindole 1a to 1-(N-acetyl-N-propy-
lamino)-1,3-butadiene13 (3) at different temperatures
(110, 130, 160, and 200 °C) and reaction times (48, 192,
72, and 72 h, respectively) always led to the decomposi-
tion of both the diene (for temperatures above 150 °C)
and/or the dienophile (for temperatures above 110 °C).
Only for the glyoxylamide substitution on the indole was
ca. 9% of a mixture of the possible diastereomeric
cycloadducts 13b and 14b obtained (Table 3, entry 2).14
The diene instability at elevated temperatures conspired
against the success of the cycloaddition, even for the more
reactive dienophile 1b.15
The reactions were then carried out under high-
pressure conditions. Considering the proven lower reac-
tivity of the 1-tosyl-3-acetylindole (1a ), the reaction was
undertaken at 12 kbar during 110 h (Table 3, entry 1).
However, the reaction led to only traces of a mixture of
the possible adducts 13a and 14a .14 Comparatively, at
12 kbar (Table 3, entry 3), dienophile 1b and dienamide
3 underwent cycloaddition with the formation of ca. 51%
of a single adduct 14b with 49% recovery of dienophile.
This reaction showed complete regio- and stereoselectiv-
(13) A readily available dienamine, 1-(N,N-diethylamine)-1,3-buta-
diene, was also tested in thermal Diels-Alder reactions with 1-tosyl-
3-formylindole, 1-tosyl-3-acetylindole, N,N-diethyl-1-tosyl-3-indoleg-
lyoxylamide, methyl 1-tosyl-3-indoleglyxolylate, and 1-tosyl-3-nitroindole,
but the instability of the diene prevented the cycloaddition, with the
formation of multiple byproducts, mainly the detosylated dienophiles
in 30-50% yield.
(14) Detected by GC-MS analyses.
(15) 1-Tosyl-3-formylindole and methyl 1-tosyl-3-indoleglyoxylate
were also tested in thermal Diels-Alder reactions with the above-
mentioned dienamide, but their low reactivity/high thermal instability
caused the failure of the cycloaddition and the decomposition of both
the diene and the dienophile. Attempts to perform the reactions under
Lewis acid catalysis conditions only led to complete diene decomposi-
tion.
(16) Therefore HR-MS or elemental analyses were not possible to
be performed.

Reactions of 1-Tosyl-3-substituted Indoles
J . Org. Chem., Vol. 66, No. 11, 2001 3909
Ta ble 4. Diels-Ald er Rea ction s of 3-Nitr oin d ole 1c w ith Dien a m id e 3
entry
indole
diene
reaction conditions
resultsa
1
2
3
4
5
1c
3, 3 equiv
3 equiv
2 equiv
1 equiv
18, 3 equiv
65 °C, 48 h
11, 12%; 15, 50%; 1c, 20%
15, 40%; 1c, 20%
14c, 25%; 15, 50%; 1c, 24%
14c, 22%; 15, 53%; 1c, 24%
11, 13%; 19, 28%; 20, 9%; 21, 1%; 1c, 49%
50 °C, 11.5 kbar, 30 h
40 °C, 11.5 kbar, 40 h
40 °C, 11.5 kbar, 40 h
65 °C, 48 h
a
Products, yield; dienophile, % recovery.
Ta ble 5. Diels-Ald er Rea ction of 3-Acylin d oles 1a a n d 1b w ith Da n ish efsk y’s Dien e (4)
entry
indole
diene
reaction conditions
resultsa
1
2
3
4
5
6
7
1a
4, 12 equiv
12 equiv
1 equiv
4, 12 equiv
12 equiv
1 equiv
120 °C, 48 h
16a :17a , traces; 1a , 75%
16a :17a (1:1), 20%; 1a , 80%
16a :17a (1:1), 20%; 1a , 80%
16b:17b (40:1), 71%; 1b, 16%
16b:17b (1:3.5),100%
40 °C, 11.5 kbar, 48 h
40 °C, 11.5 kbar, 48 h
120 °C, 48 h
40 °C, 11.5 kbar, 48 h
40 °C, 11.5 kbar, 48 h
40 °C, 11.5 kbar, 20 h
1b
16b:17b (1:3.5), 100%
16b:17b (1:3.5), 100%
12 equiv
a
Products, yield; dienophile, % recovery.
Ta ble 6. Diels-Ald er Rea ction of 3-Nitr oin d ole 1c w ith Da n ish efsk y’s Dien e (4)
entry
indole
diene
reaction conditions
resultsa
1
2
3
4
5
6
1c
4, 3 equiv
3 equiv
3 equiv
12 equiv
12 equiv
1 equiv
90 °C, 48 h
65 °C, 24 h
65 °C, 48 h
40 °C, 11.5 kbar, 48 h
40 °C, 11.5 kbar, 6 h
40 °C, 11.5 kbar, 6 h
12, 47%; 16c, 33%; 17c, 4%; 1c, 5%
12, 11%; 16c, 32%; 17c, 32%; 1c, 20%
12, 17%, 16c; 39%; 17c, 25%; 1c, 12%
16c:17c (1:1), 100%
16c:17c (1:1), 100%
16c:17c (1:1), 100%
a
Products, yield; dienophile, % recovery.
adduct 16b. The application of high pressure to this
reaction (Table 5, entries 5 and 6) led to quantitative
conversion to a ca. 1:3.5 mixture of 16b to 17b. The
optimal reaction time leading to quantitative yields was
20 h, working with a 1:1 diene/dienophile ratio. The
inversion of the stereoselectivity in the thermal reaction
demonstrated the potential of the trimethylsilyloxy and
glyoxylamide groups in electronically and sterically
directing the course of the reaction depending upon the
pressure conditions. It is of interest to note that the trans
arrangement of the glyoxylamide and methoxy groups
was produced via the highly crowded exo transition state,
which superimposed the trimethylsilyloxy group with the
aromatic system of the indole. The diastereomeric excess
of the exo isomer was attributed to the high pressures
employed in the experiment, where steric effects were
more easily overcome and the more compact exo transi-
tion state competed more favorably with its endo coun-
terpart than at ambient pressures.
When 1-tosyl-3-nitroindole (1c) was reacted with Dan-
ishefsky’s diene under thermal conditions (Table 6, entry
1), the reaction surprisingly afforded a 37% mixture of
diastereomeric cycloadducts 16c and 17c in a 30:1 ratio
after hydrolysis, with 48% of hydroxycarbazole 12. When
the reaction temperature was lowered to 65 °C (Table 6,
entry 2), the isomeric ratio changed to ca. 1:1, with only
11% of hydroxycarbazole 12. This result demonstrated
that isomer 17c is more likely to suffer thermal aroma-
tization because of the trans arrangement of its nitro and
methoxy substituents. The intermediate that suffered
nitrous acid extrusion and retained the methoxy group
was not detected in either case. In a similar behavior
pattern, the reaction carried out under high-pressure
conditions (Table 6, entry 4) now gave a quantitative
conversion of the dienophile into a ca. 1:1 mixture of the
above named cycloadducts. Under these conditions, no
hydroxycarbazole 12 was formed.17 Optimization studies
(Table 6, entries 5 and 6) found that the best conditions
were 6 h and 40 °C (1:1 diene/dienophile ratio), affording
quantitative conversion of dienophile, thus evidencing the
higher reactivity of 1-tosyl-3-nitroindole (1c) compared
to the glyoxylamide derivative 1b. These reactions were
completely regioselective. The results obtained at high
pressure are in agreement with those obtained for
substrate 1b and Danieshefsky’s diene under similar
reaction conditions. The results obtained under thermal
conditions could be due to the similarities in conformation
and activation energy of both transition states. This
means that the thermal reaction could overcome the
steric effect of the trimethylsilyloxy group to produce the
trans adduct 17c. Furthermore, the electrostatic repul-
(17) The sample had to be worked up immediately after decompres-
sion, eliminating the excess of diene, otherwise a high proportion of
carbazole was produced, showing the possibility of nitrous acid
extrusion and aromatization after decompression, presumably induced
by the excess of diene or the decomposition of the excess of diene.

3910 J . Org. Chem., Vol. 66, No. 11, 2001
Biolatto et al.
sion between the strong negative charge of the nitro and
the negative charge on the oxygen of the OTMS group
in Danishefsky’s diene in the endo transition state
(Figure 1b) could constitute an additional factor leading
to a high proportion of 17c.18
Exp er im en ta l Section
1
Gen er a l Asp ects. H and 13C NMR spectra were taken in
CDCl3 on 200 and 50, 300 and 75, and 400 and 100 MHz FT-
spectrometers, respectively, using TMS as the internal stan-
dard; coupling constants (J ) are given in Hz. GC analyses were
performed on a PE-5-type column (30 m, 0.53 mm i.d., 0.5 µm
coating). GC/MS analyses were performed in an instrument
equipped with a similar column. Transmission IR spectra were
recorded from NaCl cells as CCl4 solutions. Melting points were
observed on a Winkle-Zeiss Gottingen microhot stage and were
uncorrected. The silica gel and neutral alumina used for
chromatography were 70-230 mesh. The following reagents
were prepared by literature methods: 1-tosyl-3-acetylindole
(1a ),8b N,N-diethyl-1-tosyl-3-indoleglyoxylamide (1b),8b 1-tosyl-
3-nitroindole (1c),7 1-(N-acetyl-N-propylamino)-1,3-butadiene
(3).7 Other reagents were obtained from commercial sources
and were used as received or purified as required by standard
methods. The high-pressure reactions were performed in a
Unipress piston-cylinder apparatus for pressures up to 14
kbar. The instrument allowed the possibility of simultaneously
working with 4 pressure vessels, 1 mL each. All reactions were
carried out in a nitrogen or argon atmosphere.
To analyze the apparently different behavior of ni-
troadducts 5c, 13/14c, and 16/17c, the thermal reaction
between 1c and 1-methoxy-1,3-butadiene 18 was under-
taken (Table 4, entry 5). Nitroadducts 19 and 20 were
isolated in good yields, carbazole 11 was formed in 13%,
and only traces of the 4-substituted dihydrocarbazole 21
were detected. These results not only demonstrated the
tendency toward thermal extrusion of nitrous acid from
14c and the relative stability of the 4-substituted dihy-
drocarbazole 15 but also predicted the stereochemical
course of the reactions involving 1c and 3. The thermal
reaction would lead to a great excess of 13c, which
subsequently, would eliminate nitrous acid to produce
dihydrocarbazole 15. However, the high-pressure reac-
tions could produce a mixture of 13c and 14c, which at
low temperatures would lead to the observed mixture of
14c and 15. The extent of formation of the substituted
1-tosyldihydrocarbazole 15 would strongly depend on the
structural arrangement between the nitro and N-acetyl-
N-alkylamide groups (understood as cis or trans isomer-
ism). However, when Danishefsky’s diene (or 1-methoxy-
1,3-butadiene) was involved in the cycloaddition process,
the original adduct was very stable, under both high-
pressure and high-temperature conditions. When the
nitrous acid extrusion occurred, it was accompanied by
loss of methanol, leading to the aromatic hydroxycarba-
zole 12. The intermediate that suffered nitrous acid
extrusion and retained the methoxy group was not
detected in either case. In the thermal reaction with
Danishefsky’s diene, the nitrous acid extrusion and
methanol elimination would presumably be produced
during the process of silylenol ether hydrolysis,19 in a
concerted manner. In this case, the excess of diene or the
nucleophilic trimethylsilyloxy produced in the absence
of acid during the reaction would induce the whole
process.
Gen er a l P r oced u r e for th e Th er m a l Cycloa d d ition
Rea ction s of In d oles. The temperature, the length of the
reaction and the diene/dienophile ratio were dependent on the
starting material. An ampule containing a solution of 1.0 mmol
of the dienophile and the required amount of diene in 0.5 mL
of dry benzene was cooled in liquid nitrogen, sealed, and then
heated in an oil bath. After the reaction time was completed,
it was cooled once more in liquid nitrogen and opened. The
solution was evaporated and the residue purified by column
chromatography on silica gel or alumina using hexane/ethyl
acetate mixtures as eluent.
Gen er a l P r oced u r e for th e High -P r essu r e Cycloa d d i-
tion Rea ction s of In d oles. The temperature, the length of
the reaction, and the diene/dienophile ratio were dependent
on the starting material. Under an atmosphere of argon, neat
diene was added to a pressure vessel containing 0.25 mmol of
the dienophile, and the volume was completed with dry
dichloromethane. The vial was then pressurized and heated
to the required temperature for the desired reaction time.
(CAUTION: depending upon the type of high-pressure ap-
paratus being used, when heating the reaction attention must
be paid to the increase of pressure. To avoid exceeding the safe
operating window, the apparatus should not be fully pressur-
ized, and after reaching the required temperature, minor
adjustments should be done to keep the desired pressure).
After the reaction time was completed, the equipment was
allowed to cool to room temperature and then slowly decom-
pressed. The solvent was then evaporated, the crude material
1
was analyzed by H and 13C NMR and then chromatographed
on silica gel or alumina with heptane/ethyl acetate mixtures
as eluent. For the catalyzed reaction, a 0.4 M solution of BF3‚
Et2O in dry CH2Cl2 was added dropwise to the dienophile, the
solution was stirred for 15 min, the diene was added, and the
volume was completed with dry CH2Cl2. After decompression,
the crude reaction mixture was quenched with 5 mL of a 10%
aqueous solution of NH4Cl, the organic phase was separated,
and the aqueous solution was extracted twice with CH2Cl2.
The combined organic layers were dried (MgSO4) and evapo-
rated.
(()-4a â-Acetyl-2-m eth yl-9-tosyl-1,4,4a ,9a â-tetr a h yd r o-
9H-ca r ba zole (5a ) a n d 4a â-Acetyl-3-m eth yl-9-tosyl-1,4,-
4a ,9a â-tetr a h yd r o-9H-ca r ba zole (6a ). Elution with 5:1
hexanes-ethyl acetate (on silica gel) led to the recovery of
starting dienophile 1a . Earlier fractions afforded traces of a
mixture of 5a and 6a or only 5a in the high-pressure BF3-
catalyzed reaction. Both of the homologous benzenesulfony-
lated derivatives were reported by Wenkert.8b
As a general conclusion, high-pressure conditions
proved to be better in producing high yields of products
and affording fully substituted adducts. On the other
hand, the thermal reactions needed longer reaction times
and higher temperatures and diene:dienophile ratios, to
get acceptable yields. These could not be raised unless
lower temperatures and very long periods of reaction
were chosen. The use of either thermal of high-pressure
conditions led to changes in the regio- and/or stereose-
lectivity of adducts, allowing control of the regio- or
stereoisomer produced.
(()-4a â-(N,N-Diet h ylglyoxyla m id o)-2-m et h yl-9-t osyl-
1,4,4a ,9a â-tetr a h yd r o-9H-ca r ba zole (5b) a n d 4a â-(N,N-
Dieth ylglyoxylam ido)-3-m eth yl-9-tosyl-1,4,4a,9a â-tetr ah y-
d r o-9H-ca r ba zole (6b). Elution with 5:1 hexanes-ethyl
acetate (on silica gel) led to the recovery of starting dienophile
(18) Node M.; Nishide, K.; Imazato, H.; Kurosake, R.; Inoue, T.;
Ikariya T. Chem. Commun. 1996, 2559-2560.
(19) Danishefsky, S.; Kitahara, T.; Yan, C. F.; Morris J . J . Am.
Chem. Soc. 1979, 101, 6996-7000.

Reactions of 1-Tosyl-3-substituted Indoles
J . Org. Chem., Vol. 66, No. 11, 2001 3911
1b. Earlier fractions afforded traces of a mixture of 5b and
6b or only 5b in the high-pressure BF3-catalyzed reaction. Both
of the homologous benzenesulfonylated derivatives were re-
ported by Wenkert.8b
3 H), 4.25 (t, 1 H), 5.45 (dd, 1 H). 17a : 1H NMR (400 MHz) δ
1.37 (s, 3 H), 2.34 (s, 3 H), 3.27 (s, 3 H), 4.27 (dd, 1 H), 4.69
(dd, 1 H).
(()-4a â-(N,N-Dieth ylglyoxyla m id o)-4â-m eth oxy-2-oxo-
9-tosyl-1,2,3,4r,4a ,9a â-h exa h yd r o-9H-ca r ba zole (16b) a n d
(()-4a â-(N,N-Dieth ylglyoxyla m id o)-4r-m eth oxy-2-oxo-9-
tosyl-1,2,3,4â,4a ,9a â-h exa h yd r o-9H-ca r ba zole (17b). Elu-
tion with 5:1 hexanes-ethyl acetate (on alumina) led to the
recovery of unreacted dienophile, and further elution afforded
16b and 17b in two consecutive fractions. IR 1720, 1636, 1600,
1361, 1168 cm-1. 16b: 1H NMR (200 MHz) δ 0.67 (t, 3 H, J )
7.2), 1.12 (t, 3 H, J ) 7.2), 1.94 (dd, 1 H, J ) 18.0, 2.2), 2.10-
2.30 (m, 1 H), 2.25-2.45 (m, 1 H), 2.64 (dd, 1 H, J ) 18.0,
3.3), 2.34 (s, 3 H), 3.08 (dd, 1 H, J ) 17.0, 5.6), 3.23 (dd, 1 H,
J ) 17.0, 2.2), 3.33 (s, 3 H), 3.15-3.35 (dm, 2 H), 3.30-3.50
(dm, 2 H), 4.75 (dd, 1 H, J ) 3.3, 2.2), 5.48 (dd, 1 H, J ) 5.6,
2.2), 7.03 (td, 1 H, J ) 7.6, 1.1), 7.30 (dt, 1 H, J ) 7.6, 1.3),
7.22 (d, 2 H, J ) 8.3), 7.49 (d, 1 H, J ) 6.9), 7.66 (d, 1 H, J )
8.0), 7.73 (d, 2 H, J ) 8.3); 13C NMR (50 MHz) δ 12.1, 13.1,
21.3, 37.2, 38.9, 41.2, 44.1, 56.5, 60.8, 63.7, 80.2, 115.9, 124.5,
126.0, 127.3, 127.7, 129.4, 130.5, 133.6, 141.9, 144.2, 164.9,
194.6, 206.4. 17b: 1H NMR (200 MHz) δ 0.75 (t, 3 H, J ) 7.0),
1.12 (t, 3 H, J ) 7.0), 2.28 (dd, 1 H, J ) 18.0, 8.2), 2.56 (dd, 1
H, J ) 18.0, 3.7), 2.35 (s, 3 H), 2.55 (m, 2 H), 3.09 (d, 2 H, J
) 4.1), 3.26 (s, 3 H), 3.10-3.30 (m, 2 H), 3.35-3.55 (m, 2 H),
4.87 (dd, 1 H, J ) 8.2, 3.7), 5.27 (t, 1 H, J ) 4.1), 7.06 (td, 1 H,
J ) 7.4, 0.8), 7.30-7.40 (m, 2 H), 7.20 (d, 2 H, J ) 8.0), 7.65
(d, 2 H, J ) 8.0), 7.70 (d, 1 H, J ) 8.0); 13C NMR (50 MHz) δ
12.1, 13.1, 21.3, 38.4, 39.4, 41.3, 44.4, 57.0, 61.2, 64.4, 80.1,
115.4, 124.1, 127.6, 127.8, 127.3, 129.4, 130.0, 133.7, 142.3,
144.2, 165.1, 197.2, 205.5; MS (CI) m/z 499 (M + 1, 28), 370
(11), 201 (55), 343 (76), 100 (100) 72 (75); HRMS analysis (CI)
(()-2-Met h yl-4a â-n it r o-9-t osyl-1,4,4a ,9a â-t et r a h yd r o-
9H-ca r ba zole (5c). Elution with 20:1 heptane-ethyl acetate
(on silica gel) led to the recovery of unreacted dienophile 1c.
Earlier fractions afforded the nitroadduct 5c: IR 1560, 1600,
1
1362, 1170 cm-1; H NMR (200 MHz) δ 1.80 (s, 3 H), 2.32 (s,
3 H), 2.50-2.58 (dd, 1 H, J ) 15.4, 6.2), 2.68-2.75 (dd, 1 H, J
) 15.4, 4.8), 2.75-2.83 (dd, 1 H, J ) 15.4, 6.2), 2.99-3.04 (dd,
1 H, J ) 15.4, 4.8), 4.98 (t, 1 H, J ) 6.2), 5.42 (br t, 1 H), 7.08
(t, 1 H, J ) 7.5), 7.16 (d, 2 H, J ) 8.1), 7.28-7.39 (m, 2 H),
7.61 (d, 2 H, J ) 8.1), 7.62 (d, 1 H, J ) 7.5); 13C NMR (50
MHz) δ 21.6, 23.0, 33.4, 35.8, 66.0, 96.2, 116.0, 118.0, 124.7,
125.2, 127.4, 129.7, 131.6, 133.6, 137.6, 143.6, 144.6. Anal.
Calcd for C20H20N2O4S: C 62.48; H 5.24; N 7.29; S 8.34.
Found: C 61.88; H 5.33; N 7.39; S 8.45. Compound 5c had to
be immediately analyzed; otherwise, it rapidly decomposed into
carbazole 9.
2-Meth yl-9-tosyl-1,4-d ih yd r o-9H-ca r ba zole (7), 3-Meth -
yl-9-tosyl-1,4-d ih yd r o-9H-ca r ba zole (8), 2-Meth yl-9-tosyl-
9H-ca r ba zole (9), a n d 3-Meth yl-9-tosyl-9H-ca r ba zole (10).
Elution with 25:1 hexanes-ethyl acetate (on silica gel) led to
the recovery of unreacted dienophile 1c. Earlier fractions
afforded a 5:1 mixture of 7 and 8, and a second fraction a 5:1
mixture of 9 and 10. All the homologous benzenesulfonylated
derivatives were reported by Wenkert.8b,11
(()-4a â-(N,N-Dieth ylglyoxyla m id o)-4r-(N-p r op yla cety-
lam in o)-9-tosyl-1,4â,4a,9aâ-tetr ah ydr o-9H-car bazole (14b).
For the high-pressure reaction, elution with 2:1 heptane-ethyl
ether (on silica gel) led to the recovery of unreacted diene 3,
unreacted dienophile 1b, and finally to 14b as a light yellow
m/z calcd for C26H30N2O6S ) 498.1825, found (M + 1)+
)
499.1868, M+ ) 498.1845.
solid: mp 155 °C; IR 1705, 1645, 1630, 1599, 1360, 1171 cm-1
;
2-Hyd r oxy-9-tosyl-9H-ca r ba zole (12), (()-4â-Meth oxy-
4a â-n itr o-2-oxo-9-tosyl-1,2,3,4r,4a ,9aâ-h exa h yd r o-9H-ca r -
ba zole (16c), a n d (()-4r-Meth oxy-4a â-n itr o-2-oxo-9-tosyl-
1,2,3,4â,4a,9aâ-h exah ydr o-9H-car bazole (17c). Elution with
6:1 hexanes-ethyl acetate (on alumina) led to a first fraction
containing the hydroxycarbazole 12 (for the thermal reactions)
and a second fraction containing the unreacted dienophile 1c
(for the thermal reactions), and further elution afforded
consecutively 16c and 17c. 12: pale yellow plates; mp 41-
41.5 °C; IR 3200, 1377, 1173 cm-1; 1H NMR (200 MHz) δ 2.21
(s, 3 H), 6.89 (dd, 1 H, J ) 8.2, 2.4), 7.04 (d, 2 H, J ) 8.0),
7.24-7.38 (m, 2 H), 7.67-7.78 (m, 2 H), 7.66 (d, 2 H, J ) 8.0),
7.83 (d, 1 H, J ) 2.1), 8.22 (dd, 1 H, J ) 7.5, 1.2); 13C NMR (50
MHz) δ 21.2, 101.8, 112.6, 114.8, 118.9, 119.4, 120.7, 123.8,
125.8, 126.3, 127.6, 129.5, 134.6, 138.0, 139.5, 144.7, 156.1.
16c: white plates; mp 110 °C dec; IR 1728, 1599, 1558, 1466,
1H NMR (200 MHz) δ 0.74 (t, 3 H, J ) 7.3), 0.93 (t, 3 H, J )
7.0), 1.05 (t, 3 H, J ) 7.2), 1.25 (m, 1 H), 1.40 (m, 1 H), 1.77 (s,
3 H), 2.34 (s, 3 H), 2.25-2.35 (m, 2 H), 2.55-2.75 (m, 1 H),
2.92 (dm, 1 H, J ) 17.0), 3.12 (m, 2 H), 3.28 (m, 2 H), 4.71 (dd,
1 H, J ) 6.8, 3.4), 5.78 (dm, 1 H, J ) 10.0), 5.80 (br s, 1 H),
6.15 (m, 1 H), 6.85-7.00 (m, 1 H),7.22-7.30 (m, 2 H), 7.20 (d,
2 H, J ) 8.0), 7.62 (d, 2 H, J ) 8.0), 7.70-7.85 (m, 1 H); 13C
NMR (75 MHz) δ 11.8, 12.7, 14.0, 21.9, 22.1, 24.9, 27.4, 39.8,
42.5, 48.6, 52.4, 63.4, 65.0, 115.6, 124.7, 125.4, 126.7, 128.2,
129.3, 129.8, 130.1, 133.2, 143.8, 144.8, 165.3, 172.4, 198.8.
The main crystallographic parameters for this adduct are
available in the Supporting Information.
9-Tosyl-9-H-ca r ba zole (11),7 (()-4a â-Nitr o-4r-(N-p r o-
p yla cet yla m in o)-9-t osyl-1,4â,4a ,9a â-t et r a h yd r o-9H -ca r -
ba zole (14c), a n d (()-4-(N-P r op yla cetyla m in o)-9-tosyl-
1,4-d ih yd r o-9H-ca r ba zole (15).7 Elution with 15:1 hexanes-
ethyl acetate (on alumina) led to a first fraction of 11, then a
second fraction of unreacted indole 1c, and finally the dihy-
drocarbazole 15 for the thermal reaction or a mixture of 14c
and 15 for the high-pressure reactions. Compounds 11 and 15
were previously characterized.7 Due to nitrous acid elimination
produced by chromatography on neutral alumina, compound
14c could not be isolated, and consequently, it could not be
fully characterized.16 Selected spectral data for 14c: IR 1652,
1
1362, 1326, 1265, 1171, 1092 cm-1; H NMR (200 MHz) δ 1.9
(dd, 1 H, J ) 18.9, 2.5), 2.35 (s, 3 H), 2.67 (dd, 1 H, J ) 18.9,
3.0), 3.26 (d, 2 H, J ) 4.3), 3.35 (s, 3 H), 4.65 (br t, 1 H), 5.77
(t, 1 H), 7.05-7.25 (m, 1 H), 7.20 (d, 2 H, J ) 7.9) 7.40-7.50
(m, 1 H), 7.54 (d, 1 H, J ) 8.2), 7.66 (d, 2 H, J ) 7.9) 7.73 (d,
1 H, J ) 9.6); 13C NMR (50 MHz) δ 21.5, 37.4, 43.9, 58.0, 61.4,
80.2, 90.4, 116.5, 124.9, 125.0, 125.2, 127.5, 129.7, 132.7, 132.9,
142.4, 145.0, 204.0. 17c: white needles; mp 108-109 °C; IR
1732, 1596, 1556, 1466, 1362, 1269, 1171, 1090 cm-1; 1H NMR
(200 MHz) δ 2.06 (dd, 1 H, J ) 18.4, 10.0), 2.34 (s, 3 H), 2.72
(dd, 1 H, J ) 18.4, 4.5), 3.10 (dd, 2 H, J ) 5.5, 2.0), 3.33 (s, 3
H), 4.69 (dd, 1 H), 5.10 (br t, 1 H), 7.15 (d, 2 H, J ) 8.1), 7.15-
7.25 (m, 1 H), 7.47 (d, 2 H, J ) 8.1), 7.40-7.55 (m, 1 H), 7.6
(d, 1 H, J ) 7.6), 7.74 (d, 1 H, J ) 8.9); 13C NMR (50 MHz) δ
21.4, 39.9, 44.3, 58.0, 63.3, 77.8, 96.7, 116.7, 123.3, 125.0, 126.9,
129.4, 129.7, 132.3, 132.6, 143.0, 145.1, 202.7. The main
crystallographic parameters for this adduct are available in
the Supporting Information.
1
1600, 1590, 1371, 1158 cm-1; H NMR (200 MHz) δ 0.92 (t, 3
H, J ) 7.7), 1.60 (m, 2 H), 2.05 (s, 3 H), 2.35 (s, 3 H), 3.10 (m,
2 H), 3.1-3.25 y 3.25-3.35 (dm, 2 H, J ) 18.0), 5.53 (dm, 1 H,
J ) 9.5, 5.3), 5.69 (dd, 1 H, J ) 9.1, 4.0; m, 1 H), 6.05 (dm, 1
H, J ) 9.5), 7.1-7.8 (m, 7 H), 8.37 (d, 1 H); 13C NMR (75 MHz)
δ 11.5, 22.1, 22.3, 22.5, 23.6, 41.1, 61.9, 68.9, 97.0, 171.1.
(()-4a â-Acet yl-4â-m et h oxy-2-oxo-9-t osyl-1,2,3,4r,4a ,-
9a â-h exa h yd r o-9H -ca r b a zole (16a ) a n d (()-4a â-Acet yl-
4r-m eth oxy-2-oxo-9-tosyl-1,2,3,4â,4a ,9a â-h exa h yd r o-9H-
ca r ba zole (17a ). For the high-pressure reaction, elution with
5:1 hexanes-ethyl acetate (on alumina) led to the recovery of
unreacted dienophile, and further elution afforded a 1:1
mixture of diastereomers 16a and 17a , which were not
separated: IR 1716, 1600, 1361, 1168 cm-1. Selected data for
16a : 1H NMR (400 MHz) δ 2.07 (s, 3 H), 2.34 (s, 3 H), 3.31 (s,
(()-4â-Met h oxy-4a â-n it r o-9-t osyl-1,4r,4a ,9a â-t et r a h y-
d r o-9H-ca r ba zole (19), (()-4r-Meth oxy-4a â-n itr o-9-tosyl-
1,4â,4a ,9a â-t et r a h yd r o-9H -ca r b a zole (20), a n d (()-4-
Met h oxy-9-t osyl-1,4-d ih yd r o-9H -ca r b a zole (21). Elution
with 15:1 hexanes-ethyl acetate (on alumina) led to a first
fraction containing the carbazole 11,7 a second fraction con-
taining a mixture of 19 and 21 (which were not separated due

3912 J . Org. Chem., Vol. 66, No. 11, 2001
Biolatto et al.
to the ease of nitrous acid extrusion from 19, which readily
decomposed to form 21), and then a third fraction containing
the unreacted dienophile 1c and finally 20. Selected data for
Nos. 94-0858-007-056 and 96-00-024-161). B.B. thanks
the UNL’s Chemistry FOMEC Program Nï. 329 for the
partial contribution for her stay at the Universite´ de
Rouen, France. We also thank Professor Serge Piettre
from the Universite´ de Rouen, France, for his valuable
advice and for providing access to the high-pressure
apparatus. We thank Professor Gonza´lez Sierra from
the IQUIOS-Universidad Nacional de Rosario (Santa
Fe, Argentina) for the NMR experiments. We are
grateful to Professor Th. Eicher (Universita¨t des Saar-
landes) for the X-ray and high-resolution mass spec-
trometry facilities.
19: IR 1600, 1558, 1360, 1172 cm-1 1H NMR (200 MHz) δ
;
2.24 (s, 3 H), 2.76-2.79 and 2.82-2.87 (ddd, 1 H, J ) 16.4,
6.6, 2.7), 2.91-2.97 and 2.99-3.06 (two m, 1 H, J ) 3.0), 3.20
(s, 3 H), 4.6 (d, 1 H, J ) 5.5), 5.47 (dd, 1 H, J ) 5.9, 2.7), 5.77
(dm, 1 H, J ) 9.3, 2.7), 6.17 (m, 1 H), 6.95-7.82 (8 H); 13C
NMR (50 MHz) δ 21.4, 30.9, 56.8, 61.7, 75.7, 98.0. 20: IR 1600,
1558, 1362, 1170 cm-1 1H NMR (200 MHz) δ 2.26 (s, 3 H),
;
2.45-2.55 (dm, 1 H, J ) 16.9), 2.78-2.90 (ddd, 1 H, J ) 16.9,
6.3, 2.2), 3.44 (s, 3 H), 4.0 (dd, 1 H, J ) 4.0, 2.4), 4.17 (dd, 1 H,
J ) 6.0, 2.1), 5.61 (dm, 1 H, J ) 9.1, 2.9), 5.82 (m, 1 H), 6.90-
7.60 (8 H); 13C NMR (50 MHz) δ 21.3, 30.5, 58.4, 69.2, 82.7,
82.8, 115.3, 124.1, 126.3, 127.2, 127.5, 129.3, 129.6, 130.0,
133.1, 133.6, 143.4, 143.9. Selected data for 21: IR 1382, 1178
Su p p or tin g In for m a tion Ava ila ble: Main crystallo-
graphic parameters for adducts 14b and 16c, copies of 1H NMR
and 13C NMR spectra for compounds 12, 14b, 16b, 17b, 16c,
17c, and 20; 1H NMR spectra for compounds 14c:15, 16a :17a ,
19:21, and 15; and two-dimensional NMR for 16a :17a , 16c,
17c, 19:21, and 20. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
cm-1; H NMR (200 MHz) δ 2.27 (s, 3 H), 3.33 (s, 3 H), 4.75
(dd, 1 H, J ) 5.8, 1.9), 5.59 (dd, 1 H, J ) 9.6, 2.9), 5.91 (m, 1
H, J ) 3.5); 13C NMR (50 MHz) δ 21.5, 31.4, 58.3.
Ack n ow led gm en t. We are indebted to Universidad
Nacional del Litoral (UNL), Repu´blica Argentina. This
work received financial support from the Science and
Technology Secretariat-UNL-CAI+D Program (Project
J O0057856