New reactions of γ-halocarbanions: Simple synthesis of substituted tetrahydrofurans

Article abstract of DOI:10.1002/1521-3765(20020916)8:18<4234::AID-CHEM4234>3.0.CO;2-G

The treatment of 4-chlorobutyronitrile, 3-chloropropyl phenyl sulfone, and other related compounds with a base afforded γ-halocarbanions that undergo fast intramolecular substitution of the halogen to produce substituted cyclopropanes. We found that these short-lived carbanionic intermediates can be trapped with active external electrophilic partners, such as aldehydes, to give the aldol anions. These anions then undergo rapid intramolecular substitution of chloride to produce 2,3- disubstituted tetrahydrofurans. Under the right conditions, yields of tetrahydrofurans are excellent. Similar reactions with ketones gives 2,2,3-trisubstituted furans, but this process is usually less efficient. Ratios between the rates of intramolecular and intermolecular processes were qualitatively estimated by competitive experiments. It was shown that y-halo and y-trimethylammonium substituents substantially increase the kinetic CH acidity of alkane nitriles and sulfones.

Full text of DOI:10.1002/1521-3765(20020916)8:18<4234::AID-CHEM4234>3.0.CO;2-G

FULL PAPER
New Reactions of g-Halocarbanions:
Simple Synthesis of Substituted Tetrahydrofurans
Mieczys¯aw M aÀ kosza*and Marek Judka [a]
Dedicated to Professor Waldemar Adam on the occasion of his 65th birthday
Abstract: The treatment of 4-chlorobu-
tyronitrile, 3-chloropropyl phenyl sul-
fone, and other related compounds with
a base afforded g-halocarbanions that
undergo fast intramolecular substitution
of the halogen to produce substituted
cyclopropanes. We found that these
short-lived carbanionic intermediates
can be trapped with active external
electrophilic partners, such as aldehydes,
to give the aldol anions. These anions
then undergo rapid intramolecular sub-
stitution of chloride to produce 2,3-
disubstituted tetrahydrofurans. Under
the right conditions, yields of tetrahy-
drofurans are excellent. Similar reac-
tions with ketones gives 2,2,3-trisubsti-
tuted furans, but this process is usually
less efficient. Ratios between the rates
of intramolecular and intermolecular
processes were qualitatively estimated
by competitive experiments. It was
shown that g-halo and g-trimethylam-
monium substituents substantially in-
crease the kinetic CH acidity of alkane
nitriles and sulfones.
Keywords: aldol reaction ¥ carban-
ions ¥ kinetics ¥ ring formation ¥
tetrahydrofurans
Introduction
Carbanions that contain halogen substitutents are interesting
potential intermediates in organic synthesis. Thanks to the
presence of a strongly nucleophilic carbanionic center as well
as a leaving group in one molecule, such carbanions should be
able to enter a variety of reactions. Indeed, a-halocarbanions
have found wide application in organic synthesis as versatile
active intermediates. The most important reactions of a-
halocarbanions, namely the Darzens condensation,[ addi-
tions to electrophilic alkenes producing cyclopropanes,[ and
1]
2]
reactions with nitroarenes resulting in vicarious nucleophilic
substitution of hydrogen,[3] are shown in Scheme 1.
Scheme 1. Typical reactions of a-halocarbanions.
In contrast to a-halocarbanions, reactions of carbanions
that contain halogen atoms in other positions with respect to
the carbanionic center, namely b, g, and d, are practically
limited to intramolecular processes, such as the base-induced
halocarbanions to Michael acceptors[2] (Scheme 1b), or pro-
duced in the course of alkylation of methylenic carbanions
with 1,2-dihaloalkanes. An important group of processes
[4]
[6]
b-elimination that proceeds with a E1cb mechanism and
cyclization to form cyclopropane derivatives.[
5, 6]
Intermolec-
that proceed with g-halocarbanions are intramolecular sub-
stitution reactions, which are followed by further fast trans-
formations of the initially formed three-membered carbocy-
clic or heterocyclic rings. The Favorski reaction of a-halo-
dialkyl ketones[ and the Ramberg ± B‰cklund reaction of a-
halodialkyl sulfones[ belong to this category. The only
reported intermolecular reactions of b- and d-halocarbanions
is reprotonation observed as isotope exchange during mech-
anistic studies of E1cb b-elimination[ or formation of side-
ular reactions of such halocarbanions are essentially un-
known. It should be mentioned that the majority of examples
of intramolecular substitution giving cyclopropanes are re-
ported for g-halocarbanions generated by the addition of a-
7]
8]
[
a] Prof. M. M aÀ kosza, M. Judka
Institute of Organic Chemistry
Polish Academy of Science, ul. Kasprzaka 44
9]
0
1-224 Warszawa 42, POB 58 (Poland)
products in cycloalkylation of methylenic carbanions with 1,3-
Fax : (‡48)22-6326681
dihaloalkanes.[
6, 10]
In our literature search, we were not able
E-mail: icho-s@icho.edu.pl
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4
234±4240
to find any intermolecular reactions of g-halocarbanions. In
the only related paper, condensation of the tin enolate of g-
chlorobutyrophenone with aromatic aldehydes to give sub-
stituted tetrahydrofurans in moderate yields was reported; on
the other hand, the lithium enolate of this ketone does not
enter similar reaction with aldehydes.[
ans (Scheme 2). Yields of these products were somewhat
lower than the 3-cyano- and 3-phenylsulfonyl derivatives, but
were still of preparative value.
11]
In our preceding short communication, we reported that
the carbanion of g-chlorobutyronitrile generated under PTC
(
phase-transfer catalytic) conditions can be trapped by
external electrophilic reagents, aromatic aldehydes for exam-
ple, to produce the corresponding aldol-type anions which
enter further intramolecular reactions to give 2-aryl-3-cyano-
tetrahydrofurans.[
12]
Scheme 2. Synthesis of cyclopropanes and tetrahydrofurans through
intramolecular and intermolecular reactions of g-chlorocarbanions.
a) tBuOK, À308C, 0.5m solution of 1, 2, 3 in THF.
Substituted tetrahydrofuran rings are present in numerous
[13]
natural products and there is a great interest in methods of
constructing such rings.[ The most common strategies that
have been used to construct tetrahydrofuran rings is the
formation of carbon ± oxygen bonds by means of acid-
catalyzed cyclizations.[ Recently, a variety of functionalized
14]
Under identical conditions, but without aldehydes, all of
these carbanion precursors cyclized to the corresponding
cyclopropanes 1a ± 3a in high yields. The reaction and results
are presented in Scheme 2 and Table 1.
15]
2-alkylidenetetrahydrofuran derivatives were obtained by
cyclization reactions of 1,3-dicarbonyl dianions and 1,3-bis-
silyl enol ethers.[ Di- and trisubstituted tetrahydrofurans can
16]
Table 1. Reactions of g-chlorocarbanions with aldehydes.[a]
[17]
be produced by the oxidation of dienes,
and metal-
Reactants
R
Products
Tetra-
hydrofuran
catalyzed cycloisomerization of allyl propargyl ethers.[ On
the other hand, there are limited examples of cyclization to
form 2,3-disubstituted tetrahydrofurans.
18]
Y
Cyclo-
propane
%
89
%
trans/cis
ratio
±[b]
Ph
p-ClPh
p-MePh
CN
CN
CN
CN
CN
1
1
1
1
1
2
2
2
2
2
2
2
3
3
3
3
1a
1a
1a
1a
±
±
78
77
82
76
±
±
In this paper, we report a full account of our studies of
reactions of g-halocarbanions with aldehydes and ketones.
This represents a new and general method for the synthesis of
21 1b
16 1c
14 1d
15 1e
79/21
79/21
81/19
69/31
±
PhCHˆCH 1a
2,3-substituted tetrahydrofurans.
[
b]
PhSO
PhSO
PhSO
PhSO
PhSO
PhSO
PhSO
2
2
2
2
2
2
2
±
2a
2a
2a
2a
94
0
±
2b
Ph
p-ClPh
p-MePh
95 100/0
83 100/0
88 100/0
82 100/0
35 100/0
76 100/0
15 2c
2d
15 2e
62 2 f
10 2g
8
Results and Discussion
PhCHˆCH 2a
Et(Me)CH 2a
Because of the rather low C ± H acidity of g-chlorobutyroni-
trile, its deprotonation with concentrated aqueous NaOH
under PTC (phase-transfer catalytic) conditions is rather a
slow process; thus the PTC reactions of this nitrile with
aldehydes were accompanied by partial decomposition of the
[c]
(Me
3
)C
2a
3a
3a
3a
3a
[
b]
COOtBu
COOtBu
COOtBu
COOtBu
±
76
±
±
±
Ph
p-ClPh
p-MePh
15 3b
28 3c
32 3d
61 100/0
44 100/0
61 100/0
[
a] Notations as in Scheme 2, all reactions, except with aliphatic aldehydes,
latter. As a consequence, the yields of the substituted
cyanotetrahydrofurans reported in our communication,[12]
were carried out with 0.5m solutions of 1, 2, and 3 in THF. [b] Experiments
without aldehydes. [c] Only one isomer, apparently the trans isomer, was
produced; its geometry was not determined unambiguously.
although usually good, were far from being excellent. In
order to improve the results and expand the scope of this new
synthetic method, we have used stronger bases and also other
precursors of g-halocarbanions. In preliminary experiments,
we found that tBuOK in THF is the most convenient and
efficient base/solvent system for this reaction. Treatment of an
equimolar mixture of 4-chlorobutyronitrile (1) and benzalde-
hyde in concentrated THF solution with tBuOK at À308C
resulted in a fast reaction to give the expected 2-phenyl-3-
cyanotetrahydrofuran in 78% yield of isolated product. A
similar reaction proceeded with other aromatic aldehydes and
also cinnamaldehyde. In all cases, yields of the substituted
tetrahydrofurans exceeded 76%. The reaction was equally
efficient when 3-chloropropyl phenyl sulfone (2) and alde-
hydes in THF were treated with tBuOK. The expected 2-aryl-
Since there are two competing processes in the reaction
system, namely monomolecular reaction of intramolecular
nucleophilic substitution producing cyclopropanes and bimo-
lecular intermolecular addition as a step in the formation of
tetrahydrofurans, the outcome of this competition should be
affected, inter alia, by concentration and ratio of the reacting
partners.
The results presented in Table1 1 were obtained under
standard conditions: the carbanion precursors and aldehydes
were used in a ratio close to equimolar (1:1.2), whereas the
concentration of the carbanion precursor in the THF solution
was 0.5m. Under such conditions, the reaction of 2 with
benzaldehyde gave the corresponding substituted tetrahydro-
furan 2b exclusively with a yield of 95%. When the
concentration of the reacting species was lower, for example,
3-phenylsulfonyltetrahydrofurans were obtained in yields
exceeding 82%. Also tert-butyl-4-chlorobutyrate (3) enters
this reaction to give 2-aryl-3-carbo-tert-butoxytetrahydrofur-
Chem. Eur. J. 2002, 8, No. 18
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M. M aÀ kosza and M. Judka
FULL PAPER
the concentration of 2 was 0.1m and 0.05m, the competing
process of intramolecular cyclization become important:
yields of 2b and 2a were 79%, 17% and 74%, 22%,
respectively. Thus, the ratio of the cyclopropanes to tetrahy-
drofurans can be changed in favor of the latter when
aldehydes were used in substantial excess and the reaction
was carried out in more concentrated solutions. For example,
in the reaction of 1 with benzaldehyde, when the concen-
tration of 1 in THF was 1.14m and the ratio 1:benzaldehyde
was 1:2.4, 1a was produced with a high yield of 90%.
decided by the addition step, which can produce threo and
erythro isomers of the aldol anions that cyclize to trans- and
cis-disubstituted tetrahydrofurans, respectively. In both of
these cases, steric interactions of the aryl groups of aldehydes
and Z groups promote the formation of the less hindered
isomer of the tetrahydrofuran or the aldol. Since this
interaction is the smallest in the case of 1, in which Z is a
small cyano group, substantial amounts of the cis isomers
were formed only in these cases. To clarify which step is
decisive for the stereochemical outcome of the reaction, pure
trans 1b was subjected to the reaction conditions. It gave a
mixture of trans- and cis-1b identical to that produced in the
reaction between 1 and benzaldehyde. Therefore, it appears
that the composition of the product mixture reflects the
thermodynamic stabilities of the isomers. This conclusion is
supported by the observation that the composition of the
mixture of cis- and trans-1b produced according to Scheme 2
is not affected by the reaction time.
The possibility of synthesizing tetrahydrofurans by the
reaction of g-chlorocarbanions with aldehydes depends upon
a delicate balance between intramolecular substitution pro-
ducing cyclopropane ring, which is known to be a very fast
process, and intermolecular addition to the carbonyl groups.
To estimate the relationship between the rates of the
processes involved and the lifetime of the g-chlorocarbanions,
a solution of 1 in THF at low temperature was first treated
with base in THF, and then benzaldehyde was added after a
short time. Even when the base was added at À708C and the
mixture treated immediately with benzaldehyde, only the
cyclopropane 1b was produced. A similar result was obtained
in an identical experiment with 2. These observations indicate
that deprotonation and intramolecular cyclization are really
very fast processes that cannot be studied by simple methods.
On the other hand, when g-chlorocarbanion precursor 1 or 2
was treated with base in the presence of benzaldehyde,
practically only the tetrahydrofurans were produced. This
indicates that rate of the addition of these carbanions to
benzaldehyde is much higher than rate of the cyclization. To
estimate the rate of intramolecular substitution of the halogen
with the aldol anion, which leads to a five-membered
tetrahydrofuran ring, the reaction mixture of 2 and benzalde-
hyde upon addition of tBuOK was immediately treated with
MeI, a very active alkylating agent. No traces of the O-
methylated aldol product were observed indicating that this
intramolecular substitution is also a very fast process. The
same results were obtained when trimethylsilyl chloride was
used instead of the MeI. Even when a mixture of 2,
benzaldehyde, and MeI were treated with tBuOK, the
reaction gave exclusively tetrahydrofuran 2b. Thus, intra-
molecular substitution of a moderately active leaving group,
such as chloride, by the alkoxide anion of the aldol to form the
five-membered ring of tetrahydrofuran proceeds much faster
than its intermolecular reaction with very active alkylating
and silylating agents (Scheme 3). Surprisingly, the rate of
cyclization to produce a five-membered ring by intramolec-
ular substitution of the chloro substituent which is a moder-
ately active leaving group, was very high.
The successful synthesis of substituted tetrahydrofurans, as
shown in Scheme 2, indicates that potassium salts of the
corresponding g-chlorocarbanions stabilized with CN, SO Ph,
2
and COOtBu groups enter fast intermolecular reactions with
active external electrophilic partners, such as aromatic
aldehydes, to produce aldol anions that subsequently undergo
an intramolecular substitution of the chloride to produce
tetrahydrofurans. In the case of carbanions of 1 and 2, the rate
of intermolecular addition under the standard conditions was
much faster than intramolecular substitution, so substituted
tetrahydrofurans were the dominant products, whereas cyclo-
propanes 1a and 2a were formed in small quantities. On the
other hand, under these conditions, the rate of addition of the
carbanion of 3 to aldehydes was only somewhat higher than its
intramolecular cyclization.
Thus the base-promoted reactions of g-chlorobutyronitrile,
g-chloropropyl phenyl sulfone, and tert-butyl g-chlorobuty-
rate with aromatic aldehydes is an efficient way of synthesiz-
ing 2-aryl-3-substituted tetrahydrofurans. The reaction is less
efficient with aliphatic aldehydes. For instance, in the reaction
of 2 with butyraldehyde under the standard conditions, the
expected substituted tetrahydrofuran was formed in low yield.
A somewhat better result was obtained in the reaction of 2
with 2-methylbutyraldehyde carried out in a more concen-
trated system, namely a 1m solution of 2 in THF with a 35%
yield of 2 f. It appears that the reason for this is the high CH
acidity of the CH and CH groups a to the carbonyl group of
2
the aldehydes. Thus, their deprotonation followed by trans-
formations of the produced enolates dominated compared to
the desired reactions. Indeed, the reaction of 2 with pivalyl
aldehyde gave the expected tetrahydrofuran 2g in a yield
similar to that obtained with aromatic aldehydes.
In the reaction of the g-chlorocarbanions with aldehydes,
the substituted tetrahydrofurans can be formed as two
geometrical isomers. Indeed, in our preliminary communica-
tion, we reported that the PTC reaction of g-chlorobutyroni-
trile (1) with aldehyde gave mixtures of cis and trans isomers
of 2-aryl-3-cyanotetrahydrofurans, the latter being the major
products.[ Under the conditions used in the present studies,
the reaction of 1 with aldehydes also produced mixtures of cis
and trans tetrahydrofurans in ratios of approximately 4:1,
whereas the other carbanion precursors, 2 and 3, practically
only gave trans isomers of the tetrahydrofurans. There are two
possibilities concerning the factors which control the stereo-
chemical outcome of these reactions: 1) substituted tetrahy-
drofurans, which are still C ± H acids, can undergo epimeriza-
tion under the reaction conditions so the composition of the
products reflects their thermodynamic stability. 2) Epimeri-
zation does not proceed so that the ratio of stereoisomers is
12]
Any changes that favor intramolecular substitution or
disfavor the addition should shift the reaction towards the
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b-Halocarbanions
4234±4240
derivative of cyanophenylsulfonylotetrahydrofuran (2h).
When cyclohexanone was used in a substantial excess, fivefold
relative to 2, and in a concentrated system (concentration of
2
ˆ 0.9m), the addition was favored and the yield of 2h
improved to 35%. Under similar conditions and threefold
excess of the ketone, the reaction of 2 with the more
electrophilic a,a,a-trifluoroacetophenone proceeded satisfac-
torily to give 2-trifluoromethyl-2-phenyl-3-phenylsulfonyl-
tetrahydrofuran (2i) in 70% yield as a mixture of two
geometrical isomers, whereas 2a was formed in 13% yield
Scheme 3. Competition between intermolecular and intramolecular reac-
(
Scheme 5). The mixture was separated by chromatography to
give two products with melting points of 968C and 1028C in a
:3.4 ratio. The steric structures of these isomers were not
tions in THF solutions. a) tBuOK, À708C; b) PhCHO, c) MeI or Me
3
SiCl.
1
formation of cyclopropanes, at the expense of the formation
of tetrahydrofurans. Thus, one can expect that the corre-
sponding g-bromocarbanions, generated from 4-bromobuty-
ronitrile and 3-bromopropyl phenyl sulfone, should cyclize
faster than their chloro analogues. Indeed, the reaction of
these compounds with benzaldehyde in the presence of
tBuOK under the standard conditions (0.5m concentration
of 1 and 2 in THF) gave exclusively the corresponding
cyclopropanes 1a and 2a, while formation of the tetrahydro-
furans was not observed. One should stress that under the
same conditions, the reaction of chlorosulfone 2 with benzal-
dehyde gives the tetrahydrofuran derivative 2b in 95% yield.
When the reaction of these bromocarbanion precursors was
carried out in a more concentrated solution (0.91m) and 50%
excess of benzaldehyde (ratio 1:1.5) was used, namely
conditions that should favor the intermolecular reaction,
compounds 1b and 2b were obtained in a small, but essential,
yield of 25% and 27%, respectively.
The rate of addition of carbanions to the carbonyl group is
strongly affected by steric effects. Usually, additional sub-
stituents at the carbanionic center decelerate this process.
Indeed, the reaction of an equimolar mixture of 4-chloro-2-
phenylbutyronitrile (4) and benzaldehyde under the standard
conditions gave only 1-cyano-1-phenylcyclopropane (4a),
while the formation of the tetrahydrofuran derivative was
not observed. The substituted tetrahydrofuran 4b was only
formed when benzaldehyde was used in a substantial excess,
albeit still in low yield of 9% (Scheme 4).
determined.
Scheme 5.
These results confirm that nucleophilic addition to the
carbonyl group of ketones proceeded more slowly than that to
the aromatic aldehydes, whereas the highly electrophilic
ketone a,a,a-trifluoroacetophenone is almost as active as
aldehydes.
Halogen substituents provide stabilizing effects in a-
halocarbanions and facilitate their generation, hence many
reactions of such carbanions can be carried out in the presence
of concentrated aqueous NaOH and phase-transfer catalysts
(
PTC conditions). However, nothing is known about carban-
ion-stabilizing effects of halogens in the g-position to the
carbanionic center. The observation that g-chlorobutyroni-
trile reacts via its carbanion under the PTC conditions,
being deprotonated by concentrated aqueous NaOH in the
presence of Q X , whereas butyronitrile does not, suggests
[12, 19]
‡
À
that Cl in the g position to the CH group exerts a noticeable
2
carbanion-stabilizing effect. To make a qualitative estimation
of how strong this effect of Cl and some other g substituents is
on the CH acidity of the CH group a to CN and SO Ph, we
2
2
measured the rate of base-catalyzed deuterium exchange in
XCH CH CH Y compounds. When Y is CN or SO Ph, the
2
2
2
2
Scheme 4.
exchange takes place at the CH group a to Y. For reasons of
2
simplicity, the time to 50% conversion was measured
(Table 2).
It is known that nucleophilic addition to the carbonyl group
of ketones proceeds more slowly than that to the carbonyl
group of aldehydes. Indeed, attempts to use ketones in the
reaction with g-chlorocarbanions to produce 2,2,3-trisubsti-
tuted tetrahydrofurans were less successful. The reaction of 2
with cyclohexanone, carried out under the standard condi-
tions, which in the reaction with benzaldehyde assures a high
yield 95% of the tetrahydrofuran 2b, gave mostly cyclo-
propane 2a in 84% yield and only 5% of the expected spiro
The exchange was carried out in protic media assuring rapid
reprotonation of the generated carbanions so that the
observed rate of deuterium incorporation was limited by the
rate of deprotonation, hence it reflects the kinetic CH acidity.
The results indicate that g-halo substituents do indeed
substantially accelerate the deprotonation rate of butyroni-
trile and propyl phenyl sulfone, hence they exert a strong
carbanion-stabilizing effect. In this series of measurements,
Chem. Eur. J. 2002, 8, No. 18
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M. M aÀ kosza and M. Judka
FULL PAPER
Table 2. Deuterium exchange of g-substituted butyronitriles and propyl
phenyl sulfones.
for synthesis and open new possibilities that are presently
being explored. Strong effects of halogen and trimethylam-
monium substituents in the g-position that increase the CH
acidity needs further study and rationalization.
1
Y
X
t /
2
[s]
CN
CN
CN
CN
H
64800
324
254
13[c]
900
43
22
17
1.2[c]
Cl
Br
Me
H
Experimental Section
‡
‡
[b]
[b]
3
3
N
N
SO
SO
SO
SO
SO
2
Ph
Ph
Ph
Ph
Ph
All reactions were performed under argon in oven-dried glassware. THF
2
2
2
2
F
1
13
was freshly distilled from sodium/benzophenone. H NMR and C NMR
spectra were recorded on a Varian Gemini 200 MHz and Varian Mercury
Cl
Br
Me
4
00 MHz.
General procedure for the reaction of 1 ± 3 with aldehydes–synthesis of
tetrahydrofurans: A solution of the carbanion precursor 1 ± 3 (2.5 mmol)
and aldehyde (3 mmol) in THF (5 mL) was cooled to À308C, and
commercial (99%) potassium tert-butoxide (0.505 g, 4.5 mmol) was added
in 3 ± 4 portions at this temperature. The mixture was stirred for 20 min,
[
a] 10% NaOD/D
2
O (1 part), EtOD (1.4 parts) DMSO (1 part), 218C.
[
b] In the form of chlorides. [c] Value recalculated from experiments
without DMSO.
quenched with aqueous NH
organic phase was dried (MgSO
was purified by column chromatography on silica gel or preparative TLC
hexane/ethyl acetate). Ratio of cyclopropanes 1a ± 3a to tetrahydrofurans
was determined by gas-chromatographic analyses of the mixtures formed in
analogous experiments carried out with diphenyl as an internal standard.
4
Cl (20 mL), and extracted with CH
2 2
Cl . The
4
), and the solvent evaporated. The residue
we have also included the corresponding tetraalkylammoni-
um salts: g-trimethylammonia-butyronitrile chloride,
(
À
‡
Cl Me N CH CH CH CN (5), and 3-trimethylammoniaprop-
3
2
2
2
À
‡
yl phenyl sulfone chloride, Cl Me N CH CH CH SO Ph (6).
3
2
2
2
2
Isotope-exchange experiments:
prepared by dissolution of Na
A
solution of 10% NaOD in
2
D O
Interestingly, the deuterium exchange in these compounds
was much faster than for X ˆ Cl, Br, and F. Thus, measure-
ments were made under milder conditions and the corre-
sponding data in Table 2 was recalculated for the general
conditions. The nature of the carbanion-stabilizing action of
the electron-withdrawing substituents in the g-position is
presently unclear.
The observation that the acidity of 3-trimethylammonia
propyl phenyl sulfone chloride (6) is substantially higher than
that of the chlorosulfone 2, whereas the trimethylammonium
substituent is a less efficient leaving group than chloride,
suggested the possibility of obtaining the aldol produced by
addition of the carbanion of 6 to aldehydes. The reaction of 6
with benzaldehyde in the presence of tBuOK under the
standard conditions produced a complicated mixture of
compounds, which was not separated. Attempts to trap the
intermediate aldol with MeI resulted in the formation of
(
2
O (0.75 g) in D O (9.2 g)), EtOD (14 g),
2
and DMSO (10 g) was used. The carbanion precursor (0.5 mmol) was
dissolved in this solution (1.7 g) and stirred at 218C for a given time. The
mixture was acidified with dilute HCl, extracted with Et O, and the product
2
1
analyzed by H NMR spectroscopy. In the case of the ammonium salts 5
and 6, the acidified mixture was evaporated to dryness, the solid extracted
1
with DMSO, and the solution analyzed by H NMR spectroscopy.
Cyclopropyl cyanide (1a):[20] 1H NMR (200 MHz, CDCl
): d ˆ 0.98 ± 1.18
3
(
m, 4H), 1.30 ± 1.42 ppm (m, 1H).
2
-Phenyl-3-cyanotetrahydrofuran (1b):[12] trans Isomer: Oil; 1H NMR
(
200 MHz, CDCl
3
): d ˆ 2.32 ± 2.63 (m, 2H), 2.74 ± 2.97 (m, 1H), 4.06 ± 4.33
3
(m, 2H) , 4.99 (d, J(H,H) ˆ 7.70 Hz, 1H), 7.34 ± 7.48 ppm (m, 5H);
1
3
C NMR (50 MHz, CDCl
29.14, 129.32, 139.20 ppm.
3
): d ˆ 31.71, 37.67, 68.57, 84.25, 120.40, 126.01,
1
1
cis Isomer: Oil; H NMR (200 MHz, CDCl
3
): d ˆ 2.37 ± 2.60 (m, 2H), 3.39 ±
3
3
.48 (m, 1H), 3.97 ± 4.09 (m, 1H), 4.32 ± 4.43 (m, 1H), 5.01 (d, J(H,H) ˆ
13
6
.08 Hz, 1H), 7.34 ± 7.47 ppm (m, 5H); C NMR (50 MHz, CDCl
3
): d ˆ
31.96, 37.22, 67.91, 82.10, 119.55, 126.63, 129.03, 129.13, 137.65 ppm.
2-(4-Chlorophenyl)-3-cyanotetrahydrofuran (1c):[12]
1
-phenyl-2-phenylsulfonyl butadiene (6a) in moderate yield.
trans Isomer: Oil;
1
H NMR (200 MHz, CDCl ): d ˆ 2.37 ± 2.52 (m, 2H),
3
3
This diene was obtained as the main product, in 62% yield
when a mixture of 6, benzaldehyde, and MeI was treated with
excess tBuOK. Apparently, the methyl ether produced by
methylation of the aldol undergoes E1cb elimination followed
by the Hofmann elimination of trimethyl amine (Scheme 6).
2.74 ± 2.86 (m, 1H), 4.01 ± 4.27 (m, 2H), 4.90 (d, J(H,H) ˆ 7.74 Hz, 1H),
13
7
8
.26 ± 7.47 ppm (m, 4H); C NMR (50 MHz, CDCl
3
): d ˆ 31.63, 37.70, 68.59,
3.56, 120.06, 127.40, 129.50, 134.92, 137.68 ppm.
1
cis Isomer: Oil; H NMR (200 MHz, CDCl
3
): d ˆ 2.42 ± 2.54 (m, 2H), 3.35 ±
3
3
6
3
.45 (m, 1H), 3.97 ± 4.09 (m, 1H), 4.31 ± 4.42 (m, 1H), 4.98 (d, J(H,H) ˆ
13
.04 Hz, 1H), 7.32 ± 7.46 ppm (m, 4H); C NMR (50 MHz, CDCl
3
): d ˆ
1.93, 37.17, 67.97, 81.48, 119.29, 128.05, 129.26, 134.89, 136.17 ppm.
2
-(4-Methylphenyl)-3-cyanotetrahydrofuran (1d):[12]
1
trans Isomer: Oil; H NMR (200 MHz, CDCl
3
): d ˆ 2.40 (s, 3H), 2.31 ± 2.60
3
(
7
m, 2H), 3.38 (m, 1H), 4.04 ± 4.32 (m, 2H), 4.96 (d, J(H,H) ˆ 7.90 Hz, 1H),
13
.20 ± 7.36 ppm (m, 4H); C NMR (50 MHz, CDCl
3
): d ˆ 21.83, 31.69, 37.66,
6
8.47, 84.23, 120.47, 126.01, 129.97, 136.17, 138.94 ppm.
1
cis isomer: Oil; H NMR (200 MHz, CDCl
3
): d ˆ 2.41 (s, 3H), 2.40 ± 2.53
(
(
m, 2H), 3.35 ± 3.45 (m, 1H), 3.94 ± 4.07 (m, 1H), 4.27 ± 4.42 (m, 1H), 4.97
3
13
d, J(H,H) ˆ 6.22 Hz, 1H), 7.18 ± 7.36 ppm (m, 4H); C NMR (50 MHz,
): d ˆ 21.82, 31.93, 37.23, 67.83, 82.06, 119.55, 126.57, 129.72, 134.52,
138.82 ppm.
CDCl
3
Scheme 6. Reaction of the carbanion of 3-trimethylammoniapropyl phe-
nyl sulfone with benzaldehyde and methyl iodide. a) tBuOK, b) MeI.
-(2-Phenylvinyl)-3-cyanotetrahydrofuran (1e):[12]
2
1
trans Isomer: oil; H NMR (200 MHz, CDCl
3
): d ˆ 2.21 ± 2.56 (m, 2H), 2.84
3
(
6
dt, J(H,H) ˆ 8.92 , 7.69 Hz, 1H), 3.97 ± 4.20 (m, 2H), 4.56 ± 4.64 (m, 1H),
The observation that active electrophiles, such as alde-
hydes, can efficiently trap short-lived g-halocarbanions to
produce substituted tetrahydrofurans have substantial value
3
.20 (dd, J ˆ 6.70, 15.88 Hz, 1H), 6.81 (dd, J(H,H) ˆ 15.81, 1.12 Hz, 1H),
13
7
.30 ± 7.49 ppm (m, 5H); C NMR (50 MHz, CDCl
3
): d ˆ 31.46, 35.54,
68.18, 83.52, 120.28, 125.99, 127.30, 128.88, 129.21, 134.15, 136.24 ppm.
4238
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 0947-6539/02/0818-4238 $ 20.00+.50/0 Chem. Eur. J. 2002, 8, No. 18

b-Halocarbanions
4234±4240
1
cis Isomer: Oil; H NMR (200 MHz, CDCl
3
): d ˆ 2.37 ± 2.49 (m, 2H), 3.24 ±
141.65, 172.49 ppm; elemental analysis calcd (%) for C15
72.55, H 8.12; found: C 72.43, H 8.15.
20 3
H O (248.32): C
3
6
1
6
.34 (m, 1H), 3.89 ± 4.01 (m, 1H), 4.17 ± 4.30 (m, 1H), 4.57 ± 4.64 (m, 1H),
3
3
.34 (dd, J(H,H) ˆ 6.96, 15.79 Hz ,1H), 6.80 (dd, J(H,H) ˆ 1.02, 15.88 Hz,
trans-2-(4-Chlorophenyl)-3-tert-butoxycarbonyl tetrahydrofuran (3c): Oil;
1
3
H), 7.30 ± 7.52 ppm (m, 5H); C NMR (50 MHz, CDCl
3
): d ˆ 31.70, 35.37,
1
H NMR (400 MHz, CDCl
.83 (m, 1H), 3.99 ± 4.04 (m, 1H), 4.11 ± 4.16 (m, 1H), 4.95 (d, J(H,H) ˆ
3
): d ˆ 1.44 (s, 9H), 2.20 ± 2.35 (m, 2H), 2.77 ±
7.66, 80.64, 119.53, 124.99, 127.45, 128.85, 129.16, 135.06, 136.39 ppm.
3
2
Cyclopropyl phenylsulfone (2a):[21, 22] M.p. 338C (EtOH); 1H NMR
200 MHz, CDCl
m, 1H), 7.52 ± 7.70 (m, 2H), 7.89 ± 7.94 ppm (m, 3H).
13
7.42 Hz, 1H), 7.30 ppm (s, 4H); C NMR (100 MHz, CDCl
30.49, 53.40, 68.42, 81.24, 82.76, 127.18, 128.47, 133.26, 140.17, 172.21 ppm;
elemental analysis calcd (%) for C15 (282.77): C 63.71, H 6.77, Cl
2.54; found: C 63.52, H 6.82, Cl 12.60.
3
): d ˆ 28.02,
(
(
3
): d ˆ 0.98 ± 1.09 (m, 2H), 1.31 ± 1.40 (m, 2H), 2.41 ± 2.54
H
19ClO
3
1
trans-2-Phenyl-3-phenylsulfonyl tetrahydrofuran (2b): M.p. 848C (EtOH);
H NMR (200 MHz, CDCl
1
trans-2-(4-Methylphenyl)-3-tert-butoxycarbonyl tetrahydrofuran (3d):
3
): d ˆ 2.18 ± 2.38 (m, 1H), 2.46 ± 2.60 (m, 1H).
1
3
Oil; H NMR (400 MHz, CDCl ): d ˆ 1.44 (s, 9H), 2.18 ± 2.35 (m, 2H),
3
1
3
6
1
.65 ± 3.74 (m, 1H), 4.02 (dt, J(H,H) ˆ 6.62, 8.75 Hz, 1H), 4.12 ± 4.23 (m,
3
3
H), 5.33 (d, 3J(H,H) ˆ 5.24 Hz, 1H), 7.11 ± 7.28 (m, 5H), 7.49 ± 7.70 (m,
2.33 (s, 3H), 2.85 (dt,
J(H,H) ˆ 8.97, 7.32 Hz, 1H), 3.97 ± 4.03 (m, 1H),
3 3
1
3
4.10 ± 4.16 (m, 1H), 4.95 (d, J(H,H) ˆ 7.32 Hz, 1H), 7.14 (d, J(H,H) ˆ
H), 7.87 ± 7.93 ppm (m, 2H); C NMR (100 MHz, CDCl
3
): d ˆ 28.50,
13
7
.86Hz, 2H), 7.24 ± 7.26 ppm (m, 2H); C NMR (100 MHz, CDCl
3
): d ˆ
1.09, 28.01, 30.53, 53.27, 68.29, 80.93, 83.41, 125.71, 128.98, 137.16,
72.59 ppm; elemental analysis calcd (%) for C16 (262.35): C 73.25,
8.36, 71.10, 80.03, 125.65, 127.92, 128.47, 128.59, 129.35, 133.96, 138.09,
40.27 ppm; elemental analysis calcd (%) for C16 S(288.36): C 66.64,
H 5.59, S11.12; found: C 66.48, H 5.54, S11.15.
2
1
16 3
H O
22 3
H O
H 8.15; found: C 73.20, H 8.57.
trans-2-(4-Chlorophenyl)-3-phenylsulfonyl tetrahydrofuran (2c): M.p.
88C (EtOH); H NMR (200 MHz, CDCl
1
The reaction of 2 with cyclohexanone–synthesis of 2,2-pentamethylene-3-
phenylsulfonyl tetrahydrofuran (2h): The procedure given above was
followed with 2 (1.5 mmol), THF (1 mL), and cyclohexanone (0.735 g,
8
2
1
3
6
1
5
3
): d ˆ 2.15 ± 2.35 (m, 1H),
3
.43 ± 2.52 (m, 1H), 3.57 ± 3.62 (m, 1H), 4.00 (dt, J(H,H) ˆ 6.41, 8.75 Hz,
H), 5.31 (d, 3J(H,H) ˆ 5.34 Hz, 1H), 7.09 ± 7.27 (m, 4H), 7.51 ± 7.72 (m,
1
1
3
7.5 mmol). Yield of 2h 35%, m.p. 978C (EtOH); H NMR (400 MHz,
H), 7.87 ± 7.93 ppm (m, 2H); C NMR (100 MHz, CDCl
3
): d ˆ 28.69,
CDCl
3
): d ˆ 1.19 ± 1.31 (m, 1H), 1.52 ± 1.70 (m, 6H), 1.86 ± 2.13 (m, 4H),
8.40, 71.09, 79.34, 127.15, 128.59, 128.64, 129.44, 133.73, 134.10, 138.02,
38.85 ppm; elemental analysis calcd (%) for C16 S(322.81): C
9.53, H 4.68, S9.93, Cl 10.98; found: C 59.29, H 4.68, S9.73, Cl 10.71.
3
2
3
.45 ± 2.54 (m, 1H), 3.20 (t, J(H,H) ˆ 9.33 Hz, 1H), 3.73 ± 3.79 (m, 1H),
H
15ClO
3
3
.96 (dt, J(H,H) ˆ 4.20 , 8.97 Hz, 1H), 7.55 ± 7.67 (m, 3H), 7.88 ± 7.92 ppm
1
3
(
m, 2H); C NMR (100 MHz, CDCl
7.34, 63.43, 71.26, 83.78, 128.03, 129.23, 133.58, 140. 59 ppm; elemental
analysis calcd (%) for C15 S(280.38): C 64.26, H 7.19, S11.43; found: C
4.40, H 7.02, S11.43.
Synthesis of 2-trifluoromethyl-2-phenyl-3-phenylsulfonyl tetrahydrofuran
2i) and 2,3-diphenyl-3-cyano tetrahydrofuran (4b): The procedure given
above was used with the precursors of carbanion 2 or 4 (1 mmol), THF
0.6 mL), and the carbonyl compound (3 mmol).
3
): d ˆ 21.60, 22.96, 25.21, 28.61, 30.45,
trans-2-(4-Methylphenyl)-3-phenylsulfonyl tetrahydrofuran (2d): M.p.
3
1
9
(
8
(
48C (EtOH); H NMR (200 MHz, CDCl
3
): d ˆ 2.30 (s, 3H), 2.18 ± 2.38
20 3
H O
3
m, 1H), 2.46 ± 2.61 (m, 1H), 3.63 ± 3.72 (m, 1H), 4.00 (dt, J(H,H) ˆ 6.51,
6
3
.81 Hz, 1H), 4.11 ± 4.21 (m, 1H), 5.29 (d, J(H,H) ˆ 5.13, 1H), 6.99 ± 7.09
1
3
m, 4H) 7.49 ± 7.70 (m, 3H), 7.86 ± 7.92 ppm (m, 2H); C NMR (100 MHz,
CDCl
): d ˆ 21.03, 28.51, 68.27, 71.11, 79.99, 125.59, 128.60, 129.14, 129.33,
33.91, 137. 28, 137.67, 138.16 ppm; elemental analysis calcd (%) for
S(302.39): C 67.52, H 6.00, S10.60, found: C 67.26, H 5.99, S10.59.
(
3
1
(
17 18 3
C H O
2
-Trifluoromethyl-2-phenyl-3-phenylsulfonyltetrahydrofuran (2i): Yield 70%
trans-2-(2-Phenylvinyl)-3-phenylsulfonyl tetrahydrofuran (2e): M.p. 718C
1
1
Isomer 1: M.p. 968C (EtOH); H NMR (200 MHz, CDCl ): d ˆ 2.39 ± 2.56
(
(
6
1
(
EtOH); H NMR (200 MHz, CDCl
3
): d ˆ 2.19 ± 2.38 (m, 1H), 2.47 ± 2.63
3
3
3
(m, 1H), 2.72 ± 2.91 (m, 1H), 4.20 (q, J(H,H) ˆ 7.69 Hz, 1H), 4.34 (t,
m, 1H), 3.51 ± 3.62 (m, 1H), 3.87 ± 4.11 (m, 1H), 4.81 (dt, J(H,H) ˆ 1.04,
3
3
3
J(H,H) ˆ 7.69 Hz, 1H), 4.43 ± 4.54 (m, 1H), 7.27 ± 7.64 ppm (m, 10H);
.24 Hz, 1H), 5.92 (dd, J(H,H) ˆ 6.29, 15.86 Hz, 1H), 6.36 (dd, J(H,H) ˆ
.02, 15.86 Hz, 1H), 7.17 ± 7.32 (m, 5H), 7.52 ± 7.69 (m, 3H), 7.91 ± 7.97 ppm
m, 2H); 13C NMR (100 MHz, CDCl
): d ˆ 28.18, 67.73, 68.86, 79.37, 126.49,
26.63, 127.95, 128.46, 128.60, 129.38, 131.99, 134.03, 135.84, 138.18 ppm;
S(314.40): C 68.77, H 5.77, S
1
3
C NMR (100 MHz, CDCl
3
): d ˆ 29.61, 67.78, 68.71, 76.49, 86.58, 127.63,
127.98, 128.00, 128.04, 129.12, 129.14, 133.60, 138.90 ppm; elemental
analysis calcd (%) for C17 S(356.36): C 57.30, H 4.24; found: C
7.40, H 4.29.
Isomer 2: M.p. 1028C (EtOH);
3
15 3 3
H F O
1
5
elemental analysis calcd (%) for C18
18 3
H O
1
0.20; found: C 68.49, H 5.79, S10.17.
1
H NMR (200 MHz, CDCl ): d ˆ 1.93 ± 2.08
3
3
(
m, 1H), 2.66 ± 2.87 (m, 1H), 3.89 ± 4.07 (m, 2H), 4.42 (dt, J(H,H) ˆ 3.41,
Synthesis of 2-alkyl-3-phenylsulfonyl tetrahydrofuran (2 f, 2g): The proce-
dure above was followed with 2 (1 mmol), THF (1 mL), and aliphatic
aldehyde (1.2 mmol).
1
8
.33 Hz, 1H), 7.41 ± 7.74 (m, 6H), 7.87 ± 8.02 ppm (m, 4H); C NMR
): d ˆ 31.80, 67.69, 73.30, 87.47, 127.34, 128.97, 129.11,
29.62, 129.95, 134.66, 137.66, 140.71 ppm; elemental analysis calcd (%) for
S(356.36): C 57.30, H 4.24; found: C 57.53, H 4.44.
-Cyano-1-phenylcyclopropane (4a):[23] 1H NMH (200 MHz, CDCl
.41 ± 1.48 (m, 2H), 1.73 ± 1.60 ppm (m, 5H).
2,3-Diphenyl-3-cyano tetrahydrofuran (4b): M.p. 938C; 1H NMR
(400 MHz, CDCl
): d ˆ 2.87 ± 3.02 (m, 2H), 4.34 ± 4.45 (m, 1H), 4.52 ±
4.65 (m, 1H), 5.00 (s, 1H), 7.11 ± 7.49 ppm (m, 10H);
(100 MHz, CDCl
): d ˆ 41.13, 55.58, 67.00, 90.04, 119.94, 126.31, 126.54,
27.92, 128.04, 128.51, 128.73, 129.10, 129.37 ppm; HRMScalcd for
15NO: 249.11536; found: 249.11635
(
1
100 MHz, CDCl
3
trans-2-(1-Methylpropyl)-3-phenylsulfonyl tetrahydrofuran (2 f): Oil;
17 15 3 3
C H F O
1
H NMR (200 MHz, CDCl
.97 ± 2.17 (m, 1H), 2.31 ± 2.47 (m, 1H), 3.41 ± 3.51 (m, 1H), 3.70 ± 3.96 (m,
H), 4.20 ± 4.26 (m, 1H), 7.54 ± 7.72 (m, 3H), 7.88 ± 7.94 ppm (m, 2H);
3
): d ˆ 0.76 ± 0.88 (m, 9H), 0.99 ± 1.48 (m, 3H),
1
1
3
): d ˆ
1
1
1
3
C NMR (100 MHz, CDCl
7.62, 81.59, 128.68, 128.75, 129.33, 133.88 ppm; elemental analysis calcd
S(268.37): C 62.66, H 7.51, S11.95; found: C 62.42, H 7.44,
3
): d ˆ 11.76, 13.10, 26.39, 28.80, 38.53, 66.37,
6
(
3
1
3
%) for C14
H
20
O
3
C NMR
S11.76.
3
1
2
-tert-Butyl-3-phenylsulfonyl tetrahydrofuran (2g): M.p. 1168C (EtOH);
17
C H
1
H NMR (200 MHz, CDCl
3
): d ˆ 0.84 (s, 9H), 1.95 ± 2.17 (m, 1H), 2.36 ±
3
1-Phenyl-2-phenylsulfonyl-1,3-butadiene (6a): Potassium tert-butoxide
(0.448 g, 4 mmol) was added in 4 portions to a solution of 6 (0.194 g,
0.7 mmol), benzaldehyde (0.106 g, 1 mmol), and MeI (0.312 g, 2.2 mmol) in
DMF (5 mL) cooled to À308C. The mixture was stirred for 2 min,
2
1
1
.48 (m, 1H), 3.49 (ddd, J(H,H) ˆ 1.43, 3.63, 9.48 Hz, 1H), 3.79 ± 3.92 (m,
H), 4.02 (dt, 3J(H,H) ˆ 1.47, 8.06 Hz, 1H), 4.18 (d, 3J(H,H) ˆ 3.52 Hz,
1
3
H), 7.58 ± 7.75 (m, 3H), 7.94 ± 8.01 ppm (m, 2H); C NMR (50 MHz,
CDCl
3
): d ˆ 26.11, 29.82, 35.24, 66.31, 68.67, 86.41, 129.49, 129.91, 134.47,
quenched with aqueous NH
mixture was extracted with CH
4
Cl (5 mL), and water (30 mL) was added. The
Cl
1
38.82 ppm; elemental analysis calcd (%) for C14
20 3
H O
S(268.37): C 62.66,
(3 Â 10 mL), the organic solution was
H 7.51, S11.95; found: C 62.50, H 7.63, S, 12.09.
2
2
dried, and the solvent was evaporated. The product was purified by
preparative TLC (hexane/ethyl acetate 3:1). Yield of 6a: 0.116 g, 62%;
m.p. 838C (EtOH); H NMR (200 MHz, CDCl
1
tert-Butyl cyclopropylcarboxylate (3a): H NMR (200 MHz, CDCl
3
): d ˆ
0
1
.68 ± 0.80 (m, 2H), 0.83 ± 0.91 (m, 2H), 1.41 (s, 9H), 1.43 ± 1.51 ppm (m,
1
3
3
): d ˆ 5.50 (td, J(H,H) ˆ
H); 13C NMR (50 MHz, CDCl
): d ˆ 7.83, 13.98, 28.02, 79.90, 173.92 ppm.
trans-2-Phenyl-3-tert-butoxycarbonyl tetrahydrofuran (3b): Oil; H NMR
3
3
1
.24, 11.72 Hz, 1H), 5.95 (dd, J(H,H) ˆ 1.28, 17.91 Hz, 1H), 6.42 (ddd,
1
3
J(H,H) ˆ 1.20, 11.71, 17.84 Hz, 1H), 7.39 ± 7.68 (m, 8H), 7.90 ± 7.96 ppm (m,
3
13
(
400 MHz, CDCl
3
): d ˆ 1.44 (s, 9H), 2.22 ± 2.35 (m,2H), 2.87 (dt, J(H,H) ˆ
3H); C NMR (50 MHz, CDCl
3
): d ˆ 124.43, 126.94, 128.63, 129.16, 129.47,
7
.01 , 8.94 Hz, 1H), 3.99 ± 4.05 (m, 1H), 4.11 ± 4.17 (m, 1H), 4.98 (d,
130.52, 130.95, 133.68, 133.78, 138.60, 139.18, 140.38 ppm; elemental
analysis calcd (%) for C16
C 70.97, H 5.26, S11.70.
3
13
J(H,H) ˆ 7.15 Hz, 1H), 7.22 ± 7.40 ppm (m, 5H); C NMR (100 MHz,
14 2
H O S(270.35): C 71.03, H 5.18, S11.84; found:
CDCl
3
): d ˆ 28.00, 30.50, 53.32, 68.39, 80.99, 83.46, 125.76, 127.55, 128.30,
Chem. Eur. J. 2002, 8, No. 18
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0818-4239 $ 20.00+.50/0
4239

M. M aÀ kosza and M. Judka
FULL PAPER
[
[
[
1] M.-C. Roux-Schmitt, J. Seyden-Penne, S. Wolfe, Tetrahedron 1972, 28,
965; M. S. Newman, B. J. Magerlein, Org. React. 1949, 5, 413.
2] L. McCoy, J. Am. Chem. Soc. 1958, 80, 6568; L. McCoy, J. Am. Chem.
Soc. 1960, 82, 6416.
3] M. Mokosza, J. Winiarski, Acc.Chem.Res. 1987, 20, 282; M. M aÀ kosza,
K. Wojciechowski, Liebigs Ann./Recl. 1997, 1805; M. M aÀ kosza, A.
Kwast, J. Phys. Org. Chem. 1998, 11, 341.
[14] T. L. B. Boivin, Tetrahedron 1987, 43, 3309; J-C. Harmange, B.
Figadere, Tetrahedron: Asymmetry 1993, 4, 1711; U. Koert, Synthesis
1995, 115; M. C. Elliott, E. Williams, J. Chem. Soc. Perkin Trans. 1
2001, 2303; J. E. Semple, M. M. Joulli e¬ , Heterocycles 1980, 14, 1825.
[15] P. Li, T. Wang, T. Emge, K. Zhao, J. Am. Chem. Soc. 1998, 120, 7391.
[16] P. Langer, E. Holtz, I. Karime, N. Saleh, J. Org. Chem. 2001, 66, 6057;
P. Langer, L. Freifeld, Chem. Eur. J. 2001, 7, 565; P. Langer, T. Eckardt,
Angew. Chem. 2000, 112, 4503; Angew. Chem. Int. Ed. 2000, 39, 434; P.
Langer, H. Armbrust, T. Eckardt, J. Magull, Chem. Eur. J. 2002, 8,
1443; P. Langer, E. Holz, N. N. R. Saleh, Chem. Eur. J. 2002, 8, 917; P.
Langer, Chem. Eur. J. 2001, 7, 3858.
4
[
[
[
[
4] R. Bartsch, J. Zavada, Chem. Rev. 1980, 80, 453.
5] D. Wendisch, in Houben-Weyl, Vol. IV/3, Thieme, Stuttgart, 1971, p. 89.
6] F. F. Fleming, B. C. Shook, Tetrahedron 2002, 58, 1.
7] J. Mann, in Comprehensive Organic Synthesis, Vol. 3 (Ed.: B. Trost),
Pergamon 1991, p. 839.
[17] B. Travis, B. Borhan, Tetrahedron Lett. 2001, 42, 7741.
[18] A. Ajanian, J. L. Gleason, Org. Lett. 2001, 3, 4161.
[
8] L. A. Paquette, Org. React. 1971, 25, 1 ± 71; J. M. Clough, in
Comprehensive Organic Synthesis, Vol. 3 (Ed.: B. Trost), Pergamon
[19] S. Cohen, A. Zoran, Y. Sasson, Tetrahedron Lett. 1998, 39, 9815.
[20] K. Wilberg, D. Barth, P. Schertler, J. Org. Chem. 1973, 38, 3122.
[21] B. Issari, C. Stirling, J. Chem. Soc. Perkin Trans. 2 1984, 1043.
[22] J. B. Lambert, J. J. Napoli, K. K. Johnson, K. N. Taba, B. S. Packard,
J. Org. Chem. 1985, 50, 1291.
1
991, p. 861.
9] T. Houser, R. Bernstein, R. Miekka, J. Agnus, J. Am. Chem. Soc. 1955,
7, 6201.
[
7
[
10] M. M aÀ kosza, B. Serafinowa, Rocz. Chem. 1966, 40, 1647.
[
11] I. Shibata, H. Yamasaki, A. Baba, H. Matsuda, J. Org. Chem. 1992, 57,
[23] E. Kaiser, L. Solter, R. Schwarz, R. Beard, C. Hauser, J. Am. Chem.
Soc. 1971, 93, 4237.
6
909.
12] M. M aÀ kosza, J. Przyborowski, R. Klajn, A. Kwast, Synlett 2000, 12,
773.
[
[
1
13] J. W. Westley, Polyether antibiotics: Naturally Occurring Acid Iono-
phores, Marcel Dekker, New York 1982.
Received: March 25, 2002 [F3975]
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