Electrophilicities of 1,2-disubstituted ethylenes

Article abstract of DOI:10.1002/ejoc.201301779

The kinetics of the reactions of maleic anhydride, N-methylmaleimide, fumaronitrile, diethyl fumarate, and diethyl maleate with pyridinium and sulfonium ylides were studied in DMSO at 20 C. All of the reactions were found to follow a second-order rate law

Full text of DOI:10.1002/ejoc.201301779

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FULL PAPER
DOI: 10.1002/ejoc.201301779
Electrophilicities of 1,2-Disubstituted Ethylenes
Dominik S. Allgäuer[a] and Herbert Mayr*[a]
Dedicated to Professor Ingo-Peter Lorenz on the occasion of his 70th birthday
Keywords: Kinetics / Linear free energy relationships / Electrophilicity / Cycloaddition / Ylides / Alkenes
The kinetics of the reactions of maleic anhydride, N-methyl-
maleimide, fumaronitrile, diethyl fumarate, and diethyl ma-
leate with pyridinium and sulfonium ylides were studied in
DMSO at 20 °C. All of the reactions were found to follow a
second-order rate law, and can be described by the linear
free energy relationship logk2 (20 °C) = sN(N + E), where N
and sN are solvent-dependent nucleophile-specific param-
eters, and E is an electrophile-specific parameter. The elec-
trophilicity parameters E of the investigated acceptor-substi-
tuted alkenes were derived from the linear correlations of
(logk2)/sN vs. N, and range from –19.8 to –11.1.
linear plots of (logk2)/sN vs. the nucleophilicity parameters
N, reactivity parameters for many types of nucleophiles and
electrophiles were derived.[13]
Introduction
Acceptor-substituted ethylenes 1a–1e (Scheme 1) are fre-
quently used in organic syntheses,[1] for example as reagents
in Michael additions,[2] [3+2] cycloadditions,[3,4] and Diels–
Alder reactions,[5,6] which can be promoted by metals[7,8] or
organocatalysts.[9,10]
logk2 = sN(N + E)
(1)
We recently quantified the nucleophilic reactivities N and
sN of colored pyridinium ylides 2[14] (Table 1) and sulfo-
nium ylides 3[15] (Table 2) based on the kinetics of their re-
actions with benzhydrylium ions, quinone methides, and
benzylidene malonates. These N and sN parameters will
now be used to quantify the electrophilic reactivities of col-
orless Michael acceptors, such as 1, so that these syntheti-
cally important electrophiles may be included in our com-
prehensive reactivity scale.
Scheme 1. Michael acceptors 1a–1e investigated in this work.
Although the relative reactivities of acceptor-substituted
ethylenes 1a–1e in 1,3-dipolar cycloadditions[3,4b,11] and
Diels–Alder reactions[6a,6b,12] have been correlated with
their LUMO energies, a general quantification of their elec-
trophilicities has, to the best of our knowledge, not been
reported.
Table 1. Pyridinium ylides 2 used in this work (N and sN param-
eters in DMSO from ref.[14]). EWG = electron-withdrawing group.
We have previously shown that a multitude of reactions
of nucleophiles with carbocations and Michael acceptors
can be described by Equation (1), in which electrophiles are
characterized by one parameter E (electrophilicity), and nu-
cleophiles are characterized by the solvent-dependent pa-
rameters sN (sensitivity) and N (nucleophilicity).[13] From Ylide
R
EWG
N/sN
the linear plots of the second-order rate constants logk2 (at
20 °C) vs. the electrophilicity parameters E, and from the
2a
2b
2c
2d
2e
2f
2g
2h
2i
H
H
H
H
CO2Et
CONEt2
CN
COMe
COPh
COPh
COPh
26.71/0.37
27.45/0.38
25.94/0.42
20.24/0.60
19.46/0.58
21.61/0.58
17.98/0.63
20.08/0.57
19.38/0.50
[a] Department Chemie, Ludwig-Maximilians-Universität
München,
H
Butenandtstrasse 5–13 (Haus F), 81377 München, Germany
E-mail: Herbert.mayr@cup.uni-muenchen.de
http://www.cup.uni-muenchen.de/oc/mayr
p-NMe2
m-Cl
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301779.
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Table 2. Sulfonium ylides 3 used in this work (N and sN parameters
in DMSO from ref.[15b]).
Scheme 3. Schematic mechanism for the reaction of sulfonium
ylides 3 with Michael acceptors 1.
Ylide
R
N/sN
3a
3b
3c
3d
p-CN–C6H4
p-NO2–C6H4
p-Me2N–C6H4CO
p-MeO–C6H4CO
21.07/0.68
18.42/0.65
15.68/0.65
14.48/0.71
In reactions of alkoxycarbonyl-substituted sulfonium
ylides with cyclopentenone, the intermediate betaines are
formed irreversibly, and may undergo base-mediated epi-
merization before they cyclize to the cyclopropanes.[21] In
contrast, the formation of cyclopropanes from Michael ac-
ceptors and aminosulfoxonium ylides was concluded to
proceed by reversible formation of the intermediate beta-
ines, as diethyl maleate (1e) was observed to isomerize to
diethyl fumarate (1d) when combined with the ylide.[22]
Results and Discussion
General
Product Studies
Pyridinium ylides 2 undergo [3+2] cycloadditions with
dipolarophiles 1 (Scheme 2).[16,17] These reactions can be
either concerted (kconc) or stepwise via intermediate beta-
ines (k2) with a subsequent ring closure (krc) to give the
tetrahydroindolizines. For certain substitution patterns,
stepwise mechanisms via diradical intermediates must also
be considered.[4c,18,19] We recently reported that the 1,3-di-
polar cycloadditions of pyridinium ylides with substituted
benzylidene malononitriles and chalcones proceed in a step-
wise manner via zwitterionic intermediates.[14]
The products of the reactions of dipolarophiles 1 with
isoquinolinium, quinolinium, and pyridinium ylides were
studied with 2h and 2e as representative examples.
Treatment of DMSO solutions of dipolarophiles 1a–1e
and isoquinolinium salt 2h·HBr with NEt3 at ambient tem-
perature gave tetrahydroindolizines 4a–4e in 65–94% yields
with variable diastereoselectivities (Scheme 4). The stereo-
chemistry of the products was assigned on the basis of
NOESY correlations of the protons and substituents on the
pyrrolidine ring, and was found to be consistent with pre-
vious investigations of similar tetrahydroindolizines.[17] The
major diastereoisomers of 4a–4e shown in Scheme 4 origi-
nate from a 1-endo approach of 1a–1e to the anti form of
ylide 2h (Figure 1). The selectivity for this approach is
higher for 1,2-cis disubstituted ethylenes 1a, 1b, and 1e than
for trans compounds 1c and 1d; anti-endo-tetrahydro-
indolizines 4b and 4e were even formed exclusively.
Scheme 2. Concerted (left path) and stepwise cycloadditions (right
path) of pyridinium ylides 2 with dipolarophiles 1.
Sulfonium ylides 3 generally react in a stepwise manner
with Michael acceptors, with initial irreversible formation
of intermediate betaines (k2), which usually undergo a fast
subsequent ring closure (kЈrc) to give cyclopropanes
(Scheme 3).[15,20]
Scheme 4. Formation of tetrahydroindolizines 4a–4e in DMSO.
2
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Electrophilicities of 1,2-Disubstituted Ethylenes
Figure 1. endo-Approaches of 1a–1e to ylide 2h.
Scheme 6. Base-induced reaction of 2e·HBr with N-methylmale-
imide (1b). Stereochemistry of 5b according to ref.[24a]
The reaction of 2e·HBr with maleic anhydride (1a) in
DMF in the presence of tetrakis(pyridine)cobalt(II) dichro-
mate (TPCD) was recently reported to give indolizine 6a by
oxidative decarboxylation of the intermediate tetra-
hydroindolizine (i.e., 5a; Scheme 5).[23] Our attempts to per-
form this synthesis in DMSO under otherwise identical
conditions failed.
spectroscopy of the crude reaction mixture (Scheme 6). The
formation of 5b has previously been reported by Tsuge and
co-workers,[24] who also determined the stereochemistry of
5b to be that shown in Scheme 6.[24a]
Our attempts to purify 5b by chromatography on silica
gel with chloroform as eluent led to the formation of (E)-
itaconimide 7b in 51% yield. The configuration of the
double bond was assigned from the NOESY correlations of
the protons and substituents on the double bond, and is in
agreement with reported data.[24] The formation of 7b can
be rationalized by the mechanism shown in Scheme 6. In
this mechanism, the weak bond between C-9a and C-9b in
tetrahydroindolizine 5b is cleaved to regenerate the betaine
8b, which is then protonated to give Michael adduct 9b.
Elimination of a proton and pyridine from 9b by an E2 or
E1cB mechanism gives (E)-itaconimide 7b.
Scheme 5. Reaction of maleic anhydride (1a) with 2e·HBr under
oxidative conditions (from ref.[23]).
Combination of Michael acceptors 1c–1e with pyridin-
When we treated a mixture of pyridinium bromide ium salt 2e·HBr and base led to the formation of tetra-
2e·HBr and maleimide 1b with triethylamine in DMSO at hydroindolizines 5c–5e, which were not characterized, but
20 °C, tetrahydroindolizine 5b was obtained as a single dia- were oxidized in a one-pot procedure with chloranil
1
stereoisomer in quantitative yield, as shown by H NMR (2 equiv.) to give indolizines 10c and 10d in 63–88% yield
Scheme 7. Synthesis of indolizines 10c and 10d.
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(Scheme 7). The cycloaddition of 2e with 1c was achieved
by treatment of a mixture of 2e·HBr and 1c in CH2Cl2 with
NEt3, whereas attempts to perform this reaction under bi-
phasic conditions [CH2Cl2/NaOH (32% aq.)][25] led only to
polymerization of 1c. However, biphasic conditions were
successfully used for the reactions of 2e·HBr with 1d and
1e to give indolizine 10d after oxidation.
The reaction of sulfonium ylides 3c and 3d with 1b and
1c as representative examples resulted in the formation of
cyclopropanes 11b and 11c with complete stereocontrol in
46 and 62% yields, respectively (Scheme 8).[26] The stereo-
chemistry of cyclopropanes 11b and 11c was assigned on
basis of NOESY correlations of the protons and substitu-
ents on the cyclopropane ring. The reactions of sulfonium
ylides 3a and 3b with 1b and 1c did not lead to isolable
products, possibly due to polymerization of 1b and 1c initi-
ated by the high KOtBu concentrations required to generate
ylides 3a and 3b. For the kinetic investigations of these reac-
tions, dilute solutions of ylides 3a and 3b and ethylenes 1b
and 1c were used. Clean second-order reactions were ob-
served under these conditions, possibly because in the
highly dilute solutions the base-induced polymerization of
the ethylenes was suppressed. The kinetics of the reaction
of maleic anhydride (1a) with sulfonium ylide 3b followed
a second-order rate law, but we were not able to isolate a
product from the reaction. Thus a definite interpretation of
the determined second-order rate constant k2exp (see below)
will not be attempted.
Scheme 8. Cyclopropanations of Michael acceptors 1b–1e with
sulfonium ylides 3a, 3c, and 3d.
The reaction of diethyl fumarate (1d) with sulfonium
ylide 3a gave cyclopropane 11d in 81% yield with exclusive
formation of the diastereoisomer with the ester groups trans
to each other (stereochemistry verified by NOESY as de-
scribed above; Scheme 8). The preferred formation of cyclo-
propane 11d with the ester groups in a trans configuration
was also found in the reaction of diethyl maleate (1e) with
sulfonium ylide 3a (Scheme 8), which indicates that the cis
configuration of the double bond of diethyl maleate (1e)
was eroded during the cyclopropanation process. This ob-
servation can be rationalized by the formation of betaine
intermediate 12e, which has a sufficient life-time for the ro-
tation around the σ bond between C-1 and C-2 to take
place before cyclization with elimination of dimethyl sulfide
leads to the diastereoisomer of cyclopropane 11d shown in
Scheme 9.[20a,22a] Non-stereospecific cyclopropanations
have previously been observed in the reaction of diethyl ma-
leate (1e) with aminosulfoxonium ylides.[22a] As diethyl ma-
leate (1e) isomerized to diethyl fumarate (1d) in the presence
of aminosulfoxonium ylides, it was concluded that the beta-
ine formation from diethyl maleate (1e) and aminosulfoxon-
ium ylides was a reversible process.[22a] To clarify whether
the formation of betaine 12e (or 12d) from diethyl maleate
(1e) and the sulfonium ylide 3a is a reversible or irreversible
process, the reaction was monitored by 1H NMR spec-
troscopy in [D6]DMSO at ambient temperature. When
KOtBu (1 equiv.) in [D6]DMSO was added to a solution of
3a·HBF4 and 1e in [D6]DMSO, cyclopropane 11d, SMe2,
tBuOH, and non-identified decomposition products of
11e were observed in the 1H NMR spectrum taken immedi-
ately after mixing the reagents. The 1H NMR spectrum did
not change for the next 13 min (for details, see the Support-
ing Information). As betaines 12d and 12e were not ob-
served, one can exclude the rapid formation of 12d and 12e,
which would then undergo a subsequent slow cyclization.
1
The H NMR spectra of the reaction mixture also allowed
us to exclude the reversible formation of betaines 12d and
12e, because diethyl fumarate (1d) was not observed in the
reaction mixture.
Scheme 9. Mechanism of the cyclopropanation reaction of diethyl
ylide 3a, but also unconverted 3a·HBF4, 1e, and traces of maleate (1e) with 3a.
4
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Electrophilicities of 1,2-Disubstituted Ethylenes
calcd [a]
Kinetic Investigations
Table 3. Experimental (k2exp) and calculated (k2
)
second-or-
der rate constants for the reactions of Michael acceptors 1a–1e with
The kinetics of the reactions of 1a–1e with ylides 2 and
3 were investigated in DMSO solution at 20 °C. The reac-
tions were monitored photometrically by following the dis-
appearance of ylides 2 and 3 at or close to their absorption
maxima. Due to their low stabilities, ylides 2a–2i, 3a, and
3b were generated directly before each kinetics experiment
in the flask used for the kinetics experiment by combining
DMSO solutions of the salts 2(a–i)·HX or 3(a,b)·HBF4
with KOtBu (typically 1.05 equiv.). To perform the kinetic
measurements under pseudo-first-order conditions, an ex-
cess of at least 10 equiv. of the Michael acceptors 1a–1e
with respect to the ylides (i.e., 2 and 3) was used. The first-
order rate constants kobs were obtained by least-squares fit-
ting the exponential function At = A0 exp(–kobst) + C
(mono-exponential decrease) to the observed time-depend-
ent absorbances (Figure 2, a). Most of the correlations of
kobs with the concentrations of the Michael acceptors 1a–
1e were linear with negligible intercepts, as required by the
relation kobs = k2[1] (Figure 2, b). From the slopes of the
linear correlations, the second-order rate constants for the
reactions of Michael acceptors 1a–1e with ylides 2 and 3
were obtained (Table 3).
ylides 2a–2i, 3a, and 3b in DMSO at 20 °C.
[a] Calculated from Equation (1) using the N and sN parameters
from Tables 1 and 2 and E from this Table. [b] As the kobs vs. [1]
plots for these reactions, which proceed on the Ͻ10 ms timescale,
do not have negligible intercepts, these data are considered to be
less reliable, and they were not used for the determination of
E(1a,1c,1d) according to Equation (1). [c] These rate constants
possibly correspond to concerted, but highly unsymmetrical pro-
cesses, and were thus exempted from the determination of E. [d] By
stopped-flow method; reproduction by a spectrometer using fi-
Figure 2. a) Decay of the absorbance of 2e ([2e]0 = 5ϫ10–5 m) at
445 nm during its reaction with 1c ([1c]0 = 4.00ϫ10–3 m) in DMSO
at 20 °C. b) Correlation of kobs with the concentration of 1c.
exp
beroptics gave k2 = 3.48 m–1 s–1 (for details, see the Supporting
Information). [e] Kinetics deviate slightly from a second-order rate
law, and thus k2 values were not used for the determination of E.
When the reactions of pyridinium ylides 2 and sulfonium
ylides 3 with acceptor-substituted ethylenes 1 proceed step-
wise with rate-determining formation of zwitterionic inter-
Table 3 compares the experimental rate constants for the
mediates 8 and 12, the measured rate constants correspond reactions of ylides 2 and 3 with acceptor-substituted ethyl-
to k2, as specified in Schemes 2 and 3. As k2 refers to the enes 1 with the values calculated using Equation (1) from
formation of one new C–C bond without breaking a σ the nucleophile-specific parameters sN and N from Tables 1
bond, as with the reactions used for the parameterization and 2, and the electrophilicity parameters E listed in
of Equation (1), this correlation may also apply for the rate Table 3, which were obtained by the described least-squares
constants listed in Table 3. A linear correlation was found minimization. The 19 second-order rate constants used to
(Figure 3) when (logk2exp)/sN was plotted against the pre- derive the electrophilicity parameters E of activated ethyl-
viously published nucleophilicity parameters N, which had enes 1, as well as four rate constants that were not used for
been derived from the reactions of ylides 2 and 3 with benz- the parameterization because of their lower precision,
hydrylium ions, quinone methides, and benzylidene malon- agreed with the calculated values to within a factor of three.
ates.
The remaining eight reactions proceeded 4 to 54 times
Using the rate constants from Table 3, which could un- faster than predicted by Equation (1). Although these devi-
ambiguously be assigned to k2 (see footnotes of Table 3 and ations are within the confidence limit of Equation (1), these
the text below), the electrophilicity parameters E of 1,2- rate constants have not been used for deriving the electro-
disubstituted ethylenes 1a–1e were calculated by least- philicity parameter E, as the positive deviations might also
squares fitting, i.e., by minimizing Δ2 = Σ[logk2 – sN(N + be due to a low degree of concertedness of these [3+2]-cy-
E)]2.
cloaddition reactions.
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D. S. Allgäuer, H. Mayr
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for these compounds cover almost nine orders of magni-
tude. It remains to be examined, however, whether the treat-
ment of electrophilicities E as solvent-independent param-
eters, which has been proved for the reference electrophiles
(benzhydrylium ions and quinone methides),[13b,13c] also
holds for ordinary Michael acceptors.
Figure 3. Correlation of (logk2)/sN derived from the reactions of
dipolarophiles 1 with ylides 2 and 3 against the corresponding nu-
cleophilicity parameters N of the ylides (the slopes are fixed to 1.0
as required by Equation 1). k2 values not used for the determi-
nation of E are not shown, but are listed in Table 3.
The fact that all of the rate constants listed in Table 3
agree with the values calculated by Equation (1) to within
two orders of magnitude, and 28 out of the 31 values even
to within one order of magnitude, indicates that all the reac-
tions, even though they lead to different final products –
tetrahydroindolizines (from 2) and cyclopropanes (from 3),
share a common rate-determining step, i.e., formation of
one new C–C bond with generation of an intermediate be-
taine. However, as discussed above, concerted processes
with highly unsymmetrical transition states cannot be ex-
cluded for some 1,3-dipolar cycloadditions.
Figure 4. Comparison of the electrophilicity parameters E of 1,2-
disubstituted ethylenes 1a–1e (Table 3) and other Michael ac-
ceptors (E from refs.[27–30,32–35]).
The most reactive compound in this series of 1,2-disub-
stituted ethylenes, maleic anhydride (1a), has an electro-
philic reactivity similar to that of diethyl azodicarboxyl-
ate,[27] benzylidene indandione,[28] or an acylazolium ion,[29]
but it is less electrophilic than the gem-substituted bis(phen-
ylsulfonyl)ethene.[30] The reactivity of the double bond de-
creases by approximately three orders of magnitude when
the bridging oxygen in 1a is substituted by a methylimino
group in N-methyl maleimide (1b), which has a reactivity
similar to that of a palladium-stabilized 1,3-diarylallyl cat-
Conclusions
The relationship logk2 = sN(N + E), where electrophiles ion,[31] a 1,2-diaza-1,3-diene,[32] or β-nitrostyrene.[33] Fuma-
are characterized by one (E), and nucleophiles are charac- ronitrile (1c) is approximately two orders of magnitude less
terized by two (N, sN) parameters, was found to describe reactive than 1b, with an electrophilicity similar to that of
the rates of the stepwise 1,3-dipolar cycloadditions of pyrid- a phosphinoyl-substituted imine.[34] Exchanging the cyano
inium ylides 2 with 1,2-diacceptor substituted ethylenes 1a– groups in fumaronitrile (1c) by ethoxycarbonyl groups
1e, as well as the rates of stepwise cyclopropanations of 1a– (Ǟ 1d) decreases the electrophilic reactivity by two more
1e with sulfonium ylides 3. From the fact that the same orders of magnitude, making 1d similarly reactive to chalc-
electrophilicity parameters E can be used for both types of one.[34] The activated C=C double bond in ethyl fumarate
reactions of acceptor-substituted ethylenes 1a–1e, we con- (1d) is almost eight orders of magnitude less electrophilic
clude that all the reactions proceed with analogous rate- than the analogously substituted N=N double bond in di-
determining steps, i.e., formation of one new C–C bond ethyl azodicarboxylate. A change of the double-bond geom-
leading to zwitterionic intermediates that undergo fast sub- etry of the dipolarophile from trans (1d) to cis in diethyl
sequent reactions to give either [3+2] cycloadducts or cyclo- maleate (1e) decreases the reactivity by two orders of mag-
propanes.
nitude,[4a] so that 1e has an electrophilicity similar to that
For that reason, Michael acceptors 1a–1e can be in- of diethyl benzylidene malonate.[35] Attempts to rationalize
cluded in our comprehensive electrophilicity scale (Fig- this nucleophile-independent order of electrophilicities are
ure 4), which shows that the electrophilicity parameters E in progress.[36]
6
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Electrophilicities of 1,2-Disubstituted Ethylenes
[s–1] were obtained by fitting the single exponential At = A0
exp(–kobst) + C (mono-exponential decrease) to the observed time-
dependent absorbances (average of at least three kinetic runs for
each concentration for the stopped-flow method) of the ylides (2
or 3). Second-order rate constants k2 [m–1 s–1] were derived from
the slopes of the linear plots of kobs values against the concentra-
tions of the Michael acceptors 1a–1e used in excess.
Experimental Section
Synthesis of [3+2] Cycloadducts 4 (Procedure A): NEt3 (0.72 mmol)
was added to a solution of 2h·HBr (0.50 mmol) and 1a–1e
(0.50 mmol) in DMSO (5 mL) at room temperature. The mixture
was stirred for 5 min, then CH2Cl2 (15 mL) and water (25 mL) were
added, and the organic layer was separated. The aqueous layer was
extracted with CH2Cl2 (2ϫ 15 mL), and the combined organic lay-
ers were washed with brine (2ϫ 25 mL) and dried with Na2SO4.
The solvent was evaporated at room temperature, and the residue
was recrystallized from ethanol, ethanol/Et2O, or Et2O. Solutions
of all [3+2] cycloadducts 4 in CDCl3 or [D6]DMSO are slowly
oxidized by air when stored at room temperature.
Supporting Information (see footnote on the first page of this arti-
cle): Synthetic procedures, product characterization, detailed ki-
netic data, and copies of the NMR spectra of new compounds.
Acknowledgments
Synthesis of the Indolizines 10 (Procedure B): NaOH (30% aq.;
1 mL) or NEt3 (0.72 mmol) was added to a suspension of Michael
acceptor 1c–1e (0.50 mmol) and salt 2e·HX (0.50–0.75 mmol) in
dichloromethane (10 mL), and the mixture was stirred for 30–
60 min at room temperature. Water (30 mL) was added, and the
mixture was extracted with CH2Cl2 (3ϫ 5 mL). The combined or-
ganic layers were dried with Na2SO4. Chloranil (1.00 mmol) was
added to the solution, and stirring was continued for 30–60 min at
room temperature until TLC indicated that all the chloranil had
been consumed. The solvent was evaporated, and the residue was
subjected to column chromatography (n-pentane/EtOAc, 15:1–3:1,
depending on Rf). The resulting solids were dissolved in CHCl3,
and insoluble precipitates were removed by filtration. After evapo-
ration, the products were further purified by recrystallization from
Et2O.
The authors thank the Deutsche Forschungsgemeinschaft (DFG)
(SFB 749, Project B1) for financial support, Dr. Armin R. Ofial
for help during the preparation of this manuscript and Dr. Jörg
Bartl for reviewing of the analytical data.
[1] For reviews, see: a) S. Patai, Z. Rappoport, in: The Chemistry
of Alkenes (Eds.: S. Patai, Z. Rappoport), Wiley, New York,
1964, p. 469–584; b) C. Bianchi, C. De Micheli, R. Gandolfi,
in: The Chemistry of Double-Bonded Functional Groups, vol. 1
(Eds.: S. Patai, Z. Rappoport), Wiley, London, 1977, p. 369–
533; c) D. A. Oare, C. H. Heathcock, in: Topics in Stereochem-
istry, vol. 20 (Eds.: E. L. Eliel, S. H. Wilen), Wiley-Interscience,
Hoboken, NJ, 1991, p. 87–170; d) I. Chataigner, A. Harrison-
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Synthesis of Cyclopropanes 11b,c (Procedure C): Compound 1b or
1c (0.50–0.60 mmol) in DMSO (5 mL) was added dropwise over 5–
10 min to a solution of 3c or 3d (0.41–0.47 mmol) in DMSO (5 mL)
at room temperature. The reaction mixture was stirred for a further
5 min, then it was quenched with NH4Cl (satd. aq.; 25 mL). The
aqueous layer was extracted with CH2Cl2 (3ϫ 15 mL), and the
combined organic layers were washed with brine (2ϫ 20 mL) and
dried with Na2SO4. The solvent was evaporated, and the residue
was purified by column chromatography over silica (11b) or alox
(11c) (n-pentane/EtOAc, 3:1–2:1), and then recrystallized from
EtOH.
Synthesis of Cyclopropanes 11d,e (Procedure D): KOtBu
(0.75 mmol) in DMSO (5 mL) was added dropwise over 5–10 min
to a solution of 3a·HBF4 (0.75 mmol) and 1d or 1e (0.50 mmol) in
DMSO (5 mL) at room temperature. The reaction mixture was
stirred for a further 5 min, and then it was quenched with NH4Cl
(satd. aq.; 25 mL). The aqueous layer was extracted with CH2Cl2
(3ϫ 15 mL). The combined organic layers were washed with brine
(2ϫ 20 mL) and dried with Na2SO4. The solvent was evaporated,
and the residue was purified by column chromatography over silica
(n-pentane/EtOAc, 20:1–10:1).
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tometer systems (Applied Photophysics SX.18MV-R and Hi-Tech
SF-61DX2) as well as diode-array spectrometer systems (J&M
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bath cryostats. The ylides were generated in DMSO at 20 °C imme-
diately before each kinetic run by mixing DMSO solutions of the
pyridinium 2·HX or sulfonium 3·HBF4 salts with KOtBu (typically
1.05 equiv.). The kinetic runs were initiated by mixing DMSO solu-
tions of the ylides and electrophiles under first-order conditions,
that is, with the Michael acceptors 1a–1e in large excess
(Ͼ10 equiv.) over the ylides (2 or 3). First-order rate constants kobs
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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D. S. Allgäuer, H. Mayr
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Received: November 28, 2013
Published Online: ᭿
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O31779
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Date: 25-03-14 16:54:12
Pages: 9
Electrophilicities of 1,2-Disubstituted Ethylenes
Reactivity
D. S. Allgäuer, H. Mayr* .................. 1–9
Electrophilicities of 1,2-Disubstituted
Ethylenes
The kinetics of the reactions of 1,2-disub-
stituted ethylenes with pyridinium and sul-
fonium ylides in DMSO were investigated
photometrically. From the measured se-
cond-order rate constants, along with the
nucleophile-specific reactivity parameters
sN and N, we were able to determine the
electrophilicity parameters E of the 1,2-di-
substituted ethylenes using the relationship
logk2 = sN(N + E).
Keywords: Kinetics / Linear free energy re-
lationships / Electrophilicity / Cycload-
dition / Ylides / Alkenes
Eur. J. Org. Chem. 0000, 0–0
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