Electrophilicities of bissulfonyl ethylenes

Article abstract of DOI:10.1002/asia.201101046

Kinetics of the reactions of bissulfonyl ethylenes with various carbanions, a sulfur ylide, and siloxyalkenes have been investigated photometrically at 20°C. The second-order rate constants have been combined with the known nucleophile- specific parameters N and s_N for the nucleophiles to calculate the empirical electrophilicity parameters E of bissulfonyl ethylenes according to the linear free energy relationship log k(20°C)=s _N(N+E). Structure-reactivity relationships are discussed, and it is shown that the electrophilicity parameters E derived in this work can be employed to define the synthetic potential of bissulfonyl ethylenes as Michael acceptors. Copyright

Full text of DOI:10.1002/asia.201101046

DOI: 10.1002/asia.201101046
Electrophilicities of Bissulfonyl Ethylenes
Haruyasu Asahara and Herbert Mayr*[a]
Dedicated to Professor Stefan Toma on the occasion of his 75th birthday
Abstract: Kinetics of the reactions of bissulfonyl ethylenes with various carbanions,
a sulfur ylide, and siloxyalkenes have been investigated photometrically at 208C.
The second-order rate constants have been combined with the known nucleophile-
specific parameters N and sN for the nucleophiles to calculate the empirical elec-
Keywords: electrophilicity
kinetics · linear free-energy rela-
·
trophilicity parameters E of bissulfonyl ethylenes according to the linear free
energy relationship log k(208C)=sNA(N+E). Structure-reactivity relationships are
tionship
sulfones
·
Michael additions
·
A
CHTUNGTRENNUNG
discussed, and it is shown that the electrophilicity parameters E derived in this
work can be employed to define the synthetic potential of bissulfonyl ethylenes as
Michael acceptors.
Introduction
Bissulfonyl ethylenes 1 are widely used reagents in organic
synthesis[1] because they are active Michael acceptors, dieno-
philes, and dipolarophiles.[1–3] In particular, asymmetric con-
jugate additions of nucleophiles to bissulfonyl ethylenes are
of considerable importance for stereoselective carbon–
carbon bond-forming reactions. After the first report of or-
ganocatalytic Michael additions of aldehydes to bissulfonyl
ethylenes mediated by N-isopropyl-2,2’-bipyrrolidine by
Alexakis and coworkers,[4] there has been considerable re-
search on conjugate additions to bissulfonyl ethylenes. Cin-
Scheme 1. Bissulfonyl ethylenes 1a–g used in this study.
chona alkaloids,[5] thiourea derivatives,[6] prolinol silyl
ethers,[7] primary amines,[8] aminal-pyrrolidines,[9] chiral dia-
mines,[10] and tricyclic secondary amines[11] have been used
as catalysts.
phile-specific parameters, and E is an electrophilicity param-
To define the scope of potential reaction partners of bis-
sulfonyl ethylenes, we have now quantified the electrophili-
cities of representatives of these electron-deficient p-systems
(Scheme 1). Previously, we have shown that a large variety
of reactions of electrophiles with nucleophiles can be de-
scribed by Equation (1), in which k2 corresponds to the
second-order rate constant in mꢀ1 sꢀ1, N and sN are nucleo-
eter.[12]
log k2ð20 ꢁCÞ ¼ sNðNþEÞ
ð1Þ
By using diarylcarbenium ions and quinone methides as
reference electrophiles and donor-substituted ethylenes and
carbanions as reference nucleophiles, we have succeeded to
construct comprehensive nucleophilicity and electrophilicity
scales.[13] Michael additions of carbanions to benzylidenema-
lononitriles,[14] benzylidene-1,3-indandiones,[15] benzylidene
barbituric and thiobarbituric acids,[16] benzylidenemalo-
nates,[17] benzylidene Meldrumꢀs acids,[18] and iminium
ions[19] have previously been shown to follow Equation (1).
We now report on the kinetics of the reactions of 1a–g
with nucleophiles of known N and sN parameters, i. e., car-
banions 2a–g,[13,14] sulfur ylide 3,[20] and silyl enol ethers 4a–
d[13] (Table 1), and show that the second-order rate constants
of these reactions follow Equation (1).
[a] Dr. H. Asahara,+ Prof. Dr. H. Mayr
Department Chemie
Ludwig-Maximilians-Universitꢁt Mꢂnchen
Butenandtstrasse 5–13, 81377 Mꢂnchen (Germany)
Fax : (+49)89-2180-77717
E-mail: Herbert.Mayr@cup.uni-muenchen.de
[+] New address:
Department of Applied Chemistry,
Graduate School of Engineering,
Osaka University, Suita 565-0871 (Japan)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201101046.
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Table 1. Nucleophilicity parameters of carbanions 2a–g, sulfur ylide 3,
and silyl enol ethers 4a–d.
Nucleophile
Solvent
N
sN
Ref.
2a
2b
2c
2d
2e
DMSO
DMSO
DMSO
DMSO
DMSO
21.54
20.71
20.22
19.62
19.36
0.62
0.60
0.65
0.67
0.67
[14]
[13e]
[13b]
[13b]
[13b]
Scheme 3. Reactions of sulfur ylide 3 with the bissulfonyl ethylene 1a in
DMSO.
other cyclopropanation reactions of sulfur ylides,[21,22] and 4-
keto-1,1-bissulfonyl alkanes were obtained from the reaction
of 1a with the silylated ketene acetals and enol ethers 4a–d
(Scheme 4). Since analogous products can be expected for
other combinations of the bissulfonyl ethylenes 1a–g with
the nucleophiles 2–4, product studies have not been per-
formed for all combinations which were studied kinetically.
2 f
2g
DMSO
DMSO
18.82
17.64
0.69
0.73
[13b]
[13b]
3
DMSO
13.78
0.72
[20]
MeCN
CH2Cl2
MeCN
CH2Cl2
MeCN
CH2Cl2
MeCN
CH2Cl2
12.34
12.56
10.52
10.61
9.11
9.00
6.43
6.57
0.72
0.70
0.78
0.86
0.88
0.98
0.89
0.93
[13i]
[13a,c]
[13i]
[13a,c]
[13i]
4a
4b
4c
4d
[13a,c]
[a]
–
[13a,c]
[a] This work.
Scheme 4. Reactions of the silyl enol ethers 4a–d with the bissulfonyl
ethylene 1a in CH3CN.
Results and Discussion
Product Studies
Kinetic Measurements
The combination of the bissulfonyl ethylenes 1b–g with 1.1
equivalents of the potassium salts of 2a–g in dry DMSO, fol-
lowed by workup with aqueous acetic acid gave the adducts
5, which were isolated and characterized (Scheme 2). In
case of the reaction of 1c with the cyano-substituted carban-
ions 2d and 2e, and of the benzylidenedithiane tetroxide 1g
with 2g, the anionic adducts 5cdꢀ, 5ceꢀ, and 5ggꢀ were
To achieve pseudo-first-order kinetics, solutions of the bis-
sulfonyl ethylenes 1a–g (1.0ꢄ10ꢀ5 to 1.0ꢄ10ꢀ3 m) were
mixed with an excess of compounds 2a–g, 3, or 4a–d. The
decay of the absorption of the electrophiles was then fol-
lowed spectrophotometrically either with stopped-flow in-
struments or, for reactions with half-lives of more than
about 60 seconds, with conventional UV/Vis diode-array
spectrometers equipped with fiber optics and a submersible
probe. Because of an overlap of the absorption bands of the
bissulfonyl ethylenes and the carbanions, the absorbances
did not reach zero at the monitored wavelengths at the end
of the reactions with 1b,e. From the fit of the exponential
1
identified by H and 13C NMR spectroscopy because retro-
Michael additions occurred during acidic workup of these
adducts. The bissulfonyl ethylene 1a reacted with the sulfur
ylide 3 to form the cyclopropane 6 (Scheme 3) in analogy to
function At =A0 exp
N
At, the first-order rate constants kobs were derived. As exem-
plified in Figure 1 for the reaction of 1c with 2e, plots of
kobs versus the concentrations of the nucleophiles were
linear with intercepts near zero for all reactions of 1 with 2,
3, and 4. The slopes of the plots of kobs versus [Nu] gave the
second-order rate constants k2 [Equation (2)], which are
listed in Table 2.
kobs ¼ k2½Nuꢂ
ð2Þ
Figure 2 shows that the rate constants for the reactions of
the bissulfonyl ethylenes 1 with various types of nucleo-
philes (log k2/sN) correlate well with the corresponding nu-
cleophilicity parameters N listed in Table 1, thus showing
the applicability of Equation (1). In most cases, calculated
and experimental rate constants agree within a factor of 3
Scheme 2. Reactions of the potassium salts of the carbanions 2b–g with
the bissulfonyl ethylenes 1b–g in DMSO.
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Electrophilicities of Bissulfonyl Ethylenes
Table 2. Experimental and calculated second-order rate constants for the
reactions of 1a–g with the carbanions 2a-g, S-ylide 3, and silyl enol
ethers 4a–d at 208C in DMSO.
exp
calcd[b]
calcd
k2exp/k2
Electrophile (E)[a] Nucleophile k2
k2
[mꢀ1 sꢀ1
]
A
]
U
1a (ꢀ7.50)
1b (ꢀ12.93)
1c (ꢀ13.88)
3
1.70ꢄ104
3.42ꢄ103[c]
5.08ꢄ102[c]
9.03[c]
3.30ꢄ104
3.03ꢄ103
2.25ꢄ102
2.59ꢄ101
0.52
1.1
2.3
4a
4b
4c
4d
0.36
2.33ꢄ10ꢀ1[c] 1.11ꢄ10ꢀ1 2.1
2b
2c
2d
2e
2 f
3.97ꢄ104
3.35ꢄ104
3.13ꢄ104
3.79ꢄ104
1.13ꢄ104
4.66ꢄ104
5.49ꢄ104
3.04ꢄ104
2.04ꢄ104
1.16ꢄ104
0.85
0.61
1.0
1.9
0.97
2b
2c
2d
2e
2 f
2g
1.54ꢄ104
6.14ꢄ103
6.28ꢄ103
9.95ꢄ103
2.08ꢄ103
6.03ꢄ102
1.25ꢄ104
1.31ꢄ104
6.96ꢄ103
4.66ꢄ103
2.54ꢄ103
5.51ꢄ102
1.2
0.47
0.90
2.1
0.82
1.1
Figure 1. Exponential decay of the absorbance at 350 nm during the reac-
tion of 1c with 2e-K in DMSO at 208C ([2e]=1.00 mm; kobs =9.36 sꢀ1).
Inset: Determination of the second-order rate constant k2 =9.95ꢄ
103 mꢀ1 sꢀ1 from the slope of the correlation of the first-order rate con-
stants kobs with the concentrations of 2e.
1d (ꢀ16.53)
2a
1.04ꢄ103
4.17ꢄ102
8.01ꢄ101
1.04ꢄ102
2.77ꢄ102
3.12ꢄ101
8.31
1.27ꢄ103
3.21ꢄ102
2.50ꢄ102
1.17ꢄ102
7.85ꢄ101
3.79ꢄ101
6.45
0.82
1.3
0.32
0.89
3.5
2b
2c[d]
2d
2e[d]
2 f
0.82
1.3
2g
1e (ꢀ11.78)
1 f (ꢀ13.02)
1g (ꢀ14.55)
2b
2c[d]
2d
2e
2 f
2g
2.60ꢄ105
6.15ꢄ104
1.44ꢄ105
2.43ꢄ105
3.22ꢄ104
2.31ꢄ104
2.28ꢄ105
3.06ꢄ105
1.79ꢄ105
1.20ꢄ105
7.19ꢄ104
1.89ꢄ104
1.1
0.20
0.81
2.0
0.45
1.2
2b
2c
2d
2e
2 f
2g
8.30ꢄ104
2.10ꢄ104
1.97ꢄ104
4.24ꢄ104
5.33ꢄ103
3.04ꢄ103
4.13ꢄ104
4.81ꢄ104
2.66ꢄ104
1.78ꢄ104
1.01ꢄ104
2.37ꢄ103
2.0
0.44
0.74
2.4
0.53
1.3
2a
9.12ꢄ103
2.93ꢄ104
1.34ꢄ103
1.60ꢄ103
3.64ꢄ103
1.26ꢄ103
1.90ꢄ102
2.14ꢄ104
4.93ꢄ103
4.81ꢄ103
2.48ꢄ103
1.66ꢄ103
8.77ꢄ102
1.79ꢄ102
0.43
5.9
0.28
0.65
2.2
Figure 2. Correlations of (log k2)/sN for the reactions of bissulfonyl ethyl-
enes 1a–d with nucleophiles in DMSO at 208C versus the corresponding
N parameters [correlation lines are fixed at a slope of 1.0, as required by
Equation (1); reactions of 4a–d in CH3CN]. Open symbols were not in-
cluded for the calculation of the correlation lines. For the correlations of
the bissulfonyl ethylenes 1e-g, see Figure S1 in the Supporting Informa-
tion.
2b[d]
2c[d]
2d
2e
2 f
2g
1.4
1.1
[a] The E parameters for 1a–g result from a least-squares minimization
exp
exp
of D2, with D=log k2 ꢀs
NACHTUNGTNER(NUNG N+E); k2 is taken from this table, and N
and sN of the nucleophiles are from Table 1. [b] Calculated by using
Equation (1) with E from this table and N and sN from Table 1. [c] Sol-
vent: CH3CN. [d] Excluded for the calculation of the correlation lines be-
cause of relatively large deviations from the correlation line.
(Table 2). Though deviations of this magnitude are within
the reliability limits of Equation (1), some systematic devia-
tions are obvious. The anion of malononitrile (2e) common-
ly reacts 2–3 times faster than expected from the correla-
tions, whereas the malonate anion 2c is always 2–4 times
less reactive than expected. While analogous deviations
have also been observed for the reactions of these two car-
banions with benzylidene Meldrumꢀs acids and benzylidene
barbituric and thiobarbituric acids, the origin of these devia-
tions is still not understood.
Structure–Reactivity Relationships
According to Figure 3, the bissulfonyl ethylene 1a is about
five orders of magnitude more reactive than its benzylidene
analogue 1b. Thus, phenyl substitution at the b-position (re-
action site) of bissulfonyl ethylenes has a large retarding
effect. Figure 3 furthermore shows that the cyclic bissulfones
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Figure 4. ORTEP drawings of a) 1c and b) 1 f (for which one out of two
asymmetric formula in a unit cell is shown); 50% probability ellipsoids,
hydrogen atoms omitted for clarity (details of the X-ray single-crystal
structure determinations for 1c and 1 f are discussed in
references [24a,b]).
Figure 3. Comparison of E parameters for different bissulfonyl ethylenes
with neutral and charged electrophiles. Data are from Table 2 and
ref. [13i].
Scheme 5. Comparison of the electrophilicities of acyclic and cyclic die-
sters.
1e and 1 f are approximately one order of magnitude more
electrophilic than their acyclic counterparts 1b and 1c, re-
The somewhat lower electrophilicity of the 1,3-dithiane
derivative 1g compared with the other p-methoxybenzyli-
dene derivatives 1c and 1 f can be explained by the elec-
tron-donating effect of the saturated (CH2)3-substituent in
1g. From the almost identical reactivities of 1g and p-me-
thoxy-b-nitro-styrene (Figure 3, right) one can derive that
two sulfonyl groups have a similar activating effect as one
nitro group.
Comparison of the cyclic bissulfone 1 f with the analo-
gously substituted indane-1,3-dione (Figure 3, right) shows
that the conformationally fixed sulfonyl groups activate the
double bonds by almost two orders of magnitude less than
the carbonyl groups in the indane-1,3-dione.
spectively.
[23a]
The 3-point correlation log k versus Hammettꢀs sp
for
compounds 1b–1d, that is, E=4.40spꢀ12.8 (r2 =0.9955),
gives a Hammett reaction constant 1=2.95 for reactions
with nucleophiles of sN =0.67, which is significantly larger
than for p-substituted nitrostyrenes and quinone methides
and even exceeds that of benzylidenemalonates, which have
so far shown the strongest influence of the p-substitutents
on electrophilicity.[23b]
Comparison of the crystal structures of compounds 1c
and 1 f (Figure 4) shows the different orientation of the sul-
fonyl groups with respect to the C=C double bond in the
acyclic and cyclic compound.[24] The conformationally flexi-
ble bissulfone 1c adopts a structure in which one of the S=
O bonds of each sulfonyl group is coplanar with the C=C
bond (torsion angle of C1–C2–S1–O1; 1.128, C1–C2–S2–O4;
ꢀ178.138), while the ring structure of 1 f enforces a bisected
conformation.
From the small difference between the electrophilicities
of 1c and 1 f (as well as of 1b and 1e) one can derive that
the conformations of the sulfonyl groups have little effect
on the Michael acceptor ability of the C=C double bond. A
completely different situation has previously been found for
Michael acceptors with conformationally fixed and flexible
ester groups: Benzylidene Meldrumꢀs acid was reported to
be 10 orders of magnitude more electrophilic than diethyl
benzylidenemalonate (Scheme 5).[17]
Reactions with Other Types of Nucleophiles
As reactions of bissulfonyl ethylenes with enamines and sec-
ondary amines are key steps of the organocatalytic asym-
metric additions of aldehydes and ketones to bissulfonyl eth-
ylenes, we have examined whether the electrophilicity pa-
rameters of 1a–g listed in Table 2 are suitable for predicting
the rates of their reactions with these nucleophiles.
The reaction of the vinyl bissulfone 1a with the enamine
8 gave the ordinary Michael adduct 9a after hydrolysis
(Scheme 6). However, the reaction of the anisylidene bissul-
fone 1c with 8 did not give the expected addition product
after aqueous workup, but instead led to compounds 12 and
13, which may be formed by the mechanism depicted in
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Electrophilicities of Bissulfonyl Ethylenes
Combination of 1c with 10 to 1000 equivalents of pyrroli-
dine (16a) or piperidine (16b) resulted in monoexponential
decays of the absorbance at 340 nm, from which the first-
order rate constants kobs were derived (Figure 5). Unlike the
Scheme 6. Reaction of bissulfonyl ethylene 1a with pyrrolidinocyclohex-
ene 8.
Figure 5. Plots of kobs vs. [16b] and of [16b]/kobs vs. 1/
reaction of the bissulfonyl ethylene 1c with piperidine 16b. The k2 value
for the reaction is 1/(9.96ꢄ10ꢀ3 molLꢀ1 s)=1.00ꢄ102 Lmolꢀ1 sꢀ1
ACHTUNGTREN[NUNG 16b] (inset) for the
Scheme 7. Plausible mechanism for the reaction of 1 with enamine 8.
.
Scheme 7. The initially generated zwitterion 10 undergoes
an intra- or intermolecular 1,3-proton shift to give the enam-
ine 11, which is stable for R=H and gives the Michael
adduct 9a upon hydrolytic workup. For R=pMeO-C6H4,
the enamine 11 undergoes retro-Michael addition with for-
mation of 14 and 15 during aqueous workup because the
iminium ion 14 (R=pMeOC6H4) is stabilized by the elec-
tron-donating effect of the p-methoxy group. The generation
of the bissulfonylmethyl anion 15 by retro-Knoevenagel re-
actions has previously been observed when the bissulfonyl-
styrene 1b was treated with pyrrolidine.[4b]
situation described in Figure 1, plots of kobs versus the amine
concentrations were not linear, however. The upward curva-
tures in the plots of kobs versus [16] indicate a higher reac-
tion order in amine. A rationalization for this observation is
presented in Scheme 8, in which the addition step is as-
The kinetics of the reactions of 1c with the enamine 8
and the amines 16a,b were studied photometrically in the
same manner as described above. The second-order rate
constants for the reaction of the bissulfonyl ethylene 1c with
the enamine 8 in MeCN is in good agreement with the rate
constant calculated from Equation (1) using the reactivity
parameters N and sN of 8[25] and the E parameter of 1c
listed in Table 2 (k2exp/k2calcd =0.53, Table 3). Attempts to
measure the rate of the reaction of bissulfonyl ethylene 1a
with enamine 8 failed due to an increase in absorption
caused by unknown side products.
Scheme 8. Reaction mechanism of bissulfonyl ethylenes with secondary
amines 16.
sumed to be reversible, and a second molecule of the amine
is involved as a base catalyst, as previously reported for the
reactions of secondary amines with quinone methides[26a]
and azodicarboxylates.[26b]
The concentration of intermediate I can be represented
by Equation (3).
Table 3. Experimental and calculated second-order rate constants for the
reactions of 1c with enamine 8 and the secondary amines 16a and 16b at
208C in MeCN.
exp
calcd[a]
calcd
k2exp/k2
Nucleophile (N, sN)
k2
[mꢀ1 sꢀ1
k2
[mꢀ1 sꢀ1
]
G
]
U
Pyrrolidinocyclohexene (8) (16.42, 0.70) 3.15ꢄ101 6.00ꢄ101 0.53
Pyrrolidine (16a) (18.64, 0.60)
Piperidine (16b) (17.35, 0.68)
2.23ꢄ103 7.18ꢄ102 3.1
1.00ꢄ102 2.29ꢄ102 0.44
By assuming a steady-state concentration for the inter-
mediate I and neglecting the direct proton-transfer pathway
[a] Calculated by Equation (1) from E
sN (from reference [25] for 8 and reference [26a] for 16a,b).
(1c)=ꢀ13.88 (Table 2) and N and
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pentane was added. The precipitates were filtered and dried in vacuo to
obtain (2c–g)-K as colorless solids.
(kp), the first-order rate constant kobs can be expressed by
Equation (4), which can be transformed into Equation (5).
Bis(phenylsulfonyl) Ethylenes 1a–d
Bissulfonyl ethylenes 1a,b were prepared according to a literature proce-
dure.[4b] 1c,d were synthesized by modification of a method by Alexa-
kis.[4b] A mixture of p-substituted benzaldehyde (118 mmol), bis(phenyl-
sulfonyl)methane (5.00 g, 16.9 mmol), diethylammonium chloride
(32.1 mmol) and potassium fluoride (2.5 mmol) in dry toluene (150 mL)
was stirred and refluxed under a Dean–Stark water separator. The prod-
uct formation was followed by 1H NMR spectroscopy. After cooling, the
solvent was evaporated and the residue was partitioned between water
(50 mL) and CH2Cl2 (150 mL). The organic phase was separated and the
aqueous phase was extracted with CH2Cl2 (3ꢄ25 mL). The combined or-
ganic layers were dried over Na2SO4, filtered, and concentrated under re-
duced pressure. The crude mixture was purified by flash column chroma-
tography on silica gel (pentane/EtOAc, from 95:5 to 80:20), followed by
recrystallization from pentane/CHCl3 to afford bissulfonyl ethylenes.
As shown in the inset of Figure 5, the plot of [16]/kobs
versus 1/[16] is linear with an intercept corresponding to the
reciprocal of the second-order rate constants k2, which are
listed in Table 3. Again, one finds a fair agreement between
experimental and calculated rate constants.
Benzylidene Benzodithiole Tetroxides 1e and 1 f
The observation that pyrrolidine 16a reacts 70 times
faster with the bissulfonyl ethylene 1c than the correspond-
ing enamine 8 furthermore confirms Alexakisꢀ conclusion
that organocatalytic additions of aldehydes to nitro olefins
proceed via initial, reversible additions of the secondary
amines to the electron-deficient C=C double bond.[27]
These compounds were synthesized analogously to 1c,d using a mixture
of p-substituted benzaldehyde (5.0 mmol), benzodithiole tetroxide[29]
(220 mg, 1.00 mmol), diethylammonium chloride (1.9 mmol), and potassi-
um fluoride (0.15 mmol) in dry toluene (25 mL).
Benzylidene Dithiane Tetroxide (1g)
This compound was synthesized by following the procedure for 1c,d
using
a
mixture of p-anisaldehyde (84.5 mmol), dithiane tetroxide[30]
(2.2 g, 11.9 mmol), diethylammonium chloride (22.6 mmol), and potassi-
um fluoride (1.8 mmol) in dry toluene (100 mL), with the exception that
the obtained residue after workup was washed with diethyl ether, fol-
lowed by recrystallization from ethanol to afford 1g.
Conclusions
We have shown that the rate constants for the reactions of
the bissulfonyl ethylenes 1a–g with carbanions and siloxyal-
kenes follow the linear free-energy relationship (1), which
allows us to derive the empirical electrophilicity parameters
E of these compounds and to compare them with those of
other electrophiles (Figure 3). As a rule of thumb, one can
assume that two geminal phenylsulfonyl groups at a C=C
double bond have a similar activating effect as one nitro
group. Since the electron-withdrawing effect of sulfonyl
groups operates predominantly through polarization and not
through mesomeric effects, the electrophilicities of 1a–g are
not strongly affected by the conformations of the sulfonyl
groups. The E parameters, which have been determined in
this study, are useful to calculate rate constants for the reac-
tions with various nucleophiles and make synthetic strat-
egies more easily predictable. Analogous investigations on
bissulfinyl ethylenes (alkylidenebissulfoxides) would be de-
sirable, as these compounds have also been reported to be
potent Michael acceptors.[28]
Reactions of Bissulfonyl Ethylenes 1 with Nucleophiles 2
Method A: Bissulfonyl ethylenes 1 (1 equiv) were added to a solution of
nucleophile 2a-H or 2b-H (1.0–1.5 equiv) and tBuOK (1.1–1.6 equiv) in
DMSO at room temperature, and the solution was stirred until the disap-
pearance of the starting materials (monitored by TLC). The reaction
mixtures were then poured on ice water and acidified with acetic acid.
Subsequently, the products were extracted with diethyl ether. The com-
bined organic layers were washed with water, dried over Na2SO4, and the
solvent was evaporated under reduced pressure. The crude products were
purified by column chromatography on silica gel (pentane/EtOAc, 95:5).
Method B: As method A except that bissulfonyl ethylenes 1 (1 equiv)
were added to a solution of potassium salts 2-K (1.0–1.5 equiv) in DMSO
at room temperature.
Reactions of Bissulfonyl Ethylenes 1a with Nucleophiles 4
Bissulfonyl ethylenes 1 (1 equiv) were added to a solution of nucleophiles
4 (1.0–1.5 equiv) in CH3CN at room temperature. The solution was
stirred until the disappearance of the starting materials (monitored by
TLC) at room temperature. The reaction was then quenched by the addi-
tion of water and extracted with diethyl ether. The combined organic
layers were washed with water, dried over Na2SO4, and evaporated under
reduced pressure. The crude products were purified by column chroma-
tography on silica gel(pentane/EtOAc, 95:5).
Experimental Section
Kinetics
Materials
The rates of the reactions between the bissulfonyl ethylenes 1a–g and the
reference carbanions 2a–g, S-ylides 3, and silyl enol ether 4a–d were
measured photometrically under pseudo-first-order conditions (excess of
nucleophile; for the reactions of 1a,e with the colored S-ylides 3, the
first-order rate constants kobs were determined with 3 as the minor com-
ponent) at or close to the absorption maximum of 1 by using UV-Vis
spectrometers (conventional diode-array or stopped-flow) at 208C in dry
DMSO or acetonitrile. First-order rate constants kobs (sꢀ1) were obtained
Commercially available DMSO (Acros 99.7%, extra dry, Acro seal) and
acetonitrile (Acros 99.9%, extra dry, Acro seal) were used without fur-
ther purification.
Preparation of Potassium Salts 2 K
Potassium salts (2c–g)-K were generated by mixing solutions of tBuOK
in dry THF with a solution of the corresponding CH-acids (2c–g)-H in
dry THF under a nitrogen atmosphere. To precipitate the product, dry n-
by least-squares fitting of the mono-exponential At =A0 exp
A
the time-dependent absorbances. Since kobs =k[Nu], the second-order
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ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 0000, 00, 0 – 0
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Electrophilicities of Bissulfonyl Ethylenes
rate constants k2 (mꢀ1 sꢀ1) were derived from the slopes of the linear plots
of kobs (sꢀ1) versus [Nu].
91–95; c) H. Mayr, B. Kempf, A. R. Ofial, Acc. Chem. Res. 2003, 36,
66–77; d) H. Mayr, A. R. Ofial in Carbocation Chemistry (Eds.:
G. A. Olah, G. K. S. Prakash), Wiley, New York, 2004, Chap. 13,
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oc/mayr/DBintro.html.
Details of the individual runs of the kinetic experiments as well as prepa-
rative procedures and product characterizations are presented in the Sup-
porting Information.
Acknowledgements
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Received: December 23, 2011
Published online: && &&, 0000
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FULL PAPERS
Electrophilicity Parameters
Quantifying Electrophilicity: Kinetics
of the reactions of 1,1-bissulfonyl-eth-
ylenes with carbon nucleophiles have
been determined to integrate these
Michael acceptors in our comprehen-
sive electrophilicity scales and to com-
pare them with other electrophiles.
The electrophilicities depend only
slightly on conformational restrictions,
and as a rule of thumb, one can
Haruyasu Asahara,
Herbert Mayr*
&&&& — &&&&
Electrophilicities of Bissulfonyl Ethyl-
enes
assume that two geminal phenylsul-
fonyl groups exert a similar activation
as one nitro group.
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www.chemasianj.org
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 0000, 00, 0 – 0
ÝÝ These are not the final page numbers!