Nucleophilic reactivities of benzenesulfonyl-substituted carbanions

Article abstract of DOI:10.1039/b805604h

Kinetics of the reactions of four benzenesulfonyl-stabilized carbanions (1a-d)^- with reference electrophiles (quinone methides 2 and diarylcarbenium ions 3) have been determined in dimethyl sulfoxide solution at 20 °C in order to derive the rea

Full text of DOI:10.1039/b805604h

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Nucleophilic reactivities of benzenesulfonyl-substituted carbanions†
Florian Seeliger and Herbert Mayr*
Received 3rd April 2008, Accepted 15th May 2008
First published as an Advance Article on the web 2nd July 2008
DOI: 10.1039/b805604h
Kinetics of the reactions of four benzenesulfonyl-stabilized carbanions (1a–d)− with reference
electrophiles (quinone methides 2 and diarylcarbenium ions 3) have been determined in dimethyl
sulfoxide solution at 20 ◦C in order to derive the reactivity parameters N and s according to the linear
free-energy relationship log k(20 ◦C) = s(N + E) (eqn (1)). The additions of (1a–d)− to ordinary
Michael acceptors (e.g., benzylidene Meldrum’s acid 4a, benzylidenebarbituric acids 5a–c, and
benzylidene-indan-1,3-diones 6a–d) were also studied kinetically and found to be 5–24 times slower
than predicted by eqn (1).
a nucleophilicity parameter N and a nucleophile-specific slope-
parameter s.
Introduction
The relative inertness of the sulfone group to nucleophilic attack
and its ability to facilitate deprotonation in the a-position have ele-
vated the sulfone moiety to a premier position amongst carbanion-
stabilizing groups.1–4 Sulfonyl-stabilized carbanions can efficiently
be alkylated and acylated, and therefore are important reagents
for the formation of C–C bonds.5,6 Deprotonation of sulfones
In order to investigate whether eqn (1) can also be used
to describe the nucleophilic reactivities of sulfonyl-stabilized
carbanions, we have now investigated the addition reactions
of four sulfonyl-stabilized carbanions (1a–d)− (Scheme 1) with
quinone methides (2a–e, Scheme 2), diarylcarbenium ions (3a–
b, Scheme 2), and Michael acceptors (4a–6d, Scheme 2) in
DMSO. The reactions of nucleophiles with the Michael acceptors
4 (benzylidene Meldrum’s acids), 5 (benzylidenebarbituric acids),
and 6 (2-benzylidene-indan-1,3-diones) have only recently been
demonstrated to follow eqn (1),18–20 though with lower precision.
and subsequent reaction with carbonyl compounds yields b-
7
=
hydroxysulfones, which can easily be reduced to give C C bonds
(Julia olefination).8–11 In the Julia–Kocienski olefination reaction,
olefins are produced directly from sulfonyl-stabilized carbanions
and carbonyl compounds via Smiles rearrangement.10,11
The pKa values of sulfones have systematically been investigated
by Bordwell, who also studied the rate constants for the SN2
reactions of a family of sulfonyl-stabilized carbanions with n-
butyl chloride and n-butyl bromide in DMSO solution.12 In
contrast to the predictions of the reactivity–selectivity principle,
n-butyl bromide was found to be generally 300–400 times more
reactive than n-butyl chloride, independent of the nucleophilicity
of the carbanion. Because pKa values are only a measure of
relative nucleophilicities within classes of structurally related
compounds,13 we now set out to characterize the nucleophilicities
of the title compounds by studying the kinetics of their reactions
with reference electrophiles following the previously established
methodology.14
Scheme 1 Sulfones 1a–d studied in this work. a In DMSO, ref. 17.
The linear free-energy relationship (1), introduced in 1994,15 is
a versatile and powerful tool to organize polar organic reactivity.
The reactions of carbocations with various types of nucleophiles
as well as the reactions of carbanions with quinone methides and
Michael acceptors are described by eqn (1).16
Results
Product studies
The attack of the sulfonyl-stabilized carbanions 1− at Michael
acceptors has previously been described in the literature.21,22 In
order to examine the course of the kinetically studied reactions,
the sulfones 1b and 1c were combined with 1.05 equivalents of
potassium tert-butoxide in dry THF solution and then treated with
equimolar amounts of 5b or 6b (Scheme 3). The resultant anionic
adducts were then precipitated as potassium salts via slow addition
log k2(20 ◦C) = s(N + E)
(1)
In this equation, electrophiles are characterized by the elec-
trophilicity parameter E, and nucleophiles are characterized by
Department Chemie und Biochemie, Ludwig-Maximilians-Universita¨t, Bu-
tenandtstr. 5–13 (Haus F), 81377 Mu¨nchen, Germany. E-mail: herbert.
mayr@cup.uni-muenchen.de; Fax: +49 89-2180-77717; Tel: +49 89-2180-
77719
† Electronic supplementary information (ESI) available: Details of the
kinetic experiments and NMR spectra of all characterized compounds.
See DOI: 10.1039/b805604h
of dry Et2O. H and 13C NMR analyses in DMSO-d6 showed
1
that despite drying for 10 h at 10−2 mbar, the isolated crystalline
products contain 0.2–0.5 equivalents of tetrahydrofuran.
The observation of two sets of signals in the 1H-NMR spectra
of the anionic adducts (7–9)− indicates the formation of two
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Scheme 2 Electrophiles 2–6 employed for the kinetic investigations with the sulfonyl-stabilized carbanions (1a–d)−.
Scheme 4 Additions of the sulfonyl-stabilized carbanions (1a–c)− to the
quinone methides 2a–b. a See Scheme 2.
compounds 10–13, protons Ha and Hb absorb as doublets between
d 4.56–4.82 ppm (Ha) and d 4.86–4.96 ppm (Hb) with 3J coupling
constants of (10.4 0.4) Hz.
Because analogous reaction products can be expected for other
combinations of (1a–d)− with 2–6, product studies have not been
performed for all reactions which have been studied kinetically.
Scheme 3 Michael additions of the sulfonyl-stabilized carbanions 1b−
and 1c− to the benzylidenebarbituric acid 5b and the 2-benzylidene-in-
dan-1,3-dione 6b.
Kinetics
The electrophiles 2–6 show strong absorption bands in the UV-Vis
spectra at kmax = 375–525 nm. By attack of the nucleophiles at the
electrophilic double bond, the chromophore is interrupted, and
the reaction can be followed by the decrease of the absorbances
of the electrophiles. All reactions proceeded quantitatively, as
indicated by the complete decolourisation of the solutions. The
kinetic experiments were performed under first-order conditions
using a high excess of the nucleophiles. From the exponential
decays of the UV-Vis absorbances of the electrophiles, the first-
order rate constants k1W were obtained. Plots of k1W versus [1−] were
linear, and their slopes yielded the second-order rate constants k2
(Table 1).
diastereomers (7−: ratio 3 : 2; 8−: ratio 5 : 4; 9−: ratio 7 : 3). Protons
Ha and Hb, which absorb as doublets between d 4.51–5.08 ppm
(Ha) and d 5.95–6.57 ppm (Hb) with vicinal coupling constants
of approximately 12 Hz, are characteristic for compounds (7–
9)−. The high upfield shifts of the 1H-NMR signals of the vinylic
protons Ha in compounds 5b (d 8.41 ppm)23 and 6b (d 7.58 ppm)24
to d 4.51–5.08 ppm in products (7–9)− indicate the rehybridization
of the b-carbon of the Michael acceptors during nucleophilic
attack.25
The adducts of the carbanions (1a–c)− to the quinone methides
2a and 2b were synthesized analogously and treated with saturated
aqueous ammonium chloride solution to yield diastereomeric mix-
tures of the corresponding phenols 10–13 (Scheme 4), from which
one diastereomer was separated by column chromatography. In
The carbanions were generated in DMSO solution by treatment
of the sulfones 1a–d with 1.05 equivalents of a strong, yet steri-
cally hindered base, e.g., potassium tert-butoxide, Schwesinger’s
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Table 1 Second-order rate constants k2 (DMSO, 20 ◦C) for the reactions
of sulfonyl-stabilized carbanions (1a–d)− with the reference electrophiles
2–3 and Michael acceptors 4–6
As demonstrated for the additions of the sulfonyl-stabilized
carbanion 1b− to the quinone methides 2a–b (entries 8/9 and
10/11, Table 1) and for the reaction of 1c− with 2b (entries 19/20,
Table 1), the rate of the reaction is not significantly affected by the
nature of the base used for the deprotonation of the sulfones 1.
Analogously, for the reaction of 1c− with the Michael acceptor 5a,
a second-order rate constant of 1.48 × 104 M−1 s−1 was observed
with Verkade’s base, and k2 = 1.51 × 104 M−1 s−1 was observed
when KOtBu was used for the deprotonation of 1c (entries 24/25,
Table 1). The addition of equimolar amounts of 18-crown-6 as
complexing agent for the potassium ions does not influence the rate
either, as shown for the reactions of 1a with 2a (entries 1/2, Table 1)
and of 1c with 6a (entries 21/22, Table 1). These comparisons show
that the carbanions 1− are not paired under the conditions used
for the kinetic experiments. The situation is different when Li+ is
used as a counterion.30
No.
Sulfone
Base
Electrophile
E
k2/M−1 s−1
1
2
3
4
5
1a
KOtBua
P4-tBu
2a
2a
2b
6a
4a
5a
6b
2a
2a
2b
2b
6a
4a
5a
6b
5b
2e
2a
2b
2b
6a
6a
4a
5a
5a
6b
5b
2e
2c
2d
6c
5c
6d
3b
3a
−17.90
−17.90
−17.29
−14.68
−13.97
−13.84
−13.56
−17.90
−17.90
−17.29
−17.29
−14.68
−13.97
−13.84
−13.56
−12.76
−13.39
−17.90
−17.29
−17.29
−14.68
−14.68
−13.97
−13.84
−13.84
−13.56
−12.76
−13.39
−16.11
−15.83
−11.32
−10.37
−10.11
−10.04
−9.45
9.74 × 103
9.89 × 103
2.30 × 104
6.25 × 104
6.75 × 104
1.54 × 105
4.13 × 105
1.93 × 103
1.98 × 103
3.63 × 103
3.72 × 103
1.34 × 104
1.86 × 104
3.85 × 104
6.09 × 104
1.65 × 105
3.87 × 105
4.90 × 102
9.77 × 102
1.04 × 103
5.64 × 103
5.78 × 103
1.04 × 104
1.47 × 104
1.51 × 104
2.54 × 104
6.00 × 104
1.84 × 105
6.71 × 101
1.10 × 102
2.34 × 104
5.53 × 104
9.27 × 104
2.85 × 106
6.58 × 106
P4-tBu
KOtBu
KOtBu
KOtBu
KOtBu
P2-tBu
6
7
8b
1b
9
KOtBu
P2-tBu
10b
11
12
13
14
15
16
17
18
19b
20
21b
22
23
24b
25
26
27
28
29
30
31
32
33
34
35
KOtBu
Verkade
Verkade
Verkade
Verkade
Verkade
Verkade
P2-tBu
Due to the yellow colour of the carbanions (1a–c)− in DMSO
solution, electrophiles with UV-Vis maxima >475 nm (i.e., 2a–b,
2e, 4a, 5a–b, 6a–b) had to be employed for kinetic investigations. In
1c
P2-tBu
contrast, the p-nitro-substituted carbanion 1d− absorbs at kmax
540 nm, and electrophiles with UV-Vis maxima at k = 375–475 nm
(e.g., the yellow compounds 2c–d, 5c, 6c–d) were used to study the
reactivity of this carbanion.
=
KOtBu
KOtBua
KOtBu
KOtBu
Verkade
KOtBu
Verkade
Verkade
KOtBu
Verkade
Verkade
Verkade
Verkade
Verkade
Verkade
Verkade
Discussion
1d
In order to determine the nucleophilicity parameters N and s of
the sulfonyl-stabilized carbanions (1a–d)−, the logarithmic second-
order rate constants log k2 were plotted versus the E-parameters
of the corresponding electrophiles. As expected, the plots for
the reactions of sulfonyl-stabilized carbanions (1a–d)− with the
reference electrophiles 2 and 3 yield linear correlations. However,
systematic deviations are found for the rate constants of the
corresponding additions to the Michael acceptors 4–6 (Fig. 1 and
2). The rate constants of these reactions are about 5–24 times
smaller than expected on the basis of the correlation with the
reference electrophiles 2 and 3.
a Addition of equimolar amounts of 18-crown-6. b Rate constants not used
for further evaluations.
tBu-P2- or tBu-P4-phosphazene base, or Verkade’s football-shaped
proazaphosphatrane base (Scheme 5). In DMSO, the large differ-
ences between the pKa values of the sulfones 1 (pKa = 15.8–21.6)17
and Schwesinger’s P4-tBu base (pKBH+ = 30.2),26 potassium tert-
butoxide (pKBH = 29.4),27 and Verkade’s base (pKBH ∼ 27)28,29
warrant the quantitative formation of the carbanions under these
conditions. Complete deprotonation of the sulfones 1b and 1c by
1.05 equivalents of Schwesinger’s P2-tBu base (pKBH+ = 21.5)26
was indicated by the observation that the UV-Vis absorbances of
the solutions of the carbanions 1b− and 1c− at kmax = 350 nm and
kmax = 375 nm, respectively, could not be increased by adding a
second equivalent of the P2-tBu base.
+
+
Fig. 1 Plot of log k2 (DMSO, 20 ◦C) versus the electrophilicity parameters
E for the reactions of the carbanions 1b− and 1d− with the reference
electrophiles 2, 3 and the Michael acceptors 4–6.
Scheme 5 Sterically hindered bases used for the deprotonation of sulfones
1a–d.
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Fig. 2 Plot of log k2 (DMSO) versus electrophilicity parameters E for the
reactions of carbanion 1c− with the quinone methides 2 and the Michael
acceptors 4–6.
Table 2 N and s parameters for the sulfonyl-stabilized carbanions
(1b–d)−
Carbanion
N
s
1b−
1c−
1d−
24.3
22.6
18.5
0.51
0.57
0.75
From the correlation lines drawn in Fig. 1 and 2, which
are based on the reactions of the carbanions (1b–d)− with the
reference electrophiles 2a–e, we have derived the nucleophile-
specific parameters N and s, which are listed in Table 2. As the
reactivity of the carbanion 1a− was only investigated towards two
reference compounds of comparable electrophilicity (see ESI†),
the corresponding N and s values have not been calculated.
According to Fig. 3, the benzenesulfonyl-stabilized benzyl
anions (1b–d)− are considerably more nucleophilic than their
trifluoromethanesulfonyl-stabilized analogues31–33 (4 to 7 units in
N) and the corresponding a-nitrobenzyl anions.
Fig. 3 Comparison of the nucleophilicities of differently substituted
benzyl anions in DMSO.
To include the carbanion 1a−, detailed structure–reactivity
correlations shall, therefore, be based on individual rate constants.
Second-order rate constants for the reactions of the quinone
methide 2b have been measured with all sulfonyl-stabilized car-
banions 1− except 1d−. Because the electrophilicity of 2b is only
slightly smaller than that of 2c and 2d, the rate constant for the
reaction of 1d− with 2b can reliably be calculated from the lower
correlation line of Fig. 1 as k2 = 8.70 M−1 s−1.
Fig. 4 Correlations of the logarithmic second-order rate constants
of the reactions of quinone methide 2b with the carbanions (1a–d)−
and the trifluoromethanesulfonyl-stabilized carbanions (DMSO) with the
Hammett rp values. Filled symbols: experimental rate constants; open
symbols: k2 calculated by eqn (1).
Fig. 4 shows that the rate constants for the reactions of the
carbanions (1a–d)− with the quinone methide 2b correlate only
moderately with Hammett’s r− parameters. The correlation with
rp is even worse, and because of the deviation of p-CN and p-NO2
in opposite directions from the correlation line, a Yukawa–Tsuno
treatment34 would not improve the fit.
−
previously found in the Hammett plot (see Fig. 4). The slope
of the Brønsted correlation in Fig. 5 (b = 0.58) is 1.44 times
larger than that of the corresponding Brønsted plot for the
reactions of the carbanions 1− with n-butyl chloride (b = 0.402),12,13
in agreement with previous observations that the variation of
In agreement with a higher negative charge density at the
benzylic carbon of carbanions (1a–d)−, the Hammett reaction
constant q is more negative than for the analogous reactions of the
corresponding trifluoromethanesulfonyl-stabilized anions (Fig. 4,
lower graph).
In contrast, the Brønsted correlation shown in Fig. 5 is of
high quality though the rate constant for the p-cyano substituted
compound lies slightly above the depicted correlation line as
3
nucleophiles affects the reactivities toward Csp electrophiles to
a smaller degree than the reactivities toward Csp electrophiles.35
2
Systematic investigations of SN2 reactions with sulfonyl-stabilized
carbanions are presently under investigation.
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7−. Yellow crystals, isolated as a mixture of diastereomers (3 :
1
2), which contain 0.5 equivalents of THF (from H NMR), 41%
yield. Major diastereomer: dH(400 MHz; DMSO-d6) 2.78 (9 H, s,
NMe and NMe2), 2.87 (3 H, s, NMe), 4.99 (1 H, d, J 12.0, C−CH),
6.17 (1 H, d, J 12.0, CH), 6.30 (2 H, d, J 8.7, Ar) and 7.24–7.64
(11 H, m, Ar); dC(100 MHz; DMSO-d6) 26.3 (NMe), 27.0 (NMe),
40.3 (CH), 40.6 (NMe2), 73.0 (CH), 88.5 (C−), 112.0 (CAr-H), 123.7
(CAr-H), 127.1–127.6 and 128.2–132.1 (5 × CAr-H and CAr-CF3),
132.3–140.8 (3 × CAr), 148.6 (CAr-N), 152.5 (CO), 160.6 (CO) and
161.3 (CO). Minor diastereomer: dH(400 MHz; DMSO-d6) 2.65
(6 H, s, NMe2), 2.87 (s, 3 H, NMe), 5.07 (1 H, d, J 11.9, C−CH),
6.27 (2 H, d, J 8.7, Ar), 6.56 (1 H, d, J 11.9, CH), 7.11 (2 H, d,
J 8.7, Ar) and 7.24–7.64 (9 H, m, Ar); dC(100 MHz; DMSO-d6)
26.3 (NMe), 27.0 (NMe), 40.3 (CH), 40.6 (NMe2), 68.5 (CH), 86.8
(C−), 111.6 (CAr-H), 124.3 (CAr-H), 127.1–127.9 and 128.2–132.1
(5 × CAr-H and CAr-CF3), 132.3–140.8 (3 × CAr), 147.6 (CAr-N),
152.1 (CO), 160.6 (CO) and 161.3 (CO).
Fig. 5 Brønsted plot for the reactions of sulfonyl-stabilized carbanions
(1a–d)− with the quinone methide 2b (DMSO). Filled symbols: experimen-
tal rate constants; open symbol: calculated (eqn (1)) rate constant.
8−. Yellow crystals, isolated as a mixture of diastereomers (5 :
1
4), which contain 0.3 equivalents of THF (from H NMR), 81%
Conclusions
yield. Major diastereomer: dH(400 MHz; DMSO-d6) 2.78 (3 H, s,
NMe), 2.78 (6 H, s, NMe2), 2.87 (3 H, s, NMe), 4.97 (1 H, d, J 12.0,
C−CH), 6.12 (1 H, d, J 12.0, CH), 6.31 (2 H, d, J 8.8, Ar) and
7.08–7.68 (11 H, m, Ar); dC(100 MHz; DMSO-d6) 26.3 (NMe),
27.0 (NMe), 40.2 (CH), 40.6 (NMe2), 73.2 (CH), 88.5 (C−), 110.0
(CAr-CN), 112.0 (CAr-H), 118.9 (CN), 127.1–132.2 (6 × CAr-H),
132.2 (CAr), 140.5 (CAr), 140.6 (CAr), 148.6 (CAr-N), 152.5 (CO),
160.5 (CO) and 161.3 (CO). Minor diastereomer: dC(400 MHz;
DMSO-d6) 2.66 (6 H, s, NMe2), 2.87 (3 H, s, NMe), 5.04 (1 H, d,
J 11.8, C−CH), 6.27 (2 H, d, J 8.9, Ar), 6.56 (1 H, d, J 11.9, CH),
7.10 (2 H, d, J 8.8, Ar) and 7.08–7.68 (9 H, m, Ar); dC(100 MHz,
DMSO-d6) 26.3 (NMe), 27.0 (NMe), 40.2 (CH), 40.6 (NMe2),
68.7 (CH), 86.7 (C−), 110.0 (CAr-CN), 111.5 (CAr-H), 118.7 (CN),
127.1–132.3 (6 × CAr-H), 132.8 (CAr), 139.9 (CAr), 140.5 (CAr),
147.7 (CAr-N), 152.1 (CO), 160.5 (CO) and 161.3 (CO).
The second-order rate constants for the reactions of the
benzenesulfonyl-stabilized carbanions (1a–d)− with the elec-
trophiles 2–6 can be described by eqn (1) within the postulated
accuracy of a factor 10–100. However, all second-order rate
constants for the additions of (1a–d)− to the electrophiles 4–6
are 5–24 times smaller than predicted by eqn (1) based on the
N and s parameters derived from the reactions of 1− with the
reference electrophiles 2 and 3. This observation is in line with
the previously reported systematic deviations of the reactions
of the dimedone anion and the anion of diethyl malonate with
the Michael acceptors 4–6.20 Though these systematic deviations
suggest that one should derive correlation equations for separate
groups of electrophiles, we rather stick to a single set of universal
parameters and accept the relatively low accuracy of eqn (1) in
order to have a simple and unambiguous correlation, which makes
reliable estimates in a reactivity range of more than thirty orders
of magnitude. Nevertheless, further investigations are going on in
order to understand the origin of these deviations.
9−. Orange crystals, isolated as a mixture of diastereomers (7 :
1
3), which contain 0.2 equivalents of THF (from H NMR), 69%
yield. Major diastereomer: dH(400 MHz; DMSO-d6) 2.78 (6 H, s,
NMe2), 4.53 (1 H, d, J 11.9, C−CH), 5.97 (1 H, d, J 11.9, CH),
6.34 (2 H, d, J 8.9, Ar) and 6.69–7.63 (15 H, m, Ar); dC(100 MHz;
DMSO-d6) 40.2 (CH), 40.5 (NMe2), 72.8 (CH), 106.8 (C−), 109.9
(CAr-CN), 112.1 (CAr-H), 115.9 (CAr-H), 118.7 (CN), 127.4–132.3
(6 × CAr-H), 132.0 (CAr), 140.0–140.6 (4 × CAr), 148.6 (CAr-N) and
186.8 (2 × CO). Minor diastereomer: dH(400 MHz; DMSO-d6)
2.65 (6 H, s, NMe2), 4.57 (1 H, d, J 11.3, C−CH), 6.27–6.35
(3 H, m, CH and Ar) and 6.69–7.63 (15 H, m, Ar); dC(100 MHz,
DMSO-d6) 40.2 (CH), 40.2 (NMe2), 69.5 (CH), 105.1 (C−), 109.9
(CAr-CN), 111.7 (CAr-H), 115.8 (CAr-H), 118.7 (CN), 127.4–132.3
(6 × CAr-H), 133.0 (CAr), 140.0–140.6 (4 × CAr), 147.6 (CAr-N) and
187.3 (2 × CO).
Experimental
1H and 13C NMR chemical shifts are expressed in ppm and refer
to the corresponding solvents (dH 2.50, dC 39.5 for DMSO-d6 and
dH 7.26, dC 77.2 for CDCl3), J values are given in Hz. DEPT
and HSQC experiments were employed to assign the signals. All
reactions were performed under an atmosphere of dry argon. Dry
DMSO for kinetics was purchased (<50 ppm H2O). Sulfones 1a–
d were synthesized from the corresponding benzyl bromides and
sodium benzenesulfinate in DMSO according to ref. 36.
General procedure for the synthesis of neutral addition products
10–13
General procedure for the synthesis of anionic addition products
Under an argon atmosphere equimolar amounts of potassium
tert-butoxide (∼0.6 mmol) and sulfone 1 were dissolved in freshly
distilled THF (10 mL). The electrophile (∼0.6 mmol) was then
added to this stirred solution and after 10 min the product was
precipitated by adding diethyl ether (10 mL).
Under an argon atmosphere equimolar amounts of potassium
tert-butoxide (∼0.4 mmol) and sulfone 1 were dissolved in freshly
distilled THF (15 mL). A solution of the quinone methide 2
(∼0.4 mmol) in THF (20 mL) was then added to this solution
and stirred for 1.5 h. After removal of the solvent in the vacuum
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the residue was washed with saturated NH4Cl solution, extracted
with EtOAc, and dried over Na2SO4. In order to obtain the
major diastereomer, the crude product was purified by column
chromatography (SiO2, hexane–EtOAc) twice and crystallized
from ethanol. The absolute conformation of the diastereomer was
not determined.
149.5 (CAr) and 152.1 (CAr); m/z (EI) 594.2901 (M+. C37H42N2O3S
requires 594.2916), 594 (M+, 2%), 338 (100).
Kinetic experiments
During all kinetic studies the temperature of the solutions was kept
constant (20
0.1 ◦C) by using a circulating bath thermostat.
Dry DMSO for kinetics was purchased (<50 ppm H2O). For
the evaluation of kinetics the stopped-flow spectrophotometer
systems Hi-Tech SF-61DX2 or Applied Photophysics SX.18MV-
R stopped-flow reaction analyzer were used. Rate constants kobs
(s−1) were obtained by fitting the single exponential At = A0
exp(−kobst) + C to the observed time-dependent electrophile
absorbance (averaged from at least 3 kinetic runs for each
nucleophile concentration). For the stopped-flow experiments 2
stock solutions were used: a solution of the electrophile in DMSO
and a solution of the carbanion, which was generated by the
deprotonation of the CH acid with 1.05 equivalents of base.
4-[2-Benzenesulfonyl-2-(3-chlorophenyl)-1-(4-dimethylaminoph-
enyl)ethyl]-2,6-di-tert-butylphenol 10. Yellow crystals, 7% yield,
mp 222–224 ◦C. dH(300 MHz; CDCl3) 1.19 (18 H, s, 2 × C(CH3)3),
2.84 (6 H, s, NMe2), 4.80 (1 H, s, OH), 4.82 (1 H, d, J 10.4, CH),
4.86 (1 H, d, J 10.1, CH), 6.55 (2 H, br s, Ar), 6.75 (2 H, s, Ar) and
6.90–7.38 (11 H, m, Ar); dC(75.5 MHz; CDCl3) 30.3 (6 × CH3),
34.3 (2 × C(CH3)3), 41.0 (NMe2), 51.7 (CH), 75.9 (CH), 113.2
(CAr), 125.3 (CAr-H), 128.1 (CAr-H), 128.6 (2 × CAr-H), 128.9 (CAr-
H), 129.1 (CAr-H), 131.1 (CAr-H), 132.3 (CAr-H), 132.9 (CAr-H),
133.8 (CAr), 135.5 (CAr), 135.6 (CAr), 140.0 (CAr) and 152.1 (CAr);
m/z (EI) 603.2567 (M+. C36H42ClNO3S requires 603.2574), 603
(M+, 1%), 461 (55), 338 (100), 322 (45), 280 (17), 134 (19), 127 (17)
and 125 (55).
Acknowledgements
4-[2-Benzenesulfonyl-1-(4-dimethylaminophenyl)-2-(4-trifluoro-
methylphenyl)ethyl]-2,6-di-tert-butylphenol 11. Colourless crys-
tals, 9% yield, mp 209–211 ◦C. dH(300 MHz; CDCl3) 1.16 (18 H, s,
2 × C(CH3)3), 2.82 (6 H, s, NMe2), 4.79 (1 H, s, OH), 4.85 (1 H,
d, J 10.1 Hz, CH), 4.95 (1 H, d, J 10.1, CH), 6.50 (2 H, d, J 7.7,
Ar), 6.72 (2 H, s, Ar ) and 7.11–7.37 (11 H, m, Ar); dC(75.5 MHz;
CDCl3) 30.3 (6 × CH3), 34.2 (2 × C(CH3)3), 41.0 (N(CH3)2), 51.8
(CH), 76.1 (CH), 113.3 (CAr-H), 122.2 (CF3), 124.8 (2 × CAr-H),
125.3 (CAr-H), 128.5 (CAr-H), 128.7 (CAr-H), 128.9 (CAr-H), 129.9
(CAr), 130.4 (CAr), 131.3 (CAr-H), 132.0 (CAr), 133.0 (CAr-H), 135.6
(CAr), 137.8 (CAr), 140.0 (CAr), 149.4 (CAr) and 152.1 (CAr); m/z
(EI) 637.2820 (M+. C37H42F3NO3S requires 637.2838), 637 (M+,
2%), 338 (100).
Financial support by the Deutsche Forschungsgemeinschaft (MA
673/17) and the Fonds der Chemischen Industrie is gratefully
acknowledged.
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