Quantification of the Nucleophilic Reactivities of Cyclic β-Keto Ester Anions

Article abstract of DOI:10.1002/ejoc.201501107

Kinetics of the reactions of enolate anions derived from acyclic and cyclic β-keto esters with benzhydrylium ions and quinone methides have been determined photometrically in dimethyl sulfoxide solution at 20 C. The reactions follow second-order rate laws: first-order with respect to the electrophile and first-order with respect to the enolate. Reactions conducted in the presence of 18-crown-6 ether and in the presence of variable concentrations of K⁺ allowed the influence of ion-pairing on the nucleophilic reactivities of the various enolate ions to be determined quantitatively. Enolate ions derived from oxocycloalkanecarboxylic esters show reactivities similar to those of their acyclic analogue. Enolate ions derived from δ-lactones are less nucleophilic, which is explained by the enforced (E) conformation of the corresponding esters.

Full text of DOI:10.1002/ejoc.201501107

FULL PAPER
DOI: 10.1002/ejoc.201501107
Quantification of the Nucleophilic Reactivities of Cyclic β-Keto Ester Anions
[a]
[a]
Francisco Corral-Bautista and Herbert Mayr*
Dedicated to Professor Reinhard Brückner on the occasion of his 60th birthday
Keywords: Kinetics / Ion pairs / Anions / Enols / Reaction mechanisms
Kinetics of the reactions of enolate anions derived from
acyclic and cyclic β-keto esters with benzhydrylium ions and
quinone methides have been determined photometrically in
dimethyl sulfoxide solution at 20 °C. The reactions follow
second-order rate laws: first-order with respect to the electro-
phile and first-order with respect to the enolate. Reactions
conducted in the presence of 18-crown-6 ether and in the
ence of ion-pairing on the nucleophilic reactivities of the
various enolate ions to be determined quantitatively. Enolate
ions derived from oxocycloalkanecarboxylic esters show re-
activities similar to those of their acyclic analogue. Enolate
ions derived from δ-lactones are less nucleophilic, which is
explained by the enforced (E) conformation of the corre-
sponding esters.
+
presence of variable concentrations of K allowed the influ-
Introduction
β-Keto esters, which are readily accessible through con-
densation reactions, are important reagents in organic syn-
thesis. They react with a variety of electrophiles either via
the corresponding enols or with the enolate anions obtained
by deprotonation with a variety of bases.[
1]
As illustrated for the anion of ethyl α-methylacetoacetate
(1) in the upper row of Scheme 1, anions derived from acy-
clic β-keto esters can adopt four different configurations.
Previous studies of different alkali metal salts of β-keto es-
ters and β-keto aldehydes in N,N-dimethylformamide or
methanol showed that the corresponding anions predomi-
nately adopt the S- and U-shape. The W-configuration is
disfavored by the steric repulsion between the alkyl and alk-
oxy groups. The dynamic equilibria between the U- and
S-configurations were found to depend on the solvent po-
larity and on the counterions. Whereas the free enolates,
Scheme 1. Configurations of the studied β-keto ester anions.
In cyclic structures 2–4, these configurations are partially
[
2]
e.g., the potassium salts in the presence of crown ether, pre- fixed. Whereas in the small cycloalkanone carboxylates 2,
dominately adopt the S-configuration, the U-shape is pre- the S - and U-configurations are possible, the acetyl lactone
1
ferred when the Coulombic repulsion of the negatively 4 can adopt both U- and S -configurations, and the W-con-
2
[
3]
charged oxygen atoms is compensated by ion pairing.
figuration is fixed in the β-ketolactone 3.
Thus, lithium salts of β-keto esters exclusively adopt the U-
configuration.
Recently, we investigated the influence of counterions on
the nucleophilic reactivities of enolate ions derived from
ketones, esters, and β-dicarbonyl compounds towards benz-
[
3e]
hydrylium ions and Michael acceptors in dimethyl sulfoxide
[
a] Department Chemie, Ludwig-Maximilians-Universität
[4]
(
DMSO). The potassium salts of these compounds be-
München,
–3
–1
Butenandtstraße 5-13 (Haus F), 81377 München, Germany
E-mail: Herbert.Mayr@cup.uni-muenchen.de
http://www.cup.lmu.de/oc/mayr/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201501107.
haved as free ions at low concentrations (Յ 10 molL ),
and the addition of 18-crown-6 ether did not affect the rates
of their reactions with electrophiles. The only exceptions
were the potassium salts derived from β-keto esters and one
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Reactivity of Cyclic β-Keto Ester Anions
β-ketoamide, which showed counterion effects at concentra-
–
4
–1
tions around 10 molL . However, we only studied acyclic
secondary carbanions, which are able to rotate and adopt
all possible configurations shown in Scheme 1.
In this article, we report on the kinetics of a series of
acyclic and cyclic tertiary β-keto ester anions (Scheme 1)
with benzhydrylium ions and structurally related quinone
methides (reference electrophiles 5; Table 1) in DMSO solu-
tion. After describing the influence of the counterions on
the nucleophilic reactivities of these anions, we will analyze
the obtained rate constants with the linear free-energy rela-
tionship described by Equation (1),[ where E is an electro-
phile-specific parameter, and N and sN are nucleophile-spe-
cific parameters that are commonly derived from the rates
of the reactions of the corresponding nucleophiles with
benzhydrylium ions and/or structurally related Michael ac-
ceptors (reference electrophiles).[
Scheme 2. Synthesis of 4-H.
The potassium salts 1-K, (27–12)-K, 3-K, and 4-K were
synthesized by mixing the corresponding CH acids (1–4)-H
with potassium tert-butoxide in ethanol, in analogy to a
[
4]
previously described procedure (Scheme 3). The potas-
sium salts of the oxocyclopentane- and oxocyclohexane-
carboxylic esters 2 and 2 precipitated when the cyclic keto
5]
5
6
esters were added to a cold solution (0 °C) of potassium
hydroxide in ethanol/water as described by Mayer and Al-
[
11]
der.
The yields of the isolated potassium salts (27–12)-K
6]
were moderate because of their solubility in diethyl ether
and diethyl ether/pentane mixtures, which were used to
wash the precipitated salts.
lgk
2
(20 °C) = s
N
(N + E)
(1)
Table 1. Reference electrophiles 5 employed in this study.
[
a] E parameters taken from ref.[6b,6c,6f] [b] Given in nm in DMSO.
Results and Discussion
Synthesis of the β-Keto Ester Anions
Scheme 3. Synthesis of the potassium salts (1–4)-K and 13C NMR
Compounds 1-H and 2-H were either commercially avail-
chemical shifts (in [D
6
]DMSO) of their anionic center in the cyclic
able or synthesized by reactions of the cycloalkanone enol- β-keto ester anions 2.
ates with diethyl carbonate.[ The β-keto lactone 3-H was
7]
obtained by condensation of 1-H with paraformaldehyde
according to a previously described procedure.[ We had
8]
Product Studies
[
9]
problems to reproduce the published syntheses of 4-H;
[
9b]
therefore we modified the procedure described previously
Combination of DMSO solutions of 1-K and quinone
and found that 4-H is conveniently obtained by reaction of methide 5h gave 77% yield of the addition product 6 as a
acetyl chloride with 2-(trimethylsiloxy)dihydropyran in the mixture of two diastereoisomers after acidic aqueous
[10]
absence of any catalyst (Scheme 2).
workup and chromatographic purification (Scheme 4).
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The addition products of the lactone derivatives 3-K and
4
-K with benzhydrylium tetrafluoroborates 5a-BF and 5d-
4
BF in DMSO decomposed during aqueous workup; there-
4
1
fore, the course of these reactions was investigated by H
and 13C NMR spectroscopy. To this end, 3-K and 4-K
(
1.2 equiv.) were combined with 5a-BF4 in [D ]DMSO.
6
NMR spectroscopic analysis of the mixtures showed the
quantitative formation of the addition products 13 and 14
(Scheme 7).
Scheme 4. Reaction of 1-K with quinone methide 5h in DMSO.
[
a] Based on 1H NMR spectroscopic analysis after chromato-
graphic purification.
The cyclic keto esters (25–7)-H were mixed with quinone
methide 5j and 10 mol-% 1,5-diazabicyclo[4.3.0]non-5-ene
(DBN) in DMSO. The resulting solutions, which turned
from yellow to blue, probably due to the formation of traces
of oxidation products, were worked up by adding saturated
NaCl solution. Finally, products 7–9 were extracted with
diethyl ether and purified by column chromatography
(Scheme 5).
4 6
Scheme 7. Combination of 3-K and 4-K with 5a-BF in [D ]-
DMSO.
Kinetic Investigations
Scheme 5. Reactions of cyclic keto esters (25–7)-H with the quinone
methide 5j. [a] Based on 1H NMR spectroscopic analysis of the
crude product.
The reactions of anions 1–4 with the reference electro-
philes 5 were performed in DMSO solution at 20 °C and
monitored by UV/Vis spectroscopy at the absorption max-
ima of the electrophiles. To simplify the evaluation of the
kinetic experiments, the carbanions were used in large ex-
cess (Ͼ 10 equiv.). Thus, their concentrations remained al-
most constant throughout the reactions, and pseudo-first-
order kinetics were obtained in all runs. The first-order rate
constants kobs were derived by least-squares fitting of the
exponential function A = A exp(–kobst) + C to the time-
When quinone methide 5h was added to solutions of the
potassium salts (27–12)-K in DMSO, the color of the solu-
tions changed immediately from yellow to blue. After aque-
ous workup with acetic acid and column chromatographic
purification, the addition products 10–12 were isolated
(Scheme 6).
t
0
dependent absorbance A of the electrophiles. Second-order
t
rate constants (Tables 2 and 4) were obtained as the slopes
of plots of kobs vs. the nucleophile concentrations (Fig-
ure 1).
The reactivities of the potassium salts correspond to the
reactivities of the free anions when the pseudo-first-order
rate constants, which are obtained in the presence or in the
absence of 18-crown-6 ether, are on the same correlation
line of kobs vs. the nucleophile concentration. As exem-
plified for the reaction of 3-K with 5c in Figure 1, this be-
havior was found for the potassium salts 1-K, 3-K, and 4-
K, revealing that these β-keto ester anions do not interact
Scheme 6. Reactions of the potassium salts of the cyclic keto esters
1
2
7–12 with the quinone methide 5h. [a] Based on H NMR spectro-
scopic analysis of the crude products. [b] Only the major isomer
was isolated after column chromatographic purification.
+
–4
with K in DMSO solution at concentrations of 10 to
–3
–1
10 molL . The potassium salts of the cyclic β-keto esters
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Reactivity of Cyclic β-Keto Ester Anions
Figure 1. (Left) Plot of the absorbance A (at 627 nm) vs. time for the reaction of 3-K (1.75ϫ10–4 molL ) with 5c (1.13ϫ10 molL–1)
in DMSO at 20 °C. (Right) Plot of the first-order rate constants kobs vs. the concentration of 3-K. Filled circles: in the absence of 18-
crown-6 ether. Empty circles: in the presence of 1.6–1.9 equiv. of 18-crown-6 ether in relation to 3-K.
–1
–5
(
25–12)-K, on the other hand, reacted with slightly different Table 3. Pseudo-first-order rate constants kobs for the reactions of
rate constants when the kinetic experiments were performed carbanions 1, 2 , 212, 3, and 4 with reference electrophiles 5e or 5g
at variable concentrations of KBPh in DMSO at 20 °C. 100·krel
6
4
in the absence or in the presence of 1.2–2.5 equiv. of crown
ether (Table 2), indicating weak interactions of the carban-
ions with the potassium ions.
was calculated from the second-order rate constants of the free
anions given in Table 4.
Table 2. Second-order rate constants of the reactions of 15 and 2
with 5 in the presence and in the absence of 18-crown-6 ether.
[Lmol–1 s ]
–1
k
2
(K /crown)/k
+
(K+)
Reaction
k
2
2
+
[a]
K+
K /crown
5.48ϫ103
[b]
4.82ϫ103
1.14
1.22
1.22
1.17
1.14
1.16
1.04
1
5 + 5g
2
5
+ 5g
+ 5i
1.69ϫ104
9.34ϫ102
1.39ϫ104
2
2
5
7.67ϫ104
4
2
2
2
6
+ 5g
+ 5g
+ 5g
1.33ϫ10
1.14ϫ10
9.55ϫ104
1.09ϫ105
7
4
4
8
9.38ϫ10
8.09ϫ10
2
12 + 5g
3.09ϫ104
2.97ϫ104
+
[
a] 1.2–2.5 equiv. of 18-crown-6 ether with respect to K . [b] Taken
[
6c]
from ref.
The nucleophilic reactivity of the potassium salt of ethyl
acetoacetate (15-K) in DMSO was studied in previous
[
6c]
work. Given that all kinetic experiments were performed
in the presence of 18-crown-6 ether, the counterion effect
was not investigated at that time. Table 2 shows that the
second-order rate constant for the reaction of the potassium
salt 15-K (in the absence of 18-crown-6 ether) with quinone
methide 5g is smaller by a factor of 1.14 than that in the
presence of crown ether (1.01–1.10 equiv.). The five- and
six-membered cyclic β-keto ester anions 2 and 2 reacted
5
6
1.2 times faster in the presence (1.2–2.5 equiv. of 18-crown-
6
ether) than in the absence of crown ether, and this ratio
decreased with increasing ring size to 1.15 for 2 and 2 and
7
8
to 1.04 for 212 (Table 2).
The dependence of the counterion effect on the structure
of the carbanions was studied in more detail by performing
kinetic experiments in the presence of variable concentra-
tions of KBPh with the concentrations of the reactants
4
kept constant (Table 3).
Plots of the relative rate constants (100·k ) with respect
rel
to the rate constant in the presence of 18-crown-6 ether
(free anions) against the total concentration of potassium
ions show that kobs of the cyclic β-keto ester anion 2 de-
6
creases to around 15% of the value of the free anion at a
potassium concentration of 10 molL , whereas the rate
[
a] Calculated as kobs = k
for the corresponding reactions of the free anions (potassium salts or
constant of the 12-membered ring anion 212 remains at potassium salts in the presence of 18-crown-6 ether) given in Table 4.
2
[Nu] from the second-order rate constants
–
2
–1
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F. Corral-Bautista, H. Mayr
FULL PAPER
about 80% at the same K+ concentration (Table 3, Fig- Table 4. Second-order rate constants k
for the reactions of the free
2
carbanions 1–4 with the reference electrophiles 5 in DMSO at 20 °C
reactions of 2-K were studied in the presence of 1.2–2.5 equiv. of
8-crown-6 ether).
ure 2).
(
1
Figure 2. Plot of the relative pseudo-first-order rate constants for
the reactions of carbanions 1–4 with quinone methides 5e or 5g vs.
+
the total concentration of K in DMSO solution at 20 °C (data
from Table 3). [a] Data taken from ref.[
4]
Figure 2 also shows that α-methylation reduces the influ-
ence of ion pairing. Whereas the reactivity of 15 decreases
to around 45% of that of the free anion at a potassium
–
2
–1
concentration of 1.5ϫ10 molL , the rate constants for
the reaction of 1 remained at around 70% of the initial
value at the same concentration. The same trend has pre-
viously been observed for the ion-pair association equilibria
of the anions of pentane-2,4-dione and 3-methylpentane-
[
3f]
2
,4-dione. The reactivities of the lactone-derived anions
3
and 4 decrease to around 55–65% of the reactivities of
the free anions at
1
a
potassium concentration of
.5ϫ10– molL .
2
–1
The kinetics of the reactions of the potassium salts (1–
)-K with the reference electrophiles were determined in
[
a] Rate constants were acquired by adding different amounts of
4
conjugated CH acid (3–5 equiv.). [b] Value without CH acid; not
used for the calculation of N and s .
N
DMSO at 20 °C as described above. Given that the presence
of 18-crown-6 ether did not affect the reactivities (e.g., Fig-
ure 1), the rate constants for the reactions of the potassium
salts 1, 3, and 4 must correspond to those of the free anions.
+
As the anions 25–12 show interactions with K at the ap-
Correlation Analysis
plied concentrations, their reactions were studied in the
presence of 1.2–2.5 equiv. 18-crown-6 ether to obtain the
reactivities of the free anions (Table 4).
Plots of lgk for the reactions of the carbanions 1–4 with
2
the reference electrophiles 5 against the electrophilicity pa-
The reactions of 2 and 2 with 5k did not lead to com- rameters E were linear, as shown for some representative
6
12
plete conversion of the electrophile (equilibrium); therefore, examples in Figure 3 and for all nucleophiles in the Sup-
only 1–2 half-lives followed a monoexponential decay. porting Information, indicating that Equation (1) is appli-
However, when 3–5 equiv. of the conjugate CH acids were cable to these reactions. From the slopes of these corre-
added as a proton source, higher conversions and excellent lations, the nucleophile-specific parameters s were derived,
N
fits of the exponential A = A exp(–kobst) + C to the de- and the negative intercepts on the abscissa (lgk = 0) corre-
t
0
2
crease of the absorbance of the electrophile were observed. spond to the nucleophilicity parameters N (Table 4).
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Reactivity of Cyclic β-Keto Ester Anions
Figure 3. Correlation of the rate constants lgk
parameters E of 5.
2
for the reactions of nucleophiles 1–4 with electrophiles 5 in DMSO with the electrophilicity
Structure-Reactivity Relationships
The s parameters of the five-, six-, and seven-membered
N
rings 25–7 are almost identical (0.82, 0.84, 0.83), which is
illustrated by the parallel lines in Figure 3; that is, the rela-
tive reaction rates are independent of the nature of the elec-
trophile. When the size of the ring increases, the suscep-
tibility parameter (s ) decreases to 0.76 for 2 and 0.63 for
N
8
212
, and the relative reactivities depend on the nature of the
electrophile.
Comparison of compounds 1 and 15 shows that the in-
troduction of a methyl group into the 2-position of the ethyl
acetoacetate anion causes a slight increase of reactivity, as
previously found in the β-diketo and β-dicarboxylate series
[
12]
(Scheme 8).
Despite strongly differing absolute rate constants for the
reactions with different electrophiles, 2-methyl substitution
always activates the nucleophilic reactivities of the enolates
by a factor of 3–5, which is in line with the fact that 2-
methyl substitution also increases the pKaH values of these
Scheme 8. Second-order rate constants [Lmol–1 s–1] for the reac-
tions of secondary and tertiary β-dicarbonyl anions with electro-
[6c]
philes in DMSO at 20 °C. [a] From ref.
[b] Calculated from
[
3f]
Equation (1). [c] From ref.[
12]
anions in DMSO solution by approximately two units.
Let us now turn to the tertiary systems depicted in Fig-
ure 4. All anions 2 derived from oxocycloalkanecarboxyl-
ates have nucleophilicities N that are similar to those of mation, which is preferred by approximately 36 kJmol for
their acyclic analogue 1. Due to the different susceptibilities methyl acetate (Scheme 9).
sN, their relative reactivities vary slightly with the nature of Considering that the energy difference of the resulting
the electrophile (Figure 5), and we feel unable to interpret (Z)- and (E)-enolate ions derived from methyl acetate is cal-
–
1
[
14]
–1
these small differences.
culated to be much smaller (ca. 17 kJmol ) than that of
It is evident, however, that compounds 3 and 4 with a their precursors,[14a] one can rationalize why small lactones
lactone structure are less nucleophilic than their acyclic and with enforced (E) conformation are more acidic than acyclic
carbocyclic analogues 1 and 2. It has long been known that esters. Vice versa, the reduced basicity of the deprotonated
small lactones are more acidic than the corresponding lactones (compared with that of acyclic ester) may also ex-
[
13]
acyclic esters, because they cannot adopt the (Z) confor- plain the reduced nucleophilic reactivity of anions 3 and 4.
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F. Corral-Bautista, H. Mayr
FULL PAPER
and thus account for its lower acidity.[15,16] Given that the
constitution of 4 also prevents the formation of an anion
with W-configuration, its higher basicity (compared with
that of 3) and, as a consequence, higher nucleophilicity, can
be explained.
Conclusions
The second-order rate constants of the reactions of the
β-keto ester derived anions 1–4 with benzhydrylium ions
5b–e and quinone methides 5f–k in DMSO follow Equa-
tion (1), which allowed us to derive the nucleophilicity pa-
rameters N and susceptibilities sN of these anions in
DMSO. In line with their higher Brønsted basicities, carb-
anions 1 and 25–12 are more nucleophilic than the δ-lactone
analogues 3 and 4. Enolate ions 1–4 can thus be integrated
[
6j]
in our comprehensive nucleophilicity scales, which pro-
vides a direct comparison of C, N, O, S, and other types of
nucleophiles.
Figure 4. Nucleophilic reactivities of the carbanions 1–4 in DMSO.
Experimental Section
Materials: As specified in the Supporting Information, most rea-
gents were either commercially available or synthesized according
to reported procedures.
3-Acetyltetrahydro-2H-pyran-2-one (4-H): [(3,4-Dihydro-2H-pyran-
6-yl)oxy]trimethylsilane (5.00 g, 29.0 mmol) was dissolved in anhy-
drous CH
3
–
2
Cl
2.2 mmol) in anhydrous CH
75 °C over 3 h. The solution was stirred and slowly heated to
2
(60 mL), and a solution of acetyl chloride (2.30 mL,
2
Cl (20 mL) was added slowly at
2
room temperature overnight. The reaction mixture was washed
with brine (40 mL), sodium hydrogen carbonate solution (10%,
40 mL), again with brine (40 mL), and dried with sodium sulfate.
After evaporating the solvent, the crude product was purified by
column chromatography (silica; pentane/ethyl acetate) to give 4-H
(
1.98 g, 13.9 mmol, 48%) as a colorless solid. Analytic data are
[9b]
reported in ref.
Figure 5. Plot of the rate constants lgk
2
of the reactions of the
nucleophiles 2 with the electrophiles 5g,h,j against the ring size.
n
Synthesis of the Potassium Salts (1–4)-K: Potassium tert-butoxide
(
(
1.0 equiv.) was dissolved in ethanol, and a solution of the CH acid
1–4)-H (1.0–1.1 equiv.) in ethanol was added. After 5–10 min, the
solvent was removed under reduced pressure, and the precipitate
was washed with anhydrous diethyl ether or diethyl ether/pentane
mixtures. For specific examples, see the Supporting Information.
Reactions of the Enolate Anions (1–2)-K with the Reference Electro-
philes 5
Scheme 9. (Z) and (E) conformations of methyl acetate and com-
parison with a δ-lactone.
General Procedure 1: The cyclic keto ester 2-H (50–100 mg, 0.32–
0
0
1
.35 mmol) and the quinone methide 5j (95–110 mg, 0.31–
.32 mmol) were dissolved in anhydrous DMSO (10–15 mL), and
,5-diazabicyclo[4.3.0]non-5-ene (DBN; 2–3 drops) was added. Af-
The question can be asked: Why is lactone 3 approxi-
mately 10 times less nucleophilic than lactone 4? Both
compounds differ with respect to the alignment of the keto
group – cyclic in 3 and exocyclic in 4. The same argument
2
ter 3–5 h, brine (20 mL) was added, and the mixture was extracted
with diethyl ether (3ϫ 20 mL). The combined organic layers were
washed with brine and dried with sodium sulfate. After removing
that has been employed to rationalize the higher acidity of the solvent by distillation, the crude products were purified by col-
[
3f]
dimedone (pK = 11.2) compared with pentane-2,4-dione umn chromatography (silica; pentane/dichloromethane). For spe-
a
3f]
[
(
pK = 13.3) may apply. Only the anion of dimedone can cific examples, see the Supporting Information.
a
adopt the W-configuration with optimal charge distribu-
tion, whereas steric interactions of the methyl groups hinder (ca. 100 mg, 0.30–0.35 mmol) was dissolved in anhydrous DMSO
General Procedure 2: The potassium salt of the keto ester (1–2)-K
the formation of a W-shaped anion from pentane-2,4-dione (5–10 mL), and a solution of quinone methide 5 (ca. 100 mg, 0.29–
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Reactivity of Cyclic β-Keto Ester Anions
.31 mmol) in DMSO (5 mL) was added. When the solution be-
came dark blue, aqueous acetic acid (0.5%, 30 mL) was added,
and the mixture was extracted with diethyl ether (3ϫ 15 mL). The
combined organic layers were washed with brine and dried with
sodium sulfate before the solvent was removed under reduced pres-
sure. The crude products were purified by column chromatography
0
[3] For an overview on configurational studies and ion pairing of
β-dicarbonyl compounds, see: a) H. E. Zaugg, A. D. Schaefer,
J. Am. Chem. Soc. 1965, 87, 1857–1866; b) S. M. Esakov, A. A.
Petrov, B. A. Ershov, J. Org. Chem. USSR (Engl. Transl.) 1975,
1
1, 679–688; c) M. Raban, E. A. Noe, G. Yamamoto, J. Am.
Chem. Soc. 1977, 99, 6527–6531; d) M. Raban, D. P. Haritos,
J. Am. Chem. Soc. 1979, 101, 5178–5182; e) A. Facchetti, A.
Streitwieser, J. Org. Chem. 2004, 69, 8345–8355; f) F. G.
Bordwell, J. C. Branca, D. L. Hughes, W. N. Olmstead, J. Org.
Chem. 1980, 45, 3305–3313.
(silica; pentane/dichloromethane). For specific examples, see the
Supporting Information.
Kinetic Experiments: As the reactions of colored electrophiles 5
with colorless nucleophiles 1–4 gave colorless products (or products
with a different absorption than the reactants), the reactions could
be monitored by UV/Vis spectroscopy. All reactions were fast (τ1/2
Ͻ 10 s), therefore the kinetics were monitored by using stopped-
flow techniques. The temperature of all solutions was kept constant
at 20.0Ϯ0.1 °C by using a circulating bath thermostat. In all runs,
the concentration of the nucleophile was at least 10 times higher
than the concentration of the electrophile, resulting in pseudo-first-
order kinetics with an exponential decay of the concentration of
the electrophile (minor compound). First-order rate constants kobs
were obtained by least-squares fitting of the absorbances to a
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3
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We thank the Deutsche Forschungsgemeinschaft (SFB 749, Project
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the reference electrophiles, Dr. Ángel Puente for his help during
the preparation of 4-H, and Dr. Armin R. Ofial for help during
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Received: August 26, 2015
Published Online: October 30, 2015
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