Nucleophilic substitution in ionizable Fischer thiocarbene complexes: Steric effect of the alkyl substituent on the heteroatom

Article abstract of DOI:10.1039/c4dt03618b

A detailed kinetic study has been carried out for the aminolysis of ionizable Fischer thiocarbene complexes (CO)₅MC(SR)CH₃ (M = Cr, W; R = iPr, nBu, cHex, tBu) with five primary amines and one secondary amine in aqueous acetonitrile solutions (50% MeCN-50% water (v/v)). The observed rate constants for the reaction with primary amines showed a first-order dependence on the amine concentration, while with morpholine, the rate constant has second-order dependence. The general base catalysis process was confirmed by the variation of the rate constants with the concentration of an external catalyst and the pH. The results agree with a stepwise mechanism where the nucleophilic addition to the carbene carbon to produce a tetrahedral intermediate (T^±) is the first step, followed by a rapid deprotonation of T^± to form the anion T^- which leads to the products by general-acid catalysed leaving group (-SR) expulsion. In general, it was found that the chromium complexes are less reactive than the tungsten analogues. The obtained Br?nsted parameters for the nucleophilic addition (β_nuc) indicate that C-N bond formation has made little progress at the transition state. By using Charton's correlation, the role that the steric factor plays throughout the mechanism has been unraveled. The nucleophilic addition to the thiocarbenes is less sensitive to steric effects than the alkoxycarbenes regardless of the nature of the metal centre. Conversely, the steric effects on the general-base catalysis can be strong depending on the volume of the catalyst and the metal centre. On the basis of the structure-reactivity coefficients β and ψ and comparison with alkoxycarbene complexes, esters and thiolesters, insights into the main factors ruling the reactivity in terms of transition state imbalances are discussed.

Full text of DOI:10.1039/c4dt03618b

Dalton
Transactions
PAPER
Nucleophilic substitution in ionizable Fischer
thiocarbene complexes: steric effect of the alkyl
substituent on the heteroatom†
Cite this: Dalton Trans., 2015, 44,
5520
Diego M. Andrada,‡b Martin E. Zoloff Michoff,§a Rita H. de Rossib and
Alejandro M. Granados*b
A detailed kinetic study has been carried out for the aminolysis of ionizable Fischer thiocarbene com-
plexes (CO)5MvC(SR)CH3 (M = Cr, W; R = iPr, nBu, cHex, tBu) with five primary amines and one second-
ary amine in aqueous acetonitrile solutions (50% MeCN–50% water (v/v)). The observed rate constants for
the reaction with primary amines showed a first-order dependence on the amine concentration, while
with morpholine, the rate constant has second-order dependence. The general base catalysis process
was confirmed by the variation of the rate constants with the concentration of an external catalyst and
the pH. The results agree with a stepwise mechanism where the nucleophilic addition to the carbene
carbon to produce a tetrahedral intermediate (T ) is the first step, followed by a rapid deprotonation of T
to form the anion T− which leads to the products by general-acid catalysed leaving group (–SR) expulsion.
In general, it was found that the chromium complexes are less reactive than the tungsten analogues. The
obtained Brønsted parameters for the nucleophilic addition (βnuc) indicate that C–N bond formation has
made little progress at the transition state. By using Charton’s correlation, the role that the steric factor plays
throughout the mechanism has been unraveled. The nucleophilic addition to the thiocarbenes is less sen-
sitive to steric effects than the alkoxycarbenes regardless of the nature of the metal centre. Conversely,
the steric effects on the general-base catalysis can be strong depending on the volume of the catalyst
and the metal centre. On the basis of the structure–reactivity coefficients β and ψ and comparison with
alkoxycarbene complexes, esters and thiolesters, insights into the main factors ruling the reactivity in
terms of transition state imbalances are discussed.
Received 25th November 2014,
Accepted 28th January 2015
DOI: 10.1039/c4dt03618b
www.rsc.org/dalton
nounced electron deficiency of the carbene carbon atom since
nucleophilic attachments trigger further transformations.3
1. Introduction
Group 6 Fischer carbene complexes are invaluable organo-
Interestingly, nucleophilic substitution reactions are also
metallic building blocks for organic synthesis.1 Due to their an easy way to exchange the π-donor heteroatom linked to the
multifunctional structure, many recent investigations have aimed carbene carbon, providing an efficient method to tune both
at developing efficient diastereoselective multicomponent the reactivity and the stability of these complexes.4 Among the
sequential coupling reactions where these compounds are examples regarding the reactivity patterns, the well-known
involved.2 In most of these reactions, the key lies in the pro- Dötz reaction is one of the most attractive since when amino
groups are used instead of alkoxy groups the cyclopentannula-
tion reaction is favoured over the benzannulation reaction.5 In
addition, Aumann and co-workers have recently reported that
aDepartamento de Matemática y Física, INFIQC, CONICET and Facultad de Ciencias
Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria X5000HUA,
alkoxy- and thiocarbene complexes afford different types of
Córdoba, Argentina
products on the reaction with imidoyl derivatives.6 The
bDepartamento de Química Orgánica, INFIQC, CONICET and Facultad de Ciencias
experimental and theoretical characterizations carried out so
Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria X5000HUA,
far have shown
a great variety of electrochemical and
Córdoba, Argentina. E-mail: ale@fcq.unc.edu.ar
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
photophysical properties and how they are influenced by the
substituents on the carbene moiety.7 For instance, the syn-
thesis and photophysical characterization of novel BODIPY-
Fischer alkoxy-, thio- and aminocarbene complexes have
been recently reported,8 and it has been proved that the
c4dt03618b
‡Present address: Fachbereich Chemie, Philipps-Universität Marburg, Hans-
Meerwein-Straße, 35032-Marburg, Germany.
§Present address: Lehrstuhl für Theoretische Chemie, Ruhr-Universität
Bochum, Universitätsstraße 150, 44780-Bochum, Germany.
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corresponding absorption and emission spectra sharply 1-Cr-OMe-Ph with thiolate ions in aqueous acetonitrile and the
depend on the nature of the π-donor heteroatom. Furthermore, demonstration that the observed intermediate is indeed on the
it has been suggested that transition metal-carbonyl complexes reaction coordinate.21 Additional support to this mechanism
are attractive CO-release molecules with the same biological has been given by the early isolation of adducts such as 3 from
effects as gaseous CO in a number of applications.9 Thus, ether solutions of 1-Cr-OMe-Ph and DABCO or quinuclidine22
different substitutions offer considerable potential for modulat- and its latest kinetic study.23
ing CO-release rates, i.e., rapid CO-release is observed in the
case of sulphur- and oxygen-stabilized carbenes, whereas in the
case of amino-substituted carbenes, release is far more sluggish.
The differences in the properties of Fischer carbenes have
been ascribed to the π-donor substituent strength. A landmark
study has been reported by Wang et al., who suggested that the
π-bond character of the metal–carbene bond can be rep-
resented as a four-electron three-centre bond.10 Furthermore,
theoretical studies have agreed that stronger π-donor hetero- In a recent computational study performed by some of us, the
atoms attached to the carbene carbon lead to lower electrophili- ammonolysis of Fischer alkoxy- and thiocarbene complexes
has been addressed.24 Remarkably, all the calculations led to
city as well as weaker M–Ccarb bonds and stronger M–COtrans
bonds.11 For this reason, the aminolysis reactions have been the conclusion that the most favourable reaction pathway
regarded as one of the most extensively used transformations involves a zwitterionic intermediate; this has been attributed
because of the relative simplicity of the reaction, the increased
to the high stabilization of the negative charge on the metal
stability of the products formed and the ease of subsequent moiety in T . A thorough mechanistic study on the aminolysis
metal moiety removal.12 This methodology has been widely by Bernasconi et al. provided further information. These reac-
used for synthesizing amino acids, amides and thioamides
tions were shown to undergo a specific base-general acid cata-
with structures that cannot be accessed by conventional strat- lysis. This means that the reaction involves an additional step
egies.13 Some other applications include protein labelling of that converts the initially formed zwitterionic intermediate
amino groups,14 PEGylation of proteins,15 immobilization of
into its anionic form before it breaks down to products. This
the proteins and amines on glass and silicon surfaces16 and three-step mechanism has generated particular interest
detection methods for proteins.17
because of possible changes in the rate-limiting steps with
changing reaction conditions as well as structural fea-
Despite the extensive studies undertaken to develop syn-
thetic strategies, no comparable effort has been made to tures.18,19,23,25 All the kinetic studies carried out so far have
clearly understand the effects of the substituent on the mainly focused on the electronic effects and how they are
π-donor group in the reaction mechanism. About twenty years
changed by the π-donor heteroatom nature. But, surprisingly,
ago, Bernasconi reported a comprehensive kinetic study of the no systematic study has taken care of the steric effect on the
reaction of Fischer methoxy carbene complexes in aqueous aminolysis reactions.
acetonitrile solution with amines, and the detailed mechanism
Some years ago, we initiated a programme aimed at study-
proposed is shown in Scheme 1.18 This mechanism was then ing some reactions in which the carbene complexes are
extended to the corresponding thiomethoxy analogues.19
It has been demonstrated that the reaction proceeds in a
involved, with an emphasis on the exploration of the steric
effect in proton transfer reactions and nucleophilic substitu-
stepwise fashion with the formation of a tetrahedral zwitter- tions.11d,24,26 We have been inspired by the increasing number
ionic intermediate, T , in analogy to the aminolysis of carboxylic of asymmetric synthesis studies with the application of the
esters.12,18,20 Although no intermediate is detectable in the
linear free energy relationships (LFERs) – concerning steric
aminolysis of Fischer carbene complexes, evidence has come effects – to elucidate the interactions responsible for the asym-
from the direct detection of the intermediate in the reaction of metric inductions and hence provide a platform for improving
Scheme 1 General mechanism for the aminolysis reaction of Fischer carbene complexes.
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Dalton Transactions
the enantio- and diastereo-selectivity performances.27 We are shift in the UV-visible spectrum due to the conversion of the
aware that Fischer carbene complexes can induce such kinds thiocarbene complex into the corresponding aminocarbene.
of reactions by the modification of their structures, and the These spectral changes are similar to those reported in the
aminolysis reactions play a crucial role in most of them.28 reactions of 1-M-XR2-R1 (Scheme 1) with primary and second-
Herein, by means of classical kinetic tools, we have performed ary amines to form the amino substituted derivatives.18,19,23,25
a detailed study to establish how the size of the alkyl group The identity of the products was confirmed by comparison of
attached to the π-donor sulphur substituent may affect the the spectrum of the solution after completion of each reaction
reactivity and the aminolysis mechanism. To this end, we have with that of the corresponding aminocarbene complex syn-
explored the nucleophilic substitution for a series of Fischer thesized independently.
thiocarbene complexes 4M-R (R = n-butyl, iso-propyl, cyclo-
The reactions were monitored by following the reactants’
hexyl, tert-butyl) with several amines in 50% MeCN–50% water vanishing (λmax ≈ 450 nm and 435 nm for the complexes of Cr
(v/v) at 25 °C. We found that the steric effects not only affect and W, respectively) and the products’ formation (λmax ≈ 355
the addition of the nucleophile to form zwitterionic inter- and 335 nm for the complexes of Cr and W, respectively). Both
mediate T , but also influence the base catalysed decompo- rate constants led to the same values within the experimental
sition of it.
error, indicating that no accumulation of any intermediates is
taking place throughout the reactions. It is important to
mention that when the kinetic trace is followed at the wave-
length of maximum absorption for the reactant, two kinetic
processes can be observed (Fig. S1†). The fastest one has
already been assigned to the proton transfer reaction,26c,d and
the slowest one corresponds to the nucleophilic reaction. The
pseudo-first-order rate constants of the second process (kobs
were calculated from the exponential equation A∞ − At = (A∞
)
−
Ao) exp(−kobst). All the kobs values obtained in this way are sum-
marized in the ESI (Tables S2–S42†).
2. Results
Two kinds of kinetic experiments were carried out; some
experiments were carried out at constant pH values and
different amine concentrations while in others the concen-
tration of the amine was kept constant and the OH– or the
external buffer tertiary amine (triethyl amine, TEA) concen-
trations were varied.
2.1 General procedures
All the experiments of the reactions between the complexes
4M-R and n-butylamine, methoxyethylamine, benzylamine,
furfuryl amine, glycine ethyl ester and morpholine were per-
formed in 50% MeCN–50% water at 25 °C. The kinetic runs
were conducted under pseudo-first-order conditions with the
carbene complexes as the minor component.
2.2 Reactions with primary amines
Fig. 1, which is representative, shows time-resolved spectra
for the reaction of morpholine with 4Cr-cHex. It shows a blue
The nucleophilic reactions of the Fischer thiocarbenes 4W-R
were studied with five primary amines: n-butylamine, benzyl-
amine, 2-methoxyethylamine, furfurylamine and glycine ethyl
ester. The reactions of carbene 4Cr-R were studied with three
primary amines, namely, n-butylamine, benzylamine and
furfurylamine.
All the reactions of tungsten derivatives showed strictly
second-order kinetics, i.e., first-order with respect to carbene
concentration and first-order with respect to amine concen-
tration. Competing hydrolysis of the carbenes was negligible
and hence the observed pseudo-first-order rate constant (kobs
is given by eqn (1) where kA is the second-order rate constant.
)
kobs ¼ kA½RNH2ꢀ
ð1Þ
The carbene complexes 4M-R, under the conditions
employed, are deprotonated (Scheme 2)26c,d and the anion
Fig. 1 Time resolved spectra for the reaction of 4Cr-cHex with
morpholine in 50% MeCN–50% water at pH 8.70, 25° C, ionic strength =
0.1 M (KCl), [4Cr-cHex]0 = 1.0 × 10−4 M and [Morph]f = 0.02 M. The first
spectrum was taken immediately after mixing. The time lapse between
the first and the last spectra is 10 min.
Scheme 2 Acid–base equilibrium for ionizable Fischer carbene
complexes.
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formed does not react with the amine nucleophiles,12 and curvilinear dependence of the observed second-order rate con-
therefore the observed rate constant must be corrected as in stant (kA-corr) on the amine concentration was observed (Fig. S2†).
eqn (2).
ꢀ
ꢁ
2.3 Reactions with morpholine
½Hþꢀ þ KaCH
½Hþꢀ
kobs corr ¼ kobs
¼ kA corr½RNH2ꢀ
ð2Þ
-
-
For all the reactions of carbenes 4M-R with morpholine, the
plots of kobs-corr vs. [Morph] exhibited an upward curvature
giving hints of an observable general base catalysis (Fig. S3†).
All the plots have a negligible intercept within the experi-
mental errors. This is reminiscent of what has been reported
for the reactions of alkoxycarbene complexes with primary and
secondary amines as well as for some thiocarbene analogues
with morpholine.18,25a,c,d The observed second-order rate con-
stants (kA-corr) showed linear dependence with the amine con-
centration (Fig. 3 is representative).
The KCa H values used here for 4M-R are those reported pre-
viously.26c,d Fig. 2 shows the plots of kobs-corr vs. [RNH2] for the
complex 4W-tBu with different amines at pH = pKAaH (pKa of
the conjugated acid of the amine). The slope values (kA-corr
obtained are shown in Table 1.
The complexes 4Cr-R showed a different behaviour depend-
ing on the basicity of the amine. For n-butylamine a similar
behaviour to that previously observed with 4W-R was dis-
played (Fig. 2), whereas for furfurylamine and benzylamine, a
)
In order to test the general base catalysis of these reactions,
two different experiments were carried out. Firstly, the concen-
tration of an external catalyst (TEA) was varied in the range of
Fig. 2 Plot of kobs-corr vs. [RNH2]f for the reaction of 4W-tBu in 50%
●
○
MeCN–50% water with: ( ) n-butylamine, pH = 10.4; ( ) benzylamine,
■
□
pH = 9.12; ( ) methoxyethylamine, pH = 9.39; ( ) furfurylamine, pH =
Fig. 3 Plots of kA-corr vs. [Morph]f for the reaction of morpholine with
■
●
▲
▽
◊
8.58; ( ) glycine ethyl ester, pH = 7.43, ionic strength = 0.1 M (KCl),
(
) 4W-nBu, ( ) 4W-cHex, ( ) 4W-iPr and ( ) 4Cr-cHex in 50% MeCN–
25 °C.
50% water at pH = 8.88, ionic strength = 0.1 M (KCl), 25 °C.
Table 1 Second order rate constants (k1, M−1 s−1) for the reactions of 4M-R with primary aminesa
4Cr-R
Amine
pKAaH
nBu
iPr
cHex
tBu
n-Butylamine
Benzylamineb
Furfurylamineb
10.40
9.12
8.58
231
191
122
5
5
5
209
140
90
5
4
5
200
176
98
6
6
3
124
103
71
4
2
6
4W-R
pKAaH
nBu
iPr
cHex
tBu
n-Butylamine
2-Methoxyethylamine
Benzylamine
Furfurylamine
Glycine ethyl ester
10.40
9.39
9.12
8.58
7.43
781 70
534 13
711 60
340 13
549 35
715 15
429 25
440 12
524
9
377
279
86
9
5
5
364
9
288
96
8
3
220 40
148 26
a 50% MeCN–50% water as the solvent, ionic strength = 0.1 M (KCl), 25 °C. b The value of the rate constant reported corresponds to the value
observed at the levelling off of the plot of kA-corr vs. amine concentration (see the main text).
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3.1 Mechanism
3.1.1 Analysis of the data. As aforementioned, all the
studies carried out so far on the mechanism of aminolysis of
carbene complexes are consistent with the frame displayed in
Scheme 1.18,19,25 There is no reason to believe that any other
mechanism is occurring herein. Our findings suggest the
occurrence of a stepwise mechanism under the conditions
employed. The experiments carried out with morpholine as
the nucleophile and an external buffer resulted in a leveling
off for the second-order rate constants (Fig. 4). This result
points out the operation of at least two steps and the presence
of at least one intermediate. Indeed, the existence of the
general base catalysis was demonstrated.
The presence of an isosbestic point (Fig. 1) implies that the
transformation into products is quite clean. The fact that the
values of the rate constants measured at the reactant and
product wavelengths are equal within experimental errors indi-
cates that no accumulation of an intermediate to detectable
levels is taking place. The expression for kA-corr is given by eqn
(3) which can be easily derived considering steady state con-
ditions (see Scheme 1).
Fig. 4 Plot of kA-corr vs. [TEA]f for the reaction of morpholine with
■
●
▽
4M-R in 50% MeCN–50% water; ( ) 4W-nBu, ( ) 4W-cHex, ( ) 4W-iPr
and ( ) 4Cr-cHex. Conditions: [4M-R]0 = 1.0 × 10−4 M, [Morph]f
=
○
0.01 M for 4W-R and 0.02 M for 4Cr-cHex, pH = 10.78, ionic strength =
0.1 M (KCl), 25 °C.
À
Á
k1 k3A½RNH2ꢀ þ k3OH½OHꢁꢀ
kobsꢁcorr
kA corr
-
¼
¼
¼
½RNH2ꢀ
k
ꢁ1 þ k3A½RNH2ꢀ þ k3OH½OHꢁꢀ
ÀÀ
Á
À
Á
Á
k1 kA=k ½RNH2ꢀ þ kOH=k ½OHꢁꢀ
ꢁ1
ꢁ1
1 þ ð3k3A=kꢁ1Þ½RNH2ꢀ þ ðk3OH=kꢁ1Þ½OHꢁꢀ
3
ð3Þ
Two limiting situations can be extracted from this equation
in order to explain the observed kinetic behaviours. On the
one hand, when the nucleophilic attack of the amine, to form
T , is the rate limiting step, the relationship in eqn (4) holds,
giving kA-corr = k1. This situation applies to the reactions of
complexes 4W-R with primary amines (Fig. 2) and the reaction
of 4Cr-R with n-butylamine. On the other hand, when the base
catalysed process is the slowest step of the mechanism, eqn (5)
and (6) hold.
Fig. 5 Plot of kA-corr vs. [OH–] for the reaction of morpholine with
ðkA3 =kꢁ1Þ½RNH2ꢀ þ ðk3OH=kꢁ1Þ½OHꢁꢀ > 1
ðkA3 =kꢁ1Þ½RNH2ꢀ þ ðk3OH=kꢁ1Þ½OHꢁꢀ ꢂ 1
kA-corr ¼ k1ððkA3 =kꢁ1Þ½RNH2ꢀ þ ðkO3 H=kꢁ1Þ½OHꢁꢀÞ
ð4Þ
ð5Þ
ð6Þ
■
●
▽
4M-R in 50% MeCN–50% water; ( ) 4W-nBu, ( ) 4W-cHex, ( ) 4W-iPr
and ( ) 4Cr-cHex. Conditions: [4M-R]0 = 1.0 × 10−4 M, [Morph]f = 0.01
or 0.02 M, [TEA]f = 0.01 M, ionic strength = 0.1 M (KCl), 25 °C.
○
0.01–0.10 M at pH 10.78 and [Morph]f = 0.01 M and 0.02 M for
the 4W-R and 4Cr-R series, respectively. Secondly, a variation
of the pH from 8.18 to 11.18 at constant [TEA] = 0.01 M and
[Morph]f = 0.01 M was performed. Fig. 4 shows some represen-
tative plots of kA-corr vs. [TEA]f at constant pH while Fig. 5
shows some representative plots of kA-corr vs. [OH–] at constant
buffer concentration.
The latter situation is truly applicable to the reaction rates
of 4M-R with morpholine at low catalyst concentration (Fig. 3)
and also to the reactions of 4Cr-R with furfurylamine and ben-
zylamine. Depending on the relative values of the different rate
constants of each individual step, in some cases, it is possible
to have both situations within the range of concentrations
used. This allows the determination of the k1 values as well as
the rate constant ratios kA3/k−1 and k3OH/k−1. This turns out to
be the case for the reactions of morpholine (see Fig. 4 and 5)
and by fitting the kinetic data to eqn (3) the rate constants
3. Discussion
This section is divided as follows: in section 3.1 the general summarized in Table 2 were calculated. In all cases, the values
mechanism and the nature of the base catalysis are discussed of kT3EA/k−1 informed were calculated from the data of kA-corr vs.
and in section 3.2 the structure–reactivity relationships are [TEA] at constant pH (Fig. 4) and the values of kO3 H/k−1 from
addressed.
the dependence of kA-corr vs. [OH–] concentration at constant
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Table 2 Calculated rate constants for the reactions of 4M-R with morpholine in 50% MeCN–50% water at 25 °Ca
4M-R
k1b (M−1 s−1
)
km3 orph/k−1 (M−1
)
kT3EA/k−1 (M−1
)
kO3 H/k−1 (×103 M−1
)
kO3 H/km3 orph
kO3 H/kT3EA
4W-Mec
4W-nBu
4W-cHex
4W-iPr
883
5
1.22 0.01
1.64 0.09
1.01 0.08
0.94 0.09
1.25 0.01
0.8 0.1
386 42
261 30
34
14
11
12
39
25
3
2
1
2
3
7
2.78 × 104
0.85 × 104
1.09 × 104
1.28 × 104
3.08 × 104
2.13 × 104
87.7
53.6
123.6
169.0
169.0
1063
548 16
413 15
365 21
62.7 0.9
89
71
5
5
4Cr-Mec
4Cr-cHex
228 31
23.5 0.2
33
2
a Ionic strength = 0.1 M (KCl). b Data calculated from the variation of the rate constant with TEA. c Data taken from ref. 25d.
amine concentration (Fig. 5). On the other hand, the data for of carboxylic esters and thiolesters29 and in some SNAr reac-
the catalysis by TEA were used to calculate k1 since under these tions.30 On the other hand, the mechanism B consists of a fast
conditions the leveling off of the curve is fully reached.
acid–base equilibrium, between T and T–, followed by the
Although the reactions of benzylamine and furfurylamine general-acid catalysed leaving group departure. This late
with 4Cr-nBu showed a curvilinear behaviour (see Fig. 2), the sequence is known as specific-base general-acid catalysis31 and
leveling off occurs at a relatively low amine concentration and is normally observed for strongly activated vinylic compounds
therefore the calculation of the rate constants for the catalysed such as β-methoxy-α-nitrosostilbene compounds.32 Finally, the
step was not possible because only a few points can be mechanism C takes into account the bifunctional character of
measured before the rate becomes independent of the base some catalysts to accept and to donate a proton. This con-
concentration.
certed mechanism have been proposed for reactions in
3.1.2 General base catalysis. The nature of the general organic solvents.33 Besides, in recent computational results, C
base catalysis has been discussed in detail elsewhere.12,18,25a was suggested as the most favourable mechanism for the
However, it is noteworthy to briefly mention the main findings departure of the leaving group.24
and how they fit to our system. There are three possible
mechanisms for the general base catalysis pathways which are ruled out considering the experiments where TEA was used as
depicted in Scheme 3. an external buffer. Cleary, this tertiary amine cannot partici-
The concerted mechanism described in C can be easily
The mechanism A represents the situation where the depro- pate in a mechanism like C due to its inability to donate and
tonation of the zwitterionic intermediate T is the rate-limiting accept a proton at the same time. The observation of an
step. Such a condition is typically observed in the aminolysis enhancement in the rates when the concentration of the TEA
Scheme 3 Three different mechanisms of the general base catalysed step within the aminolysis reaction.
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is at least 10 times smaller than that of morpholine suggests
that another mechanism is operating. Critical inspection of
the values in Table 2 reveals that kT3EA/k−1 ratios are about two
orders of magnitude higher than km3 orph/k−1. This leads to
higher kO3 H/k3morph (pKAaH = 8.70 in 50% MeCN–50% water)
values than kO3 H/k3TEA (pKAaH = 10.78 in 50% MeCN–50% water)
for all the complexes. Indeed, these values are much higher
than those reported in the literature for the reaction proceed-
ing by pathway A. Normal values are within the range of 1–25
and they should be independent of the amine used.34 There-
fore, the high kO3 H/k3A ratio is considered to be a common
feature for the aminolysis reaction that proceeds through the B
pathway.12 This strong increase in the k3OH/kA3 ratio with
decreasing the basicity of the amine has already been
explained by Bernasconi and co-workers.18
Fig. 6 Brønsted plot for the reaction of 4W-tBu with primary amines in
50% MeCN–50% water at 25 °C, ionic strength = 0.1 M (KCl).
3.2 Structure–reactivity relationships
3.2.1 Nucleophilic attack (k1) by primary amines
3.2.1.1 Brønsted plots. From the comparison of both series
of metal carbene complexes (4Cr-R and 4W-R, refer to the data
in Table 1), it can be seen that the nucleophilic addition to the
tungsten complexes is slightly more favoured than that to chro-
mium complexes. The largest ratio k1(4W-R)/k1(4Cr-R) is 5.7
for 4M-tBu with n-butylamine while the lowest ratio is 2.9 for
4M-nBu with furfurylamine. Similar values for k1 ratios have
been reported for 4M-Me with less basic amines.25e These
results fall in the range of the previously reported differences
for chromium and tungsten complexes reacting with other
nucleophiles.21,23,25d,f,35 The higher rate constant for W com-
plexes in the nucleophilic attachment has been ascribed to the
difference in the electronegativity. Since W is more electro-
negative than Cr,36 the stabilization of the incipient negative
charge on the transition state is higher, leading to an
enhanced reactivity. The metal nature not only affects the rate
of the nucleophilic attack but also, to a different extent, the
equilibrium constant K1. Although no equilibrium constant
can be measured from our experiments, an indirect compari-
son can be made from the experiment with thiolate anions.
For instance, the equilibrium constant (K1) for the addition of
HOCH2CH2S– to 1-Cr-SMe-Ph (Scheme 1) is 3.07 × 105 while
that for 1-W-SMe-Ph is 3.76 × 106, from which a ratio of K1(W)/
K1(Cr) = 12.2 is obtained.21b Thus, the nature of the metal
centre may lead to some differences in this step that would
cause a different degree of C–N bond formation at the tran-
sition state.
Inspection of Table 1 suggests that the values of k1 increase
with the pKa of the amine within each series. A representative
Brønsted plot for the k1 is shown in Fig. 6. In general, for all
the remaining complexes there is a good correlation between
the log(k1) and pKaAH and the βnuc values are summarized in
Table 3.
All the values shown in Table 3 are within the range
0.24–0.42, in good agreement with previous reports.19b,25e The
values of βnuc can be considered as a measure of the bond for-
mation degree at the transition state if no other process, such
as desolvation of the nucleophile, is involved.37
Table 3 βnuc values for the reactions of complexes 4M-R with primary
amines in 50% MeCN–50% water at 25 °Ca
M = Cr
M = W
4M-R
βnuc
βnuc
R = Meb
R = nBu
R = cHex
R = iPr
0.37 0.01
0.36 0.07
0.42 0.09
0.36 0.05
0.30 0.05
0.33 0.02
0.24 0.06
0.25 0.04
0.35 0.03
0.30 0.04
R = tBu
a Ionic strength = 0.1 M (KCl). b Ref. 25e.
A small difference for the βnuc can be distinguished out of
the experimental error for complexes with nBu and cHex side
groups. It is interesting to note that βnuc is on average slightly
higher for the chromium complexes. This observation can be
interpreted in accordance with the Hammond–Leffler
effect.38 Taking into account that the formation of the zwitter-
ionic intermediate T is thermodynamically more favoured
when M = W due to its higher electronegativity, a less
advanced transition state for 4W-R is expected. It is note-
worthy to compare the βnuc values in reactions of different
heterocarbene complexes. Thus βnuc for thiocarbene com-
plexes are significantly lower than those reported for the ami-
nolysis of the alkoxycarbene complexes (0.60),18 suggesting a
smaller degree of bond formation at the transition state for
the former. This finding has been explained due to different
factors such as the inductive effect, the π-donor effect and
heteroatom sizes. The experimental results published so far
have indicated that the π-donor effect is dominant and offsets
the other factors. In this context, the stronger π-donor charac-
ter of oxygen results in a more effective stabilization of
the reactants disfavouring the thermodynamics to form the
zwitterionic intermediate T .21b Thereby, by the Hammond–
Leffler effect, the stronger the π-donor character of the
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Dalton Transactions
Paper
heteroatom, the more advanced the transition state. In con- becomes obvious that the polar effects do not adequately
trast, their organic analogues, ester and thiolester, do not describe the origins of the factors under evaluation.
present such a dramatic heteroatom effect on the position of
Steric, rather than electronic, effects appear to be primarily
the transition state. For the aminolysis reactions, βnuc values responsible for the decreasing reactivity in going from methyl
around 0.2 are considered normal for ester compounds,20a,39 to tert-butyl derivatives. A close inspection of Table 1 gives
while for thiolester, values in the range 0.1–0.3 have been clues to the main factors taking place in these reactions. As
reported.29,40 The comparison of the βnuc values in reactions can be seen, a trend following the bulkiness of the group is
of esters and carbene complexes suggests that the position of found, namely, the rate constants decrease in the order Me >
the transition state sharply depends on the π-donor hetero- nBu > cHex > iPr > tBu. Thus, the correlations are better when
46
atom for the organometallic compounds contrary to the situ- steric parameters are used, for example, Taft’s Es and Char-
47
48
ation for their organic analogues. The different behaviours of ton’s νCH R and νSR parameters. The correlations with Es
2
the two families of compounds are not clear so far; theore- and νSR are not very good (r2 values were 0.6 and 0.4, respect-
tical calculations are currently being performed in order to ively), but the correlation with νCH R is quite good (r2 = 0.987).
2
understand this issue.41
Fig. 7 (see also Fig. S4 and S5†) displays a representative plot
Remarkably, due to the strong π-donor effect of the hetero- for the reactions where glycine ethyl ester was used.
atom substituent, a minor role has been attributed to the The linear correlation between log(k1) and νCH R is clear evi-
2
steric hindrance in the kinetic studies reported. For example, dence for the role of steric effects in controlling reactivity.
Bernasconi and co-workers have evaluated the rate constant Taft’s Es parameter contains a mixture of polar and steric con-
for 1-Cr-OMe-Ph and 1-Cr-OEt-Ph in the aminolysis and basic tributions that are difficult to separate unambiguously. On the
hydrolysis reactions.25b They have attributed the changes other hand, Charton’s steric parameters are based on van der
observed to the stronger π-donor character of EtO with respect Waals radii of the constituted atoms and, therefore, should be
to the MeO substituent.42 On the other hand, a few studies free from complications caused by mixing of electronic and
have pointed out the importance of the volume of the substitu- steric effects that might contribute to other parameters
ent in the reactivity. Recently, it has been shown that alkoxy- obtained from structure–reactivity correlations. As has been
carbene complexes experience strong steric effects for the pointed out by Charton, better correlations with νCH R are
2
basis hydrolysis, even stronger than for esters.26a This obser- obtained when the substituents are not directly bonded to the
vation was connected with the presence of the bulky Cr(CO)5 reaction site.49 Indeed, this indicates that the size of the alkyl
moiety. On the basis of our discussion, an additional insight R group is influencing the rate constants. As can be observed,
can be given, since it is not only a consequence of the presence the iPr group displays a negative deviation in the correlations.
of the metal pentacarbonyl fragment, but can also be attribu- Harper et al.27g have recognized that the application of the
ted to the differences in the position of the transition states Charton parameter assumes a net conformer for the specific
(see below). Strikingly, the steric effects exerted by M(CO)5 and transition state, although the differences in energy of these
XR moieties can be high enough to inhibit the nucleophilic rotational conformers are potentially high. This spherical
attack at the carbene carbon and direct it to an aromatic ring assumption reasonably describes the steric influence of sym-
carbon43 or to the carbonyl ligands.44
metric groups, but it is a limiting premise when the substi-
Given that the transition states for the studied thiocarbene tuent is not symmetrical.
complexes are less advanced than those for the alkoxycarbene
derivatives, it is reasonable to expect that the reactivity is less
dependent on the volume of the –SR group.
3.2.1.2 Polar vs. steric effects of –SR group. In order to shed
light on the factors which determine the reactivity, we have
used different linear free energy relationships (LFER) to evalu-
ate the effects exerted by the –SR group.
The effect of changing the π-donor character was analyzed
on the basis of the correlation between rate constants and sub-
stituent parameter R+.42 Our results show a poor correlation
between log(k1) and R+ (r2 = 0.14).
In a previous study we found that the hydrophobicity of the
R group influences the rate of the proton transfer reaction
between thiocarbene complexes 4M-R and hydroxide anions in
50% MeCN–50% water.26d In this vein, we plotted log(k1)
against log P,45 but no correlation was found (r2 = 0.1). As we
have pointed out in our previous article, the hydrophobicity
only plays an important role when one of the reactants is
Fig. 7 Plot of log(k1) vs. νCH R for the reaction of 4W-R with glycine
ethyl ester in 50% MeCN–50% water at 25 °C and ionic strength = 0.1 M
2
charged; hence
a different scenario for reactions with
uncharged nucleophiles is expected. From these results it
(KCl).
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Dalton Transactions
complexes (CO)5CrvC(OR)Me, but we can gain a clue about
the minimum value that the change from Ph to Me can have
on ψ. Taking into account that the ψ values reported for the
hydrolysis of esters OvC(OR)Ph and OvC(OR)Me are −3.12
and −3.04, respectively,49 it is expected that the impact of
changing the side group from Ph to Me should be at least 0.08
unit. In fact, the contribution should be somewhat higher in
the case of the carbene complexes due to the more advanced
C–N bond formation at the transition state. Nonetheless, it is
not likely that this difference will be large enough to over-
shadow the ca. 1.9 units between alkoxy- and thiocarbene
complexes.
The different reactivities of alkoxy and thiocarbene com-
plexes have been attributed to several factors and in some
cases it appears that the steric effect due to the larger size of
the –SMe group compared with –OMe is the most important
one.23,25d,e Our data include an extensive change in size of the
group; therefore more information about the relative impor-
tance of the steric effect can be obtained. From the discussion
that follows, we conclude that the main factors that explain
the different reactivities between alkoxy and thiocarbene com-
plexes can be ascribed to the π-donor effect.
Table 4 Summary of the ψ values of the nucleophilic attachment in the
aminolysis reactions of esters and Fischer carbene complexes
OH
Reactant
Nucleophiles
ψ (ψOH, Δ
)
ψ−ψ
1
OvC(OPh)R
n-Butylamine
−1.83 0.23a
(−3.12b, 1.29c)
−1.13d
2
3
OvC(SPh)R
(CO)5CrvC(OR)Ph
Benzylamine
n-Butylamine
−2.29e
(−3.84f, 1.55c)
−0.42 0.08
−0.41 0.08g
−0.42 0.08h
4
5
6
7
(CO)5CrvC(SR)CH3 (4Cr-R) n-Butylamine
(CO)5CrvC(SR)CH3 (4Cr-R) Benzylamine
(CO)5WvC(SR)CH3 (4W-R)
(CO)5WvC(SR)CH3(4W-R)
Benzylamine
Glycine ethyl ester −0.57 0.05g,h
a Data taken from ref. 50 in MeCN at 25.4 °C. b Data taken from ref. 49.
c Difference between the ψ values for the aminolysis and hydrolysis
reactions. d Data taken from ref. 51 in MeCN at 45 °C. e Calculated with
two points taken from ref. 18 and 25b. f Data taken from ref. 26a. g This
work. h Slope of Fig. 7 excluding the point corresponding to R = iPr.
The correlation between log(k1) and νCH R can be described
2
by Charton’s equation (eqn (7)), where ψ measures the sensi-
tivity of the reaction to the steric parameter.
logðk1Þ ¼ ψνCH R þ h
ð7Þ
2
Interestingly, for alkoxycarbenes the ψ values are higher
In Table 4, the ψ parameters for nucleophilic attachment than for the esters while for thiocarbenes the ψ values are
step of the aminolysis of Fischer carbene complexes and some lower than for the thiolesters. This translates into a wider
related reactions are shown.
range of steric effects experimented by the organometallic
From the comparison of 4Cr-R and 4W-R with the same complexes (a range of ca. 1.9 ψ units) with respect to their
amine (entries 5 and 6 in Table 4), it can be seen that the organic counterparts (0.7 ψ units).
change in the metallic centre has no detectable effect on the
At this point a comparison between organometallic and
sensitivity of the reaction to the steric effect ψ. Likewise, chan- organic agents with the same heteroatom π-donor is instruc-
ging the nucleophile does not lead to any appreciable modifi- tive. Regarding the oxygen derivatives, alkoxycarbenes and
cation in the sensitivity (entries 4 and 5, Table 4).
esters, the data collected in Table 4 indicate a difference of
It might be possible that a decrease of the nucleophilicity 0.46 ψ units, in close agreement with the difference of 0.32 ψ
yields a more advanced transition state and hence it might units52 found for the hydrolysis reactions. As we mentioned
lead to a higher steric effect; however the results do not before, this might be a consequence of the higher resem-
support this statement (see Table S1†).
blance of the transition states to the zwitterionic intermedi-
Inspection of the ψ values in Table 4 shows that the value ate T in the case of the alkoxycarbenes; this can be seen by
obtained for the aminolysis of the alkoxycarbene complexes is comparing the values reported in Table 3 with those reported
five to six times greater than any of the values for the thiocar- in ref. 18. On the other hand, thiocarbene complexes exhibit
bene analogues. Since this observation is based on a ψ value steric effects that are 0.56 to 0.72 ψ units lower than
obtained with only two points, ψOH values corresponding to their organic analogues. As there is no report on the aminoly-
the basic hydrolysis reaction for both families OvC(OR)Ph sis reaction of thiolesters OvC(SR)Me, a direct comparison
and (CO)5CrvC(OR)Ph have been included in Table 4, which is not possible. Based on the data available for the alkaline
were obtained with a larger number of points. The respective hydrolysis of OvC(SR)Me48 and (CO)5Crv(SR)Ph,53
OH
ψ−ψ
differences with ψ values for the aminolysis reactions (Δ
)
additional support can be obtained. The difference in
were added too. As can be seen, the differences are similar, steric effects observed for these reactions, ψ = −1.07 for
which supports the estimated ψ value for the aminolysis reac- the hydrolysis of thioesters and ψ = −0.60 for the thio-
tion of (CO)5CrvC(OR)Ph.
carbenes, is similar to what is observed for the reactions with
According to the discussion of the previous section this amines.
result can be attributed to differences in the position of the
It is interesting to note that 4M-R complexes possess a
transition states, i.e., an earlier transition state for the thiocar- lower sensitivity to the steric effects than the thiolesters in
benes. Additionally, there must be an extra contribution due to spite of similar βnuc values.51 These results indicate that there
the different sizes of the side groups, i.e., phenyl and methyl must be significant differences in the progress of the steric
groups for the alkoxy- and thiocarbenes, respectively. To the effects with respect to the bond formation at the transition
best of our knowledge, there are no data in the literature state depending on the interplay between the π-donor and
regarding the aminolysis of ionizable Fischer alkoxycarbene π-acceptor groups attached to the reaction centre.
5528 | Dalton Trans., 2015, 44, 5520–5534
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Paper
For better comprehension of this, it is useful to discuss in
As can be seen, our results suggest that steric effects lag
terms of the intrinsic rate constant (log k0),54 which is a pure well behind bond formation for thiocarbene complexes, while
kinetic quantity corrected for differences in the equilibrium for alkoxycarbenes, esters and thiolesters it is more advanced,
constants. Changes in the intrinsic rate constant are indicative although the scene is not completely clear.
of transition state imbalances55 where one or several factors
If steric effects were the main factor ruling the reactivity, it
(like inductive, steric, solvation and π-donation) lag behind or should then be expected that, according to the PNS, the intrin-
ahead of the bond formation. Due to these imbalances, the sic rate constants for the thiocarbene derivatives would be
relative importance of these factors and how they affect the higher than for the alkoxycarbene complexes. Since our results
rate constants are different from how they affect the equilibrium suggest otherwise, i.e. that the intrinsic reactivity of the thio-
constant, and this is reflected as differences in the intrinsic rate carbenes is actually lower than that for the alkoxy derivatives,
constants. The principle of nonperfect synchronization (PNS) this means that other factors play a major role.
provides guidance as to what factors play a central role.56
The inductive effect has been pointed out as an important
Unfortunately, the equilibrium constant K1 values for these factor at the transition state of addition reactions where the
systems could not be calculated. However, based on the reac- nucleophile is bearing a negative charge (7). Although this
tion of thiolate ions with Fischer carbene complexes and ester effect is thought to develop synchronously with bond for-
derivatives, an indirect comparison can be drawn for the trend mation, its contribution to the intrinsic rate constant arises
in the reactivity. For the reaction of the propanethiolate ion from the impact on the resonance/delocalization effect.55a–c
(PrS–) with Fischer carbene complexes 1-Cr-OMe-Ph and 1-Cr- Basically, inasmuch as the negative charge is closer to X at the
SMe-Ph, k1 values are 1.34 × 104 and 5.33 × 102, respectively; transition state than in the adduct, the transition state derives
while the corresponding K1 values are 1.06 × 104 and 1.1 × a disproportionately strong stabilization from the inductive
106.21 This leads to log k0 of 2.11 and −0.29 for 1-Cr-OMe-Ph effect of X compared to the adduct. This should enhance the
57
and 1-Cr-SMe-Ph, respectively. From the side of the organic intrinsic rate constant for the oxygen derivatives more than for
derivatives the data available are remarkably limited. However, the sulphur compounds. However, this effect for neutral
it is possible to draw an approximate idea of the intrinsic rate nucleophiles should not be strong since the charges are off-
constant by taking into account the rate constants published setting each other (6).
by Hupe and Jencks58 and some approximations made by
Guthrie.59 Based on Guthrie’s estimated values for the
addition of ethanethiolate (EtS–) to acetic acid in water at
25 °C, namely, K1 ≈ 7.9 × 10−14 and k1 ≈ 7.9 × 10−4, a value of
log k0 ≈ 3.45 can be calculated.59 The thiolester reactions with
thiolates are expected to have a similar intrinsic rate constant,
and log k0 is roughly estimated as 2.7.60 Overall, the intrinsic
rate constant trend for the thiolate addition is log k0(esters) ≈ The π-donor effect influences the intrinsic rate constant in
log k0(thiolesters) > log k0 (alkoxycarbene complexes) ≫ log different ways.12 One is the loss of resonance stabilization of
k0(thiocarbene complexes) and it is expected that the nucleo- the reactant that is expected to run ahead of bond formation
philic attack step by amines follows the same order.12
and, according to PNS, lower log k0. Since the π-donor ability of
It has been claimed that there are at least three factors oxygen is stronger than that of sulphur, there will be a stronger
responsible for those differences, namely, the steric effect, the reduction in log k0 for the compound with oxygen substitu-
π-donor effect and the inductive effect.21,23,25 In some cases the ents. The other interaction mechanism is the preorganization
steric effect has been pointed out as the most important,19,21,25a,b of the structure of the M(CO)5 moiety in Fischer complexes
while in other cases the influence of the π-donor strength on toward its electronic configuration in the adducts that results
the preorganization of the (CO)5M moiety into its adduct from the π-donor effect. As a consequence, the lag in the
configuration has been suggested as the ruling factor.23,25d,e
charge delocalization into the CO ligands at the transition
Our results allow us to gain further insight into the nature state is reduced, and the intrinsic rate constant is not as
of the main factors ruling the reactivity of the nucleophilic strongly depressed by the PNS effect associated with this lag.
addition of amines to the organometallic carbene complexes.
We believe that the second mechanism of the π-donor effect is
According to the PNS, the steric hindrance is a product ruling the intrinsic rate constant in the aminolysis of Fischer
destabilizing factor and when its development is ahead of the carbene complexes. This is not because of how it affects log k0
bond formation, log k0 is lowered; conversely, when it lags per se, but because of how it influences the solvation sphere
behind bond formation, log k0 is enhanced. Predictions with around the transition state. Computational studies have
respect to whether the development of steric effects at the tran- suggested that the solvation of the zwitterionic intermediate is
sition state is generally ahead of bond formation or lags highly important, i.e., ca. 5 kcal mol−1 24
PNS predicts that sol-
.
behind it have always been difficult to make.55b Evidence from vation should lag behind bond formation.55a–c Thus, the more
previous nucleophilic vinylic substitution studies has preorganized is the compound, the less imbalanced the tran-
suggested that early development of steric hindrance appears sition state, explaining the differences found for alkoxy- and
to be the rule.61
thiocarbene derivatives.
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Dalton Transactions
On the basis of our results a decisive answer cannot be
given as it respects to which interaction is the dominant one,
but at least we can have clues to the role of the steric effects on
this step. Although steric effects command the differences in
the reactivity within the heteroatom-substituted compound
series, it is not the main factor responsible for the depression
in the intrinsic rate constant when oxygen is replaced by
sulphur. The fact that log k0 of alkoxycarbene complexes
exceeds log k0 of the thiolated derivatives by more than 2 units
suggests that the preorganization of the compound as well as
the solvation sphere may have a strong contribution. Note,
though, that this is not a firm conclusion, and that other
factors may be contributing as well. The importance of the pre-
organization of the reactants as a key factor determining the
differences in reactivity between alkoxy- and thiocarbenes has
been previously pointed out by Bernasconi.21b
) and log kT3EA/k−1
(
) vs. νCH R for the reaction
●
○
Fig. 8 Plots of log k1
(
2
of 4W-R with morpholine in 50% MeCN–50% at 25 °C and ionic
strength = 0.1 M (KCl).
3.3 Nucleophilic attack (k1) and leaving group expulsion
(kA3/k−1) for secondary amine
The obtained value of ψ = −1.68 is sensibly higher than that
The data in Table 2 show that the rate constants for the for k1. These results indicate that steric effects play a signifi-
nucleophilic addition of morpholine (k1) have a trend to cant role also in the base catalysed pathway. These changes of
decrease as R becomes bulkier, i.e., R = Me > n-Bu > cHex > iPr. the kA3/k−1 ratios with the volume of R could be a consequence
This undoubtedly indicates that the same factors, as those of an increase of k−1, a decrease of kA3 or both. The values of
already described for the primary amines, are operating. In k−1 should increase with the size of R because a bulky R group
Fig. 6 a plot of log k1 vs. Charton’s parameter νCH R is shown.
destabilizes the tetrahedral intermediate T , and therefore, its
2
The ψ value for morpholine (−0.88) is slightly higher than breakdown back to reactants should be faster. On the other
for those values obtained for primary amines (−0.41 to −0.57, hand, kA3 according to the mechanism B in Scheme 3 can be
Table 4). This higher sensitivity for the secondary amine can expressed as kA3 = k3HA Ka/KaHA. Based on the Ka/KaHA values
be easily explained in terms of the Hammond–Leffler postu- reported for similar systems,62 this ratio should be approxi-
late.38 Since the formation of the zwitterionic intermediate is mately constant for the series studied and therefore a variation
thermodynamically less favourable due to increased steric on kH3 A should be mirrored on kA3. The steric hindrance would
crowding, the transition state should be more advanced. This have two modes for affecting kH3 A. On the one hand, a more
is in good agreement with the 0.42–0.60 βnuc values reported crowded T– should enhance the kH3 A values to yield the amino-
for the reaction of secondary alicyclic amines with 1-Cr-SMe- lysis products. In this way, the effects on k−1 and kA3 would
Ph complexes.19b Strikingly, comparing the values of primary offset each other and no clear trend should be observed. This
(see Table 3) and secondary amines a 2-fold increase in βnuc is indeed the case when the catalysts are small, like with OH–
produces a concomitant 2-fold increase in the steric sensitivity or morpholine. On the other hand, if the catalyst is bulky (like
of the reaction. The nature of the metallic centre does not with TEA), the kH3 A values should decrease with increasing size
affect considerably the change in k1 with the volume of the of the R group due to the difficulty for the catalyst to approach
R. This outcome arises from the ratios k1(4W-Me)/k1(4W-cHex) the leaving group (–SR). A noticeable decrease in the reactivity
= 2.1 and k1(4Cr-Me)/k1(4Cr-cHex) = 1.9.
of the TEA base catalysis is indeed observed for the thiocar-
The analysis of the kA3/k−1 ratios in Table 2 suggests that the bene complexes 4M-R. It is noteworthy that the pKaHSR of the
volume of the R group modifies the velocity of the general base leaving groups does not change significantly throughout the
catalysed step. Due to the particular features of the system, we series studied.
were only able to measure the general base catalysis for three
of the bases used, namely, OH–, morpholine and triethylamine affected by the nature of the metal centre. As can be seen from
(TEA). The size of these bases increases in the sense OH–
Table 2, (kT3EA/k−1)(4W-Me)/(k3TEA/k−1)(4W-cHex) = 4.3 while
Interestingly, the steric effects on the kA3/k−1 are significantly
<
Morpholine < TEA while the pKHa A values follow the order Mor- (kT3EA/k−1)(4Cr-Me)/(kT3EA/k−1)(4Cr-cHex) = 9.7. This means that
pholine ≪ TEA ≪ OH–. Comparing each of the bases their by replacing the tungsten by chromium the steric effects are
values of kA3/k−1 fall in the order dictated by the pKHa A. Interest- enhanced 2-fold. This can be ascribed to the less electronega-
ingly, the smaller bases (morpholine and OH–) do not show a tive character of Cr in comparison with W, which leads to less
clear trend with the size of the R group, but TEA presents a stable T and T– intermediate and hence to less advanced tran-
similar trend to that displayed by the nucleophilic attachment sition states to either reactants or products. This is finally
step. The correlation of kT3EA/k−1 ratios with Charton’s steric reflected in the more pronounced dependence of the velocity
parameter is shown in Fig. 8.
on the volume of the R group.
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Dalton Transactions
Paper
of the metal centre can modify the steric sensitivity of this
process.
4. Conclusions
From the kinetic studies reported in this paper, the following
conclusions can be drawn:
5. Experimental section
5.1 Materials
(i) The reaction of 4M-R with amines leads to a substitution
of the thioalkyl group by a stepwise mechanism involving a
nucleophilic addition to the carbene carbon followed by
specific base-general acid catalysed leaving group expulsion.
For the reactions with primary amines (n-butylamine, methoxy-
ethylamine, benzylamine, furfuryl amine, glycine ethyl ester),
the first step is rate-limiting. On the other hand, for the reac-
tion with morpholine at low amine and OH– concentrations,
the leaving group departure step is rate-limiting, while at high
amine or OH– concentrations, the nucleophilic attack is the
rate limiting step.
The Fischer carbene complexes were synthesized according to
the procedure of Yamashita et al.63 The products were charac-
terized by NMR spectroscopy (400 MHz, CDCl3), FT-IR (KBr),
HRMS (FAB) and UV-Vis spectrophotometry. The full character-
ization of the Fischer carbene complexes 4M-R has been pub-
lished.26c,d
Acetonitrile was of reagent grade and was used without
further purification. Water was taken from a Milli-Q water puri-
fication system. The liquid amines were freshly distilled before
use. The solid amines were recrystallized from ethanol.
(ii) Tungsten complexes are more reactive than the chro-
mium derivatives in the nucleophilic addition; the k1(4W-R)/
k1(4Cr-R) ratios are between 2.9 and 5.7, indicating a small
enhancement of the electrophilicity when M = W.
5.2 Kinetic experiments
The stock solutions of the carbene complexes were prepared in
pure acetonitrile, and appropriate solutions in 50% MeCN–
50% water were prepared just prior to use. All kinetic experi-
ments were performed using a stopped-flow spectropho-
tometer. In a syringe was placed the solution of the carbene
complex and in the other one the buffer solution with the
nucleophiles. The reactions were performed under pseudo
first-order conditions with the carbene complex as the minor
component. The final concentrations of 4M-R were ca. 1 × 10−4 M.
The ionic strength was kept at 0.1 M with KCl. The reac-
tions were followed at the maximum wavelength of the amino
carbene complex reaction product, 355 nm for chromium com-
plexes and 335 nm for tungsten complexes.
For reactions with morpholine buffer, seven solutions were
prepared at pH 8.88 in the range of total buffer concentration
of 0.0125–0.1 M.
The reactions where triethylamine (TEA) buffer was the
catalyst and morpholine was the nucleophile were performed
in two different ways: (a) at constant pH = 10.78 and a constant
concentration of morpholine (0.01 M), varying the concen-
tration of TEA in the range 0.001–0.1 M. (b) At constant con-
centrations of morpholine (0.01 M) and TEA (0.01 M),
changing the pH in the range 9.60–11.19.
(iii) The βnuc values for the nucleophilic addition are small,
indicating that C–N bond formation has made little progress
at the transition state. The size of the R group has no influence
on the degree of bond formation and the metal nature exerts
a small effect on the position of the transition state. On
average, chromium complexes have slightly higher βnuc than
tungsten complexes. This is attributed to the difference in elec-
tronegativity, which leads to a better stabilization of the inter-
mediate T .
(iv) Charton’s plots revealed that the size of the R group is
mainly responsible for the decreasing reactivity within the
4M-R series. The obtained ψ coefficients for the nucleophilic
attack step suggest that the sensitivity to the steric effects
exerted by R is significantly weaker for thiocarbenes than for
alkoxycarbenes. Furthermore, neither the metal centre nor the
nucleophile has a detectable influence on the ψ values.
(v) The comparison of the Charton data between thiocar-
bene and alkoxycarbene complexes and between thiolester and
ester shows that organometallic derivatives experience a wider
range of steric effects on nucleophilic attack. While thio-
carbenes exhibit lower ψ values than thiolesters, alkoxycar-
benes exhibit higher ψ values than the thiocarbene complexes.
(vi) The fact that steric effects are more important in the
alkoxycarbene reactions than in the thiocarbene reactions indi-
cates that they cannot be responsible for the differences in the
reactivity. Based on the PNS, our data suggest that the factor
ruling the reactivity trend is the interplay between π-donor and
π-acceptor groups attached to the reaction centre and how they
affect the solvation sphere.
In all cases, the kobs values were obtained as the averages of
at least four experiments.
Acknowledgements
The financial support from the Consejo Nacional de Investiga-
(vii) The nucleophilic attachment of a secondary amine to ciones Científicas y Técnicas (CONICET), Universidad Nacional
4M-R is more sensitive to the steric effects due to a more de Córdoba and Agencia Nacional de Promoción Científica y
advanced transition state. This is in good agreement with the Técnicas (FONCYT) is acknowledged. RHR and AMG kindly
higher βnuc values.
acknowledge the positions as researchers at CONICET. DMA
(viii) The steric effects exerted by the R group are strong in and MEZM thank Deutscher Akademischer Austausch Dienst
the general base catalysed step. This is due to the fact that a for the postdoctoral fellowships (grants A/12/76196 and A/12/
bulkier R group destabilizes T and T– intermediates and 75259). We thank Prof. Dr. E. A. Castro for his valuable com-
slows down the catalyst approach. Remarkably, the nature ments in the discussion.
This journal is © The Royal Society of Chemistry 2015
Dalton Trans., 2015, 44, 5520–5534 | 5531

Paper
Dalton Transactions
(e) M. Landman, R. Liu, P. H. Van Rooyen and J. Conradie,
Electrochim. Acta, 2013, 114, 205–214; (f) M. Landman,
R. Pretorius, B. E. Buitendach, P. H. Van Rooyen and
J. Conradie, Organometallics, 2013, 32, 5491–5503;
(g) M. Landman, R. Liu, R. Fraser, P. H. Van Rooyen and
J. Conradie, J. Organomet. Chem., 2014, 752, 171–182.
8 G. M. Chu, A. Guerrero-Martínez, I. Fernández and
M. A. Sierra, Chem. – Eur. J., 2014, 20, 1367–1375.
9 (a) W. Q. Zhang, A. J. Atkin, R. J. Thatcher, A. C. Whitwood,
I. J. S. Fairlamb and J. M. Lynam, Dalton Trans., 2009,
4351–4358; (b) W. Q. Zhang, A. C. Whitwood,
I. J. S. Fairlamb and J. M. Lynam, Inorg. Chem., 2010, 49,
8941–8952.
References
1 (a) Y. T. Wu, T. Kurahashi and A. De Meijere, J. Organomet.
Chem., 2005, 690, 5900–5911; (b) M. Gómez-Gallego,
M. J. Mancheno and M. A. Sierra, Acc. Chem. Res., 2005, 38,
44–53; (c) M. A. Sierra, M. Gómez-Gallego and R. Martínez-
Álvarez, Chem. – Eur. J., 2007, 13, 736–744; (d) M. A. Sierra,
I. Fernández and F. P. Cossío, Chem. Commun., 2008, 4671–
4682; (e) K. H. Dötz and J. Stendel Jr., Chem. Rev., 2009,
109, 3227–3274; (f) I. Fernández, F. P. Cossío and
M. A. Sierra, Acc. Chem. Res., 2011, 44, 479–490;
(g) I. Fernández and M. A. Sierra, Top. Heterocycl. Chem.,
2013, 30, 65–84; (h) H. G. Raubenheimer, Dalton Trans.,
2014, 43, 16959–16973.
10 C. C. Wang, Y. Wang, H. J. Liu, K. J. Lin, L. K. Chou and
K. S. Chan, J. Phys. Chem. A, 1997, 101, 8887–8901.
2 (a) M. A. Fernández-Rodríguez, P. García-García and
E. Aguilar, Chem. Commun., 2010, 46, 7670–7687; 11 (a) M. Cases, G. Frenking, M. Duran and M. Solà, Organo-
(b) J. Barluenga, A. Álvarez-Fernández, A. L. Suárez-Sobrino
and M. Tomás, Angew. Chem., Int. Ed., 2012, 51, 183–186;
(c) T. Tobrman, I. Jurásková and D. Dvořák, Organometal-
lics, 2014, 33, 6593–6603; (d) J. González, A. Gómez,
I. Funes-Ardoiz, J. Santamaría and D. Sampedro, Chem. –
Eur. J., 2014, 20, 7061–7068; (e) J. Barluenga, A. Álvarez-Fer-
nández, T. Suárez-Rodríguez, Á. L. Suárez-Sobrino and
metallics, 2002, 21, 4182–4191; (b) G. Frenking, M. Solà and
S. F. Vyboishchikov, J. Organomet. Chem., 2005, 690, 6178–
6204; (c) I. Fernández, F. P. Cossío, A. Arrieta, B. Lecea,
M. J. Mancheno and M. A. Sierra, Organometallics, 2004,
23, 1065–1071; (d) D. M. Andrada, M. E. Zoloff Michoff,
I. Fernández, A. M. Granados and M. A. Sierra, Organo-
metallics, 2007, 26, 5854–5858.
M. Tomás, Org. Lett., 2013, 15, 488–491; (f) R. Chaudhuri 12 C. F. Bernasconi, Adv. Phys. Org. Chem., 2002, 37, 137–237.
and U. Kazmaier, Synlett, 2014, 693–695.
3 (a) J. Barluenga, M. G. Suero, I. Pérez-Sánchez and J. Flórez,
J. Am. Chem. Soc., 2008, 130, 2708–2709; (b) J. Barluenga,
13 (a) J. W. Herndon, Coord. Chem. Rev., 2011, 255, 3–100;
(b) J. W. Herndon, Coord. Chem. Rev., 2013, 257, 2899–
3003.
M. G. Suero, R. De La Campa and J. Flórez, Angew. Chem., 14 (a) M. Salmain, E. Licandro, C. Baldoli, S. Maiorana,
Int. Ed., 2010, 49, 9720–9724; (c) M. G. Suero, R. De La
Campa, L. Torre-Fernández, S. García-Granda and J. Flórez,
Chem. – Eur. J., 2012, 18, 7287–7295.
4 J. W. Herndon, Coord. Chem. Rev., 2012, 256, 1281–1376.
5 (a) J. O. C. Jimenez-Halla and M. Solà, Chem. – Eur. J.,
H. Tran-Huy and G. Jaouen, J. Organomet. Chem., 2001,
617–618, 376–382; (b) S. Maiorana, E. Licandro,
D. Perdicchia, C. Baldoli, B. Vandoni, C. Giannini and
M. Salmain, J. Mol. Catal. A: Chem., 2003, 204–205, 165–
175.
2009, 15, 12503–12520; (b) K. H. Dötz and P. Tomuschat, 15 D. Samanta, S. Sawoo, S. Patra, M. Ray, M. Salmain and
Chem. Soc. Rev., 1999, 28, 187–198; (c) K. H. Dötz, A. Sarkar, J. Organomet. Chem., 2005, 690, 5581–5590.
B. Wenzel and H. C. Jahr, Top. Curr. Chem., 2004, 248, 63– 16 (a) S. Sawoo, P. Dutta, A. Chakraborty, R. Mukhopadhyay,
103; (d) M. L. Waters, T. A. Brandvold, L. Isaacs,
W. D. Wulff and A. L. Rheingold, Organometallics, 1998, 17,
4298–4308; (e) M. L. Waters, M. E. Bos and W. D. Wulff, J.
Am. Chem. Soc., 1999, 121, 6403–6413; (f) C. Wu,
D. O. Berbasov and W. D. Wulff, J. Org. Chem., 2010, 75,
4441–4452.
O. Bouloussa and A. Sarkar, Chem. Commun., 2008, 5957–
5959; (b) P. Dutta, S. Sawoo, N. Ray, O. Bouloussa and
A. Sarkar, Bioconjugate Chem., 2011, 22, 1202–1209;
(c) P. Srivastava, A. Sarkar, S. Sawoo, A. Chakraborty,
P. Dutta, O. Bouloussa, C. Méthivier, C. M. Pradier,
S. Boujday and M. Salmain, J. Organomet. Chem., 2011, 696,
1102–1107.
6 (a) B. Karatas, I. Hyla-Kryspin and R. Aumann, Organome-
tallics, 2007, 26, 4983–4996; (b) F. Nitsche, R. Aumann and 17 N. Ray, S. Sawoo and A. Sarkar, Anal. Methods, 2014, 6, 351–
R. Fröhlich, J. Organomet. Chem., 2007, 692, 2971–2989; 354.
(c) B. Karataş and R. Aumann, Organometallics, 2010, 29, 18 C. F. Bernasconi and M. W. Stronach, J. Am. Chem. Soc.,
801–805. 1993, 115, 1341–1346.
7 (a) I. Fernández, M. J. Mancheño, M. Gómez-Gallego and 19 (a) C. F. Bernasconi and S. Bhattacharya, Organometallics,
M. A. Sierra, Org. Lett., 2003, 5, 1237–1240; (b) C. Baldoli,
P. Cerea, L. Falciola, C. Giannini, E. Licandro, S. Maiorana,
2003, 22, 1310–1313; (b) C. F. Bernasconi and
S. Bhattacharya, Organometallics, 2003, 22, 426–433.
P. Mussini and D. Perdicchia, J. Organomet. Chem., 2005, 20 (a) G. M. Blackburn and W. P. Jencks, J. Am. Chem. Soc.,
690, 5777–5787; (c) I. Hoskovcová, J. Roháčová, D. Dvořák,
T. Tobrman, S. Záliš, R. Zvěřinová and J. Ludvík, Electro-
chim. Acta, 2010, 55, 8341–8351; (d) I. Hoskovcová,
R. Zvěřinová, J. Roháčová, D. Dvořák, T. Tobrman, S. Záliš
and J. Ludvík, Electrochim. Acta, 2011, 56, 6853–6859;
1968, 90, 2638–2645; (b) W. P. Jencks, Catalysis in Chemistry
and Enzymology, McGraw-Hill, 1st edn, 1969;
(c) W. P. Jencks, D. G. Oakenfull and K. Salvesen, J. Am.
Chem. Soc., 1970, 92, 3201–3202; (d) M. J. Gresser and
W. P. Jencks, J. Am. Chem. Soc., 1977, 99, 6970–6980;
5532 | Dalton Trans., 2015, 44, 5520–5534
This journal is © The Royal Society of Chemistry 2015

Dalton Transactions
Paper
(e) M. J. Gresser and W. P. Jencks, J. Am. Chem. Soc., 1977, 32 (a) C. F. Bernasconi, R. J. Ketner, S. D. Brown, X. Chen and
99, 6963–6970.
Z. Rappoport, J. Org. Chem., 1999, 64, 8829–8839;
(b) C. F. Bernasconi, A. E. Leyes and Z. Rappoport, J. Org.
Chem., 1999, 64, 2897–2902; (c) C. F. Bernasconi,
S. D. Brown, M. Ali, Z. Rappoport, H. Yamataka and
H. Salim, J. Org. Chem., 2006, 71, 4795–4802;
(d) C. F. Bernasconi and Z. Rappoport, Acc. Chem. Res.,
2009, 42, 993–1003.
21 (a) C. F. Bernasconi, K. W. Kittredge and F. X. Flores, J. Am.
Chem. Soc., 1999, 121, 6630–6639; (b) C. F. Bernasconi and
M. Ali, J. Am. Chem. Soc., 1999, 121, 11384–11394.
22 (a) F. R. Kreissl, E. O. Fischer, C. G. Kreiker and K. Weiss,
Angew. Chem., Int. Ed. Engl., 1973, 12, 563; (b) F. R. Kreissl
and E. O. Fischer, Chem. Ber., 1974, 107, 103.
23 M. Ali, A. Dan, A. Ray and K. Ghosh, Inorg. Chem., 2005, 44, 33 (a) A. T. Talvik, A. Tuulmets and E. Vaino, J. Phys. Org.
5866–5871.
Chem., 1999, 12, 747–750; (b) I. H. Um, E. J. Lee and
S. E. Jeon, J. Phys. Org. Chem., 2002, 15, 561–565;
(c) I. H. Um, J. A. Seok, H. T. Kim and S. K. Bae, J. Org.
Chem., 2003, 68, 7742–7746; (d) I. H. Um, J. S. Kang and
J. Y. Park, J. Org. Chem., 2013, 78, 5604–5610.
24 D. M. Andrada, J. O. C. Jimenez-Halla and M. Solà, J. Org.
Chem., 2010, 75, 5821–5836.
25 (a) C. F. Bernasconi, C. Whitesell and R. A. Johnson, Tetra-
hedron, 2000, 56, 4917–4924; (b) C. F. Bernasconi and
S. Bhattacharya, Organometallics, 2004, 23, 1722–1729; 34 (a) I. H. Um, S. E. Lee and H. J. Kwon, J. Org. Chem., 2002,
(c) M. Ali, New J. Chem., 2003, 27, 349–353; (d) M. Ali and
D. Maiti, J. Organomet. Chem., 2004, 689, 3520–3527;
67, 8999–9005; (b) M. Eigen, Angew. Chem., Int. Ed. Engl.,
1964, 3, 1–19.
(e) M. Ali, S. Gangopadhyay and M. Mijanuddin, J. Organo- 35 (a) C. F. Bernasconi, F. X. Flores, J. R. Gandler and
met. Chem., 2005, 690, 4878–4885; (f) S. Biswas and M. Ali,
J. Organomet. Chem., 2007, 692, 2897–2902.
26 (a) M. E. Zoloff Michoff, R. H. de Rossi and
A. E. Leyes, Organometallics, 1994, 13, 2186–2193;
(b) C. F. Bernasconi and L. García-Río, J. Am. Chem. Soc.,
2000, 122, 3821–3829.
A. M. Granados, J. Org. Chem., 2006, 71, 2395–2401; 36 R. G. Pearson, Inorg. Chem., 1988, 27, 734.
(b) C. F. Bernasconi, M. E. Zoloff Michoff, R. H. de Rossi 37 (a) W. P. Jencks, M. T. Haber, D. Herschlag and
and A. M. Granados, J. Org. Chem., 2007, 72, 1285–1293;
(c) M. E. Zoloff Michoff, D. M. Andrada, A. M. Granados
and R. H. de Rossi, New J. Chem., 2008, 32, 65–72;
(d) D. M. Andrada, M. E. Zoloff Michoff, R. H. de Rossi and
A. M. Granados, Phys. Chem. Chem. Phys., 2010, 12, 6616–
6624.
K. L. Nazaretian, J. Am. Chem. Soc., 1986, 108, 479–483;
(b) J. P. Richard, J. Chem. Soc., Chem. Commun., 1987, 1768–
1769; (c) R. A. McClelland, V. M. Kanagasabapathy,
N. S. Banait and S. Steenken, J. Am. Chem. Soc., 1992, 114,
1816–1823; (d) A. Pross, J. Org. Chem., 1984, 49, 1811–1818;
(e) A. Pross and S. S. Shaik, Acc. Chem. Res., 1983, 16, 363–
370; (f) A. Pross and S. S. Shaik, J. Am. Chem. Soc., 1982,
104, 187–195; (g) A. Pross and S. S. Shaik, New J. Chem.,
1989, 13.
27 (a) E. N. Bess and M. S. Sigman, Linear Free Energy
Relationships (LFERs) in Asymmetric Catalysis, in
Asymmetric Synthesis II: More Methods and Applications,
ed. M. Christmann and S. Bräse, Wiley-VCH Verlag GmbH 38 (a) G. S. Hammond, J. Am. Chem. Soc., 1955, 77, 334–338;
& Co. KGaA, Weinheim, Germany, 2013, pp. 363–370; (b) J. E. Leffler, Science, 1953, 117, 340.
(b) J. J. Miller and M. S. Sigman, Angew. Chem., Int. Ed., 39 (a) E. G. Sander and W. P. Jencks, J. Am. Chem. Soc., 1968,
2008, 47, 771–774; (c) B. R. Dible and M. S. Sigman,
Inorg. Chem., 2006, 45, 8430–8441; (d) K. C. Harper and
90, 6154–6162; (b) A. C. Satterthwait and W. P. Jencks,
J. Am. Chem. Soc., 1974, 96, 7018–7031.
M. S. Sigman, J. Org. Chem., 2013, 78, 2813–2818; 40 (a) E. A. Castro, J. Sulfur Chem., 2007, 28, 407–435;
(e) K. H. Jensen and M. S. Sigman, J. Org. Chem., 2010, 75, (b) E. A. Castro, Pure Appl. Chem., 2009, 81, 685–696.
7194–7201; (f) M. S. Sigman and J. J. Miller, J. Org. Chem., 41 D. M. Andrada, M. E. Zoloff Michoff and I. Fernández, to
2009, 74, 7633–7643; (g) K. C. Harper, E. N. Bess and be published.
M. S. Sigman, Nat. Chem., 2012, 4, 366–374; 42 C. Hansch, A. Leo and R. W. Taft, Chem. Rev., 1991, 91,
(h) J. L. Gustafson, M. S. Sigman and S. J. Miller, Org. Lett.,
2010, 12, 2794–2797.
28 J. Santamaría, Curr. Org. Chem., 2009, 13, 31–46.
29 E. A. Castro, Chem. Rev., 1999, 99, 3505–3524.
30 (a) C. F. Bernasconi, R. H. de Rossi and P. Schmid, J. Am.
Chem. Soc., 1977, 99, 4090–4101; (b) C. F. Bernasconi, Acc.
165–195.
43 J. Barluenga, A. A. Trabanco, J. Flórez, S. García-Granda
and E. Martín, J. Am. Chem. Soc., 1996, 118, 13099–13100.
44 J. Barluenga, A. A. Trabanco, I. Pérez-Sánchez, R. De La
Campa, J. Flórez, S. García-Granda and Ã. Aguirre, Chem. –
Eur. J., 2008, 14, 5401–5404.
Chem. Res., 1978, 11, 147–152; (c) J. Persson, S. Axelsson 45 A. K. Ghose and G. M. Crippen, J. Chem. Inf. Comput. Sci.,
and O. Matsson, J. Am. Chem. Soc., 1996, 118, 20–23; 1987, 27, 21–35.
(d) L. García Río, J. R. Leis and E. Iglesias, J. Org. Chem., 46 R. W. Taft Jr., J. Am. Chem. Soc., 1952, 74, 3120–3128.
1997, 62, 4701–4711; (e) R. Ormazabal-Toledo, J. G. Santos, 47 (a) M. Charton, J. Org. Chem., 1976, 41, 2217–2220;
P. Ríos, E. A. Castro, P. R. Campodónico and R. Contreras,
J. Phys. Chem. B, 2013, 117, 5908–5915.
31 E. F. Caldin, The Mechanism of Fast Reactions in Solution,
Amsterdam, The Netherland, 1st edn, 2001.
(b) M. Charton, J. Am. Chem. Soc., 1975, 97, 1552–1556.
48 M. Charton and B. I. Charton, J. Org. Chem., 1978, 43,
1161–1165.
49 M. Charton, J. Org. Chem., 1977, 42, 3531–3535.
This journal is © The Royal Society of Chemistry 2015
Dalton Trans., 2015, 44, 5520–5534 | 5533

Paper
Dalton Transactions
50 D. F. DeTar and C. Delahunty, J. Am. Chem. Soc., 1983, 105, 58 D. J. Hupe and W. P. Jencks, J. Am. Chem. Soc., 1977, 99,
2734–2739. 451–464.
51 I. Lee, H. W. Lee, B. C. Lee and J. H. Choi, Bull. Korean 59 J. P. Guthrie, J. Am. Chem. Soc., 1978, 100, 5892–
Chem. Soc., 2002, 23, 201–204. 5904.
52 In the original article (ref. 26a) a difference of 0.57 unit 60 The estimation is rooted in the data published for the
was reported for the ψ values obtained in the correlation
between log(k1) vs. νOR. In the present report the values
hydrolysis of thiolesters, where for CH3C(O)SEt the value
for log KO1H = −6.3 and log kO1 H = −0.93.59 With these values
the intrinsic rate constant is ca. 2.23. This value is slightly
lower than that obtained for the hydrolysis and methanoly-
sis of benzylacetate, i.e., log k0 = 2.4 and 3.10, respective-
ly.35a Based on the fact that the carbon basicity of sulphur
in a thiolate anion is 10 times larger than similar amines
and oxygen anions and that the equilibrium constants for
the addition to carbonyl groups are approximately 103
larger for thiolates than for alcohols,39a,58,64 it is expected
that the intrinsic rate constant is around 0.5 unit higher
than the value for hydrolysis.
were recalculated with the correlation log(k1) vs. νCH R
.
2
53 D. M. Andrada, M. E. Zoloff Michoff, R. H. de Rossi and
A. M. Granados, unpublished results.
54 The intrinsic rate constant of a reaction with a forward rate
constant k1 and a reverse rate constant k−1 is defined as k0
= k1 = k−1 when the equilibrium constant K1 = 1 (ΔG0 = 0).
55 (a) C. F. Bernasconi, Acc. Chem. Res., 1987, 20, 301–308;
(b) C. F. Bernasconi, Adv. Phys. Org. Chem., 1992, 27, 119–
238; (c) C. F. Bernasconi, Acc. Chem. Res., 1992, 25, 9–16;
(d) D. A. Jencks and W. P. Jencks, J. Am. Chem. Soc., 1977, 99,
7948–7960; (e) W. P. Jencks, Chem. Rev., 1985, 85, 511–527.
56 The PNS states that if the development of a product stabi-
61 C. F. Bernasconi, R. J. Ketner, X. Chen and Z. Rappoport,
Can. J. Chem., 1999, 77, 584–594.
lizing factor lags behind bond changes or charge transfer 62 C. F. Bernasconi and M. W. Stronach, J. Org. Chem., 1991,
at the transition state, k0 is reduced. The same is true if the 56, 1993–2001.
loss of a reactant stabilizing factor runs ahead of bond 63 A. Yamashita, A. Toy, N. B. Ghazal and C. R. Muchmore,
changes or charge transfer. For product stabilizing factors J. Org. Chem., 1989, 54, 4481–4483.
that develop early or for reactant stabilizing factors that are 64 (a) J. Hine and R. D. Weimar, J. Am. Chem. Soc., 1965, 87,
lost late, k0 is enhanced. For product or reactant destabiliz-
ing factors, the opposite relationships hold.
57 (a) log k0 = log k1 − 0.5 log K1 (b) R. A. Marcus, J. Chem.
Phys., 1965, 43, 679–701.
3387–3396; (b) R. G. Kallen and W. P. Jencks, J. Biol. Chem.,
1966, 241, 5864–5878; (c) G. E. Lienhard and W. P. Jencks,
J. Am. Chem. Soc., 1966, 88, 3982–3995; (d) M. R. Crampton,
J. Chem. Soc. B, 1971, 2112–2116.
5534 | Dalton Trans., 2015, 44, 5520–5534
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