Design Platform for Sustainable Catalysis with Radicals: Electrochemical Activation of Cp2TiCl2 for Catalysis Unveiled

Article abstract of DOI:10.1002/chem.202004519

The combination of synthesis, rotating ring-disk electrode (RRDE) and cyclic voltammetry (CV) measurements, and computational investigations with the aid of DFT methods shows how a thiourea, a squaramide, and a bissulfonamide as additives affect the E

Full text of DOI:10.1002/chem.202004519

Accepted Article
Accepted Article
Title: Design Platform for Sustainable Catalysis with Radicals:
Electrochemical Activation of Cp2TiCl2 for Catalysis Unveiled
Authors: Andreas Gansäuer, Tobias Hilche, Philip H. Reinsberg, Sven
Klare, Theresa Liedtke, and Luise Schäfer
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To be cited as: Chem. Eur. J. 10.1002/chem.202004519
Link to VoR: https://doi.org/10.1002/chem.202004519
0
1/2020

Chemistry - A European Journal
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RESEARCH ARTICLE
Design Platform for Sustainable Catalysis with Radicals:
Electrochemical Activation of Cp TiCl for Catalysis Unveiled
2
2
[a]
[b]
[a]
[a]
[a]
Tobias Hilche, Philip H. Reinsberg, Sven Klare, Theresa Liedtke, Luise Schäfer, and Andreas
Gansäuer*[a]
[
a]
T. Hilche, Dr. S. Klare, Dr. T. Liedtke, L. Schäfer, Prof. Dr. A. Gansäuer
Kekulé-Institut für Organische Chemie und Biochemie
Universität Bonn
Gerhard-Domagk-Straße 1, 53121 Bonn
E-mail: andreas.gansaeuer@uni-bonn.de
Dr. P. H. Reinsberg
[
b]
Institut für Physikalische und Theoretische Chemie
Universität Bonn
Römerstraße 164, 53117 Bonn
Supporting information for this article is given via a link at the end of the document.
Abstract: The combination of synthesis, rotating ring-disk electrode
RRDE) and cyclic voltammetry (CV) measurements, and
of this reaction that we enter the synthesis lab to try our smart
guess. For catalysis in single electron steps[ or metalloradical
catalysis,[3] cyclic voltammetry (CV) is particularly an ideal
screening technique because the metals shuttle between
2]
(
computational investigations with the aid of DFT methods shows how
a thiourea, a squaramide, and a bissulfonamide as additives affect the
E
q
C
r
equilibrium of Cp
2
TiCl
2
. We have, for the first time, provided
neighboring oxidation states. Here, we demonstrate that the E
q
C
r
equilibrium[ is
4]
a
predictor for the performance of the
quantitative data for the E
q
C
r
equilibrium and have determined the
–
stoichiometry of adduct formation of [Cp
Cp Ti(IV)Cl
2
Ti(III)Cl
2
] , [Cp
2
Ti(III)Cl] and
electrochemical, titanocene catalyzed radical epoxide arylation,
[
2
2
] and the additives. By studying the structures of the
providing understanding of the catalyst formation by bulk
in THF (Scheme 1).[ For a
5]
complexes formed by DFT methods, we have established the Gibbs
energies and enthalpies of complex formation as well as the adduct
structures. The results not only demonstrate the correctness of our
electrolysis of precatalyst Cp
2
TiCl
2
successful electrochemical reduction of [Cp
2
Ti(IV)Cl
2
] the initial
–
product of electron transfer [Cp
2
Ti(III)Cl
2
] at the electrode must
use of the E
q
C
r
equilibrium as predictor for sustainable catalysis. They
be transformed into arylation catalyst [Cp
contrast to [Cp Ti(IV)Cl ] – easily soluble in THF and can diffuse
from the electrode. Increasing the concentration of [Cp Ti(III)Cl]
by halide abstraction from [Cp Ti(III)Cl
]– will therefore facilitate
bulk electrolysis of [Cp Ti(IV)Cl ]. While [Cp Ti(III)Cl] constitutes
the active catalyst for epoxide arylation, [Cp Ti(III)Cl
]– provides a
2
Ti(III)Cl], that is – in
are also a design platform for the development of novel additives in
particular for enantioselective catalysis.
2
2
2
2
2
2
2
2
2
2
Introduction
catalytic resting state, that prevents undesired catalysis
decomposition.[6c]
Catalysis has shaped our modern society, providing functional
molecules, materials, or processes both in the lab and on
industrial scale. Substituting stoichiometric reactions by catalytic
[Cp2Ti(IV)Cl2]
O
OH
alternatives offers a conceptionally straight-forward approach to a
more sustainable, green chemistry.[1] However, as simple this
[Cp2Ti(III)Cl]
Cl
N
N
Cp2TiCl2, L, THF
1
Ph
2
Ph
idea may appear in principle, identifying the optimal catalytic
conditions usually demands laborious experimental reaction
screening through expensive use of workforce, material and lab
time. To reinforce the sustainability claim of catalysis, we propose
to identify mechanistic key aspects or so-called ’predictors’ before
setting up any reaction, avoiding both the tour de force and even
the designed experimental investigation of the overall catalytic
reaction. With these mechanistic key features at hand, we can
then predict the optimal catalytic reaction condition based on
scientific arguments rather than our usual into the blue approach,
so that ideally only a few experimental combinations need to be
verified. These ’predictors’ require either the knowledge of the
overall mechanism or at least an understanding of the essentials
of the catalytic cycle. We chose to illustrate our ’predictor’ concept
with the optimization of electrochemical epoxide arylation. It is
only after we exploit widely-used and readily available cyclic
voltammetry (CV) and DFT techniques to identify the ‘predictors’
–
e–
L
Cl
Cl
TiIII
TiIV
TiIII Cl + Cl *L
–
Cl
Cl
Eq
Cr
F3C
CF3
F3C
O
N
O
N
CF3
S
F3C
N
N
H
CF3
F3C
H
H
CF3
H
L1
L2
Scheme 1. Radical arylation after electrochemical activation (top) and E
equilibrium of Cp TiCl (middle). L denotes anion receptors allowing a shift of
the E equilibrium by reversible cleaving of Cl though hydrogen bonding.
q r
C
2
2
–
q r
C
1
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RESEARCH ARTICLE
Adjusting the relative amounts of both species in a reversible way
thus allows a fine-tuning of the performance of the catalytic
– L3 with respect to Cp
agreement with the lowest amount of [Cp Ti(III)Cl] observed in the
2
2
TiCl
2
is summarized in Table 1. In
system. It turned out that the E
q
C
r
equilibrium and therefore bulk
CV-screening, L1 leads to the slowest reaction and lowest yield
of 2. L2 and L3 lead to a more active catalytic system giving
essentially identical results after 2 h.
electrolysis of [Cp Ti(IV)Cl ] in THF can be controlled by the
2
2
addition of supramolecular additives, that bind halides through
hydrogen bonding.[ We show then that the control of E
7]
C
r
q
equilibrium directly translates into the synthetic performance of
the catalytic radical arylation[6] in THF.
Here, we demonstrate that our qualitative analysis of the cyclic
–
[Cp
Ti(III)Cl
]
· L1
2
2
4
2
0
2
4
–
[
Cp Ti(III)Cl ]
2
2
[Cp Ti(III)Cl]
2
q r
voltammograms (CVs) of the E C equilibrium as predictor for the
radical arylation is applicable to bissulfonamides as another class
of supramolecular additives. Moreover, it is in accord with
quantitative measurements at the rotating ring-disk electrode
-
-
(
RRDE).[8] The combination of the experimental results with the
DFT studies of the intermediates of the E equilibrium delivers
2
mM Cp TiCl
2
2
q
C
r
2 mM Cp TiCl / 1 mM L1
2
2
a complete mechanistic analysis of our predictor. Our study not
only leads to a better understanding of the systems already
investigated. It also delivers a design platform for the use of
supramolecular halide binders in enantioselective catalysis and
for their use with complexes of metals other than titanium.
[
Cp Ti(IV)Cl ]
2 mM Cp TiCl / 2 mM L1
2 2
2
2
-6
2 mM Cp TiCl / 10 mM L1
2
2
[
Cp Ti(IV)Cl ] · L1
2
2
-2.0
-1.5
-1.0
-0.5
0.0
+
–1
]
E / V vs. Fc /Fc [

= 0.2 V s
Figure 1. CVs of 2 mM Cp
2
TiCl
2
and L1 in 0.2 M Bu
4
NPF
6
/THF at 0.2 Vs–1
.
Results and Discussion
4
Cyclic Voltammetry and Radical Arylation:
–
[
Cp Ti(III)Cl ]
[Cp Ti(III)Cl]
2
2
2
A critical aspect for efficient screening is a fast and cost-efficient
technique for a conclusive description of the investigated system.
[
Cp Ti(III)Cl] · L2
2
2
0
2
In our case, CV[9] is an ideal tool because the E
C equilibrium
q r
includes an electron transfer step and involves species with
different redox-potentials. CV not only allows a characterization of
the components of a solution. Relevant data can be obtained in
short periods of time and with minor amounts of material (0.02
mmol).
Our previous studies showed that thiourea L1[10] and squaramide
L2[11] (Scheme 1) are suitable additives for the bulk electrolysis of
-
2
2
2
2
mM Cp TiCl
2 2
mM Cp TiCl / 1 mM L2
2
2
[Cp Ti(IV)Cl ]
2
2
mM Cp TiCl / 2 mM L2
-4
2
2
mM Cp TiCl / 10 mM L2
2
2
[Cp Ti(IV)Cl ] · L2
2
2
-2.0
-1.5
-1.0
-0.5
0.0
[
2 2
Cp Ti(IV)Cl ] in THF and the use of the resulting solutions for
+
–1
radical arylation. The CVs (L1: Figure 1; L2: Figure 2) highlight
E / V vs. Fc /Fc [0.2 Vs ]
the reasons for this assessment. Compared to the CV of
[
Cp
2
Ti(IV)Cl
2
] without additives (black traces), the oxidation
Figure 2. CVs of 2 mM Cp
2
TiCl
2
and L2 in 0.2 M Bu
4
NPF
6
/THF at 0.2 Vs–1
.
–
waves pertaining to [Cp
that of [Cp
2
Ti(III)Cl
2
] have a reduced intensity and
2
Ti(III)Cl] an increased intensity. This effect is
significantly more pronounced for L2 than for L1. We assumed
that these effects predict a successful bulk electrolysis and
catalytic radical arylation.
–
[
Cp Ti(III)Cl ] · L3
4
2
2
–
[
Cp Ti(III)Cl ]
[Cp Ti(III)Cl] · L3
2
2
2
[
Cp Ti(III)Cl]
2
0
2
4
6
2
CF3
CF3
CF3
CF3
O2S
N
N
SO2
-
-
-
2
2
2
2
mM Cp TiCl
2 2
H
H
mM Cp TiCl / 1 mM L3
2
2
L3
Scheme 2. H-bonding anion receptors investigated as additives to amplify the
mechanism of Cp TiCl
mM Cp TiCl / 2 mM L3
2
2
mM Cp TiCl / 10 mM L3
2
2
E
q
C
r
2
2
.
[
Cp Ti(IV)Cl ]
[Cp Ti(IV)Cl ] · L3
2
2
2
2
-2.0
-1.5
-1.0
-0.5
0.0
0.5
+
–1
Encouraged by these successes, we extended the screening to
the bis sulfonamide L3 (Scheme 2).[12] The CVs (Figure 3)
E / V vs. Fc /Fc [ = 0.2 V s ]
2
demonstrate that the wave originating from [Cp Ti(III)Cl] is visible.
Figure 3. CVs of 2 mM Cp
2
TiCl
2
and L3 in 0.2 M Bu
4
NPF
6
/THF at 0.2 Vs–1
.
This predicts that addition of L3 results in an efficient bulk
electrolysis and a successful radical arylation (Table 1).
The performance of the epoxide arylation[7] with 1 and 10 mol%
Besides their usefulness as predictors, the CVs highlight an
interesting complexity of interactions between L1 – L3 and the
2 2
electrochemically reduced Cp TiCl in the presence of 1 eq. of L1
2
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Chemistry - A European Journal
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RESEARCH ARTICLE
titanocene species. On the reductive sweep (the lower trace) all
collection efficiency N . They can be discerned by their individual
0
ligands L form an adduct with [Cp
2
Ti(IV)Cl
2
]. This adduct has a
redox potentials. The currents measured due to their
electrochemical reactions are proportional to their concentration
at the electrode surfaces and allow quantitative analysis of the
composition of the solution. For potentials negative of the
equilibrium of a reduction at the disk, the currents reach a plateau
more positive reduction potential with L1 and L2 (+160 mV)
showing a larger shift than L3 (+80 mV). These differences in the
potentials indicate a different strength of the interactions. On the
oxidative sweep (the upper trace), for all additives a complex
[
Cp
shift of the potentials are significant. Interestingly, only L2 and L3
seem to form complexes of the type [Cp Ti(III)Cl]*L. The shift of
the potentials relative to [Cp Ti(III)Cl] suggest an electron-
2
Ti(III)Cl
2
]–*L can be detected. Again, the differences in the
representing the diffusion limited current I and can be evaluated
lim
by the Levich equation (see SI).[
13]
2
2
We started our RRDE measurements of Cp TiCl2 in THF with
2
donating interaction for L3 (–120 mV) and an electron-
withdrawing interaction for L2 (+110 mV).
0.2 M NBu PF (TBAPF ). The data are in agreement with results
4
6
6
of the Daasbjerg group[
4c-e]
by means of CV simulation (see SI)
and show that RRDE measurements are well suited for analyzing
electrochemical systems based on Cp TiCl Based on
Daasbjerg’s work we propose an extended mesh-scheme for the
species present in solutions of Cp TiCl and our additives L
Scheme 3). The monomer-dimer equilibrium of [Cp Ti(III)Cl] is
not observed in CVs with L and thus not relevant here.
2
2
.
Table 1. Results of the arylation reaction after electrochemical activation in THF
with Cp
2
TiCl
2
as precatalyst and L1 – L3 as additives.
2
2
(
2
[
Cp2Ti(IV)Cl2]
Cp2Ti(III)Cl]
0 mol% Cp2TiCl2
O
OH
[
Cl
N
N
1
Ph
Ph
Cp2TiCl2/L = 1/1, THF, reflux
1
2
F3C
CF3
F3C
O
O
CF3
S
F3C
N
N
CF3
F3C
N
H
N
H
H
H
CF3
L1
L2
2
h, 87%
2
h, 59%
Scheme 3. Proposed mesh-scheme for the Cp
L2 or L3).
2 2
TiCl /L redox system (L = L1,
CF3
F3C
F3C
CF3
O2S NH HN SO2
The RRDE measurements will provide the equilibrium constants
given in Scheme 3 and an estimate of the solution composition
before and after reduction. We will discuss the experimental
results for sulfonamide L3 and summarize the data for L1 – L3
L3
2
4
5
h, 86%
h, 93%
h, 92%
Reaction conditions: Catalyst Cp2TiCl2, additive L, 10 mM in THF, isolated yields.
(
detailed discussion see SI).
a
0.0
Studies at the Rotating Ring-Disk Electrode:
GC-Disk
A(Disk) = 0.247 cm²
2
mM Cp TiCl
2
2
Our CV experiments are an ideal tool for the rapid screening of
the additives. For a quantitative analysis, CV merely allows the
direct extraction of the redox potentials of the species detected
and their diffusion coefficients. More complex information on pre-
equilibria or follow-up reactions can only be obtained via
simulation. One general shortcoming of simulation is that,
frequently, several models fit the experimental data. This is
especially true for situations involving several steps and a large
variety of fitting parameters. We decided to provide quantitative
data for our qualitative observations made by CV. To this end, we
used the rotating ring-disk electrode (RRDE).[8] This allows
assessing the results of future screening experiments on a more
solid mechanistic basis.
-
-
-
0.5
1.0
1.5
0.2 M TBAPF /THF
+ 1 mM L3
+ 2 mM L3
+ 3 mM L3
+ 4 mM L3
6
v = 25 mV/s
f = 25 Hz
+
6 mM L3
+ 10 mM L3
0.1
-0.3
-0.2
-0.1
0.0
0.2
+
E(Disk) / V (vs. Ag|Ag )
1.2
b
c
300
1.0
GC-Ring
E(Ring) = 0.05 V
N0 = 0.37
0.8
.6
0.4
2
00
00
0
0
1
0
.2
.0
0
-
0.5
0.0
0.5
-0.5
-0.4
-0.3
+
+
E(Disk) / V (vs. Ag|Ag )
E(Disk) / V (vs. Ag|Ag )
The RRDE set-up offers major advantages over CV in stagnant
solution. In CV, asymmetrically shaped current waves are
observed. Therefore, ‘real’ systems cannot be fitted to a physical
equation. With a RRDE set-up this becomes possible as
Figure 4. Disk current densities i
transfer ratios I /I /N (c) of the RRDE measurements of a solution of 2 mM
Cp TiCl in 0.2 M NBu PF /THF with different concentrations of L3 at a ring
potential E of 0.05 V and a rotation frequency f of 25 Hz.
D R 0
(a), normalized ring currents I /N (b) and
R
D
0
2
2
4
6
R
convection results in
a time-independent and well-defined
thickness of the Nernstian diffusion layer. It is composed of a disk
and a ring electrode surrounding the disk. Rotation ensures a
steady flow of reactants from the bulk solution to the disk. From
here, the electrolyte is radially forced out to the ring and the
species generated at the disk can be detected with a theoretical
2 2
Ti(III)Cl
]– can be observed
The stabilizing effect of L3 on [Cp
directly from the positive shift of the voltammograms detected at
the disk i and the decreasing transfer ratios (I /I /N ) for
measurements with Cp TiCl and L3 at a rotation frequency f of
D
R
D
0
2
2
3
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Chemistry - A European Journal
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RESEARCH ARTICLE
and to f1/2. Figure 5 depicts the diffusion-limited i of [Cp Ti(IV)Cl ]
25 Hz and
a
ring potential
E
R
of 0.05 V (Figure 4, for
D
2
2
measurements at f = 4 Hz and E
R
= 0.23, 0.42 and 0.66 V see SI).
and with 10 mM of L3 alongside the shoulder current density
A potential of 0.05 V vs. Ag/Ag+ solely allows the oxidation of
found for the measurement of L3 (1 mM, 0.5 eq.) as a function of
]– (Figure 3, please note that the Fc /Fc scale is
+
1/2
[
Cp
2
Ti(III)Cl
2
f . The graphical representation of the data yields straight lines.
shifted by ca. –1.1 V). Thus, only this species is detected at the
ring.
The non-zero intercept of the line representing the shoulder
currents indicates that the current flow is not solely limited by
diffusion. Possibly the kinetics of the reduction of the unbound
species already play a minor role. We assume that in the solutions
0
.0
a
2 2
with 10 mM of L approximately all [Cp Ti(IV)Cl ] is bound to L.
2
mM Cp TiCl2
The different slopes observed for the experiments with base
2
+
10 mM L3
electrolyte and with 10 mM L3 yield the ratio of the diffusion
-0.5
-1.0
-1.5
+ 1 mM L3
coefficients of [Cp
the Levich equation. The diffusion coefficient D of [Cp
is 1.15 times larger than that of [Cp Ti(IV)Cl ]*L3 (1.15 with L1
and 1.33 with L2). In the measurement with 1 mM L3 the
diffusion-limited reduction of [Cp Ti(IV)Cl ]*L3 is observed as a
shoulder prior to the reduction of [Cp Ti(IV)Cl ], as the reaction
between [Cp Ti(IV)Cl ] and L3 is incomplete. From the ratio of this
shoulder to the subsequent plateau, the equilibrium constant of
association K of L3 to [Cp Ti(IV)Cl ] is accessible. With a value
2
Ti(IV)Cl
2
] and [Cp
2
Ti(IV)Cl
2
]*L3 according to
2
Ti(IV)Cl
2
]
[
Cp Ti(IV)Cl ] · L3
2 2
[
Cp Ti(IV)Cl ] · L3
2
2
2
2
shoulder
2
2
2
2
2
2
[
Cp Ti(IV)Cl ]
2 2
-0.2
-0.1
0.0
0.1
a
2
2
+
E(Disk) / V (vs. Ag|Ag )
–
1
–1
–
of 1.07 mM , L3 lies between L1 (0.69 mM ) and L2 (1.81 mM
1
/2 -1/2
1).
f
/s
0
1
2
3
4
5
0
.0
We studied the composition of the reduced solutions of Ti(III) to
obtain K to K (Scheme 3) by analyzing the effect of L on the
transfer ratios (compare Figure 4c). The fixed ring potential E
allows the detection of all species that can be oxidized up to this
1
3
b
R
-
-
-
0.5
potential. The step-wise increase of E
R
afforded transfer ratios for
[Cp Ti(III)Cl] and
2
mM Cp TiCl
–
]–*L3,
2
2
[Cp
Cp
2
Ti(III)Cl
2
] ,
[Cp
2
Ti(III)Cl
2
2
+
+
10 mM L3
1 mM L3 (shoulder)
[
2
Ti(III)Cl]*L3. These transfer ratios are shown in Figure 6 as a
1.0
1.5
function of the concentration of L3.
1
/2
-2
-2
-2
The transfer ratios allow the calculation of the equilibrium
constants between the Ti(III) species (see SI for details). The
m = -0.306 mA s cm
1/2
m = -0.278 mA s cm
1/2
1 2 2
association equilibrium constant K of L3 to [Cp Ti(III)Cl
]–
m = -0.083 mA s cm
amounts to 0.4 mM–1 (2 mM–1 for L1, 0.3 mM–1 for L2).
–
]–*L3 has an equilibrium
Dissociation of Cl *L3 from [Cp
2
Ti(III)Cl
2
constant K
formation of [Cp
L2). This adduct is not observed for L1.
2
of 3.0 mM (2.8 mM for L1, 54 mM for L2). The
Ti(III)Cl]*L3 has a K
3
of 0.7 mM–1 (0.5 mM–1 for
2
Figure 5. Cut-out of the RDE measurements shown in Figure 4a (a) highlighting
the shoulder in the 1 mM L3 measurement and diffusion limited current densities
1/2
D 2 2
(b) at the disk i as a function of f for Cp TiCl and with 10 mM of L3 or 1 mM
of L3 (shoulder). The slopes of the linear fits are given as m.
1
0
0
.0
.5
.0
[
Cp Ti(III)Cl]
2
L3 (10 mM, 5.0 eq.) leads to a positive shift of the reduction
potential and a slight decrease of i
D
in the diffusion limited region
[Cp Ti(III)Cl]·L3
Ring potential
.05 V
0.23 V
2
0
at the disk electrode from −1.54 mA cm−2 to −1.46 mA cm
−2
0
0
.42 V
.66 V
(
Figure 4a) and to a significant decrease of the normalized ring
current I
R
/N
0
by a factor of 4 (Figure 4b). The transfer ratio, which
–
[
Cp Ti(III)Cl ] ·L3
2
2
–
–
is directly proportional to the concentration of [Cp
2
Ti(III)Cl
2
]
in
[
Cp Ti(III)Cl ]
2
2
solution (Figure 4c), decreases from 0.85 in the base electrolyte
to 0.18 when adding 10 mM (5.0 eq.) L3.
0
2
4
6
8
10
L3 (1 mM, 0.5 eq.) leads to the formation of a shoulder in the disk
current at −0.05ꢀV (Figure 4a), which allows us to obtain
c(L3)/mM
equilibrium constant K
limited current at the disk indicates a reaction of [Cp
with L3 to [Cp Ti(IV)Cl ]*L3 associated with a change of the
a
(Scheme 3). The decreased diffusion-
R D 0 2 2
Figure 6. Transfer ratios I /I /N for the measurements of Cp TiCl and L3 at
different concentrations of L3 at ring potentials of 0.05, 0.23, 0.42 and 0.66 V
and at a rotation frequency f of 25 Hz.
2
Ti(IV)Cl ]
2
2
2
diffusion coefficient prior to the electrochemical reaction. If the
reaction of L3 occurred after the electrochemical reduction of
[
Cp
2
Ti(IV)Cl
2
], this should not have an impact on the diffusion-
For these equilibria we have assumed the formation of 1:1
adducts. The concentration-dependent measurements can verify
limited current.
According to the Levich equation, the limiting current density at
the disk electrode is proportional to D2/3 (D: diffusion coefficient)
this assumption. The voltammograms of i
gradual shift of the reduction potential starting from
D
(Figure 4a) show a
a
4
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Chemistry - A European Journal
10.1002/chem.202004519
RESEARCH ARTICLE
concentration of 2 mM of L3. This implies that the Nernst equation
for this redox process depends on the concentration of free L3.
When plotting the half-wave potential E1/2 against the decadic
logarithm of the concentration of L3 (Figure 7) a linear relation
with a slope m of roughly 60 mV dec–1 at all rotation frequencies
is obtained.
The equilibrium constants obtained from the RRDE-studies
together with the relative amounts of the relevant Ti(IV) (in red)
and Ti(III) species (in green) at concentrations of 2 mM in Ti and
L are summarized in Scheme 4. [Cp Ti(IV)Cl ] is complexed in
2 2
40% – 60% amounts (red numbers) by L1 – L3 with L2 being
slightly more efficient than the other additives as indicated by the
Therefore, the Nernst equation for this redox system must be
linearly dependent on log(c(L3) ) with p representing the number
a
K values.
p
The additives L1 – L3 have a stronger influence on the equilibria
of L3 ligands attached to the titanocene.[14] With L1 the same
slope of 60 mV dec–1 was obtained showing that p is equal to 1.
This verifies our initial assumption. The mechanisms of chloride
abstraction from the Ti(III) complexes and activation of the Ti(IV)
complexes are likely to be similar for L1 and L3.
involving [Cp Ti(III)Cl]. In the presence of L2, essentially no
2
–
–
[Cp Ti(III)Cl ] *L2 is formed because L2 binds Cl too strongly.
2
2
Interestingly, L2 complexes [Cp Ti(III)Cl] less efficiently than L3
2
whereas L1 forms no [Cp Ti(III)Cl]*L1. As a result, the use of L2
2
results in the highest combined relative amount (77%) of the
catalytically active [Cp
L3, the solution contains relatively high proportions of
Cp Ti(III)Cl Ti(III)Cl
]–*L and [Cp ]– that constitute the resting
state of the active catalyst. This situation may be advantageous
when catalyst stability is more important than catalyst activity.
2 2
Ti(III)Cl] and [Cp Ti(III)Cl]*L2. For L1 and
-0.02
-0.04
-0.06
-0.08
-0.10
[
2
2
2
2
L1: 56%
L2: 40%
L3: 49%
L1: 44%
L2: 60%
L3: 51%
4 Hz
9
1
2
Hz
6 Hz
5 Hz
L
[Cp2Ti(IV)Cl2]
[Cp2Ti(IV)Cl2]*L
Ka:
K1:
Linear Fit 4 Hz
Linear Fit 9 Hz
Linear Fit 16 Hz
Linear Fit 25 Hz
Ka
–1
m = 60 mV dec
–1
–1
L1: 2 mM–1
L1: 0.69 mM
L2: 1.81 mM
–1
L2: 0.3 mM
e
e
L3: 1.07 mM–1
L3: 0.4 mM–1
0
.0
0.5
log(c(L3)/mM)
1.0
L
[Cp2Ti(III)Cl2]
[Cp2Ti(III)Cl2]*L
K2:
K3:
K1
Figure 7. Plots of the half-wave potential E1/2 of the RRDE measurements with
Cp TiCl and L3 as a function of the decadic logarithm of the concentration of
L3.
L1: 14%
L2: 19%
L3: 32%
L1: 28%
L2: 4%
L3: 12%
L1: 2.8 mM
L2: 54 mM
L3: 3.0 mM
L1: n.a.
L2: 0.5 mM–1
2
2
L3: 0.7 mM–1
K2
L
L
[Cp2Ti(III)Cl] + Cl
[Cp2Ti(III)Cl] + Cl*L
[Cp2Ti(III)Cl*L] + Cl*L
For L2 a slope of 30 mV dec–1 was observed (Figure 8). Thus, the
redox potential is proportional to log(c(L2) ) and q = p/2. Thus, we
K3
L1: 58%
L2: 60%
L3: 25%
L1: 0%
L2: 17%
L3: 31%
q
propose the reversible formation of a 2:1 adduct between
[
Cp
Scheme 3. For the case that only this 2:1 adduct formation
between [Cp Ti(III)Cl] and L2 is considered (in contrast to the 1:1
adduct considered for K to K given above) a new set of
equilibrium constants for the Ti(III) species has to be calculated
2
Ti(III)Cl] and L2 in addition to the equilibria shown in
2 2
Scheme 4. Mesh-scheme for the Cp TiCl /L redox system (L = L1, L2 or L3)
including the equilibrium constants obtained in the RRDE measurements and
the solution composition in % [Ti(IV) in red, Ti(III) in green].
2
1
3
–
1
–2
(
K
1
’ = 0.2 mM , K
2
’ = K
2
= 54 mM, K
3
’ = 0.1 mM ). However, it is
The RRDE investigations underline that our use of the E Cr
q
likely that both adducts are present in the reduced solutions.
equilibrium as predictor for the performance of the bulk
2 2
electrolysis of Cp TiCl in THF as well as for the titanocene
0
.00
catalyzed radical arylation of epoxides has a sound mechanistic
basis. Moreover, the quantitative data obtained allow an accurate
prediction of the composition of an electrochemically reduced
-
-
-
0.05
0.10
0.15
2 2
solution of Cp TiCl containing additives that is essential for a
precise control of the reaction conditions. This may be essential
for applications on large scale.
4
9
Hz
Hz
16 Hz
25 Hz
Linear Fit 4 Hz
Linear Fit 9 Hz
Linear Fit 16 Hz
Linear Fit 25 Hz
–1
m = 30 mV dec
Density Functional Theory Studies:
To relate the data obtained from RRDE and CV measurements to
molecular properties, we studied the structures and energies of
the species involved in the E C equilibrium by DFT methods. The
q r
0
.0
0.5
1.0
log(c(L2)/mM)
Grimme group has recently developed a powerful multi-level
approach to address such situations. It consists of the CREST
code[15] for searching the low-energy chemical space by tight-
binding semi-empirical theory based meta-dynamics (MTD)
calculations (see Ref. [16]). The resulting conformer ensemble is
refined efficiently in multiple DFT steps with the ENSO code[ as
Figure 8. Plots of the half-wave potential E1/2 of the RRDE measurements with
Cp TiCl and L2 as a function of the decadic logarithm of the concentration of
L2.
2
2
17]
a
driver for ORCA or TURBOMOLE quantumchemistry
5
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Chemistry - A European Journal
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RESEARCH ARTICLE
packages.[18] For a recent overview of the main xTB code used for
the GFN tight-binding or force field calculations see Ref.[19].
Accordingly, we used the xTB, CREST and ENSO programs to
determine the structures with the lowest free energy in THF
solution for each ligand L and all complexes. These calculations
were conducted in the same workflow. Manually prepared starting
structures, which are initially pre-optimized with the GFN2-
xTB[GBSA] tight binding model are used in the CREST program
that employs MTD at the same level in order to obtain a relative
complete ensemble of likely structures. The ENSO program
determines the equilibrium (Boltzmann) populations for a few low-
lying conformers at higher theoretical levels in three steps. First,
already relatively accurate B97-3c[DCOSMO-RS(THF)] (a
composite low-cost DFT method[20]) single point energies are
calculated on the CREST ensemble. Structures within an energy
threshold of 4 kcal mol–1 above the lowest lying structure are then
fully optimized at the same level. In this first filtering step
thermostatistical free energies in the modified rigid-
rotor/harmonic-oscillator (mRRHO) approximation[21] calculated
with GFN2-xTB[GBSA] and the free energy of solvation in THF
calculated with the accurate COSMO-RS[22] solvation model are
added. Finally, for all structures within a 2 kcal mol–1 threshold an
even better single point energy is computed at the PW6B95-
D3/def2-TZVPP[23] hybrid DFT level which basically replaces the
corresponding B97-3c energy. In summary, the final complete
total free energy used consists of the mRRHO part from the
GFN2-xTB treatment, the COSMO-RS part in THF for solvation
and the basic electronic energy with the PW6B95-D3 functional.
In the following, the conformer of each species with the lowest
total free energy is given, if not stated otherwise.
that binding of L to [Cp
properties of [Ti] in the arylation reaction.
The structures of [Cp Ti(III)Cl
]–*L together with the
corresponding values for ΔG298.15 and ΔH298.15 are depicted in
Figure 10 and reveal that L1 and L2 bind both chloride ligands
2
with the N—H groups, providing complexes that are C -symmetric
Ti(III)Cl] directly impacts the redox
2
2
2
within the limits of accuracy. This is exemplified by the Ti—Cl
–
bond lengths ([Cp
2
Ti(III)Cl
2
] *L1: 2.545 Å and 2.540 Å,
–
[Cp
2
Ti(III)Cl
2
] *L2: 2.547 Å and 2.550 Å).
–
Cl *L1:
ΔG298.15 = –8.6 kcal mol–1
–
Cl *L2:
ΔG298.15 = –13.5 kcal mol–1
–
Cl *L3:
ΔG298.15 = –12.0 kcal mol–1
–
Figure 9. DFT structures of the Cl *L adducts of L1, L2 and L3.
–
Structures of L and Cl *L:
Curiously, for L3 a binding of both N—H groups was not observed.
In the more stable complex (Figure 10, lowest structure) L3 only
binds to one of the chloride ligands with one N—H group (Ti—Cl
bond lengths: 2.53 Å and 2.50 Å). In the second most stable
complex (3rd structure from the top of Figure 10), both N—H
groups coordinate to one chloride in a ‘side-on’ geometry. This
results in distinctly different Ti—Cl bond lengths (2.59 Å and
We started our investigations with the ligands L and their chloride
–
complexes Cl *L. As free species, L2 shows higher
conformational rigidity than L1 and L3 (for a detailed discussion
see SI). The structures of the most stable conformers were
chosen as reference points for the energies of formation of all
other complexes. A potential self-aggregation of L2 in THF is
beyond the scope of this study.[24]
2
.49 Å). Enthalpically, the less stable complex is slightly favored
–
The structures of the Cl *L and energies of complexation with
–
1
(
ΔH298.15 = –5.3 vs. –4.6 kcal mol ). However, the entropically
respect to the lowest energy conformer of the respective L are
depicted in Figure 9. Cl– is bound to both N—H groups of all
disfavored restriction of conformational freedom in this binding
mode is the more relevant contribution to ΔG298.15. According to
–
ligands. The Cl *L complexes with L1 and L2 show C2v symmetry.
the values for ΔG298.15, the binding via both N—H and Ti—Cl
–
Cl *L2 is conformationally rigid in agreement with its X-ray
–
groups by L1 and L2 results in a stronger binding of [Cp
2
Ti(III)Cl
2
] .
structure.[ Cl *L1 has a second conformer 4.6 kcal mol higher
25]
–
–1
According to the CV and RRDE measurements, L1 does not bind
to [Cp Ti(III)Cl] whereas both L2 and L3 do. However, they bind
in a different fashion as evident from the shifted oxidation
potentials for [Cp Ti(III)Cl]*L (L2: +110 mV, L3: –120 mV). We
analyzed the complex formation starting from [Cp Ti(III)Cl] and L
and included the effect of additional coordination with THF
Figure 11, also see SI).
L1 and L2 display a similar complexation behavior. Adduct
formation is substantially more favorable with [Cp Ti(III)Cl](THF).
As for [Cp Ti(III)Cl
]– both additives bind the chloride ligand with
both N—H groups. Adduct formation is disfavored with L1. This is
in agreement with the experiment, where no [Cp Ti(III)Cl]*L1 was
in energy than the one shown with one NHR group rotated by
2
–
almost 180° and the other bound to Cl . A second conformer of
Cl *L3 is 2.0 kcal mol–1 higher in energy and has a similar
structure to the one shown. In agreement with a previous study
on the chloride binding of thioureas, squaramides and
sulfonamides,[12] ΔG298.15 for Cl *L show that L2 binds chloride
stronger than L1 and L3. As also pointed out in that study, the
–
2
2
–
(
a
strength of chloride binding does not correlate with the pK values
of the different receptors.
2
2
2
Supramolecular complexes of L and Ti(III):
2
The supramolecular complexes [Cp
intermediates in the electrochemical generation of [Cp
from [Cp Ti(IV)Cl ]. They provide a mechanism for shifting the
equilibrium to [Cp
and dissolution of [Cp
2
Ti(III)Cl
2
]–*L are crucial
Ti(III)Cl]
observed. The interaction of L2 with the chloride ligand leads to
an increase of the Ti—Cl bond length by 0.13 Å. This is in
agreement with the experimentally observed positive shift of the
redox potential.
2
2
2
E
q
C
r
2
Ti(III)Cl] by facilitating chloride abstraction
–
2
Ti(III)Cl
2
] *L. Another intriguing aspect is
6
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Chemistry - A European Journal
10.1002/chem.202004519
RESEARCH ARTICLE
Ti that renders an additional complexation of THF superfluous.
The coordination of the sulfonamide increases the electron
density at Ti in agreement with the experimentally observed
–
[
Cp2Ti(III)Cl2] *L1:
2
negative shift in the redox potential for [Cp Ti(III)Cl]*L3. Only the
adjacent N—H group binds to the chloride ligand.
The slope of 30 mV dec–1 in the RRDE measurements with L2
ΔG298.15 = –2.3 kcal mol–1
ΔH298.15 = –2.0 kcal mol–1
(
2
Figure 8) suggests that a 2:1 stoichiometry of [Cp Ti(III)Cl] and
L2 in the adduct formation is possible. The computed structure of
the 2:1 complex with one molecule of THF and its ΔG298.15 and
ΔH298.15 with respect to the dissociated species are depicted in
Figure 12. Complex formation without THF is distinctly less
favorable.
–
[
Cp2Ti(III)Cl2] *L2:
ΔG298.15 = –4.4 kcal mol–1
ΔH298.15 = –3.9 kcal mol–1
–
[
Cp2Ti(III)Cl2] *L3:
ΔG298.15 = 0.3 kcal mol–1
ΔH298.15 = –5.3 kcal mol–1
([Cp2Ti(III)Cl])2(THF)*L2:
ΔG298.15 = 3.7 kcal mol–1
ΔH298.15 = –18.4 kcal mol–1
–
[
Cp2Ti(III)Cl2] *L3:
2 2
Figure 12. DFT structure of the ([Cp Ti(III)Cl]) (THF)*L2 adduct.
ΔG298.15 = –1.0 kcal mol–1
ΔH298.15 = –4.6 kcal mol–1
Enthalpically, complex formation is strongly favored and the
slightly positive ΔG298.15 is due to the entropically
disadvantageous formation of the complex from four components.
L2 binds the second titanocene through one of the carbonyl
oxygens. At the same time, the N—H groups each bind to one of
the chloride ligands of both titanocenes. This makes L2 a
bifunctional ligand and provides an explanation for the broad
2 2
Figure 10. DFT structures of the [Cp Ti(III)Cl
]–*L adducts of L1, L2 and L3.
[
Cp2Ti(III)Cl](THF)*L1:
oxidation wave in the area of Cp
and L2. On the oxidative sweep ([Cp
followed by [Cp Ti(III)Cl] and finally [Cp
2
2
TiCl found in CVs of Cp
Ti(III)Cl]) *L2 is oxidized first
Ti(III)Cl]*L2.
2 2
TiCl
2
2
ΔG298.15 = 5.2 kcal mol–1
ΔH298.15 = –6.9 kcal mol–1
2
Supramolecular complexes of L and Ti(IV):
Finally, we investigated the adduct formation between
[
2 2 q r
Cp Ti(IV)Cl ] and L. This pre-equilibrium to the E C mechanism
allows the use of a less negative reduction potential in bulk
electrolysis (–1.3 V vs. Ag/Ag with L2, –1.4 V with L1 and L3).
Figure 13 shows the structures of the hydrogen bonded adducts
[
Cp2Ti(III)Cl](THF)*L2:
+
ΔG298.15 = 1.8 kcal mol–1
ΔH298.15 = –8.0 kcal mol–1
between [Cp
structure of [Cp
.3 kcal mol–1 more stable than the complex shown (see SI for
2
Ti(IV)Cl
2
] and L1 – L3. For L2, the minimum
2
Ti(IV)Cl
2
]*L2 is a van der Waals complex that is
0
details). It is not discussed here, as it does not suggest a positive
shift of the reduction potential.
[
Cp2Ti(III)Cl]*L3:
]–*L the formation of
Compared to the complexes of [Cp
2
the adducts of [Cp Ti(IV)Cl ]*L is less favorable. The calculated
2 2
Ti(III)Cl
2
ΔG298.15 = 2.8 kcal mol–1
ΔH298.15 = –9.1 kcal mol–1
structures show that with the neutral Ti(IV) complex only L2 can
interact with both N—H groups. However, they both bind to the
same chloride ligand. In the adducts of L1 and L3 only one of the
N—H groups is coordinating chloride, the other is pointing away
from the complex resulting in a noticeable conformational change
of the additive.
Figure 11. DFT structures of the [Cp
2
Ti(III)Cl](THF)*L adducts of L1 and L2 and
of [Cp Ti(III)Cl]*L3.
2
The computed order of stability of the adducts is in agreement
The situation is different for L3. The favored complexation mode
is realized with [Cp Ti(III)Cl] as starting material. This is due to an
intramolecular interaction of one of the sulfonamide groups with
2 2
with the stronger binding affinity of L2 to [Cp Ti(IV)Cl ] observed
in the RRDE measurements.
2
7
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Chemistry - A European Journal
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RESEARCH ARTICLE
The lower stability of [Cp
L is most easily rationalized by the negative charge in
Cp Ti(III)Cl
]– that renders hydrogen bonding more attractive
2
Ti(IV)Cl
2
]*L compared to [Cp
2
Ti(III)Cl
2
]–
energies and enthalpies of complexation as well as the adduct
structures. Our studies show that a balance between activity and
stability of the catalyst are vital for reaction efficiency. Changing
*
[
2
2
because of the coulomb attraction. We investigated this point by
analyzing the exchange reactions shown in Scheme 5. The effect
of the charge is indeed substantial as highlighted by the highly
the inorganic ligand of Cp
Previous investigations[5] have shown that for Cp
catalysts halide abstraction is easier than for complexes derived
from Cp TiCl . The intricate interactions between the additives
2
TiX
2
was not investigated here.
2
TiBr derived
2
exergonic formation of the [Cp
Cp Ti(IV)Cl ]*L counterparts.
2
Ti(III)Cl
2
]–*L adducts from their
2
2
[
2
2
and the titanocenes by hydrogen bonding and coordination of
polar groups are not only in agreement with the electrochemical
data. They also provide a design platform for the development of
[
26]
[Cp2Ti(IV)Cl2]*L1:
novel additives for catalysis in single electron steps
or
metalloradical catalysis[
27]
in particular in enantioselective
ΔG298.15 = 8.3 kcal mol–1
ΔH298.15 = 2.6 kcal mol–1
catalysis.
Acknowledgements
[Cp2Ti(IV)Cl2]*L2:
We thank the DFG (Ga 619/13-1), the ‘Jürgen Manchot Stiftung’
T. H.), the ‘Studienstiftung des deutschen Volkes’ (S. K. and P.
H. R.), and the ‘Evangelisches Studienwerk Villigst’ (T. L.)
ΔG298.15 = 6.5 kcal mol–1
ΔH298.15 = 6.2 kcal mol–1
(
Keywords: catalysis • DFT calculations • electrochemistry •
radicals • screening
[Cp2Ti(IV)Cl2]・ L3:
ΔG298.15 = 7.9 kcal mol–1
ΔH298.15 = –2.9 kcal mol–1
[1]
a) P. T. Anastas, M. M. Kirchhoff, Acc. Chem. Res. 2002, 35, 686-694;
Efficient screening processes are essential for green chemistry
approaches. See: b) C. W. Coley, N. S. Eyke, K. F. Jensen, Angew.
Chem. Int. Ed. 2020, DOI: 10.1002/anie.201909987, Angew. Chem.
2020, DOI: 10.1002/ange.201909987; c) C. W. Coley, N. S. Eyke, K. F.
Jensen, Angew. Chem. Int. Ed. 2020, DOI: 10.1002/anie.201909989,
Angew. Chem. 2020, DOI: 10.1002/ange.201909989; d) S. Ahn, M. Hong,
M. Sundararajan, D. H. Ess, M.-H. Baik, Chem. Rev. 2019, 119, 6509-
Figure 13. DFT structures of the [Cp
2
Ti(IV)Cl
2
]*L adducts of L1, L2 and L3.
6560; for selected examples see: e) M. N. Hopkinson, A. Gómez-Suárez,
[Cp2Ti(IV)Cl2]*L + [Cp2Ti(III)Cl2]
[Cp2Ti(IV)Cl2] + [Cp Ti(III)Cl ]*L
2
2
M. Teders, B. Sahoo, F. Glorius, Angew. Chem. Int. Ed. 2016, 55, 4361-
4366; f) M. Teders, A. Gómez-Suárez, L. Pitzer, M. N. Hopkinson, F.
Glorius, Angew. Chem. Int. Ed. 2017, 56, 902-906; Angew. Chem. 2017,
DG298.15 / kcal mol–1
L1:
–10.6
–10.9
–7.6
129, 921-925.
L2:
L3:
[2]
[3]
a) A. Gansäuer, A. Fleckhaus, M. Alejandre Lafont, A. Okkel, K. Kotsis,
A. Anoop, F. Neese, J. Am. Chem. Soc. 2009, 131, 16989-16999; b) A.
Gansäuer, S. Hildebrandt, E. Vogelsang, R. A. Flowers II, Dalton Trans.
2016, 45, 448-452.
Scheme 5. Gibbs energies of the exchange reaction between [Cp
2
Ti(IV)Cl
2
]*L
J. I. van der Vlugt, Chem. Eur. J. 2019, 25, 2651-2662.
–
2
and [Cp Ti(III)Cl
2
] .
[4]
a) Y. Mugnier, C. Moise, E. Laviron, J. Organomet. Chem. 1981, 204,
6
1-66; b) E. Samuel, J. Vedel, Organometallics 1989, 8, 237-241; c) R.
J. Enemærke, J. Larsen, T. Skrydstrup, K. Daasbjerg, Organometallics
004, 23, 1866-1874; d) R. J. Enemærke, J. Larsen, T. Skrydstrup, K.
2
Conclusion
Daasbjerg, J. Am. Chem. Soc. 2004, 126, 7853-7864; e) R. J. Enemærke,
J. Larsen, G. H. Hjøllund, T. Skrydstrup, K. Daasbjerg, Organometallics
In summary, we have demonstrated that our approach of
screening the equilibrium as predictor for the bulk
electrolysis of Cp TiCl in THF and the titanocene catalyzed
radical arylation of epoxides has a sound mechanistic basis. This
was achieved by a combination of synthesis, the application of the
electrochemical techniques cyclic voltammetry (CV) and rotating
ring-disk electrode (RRDE) measurements, as well as DFT
investigations.
2005, 24, 1252-1262.
q r
E C
[
5]
6]
CV-Screening: a) T. Liedtke, P. Spannring, L. Riccardi, A. Gansäuer,
Angew. Chem. Int. Ed. 2018, 57, 5006-5010; Angew. Chem. 2018, 130,
5100-5104; b) T. Liedtke, T. Hilche, S. Klare, A. Gansäuer,
ChemSusChem 2019, 12, 3166-3171.
2
2
[
Arylation: a) P. Wipf, J. P. Maciejewski, Org. Lett. 2008, 10, 4383-4386;
b) A. Gansäuer, M. Behlendorf, D. von Laufenberg, A. Fleckhaus, C.
Kube, D. V. Sadasivam, R. A. Flowers II, Angew. Chem. Int. Ed. 2012,
51, 4739-4742; Angew. Chem. 2012, 124, 4819-4823; c) A. Gansäuer,
We have introduced bissulfonamides as additives for enabling
C. Kube, K. Daasbjerg, R. Sure, S. Grimme, G. D. Fianu, D. V.
Sadasivam, R. A. Flowers II, J. Am. Chem. Soc. 2014, 136, 1663-1671;
d) A. Gansäuer, D. von Laufenberg, C. Kube, T. Dahmen, A. Michelmann,
M. Behlendorf, R. Sure, M. Seddiqzai, S. Grimme, D. V. Sadasivam, G.
D. Fianu, R. A. Flowers II, Chem. Eur. J. 2015, 21, 280-289; e) A.
Gansäuer, S. Hildebrandt, A. Michelmann, T. Dahmen, D. von
Laufenberg, C. Kube, G. D. Fianu, R. A. Flowers II, Angew. Chem. Int.
Ed. 2015, 54, 7003-7007; Angew. Chem. 2015, 127, 7109-7112; f) R. B.
bulk electrolysis of Cp
catalyzed radical arylation of epoxides. For the first time, we have
provided quantitative data about the E equilibrium in the
2 2
TiCl in THF as well as for the titanocene
q
C
r
presence of a thiourea, a squaramide and a bissulfonamide and
have established the stoichiometry of adduct formations between
]–, [Cp
[
Cp
2
Ti(III)Cl
2
Ti(III)Cl] and [Cp Ti(IV)Cl ]. By studying the
2 2 2
complexes by DFT methods, we have provided the Gibbs
8
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Chemistry - A European Journal
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RESEARCH ARTICLE
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9
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10.1002/chem.202004519
RESEARCH ARTICLE
Entry for the Table of Contents
Cp2TiIVCl2
O
OH
Cp2TiIIICl Cl
N
N
Ph
CF3
Ph
L
CF3
F3C
F3C
Sustainable
Catalysis
S
N
SO2
N
F3C
CF3
N
H
H
H
N
H
S
F3C
O2
TiIII Cl
CF3
L
4
2
0
-
-
-
2
4
6
-
1.4
-1.3
vs. Fc
-1.2
/Fc
-1.1
0.2
-1.0
E
/
V
+
[
n
=
V
s
–1
]
F3C
H
H
CF3
N
N
F3C
O
O
CF3
What mechanism based screening for titanocene catalysis is all about! Combining insights from synthesis and theory with cyclic
voltammetry and the rotating disk electrode is the deal for understanding not only how but also why condition screening for the
titanocene catalyzed radical arylation works.
1
0
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