Cationic Titanocene(III) Complexes for Catalysis in Single-Electron Steps

Article abstract of DOI:10.1002/anie.201501955

Abstract By exploiting solvent and anion effects, [Cp₂Ti]⁺ complexes for atom-economical catalysis in single-electron steps were developed and applied for the first time. These complexes constitute remarkably stable and active cataly

Full text of DOI:10.1002/anie.201501955

Angewandte
Chemie
International Edition: DOI: 10.1002/anie.201501955
German Edition: DOI: 10.1002/ange.201501955
Radical Reactions
Cationic Titanocene(III) Complexes for Catalysis in Single-Electron
Steps**
Andreas Gansꢀuer,* Sven Hildebrandt, Antonius Michelmann, Tobias Dahmen,
Daniel von Laufenberg, Christian Kube, Godfred D. Fianu, and Robert A. Flowers II*
Abstract: By exploiting solvent and anion effects, [Cp2Ti]+
complexes for atom-economical catalysis in single-electron
steps were developed and applied for the first time. These
complexes constitute remarkably stable and active catalysts for
radical arylations. The reaction kinetics and catalyst compo-
sition were studied by cyclic voltammetry and in situ IR
spectroscopy.
C
atalysis in single-electron steps[1] has recently emerged as
a new concept for conducting radical reactions. It merges the
attractive features of classic radical chemistry, such as high
À
functional-group tolerance and high reactivity in C C bond
forming reactions,[2,3] with the concepts of transition-metal
catalysis. As a result of its easy shuttling between the + III and
+ IV oxidation states, the [(C5H4R)2TiCl]/[(C5H4R)2TiCl2]
redox couple is unique in inducing both oxidative addition
and reductive elimination in single-electron steps.[4] Control-
ling the performance of the elemental steps through catalyst
modification is essential for the success of these reactions. To
date, this has been achieved by modifying the cyclopenta-
dienyl ligands through the introduction of electron-with-
drawing substituents.
Scheme 1. Catalytic cycles for radical arylation with the cationic
titanocene(III) catalyst [Cp2TiIII]+ or the neutral [Cp2TiCl].
tron-deficient
derivatives
of
[Cp2TiCl],
such
as
[(C5H4Cl)2TiCl], are therefore more efficient catalysts.[1f,5b]
With the pendant cationic [OTiCp2]+ complex in B, the
oxidation to C should be much more favorable than for the
neutral [OTi(C5H4R)2Cl].
Herein, we demonstrate that the use of [Cp2Ti]+ (Cp =
cyclopentadienyl) is a more efficient way to modulate catalyst
reactivity and stability through solvent and anion effects. The
arylation of epoxide-derived radicals (Scheme 1) is an ideal
reaction to validate the potential of [Cp2Ti]+ in comparison to
[Cp2TiCl] and its ring-substituted derivatives.[1f,5] This is
because both epoxide opening to give A (single-electron
oxidative addition) and the oxidation of B to give C through
electron transfer (the crucial step of single-electron reductive
elimination) depend on the redox properties of the titanocene
complexes involved. The oxidation of the radical s-complex B
is endothermic and rate-limiting for [Cp2TiCl]. More elec-
Stephan et al. have shown that from CH3CN solutions of
Zn-reduced [Cp2TiCl2] (Zn-Cp2TiCl2 hereafter), [Cp2Ti-
(NCCH3)2]+ salts can be crystallized.[6] To examine the
identity and properties of the TiIII complex in CH3CN, the
generation of TiIII from [Cp2TiCl2] by Zn metal in CH3CN was
compared to its generation under identical conditions in THF
(Figure 1) by using in situ IR spectroscopy and cyclic voltam-
À
metry (CV). Previously, we found that the C H wag of the Cp
ligand on Ti was sensitive to the oxidation state of the
metal.[5b] Reduction of [Cp2TiCl2] in THF by Zn or Mn results
in a shift from 821 cmÀ1 to 798 cmÀ1. The generation of TiIII in
[*] Prof. Dr. A. Gansꢀuer, S. Hildebrandt, A. Michelmann, T. Dahmen,
Dr. D. von Laufenberg, Dr. C. Kube
À1
À
CH3CN gives a shift in the C H wag to 813 cm , which is
Kekulꢁ-Institut fꢂr Organische Chemie und Biochemie
Universitꢀt Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn (Germany)
E-mail: andreas.gansaeuer@uni-bonn.de
indicative of a change in the electronic character of the metal
and consistent with the formation of [Cp2Ti]+.
Analysis of the 2 mm Zn-Cp2TiCl2 solution in 0.2m
Bu4NPF6/CH3CN solution by cyclic voltammetry (CV)[7]
revealed that under these conditions, [Cp2Ti]+ is formed
exclusively. The minor amount of [Cp2TiCl] observed results
from chloride transfer to [Cp2Ti]+ in the diffusion layer of the
electrode. The difference between the oxidation potentials of
[Cp2TiCl] and [Cp2Ti]+ in CH3CN is 0.53 V. On the reductive
sweep, a wave pertaining to [Cp2TiIVCl]+ is observed. The
existence of this cationic TiIV species suggests that the
pendant [OTiCp2]+ of B can be generated in CH3CN.
G. D. Fianu, Prof. R. A. Flowers II
Department of Chemistry, Lehigh University
Bethlehem, PA 18015 (USA)
E-mail: rof2@lehigh.edu
[**] We gratefully acknowledge generous support by the SFB 813
(“Chemistry at Spin Centers”) and the National Science Foundation
(CHE-1123815). S.H. and T.D. thank the Jꢂrgen-Manchot-Stiftung
and A. M. the Hans-Bçckler-Stiftung for doctoral fellowships.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201501955.
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Table 1: Radical arylation employing Zn-Cp2TiCl2 in CH3CN in the
absence and presence of Coll·HCl.
[a] without Coll·HCl (collidine hydrochloride).
redox properties of the catalysts thus renders ligand substi-
tution superfluous. However, for the preparation of 3, 7, and
especially 8, the yields were not quite satisfactory. Previously,
2, 3, 4, 5, and 8 were obtained most efficiently with Mn-
(C5H4Cl)2TiCl2/Coll·HCl.[1f]
To understand the performance of [Cp2Ti]+ in CH3CN, its
reactions were studied by performing a kinetic analysis. Rate
studies of the reaction yielding 1 with varying concentrations
of catalyst and substrate show that the rate is approximately
first order in both. Compared to Mn-(C5H4Cl)2TiCl/Coll·HCl
in THF, the observed rate constant kobs for the arylation is
lower in CH3CN (0.032 Æ 0.008 minÀ1 at 908C in CH3CN vs.
0.79 Æ 0.09 minÀ1 at 608C in THF).
To further investigate this effect, we studied the rate of
epoxide opening by employing 9 and determined the bimo-
lecular rate constants for this process (Table 2). Rates were
determined by measuring the decay of TiIII at 800 nm with
respect to the concentration of 9 (see the Supporting
Information).[5b,7f] The reduction of 9 by Zn-Cp2TiCl2 in
CH3CN is approximately 600 times slower than by [Cp2TiCl]
in THF and on the same order of magnitude as the arylation
of 1. Epoxide opening (the generation of A in Scheme 1) is
thus the rate-limiting step of the arylation with Zn-Cp2TiCl2 in
CH3CN. This is most likely due to a strong coordination of
[Cp2Ti]+ by CH3CN that inhibits epoxide coordination and
retards its opening.
While our approach of replacing [(C5H4Cl)2TiCl] by
[Cp2Ti]+ proved successful in principle, the reaction condi-
tions chosen are not satisfactory with respect to reaction rate
and product yield in critical cases owing to the strong
coordination of CH3CN. As a consequence, catalyst stabiliza-
tion by Coll·HCl is required.
À
Figure 1. a) Shift of the C H wag of the cyclopentadienyl ligand upon
À
the addition of Zn to Cp2TiCl2 in THF. b) Shift of the C H wag of the
cyclopentadienyl ligand upon the addition of Zn to [Cp2TiCl2] in
acetonitrile. c) CV of 2 mm Zn-Cp2TiCl2 in 0.2m Bu4NPF6/CH3CN at
n=0.2 VsÀ1
.
Our results for the radical arylation with Zn-Cp2TiCl2 in
CH3CN are summarized in Table 1. For 1, conversion was
completed with or without the addition of Coll·HCl and the
yields of isolated product were excellent. [Cp2Ti]+ thus
constitutes an efficient catalyst for radical arylation in
CH3CN. However, stabilization by Coll·HCl is necessary[7g]
for reactions showing a slow oxidation of B to C, as for 2. To
avoid complications, 20 mol% Coll·HCl was routinely added
to the reaction mixtures. The reaction leading to 2 is not
efficient with Mn-Cp2TiCl2 in THF and requires Mn-
(C5H4Cl)2TiCl2 instead. The use of CH3CN for tuning the
2
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Table 2: Rate constants for the opening of 9.
The arylation reactions with the NaBH4-Cp2Ti(OTf)2
system are summarized in Table 3. For all substrates, the
NaBH4-Cp2Ti(OTf)2 system for the generation of [Cp2Ti]+ in
THF constitutes a very robust catalytic system that delivers
Entry
Catalyst
Solvent
Rate constant [mÀ1 minÀ1
]
Table 3: Radical arylation with NaBH4-Cp2Ti(OTf)2 in THF.
1
2
3
[Cp2TiIIICl][a]
[Cp2TiIIICl][b]
[Cp2TiIIIOTf][c]
THF
CH3CN
THF
36Æ6
0.06Æ0.01
3.2Æ0.4
[a] [9]=20–50 mm, [CHD]=80–200 mm (Reaction done in the presence
of 4 mm Coll·HCl) [b] [9]=40–160 mm, [CHD]=160–640 mm
[c] [9]=20–80 mm, [CHD]=80–320 mm.
Based on the findings described above, a more stable and
active catalytic system based on [Cp2Ti]+ in a less coordinating
solvent is required. To address this, [Cp2Ti(OTf)2] was chosen
as a precatalyst for the reduction since it is likely that the
weakly coordinating triflate anions will dissociate from TiIII
even in less-coordinating solvents such as THF. [Cp2TiOTf] in
THF was synthesized according to Luinstra by reducing
[Cp2Ti(OTf)2] with NaBH4 in THF.[8] Using this approach,
a sky-blue solution was formed after 2 h. Gratifyingly, in situ
IR and CV of the solution indicated the exclusive presence of
[Cp2Ti]+ (Figure 2). Although the C H wag of the cyclo-
À
pentadienyl ligand for the precatalyst [Cp2Ti(OTf)2] occurs at
À1
+
À
higher energy (843 cm ), the C H wag of [Cp2Ti] in THF
occurs at the same energy (813 cmÀ1) as in CH3CN.
[a] 0.5 h. [b] 1 h.
the products in high to excellent yields with a catalyst loading
of 5 mol%. The first example (to give 1) suggests that the
catalyst loading can be reduced even further. In the critical
cases for Zn-Cp2TiCl2 in CH3CN (2, 3, 7, and 8) the yields of
isolated product are noticeably superior with [Cp2TiOTf].
Moreover, an additive for catalyst stabilization was not
required. Therefore, the NaBH4-Cp2Ti(OTf)2 system renders
ligand substitution obsolete. It is substantially more efficient
and robust than both Zn-Cp2TiCl2 in CH3CN and Mn-
(C5H4Cl)2TiCl-Coll·HCl in THF.
The kinetic analysis of [Cp2Ti]+ in THF shows that the rate
is approximately first order with respect to the catalyst and
substrate. Compared to Zn-Cp2TiCl2 in CH3CN, epoxide
opening of 9 with [Cp2TiOTf] in THF is much faster (3.2 Æ
0.4mÀ1 minÀ1 vs. 0.06 Æ 0.01mÀ1 minÀ1, Table 2) and the kobs
value for product formation is higher at lower temperature
(0.11 Æ 0.01 minÀ1 at 608C vs. 0.032 Æ 0.008 minÀ1 at 908C).
Since epoxide opening is faster than the overall arylation, the
electron back-transfe from intermediate B to C (Scheme 1)
becomes rate-determining.
It is important to note that [Cp2Ti]+ could facilitate
a Lewis acid initiated pathway to 1. To examine this
possibility, the substrate leading to 1 was refluxed in THF
with 5 mol% [Cp2Ti(OTf)2], which resulted in decomposition
of the substrate without the formation of 1. Additionally,
performing the arylation to form 1 with stoichiometric
amounts of [Cp2TiOTf] in the presence of tert-butyl acrylate
led to isolation of the acrylate radical addition product along
Figure 2. a) In situ IR of NaBH4-Cp2Ti(OTf)2 in THF. b) CV of 2 mm
NaBH4-Cp2Ti(OTf)2 in 0.2m Bu4NPF6/THF at n=0.2 VsÀ1
.
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with 1.[5b] This finding confirms the mechanism proposed in
Scheme 1 (see the Supporting Information).
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In conclusion, we have demonstrated that [Cp2Ti]+ is
a stable catalyst for radical arylation proceeding through
single-electron steps. By employing solvent and anion effects,
we have rendered catalyst stabilization by additives and redox
tuning by ring substituted cyclopentadienyl ligands obsolete.
For [Cp2Ti]+, THF is superior to the strongly coordinating
CH3CN, which inhibits epoxide binding. Solvent coordination
to titanium can thus affect the overall rate of electron transfer
to substrate.[9]
Keywords: cyclic voltammetry · electron transfer ·
homogeneous catalysis · radical reactions · titanium
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Received: March 2, 2015
Published online: && &&, &&&&
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Radical Reactions
A. Gansꢁuer,* S. Hildebrandt,
A. Michelmann, T. Dahmen,
D. von Laufenberg, C. Kube, G. D. Fianu,
R. A. Flowers*
&&&& — &&&&
Cationic Titanocene(III) Complexes for
Catalysis in Single-Electron Steps
Much simpler Surrogate: [Cp2Ti]+ is
a stable and active catalyst for radical
arylation proceeding through catalysis in
single-electron steps. Its use renders ring
substitution for redox tuning obsolete.
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