Accelerated Ru–Cu Trinuclear Cooperative C?H Bond Functionalization of Carbazoles: A Kinetic and Computational Investigation

Article abstract of DOI:10.1002/chem.201802886

The mechanism of a trinuclear cooperative dehydrogenative C?N bond-forming reaction is investigated in this work, which avoids the use of chelate-assisting directing groups. Two new highly efficient Ru/Cu co-catalyzed systems were identified, allowing orders of magnitude greater TOFs than the previous state of the art. In-depth kinetic studies were performed in combination with advanced DFT calculations, which reveal a decisive rate-determining trinuclear Ru–Cu cooperative reductive elimination step (CRE).

Full text of DOI:10.1002/chem.201802886

A Journal of
Accepted Article
Title: Accelerated Ru-Cu trinuclear cooperative C-H bond
functionalization of carbazoles: a kinetic and computational
investigation
Authors: Alexander Jones, Christian Rank, Yanik Becker, Christian
Malchau, Ignacio Funes-Ardoiz, Feliu Maseras, and Frederic
William Patureau
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To be cited as: Chem. Eur. J. 10.1002/chem.201802886
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COMMUNICATION
Accelerated Ru-Cu trinuclear cooperative C–H bond
functionalization of carbazoles: a kinetic and computational
investigation
[
a]
[a]
[a]
[a]
Alexander W. Jones, Christian K. Rank, Yanik Becker, Christian Malchau, Ignacio Funes-
[b]
[b,c]
[a]
Ardoiz, Feliu Maseras,* and Frederic W. Patureau*
Abstract: The mechanism of
a
trinuclear cooperative
removal. Clearly, the development of synthetic methods which
avoid the coordinative assistance of a DG constitute a research
priority, wherein the catalyst is designed to control both C–H
dehydrogenative C–N bond forming reaction is investigated in this
work, which avoids the use of chelate assisting directing groups.
Two new highly efficient Ru/Cu co-catalyzed systems were identified, bond activation reactivity and selectivity. In this study, we will
allowing three orders of magnitude greater TOFs than the previous
state of the art. In-depth kinetic studies were performed in
attempt to demonstrate the suitability of a cooperative
polynuclear catalytic approach for DG-free C–H bond
functionalization in a seemingly simple test reaction (Scheme 1).
In an early 2013 communication, some of us delivered
preliminary results about a Ru/Cu co-catalyzed dehydrogenative
homo-coupling of two carbazoles to form a unique C1-N
combination with advanced DFT calculations, which reveal
a
decisive rate-determining trinuclear Ru-Cu cooperative reductive
elimination step (CRE).
[
4a,5]
bicarbazole product (Scheme 1).
This early method, however,
Most textbooks teach organometallic catalysis as simple
mononuclear catalytic cycles, with well-behaved oxidative
additions, transmetalations, and reductive elimination steps. This
simplified view is very practical to help understand catalysis. In
contrast, optimizing, characterizing and utilizing polynuclear
cooperative effects in catalysis is complicated, time consuming
and costly. This is why very few research groups have been able
suffered from very low turn-over-frequencies (TOFs), thereby
requiring up to two weeks of reaction time. We therefore decided
to re-optimize this reaction, notably by ligand/catalyst screening
1
8
(
Ru-complex1 to Ru-complex11, and ligand L to L , see SI).
This allowed the identification of two new extremely active
ruthenium pre-catalysts: [Ru-complex6] (phosphine-free), and
(ligand L : dppf, Scheme 1), the latter
affording C1-N bicarbazole product 2a in significantly improved
0% yield. Interestingly, and in contrast to the dppf ligand, the
2
4
4
[
2
Ru-complex3] L
[
1]
to integrate cooperative polynuclearity in their mechanisms.
In this context, the development of efficient and selective
8
methods for the construction of C–C and C–heteroatom bonds is
[3]
2
well-known XPhos ligand (L ) did not perform well (2a, 40%),
[
2]
of primordial importance. C–N bonds are notably prevalent in
although it had been successfully utilized in a previous Ru
the scaffold of countless biologically and pharmaceutically
[6]
catalyzed C–H functionalization reaction by Ackermann. Other
relevant
compounds.
Unfortunately,
most
established
4
iron based additives than dppf ligand L were moreover tested,
[
3]
approaches for the catalytic construction of C–N bonds require
pre-synthesized starting materials, thus lengthening synthetic
routes and their atom and step economy footprints. In contrast,
the direct transformation of a C–H bond into a C–N bond,
among which ordinary ferrocene (2a, 69%), or alternatively
Fe(OAc)
2
(2a, 69%), however none were found as efficient (2a,
80%). The main objective of the following study is to investigate
the kinetic profiles of those complex polymetallic systems and to
propose a general mechanistic model.
particularly in
a
dehydrogenative fashion, is
a
more
[
4]
straightforward strategy. Most known C–H bond activation
methods, however, require the coordinative assistance of a
directing group (DG) in order to achieve regioselective
transformations. Moreover, these DGs are rarely desired in the
targeted molecular scaffolds. Therefore, the synthetic utility of
those methods is typically undermined by the often laborious DG
The two new best catalytic systems based on [Ru-complex6]
and [Ru-complex3] L were then evaluated in the carbazole
2
2
4
substrate scope (Scheme 1). Interestingly, not only the yields of
existing C1-N bicarbazoles could be improved significantly, but
some electron-poor carbazoles were converted for the first time
as well. Importantly, no conversion is obtained in the absence of
Ru salt. Product 3e was nevertheless obtained in 36% NMR
yield in the absence of the Cu salt while utilizing the [Ru-
[
a]
A. W. Jones, C. K. Rank, Y. Becker, C. Malchau, Prof. Dr. F. W.
Patureau,
complex6]
complex3]
2
pre-catalyst, and in only 26% while utilizing the [Ru-
FB Chemie
TU Kaiserlautern
4
2
L
pre-catalyst. In both cases however, no
conversion is obtained after only 1h reaction time, highlighting
the considerable accelerating effect of the Cu salt. Once with
these significantly improved sets of reaction conditions in hand,
we then performed a series of kinetic experiments in order to
probe and characterize their suspected cooperative polynuclear
character. These should notably reveal the precise nature of the
cooperative interaction between Ru and Cu in the key steps of
Erwin Schrödinger Strasse 52, 67663 Kaiserlautern, Germany
E-mail: patureau@chemie.uni-kl.de
Dr. I. Funes-Ardois, Prof. Dr. F. Maseras,
Institute of Chemical Research of Catalonia (ICIQ)
The Barcelona Institute of Science and Technology
Avgda. Països Catalans, 16, 43007 Tarragona, Spain
E-mail: fmaseras@ICIQ.ES
Prof. Dr. F. Maseras,
Departament de Química
Universitat Autònoma de Barcelona
[
b]
c]
[
the reaction mechanism. For each of the two selected best pre-
4
catalysts ([Ru-complex6]
2
and [Ru-complex3]
2
L ), six parallel
08193 Bellaterra, Spain
reactions were first conducted and stopped after 30 min, 1 h, 2 h,
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
1
4
h, 6 h, and 24 h, respectively, and thereafter analyzed via H-
NMR. Both pre-catalysts clearly allow high initial rates (product
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4
2
e, Figure 1A). Interestingly, for both [Ru-complex6]
2
and [Ru-
L , product formation is very fast in the early stage of
the reaction, suggesting the rapid formation of the active species. concentration is small ([Cu] < [Ru], Figure 1B). Importantly,
complex3]
2
L system, and up to a surprisingly high +4.7 for the
4
complex3]
2
[Ru-complex6]
2
system, in the area in which the Cu
Further experiments revealed the kinetic orders for Ru, which
these numbers suggest that multiple Cu association processes
would be taking place in the rate determining step(s) of the
reaction. It is quite difficult to assess at this point whether these
Cu kinetic orders are exceptional or not, because C–H bond
activation studies in which these parameters are measured are
are surprisingly consistent with an order of +0.4 for both [Ru-
4
complex6]
2
and [Ru-complex3]
2
L
(see SI). This reveals a
dependency on Ru for the rate-determining step(s). However,
the broken values suggest a dissociation process of the Ru-
chloride-bridged homo-dimers.
[
7]
extremely rare. Only two computational studies by some of us
have previously suggested that the RhCp*/Cu(II) C–H bond
activation system could contain kinetically meaningful
[
8]
polynuclear intermediates.
1
Figure 1. A: H NMR conversion to product 2e over time. B: Dependency of
the initial rate (t = 1 h) on the Cu loading (mmol). C and D: Initial reactivity Job-
plots (t = 1 h): [Ru] + [Cu] = 3 mol%. Both C and D were entirely reproduced.
4
For all figures, black plots for Ru-complex6 and red plots for Ru-complex3-L ,
1,3,5-trimethylbenzene as internal standard.
Scheme 1. Comparative reaction scope, isolated yields. A: 2013 reaction
conditions: [Ru(p-cymene)Cl
AcOH (5:5:1), air, 140°C, one or two week reaction time. B and C: Carbazole
1.00 mmol), dichlorodi-μ-chlorobis[(1,2,3,6,7,8-η-2,7-dimethyl-2,6-octadiene-
,8-diyl]diruthenium(IV) ([Ru-complex6] ) (0.5 mol%) (Method B) or [Ru(p-
cymene)Cl (0.5 mol%) and 1,1'-bis(diphenylphosphino)ferrocene (0.5 mol%)
2 2 2 2 4
] (0.5 mol%), Cu(OAc) (10 mol%), PhCl, C Cl ,
In the area in which the Cu concentration is large however
([Cu] >> [Ru], Figure 1B), the Cu kinetic order breaks down
(
1
2
]
2 2
completely to –0.1 for the [Ru-complex6]
2
system, and to ‒0.2
4
(
[Ru-complex3]
2
L ) (Method C), Cu(OAc)
, 150 °C, 24 h.
2
(1.1 equiv.), C
2
Cl
4
(1 ml), PhCl
4
for the [Ru-complex3] L system. These almost zero orders
2
(0.25 ml), AcOH (0.25 ml), O
2
indicate a saturation point after which the Cu concentration is
sufficiently high to spontaneously form the active species. The
slightly negative values may even suggest the formation of less
active polynuclear aggregates at very high Cu concentrations.
This data made us curious as to the actual optimal ratio between
Ru and Cu. In order to investigate that particular point, we then
Furthermore, at a catalytic loading of 0.125 mol% of Ru, an
‒
1
initial TOF of 144 h for [Ru-complex6]
2
and an impressive 232
‒
1
4
h
2
for [Ru-complex3] L
were determined (based on the
amount of substrate converted into the product within 1 h). A
further decrease of the catalytic loading to 0.0625 mol%
improved the initial TOF of Ru-complex6 to an unprecedented
[
4a]
conducted what is best described as “reactivity Job-plots,” by
analogy with Job-plots experiments which determine the ideal
[
9]
‒
1
ratio between components of a given supramolecular system.
3
37 h . In 2013, utilizing a far less efficient catalytic system had
‒
1 [4a]
The principle here consists in monitoring the initial rate of the
reaction, in which the sum of the Ru and the Cu concentration is
constant, in this case [Ru] + [Cu] = 3 mol%, but the Ru:Cu ratio
afforded an initial TOF of 0.3 h . The current initial TOFs are
thus orders of magnitude greater than the previously reported
method. We thereafter measured the Cu kinetic orders with both
4
is variable, from 1:9 to 9:1. The results for both the [Ru-
[
Ru-complex6]
2
and [Ru-complex3]
2
L systems. In contrast to
4
complex6]
2
and [Ru-complex3]
2
L
systems are reported in
Ru, the Cu kinetic orders can reach up to +2.5 for the [Ru-
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Figure 1 (C & D, respectively). The optimal ratio for both
systems is reached somewhere around Ru:Cu = 1:2. This shows
that a surplus of Cu over Ru is needed to ensure a high catalytic
activity and initial TOF, and thereby hints to a trinuclear rate
determining step. Next, H/D scrambling experiments were
conducted in order to gain insight into the C–H activation step
characterize their cooperativity? 3) Why is the C1-N the only
regio-isomeric product?
We were able to characterize computationally a full catalytic
cycle that reproduces all experimental results. It can be
separated into four main steps: (i) N–H activation by copper
[
11]
diacetate,
(ii) Ru-based C–H activation, (iii) trinuclear
(
see SI, Fig. S3). These were conducted by replacing the acetic
cooperative reductive elimination, and (iv) catalyst regeneration.
We are going to discuss the first three of these steps in what
follows. The reaction starts with the N–H activation by the
copper diacetate dimer, shown in Figure 2A. It should be noticed
that in the drawings we are using a triple-bond between the two
copper centers to indicate the presence of three acetate bridges
between them. The mechanism, shown in Figure 2A, is formally
simple. The most remarkable feature of this step is the spin
distribution in the resulting species 3t and 4t (see Fig. S4 in the
SI). The two unpaired electrons are not fully located on the
dicopper system, but one electron is delocalized in the carbazole
ring. The process is therefore better described as an oxidative
N–H activation, with one electron moving from the nitrogen
center to the dicopper unit, which becomes thus Cu(II)-Cu(I).
acid co-solvent by AcOD, and then monitoring D-incorporation.
These experiments show a high to moderate H/D scrambling
under catalytic conditions, depending on reactions conditions,
particularly at C1 and C3 positions of the carbazole substrate
(
C1>C3). Therefore, the C–H activation step is reversible under
catalytic conditions, and thereby probably not rate-limiting. This
is an unusual result in the light of the absence of any chelate
assisting directing group. It should be noted that neither
conversion, nor any detectable H/D scrambling could be
observed in the absence of either the Copper or the Ruthenium
salt.
We thereafter looked at the mechanism through the lens of DFT
calculations, in consideration of all the above mentioned kinetic
data. For the sake of simplicity, we approximated the catalytic
systems to aggregates composed of one Ru center for two Cu
centers due to the dimeric character of [Cu(OAc) ] species (the
2
computed dissociation energy for the dimer is 14.7 kcal/mol).
We performed the calculations on the Ru-complex1 catalyst
(
point of view, in the assumption that the general mechanism will
be essentially the same for other catalysts. Some of the great
questions which we were hoping to address with DFT
calculations were: 1) Why does this process require both Ru and
Cu species? while the oxidative dimerization of other seemingly
The next reaction step is the ruthenium-based C–H activation,
shown in Figure 2B. Prior to reacting, the ruthenium pre-catalyst
must be activated by molecular oxygen to reach its active form.
One dioxygen molecule reacts with two Ru(II) complexes to
produce two complexes 5t which can be described as Ru(III)-
oxyl (with radical character on oxygen), or Ru(IV)-oxo. The Ru-
oxyl moiety has been well characterized in other organometallic
2
(benzene)RuCl ), as the most simple from a conformational
1
8
ruthenium systems by
O
2
labeling mass spectrometry
[
12]
experiments. 5t reacts with the copper complex 4t to produce
the trimetallic complex 7t. In 7t, one electron has been
transferred from the dicopper unit to the oxyl bridge which also
has been protonated, thus becoming a hydroxo group. As a
[
10]
related substrates such as phenothiazines don’t? 2) How are
the metal centers interacting in those critical steps and how to
Figure 2. A: Computed pathway for N–H activation of carbazole by copper diacetate dimer. B: Free energy profile for Ru oxidation and C–H bond activation.
Energies in kcal/mol.
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result, the oxidation states in 7t are Cu(II), Cu(II), and Ru(III),
with additional free radical character in the carbazole.
Intermediate 7t is then able to activate the C–H bond of a
second carbazole unit through a CMD (concerted metalation
activation has a lower barrier, and scrambling can take place
prior to the irreversible step. The values associated with the
transition states associated to the activation of the different
positions were 3.9 (C1), 8.5 (C2), 4.5 (C3) and 10.6 (C4)
kcal/mol with respect to the reactants. Bonds C1, C2 and C3 can
be activated, which is in agreement with experimental data.
[
13]
deptrotonation) mechanism.
From an electron-count point of
view, this complex step from 4t to 9t results in the acquisition of
two electrons per oxygen atom of the initial molecular dioxygen
reagent, one coming from ruthenium and another from the
dicopper unit. An alternative pathway for C–H activation without
formation of the trimetallic species was found to have a much
higher barrier (see SI).
The next step is reductive elimination, shown in Figure 3. The
system evolves through
a trinuclear cooperative reductive
elimination (CRE) transition state to form the C–N bond. This is
related to the process some of us characterized for the oxidative
[
8,14]
coupling of benzoic acid and alkyne.
The free energy barrier
of this process is 24.2 kcal/mol referred to the most stable
intermediate 9t. The structure of transition state TS 10t-11t is
presented in Figure 3. The electron count from this step is quite
simple: a single electron transfer from the formally anionic
carbon ligand to ruthenium, which becomes Ru(II). This is very
[8]
different from what we found for the Rh(III)/Cu(II) system,
where one electron was transferred to each metal center. The
common feature is the requirement of three metal centers, and
the relevance of single electron transfer processes throughout
the catalytic cycle. Importantly, this reductive elimination step is
irreversible and it is the rate determining step for the Ru-
complex1 catalyst. Modifications in other ligands could change
the rate-determining step to C–H cleavage through TS 8t-9t,
which is 6.6 kcal/mol below TS 10t-11t for Ru-complex1. The
finding that the key transition states contain two copper and one
ruthenium centers is an encouraging agreement with the
experimentally determined orders of reactions. We remark that
we did not consider further aggregations of copper centers for
simplicity, but they could well exist and push further the reaction
order with respect to copper. Finally, the initial catalysts are
regenerated, releasing water as byproduct, with an overall
energy release of 35.6 kcal/mol. This regeneration step, detailed
in the SI, does not involve major electron flows, as the three
metal centers have already recovered their initial oxidation
states.
Figure 3. Computational results on the cooperative reductive elimination step.
a. Free energy profile. Energies in kcal/mol. b. TS 10t-11t in 2D view.
Representative bond distances in Å. TS 10t-11t in 3D view. Copper dimer is
depicted in wireframe for clarity.
In summary, we identified two new Ru-based C–H bond
4
activation pre-catalysts: [Ru-complex6]
2
and [Ru-complex3]
2
L ,
which are orders of magnitude more active in the herein studied
C–H bond activation coupling reaction. Moreover, kinetic studies
revealed the probable involvement of cooperative polymetallic
Ru/Cu (1:2) aggregates in the rate determining step. The latter
cooperative reductive elimination (CRE) step demonstrates that
the electronic connection between metals is necessary for an
efficient process. The computed CRE transition state moreover
rationalized the exclusive C1 selectivity of the reaction, versus
C2 and C3, as the latter positions show significantly higher
reductive elimination TSs. Because of their pronounced
polynuclear cooperative character, these results might impact
the field of CDC method development, particularly those
methods which are based on bimetallic Ru/Cu, Rh/Cu and
Pd/Cu catalyzed C–H bond activation systems.
After characterizing the full mechanism, we analyzed the issue
of selectivity. We need to reproduce two sets of experimental
results from the Ru-complex3 catalyst ((p-cymene)RuCl ),
2
which is very similar to the Ru-complex1 system considered for
the calculations. Deuterium scrambling experiments show that
the C–H bond can be activated at three different positions in the
activity order of C1>C3>C2 (see SI Fig. S3), yet the formation of
a bond with nitrogen occurs only at C1. The irreversible step in
our calculations is the cooperative reductive elimination through
TS 10t-11t. The energy of this transition state with respect to
separate reactants is 10.5 kcal/mol for C1, as discussed above.
We calculated the corresponding values for C2 and C3
cooperative reductive eliminations and both are higher than TS
1
0t-11t (16.9 and 14.2 kcal/mol above the reactants,
respectively). The difference between C1 and C3 transition state
is 3.7 kcal/mol, which corresponds to a theoretical prediction of Acknowledgements
99% of the homo-coupling product at C1. In contrast, C–H
>
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This work was supported by DFG-funded transregional
collaborative research center SFB/TRR 88 “Cooperative effects
in homo and heterometallic complexes” (http://3MET.de), DFG
funded project PA 2395/2–1, COST Action CA15106 (CHAOS),
and since March 2017: by ERC project 716136:
[6]
L. Ackermann, S. I. Kozhushkov, D. S. Yufit, Chem. Eur. J. 2012, 18,
12068.
[
7]
Nevertheless, the well documented propensity of Copper-O systems to
2
form oxo-bridged polynuclear intermediates suggests that high Copper
kinetic orders should be ubiquitous in Copper catalyzed aerobic
transformations. See for example: a) M. El-Sayed, A. El-Toukhy, G.
Davies, Inorg. Chem. 1985, 24, 3387; b) P. Haack, C. Limberg, Angew.
Chem. Int . Ed. 2014, 53, 4282, and references cited therein.
a) I. Funes-Ardoiz,; F. Maseras, Angew. Chem. Int. Ed. 2016, 55, 2764;
b) I. Funes-Ardoiz, F. Maseras, Chem. Eur. J. 2018, DOI:10.1002/
chem.201800627.
“
2O2ACTIVATION”. F.M. acknowledges the financial support
from the CERCA Programme/Generalitat de Catalunya and
MINECO (Project CTQ2017-87792-R and Severo Ochoa
Excellence Accreditation 2014–2018 (SEV-2013-0319)) and I.F.-
A thanks the Severo Ochoa predoctoral training fellowship (ref:
SVP-2014-068662). We thank Dr. Agostino Biafora for fruitful
discussions. Tristan Weiser and Ann-Katrin Seitz are
acknowledged for short internships in the Patureau group.
Tatjana Wall is acknowledged for the microbalance equipment.
[
8]
9]
[
[
J. S. Renny, L. L. Tomasevich, E. H. Tallmadge, D. B. Collum, Angew.
Chem. Int. Ed. 2013, 52, 11998.
10] Several N–H heterocyclic substrates, including particularly electron-rich
carbazoles, have been known to oxidize without precious metal
catalyzed C–H bond activation, sometimes in the mere presence of a
mild oxidant. However, so far, the C1–N bicarbazole coupling products
depicted in Scheme 1 can only be obtained with the herein described
Ru-Cu co-catalyzed method. The fact that the omission of the Ru salt
completely suppresses conversion arguably suggests that a free-radical
mechanism is unlikely. In contrast, for those other more electron-rich,
easily oxidized N–H heterocyclic substrates, such as phenothiazines,
see for example: a) M. Goswami, A. Konkel, M. Rahimi, M.-L. Louillat-
Habermeyer, H. Kelm, R. Jin, B. de Bruin, F. W. Patureau, Chem. Eur.
J. 2018, 24, DOI: 10.1002/chem.201800730; b) M.-L. Louillat-
Habermeyer, R. Jin, F. W Patureau, Angew. Chem. Int. Ed. 2015, 54,
Keywords: C–H bond activation • cross dehydrogenative
coupling • dehydrogenative amination • cooperative reductive
elimination • trinuclear catalysis
[
1]
Polynuclear catalysis, see for example: a) R. G. Bergman, Acc. Chem.
Res. 1980, 13, 113; b) T. Fukuyama, N. Chatani, J. Tatsumi, F.
Kakiuchi, S. Murai, J. Am. Chem. Soc. 1998, 120, 11522; c) J. Kwak, M.
Kim, S. Chang, J. Am. Chem. Soc. 2011, 133, 3780; d) M. M. Lorion, K.
Maindan, A. R. Kapdi, L. Ackermann, Chem. Soc. Rev. 2017, 46, 7399.
C –H bond functionalization: see for example: a) C.-L. Sun, B.-J. Li, Z.-
J. Shi, Chem. Commun. 2010, 46, 677; b) C. S. Yeung, V. M. Dong,
Chem. Rev. 2011, 111, 1215; c) L. McMurray, F. O'Hara, M. J. Gaunt,
Chem. Soc. Rev. 2011, 40, 1885; d) P. B. Arockiam, C. Bruneau, P. H.
Dixneuf, Chem. Rev. 2012, 112, 5879; e) J. Yamaguchi, A. D.
Yamaguchi, K. Itami, Angew. Chem. Int. Ed. 2012, 51, 8960; f) S. I.
Kozhushkov, L. Ackermann, Chem. Sci. 2013, 4, 886; g) C. Liu, J. Yuan,
M. Gao, S. Tang, W. Li, R. Shi, A. Lei, Chem. Rev. 2015, 115, 12138;
h) T. Gensch, M. N. Hopkinson, F. Glorius, J. Wencel-Delord, Chem.
Soc. Rev. 2016, 45, 2900; i) Y. Qin, L. Zhu, S. Luo, Chem. Rev. 2017,
4
102; c) C. Schuster, C. Börger, K. K. Julich-Gruner, R. Hesse, A.
Jäger, G. Kaufmann, A. W. Schmidt, H.-J. Knölker, Eur. J. Org. Chem.
014, 4741; d) J. A. van Allan, G. A. Reynolds, D. P. Maier, J. Org.
[
2]
2
Chem. 1969, 34, 1691; e) R. F. Bridger, D. A. Law, D. F. Bowman, B. S.
Middleton, K. U. Ingold, J. Org. Chem. 1968, 33, 4329; f) Y. Tsujino,
Tetrahedron Lett. 1968, 9, 4111; g) H. Musso, Chem. Ber. 1959, 92,
2873; h) H. Wieland, A. Süßer, Liebigs Ann. 1912, 392, 169. Palladium
catalyzed examples: i) R. Gu, K. Van Hecke, L. Van Meervelt, S.
Toppet, W. Dehaen, Org. Biomol. Chem. 2006, 4, 3785; j) B. Liegault,
D. Lee, M. P. Huestis, D. R. Stuart, K. Fagnou, J. Org. Chem. 2008, 73,
5022.
[
11] Selected examples of Cu(OAc)
2
mediated oxidative N-H
117, 9433; j) D.-S. Kim, W.-J. Park, C.-H. Jun, Chem. Rev. 2017, 117,
activation/functionalization: a) G. Brasche and S. L. Buchwald, Angew.
Chem., Int. Ed. 2008, 47, 1932; b) D. Monguchi, T. Fujiwara, H.
Furukawa and A. Mori, Org. Lett. 2009, 11, 1607; c) H. Zhao, M. Wang,
W. Su and M. Hong, Adv. Synth. Catal. 2010, 352, 1301; d) A. John
and K. M. Nicholas, J. Org. Chem. 2011, 76, 4158; e) M. Miyasaka, K.
Hirano, T. Satoh, R. Kowalczyk, C. Bolm, M. Miura, Org. Lett. 2011, 13,
8
977.
[
3]
Amination methods, see for example: a) F. Ullmann, Ber. Dtsch. Chem.
Ges. 1903, 36, 2382; b) I. Goldberg, Ber. Dtsch. Chem. Ges. 1906, 39,
1691; c) J. F. Hartwig, Nature 2008, 455, 314; d) J. F. Hartwig, Acc.
Chem. Res. 2008, 41, 1534; e) D. S. Surry, S. L. Buchwald, Angew.
Chem. Int. Ed. 2008, 47, 6338; f) J. Bariwal, E. van der Eycken, Chem.
Soc. Rev. 2013, 42, 9283; g) M.-L. Louillat, F. W. Patureau, Chem. Soc.
Rev. 2014, 43, 901; h) P. Ruiz-Castillo, S. L. Buchwald, Chem. Rev.
359; f) L. D. Tran, J. Roane, O. Daugulis, Angew. Chem., Int. Ed. 2013,
52, 6043; g) H. Xu, X. Qiao,S. Yang, Z. Shen, J. Org. Chem. 2014,
79, 4414; h) B. K. Singh, A. Polley, R. Jana, J. Org. Chem. 2016, 81,
4295; i) P. Sadhu, T. Punniyamurthy, Chem. Commun. 2016, 52, 2803.
2016, 116, 12564; i) H. Yu, Z. Li, C. Bolm, Angew. Chem. Int. Ed. 2017,
56, 9532; j) Y. Park, Y. Kim, S. Chang, Chem. Rev. 2017, 117, 9247; k)
[
[
12] R. Ray, S. Chandra, D. Maiti, K. L. Lahiri, Chem. Eur. J. 2016, 22, 8814.
13] I. Özdemir, S. Demir, B. Cetinkaya, C. Gourlaouen, F. Maseras, C.
Bruneau, P. H. Dixneuf, J. Am. Chem. Soc. 2008, 130, 1156.
J. Schranck, A. Tlili, ACS Catal. 2018, 8, 405.
[
[
4]
5]
Selected examples: a) M.-L. Louillat, F. W. Patureau, Org. Lett. 2013,
15, 164; b) M.-L. Louillat, A. Biafora, F. Legros, F. W. Patureau, Angew.
[
14] I. Funes-Ardoiz, F. Maseras, ACS Catal. 2018, 8, 1161.
Chem. Int. Ed. 2014, 53, 3505; c) A. Biafora, F. W. Patureau
Synlett 2014, 25, 2525; d) J. Roane, O. Daugulis, J. Am. Chem. Soc.
2016, 138, 4601; e) J. Jiao, K. Murakami, K. Itami, ACS Catalysis 2016,
6, 610.
Natural product containing the C1-N bicarbazole: Z. Xu, M. Baunach, L.
Ding, C. Hertweck, Angew. Chem. Int. Ed. 2012, 51, 10293:
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Chemistry - A European Journal
10.1002/chem.201802886
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A. W. Jones, C. K. Rank, Y. Becker, C.
Malchau, I. Funes-Ardoiz, F. Maseras,*
and F. W. Patureau*
Page No. – Page No.
Metals unite: The mechanism of a trinuclear cooperative dehydrogenative C–N
bond forming reaction is investigated in this work, which avoids the use of chelate
assisting directing groups. A decisive rate-determining trinuclear Ru-Cu cooperative
reductive elimination step (CRE) is described.
Accelerated Ru-Cu trinuclear
cooperative C–H bond
functionalization of carbazoles: a
kinetic and computational
investigation
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