Electrooxidative Ruthenium-Catalyzed C?H/O?H Annulation by Weak O-Coordination

Article abstract of DOI:10.1002/anie.201802748

Electrocatalysis has been identified as a powerful strategy for organometallic catalysis, and yet electrocatalytic C?H activation is restricted to strongly N-coordinating directing groups. The first example of electrocatalytic C?H activation by weak O-coo

Full text of DOI:10.1002/anie.201802748

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Accepted Article
Title: Electrooxidative Ruthenium-Catalyzed C-H/O-H Annulation by
Weak O-Coordination
Authors: Youai Qiu, Cong Tian, Leonardo Massignan, Torben Rogge,
and Lutz Ackermann
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201802748
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10.1002/anie.201802748
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Electrooxidative Ruthenium-Catalyzed C–H/O–H Annulation by
Weak O-Coordination
Youai Qiu,[a] Cong Tian,[a] Leonardo Massignan,[a] Torben Rogge,[a] and Lutz Ackermann*[a,b]
Abstract: Electrocatalysis has been identified as a powerful strategy
for organometallic catalysis, but as of yet electrocatalytic C–H
activation was restricted to strongly N-coordinating directing groups.
In contrast, herein, we present the first electrocatalytic C–H
activation by weak O-coordination. Thus, a versatile ruthenium(II)
carboxylate catalyst enabled the electrooxidative C–H/O–H
functionalization for alkyne annulations in the absence of metal
oxidants, exploiting sustainable electricity as the sole oxidant.
for the envisioned electrooxidative C–H activation with weakly-
coordinating benzoic acid 1a (Table 1 and Table S-1 in the
Supporting
Information).[10]
Preliminary
experimentation
highlighted the power of ruthenium(II) catalysis in protic polar
solvents (entries 1-4). The robust ruthenium(II) carboxylate
manifold was fully tolerant of air and H2O, with optimal results
being obtained in a solvent mixture of tert-amyl alcohol and H2O
with sodium pivalate as the additive (entries 5-10). Control
experiments reflected the outstanding performance of the
ruthenium(II) carboxylates[11] (entries 8-19), while typical iridium,
cobalt and palladium catalyst fell short in delivering the desired
product 3aa (entries 11-15). In contrast to cobalt-catalyzed
annulation process with strongly coordinating bidentate directing
groups, the ruthenium catalysis enabled the conversion of
internal alkynes 2.
Mechanistic insights provided strong support for
a
facile
organometallic C–H ruthenation and an effective electrochemical
reoxidation of the key ruthenium(0) intermediate.
Electrosynthesis has emerged as an increasingly powerful tool
for molecular syntheses.[1] A significant recent momentum was
gained by the merger of electrocatalysis with organometallic[2]
C–H activation.[3] However, despite these indisputable advances,
all electrochemical C–H activations[4] are thus far limited to
palladium[3] and cobalt[5] catalysts,[1b] and severely restricted by
substrates bearing nitrogen-containing, strongly coordinating
directing groups.[3; 5] In sharp contrast, within our program on
sustainable C–H functionalization,[6] we have now developed the
first electrochemical, organometallic C–H activation with
synthetically-meaningful, weakly-coordinating[7] substrates, on
which we report herein (Figure 1). Salient features of our
findings include (i) first electrooxidative ruthenium-catalyzed[8]
C–H activation, (ii) weakly coordinating benzoic acids for C–
H/O–H alkyne annulations[9] with electricity as the sole oxidant,
(iii) mechanistic insights on the electrochemical oxidation of the
Table 1. Optimization of the electrochemical C–H annulation.[a]
Entry
Catalyst
Solvent
3aa [%][b]
1
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
---
tAmOH
10
2
H2O
44
3
TFE
35[c]
33[c]
79
key
ruthenium(0)
intermediate,
and
(iv)
C–H/N–H
4
MeOH
functionalizations by electrooxidative ruthenium catalysis.
5
tAmOH/H2O (1/1)
tAmOH/H2O (3/1)
tAmOH/H2O (3/1)
tAmOH/H2O (3/1)
tAmOH/H2O (7/1)
tAmOH/H2O (3/1)
tAmOH/H2O (3/1)
tAmOH/H2O (3/1)
tAmOH/H2O (3/1)
tAmOH/H2O (3/1)
tAmOH/H2O (3/1)
tAmOH/H2O (3/1)
tAmOH/H2O (3/1)
tAmOH/H2O (3/1)
tAmOH/H2O (3/1)
6
25[d]
27[e]
85
7
8
9
71
10
11
12
13
14
15
16
17
18
19
18[f]
---
Ru(p-cymene)(OAc)2
[Cp*IrCl2]2
62
Figure 1. Electrochemical C–H activation by weak O-coordination.
---
Cp*Co(MeCN)3(SbF6)2
Pd(OAc)2
---
Our studies were initiated by probing various reaction conditions
---
[a]
Dr. Y. Qiu, C. Tian, L. Massignan, T. Rogge, and Prof. Dr. L.
Ackermann
[Cp*RhCl2]2
82
Institut für Organische und Biomolekulare Chemie
Georg-August-Universität Göttingen
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
85[g]
26[h,i]
90[i]
Tammannstraße 2, 37077 Göttingen (Germany)
E-mail: Lutz.Ackermann@chemie.uni-goettingen.de
International Center for Advanced Studies of Energy Conversion
(ICASEC), Georg-August-Universität Göttingen
[b]
Supporting information for this article is given via a link at the end of
the document.
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respectively, were chemo-selectively converted likewise.
[a] Undivided cell, RVC anode, Pt cathode, constant current = 4.0 mA, 1a (1.0
mmol), 2a (0.5 mmol), catalyst (5.0 mol %), NaOPiv (1.0 equiv), solvent (4
mL), under air, 100 °C, 18 h. [b] Yield of isolated product. [c] 60 °C. [d] KPF6
(1.0 equiv) as additive. [e] NaOAc (1.0 equiv) as additive. [f] No electricity. [g]
Under N2. [h] No NaOPiv. [i] 80 °C. RVC = reticulated vitreous carbon, Am =
amyl.
With the optimized ruthenium(II) catalyst for the elctrooxidative
C–H/O–H functionalization in hand, we tested its versatility with
a set of representative benzoic acids 1 (Scheme 1). Thus, the
versatile ruthenium catalysis manifold proved amenable to both
electron-rich as well as electron-deficient arenes 1. Thereby,
valuable electrophilic functional groups were fully tolerated,
including bromo, cyano and heterocyclic scaffolds. The site-
selectivity of intramolecular competition experiments with meta-
substituted arenes 1b and 1e was governed by steric
interactions.
Scheme 2. Electrochemical C–H/O–H annulation of alkynes 2.
The
electrochemical
ruthenium-catalyzed
C–H
activation/alkyne annulation regime was not restricted to
benzoic acids 1. Indeed, synthetically meaningful
benzamides[13] 4 were smoothly converted into isoquinolones
5 under otherwise identical reaction conditions (Scheme 3).
Scheme 1. Electrochemical C–H/O–H alkyne annulation by weakly
coordinating acids 1.
The broadly applicable ruthenium(II) carboxylate catalyst
enabled the efficient conversion of diaryl-, diheteroaryl- and
dialkyl-substituted alkynes 2 (Scheme 2). Unsymmetrical
alkynes 2h-2n delivered the desired products 3 with high
levels of regio-control, generally placing the aromatic moiety in
proximity to the oxygen heteroatom.[12] It is noteworthy that
both aryl as well as reactive alkyl chlorides 2m and 2n,
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Finally, we probed the electrochemical C–H activation by means
of cyclovoltammetric analysis. Here, we focused on the key
oxidation of the ruthenium(0) intermediate 6 by electricity (Figure
2). Thus, we observed a significant influence of the oxidation
potential on the presence of acid ranging from 0.64-0.52 V vs
Fc/Fc+, indicating a strong beneficial effect of pivalic acid on the
anodic oxidation of the ruthenium(0) intermediates 6. In sharp
contrast, the presence of base resulted in a considerably higher
potential of up to 0.70 V (Figure S-1 in the SI).[10]
Scheme 3. Electrochemical C–H/N–H annulation by benzamides 4.
In consideration of the unique efficacy of the electrochemical
ruthenium-catalyzed C–H activation by weak coordination, we
became attracted to delineating the catalyst’s working mode. To
this end, reactions with isotopically labelled solvents CD3OD and
CD3OH were suggestive of a reversible C–H cleavage, occurring
by organometallic C–Ru formation (Scheme 4a). Moreover,
intermolecular competition experiments provided strong support
for electron-rich arenes 1 and arylalkynes 2 to inherently react
preferentially (Scheme 4b)
Figure 2. Cyclic voltammograms of 6o (1 mM) in MeCN at 100 mV/s with
nBu4NPF6 (0.1 M) as electrolyte in the absence (black) or presence of HOPiv.
Ar = 4-(F3C)C6H4. GC = glassy carbon electrode.
Based on our mechanistic studies, we propose a plausible
catalytic cycle to commence by facile organometallic C–H
activation (Scheme 5). Thereby, ruthena(II)cycle
8
is
generated,[11; 14] along with two equivalents of carboxylic acid.
Thereafter, migratory alkyne insertion furnishes the seven-
membered ruthena(II)cycle 10,[15] which rapidly undergoes
reductive elimination to deliver the ruthenium(0) sandwich
complex 6. The key reoxidation of the ruthenium(0) complex is
finally accomplished by anodic oxidation.
Scheme 4. Mechanistic studies on electrochemical C–H activation by weak O-
coordination. [a] by GC/MS analysis with n-dodecane as internal standard.
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Scheme 5. Proposed catalytic cycle.
In conclusion, we have reported on the first electrocatalytic
organometallic C–H activation with weakly O-coordinating
groups. Thus, a versatile ruthenium(II) carboxylate catalyst
enabled C–H/O–H alkyne annulations by synthetically
meaningful benzoic acids with ample scope. The C–H activation
employed electricity as the only oxidant and generated hydrogen
as the sole byproduct. Mechanistic studies provided strong
support for a fast organometallic C–H ruthenation and an
efficient electrooxidation of the key ruthenium(0) intermediate by
environmentally-benign electricity.
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Acknowledgements
Generous support by the DFG (Gottfried-Wilhelm-Leibniz award),
SGL Carbon, and the CSC (fellowship to C.T.) is gratefully
acknowledged.
Keywords: C–H activation • alkyne annulation •
electrochemistry • electrocatalysis • mechanism • ruthenium
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Youai Qiu, Cong Tian, Leonardo
Massignan, Torben Rogge, and Lutz
Ackermann*
Page No. – Page No.
Electrooxidative Ruthenium-
Catalyzed C–H/O–H Annulation by
Weak O-Coordination
-
Weak-electro: A versatile ruthenium(II) catalyst enabled electrooxidative C–H/Het–
H activations by weak coordination with electricity as sustainable oxidant.
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