About the selectivity and reactivity of active nickel electrodes in C-C coupling reactions

Article abstract of DOI:10.1039/d0ra02673e

Active anodes which are operating in highly stable protic media such as 1,1,1,3,3,3-hexafluoroisopropanol are rare. Nickel forms, within this unique solvent, a non-sacrificial active anode at constant current conditions, which is superior to the reported powerful molybdenum system. The reactivity for dehydrogenative coupling reactions of this novel active anode increases when the electrolyte is not stirred during electrolysis. Besides the aryl-aryl coupling, a dehydrogenative arylation reaction of benzylic nitriles was found while stirring the mixture providing quick access to synthetically useful building blocks.

Full text of DOI:10.1039/d0ra02673e

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About the selectivity and reactivity of active nickel
electrodes in C–C coupling reactions†
Cite this: RSC Adv., 2020, 10, 14249
ab
Sebastian B. Beil,
Manuel Breiner,a Lara Schulz,a Aaron Schull,a Timo Muller,a
¨ ¨
Dieter Schollmeyer,a Alexander Bomm,c Michael Holtkamp,d Uwe Karst,
c
Wolfgang Schaded and Siegfried R. Waldvogel
*
ab
Active anodes which are operating in highly stable protic media such as 1,1,1,3,3,3-hexafluoroisopropanol
are rare. Nickel forms, within this unique solvent, a non-sacrificial active anode at constant current
conditions, which is superior to the reported powerful molybdenum system. The reactivity for
dehydrogenative coupling reactions of this novel active anode increases when the electrolyte is not
stirred during electrolysis. Besides the aryl–aryl coupling, a dehydrogenative arylation reaction of
benzylic nitriles was found while stirring the mixture providing quick access to synthetically useful
building blocks.
Received 25th February 2020
Accepted 26th March 2020
DOI: 10.1039/d0ra02673e
rsc.li/rsc-advances
Organic electro-synthesis evolved most recently as one of the materials which turned out to be unstable. Since the electro-
major research areas in the toolbox of organic chemists.1–5 The catalytic species (mediator) remains immobilized at the elec-
development of new chemistry and reactivity requires innova- trode surface, the electrolyte is not contaminated which
tive approaches, such as material science aspects, to advance signicantly facilitates work-up and down-stream processing
this purely synthetic habit. Usually, platinum and carbon allo- (Fig. 1).
tropes perform best in anodic conversions. In particular, boron-
Combining this elegant approach with the high performance
doped diamond (BDD) facilitates anodic coupling reactions due of HFIP based electrolytes resulted in an active and non-
to the inert behaviour and clean electron transfer,6–8 exploiting sacricial molybdenum anode, which accomplished a variety
inherent reactivity of substrates, such as phenols, arenes, of dehydrodimerization and oxidative cyclization reactions.21–23
anilines and various heterocycles and leading to high yields of Obviously, these results represent only a starting point and
the desired coupling products.9–13 In particular, solvent control much more common and abundant metals are favoured. Nickel
enables distinct selectivity, wherein protic media, such as is advantageous due to its inexpensive nature as well as many
1,1,1,3,3,3-hexauoroisopropanol
(HFIP),
outperform geometries being commercially available due to battery appli-
others.14,15 To improve the morphology and allowing other cations. Noteworthy, nickel seems to play an outstanding role as
design options instead of the limited geometries of BDD, active anode in oxidations within alkaline media and anhydrous
together with a less costly anode material, we investigated HF.24–29 In addition, nickel phosphides and other nickel salt
different transition metals and their alloys with regards to their coatings have been described as electrocatalytically active
applicability in electrochemical conversions. Leaded bronze systems.30–35
enabled the selective and high yielding dehalogenation reaction
of cyclopropanes.16–20 These electrocatalytically active metal
electrodes represent elegant alternatives to commonly applied
aDepartment of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10–14,
55128 Mainz, Germany
bGraduate School of Excellence Material Science in Mainz (MAINZ), Johannes
Gutenberg University Mainz, Duesbergweg 10–14, 55128 Mainz, Germany. E-mail:
waldvogel@uni-mainz.de
cFiber Optical Sensor Systems, Fraunhofer Heinrich-Hertz Institute, Am Stollen 19H,
38640 Goslar, Germany
d
¨
Institute of Inorganic and Analytical Chemistry, University of Munster, Corrensstr. 30,
¨
48149 Munster, Germany
† Electronic supplementary information (ESI) available: Crystal structure of 4d.
CCDC 1976461. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/d0ra02673e
Fig. 1 Schematic representation of an active anode within dehydro-
genative electrolysis.
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In our previous study,23 4-uoroveratrole (1a) turned out to
be a challenging substrate at the active molybdenum anode,
since the corresponding biaryl 2a was only obtained in 12%
isolated and 21% GC yield, respectively (Table 1, Entry 1). Other
metal electrodes (see ref. 23 for a full collection), such as nickel,
were barely superior and the yield of 2a was only slightly
increased (Table 1, Entry 2). Surprisingly, the conversion and
yield of substrate could be drastically improved when stirring
was avoided. An isolated yield of 42 to 47% was obtained in high
purity without dehalogenation processes observed in the undi-
vided cell set-up for both metals (Table 1, Entries 3 and 4). Since
both results were in the same range, we evaluated the
mechanical stability of the electrodes. By subjecting the crude
electrolyte mixtures to ICP-OES (inductively coupled plasma
optical emission spectroscopy, see ESI, Section 4 for details†) we
determined the amount of trace metals. The amount of 62 ꢀ
Table 1 Effect of stirring onto the dehydrogenative coupling of 4-
fluoroveratrole (1a) at different anodes
Entry
Anode
Stirring
yielda
1
2
3
4
Molybdenum
Nickel
Molybdenum
Nickel
Yes
Yes
No
No
12 (21)
16 (25)
47 (64)
42 (55)
a
Isolated yield, GC yield in parenthesis with internal calibration (see
ESI). HFIP: 1,1,1,3,3,3-hexauoroisopropanol.
5 ppm of nickel in solution (equals corrosion of 0.19 nmol Cꢁ1
)
was at least one order of magnitude lower compared to our
previously reported protocol employing molybdenum as active
anode material (740 ꢀ 10 ppm),23 based on the higher
mechanical stability of nickel or the lower solubility of nickel
species on the surface. We therefore continued to use nickel
and tried to optimize the condition. Various electrolysis
parameters were investigated (see ESI, Section 9†), but inter-
estingly the previous conditions23 matched the best. The
During this work we observed a distinct inuence of
mechanical stirring on the formation of either homo- or cross-
coupling products, which we attribute to the interaction of the
vortex motion and the electrode double layer as described by
Huang et al.36 In the absence of stirring, local substrate
concentration is high and facilitates dimerization, whereas
cross-coupling is enhanced due to charge distribution in stirred
electrolytes.
Scheme 1 Scope obtained by anodic coupling of anisoles and veratroles 1 on an active nickel electrode. Isolated yields are displayed for all
compounds.
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applied charge was kept at 3.0 F per mole 2a. The substrate
concentration was optimal at 0.2 M, and at room temperature
the highest yield was detected by GC (for calibration details see
ESI, Sections 7 and 8†). Similar to the molybdenum system, the
use of additives like water or methanol resulted in diminished
yield or complete failure.37 Other common alloys, such as Monel
or Hastelloy, as well as several geometries25,27,38 were not able to
outperform the simple nickel electrode making this protocol
even more practical (see ESI, Sections 1 and 3†).
To obtain a better understanding of the electrode surface we
applied the same nickel electrode in many consecutive runs
(Fig. S3†). During the rst three runs, the GC yield was constant
at around 55%. Aerwards, the yield eroded constantly down to
10% aer nine cycles. Within subsequent transformations the
electro-active layer grows to a certain extend leading to a deacti-
vated and therefore diminished active surface. This kind of
deactivation is known for NiOOH electrodes, whereby nickelates
are formed.39 Nevertheless, this inactivating layer can easily be
removed by simple polishing (see ESI, Section 9†). The sponta-
neous formation of the active electrode was observed during CV
studies where it acts as a redox-lter. The same redox behaviour
was observed for either the blank electrolyte or together with the
substrate, representing only the electrochemical window of the
electro-active layer (see ESI, Section 10†).
Scheme
2
Benzylic dehydrogenative cross-coupling of 2-aryl
We conclude that by using nickel in HFIP a more stable
anode material was found, which works without stirring and
still gives higher yields for challenging substrates such as 1a.
With this novel active electrode system and handling, the scope
was evaluated with regards to anisole and veratrole substrates
(Scheme 1). Most substrates gave a higher yield on the non-
sacricial nickel anode compared to the molybdenum one.
Various 2,5-dihalo-substituted anisoles were coupled and the
dehydrodimers 2c–g were obtained in good yields up to 76%.
For the rst time, we could convert 2,6-substituted anisoles,
which gave almost no conversion at the active molybdenum
anode.23 A small library of 4-substituted veratroles was coupled
to achieve good yields up to 76% for 2a–b and 2h–i, respectively.
Even labile O-alkoxycarbonylmethyl protective groups40 could
be applied in the dehydrodimerization in an acceptable yield of
56% (2j), in agreement with previous stoichiometric MoCl5-
mediated transformations.41 The 1,3-dimethoxy arene 1k could
be transformed in a synthetically useful yield of 11% and was
obtained together with a by-product in 31%, which could be
assigned to 4,6-dibromo-1,3-dimethoxybenzene (2kb). For the
rst time a halogen scrambling reaction was observed and
could be due to the high reactivity of the active nickel electrode
in a HFIP electrolyte. Phenylacetonitrile 1l was also subjected to
the anodic coupling at the active nickel electrodes, but resulted
in the benzyl-aryl cross-coupled product 2l in 51% isolated
yield.
acetonitrile (1l) and arenes 3 by anodic treatment. Hydrogen atoms of
the X-ray single crystal structure analysis of 4d were removed for
clarity. Conditions: Nikgraphite 0.1 M NBu4PF6 in HFIP 7.5 mA cmꢁ2
,
3.0 F.
benzylcyanides.50–52 Electrochemical dehydrodimerization of
benzylcyanides was also described.53 None of them was
observed in this electrochemical transformation. The reason-
able stability of benzylic radical(-cationic) intermediates was
recently described in polar solvents,54 and led here to successful
benzylic cross-coupling on active nickel electrodes. We found,
that biphenyl 3a can be coupled selectively to the benzylic
position of 1l in 33% yield (4a, Scheme 2). Anisoles are also
suitable cross-coupling partners and selective ortho- as well as
para-coupling is accessible in yields up to 32% (4b–d). In all
these cases, stirring was crucial for successful benzylic cross-
coupling reactions, enabling enhanced convection. Some-
times, the formation of additional HFIP ethers was
observed,55–57 which could be isolated in lower yields of 12%
(4a0). Single crystals were successfully obtained for derivative 4d
proving the formation of 2,2-biaryl acetonitrile compounds
(CCDC: 1976461).
In conclusion, an active and non-sacricial nickel electrode
system, which forms spontaneously in situ in the HFIP electro-
lyte was established. The successful dehydrodimerization and
benzylic cross-coupling of arenes was performed. The expedient
nature of this abundant material became obvious when
different geometries and alloys were tested, and the crucial
effect of stirring was observed. On the basis of these ndings
further investigations on the utility of active electrodes on
valuable substrates are on-going.
This observation inspired us to investigate benzylic cross-
coupling reactions on active nickel anodes of such a-aryl
acetonitrile derivatives, which lead to highly substituted nitriles
common in natural products like cherylline dimethyl ether.42
Most reported approaches towards such targets apply
transition-metal catalysis and require leaving groups.43–49 Only
few examples described
a
direct synthesis of a-aryl
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¨
19 C. Gutz, V. Grimaudo, M. Holtkamp, M. Hartmer, J. Werra,
L. Frensemeier, A. Kehl, U. Karst, P. Broekmann and
S. R. Waldvogel, ChemElectroChem, 2018, 5, 247–252.
Conflicts of interest
There are no conicts to declare.
¨
¨
¨
20 C. Gutz, M. Selt, M. Banziger, C. Bucher, C. Romelt,
˜
N. Hecken, F. Gallou, T. R. Galvao and S. R. Waldvogel,
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