A Versatile Electrochemical Batch Reactor for Synthetic Organic and Inorganic Transformations and Analytical Electrochemistry

Inorganic Transformations and Analytical Electrochemistry

Article

A Versatile Electrochemical Batch Reactor for Synthetic Organic and

Hamish R. Stephen, Christiane Schotten, Thomas P. Nicholls, Madeleine Woodward, Richard A. Bourne,

Nikil Kapur,* and Charlotte E. Willans *

Cite This: https://dx.doi.org/10.1021/acs.oprd.0c00091

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sı Supporting Information

ABSTRACT: A standardized and versatile electrochemical batch reactor that has wide applicability in both organic and inorganic

synthesis and analytical electrochemistry has been developed. A variety of synthetic electrochemical transformations have been

performed to showcase the versatility and demonstrate the reactor, including the synthesis of ﬁve Cu(I)−NHC complexes, two

Au(I)−NHC complexes, and one Fe(II)−NHC complex as well as an Fe(III)−salen complex. The reactor is based on a

commercially available vial with an adapted lid, making it inexpensive and highly ﬂexible. It features a ﬁxed interelectrode distance,

which is crucial for reproducibility, along with the ability to accommodate a variety of interchangeable electrode materials. The

reactor has also been used in conjunction with a parallel plate, allowing rapid screening and optimization of an organic

electrochemical transformation. Cyclic voltammetry has been performed within the reactor on a range of imidazolium salt analytes

with the use of an external potentiostat. The ability to use this reactor for both analytical and synthetic organic and inorganic

chemistry is enabled by a ﬂexible and characterizable design.

KEYWORDS: electrochemistry, electrosynthesis, reactor design, cyclic voltammetry

INTRODUCTION

inert atmospheres, which is necessary for the synthesis of many

organometallic and inorganic complexes as well as several

organic transformations or analytical techniques.

■

During the past decade, synthetic electrochemistry has been

receiving renewed interest as an enabling technology that

typically provides a mild, atom-eﬃcient, and sustainable

Currently, the electrosynthesis community has limited access

to standardized, ﬂexible, and aﬀordable electrochemical batch

reactors. Herein we report the design, development, and

characterization of a simple yet versatile electrochemical batch

reactor (bottle reactor) that has been used for the synthesis of

sensitive organometallic and inorganic complexes as well as an

organic electrochemical transformation. Cyclic voltammetry

has also been performed in the reactor, showcasing the

versatility of the setup.

−8

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This

novel and well-understood redox mode of activation, coupled

with its broad applicability, has resulted in the development of

a raft of new methodologies, including the synthesis of

inorganic and organometallic complexes and many other

−13

organic transformations.

electrosynthesis have been realized in these new method-

ologies, there remains a bottleneck to widespread adoption.

One reason for this impediment is the lack of simple,

characterizable, and reproducible experimental setups.

Previously, our group and others have used three-neck ﬂasks

While many of the beneﬁts of

15−19

RESULTS AND DISCUSSION

■

Reactor Design. An electrochemical batch reactor based

upon commercially available vials with an adapted lid was

designed (Figure 1); 30 mL vials were used in this study, but

the lid is compatible with any vial that has a GL-32 thread. The

lid consists of a cap with a hole cut into it and a PTFE insert

that ﬁts into this hole. The PTFE insert has an extrusion that

overlaps with the lip of the vial such that when the cap is

screwed into place a tight seal is created between the vial and

the PTFE. The insert is machinable and exhibits four holes for

−13

to perform electrochemical transformations.

Electrode

leads were passed through the side arms of the ﬂask, allowing

electrodes to be lowered into the solution. While this approach

has led to the development of eﬃcient methodology, there

remain problems with reproducibility across experiments and

particularly for the transfer of experimental procedures to other

laboratories. One reason for the lack of reproducibility is the

inability to keep the interelectrode gap, electrode angles, and

depth of the electrode in solution constant, resulting in variable

resistance and current density across experiments, both of

Received: March 11, 2020

which have a large eﬀect on the reaction outcome.

More recently, several commercial reactors have been

developed that provide a constant interelectrode distance,

electrode angle, and depth, with many being used in

laboratories throughout the world. A common issue with

these reactors is the inability to perform transformations under

XXXX American Chemical Society

Organic Process Research & Development

Org. Process Res. Dev. XXXX, XXX, XXX−XXX

Article

to permit use of the reactor with a simple power supply unit or

potentiostat.

Synthetic Applications. The electrochemical synthesis of

metal−N-heterocyclic carbene (NHC) complexes has pre-

,12

viously been reported by our group and others.

This

procedure involves oxidation of a sacriﬁcial anode, which

releases metal ions into solution, and the cathodic reduction of

imidazolium salts to produce metal−NHC complexes via

highly reactive carbene intermediates (Scheme 1). These

Scheme 1. Electrochemical Synthesis of Metal−NHC

Complexes

Figure 1. Images of the bottle reactor. Left: Fully assembled bottle

reactor. Top right: PTFE headpiece with O-ring seal as it sits within

the bottle cap. Bottom right: PTFE headpiece showing stainless steel

electrode contacts.

intermediates are sensitive to the presence of both oxygen and

moisture, which results in the formation of imidazolone side

products. Consequently, initial testing of the bottle reactor

was performed by the preparation of a range of metal−NHC

complexes whose syntheses rely upon the use of inert

atmospheres and anhydrous solvents.

Our investigations began with the preparation of various

copper(I)−NHC complexes (Scheme 2) on a 1 mmol scale.

These reactions were performed under galvanostatic con-

ditions, as this enabled control over the number of electron

a variety of purposes. Two of these form ports that have a

standardized / -28 thread, which allows various standard

ﬁttings to be screwed into the lid. This enables the reactor to

be attached to a Schlenk line through one of the ports via a

short piece of tubing with a Luer ﬁtting on the other end, while

a blank ﬁtting in the other port may be removed to enable the

addition of reagents and solvents or the removal of aliquots for

analytical purposes or the insertion of an analytical probe for in

operando studies. In addition, this may also be ﬁtted with a

septum, and solutions can be transferred to and from the

reactor using a cannula. Alternatively, one of the ports can be

used to insert a silver wire to act as a pseudoreference

electrode and also allows the possibility for in situ analysis.

Stainless steel electrode contacts were fashioned in a conical

shape that is complementary to the shape of the remaining two

holes in the PTFE insert. When the insert is screwed into

place, the electrode contacts are pulled up and into the PTFE,

creating a good seal. The top of the steel contacts are joined to

cables that can be connected to a power supply unit. Grooves

were made in the bottom of the PTFE insert to allow the

electrodes to contact the stainless-steel contacts (Figure 1). A

small grub screw in the wall of each groove can be tightened to

hold the electrodes in place, thereby allowing any electrode

with a thickness of up to 4 mm to be used, while a constant

interelectrode distance of 5 mm is maintained.

Scheme 2. Electrochemical Synthesis of Cu(I)−NHC

Complexes

The ability to maintain a reproducible and constant

interelectrode gap while ensuring high ﬂexibility of electrode

materials was of great importance during the design process.

The distance between the electrodes remains constant to

increase the reproducibility of reactions, and a broad range of

electrode materials with an assortment of shapes, thicknesses,

and lengths can be accommodated. Furthermore, the electro-

des can be connected to a range of commercially available

power supply units using simple, readily available connectors

Yields were determined by H NMR spectroscopy; an isolated yield

is shown in parentheses. Reaction conditions: 1 mmol of ligand

−

precursor, 50 mA, 1.2 F mol , 39 min. 0.5 mmol of ligand precursor,

30 mA, 1.2 F mol , 65 min, with 0.5 equiv of Bu NBF added to the

reaction mixture.

−1

Org. Process Res. Dev. XXXX, XXX, XXX−XXX

Organic Process Research & Development

Article

−

equivalents (F mol ) delivered into solution, allowing a

comparison with previously published results. The imidazo-

lium salt plays a dual role in the reaction as both the reactant

and the electrolyte. This dispenses with the need to add an

additional supporting electrolyte in most cases. Under these

conditions, ﬁve diﬀerent copper(I)−NHC complexes were

prepared (Scheme 2).

Initially, the imidazolium salt IMes·HCl (L1) was chosen as

a model substrate, as the electrochemical synthesis of the

corresponding mono-NHC Cu(I) complex has been well-

1,12

documented.

Galvanostatic conditions utilizing a current

of 50 mA were applied for 1.2 electron equivalents, which

resulted in complete conversion to the expected neutral mono-

NHC complex Cu1. This complex could also be isolated in

Figure 2. Time course monitoring of the formation of Cu(IMes)Cl

(

Cu1) (blue) and [Cu(IMes) ]PF (Cu2) (red). Determined by H

2 6

NMR analysis.

5% yield after recrystallization. Using the same imidazolium

cation but changing the counteranion to non-coordinating

hexaﬂuorophosphate gave L2, which under identical con-

ditions resulted in 60% conversion to the expected cationic bis-

NHC Cu(I) complex Cu2. The non-coordinating nature of the

anion results in coordination of a second NHC ligand to the

Cu(I) center. The lower conversion with hexaﬂuorophosphate

relative to that with a halide anion is consistent with previously

reported results. The electrochemical synthesis of cationic bis-

NHC Cu(I) complexes typically requires a greater number of

conductivity of imidazolium salt L2, resulting in a higher

resistance in solution, which may promote side reactions.

The ability to take samples from the reaction mixture through

one of the ports machined into the PTFE headpiece while the

other is connected to a Schlenk line highlights the ease of

manipulation when the bottle reactor is used.

The synthetic methodology can be simply translated to

other metals, as the reactor provides the ﬂexibility to change

the electrodes to the material of choice. To this end,

imidazolium salts L1, L3, and L6 and salen ligand L7 were

tested using either gold or iron electrodes (Scheme 3). When

IMes·HCl (L1) was subjected to a current of 50 mA for 1.2

electron equivalents using PTFE-supported Au electrodes, a

conversion of 74% to the mono-NHC product Au1 was

observed. Interestingly, a signiﬁcant amount (10% yield) of the

11,12

electron equivalents to reach full conversion.

When the

precursor was replaced with imidazolium salt L3, which

contains a base-sensitive ester functionality, complete con-

version to Cu3 was observed after 1.2 electron equivalents.

The synthesis of this complex highlights the complementary

reactivity of the electrochemical approach to traditional

chemical methods using strong bases, as the base-sensitive

ester functionality remains intact. This is not the case if strong

bases are employed. The electrochemical approach provides a

diﬀerent mode of activation that allows access to new

complexes. When benzimidazolium salt L4 was used, full

conversion to Cu4 was observed after 1.2 electron equivalents.

The reduction of benzimidazolium salt L4 is signiﬁcantly more

facile than that of related imidazolium salts, potentially because

of the electronic eﬀect exerted by the annulated benzene ring

Scheme 3. Electrochemical Synthesis of Au−NHC, Fe−

NHC, and Fe−Salen Complexes

(vide infra), and this may explain the good reactivity observed

here. When cyclophane-derived bis(imidazolium) salt L5 was

subjected to a current of 30 mA for 1.2 electron equivalents,

5% conversion to the dicationic dinuclear complex

[Cu (NHC) ](PF ) (Cu5) was observed, as expected from

6 2

1,12

previous literature.

The addition of a supporting electro-

lyte was necessary to complete the reaction in a reasonable

time frame because of the poor solubility of the ligand

precursor L5 and the low conductivity of the solution.

Time course experiments were performed to investigate the

diﬀerent rates of formation of the mono- and bis-NHC

complexes when either ligand precursor L1 or L2 was used.

Acetonitrile solutions containing the ligand precursors were

subjected to a current of 50 mA for diﬀerent numbers of

electron equivalents. This required sampling of the reaction

mixtures at diﬀerent time points while maintaining an inert

atmosphere, which required use of both ports on the PTFE

insert. The formation of Cu(IMes)Cl (Cu1) is fast, with

quantitative conversion being achieved after 1 electron

equivalent (Figure 2). The formation of [Cu(IMes) ]PF

Yields were determined by H NMR spectroscopy; isolated yields

(

Cu2) is slower, with 85% conversion after 1.6 electron

are shown in parentheses. Reaction conditions: 1 mmol of ligand

precursor, 50 mA, 1.2 F mol , 39 min. 1 mmol of ligand precursor,

50 mA, 2.0 F mol , 65 min. 1 mmol of ligand precursor, 50 mA, 2.4

F mol , 78 min.

−1

equivalents and only slightly more (92%) after 3.5 electron

equivalents. The slower formation of Cu2 is potentially

attributed to either mass transfer limitations or lower

−

Org. Process Res. Dev. XXXX, XXX, XXX−XXX

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Article

bis-NHC complex was produced in this reaction, in contrast to

the analogous reaction with copper electrodes. Au(I)−NHC

complexes are often isostructural with Cu(I)−NHC com-

plexes, but in this case the larger size of the Au(I) cation may

provide reduced steric hindrance, resulting in the formation of

24,25

the bis-NHC Au(I) complex.

When imidazolium salt L3

was subjected to identical reaction conditions using Au

electrodes, a conversion of 63% to the mono-NHC Au(I)

complex was observed, and no bis-NHC Au(I) complex was

observed. This complex was also isolated in 77% yield with 2.0

electron equivalents (Au3). Iron foil was a suitable electrode

material for the electrosynthesis of Fe complexes of diﬀerent

oxidation states. When imidazolium salt L6 was subjected to

the standard reaction conditions, 67% conversion to the Fe(II)

complex Fe6 was observed. However, when salen ligand L7

was used in place of the imidazolium salt and the reaction was

carried out in air, full conversion to the Fe(III) complex Fe7

was obtained with an isolated yield of 99%. This reaction was

performed using 2.4 electron equivalents, as the ligand

Figure 3. Parallel screening reactions were performed to optimize an

oxidative coupling of amines and thiols.

10,26

precursor had to be reduced twice.

This highlights the

versatility of the electrochemical procedure to allow access to

diﬀerent metal oxidation states.

To expand the applicability of the bottle reactor, its utility in

synthetic organic electrochemistry was examined. Speciﬁcally, a

derived from the smaller interelectrode gap in this setup

(5 mm) compared with that used by Noel and co-workers (7

mm). Decreasing the potential further to 3.2 V resulted in an

increase in the yield to 51% (Table 1, entry 3). The

galvanostatic mode was found to be more eﬃcient, as a yield

of 58% was obtained when a constant current of 20 mA was

applied (Table 1, entry 4). This yield is comparable to that

sulfonamide synthesis recently reported by Noel and co-

workers (Table 1) was investigated. This reaction involves

Table 1. Rapid Screening and Optimization of an Oxidative

Coupling of Thiols and Amines Using a Parallel Plate

reported by Noel and co-workers. Finally, because of the

success of the galvanostatic mode, a further experiment was

performed. A constant current of 10 mA was applied for

double the time (48 h) to deliver the same number of electron

equivalents at a lower potential, but this delivered a decreased

yield of 40% (Table 1, entry 5). The successful and fast

optimization of this synthetic organic electrochemical reaction

by performing six reactions in parallel showcases the bottle

reactor’s versatility and highlights the requirement for well-

characterized experimental setups to enable interlaboratory

reproducibility.

appl,cell

average

(%)

entry

mode

yield 1 (%) yield 2 (%)

potentiostatic

galvanostatic

3.7 V

3.4 V

3.2 V

20 mA

10 mA

−

Cyclic Voltammetry. In addition to a synthetic setup, the

bottle reactor can be used to perform cyclic voltammetry and

other analytical experiments. When the reactor was connected

to an external potentiostat and a reference electrode was used,

high-quality voltammograms were obtained. This was achieved

by connecting a glassy carbon disk working electrode and

platinum wire counter electrode as they would be for synthetic

electrochemistry in the bottle reactor. A silver wire, acting as a

pseudoreference electrode, was connected using a standard

54 (48 )

60 (58 )

−

a c

galvanostatic

−

Determined by H NMR spectroscopy with the aid of an internal

standard. Isolated yield. 48 h reaction time.

the oxidative coupling of amines and thiols through an

electrochemical mechanism, with H₂gas being the only

byproduct. To begin the investigation, the reported batch

conditions were repeated. Unsurprisingly, the results obtained

^/4

‑28 ﬁtting through one of the ports. Cyclic voltammo-

grams of ligand precursors L1−L5 using ferrocene as an

internal standard were obtained in this manner (Figure 4). All

of the voltammograms showed an irreversible reduction

between −1.9 and −2.5 V vs SCE, corresponding to reduction

of the imidazolium salt (Figure 4). Also, L1, L3, and L4

were diﬀerent from those obtained by Noel and co-workers

because of the diﬀerent experimental setup, with the most

signiﬁcant diﬀerence being the interelectrode gap and lower

electrolyte concentration. Utilizing the reaction conditions

−

described by Noel

and co-workers involving a potentiostatic

displayed peaks corresponding to the oxidation of Cl and

−

mode with the potential set at 3.7 V resulted in no observed

product in our setup (Table 1, entry 1). Fortunately, the

reaction was quickly optimized by employing a parallel plate

and performing a set of three reaction conditions in duplicate

Br , and additional peaks were observed for L4 that were

potentially due to oxidation of the allyl groups.

CONCLUSIONS

■

(i.e., six reactions were performed simultaneously) (Figure 3).

A new ﬂexible and standardized electrochemical batch reactor

enabling both organic and inorganic transformations and

analytical electrochemistry has been designed, developed, and

tested. This has enabled the synthesis of Cu(I)−, Au(I)−, and

Fe(II)−NHC complexes as well as an Fe(III)−salen complex.

Both galvanostatic and potentiostatic modes with a range of

currents and potentials were screened (Table 1). The yield

dramatically increased to 39% when the potential was lowered

to 3.4 V (Table 1, entry 2). The increase in yield is potentially

Organic Process Research & Development

Org. Process Res. Dev. XXXX, XXX, XXX−XXX

https://pubs.acs.org/doi/10.1021/acs.oprd.0c00091.

Article

(

silica gel, 0−20% EtOAc in hexane) to deliver the product as

an oﬀ-white solid.

Cyclic Voltammetry. Cyclic voltammetry of L1−L5 was

performed at room temperature in the bottle reactor using a

Metrohm DropSens μSTAT 400 potentiostat, and data were

acquired with DropView 8400 software. Experiments were

performed in anhydrous degassed MeCN (1 mM) containing

Bu NPF (0.1 M) as a supporting electrolyte at a scan rate of

−

00 mV s with a Metrohm glassy carbon disk (3 mm)

working electrode, platinum wire counter electrode, and silver

wire pseudoreference electrode. Ferrocene (Fc) was added as

an internal standard (1 mM, Fc /Fc at +0.380 V vs SCE) to

reference experiments.

Figure 4. Cyclic voltammograms of imidazolium salts L1−L5

(

1 mM). Experiments were performed in MeCN with TBAPF as a

ASSOCIATED CONTENT

■

supporting electrolyte (0.1 M). Ferrocene (1 mM) was added as an

internal standard. L1, red; L2, yellow; L3, green; L4, blue; L5, purple.

sı Supporting Information

The Supporting Information is available free of charge at

Bottle reactor design, experimental methods, and

characterization data (PDF)

Furthermore, the batch reactor has been used to perform a

synthetic organic reaction in conjunction with a parallel plate

that enabled six reactions to be screened simultaneously. This

allows rapid screening and optimization of reaction conditions.

Cyclic voltammetry can be performed in the reactor with the

use of an external potentiostat. This allows low concentrations

of analyte and high sensitivity to be achieved. The design of

this batch reactor is freely available, inexpensive, and versatile,

enabling a range of synthetic and analytical electrochemistry.

AUTHOR INFORMATION

Corresponding Authors

■

Charlotte E. Willans − School of Chemistry, University of Leeds,

Leeds LS2 9JT, U.K.; orcid.org/0000-0003-0412-8821 ;

Email: C.E.Willans@leeds.ac.uk

Nikil Kapur − School of Mechanical Engineering, University of

Leeds, Leeds LS2 9JT, U.K.; orcid.org/0000-0003-1041-

8390 ; Email: N.Kapur@leeds.ac.uk

EXPERIMENTAL SECTION

Synthesis of Metal Complexes: General Procedure. A

bottle reactor vial was charged with the ligand precursor

■

Authors

Hamish R. Stephen − School of Chemistry, University of Leeds,

Leeds LS2 9JT, U.K.

Christiane Schotten − School of Chemistry, University of Leeds,

Leeds LS2 9JT, U.K.

Thomas P. Nicholls − School of Chemistry, University of Leeds,

Leeds LS2 9JT, U.K.

Madeleine Woodward − School of Chemistry, University of

Leeds, Leeds LS2 9JT, U.K.

Richard A. Bourne − School of Chemistry and School of

Chemical and Process Engineering, University of Leeds, Leeds

LS2 9JT, U.K.

(

1 mmol), and then the reactor was assembled with the

appropriate electrodes (Cu, Au, or Fe) and placed under an

atmosphere of argon. MeCN (anhydrous, 15 mL) was added,

and a constant current of 50 mA was applied for 39 min

(

−

1.2 F mol ) from a benchtop power supply (Tenma 72-

0480 from Farnell). A 0.5 mL sample was taken at the end of

the reaction and ﬁltered through Celite (under an inert

atmosphere for complexes that were not air-stable: Cu3, Cu4,

Cu5 and Fe6), after which the solvent was removed under

reduced pressure. The resultant solid was redissolved in a

suitable deuterated solvent and analyzed using H NMR

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.oprd.0c00091

spectroscopy. Integrals for the complex and ligand were used

to calculate the conversion.

Oxidative Coupling of Thiols and Amines: General

Procedure. A bottle reactor vial was charged with

tetramethylammonium tetraﬂuoroborate (32 mg, 0.2 mmol),

MeCN (15 mL), and aqueous HCl (0.3 M, 5 mL). Then

cyclohexylamine (0.345 mL, 3 mmol) and thiophenol

Author Contributions

The manuscript was written through contributions of all

authors. All of the authors approved the ﬁnal version of the

manuscript.

Funding

(

0.205 mL, 2 mmol) were added. The bottle reactor lid was

This work was funded through the EPSRC (Grant EP/

R009406/1) and industrial support from AstraZeneca,

Johnson-Matthey, and Syngenta (HRS CASE Award).

ﬁtted with an IKA graphite anode and an IKA stainless steel

cathode, and a potential diﬀerence was applied for the speciﬁc

time (potentiostatic or galvanostatic). After completion the

reaction mixture was diluted with water (10 mL) and extracted

with EtOAc (3 × 20 mL). The combined organic layers were

Notes

The authors declare no competing ﬁnancial interest.

The crystallographic data for this paper have been deposited in

the Cambridge Structural Database (CSD) as entry 1987952.

washed with brine (20 mL), dried over MgSO , and ﬁltered.

The solvent was removed under reduced pressure to deliver

the crude product as a light-brown oil, to which 2,4,6-

trimethoxybenzene (internal standard, 112 mg, 0.66 mmol)

REFERENCES

■

and CDCl (3 mL) were added to form a homogeneous

(1) Yan, M.; Kawamata, Y.; Baran, P. S. Synthetic Organic

Electrochemical Methods Since 2000: On the Verge of a Renaissance.

Chem. Rev. 2017, 117, 13230−13319.

solution that was analyzed by H NMR spectroscopy. The

sample was further puriﬁed via ﬂash column chromatography

Org. Process Res. Dev. XXXX, XXX, XXX−XXX

Organic Process Research & Development

Eisenhart, T. T.; Dempsey, J. L. A Practical Beginner ’s Guide to

Article

(

2) Wiebe, A.; Gieshoff, T.; Mo

Waldvogel, S. R. Electrifying Organic Synthesis. Angew. Chem., Int. Ed.

018, 57, 5594−5619.

3) Mohle, S.; Zirbes, M.; Rodrigo, E.; Gieshoff, T.; Wiebe, A.;

hle, S.; Rodrigo, E.; Zirbes, M.;

(23) Elgrishi, N.; Rountree, K. J.; McCarthy, B. D.; Rountree, E. S.;

Cyclic Voltammetry. J. Chem. Educ. 2018, 95, 197−206.

(

(24) Lozada-Rodríguez, L.; Pelayo-Vaz

Alvarado-Rodríguez, J. G.; Peregrina-Lucano, A. A.; Per

A.; Lopez-Dellamary-Toral, F. A.; Cortes-Llamas, S. A. From metallic

gold to [Au(NHC) ] complexes: an easy, one-pot method. Dalton

quez, J. B.; Rangel-Salas, I. I.;

Waldvogel, S. R. Modern Electrochemical Aspects for the Synthesis of

Value-Added Organic Products. Angew. Chem., Int. Ed. 2018, 57,

ez-Centeno,

8) Waldvogel, S. R.; Janza, B. Renaissance of Electrosynthetic

018−6041.

4) Yoshida, J.-I.; Kataoka, K.; Horcajada, R.; Nagaki, A. Modern

Strategies in Electroorganic Synthesis. Chem. Rev. 2008, 108, 2265−

299.

5) Kar

tion and C −N bond formation. Chem. Soc. Rev. 2018, 47, 5786−5865.

6) Waldvogel, S. R.; Lips, S.; Selt, M.; Riehl, B.; Kampf, C. J.

Electrochemical Arylation Reaction. Chem. Rev. 2018, 118, 6706−

765.

7) Noel

Use of Flow Reactors in Electrochemistry. Acc. Chem. Res. 2019, 52,

858−2869.

Trans. 2017, 46, 3809−3811.

(25) Lee, Y.-C.; Knauer, L.; Louven, K.; Golz, C.; Strohmann, C.;

Waldmann, H.; Kumar, K. Gold(I)-Catalyzed and Nucleophile-

Guided Ligand-Directed Divergent Synthesis. Eur. J. Org. Chem. 2018,

2018, 5688−5699.

kas, M. D. Electrochemical strategies for C −H functionaliza-

̈ ̈

Govaerts, S.; Browne, D. L.; Noel, T. Sulfonamide Synthesis through

(26) Laudadio, G.; Barmpoutsis, E.; Schotten, C.; Struik, L.;

, T.; Cao, Y.; Laudadio, G. The Fundamentals Behind the

Electrochemical Oxidative Coupling of Amines and Thiols. J. Am.

Chem. Soc. 2019, 141, 5664−5668.

(27) Vany’sek, P. Electrochemical Series. In CRC Handbook of

Chemistry and Physics, 83rd ed.; Lide, D. R., Ed.; CRC Press: Boca

Raton, FL, 2002; pp 21−31.

(28) Roth, H. G.; Romero, N. A.; Nicewicz, D. A. Experimental and

Methods for the Construction of Complex Molecules. Angew. Chem.,

Calculated Electrochemical Potentials of Common Organic Molecules

for Applications to Single-Electron Redox Chemistry. Synlett 2016,

Int. Ed. 2014, 53, 7122−7123.

9) Liu, B.; Zhang, Y.; Xu, D.; Chen, W. Facile synthesis of metal N-

27, 714−723.

heterocyclic carbene complexes. Chem. Commun. 2011, 47, 2883−

885.

10) Chapman, M. R.; Henkelis, S. E.; Kapur, N.; Nguyen, B. N.;

(

Willans, C. E. A Straightforward Electrochemical Approach to Imine-

and Amine-bisphenolate Metal Complexes with Facile Control Over

Metal Oxidation State. ChemistryOpen 2016, 5, 351−356.

(11) Chapman, M. R.; Shafi, Y. M.; Kapur, N.; Nguyen, B. N.;

Willans, C. E. Electrochemical flow-reactor for expedient synthesis of

copper −N-heterocyclic carbene complexes. Chem. Commun. 2015, 51,

(

282−1284.

12) Lake, B. R. M.; Bullough, E. K.; Williams, T. J.; Whitwood, A.

C.; Little, M. A.; Willans, C. E. Simple and versatile selective synthesis

of neutral and cationic copper(I) N-heterocyclic carbene complexes

using an electrochemical procedure. Chem. Commun. 2012, 48, 4887−

14) Wiebe, A.; Riehl, B.; Lips, S.; Franke, R.; Waldvogel, S. R.

889.

13) Finney, E. E.; Ogawa, K. A.; Boydston, A. J. Organocatalyzed

Anodic Oxidation of Aldehydes. J. Am. Chem. Soc. 2012, 134, 12374−

2377.

Unexpected high robustness of electrochemical cross-coupling for a

broad range of current density. Sci. Adv. 2017, 3, eaao3920.

(15) Horn, E. J.; Rosen, B. R.; Chen, Y.; Tang, J.; Chen, K.; Eastgate,

M. D.; Baran, P. S. Scalable and sustainable electrochemical allylic C −

H oxidation. Nature 2016, 533, 77−81.

(16) O’Brien, A. G.; Maruyama, A.; Inokuma, Y.; Fujita, M.; Baran,

P. S.; Blackmond, D. G. Radical C −H Functionalization of

Heteroarenes under Electrochemical Control. Angew. Chem., Int. Ed.

17) Riehl, B.; Dyballa, K. M.; Franke, R.; Waldvogel, S. R. Electro-

014, 53, 11868−11871.

organic Synthesis as a Sustainable Alternative for Dehydrogenative

Cross-Coupling of Phenols and Naphthols. Synthesis 2016, 49, 252−

(

59.

18) Kawamata, Y.; Yan, M.; Liu, Z.; Bao, D.-H.; Chen, J.; Starr, J.

T.; Baran, P. S. Scalable, Electrochemical Oxidation of Unactivated

C −H Bonds. J. Am. Chem. Soc. 2017, 139, 7448 −7451.

(19) Yan, M.; Kawamata, Y.; Baran, P. S. Synthetic Organic

Electrochemistry: Calling All Engineers. Angew. Chem., Int. Ed. 2018,

7, 4149−4155.

20) Folgueiras-Amador, A. A.; Wirth, T. Perspectives in Flow

Electrochemistry. J. Flow Chem. 2017, 7, 94−95.

21) Luo, X.; Ma, X.; Lebreux, F.; Marko

Electrochemical methoxymethylation of alcohols − a new, green

, I. E.; Lam, K.

and safe approach for the preparation of MOM ethers and other

acetals. Chem. Commun. 2018, 54, 9969−9972.

(22) Baran, P. S.; Horn, E.; Waldmann, D. Closure for an

electrochemical vessel, electrochemical vessel and laboratory device.

US 0217096 A1, August 2, 2018.