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ABSTRACT: While organic electrochemistry can look quite different to a chemist not
familiar with the technique, the reactions are at their core organic reactions. As such,
they are developed and optimized using the same physical organic chemistry principles
employed during the development of any other organic reaction. Certainly, the electron
transfer that triggers the reactions can require a consideration of new “wrinkles” to those
principles, but those considerations are typically minimal relative to the more traditional
approaches needed to manipulate the pathways available to the reactive intermediates
formed downstream of that electron transfer. In this review, three very different synthetic challengesthe generation and
trapping of radical cations, the development of site-selective reactions on microelectrode arrays, and the optimization of current
in a paired electrolysisare used to illustrate this point.
CONTENTS the attention those methods are garnering from the greater
synthetic community. Several nice reviews of these efforts
1. Introduction 4817
highlighting both direct1−6 and indirect7−11 electrolyses have
1.1. Physical Organic Chemistry, Electrochemis-
try, and Manuel M. Baizer 4818
been published including a very extensive summary by Baran
2. Intramolecular Anodic Olefin Coupling Reactions 4819 and co-workers.12 Many of the articles in this thematic issue of
2.1. Constant Current Electrolyses 4819 the journal expand upon the ideas presented therein and
2.2. Other Technical Considerations 4820 provide new insights into what is being accomplished and how
2.3. Radical Cation Polarity 4821 electrochemical methods can be employed. The presentation of
2.4. A Challenge, Curtin−Hammett Control, and these papers and the extensive literature review they provide
an Important Observation 4821 will serve to make the greater community aware of all that
2.5. An Oxidative Radical Pathway 4823 electrochemistry offers, and hopefully they will help provide
3. New Methods for the Synthesis of a Complex motivation for synthetic chemists to overcome the barrier that
Molecular Surface 4824 has long hindered the development of electroorganic synthesis.
3.1. An Array-Based Synthetic Strategy 4824 Yet as important as this effort is, the barrier to synthetic
3.2. Solving a Synthetic Challenge on an Array 4825 chemists adopting electrochemical methods is not simply a
3.3. New Chemistry Equals New Bioanalytical matter of knowing what reactions can be accomplished or
Capability 4826 having the equipment necessary to conduct them. It is also a
3.4. A Final Observation 4827 lack of familiarity with how to think about the reactions. How
4. Electrochemistry, Energy Economy, and the does one start utilizing the method, choose electrolytes, think
Valorization of Lignin 4827 about current density, and optimize a yield for a particular
4.1. Pairing Synthetic Transformations 4828
reaction?
4.2. Mechanism and the Optimization of Current
For this reason, this review will not focus on providing an
Flow 4829
exhaustive survey of electrochemical reactions that can be
5. Conclusions 4830
Author Information 4830 accomplished but rather will utilize a series of seemingly
ORCID 4830 unrelated transformations [(Scheme 1): (1) the development
Notes 4830 of radical-cation based oxidative cyclizations,13−26 (2) the use
Biography 4830 of chemical synthesis in the development of new micro-
Acknowledgments 4830 electrode array technology,27 and (3) the valorization of lignin
References 4830 derived building blocks28] to highlight how an organic chemist
can approach the development of electrochemical methods.
Scheme 1. Challenges
The reactions presented were each chosen for the specific Baizer, perhaps best known for the Monsanto adiponitrile
lesson that they have taught us. process.29−31 It was Manual Baizer that helped many of us see
1.1. Physical Organic Chemistry, Electrochemistry, and that the mechanistically guided approach used for optimizing
Manuel M. Baizer organic reactions is just as relevant for electroorganic reactions.
In the adiponitrile process (Scheme 2), the reduction of an
The development of new chemical reactions frequently benefits
from a consideration of physical organic chemistry. When a
reaction leads to a less than optimal yield, answers are found by Scheme 2. Adiponitrile Process
isolating the minor products generated, determining what
mechanistic steps led to their formation, and then adjusting
reaction conditions to maximize the rate of the desired
mechanism over the unwanted alternatives. The approach
takes advantage of conformational analysis, frontier molecular
orbital theory, stereoelectronic and steric factors, the Curtin−
Hammett Principle, the Hammond Postulate, linear free energy
relationships, etc.
While this approach is common in organic synthesis, the
development of electrochemical reactions has not always been
viewed in the same manner. Instead, problematic reactions electron-poor olefin led to the production of a highly reactive
were discarded due to worries about “specialized equipment” radical anion intermediate that was then channeled down a
and concepts that appeared outside of the normal expertise of productive dimerization pathway. This required the relative rate
an organic chemist. Fortunately, this attitude did not extend to of radical anion dimerization be optimized relative to either
Manuel Baizer, Tatsuya Shono, Hennig Lund, Sigeru Torii, protonation or polymerization of the radical anion. To this end,
Hans Schäfer, Jacques Simonet, James Utley, Jean-Michael the environment surrounding the cathode was controlled by
Savéant, Dennis Evans, Ikuzo Nishiguich, Al Fry, Dennis Peters, forming a double layer with a hydrophobic electrolyte in order
Jean Lessard, and many others. Many of these efforts are to limit the concentration of water near the electrode and slow
highlighted in refs 1−6. So, in the interest of space we will focus protonation of the reactive intermediate. At the same time, the
here on one aspect of the many contributions made by Manuel concentration of the radical anion was manipulated using
4818 DOI: 10.1021/acs.chemrev.7b00656
Chem. Rev. 2018, 118, 4817−4833
Chemical Reviews Review
current density in order to avoid polymerization. The use of the are highly selective for the substrate. The disadvantage is that
double layer and current density to control reactions will be the reactions slow down as substrate is consumed and the
discussed in more detail below. For now, it is most important to current drops. Accordingly they can be hard to push to
note that the electrolysis reaction was optimized by examining completion.
the same types of physical organic chemistry parameters one In a constant current experiment, the current passed through
needs to address for any highly reactive intermediate and then the reaction is set to a fixed value and the working potential of
using the reaction medium to manipulate the relative rates of the electrodes is allowed to float. As shown in Figure 1, at the
the relevant processes. While the electrochemical method was
new, the approach taken was not. It was this observation that
set the stage for development of complementary anodic
reactions that proceed through highly reactive radical cation
intermediates.
Scheme 4. Two Sample Reactions Both Originating from the For our part, we mainly use carbon for the working electrode
Oxidation of a Dithioketene Acetal (anode for an oxidation) because it is cheap and readily
available. For the reactions below, the counter electrode is
either a carbon rod or a simple Pt-wire. They can be used
interchangeably.
With that said, for many of the anodic olefin coupling
reactions shown you will note the use of a reticulated vitreous
carbon (RVC) anode. This is a high surface area carbon
electrode that is used for the anodic coupling reactions for two
reasons. The first is to help keep the current density used in the
reactions low. For an electrolysis reaction, current density
represents the “concentration of oxidant” used. The anodic
olefin coupling reactions proceed through a highly reactive
radical cation intermediate that can dimerize. For this reason,
the concentration of the radical cation is kept low by keeping
the effective concentration of oxidant (current density) low.
The second reason for the use of an RVC anode has a
oxidant is clear. If one were to choose an oxidant with an historical basis (Scheme 5).36 When the first anodic coupling
oxidation potential high enough to oxidize the substrate in
equation 1 in Scheme 4, then its use for the reaction shown in Scheme 5. Initial Allylsilane Trapping Studies
equation 2 would lead to an overoxidation product. If one were
to choose an oxidant with an oxidation potential suitable for the
selective oxidation required for the reaction shown in equation
2, then it would not be able to initiate the reaction shown in
equation 1. This problem was completely avoided with a
constant current electrolyses that allowed the oxidation
potential at the anode to automatically adjust to the oxidation
potential needed for both reactions while at the same time
enabling the selectivity needed throughout both processes.
2.2. Other Technical Considerations
In addition to the constant current conditions that will play
such a central role in the chemistry described below, there are a
number of other aspects concerning electrochemical reactions reactions were conducted with allylsilane trapping groups, they
that also deserve comment. led to disappointingly low yields in spite of the fact that
For the most part, the reactions to be discussed were all allylsilanes are good nucleophiles. At the time, the reactions
conducted in an undivided cell. An “undivided cell” refers to an were conducted at a Pt-anode. Efforts to optimize the reactions
electrochemical reaction that has both the anode and cathode led to the discovery of trace amounts of a vinylsilane product.
in the same reaction chamber. For the preparative scale This product was surprising since the mechanism was supposed
reactions discussed below, this amounts to a simple three neck to proceed through cationic intermediate 15, and its formation
round-bottom flask. The electrodes are introduced into the suggested that the initial cyclization led to radical 14 that was
flask with a thermometer adapter that is sized to fit the ground then slow to oxidize. A consideration of the literature11
glass joints of the flask. This setup is used because it is simple indicated the Pt-anodes often favored one electron oxidations
and takes advantage of glassware already available in any since the surface of the anode is fouled during the electrolysis.
synthetic lab. Higher surface area carbon electrodes did not have this
The other option for an electrolysis reaction is the use of a problem and led to faster two electron oxidations. Hence, a
divided cell. Divided cells have two chambers that are separated shift was made to the RVC anode in an effort to accelerate loss
by either a glass frit or a membrane: one chamber for the anode of the second electron from intermediate 14 and the problem
and another for the cathode. Such cells are commercially was solved. Since all of the olefin coupling reactions studied
available, and they can be very useful if one needs to protect a require a net two electron oxidation, the RVC anodes that favor
substrate, product, or reagent in an electrolysis from the such a process have been used ever since. They remain our
counter electrode. For example, if an oxidation reaction recommended electrode for any two electron process, especially
generates a molecule that can be reduced readily at a cathode, ones that proceed through a highly reactive intermediate.
then a divided cell may be necessary to separate the product The final electrochemical parameter that often raises
from the cathode. One such situation is the generation of an questions involves the choice of electrolyte used in the
enone at an anode. Enones can be reduced to radical anions at a reactions. In an electrochemical reaction, the electrolyte plays
cathode. Hence, the reaction might require the use of a divided a significant role in reducing resistance to the passage of
cell to protect the desired enone product. For many reactions, current. Simply put, an electrochemical reaction generates
such as all of the anodic olefin coupling reactions shown in this cations by the anode and anions by a cathode. Since the two
review, no such complication exists and the use of a simple electrodes are spatially remote from each other, there is a
round-bottom flask, or a vial for smaller scale reactions, makes buildup of charge at each. The more charge that is generated,
for an ideal electrolysis cell. the harder it is to introduce more anions into solution. The
Another common question that arises about electrochemical electrolyte serves to resolve this issue by providing counterions
reactions concerns the choice of electrodes used for a reaction. for the charges being introduced.
4820 DOI: 10.1021/acs.chemrev.7b00656
Chem. Rev. 2018, 118, 4817−4833
Chemical Reviews Review
For the majority of electroorganic reactions, the choice of an based mechanistic studies. For example, because the potential
electrolyte is very simple. The best electrolyte is one that is of the reaction will float to match that of a substrate, the
soluble in an organic solvent but even more soluble in water. substrate for an oxidative cyclization reaction can be system-
That allows for the necessary ions during the organic reaction atically varied without any other change made to the reaction
while enabling easy removal of the electrolyte during workup. conditions. This allows for structure reactivity studies like the
Along these lines, the use of tetraethylammonium tosylate is one shown in Figure 2 relating the polarity of a radical cation to
nearly ideal. It is our first electrolyte of choice and used for the
majority of reactions presented here.
Of course, there are times when the choice of electrolyte can
have a direct impact on the course of a reaction. In those cases,
it is important to consider that a positively charged anode in an
electrolyte solution becomes coated with the negative ion from
the electrolyte. This leads to a negatively charged layer that is in
turn coated with the positive ion from the electrolyte. These Figure 2. Radical cation polarity vs chemoselectivity.
two charged layers make up the electrochemical “double layer”
(or outer Helmholtz layer for a physical chemist) that defines the propensity for carbon carbon bond formation. This data
the nature of the reaction medium at the anode surface.68,69 was then used to adjust the nature of the substrates used in a
Electron transfer reactions at the anode and any rapid chemical number of synthetic studies.71,72 For example, consider the two
reactions that follow occur in this double layer. Accordingly, the reactions shown in Scheme 7. In the first, an enol ether was
nature of the double layer can have a dramatic effect on a
reaction. Consider the chemistry illustrated in Scheme 6.70 Scheme 7. Synthetic Applications of a Mechanistic Finding
Scheme 8. A Difficult Challenge and the “Need” for a Scheme 10. Curtin−Hammett Control of an Amide
Reactive Terminating Group Oxidation
works because the tetraethylammonium tosylate used as the Scheme 13. Competition Study
electrolyte for the reaction forms a “greasy” double layer at the
cathode surface. This double layer excludes the water solvent
and provides the time needed for the dimerization. So, in both
Scheme 11 and the adiponitrile process the electrolyte in the
reaction is used to provide a protective environment for the
reactive intermediates generated at an electrode surface. This
“trick” can enhance an electrochemical reaction relative to a
nonelectrochemical counterpart, and it is a common “hidden”
feature of many anodic coupling reactions. Note how in the
chemistry highlighted in Schemes 7 and 9 alcohols effectively
trapped olefin based radical cations. This occurs without the
methanol solvent trapping the intermediates first. This outcome
is a result of the double layer excluding the methanol solvent observation could be used to select the product generated. The
from the region of the reaction close to the anode. The oxygen trapping product was favored by low temperatures and
cyclizations are fast and occur close to the anode surface. high current densities that accelerated oxidation of the second
Hence, the radical cation traps the internal alcohol in the electron from 43, leading to the generation of cation 44. Once
relative absence of the methanol solvent. 44 was generated, the cyclization was no longer reversible. The
To continue the story about solving the challenge presented thermodynamic N-trapping product was favored by elevated
in Scheme 8, it is important to note that the suggestion in temperatures and lower current densities that slowed removal
Schemes 9 and 10 that intramolecular electron transfer of a second electron from 43. This provided more time for the
reactions led to ongoing mechanistic investigations that reaction to be reversible, a change that led to the generation of
eventually afforded the alternative solution currently used. 48.
Consider, for example, the chemistry shown in Scheme 12.77 In
2.5. An Oxidative Radical Pathway
Scheme 12. N-Based Systems It was the observation that the trapping of a radical cation by an
alcohol moiety was fast that suggested a solution to the
challenge of simultaneously generating a six-membered ring
and a quaternary carbon with the use of an allylsilane trapping
group presented in Scheme 8. That solution called for a
substrate (49/ Scheme 14) that again had two trapping groups
allylsilane group. That conclusion was not correct. The reaction pathway by controlling the relative rates of competing
just had to be channeled down a more productive pathway. reactions.
The use of physical organic chemistry to guide electro- 3.1. An Array-Based Synthetic Strategy
chemical reactions in this manner is not restricted to the
With that in mind, each array-based electrochemical reaction is
optimization of anodic olefin coupling reactions. It can be
a competition reaction between two processes. The best way to
utilized to develop and optimize electrochemical reactions on a
understand this is to initially focus on a single example (Scheme
variety of platforms.
15).101,102 In this example, a site-selective Suzuki reaction was
3. NEW METHODS FOR THE SYNTHESIS OF A
Scheme 15. Site-Selective Reactions on an Array
COMPLEX MOLECULAR SURFACE
One synthetic challenge that initially looks much different than
an oxidative cyclization is shown in Figure 3.
Scheme 16. Array Based Oxidation Reactions Scheme 17. Acid Catalyzed Molecule Recovery
(Scheme 19) could only be confined on a 1K array. No Scheme 20. A Successful Reaction with an Alcohol
confinement of any kind was observed on a 12K array.109 So Nucleophile on a 12K Array
why did the confinement strategy for Cu(I) that worked so well
for the click reaction on both 1K and 12K arrays only work for
a 1K array for this reaction? In the past, questions of this nature
have frequently led synthetic chemists to conclude that
electrochemical reactions are not general. However, such
failures rarely have anything to do with the electrochemical
part of the reaction. As mentioned above in connection with
the olefin coupling reactions, the electron transfer at the 3.3. New Chemistry Equals New Bioanalytical Capability
electrode almost always happens. The key is to look for the For the sake of completion, it is important to note that the
difference between the reactions and to consider chemical development of new synthetic chemistry on the arrays is not
possibilities that might occur downstream of that electron being done simply because it can be. New synthetic chemistry
transfer. The same is true for an array-based synthetic method. on an array leads to new biology. As an illustration, consider the
With this in mind, the differences between how reactions are Cu(II)-type Chan Lam coupling reaction shown in Scheme
run on a 1K array and a 12K array was considered in 21.83,110 In this example, Cu(II) generated at the selected
connection with how those differences might alter the course of
a mechanistic pathway. To this end, it was noted that 1K array Scheme 21. Placement of an Acetylene on an Array
reactions are run by simply inserting the array into a beaker
along with a remote Pt-wire counter electrode. The reactions
are essentially divided cells since the remote counter electrode
is remote from the array. In contrast, 12K array reactions are
run in a thin film flow cell format. The reaction solution is
flowed in between the array and a Pt-electrode that is separated
from the array by 0.95 mm. The cell is for all practical purposes
an undivided cell. So the difference between the two formats
has to do with the counter electrode and its relationship to the
array. This is important because for a reduction reaction on the
array (the generation of Cu(I) from Cu(II)) the counter
electrode is an anode that generates acid. The closeness of the electrodes was used to trigger a reaction between a borate ester
anode and the cathode in the 12K array flow cell means that the based coating on an array and an acetylene. The reaction was
surface of the 12K array is much more likely to become acidic confined with the use of excess acetylene in solution (Cu(II)
when compared to a 1K array. Once that observation was made, effects an oxidative dimerization of the acetylenes that
the rest was easy. For these initial experiments, the surface of consumes the oxidant). This reaction was developed so that
the array was coated with agarose. If that surface becomes peptides already functionalized with acetylenes for use in click-
acidic, then oxonium ion formation and nucleophilic addition based bioconjugate studies could be placed directly on an array
to the anomeric carbon of the sugar can occur. For a click without further modification. This enabled evaluation of their
reaction, this was not a problem because there was no binding properties to a selected target. Consider the experiment
nucleophile in solution for the oxonium ion. This was not the shown in Figure 4.83 In this case, a v107 peptide developed for
case for the alcohol addition chemistry. Under acidic PET-imaging studies was placed onto an array using the
conditions, the nucleophile could be added to the agarose acetylene initially added to the peptide so that it could be
polymer. This would afford the observed “loss of confinement”. coupled to a radiolabeling group. The binding of the peptide to
This background reaction only happened on the 12K array both human and murine VEGF protein (its intended biological
because the 1K array is essentially a divided cell with little target) was then evaluated with the array. Because of the
communication between the two electrodes. The surface of the synthetic focus of this review, the analytical study will not be
array was not exposed to the acid generated at the counter detailed here. However, the raw CV data for a block of 12
electrode. electrodes functionalized with the peptide is shown. The image
With the problem identified, finding a solution was shows the CV data for a ferrocene carboxylic acid redox
straightforward. While the reaction could be run under more mediator as the concentration of human VEGF receptor is
basic conditions, the best solution was to change the polymer increased. The decrease in the total current measured (red
surface from agarose to a nonsugar diblock copolymer that had arrow) for each sweep directly coincided to the increase in
no anomeric carbons (Scheme 20).109 Once again, the key to receptor. Note how the change in current was slow, then steep,
solving the challenge encountered was the identification of an and then slow again, a change consistent with a normal binding
organic chemistry solution to the problem. event.
4826 DOI: 10.1021/acs.chemrev.7b00656
Chem. Rev. 2018, 118, 4817−4833
Chemical Reviews Review
Scheme 24. A Preparative Oxidative Condensation To test this approach, the anodic oxidation of an alcohol was
used to generate hydrogen gas at the cathode (Scheme 25).116
earlier reactions, and the reduction of carbon dioxide proceeded oxidation of groups in solution (like the aromatic product) with
with high efficiency. a higher oxidation potential than the thioaminal. The key then
4.2. Mechanism and the Optimization of Current Flow is to make sure that the reaction has enough of the thioaminal
present.
While the reactions are easy to demonstrate, how does one
In principle, this should not have been a problem. Even the
optimize a paired electrolysis when the initial reaction is less
higher currents used for the reaction were not so high as to
that ideal? It was for this reason that the reaction shown in
cause a problem with the amount of aldehyde and thioamine
Scheme 26 was included here. As a proof-of-principle, the
used for the transformation. However, the higher current might
reaction worked well. However, it was fundamentally flawed if
be a problem if the amount of aldehyde and thioamine use led
the goal of the process was to produce useful amounts of
to only a small amount of the thioaminal. After all, there was no
carbon monoxide at the cathode.124 A more careful look at the
guarantee that the equilibrium that formed thioaminal
conditions needed for the oxidative condensation highlights the
intermediate 82 favored the formation of that intermediate.
problem. Consider again the reaction shown in Scheme 24 and
In the original reaction there was no driving force provided for
not that the current used for the reaction is highlighted in red.
this equilibrium. This omission was addressed (Scheme 28) by
This was done to call attention to the fact that the optimized
reaction conditions employed only 4 mA of current. Higher
current levels led to overoxidation of the product. Thus, the Scheme 28. A Plan To Drive the Initial Equilibrium
paired electrolysis shown in Scheme 28 was also run at a
current of 4 mA. This allowed for the production of the desired
product in a high yield, but it also meant that the rate of carbon
monoxide generated at the cathode was very low. So how can a
paired electrolysis of this type be optimized so that more
current can be passed through the cell and in so doing carbon
monoxide can be generated at the cathode at a faster rate? As in
the earlier reactions, the key to optimizing this electrochemical
reaction did not rest with the electron transfer processes but
rather with understanding the organic chemistry that governed
the transformation downstream of that event. For this
understanding, it was critical to note that the reaction did
afford good yields of the product without overoxidation at
lower current values. Consider the proposed mechanism for the
reaction highlighted in Scheme 27. The reaction begins with
stirring the reaction mixture over MgSO4 for 24 h. This
Scheme 27. Proposed Reaction Mechanism removed water, driving the initial equilibrium to form the
thioaminal before conducting the oxidation. The change in the
reaction worked well, and even at higher currents the reaction
afforded none of the overoxidation product. However, while the
reaction was clean and formed only the desired product and
recovered starting material (Scheme 29), the current efficiency
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Eithiobis(succinimidyl propionate) Modified Gold Microarray Elec- Solvolysis, Electrochemistry, and the Development of Synthetic
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diameter = 44 μm; Distance between the Pt-electrodes (square cells) = Fuchigami, T.; He, P.; Watts, P.; Haswell, S. J.; Pritchard, G. J.; Bull, S.
33 μm.. D.; Marken, F. J. Appl. Electrochem. 2006, 36 (6), 617−634.
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them can be purchased from CustomArray, Inc., 18916 North Creek
Int. J. Electrochem. Sci. 2013, 8 (5), 6566−6573.
Parkway, Suite 115, Bothell, WA 98011 (www.CustomArrayInc.com).
(120) “Paired electrochemical synthesis of new organosulfone
For a detailed discussion of how the array reactions are run see the
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(102) Hu, L.; Stuart, M.; Tian, J.; Maurer, K.; Moeller, K. D. Building (122) For a nice summary that illustrates how commonplace the
Addresable Libraries: The Site-Selective Use of Pd(0)-Catalysts on method has become and review see: Sánchez-Sánchez, C. M.; Frias-
Microelectrode Arrays. J. Am. Chem. Soc. 2010, 132, 16610−16616. Ferrer, E. E. A.; González-Garcia, J.; Montiel, V.; Aldaz, A. Chloro-
(103) Hu, L.; Graaf, M. D.; Moeller, K. D. The Use of UV-Cross- Alkali Industry: A Laboratory Scale Approach. J. Chem. Educ. 2004, 81,
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Microelectrode Arrays. J. Electrochem. Soc. 2013, 160, G3020−G3029. (123) For the optimization of cell performance in such systems see:
(104) Tesfu, E.; Maurer, K.; Ragsdale, S. R.; Moeller, K. D. Building Llorente, M.; Nguyen, B. H.; Kubiak, C. A.; Moeller, K. D. Paired
Addressable Libraries: The Use of Electrochemistry for Generating Electrolysis in the Simultaneous Production of Synthetic Intermediates
Reactive Pd(II) Reagents at Pre-Selected Sites on a Chip. J. Am. Chem. and Substrates. J. Am. Chem. Soc. 2016, 138, 15110−15113.
Soc. 2004, 126, 6212−6213. (124) Rensing, D. T.; Nguyen, B. H.; Moeller, K. D. Considering
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Microelectrode Arrays: A General Strategy for Using Oxidation Electrochemical Oxidative Condensation Reaction. Org. Chem. Front.
Reactions to Site-Selectively Modify Electrode Surfaces. Langmuir 2016, 3, 1236−1240.
2014, 30, 2280−2286. (125) Smith, J. A.; Moeller, K. D. Oxidative Cyclizations, the
(106) Bi, B.; Maurer, K.; Moeller, K. D. Building Addressable Synthesis of Aryl Substituted C-Glycosides, and the Role of the
Libraries: Site-Selective Lewis-Acid (Sc(III)) Catalyzed Reactions. Second Electron Transfer Step. Org. Lett. 2013, 15, 5818−5821.
Angew. Chem., Int. Ed. 2009, 48, 5872−5874. (126) Perkins, R. J.; Xu, H. − C.; Campbell, J. M.; Moeller, K. D. The
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Site-Selective, Cleavable Linkers: Quality Control and the Character- A Surprising Non-Kolbe Pathway to Lactones. Beilstein J. Org. Chem.
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2011, 76, 9053−9059.
(108) Bartels, J. L.; Lu, P.; Walker, A.; Maurer, K.; Moeller, K. D.
Building Addressable Libraries: A Site-Selective Click-Reaction
Strategy for Rapidly Assembling Mass Spec Cleavable Linkers. Chem.
Commun. 2009, 37, 5573−5575.
(109) Bartels, J. L.; Lu, P.; Maurer, K.; Walker, A. V.; Moeller, K. D.
Site-selectively Functionalizing Microelectrode Arrays: The Use of
Cu(I)-Catalysts. Langmuir 2011, 27, 11199−11205.
(110) For array based Chan-Lam coupling reactions see: Graaf, M.
D.; Moeller, K. D. Chemoselectivity and the Chan-Lam Coupling
Reaction: Adding Amino Acids to Polymer Coated Microelectrode
Arrays. J. Org. Chem. 2016, 81, 1527−1534.
(111) Ogibin, Y. N.; Elinson, M. N.; Nikishin, G. I. Mediator
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(112) Electrogenerated Reagents. Simonet, J.; Pilard, J-. F. In Organic
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(113) For a review of electrochemistry as a “green”-method see:
Frontana-Uribe, B. S.; Little, R. D.; Ibanez, J. G.; Palma, A.; Vasquez-
Medrano, R. Organic Electrosynthesis: A Promising Green Method-
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