Electrochemical Approaches to Organic Synthesis

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Electrochemical Approaches to Organic Synthesis
Eugene E. Kwan and Andrei K. Yudin August 2002
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Electrochemistry
Role in Synthesis Electrochemical steps are the
same as traditional reagent-based steps, only
electrons and electrogenerated species are used
as the reagents. Why Electrochemistry? -
reactions are cheap and do not produce toxic
byproducts. - transformations not available via
traditional techniques can be carried out. -
specialized electrodes and conditions allow for
high selectivity. - readily available analytical
techniques like cyclic voltammetry allow
systematic predictions of selectivity and
investigation of kinetics.
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Examples of Electrochemical Reactions
Anodic Aromatic Fluorination Cyclopropylphosphona
te Synthesis Oxidation of Sulfides
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Electrochemical Apparatus
Cells Cells control the flow of electricity and
reactants. They can be divided or
undivided Undivided

Divided Electrodes Electrodes deliver the
electrons. Different electrodes may have
different surface characteristics and
overpotentials. Examples include platinum,
graphite, nickel, and magnesium.
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Electrochemical Aziridination
- only works on Pt
electrodes - thought to occur through nitrene
intermediate - better than traditional
method, which relies on Pb(OAc)4, a toxic
oxidant - no toxic byproducts - the N-N
bond remains difficult to cleave Siu, T. and
Yudin, A. K. "Practical Electrochemical Olefin
Aziridination with a Broad Substrate Scope,"
JACS. 2002, 124, 530.
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ReactIR Characterization

Real-time attenuated total reflectance (ATR) FTIR
spectra were taken with a ReactIR 1000
spectrometer using a liquid nitrogen cooled
mercury cadmium telluride detector. Principal
components analysis (PCA) of the mid-infrared
region allowed determination of concentration
profiles.
probe made of inert alloy
internal mirrors direct beam
The probe is dipped into the reaction and scans
are periodically performed and averaged by the
computer. A waterfall profile is generated and
then analyzed. With internal standards,
quantitative kinetic data can be extracted. The
PCA algorithm does not require any internal
standards or knowledge of the reaction.
diamond tipped ATR detector
nitrogen purge line
adjustable joints
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ReactIR Data

noise generated by water and gas impurities
a PCA-generated set of spectra
region used for analysis
a preliminary waterfall profile of an
aziridination reaction
The PCA algorithm assumes the data (above) can be
represented by a linear combination (bottom
right) of eigenvector spectra (top right). It
searches for peaks which change at the same rate
and assumes they belong to the same component.
It looks for a minimum number of eigenvectors
which can reproduce the data within a set margin
of error. Further experiments are needed to
determine the identity of the eigenvectors.
PCA-calculated concentration profiles for the
reaction
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Electrochemical Alkoxylation

Intermolecular Intramolecular Cyclization a
potentiostat
This is a convenient technique for generating
alkoxylated piperidine and pyrrolidine style
structures. It works on a wide variety of
substrates and electrode surfaces and can be
carried out quickly. It is highly selective and
gives good to excellent yields. Siu, T., Li, W.,
and Yudin, A. K. J. Comb. Chem. 2000, 2,
545-549. Shono, T. Matsumura, Y., Tsubata, K.
Organic Syntheses. CV 7, 307.
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Characterization

ReactIR is unable to follow this reaction
probably because the reactant and product
have very similar IR spectra.
1H NMR shows two rotamers
axial alpha proton
various products
GC shows no significant reaction after four
electron equivalents have been passed because the
starting material has been completely
bis-methoxylated. GC was unable to resolve mono-
and bis- methoxylated product or bismethoxylated
diastereomers.
starting material
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Alkoxylation in Synthesis

We attempted the above synthesis, however the
methoxylation step failed because the SO bond
was preferentially oxidized over the alpha
position on the piperidine ring. One possible
way to get around this may be to run the reaction
completely dry so there is no oxygen source. The
products of this synthesis are useful precursors
to a number of important pharmaceuticals.
The CVs in degassed 11 MeCN/MeOH on glassy
carbon show similar profiles with significant
anodic currents which means the methoxylation
should be possible. The two anodic peaks
probably result from the stepwise generation of
radical cations and cations.
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Acknowledgements
- Yudin Group Sacha Bhinder, Leslie Fradkin,
Larissa Krasnova, Tung Siu, and Shahla Yekta. -
Lautens Group Wooseok Han and the use of their
ReactIR. - NMR Tim Burrow. - U of T Department
of Chemistry - NSERC