Practical olefin aziridination with a broad substrate scope

Article abstract of DOI:10.1021/ja0172215

The present study illustrates the possibility of a rational approach that bypasses the requirement for stoichiometric amounts of toxic oxidants and metal additives (including reagents and catalysts) in organic redox reactions. We describe an aziridination process that delivers a nitrene functionality to olefins from a readily available N-aminophthalimide. Remarkably, both electron-rich and electron-poor olefins are converted to aziridines with high efficiency. The continuum of applied potentials and the heterogeneous nature of reactions at electrode surfaces allow for the electrochemical discrimination of substrates which have similar redox potentials and therefore cannot be selectively reduced or oxidized using soluble reagents. This selectivity is due to the phenomenon of overpotential, the kinetic inhibition of electron transfer on a particular electrode surface. Copyright

Full text of DOI:10.1021/ja0172215

Published on Web 01/05/2002
Practical Olefin Aziridination with a Broad Substrate Scope
Tung Siu and Andrei K. Yudin*
Department of Chemistry, UniVersity of Toronto, 80 St. George St., Toronto, Ontario, Canada M5S 3H6
Received October 3, 2001; Revised Manuscript Received November 27, 2001
Scheme 1
Organic compounds participate in two main kinds of transforma-
tions: carbon-carbon bond forming processes and reactions
accompanied with changes in the oxidation states at carbon atoms.1
The oxidation reactions are carried out using appropriate electron
or atom transfer reagents such as metal derivatives (e.g., OsO4,
CrO3, KMnO4, MnO2, K3Fe(CN)4, Pb(OAc)4) or other oxidants
(e.g., Cl2, NaOCl, H2O2, O2, KHSO5). Despite the high levels of
selectivity these reagents can offer, the majority produce toxic waste.
The development of waste-free technologies is one of the daunting
challenges that faces chemists,2 and new approaches that eliminate
the toxic byproducts of oxidation reactions are needed.
We focused our attention on finding alternative routes for
Electrochemistry, a branch of science that studies direct electron
transfer at electrode surfaces, is frequently referred to as one of
the prototypical green technologies of the future.2d Selectivity in
the electrosynthesis of organic compounds can be obtained by
subjecting reactants to oxidizing or reducing environments of
specific and invariant electrochemical potential.3 Our goal is to find
general and practical electrochemical solutions to the selective
functionalization of hydrocarbons.4 Aziridination of olefins is of
particular interest due to the enormous synthetic potential of
aziridines.5 These nitrogen-containing heterocycles have 28 kcal/
mol of strain6 and are amenable to ring-opening reactions with a
wide range of nucleophiles. Such transformations lead to molecules
with valuable 1,2 heteroatom relationships, commonly found in
natural products and in pharmaceuticals.7 Olefin aziridination
reactions are usually accomplished via metal-mediated transfer of
a nitrene fragment to the olefin.8 The corresponding processes
produce a variety of byproducts that stem from metal additives and
from oxidants.
To date, there are no examples of catalytic oxidation systems
based on readily available oxidants that (1) convert simple amines
or amides into active nitrogen transfer species in the presence of
olefins and (2) leave no byproducts. Here we show that these
important challenges can be met electrochemically without metal-
based reagents, catalysts, and stoichiometric oxidants. We describe
an aziridination process that delivers a nitrogen-containing func-
tionality to a broad range of olefins from a readily available amine.
The continuum of applied potentials and the heterogeneous nature
of reactions at electrode surfaces allow for the electrochemical
discrimination of substrates which have similar redox potentials
and therefore cannot be selectively reduced or oxidized using
soluble reagents. This selectivity is due to the phenomenon of
oVerpotential,9 the kinetic inhibition of electron transfer on a
particular electrode surface.
reactions that typically involve stoichiometric amounts of highly
toxic lead(IV) oxidants.10 Lead tetraacetate-promoted aziridination
of olefins with N-amino derivatives (eq 1) is a valuable synthetic
transformation,11 but its widespread application is hampered by the
use of large amounts of Pb(OAc)4. We started by investigating the
feasibility of reducing the amount of Pb(OAc)4 to catalytic
quantities. The cyclic voltammetry (CV) of Pb(OAc)2 in acetonitrile
gives the value of +1.60 V (vs Ag/AgCl) for the oxidation potential
of Pb2+ to Pb4+ 12
whereas the CV of N-aminophthalimide (0.01
,
M in acetonitrile) shows two irreversible one-electron oxidation
processes with anodic peak potentials at +1.35 V and at +1.68 V
(vs Ag/AgCl).13 It was therefore possible to perform the aziridi-
nation of cyclohexene with only 10 mol % Pb(OAc)4 by reoxidizing
Pb2+ to Pb4+ electrochemically at +1.60 V.
Furthermore, we discovered that the CV of cyclohexene (0.01
M in acetonitrile) produces an anodic current of -1.0 µA at +1.68
V (vs Ag/AgCl), which is only a small fraction of the current
recorded for N-aminphthalimide (-152 µA). This indicates that the
background oxidation of olefins on a platinum electrode is
kinetically disfavored due to olefin overpotential. We reasoned that
a direct electrochemical nitrogen transfer process should take place
at around +1.60 V in the absence of eVen catalytic amounts of
Pb(OAc)4. Indeed, we have observed that a simple combination of
platinum electrodes, triethylamine, and acetic acid leads to a highly
efficient formal nitrene transfer14 from N-aminophthalimide to
cyclohexene (Scheme 1). The reaction utilizes only a small excess
of N-aminophthalimide relative to the olefin and can be performed
in a divided cell using a silver wire as a pseudo-reference electrode.
Optimization of the working potential revealed that +1.80 V
versus Ag wire15 produced the highest isolated yield of the aziridine
from cyclohexene (Table 1, entry 1). Additional increases in the
working potential were detrimental to the yield due to the
background oxidation of cyclohexene. Temperature changes had
negligible effect on the efficiency of nitrene transfer. No special
precautions to exclude moisture or air were taken. The reaction
was stopped when the cell current dropped to less than 5% of its
original value. Table 1 illustrates the wide substrate scope of this
process. Remarkably, both electron-rich and electron-poor olefins
are converted to aziridines with high efficiency. The aziridination
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10.1021/ja0172215 CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Electrochemical Aziridination of Olefins
nature of electrode, applied potential, additives, etc.) with the goal
of maximizing the difference in overpotentials between the reacting
molecules.18
Acknowledgment. We thank the National Science and Engi-
neering Research Council (NSERC), Canada Foundation for
Innovation, ORDCF, and the University of Toronto for financial
support. Andrei Yudin is a Cottrell Scholar of Research Corporation.
We are grateful to Professors M. G. Finn, Robert H. Grubbs, and
K. Barry Sharpless for reading the manuscript, helpful discussions,
and encouragement. Ms. Shahla Yekta and Mr. Yu Chen are
acknowledged for preparing some of the olefins (entries 12-14).
Supporting Information Available: Experimental procedures and
characterization data for the aziridines (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
References
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(14) Preliminary mechanistic investigation indicates that this electrochemical
aziridination is stereospecific. For instance, aziridination of the benzyl
ether of cis-2-hexen-1-ol resulted in exclusive formation of the cis-
aziridine. In addition, phthalimide has been identified as the only byproduct
of this reaction (for a study of nitrene decompositionn pathways that lead
to phthalimide, see: Hoesch, L.; Koppel, B. HelV. Chim. Acta 1981, 84,
864). Although other mechanistic possibilities cannot be ruled out at this
point, these observations support a nitrene intermediate.
a Reaction was conducted at 0 °C. b 2:1 ratio of diastereomers. c 4.4:1
ratio of diastereomers.
can be performed on a multigram scale, and even larger scales
should be accessible using readily available flow cells.3a A wide
variety of substrates other than olefins can also be considered as
suitable nitrene acceptors.16 Other amines or hydrazines may also
be used as precursors to nitrene transfer agents and are within the
scope of our future studies.
In summary, our study illustrates the possibility of a rational
approach that bypasses the requirement for stoichiometric amounts
of toxic oxidants and metal additives in organic redox reactions.17
The continuum of redox potentials provided by electrochemistry
and the possibility of differentiating substrates on the basis of their
overpotentials should be a guide to other examples of highly
selective and practical organic reactions. It is now possible to
develop a set of guidelines for emulating a variety of metal-based
redox processes via optimization of reaction conditions (such as
(15) Silver wire pseudo-reference electrode was calibrated against the ferrocene/
ferricinium couple in the electrolysis medium (Epa ) 0.47 V, Epc ) 0.30
V).
(16) Our preliminary results indicate that under similar conditions a variety of
sulfoxides participate in a highly efficient sulfoximination reaction.
(17) Ironically, the industrial origin of all readily available inorganic oxidants
is electrochemistry. For instance, approximately 3% of electricity in the
United States is spent annually on the production of chlorine.
(18) The aziridination reaction did not take place when the platinum anode
was replaced by graphite. In a marked contrast to the platinum case, our
CV study on carbon revealed that anodic current corresponding to the
background oxidation of cyclohexene (-5.3 µA) was comparable to the
current corresponding to the oxidation of N-aminophthalimide (-15.6 µA).
Such a small difference in the rate of electrochemical oxidation apparently
does not secure high selectivity in olefin aziridination.
JA0172215
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