Oxime Ether Radical Cations Stabilized by N-Heterocyclic Carbenes

Article abstract of DOI:10.1002/anie.201710530

N-heterocyclic carbene (NHC) nitric oxide (NHCNO) radicals, which can be regarded as iminoxyl radicals stabilized by NHCs, were found to react with a series of silyl and alkyl triflates to generate the corresponding oxime ether radical cations. The structures of the resulting oxime ether radical cations were determined by X-ray crystallography, along with EPR and computational analysis. In contrast, lutidinium triflate produced a 1:1 mixture of [NHCNO⁺][OTf^?] and [NHCNHOH⁺][OTf^?] upon the reaction with NHCNO. This study adds an important example of stable singlet carbenes for stabilizing main-group radicals because of their π-conjugating effect, the synthesis and structures of which have not been reported previously.

Full text of DOI:10.1002/anie.201710530

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Accepted Article
Title: Oxime Ether Radical Cations Stabilized by N-Heterocyclic
Carbene
Authors: Youngsuk Kim, Kimoon Kim, and Eunsung Lee
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Oxime Ether Radical Cations Stabilized by N-Heterocyclic
Carbene
Youngsuk Kim,[a,b] Kimoon Kim,[a,b,c] and Eunsung Lee*[a,b,c]
Abstract: N-heterocyclic carbene nitric oxide (NHCNO) radicals,
which can be regarded as iminoxyl radicals stabilized by NHCs, were
found to react with a series of silyl and alkyl triflates to generate the
corresponding oxime ether radical cations. The structures of the
resulting oxime ether radical cations were determined by X-ray
crystallography, along with EPR and computational analysis. In
contrast, lutidinium triflate produced a 1:1 mixture of [NHCNO+][OTf–]
and [NHCNHOH+][OTf–] upon the reaction with NHCNO. This study
adds an important example of stable singlet carbenes stabilizing main
group radicals due to their π-conjugating effect, the synthesis and
structures of which have never been elucidated previously.
radical cations and oxime ether radical cations had never been
isolated or characterized, and were only proposed as
intermediates of various photochemical reactions of oximes and
oxime ethers.[6]
Exploring the nature of highly reactive species is always a
common interest of chemists. In particular, radicals are one of the
most important reactive species in the field of chemistry and
biology. In general, the vast majority of radicals are
thermodynamically and kinetically unstable; therefore, the
isolation and structural characterization of novel radicals has
remained a challenge.
Scheme 1. Examples of structurally characterized NHC-stabilized main group
radical cations. (Dipp = 2,6-diisopropylphenyl; Bu = tert-butyl; Pr = isopropyl;
t
i
Carbenes, having the general formula R2C:, are another very
reactive species of interest.[1] Although carbenes were
traditionally considered as highly unstable species because of
their coordinative unsaturation and incomplete octet, numerous
stable carbenes are now being synthesized and applied in various
fields, thanks to the pioneering discoveries of Bertrand’s and
Arduengo’s singlet carbenes.[2] Very interestingly, singlet
carbenes offer a versatile platform for stabilizing reactive
species.[3] One of the most common singlet carbenes, N-
heterocyclic carbenes (NHCs), can stabilize reactive species by
donating electrons, which has led to the successful isolation and
characterization of several reactive radicals.
Radical cations are of particular interest because they occur
as transient species mainly in electron transfer reactions, or in
several ionization techniques for mass spectrometry.[4] With the
aid of NHCs, boryl, silyl, and phosphoryl radical cations were
successfully characterized including X-ray crystal structures
(Scheme 1).[5] Herein, we report the synthesis and
characterization of oxime ether radical cations H from the addition
of different electrophiles to the parent radical. Previously, oxime
TMS = trimethylsilyl; TIPS = triisopropylsilyl)
Recently, our group reported the synthesis and
characterization of the stable N-heterocyclic carbene stabilized
nitric oxide radicals (NHCNOs).[7] Interestingly, NHCNO 1 reacts
with trimethylsilyl triflate (TMSOTf) or triisopropylsilyl triflate
(TIPSOTf) to generate the corresponding radical cations 2a or 2b,
respectively (Scheme 2). This reactivity resembles the addition of
various reagents to N-heterocyclic carbene nitrous oxides
(NHCN2O), which was intensively studied by the Severin group.[8]
When 1 was treated with a stoichiometric amount of silyl triflate in
THF solution under N2 atmosphere, the color of the reaction
mixture changed immediately to dark brown. The product was
crystallized by addition of pentane, and subsequently washed
with pentane to yield 2a or 2b as a brown solid. The structure of
the radical cations 2a and 2b were unambiguously determined by
X-ray crystallography (Figure 1a,b). The C1–N3 bond length of
2a (1.334(4) Å) and 2b (1.332(5) Å) is slightly shorter than that of
1 (1.350(6) Å), and N3–O1 bond length is slightly longer in 2a
(1.358(3) Å) and 2b (1.363(4) Å ) than 1 (1.309(5) Å), while both
bond lengths indicate a bond order of 1.5. The O1–Si1 bond
length of 2b (1.747(3) Å) is slightly longer than that of 2a (1.734(2)
Å) presumably due to the large size of the triisopropylsilyl group.
The (imidazole ring)–N–O–Si groups of 2a and 2b are planar,
which suggests delocalization of the radical through π-
conjugation. The molecular structures of 2a and 2b are also in
good agreement with the structures from density functional theory
(DFT) calculations at B3LYP/6-31G(d,p) level of theory. The
calculated Wiberg bond orders for C1–N3 (1.51 for both 2a and
2b), N3–O1 (1.46 for 2a; 1.48 for 2b), and O1–Si1 (0.83 for 2a;
0.80 for 2b) are consistent with the bond length data from the
single crystal X-ray structure analysis.
[a]
Y. Kim, K. Kim, Prof. E.Lee
Center for Self–assembly and Complexity
Institute for Basic Science (IBS)
Pohang, 37673, Republic of Korea
E-mail: eslee@postech.ac.kr
[b]
[c]
Y. Kim, K. Kim, Prof. E.Lee
Department of Chemistry
Pohang University of Science and Technology
Pohang, 37673, Republic of Korea
K. Kim, Prof. E.Lee
Division of Advanced Materials Science
Pohang University of Science and Technology
Pohang, 37673, Republic of Korea
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201710530
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also shows that the singly occupied molecular orbitals (SOMOs)
of 2a and 2b are both delocalized through molecular plane
(Figure S8). The radical cations 2a and 2b are moisture-sensitive,
and should be stored under inert atmosphere of nitrogen. They
slowly decompose in ambient atmosphere to generate a mixture
of
imidazolium
salt
(IPrH+OTf–;
1,3-bis(2,6-
diisopropylphenyl)imidazolium triflate) and other unidentified
products. In the presence of an excess amount of water, 2a
decomposes to give the imidazolium salt (IPrH+OTf–) in 91%
isolated yield.
Scheme 2. Syntheses of the Radical Cations 2 and 3. a. Isolated yields.
Up to date, there have been no report of nucleophilic reactivity
of iminoxyl radicals, while the nucleophilic addition of aminoxyl
radicals to Lewis acids are well studied. For example, TEMPO
((2,2,6,6-tetramethylpiperidin-1-yl)oxyl radical) reacts with neutral
electrophiles such as FeCl3, AlCl3, and B(C6F5)3 to form neutral
radical adducts.[9] In contrast to aminoxyl radicals, both nitrogen
and oxygen atom of iminoxyl radicals may act as a nucleophilic
center. DFT calculations at B3LYP/6-31G(d,p) level of theory
revealed that O-addition is thermodynamically more favorable
than N-addition by 19.8 kcal/mol for TMS derivatives. This is
presumably due to both steric hindrance and oxophilic nature of
silicon.
After the isolation and characterization of the NHC-stabilized
silyl oxime ether radicals 2a and 2b, we wanted to expand this
reactivity between NHCNO 1 and silicon electrophiles toward
lighter, carbon analogues. In a manner similar to the synthesis of
2, methyl (3a) and isopropyl (3b) analogues were successfully
isolated (Scheme 2). The experimental EPR spectra of 3a and 3b
in benzene solution was well matched with the simulated spectra
of the expected products (Figure 2), suggesting that the reactivity
between NHCNOs and silicon electrophiles can indeed be
expanded to analogous carbon electrophiles. Unfortunately,
attempts to grow single crystals of 3a for X-ray crystallography
were unsuccessful, but single crystals of 3b were successfully
obtained after slowly layering pentane into the reaction mixture.
The C1–N3 bond length (1.345(2) Å) and N3–O1 bond length
(1.353(2) Å) of 3b indicate a bond order of 1.5, while DFT
calculation also revealed the bond order of 1.51 and 1.45 for C1–
N3 and N3–O1, respectively. SOMOs of 3a and 3b from DFT
calculation were delocalized through the molecular plane, similar
to the silyl analogues (Figure S8). The experimental EPR
spectrum of 3b shows 14 peaks, while 3a shows 16 peaks due to
the additional hyperfine interaction with the nearby methyl
hydrogens.
Figure 1. Characterization of the radical cations 2a and 2b. (a) Molecular
structure of 2a and (b) 2b from X-ray crystallography. The thermal ellipsoids are
set at a 50% probability level. Triflate anions were omitted for clarity. (c)
Experimental (bottom) and simulated (top) EPR spectra of 2a (g = 2.0083;
hyperfine coupling constants: a(14N) = 27.1, 9.5, 7.7 MHz, a(1H) = 10.5, 6.8
MHz) and (d) 2b (g = 2.0092; hyperfine coupling constants: a(14N) = 26.7, 9.6,
7.9 MHz, a(1H) = 10.3, 6.4, 1.5, 1.5, 1.5 MHz). See the Supplementary
Information for the details.
The electronic structure of the radical cations 2a and 2b were also
confirmed by electron paramagnetic resonance (EPR)
spectroscopy (Figure 1c,d). The experimental EPR spectra were
recorded using saturated benzene solution of the radical cations
at room temperature. The EPR signals of 2a and 2b were very
similar; they both split to 13 peaks mainly due to the coupling with
three nitrogen atoms and several hydrogen atoms. The hyperfine
coupling constants for 2a were calculated to be a(14N) = 27.1, 9.5,
7.7 MHz; a(1H) = 10.5, 6.8 MHz. DFT calculations suggest that
N3 has larger hyperfine coupling constant than other nitrogen
atoms, in consistent with the largest spin density on N3 (50%). It
is notable that the vinyl protons of the imidazole ring show
significant contribution on the hyperfine coupling, which confirms
the stabilization power of NHC by spin delocalization. Calculation
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Figure 3. Cyclic voltammogram of 2a and 3b. Recorded using dry and
degassed THF solution (0.1 M NBu4PF6 as electrolyte; potential versus
saturated Ag/AgCl; scan rate = 0.5 V/s).
Scheme 3. One-electron Reduction of 2a. a. Isolated yield.
Figure 2. Characterization of the radical cations 3a and 3b. (a) Molecular
structure of 3b from X-ray crystallography. The thermal ellipsoids are set at a
50% probability level. Triflate anions were omitted for clarity. (b) Experimental
(bottom) and simulated (top) EPR spectra of 3a (g = 2.0094; hyperfine coupling
constants: a(14N) = 26.1, 9.2, 7.2 MHz, a(1H) = 11.1, 7.1, 6.3, 6.3, 6.3 MHz) and
(c) 3b (g = 2.0096; hyperfine coupling constants: a(14N) = 25.7, 9.1, 7.3 MHz,
a(1H) = 10.3, 9.3, 6.5, 1.5 MHz). See the Supplementary Information for the
details.
The isolation of both silyl oxime ether radical cations 2a–b, and
alkyl oxime ether radical cations 3a–b encouraged us to attempt
the synthesis of the unprotected oxime radical cation 5 (Scheme
4). However, reaction of 1 with neither triflic acid (HOTf) nor
lutidinium triflate (LutHOTf) afforded 5, as the products from both
reactions exhibited no EPR signal. Instead of the radical cation 5,
the reaction between 1 and a stoichiometric amount of LutHOTf
resulted in
a 1:1 mixture of two non-radical products:
[IPrNO+][OTf–] (6) and [IPrNHOH+][OTf–] (7). It is notable that this
reactivity resembles the disproportionation of aminoxyl radicals
triggered by strong acids.[10] Both 6 and 7 were obtained in 37%
yields as measured by 1H NMR, and characterized by high
resolution mass spectrometry. Although the isolation of 6 or 7 in
reasonable yields was not successful, we were able to obtain their
single crystals suitable for X-ray crystallography, and so
confirmed the structures of both 6 and 7 (Figure 4).
The cyclic voltammogram of 2a and 3b showed one reversible
redox peak at E1/2 = 0.406 V and 0.563 V, respectively, versus
Ag/AgCl (saturated) electrode, which indicates that one-electron
reduction reactions of the radical cations are possible (Figure 3).
Compared to 2a, 3b has a higher oxidizing power, as expected
for the isopropyl group being a weaker electron-donor than the
trimethylsilyl group. These results suggest the potential
application of the oxime ether radical cations as a tunable organic
oxidant since the redox potential of the radicals can be easily
adjusted by changing either the electrophile or the NHC. It is
notable that their reduction potential is comparable or higher than
conventional one-electron oxidants such as ferrocenium (0.44 V)
and tetracyanoethylene (0.17 V).
To verify the redox behavior of the radical cations, a THF
solution of 2a was treated with 1.1 equivalents of ferrocene as a
one–electron donor (Scheme 3). The color of the reaction mixture
changed from dark brown to dark green, and after work up, neutral
oxime ether 4 was isolated in 66% yield and successfully
characterized.
Scheme 4. Attempted Synthesis of the Oxime Radical Cation 5. a. 1H NMR
yields obtained from a mixture of 6 and 7.
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radiation was performed at the Pohang Accelerator Laboratory
(Beamline 2D and 6D). We thank Gregory B. Boursalian and
Dmitry V. Yandulov for helpful discussions.
Keywords: carbenes • iminoxyl radicals • nucleophilic addition •
radical cations • radicals
Figure 4. (a) Molecular structure of 6 and (b) 7 from X-ray crystallography. The
thermal ellipsoids are set at a 50% probability level. Triflate anions, solvent
molecules (toluene), and minor disorders were omitted for clarity. Bond lengths
and bond angles are described in the Supplementary Information.
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In summary, we have presented the synthesis of silyl and alkyl
oxime ether radical cations 2 and 3, from the reaction of the NHC-
stabilized nitric oxide radical 1 with silicon or carbon electrophiles,
respectively. Single crystal X-ray and computational studies
suggest that the spin density of compounds 2 and 3 are
delocalized over the molecular plane. The well-defined 1e redox
behavior suggests the potential application of the radical cations
as a tunable organic oxidant. On the other hand, the reaction of 1
toward a simple proton yielded a 1:1 mixture of NHC-bound
nitrosyl (6) and hydroxylamine (7) derivatives. This work is the first
demonstration of the nucleophilicity of iminoxyl radicals, which
extends our understanding of the reactive radical species, and
was enabled by the aid of the novel properties of N-heterocyclic
carbenes. The reactivity of the iminoxyl radicals toward other
interesting electrophiles is now under active investigation.
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Acknowledgements
This work was supported by the Institute for Basic Science (IBS)
[IBS-R007-D1]. X-ray diffraction experiment with synchrotron
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Nucleophilic addition of NHC-stabilized nitric oxide radical (NHC–NO) to silyl and
alkyl triflates generate silyl and alkyl oxime ether radical cations. In addition,
disproportionation occurs when NHCNO reacts with lutidinium triflate, generating
NHC-stabilized nitrosyl cation (NHC–NO+) and a hydroxylamine derivative (NHC–
NHOH+).
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