Bottleable (amino)(carboxy) radicals derived from cyclic (alkyl)(amino) carbenes

Article abstract of DOI:10.1021/ja4104765

Monomeric (amino)(carboxy) radicals were synthesized in two steps: the addition of a stable cyclic (alkyl)(amino) carbene to an acyl chloride, followed by a one-electron reduction. Their stability toward dimerization also allows for the synthesis of related bi- and triradicals.

Full text of DOI:10.1021/ja4104765

Communication
pubs.acs.org/JACS
Bottleable (Amino)(Carboxy) Radicals Derived from Cyclic
(Alkyl)(Amino) Carbenes
Janell K. Mahoney,† David Martin,† Curtis E. Moore,‡ Arnold L. Rheingold,‡ and Guy Bertrand*,†
†UCSD-CNRS Joint Research Laboratory (UMI 3555), Department of Chemistry and Biochemistry, University of California, San
Diego, La Jolla, California 92093-0343, United States
‡UCSD Crystallography Facility, San Diego, La Jolla, California 92093-0343, United States
S
* Supporting Information
In recent years, stable carbenes11 have emerged as efficient
ABSTRACT: Monomeric (amino)(carboxy) radicals
were synthesized in two steps: the addition of a stable
cyclic (alkyl)(amino) carbene to an acyl chloride, followed
by a one-electron reduction. Their stability toward
dimerization also allows for the synthesis of related bi-
and triradicals.
tools for the preparation of stable main-group-based radicals
and diradicals.12,13 Recently we made the first foray into the
realm of purely organic radicals. Using an anti-Bredt
diaminocarbene,14 we synthesized the air-stable oxyallyl radical
cation IV,15 in which the oxygen atom is the principal spin
density carrier. On the other hand, Fukuzumi et al. reported the
observation of thiazolylidene carbene-based radicals V by EPR.
These compounds, which were generated in situ by electro-
oxidation of the corresponding enolate, decomposed within
hours at room temperature.16 Based on these results, we
decided to investigate the stability of related radicals built on
(alkyl)(amino)carbenes (CAACs).17 Herein, we report the
synthesis and the first structural study of a monomeric
(amino)(carboxy) radical. Our synthetic approach is simple
and versatile, as demonstrated by the straightforward synthesis
and isolation of related bi- and triradicals.
ersistent organic paramagnetic species have found
P
numerous applications, ranging from synthetic chemistry
(radical polymerization, oxidative catalysis) to medicine and
material science.1 Most of the known storable organic radicals
are heteroatom-centered. Apart from a few exceptions, such as
triarylmethyl radicals or highly π-delocalized phenalenyl
systems, carbon-centered radicals are observable, but non-
isolable as well-defined monomeric paramagnetic species.2 The
difference in stability is mainly due to the strength of C−C
bonds, which is significantly higher (83 kcal·mol−1) than those
of O−O, N−N, and S−S bonds (35, 38, 54 kcal·mol−1
respectively)3 and, thus, favors dimerization processes. It is
well-known that captodative substitution around a carbon
radical center can significantly decrease the strength of the C−
C bond,4−6 but not to the extent of allowing for isolation of
well-defined monomers. The 2-oxomorpholin-3-yl radical I is a
classical example (Scheme 1).7,8 Although the captodative
A precursor was readily synthesized by adding benzoyl
chloride to a THF solution of CAAC 1 at −78 °C (Scheme 2).
Scheme 2
Scheme 1
After workup, iminium salt 2a was isolated in 81% yield and
fully characterized, including a single crystal diffraction study
(Figure 1). The cyclic voltammogram of 2a features two
reversible reduction waves (E = −0.93 V and −1.86 V, against
Fc+/Fc), for the formation of the radical and the enolate,
respectively (see, Supporting Information). Half an equivalent
of tetrakis(dimethylamino)ethylene (TDAE) (E ≈ −1.2 V)18
was added to a solution of 2a in dichloromethane at −78 °C,
and after workup 3a was isolated in 94% yield, as deep red
crystals.
association of amino and carboxy groups is optimal, only the
dimeric form II could be isolated. Nonetheless the dimerization
is a reversible process; dissolution of II in well-degassed
solvents yields small, but detectable, amounts of I with
dissociation constants up to 10−9 M. Note that dimerization
of glycyl radicals III can be prevented when they are sheltered
in enzymes.9,10
A single crystal X-ray diffraction study revealed that the N1,
C1, C2, and O1 atoms are coplanar, as expected from the
captodative stabilization (Figure 1). Note that this conjugated
Received: October 18, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ja4104765 | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
Scheme 3
Figure 1. X-ray structure of 2a (left) and 3a (right). Hydrogen atoms,
solvent molecules, and the chloride anion (for 2a) were omitted for
clarity.
π-system is orthogonal to the phenyl group, in contrast with the
precursor 2a, in which the iminium moiety is orthogonal to the
planar benzoyl group. In addition, there is a significant
shortening of the C1−C2 bond [2a: 1.521(2), 3a: 1.429(2)
Å] and a lengthening of the N1−C1 [2a: 1.292(2), 3a:
1.3601(19) Å], C2−O1 [2a: 1.217(2), 3a: 1.2587(18) Å], and
C2−C3 bonds [2a: 1.465(2), 3a: 1.507(2) Å].
The SOMO of 3a (B3LYP/6-311g** level of theory) is a
bonding combination of the π*(CO) molecular orbital and the
LUMO of the carbene, with significant electronic density on all
conjugated atoms (Figure 2).19 The delocalization of the spin
Figure 3. X-ray structure of 3b (top) and 3c (bottom). Hydrogen
atoms and solvent molecules, as well as isopropyl and ethyl
substituents in the case of 3c, are omitted for clarity.
Figure 2. Left: Representation of the SOMO of 3a (isosurfaces at 0.05
au). Right: X-band EPR spectra of 3a in benzene at room temperature.
and 16.8 MHz, respectively). These preliminary data are in line
with the expected weak electron exchange couplings in
polyradicals 3b−c, which feature nonconjugating spacers, and
radical units far away from each other (C1−C1′ distances range
from 6.60 to 7.40 Å).20
To summarize, cyclic (alkyl)(amino)carbenes afford in two
simple steps (amino)(carboxy)radicals, which do not dimerize
and could be characterized for the first time by X-ray
diffractometry as monomeric species. Radicals 3a−c have
been stored at room temperature, in solution, and as a solid, for
weeks under an inert atmosphere without any apparent
decomposition. These results as a whole demonstrate that
(amino)(carboxy) radicals have now to be considered as stable
monomeric paramagnetic building blocks, similarly to verdazyl
and nitroxyl radicals.
density across the iminium and carbonyl moieties, which is a
consequence of the captodative stabilization, was confirmed by
calculations (see Supporting Information for a detailed
discussion). About 40% of the spin density is localized on the
C1 carbon atom, which is the principal spin carrier, whereas
about 28% is localized on O1, 24% on N1, 6% on C2, and less
than 2% on the phenyl group.
Our synthetic strategy affords in principle an easy entry to a
plethora of (amino)(carboxy) radicals from the corresponding
acyl chlorides. In order to showcase the versatility of the
method, we reacted CAAC 4 with terephthaloyl and trimesoyl
chlorides, respectively. The resulting di- and trichloride salts 2b
and 2c were obtained in 67% and 58% yield, respectively
(Scheme 3). Reduction with TDAE afforded the corresponding
bi- and triradicals 3b and 3c. X-ray diffraction studies revealed
structures similar to that of 3a, the phenyl linker being
orthogonal to the (amino)(carboxy) radical units (Figure 3).
The X-band EPR spectra of 3a−c in solution at room
temperature are similar. They feature a triplet with close g
values (2.0039, 2.0040, and 2.0040, respectively) and isotropic
hyperfine coupling constants with nitrogen (aN = 15.4, 16.8,
ASSOCIATED CONTENT
■
S
* Supporting Information
Full experimental details and X-ray crystallographic data for
2a−b and 3a−c. This material is available free of charge via the
Internet at http://pubs.acs.org.
B
dx.doi.org/10.1021/ja4104765 | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
(f) Jarling, R.; Sadegh, M.; Drozdowska, M.; Lahme, S.; Buckel, W.;
Rabus, R.; Widdel, F.; Golding, B. T.; Wilkes, H. Angew. Chem., Int. Ed.
2012, 51, 1334.
AUTHOR INFORMATION
Corresponding Author
guybertrand@ucsd.edu
■
(11) For reviews, see: (a) Bourissou, D.; Guerret, O.; Gabbaï, F. P.;
Notes
Bertrand, G. Chem. Rev. 2000, 100, 39. (b) Vignolle, J.; Cattoen, X.;
̈
Bourissou, D. Chem. Rev. 2009, 109, 3333. (c) Melaimi, M.;
Soleilhavoup, M.; Bertrand, G. Angew. Chem., Int. Ed. 2010, 49,
8810. (d) Droege, T.; Glorius, F. Angew. Chem., Int. Ed. 2010, 49,
6940. (e) Martin, D.; Melaimi, M.; Soleilhavoup, M.; Bertrand, G.
Organometallics 2011, 30, 5304. (f) Hahn, F. E.; Jahnke, M. C. Angew.
Chem., Int. Ed. 2008, 47, 3122. (g) N-Heterocyclic carbenes, from
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Thanks are due to the NSF (CHE-1316956) for financial
support and M. Melaimi, M. Angelella, and M. Tauber for
assistance with EPR experiments. D.M. acknowledges the
Extreme Science and Engineering Discovery Environment
(XSEDE), which is supported by the NSF (OCI-1053575).
laboratory curiosities to efficient synthetic tools; Díez-Gonzal
Royal Society of Chemistry Publishing: Cambridge, 2011.
́
ez, S., Ed.;
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