Enantiopure and racemic chiral nitronyl nitroxide free radicals: Synthesis and characterization

Article abstract of DOI:10.1002/ejoc.200400454

A synthetic route to a series of homochiral (and achiral) nitronyl nitroxides derived from rac-(and meso)-3,4-dimethyl-3,4-dinitrohexane is described. The two forms of this precursor, meso and rac, were identified unambiguously and reduced to the correspo

Full text of DOI:10.1002/ejoc.200400454

FULL PAPER
Enantiopure and Racemic Chiral Nitronyl Nitroxide Free Radicals: Synthesis
and Characterization
[a]
[a]
[b]
[b]
´
Catherine Hirel, Jacques Pecaut, Sylvie Choua, Philippe Turek,
David B. Amabilino,[c] Jaume Veciana,[c] and Paul Rey*[a]
Keywords: Chirality / Imidazolidine / Magnetism / Nitroxide
A synthetic route to a series of homochiral (and achiral) nitro-
nyl nitroxides derived from rac-(and meso)-3,4-dimethyl-3,4-
cursors by condensation with aldehydes, followed by oxida-
tion. Their structural properties were compared to those of
dinitrohexane is described. The two forms of this precursor, their achiral meso counterparts and it was found that the
meso and rac, were identified unambiguously and reduced to puckering of the five-membered ring is dependent on the
the corresponding meso- and rac-diamines. The rac-diamine chirality of the imidazolyl unit. The radicals show marked
was condensed with an enantiopure aldehyde specifically
designed to give a diastereomeric mixture of imidazolidines
easily separated by flash chromatography. Both enantiopure
diamines were then obtained by acidic hydrolysis of these
imidazolidines. The absolute configurations of the diamino
precursors were determined by X-ray crystallography of
optical activity, as explored by polarimetry and circular di-
chroism spectroscopy. These paramagnetic building blocks
of known absolute configuration include chiral centers adja-
cent to the oxyl groups, and since they exhibit C2 symmetry
they are well suited for coordination chemistry studies be-
cause stereochemical complexity is minimized. They have
been specifically designed for further developments of the
metal-radical approach to molecular magnetic materials.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
single crystals of
a
manganese(II
)
complex [(R,R,R)-
5E·Mn(hfac)2] of a nitroxide containing a third chiral center
of known configuration. A series of homochiral nitronyl nitro-
xides was then prepared from the enantiopure diamino pre- Germany, 2005)
synthetic developments,[8] any aldehyde may give rise to a
nitronyl nitroxide, and hundreds of these nitroxides dif-
Introduction
During the two last decades there has been intense inter- fering in substitution at position 2 of the imidazolyl ring
est in molecular structures exhibiting magnetic properties.[1] have been prepared (Scheme 1). Such ease of structural
Different arrangements of spin carriers have been achieved variation (in combination with high stability) is mainly re-
by several strategies, among which the purely organic and sponsible for their popularity as spin carriers. Most of the
the metal-organic approaches based on nitroxide free rad- spin density, for example, is localized on the two oxyl (or
icals have proven particularly rewarding.[2] Indeed, use of oxyl and imino) groups, but its distribution depends upon
these organic spin carriers has resulted in fascinating molec- the overall chemical structure and may involve numerous
ular species exhibiting unprecedented magnetic properties: other parts of the molecule.[9] Magnetic engineering of pu-
purely organic ferromagnets,[3] ferrimagnetically ordered rely organic species therefore benefits from the fact that de-
metal-nitroxide extended species,[2,4] molecular spin-tran- localization may increase the possibilities of magnetic coup-
sition copper(ii) nitroxide clusters,[5] and high-spin mol- ling through numerous pathways and consequently the
ecules related to single-molecule magnets.[6]
chance of bulk ordering. In the designing of nitroxide-con-
Among all the characterized nitroxide free radicals, ni- taining metal complexes, nitronyl and imino nitroxides
tronyl and imino nitroxides (Scheme 1) deserve special men- bring the advantages both of their bridging character and
tion. According to Ullman’s pioneering work,[7] and recent of the potential to introduce coordination sites in chelating
positions relative to the oxyl groups, which result in high-
dimensional molecular structures.[10]
[a]
´
CEA-Grenoble, Departement de Recherche Fondamentale sur
`
´
la Matiere Condensee, Service de Chimie Inorganique et
Biologique, Laboratoire de Chimie de Coordination,
17 rue des Martyrs, 38054 Grenoble cedex 09, France
E-mail: prey@cea.fr
Current trends in magneto-chemistry are giving import-
ance to chiral molecular structures, and organic spin car-
riers such as nitroxides are well suited as potential precur-
sors of such structures. Expected applications of chiral ni-
tronyl nitroxides in magneto-chemistry might be illustrated
as follows.
[b]
[c]
´
Institut Charles Sadron, Universite Louis Pasteur,
6 rue Boussingault, B. P. 40016, 67083 Strasbourg cedex, France
`
Institut de Ciencia de Materials de Barcelona (CSIC),
Campus Universitari, 08193 Bellaterra, Spain
348
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400454
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Enantiopure and Racemic Chiral Nitronyl Nitroxide Free Radicals
FULL PAPER
(iv) All nitroxide-containing materials would be obtained
in forms suitable for optical investigations such as magneto-
chiral dichroism studies.[12]
In nitroxide free radicals, most of the interesting proper-
ties (structural, magnetic, optical) originate from the un-
usual open-shell electronic structure of the nitroxyl
group.[13] If one is interested in the effect of chirality on
these properties, one should try to introduce a chiral center
as close as possible to the oxyl group carrying most of the
unpaired spin. In the design of metal-organic molecular
magnetic materials, for example, introduction of chiral cen-
ters close to the coordination sites offers more chance of
influencing the configuration of the bound metal center. Al-
though chiral nitroxides are described in several reports,[14]
only a few are devoted to nitronyl nitroxides and their metal
complexes, and most describe nitronyl nitroxides containing
chiral centers very remote from the oxyl sites.[15] A couple
of nitronyl nitroxides suitably substituted α to the nitroxyl
group in the 4-(or 5-)position have been described, but their
coordination properties have not been reported.[16] It may
be anticipated they should be complicated, owing to the
presence of two different coordination sites.
From these considerations and in view of the numerous
potential applications, an ideal chiral nitronyl nitroxide li-
gand should retain equivalence of the two coordination
sites in order to minimize stereochemical problems and
should also retain the functional potential of the 2-position
in the imidazolyl ring, which has critical importance for the
design of specific molecular structures. Asymmetry should
therefore be introduced at positions 4 and 5. Accordingly,
we considered the highly ‘‘symmetrical’’ (C2) precursor 3,4-
dimethyl-3,4-dinitrohexane, the synthesis of which had al-
ready been described.[17] In addition to chiral species, this
system also affords an achiral meso series, which should be
very useful for testing the effect of chirality by comparison
with achiral ligands with similar steric requirements. Here
we describe the synthesis, enantiomeric resolution, and
absolute configuration of a precursor (the diamino deriva-
tive), together with the synthesis and structural, magnetic,
and optical characterization of meso and chiral nitroxide
Scheme 1. Synthetic strategy for chiral, C2, nitronyl nitroxides; a)
LiOMe/I2, b) Sn/HCl, c) RCHO/Et2O, d) mCPBA/Et2O, NaNO2/
HCl/CH2Cl2/H2O, e) NaNO2/H2O, HCl
(i) In purely organic nitroxide-based magnetic materials, ligands of the type described in Scheme 1.
the nature and magnitude of the intermolecular interactions
are obviously dependent on crystal packing. Enantiopure
Results and Discussion
nitroxides would afford materials crystallizing in chiral
space groups and would give opportunities to characterize
new exchange pathways.
Syntheses
(ii) The few copper(ii) complexes to exhibit molecular
As stated above, one aim of this study was to preserve
spin transition behavior have centro-symmetric cyclic struc- the potential of the 2-position in the imidazolyl ring for
tures.[5] Hopefully, chiral nitroxides could afford helical infi- designing specific chiral nitroxide building blocks, to intro-
nite arrays possessing different transition temperatures and duce asymmetric centers in positions 4 and 5 and thus to
large hysteresis.
obtain a series of homochiral radicals. Therefore, resolution
(iii) Chirality governs the dimensionality of polymetallic of a racemic precursor should be performed before conden-
complexes that could be built from bis(chelating) ligands.[11] sation with an aldehyde (Scheme 1). Accordingly, Ullmann’s
In the recently reported two-dimensional manganese(ii) synthesis involving the bis(hydroxylamino) intermediate
complexes of bis(chelating) nitronyl nitroxides,[10] use of en- was not used, because neither the dinitro nor the bis(hyd-
antiopure ligands would probably produce a three-dimen- roxyamino) compounds would be good candidates for en-
sional structure displaying a different ordering tempera- antiomeric separation. Indeed, diastereomeric derivatives of
ture.
the former would be hard to design, and the latter would
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349

´
C. Hirel, J. Pecaut, S. Choua, P. Turek, D. B. Amabilino, J. Veciana, P. Rey
FULL PAPER
be unlikely to survive an extensive workup in solution and was achieved by X-ray crystallography of the rac form,
chromatographic processing. In contrast, numerous dia- which crystallized as a racemic compound.
stereomeric derivatives of the highly stable diamino com-
The Diamino Compounds
pounds can be prepared, giving consistency to the synthetic
strategy described in Scheme 1.
Reduction of the pure meso and rac dinitro species af-
Although all synthetic steps involved in the preparation fords the corresponding diastereomers of the diamino com-
of these new nitroxide free radicals are well established, the pound 3.[17] Their stereochemistry is therefore well estab-
stereochemical diversity justifies a detailed report of the dif- lished, and our efforts concentrated on the resolution of the
ferent compounds.
rac form into pure enantiomers and on the assessment of
their absolute configurations.
The Dinitro Compounds
It is notable that the hydrochloride of rac-3, of which
the crystal structure was determined, exhibited spontaneous
resolution, but this behavior had only marginal separation
value and was not further investigated. Attempts to obtain
diastereomeric salts with (ϩ)-tartaric, (Ϫ)-mandelic, and
(ϩ)-dibenzoyltartaric acids were fruitless; although en-
richment was observed after two crystallizations, it soon be-
came apparent that the yield would be so low that the
method would not have practical value for obtaining en-
antiopure nitroxides in quantities large enough for a study
of their coordination properties.)
Accordingly, we took advantage of previous studies
describing the reversible formation of imidazolidines and
the availability of chiral aldehydes that should undergo con-
densation with rac-3 to afford separable mixtures of dia-
stereomers. Among the chiral aldehydes used for this pur-
pose, (S)-(Ϫ)-O-(tert-butyldiphenylsilyl)acetaldehyde gave a
1:1 mixture of diastereomeric imidazolidines (S,S,S)-2 and
(S,R,R)-2, which were easily separated by flash chromatog-
raphy (SiO2, diethyl ether).[18] Worthy of note is the fact
that neither the benzyl analogue nor the commercially avail-
able (ϩ)-myrtenal gave satisfactory results. Recovery of the
free base [(S,S)-3 or (R,R)-3] was performed by hydrolysis
in 10% hydrochloric acid according to published pro-
cedures.[19] The enantiomeric purities both of the dia-
stereoisomeric imidazolidines and of the enantiopure diam-
ines were checked by NMR spectroscopy.
Although the dinitro compounds meso-1 and rac-1 (and
also the diamino compounds meso-3 and rac-3) had been
described previously,[17] they had been poorly characterized
and their stereochemistry was not firmly established. The
pure meso and rac forms were isolated by chromatography
on SiO2, which we adapted for large-scale preparations.
Stereochemical characterization was performed by NMR
spectroscopy and confirmed by X-ray crystallography. The
prominent feature in the NMR spectra of the two isomers
arises from the methylene groups, which show up as dia-
stereotopic pairs of enantiotopic protons with anisochromy
magnified by the presence of the nitro groups. Each exhibits
a sextuplet pattern with chemical shift differences of 0.78
(δ ϭ 2.56Ϫ1.78) and 0.49 (δ ϭ 2.59Ϫ2.10) ppm for the meso
and rac forms, respectively. Finally, full characterization
Owing to the low symmetry (Cs) of the molecules, all
groups have different features. In each imidazolidine the
methyl groups located at the asymmetric centers (C4 and
C5) show up as two sharp signals, the positions of which
are temperature-dependent. The better peak separation is
found at 30 °C in CD3OD. When the NMR spectrum of a
mixture of imidazolidines Ϫ (S,R,R)-2/(S,S,S)-2 (1:3) Ϫ was
recorded, integration of the signals gave an (S,R,R)-2/
(S,S,S)-2 ratio of 0.335. In CD3OD, the Hα (on the imida-
zolidine ring) and Hβ (carried by the third chiral center)
protons show up as a complex pattern in the middle field
region of the spectra. In [D6]DMSO, however, they are well
separated and exhibit a doublet and a quintet pattern,
respectively, with equal couplings of about 5 Hz.
A similar study was performed for diamines (S,S)-3 and
(R,R)-3, with which diastereoisomeric derivatives were equ-
ally successfully formed in situ by addition of two equiva-
lents of enantiopure (S)-mandelic acid. From these NMR
studies it was concluded that the enantiomeric excesses of
the imidazolidines (S,R,R)-2 and (S,S,S)-2 and the diamines
(S,S)-3 and (R,R)-3 were the same as that of the enantio-
Scheme 2. Strategy for the resolution of the racemic mixture of
diamines 3; a) (S)-RЈOCH(Me)CHO/Et2O, b) HCl 10%
350
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Enantiopure and Racemic Chiral Nitronyl Nitroxide Free Radicals
FULL PAPER
pure aldehyde used for the resolution: at least 96%. These Nitronyl Nitroxides
diamines are volatile compounds, not conveniently charac-
terizable in the pure form but only indirectly through their
numerous derivatives.
The synthesis of a series of homochiral nitroxides from
meso-, rac-, or enantiopure diamines is straightforward, by
the procedure described elsewhere for tetramethylated ana-
logues.[8] Condensation of meso-3, rac-3, (R,R)-3, or (S,S)-
3 with any aldehyde almost quantitatively gave the corre-
sponding imidazolidines, which were oxidized in fair to
good yields by m-chloroperoxybenzoic acid and NaIO4.[8]
Although mixtures of isomeric imidazolidines differing in
the configuration at the C2 carbon atom were obtained in
the meso series, no attempts were made to characterize each
isomer since oxidation of both results in a unique nitronyl
nitroxide. However, imidazolidine meso-4F, derived from
formaldehyde and existing as a unique isomer, was fully
characterized by X-ray diffraction. Corresponding imino
nitroxides were obtained as by-products in the latter oxi-
dation process or quantitatively from the nitronyl nitroxides
by a reported procedure.[22] Note that the imino nitroxides
P6, derived from meso-nitronyl nitroxides, are racemates,
since these compounds present planar chirality (as indicated
by the P) and no attempt was made to separate the enantio-
mers.
Unfortunately, none of the diastereoisomeric imidazolid-
ines was a crystalline compound, so no absolute configura-
tion could be determined by X-ray crystallography. More-
over, attempts to prepare the corresponding nitroxide free
radicals were frustrating, because extensive degradation of
the O-silyl group occurs during the oxidation process. How-
ever, imidazolidines derived from methyl (R)-(3-phenyl-
phenoxy)-2-propionate[15c] were safely oxidized into the
corresponding nitronyl nitroxides 5E. Although these nitro-
xides were not crystalline compounds, their complexes with
manganese(ii) bis(hexafluoroacetylacetonate) were solid
species, and single crystals of the form derived from (R,R)-
3 [(R,R,R)-5E·Mn(hfac)2] were successfully grown.
The crystal structure of (R,R,R)-5E·Mn(hfac)2
[20]
(Fig-
ure 1) shows a polymeric chain structure with parameters
close to those already described for the complex involving
the analogous tetramethylated nitronyl nitroxide.[15c] The
metal ions are cis-coordinated by oxyl oxygen atoms of two
˚
radicals at distances of 2.129 (3) and 2.138 (4) A, compar-
Table 1 reports selected properties of meso-, rac-, and en-
antiopure nitronyl and imino nitroxides derived from phe-
nyl, p-nitrophenyl, m-pyridyl, and tert-butyl aldehydes,
which were selected for comparison with tetramethylated
analogues because of the following features: (i) the phenyl
derivatives often show enhanced stability and are widely
used as reference compounds, (ii) the tetramethylated p-
nitrophenyl radical exists as a polymorph that is a purely
organic magnet,[3d] (iii) m-pyridyl derivatives are precursors
of CuII molecular spin transition species,[5] and (iv) the hin-
dered tert-butyl derivative is a test for the efficiency of the
synthesis.[8]
able to those observed in most manganese(ii) nitroxide
chain complexes reported so far.[2b]
Physical Properties
This study focuses on properties related to the presence
of ethyl groups in all compounds and on chirality in the
enantiopure series, both features that were expected to re-
sult in structural arrangements different from those seen in
the tetramethylated analogues, in particular in chiral space
groups for enantiopure compounds and in different coup-
ling pathways in the solid state. In addition, the introduc-
tion of chirality close to the oxyl groups was expected to
show up strongly in the optical properties of the enantio-
pure nitroxides.
Figure 1. Part of the chain structure of complex (R,R,R)-
5E·Mn(hfac)2; only the free radical ligand and the metal coordi-
˚
nation sphere are shown; selected parameters [A, °]: MnϪO1 ϭ
2.138, MnϪO2 ϭ 2.129, O1ϪN1 ϭ 1.288, O2ϪN2 ϭ 1.293,
MnϪO1ϪN1 ϭ 126.9, MnϪO2ϪN2 ϭ 130.0, O1ϪMnϪO2 ϭ
89.8
From the known (R) configuration at the stereogenic
center in the lactate substituent (carbon atom C16), the
configurations at C4 and C5 are also (R) and the configura-
tion at the metal center Λ. The (S,S) and (R,R) configura-
tions were therefore assigned to the samples of the enanti-
opure diamines 3 derived from 2a and 2b, respectively.
Structural Studies
These new nitroxides have lower melting points than the
As well as defining the absolute configurations of the tetramethylated analogues,[7] probably because of the pres-
synthetic precursors unambiguously, the complex (R,R,R)- ence of the ethyl groups, which do not favor close packing
5E·Mn(hfac)2 also shows that the presence of ethyl substitu- in the crystals. However, all nitronyl nitroxides belonging to
ents at the 4- and 5-positions in these chiral nitronyl nitro- the more ‘‘symmetrical’’ meso series are crystalline com-
xides does not hamper their coordination capabilities. One pounds. Of the twenty-two nitroxides described in the syn-
observes that the ligand retains its bridging character, a thetic section, eleven nitronyl nitroxides and only two imino
very important property for designing extended exchange nitroxides (the enantiomeric phenyl derivatives) were solids
coupled species.[21]
at room temperature; they were all isolated as single crystals
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FULL PAPER
Table 1. Selected properties of nitronyl nitroxides 5 and imino nitroxides 6
Compound
meso
rac
Enantiopure
R
Phenyl
M.p. [°C]
73
M.p. [°C]
Ϫ
M.p. [°C]
71
[α] (T ϭ 26 °C, CHCl3)
meso-5A
(S,S)-5A
[α]436 ϭ ϩ409 (c ϭ 0.51 mg/mL)
[α]436 ϭ Ϫ401 (c ϭ 0.49 mg/mL)
(R,R)-5A
p-Nitrophenyl
m-Pyridyl
134
Ϫ
124
(S,S)-5B
[α]546 ϭ ϩ238 (c ϭ 0.21 mg/mL)
[α]546 ϭ Ϫ220 (c ϭ 0.16 mg/mL)
meso-5B
64
meso-5C
(R,R)-5B
oil
rac-5C
oil
(S,S)-5C
[α]436 ϭ ϩ280 (c ϭ 0.2 mg/mL)
[α]436 ϭ Ϫ277 (c ϭ 0.2 mg/mL)
(R,R)-5C
tert-Butyl
18Ϫ22
meso-5D
oil
Ϫ
Ϫ
16Ϫ20
(S,S)-5D
64
[α]436 ϭ ϩ699 (c ϭ 0.16 mg/mL)
Phenyl
rac-P6A
(S,S)-6A
[α]436 ϭ ϩ101 (c ϭ 0.51 mg/mL)
[α]436 ϭ Ϫ99 (c ϭ 0.54 mg/mL)
(R,R)-6A
p-Nitrophenyl
m-Pyridyl
oil
oil
oil
rac-P6B
rac-6B
(S,S)-6B
[α]546 ϭ ϩ27 (c ϭ 0.202 mg/mL)
oil
Ϫ
oil
rac-P6C
oil
(S,S)- 6D
(R,R)-6C
Ϫ
[α]436 ϭ ϩ86 (c ϭ 0.16 mg/mL)
[α]546 ϭ Ϫ59 (c ϭ 0.084 mg/mL)
oil
tert-Butyl
rac-P6D
and were studied by X-ray diffractometry. Note that the
Flack parameter[23] (inconclusive for all compounds except
(R,R,R)-5E·Mn(hfac)2] was never used for assigning the
absolute configuration of the enantiopure radicals; safely,
absolute configurations were derived from that of the
diamino precursor 3 and the crystal data were processed
accordingly).[24] Molecular structures of (S,S)-5A and (S,S)-
6A (phenyl-substituted) are displayed in Figure 2 as illus-
trations of the enantiopure nitronyl and imino series. Both
crystallize in chiral space groups as expected: P212121 for
the former and P21 for the latter. The nitronyl nitroxide
displays two different molecules in the asymmetric unit, as
also observed for meso-5B (p-nitrophenyl), meso-5C (3-pyri-
dyl), and the tetramethylated analogue;[9a,25] in contrast
there is only one molecule in the cases of nitronyl nitroxides
meso-5A,[8] (S,S)-5B, and the imino nitroxide (S,S)-6A.
This propensity for crystallizing as different conformers
in the same crystal is already documented for nitronyl nitro-
xides,[26] but the presence of non-rigid ethyl groups in these
series may well be another important factor diminishing the
chance of having a single conformer.
The conformations of the aromatic substituted nitronyl
and imino nitroxides in the solid state were analyzed ac-
cording to a recent study,[27] by use of the torsion angles
TIM (defined as the N1ϪC5ϪC4ϪN2 angle) and APNN (the
mean of the torsion about the bond indicated in Figure 3)
to specify the puckering of the five-membered ring and the
relative orientation of the two rings respectively, and of T1
and T2 (where T1 is the angle C4ϪC5ϪCH2ϪCH3 and T2
is C5ϪC4ϪCH2ϪCH3) to describe the orientations of the
ethyl groups. Note that the sign of the angle TIM is opposite
Figure 2. Molecular structure of chiral nitronyl nitroxide (S,S)-5A
(only molecule A is represented) and imino nitroxide (S,S)-6A;
thermal ellipsoids are drawn at the 30% probability level
The mean values of TIM (25.6°) and APNN (25.6°) fall
to that of the helicity shown in the imidazolyl ring, as de- well within the statistically significant range independently
fined by the angle between planes formed by the NCN of the presence of the ethyl groups. Pseudo-eclipsed confor-
bonds and the C4ϪC5 bond.[28] The results are summarized mations, described as (MP) or (PM)[27,28] and correspond-
in Table 2.
ing to the more planar conformations, are observed in all
352
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Enantiopure and Racemic Chiral Nitronyl Nitroxide Free Radicals
FULL PAPER
takes in the tetramethyl analogues[26]) indicating a slightly
different conformational nature.
Since the torsion angles are related to chirality,[27] this
behavior was further analyzed for the few enantiopure com-
pounds. One can observe that TIM and APNN are positive
for the (R) enantiomers, corresponding to the (MP) dia-
stereomeric conformation, while they are negative for the
(S) series, corresponding to the (PM) conformation. These
situations are favorable since they minimize steric interac-
tions between the ethyl groups.
Thus, it clearly appears that the configuration at the car-
bon center drives the puckering of the imidazolyl ring and
the position of the aromatic substituent according to steric
preferences associated with chirality. However, it is not pos-
sible to make a firm statement about the helicity associated
with APNN, since its sign seems better related with the pref-
erence of the molecule to adopt a planar pseudo-eclipsed
conformation, as already reported for the tetramethylated
achiral analogues.[26,27]
Figure 3. Definition of torsion angles used in the conformational
analysis
With regard to the ethyl groups, the values of T1 and T2
are distributed between two sets, A (ca. 70°) and B (ca.
166°), corresponding to two preferred orientations of the
terminal methyl, roughly perpendicular or parallel to the
C4ϪC5 bond; the resulting conformation in each case
matches an expected preferred gauche conformation and
keeps the molecule as a whole approximately planar. Exam-
ination of Table 2 shows that all combinations (AA, AB,
BB) are found and are probably close in energy, as shown
by the presence of different conformers in the same crystal.
For each possibility, the relative sign of the torsion angles
is such that the terminal methyl groups are located as far
apart as possible. Surprisingly, however, in some com-
pounds one of these methyl groups points toward the five-
membered ring but only when the sign of TIM corresponds
to the ring distortion that minimizes interactions with the
closest oxyl group of the ring. Therefore, correlation be-
tween the orientation of the ethyl groups with chirality and
the TIM angle is only indirect.
Table 2. Selected parameters Ϫ TIM, APNN [°], the puckering ampli-
tude (ΨM), and the puckering phase angle (Φ) Ϫ for describing the
conformations of the solid aromatic-substituted nitroxides; for the
(S,S) series the angles have opposite sign
Compound TIM APNN Descriptor
T1
T2
ΨM Φ
meso-5A
meso-5B
A
27.3 31.7 (PM) and (MP) 72.6
25.5 20.4 (PM) and (MP) 72.6
163.8 29.7 Ϫ5.7
69.4 27.7 Ϫ0.5
B[a]
27.7 28.0 (PM) and (MP) 153.2 166.8 30.1 Ϫ5.7
69.9
73.8
meso-5C
A
23.0 33.2 (PM) and (MP) 67.5
23.2 29.3 (PM) and (MP) 64.3
72.5 22.9 Ϫ2.3
72.1 25.0 5.4
B
(R,R)-5A
A
B
ϩ25.6 ϩ29.3 (MP)
ϩ28.6 ϩ27.6 (MP)
ϩ169.7 ϩ80.5 27.6 4.1
ϩ167.6 ϩ168.0 30.9 0.9
ϩ160.5 ϩ163.3 31.7 Ϫ0.6
(R,R)-5B ϩ29.3 ϩ23.4 (MP)
(R,R)-6A Ϫ23.1 Ϫ21.0 (PM)
Ϫ177.3 ϩ69.9 Ϫ
68.6 72.6
Ϫ
Mean[b]
167.6
25.6 25.6
165.5
Finally, as shown in Table 3, distances and angles in all
nitroxides are within the ranges expected for nitroxide free
radicals and do not need further comments.
[a]
[b]
Disordered ethyl groups. Absolute value.
compounds. While this form is predominant in the tetra-
methyl analogues in the solid state since it favors dense
packing, it is striking that none of the compounds studied
here shows the pseudo-anti arrangement. Furthermore, the
puckering amplitudes (ΨM) Ϫ describing the maximum tor-
sion angle that one of the endocyclic bonds can adopt as a
result of out-of-plane distortion Ϫ calculated by a standard
procedure from all the angles in the imidazolyl ring came
within the range (although in general at the upper limit) of
those seen in the tetramethyl analogues, where the average
value for this parameter is 24°.[27] Most values for the ni-
tronyl nitroxides described here are close to 30° (Table 2),
indicating larger of the ring than in the case of the tetra-
methyl-substituted compounds. Furthermore, the puckering
phase angles (Φ) Ϫ describing the point on the ring where
the maximum distortion occurs Ϫ of the chiral compounds
are in general slightly displaced from 0 (the average value it
˚
Table 3. Selected structural [A, °] and Weiss (θ [K]) parameters
Compound N1ϪO1 N2ϪO2 N1ϪC1 N2ϪC1 N1ϪC1ϪN2 θ
meso-5A 1.287(1) 1.283(1) 1.346(1) 1.344(2) 108.3(2)
meso-5B
Ϫ3.9(1)
ϩ1.2(3)
A
1.282(2) 1.280(2) 1.352(3) 1.353(2) 107.7(2)
1.279(2) 1.284(2) 1.350(2) 1.349(2) 108.1(2)
B
meso-5C
A
B
Ϫ1.3(1)
Ϫ2.2(2)
1.279(1) 1.277(1) 1.345(2) 1.347(2) 108.8(1)
1.278(1) 1.277(1) 1.354(2) 1.345(2) 108.5(1)
(R,R)-5A
A
B
1.300(5) 1.274(5) 1.328(6) 1.335(6) 109.1(5)
1.264(4) 1.278(4) 1.341(6) 1.329(5) 108.7(4)
(S,S)-5B 1.280(2) 1.282(3) 1.358(3) 1.362(3) 106.9(2)
Ϫ1.8(1)
ϩ1.1(2)
(R,R)-6A 1.276(2) Ϫ
Mean
1.397(2) 1.288(2) 113.0(2)
1.280(3) 1.279(3) 1.352(4) 1.339(4) 108.8(3)
Eur. J. Org. Chem. 2005, 348Ϫ359
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353

´
C. Hirel, J. Pecaut, S. Choua, P. Turek, D. B. Amabilino, J. Veciana, P. Rey
FULL PAPER
Magnetic Properties
6A. For the sake of comparison, previously reported val-
ues[30] for a p-nitrophenyl nitronyl ntiroxide (noted as NIT-
Ph) are given in the last column of Table 4.
The magnetic behavior of the compounds described here
was investigated in the solid state by magnetometry and in
solution by EPR and ENDOR spectroscopy in order to ob-
tain insight into modifications of the spin distribution as-
sociated with the presence of ethyl groups.
ENDOR spectra were recorded as described pre-
viously.[30] For phenyl non-deuterated meso-5A and (S,S)-
5A, one observes four and three pairs of lines, respectively
1
(Figure 5a, c), each symmetrically split around the free H
In the solid state, the magnetic behavior of these nitrox-
ides is characterized by weak values of θ, which suggest
weak interactions (Table 3, last Entry). This result is not
surprising, since the magnitude of intermolecular interac-
tions would be expected to suffer from the steric demand
of the ethyl groups. Figure 4 displays the variation in χT
with temperature for meso-5B and (S,S)-5B, meso and en-
antiopure forms of the same p-nitrophenyl-substituted rad-
ical, which illustrate ferro- and antiferromagnetic behavior,
respectively. Attempts to correlate these features with crys-
tal packing and close intermolecular contacts were unsuc-
cessful. In particular, there are no close intermolecular con-
tacts between NO2 and oxyl groups of neighboring mol-
ecules in either compound, as observed in the methylated
analogue. A recent study devoted to tetramethylated ana-
logues[26] concluded that no correspondence could be estab-
lished between the nature of intermolecular magnetic inter-
actions and the geometry of close contacts. In the present
case, such a study was even more hopeless, owing to differ-
ent cell contents and different conformations.
NMR frequency, in agreement with previous studies.[30] In
all studied compounds, the 14N ENDOR resonance was ob-
served at half the hyperfine coupling of 14N (inset in Fig-
ure 5).
With reference to the 1H nuclei of the five-membered
ring, the phenyl group was fully deuterated in radicals meso-
5A, (S,S)-5A, and (R,R)-6A.[31] The ENDOR spectra of
[D5]-meso-5A, [D5]-(S,S)-5A, and [D5]-(R,R)-6A show two,
one, and four pairs of lines, respectively, attributable to the
coupling constants on methyl and ethyl hydrogen atoms
(Figure 5b, d; Table 4). In order to help in the assignment
1
of the various H signatures, DFT calculations were per-
formed. The results for all similar groups could be accu-
rately related to those of previous theoretical studies.[29,32]
The overall assignment was carried out consistently with
the trends shown by numerical calculations and with pre-
vious results.[30] Table 4 shows an interesting effect in the
apparent larger spin density distribution over the ethyl
group than over the methyl group in the corresponding
tetramethylated compound. This may be due to spin polar-
ization. The asymmetry of the spin distribution in (R,R)-
6A is readily apparent and was previously determined for
the non-hydrogen atoms.[32] The spin density is not negli-
gible up to the terminal methyl protons of the ethyl group.
The few compounds exhibiting dominant intermolecular
ferromagnetic interactions will be investigated at lower tem-
perature to verify whether or not they order.
In solution (10Ϫ3 m in CH2Cl2), the EPR spectra of meso-
5A and (S,S)-5A each exhibit the expected five-line pattern
attributable to coupling of the unpaired electron with two
equivalent 14N nuclei, whereas the hyperfine pattern of
(R,R)-6A is composed of seven lines, due to the presence
of two non-equivalent 14N nuclei.[7,29] Additional hyperfine
structure due to other magnetically active nuclei was not
observed, either in other solvents or for radicals in which
the phenyl substituent is deuterated (vide supra). Values of
hyperfine coupling constants (hfccs) are listed in Table 4.
The numbering scheme used for the various hfccs reported
in Table 4 corresponds to the one used in Figure 2 for (S,S)-
Optical Properties
The UV/Vis absorption spectra of all compounds are
identical to those of the tetramethylated analogues,[7] the
nǞπ* transition of the radical moiety for the phenyl ni-
tronyl nitroxide derivatives being centered at about 640 nm,
while the πǞπ* transition occurs at 365 nm. This study
concentrates on properties associated with the chirality of
the compounds by circular dichroism (CD).
The solution state CD spectra of the two enantiomers of
the phenyl nitronyl nitroxides 5A (Figure 6) reveal a broad
Cotton effect of moderate intensity centered on 425 nm, fol-
lowed by an intense exciton coupled effect at approximately
365 nm, which coincides with the absorption maximum for
the πǞπ* transition. There are no detectable Cotton effects
in the region corresponding to the nǞπ* transition at
640 nm. It should be pointed out that the magnitudes of
the Cotton effects are much greater than those observed for
the chiral radicals prepared to date in which the stereogenic
center is located on the phenyl substituent at the 2-position
of the imidazolyl ring, remote from the radical chromopho-
re.[15b,15c] In the compounds here, the stereogenic centers
are very close to the chromophore and in addition cause
greater conformational restrictions, both important factors
in determining the magnitude of the Cotton effects. The
intensity of the Cotton effects is dramatically lower in the
Figure 4. Solid-state magnetic behavior of the p-nitrophenyl-substi-
tuted nitronyl nitroxides meso-5B (solid circles) and (S,S)-5B (open
circles) in the form of χT vs. T and 1/χvs T
354
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Eur. J. Org. Chem. 2005, 348Ϫ359

Enantiopure and Racemic Chiral Nitronyl Nitroxide Free Radicals
FULL PAPER
Table 4. Experimentally acquired isotropic hyperfine coupling constants (in mT); the atom numbering corresponds to Figure 2 for (S,S)-
6A; NIT-Ph stands for a previously studied p-nitrophenyl nitronyl nitroxide derivative[30]
(S,S)-5A
Deuterated
meso-5A
Deuterated
(R,R)-6A
Deuterated
NIT-Ph[30]
Non-deuterated
Non-deuterated
a(N1)
a(N2)
0.747
0.747
0.019
0.027
Ϫ
0.019
0.027
Ϫ
0.747
0.747
0.019
0.027
Ϫ
0.019
0.027
Ϫ
0.752
0.752
0.018
Ϫ
Ϫ
0.018
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
0.752
0.752
0.019
Ϫ
Ϫ
0.019
Ϫ
Ϫ
0.050
Ϫ
0.907
0.413
0.066
0.035
0.021
0.012
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
a(C4H3)
a(C5H2)
a(C6H3)
a(C7H3)
a(C8H2)
a(C9H3)
a(11-H)
a(12-H)
a(13-H)
0.020
0.020[a]
Ϫ
0.020
0.020[a]
Ϫ
0.052
0.029[b]
0.047
Ϫ
Ϫ
Ϫ
0.050
Ϫ
0.044
0.043
[a]
[b]
Methyl groups instead of ethyl groups. Very weak signals reported.
imino nitroxides 6A. The absorptions are weaker and
shifted with respect to their more conjugated cousins.
In the solid state (Figure 7), all the radicals show general
CD spectral features similar to those seen in solution, ex-
cept that for the nitronyl nitroxides the band at 450 nm ap-
pears somewhat sharper than in solution and the exciton
coupled band is not observed in the solid state, an effect
possibly due either to the broadness of the bands in the
solid or to interaction of neighboring molecules with the
chromophores. In any case, we can confirm that the overall
conformation must be very similar in the two states, given
the similarities in the spectra, in line with the rigid nature
imposed on the imidazolyl ring by the bulky groups at the
4- and 5-positions. It is also interesting to note that the
signs and positions of the Cotton effects are in general
agreement with those calculated for the corresponding con-
formational isomers.[27]
1
Figure 5. Liquid-phase H-ENDOR spectra recorded at 285 K in
paraffin oil for: (a) meso-5A, (b) meso-5A with deuterated phenyl
group, (c) (S,S)- 5A, (d) (S,S)- 5A with deuterated phenyl group;
inset: 14N-ENDOR spectrum for (S,S)-5A
Figure 6. Solution-state CD spectra of the chiral nitronyl and imino
nitroxides recorded in THF at room temperature
Figure 7. Solid-state CD spectra of the chiral nitronyl and imino
nitroxides recorded in KBr discs at room temperature
Eur. J. Org. Chem. 2005, 348Ϫ359
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
355

´
C. Hirel, J. Pecaut, S. Choua, P. Turek, D. B. Amabilino, J. Veciana, P. Rey
FULL PAPER
Flack.[23] CCDC-233359 (rac-1), -233360 (rac-3·HCl), -233356
(meso-4F), -152832 (meso-5A), -233357 (meso-5B), -233358 (meso-
5C), -233364 (S,S)-5A], -233361 [(R,R)-5B], -233362 [(R,R)-6A],
and -233363 [(R,R,R)-5E·Mn(hfac)2] contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or
from the Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK; Fax: (internat.) ϩ 44-1223-336-
033; E-mail: deposit@ccdc.cam.ac.uk].
Conclusion
The chiral, enantiopure precursors (3S,4S)-(ϩ)- and
(3R,4R)-(Ϫ)-3,4-diamino-3,4-dimethylhexane have been
prepared and their absolute configurations established.
Condensation with aldehydes quantitatively afforded chiral
imidazolidines, which were oxidized into the corresponding
enantiopure nitronyl and imino nitroxides.
The nitronyl nitroxide building blocks include identical
chiral centers adjacent to the oxyl groups and since they
exhibit C2 symmetry they are well suited for coordination
chemistry studies as stereochemical complexity is mini-
mized. As an example, the complex (R,R,R)-5E·Mn(hfac)2,
which has a chain structure in which the two oxyl groups
are coordinated, not only unambiguously establishes the
absolute configurations of the precursors, but also demon-
strates that, despite the presence of ethyl groups close to the
oxyl coordination sites, these nitronyl nitroxides retain their
bridging character while presenting appreciable optical ac-
tivity, and are thus good candidates for the designing of
chiral magnetic materials that may show interesting mag-
neto-optical properties.
Circular Dichroism Measurements: Circular dichroism spectra were
recorded with a JASCO-715 spectropolarimeter, and were pro-
cessed by use of the associated software. The solution spectra have
background solvent spectra subtracted, while the solid-state spectra
were recorded in ground KBr discs of the compounds by the
method reported elsewhere.[15b]
Mixture of meso- and rac-3,4-Dimethyl-3,4-dinitrohexane (1): The
crude dinitro compound could be prepared according to a reported
procedure.[17] Alternatively, the yield was improved as follows: Li-
OMe (3.7 g, 0.097 mol) was dissolved in dry DMF (125 mL), and
rac-2-nitrobutane (10 g, 0.097 mol) was added. This solution was
stirred at room temperature for 15 min, and the solution was then
cooled in a ice bath. A solution of iodine (12.3 g, 0.0485 mol) in
DMF (100 mL) was added dropwise until the brown color had dis-
appeared. After the system had been stirred for additinal 2 h, H2O
(1.5 L) was added. A white precipitate was immediately observed
and filtered. This precipitate was dissolved in diethyl ether and
washed with three portions (100 mL) of sodium thiosulfate (20%)
solution. After drying (Na2SO4) and evaporation of the solvent,
one obtained 8.3 g (84%) of a mixture of the two dinitro isomers,
which was used in the next step.
Experimental Section
Synthesis: All reagents were from Aldrich and were used as re-
ceived, except for m-chloroperoxybenzoic acid, which was purified
by washing with a phosphate buffer (pH ϭ 7.5) and dissolved in
CH2Cl2, and the solution was dried with Na2SO4. After evapor-
ation of the solvent, the resulting solid was dispersed in n-pentane
and dried by azeotropic removal of the last traces of water. Iodo-
metric assay indicated 97% purity.
Separation of meso- and rac-3,4-Dimethyl-3,4-dinitrohexane (1):
Quantitative large-scale (50 g) separation of the meso and rac forms
was performed by HPLC on an SiO2 (60 µm) semi-preparative col-
umn eluted with hexane/ethyl acetate (90:10). The compound
1
eluted first was meso-1 (m.p. 90Ϫ91 °C). H NMR (500 MHz, 20
Magnetic Measurements: Magnetic susceptibility data were col-
lected by use of a Quantum Design SQUID susceptometer working
at a 0.5 T field strength in the 2Ϫ400 K temperature range. The
SQUID outputs were corrected for the contribution of the sample
holder, and the magnetic susceptibilities were corrected for the dia-
magnetic contribution of the constituent atoms by use of Pascal
constants. EPR and ENDOR experiments were performed at room
temperature with a BRUKER ESP 300E spectrometer operating at
X-band, and equipped with an RF amplifier ENI 300. Samples
for EPR and ENDOR measurements were prepared by dissolving
radicals in CH2Cl2, and by then mixing 10% of this solution in
paraffin oil. The resulting solution was degassed by thaw-freeze
pumping cycles.
°C, CDCl3): δ ϭ 0.93Ϫ0.95 (t, 3 H, CH3ϪCH2), 1.66 (s, 3 H, CH3),
1.76Ϫ1.80 (m, 1 H, CH2), 2.54Ϫ2.58 (m, 1 H, CH2) ppm. The
compound eluted second was rac-1 (m.p. 86Ϫ87 °C.) 1H NMR
(500 MHz, 20 °C, CDCl3): δ ϭ 0.91Ϫ0.94 (t, 3 H, CH3ϪCH2),
1.59 (s, 3 H, CH3), 2.12Ϫ2.07 (m, 1 H, CH2), 2.61Ϫ2.56 (m, 1 H,
CH2) ppm.
meso-(or rac-)3,4-Diamino-3,4-dimethylhexane (3): These were ob-
tained by a slight modification of a reported procedure;[17] meso-
(or rac-)3,4-dimethyl-3,4-dinitrohexane (1, 5.1 g, 25 mmol) was sus-
pended in concentrated hydrochloric acid (37%, 60 mL). Granular
Sn (50 g) was then added in five portions at 1/2 h intervals, and the
mixture was heated at reflux for 2 h. After cooling, the clear solu-
tion was extracted with diethyl ether, and the aqueous phase was
made strongly basic with sodium hydroxide pellets (40 g) and cen-
trifuged to get rid of a viscous precipitate. The aqueous solution
was extracted with dichloromethane (4 ϫ 50 mL), the solvent was
distilled off, and the residual oil was dried with pentane; meso-(or
rac-)3,4-diamino-3,4-dimethylhexane was obtained as a colorless
liquid (2.3 g, 64%). meso-3: 1H NMR (400 MHz, 20 °C, CDCl3):
δ ϭ 0.991 (t, 3 H, CH3ϪCH2, J ϭ 7.37 Hz), 1.176 (s, 3 H, CH3),
1.567Ϫ1.622 (m, 2 H, CH2ϪCH3) ppm. rac-3: 1H NMR (400 MHz,
20 °C, CDCl3): δ ϭ 0.994 (t, J ϭ 7.37 Hz, 3 H, CH3ϪCH2), 1.094
(s, 3 H, CH3), 1.563Ϫ1.618 (m, 2 H, CH2) ppm.
Computational Methods: The DFT calculations were performed by
use of Gaussian 03[33a] by the hybrid B3LYP method with
Becke’s[33b] three-parameter non-local exchange potential coupled
to the non-local correlation functional of Lee et al.[33c] The basis
set used for the radical Ϫ namely, 6-31ϩg* Ϫ was used in order
better to describe the region far from the nuclei covered by the
unpaired electron in open-shell systems.
Crystal Structure Determinations: These were carried out with the
˚
aid of a Bruker SMART system (Mo-Kα, λ ϭ 0.71073 A, graphite
monochromator). The data were processed by use of the
SAINT[34a] data reduction software, the structure was solved with
Resolution of rac-3,4-Diamino-3,4-dimethylhexane (2): The racemic
the aid of the SHELXTL[34b] software package, and the absolute mixture of 3 (1 g, 6.9 mmol) was treated in diethyl ether for 20
structure of the crystal used was established as described by
h with enantiopure (S)-(Ϫ)-O-(tert-butyldiphenylsilyl)acetaldehyde
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356
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Enantiopure and Racemic Chiral Nitronyl Nitroxide Free Radicals
FULL PAPER
{2.2 g, 7 mmol, [α]D ϭ Ϫ8.5 (21 °C, c ϭ 13.4 mg/mL, ethanol)},
atom C2; in contrast, only single isomers were obtained in the rac
prepared by a reported procedure.[18] The solution was dried with and enantiopure series (symmetry C2). The crude compounds were
Na2SO4 and concentrated under vacuum, and the mixture of dia-
stereoisomers, (S,S,S)-2 and (S,R,R)-2, was separated by flash chro- afforded unique free radicals. Single crystals of meso-4F were ob-
matography (SiO2, 15 µm; p ϭ 2 bar) with elution with hexane/ tained from methanol solutions at 6 °C and the crystal structure
used for the following steps since oxidation of mixtures of isomers
ethyl acetate (80:20). (S,S,S)-2: 1.4 g, 93%, [α]436 ϭ ϩ5 (25 °C, c ϭ was solved.
1
4.12 mg/mL) and [α]589 ϭ ϩ3 (25 °C, c ϭ 3.49 mg/mL). H NMR
meso-(or rac- or enantiopure)Nitronyl Nitroxides: The compounds
(400 MHz, 30 °C, CD3OD): δ ϭ 0.845 (s, 3 H, CH3), 0.889 (t, J ϭ
7.6 Hz, 3 H, CH3ϪCH2), 0.918 (t, J ϭ 7.6 Hz, 3 H, CH3ϪCH2),
1.019 (s, 3 H, CH3), 1.08 (d, J ϭ 5 Hz, 3 H, CH3ϪCHβ), 1.077 (s,
9 H, tBu), 1.28Ϫ1.42 (m, 2 H, CH2ϪCH3), 1.46Ϫ1.58 (m, 2 H,
CH2ϪCH3), 3.74Ϫ3.83 [m, 2 H, Hβ Hα (see text)], 7.38Ϫ7.77 (m,
10 H aromatic) ppm. (S,R,R)-2: 1.35 g, 90%, [α]436 ϭ Ϫ7.7 (25 °C,
c ϭ 3.5 mg/mL) and [α]589 ϭ Ϫ2.6 (25 °C, c ϭ 3.46 mg/mL). 1H
NMR (400 MHz, 30 °C, CD3OD): δ ϭ 0.898 (t, 3 H, CH2ϪCH3),
0.924 (t, 6 H, CH2ϪCH3), 0.935 (s, 3 H, CH3), 1.047 (s, 3 H, CH3),
1.09 (d, J ϭ 5 Hz, 3 H, CH3ϪCHβ), 1.082 (s, 9 H, tBu), 1.3Ϫ1.42
(m, 2 H, CH2ϪCH3), 1.48Ϫ1.58 (m, 2 H, CH2ϪCH3), 3.78Ϫ3.90
[m, 2 H, Hβ Hα (see text)], 7.38Ϫ7.77 (m, 10 H aromatic) ppm.
The two fractions (1.4 and 1.35 g) were separately poured into
H2SO4 (10%, 50 mL) and stirred at room temperature for 20 h. The
solution was extracted with diethyl ether, made strongly basic with
NaOH, and extracted again (4 ϫ 50 mL) with CH2Cl2. The two
enantiomers (S,S)-3 and (R,R)-3 were obtained in 50Ϫ60% yields
and had NMR spectra identical to that of the racemic mixture.
meso-5 or rac-5 or (S,S)-5/(R,R)-5 were obtained as recently re-
ported,[8] by oxidation of meso-4 or rac-4 or (S,S)-4/(R,R)-4 (AϪF)
with m-chloroperoxybenzoic acid and sodium periodate. In a typi-
cal experiment, meso-4A (1 g, 4.31 mmol) was dissolved in a mix-
ture of dichloromethane (100 mL) and a saturated solution of
NaHCO3 (50 mL). The solution was cooled in a ice bath, and a
solution of m-chloroperbenzoic acid (2.85 g, 2.5 equiv.) in CH2Cl2
(20 mL) was added dropwise, followed, after 1 h, by NaIO4 (1.4 g,
1.5 equiv.) in water (30 mL). Stirring was continued for 1/2 h. The
organic phase was dried with Na2SO4 and concentrated, and the
residue was chromatographed (SiO2, diethyl ether). The imino
nitroxide (rac-P6A, 198 mg, 19%) and the nitronyl nitroxide meso-
5A (810 mg, 72%), meso-5B (75%), meso-5C (52%), meso-5D (75%),
rac-5C (61%), (S,S)-5A (58%), (R,R)-5A (62%), (S,S)-5B (49%),
(R,R)-5B (53%), (S,S)-5C (46%), (R,R)-5C (49%), and (S,S)-5D
(60%) were eluted successively. Nitroxides meso-5AϪC and (S,S)-
5AϪB were obtained as single crystals suitable for X-ray diffraction
studies by slow concentration of hexane solutions, except for meso-
5B, which crystallized from methanol. Imino Nitroxides: meso-P6,
rac-6, (S,S)-6, or (R,R)-6 were obtained in low yield as by-products
in the syntheses of the corresponding nitronyl nitroxides or quanti-
tatively from the nitronyl nitroxides 5 by a reported procedure.[22]
Satisfactory elemental analyses were obtained for all compounds.
Table 1 lists selected physical properties of these new nitroxides.
(S,S)-3: [α]589 ϭ ϩ80 (25 °C, c ϭ 0.1 mg/mL, MeOH) and [α]365
ϭ
ϩ250 (25 °C, c ϭ 0.1 mg/mL, MeOH). (R,R)-3: [α]589 ϭ Ϫ78 (25
°C, c ϭ 0.1 mg/mL, MeOH) and [α]365 ϭ Ϫ238 (25 °C, c ϭ 0.1 mg/
mL, MeOH). Single crystals of the hydrochloride of the racemic
diamine were grown by slow concentration of a THF solution and
the X-ray structure was determined.
Absolute Configurations of (S,S)-3 and (R,R)-3: A solution of en-
antiopure methyl (R)-(ϩ)-(3-formylphenoxy)-2-propionate (70 mg,
0.35 mmol, [α]D ϭ ϩ59.8), (R,R)-3 (50 mg, 0.35 mmol), and p-
toluenesulfonic acid in toluene (20 mL) was heated at reflux with
azeotropic removal of water for 3 h.[35] The solvent was evaporated
off under vacuum, and the resulting oil (R,R,R)-4E was dissolved
in CH2Cl2 (15 mL). Saturated aqueous NaHCO3 (12 mL) was then
added, followed by MCPBA (137 mg) in CH2Cl2 (8 mL), and the
mixture was stirred for 2 h. The blue organic phase was separated,
dried, concentrated, and flash-chromatographed (SiO2, 15µ; Et2O/
petroleum ether, 50:50) to afford (R,R,R)-5E {73 mg, 0.2 mmol,
61%, [α]436 ϭ Ϫ191 (25 °C, 0.11 mg/mL, CHCl3)} as a blue oil.
The corresponding MnII complex, (R,R,R)-5E·Mn(hfac)2, was ob-
tained by mixing this nitronyl nitroxide and MnII hexafluoroacetyl-
acetonate (90 mg, 0.2 mmol) in heptane (10 mL) at 70 °C. Slow
concentration of the solution in the dark afforded the complex
(22 mg, 45%, m.p. 141 °C) as dark green crystals suitable for a X-
ray diffraction study, which identified the (S,S) configuration for
(S,S)-3 and the (R,R) configuration for (R,R)-3.
Acknowledgments
This work was supported by the French Commissariat a l’Energie
Atomique, le Centre National de la Recherche Scientifique and
grants from the Programa Nacional de Materiales of the DGI
(Spain, MAT2003-04699). C. H. acknowledges financial support
`
´
ˆ
from the Region Rhone-Alpes.
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