Multiple aromatic amination mediated by a diiron complex

Article abstract of DOI:10.1002/anie.200703580

(Chemical Equation Presented) Stop-frame amination: A very efficient amine transfer reaction is mediated by a biomimetic diiron complex, giving both single and double insertions of a tosylamine group into a pendant benzyl group of the ligand (see structure). The mono-insertion product has been shown by X-ray crystallography and other physical methods to be a tosylanilinato diiron(III) complex.

Full text of DOI:10.1002/anie.200703580

Angewandte
Chemie
DOI: 10.1002/anie.200703580
Iron-Mediated Amination
Multiple Aromatic Amination Mediated by a Diiron Complex
FrØdØric Avenier, Eric GourØ, Patrick Dubourdeaux, Olivier SØn›que, Jean-Louis Oddou,
Jacques PØcaut, Sylvie Chardon-Noblat, Alain Deronzier, and Jean-Marc Latour*
Metal-catalyzed amine transfer reactions constitute a field of
active research to achieve carbon–nitrogen bond formation in
synthetic organic chemistry. Following the original discovery
by Sharpless and co-workers,[1] the biomimetic approach
initiated by Breslow and Gellman[2] and Mansuy et al.[3] has
attracted the interest of many groups. Nitrene addition to
À
olefins and insertion into aliphatic C H bonds have been
reported in many instances;[4,5] however, very few examples of
arene amination are known so far.[6–9] In particular, Que
Scheme 1. Reaction of mixed-valent diiron complexes (1a: X=H; 1b:
X=Cl) to give 2 (Y=O, Z=H) or 3 (3a; Y=NTs, Z=H; 3b: Y=NTs,
Z=NHTs). R=1,3-CH2(C6H4)CH2.
et al.[8] described the intramolecular aromatic amination of a
phenyl-bearing ligand upon treatment of a ferrous complex
=
with PhI NTs (Ts = 4-methylphenylsulfonyl). It is worth
noting that the yield of the amine transfer culminates at
about 64% owing to hydrolysis of the iron nitrene active
species, giving the hydroxylated product. Herein we present a
diiron complex that can mediate the quantitative intramo-
lecular amination of a benzyl group of the ligand without
contamination of hydroxylated product, and that this amina-
tion produces both mono and bis(tosylamine) derivatives.
In the course of our biomimetic studies of iron centers in
oxygenases, we developed mixed-valent FeIIFeIII complexes of
hexadentate binucleating ligands.[10] When the complex 1a
[Fe2(L)(mpdp)(H2O)](ClO4)2 (mpdp = 1,3-benzenedipropio-
nate; for L see Scheme 1with X = H) is reacted with oxygen
donors such as m-chloroperbenzoic acid or iodosyl arenes it
mediates an intramolecular oxygen atom transfer to the
pendant benzyl residue of the ligand forming the ortho-
hydroxybenzyl complex 2 (Scheme 1, with Y= O, Z = H).[11]
In addition, we showed that complex 1b [Fe2(L’)(mpdp)-
(CH3OH)](ClO4)2 where the ligand bears a 2,6-dichloroben-
zyl residue (Scheme 1, X = Cl) is able to catalyze the
aziridination of various olefins and the sulfonamidation of
thioanisole in good to excellent yields.[12] Herein we show
that, when reacted with a tosyliminoaryliodinane[13] as nitrene
source, 1a is able to mediate the intramolecular aromatic
amination of the unprotected benzyl residue to form the
anilinate 3a, which has been characterized by X-ray crystal-
lography. Interestingly, the reaction furnished a second
product 3b in which two ortho-tosylamine groups have been
incorporated. To our knowledge, the present complexes are
the first binuclear complexes of an anilinato ligand.
Complex 1a was prepared as previously described.[14,15]
When an acetonitrile solution of 1a was titrated with ArINTs,
its blue color (lmax = 578 nm, e = 1300mÀ1 cmÀ1) became
progessively more intense, which corresponds to a two-fold
increase in absorbance at about 585 nm and which was
complete after the addition of 1.5(1) equivalents of ArINTs.
Electrospray ionization mass spectrometry (ESI-MS) of the
solution led to a spectrum that comprised two sets of three
peaks (Figure 1). The first set is dominated by a peak at m/z
1028 which is due to the monocation [FeIIFeIII(L-H+NTs)-
(mpdp)]+. In addition, two smaller peaks at m/z 514 and 1127
are associated to the dication [FeIIIFeIII(L-H+NTs)(mpdp)]2+
and the monocation [FeIIIFeIII(L-H+NTs)(mpdp)(ClO4)]+,
respectively. As is usual for these compounds, the mixed-
valent form is produced within the mass spectrometer by
reduction of the diferric complex. These observations paral-
leled the oxygenation of the benzyl group from iodosylar-
ene[11] and suggests a tosylamine transfer onto the ligand.
A second set of three peaks is observed at m/z 598.5, 1197,
and 1296 which corresponds to the analogous ions of a second
compound [Fe2(L-2H+NTs+NHTs)(mpdp)]+/2+ that has two
tosylamine groups incorporated. An NMR analysis of the
reaction mixture after reduction by sodium iodide confirmed
[*] P. Dubourdeaux, Dr. J.-M. Latour
CEA, DSV, iRTSV, Laboratoire de Chimie et Biologie des MØtaux/
PMB, CEA-Grenoble,
38054 Grenoble (France)
Fax : (+33)438783462
E-mail: Jean-Marc.Latour@cea.fr
Dr. F. Avenier, Dr. O. SØn›que
LCBM, UMR 5249, CNRS, 17 rue des Martyrs,
38054 Grenoble (France)
E. GourØ, Dr. J.-L. Oddou
UniversitØ Joseph Fourier,
Laboratoire de Chimie et Biologie des MØtaux,
38054 Grenoble (France)
Dr. J. PØcaut
Laboratoire de Chimie Inorganique et Biologique,
UMR E 3 CEA-UJF, CEA-Grenoble,
38054 Grenoble Cedex 9 (France)
Dr. S. Chardon-Noblat, Dr. A. Deronzier
DØpartement de Chimie MolØculaire, UMR CNRS 5250,
ICMG FR-2607, UniversitØ Joseph Fourier Grenoble 1, B.P. 53
38041 Grenoble Cedex 9 (France)
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2008, 47, 715 –717
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
715

Communications
both features supporting a bis ortho-benzylic substitution in
H(L-2H+2NHTs). Insertion of iron in the two ligands was
performed as usual[14] and furnished the mixed valent
derivatives
[FeIIFeIII(L-H+NTs)(mpdp)]+
(3’a)
and
[FeIIFeIII(L-2H+NTs+NHTs)(mpdp)]+ (3’b).
The two complexes had almost identical UV-Vis spectra
but slight differences could be detected by NMR spectrosco-
py. Indeed the ortho- and para-aniline resonances[17] (at ca.
d = À40.5, À43 and À30, À32 ppm, respectively) were clearly
distinguishable, as shown in Figure 2b,c. It is worth noting
that the spectrum of 3’a is identical to that obtained upon
iodide reduction of 3a. All in all, these experiments indicated
that both tosylamine transfers occurred exclusively on the
ortho-benzylic positions. Interestingly, neither NMR spec-
troscopy nor ESI-MS analyses revealed the formation of
hydroxylated derivatives.
Figure 1. ESI-MS spectrum of the reaction mixture showing the peaks
of complexes 3a (italics) and 3b (bold).
X-ray suitable crystals of the monosubstituted derivative
3a-(ClO4)2 were grown from the reaction medium by slow
evaporation. Figure 3 illustrates the structure (see also
Supporting Information, Tables S1–S4) of the dication [Fe2-
(L-H+NTs)(mpdp)]2+. The most striking feature is the
the presence of two diiron complexes (Figure 2a) in the ratio
3a/3b 60:40.[16] The reaction solution was treated with sodium
hydroxide to remove the iron atoms and the mixture of
Figure 2. 1H NMR spectra of the iodide-reduced reaction mixture (a)
and complexes 3’a (b) and 3’b (c) in CD3CN over the À10 to À50 ppm
range.
Figure 3. X-ray crystal structure of the dication 3a [Fe2(L-H+NTs)-
(mpdp)]2+ (ellipsoids are set at 30% probability, and hydrogen atoms
are omitted for clarity). Fe–ligand bond lengths [Š]: Fe(1)-O(61)
1.9639(17), Fe(1)-O(1) 2.0161(16), Fe(1)-N(6) 2.016(2), Fe(1)-O(71)
2.1230(18), Fe(1)-N(5) 2.130(2) Fe(1)-N(4) 2.182(2), Fe(2)-O(72)
1.9370(17), Fe(2)-O(62) 1.9909(19), Fe(2)-O(1) 2.0161(16), Fe(2)-N(3)
2.127(2), Fe(2)-N(2) 2.129(2), Fe(2)-N(1) 2.178(2), Fe(1)-Fe(2) 3.462.
ligands was submitted to a multiple-stage tandem ESI-MS
analysis. The peaks of the two ligands were clearly identified
at m/z 699 and 868, corresponding to the formula H(L-
H+NHTs) and H(L-2H+2NHTs), respectively. They showed
similar fragmentation patterns, which is in agreement with
addition of the tosylamine groups to the benzyl group of the
ligand. In particular, the bis(tosyl) ligand gave a fragment at
m/z 429 corresponding to the bis(tosylamino)benzyl cation
[C6H3(NHTs)2CH2]+. The two ligands were then separated by
reverse-phase HPLC and investigated by NMR spectroscopy.
The ortho-benzylic proton appearing at d = 7.19 ppm in H(L-
H+NHTs) was absent in H(L-2H+2NHTs) and the two meta-
benzylic protons appearing at d = 7.02 and 7.53 ppm in H(L-
H+NHTs) had merged to d = 7.31ppm in H(L-2H +2NHTs),
insertion of the tosylamine group into the ortho position of
the benzyl group and the coordination of the amine to the
iron. Analysis of the bond lengths showed that the iron–ligand
bonds average 2.072 Š and 2.063 Š for Fe1and Fe2,
respectively. These bonds are in the range expected for high
spin ferric ions. In addition, it is noteworthy that the Fe2–
N(Ts) bond is rather short (2.016 Š), which indicates that the
benzyltosylamine is deprotonated and the compound is best
described as a diferric anilinate. This valence description was
716
www.angewandte.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 715 –717

Angewandte
Chemie
confirmed by magnetic susceptibility and Mössbauer spec-
troscopy experiments (see Supporting Information, Figur-
es S7, S8).
Keywords: amination · arenes · bridging ligands · iron ·
N,O ligands
.
The electrochemical behavior of 3a was investigated in
acetonitrile by cyclic voltammetry and exhaustive electrolysis
coupled with coulometry. Two reversible one-electron trans-
fers were observed at À0.63 (DEp = 80 mV) and 0.10 V vs. Ag/
Ag+ 10À2 m (DEp = 60 mV) which can be assigned to the
FeIIFeII/FeIIFeIII and FeIIFeIII/FeIIIFeIII couples, respectively
(see Supporting Information, Figure S9). The low oxidation
potential of 3a is reminiscent of that of the corresponding
ortho-phenolato derivative 2 (0.08 V)[17] , showing that the
tosylanilinato ligand is electronically very similar to its
phenolato counterpart.
[1] K. B. Sharpless, D. W. Patrick, L. K. Truesdale, S. A. Biller, J.
Am. Chem. Soc. 1975, 97, 2305 – 2307.
[2] R. Breslow, S. H. Gellman, J. Chem. Soc. Chem. Commun. 1982,
1400 – 1401.
[3] J. P. Mahy, P. Battioni, D. Mansuy, J. Fischer, R. Weiss, J.
Mispelter, I. Morgenstern-Badarau, P. Gans, J. Am. Chem. Soc.
1984, 106, 1699 – 1706.
[4] C. Fruit, F. Robert-Peillard, G. Bernardinelli, P. Muller, R. H.
Dodd, P. Dauban, Tetrahedron: Asymmetry 2005, 16, 3484 –
3487.
[5] K. W. Fiori, J. Du Bois, J. Am. Chem. Soc. 2007, 129, 562 – 568.
[6] D. H. R. Barton, R. S. Hay-Motherwell, W. B. Motherwell, J.
Chem. Soc. Perkin Trans. 1 1983, 445 – 451.
In summary, we have reported the very efficient and
specific insertion of tosylamine groups into an aromatic
residue mediated by a diiron complex. This is the first
bimetallic system able to mediate such amine transfers. This
reaction had been seldom achieved and often suffers from
competition with the corresponding oxygen transfer. It is
likely that it occurs through an iron(IV) imido derivative.
Nevertheless, in the present case, this intermediate appears
far less sensitive to hydrolysis as no trace of hydroxylation
product has been detected even when the reaction was run in
undried acetonitrile. This behavior may be due to the
dinuclear nature of the active species which is probably
analogous to that reported to mediate oxygen transfer
reactions,[11] although the weak ability of 1a to mediate
oxygen atom transfers from iodosylarenes[11] is also likely to
contribute. Interestingly a bis substitution occurs to a
significant extent. This observation was unprecedented and
opens the way to catalytic processes. The present results
reveal significant differences in the reactivity of these
binuclear complexes with the chemistry developed by the
original porphyrin and mononuclear non-heme systems. The
dinuclear nature of the present systems is most likely
responsible for these differences and in depth mechanistic
studies are underway to try and understand how these amine
transfer reactions operate.
[7] J. Yang, R. Weinberg, R. Breslow, Chem. Commun. 2000, 531–
532.
[8] M. P. Jensen, M. P. Mehn, L. Que Jr, Angew. Chem. 2003, 115,
4493 – 4496; Angew. Chem. Int. Ed. 2003, 42, 4357 – 4360.
[9] M. R. Fructos, S. Trofimenko, M. M. Diaz-Requejo, P. J. Perez, J.
Am. Chem. Soc. 2006, 128, 11784 – 11791.
[10] W. Kanda, W. Moneta, M. Bardet, E. Bernard, N. Debaecker, J.
Laugier, A. Bousseksou, S. Chardon-Noblat, J.-M. Latour,
Angew. Chem. 1995, 107, 625 – 628; Angew. Chem. Int. Ed.
Engl. 1995, 34, 588 – 590.
[11] F. Avenier, L. Dubois, J.-M. Latour, New J. Chem. 2004, 28, 782 –
784.
[12] F. Avenier, J.-M. Latour, Chem. Commun. 2004, 1544 – 1545.
[13] D. Macikenas, E. Skrzypczak, J. Protasiewicz, J. Am. Chem. Soc.
1999, 121, 7164 – 7165.
[14] S. Chardon-Noblat, O. Horner, B. Chabut, F. Avenier, N.
Debaecker, P. Jones, J. PØcaut, L. Dubois, C. Jeandey, J.-L.
Oddou, A. Deronzier, J.-M. Latour, Inorg. Chem. 2004, 43,
1638 – 1648.
[15] Experimental details and the structural description of 3a are
given in the Supporting Information. CDCC-656460 contains the
supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[16] The yield of 3b was reduced when only one equivalent of
ArINTs was used, but it attained a maximum of 40% even with
four equivalents. This behavior is due to the fact that 3a and 3b
are formed by competitive mechanistic pathways. A complete
mechanistic study of the reaction is currently in progress.
[17] E. Lambert, B. Chabut, S. Chardon-Noblat, A. Deronzier, G.
Chottard, A. Bousseksou, J.-P. Tuchagues, M. Bardet, J. Laugier,
J.-M. Latour, J. Am. Chem. Soc. 1997, 119, 9424 – 9437.
Received: August 7, 2007
Revised: October 1, 2007
Published online: December 10, 2007
Angew. Chem. Int. Ed. 2008, 47, 715 –717
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
717