C-H bond amination from a ferrous dipyrromethene complex

Article abstract of DOI:10.1021/ic900219b

In this Communication, we report an intramolecular C-H bond amination reaction of a dipyrromethene ferrous complex with organic azides. Monitoring of the spectral changes (variabletemperature NMR and UV-vis) of the Fe^II complex reveals no buildup of an intermediate during conversion of the starting material into the nitrene-inserted product. The rate-determining step appears to be azide addition to the 14-electron Fe^II complex, hinting at the potential that these and related platforms may have to effect atomand group-transfer processes.

Full text of DOI:10.1021/ic900219b

Inorg. Chem. 2009, 48, 2361-2363
C-H Bond Amination from a Ferrous Dipyrromethene Complex
Evan R. King and Theodore A. Betley*
Department of Chemistry and Chemical Biology, HarVard UniVersity, 12 Oxford Street,
306E Mallinckrodt, Cambridge, Massachusetts 02138
Received February 3, 2009
In this Communication, we report an intramolecular C-H bond
amination reaction of a dipyrromethene ferrous complex with
organic azides. Monitoring of the spectral changes (variable-
temperature NMR and UV-vis) of the FeII complex reveals no
buildup of an intermediate during conversion of the starting material
into the nitrene-inserted product. The rate-determining step appears
to be azide addition to the 14-electron FeII complex, hinting at the
potential that these and related platforms may have to effect atom-
and group-transfer processes.
metal-ligand multiple bonds to effect atom- or group-
transfer processes.6 Herein we report an intramolecular C-H
bond amination mediated by the reaction of a coordinatively
and electronically unsaturated dipyrromethene iron(II) com-
plex with organic azides.
A variety of ligand platforms have been employed that
utilize strongly donating substituents (e.g., phosphines,7
amines,8 carbenes,9 and ꢀ-diketiminates10), resulting in
strongly nucleophilic metal complexes capable of supporting
metal-ligand multiple bond formation. To target metal-ligand
multiple bonds potentially more reactive toward bond-
activating pathways, we sought an oxidatively resistant ligand
system that sterically enforces minimal coordination at the
metal center while maintaining an electrophilic metal envi-
Introducing functionality into unactivated C-H bonds
remains a significant challenge both in the realm of complex
molecule synthesis and in the elaboration of simple hydro-
carbon feedstocks into value-added commodity chemicals.1
The current state-of-the-art C-H bond functionalization
techniques mainly utilize late-transition-metal catalysts that
facilitate C-H activation and functionalization. Several
limitations exist in these methods: C-H bond activation
typically requires forcing conditions where oxidation pro-
cesses can become unselective under the conditions required
for bond activation to occur2 or C-H bond activation only
occurs proximal to substrate-directing groups.3 The develop-
ment of new inorganic/organometallic catalysts to effect
atom- or group-transfer processes will mitigate the reliance
on directing groups to activate C-H bonds,4 thereby
minimizing waste generation during synthetic procedures.5
One potential strategy for sequential C-H bond activation
and functionalization is to utilize the transient formation of
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*
To whom correspondence should be addressed. E-mail:
betley@chemistry.harvard.edu.
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10.1021/ic900219b CCC: $40.75  2009 American Chemical Society
Inorganic Chemistry, Vol. 48, No. 6, 2009 2361
Published on Web 02/17/2009

COMMUNICATION
Scheme 1
ronment, which may confer unique reactivity to the resulting
metal complexes. Arylated dipyrromethene ligands are good
candidates to satisfy both desired design criteria.11 Using
pyridinium p-toluenesulfonate as a catalyst (5%), 2-mesityl-
pyrrole was condensed with mesitaldehyde dimethyl acetal
to form the dipyrromethane. Subsequent oxidation with
dichlorodicyanoquinone in acetone affords the target 1,5,9-
trimesityldipyrromethene [(pyac)H, 1] in 68% overall yield.
Dipyrromethene 1 precipitates from the acetone solution upon
oxidation, obviating the need for chromatography as a
purification step. Deprotonation of the ligand can be effected
by the treatment of 1 with 1.2 equiv of n-BuLi in thawing
tetrahydrofuran (THF) solutions to produce the solvated lithio
complex [pyac][Li(THF)] (2), which was, in turn, suitable
for installing the pyac moiety onto transition metals.
Figure 1. UV-vis spectra of 1-3 (THF). The inset shows the cyclic
voltamagram of complex 3 in THF (0.1 M) with 0.3 M Bu4NPF6; scan rate
) 100 mV/s on a glassy carbon electrode.
Reaction of the lithio complex 2 with a thawing slurry of
FeCl2 in THF furnished the four-coordinate, solvated species
(pyac)FeCl(THF) (3) as a red solid (Scheme 1). The solid-state
structure for 3 is provided in Figure 2, confirming the solvated
state adopts a pseudotetrahedral environment at iron. THF in 3
is labile and can be exchanged for stronger binding ligands like
pyridine to yield (pyac)FeCl(pyr) (4). Likewise, the ZnII
congener was synthesized by the reaction of 2 with ZnCl2 in
thawing THF, followed by treatment with pyridine to furnish
(pyac)ZnCl(pyr) (5) as an isolable orange solid. Complexes 3-5
could be isolated as analytically pure solids in 75-84% yield.
Complexes 4 and 5 adopt geometries similar to that of 3 in the
solid state (see the Supporting Information).
Much like their porphyrin congeners, dipyrromethenes and
their metal complexes exhibit intense ligand π f π*
transitions afforded by the conjugation and aromaticity of
the dipyrromethene ligand system.12 The dominant charge
transfer occurs in the range of 460-500 nm for the parent
ligand 1 and its metal complexes (Figure 1) [λmax (ꢀ) for 1
467 nm (49 000 M-1 cm-1); λmax (ꢀ) for 2 499 nm (97 000
M-1 cm-1); λmax (ꢀ) for 3 503 nm (74 000 M-1 cm-1); λmax
(ꢀ) for 4 506 nm (69 000 M-1 cm-1); λmax (ꢀ) for 5 501 nm
(140 000 M-1 cm-1)]. The observed π f π* transition for
ligand 1 is not unlike other dipyrromethene ligand derivatives
that are often employed as fluorescence tags or the parent
porphyrin constructs.12 While the zinc complex 5 is a
diamagnetic species, the room temperature solution magnetic
moments of complexes 3 and 4 are 5.21(5) and 5.29(1) µB,
respectively, both consistent with high-spin (S ) 2) iron
centers (Evans method).13 Cyclic voltammetry on 3 and 4
reveals fully reversible FeIII/II redox waves centered at -400
mV versus an internal ferrocene reference (Figure 1, inset;
scan rate ) 100 mV/s). Cyclic voltammetry on complex 5
reveals fully reversible, one-electron reduction (-2.0 V) and
oxidation (+0.55 V) events originating from the ligand
Figure 2. Solid-state structure for 3 with thermal ellipsoids set at the 50%
probablility level (H atoms omitted for clarity). Bond lengths (Å) for 3:
Fe-N1, 2.017(3); Fe-N2, 2.034(4); Fe-Cl, 2.263(1); Fe-O, 2.029(3).
platform (see the Supporting Information). Reduction waves
are observed for complexes 3 and 4 at similar potentials,
whereas the onset to oxidation is shifted by ca. -300 mV
and the processes are no longer reversible.
To test whether the dipyrromethene ligand could confer the
same reactivity at the FeII center as their porphyrin counterparts,
we canvassed the reactivity of 3 with a series of organic azides
to examine whether nitrene transfer could be effected.14
Reacting a thawing solution of 3 in dichloromethane with a
stoichiometric amount of 1-azidoadamantane quantitatively
produces a new paramagnetic, iron-containing complex, evi-
denced by the increase of observable proton resonances apparent
1
in H NMR, consistent with desymmetrization of the ligand
1
environment (see the Supporting Information for H NMR
details). Solutions of 3 in thawing CH2Cl2 react quickly with
organic azides (N3Ph, N3Mes, and N3Ad) to expel dinitrogen,
as evidenced by the disappearance of the azide stretch in the
IR spectrum, and cleanly produce a new high-spin FeII product
distinct from 3 by 1H NMR, displaying a similar desymmetri-
zation of the ligand proton resonances.
Characterization of crude reaction mixtures by electrospray
ionization mass spectrometry revealed parent ions consistent
with azide-derived nitrene insertion into a ligand C-H bond
(Scheme 2). The masses obtained from the independent reac-
t
tions of 3 with N3R (R ) Bu, 1-Ad, Ph, Mes, Tos) suggest
that multiple nitrene insertions into the ligand do not occur,
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2362 Inorganic Chemistry, Vol. 48, No. 6, 2009

COMMUNICATION
Scheme 2
appear with a concomitant decrease in the observed peaks
for 3 in a roughly 1:1 fashion. This latter observation was
confirmed by following the reaction by the absorption
spectral changes. The spectral changes for the reaction of 3
with 10 equiv of 1-adamantyl azide (Figure 4) only show
the decay of 3 and growth of the product 6 [λmax (ꢀ): 518
nm (57 000 M-1cm-1)] with an isosbestic point at 516 nm,
indicating that there is no buildup of an observable inter-
mediate in the reaction. While in situ IR analysis of the
reaction mixture did not reveal a shift in the azide stretch
even when the azide reagent is used in excess (metal dissociation
was consistently observed using this ionization method). Vapor
diffusion of Et2O into a THF solution of 3 + N3Ad produced
crystals suitable for X-ray diffraction analysis. The molecular
structure of the product reveals insertion of the [NAd] fragment
into a benzylic C-H bond from one of the ligand pyrrolic
mesityl aryl groups (Scheme 2). The molecular structure of
aminated product (pyac)FeCl(NHAd*) (6) is shown in Figure
3. The local geometry about the iron in 6 adopts a distorted
trigonal-monopyramidal structure, where the azide-derived
amine (N3) remains bound to the iron.
One mechanistic possibility for the observed insertion
reaction involves azide addition to 3 (displacing the coor-
dinated THF), followed by dinitrogen expulsion from the
azide to yield a high-valent iron(IV) imido complex. Forma-
tion of the iron(IV) imido complex could then be quickly
followed by H-atom abstraction and a radical-rebound
mechanism to form the N-C bond found in the product in
a hydroxylase-like fashion.15 Variable-temperature (VT) 1H
NMR experiments did not reveal any discernible intermediate
along the proposed pathway, only the starting material 3 and
the emergence of the C-H bond-activated product 6 begin-
ning at -30 °C. The emergence of the product peaks for 6
1
on the IR time scale, H NMR analysis of the reaction of 3
with tBuN3 did reveal a dynamic exchange of the azide ligand
(from the shift of the tBu resonance) bound to a (pyac)FeCl
complex preceding formation of the nitrene-inserted product.
Several high-valent iron(IV) imido complexes have now
been synthesized and characterized.9c,16 Furthermore, reac-
tions of phenyl-N-tosylimidoiodinane and organic azides with
FeII complexes have been reported to produce iron amido
or anilido products and have been proposed to go through
iron(IV) imido intermediates.17 Radical reactivity has also
been observed from related iron(III) and cobalt(III) imido
complexes and typically leads to H-atom abstraction
products.10c,18 While a nonredox-involved process cannot be
ruled out in the conversion of 3 to 6, reaction of the zinc
complex 5 in place of the iron complex 3 does not afford
any aminated product even after prolonged heating of 5 with
excess organic azide (7 days, 50 °C). The iron pyridine
analogue 4 does produce the same aminated product 6,
although the reaction proceeds much more slowly (50%
completion after 7 days, 50 °C), presumably because of the
presence of the less labile pyridine ligand.
In conclusion, we have reported a simple dipyrromethene-
iron complex that is capable of mediating intramolecular
C-H bond amination from an organic azide precursor. This
reaction pathway diverges from typical radical H-atom
abstraction reactions in that the entire amine is transferred
to the C-H bond substrate. The presence of the electrophilic
FeII in 6 serves to trap the aminated product, likely inhibiting
further reaction. Work is currently underway to validate our
mechanistic hypothesis and to target intermolecular versions
of this reaction and related C-C and C-O bond-forming
reactions via similar C-H activation pathways.
Figure 3. Solid-state structure for 6 with thermal ellipsoids set at the 50%
probablility level (H atoms, solvent molecules and positional disorder
omitted for clarity). Bond lengths (Å) for 6: Fe-N1, 2.079(5); Fe-N2,
2.038(5); Fe-Cl, 2.245(2); Fe-N3, 2.190(5).
Acknowledgment. The authors thank the American Chemi-
cal Society (PRF Grant Type G) and Harvard University for
financial support and Dr. Douglas M. Ho for crystallographic
assistance.
Supporting Information Available: Experimental details, spec-
1
tral data (VT H NMR and UV-vis absorption spectra), and CIF
files for all compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
IC900219B
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Figure 4. Changes in the electronic absorption spectrum during conversion
of 3 f 6 in CH2Cl2 (3 mM in 3, 23 °C, scans each 60 s). Arrows denote
evolution of the absorption spectrum with time.
Inorganic Chemistry, Vol. 48, No. 6, 2009 2363