Direct Comparison of C-H Bond Amination Efficacy through Manipulation of Nitrogen-Valence Centered Redox: Imido versus Iminyl

Article abstract of DOI:10.1021/jacs.7b08714

Reduction of previously reported iminyl radical (^ArL)FeCl(^?N(C₆H₄-p-^tBu)) (2) with potassium graphite furnished the corresponding high-spin (S = ⁵/₂) imido (^ArL)Fe(N(C

Full text of DOI:10.1021/jacs.7b08714

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Article
Direct comparison of C–H bond amination efficacy through
manipulation of nitrogen-valence centered redox: imido versus iminyl
Matthew J.T. Wilding, Diana A. Iovan, Alexandra T Wrobel, James T.
Lukens, Samantha N. MacMillan, Kyle M. Lancaster, and Theodore A. Betley
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 22 Sep 2017
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Direct comparison of C–H bond amination efficacy through
manipulation of nitrogen-valence centered redox: imido
versus iminyl
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Matthew J.T. Wilding†, Diana A. Iovan†, Alexandra T. Wrobel†, James T. Lukens‡, Samantha N.
MacMillan‡, Kyle M. Lancaster‡, and Theodore A. Betley*†.
† Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge MA 02138, United
States
‡ Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca NY 14853, United
States
ABSTRACT: Reduction of previously reported iminyl radical (ArL)FeCl(•N(C6H4-p-tBu)) (2) with potassium graphite
furnished the corresponding high-spin (S = 5/2) imido (ArL)Fe(N(C6H4-p-tBu)) (3) (ArL = 5-mesityl-1,9-(2,4,6-
Ph3C6H2)dipyrrin). Oxidation of the three-coordinate imido (ArL)Fe(NAd) (5) with chlorotriphenylmethane afforded
(ArL)FeCl(•NAd) (6) with concomitant expulsion of Ph3C(C6H5)CPh2. The respective alkyl/aryl imido/iminyl pairs (3, 2; 5,
6) have been characterized by EPR, zero-field 57Fe Mössbauer, magnetometry, single crystal X-ray diffraction, XAS, and
5
EXAFS for 6. The high-spin (S = /2) imidos exhibit characteristically short Fe–N bonds (3: 1.708(4) Å; 5: 1.674(11) Å),
whereas the corresponding iminyls exhibit elongated Fe–N bonds (2: 1.768(2) Å; 6: 1.761(6) Å). Comparison of the pre-
edge absorption feature (1s → 3d) in the X-ray absorption spectra reveal that the four imido/iminyl complexes share a
common iron oxidation level consistent with a ferric formulation (3: 7111.5 eV, 2: 7111.5 eV; 5: 7112.2 eV, 6: 7112.4 eV) as
compared with a ferrous amine adduct (ArL)FeCl(NH2Ad) (7: 7110.3 eV). N K-edge X-ray absorption spectra reveal a
common low-energy absorption present only for the iminyl species 2 (394.5 eV) and 6 (394.8 eV) that was assigned as a N
1s promotion into a N-localized, singly occupied iminyl orbital. Kinetic analysis of the reaction between the respective
iron imido and iminyl complexes with toluene yielded the following activation parameters: Ea (kcal/mol) 3: 12.1, 2: 9.2; 5:
11.5, 6: 7.1. The attenuation of the Fe–N bond interaction on oxidation from an imido to an iminyl complex leads to a
reduced enthalpic barrier [ꢀ(ꢀH‡) ~5 kcal/mol]; the alkyl iminyl 6 has a reduced enthalpic barrier (1.84 kcal/mol) as
compared with the aryl iminyl 2 (3.84 kcal/mol), consistent with iminyl radical delocalization into the aryl substituent in
2 as compared with 6.
1. Introduction
field ancillary ligand, ArL, where ArL = 5-mesityl-1,9-(2,4,6-
Ph3C6H2)dipyrrin.26 We previously have shown that
reaction of the ferrous chloride precursor (ArL)FeCl (1)
with aryl azide N3(C6H4-p-tBu) results in formation of the
ferric iminyl complex (ArL)FeCl(•N(C6H4-p-tBu)) (2)
(Scheme 1), where evidence of the iminyl radical can be
seen in disruption of the iminyl aryl substituent.25-26 For
Late transition metal complexes featuring metal-ligand
multiple bonds are investigated intensely to probe their
efficacy for functional group transfer to organic
substrates.1-15 Within this class of coordination complexes,
iron complexes to which the nitrene functional group (R–
N) is bound have now been characterized spanning a
large range of oxidation states and electronic structures
example, reaction of
bimolecular, radical coupling of the phenyl iminyl ligands
to afford the diferric product
[(ArL)FeCl]2(ꢀ-
1
with N3(C6H5) results in
(FeII S = 0;16 FeIII S = /2, S = /2,17-23 S = /2;24 FeIII(•NR) S =
1
3
5
2;25-26 FeIV S = 0, S = 1;27-31 FeV S = /232,33). Of these
1
examples, only the high-spin, ferric imido24 and iminyl
complexes25-26 have been demonstrated to be competent
for nitrene group transfer into aliphatic or olefinic
substrates. The unique electronic configuration of the two
amination agents warrants further investigation into how
the electronic structure of the reactive intermediate
impacts functional group transfer from complexes bearing
metal-ligand multiple bonds.
N(Ph)(C6H5)N), allowing for unambiguous spectroscopic
assignment of the ferric state. A room temperature
solution magnetic moment determination of 2 (5.3(1) ꢀB)
in conjunction with agreement of the spectroscopic
Mössbauer parameters between 2 and the bimolecularly-
coupled product suggest the quintet 2 is comprised of a
high-spin ferric center, antiferromagnetically coupled to
an iminyl radical [Stotal = (Sferric = /2) – (Siminyl = /2) = 2].
Although this electronic structure had been suggested
previously,34-37 2 constitutes the first structurally and
5
1
Key to the success of the two examples for which C–H
bond amination is observed is the utilization of a weak-
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Scheme 1. Synthesis of imido (3, 5) and iminyl (2, 6) species.
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Scheme 2. Inter- and intramolecular amination reactions.
spectroscopically authenticated example of a transition
metal stabilized iminyl complex. The isolated iminyl 2
was competent for both intermolecular amination of
toluene as well as azirdination of styrene in
stoichiometric reactions.26 Employing the less sterically
demanding 1,9-adamantyl substituted dipyrrin ligand
(AdL) allowed for the nitrene-transfer reaction to be run
catalytically using N3Ad as an oxidant (Scheme 2).26, 38-39
Although no reactive intermediate could be isolated or
observed during catalysis, the similarity between the
kinetic isotope effects observed for both the
stoichiometric and catalytic amination processes
suggested a common ferric iminyl reactive intermediate
was operative.
transfer with both alkyl (N3Ad) and aryl (N3Mes) azides to
the monovalent iron complex (ArL)Fe (4) resulted in
isolable ferric imido products (ArL)Fe(NAd) (5) (Scheme 1)
and (ArL)Fe(NMes).24 The imido complexes were
characterized and described as possessing metal ligand
multiple bond character with structural features similar
to those reported for ferric imidos.17-23 Unlike those
literature precedents, the imido complexes were
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spectroscopically determined to be high-spin (S = /2).
Akin to their ferric iminyl congeners,25-26 these imido
species were shown to be competent for both H-atom
abstraction and nitrene transfer to C–H bond substrates.
Given the common core electronic structure (Sferric
=
5/2) between the imido and iminyl molecular species
previously characterized,24-26 we sought to address the
We have previously demonstrated that oxidative group
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also investigated and its cyclic voltammogram reveals a
following questions through a comparative examination
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of the two distinct molecular oxidation levels: (1) what are
the redox stabilities of iminyl 2 and imido 5? Are their
respective imido and iminyl congeners electrochemically
or chemically accessible? (2) We proposed that the aryl-
substituent in iminyl 2 is critical to stabilization of the
iminyl functionality via delocalization of the radical
throughout the aromatic ring.26 If chemical oxidation of
the alkyl imido 5 is possible, would the oxidation of the
complex be iron-borne resulting in a FeIV oxidation state
quasi-reversible oxidation event at –374 mV versus
[Cp2Fe]+/0 (Figure 1). Given the reduction of 2 and
oxidation of 5 constitute the same nominal redox couple,
it is worth noting the large cathodic shift afforded by
coordination of the chloride ligand and the aryl iminyl
moiety (ꢀ = –0.676 V). The redox potential for adamantyl
imido 5 (E1/2 = –0.37 V) is also mildly anodically shifted as
compared with the more electron rich analogues reported
([(tris(carbeno)borate)Fe(NAd)]+
–0.64
V,27
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akin to the hydroxylating ferryl compound
I
in
[(bis(phosphino)pyrazolylborate)Fe(NAd)]+ –0.72 V29),
though the comparison is not straightforward given the
coordination number change between species (three- vs.
four-coordinate).
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cytochrome P450?40-41 Or would a similar ferric-stabilized
iminyl radical [e.g., FeIII(•NR)] be observed without the
ability to delocalize the radical, as proposed for the intra-
and intermolecular amination catalysts? Furthermore, can
the two redox resonance forms be spectroscopically
distinguished [FeIV(NR) ↔ FeIII(•NR)]? (3) Lastly, if the
redox isomers are accessible for both alkyl and aryl
imido/iminyl moieties, how is the change in molecular
oxidation level manifested in C–H bond amination
efficacy? Herein we report our findings concerning the
interconversion of the imido/iminyl redox forms, describe
their comparative metal oxidation states using X-ray
2.2 Synthesis and spectroscopic characterization of
imido Fe(N(C6H4-p-tBu) and iminyl FeCl(•N(C6H4-p-
tBu) pair
While oxidative group transfer to monovalent 4 can
afford imido complexes with sterically encumbered alkyl
and aryl azides,24 no terminal imido complex could be
obtained upon treatment of 2 with N3(C6H4-p-tBu) and
only the tetraazide adduct was obtained (ArL)Fe(N4(C6H4-
p-tBu)2) from net consumption of two equiv of azide.42
Given the mild reduction potential for 2 (–1.10 V vs
[Cp2Fe]+/0), chemical reduction was thus pursued as a
means for generation of the terminal imido analogue.
Accordingly, reduction of 2 with KC8 in thawing benzene-
d6 resulted in the formation of a new paramagnetic
absorption spectroscopy, and provide
a
kinetic
assessment of their reactivity in intermolecular
amination.
2. Results and Discussion
2.1 Redox stability of the imido/iminyl units
1
complex via H NMR. The molecular structure of three-
coordinate iron imido (ArL)Fe(N(C6H4-p-tBu)) (3) was
obtained by X-ray diffraction studies on single crystals
grown from a concentrated toluene solution layered with
pentane at –35 °C (Figure 2a). The molecular structure
features a distorted trigonal planar iron(III) center
supported by the dipyrrin ligand and the aryl imido. The
Fe–N3 distance of 1.708(4) Å in 3 is longer than the iron
imido bond in 5 (1.674(11) Å), and nearly identical to that
found in the mesityl imido (ArL)Fe(NMes) (1.708(2) Å),
though far shorter than the corresponding distance in 2
(1.768(2) Å). The pertinent bond distances to compare 2
and 3 are presented in Figure 2b. Notably, all of the
carbon-carbon bonds within the imide aryl ring in 3 are
equivalent within error, indicating the aromaticity of the
imido aryl framework has been restored from the iminyl 2
upon reduction.
Further spectroscopic characterization of 3 affords
data in line with that observed for the alkyl imido 5.24
Akin to 5, complex 3 features a symmetric electric field
gradient, displaying a zero-field 57Fe Mӧssbauer spectrum
with a single transition (δ: 0.44 mm/s, |ΔEQ|: 0.00 mm/s)
at 200 K that becomes broad and weakly absorbing at
lower temperature (Figure 3a).). In accordance with the
observed temperature dependent phenomena (vide
supra), 3 does not exhibit an EPR signal above ca. 50 K.
The frozen toluene EPR spectrum of 3 (2.8 K) displays a
rhombic signal (geff = 8.62, 5.35, 3.10), well reproduced by
an S = 5/2 simulation treating each intra-doublet
Figure 1. Cyclic voltammograms of 2 (blue) and 5 (red)
obtained in CH2Cl2 at 25 °C, with 0.1 M (nBu4N)(PF6); 100
mV/s; referenced to [Cp2Fe]+/0 couple.
Cyclic voltammetry (CV) was performed on iminyl 2
and imido 5 to assess their redox stability (Figure 1). CV
examination of iminyl 2 in dichloromethane shows a
quasi-reversible reduction event at –1.10
V versus
[Cp2Fe]+/0 (Figure 1). The anticipated imido complex may
well dissociate the chloride ligand, akin to the three-
coordinate (ArL)Fe(NMes).24 The quasi-reversible couple
suggests a chemical process indeed occurs following
reduction. The electrochemical behavior of imido 5 was
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transition as an effective S = 1/2 system (in accordance
parameters: g = 2.0, |E/D| = 0.05, linewidth = 15 G). The
inclusion of D-strain is necessary to
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with the weak-field limit) and including the effects of
both rhombicity (E/D) and D-strain (simulation
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Figure 2. (a) Solid state molecular structure of 3 with thermal ellipsoids at the 35% probability level. Positional disorder,
solvent molecules, and H atoms are removed for clarity. Color scheme: Fe, orange; N, blue; C, gray. (b) Selected bond
metrics (Å) for iminyl 2 in red and imido 3 in black. Mulliken spin density plots (α–β) and values calculated for 3 (c) and 2
(d).
Figure 3. (a) Zero-field 57Fe Mӧssbauer spectra [δ, |ΔEQ|, Γ (mm/s)] of iminyl 2 (top left, red trace: 0.28, 2.22, 0.14), iminyl 6 (bot-
tom left, blue trace: 0.26, 2.05, 0.24); imido 3 (top right, red trace: 0.44, 0.00, 0.74), and imido 5 (bottom right, blue trace: 0.37,
0.00, 0.50). (b) Overlaid Fe K-edge XANES with inset Fe 1s ꢀ Fe 3d pre-edge features for 3 (solid red), 2 (dashed red), 5 (solid
blue), 6 (dashed blue), 7 (solid green). (c) EXAFS for 6 with data shown in blue and theoretical fit in black dashes.
account for the randomness in spatial conformation of
the frozen solution and provide an effective powder
of zero-field splitting and rhombicity, which was
quantified by fitting the data to the spin Hamiltonian Ĥ =
2
2
2
pattern for
a
given
S
and E/D.43 The data and
DŜz + E(Ŝx – Ŝy ) + gisoμB S•H. The fit parameters
considering an S = 5/2 system that best reproduce the data
are g = 2.00, D = 13.4.0 cm–1, |E/D| = 0.29.44
corresponding simulation are shown in Figure S5.
Accordingly, solid-state magnetometry of 3 is consistent
with a high spin state as evidenced by a μeff of 4.6 μB (
χ
χ
MT
MT
The original spin-state assignment for iminyl 2 was
based on room temperature, solution magnetic moment
determination.26 Thus, we sought to probe the ground
spin state electronic structure for this molecule to
corroborate the quintet assignment. Solid-state
magnetometry was collected on a sample of 2, cleanly
isolated following removal of H-atom sources via
= 4.76 cm3 K/mol) at 295 K (Figure S4). The value of
over the temperature range surveyed is consistent with an
5
S = /2 configuration (spin-only value anticipated is 4.38
cm3 K/mol). The spin state suggested by the magnetic
susceptibility data is further corroborated by variable-
temperature, variable-field magnetization data collected
on heating from 1.8 to 10 K and at increasing fields of 1–7
T (Figure S4 inset). Magnetization saturation occurs at 3.5
μB at 1.8 K and 7 T. The lower than expected saturation (5
treatment
of
reaction
glassware
with
trimethylsilylchloride, use of perdeuterated solvents, and
immediate purification of azide prior to synthesis. The
magnetic susceptibility reveals a well-isolated ground
state with no thermal transitions apparent between 50 K
5
μB for an ideal S = /2 with g = 2) and the observation of
non-superimposable isofield curves indicate the presence
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and 300 K. Both the room temperature effective magnetic
moment of 5.1 μB
MT = 3.6 cm3 K/mol) and reduced
precipitate was washed with pentane. Dissolution of the
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3
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5
6
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maroon solids in benzene followed by lyophilization
yielded a maroon powder (80% yield). The zero-field 57Fe
Mӧssbauer spectrum of the new material displayed a
(
χ
magnetization data can be well modeled as an S = 2 spin
system (Figure S1). The spin state suggested by the
magnetic susceptibility data is further corroborated by
variable-temperature, variable-field magnetization data
collected on heating from 1.8 to 10 K and at increasing
fields of 1 to 7 T (Figure S1 inset). Magnetization
saturation occurs at 3.5 μB at 1.8 K and 7 T. The lower than
expected saturation (4 μB for an ideal S = 2 with g = 2) and
the observation of non-superimposable isofield curves
indicate the presence of zero-field splitting and
rhombicity, which was quantified by fitting the data to
clean
quadrupole
doublet
(δ: 0.26 mm/s,
|ΔEQ|: 2.05 mm/s) with parameters very similar to those
observed for 2 (δ: 0.28 mm/s, |ΔEQ|: 2.22 mm/s) (Figure
3a). The similar Mӧssbauer spectra suggest a common
iron oxidation state, spin state, and geometric
configuration between 2 and the oxidation product of 5,
leading us to formulate the product as (ArL)FeCl(•NAd)
(6). The magnetic susceptibility of 6 is shown in Figure 4,
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revealing a ꢀeff of 4.4 μB at 295 K (χ
MT = 2.46 cm3 K/mol)
2
2
2
the spin Hamiltonian Ĥ = DŜz + E(Ŝx – Ŝy ) + gisoμB S•H.
The fit parameters considering an S = 2 system that best
reproduce the data are g = 2.12, D = –8.8 cm–1, |E/D| =
0.33.44 As noted above, the magnetic susceptibility for 2
plateaus between 50 K and 300 K without variation in the
susceptibility. Thus, the strength of the antiferromagnetic
consistent with an S = 2 ground state electronic
configuration. The spin state suggested by the magnetic
susceptibility data is further corroborated by variable-
temperature, variable-field magnetization data collected
on heating from 1.8 to 10 K and at increasing fields of 1–7
T (Figure 4, inset). Magnetization saturation occurs at 2.6
μB at 1.8 K and 7 T. The lower than expected saturation (4
μB for an ideal S = 2 with g = 2) and the observation of
non-superimposable isofield curves indicate the presence
of zero-field splitting and rhombicity, which was
quantified by fitting the data to the spin Hamiltonian Ĥ =
5
coupling between the ferric site (SFe = /2) and iminyl
moiety must exceed ca. 200 cm-1, in line with the value
predicted via DFT methods45 and supporting a broken-
symmetry electronic structure of 2 (Jcalc = –673 cm-1).26
For the iminyl/imido pair of 2 and 3, respectively, the
data collectively support an assignment of 2 as a high-spin
FeIII center antiferromagnetically coupled to an iminyl
centered radical. Upon reduction of 2, the added electron
populates an orbital that is principally imide-based to
restore aromaticity to the imide aryl π-system,
maintaining the ferric oxidation state. The unusual
stability of the ferric iminyl state can potentially be
attributed to the resonance stabilization afforded via π-
delocalization within the iminyl aryl unit. To gain insight
into the location of the redox, single-point DFT45
calculations on the iminyl 2 and imido 3 complexes were
performed. The calculated spin density plots (α – β) for 2
and 3, shown in Figure 2c-d, illustrate the contributions
to the total spin contributed by iron (2: 57%; 3: 70%) and
the imido unit (2: 34%; 3: 26%). The total spin localization
within the imido aryl substituent in 3 is equal to the spin
contribution from the imido N (12% N, 14% Ar), but
increases upon oxidation to the iminyl 2 (14% N, 20% Ar).
Based on these findings, the aryl component of the
imido/iminyl fragment can play a critical role in spin
delocalization, though it was as of yet unclear if an alkyl
2
2
2
DŜz + E(Ŝx – Ŝy ) + gisoμB S•H. The fit parameters
considering an S = 2 system that best reproduce the data
are g = 1.95, D = 6.9 cm–1, and |E/D| = 0.33.44 Thus, the data
support a view of 6 as an FeIII iminyl complex even in the
absence of an iminyl aromatic π–framework throughout
which the nitrogen centered radical can delocalize.
iminyl complex could adopt
a
similar electronic
configuration to 2 without a means for stabilizing the N-
centered radical.
2.3 Synthesis and spectroscopic characterization of
an alkyl iminyl (ArL)FeCl(•NAd)
To synthesize the alkyl iminyl analogue of 2, a solution
of chlorotriphenylmethane was added to a solution of
imido 5 in thawing benzene-d6 and allowed to stir for 1 h
at room temperature. After 1 h elapsed and the reaction
solution changed in color from pink to maroon,
Figure 4. Variable-temperature susceptibility data of
(ArL)FeCl(•NAd) (6) collected at 1.0 T, with χMT = 2.46
cm3K/mol at 295 K. (Inset) Reduced magnetization data
collected at 3 fields (1, 4, 7 T) over the temperature range
1.8 K–10 K. Magnetization fit parameters obtained with
PHI44: S = 2, g = 1.95, D = 6.9 cm-1, |E/D|= 0.33.
1
assessment of the reaction progress by H NMR revealed
consumption of 5 with concomitant formation of a new
paramagnetic species and Ph3C(C6H5)CPh2. The reaction
volatiles were removed in vacuo and the resultant
2.4.1
Extended X-ray absorption fine structure
analysis of iminyl 6
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The reactive nature of 6 precluded obtaining suitable For comparison, the energy-weighted maximum of the
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2
3
4
5
6
7
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single crystals for X-ray diffraction analysis. Thus, XAS
and EXAFS analysis on a benzene solution of 6 was
undertaken. The Fourier transform of the EXAFS region
resolved pre-edge bands of the ferrous product of 1 and
adamantyl amine, (ArL)FeCl(NH2Ad) (7), is shifted to
lower energy (7110.3 eV), consistent with a more reduced
iron center in this complex as compared to the other
species studied. Comparing the aryl and alkyl
imido/iminyl pairs, the pre-edge absorption features for
the alkyl species (5, 6) are shifted to higher energy relative
to those of the aryl congeners (3, 2). These shifts are 0.7
eV for the imido complexes and 0.9 eV for the iminyl
complexes. These energy differences are nearly as great as
the difference between the ferrous complex examined (7)
and the ferric imidos (~1.2 eV).
of
the
XAS
spectrum
for
6
to
k = 10 Å-1
(resolution = 0.15 Å) is well-modeled via a first shell
simulation considering two pyrrole nitrogens, one
chloride, and one iminyl nitrogen scattering paths (Figure
3c). The values are shown in Table 1 and are nearly
identical to the crystallographically determined bond
lengths of 2 (Fe–Npyrrole 2.013(1) Å, 1.997(1) Å; Fe–Cl 2.20(1)
Å; Fe–Niminyl 1.768(2) Å). The resolution of the data is
sufficient to differentiate the Npyrrole and Niminyl scattering
paths, although it is not sufficient to detect asymmetry in
the individual Fe–Npyrrole scattering paths. The close
structural similarity of 6 to 2 strongly suggests that
oxidation of imido 5 occurs at the imido nitrogen,
preserving the high-spin ferric electronic configuration at
iron.
9
10
11
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59
60
Table 1. EXAFS simulation of 6a
path
CN
R, Å
1.987(8) 0.0003(6) –7.61 29.5
2.222(5) 0.0011(4)
1.761(6) 0.0004(7)
σ2, Å2
E0
F, %
Fe–Npyrrole
Fe–Cl
2
1
Fe–Niminyl
1
aEXAFS were fit in OPT using paths calculated by FEFF7.
Coordination numbers (CN) were held constant while dis-
tances (R) and Debye-Waller factors (σ2) were allowed to
float. Parenthetical values correspond to fitting errors in R
and σ2 in the final significant digit. Errors in coordination
number are estimated at 25%. Fits were performed over the
Figure 5. N K-edge XAS for imido (3, 5) and iminyl (2, 6)
complexes; (Inset) N 1s ꢀ iminyl N 2p pre-edge features for 2
(black) and 6 (blue).
entire (0 to 6.0 Å) Fourier transform window. Goodness of fit
n
[( [k3(EXAFSobs − EXAFScalc )i ])2 /n]1/ 2
∑
i
i
is measured by F, defined as
. Additional fitting details are included in the Supporting
Information.
To provide further evidence for the iminyl radicals in 2
and 6, the nitrogen orbital containing the iminyl was
probed directly using nitrogen K-edge X-ray absorption
spectroscopy. As seen in Figure 5, pre-edge features at
400.5 and 399.8 eV are observed for all species (2, 3, 5, and
6) that can be assigned as transitions into high-lying
antibonding molecular orbitals of N 2p parentage.
Additional lower energy features present at 398.3 and
397.7 eV for the aryl (3 and 2) and alkyl (5 and 6)
imido/iminyl pairs, respectively, represent transitions into
the Fe 3d-based antibonding singly occupied molecular
orbitals that are predicted to contain substantial mixing
with N 2p orbitals (both dipyrrin and imido/iminyl N-
donors). Most importantly, new pre-edge features found
at lowest energy at 394.5 and 394.8 eV are observed
exclusively in the iminyl species 6 and 2, respectively. In a
recently reported N K-edge XAS calibration and study of
2.4.2 Fe and N K-edge X-ray absorption near edge
spectroscopy on imidos (3, 5) and iminyls (2, 6)
In light of the challenges associated with assignment
of metal oxidation state in the presence of high-lying
ligand-based molecular orbitals, samples of both
imido/iminyl pairs (3 and 2; 5 and 6) were investigated by
X-ray absorption near edge spectroscopy and the results
shown in Figure 3b. Note that, given the coordination
number change as well as potential change in iron-
imido/iminyl covalency, comparison of the rising edge
energy will not unambiguously reflect the respective
metal oxidation levels for the three-coordinate imido and
four-coordinate iminyl complexes. Iron K-edge pre-edge
absorption features are typically assigned to Fe 1s ꢀ 3d
excitations, although in the present case appreciable
ligand character can be expected in the acceptor
molecular orbitals. Nevertheless, the maxima of the
resolved pre-edge features demonstrate that upon
reduction of iminyl 2 (7111.5 eV) to imido 3 (7111.5 eV), or
oxidation of imido 5 (7112.2 eV) to iminyl 6 (7112.4 eV),
very little change in Fe physical oxidation state is inferred.
[(PNP)•+NiIICl][OTf],
a similar low energy pre-edge
feature present upon oxidation from its neutral congener
was identified.46 This new pre-edge feature present at
396.4 eV was assigned, through collaboration with
TDDFT calculations, as a transition from N 1s into the
nitrogen localized aminyl-based SOMO on the PNP
ligand framework. Hence, we assign the pre-edge features
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observed here at 394.5 and 394.8 eV as transitions into the
nitrogen-localized iminyl radicals present in 6 and 2,
respectively.
7
0.91
0.90
7110.3
7110.3
1
2
3
4
aDFT: B3LYP,53 CP(PPP)51 on Fe, def2-TZVP-ZORA49-50, 54-56
on all other atoms. bTDDFT: B3LYP, CP(PPP) on Fe, def2-
TZVP-ZORA on all other atoms.
2.4.3 Electronic structure calculations corroborate
assignment of 6 as an alkyl iminyl species
5
6
7
8
9
Accord between calculated and experimental
geometric and electronic structural parameters further
supports assignment of 6 as a stable alkyl analogue of
iminyl 2. Electronic structure calculations support
preservation of a high-spin d5 FeIII that is strongly
antiferromagnetically coupled to AdN• (calculated J = –
2204 cm–1) (Figure 6b).57-58 Moreover, comparison of the
orbital mixing coefficients in the calculated unrestricted
corresponding orbitals (UCOs) for iminyl species 2 and 6
that is localized to the N-centered β SOMO of the
antiferromagnetically-coupled pair reveals a ratio of 1.91
(62.3% in 6 vs. 32.6% in 2). This ratio corresponds well to
the experimental 2.02 (0.141 in 6 vs. 0.071 in 2) ratio of
intensities of the iminyl pre-edge features found in the N
K-edge XAS.
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11
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48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 6. Calculated Mulliken spin density (a) and qualita-
tive molecular orbital scheme (b) for 6. Spin density is plot-
ted at an isovalue of 0.009 au. Molecular orbitals are plotted
at isovalues of 0.04 au.
2.5
Comparative kinetic analysis for the
imido/iminyl complexes undergoing C–H bond
activation with toluene
A geometry optimization45 of 6 was carried out to
produce coordinates from which to carry out electronic
structure calculations. The complete structure of 6
including full aryl substituents was optimized using the
BP8647-48 functional with the segmented all-electron
relativistically contracted (SARC) Ahlrich’s def2-TZVP-
ZORA basis set.49-50 Optimization of 6 employed the
broken symmetry (BS) approach, assuming partitioning
between 5 Fe-based and 1 ligand-based spin (BS 5,1). The
structure produced at this level of theory closely
reproduces the experimental bond lengths, yielding the
following primary coordination sphere interatomic
distances: Fe–Npyrrole 2.002 Å, 1.981 Å; Fe–Cl 2.200 Å; Fe–
Niminyl 1.707 Å (Figure 6a). These coordinates, along with
optimized structures for 2, 3, 5, and 7, were used in B3LYP
calculations of Mössbauer δ51 values as well as time-
dependent DFT (TDDFT) calculations of Fe K-edge XAS52
pre-edge bands (Table 2, Figure S21). Calculated
The isolation of iron imido/iminyl redox pairs provides
a unique opportunity to investigate the effect of altering
the valence of the transferred atom during a C–H
functionalization reaction without affecting the transition
metal oxidation state. Dissolution of iminyl complexes 2
or 6 in toluene results in immediate reaction, as
demonstrated by the change in UV/Vis absorption over
time (Figure 7). The change in absorbance at λmax was fit
as an exponential decay and the resulting observed rate
constant is shown in Table 3. In contrast, the UV/Vis
spectrum of the imido complexes 3 or 5 in toluene is
identical to that observed in benzene and does not
change over the course of four hours at room
temperature. In fact, a similar rate of reaction to those
exhibited by the iminyl species is not achieved until the
solution is heated to 80 °C, indicating a substantially
higher barrier towards reactivity with toluene for the
imidos 3 and 5. Assuming a simple kinetic profile wherein
the change in absorbance at λmax is directly related to the
consumption of staring material (imido or iminyl) and the
reaction course is not significantly altered by
temperature, the activation energy can be extracted from
these data for each complex and is presented in Table 3.
spectroscopic
experiment
parameters
after calibration with the remaining
accord
strongly
with
–
compounds in the test set (Figures S22, S23), the value of
δ for 6 is matched by theory, and the error in the 1s → 3d
excitation is 0.1 eV.
Table 2. Experimental and Calculated Spectroscopic
Parameters
Pre-edge
δ(Exp), δ (Calc)a,
Pre-edge
(Exp), eV
Complex
(Calc)b,
eV
mm•s–1
mm•s–1
2
3
5
6
0.28
0.44
0.37
0.26
0.23
0.44
0.42
0.26
7111.5
7111.5
7112.2
7112.4
7111.7
7111.6
7112.0
7112.5
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5
3
6
2
80
90
100
80
90
100
22
0.0264
0.0427
0.0633
0.0195
0.0343
0.0745
0.0299
0.0433
0.0722
0.0166
0.0256
0.0528
26
16
11
11.5
12.1
7.1
1
2
3
4
5
6
7
8
36
20
9
23
16
10
42
27
13
9
32
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60
42
22
9.2
32
42
aExponential decay of Δ(λmax) versus time was fit inde-
pendently at each temperature.
Comparison of the independent rates of reaction for 5
and 6 suggests that a rate enhancement of two orders of
magnitude occurs upon oxidation. Indeed, heating an
equimolar ratio of 5 and 6 to 60 °C in toluene results in
selective consumption of the iminyl complex 6 and
Figure 7. (Top left) UV/Vis traces of the reaction of 2 with
toluene at 22 °C with spectra recorded every 10 minutes for 4
hours. (Bottom left) Normalized absorbance at λmax (554 nm)
during the course of the reaction at various temperatures.
1
formation of a new set of paramagnetic resonances via H
1
(Right) H NMR spectra progression of a toluene solution of
NMR (Figure 7). The appearance of these chemicals shifts
can be attributed to the formation of (ArL)FeCl (1) and
equimolar imido 5 and iminyl 6 at 60 °C at the time elapsed
indicated. Chemical shifts corresponding to 5 are highlighted
in red, 6 in blue, and (ArL)FeCl (1) in green.
occurs concomitantly with
corresponding to N-benzyl-adamantylamine.
a
peak at 3.72 ppm
The
competition experiment validates the independent rate
studies and demonstrates that the iminyl complex 6 is
significantly more reactive towards C–H bonds than its
imido congener 5. The increased reactivity of 6 is not
limited to C–H amination: imido 5 is stable in neat
styrene up to 100 °C, whereas iminyl 6 reacts smoothly
with 200 equiv. styrene at room temperature to yield the
desired aziridine in 36% yield. Further, hydrogen atom
abstraction from cyclohexene occurs at room temperature
Upon oxidation of the nitrogen atom from the imide
to the iminyl state, the barrier for reaction with toluene
decreased by an average of 3.7 kcal/mol. The additional
radical density present on the nitrogen atom can account
for the enhancement of reactivity, more closely
resembling the electronic structure at the transition state
for hydrogen atom abstraction. This simple Hammond-
type analysis is in line with the higher activation energy
for the aryl imido and iminyl complexes 3 and 2,
respectively, which feature electron delocalization
through the aromatic fragment as opposed to the
localized spin density at the transferring nitrogen atom of
5 and 6. Alternatively, the higher molecular oxidation
state may also contribute to the increase in reactivity via a
Bell-Evans’-Polanyi-type correlation,59 wherein the rate
enhancement upon oxidation is attributable to the
increased driving force of the reaction as a result of a
higher oxidation potential or enhanced N–H bond
strength of the metal-amide product. Regardless, the
activation parameters for reaction of these iron imide
complexes with toluene demonstrate a higher enthalpic
barrier upon reduction or upon substitution with an
aromatic imide substituent, suggesting that both a higher
metal-imide bond order and delocalization through the
aromatic π-system stabilize the iron imide with respect to
hydrogen atom abstraction.
with iminyl
6
to produce the H2NAd adduct
(ArL)FeCl(H2NAd) (7) quantitatively, whereas the imido
congener 5 requires heating to 80 °C and arrests at
formation of the amide adduct (ArL)Fe(HNAd).24
2.6.
considerations
2.6.1 Frontier molecular orbital considerations
The electronic structure of the imido and iminyl differ
Reaction pathways and thermodynamic
in the extent to which both N 2p orbitals engage in π-
bonding with iron orbitals of appropriate symmetry. The
imido complexes feature nearly linear Fe–N–C bond
linkages, signifying maximal, though non-degenerate, π
interactions: πx [σ*(dxz
± Npx] which includes a Fe–
Lσ)
–
Ldipyrrin σ* component, and the orthogonal πy (Fe dyz
Npy). The high-spin imido complexes give rise to a
±
(πx)2(πy)2(πy )1(πx )1 configuration. The iminyl complexes,
however, lack conjugation of the two π manifolds. Indeed,
a simple description for the iminyl consistent with the
iron oxidation levels observed by 57Fe Mössbauer and
XAS, consists of only the πx interaction, leaving a largely
N-centered radical for 6. While the iminyl radical lacks
the enhanced stabilization afforded by delocalization in
*
*
Table 3. Rate constants, half-lives, and activation en-
ergies for reaction of iron complexes with toluenea.
Complex
T (°C)
k (s-1)
t1/2 (min)
Ea
(kcal/mol)
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reactions of both imido (3, 5) and iminyls (2, 6) with
the aromatic ring of 2, the radical is nonetheless stabilized
1
2
3
4
5
6
7
8
by coupling antiferromagnetically to the five iron α spins
(see Figure 6). This electronic configuration manifests in
the larger Fe–N bond lengths observed, as well as the
enhanced reactivity of the iminyl with respect to the
imido congener.
toluene suggest that the C–H bond breaking event
contributes significantly to the rate limiting step of the
reaction sequence illustrated for 6 in Figure 8a.
A consideration of the frontier molecular orbitals
(FMOs) that complete this process include the Fe–N π
interaction (πx), the N 2py orbital containing the iminyl
radical, and the toluene C–H σ bond (Figure 8b). The N-
radical (2py)1 dictates the primary orbital interaction with
the incoming toluene C–H substrate given its steric
We have previously proposed a reaction sequence for
intermolecular amination using imido 5. We can amend
that orbital description to describe qualitatively the
reactivity differences observed between the imido and
iminyl congeners. The large KIEs observed in the
9
10
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53
54
55
56
57
58
59
60
Figure 8. Frontier molecular orbital description of (ArL)FeCl(•NAd) (6) reaction profile (a) for H-atom abstraction from
PhCH3 (b) and the subsequent radical rebound event (c).
accessibility and more favorable energetic overlap. Thus
the frontier orbital interaction with respect to the iron-
iminyl is lower in energy than the analogous imido
sequence.
That the iminyl complexes will activate the C–H bonds
of toluene at lower temperatures than their respective
imido congeners is a direct result of the diminished Fe–N
bond order. Thus, the oxidizing orbital (N 2py)1 is lower in
energy than the corresponding imido reaction partner
*
amination reaction which proceeds from the (πy )1 orbital.
The H-atom abstraction step is highlighted in Figure
8b, where the homolyzed C–H orbital (yielding PhC•H2
*
and H 1s) combine with N 2py to yield three orbital
(πy ), leading to a better energetic overlap between H-
0
)
combinations: (σN–H)2 (•CH2Ph)1(σ*N–H
Unlike the imido
atom donor and acceptor orbitals. Furthermore, the
entire amination sequence for the iminyls conserves the
total spin angular momentum while the imido complexes
must change their electronic configurations (S = 5/2 → S =
3/2) concomitantly with iron reduction.
.
amination sequence where H-atom abstraction leads to
metal reduction, the H-atom abstraction step for the
iminyl is completely N-centered, leaving the iron
oxidation level unchanged. The H-atom abstraction step
conserves total spin-angular momentum as the resulting
The presence of metal-stabilized iminyl radicals have
now been observed9,
or implicated in H-atom
36
radical pair complex remains in
a
quintet spin
abstraction reactivity12-13,
and nitrene transfer
21, 37
configuration. The recombination step (Figure 8c) should
proceed combining the benzylic radical with the
remaining πx [σ*(dxz – Lσ) ± Npx] pair yielding three product
catalysis7-8,
in a number of systems.15 The
10-11, 60-61
supporting organic moiety on the bound nitrene can
promote stabilization via hetero-atom donation, akin to
Fischer-type carbene ligands,10-11 or promote reactivity by
orbitals: (σN–C)2(Fe 3dxz)2(σ*N–C)0, constituting
a net
reduction of the iron center, yet again conserving the
total spin-angular momentum for the entire reaction
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concentration of radical density on the iminyl N-atom as
is the case in 6.
2.6.2 Thermodynamic Considerations
In considering stepwise mechanism for C–H
amination, the initial hydrogen atom abstraction from
substrate can be represented via a thermodynamic square
scheme that partitions the driving force of the reaction
into the constituent proton and electron transfer
contributions, as shown in equation 1:
symmetry electronic structure, respectively.
1
2
3
4
5
6
7
8
2.5 Conclusions
We have previously demonstrated that the (dipyrrin)iron
platform is capable of stabilizing both high-spin ferric
imido species, as well as the highly unusual ferric iminyl
a
complex which features
a
high-spin iron center
antiferromagnetically coupled to the iminyl radical. Both
of the high-spin complexes are capable of effecting
nitrene transfer to C–H bonds and olefinic substrates. The
foregoing results demonstrate that the imido/iminyl
9
ΔGHAT (kcal/mol) = 23.06 E0 + 1.37 pKa + 59.5 (eq 1)
10
11
12
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48
49
50
51
52
53
54
55
56
57
58
59
60
redox
isomers
are
chemically
interchangeable.
where the final constant represents the standard potential
for proton reduction in aprotic solvent.62 Electrochemical
Furthermore, the elusive alkyl iminyl intermediate
(ArL)FeCl(•NAd), implicated in both inter- and
intramolecular C–H bond functionalization catalytic
analysis of
2 revealed a quasi-reversible reduction
potential of –1.05 V versus [Cp2Fe]+/0. Given this reduction
potential, the productive activation of toluene (C–H BDE:
90 kcal/mol)63 by 2 would require a pKa of 40 in the
resulting (ArL)FeCl(NH(C6H4-p-tBu)) complex. This
estimation is in line with both the experimentally
determined pKa of Smith’s iron(III)–amide (pKa = 37(3))27
and the calculated pKa of Borovik’s manganese(II)–
hydroxide (pKa ≥ 36) complexes,64 as well as others. The
higher calculated pKa value for 2 as compared to Smith’s
cationic tris(carbeno)borate-supported iron(IV) imide can
be rationalized via the difference in overall charge
between these molecules, and permits the activation of
the stronger C–H bond of toluene.
processes,
characterized.
was
isolated
Comparison
and
of
spectroscopically
the Mössbauer
spectroscopy, magnetometry, and bond lengths of the
alkyl iminyl complex with the aryl iminyl congener
revealed striking similarities, suggesting a common
electronic structure and indicating the nitrene aryl
component is not necessary to stabilize the iminyl
oxidation level via radical delocalization. Furthermore,
oxidation of the imido complexes to their iminyl redox
isomers largely localizes the oxidation event to the NR
fragment. The iminyl complexes feature N K-edge pre-
edge absorptions found to be characteristic for these N
radical based ligands, arising from N 1s promotion into a
singly occupied N 2p iminyl orbital. Lastly, having access
to both alkyl and aryl NR redox isomers, we were able to
assess how the change in molecular oxidation level
manifests in changes to C–H bond amination efficacy.
Oxidation of the imido complexes to their iminyl redox
isomer results in a rate enhancement of two orders in
magnitude. The rate enhancement is largely enthalpic
(entropic barriers are nearly equal). The ability of the
imido or iminyl component to delocalize the spin-density
throughout an aryl substituent also results in a greater
barrier towards functional group transfer. We infer this
latter to mean that concentration of radical density upon
the transferring group can play a large role in C–H bond
functionalization processes.
The ability of 6 to functionalize toluene allows a rough
estimation of the Fe=N bond strength via equation 2:
ΔH0(Fe=N) = ΔH0(N–H) + ΔH0(C–N) – ΔH0(C–H) – 2*23.06 E0 (eq
2)
where E0 is the standard reduction potential of 6.
Although the appropriate bond dissociation energies have
not been determined for N-benzyl-adamantyl amine,
experimental values for N-methyl-benzyl amine are
readily available63 and provide an Fe–N bond strength of
approximately 94 kcal/mol. This value is similar to the
experimentally determined ΔH0
range of Nocera’s
(Fe=O)
pacman iron(IV) oxo porphyrin system of 65–85 kcal/mol
which can promote two-electron oxidation of substrate,
but not C–H hydroxylation chemistry.65
Associated Content
A comparison of the activation energies for the
imide/iminyl pairs demonstrated a lower barrier for
reaction with toluene at the iminyl state. A Bell-Evans-
Polanyi correlation between the rate of reaction and
thermodynamic driving force would suggest that
hydrogen atom transfer is therefore less favorable at the
lower valent state. The higher Fe–N bond order, coupled
with the absence of electrochemical reduction of 5 under
experimental conditions (to –2.3 V versus [Cp2Fe]+/0),
indicate that the overall functionalization process is
likewise less favorable at the imide state. These data
support that the enhancement of reactivity at the iminyl
state is both kinetic and thermodynamic in nature, due to
the higher radical density present at the N-atom and
weaker iron–nitrogen interaction via the broken
Supporting Information
The Supporting Information is available free of charge on
the ACS Publications website at DOI: XXX. X-ray crystal
structure images; magnetic data; cyclic voltammograms;
X-ray absorption spectra; Mössbauer, UV-vis, and 1H
NMR spectra (PDF). Crystallographic data (CIF).
Author Information
Corresponding Author
*betley@chemistry.harvard.edu
Acknowledgments
10
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(14) Prier, C. K.; Zhang, R. K.; Buller, A. R.; Brinkmannꢁ
T.A.B. gratefully acknowledges support by grants from the
1
NSF (CHE-0955885) and NIH (GM-115815), and from
Harvard University. M.W. would like to thank the NSF for
a Predoctoral Graduate Fellowship. K.M.L. gratefully
acknowledges support from the NSF in the form of a
CAREER award (CHE-1454455) and from the ACS
Petroleum Research Fund (55181-DNI6). This work is
based in part on research conducted at the Stanford
Synchrotron Radiation Lightsource (SSRL), which is
supported by the U.S. Department of Energy, Office of
Science, Office of Basic Energy Sciences under Contract
No. DE-AC02-76SF00515. The SSRL Structural Molecular
Biology Program is supported by the Department of
Energy’s Office of Biological and Environmental Research,
and by NIH/HIGMS (including P41GM103393). The
content of this publication is solely the responsibility of
the authors and does not necessarily represent the official
views of NIGMS or NIH.
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