Nonheme iron-mediated amination of C(sp3)-H bonds. Quinquepyridine-supported iron-imide/nitrene intermediates by experimental studies and DFT calculations

Article abstract of DOI:10.1021/ja3122526

The 7-coordinate complex [Fe(qpy)(MeCN)₂](ClO₄) ₂ (1, qpy = 2,2′:6′,2″:6″, 2′′′:6′′′,2′′′′- quinquepyridine) is a highly active nonheme iron catalyst for intra- and intermolecular amination of C(sp³)-H bonds. This complex effectively catalyzes the amination of limiting amounts of not only benzylic and allylic C(sp³)-H bonds of hydrocarbons but also the C(sp³)-H bonds of cyclic alkanes and cycloalkane/linear alkane moieties in sulfamate esters, such as those derived from menthane and steroids cholane and androstane, using PhI=NR or "PhI(OAc)₂ + H₂NR" [R = Ts (p-toluenesulfonyl), Ns (p-nitrobenzenesulfonyl)] as nitrogen source, with the amination products isolated in up to 93% yield. Iron imide/nitrene intermediates [Fe(qpy)(NR)(X)]ⁿ⁺ (C_X, X = NR, solvent, or anion) are proposed in these amination reactions on the basis of experimental studies including ESI-MS analysis, crossover experiments, Hammett plots, and correlation with C-H bond dissociation energies and with support by DFT calculations. Species consistent with the formulations of [Fe(qpy)(NTs)₂] ²⁺ (C_NTs) and [Fe(qpy)(NTs)]²⁺ (C) were detected by high-resolution ESI-MS analysis of the reaction mixture of 1 with PhI=NTs (4 equiv). DFT calculations revealed that the reaction barriers for H-atom abstraction of cyclohexane by the ground state of 7-coordinate C _NTs and ground state of C are 15.3 and 14.2 kcal/mol, respectively, in line with the observed high activity of 1 in catalyzing the C-H amination of alkanes under mild conditions.

Full text of DOI:10.1021/ja3122526

Article
pubs.acs.org/JACS
Nonheme Iron-Mediated Amination of C(sp3)−H Bonds.
Quinquepyridine-Supported Iron-Imide/Nitrene Intermediates by
Experimental Studies and DFT Calculations
Yungen Liu, Xiangguo Guan, Ella Lai-Ming Wong, Peng Liu, Jie-Sheng Huang, and Chi-Ming Che*
Department of Chemistry and State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong
Kong
S
* Supporting Information
ABSTRACT: The 7-coordinate complex [Fe(qpy)-
(MeCN)2](ClO4)2 (1, qpy = 2,2′:6′,2″:6″,2′′′:6′′′,2′′′′-
quinquepyridine) is a highly active nonheme iron catalyst for
intra- and intermolecular amination of C(sp3)−H bonds. This
complex effectively catalyzes the amination of limiting amounts
of not only benzylic and allylic C(sp3)−H bonds of
hydrocarbons but also the C(sp3)−H bonds of cyclic alkanes
and cycloalkane/linear alkane moieties in sulfamate esters,
such as those derived from menthane and steroids cholane and
androstane, using PhINR or “PhI(OAc)2 + H2NR” [R = Ts
(p-toluenesulfonyl), Ns (p-nitrobenzenesulfonyl)] as nitrogen source, with the amination products isolated in up to 93% yield.
Iron imide/nitrene intermediates [Fe(qpy)(NR)(X)]n+ (CX, X = NR, solvent, or anion) are proposed in these amination
reactions on the basis of experimental studies including ESI-MS analysis, crossover experiments, Hammett plots, and correlation
with C−H bond dissociation energies and with support by DFT calculations. Species consistent with the formulations of
[Fe(qpy)(NTs)2]2+ (CNTs) and [Fe(qpy)(NTs)]2+ (C) were detected by high-resolution ESI-MS analysis of the reaction mixture
of 1 with PhINTs (4 equiv). DFT calculations revealed that the reaction barriers for H-atom abstraction of cyclohexane by the
ground state of 7-coordinate CNTs and ground state of C are 15.3 and 14.2 kcal/mol, respectively, in line with the observed high
activity of 1 in catalyzing the C−H amination of alkanes under mild conditions.
tion numbers17 (I−VI, Figure 1) have been structurally
INTRODUCTION
■
characterized by X-ray crystal analysis,18 some of which exhibit
Metal-mediated amination of C(sp3)−H bonds via reactive
interesting reactivity.19−23 For example, a 3-coordinate complex
metal−imide (or nitrene) intermediates is an appealing
methodology for C−N bond formation.1 Development of
(I), or a 4-coordinate complex formed by binding of tert-
iron catalysis2 for such amination reactions is important
because of the natural abundance and biocompatibility of
iron. In literature, there have been extensive works on the
butylpyridine to its 3-coordinate counterpart (I), can undergo
H-atom abstraction of allylic 2° C(sp3)−H bonds of cyclic
alkenes/dienes,15c,21a,b and a 4-coordinate complex (IV)
aminates the benzylic 1° C(sp3)−H bond of toluene.6d Iron−
functionalization of C(sp3)−H bonds catalyzed by iron-
imide complexes having coordination numbers >5 are also
containing enzymes, including alkane hydroxylation by heme
iron enzymes, such as cytochrome P-450,3 and by nonheme
iron enzymes, such as methane monooxygenase,4 both being
proposed to involve iron−oxo intermediates. Hydroxylation of
C(sp3)−H bonds using nonheme iron catalysts has also been
extensively studied over the past decades.5 Iron-imide/nitrene
complexes are nitrogen analogues of iron-oxo species. However,
studies on nonheme iron-catalyzed amination of C(sp3)−H
bonds via nitrogen group insertion are sparse,6 with the
reported examples mostly confined to benzylic C−H bonds.
Other types of catalytic nitrogen group transfer reactions such
as CC aziridination via proposed nonheme iron−imide/
nitrene intermediates have also been well documented in
literature.7−14 Characterizations of the iron−imide/nitrene
intermediates involved in these reported catalytic reactions,
however, are scarce.6d,10 Remarkably, a number of nonheme
iron−imide complexes having 3-,15 4-,6d,10,16 and 5-coordina-
reactive, presumably this is due to the elongated Fe−N(imide)
distance resulting from population of electrons in the Fe−N π
antibonding orbitals.24 An example is the 6-coordinate complex
(VII, Figure 1) which was characterized by spectroscopic
methods and examined by DFT calculations.24 Two proposed
reactive 6-coordinate nonheme iron−imide intermediates (A25a
and B,25b Figure 1) have been reported to convert to iron−
amide complexes via intramolecular amination of the C(sp2)−
H bond(s) of pendant phenyl group in their coligands.26
Development of nonheme iron catalysts for intermolecular
amination of strong C(sp3)−H bonds of alkanes27 is a
challenge. The amination of cyclohexane C(sp3)−H bond
was first reported in 1982 with synthetic heme iron catalyst28
Received: December 15, 2012
© XXXX American Chemical Society
A
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multidentate coligands would allow formation of highly reactive
cationic metal bis(imide/nitrene) species; the cationic charge
would enhance electrophilicity of the coordinated imide/
nitrene groups.
Inspired by the intriguing oxidation catalysis of the
structurally characterized 7-coordinate complex [Fe(qpy)-
(MeCN)2](ClO4)234 (1, Figure 1; qpy is a neutral pentadentate
ligand 2,2′:6′,2″:6″,2′′′:6′′′,2′′′′-quinquepyridine)35 with both
[Fe(qpy)O]2+ and [Fe(qpy)O2]2+ species detected by high-
resolution electrospray ionization mass spectrometry (ESI-
MS),36 we examined the utility of 1, which possesses two labile
coordination sites to allow possible formation of iron
bis(imide/nitrene) species, in iron imide/nitrene chemistry.
Seven-coordinate iron is well documented37 but remains little
explored in the formation of iron imide species. In a recent
report, the proposed nitrene transfer from PhINR mediated
by 7-coordinate iron complex supported by hexadentate tris(2-
picolyl)amine ligand 6,6′-(pyridin-2-ylmethylazanediyl)bis-
(methylene)bis(N-tert-butylpicolinamide) afforded iron mono-
(amide) complexes (likely from nitrene transfer with
subsequent hydrogen atom abstraction).38
Herein we report that 1 is an active nonheme iron catalyst for
intermolecular amination of the C(sp3)−H bond of cyclo-
alkanes (Figure 1) as well as for intramolecular amination of
C(sp3)−H bonds in sulfamate esters, using PhINR or
“PhI(OAc)2 + H2NR” as nitrogen source. These catalytic C−H
amination reactions feature high product yields and a broad
substrate scope and hence are of practical interest in organic
synthesis. The reactive iron−imide/nitrene intermediate(s)
[Fe(qpy)(NR)(X)]n+ (CX, Figure 1) is proposed for the
catalysis, and species assignable to [Fe(qpy)(NTs)2]2+ (CNTs,
Ts = SO2-p-MeC6H4) and [Fe(qpy)(NNs)2]2+ (CNNs, Ns =
SO2-p-NO2C6H4) have been detected by high-resolution ESI-
MS analysis. The ESI-MS detection of [Fe(qpy)(NR)2]2+ (CNR
,
Figure 1. Top: Types of nonheme iron−imide/nitrene complexes
reported in literature (I−VI: structurally characterized, VII:
characterized by spectroscopic methods; A and B: proposed) and
intermolecular reaction with C(sp3)−H bonds. Bottom: Findings in
this work including amination of C(sp3)−H bond of cyclohexane
catalyzed by 7-coordinate 1, along with proposed iron−imide/nitrene
intermediates CX based on experimental studies and DFT calculations.
For simplicity, the iron−imide/nitrene coordination is generally
depicted as FeNR.
R = NTs, NNs) and its mono(imide/nitrene) counterparts
(C), such as [Fe(qpy)(NTs)]2+, the further experimental
studies and DFT calculations altogether lend support to the
intermediacy of CX to be responsible for the C−H amination.
RESULTS
■
Prior to exploring the catalytic activity of 1 toward amination of
C(sp3)−H bonds, we found that 1 can catalyze nitrogen group
transfer to alkenes, resulting in aziridination of styrenes with
PhINTs or “PhI(OAc)2 + H2NR” (up to 89% yield) and
intramolecular aziridination of unsaturated sulfonamides with
PhI(OAc)2 (up to 97% yield) (Tables S1 and S2). We also
observed intramolecular amination of benzylic 2° C(sp3)−H
bonds of three sulfamate esters with PhI(OAc)2 catalyzed by
[Fe(Cl3terpy)2](ClO4)2 (Cl3terpy =4,4′,4″-trichloro-2,2′:6′,2″-
terpyridine).6c Earlier there had been several reports on metal-
catalyzed intramolecular amination of sulfamate esters with
PhI(OAc)2,39a,b since the first examples reported in 2001 using
dirhodium catalysts.39a A seminal study reported in 19836a on
metal-catalyzed intramolecular C−H bond amination employed
a PhINR substrate prepared from PhI(OAc)2 and H2NR,
wherein the R group contains reactive benzylic 3° C(sp3)−H
bond. In 2000 we reported that PhINR can be replaced by
“PhI(OAc)2 + H2NR” in metal-catalyzed intermolecular C−H
amination reactions.40
and in 1985 with cytochrome P-450 enzyme;29 subsequently
there have been further developments of C(sp3)−H bond
amination catalyzed by heme6a,30 and heme-like31 iron
complexes. The few literatures on nonheme iron-catalyzed
amination of saturated alkanes are in contrast to many studies
involving hydroxylation of saturated alkanes, including the
typical cycloalkanes catalyzed by nonheme iron complexes.32
In our quest for nonheme iron catalysts for amination of
C(sp3)−H bonds of alkanes, we are interested in exploring the
possibility of generating highly reactive bis(imide/nitrene) iron
species using robust, strongly chelating N-donor ligand systems.
Complex [Fe(Ar)(NAd)2] (i.e., VI in Figure 1, Ar = 3,5-iPr2-
2,6-(2′,4′,6′-iPr3C6H2)2-C6H1, Ad = adamantyl),15a the sole
iron bis(imide) complex in literature, has a low-coordinate iron
protected by sterically encumbered anionic monodentate
coligand. The reactivity of VI has not been documented. A
number of isolated reactive 6-coordinate ruthenium bis(imide)
complexes supported by dianionic porphyrin ligands have been
reported;33 these complexes aminated benzylic and allylic 2°
C(sp3)−H bonds in good yields, but the yield for amination of
C(sp3)−H bond of cyclohexane was ∼10%.33a Use of neutral
Intramolecular Amination of C(sp3)−H Bonds of
Sulfamate Esters. Using 1 as catalyst, a series of sulfamate
ester substrates (2a−p) underwent intramolecular benzylic
(2°) or aliphatic (3° or 2°) C−H amination to result in 100%
B
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Table 2. Intramolecular Amination of Various C(sp3)−H
substrate conversion and cyclic sulfamidates (3a−p) in up to
92% isolated yield (Tables 1 and 2; the product turnover
a
Bonds of Sulfamate Esters Catalyzed by 1
Table 1. Intramolecular Amination of Benzylic C(sp3)−H
a
Bonds of Sulfamate Esters Catalyzed by 1
a
Reaction conditions: substrate/1/PhI(OAc)2/MgO = 1:0.05:1.8:2.5,
b
MeCN, 80 °C, 12 h; substrate conversion: 100%. Isolated yield.
c
d
Substrate/1/PhI(OAc)2/MgO = 1:0.05:2.1:3.0. Substrate/1/PhI-
e
(OAc)2/MgO = 1:0.05:1.4:2.3. 40 °C.
number (TON) is up to 18.4). Compared with [Fe-
(Cl3terpy)2](ClO4)2 which was reported to catalyze reaction
of 2c,f,h to give 3c,f,h,6c catalyst 1 exhibited broader substrate
scope, higher substrate conversions, and higher product yields.
For benzylic substrates 2i−n that have allylic (2°) or aliphatic
(3°, 2°, or 1°) C(sp3)−H bonds, the reaction preferentially
gave benzylic 2° C−H amination products 3i−n (59−89%
isolated yields) that are mainly or completely in a cis-
configuration; allylic (2°) and 3° C−H bonds were aminated
with up to 21% product yield (Table 2). This preference of 1
for benzylic 2° C−H amination [benzylic/3° ratio = 3.2:1 (3k/
3k′), 10:1 (3l/3l′); benzylic/allylic ratio = 2.8:1 (3i/3i′)] is
different from preferential amination of 3° and allylic (2°) C−
H bonds catalyzed by dirhodium [3°/benzylic ratio = up to
14:1 (3k′/3k)39e,f] and diruthenium complexes (allylic/
benzylic ratio = 3.3:1),39f respectively. A heme-like iron catalyst
(iron phthalocyanine complex [Fe(Pc)]+) was recently
reported to prefer amination of allylic (2°) C−H bonds over
other types of C−H bonds (including benzylic 2° C−H bonds)
in the intramolecular amination of sulfamate esters with
PhI(OR)2.31 It is noteworthy that, while the 1° and nonbenzylic
2° C−H bonds in 2j,m remained unfunctionalized, the 1° C−H
bond in 2n was appreciably aminated to give 3n′, albeit in 6%
yield (TON: 1.2).
a
Reaction conditions: substrate/1/PhI(OAc)2/MgO = 1:0.05:1.4:2.3,
b
MeCN, 80 °C, 12 h; substrate conversion: 100%. Isolated yield.
c
d
e
Substrate/1/PhI(OAc)2/MgO = 1:0.05:1.8:2.5. cis/trans ratio. cis
only.
cyclic alkanes (see below). For the amination of 2o catalyzed by
1, only 3° C−H amination product (3o) was observed (86%
isolated yield, Table 2), and this is different from the formation
of a mixture of 3° and 2° C−H amination products [3°/2° ratio
= (4.5−20):1] in dirhodium-catalyzed amination of 2o.39e
Substrate 2p was previously converted to 2° C−H amination
product (3p) in yields of 51% (using a manganese catalyst)41a
and 5% (using a copper catalyst);41b catalyst [Fe(Cl3terpy)2]-
(ClO4)2 gave 3p in 23% yield (cis/trans 1:1). A higher yield of
79% was obtained for 3p using catalyst 1 (Table 2, the
corresponding 3° C−H amination product was not detected).
In view of the 1-catalyzed amination of 2o and 2p selectively
at acyclic 3° and cyclohexyl 2° C−H bonds, respectively, we
prepared menthyl sulfamate ester 2q which bears both types of
C−H bonds. Under similar reaction conditions (2q/1/
PhI(OAc)2/MgO = 1:0.05:1.4:2.3), the cyclohexyl 2° C−H
amination product of 2q was not detected, whereas the 3° C−
H amination product 3q was obtained in 93% isolated yield
(Scheme 1, substrate conversion: 100%).
The catalytic activity of 1 toward amination of the aliphatic
C(sp3)−H bonds of 2o and particularly 2p (both are devoid of
benzylic C(sp3)−H bonds) encouraged us to extend the
catalysis to intermolecular amination of cyclohexane and other
We also examined the applicability of the “1 + PhI(OAc)2”
protocol to selective amination of organic compounds with
complexity, such as steroids bearing multiple cycloalkane
C
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Scheme 1
Table 3. Intermolecular Amination of Benzylic and Allylic
a
C(sp3)−H Bonds Catalyzed by 1
moieties. The substrates synthesized for this purpose included a
spirost-5-ene derivative 2r, a cholane derivative 2s, and an
androstane derivative 2t (Scheme 1). When the reactions with
substrate/1/PhI(OAc)2/MgO ratio of 1:0.05:1.8:2.5 were
performed at 80 °C for 12 h, the substrate conversion reached
100%. For 2r, the amination occurred at allylic C−H bond to
give 3r in 78% isolated yield. Substrate 2s underwent amination
at a 2° C−H bond of the linear alkane chain moiety, with
product 3s isolated in 71% yield. Amination of 2t afforded 3t, a
product resulting from amination of the 2° C−H bond of a
cyclohexane moiety, in 70% isolated yield (Scheme 1).
Iron-catalyzed amination of steroids is rarely documented in
literature. We are aware of one example,31 in which case the
catalyst was iron phthalocyanine complex [Fe(Pc)]+ (a heme-
like catalyst) with cholesteryl sulfamate ester as substrate,
affording intramolecular allylic C−H amination product in 58%
yield.
a
Reaction conditions: substrate/1/(nitrogen source) = 1:0.05:2.0, 80
b
c
°C, 12 h; substrate conversion: 100%. Isolated yield. Substrate/1/
nitrogen source = 1:0.05:2.2.
yields (based on starting amount of substrate) using NaBrNTs
and “PhI(OAc)2 + H2NTs”, respectively, as nitrogen source.
These isolated yields were lower than those of 58% (5aa) and
64% (5ab) obtained using nitrogen sources PhINTs and
PhINNs.
Complete substrate conversion was achieved for the
reactions of 4a with PhINR (R = Ts, Ns) at substrate/1/
(PhINR) ratio of 1:0.05:2.0, leading to the isolated yields of
75% for 5aa and 81% for 5ab (entries 1 and 2, Table 3). Under
the same or similar reaction conditions, isochroman (4b),
1,2,3,4-tetrahydronaphthalene (4c), indan (4d), and ethyl-
benzene (4e) were aminated at their benzylic 2° C−H bonds to
give 5b−e in 67−86% isolated yields (entries 3−7, Table 3;
substrate conversion: 100%).
Intermolecular Amination of C(sp3)−H Bonds of
Benzylic and Allylic Hydrocarbons and Cyclic Alkanes.
We employed cyclohexane, cyclopentane, cyclooctane, and
adamantane as substrates in the study on the intermolecular
amination catalyzed by 1. Benzylic and allylic substrates were
also used. Complex 1 exhibited a high catalytic activity in
amination of alkanes as well as benzylic and allylic substrates, so
that these substrates (except cyclopentane, see below) could be
used as the limiting reagents in the reactions (like the 1-
catalyzed intramolecular reactions described above) without the
need to be used in excess amounts (see Discussion section).
The results obtained are depicted in Tables 3 and 4.
In the presence of catalyst 1 (5 mol %), reaction of the
benzylic substrate xanthene (4a) with various nitrogen sources,
including bromamine-T (NaBrNTs), PhINTs, PhINNs
(Ns = SO2-p-NO2C6H4), and “PhI(OAc)2 + H2NTs”, at 80 °C
for 12 h gave benzylic 2° C−H amination products 5aa or 5ab
(Table 3) in moderate-to-high yields. For the reactions with
substrate/1/(nitrogen source) ratio of 1:0.05:1.5, the substrate
conversions were 75%, 78%, 82%, and 81% for the four types of
nitrogen sources, respectively; 5aa was isolated in 54% and 55%
Allylic amination catalyzed by 1 was performed using natural
products α-pinene (6a) and β-pinene (6b) under the same
conditions as those for the amination of 4a. With PhINNs as
nitrogen source, α-pinene was converted to the allylic C−H
bond amination product 7a in 53% isolated yield (entry 8,
Table 3). For the reaction of β-pinene with PhINNs and
PhINTs, the rearranged amination products 7bb and 7ba
were obtained in 57% and 63% yields, respectively (entries 10
and 9, Table 3).
It is striking that 1 is active to catalyze intermolecular
amination of cyclohexane, cyclopentane, cyclooctane, and
adamantane with PhINTs, PhINNs, or “PhI(OAc)2
+
H2NR (R = Ts or Ns)”. These alkanes, compared with the
more reactive benzylic substrates 4a−e and allylic substrates
D
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Table 4. Intermolecular Amination of C(sp3)−H Bonds of
octane, and cyclohexane with PhINTs well correlates with
the C−H bond dissociation energy (BDE) of these hydro-
carbons, as shown by the plot of log k′ vs BDE (Figure S3).
In addition, we examined the catalytic behavior of [Fe-
(Cl3terpy)2](ClO4)2 and [Fe(N4Py)(MeCN)](ClO4)2 (N4Py
= N,N-bis(2-pyridylmethyl)bis(2-pyridyl)methylamine)42 to-
ward amination of benzylic and alkane substrates. For the
amination of ethylbenzene (4e) with PhINTs at a substrate/
catalyst/(PhINTs) ratio of 1:0.05:1.5 at 80 °C, examination
of the time course of the reaction (Figure 2) revealed that
a
Cycloalkanes Catalyzed by 1
a
g
Reaction conditions. Substrate/1/nitrogen source = 1:0.1:1.5, 80 °C,
b
c
24 h. Determined by GC or 1H NMR. Isolated yield based on
starting amount of substrate. Yield based on conversion. Substrate/
d
e
Figure 2. Time course plots for amination of ethylbenzene with PhI
1/(PhINNs) = 100:0.1:1 (due to the low boiling point of 10a).
f
■
NTs in MeCN catalyzed by 1 ( ) and [Fe(N4Py)(MeCN)](ClO4)2
Isolated yield based on PhINNs.
○
( ) under the same reaction conditions (substrate/catalyst/(PhI
NTs) = 1:0.05:1.5, 80 °C).
6a,b, were aminated using a higher catalyst loading of 10 mol %
and a longer reaction time of 24 h. For adamantane (8), the
amination with PhINTs and PhINNs gave 3° C−H bond
amination products 9a,b, respectively, in up to 63% isolated
yield (86% based on substrate conversion) (entries 1 and 2 in
Table 4). Cyclopentane (10a) has a relatively low boiling point;
this alkane was used in excess amount in its reaction with PhI
NNs giving 11a in 52% yield (entry 3, Table 4). The amination
of limiting reagents cyclohexane (10b) and cyclooctane (10c)
by PhINTs and PhINNs afforded 11ba/11bb and 11ca/
11cb in 33−49% isolated yields (68−82% based on substrate
conversion) (entries 4−6 and 8, Table 4).
Notably, in the 1-catalyzed amination of each of the cyclic
alkanes (8, 10a−c), only a single amination product was
detected in the reaction mixture. For comparison, a mixture of
amination products was detected in the amination of
adamantane by excess amounts of “FeCl2 + chloroamine-T”
unless trapping reagents, such as SO2Cl2 or H2S, were added
after the reaction.14
[Fe(N4Py)(MeCN)](ClO4)2 led to no detectable substrate
conversion after 12 h, in contrast to a 47% substrate conversion
obtained using catalyst 1 (the benzylic amination product was
obtained in 37% yield (79% based on conversion, TON = 7.4)
under the same reaction conditions. No amination of cyclic
alkanes (such as cyclohexane) was found for catalysts
[Fe(Cl3terpy)2](ClO4)2 and [Fe(N4Py)(MeCN)](ClO4)2 for
a reaction time of 24 h (under similar conditions to those
indicated in Table 4).
High-Resolution ESI-MS Studies. We monitored the
reaction of 1 with PhINTs (4 equiv) in MeCN by ESI-MS.
The spectrum of the reaction mixture showed a prominent
cluster peak at m/z 306.05 assignable to [Fe(qpy)(NTs)]2+
(calcd m/z 306.05) based on m/z value, isotope pattern, and
collision-induced dissociation (Figure S4).
Remarkably, a minor cluster peak at m/z 390.56 assignable to
[Fe(qpy)(NTs)2]2+ (calcd m/z 390.56) was also observed. The
formulation of [Fe(qpy)(NTs)2]2+ is consistent with collision-
induced dissociation experiment and high-resolution mass
spectral data. As depicted in Figure 3, at a collision energy of
25 eV, the [Fe(qpy)(NTs)2]2+ species dissociates into
fragments [Fe(qpy)(NTs)]2+ and [Fe(qpy)]2+ by loss of one
and two NTs moieties, respectively. The observed m/z value of
390.5479 in the high-resolution ESI-MS closely matches that of
390.5615 calculated for [Fe(qpy)(NTs)2]2+, with a good
agreement between the observed and simulated isotope
patterns (see the inset of Figure 3). Similarly, analysis of the
reaction mixture containing 1 and PhINNs by ESI-MS
revealed a minor cluster peak at m/z 421.5368 assignable to
[Fe(qpy)(NNs)2]2+ (calcd m/z 421.5332, Figure S5).
Kinetic isotope effect (KIE) was investigated for the
amination of cyclohexane with PhINTs using catalyst 1.
The kH/kD values determined at different temperatures were 3.4
(80 °C), 3.7 (50 °C), and 4.0 (25 °C).
For the amination of para-substituted ethylbenzenes p-
YC6H4Et (Y = OMe, Me, H, Cl, Br, NO2) with PhINTs
+
catalyzed by 1, the plot of log kR vs σP (kR: relative amination
rate) exhibited a linearity with R = 0.98 (ρ = −0.55) (Figure
+
S1). A linear relationship between log kR and σP was also
found for the 1-catalyzed amination of ethylbenzene with
PhINSO2-p-YC6H4 (Y = OMe, Me, H, Cl, NO2; R = 0.98, ρ
= 1.14; Figure S2). The 1-catalyzed amination of 9,10-
dihydroanthracene, fluorene, cumene, ethylbenzene, cyclo-
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immediate disappearance of the broad absorption band of 1 at
λmax 534 nm (ε = 630 cm−1 mol−1 dm3), accompanied by
immediate formation of a new broad absorption band at λmax
490 nm (Figure S8). This new band disappeared upon addition
of PPh3 (8 equiv), with formation of a broad absorption band at
λmax ∼530 nm resembling that of 1 (SFigure S9). A similar
UV−vis spectral change was observed when styrene (0.5 mL),
instead of PPh3, was added, and in the reaction mixture, the
styrene aziridination product was detected by 1H NMR
spectroscopy. These observations could be attributed to the
formation of reactive iron−imide/nitrene species in the
reaction of 1 with PhINTs.
Our numerous attempts to isolate qpy-supported iron−
imide/nitrene complexes, such as [Fe(qpy)(NR)2]2+ and
[Fe(qpy)(NR)]2+ (R = Ts, Ns), have not been successful.
Detection of these species by other spectral methods, such as
1H NMR, proved difficult, probably due to their para-
magnetism, high reactivity, or short lifetime. When 1 was
treated with PhINTs (1 or 2 equiv) in MeCN-d3 at −20 °C,
1
the H NMR spectrum of the reaction mixture was featureless,
Figure 3. Collision-induced dissociation for the ion (m/z 390.56)
revealing the formation of paramagnetic species. In the course
of isolation of the product by diffusion of diethyl ether, a μ-oxo
dimer, {[Fe(qpy)(H2O)]2O}(ClO4)4,45 was obtained. To shed
insight into the reactive iron−imide/nitrene intermediate(s),
we performed X-band EPR experiments with the reaction
mixture obtained by rapidly mixing 1 with PhINTs (8 equiv)
in MeCN at around −40 °C (this took 1−2 min) followed by
immediately freezing the as-formed reaction mixture to 4 K. No
signal attributable to FeV species46 was observed. Paramagnetic
species (or a mixture of paramagnetic species) that could be
attributed to FeIII species was observed (Figure S10). It should
be noted that FeIV species is conceived to be EPR-silent in the
X-band EPR experiments,47 and FeVI-nitride species is reported
to be diamagnetic.48
assigned to [Fe(qpy)(NTs)2]2+ (collision energy: 25 eV).
When 1 was mixed with PhINTs in a 1:1 (instead of 1:4)
ratio, analysis of the reaction mixture by ESI-MS revealed a
prominent cluster peak at m/z 711.06 which can be assigned to
[Fe(qpy)(NTs)(ClO4)]+ (calcd m/z 711.05, Figure S6). From
the mass spectra of the 1:1 mixture of 1 with PhINTs, we did
not find cluster peak assignable to [Fe(qpy)(NTs)2]2+.
As imide/nitrene intermediates might be prone to
dimerization,12 a doubly charged iron diazene complex, such
as [Fe(qpy)(RNNR)]2+ which would give the same m/z
value and isotope pattern as those of [Fe(qpy)(NR)2]2+, should
be considered. We made efforts but were not successful to
obtain TsNNTs following a procedure included in the
Supporting Information of a recent report.43 We then turned to
examine the feasibility of generating [Fe(qpy)(RNNR)]2+ (R
= p-MeOC6H4) by mixing 1 with (p-MeOC6H4)NN(C6H4-
p-MeO)44 (10 equiv) in MeCN (under the conditions similar
to those for ESI-MS analysis of the mixture of 1 with PhI
NTs (4 equiv)). Analysis of such a reaction mixture by high-
resolution ESI-MS did not reveal the cluster peak attributed to
[Fe(qpy)(RNNR)]2+ (R = p-MeOC6H4) nor to its
dimerized form [Fe2(qpy)2(RNNR)2]4+. Monitoring the
time course of the intensity of the above-mentioned cluster
peaks at m/z 306.05 (assignable to [Fe(qpy)(NTs)]2+) and m/
z 390.56 (assignable to [Fe(qpy)(NTs)2]2+) revealed that the
latter species was considerably less stable than the former and
rapidly lost intensity after ∼3 min, with concomitant increase in
the intensity of the former (Figure S7). The dimerized form of
[Fe(qpy)(TsNNTs)]2+, i.e. [Fe2(qpy)2(TsNNTs)2]4+
(calcd m/z 390.56) has not been detected; this quadruply
charged ion should have a markedly different isotope pattern
from that of the observed species at m/z 390.56. These
findings, together with the collision-induced dissociation
(Figure 3) and the absence of the cluster peak at m/z 390.56
(assignable to [Fe(qpy)(NTs)2]2+) in the mass spectrum of the
1:1 mixture of 1 with PhINTs, do not lend support for
assignment of the cluster peak at m/z 390.56 to [Fe(qpy)-
(TsNNTs)]2+ but are consistent with the assignment to
[Fe(qpy)(NTs)2]2+.
Density Functional Theory (DFT) Calculations. The
electronic structures of [Fe(qpy)(NTs)2]2+ (CNTs) and [Fe-
(qpy)(NTs)]2+ (C) and their amination reactions with
cyclohexane (including KIEs), have been examined by DFT
calculations with Gaussian 09 package49 using OLYP hybrid
functional (see Supporting Information, including Figures
S11−S14 depicted therein, for details). The computed Fe−
NTs distances in the ground states of CNTs (1.819, 1.884 Å)
and C (1.822 Å) are markedly longer than that computed for
the octahedral complex [Fe(N4Py)(NTs)]2+ (1.75 Å).24 The
imide ligands in both the CNTs and C species have radical
nitrene character and can be considered as [•NTs]−. In the
amination of cyclohexane by these CNTs and C species, the
calculated free energy barriers (with single point correction in
MeCN solvent) for the rate-determining H-atom abstraction
are 15.3 kcal/mol for CNTs and 14.2 kcal/mol for C. Upon
−
binding ClO4 or NHTs− to the trans site of C to form
[Fe(qpy)(NTs)(ClO4)]+ (CClO4) and [Fe(qpy)(NTs)-
(NHTs)]+ (CNHTs),50 the amination reaction has considerably
higher barriers of 17.6 and 24.3 kcal/mol, respectively. It is
noted that the ion [Fe(qpy)(NTs)(ClO4)]+ has actually been
detected by ESI-MS of the reaction mixture as described in
previous section.
DISCUSSION
■
Amination of C(sp3)−H bonds of alkanes via nonheme iron-
catalyzed nitrogen group insertion reactions requires a system
that can generate highly reactive nonheme iron imide (or
nitrene) intermediates. Previously reported related catalytic
UV−vis measurements revealed that treatment of 1 (1 mM)
with PhINTs (1 equiv) in MeCN at −20 °C led to
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systems6 using nonheme iron complexes or simple iron salts
resulted in the amination of relatively weak C(sp3)−H
bonds,27,51 including the following reactions: (i) intramolecular
amination of benzylic 3° C−H bond of PhI
NSO2(2,5-iPr2C6H3) catalyzed by [Fe(cyclam)Cl2]Cl (cyclam
= 1,4,8,11-tetraazacyclotetradecane) and FeCl3;6a (ii) intra-
molecular amination of benzylic 2° C−H bonds of sulfamate
esters 2c,f,h with PhI(OAc)2 catalyzed by [Fe(Cl3terpy)2]-
(ClO4)2;6c (iii) intermolecular amination of benzylic 2° C−H
bonds of ethylbenzenes with “NBS + H2NXOnAr” (NBS = N-
bromosuccinimide; X = C, n = 1; X = S, n = 2) catalyzed by
FeCl2;6b and (iv) intermolecular amination of benzylic 1° C−H
bond of toluene with N3Ad (1-azidoadamantane) catalyzed by
[Fe(AdL)Cl(OEt2)] (AdL = 1,9-bis(1-adamatanyl)-5-mesityl-
dipyrromethene).6d In all the reported intermolecular reac-
tions,6b,d the substrates were used in excess; particularly, the
amination of benzylic 1° C−H bond of toluene6d (these bonds
are usually difficult to be functionalized)52 was performed in
neat toluene.
The iron quinquepyridine complex 1 is an active catalyst for
intra- and intermolecular amination of benzylic C−H bonds
(see Tables 1−3), allylic C−H bonds (Scheme 1; entry 8, Table
3), and, remarkably, the C−H bonds of cycloalkanes or
cycloalkane/linear alkane moieties in sulfamate esters including
those of steroids (entries 7 and 8 in Table 2, Scheme 1, and
Table 4) with the substrates as limiting agents. For all of these
reactions catalyzed by 1, the amination products have been
isolated in up to 93% yield.
For the amination of steroids by metal-catalyzed nitrogen
group insertion into C−H bonds, we are not aware of previous
examples that involve nonheme iron catalysts, besides the
above-mentioned intramolecular allylic C−H bond amination
of cholesteryl sulfamate ester, an unsaturated steroid, catalyzed
by the heme-like [Fe(Pc)]+.31 There are a few reports on
intermolecular amination of unsaturated steroids with PhI
NTs or “PhI(OAc)2 + NH2R (R = Ts, Ns)” as nitrogen source
and using manganese53 or ruthenium53c porphyrins, dirhodium
complexes,54 and ruthenium−salen complexes55 as catalysts,
examples of which include amination of benzylic C−H bond of
equilenin acetate53a and amination of allylic C−H bonds of
cholesteryl acetates.53b,c,54,55 All of these intermolecular
reactions afforded the aminated steroids in up to 47% yields.
Intramolecular amination via aziridination of an unsaturated
steroid with PhIO catalyzed by [Cu(MeCN)4]PF6 (68%
aziridine yield) followed by nucleophilic aziridine opening has
also been reported.56 The substrates 2r−t (Scheme 1) used in
this work were not employed in previous amination reactions
catalyzed by metal complexes. The 1-catalyzed amination of 2s
and 2t with PhI(OAc)2 are unique examples of metal-catalyzed
amination of C(sp3)−H bonds of saturated steroids.
Intermolecular amination of pinene by reactive metal-imide/
nitrene intermediates has been documented in previous
reports57 involving the amination of α-pinene (6a) with
“PhI(OCOtBu)2 + H2NS(NTs)(O)-p-MeC6H4” catalyzed by
a dirhodium complex, affording the allylic C−H amination
product in 71−91% yields. This reaction and the iron-catalyzed
conversion of 6a to 7a reported herein (Table 3) are in contrast
with the formation of aziridines in 59−71% yields found for the
reaction of 6a with free nitrenes.58 In the case of 1-catalyzed
amination of β-pinene (6b) with PhINR (R = Ts, Ns), the
formation of rearranged products 7ba and 7bb is also different
from the amination of 6b by free nitrenes (which afforded ene-
type amination products in 42−58% yields without ring-
opening)58 but is reminiscent of some other types of
transformation of 6b reported in literature,59 such as the
59a
reactions of 6b with radicals derived from NaN3
or
alkoxyamines,59b,c to give rearranged products analogous to
7ba and 7bb.
Using catalyst 1 and with cyclohexane and cyclooctane
substrates as limiting reagents, the 2° C(sp3)−H bonds of these
alkanes were effectively aminated, resulting in high product
selectivity (yield based on substrate conversion) of up to 82%,
with TON of up to 4.9 comparable to that obtained for the
hydroxylation of cyclohexane (10 equiv) with H2O2 catalyzed
by [Fe(TPA)(MeCN)2]2+ (TON = 3.0, TPA = tris(2-
pyridylmethyl)amine).32h Recent report revealed that 1 is an
active catalyst for various organic oxidation reactions.45 The
interesting catalytic activity of 1 is possibly associated with the
lack of reactive C−H bonds (or other reactive groups) in the
qpy coligand (which disfavors degradation of the key
intermediates via intramolecular reactions such as previously
reported formation of nonheme iron amido complexes)21c,25,38
and the high coordination number supported by qpy (such as
7-coodinate iron in 1; this high-coordination number generates
reactive iron−imide/nitrene intermediates, as suggested by
DFT calculations and discussed below).
In heme iron systems reported in literature, excess amounts
of cyclohexane and cyclooctane were used for the intermo-
lecular amination of these two cyclic alkanes. The cyclohexane
amination with PhINTs mediated by [Fe(TPP)Cl] (H2TPP
= 5,10,15,20-tetraphenylporphyrin) was performed in CH2Cl2−
cyclohexane (1:1 v/v) mixed solvent.28 A 25-fold excess of
cyclooctane was employed in its amination with N3Ar (Ar = 4-
nitrophenyl) catalyzed by [Fe(F20TPP)Cl] [H2F20TPP =
5,10,15,20-tetrakis(pentafluorophenyl)porphyrin].30b
Several catalytic systems employing other metal catalysts also
use excess cyclic alkane substrates in the amination reaction.60
These include the use of neat cyclohexane in its amination
reaction with PhINTs60a or “tBuOOBut + H2NR” (R = Ad,
Cy, CH2CH2Ph)60e catalyzed by copper complexes, the use of
10 equiv of cyclohexane, cyclopentane, and cyclooctane in their
amination reactions with PhINNs catalyzed by a silver
complex60b and the use of 2−10 equiv of cyclohexane and
cyclooctane in their amination reactions with Cl3CCH2OC-
(O)NHOTs catalyzed by dirhodium complexes.60c,d
Amination of cyclic alkanes present in limiting amounts has
previously been reported using the following catalytic
systems:61 dirhodium-catalyzed amination of cyclooctane with
“PhI(OAc)2 + H2NSO3CH2CCl3” (31% yield, TON =
16.5),61a,b copper-catalyzed amination of cyclohexane with
N3Ad (32% yield, TON = 12.8),61c and dirhodium-catalyzed
amination of cyclopentane, cyclohexane, cycloheptane, cyclo-
octane with “PhI(OCOBut)2 + H2NS(NTs)(O)-p-MeC6H4”
(48−66% yields, TON = 16−22).61d
Complex 1 effectively catalyzed amination of cyclic alkanes in
limiting amounts with PhINR and “PhI(OAc)2 + H2NR” (R
= Ts, Ns) as nitrogen sources. The 1-catalyzed amination of
cyclohexane and cyclooctane gave 11a,b and 13a,b (Table 3) in
27−49% isolated yields (based on starting substrate). These
yield values are comparable to those indicated above for
dirhodium61a,b and copper61c catalysts using nitrogen sources
“PhI(OAc)2 + H2NSO3CH2CCl3” and N3Ad, respectively. So
far the highest product yields in metal-catalyzed amination of
limiting reagents cyclohexane (50% yield, TON = 16.7) and
cyclooctane (61% yield, TON = 20.3) were obtained using
dirhodium catalyst [Rh2{(S)-nta}4] (nta is a carboxylate ligand)
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with the “PhI(OCOBut)2 + H2NS(NTs)(O)-p-MeC6H4”
nitrogen source.61d
cyclohexane amination by CNTs at the other temperatures of 50
and 25 °C gave kH/kD of 3.7 and 4.2, respectively, also in good
agreement with the experimental values (50 °C: kH/kD = 3.7;
25 °C: kH/kD = 4.0). On the other hand, the computed kH/kD
values at 80 °C for C, CClO4, and CNHTs are 2.5, 5.1, and 5.6,
respectively.
Given the detection of species assignable to [Fe(qpy)-
(NTs)]2+ (C) and [Fe(qpy)(NTs)2]2+ (CNTs) by ESI-MS from
the reaction mixture of 1 and PhINTs (4 equiv), the 1-
catalyzed amination of C(sp3)−H bonds with PhINTs
possibly involves mono(imide/nitrene) and bis(imide/nitrene)
iron species. We propose the likely involvement of [Fe(qpy)-
(NR)(X)]n+ (CX) with X = NR, solvent, or anion in the 1-
catalyzed amination of C(sp3)−H bonds with PhINR.
Another species to be considered is [Fe(qpy)(NR){PhI-
(NR)}]2+, which is analogous to previously proposed [Mn-
(tpfc)(NR){ArI(NR)}] (tpfc =5,10,15-tris(pentafluorophenyl)-
corrole),62 a nitrogen analogue of the proposed M(ArIO)
intermediates in metal-catalyzed oxygen atom transfer using
ArIO.63 According to crossover experiments analogous to
that performed for [Mn(tpfc)(NR){ArI(NR)}],62 the involve-
ment of [Fe(qpy)(NR){PhI(NR)}]2+ in the 1-catalyzed
reactions is less favored. The crossover experiments were
performed using two PhINSO2-p-YC6H4 nitrogen sources:
PhINTs (Y = Me) and PhINBs (Y = H). Complex 1 was
first treated with PhINTs (1 equiv); after complete reaction,
PhINBs (1 equiv) was added with subsequent addition of
isochroman (4b). The reaction gave a ∼1:1 ratio of the
C(sp3)−H bond amination products corresponding to NTs and
NBs transfer. A similar ratio of ∼1:1 was obtained for the
aziridination products of styrene by 1 and PhINTs (1 equiv)
and subsequently PhINBs (1 equiv). In the previous report
on imide complexes of manganese corrole,62 the ratio of
styrene aziridination products corresponding to NR (R = SO2-
p-tBuC6H4) and NR′ (R′ = SO2-p-MeC6H4) transfer from
[Mn(tpfc)(NR){ArI(NR′)}] was reported to be 1:100, whereas
that from the bis(imide) intermediate [Mn(tpfc)(NR)(NR′)]
was expected to be 1:1.62 In this work, we have not been able to
observe [Fe(qpy)(NTs){PhI(NTs)}]2+ by ESI-MS analysis of
the reaction mixture of 1 with PhINTs. The crossover
experiments do not lend support to the assignment of the
major active species to the [Fe(qpy)(NR){PhI(NR)}]2+ (if
formed) that behaves like [Mn(tpfc)(NR){ArI(NR)}] (i.e.,
only the coordinated ArI(NR) undergoes nitrogen group
transfer). However, it is noted that the findings from the
crossover experiments could not distinguish the possible
oxidizing agents, such as other Fe-PhI(NR) adducts and iron
mono- and bis(imide/nitrene) species.
To provide more insight into the amination of C(sp3)−H
bonds of cyclic alkanes by [Fe(qpy)(NR)(X)]n+ (CX), we
performed the following experiments: (i) Complex 1 was
treated with 1.1 equiv of PhINTs in MeCN, followed by
addition of cyclohexane (1 equiv). From this reaction, we did
not observe formation of significant amount of the cyclohexane
amination product (11a) after the reaction mixture had been
stirred at 80 °C for 12 h. As described above, ESI-MS analysis
of 1:1 mixture of 1 and PhINTs showed cluster peaks
assigned to [Fe(qpy)(NTs)(ClO4)]+ (CClO4) but not [Fe-
(qpy)(NTs)2]2+ (CNTs). We also examined the effect of (PhI
NTs)/1 ratio on the amination of cyclohexane. Upon treatment
of excess cyclohexane with 1 and PhINTs at (PhINTs)/1
molar ratios of 0.5, 1, 2, and 3, the ratio of the corresponding
amination product 11ba formed was ∼0:1:100:400. (ii) When
bromamine-T, instead of PhINTs, was used as nitrogen
source, 1 did not catalyze the amination of cyclohexane under
the conditions indicated in Table 4. Through ESI-MS analysis
of the reaction mixture of 1 with bromamine-T, we found the
cluster peak assigned to [Fe(qpy)(NTs)Br]+ (CBr), without
observation of the cluster peak attributed to CNTs. (iii) In the
presence of pyridine additive (2 equiv), 1 was found not to
catalyze the amination of cyclohexane with PhINTs under
the conditions indicated in Table 4 but could catalyze
aziridination of styrene though the substrate conversion
decreased to 22% (from 100% obtained for the same
aziridination without pyridine additive). ESI-MS analysis of a
reaction mixture of 1 with PhINTs (4 equiv) in MeCN
containing pyridine (2 equiv) revealed a cluster peak at m/z
345.7 attributable to [Fe(qpy)(NTs)(py)]2+ (Cpy, calcd m/z
345.6, Figure S15); no cluster peak attributed to CNTs was
found.
It has been reported that the reactions of [Fe(Cl3terpy)2]2+
and [Fe(N4Py)(MeCN)]2+ with ArI=NTs (Ar = phenyl or
mesityl) generated mono(imide) species [Fe-
(Cl3terpy)2(NTs)]2+ (detected by ESI-MS)6c and [Fe(N4Py)-
(NTs)]2+ (characterized by ESI-MS, UV−vis, 1H NMR,
EXAFS, Mossbauer spectroscopy,24 and DFT calculations),24,66
̈
Generation of iron−imide/nitrene intermediates in the
reaction of 1 with PhINTs is suggested by other type of
nitrogen group transfer reactions mediated by 1, including 1-
catalyzed aziridination of alkenes with PhINTs (Table S1).
The Hammett plots (Figures S1 and S2) and the correlation
between relative amination rates and C−H BDEs (Figure S3)
are also consistent with the involvement of electrophilic metal−
imide/nitrene intermediates via H-atom abstraction. The
amination reactions of C(sp3)−H bonds catalyzed by 1 took
place under moderate conditions (at 80 °C), and these reaction
conditions are compatible with the computed activation
barriers of 14.2−15.3 kcal/mol for the amination of cyclo-
hexane by [Fe(qpy)(NTs)]2+ (5C) and [Fe(qpy)(NTs)2]2+
(3CNTs).
respectively. These iron imide species might be insufficiently
reactive toward the C(sp3)−H bond of cyclohexane, since very
little if not nil amination of cyclohexane with PhINTs was
observed using catalysts [Fe(Cl3terpy)2]2+ and [Fe(N4Py)-
(MeCN)]2+ under the reaction conditions employed in this
study.
Based on the aforementioned experiments described in (i)−
(iii) and the findings of related catalytic experiments with
[Fe(Cl3terpy)2]2+ and [Fe(N4Py)(MeCN)]2+ as catalysts, we
conceive that the intermediate [Fe(qpy)(NR)2]2+ (CNR) would
not play a minor role in the amination of C−H bonds of
cyclohexane, although the importance of other reactive
intermediates, such as [Fe(qpy)(NR)]2+ (C) and Fe-PhI(NR)
adduct, could not be excluded with the present findings.
According to DFT calculations, the ground states of CNTs and
C feature radical nitrene character of the imide ligand. Radical
nitrene character of coordinated imide ligands has been
established previously, for example, in recently reported
mono(imide) complexes [Fe(L)(NR)Cl]6d and [Co(Por)-
KIE values obtained from DFT calculations lend support to
the reaction mechanisms.64 The computed KIE values (with
Wigner correction)65 for the amination of cyclohexane at 80 °C
by CNTs (kH/kD = 3.3) is similar to the corresponding
experimental value (kH/kD = 3.4). Further calculations on the
H
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(NR)]67 and may contribute to the reactivity of CNTs and C
toward amination of saturated C−H bonds. [Fe(L)(NR)Cl] (L
= a monoanionic dipyrromethene ligand) is documented to be
an FeIII complex.6d CNTs and C could be considered as FeIV and
FeIII species, respectively, on the basis of the [•NTs]− form of
their imide ligand(s) revealed by DFT calculations. However,
formulation of the oxidation states based on DFT calculations
is highly speculative. To clearly determine the iron oxidation
state(s) in the proposed intermediates [Fe(qpy)(NR)(X)]n+
(CX), further studies are needed including characterization by,
ACKNOWLEDGMENTS
■
This work was supported by Hong Kong Research Grants
Council (HKU 1/CRF/08 and HKU 700810) and Hong Kong
Jockey Club Charities Trust. We thank Prof. Hung Kay Lee
(The Chinese University of Hong Kong) for assistance in the
X-band EPR measurements.
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for example, Mossbauer measurements.
̈
In literature, iron bis(imide) intermediates have not been
proposed for the nitrogen group transfer reactions catalyzed by
iron complexes.6,8−13,28,30,31 Metal bis(imide) complexes that
are reactive toward nitrogen group transfer to form C−N bonds
are sparse.33 Several uranium bis(imide) complexes feature 7-
coordinate uranium adopting pentagonal bipyramidal geome-
try.68 To the best of our knowledge, investigations on the
reactivity of bis(imide) complexes of the first-row transition
metals toward amination of C−H bonds have not been
reported previously, regardless of experimental studies or
theoretical calculations.
̃
CONCLUSIONS
■
We have demonstrated that the nonheme iron complex
[Fe(qpy)(MeCN)2](ClO4)2 (1) is an active catalyst for the
intra- and intermolecular amination of various C(sp3)−H
bonds, including amination of cyclic alkanes and of cyclo-
alkane/linear alkane moieties in saturated steroids. The
substrate scope spans cycloalkanes, benzylic/allylic hydro-
carbons, natural products α-pinene and β-pinene, and a wide
variety of sulfamate esters including those bearing methyl-
cyclohexane, isononane, menthane, spirost-5-ene, cholane, and
androstane backbones. The amination reactions can be
performed by employing the cyclic alkane substrates as limiting
reagents with PhINR or “PhI(OAc)2 + H2NR” (R = Ts, Ns)
as nitrogen source. The interesting catalytic activity of the “1 +
PhINR” system is likely to arise from the generation of
reactive cationic 7-coordinate iron−imide/nitrene intermedi-
ate(s) [Fe(qpy)(NR)(X)]n+ (CX, X = NR, solvent, or anion) as
proposed on the basis of experimental studies (including ESI-
MS analysis) and DFT calculations. The DFT optimized
ground states of these proposed reactive iron−imide/nitrene
species, such as CNTs, feature imide ligand(s) with radical
nitrene characters. The present work provides unique examples
of nonheme iron-catalyzed amination of cyclic alkanes and
steroid compounds and lends credence to the possible use of
nonheme iron complexes as practical catalysts for C(sp3)−H
amination reactions.
(7) For a review on catalysis involving iron imide/nitrene
intermediates, see : Che, C.-M.; Zhou, C.-Y.; Wong, E. L.-M. In Iron
Catalysis: Fundamentals and Applications; Plietker, B., Ed.; Springer-
Verlag: Berlin, 2011; p 111.
(8) Examples for nonheme iron-catalyzed sulfimidation of sulfides or
sulfoxides (a) Bach, T.; Korber, C. Tetrahedron Lett. 1998, 39, 5015.
̈
(b) Bach, T.; Korber, C. Eur. J. Org. Chem. 1999, 1033. (c) Bach, T.;
̈
Korber, C. J. Org. Chem. 2000, 65, 2358. (d) Katsuki, T. Chem. Lett.
̈
2005, 34, 1304. (e) García Mancheno, O.; Bolm, C. Org. Lett. 2006, 8,
̃
2349. (f) García Mancheno, O.; Dallimore, J.; Plant, A.; Bolm, C. Org.
̃
Lett. 2009, 11, 2429.
(9) Examples for nonheme iron-catalyzed aziridination of alkenes:
(a) Simkhovich, L.; Gross, Z. Tetrahedron Lett. 2001, 42, 8089.
(b) Heuss, B. D.; Mayer, M. F.; Dennis, S.; Hossain, M. M. Inorg.
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ASSOCIATED CONTENT
* Supporting Information
Experimental section including detailed procedures, character-
ization data and NMR spectra of compounds, computational
details, Tables S1 and S2, and Figures S1−S15. This material is
available free of charge via the Internet at http://pubs.acs.org.
■
S
́
Gottsacker, V. M.; Mas-Balleste, R.; Que, L., Jr.; Halfen, J. A. Chem.
Commun. 2007, 2063. (e) ref 6c. (f) Mayer, A. C.; Salit, A.-F.; Bolm,
C. Chem. Commun. 2008, 5975. (g) Nakanishi, M.; Salit, A. F.; Bolm,
C. Adv. Synth. Catal. 2008, 350, 1835. (h) Klotz, K. L.; Slominski, L.
M.; Riemer, M. E.; Phillips, J. A.; Halfen, J. A. Inorg. Chem. 2009, 48,
801. (i) Cramer, S. A.; Jenkins, D. M. J. Am. Chem. Soc. 2011, 133,
19342.
AUTHOR INFORMATION
Corresponding Author
cmche@hku.hk
■
Notes
(10) Nonheme iron-catalyzed hydrogenation of azides: Bart, S. C.;
The authors declare no competing financial interest.
Lobkovsky, E.; Bill, E.; Chirik, P. J. J. Am. Chem. Soc. 2006, 128, 5302.
I
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(11) Nonheme iron-catalyzed formation of carbodiimides or
isocyanates from organic azides and isocyanides or CO: Cowley, R.
E.; Eckert, N. A.; Elhaïk, J.; Holland, P. L. Chem. Commun. 2009, 1760.
(12) Nonheme iron-catalyzed N−N coupling of aryl azides to
See: Hatanaka, T.; Miyake, R.; Ishida, Y.; Kawaguchi, H. J. Organomet.
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(27) The dissociation energy of cyclohexane C(sp3)−H bond (99.5
kcal/mol) is substantially higher than that of benzylic C(sp3)−H bond
(∼85−89 kcal/mol) and allylic C(sp3)−H bond (∼76−86 kcal/mol).
See: Luo, Y.-R. Comprehensive Handbook of Chemical Bond Energies;
CRC Press: Boca Raton, FL, 2007.
azoarenes Mankad, N. P.; Muller, P.; Peters, J. C. J. Am. Chem. Soc.
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2010, 132, 4083.
(13) Nonheme iron-catalyzed intermolecular amination of C(sp2)−H
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J
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Article
our hands, besides the major products PhI and TsNH2, two minor
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1
and ESI-MS analysis; the other gave exactly the same 1H NMR
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NTs have been reported in literature.
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