New chiral phosphoramidite complexes of iron as catalytic precursors in the oxidation of activated methylene groups

Article abstract of DOI:10.3390/molecules15042631

New phosphoramidite complexes of iron were synthesized and structurally characterized. Reaction of the known chiral phosphoramidites (RO)2PNR'2 (R = binaphthyl, R' = CH3, 1a; R = binaphthyl, R' = benzyl, 1b) with [FeBr(Cp)(CO)2] afforded the title compounds [FeBr(Cp)(CO)(1a,b)] (4a,b) in 34 and 65 % isolated yields as mixtures of diastereomers, since both the metal and the ligand are stereogenic. Similarly, reaction of 1b with [Fe(Cp)I(CO)2] in the presence of catalytic [Fe(Cp)(CO)2]2 afforded [Fe(Cp)I(CO)(1b)] (5b) in 81% yield as a mixture of diastereomers. The molecular structures of 4a, 4b and 5 were determined, revealing a pseudo octahedral coordination geometry about the iron center. The new metal complexes are catalytically active in the oxidation of benzylic methylene groups to the corresponding ketones, utilizing t-BuOOH as oxidant (2 mol% catalyst, 36 h, room temperature, 31-80% yield). Copyright

Full text of DOI:10.3390/molecules15042631

Molecules 2010, 15, 2631-2650; doi:10.3390/molecules15042631
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
New Chiral Phosphoramidite Complexes of Iron as Catalytic
Precursors in the Oxidation of Activated Methylene Groups
Pushkar Shejwalkar 1, Nigam P. Rath 2 and Eike B. Bauer 1,*
1
University of Missouri - St. Louis, Department of Chemistry and Biochemistry, One University
Boulevard, St. Louis, MO 63121, USA; E-Mail: pssgk8@umsl.edu (P.S.)
2
Department of Chemistry and Biochemistry and Center for Nanoscience, University of Missouri -
St. Louis, One University Boulevard, St. Louis, MO 63121, USA; E-Mail: rathn@umsl.edu (N.P.R.)
* Author to whom correspondence should be addressed; E-Mail: bauere@umsl.edu;
Tel.: +1-314-516- 5311; Fax: +1-314-516-5342.
Received: 21 February 2010; in revised form: 31 March 2010 / Accepted: 6 April 2010 /
Published: 12 April 2010
Abstract: New phosphoramidite complexes of iron were synthesized and structurally
characterized. Reaction of the known chiral phosphoramidites (RO)2PNR’2 (R =
binaphthyl, R’ = CH3, 1a; R = binaphthyl, R’ = benzyl, 1b) with [FeBr(Cp)(CO)2] afforded
the title compounds [FeBr(Cp)(CO)(1a,b)] (4a,b) in 34 and 65 % isolated yields as
mixtures of diastereomers, since both the metal and the ligand are stereogenic. Similarly,
reaction of 1b with [Fe(Cp)I(CO)2] in the presence of catalytic [Fe(Cp)(CO)2]2 afforded
[Fe(Cp)I(CO)(1b)] (5b) in 81% yield as a mixture of diastereomers. The molecular
structures of 4a, 4b and 5 were determined, revealing a pseudo octahedral coordination
geometry about the iron center. The new metal complexes are catalytically active in the
oxidation of benzylic methylene groups to the corresponding ketones, utilizing t-BuOOH
as oxidant (2 mol% catalyst, 36 h, room temperature, 31−80% yield).
Keywords: iron; phosphoramidites; X-ray; chiral at metal; benzylic oxidations
1. Introduction
The investigation of transition metal catalyzed organic transformations is a research area of high
interest in chemistry. Catalysis can improve selectivities, decrease the energy required for reactions,
and allows for enantioselection. The mainstream of organometallic catalysis focuses on transition

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Molecules 2010, 15
metals such as Pd, Rh, Ir, Ru, or Au. Iron, however, is a cheap, abundant, non-toxic and
environmentally friendly alternative to well-established transition metals in catalysis. Consequently, an
increasing number of publications are being devoted to the development of iron based catalyst systems
[1–8] that have been applied as catalysts in a variety of organic transformations [9–21], including
oxidation reactions [22–25].
Typically, in situ catalyst systems are employed, consisting of an iron source and a ligand [22]. The
deployment of well-defined, preformed iron complexes is less common, but such complexes allow not
only for kinetic investigations but also for determination of the impact of ligand structure on the activity.
Phosphoramidites (1, Figure 1) are a monodendate ligand class, which have recently gained
prominence in transition metal complex catalyzed organic transformations [26–28]. Originally utilized
by Feringa [28], phosphoramidites have been employed as ligands in catalytically active metal
complexes for a variety of organic reactions such as conjugate enone addition reactions [29],
hydrogenations [30], allylic substitutions [31], cycloadditions [32], vinylations [33], and other
reactions. We have recently reported new ruthenium phosphoramidite complexes and their catalytic
activation in the formation of β-oxo esters from propargylic alcohols and carboxylic acids [34] and in
the Mukaiyama aldol reaction [35]. As far as we know, phosphoramidite complexes have never been
employed in oxidation reactions thus far.
Figure 1. Phosphoramidite ligands.
R
R
O
P N
O
(R)-1
R=CH3, a
= CH2Ph, b
= i-Pr, c
To the best of our knowledge, iron complexes containing the ligands 1 shown in Figure 1 are
unknown thus far. However, iron based organometallic architectures bearing ligands reminiscent of
those in Figure 1 have been previously described in the literature. For example, rearrangements in iron
phosphoranide complexes led to a phosphoramidite ligand coordinated to iron [36,37]. Nakazawa and
Miyosh showed that acyclic diaminooxyphosphine iron complexes undergo Arbuzov-like dealkylation
reactions to give amino-substituted oxophosphoranes [38]. Structurally related iron iminophosphorane
complexes are known as well [39]. Some of these complexes are not very thermally stable and they
have not been applied as catalysts.
We were interested in synthesizing iron complexes of the commonly employed phosphoramidite
ligands 1 shown in Figure 1. We were furthermore interested in applications of these new iron
phosphoramidite complexes in catalysis. We are especially attracted by iron catalyzed oxidations of
alkanes [40,41]. Alkanes are rather unreactive, and their oxidation increases a structural complexity
that allows for further transformations.

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Molecules 2010, 15
This study describes the synthesis of new iron phosphoramidite complexes of the general formula
[FeX(Cp)(CO)(1)] (X=Br, I). We furthermore applied the complexes as catalysts in the oxidation of
activated benzylic methylene groups with t-BuOOH to obtain the corresponding ketones.
2. Results and Discussion
2.1. Synthesis of the Iron Phosphoramidite Complexes
First, synthetic access to iron complexes bearing phosphoramidite ligands was targeted. The iron
carbonyl complex [FeBr(Cp)(CO)2] (2) [42] is known to undergo thermal displacement of Br– by a
neutral ligand L to give ionic complexes of the general formula [Fe(Cp)(CO)2L][Br] [43] or to undergo
CO displacement to give neutral complexes of the formula [FeBr(Cp)(CO)L] (L=phosphonite) [36].
Displacement of one of the CO ligands by phosphites or phosphonites is the major reaction when
performed under UV radiation [44]. Bromide exchange appears to take place preferably with anionic
nucleophiles such as acetylides [45,46] to give neutral iron complexes. In the same way, the iodo
complex [Fe(Cp)I(CO)2] (3) [47] undergoes ligand exchange to either give [Fe(Cp)(CO)2L][I] or
[Fe(Cp)I(CO)L] (L=PPh3) [43,48]. It has been reported that either [Fe(Cp)(CO)2]2 or Me3NO·2H2O
can catalyze the reaction [49].
Accordingly, when the complex [FeBr(Cp)(CO)2] (2) was heated with one equivalent of the
phosphoramidite ligand 1a in toluene for 3 h at 90 °C, the complex [FeBr(Cp)(CO)(1a)] (4a) was
isolated in 34% yield as a greenish solid (Scheme 1). Applying identical conditions with ligand 1b
gave the complex [FeBr(Cp)(CO)(1b)] (4b) in 65% isolated yield. Significantly, when the i-Pr ligand
1c was employed under these conditions, a clean reaction to the corresponding iron complex was not
achieved. The crude reaction mixture contained the corresponding iron complex 4c, as shown by MS
and NMR data. However, workup efforts resulted in 4c being obtained in only 60% spectroscopic (1H-
NMR) purity. The isolated material frequently contained the free phosphoramidite ligand 1c,
suggesting ongoing decomposition of 4c due to ligand loss. Among the ligands 1, the isopropyl ligand
1c is the only one bearing a secondary carbon atom on the nitrogen. Thus, 1c presumably generates too
much steric congestion about the iron center, resulting in an unstable complex.
Similarly, the iodo complex [Fe(Cp)I(CO)2] (3) was heated with ligand 1b in the presence of a
catalytic amount of [Fe(Cp)(CO)2]2 (Scheme 1), which gave the neutral complex 5b in 81% yield.
Significantly, when 1a and 1c were employed as ligands under similar conditions, incomplete reaction
occurred, resulting in an inseparable mixture of compounds.
The new iron complexes 4a, 4b and 5b were characterized by NMR (1H, 13C, 31P), MS, IR and 4a,b
by microanalysis. The coordination of the ligands 1a,b was best observed by a downfield shift of the
31P-NMR signals. The free phosphoramidite ligands 1a,b exhibited signals around 150 ppm, whereas
the corresponding complexes 4a,b and 5b showed resonances between 196.3 and 200.7 ppm. The IR
spectra showed single absorptions at 1,971 (4a, 5b) and 1,978 cm–1 (4b), as expected for
monocarbonyl complexes. The precursor complex [FeBr(Cp)(CO)2] exhibits two νC≡O absorptions at
1,995 and 2,049 cm–1 [42]. The CO ligands were also observed in the 13C NMR spectra, giving signals
between 216.9 and 217.7 ppm (JCP = 21.8 to 45.3 Hz). The MS spectra are also in accordance with the
proposed structures. For 4a and 4b, molecular ion peaks were not observed in the FAB MS spectra, but

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Molecules 2010, 15
peaks for the corresponding sodium adducts [4+Na]+ appeared. However, their FAB MS spectra
complexes exhibited a diagnostic fragmentation pattern resulting from CO and/or Br loss. For complex
5b, this pattern also was observed, including the molecular ion peak [5b]+.
Scheme 1. Iron Phosphoramidite Complex Syntheses.
ligand (R)-1
O
Fe
Br
Fe
Br
CO
CO
tol, 90 °C, 3 h
P
OC
O
N
R
2
4
R
4a, R=CH3, 34%, 77:23 mixture of diastereomers
4b, R = CH2Ph, 65%, 90:10 mixture of diastereomers
4c, R = i-Pr, detected in the crude reaction mixture, but not
isolable in analytical purity, one diastereomer
ligand (R)-1b
O
Fe
Fe
CO
P
CO
cat. [Fe(Cp)(CO)2]2
OC
O
I
N
I
hexanes, 30 min,
reflux
5b
PhH2C
CH2Ph
3
81%, 73:27 mixture of diastereomers
For the metal complex syntheses, enantiopure ligands were employed. The resulting complexes
4a,b and 5b are stereogenic at the metal and at the ligands, and accordingly, two diastereomers are
formed during synthesis, as seen in the NMR spectra. The complexes 4a,b and 5b were thus obtained
as a 77:23, 90:10 and 73:27 mixture of diastereomers, respectively. Some signals in the 1H, 13C and 31P
1
31
NMR spectra are doubled, and the diastereomeric ratios were determined by H- and P-NMR. All
efforts to isolate one of the complexes in diastereomerically pure form have failed to date, but it was
possible to enrich the major diastereomer for complex 4a to a 85:15 diastereomeric ratio. Complex 4c
1
could not be isolated analytically pure, but its crude H- and 31P-NMR spectra showed only one
diastereomer, which would be in accordance with the larger steric bulk of the phosphoramidite ligand 1c.
Although separation of the diastereomers in bulk has failed to date, we were able to obtain crystals
of X-ray quality in the recrystallized material of the complexes 4b and 5b, and the X-ray structures
were determined (Table 1 and Experimental section). The molecular structures are shown in Figures 2
and 3, and key structural data is given in Table 2, which also includes data from related compounds
from the literature.
The structures confirm the piano stool type coordination geometry around the iron, in which one of
the carbonyl ligands in the precursor complexes [FeX(Cp)(CO)2] is substituted for the
phosphoramidite ligand 1b. The bond angles around iron range from 90.76(8)° for the C(1)-Fe-P angle
between the phosphoramidite and the carbonyl ligand and 95.58(8)° for the C(1)-Fe-I angle between
the carbonyl and the iodo ligand. Thus, the coordination geometry of the complexes is best described
as slightly distorted octahedral. For complex 4a, an X-ray structure could also be determined.
Unfortunately, despite multiple attempts, we were unable to obtain crystals of high quality and due to
the poor crystal quality and weak diffraction, the resulting structure of 4a was not of high quality.

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Molecules 2010, 15
However, it establishes the connectivities for complex 4a. Details of the structure determination and
parameters as well as a graphical representation for 4a are given in the Supplementary material (Table
S1 and Figure S1).
Table 1. Crystal data and structure refinement for 4b and 5b.
Empirical formula
Formula weight
C40H31BrFeNO3P⋅(CH2Cl2)2
910.24
C40H31FeINO3P⋅(C6H14)
873.55
Temperature, Wavelength
100(2) K, 0.71073 Å
100(2) K, 0.71073 Å
Crystal system, Space group
Unit cell dimensions
Orthorhombic, P212121
Orthorhombic, P212121
a = 10.3609(5) Å
b = 17.6708(8) Å
c = 21.2889(10) Å
a = 10.2311(8) Å
b = 14.9124(11) Å
c = 26.1055(19) Å
α = β = γ = 90 °
3897.7(3) Å3, 4
α = β = γ = 90 °
3982.9(5) Å3, 4
Volume, Z
Density (calculated)
Absorption coefficient
Crystal size
1.551 Mg/m3
1.769 mm−1
0.57 x 0.13 x 0.08 mm3
1.50 to 26.78°
40286
1.457 Mg/m3
1.236 mm−1
0.31 x 0.07 x 0.06 mm3
2.07 to 24.99°
56634
Theta range for data collection
Reflections collected
Independent reflections
Absorption correction
8268 [R(int) = 0.0520]
Semi-empirical from equivalents
0.8714 and 0.4316
8268 / 0 / 478
7016 [R(int) = 0.1303]
Semi-empirical from equivalents
0.9340 and 0.7044
7016 / 72 / 472
Max. and min. transmission
Data / restraints / parameters
Goodness-of-fit on F2
1.02
1.06
Final R indices [I>2sigma(I)]
R indices (all data)
R1 = 0.0304, wR2 = 0.0555
R1 = 0.0444, wR2 = 0.0593
0.003(5)
R1 = 0.0566, wR2 = 0.1052
R1 = 0.0922, wR2 = 0.1176
0.04(3)
Absolute structure parameter
Largest diff. peak and hole
0.553 and -0.353 e.Å−3
0.993 and -0.932 e.Å−3
Figure 2. Molecular structure of one of the diastereomers of 4b (depicted with 65%
probability ellipsoids, H atoms, and solvents are omitted for clarity). Key bond lengths and
bond angles are listed in Table 2.

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Molecules 2010, 15
Figure 3. Molecular structure of one of the diastereomers of 5b (depicted with 65%
probability ellipsoids, H atoms, and solvents are omitted for clarity). Key bond lengths and
bond angles are listed in Table 2.
Table 2. Key bond lengths (Å) and angles (°).
Complex 4b
(X=Br, Y=1)
2.4399(5)
1.778(3)
5b
6
7
8
(X=I, Y=6)
2.5992(13)
1.770(10)
1.149(10)
2.150(3)
1.632(7)
91.1(3)
(X=Br)
2.437(0)
1.744(3)
1.136(4)
2.163(1)
-
(X=Br)
2.433
1.740
1.195
2.201
-
(X=I)
X-Fe
2.605(2)
1.764(6)
1.077(7)
2.149(2)
Fe-C(Y)
C(Y)-O(1)
Fe-P
1.118(3)
2.1501(7)
1.642(2)
P-N
C(Y)-Fe-P
C(Y)-Fe-X
P-Fe-X
90.76(8)
95.0(1)
96.02
91.73(3)
176.06
-
95.20
91.47
96.20
170.20
-
92.9(2)
92.8(2)
93.3(1)
177.3(7)
-
93.17(9)
89.5(3)
92.03(2)
95.58(8)
177.8(7)
121.0(3)
100.0(3)
O(1)-C(Y)-Fe
N-P-Fe
176.5(2)
121.54(8)
100.36(9)
O(3)-P-O(2)
104.32
-
-
The molecular structures of 4a, 4b and 5b do not show significant differences. However, the C(1)-
Fe-Br angle for 4b of 93.17(9)° is larger than that one of 89.5(3)° for the C(6)-Fe-I angle in 5b. In turn,
the P-Fe-Br angle for 4b of 92.03(2)° is smaller than that one of 95.58(8)° for the P-Fe-I angle in 5b. It
appears that the larger iodo ligand in 5b causes a larger angle between the iodo and the
phosphoramidite ligand, which, in turn, renders the iodo and the carbonyl ligand closer together,
resulting in a smaller angle.
In order to analyze the influence of the phosphoramidite ligand on the structure of the complex, we
compared key structural data with other complexes of the general formula [FeX(Cp)(CO)L], where L
is a phosphorus donating ligand and X either Br or I. Structurally characterized complexes of this
formula are rare, and three examples 6 [44], 7 [50] and 8 [51] from the literature are displayed in
Figure 4. The available structural parameters are listed in Table 2.

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Molecules 2010, 15
Figure 4. Structurally related pianostool type iron complexes.
It can be seen that the five complexes do not significantly differ structurally and bond lengths and
angles are comparable. Only complex 7 differs slightly from complexes 4b and 5b with respect to the
Fe-P bond length. The Fe-P bond length for 4b is 2.1501(7) Å and for 5b it is 2.150(3) Å. These bond
lengths are, thus, slightly shorter than in complex 7 (2.201 Å). This trend can be explained if it is
assumed that the phosphoramidite ligand in 4b and 5b allows for more back bonding than the PPh2R
ligand in 7. Stronger backbonding from the metal to the ligand strengthens and consequently shortens
the Fe-P bond in 4b.
2.2. Application of the New Iron Phosphoramidite Complex 4a in Catalysis
We were next interested to determine if the new iron phosphoramidite complexes 4a and 4b are
useful as catalysts in organic oxidation reactions. The original driving force to apply chiral iron
complexes was to investigate potential alkane oxidations to obtain chiral alcohols. Screening
experiments are compiled in Table 3. Activated methylene groups in such substrates as cinnamyl
alcohol, tetrahydronaphthalene, fluorene, diphenylmethane and dihydroanthracene could be oxidized
to the corresponding ketones catalyzed by iron complex 4a using t-BuOOH as the oxidant. Less
activated methylene or methyl groups in such substrates as toluene, adamantane or cyclooctene were
not oxidized under the reaction conditions in Table 3. While t-BuOOH worked well as oxidant, H2O2,
ethaneperoxoic acid and 3-chlorobenzoperoxoic acid (mCPBA) typically gave no oxidations, with the
exception of the oxidation of cinnamyl alcohol. Somewhat unexpectedly, in this case an oxidative
cleavage of the double bond to give benzaldehyde was also observed. Pyridine was determined to be
the solvent of choice, and in most cases the reactions were performed at room temperature. Ketones
were typically the only reaction products; alcohols were not observed by GC/MS. Significantly, the
precursor complexes [FeX(Cp)(CO)2] (2, 3) showed much slower rates in the oxidation reactions
(entries 17 to 20 in Table 3). No reactions were observed in the absence of the catalyst, except for the
oxidation of cinnamyl alcohol (slow and incomplete oxidation) and tetrahydronaphthalene-1-ol (entries
2 and 6 in Table 3). The catalytic performance of complexes 4b and 5b were comparable, but complex
4a was used for optimizations and further studies, as its ligand 1a is synthetically more easily accessed
than ligand 1b.

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Molecules 2010, 15
Table 3. Screening of catalyst activity.
Time /
Catalyst
Yield
(%) b
Entry Substrate
Oxidant a
Temperatu
re
Solvent
Product
Loading
1
2
toluene
t-BuOOH
t-BuOOH
48 h / 90 °C 2 mol% 4a
pyridine
NR e
cinnamyl
alcohol
24 h / 80 °C
–
acetonitrile cinnamaldehyde
30
3
4
5
6
7
cinnamyl
alcohol
H2O2
24 h / rt
10 mol% 4a
10 mol% 4a
CH2Cl2
pyridine
pyridine
pyridine
pyridine
benzaldehyde
100
cinnamyl
alcohol
t-BuOOH
t-BuOOH
24 h / rt
cinnamaldehyde
benzaldehyde
tetrahydronaph-
thalene-1-one
tetrahydronaph-
thalene-1-one
benzophenone
80
~20
100
tetrahydro-
naphthalene
18 h / 90 °C 2 mol% 4a
16 h / rt
36 h / 82 °C 2 mol% 4a
tetrahydronaph- t-BuOOH
–
100
100
thalene-1-ol
diphenyl-
methane
t-BuOOH
8
fluorene
t-BuOOH
mCPBA c
CH3COOOH d
t-BuOOH
t-BuOOH
36 h / rt
36 h / rt
36 h / rt
36 h / rt
36 h / rt
2 mol% 4a
2 mol% 4a
2 mol% 4a
2 mol% 4a
2 mol% 4a
pyridine
pyridine
pyridine
pyridine
pyridine
fluorenone
fluorenone
fluorenone
fluorenone
anthraquinone
100
traces
traces
100
9
fluorene
10
11
12
fluorene
fluorene
dihydro-
anthracene
adamantane
adamantane
diphenyl-
methane
100
13
14
15
t-BuOOH
t-BuOOH
H2O2
36 h / rt
2 mol% 4a
pyridine
pyridine
CH2Cl2
NR e
NR e
NR e
36 h / 90 °C 2 mol% 4a
36 h / rt
10 mol% 4a
16
17
18
cyclooctene
fluorene
t-BuOOH
t-BuOOH
t-BuOOH
42 h / rt
36 h / rt
36 h / rt
2 mol% 4a
2 mol% 2
2 mol% 2
pyridine
pyridine
pyridine
NR e
fluorenone
anthraquinone
30
9 f
dihydro-
anthracene
diphenyl-
methane
19
t-BuOOH
t-BuOOH
36 h / rt
36 h / rt
2 mol% 2
2 mol% 3
pyridine
benzophenone
fluorenone
27
21
20
fluorene
pyridine
c
Oxidants were applied in 3.0 fold excess.b Determined by GC/MS. 3-chlorobenzoperoxoic acid.
a
d
ethaneperoxoic acid.e No reaction. Only starting material was detected, and at most trace
quantities of oxidation products. f 59% anthracene were detected by GC/MS.
Under optimized reaction conditions, complex 4a was then utilized in the oxidation of a variety of
substrates, as compiled in Table 4. Diphenylmethane, fluorene, dihydroanthracene, cinnamyl alcohol
and phenylmethanol were oxidized to the corresponding aldehydes or ketones in 80 to 31% yields.

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Molecules 2010, 15
About three equivalents of t-BuOOH with a catalyst loading of 2 mol% in pyridine as solvent were
employed. The turnover frequencies ranged from 0.37 to 1.39 h–1.
Table 4. Iron catalyzed oxidation reactions.
Entry Starting Material
Product
Yield b TOF / h−1 c
1
diphenylmethane
benzo-phenone
56%
0.78
2
3
fluorene
dihydroanthracene
fluorenone
anthra-quinone
80%
54% d
1.11
1.39
4
5
cinnamylalcohol
phenylmethanol
cinnamyl aldehyde 31% e
0.37 e
benzaldehyde
47% e
0.56 e
a
Conditions: substrate (0.602 mmol), t-BuOOH in decane (1.8 mmol), catalyst 4a (2 mol%), 36 h
b
c
in pyridine (1 mL) at rt. Isolated yields after column chromatography. Turnover frequency
determined from isolated yield: number of moles (product) over number of moles (catalyst) times
reaction time. d The product contained ca. 10% anthracene (as assessed by 1H-NMR). e NMR yields
from reactions run in pyridine-d5; it was not possible to separate the products from the decane
(which is the solvent for the t-BuOOH employed in the reaction). The TOF was calculated from the
NMR data.
2.3. Further Experiment to Better Understand the Oxidation Reactions
To obtain further details of the oxidation reactions, additional experiments were performed. The
oxidation of fluorene catalyzed by 4a was monitored by GC for the first seven hours (entry 2 in Table 4).
Figure 5 shows a plot of the formation of fluorenone and the consumption of fluorene versus time. The
reaction appears to be pseudo zero order with respect to the substrate fluorene and fluorenone
formation. However, first order reactions might very well appear zero order in their initial stage. The
observed rate constant derived from the slope of the linear trend from the fluorene consumption and
the fluorenone formation in Figure 5 was calculated to be 0.14 h−1. No induction period was observed
for the reaction.
As the complex 4a is coordinatively saturated, an open coordination site from ligand loss is required
for catalytic activity. Proton and 31P-NMR spectra of the metal complex in pyridine-d5 showed no
decomposition after 24 h, suggesting that the pyridine solvent applied in the oxidation reactions in
Table 4 does not displace ligands. To obtain insight into the catalytically active species generated in
the reaction mixture, the catalyst 4a and the oxidant t-BuOOH were combined in the absence of
31
substrate in pyridine-d5. After 24 h, NMR (1H, P), IR and MS spectra were recorded for the residue
after solvent removal. In the 31P-NMR, a peak around 14 ppm was observed, which we tentatively
1
assigned to the oxidized phosphoramidite ligand 1a. In the H spectrum, two singlets around 2.7 ppm
for the NCH3 groups were observed, which are significantly shifted compared to their resonances in

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Molecules 2010, 15
the metal complex 4a (2.85 ppm). The MS spectrum of the residue showed a peak for ligand 1a plus
oxygen, suggesting that the loss of the phosphoramidite ligand by oxidation might be one step towards
the formation of the catalytically active species in the reaction mixture. This also could explain, why
[FeBr(Cp)(CO)2] (2) and [Fe(Cp)I(CO)2] (3) are much less active relative to 4a (Table 3, entries 17 to 20),
because the complexes do not contain ligands that can be oxidatively removed. Furthermore, after
oxidation the absorption for the terminal CO ligand in 4a in the IR spectrum disappeared, and instead, a
new band at 1713 cm−1 was observed, which could be evidence for a carbonyl bridged dimeric iron species.
Figure 5. Monitoring of substrate decay and product formation over time.
1.4
fluorenone
1.2
fluorene
1.0
0.8
0.6
0.4
0.2
0.0
time / h
0
1
2
3
4
5
6
7
As mentioned above, no alcohols were observed as the reaction products (Tables 3 and 4). To avoid
overoxidation, some authors employ a large excess of the substrate over the oxidant in test reactions to
elucidate a mechanism [52]. Accordingly, we performed a reaction with a 25-fold excess of the
substrate fluorene relative to the oxidant t-BuOOH in the presence of the iron catalyst 4a (250:10:1
substrate:t-BuOOH:4a, Scheme 2). Under these reaction conditions, the alcohol product was not
observed by GC/MS. Instead, the hydrogenated species 9 and the corresponding ketone product were
detected in a 42:58 ratio.
Scheme 2. Experiment employing an excess of substrate over the oxidant.
The mechanism of iron-catalyzed oxidation reactions utilizing H2O2 strongly depends on the
reaction conditions, the solvent, the oxidant and the relative ratio of the reactants [53]. Sawyer
proposed a mechanism which he termed “Oxygenated Fenton Chemistry” [40]. Barton published a
series of iron catalyst systems (Gif chemistry) for alkane oxidation with peroxides [41,54] and suggested

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Molecules 2010, 15
a non-radical mechanism. However, some authors suggested that free radicals were involved [55,56]
while others corroborate Barton’s non-radical mechanism [57]. Iron catalyzed reactions utilizing
t-BuOOH appear to follow a radical mechanism [53]. The formation of a peroxo species
[Fe-OOt-Bu] [58,59] is often considered to be the first step in the oxidation reactions with t-BuOOH
which gives an LMCT absorption between 500 and 600 nm in UV-vis spectra [60,61]. The peroxo
species [Fe-OOt-Bu] can undergo homolytic bond cleavage to form either t-BuO⋅ or t-BuOO⋅radicals
and oxoiron species Fe=O, which are the actual oxidants [60]. The peroxo species [Fe-OOt-Bu] could
not be observed by UV when complex 4a was combined with t-BuOOH in the absence of substrates.
Unfortunately, due to the formation of unidentified species with strong absorptions around 300 nm, the
reaction of the iron complex with t-BuOOH could not be monitored over extended periods of time by
UV-vis, as performed by other authors [60]. We thus do not have spectroscopic evidence that the
intermediate [Fe-OOt-Bu] forms during the reaction but its formation might be slow in our case (as are
the oxidation reactions in Table 4). Based on our data we cannot definitely establish a mechanism for
our oxidation reactions. It appears reasonable that slow oxidative removal of the phosphoramidite
ligand creates species 10 with an open coordination side (Scheme 3), which then further reacts to
afford the peroxo complex [Fe-OOt-Bu] (11). Based on our spectroscopic data, the exact nature of
complexes 10 and 11 cannot be established, either these are pyridyl coordinated species or carbonyl
bridged dimers. Cleavage of the peroxo bridge in 11 might provide the oxidants, and its slow
formation would explain the long reaction times and the kinetics in substrate and product for the
oxidation of fluorene (Figure 5).
Scheme 3. Potential formation of the catalytically active species in the oxidation reactions.
The square denotes an open coordination site.
Thus, placing a phosphoramidite ligand in the coordination sphere of a complex of the general
formula [FeBr(Cp)(CO)L] is a strategy to keep a steady supply of the catalytically active species 11 in
the reaction mixture, slowing catalyst and peroxide decomposition pathways. Thus, slow addition of the
peroxide oxidant to the reaction mixture is not necessary, as performed by other authors [62].
3. Experimental
3.1. General
Chemicals were treated as follows: acetonitrile and pentane were distilled from CaH2. Toluene was
distilled from Na/benzophenone. Other solvents: CHCl3, pyridine, CH2Cl2, hexanes, the substrates for
the catalytic experiments (Aldrich), and t-BuOOH (5.5 M in decane, Fluka) were used as received.
“(R)-BINOL-N,N-dimethylphosphoramidite” 1a [63] “(R)-BINOL-N,N-dibenzylphosphoramidite” 1b,
[64] “(R)-BINOL-N,N-diisopropylphosphoramidite” 1c [64], [FeBr(Cp)(CO)2] (2) [42] and

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[Fe(Cp)I(CO)2] (3) [47] were synthesized according to the literature. Metal complex syntheses were
carried out under argon employing standard Schlenk techniques. Workup as well as the catalytic
experiments were performed under aerobic conditions.
The NMR spectra were obtained at room temperature on either a Bruker Avance 300 MHz or a
Varian Unity Plus 300 MHz instrument and were referenced to a residual solvent signal. All
assignments are tentative. GC/MS spectra were recorded on a Hewlett Packard GC/MS system model
5988A. Exact masses were acquired on a JEOL MStation [JMS-700] mass spectrometer. IR spectra
were recorded on a Thermo Nicolet 360 FT-IR spectrometer. Elemental analyses were performed by
Atlantic Microlab Inc., Norcross, GA, USA.
CCDC 727527 (4b), CCDC 727535 (4a) and CCDC 765699 (5b) contain the supplementary
crystallographic data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK; Fax: +44 1223 336033; E-Mail: deposit@ccdc.cam.ac.uk).
3.2. Synthesis of “[FeBrCp(CO)(1a)]”, 4a
A Schlenk flask was charged with phosphoramidite 1a (0.078 g, 0.304 mmol) and [FeBr(Cp)(CO)2]
(2, 0.120 g, 0.334 mmol), and dry toluene (10 mL) was added. The solids dissolved and the light red
colored solution was then heated at 90 °C under an atmosphere of argon for 3 h. The color of the solution
darkens. The solvent was removed and the greenish solid was washed with dry pentane (2 × 4 mL).
The solid was dissolved in chloroform and re-precipitated by adding hexanes. The solvents were
decanted and the residue was dried for two days under high vacuum to give the complex 4a (0.061 g,
0.104 mmol, 34%) as a greenish solid, which was isolated as a mixture of diastereomers (77:23, as
assessed by 1H and 31P). Calcd for C28H23BrPFeNO3: C, 57.17; H, 3.94. Found: C, 52.38; H, 3.85 [65].
HRMS calcd for C28H2379BrNO3P54FeNa, 609.98456; found, 609.9854 [66]. MS (FAB, 4-NBA + NaI)
[67] m/z 610 ([4a+Na]+, 10%) [66], 559 ([4a–CO]+, 15%), 480 ([4a–Br–CO]+, 30%). IR (cm–1, neat
solid) νC≡O 1971 (s, sh).
To separate the diastereomers, the crude reaction mixture was allowed to cool to rt, and a solid
precipitated. The solution was decanted from the solid. The solid was washed with dry diethyl ether
(about 2 × 2 mL). The solid was dried under vacuum for 2 days at 50 °C, yielding 4a (0.052 g,
0.09 mmol, 26%) as 50:50 mixture of diastereomers (1H, 13C, 31P NMR).
From the decanted solution, the solvent was removed by vacuum. The residual solid was dissolved
in CH2Cl2 (4 mL) and the solvent was allowed to slowly evaporate, causing precipitation of a solid.
The remaining solvent was decanted, and the solid was washed with hexanes (4 mL). The solid was
dried under high vacuum at 50 °C for 2 days to yield a greenish colored solid of 4a (0.050 g,
0.09 mmol, 26%) as a mixture 85:15 mixture of diastereomers (1H-, 31P-NMR).
Based on the intensities of the signals in the NMR spectra, the data for the two isomers are given
below separately.
1
NMR (δ, CD2Cl2, major diastereomer): H: 8.05−7.95 (m, 5H, binapthyl), 7.38−7.30 (m, 9H,
binapthyl), 7.18−7.16 (d, 1H, 4.69, JHH = 6.0 Hz), 4.77 (d, 5H, JHH = 1Hz, Cp), 2.91 (s, 3H, NCH3),
13
2.87 (s, 3H, NCH3’); C{1H}: 217.4 (d, JCP = 44.7 Hz, CO), 150.3, 150.2, 148.2 (d, JCP = 5.4 Hz),
133.2 (d, JCP = 1.6 Hz), 132.8 (d, JCP = 1.6 Hz), 131.7, 131.6 (d, JCP = 1.2 Hz), 130.9 (d, JCP = 1.5 Hz),

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130.5, 128.7, 128.5, 127.2, 126.8, 126.6 (d, JCP = 4.2 Hz), 125.7, 125.4, 123.6 (d, JCP = 2.6 Hz), 123.0
(d, JCH = 2.6 Hz), 121.6 (d, JCP = 2.6 Hz), 121.3 (d, JCP = 1.9 Hz, aromatic), 82.9 (d, JCP = 1.9 Hz, Cp),
38.8 (s, NCH3), 38.7 (s, NCH3’); 31P {1H}: 198.5 (s).
1
NMR (δ, CD2Cl2, minor diastereomer, partial) [68]: H 4.73 (d, 5H, JHP = 1.0 Hz, Cp), 2.69 (s, 3H,
NCH3), 2.65 (s, 3H, NCH3’); 13C{1H}: 131.5, 130.3, 128.6, 127.5, 127.1, 126.4, 124.3, 124.1, 123.3
(aromatic), 83.1 (d, JCP = 1.5 Hz, Cp), 38.62 (s, NCH3), 38.58 (s, NCH3’); 31P {1H}: 200.4 (s).
3.3. Synthesis of “[FeBrCp(CO)(1b)]”, 4b
A Schlenk flask was charged with phosphoramidite 1b (0.132 g, 0.258 mmol) and [FeBr(Cp)(CO)2]
(2, 0.060 g, 0.234 mmol), and dry toluene (10 mL) was added. The solids dissolved and the light red
colored solution was then heated at 90 °C under an atmosphere of argon for 3 h. The color of the
solution darkened. Upon cooling, the solvent was removed under high vacuum. The brownish solid
was washed with dry pentane (about 2 × 4 mL) and then dissolved in 4 mL of CH2Cl2 and layered with
hexanes and stored at −18 °C. A precipitate formed, and the mother liquor was removed and the
residual solid was washed with hexanes. The crystallite solid was dried under vacuum (oil pump) for
two days at 40 °C to give the complex 4b as tan solid (0.125 g, 0.17 mmol, 65%) as a mixture of
1
diastereomers (90:10, as assessed by H). Calcd for C40H31FeBrPO3N: C, 64.18; H, 4.22. Found: C,
66.28; H, 4.62 [65].
HRMS calcd for C40H3179BrNO3P56FeNa, 762.04706; found, 762.0475 (FAB+). MS (FAB, 4-NBA
+ NaI) [67] m/z 764 ([4b+Na]+, 10%) [66], 713 ([4b–CO]+, 25%), 632 ([4b–CO–Br]+, 35%), 534
([1b+Na]+, 95%); IR (cm–1, neat solid) νC≡O 1978 (s).
1
NMR (δ, CD2Cl2) [68] H: 8.13−8.00 (m, 2H, aromatic), 7.88-7.74 (m, 2H, aromatic), 7.53−7.16
(m, 21H, aromatic), 5.13−5.03 (m, 2H, NCH2), 4.87 (s, 5H, Cp), 4.75 (s, 0.5H, Cp’, minor
diastereomer), 4.65−4.50 (m, 0.2H, NCH2’, minor diastereomer), 3.80−3.65 (m, 0.2H, NCH2’, minor
13
diastereomer), 3.54−3.45 (m, 2H, NCH2); C{1H}: [68] 216.9 (d, JCP = 45.3 Hz, CO), 150.2, 150.0,
148.1 (d, JCP = 4.9 Hz), 137.4 (d, JCP = 2.7 Hz), 133.3, 132.6, 131.8, 131.4, 130.8, 130.5, 129.6, 128.8,
128.6, 128.6, 126.5, 127.9, 127.7, 127.3, 126.8 (d, JCP = 3.5 Hz), 126.5, 125.8, 125.4, 123.9, 122.7,
121.5, 121.2 (aromatic), 83.3 (d, JCP = 1.5 Hz, Cp), 83.0 (d, JCP = 1.6 Hz, Cp’, minor diastereomer),
49.9 (d, JCP = 6.5 Hz, CH2); 31P{1H}: 196.3 (s, major diastereomer).
3.4. Attempted synthesis of “[FeBrCp(CO)(1c)]”, 4c
To a Schlenk flask containing phosphoramidite 1c (0.100 g, 0.251 mmol) and [FeBr(Cp)(CO)2] (2,
0.056 g, 0.219 mmol), dry toluene (10 mL) was added. The solids dissolved and the light red colored
solution was then heated at 90 °C under an atmosphere of argon for 5 h. The color of the solution
darkens. Upon cooling, the solvent was removed under high vacuum. The light green colored solid was
washed with dry pentane (about 2 × 4 mL). The solid was then dried under vacuum (oil pump) for two
days to give a greenish solid as a mixture of phosphoramidite 1c and the complex 4c as single
diastereomer (0.079 g recovered mass, ca. 60% spectroscopic purity for 4c, as assessed by 1H and 31P).
Only the analytical data for 4c is given below.

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HRMS calcd for C32H3179BrNO3P56FeNa, 666.04712; found 666.0443 (FAB+). MS (FAB, 4-NBA)
[67] m/z 644 ([4c]+, 5%), 615 ([4c–CO]+, 100%), 536 ([4c–CO–Br]+, 75%), 416 ([1c+H]+, 45%); IR
(cm–1, oil film) νC≡O 1976 (s).
NMR (δ, CD2Cl2) [68] 1H: 8.33−6.87 (m, 18H, aromatic), 4.97 (s, 5H, Cp), 4.66 (m, 2H, CH), 1.68
13
(d, 6H, JHH = 6.6 Hz, CH3), 1.21 (d, 6H, JHH = 6.2 Hz, CH3’); C{1H}: 151.5, 151.3, 148.9, 134.6,
134.1, 132.9, 132.4, 131.5, 131.3, 129.7, 129.6, 128.4, 127.9, 127.7, 127.5, 126.8, 126.3, 125.0, 123.9,
123.1 (aromatic), 83.9 (Cp), 49.7 (d, JCP = 7.2 Hz, CHCH3), 24.6 (CH3); 31P{1H}: 199.9 (s).
3.5. Synthesis of “[Fe(Cp)I(CO)(1b)]”, 5b
A Schlenk flask was charged with phosphoramidite 1b (0.185 g, 0.362 mmol) and [Fe(Cp)I(CO)2]
(3, 0.100 g, 0.329 mmol), and hexane (10 mL) was added. The flask was fitted with reflux condenser.
The suspension was heated to reflux and [CpFe(CO)2]2 (0.004 g, 0.011 mmol) was added to the
reaction mixture. The color of the solution darkened almost instantaneously. The solution was refluxed
for 30 minutes. Upon cooling, the reaction mixture was filtered through a short pad of cellulose, the
pad was washed with hexanes (2 × 5 mL) and with CH2Cl2 (2 × 5 mL). The solvent was removed from
the combined filtrates and the crystalline solid was dried under vacuum (oil pump) to give the complex
5b as green solid (0.209 g, 0.265 mmol, 81%) as diastereomeric mixture (73:27 as assessed by 1H NMR).
HRMS calcd for C39H31NO2P56FeI, 759.0487; found, 759.0486 (FAB+). MS (FAB, 4-NBA) m/z
788 ([5b+H]+, 10%), 759 ([5b–CO+H]+, 100%), 694 ([5b–CO–Cp+H]+, 25%), 633 ([5b-CO-I]+, 60%);
IR (cm−1, neat solid) νC≡O 1971 (s).
1
NMR (δ, CD2Cl2, major isomer) H: 8.16 (d, 1H, aromatic, JHH = 8.7 Hz), 8.05 (d, 1H, aromatic,
JHH = 8.3 Hz), 7.88 (d, 2H, aromatic, JHH = 8.3 Hz), 7.83 (d, 2H, aromatic, JHH = 9.2 Hz), 7.55−7.19
(m, 24H, aromatic), 5.11−5.04 (m, 2H, CH2), 4.90 (s, 5H, Cp), 3.55−3.46 (m, 2H, CH2); 13C{1H}:
217.7 (d, JCP = 21.8 Hz, CO), 150.7, 150.5, 148.6 (d, JCP = 5.3 Hz), 137.7 (d, JCP = 2.8 Hz), 133.6 (d,
JCP = 1.5 Hz), 132.9 (d, JCP = 1.5 Hz), 132.1, 131.7, 131.1, 130.8, 129.8, 129.2, 129.1, 128.9, 128.8,
128.2, 127.6, 127.2, 127.1, 126.9, 126.1, 125.8, 121.9, 121.6 (aromatic), 83.3 (Cp), 50.7 (d, JCP = 6.8
Hz, CH2); 31P{1H}: 201.8 (s).
1
NMR (δ, CD2Cl2, minor isomer) H: 4.79 (s, 0.8H, Cp), 4.74−4.66 (m, 0.4H, CH2), 3.76−3.61 (m,
0.6H, CH2); 13C{1H}: 82.9 (Cp), 51.2 (d, JCP = 6.8 Hz, CH2); 31P{1H}: 203.2 (s).
3.6. Typical Procedure for the Catalytic Experiments
The substrate fluorene (0.100 g, 0.602 mmol) and the catalyst 4a (0.007 g, 0.012 mmol) were
dissolved in pyridine (1.0 mL). The oxidant t-BuOOH (0.33 mL of a 5.5 M solution in decane,
1.8 mmol) was added and the brownish solution was shaken for 36 h at room temperature. The
pyridine was removed under vacuum. The product 9-fluorenone was isolated by column
chromatography (silica gel; CH2Cl2) as yellow-crystalline solid (0.0872 g, 0.479 mmol, 80%).
Analytical data and NMR spectra (1H, 13C) are given in the Supporting information.

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3.7. Monitoring of the Oxidation of Fluorene to Fluorenone over Time (Figure 5)
A screw capped vial was charged with fluorene (0.100 g, 0.602 mmol) and the catalyst 4a (0.007 g,
0.012 mmol). Pyridine (1 mL) was added and the solids dissolved to give a clear yellow solution.
t-BuOOH (0.33 mL of a 5.5 M solution in decane, 1.8 mmol) was then added in one portion and the
reaction mixture was shaken at rt. For analysis, aliquots were taken from the reaction mixture, filtered
through a short pad of alumina (which was washed with 2 mL CH2Cl2), and injected into the GC/MS
instrument. The substrate decay and product formation over time was determined by the ratio of its
signal intensity to the signal intensity of decane (which is the solvent for t-BuOOH and served as an
internal standard).
3.8. Reaction of the Catalyst 4a with the Oxidant t-BuOOH without Substrate.
A vial was charged with catalyst 4a (0.062 g, 0.011 mmol), and pyridine (0.5 mL) was added. To
the solution, t-BuOOH (0.150 mL of a 5.5 M solution in decane, 0.831 mmol) was added in one
portion and the solution was stirred for 24 to 36 h. The pyridine was removed under vacuum, and the
solid residue was analyzed by MS and NMR (1H, 31P).
MS (FAB, 4-NBA) m/z 376 ([1a+O]+, 40%); MS (FAB, 4-NBA + NaI) m/z 398 ([1a+O+Na]+, 55%);
1
IR (cm–1, neat solid) νC≡O 1713 (m). NMR (δ, CDCl3, partial) H: 8.01−7.94 (m, 4H, binapthyl),
7.60−7.30 (m, 8H, binapthyl), 2.70 (d, 6H, JHH = 9.61 Hz); 31P{1H}: 14.9 (s).
3.9. X-ray Structure Determination for 4b and 5b
X-ray quality crystals of 4b and 5b were obtained by layering a CH2Cl2 solution with hexanes,
which was stored at –18 °C for one to four weeks. Crystals were mounted from Paratone oil to a
Bruker Kappa Apex II single crystal X-Ray diffractometer equipped with an Oxford Cryostream LT
device. Intensity data were collected by a combinations of ϖ and φ scans. Apex II, SAINT and
SADABS software packages (Bruker Analytical X-Ray, Madison, WI, 2008) were used for data
collection, integration and correction of systematic errors, respectively.
Crystal data and intensity data collection parameters are listed in Table 1. Structure solution and
refinement were carried out using the SHELXTL- PLUS software package [69]. The structures were
solved by direct methods and refined successfully in the space group P212121. The non-hydrogen atoms
were refined anisotropically to convergence. All hydrogen atoms were treated using appropriate riding
model (AFIX m3). Complete listings of positional and isotropic displacement coefficients for
hydrogen atoms, anisotropic displacement coefficients for the non-hydrogen atoms and tables of
calculated and observed structure factors are available in electronic format.
4. Conclusions
In summary, we have synthesized the first iron complexes of the general formula [FeX(Cp)(CO)(1)]
(X=Br, I) containing common phosphoramidite ligands 1. The new complexes are chiral at the metal,
and were obtained with diastereomeric excesses between 73:27 and 90:10. The new iron complexes are
catalyst precursors in the oxidation of activated, benzylic methylene groups with t-BuOOH to give
exclusively the corresponding ketones in 31−80% isolated yields. This is the first application of iron

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Molecules 2010, 15
phosphoramidite complexes as catalyst precursors, and the work described herein sets the stage for
further catalytic applications of this class of complexes.
Acknowledgments
We thank the University of Missouri – St. Louis for support. Funding from the National Science
Foundation for the purchase of the Apex-II diffractometer (MRI, CHE-0420497), the purchase of the
NMR spectrometer (CHE-9974801) and the purchase of the mass spectrometer (CHE-9708640) is
acknowledged.
Supplementary Material
Supplementary data (experimental details and NMR data and NMR spectra for the catalysis
products in Table 3, NMR spectra of the complexes 4a and 4b and 5b, X-ray structure determination
of 4b) associated with this article can be found at http://www.mdpi.com/1420-3049/15/4/2631/S1.
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65. All efforts to obtain correct elemental analyses for 4a and 4b have failed thus far. The NMR
1
13
spectra of both compounds show baseline purity, and H and C NMR spectra are given in the
Supplementary material. After intensive drying, the product 2a contained still varying amounts of
CHCl3 as seen in the NMR. The calculated values for C28H23BrPFe(CHCl3)0.5 are C, 52.83; H,
3.66 and thus match the found values much closer.
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67. The peaks correspond to the most intense signal of the isotope envelope.
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possible. In the 13C-NMR for 4a, not all 13C-NMR signals for the minor diastereomer were
13
13
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the minor diastereomer.
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Sample Availability: Samples of the compounds 4a, 4b and 5b are available from the authors.
© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
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