Isomerization of Allylic Alcohols to Ketones Catalyzed by Well-Defined Iron PNP Pincer Catalysts

Article abstract of DOI:10.1002/chem.201705454

[Fe(PNP)(CO)HCl] (PNP=di-(2-diisopropylphosphanyl-ethyl)amine), activated in situ with KOtBu, is a highly active catalyst for the isomerization of allylic alcohols to ketones without an external hydrogen supply. High reaction rates were obtained at 80 °C, but the catalyst is also sufficiently active at room temperature with most substrates. The reaction follows a self-hydrogen-borrowing mechanism, as verified by DFT calculations. An alternative isomerization through alkene insertion and β-hydride elimination could be excluded on the basis of a much higher barrier. In alcoholic solvents, the ketone product is further reduced to the saturated alcohol.

Full text of DOI:10.1002/chem.201705454

A Journal of
Accepted Article
Title: Isomerization of Allylic Alcohols to Ketones Catalyzed by well-
defined Iron PNP Pincer Catalysts
Authors: Tian Xia, Zhihong Wei, Brian Spiegelberg, Haijun Jiao,
Sandra Hinze, and Johannes Gerardus de Vries
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201705454
Link to VoR: http://dx.doi.org/10.1002/chem.201705454
Supported by

10.1002/chem.201705454
Chemistry - A European Journal
FULL PAPER
Isomerization of Allylic Alcohols to Ketones Catalyzed by well-
defined Iron PNP Pincer Catalysts
Tian Xia+, Zhihong Wei+, Brian Spiegelberg, Haijun Jiao, Sandra Hinze and Johannes G. de Vries*
Abstract: Fe(PNP)(CO)HCl (PNP = di-(2-diisopropylphosphanyl-
ethyl)amine), activated in situ with KOtBu, is a highly active catalyst
for the isomerization of allylic alcohols to ketones without external
hydrogen supply. High rates were obtained at 80 °C but the catalyst
is also sufficiently active at room temperature with most substrates.
isomerization reaction of allylic alcohols was reported by
Corain,[7a, b] who utilized a combination of Ni(DPPB)2/HX (HX =
HCN, CF3COOH, CCl3COOH, and H2SO4) (Scheme 1b). Later,
similar acid activated nickel systems were described.[7e] Iron
carbonyl compounds were also employed successfully,
delivering acceptable yields and turnover frequencies (TOF, up
to 95 h-1).[8g] However, the major drawback of these iron carbonyl
complexes is the necessity to use UV light for their activation as
well as their toxicity. Hence, they cannot be used for large scale
production. Therefore, new low-cost iron-based catalysts that
are not toxic and do not need UV light are urgently needed. To
the best of our knowledge, there is only one report[10] on the use
of an ill-defined iron(II) compound for the isomerization of allylic
alcohols, which requires one equivalent of base and a trifluoro-
methyl moiety in the substrates. Herein, we report the first iso-
merization of non-activated allylic alcohols catalyzed by pincer
PNP-iron (II) complexes. A range of different substrates were
tested with these novel catalysts and high TOFs were achieved.
The reaction follows
a self-hydrogen-borrowing mechanism as
verified by DFT calculations. An alternative isomerization via alkene
insertion and beta-hydride elimination could be excluded on the
basis of the much higher barrier. In alcoholic solvents, the product
ketone is further reduced to the saturated alcohol.
Introduction
The catalytic isomerization of allylic alcohols to carbonyl
compounds, such as ketones and aldehydes, is 100% atom
economic and has been widely used in organic synthesis. Unlike
the classic two-step oxidation-reduction sequence or the reverse,
the isomerization reaction is green, efficient and clean as well as
environmentally sustainable and proceeds in one-step without
producing any by-products and without requiring toxic
reagents.[1] Various noble transition metal complexes, based on
iridium,[2] palladium,[3] rhodium,[4] and ruthenium,[5],[6] are known
to catalyze the isomerization of allylic alcohols in very high yields
and with excellent turnover numbers (Scheme 1a).
H
H
H
H
N
N
N
N
i
i
i
i
i
i
i
i
r
r
P
e
F
r
2P
)
P P
r
P
r
r
P
r
P
e
F
r
e
F
e
F
2P
)
P P
2P
)
P P
2P
)
P P
( )2
(
(
)2
(
(
)2
(
(
)2
(
H
r
B
r
Cl
HBH3
C
l
B
H
C
l
CO
CO
CO
CO
A
B
C
D
Scheme 2. PNP-Iron complexes (A-D) applied in the isomerization of non-
activated allylic alcohols in this work
noble transition-metal
suitable for the isomerization of
Ph
alcohols
allylic
a) Typical
complexes
Cl
Cl
Ru
N
P
source
+
BINAP
Rh
P
P
Results and Discussion
Ru
Cl
Ru
Cl
Pd
Ir
Ph3P
Cl
Me
Cl
(COD)
PPh3
Nolan[6j]
Lautens[4k]
Zhang[4l]
In recent years, pincer-ligated iron complexes have been used
for hydrogenation reactions.[11] The groups of Schneider,[11g]
Guan[12] and Beller[13] independently reported the synthesis of
iron compound A (Scheme 2) which is a decent catalyst for the
hydrogenation of esters,[12-14] nitriles[15] and heterocycles.[16]
Intrigued by this, we assumed that this and similar iron catalysts
might also be suitable for isomerization reactions and tested
them in the isomerization of oct-1-en-3-ol (1) to 3-octanone (2).
Initial tests were performed in isopropanol at 80 °C (Table 1, full
screening of catalysts in the supporting information). Traces of
product were formed in the presence of catalyst A (Entry 1). It is
known that bases play an important role in catalyst activation.
Indeed, adding 2 mol% of potassium tert-butoxide resulted in
90% conversion, albeit with low selectivity to the desired product
(Entry 2). Catalysts B and C turned out to be inactive even at
Mazet[1h]
b) Typical
Mazet[3b]
Cadierno[5f]
earth abundant
suitable for the isomerization of
alcohols
allylic
complexes
+
Ni2
HCN
Fe
HCo
(CO)
4
(CN)
2
(DPPB)
(CO)
5
3
Corain[7a]
Emerson[8a]
Goetz[9]
Scheme 1. Transition-metal complexes for the isomerization of allylic alcohols
The development of catalysts based on earth abundant metals
like nickel[7], iron[8], or cobalt[9] for isomerization reactions is an
emerging research area. The first example of a nickel catalyzed
[*]
T. Xia+, Z. Wei+, B. Spiegelberg, Dr. H. Jiao, Dr. S. Hinze and Prof.
Dr. J. G. de Vries.
Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-
Einstein-Strasse 29a, 18059 Rostock (Germany)
E-mail: johannes.devries@catalysis.de
t
catalyst loadings of 2 mol% and addition of 4 mol% BuOK
(Entries 3 and 4). Under the same conditions catalyst D gave full
conversion, yet again with poor selectivity towards the desired
ketone 2 (Entry 5). Reducing the amount of catalyst and reaction
[+]
These authors contributed equally to this work.
Supporting information for this article is given via a link at the end of
the document
This article is protected by copyright. All rights reserved.

10.1002/chem.201705454
Chemistry - A European Journal
FULL PAPER
Table 1. Catalyst screening in allyl alcohol isomerization [a]
Taking efficiency, toxicity and price into account, either toluene
or THF can be used as solvent and potassium tert-butoxide was
selected as base in all further experiments (further screening
experiments can be found in the Supporting Information). Under
the optimized conditions (Entry 5), we measured the conversion
OH
O
OH
3
1
cat.
mol%
+
C5H11
2 mL i
C5H11
C5H11
80 °C
PrOH,
1
2
of 1, taking samples every
Information); full conversion was achieved in 20 minutes at room
temperature as well as in 6 minutes at 80 °C (Figure 1).
2 minutes (See Supporting
Entry
Cat.
Time [h]
Conv. 1 [%][b]
2 [%][b]
3 [%][b]
1
A
A
B
C
D
D
D
15
15
24
24
24
24
3
trace
90
0
trace
28
0
trace
60
0
2[c]
3[d]
4[d]
5[d]
6[c]
7[c]
0
0
0
99
99
100
9
90
88
84
11
15
[a] 1 mmol substrate. [b] Determined by GC with dodecane as internal stan-
dard. [c] 2 mol% of tBuOK. [d] 2 mol% catalyst, 4 mol% tBuOK. [e] 1 mol% of
tBuOK w.r.t. to substrate.
time did not change this output significantly (Entries 6 and 7).
This preliminary investigation showed that catalyst D was
unsurpassed for good conversion. In addition, this compound is
stable for at least 6 months in the glovebox.
Next, the effect of solvent and base on the reaction selectivity
was investigated. Utilization of ethanol resulted in lower
conversion and yield (Table 2, Entries 1 and 2). THF is a
commonly used solvent in isomerization reactions and delivered
high conversion as well as high selectivity towards the desired
ketone 2 (Entry 3). Full conversion was also observed using
toluene and benzene as solvent (Entries 4-6, respectively). In
contrast, use of acetonitrile resulted in low conversion and
selectivity (Entry 7). A limited number of other bases were also
screened. Compared to potassium tert-butoxide, sodium and
lithium tert-butoxide resulted in lower conversion and selectivity
(Entries 8 and 9). No conversion was obtained with potassium
carbonate (Entry 10).
Figure 1. Monitoring the isomerization reaction over time: 1 mmol oct-1-en-3-
ol, 1 mol% catalyst D, 1 mol% of tBuOK, 1 mL D-toluene, monitored by 1H-
NMR. Data given are averaged conversions of three reactions.
In order to explore the mechanism of the isomerization reaction,
we synthesized the amido complex E (Scheme 3) according to
the protocol reported by Jones[16] and Schneider,[17] starting from
t
iron complex D (Scheme 2) by deprotonation with BuOK. When
complex E was applied to the isomerization of 1, the desired
ketone (2) was obtained in 99% yield.
Table 2. Solvent and base screening in allylic alcohol isomerization.[a]
D
cat.
1
mol%
mol%
OH
O
OH
1
base
+
C5H11
Entry
C5H11
C5H11
1 mL solvent
80
1 h
1
°C,
3
2
Scheme 3. Experiments with presumed catalytically active species E
Base
Solvent
Conv. 1 [%][b]
2 [%][b]
3 [%][b]
1[c]
2[c]
3[c]
4[c]
5
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuONa
tBuOLi
Na2CO3
iPrOH
EtOH
100
60
15
31
96
99
98
99
33
79
39
0
84
29
2
To test the scope and limitations of this catalyst system a range
of substituted allylic alcohols bearing an aromatic (Scheme 4,
2a-2l) or an aliphatic (2m-2n) substituent R2 was tested under
the optimized reaction conditions (Table 2, Entry 6). Excellent
yields of the ketones were obtained with substrates containing
electron-donating and electron-withdrawing groups on the
aromatic ring (2a to 2e). Substrate 1f bearing a naphthyl
substituent also led to outstanding results (2f). The heterocyclic
furanyl and thienyl substituted substrates were converted to the
corresponding ketones 2g and 2h with satisfying isolated yields.
Substituents (R1) on the C=C double bond had no detrimental
effect on the conversion. Smooth conversion of 1k to 2k shows
that a benzylic alcohol is not a prerequisite for this isomerization.
Interestingly, homo-allylic alcohol 1l was also isomerized to the
THF
98
Toluene
Toluene
Benzene
CH3CN
THF
100
100
100
33
1
2
6
trace
0
7
d]
8[
85
5
9[d]
THF
43
3
10
Toluene
0
0
[a] 1 mmol substrate. [b] Determined by GC with dodecane as internal stan-
dard. [c] Reaction time 3 hours. [d] Reaction time 1.5 hours. [e] Isolated yield
under neat conditions on 10 mmol scale for 2 hours.
This article is protected by copyright. All rights reserved.

10.1002/chem.201705454
Chemistry - A European Journal
FULL PAPER
as
source
hydrogen
transfer
alcohol
external
O
hydrogenation using
O
desired ketone 2l. The protocol was also applied successfully to
aliphatic allylic alcohols (2m to 2o). Aliphatic substrate 2m with
an internal double bond was also isomerized in good yield. The
isomerization can also be performed at room temperature
resulting in high yields within two hours (2e, 2g, 2h, 2i, 2k, 2n),
as well as under neat conditions at 80 °C for two hours (2o). The
cyclic allylic alcohol 1-cyclohexene-1-yl-ethanol was converted
to (2p) in 61% yield. Interestingly, trans-sobrerol only underwent
dehydrogenation to form the unsaturated ketone (2q), which is
presumably caused by the steric hindrance of the extra methyl
group, which hinders the alkene hydrogenation.
OH
OH
R
R
R
R
3
1
4
2
self-transfer
isomerization
hydrogenation
Scheme 5. Proposed reaction routes
To gain a better mechanistic understanding, B3PW91 DFT
computations were performed. The applicability of the B3PW91
functional was validated intensively and extensively.[18] In our
previous work we have done intensive and extensive testing and
benchmarking of different methods with and without solvation
effect and dispersion as well as intensive comparisons with the
available experimental data and computational data for different
transition metal PNP type complexes (M = Fe, Ru, Os, Ir, Mn,
Mo and W).[19] On the basis of these tests and comparisons, we
find full agreement between theory and experiment, which
validates the B3PW91 gas phase calculation as reasonable. All
computational details are given in the Supporting Information.
In view of the need for a strong base for complex D to function
as catalyst as well as the catalytic activity of complex E without
strong base, we first computed the self-transfer hydrogenation
isomerization of 1 to 2 based on an outer-sphere mechanism
without external hydrogen source, starting from complex E as
shown in Scheme 6. The full potential energy surface is shown
in Scheme 7.
Scheme 4. Substrate scope of iron-catalyzed allylic alcohol isomerization[a]
OH
O
+
1
cat.
D
1
tBuOK
mol%
mol%
R1
O
R2
R1
1 mL
80
1 h
°C,
R2
toluene,
1a-q
2a-q
O
O
O
O
O
O
Br
2e
[b]
2a
2f
2b
2c
2d
(99%)
(96%) (81%
O
)
(98%)
(97%)
(98%)
O
O
O
O
S
[b]
[b]
[b]
2i
2h
2g
(96%) (94%
O
)
(72%) (79%
O
)
(98%)
O
(78%) (72%
O
)
[c]
2m
[b]
O
2l
2k
(97%
OH
)
2j
(99%)
(88%)
O
(87%) (67%
)
TON=750
O
O
OH
O
OH
[b]
)
[d]
[e]
[e]
)
2n
2o
(98%) (67%
N
E
E
2p
2q
(36%
(75%
)
(61%
)
Fe
R
R
R
CO
2a
2
[1,4]
[1,2]
1
[a] 1 mmol substrate, isolated yields, bold blue bond is the position of the
original C=C bond in the substrates. [b] Room temperature, 2h [c]
H
t
=
E
Substrate is a mixture of cis and trans. [d] Neat conditions on 10 mmol scale,
0.1 mol% catalyst, t = 2 h. [e] t = 16 h, 5 mol% catalyst D, 5 mol% tBuOK.
[H]
H
H
OH
N
E
O
O4
Fe
R
1
E
CO
3
These results show two interesting mechanistic aspects. As
shown in Scheme 5, the first one is the isomerization for which
we propose a mechanism via self-transfer hydrogenation, where
allylic alcohol 1 will be first dehydrogenated into α,β-unsaturated
ketone 4, which can be further hydrogenated into ketone 2; and
this can be seen for the reactions in benzene or toluene solution
(Table 2, entries 4-6) and the major product is the isomerized
ketone 2. The second one is the transfer hydrogenation using
alcohols such as ethanol or isopropanol as solvent and
hydrogen source, where allyl alcohol 1 will be either directly
transfer hydrogenated into the saturated alcohol 3 as the major
product (Table 1, entries 5 and 6; as well as Table 2, entry 1); or
the isomerized ketone 2 is reduced via transfer hydrogenation to
the alcohol 3. The formation of ketone 2 as minor product in
these reactions in alcohols indicates that both self-transfer
hydrogenation isomerization and transfer hydrogenation using
alcohol as hydrogen source might occur simultaneously on the
basis of the kinetic and thermodynamic properties.
R
R
3
2
H
4
4
F
Scheme 6. Proposed mechanism (R = C5H11, E = P(iPr)2)
Without external hydrogen supply, the first step is the
dehydrogenation of 1 to 4 by complex E. Here the first step is
hydride transfer from the alcohol to Fe. It is found that the
transition state corresponding to hydride transfer has a Gibbs
free energy barrier of 92.1 kJ/mol and the reaction is endergonic
by 5.0 kJ/mol. As hydride transfer was proven to be the rate-
determining step for C=O bond hydrogenation on Fe as well as
on Mn and d5-, d6- metal PNP pincer complexes,[19c,
we
20]
assume that the energy barrier of dehydrogenation of 1 to 4 is
determined by the hydride transfer. Although great efforts have
been made, the transition state corresponding to proton transfer
as well as the PNHP-Fe+−RCH(O−)CH=CH2 intermediate could
not be located and all attempts to optimize such structures
resulted in reactant or transition state of hydride transfer.
This article is protected by copyright. All rights reserved.

10.1002/chem.201705454
Chemistry - A European Journal
FULL PAPER
The next step is the hydrogenation of the C=C bond from the
newly formed 4 to 2 by complex F via either 1,2-addition directly
to 2 or via 1,4-addition to form the enol 2a, which can
tautomerize into 2. For the 1,2-addition, we found a stepwise
mechanism; i.e.; the first step passes through the transition state
for Fe−H transfer to C1, by breaking the Fe−H bond and forming
the C-H bond, leading to an intermediate. The second step
passes through the transition state of N−H transfer to C2 by
breaking the N−H bond and forming the terminal C1−H bond. For
the 1,2-addition, the free energy barrier of the Fe−H hydride
transfer is 60.5 kJ/mol, the intermediate is endergonic by 18.7
kJ/mol, and the N−H proton transfer has a free energy barrier of
26.5 kJ/mol. This hydrogenation step is exergonic by 95.7
kJ/mol.
transfer to the C1 by breaking the Fe−H bond and forming the
C−H bond, leading to an intermediate. The second step passes
through the transition state of N−H transfer to the O4 by breaking
the N−H bond and forming the terminal O−H bond. From the
starting point for 1,4-addition, the free energy barrier of the Fe−H
hydride transfer is 57.3 kJ/mol, the intermediate is endergonic by
12.5 kJ/mol, and the N−H proton transfer has a free energy
barrier of 15.6 kJ/mol. This hydrogenation step is exergonic by
48.8 kJ/mol. The tautomerization from 2a to 2 is exergonic by
46.9 kJ/mol. The overall isomerization from 1 to 2 is exergonic
by 90.7 kJ/mol. This indicates that 1,4-addition is slightly more
favored kinetically than 1,2-addition by 3.2 kJ/mol; and this small
energy difference shows that both the 1,2- and 1,4-routes are
competitive and possible.
For the 1,4-addition, we also found a stepwise mechanism; i.e.;
the first step passes through the transition state for Fe−H
Scheme 7. Reaction profile for the isomerization of 1 to 2 (R1 = C5H11, E = P(iPr)2)
This shows that the hydrogenation of 4 to product 2 is more
favored kinetically (57.3 vs. 92.1 kJ/mol) and thermodynamically
(-95.7 vs. 5.0 kJ/mol) than the dehydrogenation of 1 to 4.
Therefore, 4 once formed, can be easily converted to 2.
complex F after the dehydrogenation of another one equivalent
1 into 4. We found that he hydrogenation of 2 to 3 by complex F
also is a one-step process. The computed barrier is 106.4
kJ/mol and the reaction is exergonic by 11.8 kJ/mol.
In addition, we computed the competitive hydrogenation of 1 to 3
by using complex F after the dehydrogenation of one equivalent
1 into 4. The hydrogenation of 1 to 3 proceeds via a one-step
mechanism mainly corresponding to the hydride transfer and is
exergonic by 102.5 kJ/mol and the barrier is 113.9 kJ/mol,
indicating that the isolated C=C double bond hydrogenation of 1
is less competitive kinetically than the conjugated C=C double
bond hydrogenation of 4 by 56.6 kJ/mol. Furthermore, we also
computed the consecutive hydrogenation of 2 to 3 by using
These calculations reveal that 2 is the principal and preferred
product. Without external hydrogen supply, the hydrogenation of
1 to 3 as well as 2 to 3 by using complex F are not competitive
kinetically. This agrees perfectly with the results in Table 2,
entries 4-6. Indeed, the dehydrogenation and hydrogenation
mechanism is supported by the results obtained in the attempted
isomerization of Sobrerol (1q in Scheme 4), where only the
dehydrogenation product 2q is found. This two-step mechanism
can also explain the isomerization of the homo-allyl alcohol 1l
This article is protected by copyright. All rights reserved.

10.1002/chem.201705454
Chemistry - A European Journal
FULL PAPER
into the corresponding ketone 2l (Scheme 4), where alcohol
dehydrogenation takes place at first, followed by the consecutive
C=C bond hydrogenation. The alternative mechanism by which
the double bond isomerizes first into the conjugated position was
deemed less likely in view of the high barrier for the hydride
transfer to the methyl-substituted enone
For testing the stability of the catalysts, we computed the
dehydrogenation or hydrogen elimination from complex F to
complex E (F = E + H2), which has Gibbs free energy barrier of
80.4 kJ/mol, and is slightly exergonic by 2.4 kJ/mol (Scheme 8).
Compared with the lower barrier (57.3 kJ/mol) of the facial
hydrogenation of 4 to 2a, complex F is stable under the reaction
source (Scheme 8), the effective barrier of the hydrogenation of
ketone 2 to alcohol 3 is 119.1 kJ/mol and the total reaction is
slightly endergonic by 0.9 kJ/mol. This energetic difference
should determine the observed selectivity (Table 2, entry 1).
Indeed, the computed ratio between 2 and 3 using isopropanol
as hydrogen source [isopropanol + 2 = acetone + 3] is 10 to 90
(determined by the equilibrium constant and the concentrations
of isopropanol and substrate, Supporting information S4), in
perfect agreement with the experimentally observed 9 to 90 after
24 hours (Table 1, entry 5). This shows that large excess of
isopropanol can shift the reaction towards to the saturated
product of 3 under the thermodynamically equilibrated state.
Our computations show that without external hydrogen supply,
the reaction of allyl alcohol 1 takes place via the self-transfer
hydrogenation isomerization mechanism via the α,β-unsaturated
ketone 4 as intermediate; and the principal product should be
the ketone 2. This is indeed observed for the reaction in
benzene or toluene. Using isopropanol as external hydrogen
source, the same reaction mechanism can be proposed,
however, the formed ketone 2 can be partially hydrogenated into
the saturated alcohol on the basis of their thermodynamic
properties.
condition. Consequently, once
F is formed, it will easily
hydrogenate 4 to 2 rather than eliminate H2. Since there is no
external hydrogen supply, the H2 assisted proton transfer
mechanism proposed by Dub and Gordon can be excluded in
this work.[21]
For comparison we computed the transfer hydrogenation using
isopropanol as external hydrogen source. As shown in Scheme
8, isopropanol dehydrogenation into acetone has Gibbs free
energy barrier of 102.7 kJ/mol and is endergonic by 12.7 kJ/mol.
This indicates that the dehydrogenation of allyl alcohol is more
favored kinetically (92.1 kJ/mol) and thermodynamically (5.0
kJ/mol) and allyl alcohol should be dehydrogenated at first,
although isopropanol dehydrogenation is also possible.
Using isopropanol as external hydrogen source [E + isopropanol
+ 1 = E + acetone + 3], the effective barrier of direct
hydrogenation of allyl alcohol 1 into alcohol 3 is 126.6 kJ/mol,
which is higher than the barrier (92.1 kJ/mol) of allyl alcohol
dehydrogenation into the α,β-unsaturated ketone 4 as well as
the successive hydrogenation barrier (57.3 kJ/mol) of 4 into 2a.
Therefore, direct allyl alcohol hydrogenation into 3 is kinetically
hindered, and the first step should be self-transfer hydrogenation
isomerization of allyl alcohol 1 into ketone 2; and isopropanol in
this step plays only the role of solvent.
Despite this perfect agreement between theory and experiment,
we are also interested to exclude the possibility of an
isomerization mechanism via alkene insertion using amido
complex E (Scheme 9) In this mechanism, the first step should
be the insertion of the C=C double bond of the alkene into the
Fe-H bond resulting in the formation of the alkyl complex; and
the second step should be β-hydride elimination resulting in the
formation of isomerized alkene.
CO
N
E
E
Fe
H
OH
R1
a
CH
β
CO
Fe
C
OH
E
H3C
N
E
H
C
C
H
H
R1
β−
TS(
elimination)
[149.0]
CH3
217.8
O
C
H
CH2
H
CH3
H
N
TS(alkene insertion)
162.4
H
N
H
[96.2]
E
Fe
H
E
E
CO
Fe
H
E
CO
109.4
[46.3]
TS(iPrOH)
102.7
E-Ca
H(CH3)CβH(OH)R1
TS(H2)
93.1
[41.6]
[90.2]
N
E
Fe
a
OH
CO
E
CH
R1
H3C
Cβ
OH
80.4
OH
R1
H
0.0
[0.0]
+
E
1
R1
12.7
10.3
[8.6]
[10.6]
0.0
[0.0]
−
−
41.7]
43.8
F
+
[
E
H2
+
E
iPrOH
+
CH3COCH3
+
CH3COCH3
+
E
2a
Scheme 8. Potential energy surface of iPrOH dehydrogenation by E as well as
H2 elimination from F (E = P(iPr)2).
Scheme 9. Reaction profile for isomerization of 1 to 2 via insertion of the
alkene mechanism (R1 = C5H11, E = P(iPr)2)
Next we considered the transfer hydrogenation of ketone 2 to
alcohol 3 using isopropanol as solvent and hydrogen source [E +
isopropanol + 2 = E + acetone + 3]. On the basis of the potential
energy surfaces (Scheme 7) and isopropanol as hydrogen
As shown in Scheme 9, the insertion of the Fe-H bond into the
C=C double bon of allyl alcohol 1 has Gibbs free energy barrier
of 162.4 kJ/mol and the formation of the alkyl intermediate is
highly endergonic by 109.4 kJ/mol. The subsequent following β-
This article is protected by copyright. All rights reserved.

10.1002/chem.201705454
Chemistry - A European Journal
FULL PAPER
103, 27-52; c) V. Cadierno, P. Crochet, J. Gimeno, Synlett 2008, 1105-
1124; d) L. Mantilli, C. Mazet, Chem. Lett. 2011, 40, 341-344; e) N.
Ahlsten, A. Bartoszewicz, B. Martin-Matute, Dalton Trans. 2012, 41,
1660-1670; f) P. Lorenzo-Luis, A. Romerosa, M. Serrano-Ruiz, ACS
Catal. 2012, 2, 1079-1086; g) D. Cahard, S. Gaillard, J.-L. Renaud,
Tetrahedron Lett. 2015, 56, 6159-6169; h) H. Li, C. Mazet, Acc. Chem.
Res. 2016, 49, 1232-1241.
H elimination has Gibbs free energy barrier of 108.4 kJ/mol and
the 2 formation is exergonic by 200.1 kJ/mol. The overall
isomerization from 1 to 2 has an effective Gibbs free energy
barrier of 217.8 kJ/mol, which barrier is much higher than that
(92.1 kJ/mol) of allyl alcohol 1 dehydrogenation as well as that
(102.7 kJ/mol) of isopropanol dehydrogenation. This indicates
that this alkene insertion mechanism is kinetically much
hindered and can be discarded accordingly.
[2]
a) L. Mantilli, C. Mazet, Tetrahedron Lett. 2009, 50, 4141-4144; b) L.
Mantilli, D. Gerard, S. Torche, C. Besnard, C. Mazet, Chem. Eur. J.
2010, 16, 12736-12745; c) L. Mantilli, C. Mazet, Chem. Commun.
(Cambridge, U. K.) 2010, 46, 445-447; d) J.-Q. Li, B. Peters, P. G.
Andersson, Chem. Eur. J. 2011, 17, 11143-11145; e) L. Mantchemilli, D.
Gerard, C. Besnard, C. Mazet, Eur. J. Inorg. Chem. 2012, 2012, 3320-
3330; f) H. Li, C. Mazet, Org. Lett. 2013, 15, 6170-6173; g) H. Horváth,
Á. Kathó, A. Udvardy, G. Papp, D. Szikszai, F. Joó, Organometallics
2014, 33, 6330-6340; h) H. Li, C. Mazet, J. Am. Chem. Soc. 2015, 137,
10720-10727; i) E. M. Titova, S. W. Rahaman, E. S. Shubina, R. Poli, N.
V. Belkova, E. Manoury, J. Mol. Catal. A: Chem. 2016.
Conclusions
In our study, we have found that in the presence of strong base
and without external hydrogen supply, the iron-pincer complex
Fe(PNP)(CO)HCl is an excellent catalyst for the isomerization of
allylic and homo-allylic alcohols to the corresponding ketones.
Both aliphatic and aromatic allylic alcohols are suitable
substrates. The aromatic substrates may possess electron-
withdrawing or electron-donating substituents, in all possible
positions of the phenyl ring. A two-step self-hydrogen-borrowing
mechanism via a dehydrogenation-hydrogenation isomerization
is proposed and was verified by DFT computation. Indeed, this
two-step mechanism is also applicable for reactions using
alcohol as external hydrogen source, where the isomerized
ketones can be further hydrogenated into the corresponding
alcohols. The alternative isomerization mechanism via alkene
insertion into the iron-hydride bond followed by beta-hydride
elimination can be discarded on the basis of the much higher
barrier.
[3]
[4]
a) K. Voronova, M. Purgel, A. Udvardy, A. C. Bényei, A. g. Kathó, F.
Joó, Organometallics 2013, 32, 4391-4401; b) E. Larionov, L. Lin, L.
Guenee, C. Mazet, J. Am. Chem. Soc. 2014, 136, 16882-16894; c) L.
Lin, C. Romano, C. Mazet, J. Am. Chem. Soc. 2016, 138, 10344-10350.
a) W. Strohmeier, L. Weigelt, J. Organomet. Chem. 1975, 86, C17-C19;
b) H. Alper, K. Hachem, J. Org. Chem. 1980, 45, 2269-2270; c) S. H.
Bergens, B. Bosnich, J. Am. Chem. Soc. 1991, 113, 958-967; d) C. de
Bellefon, S. Caravieilhes, É. G. Kuntz, C. R. Acad. Sci.,-Ser. IIC: Chim.
2000, 3, 607-614; e) C. de Bellefon, N. Tanchoux, S. Caravieilhes, P.
Grenouillet, V. Hessel, Angew. Chem. Int. Ed. 2000, 39, 3442-3445; f)
C. Bianchini, A. Meli, W. Oberhauser, New J. Chem. 2001, 25, 11-12;
g) D.-Y. Lee, C. W. Moon, C.-H. Jun, J. Org. Chem. 2002, 67, 3945-
3948; h) D. H. Leung, R. G. Bergman, K. N. Raymond, J. Am. Chem.
Soc. 2007, 129, 2746-2747; i) E. G. Corkum, S. Kalapugama, M. J.
Hass, S. H. Bergens, RSC Advances 2012, 2, 3473-3476; j) A. B.
Gómez, P. Holmberg, J.-E. Bäckvall, B. Martín-Matute, RSC Advances
2014, 4, 39519-39522; k) S. Kress, T. Johnson, F. Weisshar, M.
Lautens, ACS Catal. 2015, 6, 747-750; l) K. Ren, M. Zhao, B. Hu, B. Lu,
X. Xie, V. Ratovelomanana-Vidal, Z. Zhang, J. Org. Chem. 2015, 80,
12572-12579.
Experimental Section
An oven dried 4 mL pressure tube with a stirring bar was charged with
PNPFeXY(CO) (4.5 mg, 0.01 mmol, 1 mol%) and a 0.01 M solution of
base in toluene (1.2 mg, 0.01 mmol, 1 mol%) was added sequentially.
Then 1 mmol of substrate was added immediately to the pressure tube.
[5]
a) Y. Sasson, G. L. Rempel, Tetrahedron Lett. 1974, 15, 3221-3224; b)
W. Smadja, G. Ville, C. Georgoulis, J. Chem. Soc., Chem. Commun.
1980, 594-595; c) B. M. Trost, R. J. Kulawiec, Tetrahedron Lett. 1991,
32, 3039-3042; d) J.-E. Bäckvall, U. Andreasson, Tetrahedron Lett.
1993, 34, 5459-5462; e) B. M. Trost, R. J. Kulawiec, J. Am. Chem. Soc.
1993, 115, 2027-2036; f) I. E. Markó, A. Gautier, M. Tsukazaki, A.
Llobet, E. Plantalech‐Mir, C. J. Urch, S. M. Brown, Angew. Chem. Int.
Ed. 1999, 38, 1960-1962; g) C. Slugovc, E. Rüba, R. Schmid, K.
Kirchner, Organometallics 1999, 18, 4230-4233; h) R. C. van der Drift,
M. Vailati, E. Bouwman, E. Drent, J. Mol. Catal. A: Chem. 2000, 159,
163-177; i) M. K. Gurjar, P. Yakambram, Tetrahedron Lett. 2001, 42,
3633-3636; j) R. Uma, M. K. Davies, C. Crévisy, R. Grée, Eur. J. Org.
Chem. 2001, 2001, 3141-3146; k) V. Cadierno, P. Crochet, S. E.
García-Garrido, J. Gimeno, Dalton Trans. 2004, 3635-3641; l) M. Ito, S.
Kitahara, T. Ikariya, J. Am. Chem. Soc. 2005, 127, 6172-6173; m) B.
Martín‐Matute, K. Bogár, M. Edin, F. B. Kaynak, J. E. Bäckvall, Chem.
Eur. J. 2005, 11, 5832-5842; n) V. Cadierno, S. E. García-Garrido, J.
Gimeno, A. Varela-Álvarez, J. A. Sordo, J. Am. Chem. Soc. 2006, 128,
1360-1370; o) A. E. Díaz ‐ Álvarez, P. Crochet, M. Zablocka, C.
Duhayon, V. Cadierno, J. Gimeno, J. P. Majoral, Adv. Synth. Catal.
2006, 348, 1671-1679; p) A. Bouziane, B. Carboni, C. Bruneau, F.
Carreaux, J.-L. Renaud, Tetrahedron 2008, 64, 11745-11750; q) T.
Campos-Malpartida, M. Fekete, F. Joo, A. Katho, A. Romerosa, M.
Saoud, W. Wojtków, J. Organomet. Chem. 2008, 693, 468-474; r) V.
Cadierno, P. Crochet, J. Francos, S. E. García-Garrido, J. Gimeno, N.
Nebra, Green Chem. 2009, 11, 1992-2000; s) A. Azua, S. Sanz, E.
Peris, Organometallics 2010, 29, 3661-3664; t) M. Batuecas, M. A.
°
The solution was stirred for 1 hour at 80 C. GC yields were determined
with dodecane as internal standard. Isolated yields were obtained by
using silica gel chromatography (Cyclohexane: Ethyl Acetate= 50:1) after
rotary evaporation. For the neat reaction, base was added together with
PNPFeHCl(CO).
Acknowledgements
Tian Xia is grateful for the financial support of the Chinese
Scholarship Council (CSC). This work was also supported by the
state of Mecklenburg-Vorpommern and the Leibniz Foundation
(Leibniz Competition, SAW-2016-LIKAT-1). We thank Pim
Puylaert for the synthesis of a substrate.
Keywords: Isomerization • Ketone •Allylic Alcohol • Iron catalyst
• Pincer ligand • DFT
[1]
a) R. C. van der Drift, E. Bouwman, E. Drent, J. Organomet. Chem.
2002, 650, 1-24; b) R. Uma, C. Crévisy, R. Grée, Chem. Rev. 2003,
This article is protected by copyright. All rights reserved.

10.1002/chem.201705454
Chemistry - A European Journal
FULL PAPER
Esteruelas, C. García-Yebra, E. Oñate, Organometallics 2010, 29,
[11] a) P. Bhattacharya, H. Guan, Comments Inorg. Chem. 2011, 32, 88-
112; b) R. Langer, Y. Diskin-Posner, G. Leitus, L. J. W. Shimon, Y.
Ben-David, D. Milstein, Angew. Chem. Int. Ed. 2011, 50, 9948-9952; c)
R. Langer, G. Leitus, Y. Ben-David, D. Milstein, Angew. Chem. Int. Ed.
2011, 50, 2120-2124; d) R. Langer, M. A. Iron, L. Konstantinovski, Y.
Diskin-Posner, G. Leitus, Y. Ben-David, D. Milstein, Chem. Eur. J. 2012,
18, 7196-7209; e) P. Dupau, M.-L. Tran Do, S. Gaillard, J.-L. Renaud,
Angew. Chem. Int. Ed. 2014, 53, 13004-13006; f) N. Gorgas, B. Stöger,
L. F. Veiros, E. Pittenauer, G. Allmaier, K. Kirchner, Organometallics
2014, 33, 6905-6914; g) I. Koehne, T. J. Schmeier, E. A. Bielinski, C. J.
Pan, P. O. Lagaditis, W. H. Bernskoetter, M. K. Takase, C. Würtele, N.
Hazari, S. Schneider, Inorg. Chem. 2014, 53, 2133-2143; h) P. O.
Lagaditis, P. E. Sues, J. F. Sonnenberg, K. Y. Wan, A. J. Lough, R. H.
Morris, J. Am. Chem. Soc. 2014, 136, 1367-1380; i) T. Zell, Y. Ben-
David, D. Milstein, Angew. Chem. Int. Ed. 2014, 53, 4685-4689.
[12] S. Chakraborty, H. Dai, P. Bhattacharya, N. T. Fairweather, M. S.
Gibson, J. A. Krause, H. Guan, J. Am. Chem. Soc. 2014, 136, 7869-
7872.
2166-2175.
[6]
a) C. J. Brown, G. M. Miller, M. W. Johnson, R. G. Bergman, K. N.
Raymond, J. Am. Chem. Soc. 2011, 133, 11964-11966; b) J. García-
Álvarez, J. Gimeno, F. J. Suárez, Organometallics 2011, 30, 2893-
2896; c) L. Bellarosa, J. Díez, J. Gimeno, A. Lledós, F. J. Suárez, G.
Ujaque, C. Vicent, Chem. Eur. J. 2012, 18, 7749-7765; d) V. Bizet, X.
Pannecoucke, J.-L. Renaud, D. Cahard, Angew. Chem. Int. Ed. 2012,
51, 6467-6470; e) J. Díez, J. Gimeno, A. Lledos, F. J. Suárez, C.
Vicent, ACS Catal. 2012, 2, 2087-2099; f) R. o. Garcıa-Álvarez, F. J.
́
Suárez, J. Dıez, P. Crochet, V. Cadierno, A. Antiñolo, R. Fernández-
́
Galán, F. Carrillo-Hermosilla, Organometallics 2012, 31, 8301-8311; g)
C. R. Larsen, D. B. Grotjahn, J. Am. Chem. Soc. 2012, 134, 10357-
10360; h) J. Schulz, I. Císařová, P. Štěpnička, Eur. J. Inorg. Chem.
2012, 2012, 5000-5010; i) L. Menéndez-Rodríguez, P. Crochet, V.
Cadierno, J. Mol. Catal. A: Chem. 2013, 366, 390-399; j) M. Kechaou-
Perrot, L. Vendier, S. p. Bastin, J.-M. Sotiropoulos, K. Miqueu, L. a.
Menéndez-Rodríguez, P. Crochet, V. Cadierno, A. Igau,
Organometallics 2014, 33, 6294-6297; k) S. Manzini, A. Poater, D. J.
Nelson, L. Cavallo, S. P. Nolan, Chem. Sci. 2014, 5, 180-188; l) F. J.
Suáreza, C. Vidala, J. García-Álvareza, Curr. Green Chem. 2014, 1; m)
C. Vidal, F. J. Suárez, J. García-Álvarez, Catal. Commun. 2014, 44, 76-
79; n) E. Bolyog-Nagy, A. Udvardy, Á. Barczáné-Bertók, F. Joó, Á.
Kathó, Inorg. Chim. Acta 2017, 455, 514-520.
[13] S. Werkmeister, K. Junge, B. Wendt, E. Alberico, H. Jiao, W. Baumann,
H. Junge, F. Gallou, M. Beller, Angew. Chem., Int. Ed. 2014, 53, 8722-
8726.
[14] S. Elangovan, B. Wendt, C. Topf, S. Bachmann, M. Scalone, A.
Spannenberg, H. Jiao, W. Baumann, K. Junge, M. Beller, Adv. Synth.
Catal. 2016, 358, 820-825.
[7]
[8]
a) B. Corain, Gazz. Chim. Ital. 1972, 102, 687-695; b) B. Corain, G.
Puosi, J. Catal. 1973, 30, 403-408; c) C. F. Lochow, R. G. Miller, J. Org.
Chem. 1976, 41, 3020-3022; d) E. Kuntz, Societe Rhodanienne de
Transactions Immobiliaires, Fr. . 1997, p. 25 pp; e) H. Bricout, E.
Monflier, J.-F. Carpentier, A. Mortreux, Eur. J. Inorg. Chem. 1998, 1998,
1739-1744; f) E. Kuntz, G. Godard, J. Basset, O. Vittori, Oil & Gas
Science and Technology-Revue de l'IFP 2007, 62, 781-785.
[15] C. Bornschein, S. Werkmeister, B. Wendt, H. Jiao, E. Alberico, W.
Baumann, H. Junge, K. Junge, M. Beller, Nat. Commun. 2014, 5, 4111.
[16] S. Chakraborty, W. W. Brennessel, W. D. Jones, J. Am. Chem. Soc.
2014, 136, 8564-8567.
[17] E. A. Bielinski, P. O. Lagaditis, Y. Zhang, B. Q. Mercado, C. Würtele, W.
H. Bernskoetter, N. Hazari, S. Schneider, J. Am. Chem. Soc. 2014, 136,
10234-10237.
a) G. Emerson, R. Pettit, J. Am. Chem. Soc. 1962, 84, 4591-4592; b) R.
Damico, T. Logan, J. Org. Chem. 1967, 32, 2356-2358; c) W. T.
Hendrix, F. G. Cowherd, J. L. von Rosenberg, Chem. Commun.
(London) 1968, 97-99; d) F. G. Cowherd, J. Von Rosenberg, J. Am.
Chem. Soc. 1969, 91, 2157-2158; e) J. Strauss, P. Ford, Tetrahedron
Lett. 1975, 16, 2917-2918; f) N. Iranpoor, H. Imanieh, S. Iran, E. Forbes,
Synth. Commun. 1989, 19, 2955-2961; g) H. Cherkaoui, M. Soufiaoui,
R. Grée, Tetrahedron 2001, 57, 2379-2383; h) V. Branchadell, C.
Crévisy, R. Grée, Chem. Eur. J. 2003, 9, 2062-2067; i) T. S. Chong, S.
T. Tan, W. Y. Fan, Chem. Eur. J. 2006, 12, 5128-5133.
[18] a) E. Alberico, A. J. Lennox, L. K. Vogt, H. Jiao, W. Baumann, H.-J.
Drexler, M. Nielsen, A. Spannenberg, M. P. Checinski, H. Junge, J. Am.
Chem. Soc. 2016, 138, 14890-14904; b) H. Jiao, K. Junge, E. Alberico,
M. Beller, J. Comput. Chem. 2016, 37, 168-176.
[19] S. Chakraborty, P. O. Lagaditis, M. Förster, E. A. Bielinski, N. Hazari, M.
C. Holthausen, W. D. Jones, S. Schneider, ACS Catal. 2014, 4, 3994-
4003.
[20] a) S. Qu, H. Dai, Y. Dang, C. Song, Z.-X. Wang,H. Guan, ACS Catal.
2014, 4, 4377-4388; b) D. H. Nguyen, X. Trivelli, F. Capet, J.-F. Paul, F.
Dumeignil,R. M. Gauvin, ACS Catal. 2017, 7, 2022-2032.
[9]
R. W. Goetz, M. Orchin, J. Am. Chem. Soc. 1963, 85, 1549-1550.
[21] P. A. Dub,J. C. Gordon, ACS Catal. 2017, 7, 6635-6655.
[10] D. Cahard, V. Bizet, X. Dai, S. Gaillard, J.-L. Renaud, J. Fluorine Chem.
2013, 155, 78-82.
This article is protected by copyright. All rights reserved.

10.1002/chem.201705454
Chemistry - A European Journal
FULL PAPER
FULL PAPER
T. Xia+, Z. Wei+, B. Spiegelberg, H. Jiao,
S. Hinze, J. G. de Vries*
H
N
N
+
D
1mol Cat.
%
1mol tBuOK
%
(iPr)
P(iPr)
2
OH
O
2P
Fe
2P
Fe
(iPr)
P(iPr)
2
or
E
1mol Cat.
%
H
H
Cl
R2
R1
R2
R1
CO
CO
Page No. – Page No.
1 h
toluene,
E
D
Isomerization of Allylic Alcohols to
Ketones with a PNP Pincer Iron
Catalyst
A borrowing pincer The isomerization of non-activated allylic alcohols to ketones
catalyzed by an iron(II) PNP pincer complex is reported. High reaction rates were
achieved, even at room temperature. A self-borrowing hydrogen mechanism was
established via DFT calculations.
This article is protected by copyright. All rights reserved.