Effective dehydrogenation of 2-pyridylmethanol derivatives catalyzed by an iron complex

Article abstract of DOI:10.1039/c4cc01498g

An unprecedented iron complex-catalyzed dehydrogenation of alcohols was achieved using CpFe(CO)₂Cl with a base or CpFe(CO)(Py)(Ph) as a catalyst without sacrificing the hydrogen acceptors. This reaction effectively (up to TON 67000) converted 2-pyridylmethanol derivatives to the corresponding ketones or aldehydes. The mechanistic study is also discussed. the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc01498g

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Effective dehydrogenation of 2-pyridylmethanol
derivatives catalyzed by an iron complex†
Cite this: Chem. Commun., 2014,
50, 7941
Masahiro Kamitani, Masaki Ito, Masumi Itazaki and Hiroshi Nakazawa*
Received 27th February 2014,
Accepted 7th April 2014
DOI: 10.1039/c4cc01498g
www.rsc.org/chemcomm
An unprecedented iron complex-catalyzed dehydrogenation of based on the results obtained from stoichiometric and catalytic
alcohols was achieved using CpFe(CO)2Cl with a base or CpFe(CO)- reactions of the iron precursors and isolated intermediates.
(Py)(Ph) as a catalyst without sacrificing the hydrogen acceptors. This
Firstly, various combinations of alcohols and iron complexes
reaction effectively (up to TON 67000) converted 2-pyridylmethanol were examined, and CpFe(CO)2Cl (1)13 showed catalytic activity for
derivatives to the corresponding ketones or aldehydes. The mecha- the oxidation of 2-pyridylmethanol derivatives to the corresponding
nistic study is also discussed.
dehydrogenated products. The reaction of 2-pyridylmethanol
(96 mL, 1.0 mmol) with 1 (2.1 mg, 10 mmol, corresponding to
Oxidation of alcohols to ketones or aldehydes is one of the most 1 mol% based on alcohol) in toluene (20 mL) at reflux tempera-
important reactions with practical applications in organic ture for 20 h afforded 2-pyridinecarboxaldehyde in 18% yield
synthesis. Traditionally, stoichiometric amounts of harmful (Table 1, entry 1). The catalytic activity of 1 was enhanced by the
oxidants such as chromium compounds have been used for addition of 2 mol% of NaH based on the alcohol (entry 2).
oxidation.1,2 Many methods of transition metal-catalyzed oxidation Other 2-pyridylmethanol derivatives were also dehydrogenated
of alcohols have been developed because of environmental concern, under the same reaction conditions (entries 3 and 4).
using a stoichiometric amount of oxygen,3 hydrogen peroxide,4
alkenes5 and acetone6 as less harmful hydrogen acceptors that are
Table 1 Acceptorless dehydrogenation of 2-pyridylmethanol derivatives
catalyzed by an iron complexa
sacrificed. However, from the atom efficiency viewpoint, the use of
stoichiometric amounts of oxidants is undesirable. On the other
hand, oxidant-free dehydrogenation is not only an environmentally
benign reaction, but can also save the cost and time because
stoichiometric amounts of by-products are not generated, thus
Entry
R
Additive
Cat. (mol%)
Yieldb (%) (TON)
avoiding the need for a removal process. Furthermore, such reac-
tions generate hydrogen gas and thus have a potential to become a
promising hydrogen source.7,8 Several systems capable of acceptor-
less dehydrogenation of alcohols have been developed using
rhodium,9 ruthenium,10 and iridium11,12 catalysts; however, all
these catalysts are highly toxic and precious transition metals. To
the best of our knowledge, iron or other non-precious metal-based
catalysts for oxidant-free or acceptorless dehydrogenation of
alcohols have not been reported to date. Herein, we report an
unprecedented iron-catalyzed dehydrogenation of alcohols in the
absence of hydrogen acceptors. In particular, this system could
effectively convert the 2-pyridylmethanol derivatives to the corre-
sponding ketones or aldehydes. The catalytic cycle was envisioned
1
2
3
H
H
None
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
1 (1)
1 (1)
1 (1)
1 (1)
1 (1)
2 (1)
3 (1)
4 (1)
5 (1)
6 (1)
1 (0.1)
1 (0.01)
1 (0.001)
18 (18)
35 (35)c
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
62 (62)d
4
100 (100)
8 (8)
5e
6
Trace (À)
Trace (À)
Trace (À)
Trace (À)
Trace (À)
100 (1000)
87 (8700)
67 (67 000)
7
8
9
10
11f
11f
13g
a
The reaction was carried out with alcohol (1.0 mmol), catalyst
(1.0 mol%), and additive (2.0 mol%) in toluene (20 mL) under reflux
b
for 20 h, except for entries 11–13. Isolated yields of ketone/aldehyde
products. Yield is 48% based on the 1H NMR data. Yield is 65%
c
d
based on the 1H NMR data. Heated at 100 1C. Only the ratio of
e
f
Department of Chemistry, Graduate School of Science, Osaka City University,
Sumiyoshi-ku, Osaka 558-8585, Japan. E-mail: nakazawa@sci.osaka-cu.ac.jp
† Electronic supplementary information (ESI) available. CCDC 934658. For ESI and
crystallographic data in CIF or other electronic format see DOI: 10.1039/c4cc01498g
g
alcohol to catalyst was changed. The reaction was carried out with
alcohol (1.0 mmol), catalyst (0.001 mol%), and additive (1.0 mol%) in
toluene (1 mL) under reflux for 20 h.
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In particular, 2-pyridylbenzylalcohol was quantitatively converted This is supported by the fact that 1-octanol and Ph2CH(OH) did
to 2-benzoylpyridine. The yield dramatically decreased when the not undergo the iron-catalyzed dehydrogenation reaction.
reaction was performed at 100 1C (entry 5). Similar reactions were The nitrogen atom in the 2-pyridyl group is important for the
carried out using other iron complexes (FeCl2 (2), FeCl3 (3), Fe(OTf )2 iron-catalyzed dehydrogenation because 2-franylmethanol and
(4), Fe(BF4)2/6H2O (5) and Fe(CO)5 (6)). However, they displayed no 2-thiophenylmethanol did not undergo dehydrogenation.
catalytic activity toward the dehydrogenation of 2-pyridylbenzyl- 2-Dimethylaminoethanol also did not undergo dehydrogena-
alcohol (entries 6–10). The dehydrogenation could also be achieved tion, indicating that the nitrogen atom in the aromatic ring
even when the amount of catalyst 1 was reduced from 1 to (2-pyridyl) is important due to steric and/or electronic reasons.
0.001 mol% (entries 11–13). The highest turnover number (TON)
Notably, after the completion of the reaction and removal of
achieved was 67 000 (entry 13), and it is the highest value achieved the volatile materials, the products (pure ketones) could be
so far using a transition metal catalyst in the dehydrogenation of easily obtained by simple filtration of the reaction mixtures
alcohols.10k The conversions were determined by the isolated yield without any further purification.
of the dehydrogenated products (ketones/aldehydes).
Herein, we propose a catalytic cycle for the dehydrogenation
Next, we checked the applicability of various related alcohols for of 2-pyridylmethanol derivatives catalyzed by 1 and NaH
the dehydrogenation reaction catalyzed by 1, and the results are (Scheme 1). Firstly, the alcohol reacts with the co-catalyst NaH
shown in Table 2. Various para-substituted phenyl derivatives were to give the corresponding sodium alkoxide, which then reacts
effectively converted into the corresponding ketones (entries 1–4), with 1 to give the iron alkoxide complex. Next, the nitrogen atom
with both electron-donating (entries 1 and 2) and electron- in the attached pyridine moiety displaces one of the CO ligands to
withdrawing (entries 3 and 4) substituents on the phenyl rings. give A. Dissociation of the pyridine portion of A takes place,14 and
CF3 or five F groups on the phenyl ring (entries 5 and 7) gave low the subsequent b-hydride elimination produces the iron hydride
conversion yields. An ortho-disubstituted phenyl derivative did not complex (B) and 2-pyridinecarboxyaldehyde. Finally, the oxidative
diminish the catalytic activity (entry 6). It should be noted that the addition of the O–H bond of 2-pyridinylmethanol (or coordination
NMe2, Cl, and F groups in the para positions of the phenyl rings of the pyridine moiety of 2-pyridylmethanol) followed by the H2
did not diminish the catalytic activity of 1. In stark contrast, the reductive elimination (or the coupling of hydride of B and proton
compounds listed in Chart 1 did not undergo dehydrogenation. of the hydroxy group) produce A to complete the catalytic cycle.
3-Pyridylmethanol and 4-pyridylmethanol did not undergo
The main cycle in Scheme 1 consists of A and B, and NaH
dehydrogenation, indicating that the 2-pyridyl moiety of the converts the starting alcohol into the corresponding alkoxide in
2-pyridylmethanol derivatives is important for the catalytic order to activate 1. The use of NaH should be avoided because
dehydrogenation, presumably because the chelation of this moiety NaH is a strong base, in order to make the catalytic system
to the iron of the catalyst makes a stable five-membered ring. applicable to a more wide range of applications. After several
trials, we finally found that 8 serves as a good precursor of the
reactive 16e species, CpFe(CO)Ph, because the pyridine moiety of
Table
2
Acceptorless dehydrogenation of various 2-pyridylmethanol
8 might readily dissociate from the iron center compared to the
CO moiety of 1 (Scheme 2). Complex 8 was isolated in 89% yield
upon the photo-irradiation of 715 in the presence of pyridine.
Complex 8 was characterized by NMR spectroscopy, EA and X-ray
diffraction study.16 Complex 8 exhibited excellent catalytic activity
for the dehydrogenation of 2-pyridylbenzylalcohol even without
the presence of a base (NaH). The results show that the catalytic
cycle shown in Scheme 1 is reasonable. To obtain further evidence
to support the proposed reaction pathway, the stoichiometric
derivatives catalyzed by an iron complexa
Entry
C6X5
Yieldb,c (%)
1
2
3
4
5
6
7
C6H4Me-4
C6H4NMe2-4
C6H4Cl-4
99 (100)
96 (100)
98 (100)
92 (97)
42 (43)
99 (100)
15 (23)
C6H4F-4
C6H4CF3-4
C6H2Me3-2, 4, 6
C6F5
a
The reaction was carried out with alcohol (1.0 mmol), catalyst
(1.0 mol%), and NaH (2.0 mol%) in toluene (20 mL) under reflux for
20 h. Isolated yields. Yields based upon 1H NMR in parentheses.
b
c
Chart 1 Compounds shown above did not undergo dehydrogenation
under the reaction conditions listed in Table 2.
Scheme 1 Plausible reaction mechanism.
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Scheme 2 Formation of complex 8 and its reactivity.
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Scheme 3 Preparation of intermediate 10 and its catalytic activity.
reaction of 8 with 2-pyridylmethanol was carried out at room
temperature.
In the 1H NMR spectrum, the expected intermediate could not
be observed; however, the corresponding product, 2-pyridine-
carboxaldehyde, was slowly formed even at room temperature,
indicating that the intermediate was too unstable to be isolated.
Therefore, the reaction of a more stable iron analogue having a
Z5-C5Me5 group, (Z5-C5Me5)Fe(CO)(Py)(Me) (9),17 with 2-pyridyl-
methane thiol was carried out at room temperature. After the
work-up of the reaction mixture, the expected thioalkoxy complex 10,
(Z5-C5Me5)Fe(CO)(PyCH2S), was isolated in 98% yield, and charac-
¨
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1
terized by H NMR, 13C NMR, and elemental analysis (Scheme 3).
Although 10 showed a catalytic activity for the dehydrogenation
of 2-pyridylbenzylalcohol even without the presence of a base
(NaH) similar to that of 8, the corresponding ketone was
obtained in only 36% yield because of the stabilization of 10
by the Z5-C5Me5 ligand and the strong S–Fe bond compared to
the O–Fe bond of A. The formation of 10 and its catalytic
activity toward the dehydrogenation of 2-pyridylbenzylalcohol
are consistent with our proposed catalytic cycle.
In conclusion, we demonstrated the first iron-catalyzed dehydro-
genation of alcohols (hydrogen production). This reaction works
only for the 2-pyridylmethanol derivatives. The highest TON
achieved was 67 000 using a combination of 1 and NaH, as the
catalysts for the dehydrogenation reaction. Precursor 8 exhibited a
similar catalytic activity even in the absence of NaH. The mecha-
nistic study supported the proposed reaction pathway.
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¨
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7944 | Chem. Commun., 2014, 50, 7941--7944
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