Chemoselective hydrogen peroxide oxidation of allylic and benzylic alcohols under mild reaction conditions catalyzed by simple iron-picolinate complexes

Article abstract of DOI:10.1039/c4ra05819d

Chemoselective oxidation of allylic alcohols to α,β-unsaturated carbonyl compounds proceeded efficiently using hydrogen peroxide with iron-picolinate catalysts. The in situ generated [Fe(Me-Pic)₃] (Me-Pic = 6-methylpicolinate) catalyzed oxidation of the alcohol moiety of primary allylic alcohols while the [Fe(Pic)₃] (Pic = picolinate) and [Fe(Me-Pic)₂(Pic)] did not show sufficient catalytic activity. the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra05819d

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Chemoselective hydrogen peroxide oxidation of
allylic and benzylic alcohols under mild reaction
conditions catalyzed by simple iron-picolinate
complexes†
Cite this: RSC Adv., 2014, 4, 37674
Received 17th June 2014
Accepted 6th August 2014
*
*
Shinji Tanaka, Yoshihiro Kon, Takuya Nakashima and Kazuhiko Sato
DOI: 10.1039/c4ra05819d
www.rsc.org/advances
Chemoselective oxidation of allylic alcohols to a,b-unsaturated problematic for practical usage. It should be noted that a variety
carbonyl compounds proceeded efficiently using hydrogen peroxide of iron-polyamine complexes which catalyze regio-and stereo-
with iron-picolinate catalysts. The in situ generated [Fe(Me-Pic)3] (Me- selective C–H oxidation of alkanes were recently developed.10
Pic ¼ 6-methylpicolinate) catalyzed oxidation of the alcohol moiety of
Chemoselective oxidation of allylic alcohol to a,b-unsatu-
primary allylic alcohols while the [Fe(Pic)3] (Pic ¼ picolinate) and rated carbonyl compounds has long been of interest due to the
[Fe(Me-Pic)2(Pic)] did not show sufficient catalytic activity.
pharmaceutical applicability of the products.11 Iron-catalyzed
hydrogen peroxide oxidation of allylic alcohols has rarely been
reported12 presumably due to the competitive side reaction
leading to epoxide.13,14 Beller et al. demonstrated that the
combination of iron salts, base, and picolinic acid bearing a
benzimidazole moiety can catalyze the oxidation of benzylic and
allylic alcohols.12a Although their catalyst was effective for wide
variety of benzylic alcohols, the yield and selectivity for allylic
alcohol substrates remained modest. Recently, we found that
slight derivatization of the GoAggIII system altered it to realize
an effective catalyst for selective epoxidation of styrenes.15 Even
though modication of the 6-position of picolinate ligands
seems to have little impact on the catalytic activity, we
demonstrated that highly active and selective catalytic styrene
oxidation proceeded through the use of an iron-mixed picoli-
nate catalyst, where one picolinate (Pic) and two 6-methyl-
picolinate (Me-Pic) bound to an iron(III) center. Herein we
applied this unexpected impact of the 6-methyl group on
oxidation activity to another substrate, and found that this
system could be adopted for allylic alcohols. In the presented
catalyst system, the oxidation reactions proceeded efficiently in
a short amount of time under mild conditions even though the
experimental operations were simple, and no base and an
excess amount of H2O2 were required.
Chemoselective oxidation reactions are a powerful tool for the
functionalization and derivatization of organic compounds and
are widely used in both laboratories and industrial settings.1,2
However, environmentally unfriendly reagents such as heavy
metal oxidants and organic peroxides with metal catalysts have
been used for such selective reactions.3 In order to prevent the
formation of undesirable wastes and toxic reagents, the
combination of an iron compound plus molecular oxygen or
hydrogen peroxide as a terminal oxidant is ideal for such
oxidations, since iron compounds are generally very abundant
and less toxic, and no waste or only H2O would be generated
from these oxidants.4 Iron-catalyzed oxidation reactions have
been investigated for over a century and are known as Fenton5
and Gif-type chemistry.6 In general, these reaction systems show
low selectivity and thus their use has been limited.7 The
combination of an iron-picolinate complex and hydrogen
peroxide, known as the GoAggIII system, was explored by Barton
et al.8 and realized by Stavropoulos et al.,9 who used it to catalyze
the C–H oxidation of alkanes to alcohol or ketone. Because of its
potential practicality, the reaction mechanism is still debated,
but the low selectivity and narrow substrate generality are
Interdisciplinary Research Center for Catalytic Chemistry, National Institute of
Advanced Industrial Science and Technology (AIST), Central 5, Higashi 1-1-1,
Tsukuba, Japan. E-mail: y-kon@aist.go.jp; k-sato@aist.go.jp; Fax: +81-29-861-4511;
Tel: +81-29-861-4511
† Electronic supplementary information (ESI) available: General procedure,
procedure for catalytic reaction, spectral data of isolated compounds, Table S1,
S2, S3, and Scheme S1. CCDC-1000597 contains the supplementary
crystallographic data for complex 3. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c4ra05819d
We conducted oxidation of cinnamyl alcohol 1a by hydrogen
peroxide in the presence of Fe(OAc)2, PicH, and Me-PicH in
various molar ratios (Table 1). Upon treatment of Fe(OAc)2
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Table 1 Oxidation of cinnamyl alcohol by various catalystsa
2,6-Dicarboxypyridine, which has been used as a ligand of
oxidation catalysis by an iron complex,14 did not work as a good
ligand in this system (entry 11). In order to prove the practical
utility of our system, we examined 10 gram scale synthesis of 2a:
a 1.25 eq. of 35% H2O2 aq. was added in a dropwise manner over
30 min to a CH3CN solution of 1a and catalyst. Aer extraction
and distillation, 2a was isolated as pale yellow oil in 84% yield
(eqn (1)).
Catalyst [mol%]
Entry Fe(OAc)2 PicH Me-PicH Conv.b [%] Yieldb [%] Selec.c [%]
1
2
3
4
5
6
7
8
5
5
5
5
5
1
15
5
0
0
0
0
0
0
0
0
0
0
5
10
15
20
3
15
15
15f
15g
15h
11
99
84
95
98
93
54
98
5
5
78
81
89
91
84
31
93
5
45
78
96
94
92
90
58
95
99
75
75
(1)
5d
5e
5
5
5
Next we focused on the scope of the alcohols (Table 2). Lower
allylic alcohols such as allyl alcohol and trans-crotyl alcohol
were converted to the corresponding aldehydes 2b and 2c in
moderate yields. 3-Methylbutenal 2e was obtained in 77% yield
when 5 mol% of Fe(OAc)2 and 20 mol% of Me-PicH were used.
Linear allylic alcohols were also activated by iron catalyst,
affording 2-hexenal 2f and 2-octenal 2g in 73% and 71% yields,
respectively.
9
10
11
69
4
52
3
a
CH3CN solution, 25 ꢀC, dropwise addition of 1.25 eq. of 35% H2O2 aq.
for 10 min and further stirring for 5 min, unless otherwise stated.
b
Determined by GC using biphenyl as an internal standard. Average
c
d
of two runs. yield/conversion
ꢁ
100.
FeCl3$6H2O was used.
e
g
f
Fe(OAc)2(OH) was used. 6-Triuoromethylpicolinic acid was used.
6-Methoxypicolinic acid was used. h 2,6-Dicarboxypyridine was used.
(5 mol%) and PicH (15 mol%) to 1a in CH3CN solution, cin-
namaldehyde 2a was generated in 5% yield (entry 1). Surpris-
ingly, addition of Me-PicH (5 mol%) together with PicH
(5 mol%) dramatically enhanced catalytic activity, resulting in
full conversion of 1a with 78% yield of 2a (entry 2). Side prod-
ucts of this reaction were determined to be cinnamic acid (11%)
and benzaldehyde (7%), which could be produced by over-
oxidation of cinnamaldehyde and decomposition of the epoxi-
dation product, respectively. The selectivity for 2a was improved
when the mixed-ligand system was fully replaced by 15 mol% of
Me-PicH, providing 2a in 89% yield with 94% selectivity
(entry 4). Addition of a larger amount of Me-PicH increased the
yields of 2a but slightly decreased selectivity for 2a (entry 3–5),
and therefore the catalyst system was optimized as a combina-
tion of Fe(OAc)2 and Me-PicH in a 1 : 3 molar ratio. The
amounts of the catalyst components could be reduced to
1 mol% of Fe(OAc)2 and 3 mol% of Me-PicH while maintaining
the high yield and selectivity (entry 6). Use of FeCl3$6H2O
instead of Fe(OAc)2 resulted in lower yield and selectivity
(entry 7), but use of Fe(OAc)2(OH) maintained the high yield and
selectivity, suggesting that the acetate ligand contributed to the
catalytic activity. Employment of 6-triuoromethylpicolinic acid
did not show catalytic activity (entry 9), whereas that of
6-methoxypicolinic acid gave 52% yield and 75% selectivity
(entry 10). The electron withdrawing effect of the substituent of
the ligand might have had a negative effect on the catalytic
activity, since a similar phenomenon was observed in the
Table 2 Scope and limitation of the allylic and benzylic alcoholsab
a
CH3CN solution, 25 ꢀC, dropwise addition of 1.25 eq. of 35% H2O2 aq.
oxidation catalysis of iron-polyamine complexes.16 The nding for 10 min and further stirring for 5 min, unless otherwise stated.
b
Yields were determined by GC using biphenyl as an internal
that a lower yield was obtained via addition of 6-methoxy-
c
picolinic acid than via 6-methylpicolinic acid addition could be
standard. Average of two runs. Selec. ¼ yield/conversion ꢁ 100. 20
d
e
mol% of Me-PicH was used. Isolated yield. 5 mol% of Fe(OAc)2,
explained by the steric hindrance of oxidant species (vide infra). PicH and Me-PicH were used.
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Methacrolein 2d and 2-methyl-3-phenylbutenal 2h were oxidation of alcohols in the presence of radical trapping
generated in slightly lower yields (44% and 70%) than those of reagents–duroquinone, 2,6-di-tert-butyl-4-methylphenol or tert-
2b (71%) and 2a (91%), indicating that the methyl substituent at butylphenylnitrone–to examine whether the reaction proceeds
the b-position of alcohol inhibited activation of the alcohol through a free radical mechanism. However, inconsistent
moiety. Even though geraniol has another alkene group at the results were obtained among the three reagents in reactions
remote position, citral 2i was obtained in 60% yield with 76% using 1a or 1k as substrate, probably due to the association of
selectivity. In contrast to the catalyst system reported by Beller these reagents with iron complexes (Table S3†). Thus, we next
and co-workers,12a the catalytic activity for benzyl alcohol was tested the oxidation of cyclobutanol 1p under our optimized
moderate. For the oxidation of secondary allylic alcohols, the condition for secondary alcohols. An in situ generated high
optimized system used for 1a was not suitable for a-phenyl- valent iron-oxo species has been reported to oxidize 1p to
cinnamyl alcohol 1k. Thus, we performed the optimization cyclobutanone 2p without formation of a ring-opened product,
again and determined that a mixture of Fe(OAc)2, PicH, and Me- conrming that the reaction underwent through a 2-electrons
PicH in a 1 : 1 : 1 molar ratio was a good system for secondary pathway.18 Upon treatment of the iron catalyst with 1p, 2p was
allylic alcohols (Table S1†). Chalcone 2k, 1-buten-3-on 2l, 3- produced with 95% selectivity (Scheme S1†).
octen-2-on 2m, and 2-cyclohexen-1-one 2n were obtained in
Based on these results and similar catalytic systems using
high yields with high selectivity by using this catalyst system. iron compounds, we tentatively postulated that oxidation of
Here again, catalytic activity for the benzylic alcohol was alcohols proceeded via high-valent iron-oxo species
moderate, giving acetophenone 2o in 64% yield.
In order to obtain information about the reaction mecha- ligands in complex
(Scheme 1).18a,19 Substitution reaction of one of the Me-Pic
3
gave the iron–peroxo complex
nism, we isolated an iron complex that formed in the catalyst [Fe(Me-Pic)2(Me-PicH)(OOH)] (6),20 which was then transformed
solution. Reaction of Fe(OAc)2 with an excess amount of Me- into [Fe]O(Me-Pic)3] (7) with generation of water.21 In this
PicH gave a homoleptic complex [Fe(Me-pic)3] (3) as yellow stage, iron-oxo species 7 could react with allylic alcohols 1 in
crystals. Single crystal X-ray structure analysis revealed that two or more pathways: one was the attack of alkene moieties on
complex 3 holds three Me-Pic ligands in an N,O-chelating the oxo ligand of 7 to give epoxide, and another was the reaction
manner, and each donor atom is arranged in a meridional with hydrogen attached to the a-carbon of alcohol with an oxo
form, which is basically the same structural feature seen in ligand leading to a,b-unsaturated carbonyl compounds.
[Fe(Me-Pic)2(Pic)] (4)15 and [Fe(Pic)3] (5) (Fig. 1).17 In complex 3, Because of the steric hindrance of the two methyl groups of
the distance between the iron atom and the nitrogen atom of picolinate ligands, reaction with the hydrogen atom of primary
the coordinated pyridine ring located at the cis-position to the alcohols might proceed prior to attack of the alkene part,
other two pyridine rings are longer than the other Fe–N bond affording a,b-unsaturated aldehydes 2 in good selectivity. In
˚
distances in 3 by 0.1 A, and longer than all Fe–N bond distances contrast, iron-oxo species generated from the mixed picolinate
in 4 and 5. This elongation of the Fe–N bond distance was complex 4 could be approached by an alkene moiety and
attributed to steric repulsion of the Me moiety rather than trans- product compounds because of the reduced bulkiness around
inuence and indicates that one of the Me-Pic ligands in 3 is the iron-oxo moiety, and thus the selectivity of the product was
labile for ligand substitution.
decreased. In the case of secondary allylic alcohol, however, the
Complex 3 (5 mol%) was employed as a pre-catalyst for the hydrogen atom on the tertiary carbon atom did not approach
oxidation of 1a, giving 2a in 90% yield with 92% selectivity, and the oxo ligand owing to the steric hindrance of two ortho-methyl
thus oxidant species were thought to be generated via complex 3 groups attached to picolinate ligands. Thus, use of the mixed
in catalyst solution (Table S2†). In addition, we performed the picolinate system resulted in better yield and selectivity for
secondary allylic alcohols.
Fig. 1 Molecular structure of complex 3. Hydrogen atoms were
omitted for clarity. Selected bond distances (A˚) and angles (ꢀ): Fe–N1
2.1561(17), Fe–N2 2.1670(16), Fe–N3 2.2459(16), Fe–O1 1.9431(14), Scheme 1 Possible competitive reaction of high-valent iron-oxo
Fe–O2 1.9641(13), Fe–O3 1.9666(14).
species with alkene and alcohol moiety of allylic alcohols.
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Notes and references
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Scheme 2 Selective oxidation of diols 8 and 10 by iron-picolinate
catalysts. cat A: Fe(OAc)2 (5 mol%) + Me-PicH (20 mol%), cat B:
Fe(OAc)2 (5 mol%) + PicH (5 mol%) + Me-PicH (5 mol%).
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alcohols to a,b-unsaturated carbonyl compounds by a combi-
nation of hydrogen peroxide and iron-picolinate complexes,
which was a modied GoAggIII system by addition of Me-PicH in
a suitable ratio instead of pyridine and PicH. The catalyst
prepared by simple mixing of Fe(OAc)2 with Me-PicH or PicH
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Acknowledgements
This work was partially supported by the New Energy and
Industrial Technology Development Organization (NEDO),
Japan. We thank Yumiko Uesaka for technical support.
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