A bioinspired ZnII/FeIII heterobimetallic catalyst for thia-Michael addition

Article abstract of DOI:10.1021/om300275a

A novel tetranuclear Zn^II/Fe^III heterobimetallic complex was synthesized, and the complex can efficiently catalyze the Michael addition of thiophenols to α,β-unsaturated enones, even for tertiary carbon-sulfur bond formation.

Full text of DOI:10.1021/om300275a

Communication
pubs.acs.org/Organometallics
A Bioinspired ZnII/FeIII Heterobimetallic Catalyst for Thia-Michael
Addition
Way-Zen Lee,*,† Tzu-Li Wang,† Hao-Ching Chang,† Yi-Ting Chen,† and Ting-Shen Kuo‡
‡
†Department of Chemistry and Instrumentation Center, Department of Chemistry, National Taiwan Normal University,
Taipei 11650, Taiwan
S
* Supporting Information
ABSTRACT: A novel tetranuclear ZnII/FeIII heterobimetallic
complex was synthesized, and the complex can efficiently catal-
yze the Michael addition of thiophenols to α,β-unsaturated
enones, even for tertiary carbon−sulfur bond formation.
rganometallic catalysts, one of the most powerful syn-
thetic tools in industry, have been developed for clean,
O
fast, and efficient catalysis for several decades.1 Recently, many
studies have focused on discovering efficient catalytic processes
which benefit from the synergistic effect between two adjacent
active centers in multinuclear metal complexes.2 Among the
efficient examples, heterobimetallic catalysts have drawn intense
attention over the past decade.3 Several efficient catalysts, such
as rare earth-alkali metal−BINOL complexes and bimetallic
Schiff base complexes, have been reported in the literature.4
However, many of those catalysts consist of heavy or rare metals
and their toxicity and high cost are a great concern for large-scale
manufacturing.5 Therefore, the use of abundant, cheap, and
environmentally friendly metal ions, such as iron and zinc, for
developing efficient catalysts is essential for current and future
industrial applications.6 In addition to heterobimetallic catalysts,
highly efficient catalysis can be cooperatively carried out by two
different metal centers in several metalloenzymes, such as Cu/Zn
superoxide dismutases, [NiFe] hydrogenases, cytochrome c
oxidases, etc. Among those metalloenzymes, purple acid phos-
phatases (PAPs) possess a dinuclear active site composed of a
zinc and an iron center7 bridged by a monodentate aspartate and
presumably a hydroxide.8 With the structural inspiration of the
active site of PAPs, we have designed and prepared a benzoate-
based asymmetric polydentate ligand, 2-bis[(2-pyridylmethyl)-
aminomethyl]-6-[(2-hydroxybenzyl)(2-pyridylmethyl)-
aminomethyl]benzoate acid (H2PHPB), in which one side arm
has two pyridyl groups connected to a tertiary amine and the
other has one pyridyl and one hydroxyphenyl group connected
to a tertiary amine, for synthesizing novel heterobimetallic com-
plexes (Figure 1). Encouragingly, the ester form of H2PHPB
could be prepared by a one-pot reaction of di-2-picolylamine,
methyl 2,6-bis(bromomethyl)benzoate, and (2-hydroxybenzyl)-
(2-picolyl)amine in THF in the presence of NEt3. Further hydro-
lysis gives an off-white solid of H2PHPB.
Figure 1. ChemDraw sketch of H2PHPB.
a good catalyst for thia-Michael addition.9 With the newly de-
signed asymmetric polydentate ligand, a tetranuclear hetero-
bimetallic complex, [(PHPB)Zn(CH3CN)Fe(μ-OH)]2(ClO4)4
(1), was synthesized.10 It is noteworthy that complex 1 was
formed as [Zn(H2O)6](ClO4)2 and [Fe(H2O)6](ClO4)3 were
simultaneously added into a methanol solution of the de-
protonated PHPB2−. The molecular structure of 1 determined
by X-ray crystallography reveals two ZnII/FeIII dinuclear units
bridged by two hydroxyl groups between two FeIII ions, and the
ZnII and FeIII centers of each unit are bridged by the central
benzoate group of PHPB2− with a distance of 6.00 Å between
the two metal ions (Figure 2). Therefore, the geometry of 1 can
be described as a dimer of dimers. More interestingly, the ZnII
center is spontaneously bound to the neutral tridentate side
arm of PHPB2− containing three N donors, and the FeIII center
resides at the anionic tridentate side arm composed of two N
donors and one O− donor. In addition, each ZnII center is co-
ordinated by an acetonitrile molecule. With a labile acetonitrile
molecule, the ZnII center of 1 can serve as a Lewis acid for
substrate bonding. Meanwhile, the two bridging hydroxide ions
on the FeIII center adequately interact with the substrate. Two
metal ions, ZnII and FeIII, supported by the asymmetric poly-
dentate ligand of PHPB2− cooperatively function as a hetero-
bimetallic catalyst.
In a previous work, we have reported a dinuclear complex,
[Ni2(BBPAB)(CH3CN)(THF)](ClO4)3 (HBBPAB = 2,6-bis-
((2-bis(2-pyridylmethyl)aminoethoxy))benzoic acid), which is
Received: April 5, 2012
Published: May 21, 2012
© 2012 American Chemical Society
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Communication
column chromatography is almost quantitative (97%). To the
best of our knowledge, only a few reported ferric organo-
metallic complexes possessed catalytic ability toward Michael
additions.13 The optimized conditions were then applied for
screening Michael acceptors and donors. Also, all catalytic
reactions were terminated after 2 h for comparison. In fact,
many reactions were complete within 10 min. First, a series of
Michael acceptors, cycloenones with different ring size, and
Michael donors, thiophenols with a methoxy substituent in
different positions, were investigated (Table 1). When the
methoxy substituent of thiophenol was changed from para to
meta and ortho positions, the yield decreased from 97% to
88% and 80%, respectively (Table 1, entries 4−6). A logical
speculation for the decrease in reaction yield would be the
steric hindrance of the methoxy substituent of thiophenol
at a meta or ortho position. The reaction yields for the
2-cyclopentenone (2) system were much lower than those
for the system of 2-cyclohexanone, especially for 4-
methoxythiophenol, but the yield did not follow the trend
of bulkiness of methoxythiophenols. Interestingly, the
yields for the system of 2-cycloheptenone (4) were even
higher than those for the 2-cyclohexenone system. This
result could be rationalized by the flexibility of the large
ring size of cycloheptenone. To examine the catalytic ability
of complex 1 for weak Michael donors, 4-nitrothiophenol
was selected to react with 2-cyclohexenone. The yield
apparently decreased to 64% (Table 2, entry 2) under the
Figure 2. X-ray crystal structure (left) and a schematic drawing (right)
of [(PHPB)Zn(CH3CN)Fe(μ-OH)]2(ClO4)4 (1). Hydrogen atoms,
solvent molecules, and the counteranions of 1 are omitted for clarity.
Conjugate addition of thiols to α,β-unsaturated enones is one
of the most important synthetic strategies for carbon−sulfur
bond formation.11 Many reported metallocatalysts, including
that in our previous study, a dinickel [Ni2(BBPAB)(CH3CN)-
(THF)](ClO4)3 catalyst, can facilitate the catalysis of thia-Michael
addition.9,12 Complex 1, which contains bridging hydroxyl
groups on FeIII centers, is expected to be an effective catal-
yst for conjugate addition. 4-Methoxythiophenol was initially
selected as a Michael donor to react with 2-cyclohexenone (3)
by using 1 mol % of 1 in acetonitrile at room temperature for
2 h (Table 1, entry 6). The isolated yield of the product after
Table 2. Thia-Michael Addition of Thiophenols to α,β-
a
Unsaturated Enones
Table 1. Thia-Michael Addition of Thiophenols to
a
Cycloenones
a
The reaction was conducted on a 1 mmol scale in CH3CN (4 mL) at
room temperature under N2 for 2 h, and the ratio of enones and
b
thiophenols is 1:1.1. Yield of isolated product after column
c
chromatography. The catalyst loading of the reaction is 10 mol %,
and the reaction is terminated after 2 days.
same reaction condition as for 4-methoxythiophenol (97%) and
thiophenol (89%, Table 2, entry 1). Electronic effects did play a
critical role in this heterobimetallic catalytic system. A less
reactive Michael acceptor, N-crotyloxazolidinone (6), was also
employed to react with different Michael donors, such as 4-
methoxythiophenol, thiophenol, and 4-nitrothiophenol, and the
a
The reaction was conducted on a 1 mmol scale in CH3CN (4 mL) at
room temperature under N2 for 2 h, and the ratio of enones and
thiophenols is 1:1.1. Yield of isolated product after column
chromatography.
b
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Communication
yields for those reactions were all above 73% for only 1 mol %
of catalyst loading (Table 2, entries 4−6). In comparison with
our previous dinickel catalyst, [Ni2(BBPAB)(CH3CN)(THF)]-
(ClO4)3,7 complex 1 is more active toward thia-Michael addi-
tions. Furthermore, we have also selected 3-methyl-2-cyclo-
hexenone as a Michael acceptor, and the reaction yield could
reach 78% when the catalyst loading was increased to 10 mol %.
It is noteworthy that complex 1 can catalyze the formation of a
tertiary carbon−sulfur bond.
In order to catch a glimpse of the reaction mechanism of
thia-Michael addition catalyzed by complex 1 (m/z 762.0),
excess 4-methoxythiophenol was added into the acetonitrile
solution of 1. A dominant peak at m/z 835.1 for [(PHPB)-
Zn(4-SC6H4OCH3)Fe(μ-OH)]22+ was observed in the ESI-MS
spectrum of the reaction mixture, even with the presence of
excess 2-cyclohexenone (Figure 3). This result suggested that
Figure 4. Proposed mechanism for the thia-Michael addition reactions
catalyzed by heterobimetallic catalyst 1.
ASSOCIATED CONTENT
■
S
* Supporting Information
A CIF file giving X-ray crystallographic data for complex 1 and
text, tables, and figures giving details of the syntheses,
1
characterization data, and H and 13C NMR spectra of the
Michael addition products. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: wzlee@ntnu.edu.tw.
Figure 3. ESI-MS spectra of complex 1 in acetonitrile (left) and 1 with
excess 4-methoxythiophenol in acetonitrile (right).
Notes
The authors declare no competing financial interest.
the thiol group of the Michael donor first coordinates to the
ZnII center of the heterobimetallic catalyst 1, and the thiol
proton was dissociated (Figure 4). The enone substrate then
had a hydrogen interaction with the bridging hydroxyl group
of 1 to form an enolate. The deprotonated thiolate sub-
sequently attacked the β-carbon cation of the enolate to form
the carbon−sulfur bond. The produced enolate picked up a
proton from the surrounding acetonitrile to give the thia-
Michael product and to regenerate the catalyst 1 to complete
the catalytic cycle. Similar mechanisms catalyzed by mono-
nuclear metallic catalysts have also been proposed.12j
In conclusion, we have prepared the asymmetric benzoate-
based dinucleating ligand, H2PHPB, through a one-pot reac-
tion. The tetranuclear heterobimetallic catalyst [(PHPB)Zn-
(CH3CN)Fe(μ-OH)]2(ClO4)4 (1) was synthesized, and ZnII
and FeIII ions were spontaneously bound to their prospective
coordination site. This heterobimetallic catalyst possesses effec-
tive catalytic ability toward the conjugate additions of thiophenols
to α,β-unsaturated enones. The efficient catalytic ability of
complex 1 suggests the existence of a synergistic effect between
the ZnII and FeIII centers. Further investigations into developing
multinuclear ferric asymmetric catalysts are currently being
carried out.
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from the National
Science Council of Taiwan (NSC 97-2113-M-003-004-MY2 to
W.-Z.L.) and National Taiwan Normal University (101T3030B3).
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