Molecular Design Laboratory

Masakazu Hirotsu (Associate Professor)· Current Research Interests· Selected Publications

1. Current Research Interests(i) Activation of Chemical Bonds by Transition-Metal Complexes (1, 3)(ii) Metal Complexes Involved in Multi-Step Electron Transfer Reactions in Biological Systems(2, 3)(iii) Thiophene-Based Functional Materials (1, 2)(iv) Molecular Switching Materials: Structural, Magnetic, and Catalytic Properties (5)(1) Reactions of Thiophene-Based Materials. Metal-mediated activation of strong bonds, suchas C−C, C−H, C−O, and C−X (X = halogen), is a vital research area related to the catalytictransformation of organic molecules. Carbon-sulfur bonds are also activated on metal centers toprovide useful reaction pathways for novel sulfur-containing compounds. The C−S bondcleavage of thiophenes is an industrially important process in catalytic hydrodesulfurization(HDS) that removes sulfur from organosulfur compounds in petroleum feedstocks. The
reactions of dibenzothiophenes (DBT) with organometallic compounds are of particular interest
because dibenzothiophenes are especially resistant to desulfurization, which causes serious
problems for further HDS. However, the rich sulfur-metal chemistry originating from HDS
would provide new ways to produce S-containing functional materials.
We have used pyridyl-substituted dibenzothiophenes, 4-(2′-pyridyl)dibenzothiophene (PyDBT)
and its derivatives, as ligand precursors in order to facilitate the metalation reaction. For
example, the reaction of PyDBT with [Ru3(CO)12] gave the diruthenium(II) complex [Ru(μPyBPT-κ3N,C,S)(CO)2]2, where PyBPT denotes a dianion of 3′-(2′′-pyridyl)-1,1′-biphenyl-2thiol (Figure 1). The N,C,S-tridentate ligand PyBPT provides a pincer structure consisting oftwo metallacycles. The precoordination of the pyridyl group, including the N,S-chelating mode,
accelerates the oxidative addition of the C-S bond by increasing the accessibility of the C−Sbond to the vacant site on the metal center.

Figure 1. Formation of thiolate-containing pincer structures by C–S bond cleavage.
Another way to utilize C−S cleavage reactions is modification of C−S cleaved ligands intransition-metal complexes. A thiolate-bridged diiron carbonyl complex derived frombenzothiophene, [Fe2(μ-SC6H4CHCH)(CO)6], which was reported by Rauchfuss et al.
(Organometallics, 1988, 7, 1171), reacted with terminal alkynes under photoirradiation
conditions to afford diiron carbonyl complexes of p-conjugated thiolate ligands as alkyne
insertion products (Figure 2). Various functional groups were introduced on the extended
carbon chain. This reaction process involves insertion of CO and/or migration of coordinating
functional groups via C−N or C−O bond cleavage.

Figure 2. Reactions of a diiron complex containing C-S cleaved benzothiophene withalkynes.
(2) Mimics of [FeFe]-Hydrogenase Active Sites. Thiolate iron complexes are found in theactive site of hydrogenases, which catalyze the formation and consumption of dihydrogen in
biological systems. The active site of [FeFe]-hydrogenases consists of a diiron center bridged
by a dithiolate ligand and a {4Fe4S} cubane cluster. The diiron center has carbonyl and cyanide
ligands, and one of the two Fe ions is connected to the {4Fe4S} cluster via a cysteinyl residue(Figure 1a). A binding site for substrates is in the diiron unit, and the {4Fe4S} cluster isinvolved in electron transfer in the catalytic cycle of [FeFe]-hydrogenases.
We synthesized a thiolate-bridged diiron carbonyl complex [{Fe(μ-PyBPT-κ3N,C,S)(CO)2}Fe(CO)3] by the photochemical reaction of PyDBT with [Fe(CO)5] (Figure 1b). AnFe(CO)3 unit in the PyBPT complex is bound to the thiolate-containing metallacycle to form acarbon- and sulfur-bridged dinuclear structure with an Fe−Fe bond, which is similar to the diiron
unit of the [FeFe]-hydrogenase active site. The C,S-bridged diiron complex and its Schiff baseand oxazoline derivatives showed electrocatalytic ability for proton reduction.

Figure 3. Structures of (a) the active site of [FeFe]-hydrogenases in the oxidized state and (b)a diiron complex with an S,C,N-tridentate ligand.
(3) N2 Activation. Biological reduction of dinitrogen to ammonia is catalyzed by nitrogenase
enzymes under ambient conditions, which is an essential process in the biochemical nitrogencycle. The N2 binding and reduction proceed at the FeMo-cofactor in nitrogenase, in which
the iron centers are surrounded by the sulfur donor atoms. The structure of the FeMo-cofactor
has been revealed by crystallographic studies, and synthetic approaches are currently underway
to obtain the structural model. In addition, the reduction and functionalization of thecoordinated N2 using early- to middle-transition-metal complexes have become an active
research area. However, the mechanistic details of the N2 reduction on the FeMo-cofactor arestill unclear.
We recently reported that sulfur-bridged Ta2M2 complexes (M = Mo, Cr) containing a fourelectron-reduced dinitrogen ligand, [Cp*Ta(μ-SC6H4Me)2M(CO)4]2(μ-η1:η1-N2) (Cp* = η5C5Me5), were synthesized from the ditantalum complex [Cp*Ta(SC6H4Me)2]2(μ-η1:η1-N2),
which was obtained by a one-pot reaction using [Cp*TaCl4], di-p-tolyl disulfide, and KC8
under dinitrogen (Figure 4). Crystal structures of the Ta2 and Ta2M2 complexes revealed theanalogy of the Ta–N–N–Ta moieties. This new synthetic procedure provides various types ofS-bridged multinuclear N2 complexes, which should be useful for investigating the reactivityof N2 incorporated in sulfur rich metal clusters.

Figure 4. Structure of S-bridged Ta2M2 complexes with N24– (M = Mo, Cr).
(4) Mimics of Oxygen Evolving Center in Photosystem II. Photosynthetic water oxidation iscatalyzed by the oxygen evolving complex (OEC) in photosystem II (PSII). X-ray diffraction
studies of PSII revealed that the active site of the OEC has a Mn4CaO5 cluster. A variety oftetranuclear manganese clusters were synthesized to model the OEC active site, and theirstructural, spectroscopic, and magnetic properties were investigated. We recently designed 5,5′(9,9-dimethylxanthene-4,5-diyl)bis(salicylaldehyde) (H2xansal). The xansal-based Schiff baseligands secure two Mn ions in close proximity. This bimetallic platform is applicable to thetetrametallic one by dimerization. We synthesized Mn4 complexes by using a xansal-based
ligand derived from H2xansal and 3-amino-1-propanol. Figure 5 shows an acetate-bridged Mn4complex, which has an incomplete double-cubane structure of Mn4O6. This complex is apotential starting material for the model of the OEC active site, because the defective site could
be occupied by a Ca2+ ion to form a Mn3CaO4 cubane structure binding a fourth Mn ion.

Figure 5. Structure of a tetramanganese(II,II,III,III) complex supported by xanthene-bridged
Schiff base ligands.

(5) Multimetallic Catalysts. Chiral sulfoxides are useful building blocks in asymmetricsynthesis of organic compounds. Enantioselective oxidation of sulfides catalyzed by transition
metal complexes is an efficient method to prepare chiral sulfoxides. In the last two decades,
metal complex catalysts containing chiral salen-type Schiff base ligands have been developed
for the asymmetric sulfoxidaiton reactions, showing moderate to high enantioselectivity. On theother hand, chiral multimetallic complexes have recently been designed as efficient asymmetriccatalysts which cause proximity effect. If two metal centers in a catalyst act as anenantioselective Lewis-acid center to catch a sulfide and as an enantioselective oxidation site,
respectively, the sulfide is expected to be oxidized to the corresponding chiral sulfoxide in highenantioselectivity by the cooperative effect.
Several dimeric salen-type complexes, in which the monomeric units are connected byorganic linkages, have been synthesized, and their catalytic properties have been investigated.
However, structurally characterized salen-type complex dimers with a face-to-face arrangement
are very rare. We have synthesized an optically active dinuclear manganese(III) complex with acyclic ligand, in which two salen-type units are anchored by two 9,9-dimethylxanthene-4,5-diylspacers (Figure 6). The chiral dimanganese complex was found to have a face-to-face structure
in close proximity and showed catalytic activity for the asymmetric oxidation of sulfides byiodosobenzene. The enantioselectivity was improved by the addition of 4(dimethylamino)pyridine (DMAP) to the reaction system, which was not effective for thecorresponding mononuclear catalyst.

Figure 6. Structure of a chiral dimanganese(III,III) complex.

2. Selected Publications
1. “Skeletal Modification of Benzothiophene Mediated by Iron Carbonyls: Insertion ofTerminal Alkynes with Migration of Amino and Alkoxy Groups” Kyohei Kobayashi,
Masakazu Hirotsu, Isamu Kinoshita, Organometallics, 2013, 32 (18), 5030-5033.
2. “Titanium and manganese complexes supported by a xanthene-bridged bis(tripodal N2O2)
ligand: isomerization, intramolecular hydrogen bonding and metal-binding ability” Masakazu
Hirotsu, Keisuke Kawamoto, Rika Tanaka, Yuji Nagai, Keiji Ueno, Yoshio Teki, Isamu
Kinoshita, Dalton Trans., 2013, 42 (34), 12220-12227.
3. “Carbon- and Sulfur-Bridged Diiron Carbonyl Complexes Containing N,C,S-Tridentate
Ligands Derived from Functionalized Dibenzothiophenes: Mimics of the [FeFe]-Hydrogenase
Active Site” Masakazu Hirotsu, Kiyokazu Santo, Hideki Hashimoto, Isamu Kinoshita,
Organometallics, 2012, 31 (21), 7548-7557.
4. “Design, synthesis, magnetic properties of a p-radical ligand with photo-excited high-spinstate and its Fe(II) complex. The first stage of a new strategy for LIESST materials.” Koichi
Katayama, Masakazu Hirotsu, Isamu Kinoshita, Yoshio Teki, Dalton Trans., 2012, 41 (43),13465-13473.
5. “Anion-Controlled Assembly of Four Manganese Ions: Structural, Magnetic, andElectrochemical Properties of Tetramanganese Complexes Stabilized by Xanthene-Bridged
Schiff Base Ligands” Masakazu Hirotsu, Yuu Shimizu, Naoto Kuwamura, Rika Tanaka,Isamu Kinoshita, Ryoichi Takada, Yoshio Teki, Hideki Hashimoto, Inorg. Chem., 2012, 51 (2),766-768.

6. “Sulfur-Bridged Ta-M (M = Mo, Cr) Multinuclear Complexes Bearing a Four-ElectronReduced Dinitrogen Ligand” R. Takada, M. Hirotsu, T. Nishioka, H. Hashimoto, I. Kinoshita,
Organometallics, 2011, 30 (16), 4232-4235.
7. “Carbon–sulfur bond cleavage reactions of dibenzothiophene derivatives mediated by ironand ruthenium carbonyls” M. Hirotsu, C. Tsuboi, T. Nishioka, I. Kinoshita, Dalton Trans.,
2011, 40 (4), 785-787.
8. “Manganese(II), Nickel(II), and Palladium(II) Complexes of a Terpyridine-Like Ligand
Containing a Sulfur Linkage, and an Analogous NCN Pincer Palladium(II) Complex:
Synthesis, Characterization, and Pd-Catalyzed Reactions” M. Hirotsu, Y. Tsukahara, I.
Kinoshita, Bull. Chem. Soc. Jpn., 2010, 83 (9), 1058-1066.
9. “Synthesis and characterization of xanthene-bridged Schiff base dimanganese(III)complexes: bimetallic catalysts for asymmetric oxidation of sulfides” M. Hirotsu, N. Ohno, T.
Nakajima, C. Kushibe, K. Ueno, I. Kinoshita, Dalton Trans., 2010, 39 (1), 139-148.
10. “Steric, geometrical and solvent effects on redox potentials in salen-type copper(II)complexes” M. Hirotsu, N. Kuwamura, I. Kinoshita, M. Kojima, Y. Yoshikawa, K. Ueno,Dalton Trans., 2009, (37), 7678-7683.
11. “Ruthenium and Rhodium Complexes with Thiolate-Containing Pincer Ligands Producedby C-S Bond Cleavage of Pyridyl-Substituted Dibenzothiophenes” M. Shibue, M. Hirotsu, T.
Nishioka, I. Kinoshita, Organometallics, 2008, 27 (17), 4475-4483.
12. “A Thiacalix[3]pyridine Copper(I) Complex as a Highly Active Catalyst for the Olefin
Aziridination Reaction” Y. Tsukahara, M. Hirotsu, S. Hattori, Y. Usuki, I. Kinoshita, Chem.
Lett., 2008, 37 (4), 452-453.
13. “Extreme N-N Bond Elongation and Facile N-Atom Functionalization Reactions within
Two Structurally Versatile New Families of Group 4 Bimetallic “Side-on-Bridged” Dinitrogen
Complexes for Zirconium and Hafnium” M. Hirotsu, P. P. Fontaine, P. Y. Zavalij, L. R. Sita,*
J. Am. Chem. Soc., 2007, 129 (42), 12690-12692.
14. “Dinitrogen Activation at Ambient Temperatures: New Modes of H2 and PhSiH3 Additions
for an “End-On-Bridged” [Ta(IV)]2(m-h1:h1-N2) Complex and for the Bis(m-nitrido) [Ta(V)(m-N)]2 Product Derived from Facile N-N Bond Cleavage” M. Hirotsu, P. P. Fontaine, A.
Epshteyn, P. Y. Zavalij, L. R. Sita,* J. Am. Chem. Soc., 2007, 129 (30), 9284-9285.

15. “Synthesis of a Cofacial Schiff-Base Dimanganese(III) Complex for Asymmetric Catalytic
Oxidation of Sulfides” M. Hirotsu, N. Ohno, T. Nakajima, K. Ueno, Chem. Lett., 2005, 34(6), 848-849.