Research Theme

Development of Synthetic Organic Reactions Catalyzed by Organometallic Complexes and the Application to Functional Materials.

By using transition metal catalysts, we can develop the organometallic reagents and the organometallic complexes which show the reactivities and selectivities different than ones in classical methods. We can also control the reactivities of the reagents and the catalysts precisely by tuning the ligands (organic compounds) on the metals.

We are presuing the development of the new carbon-carbon bond formation reactions which become a basis for synthetic organic reactions by talking advantage of the characteristics of the organometallics complexes which consist of the metals and the organic compounds.
We are also interested in the development of the enviromentally friendly reactions for "Green Chemistry" which is one of the most important tasks for chemists in the 21th century.

Reserch Subjects
1. Palladium-Catalyzed Cyanoesterification of Unsaturated Organic Compounds
        Direct activation of C-C bonds and sequential addition to the C-C multiple bonds are of current interest in synthetic organic chemistry because the reaction can provide two different C-C bonds simultaneously. We have developed palladium-catalyzed cyanoesterification of norbornene derivatives, which can introduce cyano and ester groups as polar functionality. The reaction is believed to proceed via oxidative addition, migratory insertion, and reductive elimination.

  1. Y. Nishihara, Y. Inoue, M. Itazaki, and K. Takagi
    Palladium-Catalyzed Cyanoesterification of Norbornenes with Cyanoformates via the NC-Pd-COOR (R = Me and Et) Intermediate
    Org. Lett. 7, 2639-2641 (2005).
  2. Y. Nishihara, Y. Inoue, S. Izawa, M. Miyasaka, K. Tanemura, K. Nakajima, and K. Takagi
    Cyanoesterification of Norbornenes Catalyzed by Palladium: Facile Synthetic Methodology to Introduce Cyano and Ester Functionalities via Direct Carbon-Carbon Bond Cleavage of Cyanoformates
    Tetrahedron 62, 9872-9882 (2006).
  3. Y. Nishihara, M. Miyasaka, Y. Inoue, T. Yamaguchi, M. Kojima, and K. Takagi
    Preparation, Structures, and Thermal Reactivity of Alkoxycarbonyl(cyano)palladium(II) Complexes, trans-Pd(COOR)(CN)(PPh3)2 (R = Me, Et, nPr. iPr, nBu, tBu, and Bn) as Intermediates of the Palladium-Catalyzed Cyanoesterification of Norbornene Derivatives
    Organometallics 26, 4054-4060 (2007).
  4. Jing Li, Shintaro Noyori, Kiyohiko Nakajima, and Yasushi Nishihara
    Preparation, Structures, and Thermal Reactivity of Alkoxycarbonyl(cyano)palladium(II) Complexes, trans-Pd(COOR)(CN)(PPh3)2 (R = Me, Et, nPr. iPr, nBu, tBu, and Bn) as Intermediates of the Palladium-Catalyzed Cyanoesterification of Norbornene Derivatives
    Organometallics 33, 3500-3507 (2014).
  5. Jing Li, Yasuhiro Okuda, Jiaji Zhao, Seiji Mori, and Yasushi Nishihara
    Skeletal Rearrangement of Cyano-Substituted Iminoisobenzofurans into Alkyl 2-Cyanobenzoates Catalyzed by B(C6F5)3
    Org. Lett. 16, 5220-5223 (2014).
2. Highly regio- and stereoselective synthesis of multi-substituted olefins
        Selective synthesis of multi-substituted olefins, so far, is still a challenging work for organic chemists because of its difficulty to control the regio- and stereoselectivity. Our approach involves synthesis of multi-metalated olefins via selective zirconacycle formation of alkynylmetallic reagents and sequential cross-coupling reactions, which can be a good strategy to multi-substituted olefins. We have succeeded in synthesis of several novel multi-arylated and alkylated olefins and are trying to introduce for different aryl groups to the multi-metalated olefins sequentially with high regio- and stereoselectivities.
  1. Y. Nishihara, M. Miyasaka, M. Okamoto, H. Takahashi, E. Inoue, K. Tanemura, and K. Takagi
    Zirconocene-Mediated Highly Regio- and Stereoselective Synthesis of Multisubstituted Olefins Starting from 1-Alkynylboronates
    J. Am. Chem. Soc. 129, 12634-12635 (2007).
  2. Y. Nishihara, D. Saito, K. Tanemura, S. Noyori, and K. Takagi
    Regio- and Stereoselective Synthesis of Multi-Substituted Vinylsilanes via Zirconacycles
    Org. Lett. 11, 3546-3549 (2009).
  3. Y. Nishihara, Y. Okada, J. Jiao, M. Suetsugu, M.-T. Lan, M. Kinoshita, M. Iwasaki, and K. Takagi
    Highly Regio- and Stereoselective Synthesis of Multi-alkylated Olefins through Carbozirconation of Alkynylboronates and Sequential Negishi and Suzuki-Miyaura Coupling Reactions
    Angew. Chem. Int. Ed. 50, 8660-8664. (2011).
  4. J. Jiao, Y. Nishihara
    Alkynylboron Compounds in Organic Synthesis.
    J. Organomet Chem. 721-722, 3-16 (2012).
  5. Jiao Jiao, Kiyohiko Nakajima, and Yasushi Nishihara
    Synthesis of Multisubstituted Olefins through Regio- and Stereoselective Silylborylation of an Alkynylboronate/ Chemoselective Cross-Coupling Sequences
    Org. Lett. 15, 3294-3297 (2013)
  6. Jiao Jiao, Keita Hyodo, Hao Hu, Kiyohiko Nakajima, and Yasushi Nishihara
    Selective Synthesis of Multisubstituted Olefins Utilizing gem- and vic-Diborylated Vinylsilanes Prepared by Silylborylation of an Alkynylboronate and Diborylation of Alkynylsilanes
    J. Org. Chem. 79, 285-295 (2014).
  7. Keita Hyodo, Masato Suetsugu, and Yasushi Nishihara
    Diborylation of Alkynyl MIDA Boronates and Sequential Chemoselective Suzuki-Miyaura Couplings: A Formal Carboborylation of Alkynes
    Org. Lett. 16, 440-443 (2014).
3. Precise Synthesis of Picene Derivatives toward Organic Functional Materials
        Picene contains a condensed conjugated system with five benzene rings, which shows a high potential utility for organic field-effect transistor (OFET) and organic thin film solar cells. However, there are still few examples of the systematic synthesis of picene and its derivatives. We designed our synthetic methodology, which is more efficient than previous synthetic methods.
  1. Ning-hui Chang, Xi-chao Chen, Hikaru Nonobe, Yasuhiro Okuda, Hiroki Mori, Kiyohiko Nakajima, and Yasushi Nishihara
    Synthesis of Substituted Picenes through Pd-Catalyzed Cross-Coupling Reaction/Annulation Sequences and Their Physicochemical Properties
    Org. Lett. 15, 3558-3561 (2013).
  2. Ning-hui Chang, Hiroki Mori, Xi-chao Chen, Yasuhiro Okuda, Takeru Okamoto, and Yasushi Nishihara
    Synthesis of Substituted [6]Phenacenes through Suzuki-Miyaura Coupling of Polyhalobenzene with Alkenylboronates and Sequential Intramolecular Cyclization via C-H Bond Activation
    Chem. Lett. 42, 1257-1259 (2013).
  3. Yasushi Nishihara, Megumi Kinoshita, Keita Hyodo, Yasuhiro Okuda, Ritsuko Eguchi, Hidenori Goto, Shino Hamao, Yasuhiro Takabayashi, and Yoshihiro Kubozono
    Phenanthro[1,2-b:8,7-b']dithiophene: A New Picene-type Molecule for Transistor Applications
    RSC Advances 3, 19341-19347 (2013).
  4. Hiroki Mori, Xi-chao Chen, Ning-hui Chang, Shino Hamao, Yoshihiro Kubozono, Kiyohiko Nakajima, and Yasushi Nishihara
    Synthesis of Methoxy-Substituted Picenes: Substitution Position Effect on Their Electronic and Single-Crystal Structures
    J. Org. Chem. 79, 4973-4983 (2014).

4. Development of an Efficient Synthetic Method for Unsymmetrical Diarylethynes by a Direct Activation of Carbon-Silicon Bonds
        Unsymmetrical diarylethynes are one of the most significant compounds, which have widely been used as various synthetic intermediates of biologically active compounds and organic functional materials. We focus on the development of facile and efficient synthetic method for these intermediates by a direct coupling of alkynylsilanes with organic halides (Sila-Sonogashira-Hagihara coupling reaction) via a direct activation of carbon-silicon bonds.
  1. Y. Nishihara, E. Inoue, Y. Okada, and K. Takagi
    Sila-Sonogashira Cross-Coupling Reactions of Activated Aryl Chlorides with Alkynylsilanes
    Synlett (19), 3041-3045 (2008).
  2. Y. Nishihara, E. Inoue, D. Ogawa, Y. Okada, S. Noyori, and K. Takagi
    Palladium/Copper-Catalyzed Sila-Sonogashira Reactions of Aryl Iodides with Alkynylsilanes via a Direct C-Si Bond Activation
    Tetrahedron Lett. 50(32), 4643-4646 (2009).
  3. Y. Nishihara, S. Noyori, T. Okamoto, M. Suetsugu, and M. Iwasaki
    Copper-Catalyzed Sila-Sonogashira-Hagihara Cross-Coupling Reactions of Alkynylsilanes with Aryl Iodides under Palladium-Free Conditions
    Chem. Lett. 40, 972-974 (2011).
  4. Y. Nishihara, E. Inoue, S. Noyori, D. Ogawa, Y. Okada, and M. Iwasaki
    Synthesis of Unsymmetrical Disubstituted Ethynes by the Palladium/Copper(I)-Cocatalyzed Sila-Sonogashira-Hagihara Coupling Reactions of Alkynylsilanes with Aryl Iodides, Bromides, and Chlorides through a Direct Activation of a Carbon-Silicon Bond
    Tetrahedron 68, 4869-4881 (2012).
  5. Y. Nishihara, D. Ogawa, S. Noyori, and M. Iwasaki
    Synthesis of Unsymmetrical Diarylethynes by Pd(0)/Cu(I)-cocatalyzed Sila-Sonogashira-Hagihara Coupling Reactions of Alkynylsilanes with Aryl Tosylates or Mesylates
    Chem. Lett. 41, 1503-1505 (2012).
  6. Daisuke Ogawa, Jing Li, Masato Suetsugu, Jiao Jiao, Masayuki Iwasaki, Yasushi Nishihara
    Palladium-Free Synthesis of Unsymmetrical Diarylethynes by Cross-Coupling Reaction of Alkynylboronates with Aryl Iodides Catalyzed by CuCl
    Tetrahedron Lett. 54, 518-521 (2013).
5. Investigation of Reaction Mechanism by Quantum-Chemistry Calculation
        Recently, quantum-chemistry calculation shows remarkable development. Even in synthetic organic laboratory, computational chemistry has been used for investigation of reaction mechanism, determination of structure and so on. We are also investigating to understand various aspects of synthetic organic reactions experimentally as well as theoretically. We have revealed the reaction mechanism of the palladium-catalyzed cyanoesterification of norbornadiene by Gaussian program.
  1. Yasuhiro Okuda, Takeru Okamoto, Arisa Yamamoto, Jing Li, Kiyohiko Nakajima, and Yasushi Nishihara
    Synthesis, Structure, and Isomerization of Alkoxycarbonyl(chloro)(cyano)rhodium(III) Complexes, mer-RhCl(CO2R)(CN)(PMe3)3 (R = Me, Et, nPr, iPr, nBu, and Bn) through C-C Bond Cleavage of Cyanoformates
    Chem. Lett. 43, 417-419. (2014)
  2. Yasuhiro Okuda, Yuya Ishiguro, Seiji Mori, Kiyohiko Nakajima, and Yasushi Nishihara
    Experimental and Theoretical Studies on the Platinum-Mediated Selective C(sp)-Si Bond Cleavage of Alkynylsilanes
    Organometallics 33, 1878-1889 (2014).

6. Synthesis of Functional Polycyclic Aromatic Organic Molecules via Catalytic Annulation Reactions
         Fused π-conjugated systems are useful compounds for functional organic materials because of their unique optical and electrochemical properties, which are expected to be applied to organic light emitting displays (OLED) and organic field-effect transistors (OFET). However, their convenient preparation methods are limited by harsh reaction conditions and multistep synthesis. Our research involves development of convenient synthetic methods of polycyclic aromatic hydrocarbons (PAH) by annulation reactions catalyzed by transition metal complexes. We have developed palladium-catalyzed sequential carbon-carbon forming reactions to afford triphenylenes efficiently.

  1. Masayuki Iwasaki, Shohei Iino, and Yasushi Nishihara
    Palladium-Catalyzed Annulation of o-Iodobiphenyls with o-Bromobenzyl Alcohols: Synthesis of Functionalized Triphenylenes via C-C and C-H Bond Cleavages
    Org. Lett. 15, 5326-5329 (2013).
7. Development of Direct Thiolation of C-H Bonds Catalyzed by Transition Metal Complexes
        Organosulfur compounds are one of the most important materials in synthetic organic chemistry, which are often found in natural products and pharmaceutical intermediates. Cross-coupling reactions of aryl halides with thiols represent conventionally the most useful method for the synthesis of highly functionalized aryl sulfides. However, the requirement of preparation of aryl halides limits the scope of the reactions. Thus, a new efficient method for constructing carbon-sulfur bonds has been developed, and we have found efficient synthesis of aryl sulfides via palladium-catalyzed direct thiolation of C-H bonds.

  1. Masayuki Iwasaki, Miki Iyanaga, Yuta Tsuchiya, Yugo Nishimura, Wenjuan Li, Zhiping Li, and Yasushi Nishihara
    Palladium-Catalyzed Direct Thiolation of Aryl C-H Bonds with Disulfides
    Chem. Eur. J. 20, 2459-2462 (2014).
  2. Masayuki Iwasaki, Yuta Tsuchiya, Kiyohiko Nakajima, and Yasushi Nishihara
    Chelate-Assisted Direct Selenation of Aryl C-H Bonds with Diselenides Catalyzed by Palladium
    Org. Lett. 16, 4920-4923 (2014).
  3. Masayuki Iwasaki, Wataru Kaneshika, Yuta Tsuchiya, Kiyohiko Nakajima, and Yasushi Nishihara
    Palladium-Catalyzed peri-Selective Chalcogenation of Naphthylamines with Diaryl Disulfides and Diselenides via C-H Bond Cleavage
    J. Org. Chem. 79, 11330-11338 (2014).
8. Development of Sulfur-Containing Polycyclic Aromatic Hydrocarbons (PAHs) and Their Application to Organic Field-effect transistors
        Thiophene-fused polycyclic aromatic hydrocarbons (PAHs) have strong intermolecular interaction and extremely high carrier mobility, because the large atomic radius of sulfur atoms can serve as an effective π-π overlap between the neighboring molecules. Thus, thiophene-fused PAHs are very useful class of compounds for high-performance organic field-effect transistors (OFETs). By using precisive organic synthesis, recently, we have successfully synthesized new phenacene-type thiophene-fused PAHs. In addition, we have developed an efficient and readily scalable synthetic method to afford the large amount of them. OFET devices based on these new compound exhibited high field-effect mobility of up to 2 cm2 V-1 s-1, which are comparable to the conventional amorphous silicon FETs.

  1. Yasushi Nishihara, Megumi Kinoshita, Keita Hyodo, Yasuhiro Okuda, Ritsuko Eguchi, Hidenori Goto, Shino Hamao, Yasuhiro Takabayashi, and Yoshihiro Kubozono
    Phenanthro[1,2-b:8,7-b']dithiophene: A New Picene-type Molecule for Transistor Applications
    RSC Adv. 3, 19341-19347 (2013).
  2. Keita Hyodo, Hikaru Nonobe, Shuhei Nishinaga, and Yasushi Nishihara
    Synthesis of 2,9-dialkylated phenanthro[1,2-b:8,7-b']dithiophenes via cross-coupling reactions and sequential Lewis acid-catalyzed regioselective cycloaromatization of epoxide
    Tetrahedron Lett. 55, 4002-4005 (2014).
  3. Yoshihiro Kubozono, Keita Hyodo, Hiroki Mori, Shino Hamao, Hidenori Goto, and Yasushi Nishihara
    Transistor application of new picene-type molecules, 2,9-dialkylated phenanthro[1,2-b:8,7-b']dithiophenes
    J. Mater. Chem. C 3, 2413-2421 (2015).
9. Development of Phenacene-based Semiconducting polymers and Their Application to High-Performance Organic Solar Cells
        Thiophene-fused polycyclic aromatic hydrocarbons are also a useful building unit for high-performance semiconducting polymers. Among them, thiophene-fused phenacene-type molecules are promising building unit due to their low-lying HOMO energy levels. However, such building units still limited because of their synthetic difficulty. Recently, we have succeeded the synthesis of new semiconducting polymers containing newly developed phenacene-type molecules. At the present time, the fabricated solar cells using such new phenacene-based polymers exhibited high power conversion efficiency of over 5%.

  1. Hiroki Mori, Masato Suetsugu, Shuhei Nishinaga, Ning-hui Chang, Hikaru Nonobe, Yasuhiro Okuda, , and Yasushi Nishihara
    Synthesis, Characterization, and Solar Cell and Transistor Applications of Phenanthro[1,2-b:8,7-b']dithiophene-Diketopyrrolopyrrole Semiconducting Polymers
    J. Polym. Sci., Part A: Pol. Chem. 53, 709-718 (2015).
10. Transition-Metal-Catalyzed Regio- and Stereoselective Halothiolation of Alkynes
        The vic-difunctionalization of carbon-carbon unsaturated bonds represents an ideal synthetic method in organic chemistry, which can install two functional groups to organic unsaturated molecules in one step. Among them, halothiolation of alkynes, the addition reaction of a halogen-sulfur bond to an alkyne is a well-established approach to 2-haloalkenyl sulfides that are useful and versatile synthetic intermediates to various complex alkenyl sulfides. However, despite their synthetic utility, the regio- and stereoselective synthesis has not been disclosed. We revealed that transition-metal-catalyst could control the selectivity of the chlorothiolation of alkynes to yield the corresponding adducts with high selectivities.

  1. Masayuki Iwasaki, Tomoya Fujii, Arisa Yamamoto, Kiyohiko Nakajima, and Yasushi Nishihara
    Palladium-Catalyzed Regio- and Stereoselective Chlorothiolation of Terminal Alkynes with Sulfenyl Chlorides
    Chem. Asian J. 9, 58-62 (2014).
  2. Masayuki Iwasaki, Tomoya Fujii, Kiyohiko Nakajima, and Yasushi Nishihara
    Iron-Induced Regio- and Stereoselective Addition of Sulfenyl Chlorides to Alkynes via a Radical Pathway
    Angew. Chem. Int. Ed. 53, 13880-13884 (2014).




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