I TOP I ACCESS I
〒606-8585 京都市左京区松ケ崎御所海道町
京都工芸繊維大学 大学院工芸科学研究科
生命物質科学域 物質合成化学専攻
11号館2階 234B(今野), 234A(山田)
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2022年


Haruka Ohsato, Masato Morita, Shigeyuki Yamada*, Tomohiro Agou, Hiroki Fukumoto, Tsutomu Konno*, Mol. Syst. Des. Eng. 2022, 7, in press [DOI: 10.1039/D2ME00055E]

With our accumulated understanding on CF2CF2-containing organic molecules, we recently achieved synthesis of π-conjugated tricarbocycles with a CF2CF2-containing cyclohexa-1,3-diene skeleton, which was prepared in eight steps from commercially available 4-bromo-3,3,4,4-tetrafluorobut-1-ene. Based on the knowledge that the fluorine atoms in molecular structures are responsible for the enhanced luminescence efficiency through H···F hydrogen bonds, the purpose of this study was to clarify the applicability of π-conjugated tricarbocycles with a CF2CF2-containing cyclohexa-1,3-diene skeleton as a new molecular design for solid-state luminophores. The π-conjugated tricarbocycles showed fluorescence in a dilute solution, but the low fluorescence efficiency was observed. However, adding 80% water to a tetrahydrofuran solution dramatically increased the fluorescence efficiency. In the crystalline state, the tricarbocycles showed blue or green fluorescence with a very high fluorescence efficiency, owing to the formation of intermolecular H···F hydrogen bonds. This proved that tricyclic π-conjugated molecules have aggregate-induced emission enhancement properties. These results indicate that π-conjugated tricarbocycles with a CF2CF2-containing cyclohexa-1,3-diene skeleton have promising solid-state luminescence performance, paving the way for the development of new solid-state luminophores, like organic-light emitting diodes or lighting devices.


Shigeyuki Yamada*, Keigo Yoshida, Tsuneaki Sakurai, Mitsuo Hara, Tsutomu Konno, Mol. Syst. Des. Eng. 2022, 7, in press [DOI: 10.1039/D2ME00057A]

D-π-A-type 4-alkoxy-4'-cyanodiphenylacetylenes bearing a decyloxy chain show a nematic liquid crystalline (LC) phase, whereas the incorporation of a semifluoroalkyl fragment results in a switch to the smectic A phase. The D-π-A-type π-conjugated mesogen exhibits photoluminescence, not only in solution and in the crystalline phase, but also in the molecular aggregated structure of the LC phase.


Shigeyuki Yamada*, Masaya Sato, Eiji Uto, Mitsuki Kataoka, Masato Morita, Tsutomu Konno, New J. Chem. 2022, 46, 3392–3400 [DOI: 10.1039/D1NJ05822C]

Small fluorescent molecules like tolanes are advantageous for broad applications, such as those in luminescence sensors and organic light-emitting devices. However, tolane derivatives are non-fluorescent in solution because of their immediate internal conversion from ππ* to dark πσ* excited states with a trans-bend structural shape. We focused on the development of tolane-based fluorescent molecules are found that the incorporation of fluorine atoms into one aromatic ring of tolane contributed to the emission of fluorescence owing to the electron density distribution and rigid molecular aggregated structure formed by intermolecular hydrogen bonding. Then, we focused on the molecular modulation, particularly the introduction of a branched structure, of a flexible unit that does not influence the electron density distribution; this could increase the interfacial distance between two tolanes to suppress non-radiative processes through energy transfer. Fluorinated tolanes were found to luminesce in dilute solutions with a relatively weak photoluminescence (PL) efficiency, whereas it was revealed that a cyclic flexible unit, such as a tetrahydrofuran ring, was the optimal structure for the flexible unit to exhibit intense PL in the crystalline state with high PL efficiency. Additionally, fluorinated tolane-based fluorophores bearing a cyclic flexible unit were found to exhibit aggregation-induced emission enhancement characteristics. The finding of this study offer a novel molecular design strategy to develop intense solid-state tolane-based luminophores.

 
Maasto Morita, Shigeyuki Yamada*, Tsutomu Konno, New J. Chem. 2022, 46, 4562–4567 [DOI: 10.1039/D1NJ05539A] ★New J. Chem.誌のフロントカバーピクチャーに選ばれました★

Halogens are the chemical elements in group 17 of the periodic table, with an electronic configuration of s2p5. Incorporation of the halogen atoms into molecular structures is well recognized as a powerful means to control the electron density of the molecule and molecular arrangement in molecular aggregate structures. Therefore, tailoring the halogen atoms in a molecular structure is a commonly used approach in the development of functional molecules with unique physical characteristics. Herein, fluorinated tolanes with various halogen atoms, for example, chlorine (Cl), bromine (Br), and iodine (I), were developed, and their photophysical behavior was evaluated in detail. Their photoluminescence (PL) behavior in toluene solution was found to be emissive, achieving a PL efficiency (ΦPL) up to 0.60, while a simple tolane solution is generally reported to show lower emission than this at room temperature. The significant enhancement of PL efficiency in these molecules likely stems from the arene/fluoroarene interaction that suppresses internal conversion to dark excited states. In crystalline states, Cl-substituted fluorinated tolane showed intense fluorescence with high ΦPL, whereas replacing Cl with Br or I atoms notably reduced the fluorescence, resulting in low ΦPL; however, I-substituted fluorinated tolane was found to show dual emission (fluorescence and phosphorescence) in the crystal at room temperature. Crystal structural analyses revealed that the dual emission is likely attributable to the combination of hydrogen and halogen bonding interactions as key intermolecular interactions in the crystal.


Shigeyuki Yamada*, Kazuki Kobayashi, Masato Morita, Tsutomu Konno, CrystEngComm 2022, 24, xx–yy [DOI: 10.1039/D1CE01671G]

Novel D-π-A-type fluorinated tolane with a diphenylamino group was synthesized, yielding two crystal polymorphisms induced by fluorine atoms in the tolane scaffold. The two crystal polymorphisms exhibited distinct photophysical behavior, with one displaying a significant photoluminescence behavior change upon the application of external stimuli.

130. Synthesis and photoluminescence properties of fluorine-containing poly(phenylene vinylene) bearing hexafluorocyclopentene-fused phenanthrene unit


Hiroki Fukumoto, Kazuki Shiitsuka, Keisuke Yamada, Shigeyuki Yamada, Tsutomu Konno, Toshio Kubota, Tomohiro Agou, Polym. Int. 2022, 71(1), 117–123 [DOI: 10.1002/pi.6291](*茨城大学の福元•吾郷研究室の,ヘキサフルオロシクロペンテン縮環フェナントレン誘導体に関する研究成果)


Chihiro Kajimoto, Takuto Kataoka, Shota Kageyama, Haruka Ohsato, Shigeyuki Yamada, Tsutomu Konno*, J. Fluorine Chem. 2022, 253, 109929 [DOI: 10.1016/j.jfluchem.2021.109929]

Treatment of (4-bromo-3,3,4,4-tetrafluorobut-1-yn-1-yl)dimethylphenylsilane with 2.0 equiv. of zinc-silver (Zn-Ag) alloy in acetonitrile at 40 ℃ for 7 h generated a novel tetrafluoroethylenated zinc reagent with a triple bond in good yield. This zinc reagent reacted smoothly with various acid chlorides at 40 ℃ in the presence of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) as a cosolvent and 30 mol% each of copper(I) bromide (CuBr) and 1,10-phenanthroline, affording the corresponding tetrafluoroethylenated ketones in high yield. However, in the cross-coupling reaction with iodoarenes, only reactions with iodoarenes having a directing group at the ortho position proceeded very efficiently in the presence fo 1,4-dioxane as a cosolvent and 30 mol% of CuBr at 60 ℃, and the corresponding products were obtained in high yield.

2021年


Shigeyuki Yamada*, Akito Nishizawa, Kazuki Kobayashi, Keigo Yoshida, Masato Morita, Tomohiro Agou, Takaaki Hosoya, Hiroki Fukumoto, Tsutomu Konno, Symmetry 2021, 13(10), 1885 [DOI: 10.3390/sym13101885]

Dual-state emissive (DSE) luminophores, which can luminesce both in solution and in solid states, have recently attracted significant attention because of their broad applications. However, their development is difficult due to the difference in molecular design between solution- and solid-state luminophores. In this study, DSE luminophores based on unsymmetrical hexafluorocyclopentene-linked twisted π-conjugated structures carrying various substituents to tune the electron-density were designed and synthesized in a single-step reaction from heptafluorocyclopentene or perfluoro-1,2-diphenylcyclopentene derivatives. The twisted π-conjugated luminophores exhibited absorption in the UV region at approximately 330 nm, along with several signals in the high-energy region. Upon irradiating the luminophore solution (wavelength 330 nm), light-green to yellow photoluminescence (PL) was observed in the range pf 422–471 nm with high PL efficiency. Theoretical calculations revealed that excitation from ground to excited states altered the structural shape of the luminophores from twisted to planar, leading to red-shifted PL and high PL efficiency (ΦPL). The intense blue PL exhibited by the luminophores in the crystalline state was attributed to their twisted molecular structures that suppressed non-radiative deactivation via the effective blocking of π/π stacking interactions.


Shigeyuki Yamada*, Yizhou Wang, Masato Morita, Qingzhi Zhang, David O'Hagan, Masakazu Nagata, Tomohiro Agou, Hiroki Fukumoto, Toshio Kubota, Mitsuo Hara, Tsutomu Konno, Crystals 2021, 11(4), 450 [DOI: 10.3390/cryst11040450]

Photoluminescent liquid crystals (PLLCs) have attracted significant attention owing to their broad applicability in thermosensing and PL switching. Extensive efforts have been made to develop bistolane-based PLLCs containing flexible units at both molecular terminals, and it has been revealed that their PL behavior can switch with the phase transition between the crystalline and LC phases. Although slight modulation of the flexible unit structure dramatically alters the LC and PL behaviors, few studies into the modification of the flexible units have been conducted. With the aim of achieving dynamic changes in their physical behaviors, we developed a family of bistolane derivatives containing a simple alkyl or a fluoroalkyl flexible chain and carried out a detailed systematic evaluation of their physical behaviors. Bistolanes containing a simple alkyl chain showed a nematic LC phase, whereas switching the flexible chain in the bistolane to a fluoroalkyl moiety significantly altered the LC phase to generate a smectic phase. The fluoroalkyl-containing bistolanes displayed a stronger deep blue PL than their corresponding non-fluorinated counterparts, even in the crystalline phase, which was attributed to the construction of rigid molecular aggregates through intermolecular F···H and F···F interactions to suppress non-radiative deactivation.


Masato Morita, Shigeyuki Yamada*, Tsutomu Konno, Molecules 2021, 26(8), 2274 [DOI: 10.3390/molecules26082274]

In this study, we synthesized a series of fluorinated and non-fluorinated tolanes, in which one or more fluorine atoms were systematically introduced into one aromatic ring of a tolane scaffold, and systematically evaluated their photophysical properties. All the tolanes without or with fluorine substituents were found to have poor photoluminescence (PL) in tetrahydrofuran (THF) solutions. One the other hand, in the crystalline state, non-fluorinated and fluorinated tolanes with one or four fluorine atoms were less emissive, whereas fluorinated tolanes with three or five fluorine atoms exhibited high PL efficiencies (ΦPL) up to 0.51. X-ray crystallographic analyses of the emissive fluorinated tolanes revealed that the position of the fluorine substituent played a key role in achieving high ΦPL. Fluorine substituents at the ortho (2/6) and para (4) positions lead to tight and rigid packing due to plural π-π stacking and/or hydrogen bonding interactions, resulting in enhanced ΦPL caused by the suppression of non-radiative deactivation. Additionally, fluorinated tolanes with three fluorine atoms exhibited notable aggregation-induced PL emission enhancement in THF/water mixed solvents. This demonstrates that the PL characteristics of small PL materials can be tuned depending on the usage requirements.


Chihiro Kajimoto, Shigeyuki Yamada, Tsutomu Konno*, J. Fluorine Chem. 2021, 245, 109781. [DOI: 10.1016/j.jfluchem.2021.109781]

On treating 2,4-dibromo-3,3,4,4-tetrafluorobut-1-ene, readily prepared from commercially available 4-bromo-3,3,4,4-tetrafluorobut-1-ene (1), with 2.0 eq. of zinc-silver alloy at 40 °C in CH3CN, zinc insertion at the terminal C(sp3)–Br site proceeded selectively, giving the corresponding (3-bromo-1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide in high yield. This organozinc reagent was found to be thermally stable and easily handled. It was found that this organozinc reagent could participate in the cross-coupling reaction with various acyl chlorides or iodoarenes to give the corresponding CF2CF2-containing organic molecules in good yields. It was also revealed that Suzuki-Miyaura cross-coupling reactions at the C(sp2)-Br site of these CF2CF2-substituted products also proceeded in good to excellent yields.


Tatsuya Kumon, Jianyan Wu, Miroku Shimada, Shigeyuki Yamada, Tomohiro Agou, Hiroki Fukumoto, Toshio Kubota, Gerald B. Hammond, Tsutomu Konno*, J. Org. Chem. 2021, 86(7), 5183–5196. [DOI: 10.1021/acs.joc.1c00080]

C–H actiation/annulation reaction of various benzamides with fluoroalkylated alkynes in the presence of Co(acac)2•2H2O catalyst proceeded very smoothly to give the corresponding 3- and 4-fluoroalkylated isoquinolinones in excellent yields with approximately 70% regioselectivities. These regioisomers could be successfully separated and obtained in pure form. Major or minor regioisomers were determined as 4- or 3-fluoroalkylated isoquinolinones, respectively, based on X-ray crystallographic analyses.


Tatsuya Kumon, Shigeyuki Yamada, Tomohiro Agou, Hiroki Fukumoto, Toshio Kubota, Gerald B. Hammond, Tsutomu Konno*, Adv. Synth. Catal. 2021, 363 (7), 1912–1922. [DOI: 10.1002/adsc.202001433]

Regioselective cobalt-catalyzed [2+2+2] cycloaddition using fluorine-containing diynes with nitriles was described. Cycloaddition of fluorinated diynes with nitriles under the influence of CoCl2(Phen), zinc bromide, and zinc dust in dichloroethane at 80 °C for 3 h took place smoothly, exclusively affording the corresponding α-fluoroalkylated pyridines in excellent yields. In addition, dinitriles as substrate were also found to be suitable for this reaction, giving the corresponding fluoroalkylated bipyridine derivatives in excellent yields.

2020年


Tatsuya Kumon, Miroku Shimada, Jianyan Wu, Shigeyuki Yamada, Tsutomu Konno*, Beilstein J. Org. Chem. 2020, 16, 2193–2200. [DOI: 10.3762/bjoc.16.184]

[2+3] cycloaddition reaction of fluorinated alkynes with 2-formylphenylboronic acids under the influence of Co(acac)2•2H2O in two-component solvents of acetonitrile/2-propanol at reflux temperature for 18 h took place smoothly, affording the corresponding fluoroalkylated indenol derivatives in good yields. This reaction shows excellent regioselectivity, giving 2-fluoroalkylated indenols, together with a very small amount of 3-fluoroalkylated indanones as side products.


Kaveendra Maduwantha, Shigeyuki Yamada, Kaveenga Rasika Koswattage, Tsutomu Konno, Takuya Hosookai*, Materials 2020, 13, 3904. [DOI: 10.3390/ma13173904]

Room-temperature phosphorescent (RTP) materials have been attracting tremendoous interest, owing to their unique material characteristics and potential applications for state-of-the-art optoelectronic devices. Recently, we reported the synthesis and fundamental photophysical properties of new RTP materials based on benzil, i.e., fluorinated monobenzil derivative and fluorinated and non-fluorinated bisbenzil derivative analogues [Yamada, S. et al., Beilstein J. Org. Chem. 2020, 16, 1154–1162]. To deeply understand their RTP properties, we investigated the excited-state dynamics and photostability of the derivatives by means of time-resolved and steady-state photoluminescence spectroscopies. For these derivatives, clear RTP emissions with lifetimes on the microsecond timescale were identified. Among them, the monobenzil derivative was found to be the most efficient RTP material, showing both the longest lifetime and highest amplitude RTP emission. Time-resolved photoluminescence spectra, measured at 77 K, and density functional theory calculations revealed the existence of a second excited triplet state in the vicinity of the first excited singlet state for the monobenzil derivative, indicative of the presence of a fast intesystem crossing pathway. The correlation between the excited state dynamics, emission properties, and conformational flexibility of the three derivatives is discussed.


Shigeyuki Yamada,* Eiji Uto, Tomohiro Agou, Toshio Kubota, Tsutomu Konno, Crystals 2020, 10, 711. [DOI: 10.3390/cryst10080711]

Light-emitting materials have received considerable attention because of their broad applications as substrates in bio-imaging and sensing componetns, light-emitting displays, and lighting devices. Herein, we developed fluorinated tolane and bistolane derivatives containing fluorinated aromatic rings and demonstrated their intense photoluminescence (PL) characteristics in crystalline powder states. We focused on molecules showing varied PL behavior with a change in the molecular aggregated structures. We synthesized novel fluorinated tolane dyads consisting of fluorinated tolane-based π-conjugated scaffolds and flexible alkylene linkages to control both the elecron-density distribution and molecular aggregated states. Fluorinated tolane dyads connected with an alkylene linkage showed blue PL in a dilute solution, but the PL efficiency achieved was low. In contrast, the crystalline powder of tolane dyad substrates exhibited dual emission–relatively intense blue to deep blue PL–originating from monomer and aggregate emission. The PL behavior changed significantly with the alkylene linkage and the application of a mechanical stimulus to the crystalline powder sample. The fluorinated tolane dyads developed in this study could serve as stimulus-responsive photoluminescence materials suitable for optical applications.


Shigeyuki Yamada,* Masaya Sato, Tsutomu Konno, Crystals 2020, 10, 603. [DOI: 10.3390/cryst10070603]

The liquid-crystalline (LC) and photophysical properties of molecules are very sensitive to their electronic and molecular aggregate structures. Herein, to shed light on the structure-property relationships of pentafluorinated bistolane-based photoluminescence (PL) liquid crystals (PLLCs) previously reported by our group, we synthesized pentafluorinated bistolanes with variable flexible chains and evaluated their LC and photophysical properties. The incorporation of an oxygen atom (to afford a 2-methoxyethoxy unit) or an oxygenatom and a methyl group (to afford a 1-methoxyprop-2-oxy unit) into the flexible butoxy chain significantly decreased the temperature of the crystalline-to-LC phase transition, and a chiral nematic phase comprising helical molecular aggregates was observed for the chiral 1-methoxyprop-2-oxy group-bearing bistolane. The synthesized bistolanes exhibited strong blue PL in both solution and crystalline phases; the featuring PL characteristics were maintained in the LC phase (produced by the crystalline-to-LC phase transition) except for a slight PL color change. Thus, it was concluded that the PL behavior of pentafluorinated bistolanes can be modulated by the choice of a suitable flexible chain, and the obtained insights are believed to facilitate the application of PLLCs in thermosensing PL materials.


Shigeyuki Yamada,* Takuya Higashida, Yizhou Wang, Masato Morita, Takuya Hosokai, Kaveendra Maduwantha, Kaveenga Rasika Koswattage, Tsutomu Konno, Beilstein J. Org. Chem. 2020, 16, 1154–1162. [DOI: 10.3762/bjoc.16.102]

Pure organic phosphorescent molecules are attractive alternatives to transition-metal-complex-based phosphores for biomedical and technological applications owing to their abundance and nontoxicity. This article discloses the design, synthesis, and photophysical property of fluorinated benzil and bisbenzil derivatives as potential pure organic room-temperature phosphorescent molecules. These compounds were separately converted from the corresponding fluorinated bistolanes via PdCl2-catalyzed oxidation by dimethyl sulfoxide, while non-fluorinated bistolane provided the corresponding bisbenzil derivatives exclusively in a similar manner. Intensive investigation of the photophysical properties of the benzil and bisbenzil derivatives in toluene at 25 °C showed both fluorescence with a photoluminescence (PL) band at a maximum wavelength (λPL) of around 400 nm and phosphorescence with a PL band at a λPL of around 560 nm. Interestingly, intersystem crossing effectively caused fluorinated benzils to emit phosphorescence, which may arise from immediate spin-orbit coupling involving the 1(n, π)→3(π, π) transition, unlike the case of fluorinated or non-fluorinated bisbenzil analogues. These findings offer a useful guide for developing novel pure organic room-temperature phosphorescent materials.


Masato Morita, Shigeyuki Yamada,* Tsutomu Konno, New J. Chem. 2020, 44, 6704–6708. [DOI: 10.1039/D0NJ01268H]

Fluorinated tolanes were found to show aggregation-induced emission characteristics and significantly enhanced photoluminescence efficiencies in molecular aggregates when compared with non-fluorinated tolanes. The fluorine atom play important roles in the formation of tight crystal packing structures to suppress molecular motion in the crystalline state via electrostatic or hydrogen bonding interactions.


Tomohiro Agou, Kazuto Yoshinari, Tomohiro Shirai, Shigeyuki Yamada, Tsutomu Konno, Yoshiyuki Mizuhata, Norihiro Tokitoh, Sana Yasuda, Takashi Yamazaki, Hiroki Fukumoto, Toshio Kubota, Macromolecules 2020, 53, 2942–2949. [DOI: 10.1021/acs.macromol.0c00157]

A Poly condensation of 1,4-dimethoxy-2,5-bis(trifluorovinyl)benzene (1) with bisphenols in the presence of K2CO3 afforded aromatic polymers 3 consisting of both the (E)- and (Z)-Ar-CF=CF-OAr' moieties in the main chains. The Mn and Mw values of polymer 3c prepared from bisphenol-AF were up to 6.62x10^4 and 1.29x10^5, respectively. The polymers 3 were transparent in the visible region (>400 nm) and exhibited good thermal stability (Td5% > 320 °C). Fluorescence spectroscopy and X-ray diffraction analysis indicated the amorphous character of polymer 3c. The drop-cast film of 3c showed that the refractive indices and the Abbe's number were comparable to those for widely used polymers having optical applications, such as polycarbonate and polystyrene.


Tomohiro Agou, Shogo Saruwatari, Tomohiro Shirai, Tatsuya Kumon, Shigeyuki Yamada, Tsutomu Konno, Yoshiyuki Mizuhata, Norihiro Tokitoh, Yoshihisa Sei, Hiroki Fukumoto, Toshio Kubota, J. Fluorine Chem. 2020, 234, 109512. [DOI: 10.1016/j.jfluchem.2020.109512]

α,ω-Diynes bearing a perfluoroalkylene linker HC≡C(CF2)nC≡CH (n = 4, 6) were obtained from commercially available α,ω-dienes H2C=CH(CF2)nCH=CH2 via bromination and dehydrobromination. In the presence of CoCl2-Zn-ZnI2 catalyst, the diyne HC≡C(CF2)4C≡CH underwent [2+2+2] cycloaddition reactions with terminal alkynes to afford benzene derivatives fused with an octafluorocyclohexene moiety. In this reaction, trimerization of the diyne was observed as a major side reaction. Rh-catalyzed aromatization polymerization of the diyne HC≡C(CF2)6C≡CH afforded an insoluble polymer consisting of a densely cross-linked, aromatic skeleton, which was characterized by solid^state CP-MAS, 13C NMR and IR spectroscopy. This insoluble polymer exhibited high thermal stability, and engineering applications of the product polymer are being evaluated.


Shigeyuki Yamada*, Akira Mitsuda, Kaoru Adachi, Mitsuo Hara, Tsutomu Konno, New J. Chem. 2020, 44, 5684–5691. [DOI: 10.1039/D0NJ00659A]

Herein, the synthesis and evaluation of light-emitting liquid-crystalline (LELC) polymers bearing a pentafluorinated bistolane-based luminophore are reported. Methacrylate monomers, prepared in five steps from readily available 4-alkoxy-substituted phenylacetylene derivatives, were subjected to radical polymerisation to produce polymers with 10–23 repeating units with a 48–89% yield. The polymers possess a high thermal stability of up to 353 °C and display a smectic (Sm) LC phase over a broad temperature range. They also exhibit a photophysical behaviour, whereby they demonstrate an intense photoluminescence (PL) in the solution and pristine powdered solid states. These PL emissions can be shifted from blue to light blue by modulating the length of the flexible alkylene-linkage. Interestingly, the LELC polymer materials exhibited PL even in the Sm phase, and the PL colour changed from blue to light-blue via a thermal phase transition.


Gen Egashira, Chihiro Kajimoto, Takuto Kataoka, Shigeyuki Yamada, Tsutomu Konno*, Synthesis 2020, 52, 1947–1958. [DOI: 10.1055/s-0039-1691744]

On treating 1,3,4-tribromo-1,1,2,2-tetrafluorobutane, readily prepared from commercially available 4-bromo-3,3,4,4-tetrafluorobut-1-ene, with 3,3 equivalents of LHMDS at 0 °C in THF, the corresponding lithium acetylide could be prepared quantitatively. The acetylide reacted well with various aldehydes, ketones, or chlorosilanes to give the corresponding acetylene derivatives in high yields. It was also found that various iodoarenes could participate in the cross-coupling reaction with the zinc acetylide, readily prepared from the lithium acetylide and ZnCl2·TMEDA complex, in the presence of Pd(PPh3)4to bring about the adducts in high yields. Thus-obtained acetylene derivatives underwent smooth Diels-Alder reaction with various 1,3-dienes to afford the corresponding 1,4- or 1,3-cyclohexadiene derivatives. In addition, it was revealed that the oxidative aromatization of the resulting cyclohexadiene derivatives with DDQ took place very smoothly, providing mulit-substituted benzene derivatives having a tetrafluoroethylene group.


Tomohiro Agou, Masaki Kohara, Yuuki Tamura, Keisuke Yamada, Kazuki Shiitsuka, Takaaki Hosoya, Yoshiyuki Mizuhata, Norihiro Tokitoh, Yuki Hayashi, Yusuke Moronuki, Akihiro Ishii, Yusuke Tanaka, Atsuya Muranaka, Masanobu Uchiyama, Shigeyuki Yamada, Tsutomu Konno, Hiroki Fukumoto, Toshio Kubota, Eur. J. Org. Chem. 2020, 1871–1880. [DOI: 10.1002/ejoc.202000152]

Helicenes fused with hexafluorocyclopentene (HFCP) were synthesized via oxidative photocyclization of stilbene derivatives (the Mallory reaction). Of the newly-obtained fluorinated helicenes, the [7]helicenes bearing one- or three-HFCP units were structurally characterized by X-ray crystallographic analysis. The attempted synthesis of [9]helicene fused with three HFCP units resulted in the unexpected formation of a novel double helicene consisting of [4]- and [6]-helicenes sharing peripheral benzene rings. Optical properties and chiral resolutions of the newly obtained HFCP-substituted helicenes are also described.


Shigeyuki Yamada*, Akito Nishizawa, Tomohiro Agou, Takaaki Hosoya, Toshio Kubota, Tsutomu Konno, Eur. J. Org. Chem. 2020, 870–877. [DOI: 10.1002/ejoc.201901794]

Herein, a series of 1,2-disubstituted 3,3,4,4,5,5-hexafluorocyclopentene derivatives is synthesized from the commercially available octafluorocyclopentene via addition-elimination reactions, and their photophysical properties are investigated in detail. 1,2-Bis[2-(4-alkoxyaryl)ethyn-1-yl]-3,3,4,4,5,5-hexafluorocyclopentene exhibits UV-absorption at 345 nm in CH2Cl2 and deep blue photoluminescence (PL). The PL properties of these derivatives, including color and maximum wavelength (λPL), are strongly affected by the electron-density distribution induced by the electronic characteristics of the alkoxy-substituents at the 4-position of the benzene ring, with more electron-donating substituents resulting in a larger shift of λPL to longer wavelengths. Note that the present light-emitting π-conjugated luminophores also exhibit relatively strong PL in the crystalline state, where λPL shifts can be introduced by modulation of the terminal alkoxy-chain length, resulting in different PL colors from light-blue to orange.

2019年


Shigeyuki Yamada*, Akito Nishizawa, Masato Morita, Takuya Hosokai, Yusuke Okabayashi, Tomohiro Agou, Takaaki Hosoya, Toshio Kubota, Tsutomu Konno, Org. Biomol. Chem. 2019, 17, 6911–6919. [DOI: 10.1039/c9ob01300h]

Herein, we prepared novel bent fluorine-containing donor-π-acceptor (D-π-A) molecules from commercially available octafluorocyclopentene using a facile two-step procedure, revealing that the above molecules absorb UV-light and exhibit yellow photoluminescence (PL) with high PL efficiencies (ΦPL) in solution. The corresponding Stokes shifts exceeded 10000 cm–1, and the maximum PL wavelength (λPL) strongly depended on solvent polarity or intermolecular interactions in the solid state. On the basis of a Lippert-Mataga plot, PL was confidently assigned to radiative relaxation from an intramolecular charge-transfer excited state. Moreover, the synthesized luminophores showed intense PL even in the crystalline state and exhibited alkoxy chain length-dependent PL behavior (e.g., high ΦPL, λPL = 486–540 nm).


Ryosuke Yakushijin, Shigeyuki Yamada, Tsutomu Konno*, J. Fluorine Chem. 2019, 225, 35–43. [DOI: 10.1016/j.jfluchem.2019.06.001]

In this article, we revealed synthetic utilization of thermally stable as well as easy-handling triethyl (1,1,2,2-tetrafluorobut-3-en-1-yl)silane as the tetrafluoroethylenating agent through Cu(I)-mediated cross-coupling reaction with various iodoarenes, in which would offer promising building block for versatile CF2CF2-containing organic molecules through easy carbon chain elongation at both ends. Specifically, the above tetrafluoroethylene-containing silyl reagent, readily prepared from commercially available 4-bromo-3,3,4,4-tetrafluorobut-1-ene, smoothly reacted with various iodoarenes in the presence of Cu(I), Ag(I), and pyridine in DMF at 60 °C for 16 h, the corresponding CF2CF2-containing aromatic compounds being afforded in moderate to good yields. Additioanlly, it was revealed that the coupling reaction dramatically facilitated when iodoarenes with an ortho-directing group, e.g., COOMe, were used as an electrophile, in which the acceleration effect was theoretically proved to stabilize the whole reaction system by coordination of the carbonyl oxygen to the copper atom.


Tatsuya Kumon, Kazuhiro Yoshida, Shigeyuki Yamada, Tomohiro Agou, Toshio Kubota, Tsutomu Konno*, Tetrahedron 2019, 75, 3713–3721. [DOI: 10.1016/j.tet.2019.05.042]

[2+3] Cycloaddition reaction of fluorine-containing alkynes with various 2-iodoaryl ketones in the presence of CoCl2(dppf) catalyst proceeded very smoothly to give the corresponding 2- or 3-fluoroalkylated indenols in 57–98% yields. These regioisomers could be successfully separated and obtained in a pure form. From X-ray crystallographic and NOESY analyses, major or minor regioisomers were determined as 3- or 2-fluoroalkylated indenols, respectively.


Masato Morita, Shigeyuki Yamada*, Tomohiro Agou, Toshio Kubota, Tsutomu Konno, Appl. Sci. 2019, 9, 1905. [DOI: 10.3390/app9091905]

Organic luminescent materials have a wide range of practical applications, but the understanding of the relationship between molecular structure and luminescent behavior is lacking. Herein, we synthesized fluorinated bistolanes with an electron-donating alkoxy substituent at one terminal and an electron-withdrawing substituent at the other to realize systematic control of the electron-density distribution. Evaluation of the phase transition behavior revealed that most of the fluorinated bistolanes showed liquid-crystalline (LC) behavior, with the phase transition temperature depending on the terminal substituents. Additionally, the fluorinated luminophores displayed intense photoluminescence (PL) in solution and in their crystal phases. Remarkably, the PL color shifted dramatically depending on the dipole moment (m||) along the long molecular axis; thus, PL tuning can be achieved through electronic modulation by precise control of the m|| of the luminophore. Interestingly, in the LC phases under thermal conditions, the maximum PL band shifted by 0.210 eV upon phase transition from the crystal to smectic A LC phases, indicating that PL tuning can also be achieved by controlling the aggregated structure. These results offer a new molecular design for easily tunable PL materials using the molecular properties or external stimuli for promising applications, including light-emitting displays and PL sensing materials.


Shigeyuki Yamada*, Kazuya Miyano, Tomohiro Agou, Toshio Kubota, Tsutomu Konno, Crystals 2019, 9, 195. [DOI: 10.3390/cryst9040195]

In this study, we designed and synthesized novel pentafluorinated bistolane derivatives with 2-chloropentyl or 2-chlorohexyl flexible units as novel light-emitting liquid crystals (LELCs). By measuring the phase-transition behaviors, all derivatives were found to display liquid-crystalline (LC) phases during both heating and cooling processes. Among the novel bistolanes, the S- and R-configured derivatives exhibited a chiral nematic (N*) phase with a typical Grandjean optical texture. Interestingly, the chiral derivatives also exhibited a blue phase with a typical platelet texture in a narrow temperature range (2–4 °C). Photophysical measurements revealed that the 2-chloroalkoxy-substituted pentafluorinated bistolanes exhibited intense photoluminescence (PL) both in solution and in crystalline phases. The PL characteristics, especially the maximum PL wavelength, were found to switch sensitively during the heating and cooling cycles depending on the molecular aggregates through the Cr ⇄ N* phase transition. The 2-chloroalkoxy flexible units induced dynamic changes in the LC and PL properties, providing valuable insight into the potential of various LELCs as PL sensing materials.


Shigeyuki Yamada*, Tsuyoshi Tanaka, Takahiro Ichikawa, Tsutomu Konno, ACS Omega 2019, 4, 3922–3932. [DOI: 10.1021/acsomega.8b03543]

Herein, we describe the synthesis of novel light-emitting liquid-crystalline (LC) compounds bearing pentafluorinated bistolane-based luminophores with a V- or a Y-shaped molecular geometry and the evaluation of their LC and photophysical characteristics. The V- or Y-shaped compounds exhibited a unique LC phase and showed photoluminescence (PL) behavior under various circumstances, such as in dilute solution or in the solid state. Notably, PL characteristics were observed even under high-temperature conditions with a crystal (Cr) to LC phase transition, although the PL efficiency (ΦPL) was gradually reduced due to thermal molecular motion. Interestingly, ΦPL was found to be completely recovered through the LC → Cr phase transition during the cooling process; the PL characteristics of the V- or Y-shaped compounds were sensitively changed by external thermal stress, giving these compounds the ability to act as thermoresponsive PL sensing materials.

2018年


Kazuhiko Matsumoto*, Yuki Haruki, Shunsuke Sawada, Shigeyuki Yamada, Tsutomu Konno, Rika Hagiwara, Inorg. Chem. 2018, 57, 14882–14889. [DOI: 10.1021/acs.inorgchem.8b02655]

The stabilization of complex fluoroanions derived from weakly acidic parent fluorides is a significant and ongoing challenge. The [SF5]– anion is recognized as one such case and only a limited number of [SF5]– salts are known to be stable at room temperature. In the present study, glyme-coordinated alkali metal cations (K+, Rb+, and Cs+) are employed to stabilize [SF5]–, which provides a simple synthetic route to a [SF5]– salt. The reactivities of KF and RbF with SF4 is significantly enhanced by complexation with G4, based on Raman spectroscopic analyses. A new room-temperature stable salt, [Cs(G4)2][SF5] (G4 = tetraglyme), was synthesized by stoichiometric reaction of CsF, G4, SF4. The vibrational frequencies of [SF5]– were assigned based on quantum-chemical calculations, and the shift of the G4 breathing mode accompanying coordination to metal cations was confirmed by Raman spectroscopy. Single-crystal X-ray diffraction revealed that Cs+ is completely isolated from [SF5]– by two G4 lignads and [SF5]– is disordered along the crystallographic two-fold axis. Hirshfeld surface analysis reveals that the H•••H interaction between two neighboring [Cs(G4)2]+ moieties is more dominant on the Hirshfeld surface than the interaction between the H atom in glyme molecules and the F atom in [SF5]–, providinga CsCl-type structural model where the large and spherical [Cs(G4)2]+ cations contact each other and the [SF5]– anions occupy interstitial spaces in the crystal lattice. The [SF5]– anion, combined with [Cs(G4)2]+, exhibits a very limited deoxofluorinating ability towards hydroxyl groups in both neat conditions and THF solutions.


Tomohiro Agou*, Seiya Nemoto, Shigeyuki Yamada, Tsutomu Konno, Yoshiyuki Mizuhata, Norihiro Tokitoh, Ryota Ebina, Akihiko Ishii, Takaaki Hosoya, Hiroki Fukumoto, Toshio Kubota, Asian J. Org. Chem. 2018, 7, 2484–2489. [DOI: 10.1002/ajoc.201800454]

An abbreviated synthesis of hexafluorocyclopentane-annulated 2,5-diarylfurans has been developed. 1,2-Dichloro-3,3,4,4,5,5-hexafluorocyclopentene was converted to corresponding polyfluorinated 1,2-diaroylalkenes, treatment of which with P(OEt)3 afforded the polyfluorinated 2,5-diarylfurans. Solid-state photo-luminescence of the furan derivatives exhibited remarkable red-shifts compared to fluorescence emissions in solution, probably because of intermolecular interactions in the solid state. Comparisons of the optical and electrochemical data of the fluorinated furan derivatives with those of a non-fluorinated 2,5-diarylfuran suggest that the perfluorocycloalkane-annulation effectively enhances the electron-accepting ability of the 2,5-diarylfuran framework.


Shigeyuki Yamada*, Akira Mitsuda, Kazuya Miyano, Tsuyoshi Tanaka, Masato Morta, Tomohiro Agou, Toshio Kubota, Tsutomu Konno, ACS Omega 2018, 3, 9105–9113. [DOI: 10.1021/acsomega.8b01490]

We herein describe the synthesis of novel pentafluorinated tolane fluorophores, which possess an extended π-conjugated structure with a large molecular dipole moment along the longitudinal axis. We also report a detailed evaluation of both the photophysical and thermal behaviors of these fluorophores. All molecules displayed photoluminescence (PL) characteristics in both the crystalline state and in dilute solutions. The large longitudinal dipole moment induced solvatochromic PL behavior, which switched sensitively with changes in the solvent polarity. In addition, incorporation of the fluorinated tolane-based solid-state light-emitting moiety into the polymer side chain was found to be responsible for the PL characteristics observed in the solid state. It was also noteworthy that the polymerization protocol led to a significant enhancement in the thermal stability, with the thermal decomposition temperature increased by 90 °C. Accordingly, novel solid-state light-emitting materials with high thermal stabilities were successfully developed as promising candidates for use in light-emitting and optoelectronic applications.


Shigeyuki Yamada*, Masato Morta, Tomohiro Agou, Toshio Kubota, Takahiro Ichikawa, Tsutomu Konno, Org. Biomol. Chem. 2018, 16, 5609–5617. [DOI: 10.1039/C8OB01497C]

We developed and characterized four polyfluorinated bistolane derivatives. These compounds, which possess either two alkoxy substituents or an alkoxy group and a bromine atom in their two molecular terminals, were synthesized from readily available 4-alkoxy-1-ethynylbenzene with a facile three-step procedure. Their thermodynamic and photophysical properties were evaluated in detail, and they were found to display both liquid-crystalline (LC) and photoluminescence properties. Remarkably, the photoluminescence behaviors dramatically changed during the thermal phase transition between the crystal and LC phases. Thus, these polyfluorinated bistolanes may be promising candidate for the thermoresponsive luminous molecules.


Ken Tamamoto, Shigeyuki Yamada, Tsutomu Konno*, Beilstein J. Org. Chem. 2018, 14, 2375–2383. [DOI: 10.3762/bjoc.14.213]

(1,1,2,2-Tetrafluorobut-3-en-1-yl)zinc bromide was prepared by insertion of zinc-silver couple into the CF2–Br bond of 4-bromo-3,3,4,4-tetrafluorobut-1-ene in DMF at 0 °C for 0.5 h, and the resultant polyfluorinated zinc reagent was found to be thermally stable at ambient temperature and storable for over a year in the refrigerator. This CF2CF2-containing organozinc reagent could be easily transmetallated to copper species, which underwent cross-coupling reactions with aromatic iodides or acyl chlorides promoted by copper(I) catalyst to produce a broad range of CF2CF2-containing organic molecules with good-to-excellent yields. Therefore, it could become a new and practical synthetic tool for producing functional molecules with a CF2CF2 fragment.


Tatsuya Kumon, Shigeyuki Yamada, Tomohiro Agou, Toshio Kubota, Tsutomu Konno*, J. Fluorine Chem. 2018, 213, 11–17 (DOI: 10.1016/j.jfluchem.2018.06.004).

Novel cobalt-catalyzed [2+2+2] cycloaddition using fluorine-containing alkynes was described. Cyclotrimerization of fluorinated alkynes under the influence of CoCl2(dppb) in acetonitrile at 80 °C for 3 h took place smoothly, affording the corresponding benzene derivatives in excellent yields with high regioselectivity. Additionally, intermolecular cycloaddition of fluorinated alkynes with non-fluorinated diynes also proceeded in the presence of a catalytic amount of CoCl2((S)-BINAP) and ZnI2 to give various bicyclic aromatic compounds in high yields.


山田重之,山崎 孝*, 有機合成化学協会誌 2018, 76, 111–121 (DOI: 10.5059/yukigoseikyokaishi.76.111).

Enormous attention has been paid to the fluorine-containing organic molecules in the field of medicinal, pharmaceutical, and material chemistry since fluorine or fluoroalkyl substituents incorporated into organic molecules often affect their chemical and physical properties. Therefore, significant effort has been devoted to the development of effective synthetic methods for organofluorine compounds. Recently, we have developed a regioselective synthetic method for perfluoroalkyl-substituted condensed polycyclic aromatic compounds, e.g. anthracenes, pentacenes, and pentaphenes. This article describes the effective introduction of perfluoroalkyl substituents into the condensed polycyclic aromatic compounds in a regioselective manner. In addition, evaluation of physical properties of the fluorine-containing pentacenes is described as well.


Keigo Yamashika, Suguru Morishitabara, Shigeyuki Yamada, Tsutomu Konno*, J. Fluorine Chem. 2018, 207, 24–37 (DOI: 10.1016/j.fluchem.2017.12.013).

An asymmetric carbon center with a tetrafluoroethylene fragment can be efficiently constructed via a highly enantioselective conjugate addition reaction of various arylboronic acids with β-(bromotetrafluoroethyl)-α,β-unsaturated ketones. This system can be successfully applied to an enantiomerically enriched tetrafluoroethylenated liquid crystalline molecule.


Tatsuya Kumon, Shohei Hashishita, Takumi Kida, Shigeyuki Yamada, Takashi Ishihara, Tsutomu Konno*, Beilstein J. Org. Chem. 2018, 14, 148–154 (DOI: 10.3762/bjoc.14.10)

Herein, we demonstrate an improved short-step protocol for the synthesis of multi-cyclic molecules having a CF2CF2-containing cyclohexadiene or cyclohexane framework in a mesogenic structure. These molecules are promising candidates for vertical alignment (VA)-mode liquid crystal (LC) display devices owing to their large negative dielectric constant. The tetrafluorinated multi-cyclic molecules were successfully obtained in only five or six reaction steps without the need for special handling techniques, as is generally required for thermally unstable organometallic species, representing a reduction of three reaction steps. The improved short-step synthetic protocol was also amenable to multi-gram preparation of these promising molecules, which may contribute significantly to the development of novel negative-type LC molecules containing CF2CF2-carbocycles.


Tatsuya Kumon, Siti Asiah Binti Mohd, Shigeyuki Yamada, Tsutomu Konno*, J. Fluorine Chem. 2018, 206, 8–18 (DOI: 10.1016/j.jfluchem.2017.12.003)

Hydrosilylation of fluorine-containing aromatic ketones with triethylsilane in the presence of a catalytic amount of a low-cost and an environmentally benign cobalt catalyst proceeded very smoothly to give the corresponding adducts. Interestingly, this hydrosilylation reaction was not applicable to non-fluorinated ketones. As revealed by density functional theory analysis, a fluorine substituent at the a-position plays a crucial role in facilitating the hydrosilylation reaction.


Shigeyuki Yamada, Junko Bessho, Hitoya Nakasato, Osamu Tsutsumi*, Dyes and Pig. 2018, 150, 89–96 (DOI: 10.1016/j.dyepig.2017.11.002).

Two series of donor–acceptor (D–A)-type azobenzene dyes with a tertiary amine as the donor were synthesized, and their photophysical and thermal properties were investigated. Although tertiary amines with the same Hammett constant were used, the properties of the molecules varied considerably depending on the molecular geometry of the tertiary amine. We found that the electron-donating properties could be controlled by the molecular geometry of the donor, as the geometry strongly affected the orientation of the n orbital of the donor relative to the p orbitals of the π-conjugated system of the phenyl ring. When the n orbital was fixed parallel to the p orbitals, the donor exhibited strong electron-donating properties. These results suggest that the molecular geometry should be considered in addition to the primary molecular structure for the design of highly functional materials.

2017年


Shigeyuki Yamada, Ken Tamamoto, Takumi Kida, Tomoyuki Asai, Takashi Ishihara, Tsutomu Konno*, Org. Biomol. Chem. 2017, 15, 9442–9454 (DOI: 10.1039/c7ob02399e)

Guided by theoretical calculations, we predicted that 5,5,6,6-tetrafluoro-1-methoxycyclohex-1-ene, a new structural motif, exhibits a large negative dielectric anisotropy, and then developed a synthetic strat- egy for the preparation of the novel tetrafluorinated tricyclic mesogen in twelve reaction steps starting from a commercially available fluorinated starting material. During the evaluation of its liquid-crystalline charac- teristics, the tetrafluorinated mesogen was found to display low birefringence and a large negative dielectric anisotropy, confirming that its molecular structure is a reasonable design for the further devel- opment of novel mesogenic molecules with large negative dielectric anisotropies.


Shigeyuki Yamada*, Masato Morita, Tsutomu Konno, J. Fluorine Chem. 2017, 202, 54–64 (DOI: 10.1016/j.jfluchem.2017.09.003)

The aim of this study was to design and develop new fluorinated light-emitting materials with multi-color photoluminescence that are not limited by their states. For this purpose, fluorinated bistolanes with an amino substituent, such as carbazol-9-yl, diphenylamino, and dimethylamino groups, as an electron-donating moiety were synthesized from readily available N,N-disubstituted 4-bromoaniline derivatives through five easy steps. The new fluorinated bistolane derivatives were found to display photoluminescence in dilute solutions as well as in the solid state. The luminescent color varied depending on the type of electron-donating group, and the emission color could be controlled from blue to yellowish-green depending on the electron-density distribution induced by electron-withdrawing pentafluorophenyl and electron-donating amino moieties. Moreover, the bistolanes with a large molecular dipole were found to exhibit solvatochromic photoluminescence. Therefore, multi-color luminescence from blue to yellow could be achieved in a single molecule depending on solvent polarity.


Shigeyuki Yamada*, Kazuya Miyano, Tsutomu Konno, Tomohiro Agou, Toshio Kubota, Takuya Hosokai, Org. Biomol. Chem. 2017, 15, 5949–5958 (DOI: 10.1039/c7ob01369h)
[Selected as OBC HOT Articles 2017]

We synthesised a series of dissymmetric bistolane derivatives and evaluated their liquid-crystallline (LC) and photoluminescence properties in detail. In measuring LC behaviours, rational structural design based on dissymmetric molecular structure and electron-density distribution facilitated production of LC phase with wide temperature range (up to 97 °C). In addition, dissymmetric bistolane derivatives were shown to strongly emit blue-photoluminescence in dilute solution and in crystalline states. It was found that dissymmetric bistolanes possess emissive features in even the LC phase and photoluminescence behaviours such as emission intensity and colour were sensitively switched depending on molecular aggregate structure caused by applying a thermal stimulus.


Shigeyuki Yamada, Shohei Hashishita, Hideaki Konishi, Yuji Nishi, Toshio Kubota, Tomoyuki Asai, Takashi Ishihara, Tsutomu Konno*, J. Fluorine Chem. 2017, 200, 47–58 (DOI: 10.1016/j.jfluchem.2017.05.013)

The synthetic protocols for symmetrical/unsymmetrical 3,6-disubstituted 1,1,2,2-tetrafluorocyclohexane molecules were successfully established for the first time. Some of thus obtained tetrafluorinated cyclohexanes underwent recrystallization to afford trans-configured products preferentially. One of the unsymmetrical trans-disubstituted tetrafluorocyclohexanes, trans-1-ethyl-2,2,3,3-tetrafluoro-4-[4-(trans-4-n-propylcyclohex-1-yl)phenyl]cyclohexane, was found to possess a low birefringence Δn (0.073) and a large negative dielectric anisotropy Δε (–9.4) in a binary mixture system, which were very prominent as characteristics of LC molecules in VA-mode driving LC displays.


Shigeyuki Yamada, Shohei Hashishita, Tomoyuki Asai, Takashi Ishihara, Tsutomu Konno*, Org. Biomol. Chem. 2017, 15, 1495–1509 (DOI: 10.1039/c6ob02431a).
[Highlighted in Synfacts 2017, 13, 0367]

We designed unprecedented negative dielectric molecules, which were tricyclic compounds with 5,5,6,6-tetrafluorocyclohexa-1,3-diene moiety in the mesogen, and firstly developed the effective synthetic protocol from commercially available 4-bromo-3,3,4,4-tetrafluorobut-1-ene. We also evaluated their physical properties for new mesogenic compounds, such as birefringence, dielectric anisotropy, and shear viscosity that were important characteristics to apply to a prominent flat LC display devices, which clearly showed not only a large negative dielectric anisotropy and birefringence but also even high viscosity.


Yukiho Sakaguchi, Shigeyuki Yamada, Tsutomu Konno*, Tomohiro Agou, Toshio Kubota, J. Org. Chem. 2017, 82, 1618–1631 (DOI: 10.1021/acs.joc.6b02793).

Highly regio- and stereoselective transformation of commercially available 4-bromo-3,3,4,4-tetrafluoro-1-butene into multisubstituted alkenes having a tetrafluoroethylene fragment through Heck reaction and/or Suzuki-Miyaura cross coupling reaction was established. Thus obtained alkenes underwent a smooth reductive coupling reaction with aldehydes under the influence of MeLi/LiBr-free, affording structurally unprecedented fluorinated materials.


Shigeyuki Yamada, Shun Yamaguchi, Osamu Tsutsumi*, J. Mater. Chem. C, 2017, 5, 7977–7984 (DOI: 10.1039/C7TC00728K).

Structure–property relationships of newly synthesized luminescent gold complexes were examined from the viewpoint of material applications. In particular, we investigated the effect of controlling the molecular electron-density distribution by introducing trifluoromethyl substituents into the complexes. The structures of the molecular aggregates were not affected by the trifluoromethyl substituents, as all the complexes formed antiparallel dimers in the crystal state. Moreover, we found that the trifluoromethyl substituents enhanced the thermal stability of the complexes without significantly changing the luminescence behaviour. Thus, while the thermal stability of these materials depends on the molecular structure, i.e. the molecular electron-density distribution, the luminescence behaviour mainly depends on the molecular aggregate structure. These results suggest that various material properties, e.g. luminescence colour and thermal stability, can be controlled independently by tuning the structures of molecules and molecular aggregates using trifluoromethyl substituents.


Shigeyuki Yamada, Keita Kinoshita, Shota Iwama, Takashi Yamazaki*, Toshio Kubota, Tomoko Yajima, Kyoko Yamamoto, Shinya Tahara, Org. Biomol. Chem. 2017, 15, 2522–2535 (DOI: 10.1039/C7OB00043J).

Symmetrical and unsymmetrical pentacenes carrying two perfluoroalkyl (Rf) chains, at the 6 and 13 positions, were synthesized from easily available pentacene-6,13-quinone via facile three or four step reactions. After extensive evaluation, it was clearly found that the control of both the electron density of the aromatic rings on the pentacene core and molecular alignment in the crystalline state nicely affected their physical properties. Thus, we successfully prove in this article that (1) their anti-oxidation ability was significantly enhanced due to a decrease in the HOMO and LUMO energy and (2) a distinct difference in charge-transporting properties was observed between the symmetrical and unsymmetrical pentacenes.


Shigeyuki Yamada, Yuki Rokusha, Ryo Kawano, Kaori Fujisawa, Osamu Tsutsumi*, Faraday Discuss. 2017, 196, 269–283 (DOI: 10.1039/C6FD00157B).

Mesogenic Au complexes with a biphenyl core were synthesized as new AIEgens, and their thermodynamic and photophysical properties were discussed. Similar to Au complexes with a phenyl core which have been reported previously, the complexes with a short alkoxy chain formed dimers in the crystal form. However, the complexes with a long alkoxy chain formed two-dimensional layer structures through multiple intermolecular interactions in both the crystalline and liquid-crystalline (LC) phases. The present Au complexes showed a high thermochemical stability against thermal decomposition and a high thermodynamic stability of the LC phase. Moreover, these materials exhibited intensive phosphorescence with a large quantum yield (66%) in the crystals. In the crystal and LC phase with a layer structure, the phosphorescence intensity was enhanced only on aggregation. Thus, these mesogenic Au complexes can be expected to be useful as phosphorescent AIEgens.

2016年


Ken Tamamoto, Shigeyuki Yamada, Masao Higashi, Tsutomu Konno*, Takashi Ishihara, J. Fluorine Chem. 2016, 190, 23–30 (DOI: 10.1016/j.jfluchem.2016.08.011).

In this paper are disclosed new aspects for chemical reactivity of benzyl α,β,β-trifluoroacrylate, which is already known to undergo C-C bond formation reactions via nucleophilic addition-elimination reaction or Diels-Alder cycloaddition reaction. The α,β,β-trifluoroacrylate reacted well with nucleophilic radical species, generated from cyclic ethers, to afford the corresponding radical adducts in good to excellent yield as a diastereomeric mixture. The radical addition protocol is successfully evolved into the new synthetic approach to γ-silyloxy-α,β,β-trifluorobutanoic acid derivatives, which fascinates as a promising precursors for medicinally as well as pharmaceutically-important organic molecules.


Shigeyuki Yamada, Masao Higashi, Tsutomu Konno*, Takashi Ishihara, Eur. J. Org. Chem. 2016, 2016, 4561–4568 (DOI: 10.1002/ejoc.201600837).

New 3,3,4-trifluoropyrrolidines were easily obtained by 1,3-dipolar cyclo- addition reactions of 2,3,3-trifluoroacrylate with imino esters derived from various phenylglycinates. The 1,3- dipolar cycloaddition was found to take place diastereoselectively. With the aid of a chiral auxiliary, the highly enantio- and diastereoselective synthesis of fluorinated pyrrolidine derivatives was achieved.


Shigeyuki Yamada, Kazunori Hondo, Tsutomu Konno*, Takashi Ishihara, RSC Adv. 2016, 6, 28458–28469 (DOI: 10.1039/c6ra00569a).

The Diels-Alder reaction of trifluorovinyl substances with various dienes proceeded well to give the corresponding trifluorinated cyclohexane derivatives in a regiospecific manner, while 2,3-difluorobuta-1,3-diene molecules also underwent a smooth Diels-Alder reaction with various dienophiles to afford the corresponding vic-difluorocyclohexene structure.


Takashi Nihei, Yuji Nishi, Natsumi Ikeda, Saya Yokotani, Takashi Ishihara, Satoru Arimitsu, Tsutomu Konno*, Synthesis 2016, 48, 865–881 (DOI: 10.1055/s-0035-1560390).

An efficient chromium(II)-mediated reductive coupling reaction of various CBrF2-containing molecules and aldehydes has been developed. This reaction proceeds presumably via the monofluorinated dichromium(III) intermediate generated by the carbon-fluorine bond activation, and provides a general and straightforward access to synthesize a variety of (E)- and (Z)-b-fluoroallylic alcohols in a highly stereoselective manner. Based on the novel reductive coupling, four types of fluoroalkene dipeptide analogues could be stereoselectively prepared.


Ryo Kawano, Osama Younis, Akihiro Ando, Yuki Rokusha, Shigeyuki Yamada, Osamu Tsutsumi*, Chem. Lett. 2016, 45, 66–68 (DOI: 10.1246/cl.150944). [Selected as Editor's Choice]

Gold(I) complexes with a flexible chain were synthesized, and their photophysical properties were discussed. Particular attention was focused on the effect of a slight difference at the chain terminal on their luminescence properties. Both complexes exhibited strong luminescence in crystals, albeit with no luminescence in isotropic liquids. The luminescence properties of those complexes were very sensitive to not only the primary structure but also the structure of molecular aggregates.

2015年


Yukiho Sakaguchi, Yoshitomo Nakazaki, Kazuki Moriyasu, Tsutomu Konno*, J. Fluorine Chem. 2015, 179, 64–70 (DOI: 10.1016/j.jfluchem.2015.06.013).

The reaction of various fluoroalkylated alkynes with 1.2 equiv of Co2(CO)8 in toluene at room temperature for 30 min took place smoothly to give the corresponding alkyne-cobalt complex quantitatively. Without its purification, treatment of the in situ-generated complex with 6.0 equiv of various non fluorinated alkynes at 130 °C for 4 h provided monofluoroalkylated multisubstituted benzenes in moderate to good yields.


Yusuke Watanabe, Tsutomu Konno*, J. Fluorine Chem. 2015, 174, 102–107 (DOI: 10.1016/j.jfluchem.2014.12.008).

Treatment of 4-bromo-3,3,4,4-tetrafluorobu-1-ene with 6.0 equiv. of various aryl halides in the presence of 9.0 equiv. of copper metal in DMSO at 160 °C for 24 h in a sealed tube gave the corresponding (1,1,2,2-tetrafluoro-3-buten-1-yl) group-substituted aromatics in acceptable yields.


Natsumi Ikeda, Tsutomu Konno*, J. Fluorine Chem. 2015, 173, 69–71 (DOI: 10.1016/j.jfluchem.2015.02.010).

Treatment of 4-bromo-3,3,4,4-tetrafluorobu-1-ene with 6.0 equiv. of various aryl halides in the presence of 9.0 equiv. of copper metal in DMSO at 160 °C for 24 h in a sealed tube gave the corresponding (1,1,2,2-tetrafluoro-3-buten-1-yl) group-substituted aromatics in acceptable yields.


Takashi Nihei, Tomoko Hoshino, Tsutomu Konno*, Org. Biomol. Chem. 2015, 13, 3721–3731 (DOI: 10.1039/c5ob00046g).

Treatment of various gem-difluorocyclopropenes with 1.2 equiv of n-Bu3SnH in the presence of 20 mol% of Et3B at 80 °C for 4 h led to the quantitative formation of the hydrostannylated products in a highly regio- and trans-selective manner. Additionally, the prepared trans-gem-difluorocyclopropylstannanes were treated with various agents, such as H2O, alcohols, carboxylic acids, and tosylamide, to give the corresponding β-fluoroallylic alcohols, ethers, esters, and amides respectively with exclusive Z selectivity in acceptable yields.


Takashi Yamazaki*, Noriko Mano, Reo Hikage, Tsutomu Kaneko, Tomoko Kawasaki-Takasuka, Shigeyuki Yamada, Tetrahedron 2015, 71, 8059–8066 (DOI: 10.1016/j.tet.2015.08.048).

Condensation of Hörner–Wadsworth–Emmons reagents 3 and ketones 2 with a perfluoroalkyl (Rf) moiety prepared in situ was proved to be significantly efficient and powerful methods for the construction of a wide variety of α,β-unsaturated esters with Rf and R1 groups both at the β-position due to convenient avoidance of usually tedious as well as troublesome isolation steps of these ketones 2.


Osama Younis, Yuki Rokusha, Nana Sugimoto, Kaori Fujisawa, Shigeyuki Yamada, Osamu Tsutsumi*, Mol. Cryst. Liq. Cryst. 2015, 617, 21–31 (DOI: 10.1080/15421406.2015.1075367).

Rod-like gold(I) complexes with phenyl, biphenyl, or naphthyl rings in a mesogenic core were synthesized by complexation of ethynyl-substituted aromatic derivatives with (tetrahydrothiophene)AuCl, followed by ligand exchange with alkyl isocyanide, to investigate the effects of molecular and molecular-aggregated structures on their liquid-crystalline (LC) behavior and photoluminescence properties. The gold complexes exhibited enantiotropic liquid crystallinity. Introduction of multi-ring systems into the mesogenic core effectively expanded the LC temperature range. A comparison of the photoluminescence properties in the crystalline phase showed that the molecular-aggregated structure plays a crucial role in the luminescence of these gold complexes.


Ryohei Watanabe, Kenjiro Uno, Makoto Muto, Shigeyuki Yamada, Osamu Tsutsumi*, Mol. Cryst. Liq. Cryst. 2015, 617, 32–39 (DOI: 10.1080/15421406.2015.1075368).

A highly ordered nanochannel array consisting of giant-ring-shaped polyoxomolybdate (POMo) was prepared via self-assembly of the oxomolybdate monomers. Concentration and pH optimization of the reaction solution favored the self-assembly; the nanochannel structure spontaneously self-constructed during the crystallization process. The obtained crystal showed a highly ordered nanochannel with a diameter of 2.0 nm and no distribution in the channel size. In addition, the material was found to be very stable at ambient temperature in atmospheric air due to the formation of three-dimensional crosslinks via Mo–O–Mo covalent bonds between neighboring molecules in the crystal.


Kaori Fujisawa, Shigeyuki Yamada, Yukihiro Yanagi, Yasunori Yoshioka, Ayumi Kiyohara, Osamu Tsutsumi*, Sci. Rep. 2015, 5, 7934 (DOI: 10.1038/srep07934).

A series of new cyclic trinuclear Au(I) complexes with alkoxy side chains of various lengths were synthesized as photoluminescence materials. None of the complexes emitted luminescence in solution; however, some showed photoluminescence in the crystalline phase. Single crystal X-ray structural analyses revealed that an intermolecular interaction between two Au atoms (aurophilic interaction) existed only in the emissive complexes, which formed molecular aggregates in the crystal. Because isolated molecules show no luminescence in the present system, we conclude that only molecules aggregated via aurophilic interactions can luminesce. We demonstrated that luminescence properties, such as colour and intensity, were very sensitive to the aggregated structure of the molecules. We also found that such luminescence properties can be controlled by a change in the aggregated structure induced by external stimuli, such as heat, solvent, and mechanical stress.

2014年


Takashi Nihei, Tomoko Hoshino, Tsutomu Konno*, Org. Lett. 2014, 16, 4170–4173 (DOI: 10.1021/ol5018596).

On treating gem-difluorocyclopropylstannanes, derived from the radical hydrostannation of gem-difluorocyclopropenes, with 1.5 equiv of MeLi in THF at –78 °C for 5 min, followed by quenching the reaction with various agents, such as H2O, alcohols, carboxylic acids, and tosylamide, the corresponding β-fluoroallylic alcohols, ethers, esters, and amide were obtained with exclusive Z-selectivity in acceptable yields.


Takashi Nihei, Yusuke Kubo, Takashi Ishihara, Tsutomu Konno*, J. Fluorine Chem. 2014, 167, 110–121 (DOI: 10.1016/j.jfluchem.2014.06.012).

Treatment of β-fluoroallyl phosphates with 2.2 equiv. of organocuprates, prepared readily from 2.2 equiv. each of CuCN and organometallic (organolithium reagents, Grignard reagents, and organizing reagents), in THF at –40 to 0 °C for 0.25 to 24 h gave γ-products in a highly regioselective manner. Thus obtained γ-adducts were subjected to the ring-closing metathesis, the corresponding cyclic fluoroalkenes being afforded in good yields.


Tsutomu Konno*, Misato Kishi, Takashi Ishihara, Shigeyuki Yamada, Tetrahedron 2014, 70, 2455–2463 (DOI: 10.1016/j.tet.2014.02.015).

CF3-containing diyne, readily prepared from (Z)-2,3,3,3-tetrafluoro-1-iodoprop-1-ene in two steps, was smoothly subjected to carbocupration reaction with various organocuprates, followed by treatment of the resultant carbocupration adducts with iodine, the corresponding vinyl iodides being formed in good yields in a cis-addition manner. Thus obtained iodide could be successfully converted into CF3-substituted trans-enediynes in high yields. Also hydrostannation reaction of the diyne proceeded well in a trans-addition manner to give the corresponding vinylstannane in high yield. The vinylstannane was also found to be effectively convertible to CF3-substituted cis-enediynes in high yields.


Tsutomu Konno*, Ryoko Kinugawa, Takashi Ishihara, Shigeyuki Yamada, Org. Biomol. Chem. 2014, 12, 1611–1617 (DOI: 10.1039/c3ob41903g).

On treating fluorine-containing internal alkynes with 1.2 equiv. of (trimethylsilyl)tributyltin in the presence of 2.5 mol% of Pd(PPh3)2Cl2 in THF at the reflux temperature for 6 h, the silylstannylation reaction proceeded smoothly to afford the corresponding silylstannylated adducts in high yields in a highly regio- and cis-selective manner. Switching the palladium catalyst from Pd(PPh3)2Cl2 to Pd(t-BuNC)2Cl2 promoted the formation of silylstannylated adducts with opposite regioselectivity. The thus obtained silylstannylated adducts were subjected to Stille cross-coupling reactions to furnish the corresponding fluoroalkylated vinylsilanes whose C–Si bond was converted to a C–C bond by treating with aldehyde in the presence of TBAF and Zn(OTf)2, the corresponding fluoroalkylated tetra-substituted alkenes being afforded in moderate to good yields with a defined stereochemistry.


Takashi Nihei, Saya Yokotani, Takashi Ishihara, Tsutomu Konno*, Chem. Commun. 2014, 50, 1543–1545 (DOI: 10.1039/c3cc47219a).

Highly nucleophilic (Z)- or (E)-α-fluoroalkenylchromium species could be generated in a stereoselective manner via C–F bond activation of CBrF2-containing molecules, and they reacted smoothly with various aldehydes to give (E)- or (Z)-β-fluoroallylic alcohol derivatives in high yields, respectively.


Shigeyuki Yamada, Shota Iwama, Keita Kinoshita, Takashi Yamazaki*, Toshio Kubota, Tomoko Yajima, Tetrahedron 2014, 70, 6749–6756 (DOI: 10.1016/j.tet.2014.07.069).

Novel syntheses of 13,14-bis(perfluoroalkyl)-substituted 5,8-diazapentaphene derivatives were realized by such a facile two-step protocol as consecutive benzyne insertion into C(O)–NH bonds of p-phenylene-bis(perfluoroalkanamides), followed by Friedel–Crafts type cyclization reaction, yielding the corresponding title compounds especially for the case of Rf=CF3 or C2F5. Additionally, an alternative approach based on condensation of cyclohexane-1,4-dione with (o-aminophenyl) perfluoroalkyl ketones, followed by dehydrogenation enabled us to effectively access to the same final products in better yields.

2013年


Tsutomu Konno*, Misato Kishi, Takashi Ishihara, Shigeyuki Yamada, J. Fluorine Chem. 2013, 156, 144–151 (DOI: 10.1016/j.jfluchem.2013.09.010).

Palladium(0)-catalyzed Sonogashira cross-coupling reaction of 2-fluoroalkylated (Z)-2-fluoro-1-iodoethene, which is easily prepared from commercially available polyfluorinated alcohols in facile three steps, with terminal alkynes in DMF at room temperature for 24 h took place stereospecifically to give the corresponding 1-fluoroalkylated (Z)-1-fluorobut-1-en-3-yne derivatives in good to excellent yield. Thus obtained fluoroalkylated 1-fluoroenynes were effectively subjected to addition–elimination reaction with various alkynyllithiums at room temperature, leading to 3-fluoroalkylated hex-3-ene-1,5-diyne derivatives in good to high yields with an excellent E selectivity.


Tsutomu Konno*, Tomoko Hoshino, Takumi Kida, Shinya Takano, Takashi Ishihara, J. Fluorine Chem. 2013, 152, 106–113 (DOI: 10.1016/j.jfluchem.2013.02.013).

Novel and short synthetic approaches to 2,3-dideoxy-2,2,3,3-tetrafluoropyranoses or azapyranoses have been developed successfully using commercially available reagents, such as 4-bromo-3,3,4,4-tetrafluoro-1-butene. This synthetic strategy involves an intermolecular reductive coupling of 4-bromo-3,3,4,4-tetrafluoro-1-butene and various chiral aldehydes using LiBr-free MeLi as a key transformation.


Atsunori Morigaki, Mio Kawamura, Satoru Arimitsu, Takashi Ishiahra, Tsutomu Konno*, Asian J. Org. Chem. 2013, 2, 239–243 (DOI: 10.1002/ajoc.201300007).

The synthesis of enamines from only tertiary amines has been developed by using a catalytic amount of Pd(OAc)2 (5 mol%) in air. These generated enamines were successfully used for 1,4-conjugated addition reactions with fluoroalkylated olefins as an alternative synthetic route for the formylmethylation of olefins. This reaction adds potential for the use of tertiary amines as a nucleophilic C2 synthon.


Shigeyuki Yamada, Toshio Takahashi, Tsutomu Konno, Takashi Ishihara*, J. Fluorine Chem. 2013, 149, 95–103 (DOI: 10.1016/j.jfluchem.2013.01.031).

Reaction of α,β,γ,γ,γ-pentafluorocrotonates with organocuprates derived from organomagnesium or zinc reagents in THF at −78 °C for 1 h took place smoothly to generate β-metallated intermediate, of which hydrolysis gave the β-reduction product in good yield. The fluorinated vinylcopper intermediate formed by fluorine–copper exchange was found to be stable at low temperature due to the strong electron-withdrawing effect of a CF3 group, and was readily converted to various types of β-substituted products in good yields with high stereoselectivity by treating with electrophiles, such as iodine and allylic bromides.


Atsunori Morigaki, Kazuki Tsukade, Satoru Arimitsu, Tsutomu Konno*, Toshio Kubota, Tetrahedron 2013, 69, 1521–1525 (DOI: 10.1016/j.tet.2012.12.012).

The reaction of β-fluoroalkylated α,β-unsaturated ketones with various enamines gave 4-fluoroalkylated 3,4-dihydro-2H-pyrans as a major product in good yields by a one-pot operation, and these products display the high diastereoselection just after single recrystallization. This unexpected result is rationalized by the unique reactivity of β-fluoroalkylated α,β-unsaturated ketones. As the synthetic application, 4-trifluoromethyl tetrahydropyran was synthesized in moderate isolated yield with high diastereoselectivity.


Atsunori Morigaki, Tomoo Tanaka, Tomotsugu Miyabe, Takashi Ishihara, Tsutomu Konno*, Org. Biomol. Chem. 2013, 11, 586–595 (DOI: 10.1039/c2ob26708j).

Treatment of β-fluoroalkylated-α,β-unsaturated ketones with 1.2 equiv. of various arylboronic acids in the presence of 5 mol% of [Rh(COD)2]BF4 and 6 mol% of (S)-BINAP in toluene/H2O (v/v = 4/1) at the reflux temperature for 3 h gave the corresponding Michael adducts in high yields with over 90% enantioselectivity. Though other electron-deficient alkenes, such as vinylsulfone and vinylphosphonate, were found to be much less reactive in the rhodium-catalyzed conjugate addition with arylboronic acids, the reaction of various arylstannanes toward such electron-deficient alkenes took place very smoothly to afford the corresponding adducts in high yields.


Atsunori Morigaki, Tomotsugu Miyabe, Kazuki Tsukade, Satoru Arimitsu, Takashi Ishihara, Tsutomu Konno*, Synthesis 2013, 45, 101–105 (DOI: 10.1055/s-0032-1317707).

1,4-Conjugated alkylation of fluoroalkylated olefins with organozinc reagents, such as RZnI and R2Zn, was conducted smoothly to give the corresponding products in moderate yields without the use of either transition metals or Lewis acids. This reaction protocol allows not only a wide range of alkyl groups but also electron-withdrawing groups to be incorporated as 1,4-conjugated adducts.


Takashi Yamazaki*, Masashi Ichikawa, Tomoko Kawasaki-Takasuka, Shigeyuki Yamada, J. Fluorine Chem. 2013, 155, 151–154 (DOI: 10.1016/j.jfluchem.2013.07.016).

A useful one-pot preparation method of allylic alcohols with fluorinated alkyl groups at the γ position was developed from the corresponding enoates by way of the DIBAL-mediated half reduction, followed by nucleophilic attack of Grignard reagents to aldehydes equilibrating with aluminium acetals.


Christoph Sämann, Matthias A. Schade, Shigeyuki Yamada, Paul Knochel*, Angew. Chem. Int. Ed. 2013, 52, 9495–9499 (DOI: 10.1002/anie.201302058).

Highly functionalized cyclic and acyclic alkenylzinc reagents bearing functional groups such as aldehyde, keto, and ester groups were readily prepared by either direct zinc insertion in the presence of LiCl or by magnesium insertion in the presence of LiCl and ZnCl2. Subsequent functionalization reactions, such as Negishi cross-couplings, acylations, and allylations, furnished polyfunctional compounds in excellent yields.


Shigeyuki Yamada, Keita Kinoshita, Shota Iwama, Takashi Yamazaki*, Toshio Kubota, Tomoko Yajima, RSC Adv. 2013, 3, 6803–6806 (DOI: 10.1039/C3RA40974K).

Commercially available anthraquinones were smoothly converted to either symmetrically or unsymmetrically substituted 9,10-bis(perfluoroalkyl)anthracene-9,10-diols by way of bistrifluoromethylation or successive trifluoromethylation-nucleophilic perfluoroalkylation, respectively, and these diols can be easily aromatized to form bis(perfluoroalkyl)anthracene derivatives in good yields by treatment with a mixture of CBr4 and PPh3. Further cross-coupling reactions using halogen-containing anthracene derivatives realized a successful extension of the original π-conjugation systems.


Aiichiro Nagaki, Daisuke Yamada, Shigeyuki Yamada, Masatomo Doi, Daisuke Ichinari, Yutaka Tomida, Naofumi Takabayashi, Jun-ichi Yoshida*, Aust. J. Chem. 2013, 66, 199–207 (DOI: 10.1071/CH12440).

A continuous flow microreactor method for generating and carrying out reactions on pyridyllithiums has been developed based on Br/Li exchange reactions of bromopyridines and dibromopyridines. The reactions can be carried out without using cryogenic conditions by virtue of short residence times and efficient heat transfer, while very low temperatures such as –78 or –110°C are required for conventional batch macro methods. Moreover, sequential introduction of two different electrophiles has been successfully achieved using dibromopyridines in an integrated flow microreactor system composed of four micromixers and four microtube reactors.


Tomoaki Ichikawa, Tomoko Kawasaki-Takasuka, Shigeyuki Yamada, Takashi Yamazaki*, Toshio Kubota, J. Fluorine Chem. 2013, 152, 38–45 (DOI: 10.1016/j.jfluchem.2012.10.013).

We have succeeded in establishment of a novel route for the construction of optically active CF3-containing carboxylic acids in a stereochemically predictable manner starting from easily available mandelic acid by convenient combination of the copper-mediated anti-SN2 type substitution and Ireland-Claisen rearrangement.

2012年


Tsutomu Konno*, Misato Kishi, Takashi Ishihara, Beilstein J. Org. Chem. 2012, 8, 2207–2213 (DOI: 10.3762/bjoc.8.249).

Treatment of readily prepared (Z)-6-benzyloxy-1,1,1,2-tetrafluoro-6-methyl-2-hepten-4-yne with 1.5 equiv of LHMDS in −78 °C for 1 h gave the corresponding trifluoromethylated diyne in an excellent yield. This diyne was found to be a good substrate for the carbocupration with various higher-ordered cyanocuprates to give the corresponding vinylcuprates in a highly regio- and stereoselective manner. The in situ generated vinylcuprates could react very smoothly with an excess amount of iodine, the vinyl iodides being obtained in high yields. Thus-obtained iodides underwent a very smooth Sonogashira cross-coupling reaction to afford various trans-enediynes in high yields.


Tsutomu Konno*, Takumi Kida, Akinori Tani, Takashi Ishihara, J. Fluorine. Chem. 2012, 144, 147–156 (DOI: 10.1016/j.jfluchem.2012.08.006).

Intermolecular Pauson–Khand reaction of fluoroalkylated alkynes with 2-norbornene or 2,5-norbornadiene at the reflux temperature of dichloroethane proceeded smoothly to give the corresponding cyclopentenone derivatives in high yields as a mixture of regioisomers. On the other hand, intramolecular Pauson–Khand reaction of fluorine-containing 1,6-enyne proceeded in the presence of NMO or TMANO to give the bicyclic adducts in good yields. Additionally, allyl CF3-propargyl ether also underwent a smooth Pauson–Khand reaction in the presence of amine oxide, the corresponding bicyclic compounds being obtained in a highly diastereoselective manner.


Tsutomu Konno*, Atsushi Ikemoto, Takashi Ishihara, Org. Biomol. Chem. 2012, 10, 8154–8163 (DOI: 10.1039/c2ob25718a).

Treatment of γ-fluoroallylic phosphate with various lower-ordered cyanocuprates derived from Grignard reagents, organolithium, and organozincs gave the corresponding SN2′ products having a fluorine atom at a quaternary carbon center in excellent yields. This system could be successfully extended to the chiral version, enantiomerically pure fluorine-containing materials also being obtained in high yield.


Yusuke Tanaka, Takashi Ishihara, Tsutomu Konno*, J. Fluorine Chem. 2012, 137, 99–104 (DOI: 10.1016/j.jfluchem.2012.03.002).

Oxidation of various fluoroalkyl-substituted methanol derivatives under the influence of a catalytic amount of sodium 2-iodobenzenesulfonate and Oxone® in CH3CN or CH3NO2 was investigated in detail. The efficiency of the newly developed oxidation was also evaluated by comparison to other oxidations, such as Dess–Martin, PDC, and Swern oxidation.


Aiichiro Nagaki, Yusuke Takahashi, Shigeyuki Yamada, Chika Matsuo, Suguru Haraki, Yuya Moriwaki, Songhee Kim, Jun-ichi Yoshida*, J. Flow Chem. 2012, 2, 70–72 (DOI: 10.1556/JFC-D-12-00004).

Vinyllithiums were effectively generated by bromine–lithium exchange reaction of vinyl bromides with one eq of s-BuLi in a flow microreactor system at 0 °C or 20 °C, although two eq of t-BuLi and much lower temperatures are required for a conventional macro batch reaction. Subsequent reactions with various electrophiles in the flow microreactor system gave the corresponding vinyl compounds in good yields.

2011年


Shigeyuki Yamada, Masahiro Kato, Yudai Komori, Tsutomu Konno, Takashi Ishihara*, Org. Biomol. Chem. 2011, 9, 5493–5502 (DOI: 10.1039/c1ob05545c).

2,2,3,3-Tetrafluorooxetane reacted easily with organolithium reagents to give 1,1,3-trisubstituted 2,2-difluoropropan-1-ols in good to excellent yields. On the other hand, the reaction with Grignard reagent led to 3-bromo-1,1-disubstituted 2,2-difluoropropan-1-ols in good yields. On treating with lithium enolates, generated from enol silyl ethers and MeLi/LiBr, the corresponding 1-bromo-2,2-difluoro-3,5-dicarbonyl compounds were obtained in fair to good yields. 3-Iodo-2,2-difluoropropanoate, prepared readily from 2,2,3,3-tetrafluorooxetane and NaI, reacted successfully with various silyl enol ethers in the presence of a radical initiator to provide the corresponding coupling products in good yields.


Tsutomu Konno*, Shinya Takano, Yoshikazu Takahashi, Hideaki Konishi, Yusuke Tanaka, Takashi Ishihara, Synthesis 2011, 33–44 (DOI: 10.1055/s-0030-1258330).

The reductive coupling of 4-bromo-3,3,4,4-tetrafluorobut-1-ene with 2.4 equivalents of various carbonyl compounds proceeded very smoothly in the presence of 2.4 equivalents of MeLi/LiBr-free at -78 ˚C for two hours, giving the corresponding adducts in high to excellent yields. On the other hand, triethyl(1,1,2,2-tetrafluorobut-3-enyl)silane, which could be prepared by treatment of 4-bromo-3,3,4,4-tetrafluorobut-1-ene and chlorotriethylsilane with magnesium at 0 ˚C for three hours, reacted with some aldehydes in the presence of 1 mol% of tetrabutylammonium fluoride, the desired adducts being obtained in good to high yields.


Aiichiro Nagaki, Shinya Tokuoka, Shigeyuki Yamada, Yutaka Tomida, Kojun Oshiro, Hideki Amii, Jun-ichi Yoshida*, Org. Biomol. Chem. 2011, 9, 7559–7563 (DOI: 10.1039/C1OB06350B).

Perfluoroalkyllithiums were effectively generated from perfluoroalkyl halides in the presence and absence of electrophiles using flow microreactor systems. The in situ trapping with electrophile is conducted at much higher temperatures than those required for batch macro reactors. The subsequent trapping method is quite effective for highly reactive electrophiles that are not compatible with the lithiation process.


Aiichiro Nagaki, Shigeyuki Yamada, Masatomo Doi, Naofumi Takabayashi, Jun-ichi Yoshida*, Green Chem. 2011, 13, 1110–1113 (DOI: 10.1039/C0GC00852D).

A flow microreactor method for the synthesis of disubstituted pyridines by generation of pyridyllithiums followed by reactions with electrophiles has been developed. By using a short residence time and efficient temperature control, the cryogenic conditions required for conventional batch macro processes can be avoided. Sequential introduction of two different electrophiles into dibromopyridines has been achieved using an integrated flow microreactor system composed of four micromixers and four microtube reactors, to obtain disubstituted pyridine compounds.


Matthias A. Schade, Shigeyuki Yamada, Paul Knochel*, Chem. Eur. J. 2011, 17, 4232–4237 (DOI: 10.1002/chem.201003273).

Readily available 1,1-dichloro-2-alkynes are versatile starting materials for the synthesis of polyfunctionalized allenes. They can be prepared from commercially available terminal alkynes in a two-step procedure. The Cu-mediated reaction of several 1,1-propargylic derivatives with functionalized alkyl, benzylic, or allylic zinc reagents proceeds exclusively with SN2 selectivity and allows a rapid and efficient synthesis of functionalized chloroallenes. These chloroallenes undergo a novel CuI-catalyzed substitution reaction with functionalized arylmagnesium reagents with excellent SN2 selectivity to give trisubstituted polyfunctionalized allenes. The functional group tolerance is excellent and functionalities, such as cyano, keto, ester, phosphate, trifluoromethyl, and halogens, are well tolerated.

2010年


Maiko Matsuoka, Minoru Yamamoto, Kaoru Adachi, Yasuhisa Tsukahara*, Tsutomu Konno, Design Monom. Polym. 2010, 13, 387–397 (DOI: 10.1163/138577210X509615).

Various effects on dispersion of multi-walled carbon nanotubes (MWCNTs) in organic solvent and in polymer film by means of pyrene-containing polymeric surface modifiers were investigated. Graft surface modifiers of poly(ethylene oxide) and of polystyrene with pyrene groups were synthesized by radical co-polymerization of corresponding macromonomers and a pyrene-containing methacrylate monomer. The effect of pyrene content on MWCNT dispersion was examined in THF with polymers of different unit ratio of macromonomer to pyrene monomer. The effect of the polymer architecture was explored with a linear polymer having a pyrene end-group and graft polymers having pyrene units. As a result, the dispersibility of MWCNT in THF was improved with increasing pyrene content in the graft polymer and was also improved by a branched architecture of the polymeric non-covalent surface modifier. Preparation of a homogeneously MWCNT dispersed polystyrene film was investigated with a pyrene-containing graft polystyrene as a compatibilizer between the polystyrene matrix and MWCNT as well.


Shigeyuki Yamada, Kanoko Shimoji, Toshio Takahashi, Tsutomu Konno, Takashi Ishihara*, Chem. Asian J. 2010, 5, 1846–1853 (DOI: 10.1002/asia.20100022).

Treatment of trifluorovinyl- or pentafluoropropen-1-yl sulfone or sulfoxide, which are easily prepared from commercially available 1,2-dibromofluoroalkanes, with various organocuprates affords substitution or β-reduction products in good to excellent yields through an addition–elimination reaction sequence.


Tsutomu Konno*, Kazuki Moriyasu, Ryoko Kinugawa, Takashi Ishihara, Org. Biomol. Chem. 2010, 8, 1718–1724 (DOI: 10.1039/b926192c).

Treatment of various fluorinated internal alkynes with 10 mol% of RhCl3·H2O and 30 mol% of i-Pr2NEt in toluene at the reflux temperature for 18 h gave the corresponding trimerization products as an isomeric mixture in high yields. Cycloaddition using 1.0 equiv. of fluorinated alkynes and 2.0 equiv. of non-fluorinated alkynes under the same reaction conditions as in the trimerization led to mono- and bis-fluoroalkylated benzene derivatives in high yields, together with small amounts of trimerization products. The reaction of fluorine-containing bispropargyl ether with non-fluorinated alkynes took place smoothly to afford the corresponding bicyclic molecules in good to high yields.


Shigeyuki Yamada, Paul Knochel*, Synthesis 2010, 2490–2494 (DOI: 10.1055/s-0029-1218816).

Functionalized aryl- or heteroarylmagnesium reagents, prepared from the corresponding bromides or iodides using halogen-magnesium exchange or direct magnesium insertion in the presence of lithium chloride, reacted smoothly with N-fluorobenzenesulfon­imide, (PhSO2)2NF, in the mixed solvent (4:1 CH2Cl2-perfluorodecalin) to give the corresponding aromatic fluorides in moderate to good yields.


Shigeyuki Yamada, Andrei Gavryushin, Paul Knochel*, Angew. Chem. Int. Ed. 2010, 49, 2215–2218 (DOI: 10.1002/anie.200905052).

Give me an “F”: Electrophilic fluorination of various aromatic and heteroaromatic Grignard reagents is smoothly performed with (PhSO2)2NF as fluorinating agent in a 4:1 mixture of CH2Cl2/perfluorodecalin (see scheme). This solvent system allows minimization of most side reactions.

2009年


Tsutomu Konno*, Ryoko Kinugawa, Atsunori Morigaki, Takashi Ishihara, J. Org. Chem. 2009, 74, 8456–8459 (DOI: 10.1021/jo9017028).

On treatment of various fluorinated internal alkynes with 1.2 equiv of hexabutylditin under the influence of 2.5 mol % of Pd(t-BuNC)2Cl2 in THF at room temperature for 4 h, the bisstannylation proceeded smoothly to afford the corresponding bisstannylated cis-adducts in high yields. Thus obtained adducts were subjected to the Stille cross-coupling reaction to give the corresponding tetrasubstituted fluorine-containing alkenes with defined stereochemistry in good yields.


Tsutomu Konno*, Shigeyuki Yamada, Akinori Tani, Masataka Nishida, Tomotsugu Miyabe, Takashi Ishihara, J. Fluorine. Chem. 2009, 130, 913–921 (DOI: 10.1016/j.jfluchem.2009.07.002).

Treatment of (E)-4,4,4-trifluoro-1-aryl-2-buten-1-one with various aryldiazonium salts in the presence of palladium catalyst gave the corresponding α-arylated Heck adducts with high regio- and stereoselectivity in good to high yields.


Tsutomu Konno*, Kazuki Moriyasu, Takashi Ishihara, Synthesis 2009, 1087–1094 (DOI: 10.1055/s-0028-1087988).

The reactions of fluoroalkylated acetylides with various nitrones were investigated. When nitrones with an alkyl substituent were employed, hydroxylamines were obtained in high yields, and smooth dehydroxylation followed, to give the corresponding propargylamines. Nitrones with an aryl substituent underwent nucleophilic addition and subsequent intramolecular cyclization, affording the corresponding fluoroalkylated dihydroisoxazoles in moderate yields. These sequences were also extended to chiral versions.


Tsutomu Konno*, Ken-ichi Taku, Shigeyuki Yamada, Kazuki Moriyasu, Takashi Ishihara, Org. Biomol. Chem. 2009, 7, 1167–1170 (DOI: 10.1039/b819476a).

Hydrosilylation reaction of various fluoroalkylated alkynes with Et3SiH in the presence of a catalytic amount of Co2(CO)8 was investigated. The hydrosilylation of the alkynes having fluoroalkyl and aryl groups took place smoothly with good regioselectivity (ca. 80:20). In sharp contrast, the reaction of the alkynes having a fluoroalkyl group and a benzyl-type substituent, or various propargyl alcohols gave the corresponding vinylsilanes in an excellent regio- and stereoselective manner. Treatment of the vinylsilanes with various aldehydes in the presence of Zn(OTf)2 and TBAF afforded the coupling products in good yields.

2008年


Shigeyuki Yamada, Emi Ishii, Tsutomu Konno, Takashi Ishihara*, Tetrahedron 2008, 64, 4215–4223 (DOI: 10.1016/j.tet.2008.02.089).

On treating perfluorocyclopentene with bis(tributylstannyl)cyanocuprate in THF at −78 °C for 1 h, perfluorocyclopentenylstannane was obtained in good yield. The reaction of the fluorinated vinylstannane with n-BuLi in THF at −78 °C for 1 h, followed by addition of carbonyl compounds, gave the corresponding allyl alcohols in good yields. On the other hand, Pd(0)-catalyzed cross-coupling reaction of perfluorocyclopentenylstannane with benzyl chloroformate in THF at reflux temperature for 2 h proceeded smoothly to form the decarbonated coupling product in high yield.


Tsutomu Konno*, Tomoo Tanaka, Tomotsugu Miyabe, Atsunori Morigaki, Takashi Ishihara, Tetrahedron Lett. 2008, 49, 2106–2110 (DOI: 10.1016/j.tetlet.2008.01.122).

Treatment of fluoroalkylated electron-deficient olefins with various boronic acids in the presence of a catalytic amount of Rh(I) coordinated with (S)-BINAP in toluene/H2O at the reflux temperature for 3 h gave the corresponding conjugate addition products with high enantioselectivity in high yields.


Tsutomu Konno*, Atsunori Morigaki, Kazuo Ninomiya, Tomotsugu Miyabe, Takashi Ishihara, Synthesis 2008, 564–572 (DOI: 10.1055/s-2008-1032143).

The hydrostannation, carbocupration, and carbozincation reactions of fluorinated alkynylphosphonates were investigated. The hydrostannation reaction proceeded smoothly without an additive (e.g., BEt3/O2, AIBN) to give the corresponding vinylstannanes in a highly regio- and stereoselective manner. Various cuprates, prepared from organolithium, Grignard, and organozinc reagents, could participate nicely in the carbocupration reactions, the corresponding adducts were obtained in good to high yields. Dialkylzinc reagents reacted smoothly with the alkynylphosphonates even in the absence of copper salt to afford the corresponding adducts in good yields.


Shigeyuki Yamada, Mayumi Noma, Kazunori Hondo, Tsutomu Konno, Takashi Ishihara*, J. Org. Chem. 2008, 73, 522–528 (DOI: 10.1021/jo701975y).

Benzyl α,β,β-trifluoroacrylate (1) was prepared in good yield via the reductive Br-F elimination of benzyl 2-bromo-2,3,3,3-tetrafluoropropanoate or the palladium-catalyzed cross-coupling reaction of 1,2,2- trifluorovinylstannane with benzyl chloroformate. On treating 1 with various Grignard reagents or dialkylzinc reagents in the presence of copper(I) salt, the corresponding β-substituted α,β-difluoroacrylates were obtained in high yields with high Z-selectivity. Additionally, trialkylaluminum reagents were also found to be good nucleophiles, the corresponding addition-elimination products being afforded in good yields but with low stereoselectivity.

2007年


Shigeyuki Yamada, Toshio Takahashi, Tsutomu Konno, Takashi Ishihara*, Chem. Commun. 2007, 3679–3681 (DOI: 10.1039/b705408d).

Fluorine–metal exchange reaction of 2,3,4,4,4-pentafluorocrotonates with organocuprate derived from Grignard reagent and CuCN takes place efficiently to generate the β-metallated tetrafluorocrotonate intermediate, which reacts with various electrophiles to give β-substituted 2,4,4,4-tetrafluorocrotonates.


Taichi Shimada, Tsutomu Konno, Takashi Ishihara*, Chem. Lett. 2007, 36, 636–637 (DOI: 10.1246/cl.2007.636).

On the treatment of silyl enolates derived from N-(3,3,3-trifluoropropanoyl)oxazolidinones with 2.0 equiv. of titanium(IV) halide at −20 °C for 2 h, a novel fluorine–halogen exchange reaction occurred efficiently to give 3-halo-3,3-difluoropropanoic imides in high yields.


Shigeyuki Yamada, Emi Ishii, Tsutomu Konno, Takashi Ishihara*, Org. Biomol. Chem. 2007, 5, 1442–1449 (DOI: 10.1039/b701702b).

The addition of heteroaromatic lithium reagents 2 to a THF solution of perfluorocyclopentene (1) provided preferentially the corresponding monosubstituted products 5, while the addition of 1 to 2 effectively gave the 1,2-disubstituted products 6 in good to excellent yields. The reaction of 1 with sodiomalonate 3 or phosphonium ylide 4 also proceeded smoothly to form the 1,3-disubstituted product 8 or 10 in high yield, respectively.

2006年


Tsutomu Konno*, Shigeyuki Yamada, Akinori Tani, Tomotsugu Miyabe, Takashi Ishihara, Synlett 2006, 3025–3028 (DOI: 10.1055/s-2006-951496).

Treatment of (E)-4,4,4-trifluoro-1-phenyl-2-buten-1-one with various aryldiazonium salts in the presence of a palladium catalyst led to a smooth Heck reaction, furnishing α-arylated adducts in good yields.


Satoru Arimitsu, Tsutomu Konno, John T. Gupton, Takashi Ishihara, Hiroki Yamanaka*, J. Fluorine Chem. 2006, 127, 1235–1241 (DOI: 10.1016/j.jfluchem.2006.07.001).

The reaction of β-fluoro vinamidinium salt 1 with Horner–Wadsworth–Emmons reagents (HWE) such as diethyl(ethoxycarbonyl)methylphosphonate (2a), diethyl(methoxycarbonyl)methylphosphonate (2b), diethyl-2-oxopropylphosphonate (2c), diethyl benzylphosphonate (2d), tetraethyl methylenediphosphonate (2e) and diethyl cyanomethylphosphonate (2f) under basic conditions gave the fluorinated 1,3-butadienylphosphonates 3 in moderate to good yields. The phosphonates 3 could be hydrolyzed with a 10% HCl aqueous solution to afford the corresponding γ-(diethylphosphono)-α-fluoro-α,β-unsaturated aldehydes 7 in good yields. The treatment of the phosphonate 3c with an NH3 aqueous solution at 70 °C produced the pyridine derivative 8 in 60% yield.


Taichi Shimada, Masamitsu Yoshioka, Tsutomu Konno, Takashi Ishihara*, Chem. Commun. 2006, 3628–3630 (DOI: 10.1039/b603882d).

The Reformatsky-type reaction of 2-bromo-3,3,3-trifluoropropanoic imide with various types of imines, in the presence of ZnBr2 as a Lewis acid in THF at 0 °C for 3 h, gave the corresponding α-trifluoromethyl-β-amino acid derivatives in a highly anti-selective manner.


Tsutomu Konno*, Ken-ichi Taku, Takashi Ishihara, J. Fluorine Chem. 2006, 127, 966–972 (DOI: 10.1016/j.jfluchem.2006.04.012).

Treatment of fluoroalkylated alkynes with various aryl halides and arylboronic acids in the presence of Pd(0) in DMF/H2O at 100 °C for 2 h led to the smooth three-component coupling reaction, the corresponding tetrasubstituted alkenes being obtained in high yields stereoselectively.


Tsutomu Konno*, Go Nagai, Takashi Ishihara, J. Fluorine Chem. 2006, 127, 510–518 (DOI: 10.1016/j.jfluchem.2005.11.009).

The fluorine-containing dicobalthexacarbonyl complex, prepared readily from γ-fluoroalkylated propargyl acetates and Co2(CO)8, reacted smoothly with various nucleophiles at the propargylic position, followed by oxidative decomplexation under the influence of Fe(NO3)3, to afford fluoroalkylated alkynes bearing various types of alkyl side chains in good to high yields.


Tsutomu Konno*, Tsuyoshi Takehana, Makoto Mishima, Takashi Ishihara, J. Org. Chem. 2006, 71, 3545–3550 (DOI: 10.1021/jo0602120).

The regioselective palladium-catalyzed formate reduction of γ-fluoroalkylated allylic esters is described. Reduction of the allylic esters under the influence of palladium with a monodentate phosphine ligand proceeded preferentially at the γ position, the corresponding reduction products with a fluoroalkyl group at the tertiary carbon being afforded in high yields. When the chiral allylic ester was employed, complete chirality transfer was observed, leading to the optically active materials in high yields.


Takashi Ishihara*, Toshiya Mantani, Tsutomu Konno, Hiroki Yamanaka, Tetrahedron 2006, 62, 3783–3793 (DOI: 10.1016/j.tet.2005.11.086).

N,N-Dialkyl(3,3,3-trifluoro-1-propynyl)amines were prepared by a three-step procedure starting from commercially available 2,2,3,3,3-pentafluoropropanol. The reactions of these trifluoromethylated ynamines with some electrophiles, such as aldehydes, halogens or N-halosuccinimides (NXS), were investigated. The fluorinated ynamines reacted with aldehydes in the presence of a catalytic amount of Lewis acid to provide the corresponding α-(trifluoromethyl)-α,β-unsaturated amides in good to excellent yields with high Z-stereoselectivity. These ynamines reacted with molecular bomine to give, after treatment with sodium hydrogen carbonate, N,N-dialkyl-2-bromo-3,3,3-trifluoropropanamides in good yields. The reaction with an equimolecular amount of NXS in aqueous acetonitrile also gave the corresponding 2-halo-3,3,3-trifluoropropanamides in good to excellent yields. On the other hand, the reaction of the ynamine with NXS in anhydrous acetonitrile led to the formation of the addition products in high yields. Upon treating the addition products with an equimolecular amount of NX′S in aqueous acetonitrile, the corresponding 2,2-dihalo(X,X′)-3,3,3-trifluoropropanamides were produced in nearly quantitative yields.


Taichi Shimada, Masamitsu Yoshioka, Tsutomu Konno, Takashi Ishihara*, Org. Lett. 2006, 8, 1129–1131 (DOI: 10.1021/ol0531435).

The TiCl4-catalyzed Evans−aldol reaction of optically active 3,3,3-trifluoropropanoic imide gave the non-Evans syn product stereoselectively, whereas the Reformatsky reaction of 2-bromo-3,3,3-trifluoropropanoic imide in the presence of Et3Al led to the Evans anti product. These new approaches enabled us to synthesize all stereoisomers of trifluoromethylated aldol products for the first time.


Shigeyuki Yamada, Mayumi Noma, Tsutomu Konno, Takashi Ishihara*, Hiroki Yamanaka, Org. Lett. 2006, 8, 843–845 (DOI: 10.1021/ol052897g).

On treating readily prepared benzyl 2,3,3-trifluoroacrylate with various Grignard reagents, e.g., aryl-, alkyl-, or alkenylmagnesium halide, in the presence of a catalytic amount of copper(I) salt in THF at −78 °C for 1 h, the corresponding α,β-difluoroacrylates were obtained in 54−98% yields with high Z-selectivity.


Tsutomu Konno*, Jungha Chae, Tomoo Tanaka, Takashi Ishihara, Hiroki Yamanaka, J. Fluorine. Chem. 2006, 127, 36–43 (DOI: 10.1016/j.fluchem.2005.09.015).

Hydroalumination, hydrocupration, and hydroboration reactions of various fluorine-containing alkynes were investigated. The alkyne reacted smoothly with 2.0 equiv. of Red-Al at −78 °C to give the hydroaluminated adduct in a highly regio- and stereoselective manner, which was treated with iodine, the corresponding vinyliodide being produced in moderate yield. Hydrocupration of the alkynes also took place, but the resulting vinylmetal reacted with various electrophiles sluggishly. In sharp contrast, the reaction with dicyclohexylborane proceeded smoothly to afford the cis-addition products preferentially, which were subjected to Suzuki-Miyaura cross-coupling reaction, leading to trisubstituted alkenes in high yields.

2005年


Tsutomu Konno*, Masashi Kanda, Takashi Ishihara, Hiroki Yamanaka, J. Fluorine Chem. 2005, 126, 1517–1523 (DOI: 10.1016/j.jfluchem.2005.08.013).

The palladium-catalyzed allylation reaction of trifluoroalanine derivatives with various allyl carbonates was examined. When N-Cbz-protected alanine derivative was employed, the desired C-monoallylated product was obtained in good yield, together with C,N-diallylated and N-monoallylated ones. Changing the protecting group from Cbz to PMP group caused an exclusive formation of C-monoallylated products in high yields. The reaction with various types of allyl carbonates also proceeded smoothly. Based on the present palladium-catalyzed allylation reaction, the total synthesis of α-CF3 leucine analogue was achieved.


Tsutomu Konno*, Jungha Chae, Tomotsugu Miyabe, Takashi Ishihara, J. Org. Chem. 2005, 70, 10172–10174 (DOI: 10.1021/jo051700v).

The palladium-catalyzed annulation reaction of fluoroalkylated alkynes with various 2-iodobenzylidenamines was investigated. In the presence of a catalytic amount of Pd(PPh3)4, the reaction took place smoothly to give the corresponding 4-fluoroalkylated isoquinoline in high yield as a single isomer. No other regioisomer was detected.


Tsutomu Konno*, Takeshi Daitoh, Atsushi Noiri, Jungha Chae, Takashi Ishihara, Hiroki Yamanaka, Tetrahedron 2005, 61, 9391–9404 (DOI: 10.1016/j.tet.2005.07.022).

The carbometallation reactions of fluoroalkylated internal alkynes with various organocopper reagents derived from organolithium, Grignard, and organozinc reagents were examined. All carbocupration reactions proceeded smoothly in a highly regio- and stereo-selective manner to give the corresponding vinylcopper intermediates. The intermediates reacted with H+ smoothly, leading to the trisubstituted alkenes in high to excellent yields, whereas they reacted only with strictly limited carbon electrophiles such as allyl-, crotyl-, methallyl bromide, etc, probably due to the low reactivity exerted by an electron-withdrawing fluoroalkyl group. Treatment of vinylcopper with iodine resulted in a high yield of the corresponding vinyl iodide, which was employed successfully for Suzuki–Miyaura and Sonogashira cross-coupling reactions. In addition, two key reactions, the carbocupration and the Suzuki–Miyaura cross-coupling reaction realized the first highly stereoselective total synthesis of anti-estrogen drug, panomifene.


Shigeyuki Yamada, Tsutomu Konno, Takashi Ishihara*, Hiroki Yamanaka, J. Fluorine Chem. 2005, 126, 125–133 (DOI: 10.1016/j.fluchem.2004.10.047).

The treatment of octafluorocyclopentene with organolithium reagents gave the corresponding symmetrical disubstituted perfluorocyclopentenes in good to high yields. The reaction with Grignard reagents led to the monosubstituted perfluorocyclopentenes, which were subjected to the further nucleophilic substitution reaction using another Grignard or aryllithium reagents, unsymmetrical disubstituted perfluorocyclopentenes being obtained in high yields.

2004年


Tsutomu Konno*, Jungha Chae, Takashi Ishihara, Hiroki Yamanaka, Tetrahedron 2004, 60, 11695–11700 (DOI: 10.1016/j.tet.2004.10.005).

The palladium-catalyzed annulation reaction of a variety of fluorine-containing internal alkynes with 2-iodophenol derivatives was investigated. The use of P(t-Bu)3 as a ligand on palladium was found to be crucial in this annulation reaction, resulting in the exclusive formation of 3-fluoroalkylated benzofurans in high yields. 19F NMR analysis of the reaction mixture revealed that the addition of phenol to the fluoroalkylated alkynes was followed by intramolecular Heck reaction, giving to the corresponding 3-fluoroalkylated benzofurans.


Tsutomu Konno*, Jungha Chae, Takashi Ishihara, Hiroki Yamanaka, J. Org. Chem. 2004, 69, 8258–8265 (DOI: 10.1021/jo048872x).

Treatment of various types of fluoroalkylated alkynes with o-iodoaniline in the presence of Pd(PPh3)4 in DMF at 80 °C for 8 h mainly gave 2-fluoroalkylated indoles in high yields. The use of P(o-Tol)3 instead of PPh3 as a ligand led to the preferential formation of 3-fluoroalkylated indoles in high yields. Interestingly, the reaction of trifluoromethylated alkynes bearing a benzylic substituent afforded 2- or 3-trifluoroethylated indole derivatives in good yields.


Kei Sato, Takashi Sekiguchi, Takashi Ishihara*, Tsutomu Konno, Hiroki Yamanaka, J. Org. Chem. 2004, 69, 5041–5047 (DOI: 10.1021/jo0358729).

The reductive coupling reaction of N-methoxy-N-methyl-2-bromo-2,3,3,3-tetrafluoropropanamide (Weinreb amide) with various aldehydes under the influence of the combined reagent, 1.2 equiv each of triphenylphosphine and titanium(IV) isopropoxide, took place smoothly at ambient temperature to give the corresponding α-fluoro-α-(trifluoromethyl)-β-hydroxy amides in a highly erythro-selective manner. The high erythro selectivity was also obtained even by employing a combination of triphenylphosphine (1.2 equiv) and a catalytic amount of titanium(IV) isopropoxide.


Takashi Sekiguchi, Kei Sato, Takashi Ishihara*, Tsutomu Konno, Hiroki Yamanaka, Chem. Lett. 2004, 33, 666–667 (DOI: 10.1246/cl.2004.666).

The reactions of benzyl 2-bromo-2,3,3,3-tetrafluoropropanoate with various types of chiral imines in the presence of zinc in THF at room temperature were revealed to afford the threo- and erythro-isomers of α-fluoro-α-(trifluoromethyl)-β-amino esters with high diasteremeric excesses in fair to good chemical yields.


Jungha Chae, Tsutomu Konno*, Takashi Ishihara, Hiroki Yamanaka, Chem. Lett. 2004, 33, 314–315 (DOI: 10.1246/cl.2004.314).

The palladium-catalyzed annulation reaction of a variety of fluorine-containing internal alkynes with 2-iodoaniline derivatives took place smoothly to give the corresponding 2,3-disubstituted indole derivatives in good to excellent yields.


Tsutomu Konno*, Takeshi Daitoh, Atsushi Noiri, Jungha Chae, Takashi Ishihara, Hiroki Yamanaka, Org. Lett. 2004, 6, 933–936 (DOI: 10.1021/ol036440n).

A highly regio- and stereoselective carbometalation reaction of fluoroalkylated internal alkynes with organocopper reagents is described. This reaction is utilized successfully in the short, stereoselective total synthesis of the antiestrogenic drug panomifene.


Tsutomu Konno*, Tsuyoshi Takehana, Jungha Chae, Takashi Ishihara, Hiroki Yamanaka, J. Org. Chem. 2004, 69, 2188–2190 (DOI: 10.1021/jo030272v).

Carbostannylation of fluoroalkylated alkynes with various allylstannanes in the presence of AIBN was investigated. In the case of the allylstannane having an electron-withdrawing group at the β position, the reaction proceeded highly regio- and stereoselectively to give the corresponding allylstannylated products in high yields. Even in the absence of AIBN, the reaction took place smoothly in a highly regio- and stereoselective manner under an atmosphere of air. Thus-obtained vinylstannanes were subjected to the Migita−Kosugi−Stille coupling reaction conditions, affording the tetrasubstituted alkenes in excellent yields.


Tsutomu Konno*, Jungha Chae, Tomoo Tanaka, Takashi Ishihara, Hiroki Yamanaka, Chem. Commun. 2004, 690–691 (DOI: 10.1039/b316065c).

The one-pot synthesis of trisubstituted alkenes starting from fluoroalkylated internal alkynes was investigated. Hydroboration of the alkynes proceeded in a highly regio- and stereoselective manner to give the corresponding vinylboranes in excellent yields. Without isolation, treatment of the vinylboranes with various aryl halides under the Suzuki–Miyaura cross-coupling conditions gave the fluoroalkylated trisubstituted alkenes in high yields with complete retention of the olefinic geometry.


Kei Sato, Takashi Sekiguchi, Takashi Ishihara*, Tsutomu Konno, Hiroki Yamanaka, Chem. Lett. 2004, 33, 154–155 (DOI: 10.1246/cl.2004.154).

N-Methoxy-N-methyl-2-bromo-2,3,3,3-tetrafluoropropanamide underwent highly stereoselective aldol-type reaction with various aldehydes under the influence of triphenylphosphine—a catalytic amount of titanium(IV) isopropoxide at room temperature to give the erythro-isomers of α-fluoro-α-(trifluoromethyl)-β-hydroxy amides preferentially in good to excellent yields.


Tsutomu Konno*, Tsuyoshi Takehana, Takashi Ishihara, Hiroki Yamanaka, Org. Biomol. Chem. 2004, 2, 93–98 (DOI: 10.1039/b310950j).

The allylic substitution reaction of α-fluoroalkylated allyl mesylates with various carbon nucleophiles in the presence of transition metal catalyst (Pd and Mo) proceeded with high regioselectivity to give the corresponding γ-fluoroalkylated products in excellent yields.

2003年


Tsutomu Konno*, Jungha Chae, Masashi Kanda, Go Nagai, Kazushige Tamura, Takashi Ishihara, Hiroki Yamanaka, Tetrahedron 2003, 59, 7571–7580 (DOI: 10.1016/s0040-4020(03)01199-2).

Treatment of per- or polyfluoroalkylated vinyl iodides 5 with 2 equiv. of n-BuLi in THF produced the corresponding lithium acetylides in situ, which were transformed into zinc acetylides by the addition of ZnCl2·TMEDA complex into the reaction mixture. The in situ generated zinc acetylides were exposed to the cross-coupling conditions such as ArI/cat. Pd(PPh3)4, reflux, 6–12 h, giving rise to the desired per- or polyfluoroalkylated acetylenes in high yields. In the case of trifluoromethylated acetylene, commercially available 2-bromo-3,3,3-trifluoropropene 6 could also be used instead of 5 as the starting material. In the acetylenes having a fluoroalkyl group and an aliphatic side chain, vinyl iodides 7, prepared by radical addition of perfluoroalkyl iodide to terminal acetylenes, were treated with t-BuOK at room temperature or at the reflux temperature of benzene, affording the desired compounds in good yields.


Jungha Chae, Tsutomu Konno*, Masashi Kanda, Takashi Ishihara, Hiroki Yamanaka, J. Fluorine Chem. 2003, 120, 185–193 (DOI: 10.1016/s0022-1139(02)00328-7).

The hydrostannation reaction of various fluoroalkylated acetylene derivatives with tributyltin hydride was investigated using a variety of catalysts in toluene. Among them, the Et3B-induced hydrostannation reaction gave the highest regio- and stereo-selectivity. Their selectivity was mostly influenced upon the difference of the substituent X at the aromatic ring of the aryl-substituted internal acetylenes. Thus, the acetylenes having a halogen atom or an electron-donating group as X reacted smoothly with tributyltin hydride, affording the vinylstannane 4Z exclusively, while the acetylenes having an electron-withdrawing group (X=CO2Et, NO2) resulted in the preferential formation of 5E. The plausible mechanism of the formation of these products was discussed.


Koichiro Kase, Mitsuhiko Katayama, Tsutomu Konno, Takashi Ishihara, Hiroki Yamanaka*, J. Fluorine Chem. 2003, 120, 33–39 (DOI: 10.1016/s0022-1139(02)00281-6).

β-Trifluoroethoxy vinamidinium salts 1 reacted smoothly with various types of the carbanions, generated by treatment of ketones, esters, amide and nitriles with LDA, to give the corresponding trifluoroethoxylated multifunctional dienamine derivatives 3 in moderate to good yields. On the other hand, the reaction of 1 with lithium acetylide and other carbanions derived from methyl compounds bearing sulfonyl, sulfinyl, and phosphonyl groups produced the corresponding α,β-unsaturated aldehydes 5 in good yields.

2002年


Tsutomu Konno*, Mitsuru Tanikawa, Takashi Ishihara, Hiroki Yamanaka, Collect. Czech. Chem. Commun. 2002, 67, 1421–1435 (DOI: 10.1135/cccc20021421).

The reaction of fluoroalkylated propargyl mesylates with various nucleophiles, such as zinc reagents and enolates derived from 1,3-dicarbonyl compounds, in the presence of a palladium catalyst was investigated in detail. Various zinc reagents participated in the coupling reaction to give the corresponding fluoroalkylated allenes in good yields. When chiral mesylates were employed, the corresponding optically active allenes were obtained without any loss of enantiomeric purity in the reaction. On the other hand, treatment of trifluoromethylated propargyl mesylate with stabilized carbanions derived from methyl acetoacetate, acetylacetone, and diethyl malonate afforded fluorine-containing furan derivatives in moderate to high yields.


Kazuhide Mima, Kei Sato, Takashi Ishihara*, Tsutomu Konno, Hiroki Yamanaka, J. Fluorine Chem. 2002, 115, 55–65 (DOI: 10.1016/s0022-1139(02)00005-2).

When isomerically pure erythro- and threo-α-allylated-α-fluoro-β-hydroxy carboxylic acid esters were subjected to the intramolecular cyclization reaction with iodine and pyridine at −15 °C to ambient temperature for 6–9 h, the corresponding 3-fluorotetrahydrofuran-3-carboxylate derivatives were obtained in good yields as isomeric mixtures of the ratio of 3A:3B = 10–20:90–80 or 4C:4D = 28–39:72–61, respectively.


Takashi Ishihara*, Kazuhide Mima, Tsutomu Konno, Hiroki Yamanaka, Tetrahedron Lett. 2002, 43, 3493–3497 (DOI: 10.1016/s0040-4039(02)00608-1).

Treatment of α-bromo-α-fluoro-β-hydroxy esters with trimethylaluminum in dichloromethane, followed by reaction with allylic stannanes and a catalytic amount of triethylborane at −15°C, gave the corresponding threo-α-allylated α-fluoro-β-hydroxy esters in a highly stereoselective manner. On the other hand, the reaction of the β-hydroxy esters with allylic stannanes under the influence of a catalytic amount of triethylborane in tetrahydrofuran or isopropyl alcohol at −78°C proceeded erythro-selectively, leading preferentially to the erythro-isomers of the corresponding α-allylated esters.


Kazuhide Mima, Takashi Ishihara*, Saki Kuwahata, Hiroki Yamanaka, Tetrahedron 2002, 58, 2369–2376 (DOI: 10.1016/s0040-4020(02)00119-9).

When α-bromo-α-fluoro-β-hydroxy esters were allowed to react successively with trimethylaluminum in toluene at −15°C for 0.5 h and with tributyltin hydride in the presence of a catalytic amount of triethylborane at −15°C for 4 h, the corresponding threo-α-fluoro-β-hydroxyalkanoates were obtained highly diastereoselectively in good yields. On the other hand, the α-bromo-β-hydroxy esters having an aromatic substituent were subjected to the reaction with tris(trimethylsilyl)silane in the presence of a catalytic amount of triethylborane in THF at −78°C for 10 h to give the corresponding erythro-α-fluoro-β-hydroxyalkanoates with high erythro-selectivity in good yields, but those carrying an aliphatic substituent being reduced in an almost nonstereoselective manner.


Tsutomu Konno*, Kensuke Nagata, Takashi Ishihara, Hiroki Yamanaka J. Org. Chem. 2002, 67, 1768–1775 (DOI: 10.1021/jo011013d).

α-Fluoroalkylated allyl mesylates reacted with various carboxylates and amines in the presence of tetrakis(triphenylphosphine)palladium(0) catalyst to give the corresponding γ-fluoroalkylated (E)-allylic alcohol derivatives and amines, respectively, in excellent yields. In almost all cases, no other regio- and stereoisomers were produced. Application of this palladium-catalyzed allylic substitution reaction to various nonracemic mesylates afforded chiral γ-fluoroalkylated allylic alcohol derivatives and amines without any loss of enantiomeric excess through the reaction.


Kazuhide Mima, Takashi Ishihara*, Saki Kuwahata, Tsutomu Konno, Hiroki Yamanaka, Chem. Lett. 2002, 31, 192–193 (DOI: 10.1246/cl.2002.192).

α-Bromo-α-fluoro-β-hydroxy esters, prepared as isomeric mixtures by the zinc-mediated coupling reaction of dibromo-fluoroacetate with aldehydes at -20 °C, were successively treated with trimethylaluminium at -15 °C for 0.5 h and with tributyltin hydride in the presence of a catalytic amount of triethylborane at -15 °C for 4 h or at -78 °C for 6 h to give preferentially the threo-isomers of the corresponding α-fluoro-β-hydroxy esters in good yields.

2001年


Tsutomu Konno*, Takeshi Daitoh, Takashi Ishihara, Hiroki Yamanaka, Tetrahedron: Asymmetry 2001, 12, 2743–2748 (DOI: 10.1016/s0957-4166(01)00485-2).

The allylic substitution reactions of various chiral α-fluoroalkylated mesylates with carboxylic acids in the presence of a palladium catalyst proceeded smoothly to give γ-fluoroalkylated allyl esters in excellent yields. The esters were subsequently subjected to Ireland–Claisen rearrangement without isolation, leading to the corresponding homochiral α-fluoroalkylated-β,γ-unsaturated amino acids in good yields.


Satoru Shibayama, Tsutomu Konno, Takashi Ishihara, Hiroki Yamanaka*, J. Fluorine Chem. 2001, 111, 91–100 (DOI: 10.1016/s0022-1139(01)00438-9).

1,1,5,5-Tetramethyl-3-trifluoromethyl-1,5-diaza-1,3-pentadienium chloride (β-trifluoromethyl vinamidinium salt) 1 reacted smoothly with various types of enolates generated from ketones and esters to give the corresponding mono-addition–deamination products, dienaminones 2 and dienaminoates 3, respectively, in moderate to good yields. The reaction with carbanions from nitromethane, methyl phenyl sulfone, and acetonitrile also produced the corresponding dienamine derivatives 4, 6 in moderate yields. Interestingly, the carbanion from malononitrile participated well in the reaction with 1 to afford di-addition–deamination product, diisopropylammonium 1,1,5,5-tetracyano-3-trifluoromethyl-1,3-pentadienide (5) in quantitative yield.


Nadia Valiaeva, David Bartley, Tsutomu Konno*, James K. Coward, J. Org. Chem. 2001, 66, 5146–5154 (DOI: 10.1021/jo010283t).

Several routes to a complex phosphinate phosphapeptide analogous to the γ-glutamyl peptide Glu-γ-Glu have been investigated. Formation of γ-phosphono glutamate derivatives via addition of a phosphorus-based radical to protected vinylglycine was found to be of limited value because of the elevated temperatures required. Alkylation and conjugate addition reactions of trivalent phosphorus (PIII) species were investigated. In situ generation of bis-trimethylsilyl esters of phosphinous acids proved to be an effective route to phosphinates of modest structural complexity. However, this chemistry could not be extended to the incorporation of an amino acid moiety at the N-terminal side of the desired phosphinate. A successful synthesis of the target phosphinate phosphapeptide was effected using PIII chemistry and dehydrohalogenation to yield an α,β-unsaturated phosphinic acid ester, following which conjugate addition of diethylacetamido malonate and acid-mediated hydrolysis afforded the desired phosphinate phosphapeptide. Coupling of the unprotected phosphinate phosphapeptide with two acyl azides derived from folic acid and methotrexate led to the corresponding pteroylphosphapeptides of interest as possible mimics of tetrahedral intermediates in the reaction catalyzed by folylpolyglutamate synthetase.


Toshiya Mantani, Takashi Ishihara*, Tsutomu Konno, Hiroki Yamanaka, J. Fluorine. Chem. 2001, 108, 229–237 (DOI: 10.1016/s0022-1139(01)00358-x).

The reaction of trifluoromethylated ynamine with various halogenating agents was investigated. N,N-dialkyl(3,3,3-trifluoro-1-propynyl)amines (1) smoothly reacted with bromine to give, after treatment with sodium hydrogen carbonate, N,N-dialkyl-2-bromo-3,3,3-trifluoropropanamide (3-Br) in good yields. The reaction of 1 with an equimolecular amount of N-halosuccinimide (NXS) in acetonitrile–water (3/2 v/v) gave the corresponding 2-halo-3,3,3-trifluoropropanamides (3-X) in good to excellent yields. On the other hand, the treatment of 1 with NXS in anhydrous acetonitrile led to the formation of the addition products 7-X in high yields. Upon treating 7-X with an equimolecular amount of NXS in aqueous acetonitrile, the corresponding 2,2-dihalo-3,3,3-trifluoropropanamides (8-X1X2) were produced in nearly quantitative yields.


Hiroki Yamanaka*, Yasumasa Odani, Takashi Ishihara, Tsutomu Konno, John T. Gupton, J. Fluorine. Chem. 2001, 108, 199–205 (DOI: 10.1016/s0022-1139(01)00349-9).

β-Fluorinated vinamidinium salts (1) readily reacted with a series of Grignard reagents in tetrahydrofuran, followed by the action of reducing agents at room temperature, to produce stereospecifically the corresponding fluorinated allylamines (4 and 5) in good to excellent yields.


Toshiya Mantani, Keisuke Shiomi, Tsutomu Konno, Takashi Ishihara*, Hiroki Yamanaka, J. Org. Chem. 2001, 66, 3442–3448 (DOI: 10.1021/jo001760v).

N,N-Dialkyl(3,3,3-trifluoro-1-propynyl)amines were readily prepared by a three-step procedure starting from commercially available 2,2,3,3,3-pentafluoropropanol. These fluorinated alkynylamines reacted smoothly with a variety of aldehydes or ketones in the presence of a catalytic amount of Lewis acid and molecular sieves 4Å at ambient temperature to produce the corresponding α-(trifluoromethyl)-α,β-unsaturated amides in good to excellent yields with high Z-stereoselectivity.

2000年


Tsutomu Konno*, Mitsuru Tanikawa, Takashi Ishihara, Hiroki Yamanaka, Chem. Lett. 2000, 29, 1360–1361 (DOI: 10.1246/cl.2000.1360).

In the presence of 5 mol% of tetrakis(triphenylphosphine)palladium(0), the reaction of chiral fluorinated propargyl mesylates with a variety of organozinc reagents proceeded smoothly in a highly stereoselective fashion to give the corresponding optically active fluorine-containing trisubstituted allenes in good yields without any loss of optical purity through the reaction.


Tsutomu Konno*, Takashi Ishihara, Hiroki Yamanaka, Tetrahedron Lett. 2000, 41, 8467–8472 (DOI: 10.1016/s0040-4039(00)01485-4).

Pd(0)-catalyzed nucleophilic substitution reaction of optically active α-(fluoroalkyl)allyl mesylates with various types of carboxylates proceeded regioselectively to afford the corresponding chiral γ-fluoroalkylated allylic alcohol derivatives in excellent yields without any loss of optical purities.


Koichiro Kase, Mitsuyoshi Katayama, Tsutomu Konno, Takashi Ishihara, Hiroki Yamanaka*, J. Fluorine Chem. 2000, 104, 225–231 (DOI: 10.1016/s0022-1139(00)00220-7).

β-Polyfluoroalkoxy vinamidinium salts 1 were allowed to react with a variety of Grignard reagents in tetrahydrofuran at room temperature for 3 h, after an acidic workup of the reaction, to produce the corresponding (Z)-α-polyfluoroalkoxy-α,β-unsaturated aldehydes 2 in good to excellent yields.


Toshiya Mantani, Tsutomu Konno, Takashi Ishihara*, Hiroki Yamanaka, Chem. Lett. 2000, 29, 666–667 (DOI: 10.1246/cl.2000.666).

N,N-Dibutyl(3,3,3-trifluoro-1-propynyl)amine readily reacts with α,β-unsaturated ketones or aldehydes in refluxing benzene for 3–36 h to form the corresponding Diels-Alder adducts, 2-(dibutylamino)-3-(trifluoromethyl)-4H-pyrans, of which the successive treatment with alumina at ambient temperature for 1 h leads to the ring-opening products, α-trifluoromethylated δ-keto amides in fairly good to excellent yields.

1999年


Hee Moon Park, Tomonori Uegaki, Tsutomu Konno, Takashi Ishihara, Hiroki Yamanaka*, Tetrahedron Lett. 1999, 40, 2985–2988 (DOI: 10.1016/s0040-4039(99)00399-8).

Trifluoromethylated enamine, N-(2,3,3,3-tetrafluoro-1-propenyl)dimethylamine (1), readily reacted with a variety of Grignard reagents 2 at room temperature to afford the trifluorovinyl compounds 3 in good yields.

~1998年


Tsutomu Konno, Hirofumi Nakano, Tomoya Kitazume*, J. Fluorine Chem. 1997, 86, 81–87 (DOI: 10.1016/s0022-1139(97)00049-3).

Johnson-Claisen and Eshenmoser-Claisen rearrangements of chiral γ-trifluoromethylated allylic alcohols, which were prepared viaeffective enzymatic resolution of the corresponding propargylic alcohols, are demonstrated. As a result, it is shown that both reactions could become important methods for the preparation of highly functionalized chiral trifluoromethylated materials.


Tsutomu Konno, Tomoya Kitazume*, Tetrahedron: Asymmetry 1997, 8, 223–230 (DOI: 10.1016/s0957-4166(96)00492-2).

Iodolactonization and osmylation of enantiomerically pure α-methoxy-β-trifluoromethyl-γ,δ-unsaturated carboxylic acid derivatives, which were prepared via [3,3]-Ireland-Claisen rearrangement of α-methoxyacetic acid (γ-trifluoromethyl)allylesters, were investigated. The former proceeded in a highly stereoselective manner, and the construction of four successive asymmetric centers was achieved in a high yield. On the other hand, the latter gave the desired γ-lactone in moderate yield. The mechanism is also discussed by using MOPAC AM1 calculation.


Tsutomu Konno, Hideki Umetani, Tomoya Kitazume*, J. Org. Chem. 1997, 62, 137–150 (DOI: 10.1021/jo961246i).

γ-Trifluoromethylated propargylic alcohols have been obtained in optically pure forms via effective enzymatic kinetic resolution and then converted into (E)- or (Z)-allylic alcohols. [2,3]-Wittig rearrangement of the corresponding [[γ-(trifluoromethyl)allyl]oxy]acetic acid methyl esters afforded α-hydroxy-β-(trifluoromethyl)-γ,δ-unsaturated carboxylic acid methyl esters in good yields. The rearrangement of (Z)-substrates proceeded in a highly stereoselective manner to give anti-isomers with E configuration at a newly created olefinic bond via complete chirality transfer. (E)-Substrates, however, showed relatively low stereoselectivities resulting in mixtures of syn- and anti-products. The trifluoromethylated allylic alcohols were also converted into the corresponding α-methoxyacetic acid γ-(trifluoromethyl)allyl esters and evaluated as substrates for [3,3]-Ireland−Claisen rearrangement. (E)-Substrates were efficiently transformed into syn-products while (Z)-substrates exhibited relatively low stereoselectivities. The two complementary methods provide facile routes to highly functionalized trifluoromethyl-containing molecules with a high degree of stereocontrol.


Tsutomu Konno, Tomoya Kitazume*, Chem. Commun. 1996, 2227–2228 (DOI: 10.1039/cc9960002227).

The reaction of chlorodifluoromethane with various acetylides derived from the corresponding prop-2-ynylic alcohols proceeds smoothly to afford difluoromethylated compounds in high yields; synthetic applications of the materials are also given.


Tsutomu Konno, Takashi Yamazaki, Tomoya Kitazume*, Tetrahedron 1996, 52, 199–208 (DOI: 10.1016/s0040-4020(95)00863-4).

Two methods for the synthesis of α-trifluoromethylated aldehydes are described. One is a synthetic method via Pummerer rearrangement followed by the hydrolysis under the weakly basic condition, giving the recemic aldehyde. The other is via the oxidative cleavage of the corresponding diol under the acidic condition, affording the optically active compound for the first time. Furthermore, both aldehydes underwent the reaction with some nucleophiles in good yields.