Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Current periodontal treatment focuses on the mechanical removal of the source of infection, such as bacteria and their products, and there is no approach to control the host inflammatory response that leads to tissue destruction. In order to control periodontal inflammation, we have previously reported the optimization of (+)-terrein synthesis methods and the inhibitory effect of (+)-terrein on osteoclast differentiation in vitro. However, the pharmacological effect of (+)-terrein in vivo in the periodontitis model is still unknown. In this study, we investigated the effect of synthetic (+)-terrein on inflammatory bone resorption using a ligature-induced periodontitis mouse model. Synthetic (+)-terrein (30 mg/kg) was administered intraperitoneally twice a week to the mouse periodontitis model. The control group was treated with phosphate buffer. One to two weeks after the induction of periodontitis, the periodontal tissues were harvested for radiological evaluation (micro-CT), histological evaluation (HE staining and TRAP staining), and the evaluation of inflammatory cytokine production in the periodontal tissues and serum (quantitative reverse-transcription PCR, ELISA). The synthetic (+)-terrein-treated group suppressed alveolar bone resorption and the number of osteoclasts in the periodontal tissues compared to the control group (p < 0.05). In addition, synthetic (+)-terrein significantly suppressed both mRNA expression of TNF-α in the periodontal tissues and the serum concentration of TNF-α (both p < 0.05). In conclusion, we have demonstrated that synthetic (+)-terrein abrogates alveolar bone resorption via the suppression of TNF-α production and osteoclast differentiation in vivo. Therefore, we could expect potential clinical effects when using (+)-terrein on inflammatory bone resorption, including periodontitis.

DOI： 10.3390/jof9030314

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Publishing type：Research paper (scientific journal)   Publisher：Georg Thieme Verlag KG  

Abstract

An electrochemical cross-coupling reaction between arylboronic esters and aryllithiums was developed. The presence of Br– in the electrolyte was found to be essential for the reaction. NaBr was chosen as the electrolyte for its inexpensiveness and abundance, and also acted as a halogen mediator. The reaction proceeded under mild conditions to afford biaryls.

DOI： 10.1055/a-2034-9821

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.oprd.2c00267

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Publishing type：Research paper (scientific journal)   Publisher：The Electrochemical Society of Japan  

DOI： 10.5796/electrochemistry.23-67079

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Publishing type：Research paper (scientific journal)   Publisher：The Electrochemical Society of Japan  

DOI： 10.5796/electrochemistry.23-67078

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Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acs.orglett.2c03574

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Publishing type：Research paper (scientific journal)   Publisher：The Chemical Society of Japan  

DOI： 10.1246/cl.220368

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Publishing type：Research paper (scientific journal)   Publisher：Beilstein Institut  

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor is described. The reduction of enones proceeded smoothly under mild conditions to afford ketones or alcohols. The reaction occurred chemoselectively with the use of different cathode catalysts (Pd/C or Ir/C).

DOI： 10.3762/bjoc.18.107

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Other Link： https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-18-107.pdf

Publishing type：Research paper (scientific journal)  

DOI： 10.1149/MA2022-01421838mtgabs

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DOI： 10.1149/MA2022-01421832mtgabs

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Publishing type：Research paper (scientific journal)   Publisher：The Chemical Society of Japan  

DOI： 10.1246/cl.220112

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Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acs.joc.1c01242

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Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from <italic>Aspergillus terreus</italic>, has shown receptor activator of nuclear factor-κB ligand (RANKL)–induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). <italic>In vivo</italic> administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (<italic>p</italic> &amp;lt; 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (<italic>p</italic> &amp;lt; 0.01). In an <italic>in vitro</italic> study, TER suppressed RANKL-induced phosphorylation of PKCα/βII, which is involved in the expression of NFATc1 (<italic>p</italic> &amp;lt; 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as <italic>Ocstamp</italic>, <italic>Dcstamp</italic>, <italic>Calcr</italic>, <italic>Atp6v0d2</italic>, <italic>Oscar</italic>, and <italic>Itgb3</italic> (<italic>p</italic> &amp;lt; 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis.

DOI： 10.3389/fphar.2021.674366

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Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acs.orglett.1c01256

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Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acs.orglett.1c00807

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Publishing type：Research paper (scientific journal)   Publisher：The Chemical Society of Japan  

DOI： 10.1246/cl.200809

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Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acs.orglett.0c03956

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Publishing type：Research paper (scientific journal)  

An efficient enantioselective acylative desymmetrization of glycerol was developed by using a chiral DMAP derivatives 1e having a 1,1-binaphthyl unit. The reactions required only 0.1 mol% of the catalyst and showed moderate to good enantioselectivity (up to 94:6 er). Control experiments revealed that the first acylation of a glycerol derivative proceeded selectively rather than the second acylation to give diacylate.

DOI： 10.3987/COM-21-14433

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Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

<p>4,4′-Bibenzo[<italic>c</italic>]thiophene <bold>4,4′-BBT</bold> and its silyl-substituted derivatives <bold>1,1′-Si-4,4′-BBT</bold> and <bold>1,1′,3,3′-Si-4,4′-BBT</bold> have been designed and developed as new π-building blocks.</p>

DOI： 10.1039/d1ra01189h

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：GEORG THIEME VERLAG KG  

A one-pot procedure for the synthesis of thienyl thioethers is described. Several thienyl thioethers were synthesized by a TfOH-promoted Friedel-Crafts-type cyclization, a subsequent nucleophilic attack by an arenethiol, and dehydration. This protocol was successfully applied to the synthesis of thienoacene derivatives by using a Pd-catalyzed dehydrogenative cyclization.

DOI： 10.1055/s-0040-1707280

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER  

Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-kappa B ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 mu M synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease.

DOI： 10.1016/j.intimp.2020.106429

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Publishing type：Research paper (scientific journal)   Publisher：The Electrochemical Society  

DOI： 10.1149/MA2020-01432507mtgabs

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Publishing type：Research paper (scientific journal)   Publisher：The Electrochemical Society  

DOI： 10.1149/MA2020-01432489mtgabs

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

The first electrochemical dehydrogenative C-S bond formation leading to thienoacene derivatives is described. Several thienoacene derivatives were synthesized by dehydrogenative C-H/S-H coupling. The addition of (Bu4NBr)-Bu-n, which catalytically promoted the reaction as a halogen mediator, was essential.

DOI： 10.1002/anie.202001149

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Language：Japanese   Publisher：SOC SYNTHETIC ORGANIC CHEM JPN  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：GEORG THIEME VERLAG KG  

A 1,10-phenanthroline-promoted cyanation of aryl iodides has been developed. 1,10-Phenanthroline worked as an organocatalyst for the reaction of aryl iodides with tetraalkylammonium cyanide to afford aryl cyanides. A similar reaction occurred through an electroreductive process.

DOI： 10.1055/s-0037-1611793

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The first synthesis of dithieno-1,2-oxaborine derivatives was achieved via iodide-mediated or iodide-catalyzed demethylation of 3-methoxy-2,2'-bithiophene and subsequent C-H borylation. A wide variety of thiophene-fused oxaborines could be synthesized by the procedure.

DOI： 10.1021/acs.orglett.9b00485

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

An efficient enantioselective acyl migration reaction of furanyl carbonates was developed to construct all-carbon quaternary stereogenic centers. In some cases, the reactions required only 0.05 mol% (minimum 500 ppm) of catalyst and showed a high turnover frequency value (TOF; 3640 h(-1)). Multigram-scale reactions (10 grams) also proceeded with high enantioselectivity (> 99:1 e.r.) in quantitative yield. The catalyst was robust and easily recovered in 98% yield. A wide range of functional groups were tolerated (15 examples, > 98% yield, up to > 99:1 e.r.), and a variety of optically active 3,3'-disubstituted benzofuranone derivatives, which are useful intermediates for the synthesis of natural products and pharmaceuticals, were efficiently obtained. Control experiments on the catalyst structure (e.g., catalyst 1 a vs. 1 a' and 1 a") and computational calculations revealed that both the catalytic activity and enantioselectivity should be enhanced by hydrogen bonding between catalyst and substrate. Moreover, this system was applied to the challenging gamma-selective acyl migration reaction of furanyl carbonates with high gamma-selectivity and high enantioselectivity (a:gamma=10:90, 95:5 e.r.).

DOI： 10.1002/chem.201806050

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

We developed an enantioselective desymmetrization of 1,3-diols by a chiral N,N-dimethyl-4-aminopyridine (DMAP) derivative containing a 1,1'-binaphthyl with tert-alcohol units. The reactions required only 0.1 mol % of catalyst and showed moderate to high chemoselectivity (monoacylation vs. diacylation) and enantioselectivity (14 examples, up to 95:5 er). Several control experiments revealed that diol units in both the substrate and the catalyst are important to achieve high enantioselectivity.

DOI： 10.1246/cl.180697

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

DOI： 10.1016/j.heliyon.2018.e00979

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The first synthesis of dithieno[3,2-b:2',3'-e][1,4]azaborinine (DTAB) derivatives has been achieved by Buchwald-Hartwig coupling and subsequent Friedel-Crafts-type C-H borylation. A facile method for further pi-extension of DTAB was also developed via stannylation and subsequent Kosugi-Migita-Stille cross-coupling reaction. The fundamental properties of DTAB derivatives were also investigated.

DOI： 10.1021/acs.orglett.8b03316

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

Cu/Fe-cocatalyzed cross-coupling reactions between 3-bromobenzo[b]thiophene and hydroxyaryls are described herein. The combination of Cu and Fe catalysts is important for the progress of the reactions, and the use of triphenylphosphine oxide as a ligand suppresses the dehalogenation of 3-bromobenzo[b]thiophene, and promptly facilitates the reaction. The obtained aryl benzo[b]thienyl ethers can be converted to pextended thienobenzofuran derivatives via Pd-catalyzed dehydrogenative cyclizations.

DOI： 10.1246/cl.180425

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

A dynamic kinetic resolution (DKR) of azlactones in the presence of benzoic acid and a binaphthyl-based N,N-4-dimethylaminopyridine (DMAP) derivative 1i having two amide groups at the 3,3'-positions of a binaphthyl unit is developed. The reaction proceeded smoothly with a wide range of azlactones to provide alpha-amino acid derivatives with good to high enantiomeric ratios (er's). A multigram-scale reaction (2.5 g) for the DKR of azlactone 2d was also demonstrated, and the resulting product was converted to unnatural alpha-amino acid 6d'.

DOI： 10.1021/acs.orglett.8b01960

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The reaction of N-allylamides with ArS(ArSSAr)(+), which was generated and accumulated by the low-temperature anodic oxidation of ArSSAr, afforded the corresponding ArS-substituted oxazolines in moderate to good yields. In-situ electrochemical oxidation of ArSSAr in the presence of N-allylamides was also applicable. Oxazolines bearing various substituents were successfully synthesized by using the present reactions.

DOI： 10.3987/COM-18-13942

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

Efficient syntheses of benzodithienofuran (BDTF; [1]benzothieno[3,2-b]thieno[2,3-d]furan) and benzodithienothiophene (BDTT; [1]benzothieno[3,2-b]thieno[2,3-d]thiophene) were achieved by the combination of an addition-elimination reaction, reduction, and Pd-catalyzed dehydrogenative cyclization. We also achieved the synthesis of pi-ex- tended BDTF and BDTT derivatives through the use of coupling reactions. The detailed physical properties of these compounds were investigated. The newly synthesized BDTFs exhibited strong fluorescence compared with BDTTs. 2,2'-Bis([1]benzothieno[3,2-b]thieno[2,3-d]furan) (BBTTF) exhibited p-type organic field-effect transistor (OFET) properties.

DOI： 10.1002/ajoc.201800270

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Language：English   Publisher：AMER CHEMICAL SOC  

Recent advances in electro-organic chemistry involving miniaturization, integration, and combinatorial chemistry were reviewed. Microelectrode array technology for site-selective electro-organic reactions and addressable libraries provides a direct and unlabeled method for measuring small-molecule-protein interactions. Electrochemical systems using solid-supported bases and acids ("site separation") can realize electrolysis without the addition of supporting electrolytes. Well-designed "bipolar electrodes" have enabled the production of patterned gradient polymer brushes and microfibers. For the display of combinatorial organic electrochemistry, batch and flow electrolysis systems for the optimization and screening of electro-organic reactions as well as the building of chemical libraries for organic compounds are described.

DOI： 10.1021/acs.chemrev.7b00532

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

This digest focuses on recent topics in intra- and intermolecular enantioselective acyl transfer reactions with dialkylaminopyridine-based catalysts over the past decade (2007-2017). The structures of the catalysts are divided into four categories according to the location of the chiral environment (C2, C3, or C4 position of pyridine, and miscellaneous). The role of the structure in the enantioselective acyl transfer reaction and the reaction mechanism will be discussed briefly. (C) 2018 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2018.03.016

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BEILSTEIN-INSTITUT  

In this study, six-membered N-acyliminium ions were generated by the "indirect cation pool" method and reacted with several nucleophiles. These reactions afforded disubstituted piperidine derivatives with high diastereoselectivities and good to excellent yields. The conformations of the obtained N-acyliminium ions were studied by low temperature NMR analyses and DFT calculations and were found to be consistent with the Steven's hypothesis.

DOI： 10.3762/bjoc.14.100

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Language：English   Publisher：ELSEVIER  

In this study, recent advances in electro-organic chemistry based on combinatorial approaches are reviewed. As examples of combinatorial organic electrosynthesis, some batch and flow electrolysis systems for the screening and optimization of electro-organic reactions are described along with the construction of chemical libraries of organic compounds.

DOI： 10.1016/j.coelec.2017.10.026

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

An extremely efficient acylative kinetic resolution of d,l-1,2-diols in the presence of only 0.5 mol% of binaphthyl-based chiral N,N-4-dimethylaminopyridine was developed (selectivity factor of up to 180). Several key experiments revealed that hydrogen bonding between the tert-alcohol unit(s) of the catalyst and the 1,2-diol unit of the substrate is critical for accelerating the rate of monoacylation and achieving high enantioselectivity. This catalytic system can be applied to a wide range of substrates involving racemic acyclic and cyclic 1,2-diols with high selectivity factors. The kinetic resolution of d,l-hydrobenzoin and trans-1,2-cyclohexanediol on a multigram scale (10 g) also proceeded with high selectivity and under moderate reaction conditions: (i) very low catalyst loading (0.1 mol%); (ii) an easily achievable low reaction temperature (0 degrees C); (iii) high substrate concentration (1.0M); and (iv) short reaction time (30 min).

DOI： 10.1002/adsc.201700057

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

We developed an acylative desymmetrization of meso-1,2-diols using a binaphthyl-based N,N-4-dimethylamino-pyridine (DMAP) derivative lh with tert-alcohol substituents. The reaction proceeds with a wide range of acyclic meso-1,2-diols and six-membered-ring meso-1,2-diols to provide a monoacylate selectively with a high enantiomeric ratio (er). Only 0.1 mol % of the catalyst facilitated the reaction within a short reaction time (3 h) to afford enantio-enriched monoacylated products in moderate to good yield. Several control experiments revealed that the tert-alcohol units of catalyst lh play a significant role in achieving high catalytic activity, chemoselectivity of monoacylation, and enantioselectivity.

DOI： 10.1021/acs.joc.7b00992

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：SOC SYNTHETIC ORGANIC CHEM JPN  

Catalysts that can promote acyl transfer processes are important for enantioselective synthesis and their development has received significant attention in recent years. Very recently, we developed a method for the synthesis of chiral DMAP derivatives starting from an alpha-amino acid as a chiral source using a diastereoselective Ugi multicomponent reaction, and the protocol allowed us to access a variety of chiral catalysts in a one-step and one-pot manner. Such catalysts could be applied to various enantioselective acyl transfer reactions. In addition, we also reported a conceptually new type of kinetic resolution of secondary alcohols with a chiral phosphoric acid for the first time. Finally, we developed a binaphthyl-based chiral DMAP derivatives utilizing H-bonding interactions for enantioselective intra- and intermolecular acyl transfer reactions with high enantioselectivity. tert-Alcohol units of the catalyst play important roles in the acceleration of the rate of the reaction and achieving high enantioselectivity.

DOI： 10.5059/yukigoseikyokaishi.75.632

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The synthesis of 3-benzo[b]thienyl 3-thienyl ether and its dehydrogenative cyclization leading to benzodithienofuran (BDTF; [1]benzothieno[3,2-b]thieno[2,3-d]furan) are described for the first time. Further transformation of BDTF to more p-extended BDTF derivatives and their fundamental physical properties are also studied.

DOI： 10.1021/acs.orglett.7b00969

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Straightforward syntheses leading to pi-extended benzosilolothiophene (BST) derivatives by Rh-catalyzed dehydrogenative cyclization reactions have been developed. Electron-deficient ligands were effective for the reactions, and dppe-F-20 gave the best result. This method could be applied to the synthesis of highly pi-extended ladder-type BST derivatives, which exhibited fluorescence.

DOI： 10.1021/acs.orglett.7b00878

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：GEORG THIEME VERLAG KG  

A PTFE microtube reactor was constructed with lipase immobilized on magnetized bacteriogenic iron oxide, which was retained inside of the tube by attraction to an external magnet. The reactor was used for the lipase-promoted kinetic resolution of secondary alcohols and gave sufficient catalytic activity, which was maintained during long-term flow over 14 days.

DOI： 10.1055/s-0036-1589953

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

We have developed an intramolecular nucleophile-catalyzed aldol-lactonization (NCAL) reaction of S-aryl-(E)-6-oxohex-2-enethiolate with N,N-4-dimethylaminopyridine N-oxide (DMAPO) to afford densely functionalized bicyclic beta-lactones in moderate yield. This unique transformation may be explained in terms of nucleophilic substitution of the S-aryl moiety by DMAPO, followed by 1,4-addition of aryl thiolate to generate a zwitterionic enolate and an intramolecular C-C bond-forming reaction (aldol-lactonization).

DOI： 10.3987/COM-16-13614

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：GEORG THIEME VERLAG KG  

Facile synthetic methods for constructing naphthothiophenone and its -extended derivatives were developed. Naphthothiophenone and anthradithiophenedione were synthesized by the S-acylation of thiol to form chlorothioformate and subsequent Friedel-Crafts acylation. A bromination reaction of naphthothiophenone and its application to Suzuki-Miyaura cross-coupling was also carried out. The fundamental physical properties of these compounds were also investigated.

DOI： 10.1055/s-0035-1562470

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

We developed an acylative kinetic resolution of secondary carbinols using a binaphthyl-based N,N-4-dimethylaminopyridine (DMAP) derivative 1d with tert-alcohol substituents. The reaction proceeded with a wide range of carbinols with moderate to high selectivity (s) (up to s = 79.5). Kinetic studies revealed that catalyst 1d was more catalytically active than the corresponding bis-methyl ether 1d' or DMAP. Hydrogen bonding between tert-alcohols of the catalyst and secondary carbinols was responsible for the enhanced reaction rate and high enantioselectivity.

DOI： 10.1246/bcsj.20160135

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

Background/Aim: Head and neck cancers are the fifth most common cancer type worldwide, affecting more than half a million patients annually. Development of effective therapeutic drugs is, therefore, required for this type of disease. This study assessed the effects of synthetic terrein on head and neck cancer. Materials and Methods: Synthetic terrein was prepared by using the modified Altenhach's procedure. The effect of synthetic terrein on cell proliferation of head and neck cancer cells and HUVECs was assessed. Angiogenin secretion and ribosome biogenesis were examined by ELISA and silver staining of the nucleolar organizer region. A mouse xenograft model was prepared by inoculating mice with suspensions of cells of the human head and neck cancer cell line OSC-19 subcutaneously into the dorsal region of each mouse. Ki-67, CD31 and angiogenin expression in xenografted tumors was examined by immunohistochemistry. Results: Synthetic terrein inhibited the growth of various head and neck cancer cells. In addition, an in vivo experiment revealed that synthetic terrein inhibited a xenograft tumor growth in athymic mice. Immunohistochemical analysis revealed that expression of Ki-67, CD31 and ANG was down-regulated in synthetic terrein-treated tumors, compared to controls. Synthetic terrein suppressed the ANG secretion and ribosome biogenesis in cancer cells, and cell proliferation in vascular endothelial cells. Conclusion: The mechanism underlying the anti-tumor effects of synthetic terrein against head and neck cancer consists of the inhibition of both tumor cell proliferation and angiogenesis via the suppression of ANG production.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Catalysts that can promote acyl transfer processes are important to enantioselective synthesis and their development has received significant attention in recent years. Despite noteworthy advances, discovery of small-molecule catalysts that are robust, efficient, recyclable and promote reactions with high enantioselectivity can be easily and cost-effectively prepared in significant quantities (that is, >10 g) has remained elusive. Here, we demonstrate that by attaching a binaphthyl moiety, appropriately modified to establish H-bonding interactions within the key intermediates in the catalytic cycle, and a 4-aminopyridyl unit, exceptionally efficient organic molecules can be prepared that facilitate enantioselective acyl transfer reactions. As little as 0.5 mol% of a member of the new catalyst class is sufficient to generate acyl-substituted all-carbon quaternary stereogenic centres in quantitative yield and in up to 98: 2 enantiomeric ratio (er) in 5 h. Kinetic resolution or desymmetrization of 1,2-diol can be performed with high efficiency and enantioselectivity as well.

DOI： 10.1038/ncomms11297

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

Bis(diaryl)-1,3-butadiynes bearing two amino moieties were easily synthesized by a sequential coupling reaction by using an electrochemical method. This sequential reaction consists of electrochemical oxidative homocoupling and Suzuki-Miyaura coupling. The fluorescence of the obtained bis(diaryl)-1,3-butadiynes is solvatochromic despite their symmetric linear structure and lack of a strong acceptor moiety.

DOI： 10.1002/ajoc.201500502

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Iron oxide produced by iron-oxidizing bacteria, Leptothrix ochracea, (L-BIOX) obtained from a freshwater purification plant, Joyo City in Kyoto, Japan catalyzed Baeyer-Villiger oxidation with molecular oxygen in the presence of benzaldehyde at 25 degrees C more efficiently than usual iron compounds. L-BIOX can promote the reactions of various substrates to give the desired products in sufficient yields and was found to be reusable. Scanning transmission electron microscopy and Fe-57 Mossbauer spectroscopy revealed that no change of the surface structure of L-BIOX was observed even after four times of the recycling test and the oxidation state of iron in L-BIOX is trivalent before and after the oxidation of cyclohexanone. An investigation with analogous amorphous iron oxides which contain silicon revealed that the catalytic activity of L-BIOX might stem from a synergetic effect of iron and silicon in the structure. (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2015.10.057

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

A method for the facile synthesis of ethene-bridged terthiophenes (EBTTs) in two steps has been developed. The first step is a double Sonogashira coupling between 3',4'-dibromo-2,2':5',2 ''-terthiophene and terminal alkynes to give dialkynylated terthiophenes, and the second step is a cyclization reaction to afford EBTTs. The fundamental physical properties of EBTTs were also studied.

DOI： 10.1021/acs.orglett.5b02417

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Chiral N,N-4-(dimethylamino)pyridine (DMAP) derivatives, which can be readily prepared by the Ugi multicomponent reaction in a one-pot manner, have been efficiently applied to the enantioselective Steglich rearrangement of oxindole derivatives to give the desired products bearing a quaternary carbon center in high yield (>98% yield) and with high enantioselectivity (up to 99:1 er).

DOI： 10.1021/acs.orglett.5b02089

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

Palladium-catalyzed domino CH/NH functionalization for the synthesis of novel nitrogen-bridged thienoacenes and 10H-benzo[4,5]thieno[3,2-b]indole derivatives from dihaloarene is reported. This domino sequence consists of initial CH functionalization of the benzo[b]thiophene moiety, followed by Buchwald-Hartwig coupling. This transformation is also useful for the synthesis of highly -extended compounds.

DOI： 10.1002/chem.201500897

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Language：Japanese   Publisher：SOC SYNTHETIC ORGANIC CHEM JPN  

An electrochemical method to synthesize cationic palladium complexes has been developed. Their counter anions could be changed readily by the electrolyte. The reaction could be incorporated into electro-oxidative palladium catalyzed reactions, such as Wacker-type reaction, homo-coupling of arylboronic acids, oxidative Sonogashira-type coupling, and Glaser-type coupling of terminal alkynes. These reactions exhibited a wide scope and a variety of products were obtained in high yields due to high activity of electrogenerated palladium species. We also developed site-selective sequential reactions by the integration of the electro-oxidative coupling reactions with non-electrochemical reactions. The reaction site could be controlled completely by the on/off application of electricity.

DOI： 10.5059/yukigoseikyokaishi.73.171

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

A low temperature in situ Raman spectroscopic method was developed for the detection of unstable intermediates in electro-organic chemistry. It was effective for monitoring the generation of ArS(ArSSAr)(+) by the electrochemical oxidation of ArSSAr (Ar = p-FC6H4) in Bu4NBF4/CH2Cl2 at 195 K. The intensity of a Raman band at 427 cm(-1), which is attributable to the S-S vibration of ArS(ArSSAr)(+), increased with an increase in the electricity until 2/3 F of the electricity was consumed, whereas decreased with a further increase in the electricity indicating the decomposition of ArS(ArSSAr)(+).

DOI： 10.1039/c5cc03585f

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Language：English   Publisher：The Electrochemical Society of Japan  

DOI： 10.5796/electrochemistry.83.477

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Other Link： https://jlc.jst.go.jp/DN/JLC/20011551902?from=CiNii

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELECTROCHEMICAL SOC JAPAN  

The porous carbon material was prepared from sawdust impregnated with a 0.1 M FeCl3 aqueous solution with CO2 activation at 800 degrees C. Pores were found to develop with increasing activation time. The BET surface area, average pore diameter and volume of the mesopores also became greater with increasing activation time. The ratio of the mesopore to total pore volume in the activated carbon was more than 90% after 5 min of activation. Precise control of the pore size distribution is possible by finely tuning the activation time. The porous carbonized material was examined for use in electric double layer capacitor (EDLC) electrodes. The charge and discharge characteristics of EDLC electrodes using these carbonized materials were studied. Cyclic voltammetry and rate performance indicated good correlation between the pore structure of the carbonaceous materials and the magnitude of the electrolyte. These relationships were in good agreement with the Nyquist plot obtained by measuring the impedance. These results were also in accordance with pore structure analysis obtained using the nitrogen adsorption method. It is suggested that the Nyquist diagram characterizes the pore structure of porous carbon from the viewpoint of ion transfer. (C) The Electrochemical Society of Japan, All rights reserved.

DOI： 10.5796/electrochemistry.82.1067

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Interleukin (IL)-6 is a proinflammatory cytokine that performs a wide variety of biological functions, including important roles in the progression of chronic inflammatory diseases such as periodontal disease. (+)-Terrein, a secondary bioactive fungal metabolite isolated from Aspergillus terreus, has various biological activities; however, its anti-inflammatory effects are still unknown. The purpose of this study was to examine the effect of synthetic (+)-terrein on IL-6 signaling and related protein production in human gingival fibroblasts. To our knowledge, this study is the first to report that synthetic (+)-terrein is not cytotoxic at concentrations less than 20 mu M and suppresses IL-6/soluble IL-6 receptor (sIL-6R)-induced phosphorylation of signal transducer and activator of transcription-3, extracellular signal-regulated kinase 1/2, and c-jun N-terminal kinase 1/2-signaling proteins that are downstream of IL-6 signaling. In addition, synthetic (+)-terrein suppresses IL-6/sIL-6R-induced vascular endothelial growth factor (VEGF) secretion in a concentration-dependent manner (p < 0.01). These data suggest that synthetic (+)-terrein has potential anti-IL-6 signaling activity and suppresses VEGF-associated inflammatory disease progression. (C) 2014 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmc.2014.07.047

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：GEORG THIEME VERLAG KG  

Optically active polyhydroxy trans-1,2-amino alcohols were efficiently synthesized in good to excellent yields by the Petasis boronic-Mannich reaction of an amine, an organoboronic acid, and a chiral lactol, which was prepared from D-araboascorbic acid or its diastereomer. Further transformations of the resulting Petasis products were investigated in detail to obtain chiral building blocks containing three continuous stereogenic centers.

DOI： 10.1055/s-0034-1378900

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

The rate of the intramolecular Morita-Baylis-Hillman (MBH) reaction is remarkably enhanced by the combination of catalytic amounts of a nucleophilic catalyst (4-dimethylaminopyridine (DMAP), 4-pyrrolidinopyridine (PPY), or PBu3) and 1,3-diphenyl-2-thiourea, and the desired MBH adducts are obtained in good to high yields within a few hours.

DOI： 10.1002/ajoc.201402001

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

The reaction of electrochemically generated N-acyliminium ion pools with alkenes bearing a heteroatom nucleophilic functionality such as a hydroxy group, a carboxy group, and an oxime moiety led to intermolecular carbon carbon bond formation followed by intramolecular carbon heteroatom bond formation to give the corresponding heterocyclic compounds such as cyclic ethers, lactones, and 2-isoxazolines, respectively.

DOI： 10.1246/cl.130947

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

Addition of diaryl disulfides to carbon-carbon multiple bonds was achieved with a catalytic amount of an electrogenerated acid (EGA), which was produced by the electrolysis of Bu4N+B(C6F5)(4)(-)/CH2Cl2. The anti-addition products of two ArS groups across the carbon-carbon multiple bond were obtained in good yields.

DOI： 10.1246/cl.130255

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELECTROCHEMICAL SOC JAPAN  

Electro-oxidative Wacker-type reaction has been developed in PEG/CH3CN thermomorphic biphasic system. The heterogeneous solution was turned into homogeneous solution with heating to 60 degrees C, and electro-oxidative Wacker-type reactions of alkenes bearing long alkyl chains proceeded smoothly to afford methyl ketones in good yields. The recycling of PEG phase containing Pd has also been achieved. (C) The Electrochemical Society of Japan, All rights reserved.

DOI： 10.5796/electrochemistry.81.347

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELECTROCHEMICAL SOC JAPAN  

An electro-reductive halogen-deuterium exchange reaction in CD3CN has been developed. Using 9-fluorenone as a mediator, the electro-reduction of several aryl halides proceeded smoothly to give the deuterated products selectively. A methylation reaction of aryl halides also proceeded under similar conditions. (C) The Electrochemical Society of Japan, All rights reserved.

DOI： 10.5796/electrochemistry.81.362

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

The addition reactions of diaryl disulfides (ArSSAr) to alkenes and alkynes were achieved with a catalytic amount of an arylbis(arylthio)sulfonium ion (ArS(ArSSAr)(+)), which was generated and accumulated by low-temperature electrolysis of ArSSAr, to give the corresponding diarylthiolated products. The electrolysis of a mixture of ArSSAr and an alkene with a catalytic amount of electricity was also effective to drive the reactions. A cation chain mechanism mediated by ArS(ArSSAr)(+) as a chain carrier is suggested.

DOI： 10.1002/ajoc.201300017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The first synthesis of hexa(furan-2-yl)benzene derivatives is described. The RhCl3/i-Pr2NEt-catalyzed cyclotrimerization of di(furan-2-yl)acetylenes was an effective method for constructing hexa(furan-2-yl)benzene derivatives in good yields. Their pi-extended derivatives were also synthesized by Suzuki-Miyaura coupling between hexakis(5-Bpinfuran-2-yl)benzene (Bpin = (pinacolato)boryl) and several aryl iodides.

DOI： 10.1021/jo302652r

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The kinetic resolution of secondary alcohols was examined by new chiral DMAP derivatives, which can readily be prepared by the Ugi multicomponent reaction in a one-pot operation. The initial screening of DMAP derivatives indicated that the catalyst bearing L-valine with an S configuration at the a-position of amide showed the best stereoselectivity factor. After the reaction conditions were optimized with (S,S)-4a in the kinetic resolution of secondary alcohols, various acyclic and cyclic secondary alcohols could be resolved with an s-factor of up to 12.

DOI： 10.3987/COM-12-12624

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

In the presence of fluorene derivatives, the electro-reduction of aryl chlorides, bromides, and iodides bearing an ethylene moiety proceeded smoothly to afford the corresponding cyclized products. Noteworthy is that aryl chlorides, which have more negative reduction potential than aryl bromides and iodides, exhibited high reactivity in the reaction, and the corresponding five-membered and six-membered cyclized products were obtained in good to high yields. Mechanistic study suggests that the electro-reduction of fluorene derivatives was essential for the reactions, indicating that they work as a mediator. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.electacta.2012.03.130

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

An efficient and simple protocol for the kinetic resolution of secondary alcohols is presented. The new system is based on a combination of chiral Bronsted acid, DABCO, and acetyl chloride and gives various enantioenriched alcohols with selectivity factors up to 105.

DOI： 10.1021/ol301373x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The Petasis reaction of various 2-pyridinecarbaldehydes with secondary amines and boronic acids in refluxed acetonitrile proceeded to afford desired products up to 96% yield. The reaction proceeded under mild conditions to afford wide range of amines adjacent to heteroaromatic rings. Interestingly, the aldehyde possessing a nucleophilic moiety, 4-(dimethylamino)-2-pyridinecarbaldehyde, with (S)-(-)-N-methyl-1-phenylethylamine and 2 equivalent of trans-2-phenylvinylboronic acid afforded unexpected product, (E)-N-benzyl-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-amine, in high yield. This product might be formed through the direct alkylation of aldehyde by trans-2-phenylvinylboronic acid, followed by anion/enolate isomerization. Derivatization of the Petasis products were also employed and 2-alkyl substituted pyridine derivatives can be obtained through deamination of the Petasis products under the simple hydrogenation conditions.

DOI： 10.3987/COM-12-12500

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The first synthesis of nitrogen-bridged terthiophenes (NBTTs) has been achieved by a tandem Buchwald-Hartwig coupling of 3,3',3 '', 4'-tetrabromo-2,2':5',2 ''-terthiophene. Several NBTT derivatives bearing aryl or alkyl moieties on the N-atoms could be synthesized. Their fundamental electrochemical characteristics and HOMO-LUMO levels were found to be influenced by the substituents on the N-atoms.

DOI： 10.1021/ol300887t

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Arylbis(arylthio)sulfonium ions (ArS(ArSSAr)(+)), which were generated and accumulated by the low-temperature electrolysis of diary! disulfide (ArSSAr), were found to serve as ArS+ equivalent in electrophilic substitution reactions of aromatic compounds, enolizable ketones, enol acetates, ketene silyl acetals and allylsilanes to give the corresponding arylthiolated products. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2012.01.131

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Site-selective sequential coupling reactions directed toward bis(diaryl)butadiynes are described. The reaction site could be controlled completely by the on/off application of electricity. The electro-oxidative homo-coupling of terminal alkynes (electricity ON) and the subsequent Suzuki-Miyaura coupling (electricity OFF) afforded bis(diaryl) butadiynes in high yields. The obtained 1,4-bis(diaryl)butadiynes could be converted to a 2,5-bis(diaryl)thiophene derivative, which exhibited blue fluorescence.

DOI： 10.1039/c2ob26567b

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI  

Diastereoselective Ugi reactions of DMAP-based aldehydes with alpha-amino acids and tert-butyl isocyanide were examined. The reactions of 4-(dimethylamino)-2-pyridine-carboxaldehyde with various alpha-amino acids afforded 2-substituted DMAP derivatives with low diastereoselectivity. On the contrary, reactions with 4-(dimethylamino)-3-pyridine-carboxaldehyde delivered 3-substituted DMAP derivatives with moderate to high diastereoselectivity. The combination of alpha-amino acid and DMAP-based aldehyde is thus important to achieve high diastereoselectivity. Kinetic resolution of a secondary alcohol using a chiral DMAP derivative obtained through these reactions was also examined.

DOI： 10.3390/molecules16108815

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Oxygen (O-2) is a prerequisite for cellular respiration in aerobic organisms but also elicits toxicity. To understand how animals cope with the ambivalent physiological nature of O-2, it is critical to elucidate the molecular mechanisms responsible for O-2 sensing. Here our systematic evaluation of transient receptor potential (TRP) cation channels using reactive disulfides with different redox potentials reveals the capability of TRPA1 to sense O-2. O-2 sensing is based upon disparate processes: whereas prolyl hydroxylases (PHDs) exert O-2-dependent inhibition on TRPA1 activity in normoxia, direct O-2 action overrides the inhibition via the prominent sensitivity of TRPA1 to cysteine-mediated oxidation in hyperoxia. Unexpectedly, TRPA1 is activated through relief from the same PHD-mediated inhibition in hypoxia. In mice, disruption of the Trpa1 gene abolishes hyperoxia- and hypoxia-induced cationic currents in vagal and sensory neurons and thereby impedes enhancement of in vivo vagal discharges induced by hyperoxia and hypoxia. The results suggest a new O-2-sensing mechanism mediated by TRPA1.

DOI： 10.1038/NCHEMBIO.640

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

Carbene ligands bearing a pyridyl group and an ethylenedioxyl moiety were developed, and utilized as efficient ligands for the nickel-catalyzed Kumada-Tamao-Corriu coupling. A wide variety of aryl chlorides could be used for the cross-coupling reaction with aryl Grignard reagents to afford the corresponding products in high yields in short time.

DOI： 10.1246/cl.2011.936

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Low-temperature electrochemical oxidation of ArSSAr was carried out to generate a pool of "ArS+". Spectroscopic studies (H-1 NMR and CSI-MS) of the resulting solution revealed the accumulation of ArS(ArSSAr)(+). The resulting "ArS+" pool reacted with alkenes and alkynes to give diarylthio-substituted products. The "ArS+" pool rapidly reacted with thioacetals to give the corresponding alkoxycarbenium ion pools, which reacted with various carbon nucleophiles (indirect cation pool method). The reaction of the alkoxycarbenium ion pools with stilbene derivatives in the presence of ArSSAr gave thiochroman derivatives. In addition to such stoichiometric reactions, a catalytic amount of "ArS+" serves as an initiator and a chain carrier of some cationic chain reactions involving intramolecular carbon-carbon bond formation. In situ generation of "ArS+" by electrochemical oxidation of ArSSAr with a catalytic amount of electricity in the presence of a substrate is also effective for such cationic chain reactions.

DOI： 10.1039/c0ob01070g

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

DOI： 10.1002/anie.201100854

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

Three-component coupling of an N-acyliminium cation pool, an optically active 2-t-butyloxazole derivative, and a carbon nucleophile such as allyltrimethylsilane was effectively achieved by a rapid one-pot method at -78 degrees C and a flow microreactor method at 0 degrees C.

DOI： 10.1246/cl.2010.404

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

ArS(ArSSAr)(+) (arylbis(arylthio)sulfonium ions), which were generated and accumulated by the electro-chemical oxidation of diaryl disulfides (ArSSAr) in CH(2)Cl(2) at -78 degrees C, reacted with alkenes to give the corresponding diarylthio-substituted compounds in a stereospecific manner in good yields, when the reaction was quenched with a soft nucleophile, such as allylsilanes, ketene silyl acetals, and triethylamine. A mechanism involving the initial formation of an episulfonium ion followed by ring-opening by the attack of ArSSAr has been suggested. The reactions of ArS(ArSSAr)(+) with alkynes also took place to give 1,2-diorganothio-substitued alkenes stereoselectively under similar conditions. (C) 2010 Published by Elsevier Ltd.

DOI： 10.1016/j.tet.2010.02.049

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An electro-oxidative method for generating silver acetylides from acetylenes with a Ag anode was developed. The reaction could be integrated into a Pd-catalysed electrochemical Sonogashira-type reaction. In the presence of the catalytic amount of Pd(OAc)(2) and 4-BzO-TEMPO, electro-generated silver acetylides reacted immediately with arylboronic acids to afford the corresponding coupling adducts in high yields.

DOI： 10.1039/c0cc02633f

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Thioacetals were found to be effective precursors to generate and accumulate alkoxycarbenium ions based on direct and indirect cation pool methods. Alkoxycarbenium ions thus generated reacted with carbon nucleophiles such as allylsilanes and enol silyl ethers to give C-C bond formation products in good yields. © 2009 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2009.09.020

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

The reaction of alkenes and alkynes with ArS(ArSSAr)(+)BF4-, which was generated and accumulated by the low-temperature anodic oxidation of ArSSAr in Bu4NBF4/CH2Cl2, led to the addition of an ArS group and fluoride across the carbon-carbon multiple bond to give thio-fluorinated compounds in good yields.

DOI： 10.1246/cl.2009.1186

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

A catalytic amount of electrochemically generated "ArS +" ("ArS+" = ArS(ArSSAr)+) initiates a cation chain reaction of dienes that involves the addition of ArSSAr associated with stereoselective intramolecular carbon-carbon bond formation, and the direct (in-cell) electrolysis of a mixture of a diene and ArSSAr with a catalytic amount of electricity also effectively initiates the reaction. © The Royal Society of Chemistry 2009.

DOI： 10.1039/b910821a

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

The "cation pools" of diarylcarbenium ions have been generated by the low-temperature electrochemical oxidation of diphenylmethane derivatives. In addition to diphenylmethanes having various substituents, 9,10-dihydroanthracene, dibenzosuberane, and xanthenes, which are annulated derivatives of diphenylmethane were also found to serve as a precursor of cation pools. The generation of the diarylcarbenium ion was confirmed by low-temperature NMR analysis and cold-spray mass analysis. Reactivity was also investigated by reactions with various carbon nucleophiles such as allyltrimethylsilane, 1,3,5-trimethylbenzene, and anisole. © 2009 The Chemical Society of Japan.

DOI： 10.1246/bcsj.82.594

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

A practical method for electrochemical iodination of aromatic compounds was developed. The method involves the generation of I+ by electrochemical oxidation of I2 in CH3CN using H 2SO4 as supporting electrolyte followed by the reaction with aromatic compounds. The para/ortho selectivity for the reaction of mono-substituted benzenes was significantly improved using dimethoxyethane as cosolvent in the second step. The reaction with highly reactive aromatic compounds led to the formation of significant amounts of diiodo compounds in a macrobatch reactor. This problem was solved by fast 1:1 mixing of I+ with an aromatic compound using a microflow system consisting of a T-shaped micromixer and a microtube reactor. © 2008 American Chemical Society.

DOI： 10.1021/op800155m

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

A method for the synthesis of thiochromans based on the reactions of stilbenes and alkoxycarbenium ion pools, which were generated and accumulated by the reaction of anodically generated ArS(ArSSAr)+ with thioacetals, has been developed. © 2008 The Japan Institute of Heterocyclic Chemistry All rights reserved.

DOI： 10.3987/COM-08-S(N)64

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

Electro-initiated coupling reactions of N-acyliminium ion with arylthiomethylsilanes and aryloxymethylsilanes were developed. Pulse electrolyses with intervals were found to be quite effective for the initiation. A chain mechanism involving cation, radical cation, and radical intermediates has been proposed. Copyright © 2008 The Chemical Society of Japan.

DOI： 10.1246/cl.2008.1008

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

A "cation pool" of an Nacyliminium ion was found to serve as an effective initiator of cationic polymerization of vinyl ethers in a microflow system consisting of two micromixers (IMM micromixer) and two microtube reactors. The cationic polymerization of n-butyl vinyl ether in CH 2Cl2 at -78°C led to very narrow molecular weight distribution (Mw/Mn=1.14). The molecular weight (M n) increased linearly with an increase in monomer/initiator ratio. The carbocationic polymer end was effectively trapped by allyltrimethylsilane. Additionally, the synthesis of block polymers was accomplished by the present microflow system controlled method. The polymerization was also conducted using commercially available trifluoromethanesulfonic acid (TfOH) as an initiator. A high level of molecular weight control was attained even at -25°C. The TfOH-initiated polymerization could be conducted using a microflow system based on T-shaped micromixers, which serves as a practical tool for microflow system controlled carbocationic polymerization. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

DOI： 10.1002/asia.200800081

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

An iterative method for molecular assembly has been developed based on the cation-pool method using (trimethylsilyl)diphenylmethane as a building block. The silyl group works as both an activating group of the benzene ring in the Friedel-Crafts type reaction and an electroauxiliary in the subsequent low temperature anodic oxidation to generate dendritic diarylcarbenium ions, which were well characterized by low-temperature NMR spectroscopy. The convergent synthesis of dendritic molecules has been achieved by repeating the sequence. Copyright © 2008 American Chemical Society.

DOI： 10.1021/ja803487q

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

(Figure Presented) The treatment of an olefinic thioacetal with a catalytic amount of ArS(ArSSAr)-+B(C6F5) 4-, or the electrolysis of a mixture of an olefinic thioacetal and ArSSAr, gives rise to effective intramolecular carbon-carbon bond formation (see scheme). This transformation opens up great potential for electroinitiated cation chain reactions in organic synthesis. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

DOI： 10.1002/anie.200705748

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Glycosyl triflates, which serve as important intermediates in glycosylation reactions, were generated and accumulated by the low-temperature electrochemical oxidation of thioglycosides such as thioglucosides, thiogalactosides, and thiomannosides in the presence of tetrabutylammonium triflate (Bu4-NOTf) as a supporting electrolyte. Thus-obtained solutions of glycosyl triflates (glycosyl triflate pools) were characterized by low-temperature NMR measurements. The thermal stability of glycosyl triflates and their reactions with glycosyl acceptors were also examined. © 2007 American Chemical Society.

DOI： 10.1021/ja072440x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The reaction of a N-acyliminium ion pool with benzylsilane proceeds by a chain mechanism involving oxidative C-Si bond cleavage. A radical/cation/radical cation crossover mechanism involving single electron transfer has been proposed. The effective binary system consisting of a stoichiometric amount of a benzylsilane and a catalytic amount of a more easily oxidized benzylstannane has been developed. Copyright © 2007 American Chemical Society.

DOI： 10.1021/ja068589a

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

(Figure Presented) "Cation pools" of diarylcarbenium ions have been generated by the oxidative C-H bond dissociation of diarylmethanes using anodic oxidation. "Diarylcarbenium ion pools" thus generated react with various nucleophiles, such as allylsilanes, ketene silyl acetals, and aromatic compounds. The reductive homocoupling of the "diarylcarbenium ion pool" has been achieved. The dimer thus obtained also serves as a precursor of the "diarylcarbenium ion pool" via oxidative C-C bond dissociation. © 2006 American Chemical Society.

DOI： 10.1021/ol061647c

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：SOC SYNTHETIC ORGANIC CHEM JPN  

We have developed the "cation pool" method in which carbocations such as alkoxycarbenium ions and N-acyliminium ions are generated and accumulated in conventional reaction media by low temperature electrochemical oxidation. The carbocations thus produced are allowed to react with a variety of nucleophiles. Various organic transformations using the cation pool method, such as reductive radical couplings, cationic carbohydroxylations, three-component couplings, and additions of organic radicals, have also been developed. Combinatorial sequential synthesis using the "cation flow" method, in which carbocations are generated in an electrochemical microflow system, has been achieved as well.

DOI： 10.5059/yukigoseikyokaishi.64.1010

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELECTROCHEMICAL SOC JAPAN  

A method for sequential introduction of two organic groups on the same or the different α-carbons of nitrogen has been developed based on a combination of the concept of electroauxiliary and the cation pool method. Selective introduction of two carbon nucleophiles into 2,5- or 2,2-position of pyrrolidine has been accomplished via sequential electrochemical oxidation of pyrrolidine derivatives containing two silyl groups as the electroauxiliaries. Introduction of two carbon nucleophiles into 2,6-position of piperidine was also successful. The products having two olefinic groups were effectively converted to nitrogen-containing spiro compounds using ring closing metathesis, and an application to formal synthesis of cephalotaxine was also carried out. These results clearly illustrate the synthetic utility and potential of the present approach, and open a new aspect of the synthesis of nitrogen-containing compounds.

DOI： 10.5796/electrochemistry.74.672

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Hexabutyldistannane was found to be an effective mediator allowing the reaction of N-acyliminium ion pools with alkyl halides. A chain mechanism involving the addition of an alkyl radical generated from an alkyl halide to an N-acyliminium ion followed by the one-electron reduction of the resulting radical-cation by distannane was proposed. © 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2006.03.114

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

A sequential one-pot indirect cation pool method has been developed. The method involves the electrochemical generation and accumulation of ArS(ArSSAr)+ at low temperature (step 1) and the follow-up reaction with a thioacetal to generate an alkoxycarbenium ion pool (step 2), which reacts with various carbon nucleophiles (step 3). Steps 2 and 3 are extremely fast. The electrogenerated ArS(ArSSAr)+ was well-characterized by 1H NMR and CSI-MS. The alkoxycarbenium ion pool generated by the present indirect method exhibited 1H and 13C NMR spectra and thermal stability similar to those of the alkoxycarbenium ion pool generated by the direct electrochemical method. Copyright © 2006 American Chemical Society.

DOI： 10.1021/ja0625778

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Selective monoiodination of aromatic compounds such as dimethoxybenzene has been successfully achieved with I+, which is generated by anodic oxidation of I2 in acetonitrile, using micromixing. © The Royal Society of Chemistry 2006.

DOI： 10.1039/b607284d

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(Chemical Equation Presented) Alkoxycarbenium ions having no substituents on the cationic carbon have been accumulated as "cation pools" by the introduction of an ether group in an appropriate position. Intramolecular participation of the ether oxygen is suggested to be responsible for stabilization of the alkoxycarbenium ions. © 2005 American Chemical Society.

DOI： 10.1021/ol051915r

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Friedel-Crafts reactions of aromatic and heteroaromatic compounds with an N-acyliminium ion pool were studied. The reaction of 1,3,5-trimethylbenzene in a batch reactor gave rise to the selective formation of a monoalkylation product (69%). Presumably, the second alkylation is slower than the first alkylation because of the protonation of the monoalkylation product that decreases its reactivity. The reaction of 1,3,5-trimethoxybenzene, however, gave rise to the formation of both monoalkylation (37%) and dialkylation (32%) products. Disguised chemical selectivity due to faster reaction than mixing seems to be responsible for the lack of selectivity. The use of micromixing was found to be quite effective to solve this problem to increase the selectivity. The monoalkylation product was obtained in 92% yield together with a small amount of the dialkylation product (4%). The reaction with various aromatic and heteroaromatic compounds revealed that the low mono/dialkylation selectivity was observed only for highly reactive aromatics. In such cases, the use of micromixing was quite effective to improve the selectivity. On the basis of micromixing, the selective sequential dialkylation using two different N-acyliminium ions was achieved. CFD simulations using a laminar flow and finite-rate model are consistent with the experimental observations and clearly indicate the importance of mixing. © 2005 American Chemical Society.

DOI： 10.1021/ja0527424

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The "cation flow" method, in which highly reactive carbocations are generated in the absence of nucleophiles by low temperature electrolysis and are allowed to react with carbon nucleophiles in the microflow system to achieve direct electrooxidative C-C bond formation, has been developed. As an extension of the cation flow method, an electrochemical paired microflow system that involves concurrent anodic generation of carbocations and cathodic generation of carbon nucleophiles followed by their reactions to achieve straightforward C-C bond formation has also been developed. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.

DOI： 10.1002/qsar.200440003

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N-Acyliminium ion pools, which are generated from α-silyl carbamates, were found to react with a variety of alkenes and alkynes to give the corresponding cycloadducts. The reaction with styrene derivatives gave rise to the formation of a significant amount of polymeric products. The use of micromixing, however, resulted in a significant increase in the yield of the cycloadduct at the expense of the polymer. Mechanistic studies indicated that a concerted mechanism seems to be most likely for alkyl-substituted alkenes, whereas a stepwise mechanism seems to be reasonable for aryl-substituted alkenes. © 2005 The Chemical Society of Japan.

DOI： 10.1246/bcsj.78.1206

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The reaction of an N-acyliminium ion with an alkyl iodide and hexabutyldistannane took place to give the alkylation product. A mechanism involving the addition of an alkyl radical to an N-acyliminium ion to produce the corresponding radical cation has been suggested. Copyright © 2005 American Chemical Society.

DOI： 10.1021/ja0511218

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The "cation pools" of alkoxyarylcarbenium ions were effectively generated by the oxidative C-C bond dissociation using low temperature electrolysis. The present method is especially effective for the generation and accumulation of dications, which react with carbon nucleophiles. Copyright © 2005 American Chemical Society.

DOI： 10.1021/ja050414y

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Organic reactions using microreactors have attracted significant research interest because of their inherent features such as fast mixing, precise temperature control, and precise residence time control. These features are especially advantages for fast and exothermic reactions, which are difficult to perform using conventional macro-scale batch reactors in a controlled manner. Some examples of such reactions including Friedel-Crafts alkylation, cationic polymerization, and Swern oxidation are described in this article. Other examples are also demonstrated with the special emphasis on multiphase reactions. These examples speak well for the potentiality of microreactors in the enhancement of the ability of organic synthesis to meet demanding expectations in future.

DOI： 10.5059/yukigoseikyokaishi.63.511

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Anodic methoxylation of several organic compounds has been successfully achieved in the absence of intentionally added supporting electrolyte using an electrochemical microflow system. © The Royal Society of Chemistry 2005.

DOI： 10.1039/b417388k

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This article provides a brief outline of the state of the art reactions using microreactors with special emphasis on the enhancement of product selectivity. The efficient micromixing possible with a short diffusion path increases the product selectivity of competitive parallel reactions and competitive consecutive reactions. This concept has been expanded to control of the molecular weight and molecular weight distribution in carbocationic polymerization. The efficient heat transfer, based on high surface to volume ratios, allows precise temperature control and is also effective for the control of highly exothermic reactions, such as free radical polymerization. © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOI： 10.1002/ceat.200407127

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Publishing type：Research paper (international conference proceedings)  

The cation pool of an N-acyliminium ion was found to serve as an effective initiator of cationic polymerization of vinyl ethers in a microsystem consisting of two micromixers and a micro tube reactor. The polymerization led to very narrow molecular weight distribution (Mw/Mn = 1.14). The molecular weight (Mn) increased linearly with an increase of the amount of the monomer. The carbocationic polymer end was effectively trapped by allyltrimethylsilane. The present observations illustrate the potential of microsystems, in conjunction with the cation pool, to effect polymerization in a highly controlled manner without the deceleration inherent in the dynamic equilibrium between active and dormant species.

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The "cation pool" of an N-acyliminium ion was found to serve as an effective initiator of cationic polymerization of vinyl ethers in a microsystem consisting of two micromixers and a microtube reactor. The polymerization led to very narrow molecular weight distribution (Mw/Mn = 1.14). The molecular weight (Mn) increased linearly with an increase in the amount of the monomer. The carbocationic polymer end was effectively trapped by allyltrimethylsilane. The present observations illustrate the potential of microsystems, in conjunction with the cation pool, to effect polymerization in a highly controlled manner without the deceleration inherent in the dynamic equilibrium between active and dormant species. Copyright © 2004 American Chemical Society.

DOI： 10.1021/ja044879k

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Sequential one-pot three-component coupling reactions have been developed based on the "cation pool" method. An N-acyliminium ion generated by the "cation pool" method adds to an electron-rich carbon-carbon double bond, such as enamine derivatives and vinyl sulfides, to form the second "cation pool". The addition of nucleophiles such as allylsilanes, enol silyl ethers, Grignard reagents, and organoaluminum compounds led to the formation of the corresponding three-component coupling products. Copyright © 2004 American Chemical Society.

DOI： 10.1021/ja0455704

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(Chemical Equation Presented) Alkoxycarbenium ions have been generated and accumulated as "cation pools" by the low-temperature electrochemical oxidation of α-phenylthioethers. Although an unsuccessful attempt to accumulate glycosyl cations was made, a one-pot method for electrochemical glycosylation, which involves anodic oxidation of thioglycosides to generate glycosyl cation equivalents followed by their reactions with glycosyl acceptors, has been developed.

DOI： 10.1021/ol048524h

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The reactions of an N-acyliminium ion pool with alkenes and alkynes gave γ-amino alcohols and β-amino carbonyl compounds, respectively, after treatment with H2O/Et3N. The present reaction serves as an efficient method for cationic carbohydroxylation of alkenes and alkynes. When vinyltrimethylsilane was used as an alkene, the reaction was highly diastereoselective and served as an access to an enantiomerically pure α-silyl-γ-amino alcohol.

DOI： 10.1021/ol049049q

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The electrochemical reduction of N-acyliminium ions, which were generated by the "cation pool" method, led to the formation of carbon free radicals. Carbon radicals thus generated underwent homo-coupling reactions and the reactions with activated olefins, such as methyl acrylate. In the latter case, a mechanism involving the addition of a carbon radical to the carbon-carbon double bond, followed by one-electron reduction to give carbanions, has been proposed. The present study opens a new possibility for radical-mediated carbon-carbon bond formation based on the reduction of carbocations.

DOI： 10.1246/bcsj.77.1545

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Publishing type：Research paper (international conference proceedings)  

Highly selective Friedel-Crafts monoalkylation, which was intrinsically difficult to be achieved by conventional methods, has been accomplished by micromixing. N-Acyliminium ion generated by the "cation pool" method was used as an alkylating agent and 1,3,5-trimethoxybenzene was used as an aromatic compound. The reaction in a macro-scale batch reactor (magnetic stirring) gave rise to the formation of a mixture of the monoalkylation product and the dialkylation product in ca. 1:1 ratio, but the use of a multilamination-type micromixer led to selective monoalkylation (92% yield). Based on the micromixing, the selective sequential dialkylation using two different alkylating agents was achieved.

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(Matrix presented). An N-acyliminium ion pool was found to undergo cycloaddition reaction with a variety of dienophiles such as alkenes and alkynes. A concerted mechanism seems to be most likely for alkyl-substituted alkenes as suggested by the DFT calculations, whereas a stepwise mechanism plays the major role for aryl-substituted alkenes. It is also noteworthy that the present study demonstrates the potential of the combination of the cation pool method and the micromixing in both mechanistic and synthetic aspects.

DOI： 10.1021/ol0341243

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Highly selective Friedel-Crafts monoalkylation of aromatic compounds with N-acyliminium ions has been achieved by efficient 1:1 mixing using a multilamination-type micromixer. © 2003 The Royal Society of Chemistry.

DOI： 10.1039/b211433j

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The sequential introduction of two carbon nucleophiles on the same α-carbon of nitrogen by using selective oxidative cleavage of two silyl groups as electroauxilialies has been accomplished. The combination of this expedient transformation and ring-closing metathesis enables reliable and straightforward syntheses of nitrogen-containing spiro compounds, such as cephalotaxine. Copyright © 2002 American Chemical Society.

DOI： 10.1021/ja028663z

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Carbocations have been generally considered to be relatively unstable and transient species. But the "cation pool" method enables the easy accumulation of carbocations in conventional reaction media such as dichloromethane. In the "cation pool" method, carbocations are generated by low-temperature electrochemical oxidation and accumulated in a solution. In the next step, the carbocations thus produced are allowed to react with various nucleophiles. Combinatorial parallel synthesis based upon the "cation pool" method has also been developed. The applicability of the "cation pool" method depends upon the stability of the cation that is accumulated. This problem can be overcome by the "cation flow" method. In the "cation flow" method, carbocations are generated in a microflow electrochemical system. Short residence times and efficient temperature control of the microflow system are advantageous. Combinatorial sequential synthesis has been achieved based on the "cation flow" method.

DOI： 10.1002/1521-3765(20020617)8:12<2650::AID-CHEM2650>3.0.CO;2-S

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Carbocations, carbon radicals, and carbanions are important reactive carbon intermediates in organic chemistry, and their interconversions can be carried out by redox processes. Although, such relationships have been well recognized, experimental work has been limited to analytical studies on highly stabilized intermediates. In this study such interconversions were examined using electrochemical reduction of "cation pools". Acyliminium cations, which were generated by low-temperature electrolysis of carbamates, were reduced electrochemically in the absence of radical acceptors. The homo coupling products formed effectively, suggesting that the one-electron reduction of the acyliminium cation produced the corresponding carbon-centered radical. Next, the electrochemical reduction of the acyliminium cations in the presence of electron-deficient olefins was examined. The cross coupling products were obtained in good-to-moderate yields. A mechanism involving radical addition to the double bond followed by the reduction of the resulting radical to the carbanion was suggested. The overall transformation serves as redox-mediated formal addition of C-H to C=C. The present strategy opens new opportunities to manipulate reactive carbon species using redox processes in organic synthesis. Copyright © 2002 American Chemical Society.

DOI： 10.1021/ja0171759

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DOI： 10.15227/orgsyn.079.0139

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The selective electrochemical oxidation of heteroatom compounds having two different electroauxiliaries, i.e. silicon and tin, on the same α-carbon was examined. The oxidation potentials of such compounds were found to be similar to those of the corresponding compounds having only tin, indicating the predominant role of tin over that of silicon. The HOMO levels obtained by the molecular orbital calculations were consistent with the experimental results. The molecular orbital calculation of the cation radical suggests the selective cleavage of the C-Sn bond by the oxidation. Preparative electrochemical oxidation gave rise to selective cleavage of the C-Sn bond and the introduction of a nucleophile to the carbon. The C-Si bond was not affected at all. The product can also be further oxidized using the silyl group as an electroauxiliary. The second oxidation proceeded smoothly to cleave the C-Si bond and a second nucleophile was introduced on the same carbon. The present study indicates the feasibility of the redox potential based selective sequential transformation using electroauxiliaries. © 2001 Elsevier Science B.V.

DOI： 10.1016/S0022-0728(01)00402-8

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We have developed an efficient direct oxidative α-alkylation and -arylation of carbamates based on the 'cation pool' method. Grignard reagents, organozinc compounds, and organoaluminum compounds are effective as carbon nucleophiles toward iminium cation pools generated by low temperature electrolysis of carbamates. © 2001 Elsevier Science Ltd.

DOI： 10.1016/S0040-4039(01)00128-9

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Asymmetric addition of dialkylzincs to aldehydes in the presence of (2S)-3-exo(dimethylamino)isoborneol [(5)-DAIB] exhibits various nonclassical phenomena. The enantiomeric excess (ee) of the alkylation product, obtained with partially resolved DAIB, is much higher than that of the chiral amino alcohol, while the rate decreases considerably as the ee of DAIB is lowered. The asymmetric amplification effects reflect the relative turnover numbers of two enantiomorphic catalytic cycles, where an essential feature is the reversible homochiral and heterochiral dimerization of the coexisting enantiomeric DAIB-based Zn catalysts. The interplay between the thermodynamics of the monomer/dimer equilibration and the kinetics of alkylation reaction strongly affect the overall profile of asymmetric catalysis. The self and nonself recognition of the chiral Zn catalysts is a general phenomenon when (5)-DAIB is mixed with its enantiomer, diastereomer, or even an achiral -amino alcohol. The degree of nonlineariry is highly affected not only by the structures and purity of catalysts but also by various reaction parameters. The salient features have been clarified on the basis of molecular weight measurements, NMR and X-ray crystallographic studies of organozinc complexes, and kinetic experiments, as well as computer-aided quantitative analysis. ©2001 The Jaoan Chemical Tournai Forum and lohn Wilev & Sons. Inc.

DOI： 10.1002/tcr.1.abs

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Organoheteroatom compounds having a 2-(2-pyridyl)ethyl group were synthesized and their oxidation potentials were determined by rotating disk electrode voltammetry. The oxidation potentials were found to be less positive than those of the corresponding compounds having a phenyl group in place of the pyridyl group. The dynamic coordination of the pyridyl group to the heteroatom, which stabilizes the cation radical intermediate, seems to be responsible for facilitating the electron transfer. The magnitude of the intramolecular assistance increases along with an increase in the oxidation potential of the parent compounds. This tendency can be explained in terms of the energy match between the nonbonding p orbital of the pyridyl nitrogen and the HOMO of the parent heteroatom compound.

DOI： 10.1246/bcsj.73.243

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We have developed a method that involves the generation of a 'cation pool' using low-temperature electrolysis, and then its reaction with nucleophiles under non-oxidative conditions. This one-pot method solves problems associated with conventional oxidative generation of cations and their in situ reaction with nucleophiles, and provides an efficient method for direct oxidative carbon-carbon bond formation. As an example of this method, generation of cation pools from carbamates by low-temperature electrolysis (-72 °C) and their reactions with carbon nucleophiles such as allylsilanes, enol silyl ethers, and enol acetates were examined and the desired products were obtained in good yields. Aromatic compounds and 1,3- dicarbonyl compounds can also be utilized as carbon nucleophiles. The present method was also applied to combinatorial parallel synthesis using a robotic synthesizer.

DOI： 10.1021/ja9920112

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Tin hydrides having one or two pyridyl groups show unique reactivity in the reduction of alkyl halides under radical conditions, indicating the potential of intramolecular coordination for the control of radical reactions.

DOI： 10.1039/a903795k

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2-Pyridyldimethylsilyl (2-PyMe2Si) group was found to serve as effective 'phase tag' for acid-base extraction for solution phase synthesis. Acid-base extraction of octyl(2-pyridyl)dimethylsilane gave rise to 98% recovery. The introduction of 2-PyMe2Si group to organic molecules was easily accomplished by Rh catalyzed hydrosilylation of alkenes with 2- PyMe2SiH. The removal of 2-PyMe2Si group was achieved by the oxidation with H2O2/KF (Tamao oxidation). In order to demonstrate the utility of 2- PyMe2Si group as a 'phase tag', a sequential multi-step transformation was conducted. The products of each steps were easily isolated by acid-base extraction, and were sufficiently pure for the direct use in the next step of the sequence.

DOI： 10.1016/S0040-4039(99)00474-8

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Although alkoxymethylsilanes serve as useful building blocks, various efforts to synthesize them by substitution reaction with an alkoxide ion at the carbon adjacent to the silicon failed. To solve this synthetic problem a new route which is very simple to perform was developed. Bromination of (methoxymethyl)trimethylsilane by using N-bromosuccinimide/2,2′-azobisisobutyronitrile (NBS/AIBN) was followed by a substitution by alcohols in the presence of triethylamine to give the corresponding [alkoxy-(methoxy)methyl]trimethylsilanes. These acetals can be used directly for the next reduction with di-isobutylaluminium hydride (DIBAL-H) or Et3SiH/BF3·OEt2 to give alkoxymethylsilanes in good to moderate yields. The success of the substitution reaction with the alcohols suggests that the mechanism is of somewhat SN1 by nature and formation of the cationic intermediate seems to release the steric hindrance around the carbon, allowing the attack of alcohols. Copyright © 1999 John Wiley & Sons, Ltd.

DOI： 10.1002/(SICI)1099-0739(199906)13:6<469::AID-AOC872>3.0.CO;2-A

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The introduction of 2-(2-pyridyl)ethyl group on silicon decreases the oxidation potentials of silyl-substituted heteroatom compounds. The molecular orbital calculations indicate that this effect is attributed to the dynamic coordination of the pyridyl group to silicon in the cation radical intermediate. Such coordination also facilitates the selective C-Si bond cleavage.

DOI： 10.1246/cl.1999.251

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Asymmetric reaction of dimethylzinc and benzaldehyde in the presence of (2S)-3-exo-(dimethyl-amino)isoborneol [(2S)-DAIB] exhibits unusual nonlinear phenomena. The enantiomeric purity of the product is much higher than that of the chiral source, DAIB, while the rate of the enantioselective catalysis decreases considerably as the enantiomeric excess (ee) of DAIB is lowered. Such effects originate from the reversible homochiral and heterochiral interaction of the coexistent enantiomeric zinc amino alkoxide catalysts which are formed from dimethylzinc and (2S)- and (2R)-DAIB. The thermodynamics of the five-component equilibration between the two monomers and three dimers, when coupled with the kinetics of the alkylation, strongly affects the extent of enantioselectivity and the reaction rate of the alkylation reaction. The overall profile of the nonlinear effects has been clarified mathematically using experimentally available parameters, viz., the equilibrium constants of the dimer/monomer conversion and the association of the monomeric catalyst with the organozinc and aldehyde, the rate constant of alkyl transfer from the catalyst/dimethylzinc/aldehyde mixed complex, the ee of DAIB, and the concentrations of DAIB, dimethylzinc, and aldehyde. 3D graphics are presented for the correlation of the enantiomeric purity of the product with DAIB ee and the concentrations of dimethylzinc and aldehyde and for the relationship between the reaction rate, DAIB ee, and the concentrations of the organozinc and aldehyde. The computer simulation is in good agreement with the experimental results, confirming thai the nonlinear effects result from the competition of two enantiomorphic catalytic cycles involving the monomeric chiral zinc catalysts rather than the diastereomorphic catalytic cycles with dinuclear zinc catalysts. Furthermore, this study indicates that the degree of nonlinear effects in asymmetric catalysis could be affected not only by the catalyst ee but also by various reaction parameters, particularly the concentrations of the catalyst, reagent, and substrate as well as the extent of conversion.

DOI： 10.1021/ja981740z

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The selective electrochemical oxidation of heteroatom compounds having two different types of electroauxiliaries, i.e. silicon and tin on the same α carbon has been achieved. The C-Sn bond was cleaved selectively and a nucleophile was introduced. The second oxidation of the compound thus obtained gave rise to the cleavage of the C-Si bond and the introduction of a second nucleophile. The present study indicates the feasibility of the redox potential based strategies using electroauxiliaries.

DOI： 10.1246/cl.1998.1011

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Dimethylzinc reacts with (2S)or (2 R)-3-exo-(dimethylamino)isoborneol [(2S)- or (2R)-DAIB] to eliminate methane and produce a tricoordinate methylzinc aminoalkoxide, which forms a dimeric structure. The homochiral dimerization of the enantiomeric compound leads to the chiral, (S,S) or (R.R) dinuclear Zn complex, while the heterochiral interaction forms the meso (S,R) dinuclear compound. In both solution anti crystalline state, the heterochiral dimer is more stable than the homochiral dimer. This stability difference in solution is the origin of the chirality amplification observed in the amino alcohol promoted asymmetric addition of dimethylzinc to benxaldehyde. In toluene, the homochiral dimer dissociates more readily into the monomer than the heterochiral isomer and also undergoes dissociation of the N Zn dative bond making the two N-methyl groups equivalent. The differences in solution behavior between the diastereomers can be understood by comparing their crystal structures. X-ray analysis indicates that the labile Zn O and Zn N bonds in the (S,S) dimer are longer than those in the (S,R) isomer. Skeletal congestion caused by the polycyclic framework is the prime factor determining the properties of the dinuclear Zn complexes, with both steric and electronic factors governing their geometries. The distances between the C-2 proton and N-CH3 of the other DAIBmoiety in the homochiral dimer are close to the sum of the van der Waals radii. A significant nuclear Overhauser effect is seen between these protons in the homochiral dimer. The tetrahedral Zn atoms in the dinuclear complexes are linked covalently to the methyl group, to two oxygen atoms through covalent/electrostatic hybrid bonds, and to the dimethylamino group through electrostatic interaction. The repulsive interaction of the 1,3-syn-oriented Zn CH3 bonds significantly contributes to the lower stability of the homochiral dimeric complex. The N Zn interaction in the homochiral dimer is labile, owing to the increase in the electrostatic interaction between the Zn atom and the neighboring oxygen atoms. This view is supported by the ab initio molecular orbital calculations of the model systems.

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Dimethylzinc reacts with (2S)-or (2R)-3-exo-(dimethylamino)isoborneol [(2S)- or (2R)-DAIB] to eliminate methane and produce a tricoordinate methylzinc aminoalkoxide, which forms a dimeric structure. The homochiral dimerization of the enantiomeric compound leads to the chiral, (S,S) or (R,R) dinuclear Zn complex, while the heterochiral interaction forms the meso (S,R) dinuclear compound. In both solution and crystalline state, the heterochiral dimer is more stable than the homochiral dimer. This stability difference in solution is the origin of the chirality amplification observed in the amino alcohol promoted asymmetric addition of dimethylzinc to benzaldehyde. In toluene, the homochiral dimer dissociates more readily into the monomer than the heterochiral isomer and also undergoes dissociation of the N-Zn dative bond making the two N-methyl groups equivalent. The differences in solution behavior between the diastereomers can be understood by comparing their crystal structures. X-ray analysis indicates that the labile Zn-O and Zn-N bonds in the (S,S) dimer are longer than those in the (S,R) isomer. Skeletal congestion caused by the polycyclic framework is the prime factor determining the properties of the dinuclear Zn complexes, with both steric and electronic factors governing their geometries. The distances between the C-2 proton and N-CH3 of the other DAIB moiety in the homochiral dimer are close to the sum of the van der Waals radii. A significant nuclear Overhauser effect is seen between these protons in the homochiral dimer. The tetrahedral Zn atoms in the dinuclear complexes are linked covalently to the methyl group, to two oxygen atoms through covalent/electrostatic hybrid bonds, and to the dimethylamino group through electrostatic interaction. The repulsive interaction of the 1,3-synoriented Zn-CH3 bonds significantly contributes to the lower stability of the homochiral dimeric complex. The N-Zn interaction in the homochiral dimer is labile, owing to the increase in the electrostatic interaction between the Zn atom and the neighboring oxygen atoms. This view is supported by the ab initio molecular orbital calculations of the model systems. © VCH Verlagsgesellschaft mbH, 1996.

DOI： 10.1002/chem.19960020921

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Chiral β-dialkylamino alcohols promote enantioselective alkylation of aldehydes by dialkylzincs, where a tricoordinate alkylzinc aminoalkoxide in equilibrium with its dimer acts as a true catalyst. The presence of other aminoalkoxides causes nonlinear effects on the rate and stereoselectivity of the enantioselective catalysis. This is a general phenomenon where the extent of the departure from the linearity is highly affected by the nature of the amino alcohols. Systematic investigation using (2S)-3-exo-(dimethylamino)isobomeol and its stereoisomers as well as achiral 2-(dimethylamino)-1,1-dimethylethanol has revealed that the self and nonself recognition of the asymmetric catalysts are the major source of this unusual phenomena. The relative significance of these recognitions affects the overall profile of asymmetric catalysis. © 1995, American Chemical Society. All rights reserved.

DOI： 10.1021/ja00122a013

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Reaction of dimethylzinc and (2S)- or (2R)-3-exo-(dimethylamino)isoborneol forms methylzinc alkoxide 1, which forms a dimeric structure 2 in a reversible manner. Depending on the chirality of the monomer 1, three stereoisomeric dinuclear complexes are formed; the homochiral dimerization of 1 leads to (S,S)- or (R,R)-2, whereas the heterochiral interaction forms (S,R)-2. The heterochiral dimer is thermodynamically favored over the homochiral dimer in both toluene solution and crystalline states. The vapor pressure osmometry method has revealed that the stereoisomeric dimers 2 in toluene are in equilibrium with the monomer 1 with dissociation constants Khomo = (3.0 ± 1.0) × 10-2 and Khetero ≅ 1 × 10-5 at 40°C, respectively. Calorimetric determination of the enthalpies of solution of the crystalline compounds indicates that the S,R heterochiral dimer is more stable than the S,S or R,R homochiral dimer by 3.4 ± 0.8 kJ mol-1 in the solid state. © 1994 American Chemical Society.

DOI： 10.1021/j100099a048

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Reaction of 2,2′‐dilithio‐1,1′‐binaphthyl with selenium followed by air oxidation gives a mixture of dinaph‐thoselenophene and dimer and oligomers of 2,2′‐diseleno‐1,1′‐binaphthyl. 2,2′‐Dilithio‐1,1′‐biphenyl reacts with selenium to afford dibenzo[c,e][1,2]diselenin. Structures of the dimeric 2,2′‐diseleno‐1,1′‐binaphthyl and dibenzo[c,e][1,2]diselenin have been confirmed by X‐ray crystallographic analyses. Similar reaction of 2,2′‐dilithio‐1,1′‐binaphthyl with sulfur or tellurium gives a mixture of dinaphthothiophene and dinaphtho[2,1‐c:‐1′,2′‐e][1,2]dithiin or a mixture of dinaphthotellurophene and oligomer of 2,2′‐ditelluro‐1,1′‐binaphthyl, respectively. Dibenzotellurophene and oligomer of 2,2′‐ditelluro‐1,1′‐biphenyl are obtained from reaction of 2,2′‐dilithio‐1,1′‐biphenyl with tellurium. Copyright © 1991 Journal of Heterocyclic Chemistry

DOI： 10.1002/jhet.5570280243

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Nucleophilic addition of dialkylzincs to aldehydes in hydrocarbon solvents is markedly accelerated by the presence of a catalytic amount of a β-dialkylamino alcohol. Use of certain sterically constrained chiral amino alcohols such as 3-exo-(dimethylamino)isoborneol or 1-t-butyl-2-piperidinoethanol effects highly enantioselective catalysis giving secondary alcohols in up to 99% ee. Dimethyl-, diethyl-, di-n-butyl-, and di-n-pentyl-zincs have been employed for the alkylation of substituted benzaldehydes and some olefinic or aliphatic aldehydes. Configurational correlation between the chiral auxiliary and alkylation products is discussed. © 1990.

DOI： 10.1016/0022-328X(90)85212-H

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In the presence of a catalytic amount of (-)-3-exo-(dimethylamino)isoborneol (DAIB), reaction of dialkylzincs and aldehydes is accelerated markedly to give, after hydrolysis, the corresponding S-alcohols in high enantiomeric purity. The reaction mechanism and origin of the enantioselection have been elucidated on the basis of the kinetic measurement, alkylscrambling experiments, single-crystal X-ray analysis, 1H NMR study, molecular weight determination of certain key intermediates. Reaction of DAIB and dimethylzinc in a 1:1 molar ratio produces a single dinuclear zinc chelate complex, which does not alkylate benzaldehyde but acts as catalyst precursor. The alkylation proceeds via a dinuclear zinc species containing the DAIB auxiliary, an aldehyde ligand, and three alkyl groups, where it is the bridging alkyl group, rather than the terminal alkyls, that migrates from zinc to the aldehyde carbon. Kinetic measurements and temperature effects on the enantioselectivity indicate that the alkyl transfer process is the turnover-limiting and stereodetermining step. A new type of nonlinear effect has been observed in this enantioselective alkylation. For example, reaction of benzaldehyde and diethylzinc in the presence of 8 mol % of (-)-DAIB in 15% ee leads to (S)-1-phenyl-1-propanol in 95% ee. This unusual phenomenon is a result of a marked difference in chemical properties of the diasteromeric dinuclear complexes formed from dialkylzincs and the DAIB auxiliary. Reaction of equimolar amounts of dimethylzinc and enantiomerically pure DAIB affords a dinuclear chelate complex with C2 chirality, which acts as the active catalyst precursor of the alkylation. By contrast, dimethylzinc and racemic DAIB generate a more stable, but much less reactive, dinuclear complex possessing a meso, C1 structure, rather than a racemic mixture of the chiral complex. © 1989, American Chemical Society. All rights reserved.

DOI： 10.1021/ja00193a040

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Multinuclear organometallic species play a significant role in alkylation of carbonyl compounds. Enantioselective alkylation of aldehydes using a 1:1 reagent/substrate stoichiometry is achievable by chirally modified lithium/magnesium binary organometallic reagents. For example, diethylmagnesium treated with di-O-lithio-(S)-2,2' ‘-dihydroxy-1,1’-binaphthyl reacts with benzaldehyde in a THF—dimethoxyethane mixture at-100 °C to give (S)-1-phenyl-1-propanol in 92% ee. In the presence of a catalytic quantity of (-)-3-exo-(dimethylamino)isoborneol (DAIB), reaction of dialkylzincs and aldehydes in nonpolar media is accelerated greatly to lead to the corresponding S alcohols in very high enantiomeric excesses (up to 99% ee). The enantioselective catalysis involves fluxional organozinc species and the product-forming dinuclear intermediate possesses DAIB auxiliary, an aldehyde ligand, and three alkyl groups, where it is the bridging alkyl group, rather than the terminal alkyls, that migrates from zinc to the carbonyl carbon. © 1988 IUPAC

DOI： 10.1351/pac198860111597

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DOI： 10.1021/ja00279a083

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