論文 - 宮本　和範

Room-temperature synthesis of m-benzyne

Koyamada K., Miyamoto K., Uchiyama M.

Nature Synthesis 3 （ 9 ） 1083 - 1090 2024年09月

研究論文（学術雑誌）, 責任著者, 査読有り

　概要を見る

For over a century, scientists have been fascinated by the unique electronic, structural and bonding properties of the three isomers of benzyne, a highly reactive organic intermediate derived from benzene by removing two hydrogen atoms. Although o- and p-benzynes have been extensively studied following the establishment of reliable synthetic methods to prepare them, m-benzyne in the ground state has remained experimentally inaccessible. We report herein the room-temperature and atmospheric-pressure synthesis of m-benzyne in solution. Experimental and theoretical investigations revealed that owing to the inner bond inside the benzene ring between C1 and C3 atoms, m-benzyne behaves as a potent electrophile with a Mayr’s electrophilicity parameter E of around −2 but shows weak free-radical character. The bonding appears similar to the inverted σ-bond, the so-called charge-shift bond, in [1.1.1]propellane. By utilizing the unique bonding character of m-benzyne, we established halogenations and C–N and C–C coupling reactions, as well as a successive m-benzyne generation and trapping sequence that provides access to 1,3,5-trisubstituted benzenes. (Figure presented.)

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Transition-Metal-Free Thioboration of Terminal Alkynes

Matsuyama T., Ishida H., Wang C., Miyamoto K., Nakajima M., Toriumi N., Nagashima Y., Uchiyama M.

JACS Au （American Chemical Society (ACS)）  4 （ 12 ） 4927 - 4933 2024年

研究論文（学術雑誌）, 査読有り,  ISSN  2691-3704

　概要を見る

We present a new type of elementoboration reaction, the thioboration of terminal alkynes. This method enables highly controllable regio-/stereo-/chemoselective cis- and trans-thioboration on demand, affording synthetically versatile and densely functionalized vinyl boron/vinyl sulfide derivatives in a straightforward manner without the need for a transition-metal catalyst.

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Dearomative triple elementalization of quinolines driven by visible light

Ishigaki S., Nagashima Y., Yukimori D., Tanaka J., Matsumoto T., Miyamoto K., Uchiyama M., Tanaka K.

Nature Communications 14 （ 1 ）  2023年12月

研究論文（学術雑誌）, 査読有り

　概要を見る

Organoboron and organosilicon compounds are used not only as synthetic building blocks but also as functional materials and pharmaceuticals, and compounds with multiple boryl and silyl groups are beginning to be used for these purposes. Especially in drug discovery, methodology providing easy stereoselective access to aliphatic nitrogen heterocycles bearing multiple boryl or silyl groups from readily available aromatic nitrogen heterocycles would be attractive. However, such transformations remain challenging, and available reactions have been mostly limited to dearomative hydroboration or hydrosilylation reactions. Here, we report the dearomative triple elementalization (carbo-sila-boration) of quinolines via the addition of organolithium followed by photo-boosted silaboration, affording the desired products with complete chemo-, regio-, and stereoselectivity. The reaction proceeds via the formation of silyl radicals instead of silyl anions. We also present preliminary studies to illustrate the potential of silaboration products as synthetic platforms.

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Mechanistic Analysis of Stereodivergent Nitroalkane Cyclopropanation Catalyzed by Nonheme Iron Enzymes

Ushimaru R., Cha L., Shimo S., Li X., Paris J.C., Mori T., Miyamoto K., Coffer L., Uchiyama M., Guo Y., Chang W.C., Abe I.

Journal of the American Chemical Society 145 （ 44 ） 24210 - 24217 2023年11月

研究論文（学術雑誌）, 査読有り,  ISSN  00027863

　概要を見る

BelL and HrmJ are α-ketoglutarate-dependent nonheme iron enzymes that catalyze the oxidative cyclization of 6-nitronorleucine, resulting in the formation of two diastereomeric 3-(2-nitrocyclopropyl)alanine (Ncpa) products containing trans-cyclopropane rings with (1′R,2′R) and (1′S,2′S) configurations, respectively. Herein, we investigate the catalytic mechanism and stereodivergency of the cyclopropanases. The results suggest that the nitroalkane moiety of the substrate is first deprotonated to produce the nitronate form. Spectroscopic analyses and biochemical assays with substrates and analogues indicate that an iron(IV)-oxo species abstracts proS-H from C4 to initiate intramolecular C-C bond formation. A hydroxylation intermediate is unlikely to be involved in the cyclopropanation reaction. Additionally, a genome mining approach is employed to discover new homologues that perform the cyclopropanation of 6-nitronorleucine to generate cis-configured Ncpa products with (1′R,2′S) or (1′S,2′R) stereochemistries. Sequence and structure comparisons of these cyclopropanases enable us to determine the amino acid residues critical for controlling the stereoselectivity of cyclopropanation.

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Total Biosynthesis of Melleolides from Basidiomycota Fungi: Mechanistic Analysis of the Multifunctional GMC Oxidase Mld7

Fukaya M., Nagamine S., Ozaki T., Liu Y., Ozeki M., Matsuyama T., Miyamoto K., Kawagishi H., Uchiyama M., Oikawa H., Minami A.

Angewandte Chemie - International Edition 62 （ 44 ）  2023年10月

研究論文（学術雑誌）, 査読有り,  ISSN  14337851

　概要を見る

Mushroom terpenoids are biologically and chemically diverse fungal metabolites. Among them, melleolides are representative sesquiterpenoids with a characteristic protoilludane skeleton. In this study, we applied a recently established hot spot knock-in method to elucidate the biosynthetic pathway leading to 1α-hydroxymelleolide. The biosynthesis of the sesquiterpene core involves the cytochrome P450 catalyzing stepwise hydroxylation of the Δ6-protoilludene framework and a stereochemical inversion process at the C5 position catalyzed by short-chain dehydrogenase/reductase family proteins. The highlight of the biosynthesis is that the flavoprotein Mld7 catalyzes an oxidation-triggered double-bond shift accompanying dehydration and acyl-group-assisted substitution with two different nucleophiles at the C6 position to afford the Δ7-protoilludene derivatives, such as melleolide and armillarivin. The complex reaction mechanism was proposed by DFT calculations. Of particular importance is that product distribution is regulated by interaction with the cell membrane.

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Structural and Mechanistic Insights into the C-C Bond-Forming Rearrangement Reaction Catalyzed by Heterodimeric Hinokiresinol Synthase

Ushimaru R., Ding Y., Mori T., Miyamoto K., Uchiyama M., Abe I.

Journal of the American Chemical Society 145 （ 40 ） 21966 - 21973 2023年10月

研究論文（学術雑誌）, 査読有り,  ISSN  00027863

　概要を見る

Hinokiresinol synthase (HRS) from Asparagus officinalis consists of two subunits, α and β, and catalyzes an unusual decarboxylative rearrangement reaction of 4-coumaryl 4-coumarate to generate (Z)-hinokiresinol with complete stereoselectivity. Herein, we describe the mechanism of rearrangement catalysis and the role played by the heterodimeric HRS, through structural and computational analyses. Our results suggest that the HRS reaction is unlikely to proceed via the previously hypothesized Claisen rearrangement mechanism. Instead, we propose that the 4-coumaryl 4-coumarate substrate is first cleaved into coumarate and an extended p-quinone methide, which then recombine to generate a new C-C bond. These processes are facilitated by proton transfers mediated by the basic residues (α-Lys164, α-Arg169, β-Lys168, and β-Arg173) in the cavity at the heterodimer interface. The active site residues, α-Asp165, β-Asp169, β-Trp17, β-Met136, and β-Ala171, play crucial roles in controlling the regioselectivity of the coupling between the fragmented intermediates as well as the stereoselectivity of the decarboxylation step, leading to the formation of the (Z)-hinokiresinol product.

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Mechanistic Investigation of the Degradation Pathways of α-β/α-α Bridged Epipolythiodioxopiperazines (ETPs)

Kurita D., Sato H., Miyamoto K., Uchiyama M.

Journal of Organic Chemistry 88 （ 17 ） 12797 - 12801 2023年09月

研究論文（学術雑誌）, 査読有り,  ISSN  00223263

　概要を見る

Epipolythiodioxopiperazines (ETPs) make up a class of biologically active fungal metabolites with a transannular disulfide bridge. In this work, we used DFT calculations to examine in detail the degradation (desulfurization) pathways of α-β/α-α bridged ETPs. The chemical stability of ETPs is influenced by the type of sulfur bridge, the structural features, and the storage conditions. Our results suggest appropriate protection of the phenolic OH of ETPs would improve various pharmaceutically relevant properties, including bioavailability.

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Catalytic stereoselective synthesis of doubly, triply and quadruply twisted aromatic belts

Nogami J., Hashizume D., Nagashima Y., Miyamoto K., Uchiyama M., Tanaka K.

Nature Synthesis 2 （ 9 ） 888 - 897 2023年09月

　概要を見る

Twisted aromatic belt molecules provide unique topologies and complex chiralities for nanocarbon materials. However, a synthetic method for aromatic belts with multiple twists remains elusive. Here we report the catalytic and stereoselective synthesis of doubly, triply and quadruply twisted aromatic belts (up to e.r. = 98:2) via rhodium(I)-catalysed asymmetric [2 + 2 + 2] cycloadditions. The hybrid substrate design, consisting of curved metaphenylene units and linear paraphenylene units, overcomes the hurdles of conventional methods, that is, large twist strain and unravelling of twists during belt formation, allowing the coexistence of multiple P- and M-twists in a single belt molecule. Three-dimensional structures of the multiply twisted aromatic belts were confirmed by X-ray crystallography, revealing that their topology depends on the sequence of P- and M-twists. Decomposition analysis of the linking number (Lk) shows that the twisting number (Tw) of the triply twisted Möbius belt is Tw = 2.45, among the highest Tw found for twisted conjugated macrocycles. Analysis of the electron density of delocalized bonds reveals that the electronic structure has unique Lk-dependent topologies, such as a catenane and a trefoil knot. [Figure not available: see fulltext.].

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A Switchable Near-Infrared-Absorbing Dye Based on Redox-Bistable Benzitetraazaporphyrin

Yanagi S., Matsumoto A., Toriumi N., Tanaka Y., Miyamoto K., Muranaka A., Uchiyama M.

Angewandte Chemie - International Edition 62 （ 11 ）  2023年03月

研究論文（学術雑誌）, 査読有り,  ISSN  14337851

　概要を見る

Activatable near-infrared (NIR) dyes responsive to external stimuli are used in medical and other applications. Here, we describe the design and synthesis of bench-stable 18π- and 20π-electron benzitetraazaporphyrins (BzTAPs) possessing redox-switchable NIR properties. X-Ray, NMR, and UV/Visible-NIR analyses revealed that 20π-electron BzTAP 1 exhibits NIR absorption and antiaromaticity with a paratropic ring-current, while 18π-electron BzTAP 2 shows weakly aromatic character with NIR inertness. Notably, the NIR-silent BzTAP 2 was readily converted to the NIR-active BzTAP 1 in the presence of mild reducing agents such as amine. The intense NIR absorption band of BzTAP 1 is in sharp contrast to the very weak absorption bands of previously reported antiaromatic porphyrinoids. Molecular orbital analysis revealed that symmetry-lowering perturbation of the 20π-electron porphyrinoid skeleton enables the HOMO–LUMO transition of 1 to be electric-dipole-allowed. BzTAPs are expected to be useful for constructing activatable NIR probes working in reductive environments.

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A Switchable Near‐Infrared‐Absorbing Dye Based on Redox‐Bistable Benzitetraazaporphyrin

Shunsuke Yanagi, Akihisa Matsumoto, Naoyuki Toriumi, Yusuke Tanaka, Kazunori Miyamoto, Atsuya Muranaka, Masanobu Uchiyama

Angewandte Chemie 2023年03月

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Synthesis, Characterization, and Reaction of Hypervalent Organo-λ³-bromanes and Chloranes

Miyamoto K., Uchiyama M., Ochiai M.

Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry （公益社団法人 有機合成化学協会）  81 （ 5 ） 416 - 427 2023年

ISSN  00379980

　概要を見る

Hypervalent organoiodine(III/V) reagents (λ3-/λ5-iodane) have enjoyed widespread application as oxidant/electrophile in synthetic organic chemistry. In contrast, the development of the chemistry of hypervalent organo-λ3-bromane and λ3-chlorane is still just beginning. We have developed a versatile, high-yield synthesis of λ3-chloranes and λ3-bromanes through the reaction of various haloarenes/chloroalkenes with readily prepared arenediazonium tetrakis(pentafluorophenyl) borate under mild conditions. The improved accessibility enabled us to investigate the unique physico-chemical characters and unprecedented reactivity of these hypervalent organo- λ3-haloganes (e.g. onium structure, enhanced electrophilicity, etc.). The leaving group ability of λ3-haloganyl groups was also evaluated as it governs the rate of a variety of chemical transformations.

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Cycloisomerization of enynones by aluminum halides: construction of bicyclo[3.1.0]hexanes by introducing halides

Sato D., Tsubouchi A., Watanabe Y., Noguchi K., Miyamoto K., Uchiyama M., Saito A.

Organic Chemistry Frontiers 10 （ 5 ） 1112 - 1118 2022年12月

ISSN  20524110

　概要を見る

Alkyne π-bond activation by transition metal complexes has been well studied for cycloisomerization of enynes into bicyclo[3.1.0]hexanes, which can allow the introduction of carbon and oxygen functional groups concomitant with the construction of the core structures. However, the cycloisomerization of enynones through the activation of carbonyl groups into bicyclo[3.1.0]hexanes has not been achieved. Herein, we report the aluminum halide-mediated cycloisomerization of 7-en-2-ynones into halogenated bicyclo[3.1.0]hexanes.

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Practical and Facile Access to Bicyclo[3.1.1]heptanes: Potent Bioisosteres of meta-Substituted Benzenes

Iida T., Kanazawa J., Matsunaga T., Miyamoto K., Hirano K., Uchiyama M.

Journal of the American Chemical Society 144 （ 48 ） 21848 - 21852 2022年12月

ISSN  00027863

　概要を見る

There is increasing interest in replacement of the planar aromatic rings of drug candidates with three-dimensional caged scaffolds in order to improve the physical properties, but bioisosteres of meta-substituted benzenes have remained elusive. We focused on the bicyclo[3.1.1]heptane (BCH) scaffold as a novel bioisostere of meta-substituted benzenes, anticipating that [3.1.1]propellane (2) would be a versatile precursor of diversely functionalized BCHs. Here, we describe a practical preparative method for [3.1.1]propellane from newly developed 1,5-diiodobicyclo[3.1.1]heptane (1), as well as difunctionalization reactions of 2 leading to functionalized BCHs. We also report postfunctionalization reactions of these products.

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A combined DFT-predictive and experimental exploration of the sensitivity towards nucleofuge variation in zwitterionic intermediates relating to mechanistic models for unimolecular chemical generation and trapping of free C<inf>2</inf> and alternative bimolecular pathways involving no free C<inf>2</inf>

Rzepa H.S., Arita M., Miyamoto K., Uchiyama M.

Physical Chemistry Chemical Physics 24 （ 42 ） 25816 - 25821 2022年10月

ISSN  14639076

　概要を見る

Following the recent report of the chemical generation and trapping at room temperatures of C2, generated from an alkynyl phenyl iodonium salt, a computational analysis had indicated that both unimolecular fragmentation and bimolecular substitution mechanisms for the process could be envisaged. Here a combined theoretical and experimental analysis explores how the energetics of these mechanisms and resulting experimental products respond to variation in the nucleofuge. When the phenyl iodonium nucleofuge is replaced by pyridinium, trapping products are again obtained, which we conclude favours a bimolecular mechanism involving no free C2. Trapped products in greater yield were also observed using dibenzothiophenium as the nucleofuge in both condensed solution phase and most significantly in a two-flask room temperature experiment in which a volatile species, presumed to be C2, is transferred and trapped in a second flask. The energetics of the unimolecular fragmentation process producing C2 are predicted to be too high to correspond to a facile thermal reaction, which means that an experimental/theoretical dichotomy remains to be explained.

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Diamond-rich crystalline nanosheets seeded with a Langmuir monolayer of arachidic acid on water

Tanaka T., Miura Y.F., Aoyama T., Miyamoto K., Akagi Y., Uchiyama M., Osawa E.

RSC Advances 12 （ 41 ） 26575 - 26579 2022年09月

　概要を見る

The enigmatic self-assembling ability of nanodiamond (ND) particles has been discovered herein. Diamond-rich crystalline nanosheets with thickness of approximately ∼25 nm were grown from a Langmuir monolayer of arachidic acid (AA) at the interface between air and a dilute aqueous ND solution. Their fine rectangular shapes with uniform uniaxial birefringence indicate appreciable crystallinity, thus supporting that they are hydrated colloidal crystals of homogeneous ND particles.

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In Situ Generation of N-Triflylimino-λ³-iodanes: Application to Imidation of Phosphines and Catalytic α-Amidation of 1,3-Dicarbonyl Compounds

Sunagawa S., Morisaki F., Baba T., Tsubouchi A., Yoshimura A., Miyamoto K., Uchiyama M., Saito A.

Organic Letters 24 （ 28 ） 5230 - 5234 2022年07月

ISSN  15237060

　概要を見る

We describe the imidation of phosphines and α-amidation of 1,3-dicarbonyl compounds using N-triflylimino-λ3-iodane, which is generated in situ from iodosylarene and triflylamide without any other additives. Furthermore, the imino-λ3-iodane catalytically generated from an iodoarene precatalyst with oxone and triflylamide promotes α-amidation of 1,3-dicarbonyl compounds, representing the first method catalyzed by imino-λ3-iodane.

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Synthesis of Cyclophenacene- and Chiral-Type Cyclophenylene-Naphthylene Belts

Nogami J., Nagashima Y., Sugiyama H., Miyamoto K., Tanaka Y., Uekusa H., Muranaka A., Uchiyama M., Tanaka K.

Angewandte Chemie - International Edition （Wiley）  61 （ 15 ）  2022年04月

ISSN  14337851

　概要を見る

We report the synthesis of a [20]cyclophenacene-type cyclophenylene-naphthylene (CPN) belt and the enantioselective synthesis of chiral-type CPN belts (up to >99 % ee) by the cationic rhodium(I)-catalyzed intramolecular [2+2+2] cycloaddition of naphthalene-embedded cyclic polyynes. The synthesis of a depth-expanded CPN belt was also attempted, but the final intramolecular [2+2+2] cycloaddition was unsuccessful. Theoretical calculations clarified that the reactivity depends on the stability of the transition state in the initial oxidative cycloaddition step which is subject to molecular strain. The cylindrical structures of these CPN belts were confirmed by X-ray crystallographic analyses. As a result of π-extension through the introduction of naphthalenes in the chiral-type CPN belts, the anisotropy dissymmetry factors of electronic circular dichroism and circularly polarized luminescence are amplified compared with the corresponding zigzag-type chiral cyclophenylene belts.

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Improvement in aqueous solubility of achiral symmetric cyclofenil by modification to a chiral asymmetric analog

Morimoto J., Miyamoto K., Ichikawa Y., Uchiyama M., Makishima M., Hashimoto Y., Ishikawa M.

Scientific Reports 11 （ 1 ）  2021年12月

　概要を見る

Decreasing the partition coefficient (LogP) by the introduction of a hydrophilic group is the conventional approach for improving the aqueous solubility of drug candidates, but is not always effective. Since melting point is related to aqueous solubility, we and other groups have developed alternative strategies to improve solubility by means of chemical modification to weaken intermolecular interaction in the solid state, thereby lowering the melting point and increasing the solubility. Here, we show that converting the symmetrical molecular structure of the clinically used estrogen receptor (ER) antagonist cyclofenil (1) into asymmetrical form by introducing an alkyl group enhances the aqueous solubility. Among the synthesized analogs, the chiral methylated analog (R)-4c shows the highest solubility, being 3.6-fold more soluble than 1 even though its hydrophobicity is increased by the methylation. Furthermore, (R)-4c also showed higher membrane permeability than 1, while retaining a comparable metabolic rate, and equivalent biological activity of the active forms (R)-13a to 2. Further validation of this strategy using lead compounds having symmetric structures is expected.

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Stereodivergent Nitrocyclopropane Formation during Biosynthesis of Belactosins and Hormaomycins

Shimo S., Ushimaru R., Engelbrecht A., Harada M., Miyamoto K., Kulik A., Uchiyama M., Kaysser L., Abe I.

Journal of the American Chemical Society （American Chemical Society ({ACS})）  143 （ 44 ） 18413 - 18418 2021年11月

ISSN  00027863

　概要を見る

Belactosins and hormaomycins are peptide natural products containing 3-(2-aminocyclopropyl)alanine and 3-(2-nitrocyclopropyl)alanine residues, respectively, with opposite stereoconfigurations of the cyclopropane ring. Herein we demonstrate that the heme oxygenase-like enzymes BelK and HrmI catalyze the N-oxygenation of l-lysine to generate 6-nitronorleucine. The nonheme iron enzymes BelL and HrmJ then cyclize the nitroalkane moiety to the nitrocyclopropane ring with the desired stereochemistry found in the corresponding natural products. We also show that both cyclopropanases remove the 4-proS-H of 6-nitronorleucine during the cyclization, establishing the inversion and retention of the configuration at C4 during the BelL and HrmJ reactions, respectively. This study reveals the unique strategy for stereocontrolled cyclopropane synthesis in nature.

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Molecular and Computational Bases for Spirofuranone Formation in Setosusin Biosynthesis

Wei X., Matsuyama T., Sato H., Yan D., Chan P.M., Miyamoto K., Uchiyama M., Matsuda Y.

Journal of the American Chemical Society （American Chemical Society ({ACS})）  143 （ 42 ） 17708 - 17715 2021年10月

ISSN  00027863

　概要を見る

The 3(2H)-furanone unit is observed in many biologically active natural products, as represented by the antifungal medication griseofulvin. Setosusin (1) is a fungal meroditerpenoid featuring a unique spiro-fused 3(2H)-furanone moiety; however, the biosynthetic basis for spirofuranone formation has not been investigated since its isolation. Therefore, in this study we identified the biosynthetic gene cluster of 1 in the fungus Aspergillus duricaulis CBS 481.65 and elucidated its biosynthetic pathway by heterologous reconstitution of related enzyme activities in Aspergillus oryzae. To understand the reaction mechanism to afford spirofuranone, we subsequently performed a series of in vivo and in vitro isotope-incorporation experiments and theoretical calculations. The results indicated that SetF, the cytochrome P450 enzyme that is critical for spirofuranone synthesis, not only performs the epoxidation of the polyketide portion of the substrate but also facilitates the protonation-initiated structural rearrangement to yield 1. Finally, a mutagenesis experiment using SetF identified Lys303 as one of the potential catalytic residues that are important for spirofuranone synthesis.

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Theoretical Study on the Mechanism of Spirocyclization in Spiroviolene Biosynthesis

Sato H., Takagi T., Miyamoto K., Uchiyama M.

Chemical and Pharmaceutical Bulletin （Pharmaceutical Society of Japan）  69 （ 10 ） 1034 - 1038 2021年10月

ISSN  00092363

　概要を見る

Spiroviolene is a spirocyclic triquinane diterpene produced by Streptomyces violens. Recently, a biosynthetic pathway that includes secondary carbocation intermediates and a complicated concerted skeletal rearrangement was proposed for spiroviolene, based upon careful labeling experiments. On the basis of density functional theory (DFT) calculations, we propose a revised pathway for spiroviolene biosynthesis, involving a multistep carbocation cascade that bypasses the formation of unstable secondary carbocations by breaking the adjacent C–C bond to form a more stable tertiary carbocation (IM3) and by Wagner–Meerwein 1,2-methyl rearrangement (IM7).

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DFT Study on the Biosynthesis of Verrucosane Diterpenoids and Mangicol Sesterterpenoids: Involvement of Secondary-Carbocation-Free Reaction Cascades

Sato H., Li B.X., Takagi T., Wang C., Miyamoto K., Uchiyama M.

JACS Au （American Chemical Society ({ACS})）  1 （ 8 ） 1231 - 1239 2021年08月

　概要を見る

Some experimental observations indicate that a sequential formation of secondary (2°) carbocations might be involved in some biosynthetic pathways, including those of verrucosane-type diterpenoids and mangicol-type sesterterpenoids, but it remains controversial whether or not such 2° cations are viable intermediates. Here, we performed comprehensive density functional theory calculations of these biosynthetic pathways. The results do not support previously proposed pathways/mechanisms: in particular, we find that none of the putative 2° carbocation intermediates is involved in either of the biosynthetic pathways. In verrucosane biosynthesis, the proposed 2° carbocations (II and IV) in the early stage are bypassed by the formation of the adjacent 3° carbocations and by unusual skeletal rearrangement reactions, and in the later stage, the putative 2° carbocation intermediates (VI, VII, and VIII) are not present as the proposed forms but as nonclassical structures between homoallyl and cyclopropylcarbinyl cations. In the mangicol biosynthesis, one of the two proposed 2° carbocations (X) is bypassed by a C-C bond-breaking reaction to generate a 3° carbocation with a C=C bond, while the other (XI) is bypassed by a strong hyperconjugative interaction leading to a nonclassical carbocation. We propose new biosynthetic pathways/mechanisms for the verrucosane-type diterpenoids and mangicol-type sesterterpenoids. These pathways are in good agreement with the findings of previous biosynthetic studies, including isotope-labeling experiments and byproducts analysis, and moreover can account for the biosynthesis of related terpenes.

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Benchtop-Stabssle Hypervalent Bromine(III) Compounds: Versatile Strategy and Platform for Air- And Moisture-Stable λ³-Bromanes

Miyamoto K., Saito M., Tsuji S., Takagi T., Shiro M., Uchiyama M., Ochiai M.

Journal of the American Chemical Society （American Chemical Society ({ACS})）  143 （ 25 ） 9327 - 9331 2021年06月

ISSN  00027863

　概要を見る

We present the first synthesis of air/moisture-stable λ3-bromanes (9and10) by using a cyclic 1,2-benzbromoxol-3-one (BBX) strategy. X-ray crystallography and NMR and IR spectroscopy ofN-triflylimino-λ3-bromane (12) revealed that the bromine(III) center is effectively stabilized by intramolecular R-Br-O hypervalent bonding. This strategy enables the synthesis of a variety of air-, moisture-, and benchtop-stable Br-hydroxy, -acetoxy, -alkynyl, -aryl, and bis[(trifluoromethyl)sulfonyl]methylide λ3-bromane derivatives.

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Rhodium-Catalyzed Enantioselective Synthesis, Structures, and Properties of Single and Double Azahelicene-Like Molecules

Hanada K., Nogami J., Miyamoto K., Hayase N., Nagashima Y., Tanaka Y., Muranaka A., Uchiyama M., Tanaka K.

Chemistry - A European Journal （Wiley）  27 （ 36 ） 9313 - 9319 2021年06月

ISSN  09476539

　概要を見る

The enantioselective synthesis of aza[6] and [7]helicene-like molecules have been achieved by the cationic rhodium(I)/axially chiral biaryl bisphosphine complex-catalyzed intramolecular [2+2+2] cycloaddition of cyanodiynes. This protocol was successfully applied to the diastereo- and enantioselective synthesis of an S-shaped double aza[6]helicene-like molecule with a high ee value of 89 %. Although no epimerization and racemization were observed in the double carbo[6]helicene-like molecule at 80 °C, epimerization and racemization of the double aza[6]helicene-like molecule proceeded at 80 °C. This double aza[6]helicene-like molecule showed good fluorescent quantum yields and chiroptical responses under both neutral and acidic conditions.

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Asymmetric synthesis, structures, and chiroptical properties of helical cycloparaphenylenes

Nogami J., Nagashima Y., Miyamoto K., Muranaka A., Uchiyama M., Tanaka K.

Chemical Science （Royal Society of Chemistry ({RSC})）  12 （ 22 ） 7858 - 7865 2021年06月

ISSN  20416520

　概要を見る

Planar chiral carbon nanorings and nanobelts (CNRs and CNBs), the sidewall segment molecules of chiral-type carbon nanotubes (CNTs), have attracted attention owing to their characteristic chiroptical properties. From the appropriate CNTs, axially or planar chiral CNRs and CNBs have been designed and synthesized, but multiply helical sidewall segments were almost unexplored due to the difficulty in simultaneous control of multiple chiralities. In this article, we have succeeded in the perfectly diastereo- and enantiocontrolled catalytic synthesis of a cycloparaphenylene with four helical and two planar chiralities showing good chiroptical responses as chiral organic molecules. The perfectly stereocontrolled multiply helical structure was confirmed by a single-crystal X-ray diffraction analysis. The experimental and theoretical studies established the importance of the highly symmetric multiply helical structure in the cylindrical axis in obtaining good chiroptical responses.

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CO2-activated NaClO-5H2O enabled smooth oxygen transfer to iodoarene: A highly practical synthesis of iodosylarene

Miyamoto K., Watanabe Y., Takagi T., Okada T., Toyama T., Imamura S., Uchiyama M.

Arkivoc （Arkat）  2021 （ 7 ）  2021年05月

ISSN  15517004

　概要を見る

A safe, rapid, and environmentally friendly synthesis of iodosylarene (ArIO) has been developed using NaClO under a carbon dioxide (CO2) atmosphere. Exposure of iodoarene to NaClO-5H2O in acetonitrile under CO2 (1 atm) resulted in the clean formation of ArIO within 10 minutes in high yield. The absence of a base in this method enables the direct use of in-situ-generated iodosylarene not only for a variety of oxidative transformations (synthesis of sulfilimine, pentavalent bismuth, benzyne adduct, etc.), but also for the synthesis of iodonium ylide and imino-λ3-iodane in one pot.

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Illuminating Stannylation

Sakamoto K., Nagashima Y., Wang C., Miyamoto K., Tanaka K., Uchiyama M.

Journal of the American Chemical Society （American Chemical Society ({ACS})）  143 （ 15 ） 5629 - 5635 2021年04月

ISSN  00027863

　概要を見る

We have developed photoboosted stannylation reactions of terminal alkynes (linear-selective hydrostannylation) and fluoroarenes (defluorostannylation), in which the stannyl anion is photoexcited to an excited triplet (T1) stannyl diradical species. This unprecedented T1-stannyl diradical species shows completely different reactivity and selectivity from those of stannyl anions and stannyl radicals. This methodology is operationally simple, has broad functional group tolerance, and proceeds in high yield without the need for any catalyst.

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α-Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane

Matsunaga T., Kanazawa J., Ichikawa T., Harada M., Nishiyama Y., Duong N.T., Matsumoto T., Miyamoto K., Uchiyama M.

Angewandte Chemie - International Edition （Wiley）  60 （ 5 ） 2578 - 2582 2021年02月

ISSN  14337851

　概要を見る

The bicyclo[1.1.1]pentane (BCP) scaffold is useful in medicinal chemistry, and many protocols are available for synthesizing BCP derivatives from [1.1.1]propellane. Here, we report (1) the α-cyclodextrin (α-CD) encapsulation of BCP derivatives, affording a stable, readily storable material from which BCPs can be easily and quantitatively recovered and (2) new and simple protocols for deiodination reaction of 1,3-diiodo BCP to afford [1.1.1]propellane in protic/aprotic/polar/non-polar solvents. The combination of these methodologies enables simple, on-demand preparation of [1.1.1]propellane in various solvents under mild conditions from α-CD capsules containing 1,3-diiodo BCP.

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Cover Picture: α‐Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane (Angew. Chem. Int. Ed. 5/2021)

Tadafumi Matsunaga and Junichiro Kanazawa and Tomohiro Ichikawa and Mei Harada and Yusuke Nishiyama and Nghia Tuan Duong and Takashi Matsumoto and Kazunori Miyamoto and Masanobu Uchiyama

Angewandte Chemie International Edition （Wiley）  60 （ 5 ） 2169 - 2169 2021年02月

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Titelbild: α‐Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane (Angew. Chem. 5/2021)

Tadafumi Matsunaga and Junichiro Kanazawa and Tomohiro Ichikawa and Mei Harada and Yusuke Nishiyama and Nghia Tuan Duong and Takashi Matsumoto and Kazunori Miyamoto and Masanobu Uchiyama

Angewandte Chemie （Wiley）  133 （ 5 ） 2197 - 2197 2021年02月

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α‐Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane

Tadafumi Matsunaga and Junichiro Kanazawa and Tomohiro Ichikawa and Mei Harada and Yusuke Nishiyama and Nghia Tuan Duong and Takashi Matsumoto and Kazunori Miyamoto and Masanobu Uchiyama

Angewandte Chemie （Wiley）  133 （ 5 ） 2610 - 2614 2021年02月

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Synthetic Access to gem-Difluoropropargyl Vinyl Ethers and Their Application to Propargyl Claisen Rearrangement

Okamura T., Koyamada K., Kanazawa J., Miyamoto K., Iwabuchi Y., Uchiyama M., Kanoh N.

Journal of Organic Chemistry （American Chemical Society ({ACS})）  86 （ 2 ） 1911 - 1924 2021年01月

ISSN  00223263

　概要を見る

With the increasing importance of fluorine to medicinal chemistry and other areas, methods to access various fluorinated compounds are needed. Herein, we report the synthesis of difluoropropargyl vinyl ethers from ketones and aldehydes using difluoropropargyl bromide dicobalt complexes. We applied difluoropropargyl vinyl ethers to the synthesis of difluorodienone or difluoroallene under thermal conditions and trifluoro-pyran under acid-catalyzed conditions.

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Boron-vertex modification of carba-: Closo -dodecaborate for high-performance magnesium-ion battery electrolyte

Watanabe M., Kanazawa J., Hamamura T., Shimokawa T., Miyamoto K., Hibino M., Nakura K., Inatomi Y., Kitazawa Y., Uchiyama M.

Materials Advances （Royal Society of Chemistry ({RSC})）  2 （ 3 ） 937 - 941 2021年

　概要を見る

Further advances in magnesium ion batteries (MIBs) require the development of electrolyte solutions with highly optimized properties. Here we report the design, synthesis and electrolytic properties of a new family of Mg salts of carba-closo-dodecaborate anions (CCAs). Detailed calculations suggested that modification at the boron vertices, previously considered inappropriate for MIB electrolytes, would be effective. Experimental studies showed that simple halogenation at the 12-B vertex of CCA drastically improves the solubility in low viscosity solvents without compromising the chemical and redox stability, and the ionic conductivity reached 6.2 mS/cm. The synthesized electrolytes showed low overpotential (≤200 mV) for Mg deposition and excellent reversible magnesium deposition/stripping with high Coulombic efficiency (≥95%). This journal is

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Hypervalent organo-λ³-chloranes

Miyamoto K., Uchiyama M.

Chemistry Letters （Chemical Society of Japan）  50 （ 4 ） 832 - 838 2021年

ISSN  03667022

　概要を見る

Hypervalent halogen species such as organoiodine(III and V) compounds have long been used as electrophiles/oxidants in organic synthesis, but recent years have seen the emergence of a new class of hypervalent halogen species, organobromine(III) and organochlorine(III) compounds (also termed organo-λ3bromanes and λ3-chloranes). In this review, we will cover recent developments in the synthesis and synthetic applications of functionalized λ3-chloranes.

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Facile preparation of 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide (IBX) and dess-martin reagent using sodium hypochlorite under carbon dioxide

Miyamoto K., Okada T., Toyama T., Imamura S., Uchiyama M.

Heterocycles （Japan Institute of Heterocyclic Chemistry）  103 （ 2 ）  2021年

ISSN  03855414

　概要を見る

We have developed a safe, convenient, and inexpensive method for preparation of the widely used oxidizing agent 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide (IBX), by treatment of 2-iodobenzoic acid with aqueous sodium hypochlorite under CO2 at room temperature. As the only by-product is NaCl, this reaction can be utilized for one-pot synthesis of 1,1,1-triacetoxy-1,2-benziodoxol-3(1H)-one (Dess-Martin reagent) in excellent yield.

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Room-temperature chemical synthesis of C<inf>2</inf>

Miyamoto K., Narita S., Masumoto Y., Hashishin T., Osawa T., Kimura M., Ochiai M., Uchiyama M.

Nature Communications 11 （ 1 ）  2020年12月

　概要を見る

Diatomic carbon (C2) is historically an elusive chemical species. It has long been believed that the generation of C2 requires extremely high physical energy, such as an electric carbon arc or multiple photon excitation, and so it has been the general consensus that the inherent nature of C2 in the ground state is experimentally inaccessible. Here, we present the chemical synthesis of C2 from a hypervalent alkynyl-λ3-iodane in a flask at room temperature or below, providing experimental evidence to support theoretical predictions that C2 has a singlet biradical character with a quadruple bond, thus settling a long-standing controversy between experimental and theoretical chemists, and that C2 serves as a molecular element in the bottom-up chemical synthesis of nanocarbons such as graphite, carbon nanotubes, and C60.

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DFT Study of a Missing Piece in Brasilane-Type Structure Biosynthesis: An Unusual Skeletal Rearrangement

Sato H., Hashishin T., Kanazawa J., Miyamoto K., Uchiyama M.

Journal of the American Chemical Society （American Chemical Society ({ACS})）  142 （ 47 ） 19830 - 19834 2020年11月

ISSN  00027863

　概要を見る

Brasilane-type sesquiterpenes have been known for a long time, but their biosynthetic pathways and mechanisms remain elusive. Recently, two groups independently characterized a Trichoderma terpene cyclase that produces trichobrasilenol, a brasilane-type sesquiterpene, and a plausible biosynthetic pathway was proposed based on isotopic labeling experiments. In the proposed mechanism, the characteristic brasilane-type 5/6 bicyclic skeleton is synthesized from a 5/7/3 tricyclic intermediate via a complicated concerted reaction, including six chemical events of C-C σ bond metathesis and rearrangements, ring-contraction, πbond formation, and regioselective hydroxylation. However, our density functional theory (DFT) calculations do not support this mechanism. On the basis of DFT calculations, we propose a new pathway for trichobrasilenol biosynthesis, involving a multistep carbocation cascade in which cyclopropylcarbinyl cations in equilibrium with homoallyl cations play a pivotal role. This pathway and mechanism is in good agreement with previous biosynthetic studies on brasilane-type compounds and related terpenoids, including isotope-labeling experiments and byproducts analysis.

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Nucleophilic Diboration Strategy Targeting Diversified 1-Boraphenarene Architectures

Hirano K., Morimoto K., Fujioka S., Miyamoto K., Muranaka A., Uchiyama M.

Angewandte Chemie - International Edition （Wiley）  59 （ 48 ） 21448 - 21453 2020年11月

ISSN  14337851

　概要を見る

1-Boraphenalenes, a class of boron-doped polyaromatic hydrocarbons, were synthesized by nucleophilic diboration reaction of alkynes. Activation of diboron reagents with a highly basic sp2-carbanion results in very fast successive C−B bond formations to construct the boracycle. This methodology is characterized by high chemoselectivity, affording a wide variety of 1-boraphenarenes with diverse polar substituents. The endocyclic boron can be arylated conveniently in one pot, and the peripheral boron is available for various chemical transformations. Highly diastereoselective diboration gives pseudo-enantio-enriched boraphenarene, which emits circularly polarized fluorescence (CPL).

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Nucleophilic Diboration Strategy Targeting Diversified 1‐Boraphenarene Architectures

Keiichi Hirano and Kensuke Morimoto and Shota Fujioka and Kazunori Miyamoto and Atsuya Muranaka and Masanobu Uchiyama

Angewandte Chemie （Wiley）  132 （ 48 ） 21632 - 21637 2020年11月

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Biosynthesis of Indole Diterpene Lolitrems: Radical-Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton

Jiang Y., Ozaki T., Harada M., Miyasaka T., Sato H., Miyamoto K., Kanazawa J., Liu C., Maruyama J.i., Adachi M., Nakazaki A., Nishikawa T., Uchiyama M., Minami A., Oikawa H.

Angewandte Chemie - International Edition 59 （ 41 ） 17996 - 18002 2020年10月

ISSN  14337851

　概要を見る

Lolitrems are tremorgenic indole diterpenes that exhibit a unique 5/6 bicyclic system of the indole moiety. Although genetic analysis has indicated that the prenyltransferase LtmE and the cytochrome P450 LtmJ are involved in the construction of this unique structure, the detailed mechanism remains to be elucidated. Herein, we report the reconstitution of the biosynthetic pathway for lolitrems employing a recently established genome-editing technique for the expression host Aspergillus oryzae. Heterologous expression and bioconversion of the various intermediates revealed that LtmJ catalyzes multistep oxidation to furnish the lolitrem core. We also isolated the key reaction intermediate with an epoxyalcohol moiety. This observation allowed us to establish the mechanism of radical-induced cyclization, which was firmly supported by density functional theory calculations and a model experiment with a synthetic analogue.

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Decarboxylative Bromination of Sterically Hindered Carboxylic Acids with Hypervalent Iodine(III) Reagents

Watanabe A., Koyamada K., Miyamoto K., Kanazawa J., Uchiyama M.

Organic Process Research and Development （American Chemical Society ({ACS})）  24 （ 7 ） 1328 - 1334 2020年07月

ISSN  10836160

　概要を見る

Sterically hindered three-dimensional (3D) alkyl halides are promising precursors for various reactions; however, they are difficult to synthesize via conventional reactions. We present an efficient and practical method for decarboxylative bromination of sterically hindered 3D aliphatic carboxylic acids using commercially available (diacetoxyiodo)benzene and potassium bromide, one of the most stable and cheapest bromine sources in nature. The present method features a metal-free/Br2-free system, mild reaction conditions, one-pot operation under air at room temperature, wide functional group compatibility, and gram-scale synthetic capability. This highly efficient reaction cleanly converts a broad range of carboxylic acids, the most inexpensive and readily available sources of highly strained/naturally occurring/drug-related scaffolds, into the corresponding alkyl bromides in good to high yields.

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Rhodium-Catalyzed Highly Diastereo- and Enantioselective Synthesis of a Configurationally Stable S-Shaped Double Helicene-Like Molecule

Kinoshita S., Yamano R., Shibata Y., Tanaka Y., Hanada K., Matsumoto T., Miyamoto K., Muranaka A., Uchiyama M., Tanaka K.

Angewandte Chemie - International Edition 59 （ 27 ） 11020 - 11027 2020年06月

ISSN  14337851

　概要を見る

An S-shaped double helicene-like molecule (>99 % ee), possessing stable helical chirality, has been synthesized by the rhodium(I)/difluorphos complex-catalyzed highly diastereo- and enantioselective intramolecular double [2+2+2] cycloaddition of a 2-naphthol- and benzene-linked hexayne. The collision between two terminal naphthalene rings destabilizes the helical chirality of the S-shaped double helicene-like molecule, but the introduction of two additional fused benzene rings significantly increases the configurational stability. Thus, no epimerization and racemization were observed even at 100 °C. The enantiopure S-shaped double helicene-like molecule forms a trimer through the multiple C−H⋅⋅⋅π and C−H⋅⋅⋅O interactions in the solid-state. The trimers stack to form columnar packing structures, in which neighboring stacks have opposite dipole directions. The accumulation of helical structures in the same direction in the S-shaped double helicene-like molecule enhanced the chiroptical properties.

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BF<inf>3</inf>-Catalyzed Skeletal Rearrangement of 7-En-2-ynones to endo-Type Cyclic Dienes

Sato D., Watanabe Y., Noguchi K., Kanazawa J., Miyamoto K., Uchiyama M., Saito A.

Organic Letters （American Chemical Society ({ACS})）  22 （ 11 ） 4063 - 4067 2020年06月

ISSN  15237060

　概要を見る

Transition-metal-catalyzed cycloisomerization reactions with skeletal rearrangement of 1,n-enynes to afford cyclic dienes (particularly exo-cyclization products) have been well studied. However, there are few reports on the nonmetal-catalyzed skeletal rearrangement of enynes and skeletal rearrangement of electron-deficient enynes such as n-en-2-ynones. Here, we describe BF3·MeCN-catalyzed synthesis of 3-alkylidenecyclohexenes from 7-en-2-ynones, representing the first nonmetal-catalyzed skeletal rearrangement of 1,6-enynes to endo-type cyclic dienes.

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Shelf-Stable (E)- A nd (Z)-Vinyl-λ³-chlorane: A Stereospecific Hyper-vinylating Agent

Watanabe Y., Takagi T., Miyamoto K., Kanazawa J., Uchiyama M.

Organic Letters （American Chemical Society ({ACS})）  22 （ 9 ） 3469 - 3473 2020年05月

ISSN  15237060

　概要を見る

We report the first stereoselective synthesis of stable (E)- A nd (Z)-β-chlorovinyl-λ3-chlorane via direct mesitylation of 1,2-dichloroethylene with mesityldiazonium tetrakis(pentafluorophenyl)borate under mild reaction conditions. The structure of the (E)-vinyl-λ3-chlorane was established by single-crystal X-ray analysis. Because of the enormously high leaving group ability of the aryl-λ3-chloranyl group, vinyl-λ3-chloranes undergo not only SNVσ-type reaction with extremely weak nucleophiles such as perfluoroalkanesulfonate, iodobenzene, and aromatic hydrocarbons but also coupling with phenylcopper(I) species.

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Lipshutz-type bis(amido)argentates for directed: Ortho argentation

Tezuka N., Hirano K., Peel A.J., Wheatley A.E.H., Miyamoto K., Uchiyama M.

Chemical Science （Royal Society of Chemistry ({RSC})）  11 （ 7 ） 1855 - 1861 2020年02月

ISSN  20416520

　概要を見る

Bis(amido)argentate (TMP)2Ag(CN)Li2 (3, TMP-Ag-ate; TMP = 2,2,6,6-tetramethylpiperidido) was designed as a tool for chemoselective aromatic functionalization via unprecedented directed ortho argentation (DoAg). X-Ray crystallographic analysis showed that 3 takes a structure analogous to that of the corresponding Lipshutz cuprate. DoAg with this TMP-Ag-ate afforded multifunctional aromatics in high yields in processes that exhibited high chemoselectivity and compatibility with a wide range of functional groups. These included organometallics- A nd transition metal-susceptible substituents such as methyl ester, aldehyde, vinyl, iodo, (trifluoromethanesulfonyl)oxy and nitro groups. The arylargentates displayed good reactivity with various electrophiles. Chalcogen (S, Se, and Te) installation and azo coupling reactions also proceeded efficiently.

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Chennat-Type Synthesis of 1,4-Dihydropyridine Derivatives in Water: Role of a Hydrogen-Bonding Network

Isomura S., Anzai M., Kobayashi C., Okuno Y., Miyamoto K., Uchiyama M., Sato Y.

ChemistrySelect （Wiley-Blackwell）  5 （ 6 ） 2075 - 2077 2020年02月

ISSN  2365-6549

　概要を見る

An environmentally benign Chennat-type synthesis of 4-aryl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl esters was achieved by heating aldehyde, methyl propiolate and an amine salt in water. Excess amine salt accelerated the reaction, while stoichiometric amounts of reagents resulted in lower yield. Various 1,4-dihydropyridine (1,4-DHP) derivatives, some of which would be difficult to synthesize in organic solvents, could be obtained in up to 74 % isolated yield. The reaction utilizes a hydrogen-bonding network with water to accelerate hydroxyl group elimination from the reaction intermediate. Free amine and protons in water might be act as a nucleophile and electrophilic catalyst, respectively.

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Practical Synthesis of Ethynyl(phenyl)-λ³-Iodane Using Calcium Carbide as an Ethynyl Group Source

Hashishin T., Osawa T., Miyamoto K., Uchiyama M.

Frontiers in Chemistry （Frontiers Media S.A.）  8 2020年02月

ISSN  2296-2646

　概要を見る

Stannylation of calcium carbide followed by Sn–hypervalent iodine(III) exchange reaction cleanly afforded the electrophilic ethynylating agent ethynyl(phenyl)-λ3-iodane in high yield. This two-step method uses very inexpensive materials and is readily operable without any special precautions.

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Silaboration of [1.1.1]Propellane: A Storable Feedstock for Bicyclo[1.1.1]pentane Derivatives

Masaki Kondo, Junichiro Kanazawa, Tomohiro Ichikawa, Takumi Shimokawa, Yuki Nagashima, Kazunori Miyamoto, Masanobu Uchiyama

Angewandte Chemie （Wiley）  132 （ 5 ） 1986 - 1990 2020年01月

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Silaboration of [1.1.1]Propellane: A Storable Feedstock for Bicyclo[1.1.1]pentane Derivatives

Kondo M., Kanazawa J., Ichikawa T., Shimokawa T., Nagashima Y., Miyamoto K., Uchiyama M.

Angewandte Chemie - International Edition 59 （ 5 ） 1970 - 1974 2020年01月

ISSN  14337851

　概要を見る

The silaboration of [1.1.1]propellane enables direct introduction of B and Si functional groups onto the bicyclo[1.1.1]pentane (BCP) scaffold in high yield under mild, additive-free conditions. The silaborated BCP can be obtained on a gram-scale in a single step without the need for column-chromatographic purification, and is storable and easy to handle, providing a versatile synthetic intermediate for BCP derivatives. We also describe various conversions of the C−B/C−Si bonds on the BCP scaffold, including development of a modified Suzuki–Miyaura cross-coupling reaction at the highly sterically hindered bridgehead sp3 carbon center of the BCP skeleton using a combination of highly activated BCP boronic esters, copper(I) oxide, and a PdCl2(dppf) catalyst system.

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Silaboration of [1.1.1]Propellane: A Storable Feedstock for Bicyclo[1.1.1]pentane Derivatives

Masaki Kondo, Junichiro Kanazawa, Tomohiro Ichikawa, Takumi Shimokawa, Yuki Nagashima, Kazunori Miyamoto, Masanobu Uchiyama

Angewandte Chemie International Edition （Wiley）  59 （ 5 ） 1970 - 1974 2020年01月

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Alkynylboration Reaction Leading to Boron-Containing π-Extended cis-Stilbenes as a Highly Tunable Fluorophore

Nogami M., Hirano K., Morimoto K., Tanioka M., Miyamoto K., Muranaka A., Uchiyama M.

Organic Letters （American Chemical Society ({ACS})）  21 （ 9 ） 3392 - 3395 2019年05月

ISSN  15237060

　概要を見る

An unprecedented boron-containing fluorophore, π-extended cis-stilbene, obtained via alkynylboration reaction of alkynamide is reported. Boron-containing π-extended cis-stilbenes emit fluorescence with high quantum yields in the solid state and exhibit aggregation-induced emission enhancement. The broad substrate scope of the alkynylboration reaction offers facile access to electronically diverse structures, enabling fine-tuning of light absorption/emission characteristics. The boron-containing π-extended cis-stilbene with a diphenylamino group displays solvatofluorochromism via an intramolecular charge-transfer transition.

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Diaryl-λ³-chloranes: Versatile Synthesis and Unique Reactivity as Aryl Cation Equivalent

Nakajima M., Miyamoto K., Hirano K., Uchiyama M.

Journal of the American Chemical Society （American Chemical Society ({ACS})）  141 （ 16 ） 6499 - 6503 2019年04月

ISSN  00027863

　概要を見る

We have developed a versatile, high-yield synthesis of diarylchloroniums/λ3-chloranes through the reaction of various chloroarenes with readily prepared mesityldiazonium tetrakis(pentafluorophenyl)borate under mild conditions. The scope of the reaction is broad, including ArCl, ArBr, and ArI. The diarylchloroniums/λ3-chloranes prepared here show unique reactivity in various respects, enabling intermolecular electrophilic arylation reaction of weak nucleophiles, and chlorane-halogane exchange reaction.

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Stable Thiele's Hydrocarbon Derivatives Exhibiting Near-Infrared Absorption/Emission and Two-Step Electrochromism

Okamoto Y., Tanioka M., Muranaka A., Miyamoto K., Aoyama T., Ouyang X., Kamino S., Sawada D., Uchiyama M.

Journal of the American Chemical Society （American Chemical Society ({ACS})）  140 （ 51 ） 17857 - 17861 2018年12月

ISSN  00027863

　概要を見る

We report synthesis and characterization of near-infrared (NIR)-absorbing/emitting Thiele's hydrocarbon derivatives, in which four aryl groups are bridged to a quinodimethane skeleton. The quinoid structure of the bridged-tetra-aryl-p-quinodimethanes (BTAQs) was confirmed by spectroscopic, X-ray crystallographic, and computational methods. Although quinodimethane derivatives with a small HOMO-LUMO energy gap often exhibit biradical character, BTAQs showed no biradical character. Instead, they exhibited two-step near-infrared electrochromism. The donor/acceptor properties of the aryl groups were found to play a key role in the unique properties of BTAQs.

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Safer Synthesis of (Diacetoxyiodo)arenes Using Sodium Hypochlorite Pentahydrate

Watanabe A., Miyamoto K., Okada T., Asawa T., Uchiyama M.

Journal of Organic Chemistry （American Chemical Society ({ACS})）  83 （ 23 ） 14262 - 14268 2018年12月

ISSN  00223263

　概要を見る

A practical method for the preparation of (diacetoxyiodo)arene ArI(OAc) 2 is described. The use of commercially available sodium hypochlorite pentahydrate (NaClO·5H 2 O) enabled safe, rapid, and inexpensive oxidation of iodoarenes with electron-withdrawing and -donating substituents. The method allows tandem divergent access to synthetically useful organo-λ 3 -iodanes such as hydroxyl(tosyloxy)iodobenzene, iodosylbenzene, iodonium ylide, etc.

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Oxidative α-Acetoxylation of a β-Oxime Ester with (Diacetoxyiodo)benzene Catalyzed by Sc^III Salts: An Approach to the Docetaxel Side Chain

Miyamoto K., Hoque M., Senoh Y., Ali M., Nemoto H., Mandai T.

European Journal of Organic Chemistry 2018 （ 22 ） 2841 - 2845 2018年06月

ISSN  1434193X

　概要を見る

Hypervalent iodine(III) compounds have emerged as reagents of choice for α-oxidation of various ketones under mild reaction conditions. We report herein a simple method for α-hydroxylation of a β-oxime ester, which involves an oxidative α-acetoxylation using PhI(OAc)2 with a catalytic amount of Sc(OTf)3 or Sc2O3-TMSOTf, followed by careful hydrolysis. The scandium(III) salt serves as an excellent reusable catalyst in this system.

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One-pot Annulation for Biaryl-fused Monocarba-closo-dodecaborate through Aromatic B−H Bond Disconnection

Akimoto G., Otsuka M., Miyamoto K., Muranaka A., Hashizume D., Takita R., Uchiyama M.

Chemistry - An Asian Journal 13 （ 8 ） 913 - 917 2018年04月

ISSN  18614728

　概要を見る

We have developed a one-pot annulation reaction of monocarba-closo-dodecaborate with cyclic diaryliodonium salts to afford biaryl-fused derivatives. Aryl functionalities are introduced at both the 1-carbon and unreactive ortho-boron vertices of the “σ-aromatic” carborane cage without the need for pre-functionalization. DFT calculations revealed that the palladium-catalyzed C−B bond-formation step in this process proceeds through a concerted metalation–deprotonation (CMD)-type pathway for the B−H bond disconnection on the aromatic cage, though such bonds are generally regarded as hydridic.

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N -Alkynylpyridinium Salts: Highly Electrophilic Alkyne-Pyridine Conjugates as Precursors of Cationic Nitrogen-Embedded Polycyclic Aromatic Hydrocarbons

Toriumi N., Asano N., Miyamoto K., Muranaka A., Uchiyama M.

Journal of the American Chemical Society （American Chemical Society ({ACS})）  140 （ 11 ） 3858 - 3862 2018年03月

ISSN  00027863

　概要を見る

We achieved the first synthesis of N-alkynylpyridinium salts, by reacting pyridines with alkynyl-λ3-iodanes. The N-alkynylpyridiniums exhibit highly electron-accepting character with extended π-conjugation. The electrophilic alkynyl groups were readily susceptible to Michael addition and 1,3-dipolar cycloaddition to afford various N-alkenylpyridiniums. Ring-fused pyridiniums were synthesized through intramolecular cyclization, demonstrating the utility of N-alkynylpyridiniums for the design of various electron-deficient cationic nitrogen-embedded polycyclic aromatic hydrocarbons with unique optical and electrochemical properties.

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“Dumbbell”- and “Clackers”-Shaped Dimeric Derivatives of Monocarba-closo-dodecaborate

Kitazawa Y., Watanabe M., Masumoto Y., Otsuka M., Miyamoto K., Muranaka A., Hashizume D., Takita R., Uchiyama M.

Angewandte Chemie - International Edition 57 （ 6 ） 1501 - 1504 2018年02月

ISSN  14337851

　概要を見る

We designed, synthesized, and characterized two types of dimeric forms of monocarba-closo-dodecaborate, namely, a “dumbbell”-shaped dianion having a C−C bond and a “clackers”-shaped monoanion having an iodonium linker. The unique architectures of these anionic molecules were established by X-ray analysis. Spectroscopic analysis, DFT calculations, and reactivity experiments revealed high anionic and chemical stability of both anions, which are crucial properties for weakly coordinating anions.

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“Dumbbell”‐ and “Clackers”‐Shaped Dimeric Derivatives of Monocarba‐closo‐dodecaborate

Yu Kitazawa, Mamoru Watanabe, Yui Masumoto, Mai Otsuka, Kazunori Miyamoto, Atsuya Muranaka, Daisuke Hashizume, Ryo Takita, Masanobu Uchiyama

Angewandte Chemie 2018年02月

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Mechanistic Study on Aryl-Exchange Reaction of Diaryl-λ³-iodane with Aryl Iodide

Masumoto Y., Miyamoto K., Iuchi T., Ochiai M., Hirano K., Saito T., Wang C., Uchiyama M.

Journal of Organic Chemistry （American Chemical Society ({ACS})）  83 （ 1 ） 289 - 295 2018年01月

ISSN  00223263

　概要を見る

Because of its hyper-leaving ability, as well as its strong oxidizing ability, diaryl(triflato)-λ3-iodane transfers one of the aryl groups to iodoarenes simply upon gentle heating (>85 °C) in nonpolar solvents. We have performed an in-depth mechanistic study of this unusual aryl transfer reaction. A combination of experimental (product analysis, kinetic study, and substituent effects) and density functional theoretical approaches revealed that the reaction proceeds through a concerted bimolecular transition state, in which ipso-carbon binds loosely to both iodine centers. We also evaluated electronic effects on the thermodynamic stability of diaryl-λ3-iodanes.

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One-step Conversion of Levulinic Acid to Succinic Acid Using I<inf>2</inf>/t-BuOK System: The Iodoform Reaction Revisited

Kawasumi R., Narita S., Miyamoto K., Tominaga K.I., Takita R., Uchiyama M.

Scientific Reports 7 （ 1 ）  2017年12月

査読有り

　概要を見る

The iodoform reaction has long been used as a qualitative test for acetyl and/or ethanol units in organic molecules. However, its synthetic applications are quite limited. Here, we describe a tuned iodoform reaction for oxidative demethylation reaction with I2 and t-BuOK in t-BuOH, in which in situ-generated t-BuOI serves as the chemoselective iodinating agent. This system enables one-step conversion of levulinic acid to succinic acid, a major four-carbon chemical feedstock. This oxidative demethylation is also applicable to other compounds containing an acetyl group/ethanol unit, affording the corresponding carboxylic acids in a selective manner.

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Transition Metal-Free trans-Selective Alkynylboration of Alkynes

Nogami M., Hirano K., Kanai M., Wang C., Saito T., Miyamoto K., Muranaka A., Uchiyama M.

Journal of the American Chemical Society （American Chemical Society ({ACS})）  139 （ 36 ） 12358 - 12361 2017年09月

ISSN  00027863

　概要を見る

We report the first transition metal-free and trans-selective alkynylboration reaction of alkynes. This unprecedented carboboration reaction is enabled by pseudo-intramolecular activation of alkynylboronates using propargylic alcohols. The carboboration affords 4-alkynyl-1,2-oxaborol-2(5H)-ols, which are not only versatile building blocks but also exhibit strong violet-blue fluorescence emission.

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Iodoarene-catalyzed oxidative transformations using molecular oxygen

Miyamoto K., Yamashita J., Narita S., Sakai Y., Hirano K., Saito T., Wang C., Ochiai M., Uchiyama M.

Chemical Communications （Royal Society of Chemistry ({RSC})）  53 （ 70 ） 9781 - 9784 2017年

ISSN  13597345

　概要を見る

Molecular oxygen serves as a useful oxidant for the glycol scission of 1,2-diols and the Hofmann rearrangement of primary amides using pentamethyliodobenzene as a catalyst. The use of isobutyraldehyde and Lewis basic nitriles under O2 enabled the iodine(i)/(iii) catalytic cycle, where in situ-generated peracid acts as a terminal oxidant.

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Cross-Coupling of Organolithium with Ethers or Aryl Ammonium Salts by C−O or C−N Bond Cleavage

Yang Z.K., Wang D.Y., Minami H., Ogawa H., Ozaki T., Saito T., Miyamoto K., Wang C., Uchiyama M.

Chemistry - A European Journal （WILEY-V C H VERLAG GMBH）  22 （ 44 ） 15693 - 15699 2016年10月

査読有り,  ISSN  09476539

　概要を見る

Various aryl-, alkenyl-, and/or alkyllithium species reacted smoothly with aryl and/or benzyl ethers with cleavage of the inert C−O bond to afford cross-coupled products, catalyzed by commercially available [Ni(cod)2] (cod=1,5-cyclooctadiene) catalysts with N-heterocyclic carbene (NHC) ligands. Furthermore, the coupling reaction between the aryllithium compounds and aryl ammonium salts proceeded under mild conditions with C−N bond cleavage in the presence of a [Pd(PPh3)2Cl2] catalyst. These methods enable selective sequential functionalizations of arenes having both C−N and C−O bonds in one pot.

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Stille coupling via C-N bond cleavage

Wang D.Y., Kawahata M., Yang Z.K., Miyamoto K., Komagawa S., Yamaguchi K., Wang C., Uchiyama M.

Nature Communications （NATURE PUBLISHING GROUP）  7   12937 2016年09月

査読有り,  ISSN  2041-1723

　概要を見る

Cross-coupling is a fundamental reaction in the synthesis of functional molecules, and has been widely applied, for example, to phenols, anilines, alcohols, amines and their derivatives. Here we report the Ni-catalysed Stille cross-coupling reaction of quaternary ammonium salts via C-N bond cleavage. Aryl/alkyl-trimethylammonium salts [Ar/R-NMe 3[+ react smoothly with arylstannanes in 1:1 molar ratio in the presence of a catalytic amount of commercially available Ni(cod)2 and imidazole ligand together with 3.0 equivalents of CsF, affording the corresponding biaryl with broad functional group compatibility. The reaction pathway, including C-N bond cleavage step, is proposed based on the experimental and computational findings, as well as isolation and single-crystal X-ray diffraction analysis of Ni-containing intermediates. This reaction should be widely applicable for transformation of amines/quaternary ammonium salts into multi-aromatics.

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Direct Hydroxylation and Amination of Arenes via Deprotonative Cupration

Tezuka N., Shimojo K., Hirano K., Komagawa S., Yoshida K., Wang C., Miyamoto K., Saito T., Takita R., Uchiyama M.

Journal of the American Chemical Society （American Chemical Society）  138 （ 29 ） 9166 - 9171 2016年07月

ISSN  00027863

　概要を見る

Deprotonative directed ortho cupration of aromatic/heteroaromatic C-H bond and subsequent oxidation with t-BuOOH furnished functionalized phenols in high yields with high regio- and chemoselectivity. DFT calculations revealed that this hydroxylation reaction proceeds via a copper (I → III → I) redox mechanism. Application of this reaction to aromatic C-H amination using BnONH2 efficiently afforded the corresponding primary anilines. These reactions show broad scope and good functional group compatibility. Catalytic versions of these transformations are also demonstrated.

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Allylic borylation of tertiary allylic alcohols: A divergent and straightforward access to allylic boronates

Harada K., Nogami M., Hirano K., Kurauchi D., Kato H., Miyamoto K., Saito T., Uchiyama M.

Organic Chemistry Frontiers （ROYAL SOC CHEMISTRY）  3 （ 5 ） 565 - 569 2016年05月

査読有り,  ISSN  20524110

　概要を見る

A facile and divergent synthetic process for converting tertiary allylic alcohols to multiply substituted allylic boronates is reported. This methodology is especially effective for tertiary alcohol substrates, providing the corresponding allylic boronates in moderate to good yields.

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Mechanistic Studies on the Generation and Properties of Superelectrophilic Singlet Carbenes from Bis(perfluoroalkanesulfonyl)bromonium Ylides

Miyamoto K., Iwasaki S., Doi R., Ota T., Kawano Y., Yamashita J., Sakai Y., Tada N., Ochiai M., Hayashi S., Nakanishi W., Uchiyama M.

Journal of Organic Chemistry （American Chemical Society）  81 （ 8 ） 3188 - 3198 2016年04月

査読有り,  ISSN  00223263

　概要を見る

Pyrolysis of bis(perfluoroalkanesulfonyl)bromonium ylides in various olefins results in highly stereospecific formation of cyclopropanes via unimolecular decomposition. Product analysis, kinetic study, substituent effects, and theoretical study revealed the generation of singlet bis(perfluoroalkanesulfonyl)carbenes stabilized by intramolecular coordination of sulfonyl oxygen.

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Rhodium-catalyzed (perfluoroalkyl)olefination of acetanilides leading to perfluoroalkylated aromatics

Harada K., Tezuka N., Hirano K., Miyamoto K., Saito T., Uchiyama M.

Chemical and Pharmaceutical Bulletin （Pharmaceutical Society of Japan）  64 （ 10 ） 1442 - 1444 2016年

査読有り,  ISSN  00092363

　概要を見る

We have developed an efficient Rh-catalyzed (perfluoroalkyl)olefination reaction of acetanilides, which provides a versatile synthetic entry to a range of perfluoroalkylated compounds.

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Gold-catalyzed cyclization of alkyne alcohols: Regioselective construction of functionalized 6,6- and 6,7-bicyclic ethers

Kubota M., Saito T., Miyamoto K., Hirano K., Wang C., Uchiyama M.

Chemical and Pharmaceutical Bulletin （Pharmaceutical Society of Japan）  64 （ 7 ） 845 - 855 2016年

ISSN  00092363

　概要を見る

We describe an efficient regioselective formation of six-/seven-membered cyclic ethers based on goldcatalyzed intramolecular hydroalkoxylation. Sequential gold-catalyzed cyclization and palladium-catalyzed cross-coupling reactions afforded 6,6-bicyclic ethers, while reversing the reaction sequence (cross-coupling then cyclization) afforded 6,7-bicyclic ethers. This methodology should provide access to a range of functional polycyclic ethers.

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Conjugation between σ- And π-Aromaticity in 1-C-Arylated Monocarba-closo-dodecaborate Anions

Otsuka M., Takita R., Kanazawa J., Miyamoto K., Muranaka A., Uchiyama M.

Journal of the American Chemical Society 137 （ 48 ） 15082 - 15085 2015年12月

査読有り,  ISSN  00027863

　概要を見る

Conjugation between σ- and π-aromatic moieties in 1-C-arylated monocarba-closo-dodecaborate anion derivatives 2 has been identified by means of kinetic experimental studies combined with theoretical calculations. We found that the reaction rate of iodination at the 12-B vertex of the carborane anion cage was affected by distal substituents on the benzene ring connected at the antipodal carbon vertex. Hammett and Yukawa-Tsuno plots indicated that substantial resonance effects are involved. Density functional theory calculations enabled detailed interpretation of the electronic interaction.

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Dialkylzinc-mediated allylic polyfluoroarylation reaction

Kurauchi D., Hirano K., Kato H., Saito T., Miyamoto K., Uchiyama M.

Tetrahedron （PERGAMON-ELSEVIER SCIENCE LTD）  71 （ 35 ） 5849 - 5857 2015年07月

査読有り,  ISSN  00404020

　概要を見る

Abstract We present an allylic polyfluoroarylation reaction with broad substrate scope and excellent functional group tolerance, using organozinc reagents under mild conditions. A catalytic amount of triphenylphosphine oxide efficiently promotes iodine-zinc exchange reaction between polyfluoroaryl iodide and dimethylzinc, and the resulting phosphine oxide-activated polyfluoroarylzinc undergoes substitution reaction with allylic halides to afford the corresponding polyfluoroarylated products.

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Stereoselective synthesis and reaction of gold(I) (Z)-enethiolates

Miyamoto K., Hirobe M., Uchiyama M., Ochiai M.

Chemical Communications （Royal Society of Chemistry）  51 （ 37 ） 7962 - 7965 2015年05月

査読有り,  ISSN  13597345

　概要を見る

Bench-top-storable (Z)-enethiol reagents: gold (Z)-1-decenylthiolates were synthesized stereoselectively in high yields. They are stable upon storage at room temperature without protection from light, and react smoothly with various alkyl halides, α,β-unsaturated ketones, and electron-deficient aryl halides with excellent stereoselectivity.

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Unexpected metal-free transformation of gem-dibromomethylenes to ketones under acetylation conditions

Kimura R., Sawayama Y., Nakazaki A., Miyamoto K., Uchiyama M., Nishikawa T.

Chemistry - An Asian Journal （John Wiley and Sons Ltd）  10 （ 4 ） 1035 - 1041 2015年04月

査読有り,  ISSN  18614728

　概要を見る

Novel conditions for the transformation of gem-dibromomethylenes to ketones are described. gem-Dibromo compounds were treated with acetic anhydride and triethylamine in dichloromethane/water at room temperature under an air atmosphere to give the corresponding ketones in moderate yields. A radical mechanism is proposed based on experimental results.

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Identification of polyethylene glycol-resistant macrophages on stealth imaging in vitro using fluorescent organosilica nanoparticles

Nakamura M., Hayashi K., Nakano M., Kanadani T., Miyamoto K., Kori T., Horikawa K.

ACS Nano 9 （ 2 ） 1058 - 1071 2015年02月

ISSN  19360851

　概要を見る

An in vitro imaging system to evaluate the stealth function of nanoparticles against mouse macrophages was established using fluorescent organosilica nanoparticles. Surface-functionalized organosilica nanoparticles with polyethylene glycol (PEG) were prepared by a one-step process, resulting in a brush-type PEG layer. A simultaneous dual-particle administration approach enabled us to evaluate the stealth function of nanoparticles with respect to single cells using time-lapse fluorescent microscopic imaging and flow cytometry analyses. Single-cell imaging and analysis revealed various patterns and kinetics of bare and PEGylated nanoparticle uptake. The PEGylated nanoparticles revealed a stealth function against most macrophages (PEG-sensitive macrophages); however, a stealth function against certain macrophages (PEG-insensitive macrophages) was not observed. We identified and characterized the PEG-resistant macrophages that could take up PEGylated nanoparticles at the same level as bare nanoparticles.

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Metal-free C-H amination of unactivated hydrocarbons with sulfonylimino-λ³-bromanes generated in situ from (diacetoxybromo)benzene

Miyamoto K., Ota T., Hoque M.M., Ochiai M.

Organic and Biomolecular Chemistry 13 （ 7 ） 2129 - 2133 2015年02月

ISSN  14770520

　概要を見る

A simple method for direct metal-free C-H amination of unactivated hydrocarbons using easy-handling diacetoxy-λ3-bromane and triflylamide or sulfamate esters was developed. The high 2°/3° regioselectivities and deuterium isotope effects suggest a concerted organonitrenoid transition state, analogous to C-H amination with N-triflylimino-λ3-bromane. This journal is

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Reactivity of hydroxy- and aquo(hydroxy)-λ³-iodane-crown ether complexes

Miyamoto K., Yokota Y., Suefuji T., Yamaguchi K., Ozawa T., Ochiai M.

Chemistry - A European Journal （WILEY-V C H VERLAG GMBH）  20 （ 18 ） 5447 - 5453 2014年04月

査読有り,  ISSN  09476539

　概要を見る

We have designed a series of hydroxy(aryl)-λ3-iodane-[18] crown-6 complexes, prepared from the corresponding iodosylbenzene derivatives and superacids in the presence of [18]crown-6, and have investigated their reactivities in aqueous media. These activated iodosylbenzene monomers are all non-hygroscopic shelf-storable reagents, but they maintain high oxidizing ability in water. The complexes are effective for the oxidation of phenols, sulfides, olefins, silyl enol ethers, and alkyl(trifluoro)borates under mild conditions. Furthermore, hydroxy-λ3-iodane-[18]crown-6 complexes serve as efficient progenitors for the synthesis of diaryl-, vinyl-, and alkynyl-λ3-iodanes in water. Other less polar organic solvents, such as methanol, acetonitrile, and dichloromethane, are also usable in some cases. Aqua-friendly iodosylbenzene equivalents: Hydroxy- and aquo(hydroxy)-λ3-iodane-[18]crown-6 complexes (see graphic), readily prepared from commercial PhI(OAc)2 or PhIO, serve as excellent oxygen atom donors toward olefins, phenols, sulfides, and alkyl(trifluoro)borates. They also serve as progenitors for diaryl-, vinyl-, and alkynyl-λ3-iodane-[18]crown-6 complexes. These reactions can be carried out in aqueous media under mild reaction conditions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Synthesis of hypervalent organo-λ³-bromanes and their reactions by using leaving group ability of λ³-bromanyl group

Miyamoto K.

Yakugaku Zasshi （公益社団法人 日本薬学会）  134 （ 12 ） 1287 - 1300 2014年

ISSN  00316903

　概要を見る

Hypervalent organo-λ3-iodanes have attracted great interest in organic synthesis; however, the chemistry of hypervalent organo-λ3-bromanes remains largely unexplored, mainly because of synthetic difficulties. Iodobenzene is readily oxidized by common oxidants such as peracids under mild conditions, whereas bromobenzene is inert. Since the ionization potential of bromobenzene (8.98 eV) is higher than that of iodobenzene (8.69 eV), hypervalent-λ3-bromane would show much higher reactivity. We overcame this problem by using difluoro (aryl)-λ3-bromane (Frohn's reagent), which serves as a pivotal progenitor of various l3-bromanes including imino-λ3-bromane, cyclopent-1-enyl-λ3-bromane, (E)-ß-alkylvinyl-λ3-bromane, and diacetoxy-λ3-bromane. These reagents possess highly unusual reactivity based on the enormously enhanced nucleofugality of the aryl-λ3-bromanyl group.

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In situ generation technology of β-butoxycarbonyliodonium ylide: A hypervalent analogue of the Darzens reagent

Miyamoto K., Suzuki M., Suefuji T., Ochiai M.

European Journal of Organic Chemistry  （ 18 ） 3662 - 3666 2013年06月

ISSN  1434193X

　概要を見る

An ester exchange reaction of β-butoxy-β-acyloxyvinyl- λ3-iodane with lithium bases (ROLi and nBuLi) efficiently generates highly labile monoester iodonium ylide at low temperature. The iodonium ylide generated in situ cleanly undergoes Darzens condensation with aromatic aldehydes to afford trans-epoxy ester selectively. The reactivity of monoester iodonium ylide is investigated. Highly labile mono ester iodonium ylide generated in situ from β-butoxy-β-acyloxyvinyl- λ3-iodane through an ester exchange reaction cleanly undergoes Darzens-type condensation with aromatic aldehydes to afford trans-epoxy ester selectively. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Time-lapse fluorescence imaging and quantitative single cell and endosomal analysis of peritoneal macrophages using fluorescent organosilica nanoparticles

Nakamura M., Miyamoto K., Hayashi K., Awaad A., Ochiai M., Ishimura K.

Nanomedicine: Nanotechnology, Biology, and Medicine 9 （ 2 ） 274 - 283 2013年02月

ISSN  15499634

　概要を見る

Fluorescent thiol-organosilica nanoparticles with 100 nm diameter (F-thiol-OS-100) were applied for time-lapse fluorescence imaging. The evaluation of F-thiol-OS-100 for quantitative analysis demonstrated great advantages as compared with quantum dots and organic fluorescent dye. Time-lapse fluorescence imaging of mouse peritoneal macrophages using F-thiol-OS-100 clearly demonstrated cellular uptake, and single cell analysis showed various patterns of uptake kinetics that could be quantitatively evaluated. We also performed quantitative analysis of endosomal uptake and movements in single cells. A correlation between morphologic findings and endosomal uptake and movement over time was also observed and analyzed quantitatively. The F-thiol-OS-100 showed high potential as a new fluorescence marker for time-lapse fluorescence imaging and quantitative single cell functional analysis for nanomedicine development. From the Clinical Editor: In this study the authors report on 100 nm thiol-organosilica nanoparticles as time-lapse flurescent markers. F-thiol-OS-100 proved to be superior to quantum dots and organic flurescent dyes, and enabled quantitative single cell functional analysis. © 2013 Elsevier Inc.

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Reductive detriflylation of N-triflylamides with Red-Al

Miyamoto K., Hoque M., Ogasa S.

Journal of Organic Chemistry 77 （ 18 ） 8317 - 8320 2012年09月

ISSN  00223263

　概要を見る

Reduction of cis-N-triflylaziridines with 10 equiv of Red-Al in toluene at-40 to 0 °C selectively afforded corresponding deprotected parent aziridines in good to high yields. N,N-Dialkyltriflylamides were also successfully cleaved under similar reaction conditions. © 2012 American Chemical Society.

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Metal-free α-CH amination of ethers with hypervalent sulfonylimino-λ³-bromane that acts as an active nitrenoid

Ochiai M., Yamane S., Hoque M.M., Saito M., Miyamoto K.

Chemical Communications 48 （ 43 ） 5280 - 5282 2012年05月

ISSN  13597345

　概要を見る

Hypervalent N-triflylimino-λ3-bromane undergoes direct and regioselective α-C-H amination of ethers at room temperature under transition metal-free conditions. Kinetic results, substituent and deuterium isotope effects suggest an asynchronous concerted organonitrenoid transition state with some hydride transfer character, analogous to that for alkane C-H insertions. © 2012 Royal Society of Chemistry.

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A catalytic version of hypervalent aryl-λ³-iodane-induced Hofmann rearrangement of primary carboxamides: Iodobenzene as an organocatalyst and m-chloroperbenzoic acid as a terminal oxidant

Miyamoto K., Sakai Y., Goda S., Ochiai M.

Chemical Communications 48 （ 7 ） 982 - 984 2012年01月

ISSN  13597345

　概要を見る

The first catalytic version of hypervalent aryl-λ3-iodane-induced Hofmann rearrangement of primary carboxamides, which probably involves in situ generation of a tetracoordinated bis(aqua)(hydroxy)phenyl-λ3-iodane complex as an active oxidant from a catalytic amount of iodobenzene by the reaction with m-chloroperbenzoic acid in the presence of HBF4 in dichloromethane–water under mild conditions, was developed. © 2012 The Royal Society of Chemistry.

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Oxidation of primary aliphatic and aromatic aldehydes with difluoro(aryl)-λ ³-bromane

Ochiai M., Yoshimura A., Hoque M., Okubo T., Saito M., Miyamoto K.

Organic Letters 13 （ 20 ） 5568 - 5571 2011年10月

ISSN  15237060

　概要を見る

Oxidation of primary aliphatic aldehydes with p- trifluoromethylphenyl(difluoro)-λ 3-bromane in dichloromethane at 0 °C afforded acid fluorides selectively in good yields, while that of aromatic aldehydes in chloroform at room temperature produced aryl difluoromethyl ethers. A larger migratory aptitude of aryl groups compared to primary alkyl groups during a 1,2-shift from carbon to an electron-deficient oxygen atom in bromane(III) Criegee-type intermediates will result in these differences in the reaction courses. © 2011 American Chemical Society.

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Synthesis and structure of hypervalent diacetoxybromobenzene and aziridination of olefins with imino-λ ³-bromane generated in situ under metal-free conditions

Hoque M., Miyamoto K., Tada N., Shiro M., Ochiai M.

Organic Letters （AMER CHEMICAL SOC）  13 （ 20 ） 5428 - 5431 2011年10月

査読有り,  ISSN  15237060

　概要を見る

Ligand exchange of p-CF 3C 6H 4BrF 2 with acetoxy groups using AcOH and Ac 2O affords (diacetoxybromo)benzene in a high yield, which undergoes aziridination of alkenes in the presence of TfNH 2 and sulfamate esters in one pot under mild conditions. The aziridination with TfNH 2 proceeds stereospecifically with retention of stereochemistry of olefins at room temperature using limiting amounts of olefins under transition-metal-free conditions. The one-pot aziridination procedure using sulfamate esters can be applied to the intramolecular versions. © 2011 American Chemical Society.

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Highly regioselective amination of unactivated alkanes by hypervalent sulfonylimino-δ³-bromane

Ochiai M., Miyamoto K., Kaneaki T., Hayashi S., Nakanishi W.

Science （American Association for the Advancement of Science (AAAS)）  332 （ 6028 ） 448 - 451 2011年04月

査読有り,  ISSN  00368075

　概要を見る

Amination of alkanes has generally required metal catalysts and/or high temperatures. Here we report that simple exposure of a broad range of alkanes to N-triflylimino-δ3-bromane 1 at ambient temperature results in C-H insertion of the nitrogen functionality to afford triflyl-substituted amines in moderate to high yields. Marked selectivity for tertiary over secondary C-H bonds was observed; primary (methyl) C-H bonds were inert. Addition of hexafluoroisopropanol to inhibit decomposition of 1 dramatically improved the C-H amination efficiencies. Second-order kinetics, activation parameters (negative activation entropy), deuterium isotope effects, and theoretical calculations suggest a concerted asynchronous bimolecular transition state for the metal-free C-H amination event.

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Synthesis and reaction of hypervalent λ³-Iodane-crown ether complexes

Miyamoto K.

Yakugaku Zasshi （公益社団法人 日本薬学会）  131 （ 4 ） 545 - 552 2011年04月

ISSN  00316903

　概要を見る

In this review, we show that intermolecular hypervalent I(III)...O interactions play an essential role in the complexation of organo-λ3-iodanes with crown ethers. In addition to the well-known driving force for the complexation of crown ethers, ion-dipole interaction, and hydrogen bonding interaction, our result provides a new class of interaction in supramolecular chemistry of crown ethers. Both solid state structure analysis and solution chemistry indicate that diaryl-, 1-alkenyl(phenyl)-, 1-alkynyl(phenyl)-, and hydroxy(phenyl)-λ3-iodanes form stable complexes with 18-crown-6 through hypervalent I(III)...O interactions. The complexation not only increases the stability of these hypervalent λ3-iodanes but also holds its high reactivity toward nucleophiles. The complex of hydroxy(phenyl)-λ3 -iodanes with 18-crown- 6 serve as versatile oxidizing agents, especially in water. © 2011 The Pharmaceutical Society of Japan.

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Synthesis and structure of aliphatic phenylchloronium ylide

Ochiai M., Tada N., Miyamoto K., Shiro M.

Heteroatom Chemistry （WILEY-BLACKWELL）  22 （ 3-4 ） 325 - 330 2011年04月

査読有り,  ISSN  10427163

　概要を見る

Aliphatic phenylchloronium ylide with bis(trifluoromethylsulfonyl)- methylidene group was synthesized. Thermal transylidation of 4-(trifluoromethyl)phenylbromonium bis(trifluoromethylsulfonyl)methylide in chlorobenzene as a solvent at 130°C afforded phenylchloronium bis(trifluoromethylsulfonyl)methylide in a moderate yield. Phenylbromonium and phenyliodonium ylides were also prepared by the thermal transylidation to bromo- and iodobenzenes. The reaction probably involves initial thermal generation of bissulfonylcarbene (Tf2C:), followed by nucleophilic attack of a halobenzene toward the electron-deficient carbene center. Solid-state structures of these aliphatic phenylhalonium ylides were analyzed and compared with each other. © 2011 Wiley Periodicals, Inc.

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Weakly nucleophilic conjugate bases of superacids as powerful nucleophiles in vinylic bimolecular nucleophilic substitutions of simple β- alkylvinyl(aryl)-λ³-bromanes

Ochiai M., Okubo T., Miyamoto K.

Journal of the American Chemical Society 133 （ 10 ） 3342 - 3344 2011年03月

ISSN  00027863

　概要を見る

We report herein, for the first time, the stereoselective synthesis of simple (E)-β-alkylvinyl(aryl)-λ3-bromanes via a boron-λ3-bromane exchange reaction and their unique bimolecular nucleophilic substitutions at the vinylic ipso carbon atom under mild conditions. Interestingly, even weakly nucleophilic anions such as conjugate bases of superacids (HBF4, TfOH, Tf2CH 2, Tf3CH, Tf2NH, etc.) function as nucleophiles toward the vinyl-λ3-bromanes. For instance, the vinylic SN2 reaction of (E)-vinyl-λ3-bromanes with potassium bis(triflyl)methanide stereoselectively produced (Z)-vinyloxy oxosulfonium ylides with exclusive inversion of configuration via oxygen attack, while that with potassium bis(triflyl)imide afforded predominantly (Z)-vinyloxysulfoximines. In marked contrast, (E)-β-alkylvinyl- λ3-iodanes do not undergo the vinylic SN2 reaction with these conjugate bases of superacids. The differences between the nucleofugalities of aryl-λ3-iodanyl and aryl- λ3-bromanyl groups (the latter being greater) probably play a pivotal role in these unique reactions. © 2011 American Chemical Society.

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Hypervalent phenyl-λ³-iodane-mediated para-selective aromatic fluorination of 3-phenylpropyl ethers

Saito M., Miyamoto K., Ochiai M.

Chemical Communications 47 （ 12 ） 3410 - 3412 2011年03月

ISSN  13597345

　概要を見る

Exposure of 3-phenylpropyl ethers to an activated iodosylbenzene monomer·18-crown-6 complex [PhI(OH)BF4·18C6] in the presence of BF3–Et2O and water results in the para-selective monofluorination of benzene ring via neighboring alkoxy group participation and directly affords 3-(4-fluorophenyl)propyl ethers regioselectively in good yields. © 2011 The Royal Society of Chemistry.

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Effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy in patients with type 2 diabetes, in relation to suppression of N^ε-carboxymethyl lysine

Kawai T., Takei I., Tokui M., Funae O., Miyamoto K., Tabata M., Hirata T., Saruta T., Shimada A., Itoh H.

Journal of Diabetes and its Complications 24 （ 6 ） 424 - 432 2010年11月

ISSN  10568727

　概要を見る

Objective: We investigated the efficacy of epalrestat, an aldose reductase inhibitor, for diabetic peripheral neuropathy in Japanese patients with type 2 diabetes. Methods: A total of 38 type 2 diabetic patients (22 men and 16 women; mean±S.E.M. age 63.3±1.0 years; duration of diabetes 9.6±0.8 years) with diabetic neuropathy were newly administered 150 mg/day epalrestat (EP group). Motor nerve conduction velocity (MCV), sensory nerve conduction velocity (SCV), and minimum F-wave latency were evaluated before administration of epalrestat and after 1 and 2 years. Serum N ε-carboxymethyl lysine (CML) as a parameter of advanced glycation end products (AGEs), lipid peroxide, and soluble vascular cell adhesion molecule (sVCAM)-1 as a parameter of angiopathy were measured before administration and after 1 year. We compared the results with those of 36 duration of diabetes-matched type 2 diabetic patients (mean±S.E.M. duration of diabetes 8.2±0.7 years) as control (C group). Results: The EP group showed significant suppression of deterioration of MCV (P<.01) and minimum F-wave latency (P<.01) in the tibial nerve and SCV (P<.05) in the sural nerve compared to those in the C group after 2 years. There was a significant difference in change in CML level between groups (-0.18±0.13 mU/ml in the EP group vs. +0.22±0.09 mU/ml in the C group, P<.05) after 1 year. Conclusions: Epalrestat suppressed the deterioration of diabetic peripheral neuropathy, especially in the lower extremity. Its effects might be mediated by improvement of the polyol pathway and suppression of production of AGEs. © 2010 Elsevier Inc. All rights reserved.

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Imination of sulfides and sulfoxides with sulfonylimino- λ³-bromane under mild, metal-free conditions

Ochiai M., Naito M., Miyamoto K., Hayashi S., Nakanishi W.

Chemistry - A European Journal 16 （ 29 ） 8713 - 8718 2010年08月

ISSN  09476539

　概要を見る

Exposure of sulfides and sulfoxides to trifluoromethanesulfonylimino(aryl)- λ3-bromane in dichloromethane at 0°C results in a facile transfer of the sulfonylimino group to sulfur atoms and affords N-triflylsulfilimines and -sulfoximines in high yields under transition-metal-free conditions. Imination of (R)-methyl p-tolyl sulfoxide proceeded with predominant retention of configuration at the stereogenic sulfur center. The Hammett plot afforded ρ values of -0.58 for para-substituted thioanisoles and -0.49 for their equivalent sulfoxides, which suggests a buildup of positive charge on the sulfur atoms of sulfides and sulfoxides in the transition state. Calculations suggest a bimolecular nucleophilic-substitution mechanism on the negatively charged nitrogen atom of the sulfonylimino- λ3-bromane, which involves the attack of a sulfide from the opposite side to bromine(III). © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Effects of stereochemistry and β-substituents on the rates of vinylic S<inf>N</inf>2 reaction of hypervalent vinyl(phenyl)-λ³- iodanes with tetrabutylammonium halides

Miyamoto K., Okubo T., Hirobe M., Kunishima M., Ochiai M.

Tetrahedron 66 （ 31 ） 5819 - 5826 2010年07月

査読有り,  ISSN  00404020

　概要を見る

Both stereoisomers of β-(2-phenylethoxy)vinyl-λ3- iodane and (Z)-β-aroyloxyvinyl-λ3-iodane were prepared stereoselectively. These substituted vinyl-λ3-iodanes undergo nucleophilic vinylic substitutions with n-Bu4NX (X=Cl, Br, I) under mild conditions, yielding vinyl halides. The observed inversion of configuration at the ipso vinylic carbon atom is compatible with a concerted vinylic S N2 mechanism. Kinetic measurements indicated that the rates for vinylic SN2 reaction of (Z)-vinyl-λ3-iodane are greater than those of the E-isomer, probably because of the higher ground state energy of the Z-isomer. Electronic effects of β-substituents of vinyl-λ3-iodanes in the vinylic SN2 reaction are also discussed. © 2010 Elsevier Ltd.

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Hypervalent λ³-bromane strategy for Baeyer-Villiger oxidation: Selective transformation of primary aliphatic and aromatic aldehydes to formates, which is missing in the classical Baeyer-Villiger oxidation

Ochiai M., Yoshimura A., Miyamoto K., Hayashi S., Nakanishi W.

Journal of the American Chemical Society 132 （ 27 ） 9236 - 9239 2010年07月

ISSN  00027863

　概要を見る

A conceptually distinct, modern strategy for Baeyer-Villiger oxidation (BVO) was developed. Our novel method involves initial hydration of water to carbonyl compounds, followed by ligand exchange of hypervalent aryl-λ3-bromane on bromane(III) with the resulting hydrate, yielding a new type of activated Criegee intermediate. The intermediate undergoes BV rearrangement and produces an ester via facile reductive elimination of an aryl-λ3-bromanyl group, because of the hypernucleofugality. The novel strategy makes it possible to induce selectively the BV rearrangement of straight chain primary aliphatic as well as aromatic aldehydes, which is missing in the classical BVO: for instance, octanal and benzaldehyde afforded rearranged formate esters with high selectivity (>95%) under our conditions, while the attempted classical BVO produced only carboxylic acids. This firmly establishes the powerful nature of new methodology for BVO. © 2010 American Chemical Society.

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Organocatalytic oxidative cleavage of carbon-carbon double bonds

Miyamoto K., Ochiai M.

Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry （公益社団法人 有機合成化学協会）  68 （ 3 ） 228 - 237 2010年03月

ISSN  00379980

　概要を見る

Oxidative cleavage of carbon-carbon double bonds to carbonyl compounds is an essential operation in organic synthesis. Ozonolysis is generally accepted as the standard method for this direct transformation. However, its utility is often limited by safety concerns. Use of high-valent oxometals such as RuO 4, OsO4, and MeReO3 in combination with a number of oxygen donors as stoichiometric oxidants is suitable for the oxidative catalytic cleavage of olefins, but they are expensive and/or toxic. Therefore, the development of a safe and environmentally friendly procedure for the cleavage of carbon-carbon double bonds is highly desirable. In this review, we report a safe, environment-friendly, and heavy metal-free ozonolysis of olefins, which involves activated iodosylbenzene monomers, hydroxy-λ3- iodanes, as active species. Organocatalytic version of the oxidative cleavage of olefins that involves in situ generation of hypervalent aryl- λ3-iodanes as effective organocatalysts and the use of m-chloroperbenzoic acid as a stoichiometric terminal oxidant under metal-free conditions is described. Cyclic and acyclic olefins as well as aliphatic and aromatic alkynes were cleaved to carboxylic acids under the organocatalytic conditions.

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Hypervalent N-sulfonylimino-λ³-bromane: Active nitrenoid species at ambient temperature under metal-free conditions

Ochiai M., Miyamoto K., Hayashi S., Nakanishi W.

Chemical Communications 46 （ 4 ） 511 - 521 2010年

ISSN  13597345

　概要を見る

The synthesis and reactions of N-triflylimino-λ3-bromane are summarized. The hypervalent iminobromane functions as a highly active nitrenoid species at ambient temperature under transition metal-free conditions, probably because of the increased hypernucleofugality of aryl- λ3-bromanyl groups compared to that of aryl- λ3-iodanyl groups. The imino-λ3-bromane undergoes stereospecific aziridination of olefins and transylidation to aromatic nitrogen heterocycles, trialkylamines and iodobenzenes. Difluoro- λ3-bromane-induced Hofmann rearrangement of primary arylsulfonamides is also discussed. © 2010 The Royal Society of Chemistry.

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Facile generation of a strained cyclic vinyl cation by thermal solvolysis of cyclopent-1-enyl-λ³-bromanes

Miyamoto K., Shiro M., Ochiai M.

Angewandte Chemie - International Edition 48 （ 47 ） 8931 - 8934 2009年11月

ISSN  14337851

　概要を見る

Last of the cyclic vinyl cations: The simple solvolysis of cyclopent-1 -enyl-13-bromane efficiently generates the highly strained cyclopent-1 -enyl cation at room temperature (see scheme). The very high nucleofugality of the aryl-13-bromanyl groups are responsible for this unique unimolecular dissociation. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

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Oxidation of benzyl alcohols with difluoro(aryl)-λ³-bromane: formation of benzyl fluoromethyl ethers via oxidative rearrangement

Ochiai M., Yoshimura A., Miyamoto K.

Tetrahedron Letters 50 （ 33 ） 4792 - 4795 2009年08月

ISSN  00404039

　概要を見る

Oxidative rearrangement of benzyl alcohols with difluoro(p-trifluoromethylphenyl)-λ3-bromane (5 × 10-2 M) in chloroform at room temperature afforded aryl fluoromethyl ethers selectively in good yields, probably via 1,2-shift of aryl groups from benzylic carbon to oxygen atoms. © 2009 Elsevier Ltd. All rights reserved.

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Difluoro-λ³-bromane-induced hofmann rearrangement of sulfonamides: Synthesis of sulfamoyl fluorides

Ochiai M., Okada T., Tada N., Yoshimura A., Miyamoto K., Shiro M.

Journal of the American Chemical Society 131 （ 24 ） 8392 - 8393 2009年06月

ISSN  00027863

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(Chemical Equation Presented) We report the first example of Hofmann rearrangement of primary arenesulfonamides, which relies on the use of p-trifluoromethylphenyl(difluoro)-λ3-bromane and affords N-arylsulfamoyl fluorides selectively at room temperature. Reaction of aryl-λ3-iodanes with p-toluenesulfonamide affords sulfonylimono-λ3-iodanes, being excellent progenitors for generation of metal-nitrenoid species. In marked contrast, reaction of the difluoro-λ3-bromane with p-toluenesulfonamide in benzene produced unique N-p-tolylsulfamoyl fluoride in a high yield, through Hofmann rearrangement. Arenesulfonamides with electron-donating (p-MeO and o-Me) and -withdrawing substituents (p-F, p-Cl, and p-CF3) efficiently undergoes the λ3-bromane-induced Hofmann rearrangement. The structure of N-p-tolylsulfamoyl fluoride was determined by a single-crystal X-ray analysis. The differences in nucleofugality between aryl- λ3-iodanyl and aryl-λ3-bromanyl groups, the later being greater, probably play a pivotal role in determining the reaction course. The results obtained from the reaction of 2,3,5,6- tetramethylbenzenesulfonamide strongly suggest that generation of sulfonyl nitrene will not be involved in this rearrangement. Copyright © 2009 American Chemical Society.

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Lodomesitylene-catalyzed oxidative cleavage of carbon-carbon double and triple bonds using m-chloroperbenzoic acid as a terminal oxidant

Miyamoto K., Sei Y., Yamaguchi K., Ochiai M.

Journal of the American Chemical Society 131 （ 4 ） 1382 - 1383 2009年02月

ISSN  00027863

　概要を見る

Transition metal-catalyzed oxidative cleavage of carbon-carbon multiple bonds has emerged as a powerful tool in organic synthesis. High-valent oxometals, mostly of Ru, Os, Mn, Mo, W, and Re, were used catalytically as reactive oxygen transfer agents to the multiple bonds. Reported here for the first time are the organocatalytic versions of the oxidative cleavage reactions. Our method involves use of iodomesitylene as an effective organocatalyst, which generates an active aryl(hydroxy)-B3-iodane 5 in situ, and m-chloroperbenzoic acid (m-CPBA) as a terminal oxidant under metal-free conditions. Cyclic and acyclic olefins as well as aliphatic and aromatic alkynes were smoothly cleaved to carboxylic acids under the organocatalytic conditions. Copyright © 2009 American Chemical Society.

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Direct transfer of the sulfonylimino group of imino-λ³- bromane to N-heterocycles and trialkylamines: Synthesis of N-iminoammonium ylides under metal-free conditions

Ochiai M., Kawano Y., Kaneaki T., Tada N., Miyamoto K.

Organic Letters （AMER CHEMICAL SOC）  11 （ 2 ） 281 - 284 2009年01月

査読有り,  ISSN  15237060

　概要を見る

(Chemical Equation Presented) Exposure of N-heterocycles and aliphatic trialkylamines to trifluoromethanesulfonylimino-λ3-bromane at room temperature results in direct transfer of the sulfonylimino group to the nitrogen atoms and affords a variety of iminoammonium ylides under transition-metal-free conditions. The imino-λ3-bromane probably serves as an active nitrenoid species without any activation and produces the ammonium ylides via a bimolecular nucleophilic substitution process. © 2009 American Chemical Society.

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Imido transfer of sulfonylimino-λ³-bromane makes possible the synthesis of sulfonylimino-λ³-iodanes

Ochiai M., Nakano A., Yoshimura A., Miyamoto K., Hayashi S., Nakanishi W.

Chemical Communications （Royal Society of Chemistry (RSC)）   （ 8 ） 959 - 961 2009年

査読有り,  ISSN  13597345

　概要を見る

Sulfonylimino-λ3-bromane functions as a reactive nitrenoid, because of the hyperleaving group ability of aryl- λ3-bromanyl groups, and undergoes transimidations to iodobenzenes at room temperature under metal-free conditions probably via an SN2-type nitrenoid transition state, yielding sulfonylimino- λ3-iodanes. © The Royal Society of Chemistry 2009.

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Thermal and catalytic transylidations between halonium ylides and synthesis and reaction of stable aliphatic chloronium ylides

Ochiai M., Tada N., Okada T., Sota A., Miyamoto K.

Journal of the American Chemical Society （AMER CHEMICAL SOC）  130 （ 7 ） 2118 - 2119 2008年02月

査読有り,  ISSN  00027863

　概要を見る

Intermolecular transylidation between halonium ylides under thermal and catalytic (rhodium(II) acetate) conditions, which makes it possible to synthesize a hitherto unknown kind of aliphatic chloronium ylides as well as a variety of bromonium and iodonium ylides, was developed. The uncatalyzed thermal transylidations of bromonium to iodonium ylides probably involve generation of a reactive carbene :C(SO2CF3)2, being electrophilic in nature. Compared to the bromonium and iodonium ylides, the chloronium ylide serves as a much better progenitor for generation of carbenes (or carbenoids) and efficiently undergoes cyclopropanation of olefins such as cyclooctadiene under uncatalyzed thermal conditions. A greater leaving group ability of the λ3-chloranyl and λ3-bromanyl groups compared to that of the λ3-iodanyl group seems to be responsible for the observed differences in reactivity between these halonium ylides. Copyright © 2008 American Chemical Society.

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A new type of imido group donor: Synthesis and characterization of sulfonylimino-Δ³-bromane that acts as a nitrenoid in the aziridination of olefins at room temperature under metal-free conditions

Ochiai M., Kaneaki T., Tada N., Miyamoto K., Chuman H., Shiro M., Hayashi S., Nakanishi W.

Journal of the American Chemical Society （American Chemical Society (ACS)）  129 （ 43 ） 12938 - 12939 2007年10月

査読有り,  ISSN  00027863

　概要を見る

A stable sulfonylimino-λ3-bromane, CF3SO2N--Br+C6H4-p-CF3, has been synthesized and structurally characterized for the first time. X-ray crystallographic analyses indicated a centrosymmetric dimer structure with little double-bond character for the "ylidic" Br-N bond. The iminobromane serves as an efficient imido group donor and directly undergoes aziridination of olefins stereospecifically with retention of original stereochemistry. Very interestingly, the aziridination proceeds at room temperature using limiting amounts of alkenes under transition-metal-free conditions. The observed rate constants for aziridination of cis-cyclooctene are proportional to concentration of the olefin. The results suggest the involvement of a bimolecular transition state, in which an olefin attacks the σ* N-Br orbital of iminobromane in the nitrenoid transfer process. Copyright © 2007 American Chemical Society.

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One-pot regioselective synthesis of chromanyl(phenyl)-λ³- iodanes: Tandem oxidative cyclization and λ³-iodanation of 3-phenylpropanols

Miyamoto K., Hirobe M., Saito M., Shiro M., Ochiai M.

Organic Letters 9 （ 10 ） 1995 - 1998 2007年05月

ISSN  15237060

　概要を見る

Reaction of 3-phenylpropanol with an activated iodosylbenzene - 18-crown-6 complex [Phl(OH)BF4-18C6] in dichloromethane in the presence of BF3-Et2O afforded directly the 6-chromanyl(phenyl)- λ3-iodane-18C6 complex through tandem oxidative intramolecular cyclization yielding chroman and its regioselectlve phenyl- λ3-iodanation. © 2007 American Chemical Society.

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Activated iodosylbenzene monomer as an ozone equivalent: Oxidative cleavage of carbon-carbon double bonds in the presence of water

Miyamoto K., Tada N., Ochiai M.

Journal of the American Chemical Society 129 （ 10 ） 2772 - 2773 2007年03月

ISSN  00027863

　概要を見る

Reported here for the first time are the developments of an efficient method for oxidative cleavage of carbon-carbon double bonds yielding carbonyl compounds by using aryl-λ3-iodanes, which involve a combination of iodosylbenzene and HBF4 in the presence of water. The method serves as a safety alternative to ozonolysis. The oxidative cleavage of olefins probably involves the hitherto unknown direct vicinal dihydroxylations of double bonds with aryl-λ3-iodanes and the subsequent oxidative glycol fissions. Cyclic (cyclopentenes, cyclohexenes, etc.) and acyclic olefins are cleaved smoothly under our conditions. In the reaction of electron-deficient styrenes such as m-nitrostyrene, intermediate formation of the corresponding epoxide was detected. A variety of aryloxiranes also undergo an oxidative cleavage of the epoxide rings under our conditions, and aromatic aldehydes were obtained in good yields. Copyright © 2007 American Chemical Society.

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trans influences on hypervalent bonding of aryl λ³- iodanes: Their stabilities and isodesmic reactions of benziodoxolones and benziodazolones

Ochiai M., Sueda T., Miyamoto K., Kiprof P., Zhdankin V.V.

Angewandte Chemie - International Edition 45 （ 48 ） 8203 - 8206 2006年12月

ISSN  14337851

　概要を見る

Large and small or twice moderate: Both combinations of trans influences of the substituents favor the formation of highly stable aryl λ 3-iodanes ArILL' (examples: PhI(OH)OTs and PhI(OAc)2). trans influences also seem to explain why iodosylbenzene adopts an oxo-bridged zigzag polymer structure in contrast to PhI(OH)2, which is monomeric. (Chemical Equation Presented). © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.

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Silver technology for stabilization of simple (Z)-enethiols: Stereoselective synthesis and reaction of silver (Z)-enethiolates

Ochiai M., Hirobe M., Miyamoto K.

Journal of the American Chemical Society 128 （ 28 ） 9046 - 9047 2006年07月

ISSN  00027863

　概要を見る

Reported here for the first time are the stereoselective synthesis and reaction of simple silver (Z)-enethiolates, which serve as stabilized (Z)-enethiol storage. In contrast to labile enethiols, silver (Z)-enethiolates are stable even in solutions, and their isolation and purification are very simple. The method for synthesis of silver (Z)-enethiolates involves an unusual vinylic SN2 reaction of (E)-vinyl-λ3-iodanes with thiobenzamides yielding the inverted (Z)-S-vinylthioimidonium salts, followed by their regioselective C-S bond cleavage with silver acetate. Alkylation, arylation, and Michael addition of silver (Z)-enethiolates yielding (Z)-vinyl sulfides were dramatically accelerated by the addition of Bu4NI (LiI), which probably generates reactive ammonium (Z)-enethiolates with an increased nucleophilicity. Copyright © 2006 American Chemical Society.

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Thiazole synthesis by cyclocondensation of 1-alkynyl(phenyl)- λ³-iodanes with thioureas and thioamides

Miyamoto K., Nishi Y., Ochiai M.

Angewandte Chemie - International Edition 44 （ 42 ） 6896 - 6899 2005年10月

ISSN  14337851

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(Chemical Equation Presented) The isolation and intramolecular cyclization of (S)-(1-alkynyl)isothiouronium and (S)-(1-alkynyl)thiobenzimidonium salts suggest the mechanism for the one-pot synthesis of 2,4-disubstituted thiazoles (see scheme; Ms = methanesulfonyl): Michael addition of sulfur nucleophiles to hypervalent iodanes followed by the 1,2-rearrangement of sulfenyl groups in the resulting alkylidene carbenes. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.

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Iodobenzene-catalyzed α-acetoxylation of ketones. In situ generation of hypervalent (diacyloxyiodo)benzenes using m-chloroperbenzoic acid

Ochiai M., Takeuchi Y., Katayama T., Sueda T., Miyamoto K.

Journal of the American Chemical Society 127 （ 35 ） 12244 - 12245 2005年09月

研究論文（学術雑誌）, 査読有り,  ISSN  00027863

　概要を見る

Reported here for the first time is the iodobenzene-catalyzed α-oxidation of ketones, in which diacyloxy(phenyl)-λ3-iodanes generated in situ act as real oxidants of ketones and m-chloroperbenzoic acid serves as a terminal oxidant. Oxidation of a ketone with m-chloroperbenzoic acid in acetic acid in the presence of a catalytic amount of iodobenzene, BF3·Et2O, and water at room temperature under argon affords an α-acetoxy ketone in good yield. p-Methyl- and p-chloroiodobenzene also serve as efficient catalysts in this direct oxidation. We found that when the reaction was carried out in the absence of a catalytic amount of iodobenzene, Baeyer-Villiger oxidation of a ketone took place. It is noted that use of water and BF3·Et2O is crucial to the success of this α-acetoxylation. Copyright © 2005 American Chemical Society.

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Effects of complexation with 18-crown-6 on the hypernucleofugality of phenyl-λ³-iodanyl groups. Synthesis of vinyl- λ³-iodane·18-crown-6 complex

Ochiai M., Suefuji T., Miyamoto K., Shiro M.

Organic Letters 7 （ 14 ） 2893 - 2896 2005年07月

研究論文（学術雑誌）, 査読有り,  ISSN  15237060

　概要を見る

(Chemical Equation Presented) 4-tert-Butyl-1-cyclohexenyl(phenyl) (tetrafluoroborato)-λ3-iodane forms a discrete supramolecular complex by the reaction with 18-crown-6. Solvolysis of the cyclohexenyl- λ3-iodane in the presence of 18-crown-6 indicates that the complexation with 18-crown-6 tends to decrease the leaving group ability of hypervalent phenyl-λ3-iodanyl groups. © 2005 American Chemical Society.

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Synthesis, characterization, and reaction of crown ether complexes of aqua(hydroxy)(aryl)iodonium ions

Ochiai M., Miyamoto K., Yokota Y., Suefuji T., Shiro M.

Angewandte Chemie - International Edition 44 （ 1 ） 75 - 78 2004年12月

研究論文（学術雑誌）, 査読有り,  ISSN  14337851

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Oxidation of 3-hydroxypiperidines with iodosylbenzene in water: Tandem oxidative grob fragmentation-cyclization reaction

Tada N., Miyamoto K., Ochiai M.

Chemical and Pharmaceutical Bulletin （PHARMACEUTICAL SOC JAPAN）  52 （ 9 ） 1143 - 1144 2004年09月

研究論文（学術雑誌）, 査読有り,  ISSN  00092363

　概要を見る

Oxidation of 3-hydroxypiperidine with iodosylbenzene in water afforded 2-pyrrolidinone directly in good yields. The reaction probably involves oxidative Grob fragmentation yielding imino aldehyde, which upon hydrolysis produces 2-pyrrolidinone via a cyclization-oxidation sequence. © 2004 Pharmaceutical Society of Japan.

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Synthesis and structure of supramolecular complexes between 1-alkynyl(phenyl)(tetrafluoroborato)-λ³-iodanes and 18-crown-6

Ochiai M., Miyamoto K., Suefuji T., Shiro M., Sakamoto S., Yamaguchi K.

Tetrahedron （PERGAMON-ELSEVIER SCIENCE LTD）  59 （ 51 ） 10153 - 10158 2003年12月

研究論文（学術雑誌）, 査読有り,  ISSN  00404020

　概要を見る

Slow evaporation of a solution of 1-decynyl(phenyl)(tetrafluoroborato)- λ3-iodane and 18-crown-6 in dichloromethane-diethyl ether-hexane gave a supramolecular 1:1 complex, while 3,3-dimethyl-1-butynyl- and phenylethynyl(phenyl)(tetrafluoroborato)-λ3-iodanes afforded 2:1 complexes. Complexation with 18-crown-6 increased the thermal stability of the phenylethynyl-λ3-iodane. Solid state and solution structures of these complexes were examined by single crystal X-ray analyses, 1H and 13C NMR spectra, and cold-spray ionization MS. Binding constants were measured by 1H NMR titrations. © 2003 Elsevier Ltd. All rights reserved.

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Isolation, Characterization, and Reaction of Activated Iodosylbenzene Monomer Hydroxy(phenyl)iodonium Ion with Hypervalent Bonding: Supramolecular Complex PhI⁺OH·18-Crown-6 with Secondary I⋯O Interactions

Ochiai M., Miyamoto K., Shiro M., Ozawa T., Yamaguchi K.

Journal of the American Chemical Society （AMER CHEMICAL SOC）  125 （ 43 ） 13006 - 13007 2003年10月

研究論文（学術雑誌）, 査読有り,  ISSN  00027863

　概要を見る

The isolation, characterization, and reaction of the active species hydroxy(phenyl)iodonium ion with hypervalent bonding are reported. Reaction of iodosylbenzene with HBF4-Me2O in the presence of equimolar 18-crown-6 in dichloromethane afforded the hydroxy-λ3-iodane complex PhI(OH)BF4·18-crown-6 as stable yellow prisms. X-ray structure analysis indicated that both the close contacts between the iodine(III) and the three adjacent oxygen atoms of 18-crown-6, and the hydrogen bonding OH⋯O(crown ether) will be responsible for the increased stability of the complex as compared to the uncomplexed PhI(OH)BF4. The crown ether complex is highly reactive and serves as a versatile oxidant even in water: thus, the complex undergoes oxidative transformations of a variety of functional groups such as olefins, alkynes, enones, silyl enol ethers, sulfides, and phenols under mild conditions. Copyright © 2003 American Chemical Society.

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Synthesis, characterization, and reaction of ethynyl(phenyl)-λ³-iodane complex with [18]crown-6

Ochiai M., Miyamoto K., Suefuji T., Sakamoto S., Yamaguchi K., Shiro M.

Angewandte Chemie - International Edition （WILEY-V C H VERLAG GMBH）  42 （ 19 ） 2191 - 2194 2003年05月

研究論文（学術雑誌）, 査読有り,  ISSN  14337851

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Iodine(III) crowned: Slow evaporation of solvents afforded the 1:1 complex 1 between [H-C≡C-I-Ph]BF4 and [18]crown-6 (18C6). Both the solid-state and solution structures of 1 were determined. Reaction of 1 with methanol proceeds in a Michael-type fashion. The complexation with 18C6 increases the stability of labile λ3-iodanes, such as 1.

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Synthesis of 1-alkynyl(diphenyl)onium salts of group 16 elements via heteroatom transfer reaction of 1-alkynyl(phenyl)-λ³-iodanes

Ochiai M., Nagaoka T., Sueda T., Yan J., Chen D.W., Miyamoto K.

Organic and Biomolecular Chemistry 1 （ 9 ） 1517 - 1521 2003年05月

研究論文（学術雑誌）, 査読有り,  ISSN  14770520

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1-Alkynyl(phenyl)-λ3-iodanes undergo selective transfer of the alkynyl groups over the phenyl group onto diphenyl chalcogens. Exposure of 1-alkynyl(phenyl)-λ3-iodanes to diphenyl chalcogens (S, Se, and Te) in dichloromethane or 1,2-dichloroethane affords 1-alkynyl(diphenyl)sulfonium, -selenonium, and -telluronium salts in high yields.

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Secondary hypervalent I(III)⋯O interactions: Synthesis and structure of hypervalent complexes of diphenyl-λ³-iodanes with 18-crown-6

Ochiai M., Suefuji T., Miyamoto K., Tada N., Goto S., Shiro M., Sakamoto S., Yamaguchi K.

Journal of the American Chemical Society （AMER CHEMICAL SOC）  125 （ 3 ） 769 - 773 2003年01月

研究論文（学術雑誌）, 査読有り,  ISSN  00027863

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Reported here for the first time are the synthesis and characterization of supramolecular complexes between diaryl-λ3-iodanes and 18-crown-6 (18C6). Slow evaporation of solvents afforded 1:1 and 2:1 complexes between Ph2IBF4 and 18C6 as stable crystals, depending on the conditions. X-ray crystal structures of these complexes indicated that each iodine atom contacts with the three adjacent oxygen atoms of 18C6 through two hypervalent secondary bonding and a weak interaction. 1H NMR analyses and CSI-MS spectra showed that, in dichloromethane solution, Ph2IBF4 exclusively forms the 1:1 complex with 18C6 (binding constant Ka, 1.02 x 103 M-1). The binding constants decrease with the increased solvent donor ability (Gutmann's DN). Changing the heteroatom ligand from BF4 to the less nucleophilic PF6 and AsF6 increased the binding constant by about six times. Substitution of an electron-withdrawing group onto the para position of Ph2IBF4 tends to increase in the complex stability. A linear Hammett relationship (p = 0.59) between log Ka and σp+ values of substituents indicates that the diaryl-λ3-iodanes with electropositive iodine(III) interact more efficiently with 18C6. Decreased binding magnitude was measured with 15C5, dibenzo-18C6, dibenzo-21C7, and dibenzo-30C10.

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Solid state structures of pentacoordinated λ³-iodanes with a trigonal bipyramidal geometry: Synthesis of diphenyl- and alkynyl(phenyl)-λ³-iodane complexes with 1,10-phenanthroline

Ochiai M., Suefuji T., Miyamoto K., Shiro M.

Chemical Communications 3 （ 12 ） 1438 - 1439 2003年

研究論文（学術雑誌）, 査読有り,  ISSN  13597345

　概要を見る

The single crystal X-ray structure of the supramolecular complex formed between diphenyl-λ3-iodane (Ph2IBF4) or 1-alkynyl(phenyl)-λ3-iodane [ButCCI(Ph)BF4] and 1,10-phenanthroline indicates a hitherto unknown distorted trigonal bipyramidal geometry around iodine(III), in which 1,10-phenanthroline acts as a bidentate ligand and occupies equatorial sites. © 2003 Royal Society of Chemistry.

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