Papers - Miyamoto, Kazunori

Theoretical Study on the Mechanism of Spirocyclization in Spiroviolene Biosynthesis

Hajime Sato, Taisei Takagi, Kazunori Miyamoto, Masanobu Uchiyama

Chemical and Pharmaceutical Bulletin (Pharmaceutical Society of Japan)  69 ( 10 ) 1034 - 1038 2021.10

ISSN  00092363

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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

Hajime Sato, Bi-Xiao Li, Taisei Takagi, Chao Wang, Kazunori Miyamoto, Masanobu Uchiyama

JACS Au (American Chemical Society ({ACS}))  1 ( 8 ) 1231 - 1239 2021.08

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

Kazunori Miyamoto, Motomichi Saito, Shunsuke Tsuji, Taisei Takagi, Motoo Shiro, Masanobu Uchiyama, Masahito Ochiai

Journal of the American Chemical Society (American Chemical Society ({ACS}))  143 ( 25 ) 9327 - 9331 2021.06

ISSN  00027863

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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

Kyoichi Hanada, Juntaro Nogami, Kazunori Miyamoto, Norihiko Hayase, Yuki Nagashima, Yusuke Tanaka, Atsuya Muranaka, Masanobu Uchiyama, Ken Tanaka

Chemistry – A European Journal (Wiley)  27 ( 36 ) 9313 - 9319 2021.06

ISSN  09476539

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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

Juntaro Nogami, Yuki Nagashima, Kazunori Miyamoto, Atsuya Muranaka, Masanobu Uchiyama, Ken Tanaka

Chemical Science (Royal Society of Chemistry ({RSC}))  12 ( 22 ) 7858 - 7865 2021.06

ISSN  20416520

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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

Kazunori Miyamoto, Yuichiro Watanabe, Taisei Takagi, Tomohide Okada, Takashi Toyama, Shinji Imamura, Masanobu Uchiyama

Arkivoc (Arkat)  2021 ( 7 )  2021.05

ISSN  15517004

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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

Kyoka Sakamoto, Yuki Nagashima, Chao Wang, Kazunori Miyamoto, Ken Tanaka, Masanobu Uchiyama

Journal of the American Chemical Society (American Chemical Society ({ACS}))  143 ( 15 ) 5629 - 5635 2021.04

ISSN  00027863

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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

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

Angewandte Chemie International Edition (Wiley)  60 ( 5 ) 2578 - 2582 2021.02

ISSN  14337851

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

Angewandte Chemie International Edition (Wiley)  60 ( 5 ) 2169 - 2169 2021.02

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

Angewandte Chemie (Wiley)  133 ( 5 ) 2197 - 2197 2021.02

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

Angewandte Chemie (Wiley)  133 ( 5 ) 2610 - 2614 2021.02

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

Toshitaka Okamura, Kenta Koyamada, Junichiro Kanazawa, Kazunori Miyamoto, Yoshiharu Iwabuchi, Masanobu Uchiyama, Naoki Kanoh

The Journal of Organic Chemistry (American Chemical Society ({ACS}))  86 ( 2 ) 1911 - 1924 2021.01

ISSN  00223263

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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

Mamoru Watanabe, Junichiro Kanazawa, Tomofumi Hamamura, Takumi Shimokawa, Kazunori Miyamoto, Mitsuhiro Hibino, Kensuke Nakura, Yuu Inatomi, Yu Kitazawa, Masanobu Uchiyama

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

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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

Kazunori Miyamoto, Masanobu Uchiyama

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

ISSN  03667022

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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

Kazunori Miyamoto, Tomohide Okada, Takashi Toyama, Shinji Imamura, Masanobu Uchiyama

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

ISSN  03855414

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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 C2

Kazunori Miyamoto, Shodai Narita, Yui Masumoto, Takahiro Hashishin, Taisei Osawa, Mutsumi Kimura, Masahito Ochiai, Masanobu Uchiyama

Nature Communications 11 ( 1 )  2020.12

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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

Hajime Sato, Takahiro Hashishin, Junichiro Kanazawa, Kazunori Miyamoto, Masanobu Uchiyama

Journal of the American Chemical Society (American Chemical Society ({ACS}))  142 ( 47 ) 19830 - 19834 2020.11

ISSN  00027863

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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

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

Angewandte Chemie International Edition (Wiley)  59 ( 48 ) 21448 - 21453 2020.11

ISSN  14337851

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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, Kensuke Morimoto, Shota Fujioka, Kazunori Miyamoto, Atsuya Muranaka, Masanobu Uchiyama

Angewandte Chemie (Wiley)  132 ( 48 ) 21632 - 21637 2020.11

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

Yulu Jiang, Taro Ozaki, Mei Harada, Tadachika Miyasaka, Hajime Sato, Kazunori Miyamoto, Junichiro Kanazawa, Chengwei Liu, Jun-Ichi Maruyama, Masaatsu Adachi, Atsuo Nakazaki, Toshio Nishikawa, Masanobu Uchiyama, Atsushi Minami, Hideaki Oikawa

Angewandte Chemie (International ed. in English) 59 ( 41 ) 17996 - 18002 2020.10

ISSN  14337851

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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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