論文 - 熊谷　直哉

Strategic Immobilization of Molecular Catalysts onto Carbon Nanotubes via Noncovalent Interaction for Catalytic Organic Transformations

Kumagai, N. and Shibasaki, M.

Israel Journal of Chemistry 57 （ 3-4 ） 270 - 278 2017年04月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0021-2148

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Since their discovery, carbon nanotubes (CNTs) continue to attract growing interest from scientists in a wide range of fields, likely due to their fascinating nanoarchitecture as well as their electronic and physical properties. From the viewpoint of synthetic chemistry, the chemical and physical stability, high surface area, and -stacking nature of CNTs are attractive features for their application as solid supports for molecular catalysts. The chemical functionalization of CNTs has been explored for various applications, including covalent and noncovalent grafting of molecular catalysts. Although noncovalent grafting provides less stable immobilized catalysts compared with covalently grafted hybrid molecular catalysts and CNTs, the preparation protocol is expeditious and repetitive use of the catalysts is well demonstrated, confirming their potential broad utility in synthetic organic chemistry.

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Asymmetric flow catalysis: Mix-and-go solid-phase Nd/Na catalyst for expeditious enantioselective access to a key intermediate of AZD7594

Nonoyama, A., Kumagai, N. and Shibasaki, M.

Tetrahedron 73 （ 11 ） 1517 - 1521 2017年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0040-4020

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An anti-selective catalytic asymmetric nitroaldol reaction was implemented in a continuous-flow reaction platform for the synthesis of a key intermediate of a drug candidate. The requisite solid-phase catalyst was readily prepared by mixing an amide-based chiral ligand and inexpensive inorganic salts, NdCl3 center dot 6H(2)O and (NaOBu)-Bu-t, without covalent bond linkages. The flow system was operated with 2-Me-THE as the eluent for ca. 400 h to provide a crude nitroaldol adduct in a highly stereoselective manner with no work-up procedure, reaching turnover number over 1600. Facile reduction of the nitro group of the product afforded a key intermediate of AZD7594, a therapeutic candidate for asthma and chronic obstructive pulmonary disease. (C) 2017 Elsevier Ltd. All rights reserved.

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Reversible Stereoselective Folding/Unfolding Fueled by the Interplay of Photoisomerism and Hydrogen Bonding

Opie, C. R., Kumagai, N. and Shibasaki, M.

Angewandte Chemie-International Edition 56 （ 12 ） 3349 - 3353 2017年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1433-7851

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A linear molecular architecture equipped with complementary three-fold hydrogen-bonding units embedded with a photoswitchable trans-tetrafluoroazobenzene moiety was synthesized. The transto cis photoisomerism of the azobenzene unit induced drastic changes in the molecular architecture as a result of intramolecular hydrogen bonding as evidenced by NMR spectroscopy and size exclusion chromatography. A minute stereogenic element in the linear trans state enabled stereoselective folding into the cis state, thus producing a globular architecture with enhanced chiroptical property.

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Direct Catalytic Asymmetric Aldol Reaction of alpha-Alkylamides

Liu, Z., Takeuchi, T., Pluta, R., Arteaga, F. A., Kumagai, N. and Shibasaki, M.

Organic Letters 19 （ 3 ） 710 - 713 2017年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1523-7060

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A catalytic asymmetric aldol reaction directly employing amides as latent enolates has remained elusive because of the resistance of amides to enolization. A direct aldol reaction of alpha-alkylarnides without any electron-withdrawing group harnessed by specific activation of 7-azaindoline amides under soft Lewis acid/Bronsted base cooperative catalysis is reported. Diastereo- and enantioselective coupling with ynals and aromatic aldehydes as well as divergent functional group interconversion of the amide provided expeditious access to a variety of aliphatic and aromatic chiral building blocks.

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Catalytic asymmetric synthesis of 2,3,3,3-tetrafluoro-2-methyl-1-arylpropan-1-amines as useful building blocks for SAR-studies

Brewitz, L., Kumagai, N. and Shibasaki, M.

Journal of Fluorine Chemistry 194   1 - 7 2017年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0022-1139

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The first protocol for the asymmetric synthesis of 2,3,3,3-tetrafluoro-2-methyl-1-arylpropan-1-amines which function as fluorinated surrogates for alpha-isopropylbenzylamines in SAR-studies is presented herein. Crucial for the successful synthesis was the application of a recently developed direct catalytic asymmetric Mannich-type reaction of fluorinated amide for the key bond-forming step. The utility of this versatile protocol was demonstrated by the synthesis of fluorinated analogues of a T-type selective Ca2+ channel blocker and a prolylcarboxypeptidase inhibitor. The predominant conformation of their fluorinated analogues was investigated by X-ray crystallography and NMR spectroscopy which revealed a strong influence of a fluorine mediated gauche effect. (C) 2016 Elsevier B.V. All rights reserved.

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Pyramidalization/twisting of the amide functional group via remote steric congestion triggered by metal coordination

Adachi, S., Kumagai, N. and Shibasaki, M.

Chemical Science 8 （ 1 ） 85 - 90 2017年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2041-6520

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For decades, the planarity of the amide functional group has garnered sustained interest in organic chemistry, enticing chemists to deform its usually characteristic high-fidelity plane. As opposed to the construction of amides that are distorted by imposing rigid covalent bond assemblies, we demonstrate herein the deformation of the amide plane through increased steric bulk in the periphery of the amide moiety, which is induced by coordination to metal cations. A crystallographic analysis revealed that the thus obtained amides exhibit significant pyramidalization and twisting upon coordination to the metals, while the amide functional group remained intact. The observed deformation, which should be attributed to through-space interactions, substantially enhanced the solvolytic cleavage of the amide, providing compelling evidence that temporary crowding in the periphery of the amide functional group may be used to control the reactivity of amides.

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Recent Advances in Rare Earth Metal Asymmetric Catalysis Toward Practical Synthesis of Therapeutics

Kumagai, N. and Shibasaki, M.

New Horizons of Process Chemistry: Scalable Reactions and Technologies    1 - 10 2017年

研究論文（学術雑誌）, 共著, 査読有り

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Two case studies regarding the development of rare earth metal-based asymmetric catalysts are summarized, with particular focus on the process of refining catalysts amenable to industrial applications. Amide-based chiral ligands in combination with lanthanum or neodymium cations furnished robust catalytic systems for asymmetric amination or nitroaldol reactions, respectively. Although rare earth metal catalysis is generally characterized by a peculiar coordination chemistry and Lewis acidic catalytic functions, its wide availability and moderate tolerance to moisture are also important features to be noted, making the application of rare earth metal catalysis beneficial for industrial large-scale synthesis.

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An efficient method for the synthesis of versatile intermediates leading to 13-deoxy- and 9,13-dideoxyphorbols

Sekine, A., Kumagai, N., Uotsu, K., Ohshima, T. and Shibasaki, M.

Tetrahedron Letters 41 （ 4 ） 509 - 513 2000年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0040-4039

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An efficient method for the synthesis of versatile intermediates for biologically interesting 13-deoxy- and 9,13-dideoxyphorbol ester analogs is described. First,more efficient synthetic routes to the bicyclic ketones 7 and 8, which are well-known intermediates for the synthesis of 13-deoxyphorbols, than the previous one were established. Second, 7 and 8 were successfully converted to the intermediates 19, 25 and 27 for the synthesis of 9,13-dideoxyphorbols using Peterson reaction, oxymercuration and nitrile oxide cycloaddition as key steps. (C) 2000 Elsevier Science Ltd. All rights reserved.

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