論文 - 熊谷　直哉

Direct Catalytic Asymmetric Mannich-Type Reaction of an α-CF <inf>3</inf> Amide to Isatin Imines

Yu J., Noda H., Kumagai N., Shibasaki M.

Synlett （Synlett）  30 （ 4 ） 488 - 492 2019年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09365214

　概要を見る

An α-CF 3 amide underwent direct asymmetric Mannich-type reaction to isatin imines in the presence of a chiral catalyst comprising a soft Lewis acid Cu(I), a chiral bisphosphine ligand, and Barton's base. The Mannich adduct was converted in one step into a unique tricycle bearing a trifluoromethylated chiral center and an α-tertiary amine moiety.

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Catalytic Asymmetric Synthesis of syn Aldols with Methyl Ketone Functionality and anti Aldols with a Thioamide Group

Ota Y., Li Z., Kumagai N., Shibasaki M.

Synlett （Synlett）  30 （ 5 ） 620 - 624 2019年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09365214

　概要を見る

Catalytic asymmetric syntheses of syn aldols with a methyl ketone functionality were studied to confirm the generality of the methodology. In addition, catalytic asymmetric synthesis of anti aldols with a thioamide group was carefully examined, giving the desired products, albeit with moderate diastereoselectivity.

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A thirst for enantioselectivity in catalytic addition of alkylnitriles

Kumagai N., Shibasaki M.

Chemistry Letters （Chemistry Letters）  48 （ 11 ） 1322 - 1327 2019年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  03667022

　概要を見る

This Highlight Review sheds light on a neglected aspect of alkylnitriles in synthetic organic chemistry. The chemical inertness and highly polar nature of alkylnitriles have particular utility as a reaction solvent. Alkylnitriles, however, also serve as potential building blocks for constructing carbon frameworks of interest. Two decades of exploratory studies of this elusive reaction revealed competent catalytic systems that allow for catalytic and enantioselective coupling of alkylnitriles with electrophiles.

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A fluorogenic C4N4 probe for azide-based labelling

Noda H., Asada Y., Shibasaki M., Kumagai N.

Organic and Biomolecular Chemistry （Organic and Biomolecular Chemistry）  17 （ 7 ） 1813 - 1816 2019年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  14770520

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The design, synthesis and photophysical properties of a new fluorogenic probe are described. The structure is based on the recently identified 2,5-diaminopyrimidine (C4N4) fluorophore. The strain-promoted [3 + 2] cycloaddition of the azido-C4N4 probe furnished a triazole that exhibited more than 30-fold enhancement in fluorescence intensity as compared to the azide.

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7-Azaindoline Auxiliary: A Versatile Attachment Facilitating EnantioselectiveC-C Bond-Forming Catalysis

Kumagai N., Shibasaki M.

Synthesis (Germany) （Synthesis (Germany)）  51 （ 1 ） 185 - 193 2019年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00397881

　概要を見る

This short review provides an overview of 7-azaindoline auxiliaries in asymmetric catalysis. 7-Azaindoline serves as a useful attachment to carboxylic acids, and the thus-formed 7-azaindoline amides are amenable to atom-economical C-C bond-forming reactions with high stereoselectivity. The attachment is used for the sake of gaining traction in promoting the reaction of interest and can be easily removed after enantioselective reactions. Both nucleophilic and electrophilic catalyses are realized with broad tolerance for functional groups, showcasing the usefulness of 7-azaindoline auxiliaries for practical and streamlined synthesis of a wide range of acyclic chiral building blocks. 1 Introduction 2 7-Azaindoline as a Key Auxiliary 3 7-Azaindoline Amide as a Pronucleophile 3.1 α-Carbon-Substituted 7-Azaindoline Amide 3.2 α-Nitrogen-Substituted 7-Azaindoline Amide 3.3 α-Oxygen-Substituted 7-Azaindoline Amide 3.4 α-Fluorocarbon-Substituted 7-Azaindoline Amide 3.5 α-Halogen-Substituted 7-Azaindoline Amide 3.6 α-Sulfur-Substituted 7-Azaindoline Amide 4 7-Azaindoline Amide as an Electrophile 4.1 Conjugate Addition of Butenolides 4.2 1,3-Dipolar Cycloaddition of Nitrones 5 Transformation of 7-Azaindoline Amide 6 Conclusion.

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Anti-Selective Catalytic Asymmetric Nitroaldol Reaction of α-Keto Esters: Intriguing Solvent Effect, Flow Reaction, and Synthesis of Active Pharmaceutical Ingredients

Karasawa T., Oriez R., Kumagai N., Shibasaki M.

Journal of the American Chemical Society （Journal of the American Chemical Society）  140 （ 38 ） 12290 - 12295 2018年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00027863

　概要を見る

A rare-earth metal/alkali metal bimetallic catalyst proved particularly effective for enantioselectively coupling nitroalkanes and α-keto esters in an anti-selective manner to afford synthetically versatile, densely functionalized, and optically active α-nitro tertiary alcohols. A chiral diamide ligand captured two distinct metal cations, giving rise to a catalytically competent solid-phase heterobimetallic catalyst by simple mixing via self-assembly. The advantage of the solid-phase asymmetric catalyst was realized by successful application to the enantio- and diastereoselective reaction in a continuous-flow platform. The use of closely related solvents in terms of structures and polarity parameters, THF and its methylated congener 2-Me-THF, had an unexpectedly large solvent effect both on the reaction rate and the stereoselectivity. The nitroaldol products share a privileged unit for active pharmaceutical ingredients, as demonstrated by the streamlined enantioselective synthesis of the marketed antifungal agents efinaconazole and albaconazole.

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Direct enolization chemistry of 7-azaindoline amides: A case study of bis(tetrahydrophosphole)-type ligands

Li Z., Noda H., Kumagai N., Shibasaki M.

Tetrahedron （Tetrahedron）  74 （ 26 ） 3301 - 3305 2018年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00404020

　概要を見る

7-Azaindoline amides are particularly useful in direct enolization chemistry due to their facilitated enolization in soft Lewis acid/Brønsted base cooperative catalysis. The Cu(I) complex of (R,R)-Ph-BPE, a bis(tetrahydrophosphole)-type chiral bisphosphine ligand, exhibits consistently high catalytic performance and stereoselectivity irrespective of the nature of the α-substituent of the amides. Unexpectedly, however, alkyl-substituted bis(tetrahydrophosphole)-type ligands have substantially inferior catalytic performance. Evaluation of the optimized structures of Cu(I)/amide and Cu(I)/enolate complexes provided clues to dissecting the diverted reaction outcomes.

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Catalytic enantioselective addition of diethyl phosphite to N-thiophosphinoyl ketimines: Preparation of (R)-diethyl (1-amino-1-phenylethyl)phosphonate

Lin S., Otsuka Y., Yin L., Kumagai N., Shibasaki M.

Organic Syntheses （Organic Syntheses）  94 2018年06月

研究論文（国際会議プロシーディングス）, 共著, 査読有り,  ISSN  00786209

　概要を見る

Procedures yielding phosphinothioic amide 2 and ketimine 4 as colorless crystals and phosphonate 6 as a brown viscous oil are presented. Notes on instruments and chemicals required are provided.A brief discussion on construction of tetrasubstituted stereogenic centers in a catalytic and enantioselective manner as a significant progress in asymmetric catalysis.

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Direct Catalytic Asymmetric 1,6-Conjugate Addition of Amides to p-Quinone Methides

Sun Z., Sun B., Kumagai N., Shibasaki M.

Organic Letters （Organic Letters）  20 （ 10 ） 3070 - 3073 2018年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  15237060

　概要を見る

Amide pronucleophiles were successfully incorporated into a 1,6-conjugate addition reaction manifold using p-quinone methides (p-QMs) as electrophiles. Four different types of functionalities were tolerated as α-substituents of the amides, allowing for expeditious access to a range of enantiomerically enriched diarylmethine products. The 7-azaindoline unit is critically important for in situ catalytic enolization of the amide pronucleophile, engaging in 1,6-conjugate addition to p-QMs with readily available catalyst components.

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Direct Catalytic Asymmetric Aldol Reaction of α-Vinyl Acetamide

Takeuchi T., Kumagai N., Shibasaki M.

Journal of Organic Chemistry （Journal of Organic Chemistry）  83 （ 10 ） 5851 - 5858 2018年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00223263

　概要を見る

A direct catalytic asymmetric aldol addition of an α-vinyl 7-azaindoline amide to both aromatic and aliphatic aldehydes was promoted by a cooperative acid/base catalyst in a stereodivergent manner. The key structural element, a 7-azaindoline moiety, facilitated catalytic enolization, allowing for subsequent stereoselective aldol addition. Enantioselective synthesis of the key intermediate of blumiolide C and kainic acid supported the synthetic utility of this protocol.

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Catalytic Asymmetric Synthesis of α-Trifluoromethylated Carbinols: A Case Study of Tertiary Propargylic Alcohols

Noda H., Kumagai N., Shibasaki M.

Asian Journal of Organic Chemistry （Asian Journal of Organic Chemistry）  7 （ 4 ） 599 - 612 2018年04月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  21935807

　概要を見る

Enantioenriched CF3-substituted tertiary alcohols have been applied in a broad range of chemical disciplines, including medicinal chemistry and agrochemistry. The widely prescribed anti-HIV pharmaceutical efavirenz is one particular example of the application of these chiral building blocks. Because the typical synthetic route to this small drug molecule involves the stoichiometric use of a chiral promoter, significant effort has been devoted to the development of catalytic alternatives for accessing this building block. In this Focus Review, we summarize the catalytic asymmetric synthesis of CF3-substituted tertiary propargylic alcohols based on three retrosynthetic approaches, namely one trifluoromethylation approach and two building-block strategies. The general challenges that are involved in the construction of a CF3-substituted tetrasubstituted stereogenic carbon species are highlighted and possible future directions in the field are discussed.

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Conquering amide planarity: Structural distortion and its hidden reactivity

Adachi S., Kumagai N., Shibasaki M.

Tetrahedron Letters （Tetrahedron Letters）  59 （ 13 ） 1147 - 1158 2018年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00404039

　概要を見る

Amides are generally considered as a low-reactive chemical entity among the carbonyl group, and therefore fewer opportunities to be involved in catalytic transformations as substrates. The origin of the stable nature of amides is resonance stabilization in the planar structure, which has drawn considerable attention from organic and physical chemists, leading to the discovery of distorted amides that exhibit a substantially reactive nature. Recent focus in this field is on the catalytic transformation of designed amides with moderate distortion or reduced resonance stabilization. This digest reviews the brief history of the quest for highly distorted amides and introduces a collection of recent studies on catalytic transformations of designed amides.

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Direct Catalytic Asymmetric Aldol Reaction of Thioamide with an α-Vinyl Appendage

Cui J., Ohtsuki A., Watanabe T., Kumagai N., Shibasaki M.

Chemistry - A European Journal （Chemistry - A European Journal）  24 （ 11 ） 2598 - 2601 2018年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09476539

　概要を見る

The direct catalytic asymmetric aldol reaction is an emerging catalytic methodology that provides atom-economical access to functionalized chiral building blocks. Thioamides are useful aldol donors due to their high-fidelity chemoselective enolization and divergent post-aldol transformations. Herein we describe the incorporation of an α-vinyl appendage on a thioamide, which expands the utility of aldol adducts for natural product synthesis. This vinylated thioamide was not accommodated under the previously identified catalyst settings, but the newly developed catalytic conditions furnished aldol products containing the pendant vinyl group.

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Structural and Computational Investigation of Intramolecular N···H Interactions in α- and β-Fluorinated 7-Azaindoline Amides

Brewitz L., Noda H., Kumagai N., Shibasaki M.

European Journal of Organic Chemistry （European Journal of Organic Chemistry）  2018 （ 6 ） 714 - 722 2018年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1434193X

　概要を見る

Novel fluorinated N1-acylated 7-azaindolines have been synthesized and their conformations analyzed by X-ray diffraction and NMR spectroscopy: Unusual intramolecular interactions between the 7-nitrogen and amide α-hydrogen atoms were identified. The strength of these interactions correlate with the electron-withdrawing character of the amide α substituents. A combination of experimental and computational approaches revealed a significant substituent effect when the substituent (H, OMe, F, CN) at the 4-position of the 7-azaindoline scaffold was varied. As these intramolecular interactions also occur in non-fluorinated N1-acylated 7-azaindolines and similar heterocycles, this study is relevant to medicinal chemistry: The results will facilitate the prediction of the predominant conformations of N1-acylated-7-azaindoline-containing bioactive molecules and thus potentially contribute to drug discovery programs.

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Thieme Chemistry Journals Awardees - Where Are They Now? Bis(2-pyridyl)amides as Readily Cleavable Amides under Catalytic, Neutral, and Room-Temperature Conditions

Adachi S., Kumagai N., Shibasaki M.

Synlett （Synlett）  29 （ 3 ） 301 - 305 2018年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09365214

　概要を見る

Mild solvolytic cleavage of bis(2-pyridyl)amide under neutral and room-temperature conditions is described. The inherently stable amide was readily activated by catalytic amounts of metal cations to react with alcohols. Based on X-ray crystallographic analysis, the primary driving force was considered to be amide distortion induced by the metal coordination of two pyridyl groups in a bidentate fashion without affecting the amide functionality. The compatibility of the acid/base-sensitive functionalities and the absence of racemization during solvolysis highlight the mildness of the present protocol.

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Catalytic Oligopeptide Synthesis

Liu Z., Noda H., Shibasaki M., Kumagai N.

Organic Letters （Organic Letters）  20 （ 3 ） 612 - 615 2018年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  15237060

　概要を見る

Waste-free catalytic assembly of α-amino acids is fueled by a multiboron catalyst that features a characteristic B3NO2 heterocycle, providing a versatile catalytic protocol wherein functionalized natural α-amino acid units are accommodated and commonly used protecting groups are tolerated. The facile dehydrative conditions eliminate the use of engineered peptide coupling reagents, exemplifying a greener catalytic alternative for peptide coupling. The catalysis is sufficiently robust to enable pentapeptide synthesis, constructing all four amide bond linkages in a catalytic fashion.

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Direct Catalytic Asymmetric Mannich-Type Reaction en Route to α-Hydroxy-β-amino Acid Derivatives

Sun B., Pluta R., Kumagai N., Shibasaki M.

Organic Letters （Organic Letters）  20 （ 3 ） 526 - 529 2018年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  15237060

　概要を見る

A direct catalytic Mannich-type reaction of α-oxygen-functionalized amides was achieved. The use of 7-azaindoline amide was crucial to facilitate direct enolization and subsequent stereoselective addition to imines in a cooperative catalytic system comprising a soft Lewis acid and Brønsted base. The operationally simple room-temperature protocol furnished a syn-Mannich adduct with high stereoselectivity. Divergent functional group transformation of the amide moiety of the product allowed for expeditious access to enantioenriched syn-configured α-hydroxy-β-amino carboxylic acid derivatives, highlighting the synthetic utility of the present catalysis.

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Heterogeneous Heterobimetallic Catalysis Enabling Expeditious Access to CF<inf>3</inf>-Containing vic-Amino Alcohols

Karasawa T., Kumagai N., Shibasaki M.

Organic Letters （Organic Letters）  20 （ 1 ） 308 - 311 2018年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  15237060

　概要を見る

A highly anti-selective catalytic asymmetric nitroaldol reaction of trifluoromethyl ketones based on Nd/Na and Pr/Na heterobimetallic catalysts was developed. These catalysts function as heterogeneous catalysts to engage nitroethane and a range of trifluoromethyl ketones in a stereoselective assembly to afford CF3-appended vic-nitroalkanols that could be readily converted to enantioenriched vic-amino alcohols, which are privileged structural motifs in medicinal chemistry.

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Synthetic studies of viridiofungins, broad-spectrum antifungal agents and serine palmitoyl transferase inhibitors

Kumagai N., Shibasaki M.

Journal of Antibiotics （Journal of Antibiotics）  71 （ 1 ） 53 - 59 2018年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00218820

　概要を見る

Viridiofungins are alkyl citrate natural products characterized by their inhibitory effects on squalene synthase and serine palmitoyl transferase. Their activities as broad-spectrum antifungal agents as well as blocking agents for the biosynthesis of sphingolipids have inspired the development of several approaches toward their stereoselective total synthesis. Structurally, these natural products are a family of hybrid molecules comprising a longer alkyl chain and a citric acid unit, rendering an asymmetric structure that is difficult to access. Herein, we summarize the synthetic approaches to this attractive class of natural products, including proficient synthetic strategies for constructing the densely and chirally functionalized citric acid unit with high polarity. Particular emphasis is placed on methods for furnishing stereogenic centers in the highly constrained carbon framework.

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Unique Physicochemical and Catalytic Properties Dictated by the B3NO2 Ring System

Noda, H., Furutachi, M., Asada, Y., Shibasaki, M. and Kumagai, N.

Synlett 28 （ 16 ） A165 - A168 2017年10月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0936-5214

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