Keio University · Materials Science
Professor Naoya Kumagai's research lab specializes in the development of innovative catalytic systems for stereoselective organic synthesis, with a strong focus on asymmetric catalysis using earth-abundant metals such as zinc and copper. The lab pioneers cooperative catalysis strategies that combine multiple catalytic components—such as transition metals, organic bases, and additives—to achieve high enantio- and diastereoselectivity under mild reaction conditions. Key research directions include the design of chiral ligands and bimetallic complexes for aldol and Mannich-type reactions, as well as the enantioselective construction of challenging stereogenic centers, including those bearing trifluoromethyl groups. The lab also explores atom-economical transformations and mechanistic understanding to guide the rational design of new catalytic systems.
Figures are computed from collected data and may differ slightly.
Full details of our newly developed catalyses with asymmetric zinc complexes as mimics of class II zinc-containing aldolase are described. A Et(2)Zn/(S,S)-linked-BINOL complex was developed and successfully applied to direct catalytic asymmetric aldol reactions of hydroxyketones. A Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was initially developed, which efficiently promoted the direct aldol reaction of 2-hydroxy-2'-methoxyacetophenone (7d). Using 1 mol % of (S,S)-linked-BINOL 1 and 2 mol % of Et
Cooperative catalysis has proven to be a particularly powerful strategy for promoting stereoselective organic transformations under mild reaction conditions. The specific interactions between the catalyst components and substrates are precisely orchestrated to elicit high catalytic efficiency and excellent control of the stereochemical course. By harnessing the power of cooperativity, various sets of stereoselective reactions proceed under mild proton-transfer conditions with perfect atom econom
Cooperative catalysis of a cationic Ru complex, DBU, and NaPF6 is described. An exquisite combination of the catalytic triad enabled catalytic activation of acetonitrile as a nucleophile under mild amine-basic conditions. Addition of in situ-generated, Ru-bound, metalated nitrile to aldehydes and imines proceeded smoothly with 2.5-5 mol % Ru complex and 2.5-10 mol % DBU in the presence of 10 mol % NaPF6. Preliminary mechanistic studies suggested a role for each of the three catalytic components.
An efficient synthetic pathway to skeletally and stereochemically diverse molecules is described. Densely functionalized amino alcohols were readily synthesized through a Petasis three-component, boronic acid Mannich reaction. Their intramolecular cyclization provided a collection of diverse single-isomer compounds with 15 different types of skeletons in three to five steps. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Please
[reaction: see text] The direct catalytic enantio- and diastereoselective aldol reaction with 2-hydroxy-2'-methoxyacetophenone proceeded smoothly using as little as 1 mol % of a dinuclear zinc catalyst, Zn-Zn-linked-BINOL complex 2, to afford alpha,beta-dihydroxy ketones in a highly syn-selective manner (up to syn/anti 97/3) and in excellent yields (up to 95%) and ees (up to 99%). Efficient transformations of the alpha,beta-dihydroxy ketone into an alpha,beta-dihydroxy ester and an alpha,beta-di
Despite the burgeoning demand for fluorine-containing chemical entities, the construction of CF<sub>3</sub> -containing stereogenic centers has remained elusive. Herein, we report the strategic merger of Cu<sup>I</sup> /base-catalyzed enolization of an α-CF<sub>3</sub> amide and Pd<sup>0</sup> -catalyzed allylic alkylation in an enantioselective manner to deliver chiral building blocks bearing a stereogenic carbon center connected to a CF<sub>3</sub> , an amide carbonyl, and a manipulable allyli
Soft Lewis acid/Brønsted base cooperative catalysts have enabled direct catalytic asymmetric vinylogous conjugate addition of α,β- and β,γ-unsaturated butyrolactones to α,β-unsaturated thioamides with perfect atom economy. When using α-angelica lactone and its derivatives as pronucleophiles, as little as 0.5 mol% catalyst loading was sufficient to complete the reaction necessary to construct consecutive tri- and tetrasubstituted stereogenic centers in a highly diastereo- and enantioselective fas
A dual catalyst system: The cooperative function of a hard and soft Lewis acid (LaIII and AgI, respectively) in a catalyst system that includes an amide-based ligand 1 is crucial for simultaneous activation of intramolecular 1,3-dicarbonyl and alkyne moieties to afford enantioenriched cyclopentane derivatives (see scheme).
Abstract Recent progress (post-2010) in the field of metal-catalyzed asymmetric C–C bond-forming reactions using ketimines as electrophiles is reviewed. Compared with the corresponding aldimines, ketimines generally display less inherent reactivity and the two substituents on the imine carbon hamper prochiral-face-selection for enantioselective reactions. Recent advances with newly developed catalytic systems have resulted in several solutions to these long-standing problems. The construction of
A cooperative catalyst consisting of a soft Lewis acid and a hard Brønsted base promoted the title reaction. The N-thiophosphinoyl group on the ketimines was critical to surpass the high activation barrier through the soft–soft interaction of sulfur and copper. Mannich adducts with a tetrasubstituted stereogenic center were produced with excellent diastereo- and enantioselectivities. TANIAPHOS= ferrocenyl ligand. As a service to our authors and readers, this journal provides supporting informati
Twice the catalyst: The simultaneous activation of an allyl cyanide (pronucleophile) and an α,β-unsaturated thioamide (electrophile) was achieved using a Cu-based soft Lewis acid/hard Brønsted base cooperative catalyst, thus resulting in the formation of enethioamides 1 in a highly enantio- and Z-selective manner (see scheme). The sequential Cu-catalyzed intramolecular cyclization gave rise to enantioenriched fused isothiazoles 2. Detailed facts of importance to specialist readers are published
A direct aldol reaction of an α-azido 7-azaindolinylamide, promoted by a Cu-based cooperative catalyst, is documented. Aromatic aldehydes bearing an ortho substituent exhibited diastereodivergency depending on the nature of the chiral ligands used. Smooth reactions with ynals highlighted the broad substrate scope. A vicinal azido alcohol unit in the product allowed direct access to the corresponding aziridine and facile hydrolysis of the 7-azaindolinylamide moiety furnished enantioenriched β-hyd
Abstract Die kooperative Katalyse hat sich als eine leistungsfähige Strategie für stereoselektive Umwandlungen unter milden Bedingungen bewährt. Hierbei sind die spezifischen Wechselwirkungen zwischen den Katalysatorkomponenten und den Substraten so aufeinander abgestimmt, dass hohe Katalyseeffizienzen und eine ausgezeichnete Kontrolle des stereochemischen Verlaufs resultieren. Durch Ausnutzen des Kooperativitätsprinzips lassen sich zahllose stereoselektive Reaktionen unter milden Protonentransf
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