Shinagawa-ku, Japan
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Gopinath P.,Institute of Microbial Chemistry | Watanabe T.,Institute of Microbial Chemistry | Shibasaki M.,Institute of Microbial Chemistry
Organic Letters | Year: 2012

We describe the desymmetrization of meso-glutaric anhydrides to chiral hemiesters using a bench-stable homodinuclear Ni 2-(Schiff base) complex as the catalyst in good to excellent yield (up to 99%) and enantioselectivity (up to 94%). Using the opposite enantiomer of the catalyst, we obtained the same yield and enantioselectivity with the opposite configuration, thereby gaining access to both hemiester enantiomers. © 2012 American Chemical Society.


Nitabaru T.,Institute of Microbial Chemistry | Nitabaru T.,University of Tokyo | Kumagai N.,Institute of Microbial Chemistry | Shibasaki M.,Institute of Microbial Chemistry
Angewandte Chemie - International Edition | Year: 2012

Battling the flu: Zanamivir (Relenza) is widely prescribed as an anti-influenza drug. It contains a vicinal amino alcohol, which is in an anti orientation, and is readily accessed by an anti-selective catalytic asymmetric nitroaldol (Henry) reaction promoted by a heterobimetallic complex (see scheme; PMB=p-methoxybenzyl). Additional synthetic manipulation of the nitroaldol product allowed the enantioselective synthesis of zanamivir. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Kumagai N.,Institute of Microbial Chemistry | Shibasaki M.,Institute of Microbial Chemistry
Catalysis Science and Technology | Year: 2013

Proteins, RNA, and other functional biomacromolecules are sophisticated chemical entities that have evolved over billions of years. Their catalytic, constitutional, and communicating functions are intimately related to their three-dimensional molecular architecture and are exquisitely regulated in a spatiotemporal manner by conformational changes through allosteric regulators and a myriad of reversible and unidirectional posttranslational modifications. Their organized functional diversity is the key to the orderly and timely progression of complicated biological events. The main focus in the development of artificial catalysts is to accelerate a specific chemical transformation of interest, and extensive efforts have been devoted to fine-tuning catalytic activity. Here, we review recent developments of multistate catalysts able to perform distinct catalytic functions, with emphasis on the tight link between the structural modification of the conformationally flexible catalysts and the functional change. Although this field is still in its infancy with a simple output, continued advances will allow us to create intriguing systems with organized multitask output in an intricate molecular ensemble. © The Royal Society of Chemistry 2013.


Kumagai N.,Institute of Microbial Chemistry | Shibasaki M.,Institute of Microbial Chemistry
Angewandte Chemie - International Edition | Year: 2013

A series of asymmetric catalysts composed of conformationally flexible amide-based chiral ligands and rare-earth metals was developed for proton-transfer catalysis. These ligands derived from amino acids provide an intriguing chiral platform for the formation of asymmetric catalysts upon complexation with rare-earth metals. The scope of this arsenal of catalysts was further broadened by the development of heterobimetallic catalytic systems. The cooperative function of hydrogen bonding and metal coordination resulted in intriguing substrate specificity and stereocontrol, and the dynamic nature of the catalysts led to a switch of their function. Herein, we summarize our recent exploration of this class of catalysts. © 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


Kumagai N.,Institute of Microbial Chemistry | Shibasaki M.,Institute of Microbial Chemistry
Angewandte Chemie - International Edition | Year: 2011

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 economy. This Minireview summarizes our recent contributions to several C-N and C-C bond-forming reactions in this field and related transformations. Give me an H: The sophisticated synergism of the two concepts of asymmetric catalysis and atom economy offers a truly efficient synthetic strategy for the production of requisite chemical entities with high enantiomeric purity. Recent advances in this field are highlighted, with a particular emphasis on catalytic asymmetric reactions that proceeds under proton-transfer conditions. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Yin L.,University of Tokyo | Kanai M.,University of Tokyo | Shibasaki M.,Institute of Microbial Chemistry
Angewandte Chemie - International Edition | Year: 2011

Less metal wastes: The first catalytic, enantioselective intramolecular aryl-transfer reaction of aryl triflates to ketones has been developed (see scheme; R 1=R 2=aromatic and aliphatic). This method features overall practicality, including substrate stability and accessibility (protecting-group free) plus no need for the use of stoichiometric amounts of metals. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Matsunaga S.,University of Tokyo | Matsunaga S.,Japan Science and Technology Agency | Shibasaki M.,Institute of Microbial Chemistry
Chemical Communications | Year: 2014

Cooperative catalysis has proven to be a powerful strategy for realizing high reactivity and selectivity in asymmetric transformations. A variety of cooperative asymmetric catalysts have been developed over the last two decades. In this feature article, recent advances from our research on cooperative asymmetric catalysis, focusing on dinuclear Schiff base catalysis, are described. Design of dinuclear Schiff base catalysts and their applications in several asymmetric C-C and C-N bond-forming reactions under simple proton transfer conditions with perfect atom-economy are discussed in detail. © 2014 The Royal Society of Chemistry.


Yazaki R.,Institute of Microbial Chemistry | Yazaki R.,University of Tokyo | Kumagai N.,Institute of Microbial Chemistry | Shibasaki M.,Institute of Microbial Chemistry
Journal of the American Chemical Society | Year: 2010

Direct catalytic asymmetric conjugate addition of terminal alkynes to α,β-unsaturated thioamides under proton transfer conditions is described. Soft Lewis acid/hard Brønsted base cooperative catalysis is crucial for simultaneous activation of terminal alkynes and thioamides, affording the β-alkynylthioamides in a highly enantioselective manner. Control experiments suggested that the intermediate copper thioamide enolate can work as Brønsted base to drive the catalytic cycle via proton transfer. The divergent transformation of the thioamide functionality highlights the synthetic utility of the alkynylation products. © 2010 American Chemical Society.


News Article | February 15, 2017
Site: cen.acs.org

Chemists over the years have combined boron, carbon, nitrogen, and oxygen in various ways to create a variety of six-membered heterocyclic ring systems. One of the reasons they make these rings is to expand the array of available polycyclic aromatic materials used for making optoelectronic devices and used as organocatalysts. In particular, researchers have been looking at graphite-type materials based on six-membered ring core structures containing electron-deficient boron atoms. But incorporating both nitrogen and oxygen along with boron has remained elusive. A research team at Japan’s Institute of Microbial Chemistry has now designed and synthesized oxaazaborinanes—molecules that contain a B NO ring—that are a cross between previously known borazines (B N ) and boroxines (B O ). The new ring had been a missing link in the collection of six-membered ring compounds containing B, C, N, and O (Nat. Chem. 2017, DOI: 10.1038/nchem.2708). The team led by Masakatsu Shibasaki and Naoya Kumagai prepared a set of the 1,3-dioxa-5-aza-2,4,6-triborinanes (DATBs) in a stepwise fashion starting from bromine-substituted aniline. The process required building a terphenyl template as a framework to support the B NO ring. Kumagai says the peripheral architecture is important for the ring’s stability, explaining that the instability of the stand-alone B NO ring is likely why chemists were not able to readily prepare it in the past. The Japanese researchers realized the multiple Lewis acidic boron atoms in their DATBs should make the new molecules good catalysts. As a test case, they selected the direct amidation of carboxylic acids with amines, a key reaction for making pharmaceuticals. Chemists currently rely on boron-based acid organocatalysts with or without a supplemental metal to carry out this transformation. The team found that its initial DATB molecule with a phenyl substituent produced modest results. But DATB derivatives with bulkier substituted phenyl groups containing a hydroxy azaborine moiety provide high yields for a broad range of amidations, in particular for sterically hindered substrates, outperforming previously known direct amidation catalysts. “Accessing these compounds represents a significant achievement in heterocyclic chemistry,” says Jose M. Goicoechea of the University of Oxford, who focuses on the synthesis of new main-group-element molecules. “This report contributes to a burgeoning area of research aimed at developing catalysts from environmentally abundant main-group elements, which may ultimately provide an inexpensive and nontoxic alternative to compounds based on precious metals.” “This paper illustrates wholly the state of the art and beauty of the chemical sciences,” adds Hansjörg Grützmacher of ETH Zurich, whose group recently reported the synthesis of another new heterocycle, triphosphabenzene. The work doesn’t just describe “a new and rather unusual boron heterocycle,” Grützmacher says, but also a remarkable application. “This represents a breakthrough in organocatalysis.” “We believe that the substrate generality of DATB catalysis will convince chemists in academia and industry to replace reagent-based amidation with catalytic amidation,” Kumagai says. The Japanese researchers have a collaboration with a company to commercialize DATBs, he adds, and they continue to work on defining the catalytic mechanism as well as the synthesis of more active DATB derivatives.


News Article | February 15, 2017
Site: cen.acs.org

Chemists over the years have combined boron, carbon, nitrogen, and oxygen in various ways to create a variety of six-membered heterocyclic ring systems. One of the reasons they make these rings is to expand the array of available polycyclic aromatic materials used for making optoelectronic devices and used as organocatalysts. In particular, researchers have been looking at graphite-type materials based on six-membered ring core structures containing electron-deficient boron atoms. But incorporating both nitrogen and oxygen along with boron has remained elusive. A research team at Japan’s Institute of Microbial Chemistry has now designed and synthesized oxaazaborinanes—molecules that contain a B NO ring—that are a cross between previously known borazines (B N ) and boroxines (B O ). The new ring had been a missing link in the collection of six-membered ring compounds containing B, C, N, and O (Nat. Chem. 2017, DOI: 10.1038/nchem.2708). The team led by Masakatsu Shibasaki and Naoya Kumagai prepared a set of the 1,3-dioxa-5-aza-2,4,6-triborinanes (DATBs) in a stepwise fashion starting from bromine-substituted aniline. The process required building a terphenyl template as a framework to support the B NO ring. Kumagai says the peripheral architecture is important for the ring’s stability, explaining that the instability of the stand-alone B NO ring is likely why chemists were not able to readily prepare it in the past. The Japanese researchers realized the multiple Lewis acidic boron atoms in their DATBs should make the new molecules good catalysts. As a test case, they selected the direct amidation of carboxylic acids with amines, a key reaction for making pharmaceuticals. Chemists currently rely on boron-based acid organocatalysts with or without a supplemental metal to carry out this transformation. The team found that its initial DATB molecule with a phenyl substituent produced modest results. But DATB derivatives with bulkier substituted phenyl groups containing a hydroxy azaborine moiety provide high yields for a broad range of amidations, in particular for sterically hindered substrates, outperforming previously known direct amidation catalysts. The Japanese researchers have a collaboration with a company to commercialize DATBs, Kumagai notes, and they continue to work on defining the catalytic mechanism as well as the synthesis of more active DATB derivatives. “This paper illustrates wholly the state of the art and beauty of the chemical sciences,” says Hansjörg Grützmacher of ETH Zurich, whose group recently reported the synthesis of another new heterocycle, triphosphabenzene. The work doesn’t just describe “a new and rather unusual boron heterocycle,” Grützmacher says, but also a remarkable application. “This represents a breakthrough in organocatalysis.”

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