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Yujiro Hayashi - One of the best experts on this subject based on the ideXlab platform.

Jian Wang - One of the best experts on this subject based on the ideXlab platform.

Fumin Zhang - One of the best experts on this subject based on the ideXlab platform.

Hayato Ishikawa - One of the best experts on this subject based on the ideXlab platform.

  • one pot synthesis of oseltamivir and mechanistic insights into the organocatalyzed michael reaction
    Chemistry: A European Journal, 2013
    Co-Authors: Yujiro Hayashi, Hayato Ishikawa, Takasuke Mukaiyama, Hiroyuki Koshino
    Abstract:

    The one-pot sequential synthesis of (−)-oseltamivir has been achieved without evaporation or solvent exchange in 36 % yield over seven reactions. The key step was the asymmetric Michael reaction of pentan-3-yloxyacetaldehyde with (Z)-N-2-nitroethenylacetamide, catalyzed by a diphenylprolinol Silyl Ether. The use of a bulky O-Silyl-substituted diphenylprolinol catalyst, chlorobenzene as a solvent, and HCO2H as an acid additive, were key to produce the first Michael adduct in both excellent yield and excellent diastereo- and enantioselectivity. Investigation into the effect of acid demonstrated that an acid additive accelerates not only the E–Z isomerization of the enamines derived from pentan-3-yloxyacetaldehyde with diphenylprolinol Silyl Ether, but also ring opening of the cyclobutane intermediate and the addition reaction of the enamine to (Z)-N-2-nitroethenylacetamide. The transition-state model for the Michael reaction of pentan-3-yloxyacetaldehyde with (Z)-N-2-nitroethenylacetamide was proposed by consideration of the absolute configuration of the major and minor isomers of the Michael product with the results of the Michael reaction of pentan-3-yloxyacetaldehyde with phenylmaleimide and naphthoquinone.

  • organocatalyst mediated dehydrogenation of aldehydes to α β unsaturated aldehydes and oxidative and enantioselective reaction of aldehydes and nitromethane catalyzed by diphenylprolinol Silyl Ether
    Advanced Synthesis & Catalysis, 2013
    Co-Authors: Yujiro Hayashi, Hayato Ishikawa, Takahiko Itoh
    Abstract:

    A one-pot transformation of aldehydes into α,β-unsaturated aldehydes was developed using both N-benzyl-N-methylamine and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as catalysts and MnO2 as a terminal oxidant. An oxidative and enantioselective reaction of aldehydes and nitromethane was established using both diphenylprolinol Silyl Ether and DDQ as a catalyst with MnO2 as a terminal oxidant, in which synthetically important β-substituted γ-nitro aldehydes were obtained with excellent enantioselectivity.

  • organocatalytic enantioselective intramolecular 6 2 cycloaddition reaction for the formation of tricyclopentanoids and insight on its mechanism from a computational study
    Journal of the American Chemical Society, 2011
    Co-Authors: Yujiro Hayashi, Hiroaki Gotoh, Hayato Ishikawa, Seiji Tsuzuki, Masakazu Honma, Kuppusamy Sankar, Indresh Kumar, Kohzo Konno, Hiroharu Yui, Tadafumi Uchimaru
    Abstract:

    Diphenylprolinol Silyl Ether was found to be an effective organocatalyst for promoting the asymmetric, catalytic, intramolecular [6 + 2] cycloaddition reactions of fulvenes substituted at the exocyclic 6-position with a δ-formylalkyl group to afford synthetically useful linear triquinane derivatives in good yields and excellent enantioselectivities. The cis-fused triquinane derivatives were obtained exclusively; the trans-fused isomers were not detected among the reaction products. The intramolecular [6 + 2] cycloaddition occurs between the fulvene functionality (6π) and the enamine double bond (2π) generated from the formyl group in the substrates and the diphenylprolinol Silyl Ether. The absolute configuration of the reaction products was determined by vibrational circular dichroism. The reaction mechanism was investigated using molecular orbital calculations, B3LYP and MP2 geometry optimizations, and subsequent single-point energy evaluations on model reaction sequences. These calculations revealed the...

  • enantio and diastereoselective synthesis of piperidines by coupling of four components in a one pot sequence involving diphenylprolinol Silyl Ether mediated michael reaction
    Organic Letters, 2010
    Co-Authors: Tatsuya Urushima, Daisuke Sakamoto, Hayato Ishikawa, Yujiro Hayashi
    Abstract:

    An efficient, asymmetric, four-component, one-pot synthesis of highly substituted piperidines with excellent diastereo- and enantioselectivity was established through the diphenylprolinol Silyl Ether mediated Michael reaction of aldehyde and nitroalkene, followed by the domino aza-Henry reaction/hemiaminalization reaction and a Lewis acid mediated allylation or cyanation reaction. All carbons of the piperidine ring are substituted with different groups, and its five contiguous stereocenters are completely controlled in both relative and absolute senses.

  • one pot synthesis of chiral bicyclo 3 3 0 octatrienes using diphenylprolinol Silyl Ether mediated ene type reaction
    Tetrahedron, 2010
    Co-Authors: Hiroaki Gotoh, Hayato Ishikawa, Hiroshi Ogino, Yujiro Hayashi
    Abstract:

    Chiral bicyclo[3.3.0]octatrienes with excellent enantioselectivity were synthesized from the simple starting materials of α,β-unsaturated aldehyde and cyclopentadiene via one-pot operation, which consisted of a diphenylprolinol Silyl Ether-mediated ene-type reaction, intramolecular addition reaction of cyclopentadiene moiety with aldehyde and dehydration reaction.

Tadafumi Uchimaru - One of the best experts on this subject based on the ideXlab platform.

  • two reaction mechanisms via iminium ion intermediates the different reactivities of diphenylprolinol Silyl Ether and trifluoromethyl substituted diarylprolinol Silyl Ether
    ChemInform, 2015
    Co-Authors: Hiroaki Gotoh, Tadafumi Uchimaru, Yujiro Hayashi
    Abstract:

    The reaction of cinnamaldehyde with cyclopentadiene in the presence of DPPL as catalyst leads to substituted cyclopentadiene Michael-type adducts (III) and (IV), whilst the reaction with DTFP catalyst affords Diels—Alder adducts (V) and (VI).

  • asymmetric nitrocyclopropanation of α substituted α β enals catalyzed by diphenylprolinol Silyl Ether for the construction of all carbon quaternary stereogenic centers
    European Journal of Organic Chemistry, 2015
    Co-Authors: Yujiro Hayashi, Tatsuya Yamazaki, Yuki Nakanishi, Tsuyoshi Ono, Tohru Taniguchi, Kenji Monde, Tadafumi Uchimaru
    Abstract:

    The diphenylprolinol Silyl Ether mediated asymmetric nitrocyclopropanation of α-substituted α,β-unsaturated aldehydes with bromonitromethane, followed by base-promoted isomerization was found to afford trans-nitrocyclopropanecarbaldehydes with all-carbon quaternary stereogenic centers with excellent diastereo- and enantioselectivities. DFT calculations indicated that the s-trans conformer of the iminium ion intermediate is more stable than the s-cis conformer. In addition, nucleophilic attack of the bromonitromethane anion to the iminium ion intermediate was calculated to occur preferentially from the opposite side of the bulky substituents of the pyrrolidine iminium intermediate.

  • Two Reaction Mechanisms via Iminium Ion Intermediates: The Different Reactivities of Diphenylprolinol Silyl Ether and Trifluoromethyl-Substituted Diarylprolinol Silyl Ether.
    Chemistry (Weinheim an der Bergstrasse Germany), 2015
    Co-Authors: Hiroaki Gotoh, Tadafumi Uchimaru, Yujiro Hayashi
    Abstract:

    The reactions of α,β-unsaturated aldehydes with cyclopentadiene in the presence of diarylprolinol Silyl Ethers as catalyst proceed via iminium cations as intermediates, and can be divided into two types; one involving a Michael-type reaction (type A) and one involving a cycloaddition (type B). Diphenylprolinol Silyl Ethers and trifluoromethyl-substituted diarylprolinol Silyl Ethers, which are widely used proline-type organocatalysts, have been investigated in this study. As the LUMO of the iminium ion derived from trifluoromethyl-substituted diarylprolinol Silyl Ether is lower in energy than that derived from diphenylprolinol Silyl Ether, as supported by ab initio calculations, the trifluoromethyl-substituted catalyst is more reactive in a type B reaction. The iminium ion from an α,β-unsaturated aldehyde is generated more quickly with diphenylprolinol Silyl Ether than with the trifluoromethyl-substituted diarylprolinol Silyl Ether. When the generation of the iminium ion is the rate-determining step, the diphenylprolinol Silyl Ether catalyst is the more reactive. Because acid accelerates the generation of iminium ions and reduces the generation of anionic nucleophiles in the Michael-type reaction (type A), it is necessary to select the appropriate acid for specific reactions. In general, diphenylprolinol Silyl Ether is a superior catalyst for type A reactions, whereas the trifluoromethyl-substituted diarylprolinol Silyl Ether catalyst is preferred for type B reactions.

  • a theoretical and experimental study of the effects of Silyl substituents in enantioselective reactions catalyzed by diphenylprolinol Silyl Ether
    Chemistry: A European Journal, 2014
    Co-Authors: Hiroaki Gotoh, Tadafumi Uchimaru, Yujiro Hayashi, Daichi Okamura, Tatsuya Yamazaki, Yasuto Ameda, Seiji Tsuzuki, Dieter Seebach
    Abstract:

    The effect of Silyl substituents in diphenylprolinol Silyl Ether catalysts was investigated. Mechanistically, reactions catalyzed by diphenylprolinol Silyl Ether can be categorized into three types: two that involve an iminium ion intermediate, such as for the Michael-type reaction (type A) and the cycloaddition reaction (type B), and one that proceeds via an enamine intermediate (type C). In the Michael-type reaction via iminium ions (type A), excellent enantioselectivity is realized when the catalyst with a bulky Silyl moiety is employed, in which efficient shielding of a diastereotopic face of the iminium ion is directed by the bulky Silyl moiety. In the cycloaddition reaction of iminium ions (type B) and reactions via enamines (type C), excellent enantioselectivity is obtained even when the Silyl group is less bulky and, in this case, too much bulk reduces the reaction rate. In other cases, the yield increases when diphenylprolinol Silyl Ethers with bulky substituents are employed, presumably by suppressing side reactions between the nucleophilic catalyst and the reagent. The conformational behaviors of the iminium and enamine species have been determined by theoretical calculations. These data explain the effect of the bulkiness of the Silyl substituent on the enantioselectivity and reactivity of the catalysts.

  • organocatalytic enantioselective intramolecular 6 2 cycloaddition reaction for the formation of tricyclopentanoids and insight on its mechanism from a computational study
    Journal of the American Chemical Society, 2011
    Co-Authors: Yujiro Hayashi, Hiroaki Gotoh, Hayato Ishikawa, Seiji Tsuzuki, Masakazu Honma, Kuppusamy Sankar, Indresh Kumar, Kohzo Konno, Hiroharu Yui, Tadafumi Uchimaru
    Abstract:

    Diphenylprolinol Silyl Ether was found to be an effective organocatalyst for promoting the asymmetric, catalytic, intramolecular [6 + 2] cycloaddition reactions of fulvenes substituted at the exocyclic 6-position with a δ-formylalkyl group to afford synthetically useful linear triquinane derivatives in good yields and excellent enantioselectivities. The cis-fused triquinane derivatives were obtained exclusively; the trans-fused isomers were not detected among the reaction products. The intramolecular [6 + 2] cycloaddition occurs between the fulvene functionality (6π) and the enamine double bond (2π) generated from the formyl group in the substrates and the diphenylprolinol Silyl Ether. The absolute configuration of the reaction products was determined by vibrational circular dichroism. The reaction mechanism was investigated using molecular orbital calculations, B3LYP and MP2 geometry optimizations, and subsequent single-point energy evaluations on model reaction sequences. These calculations revealed the...