Development of tough S_N2 reactions at the α-carbon to trifluoromethyl group

α-碳到三氟甲基的艰难 S_N2 反应的发展

• 批准号: 12650854
• 负责人: KATAGIRI Toshimasa
• 金额: $ 2.37万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12650854/
• 关键词: Fluoninated Organic Compounds; Intra-molecular Nuclecphilic Ssubstitution; Amlno Acid; Trifluoromenthyl Group; Optically Aclive; Electronic Reculsion; Steric Effect; 有機フッ素化合物; ピロリジン; シクロプロパン; ジアステレオ選択性

Intramolecular S_N2 reactions of α-trifluoromethylated secondary alcohols and utilization of them to preparations of fluorinated amino acids have been studied.2-Trifluoromethyl aziridines are synthesized from N-alkyl-3,3,3-trifluoro-2-hydroxypropylamine with triphenylphosphine-tetrachloromethane or dichlorotriphenyl-phosphorane. Similarly, 2-trifluoromethylated pyrroridines was prepared. A stereoselective intramolecular cyclization of 3-substituted-3-cyano-l-trifluoromefliylpropyl sulfonate via the cyano stabilized carbanion provides l-substituted-1-cyano-2-trifluoromefliylcyclopropanes in good yields. The stereochemistry of the product at the carbon attached to trifluoromethyl group was completely inverted its configuration from the starting alcohol, revealing the reaction underwent in S_N2 manner with Walden inversion at the reaction center. Intramolecular electrostatic repulsions between the local negative charge on a trifluoromethyl group and that on ortho positions of aryl moiety of nucleophile was found to be a controlling factor of the diastereoselectivity in the cyclopropanation. The reaction was applied for syntheses of optically active trifluoro-norcoronamic acid and its diastereomer.

Intramolecular S_N2 reactions of α-trifluoromethylated secondary alcohols and utilization of them to prepares of fluorinated amino acids have been studiod.2-Trifluoromethyl aziridines are synthesized from N-alkyl-3,3,3-trifluoro-2-hydroxypropylamine with三苯基磷酸四氯甲烷或二氯苯基磷酸酯。同样，制备了2-三氟甲基化的吡咯烷。通过氰基稳定碳酸盐的3-取代-3-Cyano-L-三氟丙基磺酸盐磺酸盐的立体选择性分子环化环化，可提供L-取代的1-甲氧烷-2-三氟氟氟氟甲基环丙烷的L-核定含量。碳与三氟甲基相连的碳的立体化学完全从起始酒精中完全倒置，从而揭示了反应中心与瓦尔登倒置的反应。发现三氟甲基的局部负电荷之间的分子内静电排斥，并且发现在核腓杆菌的芳基部分位置上是环丙烷中映射性的一个控制因子。该反应用于光学活性三氟甲甲酸及其非对映异构体的合成。

项目成果

Y Matsukawa, J. S. Dileep Kumar, Y. Yoneyama, T. Katagiri, K. Uneyama: "Reversed Diastereoselectivity in the Ring Opening Reaction of (S)-TFPO with a Chiral Aminoacetonrtrile Shiff Base,"Tetrahedron : Asymmetry. 11. 4521-4528 (2000)

Y Matsukawa、J. S. Dileep Kumar、Y. Yoneyama、T. Katagiri、K. Uneyama：“(S)-TFPO 与手性氨基乙腈移位碱的开环反应中的反向非对映选择性”，四面体：不对称性。

T.Katagiri, M.Handa, Y.Matsukawa, J.S.Dileep Kumar, K.Uneyama: "Efficient Synthesis of an Optically Pure β-Bromo-β,β-difluoroalanine Derivative, a General Precursor for β,β-Difluoroamino Acids"Tetrahedron : Asymmetry. 12. 1303-1311 (2001)

T.Katagiri、M.Handa、Y.Matsukawa、J.S.Dileep Kumar、K.Uneyama：“高效合成光学纯 β-溴-β,β-二氟丙氨酸衍生物，β,β-二氟氨基酸的通用前体”四面体：不对称性。12。1303-1311（2001）

T.Katagiri,M.Irie,K.Uneyama: "Syntheses of Optically Active Trifluoronorcoronamic Acids"Organic Letters. 2巻、16号. 2423-2425 (2000)

T.Katagiri、M.Irie、K.Uneyama：“光学活性三氟去冠酸的合成”有机快报第 2 卷，第 16 期。2423-2425 (2000)

T.Katagiri, K.Uneyama: "A Chemistry of 2,3-Epoxy-1,1,1-trifluoropropane"Journal of Fluorine Chemistry. 105. 285-293 (2000)

T.Katagiri, K.Uneyama：“2,3-环氧-1,1,1-三氟丙烷的化学”氟化学杂志。

T.Katagiri, M.Handa, Y.Matsukawa, J.S.Deleep Kumar, K.Uneyama: "Efficient synthesis of an optically pure β-bromo-β, β-difluroalanine derivative, a general precursor for β, β-difluoroamino acids"Tetrahedron Asymmetry. 12巻. 1303-1311 (2001)

T.Katagiri、M.Handa、Y.Matsukawa、J.S.Deleep Kumar、K.Uneyama：“高效合成光学纯 β-溴-β, β-二氟丙氨酸衍生物，它是 β, β-二氟氨基酸的通用前体”不对称，1303-1311（2001）。