Creation of New Medicines Based on the Characteristic Reactivity of Allenes

基于丙二烯特征反应性的新药创制

• 批准号: 11555240
• 负责人: TAMARU Yoshinao
• 金额: $ 8.83万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11555240/
• 关键词: allenes; [2+2] cycloaddition; exazolidinone; alkenes; alkynes; alcohols; Woodward-Hoffmann rule; indoles; sulfonamide; Diels-Alder; オキサゾリジノン; 複素環化合物; スピロ化合物; 環化付加; 転位反応; 環化付加反応

The allene bond of allene carbamate (1, 4-vinylidene-2-oxazolidinone) shows a chameleonic reactivity, changing the reaction patters widely depending on the kinds of its reaction partners. With terminal alkenes and alkynes, 1 undergoes [2+2]cycloaddition in a concerted manner and provides methylene cyclobutanes and methylenecyclobutenes. Respectively in good yields. The cycloaddition proceeds under strictly thermal activation conditions (70-100 ℃) with retention of the configuration of the alkene double bonds. Usually, [2+2]cycloaddition is a thermally forbidden process and the unique reactivity of 1 is explained on the basis of a [2π+2π+2π] Huckel transition state. With enols and allylsilanes, 1 undergoes unique 1,3-sulfonyl migration followed by the inverse electron demand Diels-Alder reaction giving rise to tetrehydropyridine derivatives. With silanes (RnSiH4-n, n = 1-3), alcohols, and thiols, 1 undergoes the 1,3-sulfonyl migration and provides a variety of 4-propylidene-2- oxazolidinones in excellent yields.

氨基甲酸烯丙酯(1，4-亚乙叉-2-恶唑烷酮)的烯基键表现出变色龙反应活性，反应模式随反应伙伴的种类而变化。与末端烯烃和炔烃一起，1以协同方式进行[2+2]环加成反应，得到亚甲基环丁烷和亚甲基环丁烯。分别以良好的产量。环加成反应在严格的热活化条件下(70-100℃)进行，保留了烯烃双键的构型。通常，[2+2]环加成反应是一个热禁止的过程，1的独特反应活性是基于[2π+2π+2π]休克尔过渡态来解释的。对于烯醇和烯丙基硅烷，1经历了独特的1，3-磺酰基迁移，随后发生了反向电子需求Diels-Alder反应，产生了四氢吡啶衍生物。与硅烷(RnSiH4-n，n=1-3)、醇和硫醇一起，1经历了1，3-磺酰基迁移并以优异的产率提供了多种4-亚丙基-2-恶唑烷酮。

项目成果

柴田 和文: "Nickel-catalyzed three-component connection reaction of a phenyl group, conjugated dienes, and aldehydes : stereoselective synthesis of(E)-5-phenyl-3-penten-1-ols"J Organimet. Chem.. 624. 348-353 (2001)

Kazufumi Shibata：“镍催化的苯基、共轭二烯和醛的三组分连接反应：(E)-5-苯基-3-戊烯-1-醇的立体选择性合成”J Organimet.. 624。 348-353 (2001)

M. Kimura, T. Tomizawa, Y. Horino, S. Tanaka, Y. Tamaru: "Et_3B- Pd-promoted Allylation of Benzaldehyde with Allylic Alcohols"Tetrahedron Lett.. 41. 3627-3629 (2002)

M. Kimura、T. Tomizawa、Y. Horino、S. Tanaka、Y. Tamaru：“Et_3B-Pd 促进的苯甲醛与烯丙醇的烯丙基化”Tetrahedron Lett.. 41. 3627-3629 (2002)

M. Naito, A. Ezoe, M. Kimura, Y Tamara: "Practical Synthesis of Myrcene Derivatives Possessing Oxidized Methyl Groups"J. Org. Chem. 66. 4447-4449 (2001)

M. Naito、A. Ezoe、M. Kimura、Y Tamara：“具有氧化甲基的月桂烯衍生物的实际合成”J。

Yoshikazu Horino, Masanari Kimura, Shuji Tanaka, Toshiya Okajima Yoshinao Tamaru: "Preparation, Structure, and Unique Thermal [2 + 2], [4 + 2], and [3 + 2] Cycloaddition Reactions of 4- Vinylidene-2-oxazolidinone"Chem. Eur. J.. in press. (2003)

Yoshikazu Horino、Masanari Kimura、Shuji Tanaka、Toshiya Okajima Yoshinao Tamaru：“4-亚乙烯-2-恶唑烷酮的制备、结构和独特的热反应 [2 2]、[4 2] 和 [3 2] 环加成反应”Chem。

田丸良直: "Palladium-Catalyzed Reaction of Allyl and Related Derivatives with Organoelectrophiles in Handbook of Organopalladium Chemistry for Organic Synthesis, E.Negishi, Ed"Wiley. 123 (2002)

Yoshinao Tamaru：“有机合成有机钯化学手册中烯丙基和相关衍生物与有机亲电子试剂的钯催化反应，E.Negishi，Ed”Wiley 123 (2002)。