Tandem aminopalladation/Suzuki cyclization cascades

串联氨基钯化/Suzuki 环化级联

• 批准号: 7055280
• 负责人: Andrew Michael Harned
• 金额: $ 4.6万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7055280
• 关键词: alkaloids; antineoplastics; biological products; catalyst; chemical reaction; chemical synthesis; drug design /synthesis /production; heterocyclic compounds; leukemia; palladium; postdoctoral investigator

DESCRIPTION (provided by applicant): This proposal describes the development and utilization of an aerobic, Pd(ll)-catalyzed tandem aminopalladation/Suzuki reaction. Two different strategies are illustrated. One involves the formation of an allylpalladium complex via an intramolecular aminopalladation, while the other utilizes the aminopalladation step to form an intermediate Pd-enolate. Both of these intermediates will then undergo an intramolecular cross-coupling with a tethered aryl boronic acid. While the cross-coupling event will result in the production of a Pd(0) species, conducting the reaction under aerobic conditions will regenerate the required Pd(ll) catalyst. In addition, this proposal outlines the use of this methodology in the total synthesis of the cephalezomines; a recently discovered subfamily of natural products that are structurally related to the antileukemic cephalotaxine esters, and have shown potent activity against leukemia themselves.

描述（由申请人提供）：该提案描述了需氧 Pd(II) 催化的串联氨基钯化/Suzuki 反应的开发和利用。说明了两种不同的策略。一种涉及通过分子内氨基钯化形成烯丙基钯络合物，而另一种利用氨基钯化步骤形成中间体钯-烯醇化物。然后，这两种中间体将与束缚芳基硼酸进行分子内交叉偶联。虽然交叉偶联事件将导致 Pd(0) 物质的产生，但在有氧条件下进行反应将再生所需的 Pd(II) 催化剂。此外，该提案概述了该方法在头孢唑明全合成中的应用；最近发现的一个天然产物亚家族，其结构与抗白血病头孢噻嗪酯相关，并且本身已显示出有效的抗白血病活性。