Tandem aminopalladation/Suzuki cyclization cascades

串联氨基钯化/Suzuki 环化级联

• 批准号: 6881882
• 负责人: Andrew Michael Harned
• 金额: $ 4.21万
• 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/6881882
• 关键词: alkaloids; antineoplastics; biological products; catalyst; chemical reaction; chemical synthesis; drug design /synthesis /production; heterocyclic compounds; leukemia; palladium; postdoctoral investigator; 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）：该提案描述了有氧，PD（LL）催化的串联氨基化/铃木反应的发展和利用。说明了两种不同的策略。一种涉及通过分子内氨基化形成烯丙基丙酰胺复合物，而另一个则利用氨基化步骤形成中间的PD-隔离。然后，这两个中间体都将与拴系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）物种的产生，但在有氧条件下进行反应将再生所需的PD（LL）催化剂。此外，该建议概述了这种方法在头孢菌素的总合成中的使用。最近发现的天然产物的亚家族在结构上与抗白血病头孢霉素酯相关，并显示出针对白血病本身的有效活性。