NSF Young Investigator: Pi-Base Promoted Activation of Aromatic Molecules

NSF 青年研究员：Pi 基促进芳香分子的活化

• 批准号: 9357125
• 负责人: Walter Harman
• 金额: $ 31.25万
• 依托单位: University of Virginia Main Campus
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-15 至 1998-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9357125&HistoricalAwards=false
• 关键词: NSF; Young; Investigator; Pi; Base

Aromatic molecules (including aromatic heterocycles), complexed to metal ions via two carbon atoms, will be used to for regioselective activation of the aromatic ring, stereoselective addition of reagents to one ring face, regioselective protection of the olefinic binding site, and the application of these features to current synthetic targets. This methodology will be used to prepare epibatidine, a pyridyl-substituted 7-azabicycloheptane that has been shown to be a potent non-opioid analgesic. An osmium(II) complex will be used in these reactions. In a second phase of this research, alternative Re ion-based dearomatization agents will be developed. By varying the electronic and steric character of the metal center: (1) the affinity for aromatic ligands will be optimized, (2) a chiral coordination environment will be prepared for asymmetric induction, and (3) metal-aromatic bond strengths will be adjusted to facilitate a catalytic process. %%% This grant from the Organic Synthesis Program supports the work of Professor W. Dean Harman at the University of Virginia. Complexes of cyclic organic molecules will be prepared with certain metal ions that will be useful in the synthesis of intricate molecules, such as a potent analgesic that has non-opioid properties. Metal ion complexation will increase the reactivity of the cyclic organic compounds as well as direct the attack of another molecule to a particular atom or face of the cyclic organic molecule. These features of the metal ion-cyclic organic molecule complexes will allow for broad synthetic applications.

芳族分子（包括芳族杂环）通过两个碳原子复合到金属离子，用于区域选择性激活芳族环，对一个环面的立体选择性添加，对烯烃的区域性保护，对烯烃结合位点的区域性选择保护，以及这些特征在当前合成目标中的应用。该方法将用于制备Epibatidine，这是一种吡idy-取代的7-偶然蛋白酶，已被证明是一种有效的非阿片类镇痛药。这些反应将使用osmium（ii）复合物。在这项研究的第二阶段中，将开发基于RE离子的替代性亲爱的剂。通过改变金属中心的电子和空间特征：（1）将优化对芳族配体的亲和力，（2）将准备一个手性配位环境以进行非对称诱导，并且（3）将调整金属 - 芳族键强度以促进催化过程。 %% %%来自有机合成计划的这笔赠款支持弗吉尼亚大学W. Dean Harman教授的工作。环状有机分子的复合物将使用某些金属离子制备，这些金属离子将在复杂分子的合成中有用，例如具有非阿片类药物特性的有效镇痛药。金属离子络合物将增加环状有机化合物的反应性，并将另一个分子的攻击引向特定的原子或循环有机分子的面部。 金属离子循环有机分子络合物的这些特征将允许广泛的合成应用。