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

芳族分子（包括芳族杂环）， 通过两个碳原子与金属离子络合， 为了区域选择性活化芳环， 将试剂立体选择性加成到一个环面上， 区域选择性保护烯属结合位点，和 将这些特征应用于当前的合成 目标的该方法将用于编写 地棘蛙素，吡啶基取代的7-氮杂双环庚烷， 已被证明是一种有效的非阿片类镇痛药。一个 锇（II）络合物将用于这些反应中。中 这项研究的第二阶段，替代Re离子为基础的 将开发脱芳构化剂。通过改变 金属中心的电子和空间性质：（1） 将优化对芳族配体的亲和力，（2） 手性配位环境将准备 不对称诱导，和（3）金属-芳香键强度 将被调整以促进催化过程。 %%% 有机合成计划的这笔赠款支持 W教授的工作。哈尔曼院长， 弗吉尼亚环状有机分子的复合物将是 用某些金属离子制备，这些金属离子将用于 复杂分子的合成，如强效止痛剂 非阿片类药物金属离子络合将 增加环状有机化合物的反应性， 并将另一个分子的攻击指向 环状有机分子的特定原子或面。 金属离子环状有机分子的这些特征 配合物将允许广泛的合成应用。

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.