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

芳香族分子(包括芳香族杂环)通过两个碳原子与金属离子络合，将用于芳环的区域选择性活化、试剂在一个环面上的立体选择性加成、区域选择性保护烯烃结合部位，以及将这些特征应用于当前的合成目标。这一方法将用于制备表巴替丁，这是一种吡啶取代的7-氮杂环庚烷，已被证明是一种有效的非阿片类止痛剂。在这些反应中将使用一种Os(II)络合物。在这项研究的第二阶段，将开发替代的稀土离子脱芳烃试剂。通过改变金属中心的电子和空间性质：(1)芳香族配体的亲和力将被优化；(2)手性配位环境将被准备用于不对称诱导；(3)金属-芳香键强度将被调整以促进催化过程。来自有机合成项目的这笔资金支持弗吉尼亚大学W·迪恩·哈曼教授的工作。环状有机分子的络合物将与某些金属离子一起制备，这些金属离子将用于合成复杂的分子，例如具有非阿片类药物特性的强效止痛剂。金属离子络合将增加环状有机化合物的反应活性，并将另一个分子的攻击定向到环状有机分子的特定原子或面上。金属离子-环状有机分子络合物的这些特点将使其在合成上有广阔的应用前景。

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.