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、试剂在环面立体选择性加成、烯烃结合位点的区域选择性保护，以及这些特征在当前合成靶标中的应用。这种方法将用于制备依比替丁，一种吡啶取代的7-阿扎比环庚烷，已被证明是一种有效的非阿片类镇痛药。在这些反应中使用锇（II）配合物。在本研究的第二阶段，将开发替代的基于Re的脱芳剂。通过改变金属中心的电子和空间特征：(1)优化对芳香配体的亲和力；(2)为不对称诱导制备手性配位环境；(3)调整金属-芳香键的强度以促进催化过程。这项来自有机合成计划的资助用于支持弗吉尼亚大学的W. Dean Harman教授的工作。环状有机分子的配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分子，例如具有非阿片性质的强效镇痛药。金属离子络合会增加环有机化合物的反应性，并引导另一个分子的攻击到环有机分子的特定原子或表面。金属离子环有机分子配合物的这些特点将使其具有广泛的合成应用。

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.