New Catalytic Stereoselective Strategies for Hydrocarbon Functionalization Via Ionic Intermediates

项目摘要 碳氢化合物可预测转化为功能性合成中间体的化学方法 使小分子疗法的制备发生了革命性的变化。尽管如此， 新的化学工具与现有技术相辅相成，并解决合成战略产品中的差距 进一步加快药物创新和成像技术的潜力。这项拟议研究的目标是 计划是通过手性离子中间体开发不对称催化的新领域。更多 具体地说，这里提出的两个研究领域集中在促进 立体选择性捕获阳离子中间体，以解决合成中长期存在的挑战。第一 研究领域将集中在开发催化对映选择性卤化反应的新策略。 手性路易斯碱催化。这项工作借鉴了我们在这一领域关于Lewis碱的初步发现 用于催化生成手性卤化试剂的潜在卤化物源的激活。第二 研究领域详细介绍了一种通过氢化物抽提产生手性分子的概念上的新方法 流程。具体地说，我们的目标是开发超强酸催化剂的反应性和选择性，以使区域- 饱和烃的立体选择性官能化。这一战略代表了一个 更广泛的研究计划，旨在开发不对称Csp3-H官能化的新模式。已被占用 这些研究项目将共同扩大现有的化学空间，简化化学合成。 用于药物发现和开发。

Project Summary Chemical methodologies for the predictable transformation of hydrocarbons to functional synthetic intermediates have revolutionized the preparation of small-molecule therapeutics. Nonetheless, the continued development of new chemical tools that compliment current existing technologies and address gaps in synthetic strategy offer the potential to further accelerate drug innovation and imaging techniques. The goal of this proposed research program is to develop new areas of asymmetric catalysis by means of chiral ionic intermediates. More specifically, the two research areas proposed here are centered on the study of catalysts that promote the stereoselective trapping of cationic intermediates to address longstanding challenges in synthesis. The first research area will focus on the development of novel strategies for catalytic enantioselective halogenation via chiral Lewis base catalysis. This work draws upon our initial findings in this area regarding the Lewis base activation of latent halide sources for the catalytic generation of chiral halogenating reagents. The second research area details a conceptually novel approach for the generation of chiral molecules via hydride abstraction processes. Specifically, we aim to exploit the reactivity and selectivity of superacid catalysts to enable the regio- and stereoselective functionalization of saturated hydrocarbons. This strategy represents the starting point for a broader research program aimed at developing a new mode of asymmetric Csp3–H functionalization. Taken together, these research programs will expand the available chemical space and streamline chemical synthesis for drug discovery and development.