New Catalytic Stereoselective Strategies for Hydrocarbon Functionalization Via Ionic Intermediates

项目概要 碳氢化合物可预测转化为功能性合成中间体的化学方法 彻底改变了小分子疗法的制备。尽管如此，在持续发展 新的化学工具可以补充当前的现有技术并解决合成策略提供的差距 进一步加速药物创新和成像技术的潜力。这项研究的目标 该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 具体来说，这里提出的两个研究领域集中于促进催化剂的研究 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。第一个 研究领域将重点开发催化对映选择性卤化的新策略 手性路易斯碱催化。这项工作借鉴了我们在该领域关于刘易斯基地的初步发现 激活潜在卤化物源以催化生成手性卤化试剂。第二个 研究领域详细介绍了一种通过氢化物提取生成手性分子的概念新颖方法 流程。具体来说，我们的目标是利用超强酸催化剂的反应性和选择性，使区域 以及饱和烃的立体选择性官能化。该战略代表了 更广泛的研究计划旨在开发一种新的不对称 Csp3-H 功能化模式。采取 这些研究项目将共同扩大可用的化学空间并简化化学合成 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.