New Catalytic Stereoselective Strategies for Hydrocarbon Functionalization Via Ionic Intermediates

项目摘要 碳氢化合物向功能合成中间体可预测转化的化学方法学 彻底改变了小分子治疗剂的制备。尽管如此， 补充现有技术并解决合成战略差距的新化学工具， 进一步加速药物创新和成像技术的潜力。这项研究的目标是 计划是通过手性离子中间体开发不对称催化的新领域。更 具体地说，这里提出的两个研究领域集中在催化剂的研究上， 立体选择性捕获阳离子中间体，以解决合成中的长期挑战。第一 研究领域将集中在发展新的战略，催化对映体选择性卤化，通过 手性刘易斯碱催化。这项工作借鉴了我们在这方面的初步调查结果有关的刘易斯基地 用于催化生成手性卤化试剂的潜在卤化物源的活化。第二 研究领域详细介绍了一种概念新颖的方法，通过氢化物提取产生手性分子 流程.具体而言，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- 和饱和烃的立体选择性官能化。这一战略是一个起点， 更广泛的研究计划，旨在开发不对称Csp3-H官能化的新模式。采取 这些研究计划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.