Regio- and Enantioselective Alkene Difunctionalizations for the Synthesis of Bioactive Molecules.

项目摘要/摘要 手性β-氨基官能化分子是各种饱和杂环中常见的基序 重要的药物分子。它们也是有机合成中普遍存在的手性构件，用于 例如，在不对称催化中广泛应用的手性恶唑啉配体。功能界别 这些分子的重要性使得它们的合成需求一直很高。烯烃双官能化 代表了针对这些结构主题的高度模块化战略，由德高望重的 由夏普莱斯和他的同事开发的Os催化的方案。然而，仍然存在重大挑战。 对于这类反应。该计划的主要目标是开发新型催化烯烃。 将满足这些挑战的要求并加速获得手性β-氨基的官能化 功能化的图案。具体地说，这项提案将引入卤素和高价碘催化，如 解决在这些反应中经常遇到的区域化学和对映体选择性挑战的平台。 根据可靠的初步数据，拟议的研究将使我们能够：1)论证 一系列双功能亲核试剂在卤素催化中区域化学控制的亲核性控制；2) 利用高价碘催化剂作为烯烃双官能化区域控制的新元素； 提出了采用手性高价碘催化剂进行不对称诱导反应的建议。我们的建议是 创新地引入了几种区域控制和不对称诱导的方法，基于单个 基本的一步。此外，这些方法使用简单和普遍存在的双功能试剂，例如酰胺， 用于烯烃双官能化的尿素、氨基甲酸酯等。最后，拟议战略的实现将使 手性β-氨基功能化基序的直接合成。

Project Summary/Abstract Chiral β-amino functionalized molecules are common motifs often found in a variety of saturated heterocycles of important drug molecules. They are also ubiquitous chiral building blocks in organic synthesis to access, for example, chiral oxazoline-based ligands that are broadly useful in asymmetric catalysis. The functional importance of these molecules renders their syntheses continuously in high demand. Alkene difunctionalization represents a highly modular strategy towards these structural motifs as benchmarked by the venerable osmium-catalyzed protocols developed by Sharpless and coworkers. However, significant challenges remain for this class of reactions. The main objective of this program is to develop new classes of catalytic alkene difunctionalizations that will meet the demands of these challenges and expedite access to chiral β-amino functionalized motifs. Specifically, this proposal will introduce halonium and hypervalent iodine catalysis as platforms to resolve the regiochemical and enantioselective challenges often encountered in these reactions. Based on solid preliminary data, the proposed studies will enable us to: 1) demonstrate the feasibility of nucleophile-control for regiochemical control in halonium catalysis with a range of bifunctional nucleophiles; 2) utilize hypervalent iodine catalysts as a new element for regiocontrol in alkene difunctionalizations; and 3) adopt chiral hypervalent iodine catalyst for asymmetric induction of the reactions proposed. Our proposal is innovative by introducing several means of regiocontrol and asymmetric induction based on a single elementary step. Additionally, these methods use simple and ubiquitous bifunctional reagents such as amide, urea, carbamate, etc. for alkene difunctionalizations. Finally, realization of the proposed strategy will enable straightforward synthesis of chiral β-amino functionalized motifs.