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

用于合成生物活性分子的区域选择性和对映选择性烯烃双官能化。

基本信息

批准号：
10046958
负责人：
Wei Li
金额：
$ 45.15万
依托单位：
UNIVERSITY OF TOLEDO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2023-08-31
项目状态：
已结题

项目摘要

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.

项目概要/摘要手性 β-氨基功能化分子是各种饱和杂环中常见的常见基序它们也是有机合成中普遍存在的手性结构单元。例如，广泛用于不对称催化的手性恶唑啉基配体。这些分子的重要性使得它们的合成对烯烃双官能化的需求不断增加。代表了针对这些结构主题的高度模块化策略，以令人尊敬的为基准 Sharpless 及其同事开发的锇催化方案仍然存在重大挑战。该计划的主要目标是开发新类别的催化烯烃。双官能化将满足这些挑战的需求并加速获得手性 β-氨基具体来说，该提案将引入卤鎓和高价碘催化作用。解决这些反应中经常遇到的区域化学和对映选择性挑战的平台。基于可靠的初步数据，拟议的研究将使我们能够：1）证明可行性使用一系列双功能亲核试剂进行卤鎓催化中的区域化学控制的亲核试剂控制；高价碘催化剂用作烯烃双官能化中的区域控制的新元素；以及3) 采用手性高价碘催化剂进行不对称诱导反应我们的建议是。通过引入基于单一区域控制和不对称感应的多种手段进行创新此外，这些方法使用简单且普遍存在的双功能试剂，例如酰胺、最后，所提出的策略的实现将能够实现。手性β-氨基功能化基序的直接合成。