Pd-Catalyzed Olefin Functionalization Reactions for Organic Synthesis

描述（由申请人提供）：烯烃是一种非常有吸引力的合成官能团。新发现和显著改进的烯烃功能化反应可以直接影响目标合成的效率。因此，发展选择性的、实用的烯烃功能化反应是学术界和工业界化学家面临的一个持续的挑战。在本提案中，我们的目标是一组新的烯烃功能化反应，利用Pd(II)-催化及其促进烯烃亲核加成反应和交叉偶联过程的能力，在烯烃框架上形成多个新的C-C， C-H或C-X键。这种反应方法的发展与细致的机理研究相结合，旨在阐明控制反应结果的基本特征，并刺激新的反应发展和催化剂设计。目前的建议是针对开发新的pd催化烯烃功能化反应，使用氧化和经典的方法来生成pd -烷基中间体。本文描述的反应发展主要集中在两个重要目标上：A)通过使用创新的方法来功能化最初来自烯烃的pd -烷基中间体，从而实现新的机械衍生的分子合成策略（目标1和2）；B)利用我们最近开发的电子非偏倚烯烃Heck反应来获取重要的手性构建块，同时还探索控制选择性pd -氢化物插入和？-氢化物消除（Aim 3）。

DESCRIPTION (provided by applicant): Alkenes are exceptionally attractive functional groups for synthesis. Newly discovered and significantly improved alkene functionalization reactions can have a direct impact on the efficiency of targeted synthesis. Therefore, the development of selective, practical alkene functionalization reactions is a continuing challenge facing chemists in both academia and industry. In this proposal, we target a new collection of alkene functionalization reactions that exploit Pd(II)-catalysis and its ability to promote both alkene nucleophilic addition reactions and cross-coupling processes to form multiple new C-C, C-H, or C-X bonds across the alkene framework. This reaction method development is coupled to careful mechanistic studies, which are designed to elucidate the fundamental features governing reaction outcomes, as well as to stimulate new reaction development and catalyst design. The current proposal is directed toward the development of new Pd-catalyzed olefin functionalization reactions using both oxidative and classical methods to generate Pd-alkyl intermediates. The reaction development described herein is focused on two significant goals: A) enabling new mechanistically-derived tactics for molecule synthesis by using innovative approaches to functionalize Pd-alkyl intermediates originally derived from an alkene (Aims 1 & 2), and B) exploiting our recently developed Heck reactions of electronically non-biased olefins to access important chiral building blocks, while also probing the factors that govern selective Pd-hydride insertion and ?-hydride elimination (Aim 3). PUBLIC HEALTH RELEVANCE: The goal of the proposed research is to develop new palladium-catalyzed alkene functionalization reactions to enable the facile synthesis of biologically-relevant targets and novel small molecules through unique bond disconnections. Advances in the proposed methodology will directly impact the biomedical mission by providing efficient access to derivatives of biologically-active core structures.