Development of Regioselective Alkene Dicarbofunctionalization Reactions

区域选择性烯烃二碳官能化反应的进展

• 批准号: 9796785
• 负责人: Ramesh Giri
• 金额: $ 37.25万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9796785
• 关键词: Achievement; Address; Alkenes; Biological; Carbon; Catalysis; Cations; Complex; Contracts; Coupling; Development; Drug Targeting; Goals; In Situ; Intercept; Methodology; Methods; Mission; Molecular; Pharmacologic Substance; Positioning Attribute; Process; Reaction; Reagent; Research; United States National Institutes of Health; carbonyl compound; catalyst; cost; design; novel; programs; rapid technique

Project Summary/Abstract Catalytic dicarbofunctionalization of unactivated alkenes offers a powerful method to create two carbon-carbon bonds simultaneously. Achievement of this objective offers to construct the cores of many biologically important molecules rapidly, concisely and cost-effectively. Our long-term goal is to devise and create such reactions by intercepting alkylmetal intermediates, generated in situ after the addition of organic halides to alkenes, with carbon nucleophiles. The development of these processes with simple unactivated alkenes has been shown to be exceptionally challenging, however, because of two key issues; slow migratory insertion of alkenes leading to the formation of cross-coupling products, and faster -H elimination from alkylmetal intermediates than transmetalation leading to the formation of Heck products. In the proposed research, we will implement three strategies to difunctionalize unactivated alkenes regioselectively with organic halides and organometallic reagents. First, we will introduce a strategy of Synergistic Bimetallic Cationic Catalysis, where cationic Ni(II) catalysts are generated in situ to address the key issues identified above. This process will enable us to perform regioselective ,-difunctionalization of unactivated alkenes located at the ,-position of carbonyl compounds. In our second strategy, we introduce the concept of Metallacycle Contraction Process, a reaction that harnesses the potential of alkylmetal intermediates to undergo -H elimination to contract a six-membered metallacycle to a five-membered metallacycle, and difunctionalizes unactivated alkenes at the unusual 1,3-position rather than the usual 1,2-position of alkenes. This unprecedented reaction allows us to create two new carbon-carbon bonds at the - and -positions of carbonyl compounds containing ,-alkenes. Third, our ultimate goal is to develop novel catalysts to modulate migratory insertion and -H elimination processes, and enable difunctionalization to proceed with simple alkenes without requiring a coordinating group. We present different catalytic conditions, which enable dicarbofunctionalization of alkenes lacking a coordinating group. The catalytic alkene dicarbofunctionalization reactions proposed and for which we have strong preliminary results are unique transformations that cannot be achieved with using other methodology.

项目总结/摘要 未活化烯烃的催化双碳官能化提供了一种强有力的方法， 债券同时这一目标的实现提供了构建许多生物学上重要的核心， 快速、简洁、经济高效地分析分子。我们的长期目标是设计和创造这样的反应， 在将有机卤化物加成到烯烃上后原位生成的烷基金属中间体， 碳亲核试剂。已经表明，用简单的未活化烯烃开发这些方法， 然而，由于两个关键问题， 形成交叉偶联产物，以及从烷基金属中间体中更快消除α-H， 金属转移导致Heck产物的形成。在拟议的研究中，我们将实施三个 用有机卤化物和有机金属化合物区域选择性地双官能化未活化烯烃的策略 试剂首先，我们将介绍一种协同双金属阳离子催化策略，其中阳离子Ni（II） 原位生成催化剂以解决上述关键问题。这一过程将使我们能够执行 位于羰基化合物的α，β-位的未活化烯烃的区域选择性α，β-双官能化。 在我们的第二个策略中，我们引入了金属乳酸收缩过程的概念，这是一种利用 烷基金属中间体经历β-H消除以收缩六元金属配位化合物以 一个五元金属配合物，并在不寻常的1，3-位双官能化未活化的烯烃，而不是 通常的烯烃的1，2-位。这个前所未有的反应让我们创造了两个新的碳-碳键 在含α，β-烯烃的羰基化合物的α-和β-位上。第三，我们的最终目标是发展 调节迁移插入和β-H消除过程的新型催化剂， 用简单的烯烃进行，而不需要配位基团。我们提出了不同的催化条件， 其能够使缺少配位基团的烯烃二碳官能化。催化烯烃 提出的双碳官能化反应，我们有很强的初步结果是独特的 这是其他方法无法实现的。