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: 10408069
• 负责人: Ramesh Giri
• 金额: $ 36.97万
• 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/10408069
• 关键词: Achievement; Address; Alkenes; 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.

项目概要/摘要 未活化烯烃的催化二碳官能化提供了一种强大的方法来产生两个碳-碳 同时实现这一目标可以构建许多具有重要生物学意义的核心。 我们的长期目标是快速、简洁且经济高效地设计和创建此类反应。 拦截有机卤化物与烯烃加成后原位生成的烷基金属中间体， 碳亲核试剂的这些过程的发展已被证明是简单的未活化的烯烃。 然而，由于两个关键问题，导致烯烃迁移插入速度缓慢； 与交叉偶联产物的形成相比，并且从烷基金属中间体中更快地消除 -H 金属交换导致 Heck 产品的形成 在拟议的研究中，我们将实施三种方法。 用有机卤化物和有机金属对未活化的烯烃进行区域选择性双官能化的策略 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) 催化剂是在原位产生的，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 ,-位的未活化烯烃的区域选择性 ,-双官能化。 在我们的第二个策略中，我们引入了金属循环收缩过程的概念，这是一种利用 烷基金属中间体经历-H消除以收缩六元金属环的潜力 一个五元金属环，并在不寻常的 1,3 位而不是未活化的烯烃上双官能化 这种前所未有的反应使我们能够创建两个新的碳-碳键。 第三，我们的最终目标是开发含有α,β-烯烃的羰基化合物。 调节迁移插入和-H消除过程的新型催化剂，并使双功能化能够 我们提出了不同的催化条件，无需配位基团即可进行简单的烯烃， 这使得缺乏配位基团的烯烃能够双碳官能化。 所提出的二碳官能化反应以及我们拥有的强有力的初步结果是独一无二的 使用其他方法无法实现的转换。