Development of Regioselective Alkene Dicarbofunctionalization Reactions

项目摘要/摘要 未活化烯烃的催化二碳官能化提供了一种生成两个碳-碳的有效方法 债券同时发行。这一目标的实现为构建许多具有生物重要性的核心提供了条件 快速、简明且经济高效的分子。我们的长期目标是设计和创造这样的反应，通过 截留在将有机卤化物加到烯烃中后就地产生的烷基金属中间体， 碳亲核试剂。用简单的未活化的烯烃开发的这些工艺已经被证明 然而，由于两个关键问题，这是非常具有挑战性的；缓慢的烯烃迁移插入导致 促进交叉偶联产物的形成，并比烷基金属中间体更快地消除-H 转金属作用导致Heck产物的形成。在拟议的研究中，我们将实施三项 有机卤化物和有机金属对未活化烯烃区域选择性去功能化的策略 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) 催化剂是在现场产生的，以解决上述关键问题。这一过程将使我们能够执行 区域选择性，-位于羰基化合物，-位的未活化烯烃的二官能化。 在第二个策略中，我们引入了金属循环收缩过程的概念，这是一种利用 烷基金属中间体进行-H消除以收缩六元金属环的潜力 一个五元金属环，并使不寻常的1，3-位的未活化的烯烃去功能化，而不是 通常的烯烃的1，2位。这一史无前例的反应使我们能够产生两个新的碳-碳键 在-和-位上，含有，-烯烃的羰基化合物。第三，我们的最终目标是发展 调节迁移插入和-H消除过程的新型催化剂，并使去功能化能够 在不需要协调基团的情况下继续进行单烯烃。我们提出了不同的催化条件， 这使得缺少配位基团的烯烃能够进行二碳官能化。催化烯烃 所提出的并且我们有很强的初步结果的二碳官能化反应是独一无二的 使用其他方法无法实现的转变。

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.