Hybrid Magnesium-Zinc Reagents:Structural Tailoring for Synthetic and Catalytic Applications

该提案旨在快速开辟新领域，并在混合金属化学领域建立新的前沿，重点关注合成领域，特别是开发和开发一种基本的新型有机金属试剂，即Mg-Zn杂化物，具有两种环境友好的金属。合成化学家的主要任务之一是改进和添加可用试剂的目录，寻找能够提供增强的反应性以及上级选择性和与各种不同底物的相容性的新化合物。在有机金属化学中，有机锂试剂构成合成中最重要的试剂之一，这反映在以下事实中：据估计，制药工业中制造的95%的药物在其合成中的一个或多个步骤中涉及使用这些试剂。有机锂化合物表现出高反应性，然而它们的主要限制是它们经常缺乏与许多常见有机官能团的相容性，这通常迫使使用低于环境温度。在本申请中，我们提出开发常规有机锂试剂的替代类型的试剂，即混合镁-锌试剂（Mg-Zn杂化物），其通过组合两种重要但基本上不同的经典有机金属试剂家族来制备：极性硬有机镁（R2 Mg或RMgX）和非极性软有机锌（R* 2 Zn或R*ZnX）化合物。通过使用这种混合金属方法，我们将向这些化合物中注入一组新的化学性质和反应性特征，这将超越传统的monoclonal化学的范围。该项目的一个关键方面将是筛选这些新的混合物在基本的有机反应，包括金属-卤素交换，去质子化金属或亲核加成，不仅化学计量，但也催化，通过导入有机镁试剂的高反应性有机锌试剂赋予高官能团耐受性的反应。

Drawn up to break new ground quickly and to establish new frontiers in the area of mixed-metal chemistry, this proposal focuses on the general area of Synthesis, and specifically on the development and exploitation of a fundamental new type of organometallic reagent, namely Mg-Zn hybrids, featuring two environmentally friendly metals.One of the main missions for synthetic chemists is to improve and to add to the catalogue of reagents available, searching for new compounds that can offer enhanced reactivities but also superior selectivities and compatibility with a wide range of different substrates. In organometallic chemistry, organolithium reagents constitute one of the most important reagents in synthesis as reflected by that fact that it is estimated that 95% of the drugs manufactured in the pharmaceutical industry involve the use of these reagents at one or more steps in their synthesis. Organolithium compounds exhibit high reactivities, however their main limitation is their frequent lack of compatibility with many common organic functional groups, which ussually impose the use of sub-ambient temperatures. In this application we propose the development of an alternative type of reagent to conventional organolithium reagents, namely mixed magnesium-zinc reagents (Mg-Zn hybrids), prepared by combining two important but fundamentally distinct families of classical organometallic reagent: polar hard organomagnesium (R2Mg or RMgX) and non-polar soft organozinc (R*2Zn or R*ZnX) compounds. By using this mixed-metal approach we will instil into these compounds a new cooperative set of chemical properties and reactivity profiles, which will extend beyond the confines of traditional monometallic chemistry. A key aspect of the project will be to screen the reactivity of these new hybrids in fundamental organic reactions including metal-halogen exchange, deprotonative metallation or nucleophilic addition, not only stoichiometrically but also catalytically, by importing the high reactivity of organomagnesium reagents into organozinc reagents endowed with high functional group tolerance.