Understanding Selectivity of Lithiated Intermediates for Synthesis

锂化学位于有机化学和无机化学的交界处，有机锂化合物经常被用作合成药物、农用化学品、香料、香料和其他合成中间体的通用化学工具。该项目的重点是深入了解有机锂碳化反应中观察到的化学、区域和立体选择性以及与Schlosers碱混合物的去质子化反应的机理。虽然有机锂作为强碱的使用在合成化学中普遍存在，但它们在与未活化的烯烃的加成反应中的应用相对来说还没有被探索过，很少被利用。该项目的A部分侧重于这些碳化反应，并研究了通过去质子化制备的氨化反应的中间体。将研究有机锂、钠和钾与(有氨基功能的)烯烃的竞争加成和去质子化反应，以及它们在一般合成用途中的潜力。施洛瑟斯基础混合物是该项目第一阶段的重要试剂。根据A部分所述Schlosers碱的首次结构表征和所研究的金属中间体的重要反应模式，提案的B部分将重点介绍Schlosers碱混合物的结构/反应模式，用于A部分相关研究和一般合成用途。在这里，我们建议通过计算、结构和合成化学的共同努力来全面理解竞争的碳金属化反应和去质子化。关键目标将是绘制反应性图谱，获得反应路径和过渡态的计算和结构证据，并将这些知识应用于完善不对称变体。

Lithium chemistry is positioned at the interface of Organic and Inorganic Chemistry with organolithium compounds frequently employed as versatile chemical tools for the synthesis of pharmaceuticals, agrochemicals, flavours, fragrances and other synthetic intermediates. The project focuses on the in-depth mechanistic understanding of the observed chemo-, regio- and stereo-selectivity in organolithium carbometallation reactions and deprotonations with Schlossers Base Mixtures. While the use of organolithiums as strong bases is ubiquitous in synthetic chemistry, their application for addition reactions with unactivated alkenes is relatively unexplored and is rarely utilised. Part A of the project focuses on these carbometallations and studies the intermediates of aminometallation, prepared by deprotonation. The understanding of competing addition and deprotonation reactions of organolithiums, -sodiums and -potassiums with alkenes (with amino functions) and their potential for general synthetic usage will be studied. Schlossers Base Mixtures were important reagents in the first period of the project. Based on the first structural characterization of a Schlossers Base and the important reactivity pattern for the studied metallated intermediates in part A, part B of the proposal will focus on the structure/reactivity pattern of Schlossers Base Mixtures for part A related studies and general synthetic usage. Herein we propose a comprehensive understanding of competing carbometallation reactions and deprotonations through the combined efforts of computational, structural and synthetic chemistry. Key goals will be to map reactivity profiles, gain computational and structural evidence for reaction pathways and transition states and apply this knowledge to perfecting asymmetric variants.