Understanding Selectivity of Lithiated Intermediates for Synthesis

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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.