Exploration of Brønsted Base Catalysis for Formal C–H Bond Activations

Abstract

This PhD project investigates the use of (Lewis or Brønsted) bases in catalysis. While the first chapter explores the use of main group metal amides in C–H bond activation reactions, the second chapter focusses on metal-free organocatalysis using so-called carbones. In the first chapter, formal allylic C(sp3)–H bond activations of unfuctionalised alkenes for C–C bond formations with imines were investigated. Alkali metal amides were used as catalysts for these transformations, giving homoallylic amine products. The investigations showed the unique reactivity of the Na-amide catalyst compared to other metal base complexes. The reaction scope and robustness was explored and initial insights into the reaction mechanism were obtained.A related K-amide catalyst was then developed for the isomerisation of allyl benzenes, as well as functionalised olefins such as allylic silanes, boronic esters, phosphines, amines, ethers, and thioethers. This part explored the use of ligands to increase the catalyst’s selectivity. Finally, the metal- or functional group-substituted classes of reagents were used in the functionalised allylation of imines, giving highly complex molecules with a diverse range of applications. Here, unprecedented reactivities were observed for the use of allyl–M reagents, as the allylation involved the activation of C–H bonds rather than C–X bonds. Furthermore, new catalytic formations of heteroatom-substituted homoallylic amines were described.The following chapter focussed on the use of carbodiphosphoranes (CDPs) in catalysis. These C(0) bases, or carbones, represent a class of heteroallene compounds that exhibit a high electron density on a P(V)-flanked carbon centre. Their potential as either a Lewis or Brønsted base was examined. Different CDPs were synthesised and reacted stoichiometrically with CO2, boron Lewis acids and metal salts. The generated intermediates were then studied in their reaction behaviour, taking advantage of a potentially available second pair of electrons. The results of these reactions were compared to other carbon bases, such as carbenes or other carbones. Finally, the Brønsted basicity of the CDP was examined in reactions with acidic pro-nucleophiles. The conjugate addition of alkylnitriles to α,β- unsaturated amides was developed using a catalytic amount of CDP. To the best of our knowledge, the first catalytic use of a CDP, as well as the first C–H bond activation of acetonitrile in Michael additions was reported.