Camphor as Chiral Motif in Ligand Design - Applications in Catalysis and Complexation Gas-Chromatography

Abstract

This thesis is intended to further extend the scope of camphor and camphor-derived building blocks in the synthesis of chiral ligands, catalysts and selectors, their successful application in catalysis and in enantioseparation sciences. The thesis is divided into four independent chapters each focusing on the development of novel camphor-based compounds and their application as catalysts or metal-selectors. A short introduction is given for each chapter dealing with recent progress in the field of interest as well as providing essential basics of the affected chemistry, like Pd-catalysis, polymer and separation science. In chapter 1, after an introduction about general aspects of chiral stationary phases (CSPs) and their application in complexation gas chromatography (CGC) the total synthesis of novel, extended CSPs derived from 1S-(+)-camphorsulfonic acid is presented. The developed Chirasil-Metal-OC3 phases are synthesized with overall high yield in six steps. Overall seven different Chirasil-Metal polymers with different separation capabilities are reported by metal-incorporation of nickel(II), oxovanadium(IV), europium(III), lanthanum(III) and variation of the amount of ligand content on the polymer. Their performance in enantioselective complexation gas chromatography (CGC) is studied in terms of selector-type, selector-concentration, polymer film thickness, polymer composition and column length. Superior activity and separation of 29 small-sized compounds, encompassing inter alia epoxides, derivatized alkenes and alkynes as well as alcohols and amides, is presented with throughout high separation factors. The thermal stability and the broad applicability, synthetic versatility and effectiveness of the newly derived Chirasil-Metal-OC3 phase is reported. The 2nd chapter of deals with the synthesis of a novel bidentate N,N-heterocyclic ligand motif derived from d-(+)-camphor. After a short introduction into isomerization reactions and the Wacker-oxidation of olefins, the synthesis and structural analysis of overall 11 new ligands is reported and the coordination to palladium, copper and cobalt is investigated. The 3rd Chapter of this thesis aims at the synthesis of a chiral NHC-pincer ligand derived from camphoric acid as the chiral building block. Preparation is presented in overall five steps in moderate to good overall yield. The molecular structures of the NHC- and triazole pincer ligand is presented and the structural characteristics are discussed in detail. The results are supported by X-ray chrystallographic measurements and an explaination for the observed coordination properties is given. The 4th chapter of this thesis focuses on the structure-reactivity relationship in the asymmetric intramolecular oxindole synthesis using Pd-NHC isonitrile catalysts featuring a successively increasing steric demand while maintaining the same chiral substitution pattern (camphor). After a short introduction into chiral NHCs used for this transformation, three six-membered hexahydropyrimidine core based, camphor-derived (bornylamine) NHC-Pdisonitrile complexes are presented and their application in the enantioselective alpha-amide arylation to form 3,3-disubstituted oxindoles is described. The results are discussed taking steric effects at the catalyst metal-center and steric demand of the substrates into account.