Selective Homogeneous Catalysis in Asymmetric Synthesis

Peter Fristrup

Research output: Book/ReportPh.D. thesisResearch

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Abstract

The subject of this thesis is selectivity in homogeneous asymmetric transition metalcatalyzedreactions. Four different reactions within organic chemistry have been studied bykinetic measurements, computational chemistry (modelling) or both of them in parallel.A Hammett study was performed on the Heck reaction between phenyl triflate and a seriesof para-substituted styrenes. A linear correlation was obtained only for substitution in the α-position, where the developing positive charge is in direct conjugation with the group in thepara-position.The palladium-catalyzed allylic alkylation has been the subject of several smaller projects.With bidentate nitrogen-based ligands experimental selectivities were used as a benchmark for acomputational study. When a large enough part of the experimental system was included, theselectivity could be predicted with reasonable accuracy.When using PPh3 as ligand, the effect of chloride has been the subject of both experimentaland computational studies. The effect on the regioisomeric distributions resulting from allylicalkylation of a branched starting material was investigated experimentally and could berationalized computationally. A thorough computational study succeeded in explaining theobserved results, although other significant results were also obtained during this study. Finally,an intramolecular reaction was studied computationally, and the rate increase observed underphase transfer catalysis conditions could be related directly to the absence of Na+. Thisexplanation was supported by new experimental investigations.A kinetic study was conducted on the Mn(salen)-catalyzed asymmetric epoxidation reactionemploying a series of methyl-substituted styrenes. The observed reactivities and selectivitiescould be rationalized by the existence of two different approach vectors, which are bothfavoured for these substrates. In addition, the study could serve as a testing ground for thedevelopment of new theoretical methods.The reactivity and selectivity in the osmium-catalyzed asymmetric dihydroxylation wasstudied using a series of twelve “substrate-probes”, which were designed and synthesizedspecifically for this purpose. Both the stoichiometric reaction with OsO4 in toluene and the moreenvironmentally benign catalytic reaction in a two-phase system were studied. The obtainedexperimental results were in good agreement with predictions based on computational modellingof the transition states. Visualization of the determined transition states allowed for theconstruction of the new mnemonic device for prediction of absolute configuration, which alsoincluded a mapping of the important features onto an overlaid transition state.
Original languageEnglish
Place of PublicationKgs. Lyngby, Denmark
PublisherTechnical University of Denmark
Number of pages160
Publication statusPublished - May 2006

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