Thesis (Ph. D.) -- California Institute of Technology, 2010. / Title from home page (viewed 02/24/2010). Advisor and committee chair names found in the thesis' metadata record in the digital repository. Includes bibliographical references.

Reactive distillation is a combination of a traditional multi-stage distillation column with a chemical reaction. The primary benefits of a reactive distillation process are reduced capital costs for equipment and energy in addition to enhanced conversion for equilibrium-limited reactions. One such equilibrium-limited reaction is an olefin metathesis. Olefin metathesis is a catalyzed reaction that breaks the double bond in olefins and rearranges the alkene fragments into new olefinic products. A comprehensive investigation of a reactive distillation based olefin metathesis and supporting experimentation is documented here. A small pilot plant study was performed for pilot scale performance comparison. Bench reactor experimentation was conducted for the purposes of learning detailed information on specific metathesis reactions. Lastly, a process simulation study was completed for comparison in performance with the small pilot plant process. The small pilot plant study involved the design, construction, testing, operation, and optimization of a reactive distillation column. Continuous operation campaigns at two different hydraulic capacities within the reactive zone were performed and their performances were compared. A higher hydraulic capacity proved to be more efficient and more selective for the conversion of medium molecular weight olefins into both lighter and heavier olefinic products. Bench reactor experiments were designed with the intent of investigating specific alpha olefin metathesis reactions and obtaining conversions, selectivities, and yield structures for future simulation work. However, under conditions similar to that within the small pilot plant process, there existed a high frequency of secondary double bond isomerization (possibly due to an isomerization activity for alumina). There was also an observed dependence on temperature for both the primary metathesis and secondary isomerization reactions. A process simulation representative of the small pilot plant process was constructed in AspenPlus. Using a simplified reaction network based on assumptions and analysis of the reactive zone, its performance was compared with that of the small pilot plant process. The simulation performance tended to underpredict overhead compositions, but accurately simulated the bottoms product composition. Because reactive distillation has not been used with a heavy olefin metathesis reaction, this dissertation demonstrates the uniqueness and effectiveness of a reactive distillation based heavy olefin metathesis. / text

Ring-closing metathesis (RCM) has proven to be a valuable tool for constructing alkaloid-like, poly-cyclic compounds. The syntheses of alkaloid structures we were interested in developing, could utilize RCM to construct a spirocyclic structure for the immunosuppressant FR901483 and the tetracyclic framework of lundurines A-C asymmetrically. The azaspirane core of FR901483 was obtained via an addition of an allylsilane to an N-acyl iminium ion, and a RCM. Other key functional group manipulations were a stereoselective hydroboration and a subsequent lactonization that provided a precursor for a lactone-lactam rearrangement. This rearrangement provided the azatricyclic core of FR901483. In the enantioselective approach to FR901483 a new mildly cleavable protecting group was developed. Addition of a zinc nucleophile to a chiral N-acyl iminium ion, and a RCM provided the desired precursor for the hydroboration/lactone-lactam rearrangement sequence but without a sufficient stereoselection. A novel approach toward the total synthesis of lundurines A-C has been developed. The key features of the approach involve an intramolecular cyclopropanation of the indole C(2)-C(3) double bond, an enantioselective tandem RCM to construct the tetracyclic core and a concise synthesis to access the RCM precursor. An Ugi reaction was utilized with both cyclic and acyclic ketones, 2-vinyltryptamine derivative, a carboxylic acid and an isocyanide to access diverse compounds, including RCM precursors. An alternative reductive amination route to construct the RCM precursor for the lundurines was found to be more efficient and high yielding than the Ugi approach. An RCM was utilized to affect the closure of the five-and eight-membered rings of the tetracyclic core. This constitutes as the first example of RCM of a 2-vinylindole derivative to give an indole-fused eight-membered ring. / text

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Includes bibliographical references (p. 149-156).

Thesis (Ph. D.)--University of Texas at Austin, 2005. / Supervisor: Stephen F. Martin. Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

The past two years have witnessed groundbreaking advances in the industrial deployment of olefin metathesis. While metathesis methodologies have been an integral part of the chemical manufacturing landscape for 60 years, implementation in pharmaceutical and specialty chemicals manufacturing represents a new frontier. The imperative to develop greener and more cost-effective manufacturing processes is anticipated to spur further improvements in sustainable synthesis. Advances in catalyst productivity, however, are critical to expansion of the uptake of metathesis methodologies in this and other manufacturing sectors. Key to increased catalyst productivity is elimination of side reactions that lower yield and errode selectivity. Among such reactions, double-bond isomerization is by far most common. Accumulating evidence suggests that unwanted isomerization during olefin metathesis is due to ruthenium species generated via catalyst decomposition. The identification of these species and how they are formed is thus of great importance. Two hydride complexes, RuHCl(CO)(H2IMes)(PCy3) and a dinuclear hydride, are known to form under some circumstances by decomposition of the second-generation Grubbs catalyst, RuCl2(H2IMes)(PCy3)(=CHPh), GII. These complexes have been widely viewed as responsible for unintended isomerization reactions. However, examination of their performance in olefin isomerization under conditions relevant to metathesis reveals that their activity is too feeble to account for the levels of isomerization observed during metathesis. Alternatively, kinetically competent culprits emerge from decomposition studies that reveal unexpected ruthenium products on decomposition of GII during metathesis; specifically, formation of ruthenium nanoparticles. The formation and catalytic non-innocence of RuNPs constitutes a new paradigm in this field, which opens the door to new approaches to prevent or to harness olefin isomerization. Key to prevention, clearly, is circumventing the decomposition pathways that enable ligand stripping from the active catalyst. New approaches to catalyst design that involve use of truncated NHC ligands are also examined. Finally, the power and utility of isomerization when coupled with metathesis is explored. The opportunities and limitations of orthogonal isomerization–metathesis catalysis are examined in the context of the two-step synthesis of cinnamates from 1-allylbenzenes abundant in essential oils. An efficient one-pot, two-catalyst protocol is developed for conversion of these biorenewable feedstocks to high-value-added chemicals.