Dissertation/Thesis Abstract

Applications of chiral guanidine organocatalysts in asymmetric transformations probing structure activity relationships of artificial enzyme active sites and development of metal -free oxidative cyclization reactions
by Lovick, Helena M., Ph.D., University of Washington, 2009, 196; 3393992
Abstract (Summary)

The common theme throughout this research was the search for new tools and routes to effect useful chemical transformations. During these investigations we utilized a several distinctly different approaches. First, a wide variety of organocatalysts were synthesized and applied to epoxide and aziridine ring openings. The organocatalysts served as efficient, albeit non-stereoselective catalysts of the ring opening. However, several novel chiral guanidine organocatalysts were capable of asymmetric induction in the aza-Henry reaction. A number of structural modifications were examined, revealing a unique enhancement in stereoselectivity for an ethylene-linked bisguanidine. Furthermore, the major enantiomeric form of the β-nitroamine products could be selectively reversed when a bisguanidine was used instead of a monoguanidine.

In collaboration with other researchers, we examined the substrate specificity and selectivity of artificial enzymes. A series of compounds was synthesized to probe structure activity relationships and explore the scope of catalyzable reactions. Our efforts aided studies of the properties of the synthesized enzymes and also aided the use of these enzymes for more challenging chemical transformations.

In addition to our efforts in catalysis, we have developed a broadly applicable, high yielding oxyamination reaction of alkenes promoted by Brønsted acids. Under these conditions the acid is incorporated into the cyclized products providing an overall aminohydroxylation of the alkene. Multiple ring sizes were formed generating pyrrolidines, piperidines, and azepanes with a general preference for endo cyclization. This highly endo selective aminohydroxylation provides an alternative synthetic route to useful nitrogen-containing heterocycles. This system also exhibits an unusual preference for endo ring closure in contrast to existing exo selective methods. Consequently we propose in situ formation of an aziridinium ion is responsible for both the endo and anti selectivity of the process.

Indexing (document details)
Advisor: Michael, Forrest E.
School: University of Washington
School Location: United States -- Washington
Source: DAI-B 71/02, Dissertation Abstracts International
Subjects: Organic chemistry
Keywords: Artificial enzymes, Asymmetric transformations, Guanidine, Metal-free oxidative cyclization, Organocatalysts
Publication Number: 3393992
ISBN: 9781109609349
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