The development and application of metal-catalyzed diamination reactions
| dc.contributor.author | Cornwall, Richard G., author | |
| dc.contributor.author | Shi, Yian, advisor | |
| dc.contributor.author | Kennan, Alan, committee member | |
| dc.contributor.author | McNaughton, Brian, committee member | |
| dc.contributor.author | Henry, Charles, committee member | |
| dc.contributor.author | Chatterjee, Delphi, committee member | |
| dc.date.accessioned | 2007-01-03T05:57:14Z | |
| dc.date.available | 2007-01-03T05:57:14Z | |
| dc.date.issued | 2014 | |
| dc.description.abstract | Nitrogen-rich molecules are of great interest in chemistry and incorporation of nitrogen into molecules is an on-going active field of study. In particular, vicinal diamines are important functional moieties that are found throughout biologically active molecules and natural products as well as highly effective chiral control agents in organic synthesis. There has been much effort directed toward the efficient synthesis of vicinal diamines; however the development of a direct route has proven to be challenging. This dissertation discusses the application of diamination products from existing methods to synthesize biologically active motifs, as well as the development of new metal-catalyzed diamination methods for the synthesis of biologically interesting motifs from readily available starting materials. The β, γ-diamino acid motif is an area of active research because of its prevalence in biologically active molecules and its use in peptide library syntheses. Cyclization of β, γ-diamino acids give the closely related 4-aminopyrrolidinones. These five-membered amino lactams have been reported to potentiate insulin activity when incorporated into hypoglycemic peptide analogues and made the analogues more stable towards physiological degradation. Current methods for the synthesis of these compounds require multi-step procedures and rely heavily on commercially available amino acids as starting materials, thus limiting the structural variability for biological studies. Using a diamination method discovered in our lab, 4-aminopyrrolidinones were efficiently synthesized in 40% overall yield, over five steps from readily available terminal olefins or conjugated dienes, providing a comparable process in the synthesis of these compounds. As part of our ongoing efforts to study the mechanism of metal-catalyzed diaminations using diaziridinone as nitrogen source, it was found that regioselectivity in the diamination of conjugated dienes could be controlled using Cu(I) as catalyst and varying reaction conditions. An alternative nitrogen source, thiadiaziridine 1,1-dioxide, which has shown to display interesting reactivity, was chosen to further investigate the Cu(I)-catalyzed regioselective diamination. Upon varying reaction conditions with Cu(I) catalysts, regioselective diamination occurred for various conjugated dienes and allowed direct access to a range of diverse cyclic sulfamides which have interesting biological potential. With the racemic synthesis of cyclic sulfamides, it was of interest to obtain these compounds asymmetrically, as their biological properties are of value and current methods for their asymmetric synthesis do not allow much variation in substitution patterns. Using Pd2(dba)3 and a chiral phosphoramidite ligand, a variety of chiral cyclic sulfamides were synthesized in moderate to high yields and with ee's greater than 90%, providing direct access to these valuable compounds in one step from readily available conjugated diene substrates. Lastly, N,N-Di-tert-butyl thiadiaziridine 1,1-dioxide has been found to be a versatile reagent for interesting reactivity. Other uses of this reagent include the Pd(II)-catalyzed terminal diamination of conjugated dienes, diamination of allenes, and the Pd-catalyzed oxidation of alcohols to form α, β-unsaturated compounds. | |
| dc.format.medium | born digital | |
| dc.format.medium | doctoral dissertations | |
| dc.identifier | Cornwall_colostate_0053A_12663.pdf | |
| dc.identifier.uri | http://hdl.handle.net/10217/88420 | |
| dc.language | English | |
| dc.language.iso | eng | |
| dc.publisher | Colorado State University. Libraries | |
| dc.relation.ispartof | 2000-2019 | |
| dc.rights | Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. | |
| dc.subject | catalysis | |
| dc.subject | organometallic | |
| dc.subject | organic synthesis | |
| dc.subject | diamination | |
| dc.title | The development and application of metal-catalyzed diamination reactions | |
| dc.type | Text | |
| dcterms.rights.dpla | This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). | |
| thesis.degree.discipline | Chemistry | |
| thesis.degree.grantor | Colorado State University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |
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