2026-09-20T03:26:29Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/733882022-01-13T07:54:21Zcom_1721.1_7582com_1721.1_7581col_1721.1_131024
Stephen L. Buchwald and K. Dane Wittrup.
McAvoy, Camille Z
Massachusetts Institute of Technology. Dept. of Chemical Engineering.
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Chemistry
2012-09-27T15:27:58Z
2012-09-27T15:27:58Z
2012
2012
http://hdl.handle.net/1721.1/73388
809804704
Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Chemistry; and, (S.B.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2012.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. ).
The development of methodologies for C-N bond formation reactions is an important scientific challenge because of many academic and industrial applications. This work will focus particularly on palladium-catalyzed cross-couplings of amine-containing compounds with aryl halides. The scope of the BrettPhos precatalyst for the cross-coupling of ortho-substituted aryl iodides with amides is studied using substrates with a variety of functional groups. Due to potential metal-chelating issues with some of the substrates used in this study, a proposed ligand synthesis is discussed in which one of the methoxy groups of BrettPhos is replaced with a morpholine capable of occupying palladium's open coordination site during its catalytic cycle. A final C-N bond formation study focuses on the cross-coupling of aryl halides with amidine salts. For this cross-coupling, a methodology has been developed that can be applied to various electron-rich, electron-poor, and electron-neutral substrates. Furthermore, the products of this cross-coupling can be used for a subsequent electrocyclization through a reaction with aldehyde, demonstrating that a relatively simple two-pot methodology can be used to make relatively complex substrates with pharmaceutical applications. Both amides and amidines are common moieties in drug-like molecules because of the various biological activities of these functional groups. Potential medicinal applications of the developed cross-coupling of amidine salts with aryl halides methodology are described. Thus, methodologies for various palladium-catalyzed, C-N cross-couplings as well as a potential ligand synthesis to be used for palladium catalysis are herein discussed.
by Camille Z. McAvoy.
S.B.
p.
eng
Massachusetts Institute of Technology
M.I.T. theses are protected by
copyright. They may be viewed from this source for any purpose, but
reproduction or distribution in any format is prohibited without written
permission. See provided URL for inquiries about permission.
http://dspace.mit.edu/handle/1721.1/7582
Chemistry.
Chemical Engineering.
Palladium-catalyzed C-N cross-coupling reactions toward the synthesis of drug-like molecules
Thesis
application/pdf
false
Publication
unknown
unknown
<Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="b6b2e97b-d2f0-4eb1-8377-3f6093edc6f7">
<Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type>
<Language>eng</Language>
<Title>Palladium-catalyzed C-N cross-coupling reactions toward the synthesis of drug-like molecules</Title>
<PublishedIn>
<Publication>
</Publication>
</PublishedIn>
<PublicationDate>2012</PublicationDate>
<Authors>
<Author>
<DisplayName>McAvoy, Camille Z</DisplayName>
<Affiliation>
<OrgUnit>
</OrgUnit>
</Affiliation>
</Author>
</Authors>
<Editors>
</Editors>
<Publishers>
<Publisher>
<DisplayName>Massachusetts Institute of Technology</DisplayName>
<OrgUnit />
</Publisher>
</Publishers>
<License>http://dspace.mit.edu/handle/1721.1/7582</License>
<Keyword>Chemistry.</Keyword>
<Keyword>Chemical Engineering.</Keyword>
<Abstract>The development of methodologies for C-N bond formation reactions is an important scientific challenge because of many academic and industrial applications. This work will focus particularly on palladium-catalyzed cross-couplings of amine-containing compounds with aryl halides. The scope of the BrettPhos precatalyst for the cross-coupling of ortho-substituted aryl iodides with amides is studied using substrates with a variety of functional groups. Due to potential metal-chelating issues with some of the substrates used in this study, a proposed ligand synthesis is discussed in which one of the methoxy groups of BrettPhos is replaced with a morpholine capable of occupying palladium's open coordination site during its catalytic cycle. A final C-N bond formation study focuses on the cross-coupling of aryl halides with amidine salts. For this cross-coupling, a methodology has been developed that can be applied to various electron-rich, electron-poor, and electron-neutral substrates. Furthermore, the products of this cross-coupling can be used for a subsequent electrocyclization through a reaction with aldehyde, demonstrating that a relatively simple two-pot methodology can be used to make relatively complex substrates with pharmaceutical applications. Both amides and amidines are common moieties in drug-like molecules because of the various biological activities of these functional groups. Potential medicinal applications of the developed cross-coupling of amidine salts with aryl halides methodology are described. Thus, methodologies for various palladium-catalyzed, C-N cross-couplings as well as a potential ligand synthesis to be used for palladium catalysis are herein discussed.</Abstract>
<Access xmlns="http://purl.org/coar/access_right"
>
</Access>
</Publication>