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Synthesis of Nitrogen-Containing Heterocycles Through Catalytic Dehydrative Cyclization and Carbon-Hydrogen Oxidative Cycloaddition Reactions

Rodriguez del Rey, Freddy O. (2022) Synthesis of Nitrogen-Containing Heterocycles Through Catalytic Dehydrative Cyclization and Carbon-Hydrogen Oxidative Cycloaddition Reactions. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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The synthetic importance of dehydrative cyclization reactions in the formation of nitrogen-containing heterocycles has been thoroughly documented. Most classical methods require the use of stoichiometric or excess amounts of dehydrating reagents. Here we present an environmentally benign, metal-catalyzed dehydrative cyclization reaction under mild conditions to form nitrogen-containing heterocycles. A wide range of β- or γ-hydroxy amides or thioamides were converted to the corresponding nitrogen-containing heterocycles. Diastereocontrol was observed in several oxazolines, oxazines and isoxazolines. Oxazolines containing a chiral amino acid side chain were synthesized using this method. The reaction rates for different diastereomers were studied, and a tight ion pair mechanism was proposed for these transformations. HFIP was found to be the optimal solvent for these transformations due to its ability to stabilize cationic intermediates, sequester water and mitigate basicity through hydrogen bonding interactions.
Carbon Hydrogen (C-H) functionalization strategies have gathered much interest from the synthetic community and have been an instrumental tool in the functionalization of pharmaceutical targets and natural product syntheses. Herein we report a method for an oxoammonium salt mediated C-H oxidation and cycloaddition reaction. The reaction increases molecular complexity, generating two rings and four stereocenters. The stereochemistry of the products is derived from an endo-transition state and in most cases results in a single diastereomer. This method is still being studied and optimized to provide a more robust method and increased yields.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Rodriguez del Rey, Freddy O.for3@pitt.edufor3
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairFloreancig, Paul
Committee MemberLiu,
Committee MemberWang,
Committee MemberMckone, James
Date: 12 October 2022
Date Type: Publication
Defense Date: 5 May 2022
Approval Date: 12 October 2022
Submission Date: 13 June 2022
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 242
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: oxazoline, isoxazolie, ionic-Diels-Alder, oxidative cycloaddition
Date Deposited: 12 Oct 2022 16:19
Last Modified: 12 Oct 2022 16:19


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