Development of new multicomponent reactions for 1,3,4-oxadiazole synthesis
<p>Chapter 1 introduces the chemistry of 1,3,4-oxadiazoles with a specific focus on currently available strategies, and methodologies for their synthesis. Five distinct synthetic approaches – 1) dehydration of 1,2-diacylhydrazines; 2) oxidative cyclizations of N-acyl hydrazones; 3) C-H functio...
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| Format: | Thesis |
| Language: | English |
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2022
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| _version_ | 1826310199595499520 |
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| author | Matheau-Raven, D |
| author2 | Dixon, D |
| author_facet | Dixon, D Matheau-Raven, D |
| author_sort | Matheau-Raven, D |
| collection | OXFORD |
| description | <p>Chapter 1 introduces the chemistry of 1,3,4-oxadiazoles with a specific focus on currently available strategies, and methodologies for their synthesis. Five distinct synthetic approaches – 1) dehydration of 1,2-diacylhydrazines; 2) oxidative cyclizations of N-acyl hydrazones; 3) C-H functionalization of 2-substituted 1,3,4-oxadiazoles; 4) rearrangements of N-H tetrazoles; 5) reactions using (N-isocyanoimino)triphenylphosphorane (NIITP) as a three atom CNN source – are discussed in detail and their limitations evaluated.</p>
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<p>Chapter 2 focuses on a novel three-component reaction for the reductive synthesis of α-amino 1,3,4-oxadiazoles (or heterodiazoles), from tertiary amides and lactams, feedstock carboxylic acids (or appropriate C-, S-, N-Brønsted acids), and NIITP. Taking advantage of the mild and chemoselective reductive activation of tertiary amides provided by the combination of Vaska’s complex and 1,1,3,3-tetramethyldisiloxane (TMDS) the reaction was applied to the late-stage functionalization of ten drug-like amides and carboxylic acids and culminated in the synthesis of three heterodiazole-fused drug-drug conjugates.</p>
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<p>Chapter 3 demonstrates that N-carbamoyl imines, with carboxylic acid (or N-acyl sulfonamide) coupling partners and NIITP, can efficiently generate N-carbamoyl α-amino 1,3,4-oxadiazole (or 1,2,4-triazole) structures in a three-component reaction – expanding the existing scope of C=N electrophiles used with NIITP. A successful scale-up of this methodology allowed the gram-scale synthesis of a primary α-amino 1,3,4-oxadiazole, and a subsequent investigation into its derivatization.</p>
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<p>Chapter 4 presents the merger of two modern approaches for 1,3,4-oxadiazole synthesis – 2-substituted 1,3,4-oxadiazole construction using NIITP and the C-H functionalization of 2-substituted 1,3,4-oxadiazoles – into a one-pot and multicomponent protocol for synthesis of 2,5-disubstituted, or 2-amino-5-substituted, 1,3,4-oxadiazoles. A preliminary investigation into the use of nucleophilic secondary amine coupling partners for synthesis of 2-amino-5-substituted 1,3,4-oxadiazoles is additionally discussed.</p> |
| first_indexed | 2024-03-07T07:48:33Z |
| format | Thesis |
| id | oxford-uuid:787cf1d8-18e0-4c0b-86cf-ebee0a45cd21 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:48:33Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | oxford-uuid:787cf1d8-18e0-4c0b-86cf-ebee0a45cd212023-06-22T07:51:10ZDevelopment of new multicomponent reactions for 1,3,4-oxadiazole synthesisThesishttp://purl.org/coar/resource_type/c_db06uuid:787cf1d8-18e0-4c0b-86cf-ebee0a45cd21Organic ChemistryEnglishHyrax Deposit2022Matheau-Raven, DDixon, D<p>Chapter 1 introduces the chemistry of 1,3,4-oxadiazoles with a specific focus on currently available strategies, and methodologies for their synthesis. Five distinct synthetic approaches – 1) dehydration of 1,2-diacylhydrazines; 2) oxidative cyclizations of N-acyl hydrazones; 3) C-H functionalization of 2-substituted 1,3,4-oxadiazoles; 4) rearrangements of N-H tetrazoles; 5) reactions using (N-isocyanoimino)triphenylphosphorane (NIITP) as a three atom CNN source – are discussed in detail and their limitations evaluated.</p> <br> <p>Chapter 2 focuses on a novel three-component reaction for the reductive synthesis of α-amino 1,3,4-oxadiazoles (or heterodiazoles), from tertiary amides and lactams, feedstock carboxylic acids (or appropriate C-, S-, N-Brønsted acids), and NIITP. Taking advantage of the mild and chemoselective reductive activation of tertiary amides provided by the combination of Vaska’s complex and 1,1,3,3-tetramethyldisiloxane (TMDS) the reaction was applied to the late-stage functionalization of ten drug-like amides and carboxylic acids and culminated in the synthesis of three heterodiazole-fused drug-drug conjugates.</p> <br> <p>Chapter 3 demonstrates that N-carbamoyl imines, with carboxylic acid (or N-acyl sulfonamide) coupling partners and NIITP, can efficiently generate N-carbamoyl α-amino 1,3,4-oxadiazole (or 1,2,4-triazole) structures in a three-component reaction – expanding the existing scope of C=N electrophiles used with NIITP. A successful scale-up of this methodology allowed the gram-scale synthesis of a primary α-amino 1,3,4-oxadiazole, and a subsequent investigation into its derivatization.</p> <br> <p>Chapter 4 presents the merger of two modern approaches for 1,3,4-oxadiazole synthesis – 2-substituted 1,3,4-oxadiazole construction using NIITP and the C-H functionalization of 2-substituted 1,3,4-oxadiazoles – into a one-pot and multicomponent protocol for synthesis of 2,5-disubstituted, or 2-amino-5-substituted, 1,3,4-oxadiazoles. A preliminary investigation into the use of nucleophilic secondary amine coupling partners for synthesis of 2-amino-5-substituted 1,3,4-oxadiazoles is additionally discussed.</p> |
| spellingShingle | Organic Chemistry Matheau-Raven, D Development of new multicomponent reactions for 1,3,4-oxadiazole synthesis |
| title | Development of new multicomponent reactions for 1,3,4-oxadiazole synthesis |
| title_full | Development of new multicomponent reactions for 1,3,4-oxadiazole synthesis |
| title_fullStr | Development of new multicomponent reactions for 1,3,4-oxadiazole synthesis |
| title_full_unstemmed | Development of new multicomponent reactions for 1,3,4-oxadiazole synthesis |
| title_short | Development of new multicomponent reactions for 1,3,4-oxadiazole synthesis |
| title_sort | development of new multicomponent reactions for 1 3 4 oxadiazole synthesis |
| topic | Organic Chemistry |
| work_keys_str_mv | AT matheauravend developmentofnewmulticomponentreactionsfor134oxadiazolesynthesis |