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Part I: Total Synthesis of Pleurotinoid Natural Products via a Nontraditional C-H Epimerization Part II: Synthesis of Benzocyclobutenes via Palladium-Catalyzed β-Methylene-Selective C-H Activation
Part I: Total Synthesis of Pleurotinoid Natural Products via a Nontraditional C-H Epimerization Part II: Synthesis of Benzocyclobutenes via Palladium-Catalyzed β-Methylene-Selective C-H Activation
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151423
- ISBN
- 9798382810102
- DDC
- 547
- 서명/저자
- Part I: Total Synthesis of Pleurotinoid Natural Products via a Nontraditional C-H Epimerization Part II: Synthesis of Benzocyclobutenes via Palladium-Catalyzed β-Methylene-Selective C-H Activation
- 발행사항
- [Sl] : Princeton University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 300 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Sorensen, Erik J.
- 학위논문주기
- Thesis (Ph.D.)--Princeton University, 2024.
- 초록/해제
- 요약Pleurotin, isolated in 1947, is an architecturally-complex hexacyclic benzoquinone natural product which displays significant anticancer and antibiotic properties. Since as early as 2010, our group pursued a synthesis of pleurotin based on a proximity-induced intramolecular Diels-Alder cycloaddition of a transient ortho-quinodimethide generated from a benzocyclobutene. Revisiting a prior model system in a more structurally-relevant context, we found this approach untenable and instead we developed an alternative construction featuring Gao's titanium(IV)-mediated photoenolization Diels-Alder coupling of an ortho-tolualdehyde with a functionalized hydrindenone. While this pairing displayed excellent stereofacial selectivity, it produced an undesired cis-locked hydrindane. The stereochemistry was corrected to the required trans-hydrindane through alkoxy-radical induced epimerization of the unactivated hydrogen-bearing methine stereocenter at C-5. These efforts culminated in an 8-step synthesis of a known pentacyclic intermediate towards pleurotin, as well as the first total syntheses of the related pleurotinoid natural products pleurogrisein and 4-hydroxypleurogrisein.Benzocyclobutenes are useful synthetic building blocks and are also present in natural product scaffolds, but there are relatively few methods for their synthesis. By adapting our previous methodology for the synthesis of indanes via methylene-selective C-H functionalization, we developed a methodology for the synthesis of structurally unique benzocyclobutenes. The reaction utilizes glycine as a transient directing group and a 2-pyridone ligand, which may govern methylene selectivity by making intimate molecular associations with the substrate during concerted metallation deprotonation. This reaction is shown to be highly selective for intramolecular methylene C(sp3)‒H arylation, thus enabling sequential C(sp3)‒H functionalization.
- 일반주제명
- Organic chemistry
- 일반주제명
- Chemistry
- 일반주제명
- Analytical chemistry
- 키워드
- Epimerization
- 키워드
- Palladium
- 키워드
- Pleurotin
- 키워드
- Total synthesis
- 기타저자
- Princeton University Chemistry
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798382810102
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■040 ▼aMiAaPQ▼cMiAaPQ
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■1001 ▼aHoskin, John Francis.▼0(orcid)0000-0002-8427-5946
■24510▼aPart I: Total Synthesis of Pleurotinoid Natural Products via a Nontraditional C-H Epimerization Part II: Synthesis of Benzocyclobutenes via Palladium-Catalyzed β-Methylene-Selective C-H Activation
■260 ▼a[Sl]▼bPrinceton University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a300 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Sorensen, Erik J.
■5021 ▼aThesis (Ph.D.)--Princeton University, 2024.
■520 ▼aPleurotin, isolated in 1947, is an architecturally-complex hexacyclic benzoquinone natural product which displays significant anticancer and antibiotic properties. Since as early as 2010, our group pursued a synthesis of pleurotin based on a proximity-induced intramolecular Diels-Alder cycloaddition of a transient ortho-quinodimethide generated from a benzocyclobutene. Revisiting a prior model system in a more structurally-relevant context, we found this approach untenable and instead we developed an alternative construction featuring Gao's titanium(IV)-mediated photoenolization Diels-Alder coupling of an ortho-tolualdehyde with a functionalized hydrindenone. While this pairing displayed excellent stereofacial selectivity, it produced an undesired cis-locked hydrindane. The stereochemistry was corrected to the required trans-hydrindane through alkoxy-radical induced epimerization of the unactivated hydrogen-bearing methine stereocenter at C-5. These efforts culminated in an 8-step synthesis of a known pentacyclic intermediate towards pleurotin, as well as the first total syntheses of the related pleurotinoid natural products pleurogrisein and 4-hydroxypleurogrisein.Benzocyclobutenes are useful synthetic building blocks and are also present in natural product scaffolds, but there are relatively few methods for their synthesis. By adapting our previous methodology for the synthesis of indanes via methylene-selective C-H functionalization, we developed a methodology for the synthesis of structurally unique benzocyclobutenes. The reaction utilizes glycine as a transient directing group and a 2-pyridone ligand, which may govern methylene selectivity by making intimate molecular associations with the substrate during concerted metallation deprotonation. This reaction is shown to be highly selective for intramolecular methylene C(sp3)‒H arylation, thus enabling sequential C(sp3)‒H functionalization.
■590 ▼aSchool code: 0181.
■650 4▼aOrganic chemistry
■650 4▼aChemistry
■650 4▼aAnalytical chemistry
■653 ▼aEpimerization
■653 ▼aMethylene selectivity
■653 ▼aPalladium
■653 ▼aPleurotin
■653 ▼aTotal synthesis
■690 ▼a0490
■690 ▼a0486
■690 ▼a0485
■71020▼aPrinceton University▼bChemistry.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0181
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161627▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
